WorldWideScience

Sample records for biological systems represents

  1. 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.

  2. 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…

  3. Compartmental study of biological systems

    International Nuclear Information System (INIS)

    Moretti, J.L.

    1975-01-01

    The compartmental analysis of biological system is dealt with on several chapters devoted successively to: terminology; a mathematical and symbolic account of a system at equilibrium; different compartment systems; analysis of the experimental results. For this it is pointed out that the application of compartmental systems to biological phenomena is not always without danger. Sometimes the compartmental system established in a reference subject fails to conform in the patient. The compartments can divide into two or join together, completely changing the aspect of the system so that parameters calculated with the old model become entirely false. The conclusion is that the setting up of a compartmental system to represent a biological phenomenon is a tricky undertaking and the results must be constantly criticized and questioned [fr

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

    DEFF Research Database (Denmark)

    Green, Sara; Serban, Maria; Scholl, Raphael

    2018-01-01

    of biological networks using tools from graph theory to the application of dynamical systems theory to understand the behavior of complex biological systems. We show how network approaches support and extend traditional mechanistic strategies but also offer novel strategies for dealing with biological...... strategies? When and how can network and mechanistic approaches interact in productive ways? In this paper we address these questions by focusing on how biological networks are represented and analyzed in a diverse class of case studies. Our examples span from the investigation of organizational properties...

  5. Dynamic neuronal ensembles: Issues in representing structure change in object-oriented, biologically-based brain models

    Energy Technology Data Exchange (ETDEWEB)

    Vahie, S.; Zeigler, B.P.; Cho, H. [Univ. of Arizona, Tucson, AZ (United States)

    1996-12-31

    This paper describes the structure of dynamic neuronal ensembles (DNEs). DNEs represent a new paradigm for learning, based on biological neural networks that use variable structures. We present a computational neural element that demonstrates biological neuron functionality such as neurotransmitter feedback absolute refractory period and multiple output potentials. More specifically, we will develop a network of neural elements that have the ability to dynamically strengthen, weaken, add and remove interconnections. We demonstrate that the DNE is capable of performing dynamic modifications to neuron connections and exhibiting biological neuron functionality. In addition to its applications for learning, DNEs provide an excellent environment for testing and analysis of biological neural systems. An example of habituation and hyper-sensitization in biological systems, using a neural circuit from a snail is presented and discussed. This paper provides an insight into the DNE paradigm using models developed and simulated in DEVS.

  6. 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...

  7. Integrating systems biology models and biomedical ontologies.

    Science.gov (United States)

    Hoehndorf, Robert; Dumontier, Michel; Gennari, John H; Wimalaratne, Sarala; de Bono, Bernard; Cook, Daniel L; Gkoutos, Georgios V

    2011-08-11

    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. 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. 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.

  8. 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."

  9. Atypical biological motion kinematics are represented by complementary lower-level and top-down processes during imitation learning.

    Science.gov (United States)

    Hayes, Spencer J; Dutoy, Chris A; Elliott, Digby; Gowen, Emma; Bennett, Simon J

    2016-01-01

    Learning a novel movement requires a new set of kinematics to be represented by the sensorimotor system. This is often accomplished through imitation learning where lower-level sensorimotor processes are suggested to represent the biological motion kinematics associated with an observed movement. Top-down factors have the potential to influence this process based on the social context, attention and salience, and the goal of the movement. In order to further examine the potential interaction between lower-level and top-down processes in imitation learning, the aim of this study was to systematically control the mediating effects during an imitation of biological motion protocol. In this protocol, we used non-human agent models that displayed different novel atypical biological motion kinematics, as well as a control model that displayed constant velocity. Importantly the three models had the same movement amplitude and movement time. Also, the motion kinematics were displayed in the presence, or absence, of end-state-targets. Kinematic analyses showed atypical biological motion kinematics were imitated, and that this performance was different from the constant velocity control condition. Although the imitation of atypical biological motion kinematics was not modulated by the end-state-targets, movement time was more accurate in the absence, compared to the presence, of an end-state-target. The fact that end-state targets modulated movement time accuracy, but not biological motion kinematics, indicates imitation learning involves top-down attentional, and lower-level sensorimotor systems, which operate as complementary processes mediated by the environmental context. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. The Systems Biology Research Tool: evolvable open-source software

    Directory of Open Access Journals (Sweden)

    Wright Jeremiah

    2008-06-01

    Full Text Available Abstract Background Research in the field of systems biology requires software for a variety of purposes. Software must be used to store, retrieve, analyze, and sometimes even to collect the data obtained from system-level (often high-throughput experiments. Software must also be used to implement mathematical models and algorithms required for simulation and theoretical predictions on the system-level. Results We introduce a free, easy-to-use, open-source, integrated software platform called the Systems Biology Research Tool (SBRT to facilitate the computational aspects of systems biology. The SBRT currently performs 35 methods for analyzing stoichiometric networks and 16 methods from fields such as graph theory, geometry, algebra, and combinatorics. New computational techniques can be added to the SBRT via process plug-ins, providing a high degree of evolvability and a unifying framework for software development in systems biology. Conclusion The Systems Biology Research Tool represents a technological advance for systems biology. This software can be used to make sophisticated computational techniques accessible to everyone (including those with no programming ability, to facilitate cooperation among researchers, and to expedite progress in the field of systems biology.

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

    Science.gov (United States)

    Chen, Bor-Sen; Wu, Chia-Chou

    2013-01-01

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

  12. 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.

  13. Identifying optimal models to represent biochemical systems.

    Directory of Open Access Journals (Sweden)

    Mochamad Apri

    Full Text Available Biochemical systems involving a high number of components with intricate interactions often lead to complex models containing a large number of parameters. Although a large model could describe in detail the mechanisms that underlie the system, its very large size may hinder us in understanding the key elements of the system. Also in terms of parameter identification, large models are often problematic. Therefore, a reduced model may be preferred to represent the system. Yet, in order to efficaciously replace the large model, the reduced model should have the same ability as the large model to produce reliable predictions for a broad set of testable experimental conditions. We present a novel method to extract an "optimal" reduced model from a large model to represent biochemical systems by combining a reduction method and a model discrimination method. The former assures that the reduced model contains only those components that are important to produce the dynamics observed in given experiments, whereas the latter ensures that the reduced model gives a good prediction for any feasible experimental conditions that are relevant to answer questions at hand. These two techniques are applied iteratively. The method reveals the biological core of a model mathematically, indicating the processes that are likely to be responsible for certain behavior. We demonstrate the algorithm on two realistic model examples. We show that in both cases the core is substantially smaller than the full model.

  14. Biological Dynamics Markup Language (BDML): an open format for representing quantitative biological dynamics data.

    Science.gov (United States)

    Kyoda, Koji; Tohsato, Yukako; Ho, Kenneth H L; Onami, Shuichi

    2015-04-01

    Recent progress in live-cell imaging and modeling techniques has resulted in generation of a large amount of quantitative data (from experimental measurements and computer simulations) on spatiotemporal dynamics of biological objects such as molecules, cells and organisms. Although many research groups have independently dedicated their efforts to developing software tools for visualizing and analyzing these data, these tools are often not compatible with each other because of different data formats. We developed an open unified format, Biological Dynamics Markup Language (BDML; current version: 0.2), which provides a basic framework for representing quantitative biological dynamics data for objects ranging from molecules to cells to organisms. BDML is based on Extensible Markup Language (XML). Its advantages are machine and human readability and extensibility. BDML will improve the efficiency of development and evaluation of software tools for data visualization and analysis. A specification and a schema file for BDML are freely available online at http://ssbd.qbic.riken.jp/bdml/. Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press.

  15. Category of Metabolic-Replication Systems in Biology and Medicine

    OpenAIRE

    I. C. Baianu

    2012-01-01

    Metabolic-repair models, or (M,R)-systems were introduced in Relational Biology by Robert Rosen. Subsequently, Rosen represented such (M,R)-systems (or simply MRs)in terms of categories of sets, deliberately selected without any structure other than the discrete topology of sets. Theoreticians of life's origins postulated that Life on Earth has begun with the simplest possible organism, called the primordial. Mathematicians interested in biology attempted to answer this important questio...

  16. Multi-level and hybrid modelling approaches for systems biology.

    Science.gov (United States)

    Bardini, R; Politano, G; Benso, A; Di Carlo, S

    2017-01-01

    During the last decades, high-throughput techniques allowed for the extraction of a huge amount of data from biological systems, unveiling more of their underling complexity. Biological systems encompass a wide range of space and time scales, functioning according to flexible hierarchies of mechanisms making an intertwined and dynamic interplay of regulations. This becomes particularly evident in processes such as ontogenesis, where regulative assets change according to process context and timing, making structural phenotype and architectural complexities emerge from a single cell, through local interactions. The information collected from biological systems are naturally organized according to the functional levels composing the system itself. In systems biology, biological information often comes from overlapping but different scientific domains, each one having its own way of representing phenomena under study. That is, the different parts of the system to be modelled may be described with different formalisms. For a model to have improved accuracy and capability for making a good knowledge base, it is good to comprise different system levels, suitably handling the relative formalisms. Models which are both multi-level and hybrid satisfy both these requirements, making a very useful tool in computational systems biology. This paper reviews some of the main contributions in this field.

  17. 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.

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

    Science.gov (United States)

    Wolkenhauer, Olaf; Mesarovic, Mihajlo

    2005-05-01

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

  19. 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 ...

  20. Heavy-ion microbeam system at JAEA-Takasaki for microbeam biology

    International Nuclear Information System (INIS)

    Funayama, Tomoo; Wada, Seiichi; Yokota, Yuichiro

    2008-01-01

    Research concerning cellular responses to low dose irradiation, radiation-induced bystander effects, and the biological track structure of charged particles has recently received particular attention in the field of radiation biology. Target irradiation employing a microbeam represents a useful means of advancing this research by obviating some of the disadvantages associated with the conventional irradiation strategies. The heavy-ion microbeam system at Japan Atomic Energy Agency (JAEA)-Takasaki, which was planned in 1987 and started in the early 1990's, can provide target irradiation of heavy charged particles to biological material at atmospheric pressure using a minimum beam size 5 μm in diameter. A variety of biological material has been irradiated using this microbeam system including cultured mammalian and higher plant cells, isolated fibers of mouse skeletal muscle, silkworm (Bombyx mori) embryos and larvae, Arabidopsis thaliana roots, and the nematode Caenorhabditis elegans. The system can be applied to the investigation of mechanisms within biological organisms not only in the context of radiation biology, but also in the fields of general biology such as physiology, developmental biology and neurobiology, and should help to establish and contribute to the field of 'microbeam biology'. (author)

  1. Computational Systems Chemical Biology

    OpenAIRE

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

    2011-01-01

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

  2. System biology and the project Encode

    Directory of Open Access Journals (Sweden)

    M. Yu. Obolenskaya

    2014-08-01

    Full Text Available The goal of this review is to give an incipient knowledge on the background of system biology, the premises to its assignment as a new branch of biology, its principles, methodology and its great achievements in identification of functional elements of human genome and regulation of their concordant­ and differential activity. The short characteristics of functional elements including the protein-coding sequences and those coding noncoding RNAs, the DNAse 1 hypersensitivity sites and methylated CpG islets, modified histones and specific 3D structure of chromatin, are represented. The topology of transcription factors network with its main motifs, hierar­chy, combination and association of transcription factors and their allelic specificity are highlighted­.

  3. 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.

  4. Genome Scale Modeling in Systems Biology: Algorithms and Resources

    Science.gov (United States)

    Najafi, Ali; Bidkhori, Gholamreza; Bozorgmehr, Joseph H.; Koch, Ina; Masoudi-Nejad, Ali

    2014-01-01

    In recent years, in silico studies and trial simulations have complemented experimental procedures. A model is a description of a system, and a system is any collection of interrelated objects; an object, moreover, is some elemental unit upon which observations can be made but whose internal structure either does not exist or is ignored. Therefore, any network analysis approach is critical for successful quantitative modeling of biological systems. This review highlights some of most popular and important modeling algorithms, tools, and emerging standards for representing, simulating and analyzing cellular networks in five sections. Also, we try to show these concepts by means of simple example and proper images and graphs. Overall, systems biology aims for a holistic description and understanding of biological processes by an integration of analytical experimental approaches along with synthetic computational models. In fact, biological networks have been developed as a platform for integrating information from high to low-throughput experiments for the analysis of biological systems. We provide an overview of all processes used in modeling and simulating biological networks in such a way that they can become easily understandable for researchers with both biological and mathematical backgrounds. Consequently, given the complexity of generated experimental data and cellular networks, it is no surprise that researchers have turned to computer simulation and the development of more theory-based approaches to augment and assist in the development of a fully quantitative understanding of cellular dynamics. PMID:24822031

  5. International Conference on Intelligent Systems for Molecular Biology (ISMB)

    Energy Technology Data Exchange (ETDEWEB)

    Goldberg, Debra; Hibbs, Matthew; Kall, Lukas; Komandurglayavilli, Ravikumar; Mahony, Shaun; Marinescu, Voichita; Mayrose, Itay; Minin, Vladimir; Neeman, Yossef; Nimrod, Guy; Novotny, Marian; Opiyo, Stephen; Portugaly, Elon; Sadka, Tali; Sakabe, Noboru; Sarkar, Indra; Schaub, Marc; Shafer, Paul; Shmygelska, Olena; Singer, Gregory; Song, Yun; Soumyaroop, Bhattacharya; Stadler, Michael; Strope, Pooja; Su, Rong; Tabach, Yuval; Tae, Hongseok; Taylor, Todd; Terribilini, Michael; Thomas, Asha; Tran, Nam; Tseng, Tsai-Tien; Vashist, Akshay; Vijaya, Parthiban; Wang, Kai; Wang, Ting; Wei, Lai; Woo, Yong; Wu, Chunlei; Yamanishi, Yoshihiro; Yan, Changhui; Yang, Jack; Yang, Mary; Ye, Ping; Zhang, Miao

    2009-12-29

    The Intelligent Systems for Molecular Biology (ISMB) conference has provided a general forum for disseminating the latest developments in bioinformatics on an annual basis for the past 13 years. ISMB is a multidisciplinary conference that brings together scientists from computer science, molecular biology, mathematics and statistics. The goal of the ISMB meeting is to bring together biologists and computational scientists in a focus on actual biological problems, i.e., not simply theoretical calculations. The combined focus on "intelligent systems" and actual biological data makes ISMB a unique and highly important meeting, and 13 years of experience in holding the conference has resulted in a consistently well organized, well attended, and highly respected annual conference. The ISMB 2005 meeting was held June 25-29, 2005 at the Renaissance Center in Detroit, Michigan. The meeting attracted over 1,730 attendees. The science presented was exceptional, and in the course of the five-day meeting, 56 scientific papers, 710 posters, 47 Oral Abstracts, 76 Software demonstrations, and 14 tutorials were presented. The attendees represented a broad spectrum of backgrounds with 7% from commercial companies, over 28% qualifying for student registration, and 41 countries were represented at the conference, emphasizing its important international aspect. The ISMB conference is especially important because the cultures of computer science and biology are so disparate. ISMB, as a full-scale technical conference with refereed proceedings that have been indexed by both MEDLINE and Current Contents since 1996, bridges this cultural gap.

  6. From systems biology to systems biomedicine.

    Science.gov (United States)

    Antony, Paul M A; Balling, Rudi; Vlassis, Nikos

    2012-08-01

    Systems Biology is about combining theory, technology, and targeted experiments in a way that drives not only data accumulation but knowledge as well. The challenge in Systems Biomedicine is to furthermore translate mechanistic insights in biological systems to clinical application, with the central aim of improving patients' quality of life. The challenge is to find theoretically well-chosen models for the contextually correct and intelligible representation of multi-scale biological systems. In this review, we discuss the current state of Systems Biology, highlight the emergence of Systems Biomedicine, and highlight some of the topics and views that we think are important for the efficient application of Systems Theory in Biomedicine. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Systems Biology and Health Systems Complexity in;

    NARCIS (Netherlands)

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

    2016-01-01

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

  8. Systems Biology-an interdisciplinary approach.

    Science.gov (United States)

    Friboulet, Alain; Thomas, Daniel

    2005-06-15

    System-level approaches in biology are not new but foundations of "Systems Biology" are achieved only now at the beginning of the 21st century [Kitano, H., 2001. Foundations of Systems Biology. MIT Press, Cambridge, MA]. The renewed interest for a system-level approach is linked to the progress in collecting experimental data and to the limits of the "reductionist" approach. System-level understanding of native biological and pathological systems is needed to provide potential therapeutic targets. Examples of interdisciplinary approach in Systems Biology are described in U.S., Japan and Europe. Robustness in biology, metabolic engineering and idiotypic networks are discussed in the framework of Systems Biology.

  9. Evolving a lingua franca and associated software infrastructure for computational systems biology: the Systems Biology Markup Language (SBML) project.

    Science.gov (United States)

    Hucka, M; Finney, A; Bornstein, B J; Keating, S M; Shapiro, B E; Matthews, J; Kovitz, B L; Schilstra, M J; Funahashi, A; Doyle, J C; Kitano, H

    2004-06-01

    Biologists are increasingly recognising that computational modelling is crucial for making sense of the vast quantities of complex experimental data that are now being collected. The systems biology field needs agreed-upon information standards if models are to be shared, evaluated and developed cooperatively. Over the last four years, our team has been developing the Systems Biology Markup Language (SBML) in collaboration with an international community of modellers and software developers. SBML has become a de facto standard format for representing formal, quantitative and qualitative models at the level of biochemical reactions and regulatory networks. In this article, we summarise the current and upcoming versions of SBML and our efforts at developing software infrastructure for supporting and broadening its use. We also provide a brief overview of the many SBML-compatible software tools available today.

  10. Standards, Data Exchange and Intellectual Property Rights in Systems Biology

    DEFF Research Database (Denmark)

    van Zimmeren, Esther; Rutz, Berthold; Minssen, Timo

    2016-01-01

    ” of scientists. In 2015, Biotechnology Journal published a report from an expert meeting on “Synthetic Biology & Intellectual Property Rights” organized by the Danish Agency for Science, Technology and Innovation sponsored by the European Research Area Network (ERA-Net) in Synthetic Biology (ERASynBio), in which...... we provided a number of recommendations for a variety of stakeholders. The current article offers some deeper reflections about the interface between IPRs, standards and data exchange in Systems Biology resulting from an Expert Meeting funded by another ERA-Net, ERASysAPP. The meeting brought...... together experts and stakeholders (e.g. scientists, company representatives, officials from public funding organizations) in systems biology (SysBio) from different countries.  Despite the different profiles of the stakeholders at the meeting and the variety of interests, many concerns and opinions were...

  11. Distribution and Biological Effects of Nanoparticles in the Reproductive System.

    Science.gov (United States)

    Liu, Ying; Li, Hongxia; Xiao, Kai

    2016-01-01

    Nanoparticles have shown great potential in biomedical applications such as imaging probes and drug delivery. However, the increasing use of nanoparticles has raised concerns about their adverse effects on human health and environment. Reproductive tissues and gametes represent highly delicate biological systems with the essential function of transmitting genetic information to the offspring, which is highly sensitive to environmental toxicants. This review aims to summarzie the penetration of physiological barriers (blood-testis barrier and placental barrier), distribution and biological effects of nanoparticles in the reproductive system, which is essential to control the beneficial effects of nanoparticles applications and to avoid their adverse effects on the reproductive system. We referred to a large number of relevant peer-reviewed research articles about the reproductive toxicity of nanoparticles. The comprehensive information was summarized into two parts: physiological barrier penetration and biological effects of nanoparticles in male or female reproductive system; distribution and metabolism of nanoparticles in the reproductive system. The representative examples were also presented in four tables. The in vitro and in vivo studies imply that some nanoparticles are able to cross the blood-testis barrier or placental barrier, and their penetration depends on the physicochemical characteristics of nanoparticles (e.g., composition, shape, particle size and surface coating). The toxicity assays indicate that nanoparticles might induce adverse physiological effects and impede fertility or embryogenesis. The barrier penetration, adverse physiological effects, distribution and metabolism are closely related to physicochemical characteristics of nanoparticles. Further systematic and mechanistic studies using well-characterized nanoparticles, relevant administration routes, and doses relevant to the expected exposure level are required to improve our

  12. 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.

  13. SBRML: a markup language for associating systems biology data with models.

    Science.gov (United States)

    Dada, Joseph O; Spasić, Irena; Paton, Norman W; Mendes, Pedro

    2010-04-01

    Research in systems biology is carried out through a combination of experiments and models. Several data standards have been adopted for representing models (Systems Biology Markup Language) and various types of relevant experimental data (such as FuGE and those of the Proteomics Standards Initiative). However, until now, there has been no standard way to associate a model and its entities to the corresponding datasets, or vice versa. Such a standard would provide a means to represent computational simulation results as well as to frame experimental data in the context of a particular model. Target applications include model-driven data analysis, parameter estimation, and sharing and archiving model simulations. We propose the Systems Biology Results Markup Language (SBRML), an XML-based language that associates a model with several datasets. Each dataset is represented as a series of values associated with model variables, and their corresponding parameter values. SBRML provides a flexible way of indexing the results to model parameter values, which supports both spreadsheet-like data and multidimensional data cubes. We present and discuss several examples of SBRML usage in applications such as enzyme kinetics, microarray gene expression and various types of simulation results. The XML Schema file for SBRML is available at http://www.comp-sys-bio.org/SBRML under the Academic Free License (AFL) v3.0.

  14. UltraPse: A Universal and Extensible Software Platform for Representing Biological Sequences.

    Science.gov (United States)

    Du, Pu-Feng; Zhao, Wei; Miao, Yang-Yang; Wei, Le-Yi; Wang, Likun

    2017-11-14

    With the avalanche of biological sequences in public databases, one of the most challenging problems in computational biology is to predict their biological functions and cellular attributes. Most of the existing prediction algorithms can only handle fixed-length numerical vectors. Therefore, it is important to be able to represent biological sequences with various lengths using fixed-length numerical vectors. Although several algorithms, as well as software implementations, have been developed to address this problem, these existing programs can only provide a fixed number of representation modes. Every time a new sequence representation mode is developed, a new program will be needed. In this paper, we propose the UltraPse as a universal software platform for this problem. The function of the UltraPse is not only to generate various existing sequence representation modes, but also to simplify all future programming works in developing novel representation modes. The extensibility of UltraPse is particularly enhanced. It allows the users to define their own representation mode, their own physicochemical properties, or even their own types of biological sequences. Moreover, UltraPse is also the fastest software of its kind. The source code package, as well as the executables for both Linux and Windows platforms, can be downloaded from the GitHub repository.

  15. Metabolic, Replication and Genomic Category of Systems in Biology, Bioinformatics and Medicine

    OpenAIRE

    I. C. Baianu

    2012-01-01

    Metabolic-repair models, or (M,R)-systems were introduced in Relational Biology by Robert Rosen. Subsequently, Rosen represented such (M,R)-systems (or simply MRs)in terms of categories of sets, deliberately selected without any structure other than the discrete topology of sets. Theoreticians of life’s origins postulated that Life on Earth has begun with the simplest possible organism, called the primordial. Mathematicians interested in biology attempted to answer this important quest...

  16. 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.

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

    International Nuclear Information System (INIS)

    Min Rui

    2010-01-01

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

  18. Polynomial algebra of discrete models in systems biology.

    Science.gov (United States)

    Veliz-Cuba, Alan; Jarrah, Abdul Salam; Laubenbacher, Reinhard

    2010-07-01

    An increasing number of discrete mathematical models are being published in Systems Biology, ranging from Boolean network models to logical models and Petri nets. They are used to model a variety of biochemical networks, such as metabolic networks, gene regulatory networks and signal transduction networks. There is increasing evidence that such models can capture key dynamic features of biological networks and can be used successfully for hypothesis generation. This article provides a unified framework that can aid the mathematical analysis of Boolean network models, logical models and Petri nets. They can be represented as polynomial dynamical systems, which allows the use of a variety of mathematical tools from computer algebra for their analysis. Algorithms are presented for the translation into polynomial dynamical systems. Examples are given of how polynomial algebra can be used for the model analysis. alanavc@vt.edu Supplementary data are available at Bioinformatics online.

  19. 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.

  20. Systems Biology Graphical Notation: Process Description language Level 1 Version 1.3.

    Science.gov (United States)

    Moodie, Stuart; Le Novère, Nicolas; Demir, Emek; Mi, Huaiyu; 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 Process Description language represents biological entities and processes between these entities within a network. SBGN PD focuses on the mechanistic description and temporal dependencies of biological interactions and transformations. The nodes (elements) are split into entity nodes describing, e.g., metabolites, proteins, genes and complexes, and process nodes describing, e.g., reactions and associations. The edges (connections) provide descriptions of relationships (or influences) between the nodes, such as consumption, production, stimulation and inhibition. Among all three languages of SBGN, PD is the closest to metabolic and regulatory pathways in biological literature and textbooks, but its well-defined semantics offer a superior precision in expressing biological knowledge.

  1. Fostering synergy between cell biology and systems biology.

    Science.gov (United States)

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

    2015-08-01

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

  2. Efficient Analysis of Systems Biology Markup Language Models of Cellular Populations Using Arrays.

    Science.gov (United States)

    Watanabe, Leandro; Myers, Chris J

    2016-08-19

    The Systems Biology Markup Language (SBML) has been widely used for modeling biological systems. Although SBML has been successful in representing a wide variety of biochemical models, the core standard lacks the structure for representing large complex regular systems in a standard way, such as whole-cell and cellular population models. These models require a large number of variables to represent certain aspects of these types of models, such as the chromosome in the whole-cell model and the many identical cell models in a cellular population. While SBML core is not designed to handle these types of models efficiently, the proposed SBML arrays package can represent such regular structures more easily. However, in order to take full advantage of the package, analysis needs to be aware of the arrays structure. When expanding the array constructs within a model, some of the advantages of using arrays are lost. This paper describes a more efficient way to simulate arrayed models. To illustrate the proposed method, this paper uses a population of repressilator and genetic toggle switch circuits as examples. Results show that there are memory benefits using this approach with a modest cost in runtime.

  3. Introductory Biology Textbooks Under-Represent Scientific Process

    Directory of Open Access Journals (Sweden)

    Dara B. Duncan

    2011-08-01

    Full Text Available Attrition of undergraduates from Biology majors is a long-standing problem. Introductory courses that fail to engage students or spark their curiosity by emphasizing the open-ended and creative nature of biological investigation and discovery could contribute to student detachment from the field. Our hypothesis was that introductory biology books devote relatively few figures to illustration of the design and interpretation of experiments or field studies, thereby de-emphasizing the scientific process.To investigate this possibility, we examined figures in six Introductory Biology textbooks published in 2008. On average, multistep scientific investigations were presented in fewer than 5% of the hundreds of figures in each book. Devoting such a small percentage of figures to the processes by which discoveries are made discourages an emphasis on scientific thinking. We suggest that by increasing significantly the illustration of scientific investigations, textbooks could support undergraduates’ early interest in biology, stimulate the development of design and analytical skills, and inspire some students to participate in investigations of their own.

  4. Models with Men and Women: Representing Gender in Dynamic Modeling of Social Systems.

    Science.gov (United States)

    Palmer, Erika; Wilson, Benedicte

    2018-04-01

    Dynamic engineering models have yet to be evaluated in the context of feminist engineering ethics. Decision-making concerning gender in dynamic modeling design is a gender and ethical issue that is important to address regardless of the system in which the dynamic modeling is applied. There are many dynamic modeling tools that operationally include the female population, however, there is an important distinction between females and women; it is the difference between biological sex and the social construct of gender, which is fluid and changes over time and geography. The ethical oversight in failing to represent or misrepresenting gender in model design when it is relevant to the model purpose can have implications for model validity and policy model development. This paper highlights this gender issue in the context of feminist engineering ethics using a dynamic population model. Women are often represented in this type of model only in their biological capacity, while lacking their gender identity. This illustrative example also highlights how language, including the naming of variables and communication with decision-makers, plays a role in this gender issue.

  5. Nutritional Systems Biology

    DEFF Research Database (Denmark)

    Jensen, Kasper

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

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

    Science.gov (United States)

    Smolke, Christina D; Silver, Pamela A

    2011-03-18

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

  7. The necessity of a theory of biology for tissue engineering: metabolism-repair systems.

    Science.gov (United States)

    Ganguli, Suman; Hunt, C Anthony

    2004-01-01

    Since there is no widely accepted global theory of biology, tissue engineering and bioengineering lack a theoretical understanding of the systems being engineered. By default, tissue engineering operates with a "reductionist" theoretical approach, inherited from traditional engineering of non-living materials. Long term, that approach is inadequate, since it ignores essential aspects of biology. Metabolism-repair systems are a theoretical framework which explicitly represents two "functional" aspects of living organisms: self-repair and self-replication. Since repair and replication are central to tissue engineering, we advance metabolism-repair systems as a potential theoretical framework for tissue engineering. We present an overview of the framework, and indicate directions to pursue for extending it to the context of tissue engineering. We focus on biological networks, both metabolic and cellular, as one such direction. The construction of these networks, in turn, depends on biological protocols. Together these concepts may help point the way to a global theory of biology appropriate for tissue engineering.

  8. Excited states in biological systems

    International Nuclear Information System (INIS)

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

    1979-01-01

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

  9. [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.

  10. Request for Travel Funds for Systems Radiation Biology Workshop

    Energy Technology Data Exchange (ETDEWEB)

    Barcellos-Hoff, Mary Helen [NYU School of Medicine

    2014-03-22

    The 3rd International Systems Radiation Biology Workshop brought together the major European, US and Japanese research programs on radiation risk as well as selected experts representing systems biological approaches to discuss how the new methodologies could be best exploited for low dose research. A significant part of the workshop was devoted to discussions organised as breakout group sessions. To facilitate discussions number of participants was limited to 60 persons. To achieve the goals of this symposium in this international conference, support from DOE is vital. Hence, this proposal requested support in the amount of $15,000 to cover the travel expenses of international experts and radiation biology scientists from the United States. This supporting mechanism was clearly identified to the selected US participants as a conference support award from the DOE (See attached PDF). The workshop was an outstanding opportunity to strengthen interactions between leading experts in the emerging areas of radiation sciences, and will also provide opportunities for younger scientists to meet with experts and discuss their results. This workshop was designed to endorse active engagement in international collaboration. A major objective of this conference was to effectively communicate research results, in order to ensure that current thinking reflects sound science of radiation biology. Further, this international event addressed the use and success of scientific initiatives in radiation biology for policymakers, standard-setters, and the general public.

  11. ‘Can Simple Biological Systems be Built from Standardized Interchangeable Parts?’:Negotiating Biology and Engineering in a Synthetic Biology Competition

    OpenAIRE

    Frow, Emma; Calvert, Jane

    2013-01-01

    Synthetic biology represents a recent attempt to bring engineering principles and practices to working with biology. In practice, the nature of the relationship between engineering and biology in synthetic biology is a subject of ongoing debate. The disciplines of biology and engineering are typically seen to involve differentways of knowing and doing, and to embody different assumptions and objectives. Tensions between these approaches are playing out as the field of synthetic biology is bei...

  12. 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.

  13. Is synthetic biology mechanical biology?

    Science.gov (United States)

    Holm, Sune

    2015-12-01

    A widespread and influential characterization of synthetic biology emphasizes that synthetic biology is the application of engineering principles to living systems. Furthermore, there is a strong tendency to express the engineering approach to organisms in terms of what seems to be an ontological claim: organisms are machines. In the paper I investigate the ontological and heuristic significance of the machine analogy in synthetic biology. I argue that the use of the machine analogy and the aim of producing rationally designed organisms does not necessarily imply a commitment to mechanical biology. The ideal of applying engineering principles to biology is best understood as expressing recognition of the machine-unlikeness of natural organisms and the limits of human cognition. The paper suggests an interpretation of the identification of organisms with machines in synthetic biology according to which it expresses a strategy for representing, understanding, and constructing living systems that are more machine-like than natural organisms.

  14. 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....

  15. Systems Biology Graphical Notation: Activity Flow language Level 1 Version 1.2.

    Science.gov (United States)

    Mi, Huaiyu; Schreiber, Falk; Moodie, Stuart; Czauderna, Tobias; Demir, Emek; Haw, Robin; Luna, Augustin; Le Novère, Nicolas; Sorokin, Anatoly; 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 Activity Flow language represents the influences of activities among various entities within a network. Unlike SBGN PD and ER that focus on the entities and their relationships with others, SBGN AF puts the emphasis on the functions (or activities) performed by the entities, and their effects to the functions of the same or other entities. The nodes (elements) describe the biological activities of the entities, such as protein kinase activity, binding activity or receptor activity, which can be easily mapped to Gene Ontology molecular function terms. The edges (connections) provide descriptions of relationships (or influences) between the activities, e.g., positive influence and negative influence. Among all three languages of SBGN, AF is the closest to signaling pathways in biological literature and textbooks, but its well-defined semantics offer a superior precision in expressing biological knowledge.

  16. Institute for Genomics and Systems Biology

    Science.gov (United States)

    Institute for Genomics and Systems Biology Discover. Predict. Improve. Advancing Human and , 2015 See all Research Papers Featured Video Introduction to Systems Biology Video: Introduction to Systems Biology News Jack Gilbert Heading UChicago Startup that Aims to Predict Behavior of Trillions of

  17. Biophysics and systems biology.

    Science.gov (United States)

    Noble, Denis

    2010-03-13

    Biophysics at the systems level, as distinct from molecular biophysics, acquired its most famous paradigm in the work of Hodgkin and Huxley, who integrated their equations for the nerve impulse in 1952. Their approach has since been extended to other organs of the body, notably including the heart. The modern field of computational biology has expanded rapidly during the first decade of the twenty-first century and, through its contribution to what is now called systems biology, it is set to revise many of the fundamental principles of biology, including the relations between genotypes and phenotypes. Evolutionary theory, in particular, will require re-assessment. To succeed in this, computational and systems biology will need to develop the theoretical framework required to deal with multilevel interactions. While computational power is necessary, and is forthcoming, it is not sufficient. We will also require mathematical insight, perhaps of a nature we have not yet identified. This article is therefore also a challenge to mathematicians to develop such insights.

  18. Inverse problems in systems biology

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  19. Systems biology in critical-care nursing.

    Science.gov (United States)

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

    2011-01-01

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

  20. Philosophy of Systems and Synthetic Biology

    DEFF Research Database (Denmark)

    Green, Sara

    2017-01-01

    This entry aims to clarify how systems and synthetic biology contribute to and extend discussions within philosophy of science. Unlike fields such as developmental biology or molecular biology, systems and synthetic biology are not easily demarcated by a focus on a specific subject area or level...... of organization. Rather, they are characterized by the development and application of mathematical, computational, and synthetic modeling strategies in response to complex problems and challenges within the life sciences. Proponents of systems and synthetic biology often stress the necessity of a perspective...... that goes beyond the scope of molecular biology and genetic engineering, respectively. With the emphasis on systems and interaction networks, the approaches explicitly engage in one of the oldest philosophical discussions on the relationship between parts and wholes, or between reductionism and holism...

  1. Systems theoretic analysis of the central dogma of molecular biology: some recent results.

    Science.gov (United States)

    Gao, Rui; Yu, Juanyi; Zhang, Mingjun; Tarn, Tzyh-Jong; Li, Jr-Shin

    2010-03-01

    This paper extends our early study on a mathematical formulation of the central dogma of molecular biology, and focuses discussions on recent insights obtained by employing advanced systems theoretic analysis. The goal of this paper is to mathematically represent and interpret the genetic information flow at the molecular level, and explore the fundamental principle of molecular biology at the system level. Specifically, group theory was employed to interpret concepts and properties of gene mutation, and predict backbone torsion angle along the peptide chain. Finite state machine theory was extensively applied to interpret key concepts and analyze the processes related to DNA hybridization. Using the proposed model, we have transferred the character-based model in molecular biology to a sophisticated mathematical model for calculation and interpretation.

  2. Systems Biology Modeling of the Radiation Sensitivity Network: A Biomarker Discovery Platform

    International Nuclear Information System (INIS)

    Eschrich, Steven; Zhang Hongling; Zhao Haiyan; Boulware, David; Lee, Ji-Hyun; Bloom, Gregory; Torres-Roca, Javier F.

    2009-01-01

    Purpose: The discovery of effective biomarkers is a fundamental goal of molecular medicine. Developing a systems-biology understanding of radiosensitivity can enhance our ability of identifying radiation-specific biomarkers. Methods and Materials: Radiosensitivity, as represented by the survival fraction at 2 Gy was modeled in 48 human cancer cell lines. We applied a linear regression algorithm that integrates gene expression with biological variables, including ras status (mut/wt), tissue of origin and p53 status (mut/wt). Results: The biomarker discovery platform is a network representation of the top 500 genes identified by linear regression analysis. This network was reduced to a 10-hub network that includes c-Jun, HDAC1, RELA (p65 subunit of NFKB), PKC-beta, SUMO-1, c-Abl, STAT1, AR, CDK1, and IRF1. Nine targets associated with radiosensitization drugs are linked to the network, demonstrating clinical relevance. Furthermore, the model identified four significant radiosensitivity clusters of terms and genes. Ras was a dominant variable in the analysis, as was the tissue of origin, and their interaction with gene expression but not p53. Overrepresented biological pathways differed between clusters but included DNA repair, cell cycle, apoptosis, and metabolism. The c-Jun network hub was validated using a knockdown approach in 8 human cell lines representing lung, colon, and breast cancers. Conclusion: We have developed a novel radiation-biomarker discovery platform using a systems biology modeling approach. We believe this platform will play a central role in the integration of biology into clinical radiation oncology practice.

  3. Systems Biology

    Indian Academy of Sciences (India)

    IAS Admin

    study and understand the function of biological systems, particu- larly, the response of such .... understand the organisation and behaviour of prokaryotic sys- tems. ... relationship of the structure of a target molecule to its ability to bind a certain ...

  4. Calculating life? Duelling discourses in interdisciplinary systems biology.

    Science.gov (United States)

    Calvert, Jane; Fujimura, Joan H

    2011-06-01

    A high profile context in which physics and biology meet today is in the new field of systems biology. Systems biology is a fascinating subject for sociological investigation because the demands of interdisciplinary collaboration have brought epistemological issues and debates front and centre in discussions amongst systems biologists in conference settings, in publications, and in laboratory coffee rooms. One could argue that systems biologists are conducting their own philosophy of science. This paper explores the epistemic aspirations of the field by drawing on interviews with scientists working in systems biology, attendance at systems biology conferences and workshops, and visits to systems biology laboratories. It examines the discourses of systems biologists, looking at how they position their work in relation to previous types of biological inquiry, particularly molecular biology. For example, they raise the issue of reductionism to distinguish systems biology from molecular biology. This comparison with molecular biology leads to discussions about the goals and aspirations of systems biology, including epistemic commitments to quantification, rigor and predictability. Some systems biologists aspire to make biology more similar to physics and engineering by making living systems calculable, modelable and ultimately predictable-a research programme that is perhaps taken to its most extreme form in systems biology's sister discipline: synthetic biology. Other systems biologists, however, do not think that the standards of the physical sciences are the standards by which we should measure the achievements of systems biology, and doubt whether such standards will ever be applicable to 'dirty, unruly living systems'. This paper explores these epistemic tensions and reflects on their sociological dimensions and their consequences for future work in the life sciences. Copyright © 2010 Elsevier Ltd. All rights reserved.

  5. Heuristic Strategies in Systems Biology

    Directory of Open Access Journals (Sweden)

    Fridolin Gross

    2016-06-01

    Full Text Available Systems biology is sometimes presented as providing a superior approach to the problem of biological complexity. Its use of ‘unbiased’ methods and formal quantitative tools might lead to the impression that the human factor is effectively eliminated. However, a closer look reveals that this impression is misguided. Systems biologists cannot simply assemble molecular information and compute biological behavior. Instead, systems biology’s main contribution is to accelerate the discovery of mechanisms by applying models as heuristic tools. These models rely on a variety of idealizing and simplifying assumptions in order to be efficient for this purpose. The strategies of systems biologists are similar to those of experimentalists in that they attempt to reduce the complexity of the discovery process. Analyzing and comparing these strategies, or ‘heuristics’, reveals the importance of the human factor in computational approaches and helps to situate systems biology within the epistemic landscape of the life sciences.

  6. Stress-associated synchronization and desynchronization in geologic and biologic systems

    Science.gov (United States)

    Kluchevsky, A. V.; Kluchevskaya, A. A.

    2010-12-01

    Variations in the annual numbers of representative earthquakes in three areas and six districts of the Baikal rift zone in 1964-2002 were subjected to correlation analysis. Episodes of significant correlations of shock flow rates were found against the background of chaotic seismic activity. They followed the rearrangements (catastrophes) of stresses in the lithosphere, which are also stressing factors for the whole rift geodynamic system. The episode of the late 1970s-early 1980s was particularly long and showed the maximum correlation. Therefore, it can be considered the principal event in seismic process synchronization in the Baikal Rift Zone. The same approach to data analysis revealed similar synchronization and desynchronization phenomena in the behavior of Baikalian turbellaria when they deviated from homeostasis as a result of illumination, which is a stress for this biologic system. Possible reasons for the behavior of biologic and geodynamic systems are discussed in terms of the synergetic concept of phenomena in living and nonliving nature.

  7. Biologically Inspired Object Localization for a Modular Mobile Robotic System

    Directory of Open Access Journals (Sweden)

    Zlatogor Minchev

    2005-12-01

    Full Text Available The paper considers a general model of real biological creatures' antennae, which is practically implemented and tested, over a real element of a mobile modular robotic system - the robot MR1. The last could be utilized in solving of the most classical problem in Robotics - Object Localization. The functionality of the represented sensor system is described in a new and original manner by utilizing the tool of Generalized Nets - a new likelihood for description, modelling and simulation of different objects from the Artificial Intelligence area including Robotics.

  8. Mammalian Synthetic Biology: Engineering Biological Systems.

    Science.gov (United States)

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

    2017-06-21

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

  9. Applicability of Computational Systems Biology in Toxicology

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  10. 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.

  11. Editorial overview : Systems biology for biotechnology

    NARCIS (Netherlands)

    Heinemann, Matthias; Pilpel, Yitzhak

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

  12. 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),...

  13. Use of normalized total dose to represent the biological effect of fractionated radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Flickinger, J C; Kalend, A [Pittsburgh University School of Medicine (USA). Department of Radiation Oncology Pittsburg Cancer Institute (USA)

    1990-03-01

    There are currently a number of radiobiological models to account for the effects of dose fractionation and time. Normalized total dose (NTD) is not another new model but is a previously reported, clinically useful form in which to represent the biological effect, determined by any specific radiobiological dose-fractionation model, of a course of radiation using a single set of standardized, easily understood terminology. The generalized form of NTD reviewed in this paper describes the effect of a course of radiotherapy administered with nonstandard fractionation as the total dose of radiation in Gy that could be administered with a given reference fractionation such as 2 Gy per fraction, 5 fractions per week that would produce an equivalent biological effect (probability of complications or tumor control) as predicted by a given dose-fractionation formula. The use of normalized total dose with several different exponential and linear-quadratic dose-fraction formulas is presented. (author). 51 refs.; 1 fig.; 1 tab.

  14. Use of normalized total dose to represent the biological effect of fractionated radiotherapy

    International Nuclear Information System (INIS)

    Flickinger, J.C.; Kalend, A.

    1990-01-01

    There are currently a number of radiobiological models to account for the effects of dose fractionation and time. Normalized total dose (NTD) is not another new model but is a previously reported, clinically useful form in which to represent the biological effect, determined by any specific radiobiological dose-fractionation model, of a course of radiation using a single set of standardized, easily understood terminology. The generalized form of NTD reviewed in this paper describes the effect of a course of radiotherapy administered with nonstandard fractionation as the total dose of radiation in Gy that could be administered with a given reference fractionation such as 2 Gy per fraction, 5 fractions per week that would produce an equivalent biological effect (probability of complications or tumor control) as predicted by a given dose-fractionation formula. The use of normalized total dose with several different exponential and linear-quadratic dose-fraction formulas is presented. (author). 51 refs.; 1 fig.; 1 tab

  15. Static Analysis for Systems Biology

    DEFF Research Database (Denmark)

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

    2004-01-01

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

  16. Omics/systems biology and cancer cachexia.

    Science.gov (United States)

    Gallagher, Iain J; Jacobi, Carsten; Tardif, Nicolas; Rooyackers, Olav; Fearon, Kenneth

    2016-06-01

    Cancer cachexia is a complex syndrome generated by interaction between the host and tumour cells with a background of treatment effects and toxicity. The complexity of the physiological pathways likely involved in cancer cachexia necessitates a holistic view of the relevant biology. Emergent properties are characteristic of complex systems with the result that the end result is more than the sum of its parts. Recognition of the importance of emergent properties in biology led to the concept of systems biology wherein a holistic approach is taken to the biology at hand. Systems biology approaches will therefore play an important role in work to uncover key mechanisms with therapeutic potential in cancer cachexia. The 'omics' technologies provide a global view of biological systems. Genomics, transcriptomics, proteomics, lipidomics and metabolomics approaches all have application in the study of cancer cachexia to generate systems level models of the behaviour of this syndrome. The current work reviews recent applications of these technologies to muscle atrophy in general and cancer cachexia in particular with a view to progress towards integration of these approaches to better understand the pathology and potential treatment pathways in cancer cachexia. Copyright © 2016. Published by Elsevier Ltd.

  17. 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,...

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

    Science.gov (United States)

    Degrazio, Dominick

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

  19. Multilayer network modeling creates opportunities for novel network statistics. Comment on "Network science of biological systems at different scales: A review" by Gosak et al.

    Science.gov (United States)

    Muldoon, Sarah Feldt

    2018-03-01

    As described in the review by Gosak et al., the field of network science has had enormous success in providing new insights into the structure and function of biological systems [1]. In the complex networks framework, system elements are network nodes, and connections between nodes represent some form of interaction between system elements [2]. The flexibility to define network nodes and edges to represent different aspects of biological systems has been employed to model numerous diverse systems at multiple scales.

  20. 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.

  1. 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...

  2. Ten questions about systems biology

    DEFF Research Database (Denmark)

    Joyner, Michael J; Pedersen, Bente K

    2011-01-01

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

  3. 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.

  4. On Designing Multicore-Aware Simulators for Systems Biology Endowed with OnLine Statistics

    Directory of Open Access Journals (Sweden)

    Marco Aldinucci

    2014-01-01

    Full Text Available The paper arguments are on enabling methodologies for the design of a fully parallel, online, interactive tool aiming to support the bioinformatics scientists .In particular, the features of these methodologies, supported by the FastFlow parallel programming framework, are shown on a simulation tool to perform the modeling, the tuning, and the sensitivity analysis of stochastic biological models. A stochastic simulation needs thousands of independent simulation trajectories turning into big data that should be analysed by statistic and data mining tools. In the considered approach the two stages are pipelined in such a way that the simulation stage streams out the partial results of all simulation trajectories to the analysis stage that immediately produces a partial result. The simulation-analysis workflow is validated for performance and effectiveness of the online analysis in capturing biological systems behavior on a multicore platform and representative proof-of-concept biological systems. The exploited methodologies include pattern-based parallel programming and data streaming that provide key features to the software designers such as performance portability and efficient in-memory (big data management and movement. Two paradigmatic classes of biological systems exhibiting multistable and oscillatory behavior are used as a testbed.

  5. On designing multicore-aware simulators for systems biology endowed with OnLine statistics.

    Science.gov (United States)

    Aldinucci, Marco; Calcagno, Cristina; Coppo, Mario; Damiani, Ferruccio; Drocco, Maurizio; Sciacca, Eva; Spinella, Salvatore; Torquati, Massimo; Troina, Angelo

    2014-01-01

    The paper arguments are on enabling methodologies for the design of a fully parallel, online, interactive tool aiming to support the bioinformatics scientists .In particular, the features of these methodologies, supported by the FastFlow parallel programming framework, are shown on a simulation tool to perform the modeling, the tuning, and the sensitivity analysis of stochastic biological models. A stochastic simulation needs thousands of independent simulation trajectories turning into big data that should be analysed by statistic and data mining tools. In the considered approach the two stages are pipelined in such a way that the simulation stage streams out the partial results of all simulation trajectories to the analysis stage that immediately produces a partial result. The simulation-analysis workflow is validated for performance and effectiveness of the online analysis in capturing biological systems behavior on a multicore platform and representative proof-of-concept biological systems. The exploited methodologies include pattern-based parallel programming and data streaming that provide key features to the software designers such as performance portability and efficient in-memory (big) data management and movement. Two paradigmatic classes of biological systems exhibiting multistable and oscillatory behavior are used as a testbed.

  6. 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....

  7. 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....

  8. Systems Biology, Systems Medicine, Systems Pharmacology: The What and The Why.

    Science.gov (United States)

    Stéphanou, Angélique; Fanchon, Eric; Innominato, Pasquale F; Ballesta, Annabelle

    2018-05-09

    Systems biology is today such a widespread discipline that it becomes difficult to propose a clear definition of what it really is. For some, it remains restricted to the genomic field. For many, it designates the integrated approach or the corpus of computational methods employed to handle the vast amount of biological or medical data and investigate the complexity of the living. Although defining systems biology might be difficult, on the other hand its purpose is clear: systems biology, with its emerging subfields systems medicine and systems pharmacology, clearly aims at making sense of complex observations/experimental and clinical datasets to improve our understanding of diseases and their treatments without putting aside the context in which they appear and develop. In this short review, we aim to specifically focus on these new subfields with the new theoretical tools and approaches that were developed in the context of cancer. Systems pharmacology and medicine now give hope for major improvements in cancer therapy, making personalized medicine closer to reality. As we will see, the current challenge is to be able to improve the clinical practice according to the paradigm shift of systems sciences.

  9. 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 ...

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

    Science.gov (United States)

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

    2017-09-01

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

  11. Biological Systems Thinking for Control Engineering Design

    Directory of Open Access Journals (Sweden)

    D. J. Murray-Smith

    2004-01-01

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

  12. Dynamics and thermodynamics in hierarchically organized systems applications in physics, biology and economics

    CERN Document Server

    Auger, P

    2013-01-01

    One of the most fundamental and efficient ways of conceptualizing complex systems is to organize them hierarchically. A hierarchically organized system is represented by a network of interconnected subsystems, each of which has its own network of subsystems, and so on, until some elementary subsystems are reached that are not further decomposed. This original and important book proposes a general mathematical theory of a hierarchical system and shows how it can be applied to very different topics such as physics (Hamiltonian systems), biology (coupling the molecular and the cellular levels), e

  13. The mammary gland in domestic ruminants: a systems biology perspective.

    Science.gov (United States)

    Ferreira, Ana M; Bislev, Stine L; Bendixen, Emøke; Almeida, André M

    2013-12-06

    Milk and dairy products are central elements in the human diet. It is estimated that 108kg of milk per year are consumed per person worldwide. Therefore, dairy production represents a relevant fraction of the economies of many countries, being cattle, sheep, goat, water buffalo, and other ruminants the main species used worldwide. An adequate management of dairy farming cannot be achieved without the knowledge on the biological mechanisms behind lactation in ruminants. Thus, understanding the morphology, development and regulation of the mammary gland in health, disease and production is crucial. Presently, innovative and high-throughput technologies such as genomics, transcriptomics, proteomics and metabolomics allow a much broader and detailed knowledge on such issues. Additionally, the application of a systems biology approach to animal science is vastly growing, as new advances in one field of specialization or animal species lead to new lines of research in other areas or/and are expanded to other species. This article addresses how modern research approaches may help us understand long-known issues in mammary development, lactation biology and dairy production. Dairy production depends upon the knowledge of the morphology and regulation of the mammary gland and lactation. High-throughput technologies allow a much broader and detailed knowledge on the biology of the mammary gland. This paper reviews the major contributions that genomics, transcriptomics, metabolomics and proteomics approaches have provided to understand the regulation of the mammary gland in health, disease and production. In the context of mammary gland "omics"-based research, the integration of results using a Systems Biology Approach is of key importance. © 2013.

  14. Systematic synergy modeling: understanding drug synergy from a systems biology perspective.

    Science.gov (United States)

    Chen, Di; Liu, Xi; Yang, Yiping; Yang, Hongjun; Lu, Peng

    2015-09-16

    Owing to drug synergy effects, drug combinations have become a new trend in combating complex diseases like cancer, HIV and cardiovascular diseases. However, conventional synergy quantification methods often depend on experimental dose-response data which are quite resource-demanding. In addition, these methods are unable to interpret the explicit synergy mechanism. In this review, we give representative examples of how systems biology modeling offers strategies toward better understanding of drug synergy, including the protein-protein interaction (PPI) network-based methods, pathway dynamic simulations, synergy network motif recognitions, integrative drug feature calculations, and "omic"-supported analyses. Although partially successful in drug synergy exploration and interpretation, more efforts should be put on a holistic understanding of drug-disease interactions, considering integrative pharmacology and toxicology factors. With a comprehensive and deep insight into the mechanism of drug synergy, systems biology opens a novel avenue for rational design of effective drug combinations.

  15. A system for success: BMC Systems Biology, a new open access journal.

    Science.gov (United States)

    Hodgkinson, Matt J; Webb, Penelope A

    2007-09-04

    BMC Systems Biology is the first open access journal spanning the growing field of systems biology from molecules up to ecosystems. The journal has launched as more and more institutes are founded that are similarly dedicated to this new approach. BMC Systems Biology builds on the ongoing success of the BMC series, providing a venue for all sound research in the systems-level analysis of biology.

  16. Hierarchical structure of biological systems: a bioengineering approach.

    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.

  17. Citizen's initiatives and the representative system

    International Nuclear Information System (INIS)

    Guggenberger, B.; Kempf, U.

    1978-01-01

    This anthology containing contributions of 19 sociologists is a systematic investigation of the locality, the possibilities and the effective radius of citizen's initiatives under the functional conditions of the parliamentary - representative system. The intellectual and political surroundings, the sociologic context, the institutional, political and judical overall conditions as well as the consequences of this movement for the whole political system of the Federal Republic of Germany. (orig.) [de

  18. An engineering design approach to systems biology.

    Science.gov (United States)

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

    2017-07-17

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

  19. Answering biological questions: Querying a systems biology database for nutrigenomics

    NARCIS (Netherlands)

    Evelo, C.T.; Bochove, K. van; Saito, J.T.

    2011-01-01

    The requirement of systems biology for connecting different levels of biological research leads directly to a need for integrating vast amounts of diverse information in general and of omics data in particular. The nutritional phenotype database addresses this challenge for nutrigenomics. A

  20. Ultra-Structure database design methodology for managing systems biology data and analyses

    Directory of Open Access Journals (Sweden)

    Hemminger Bradley M

    2009-08-01

    Full Text Available Abstract Background Modern, high-throughput biological experiments generate copious, heterogeneous, interconnected data sets. Research is dynamic, with frequently changing protocols, techniques, instruments, and file formats. Because of these factors, systems designed to manage and integrate modern biological data sets often end up as large, unwieldy databases that become difficult to maintain or evolve. The novel rule-based approach of the Ultra-Structure design methodology presents a potential solution to this problem. By representing both data and processes as formal rules within a database, an Ultra-Structure system constitutes a flexible framework that enables users to explicitly store domain knowledge in both a machine- and human-readable form. End users themselves can change the system's capabilities without programmer intervention, simply by altering database contents; no computer code or schemas need be modified. This provides flexibility in adapting to change, and allows integration of disparate, heterogenous data sets within a small core set of database tables, facilitating joint analysis and visualization without becoming unwieldy. Here, we examine the application of Ultra-Structure to our ongoing research program for the integration of large proteomic and genomic data sets (proteogenomic mapping. Results We transitioned our proteogenomic mapping information system from a traditional entity-relationship design to one based on Ultra-Structure. Our system integrates tandem mass spectrum data, genomic annotation sets, and spectrum/peptide mappings, all within a small, general framework implemented within a standard relational database system. General software procedures driven by user-modifiable rules can perform tasks such as logical deduction and location-based computations. The system is not tied specifically to proteogenomic research, but is rather designed to accommodate virtually any kind of biological research. Conclusion We find

  1. Interactomes, manufacturomes and relational biology: analogies between systems biology and manufacturing systems

    Science.gov (United States)

    2011-01-01

    Background We review and extend the work of Rosen and Casti who discuss category theory with regards to systems biology and manufacturing systems, respectively. Results We describe anticipatory systems, or long-range feed-forward chemical reaction chains, and compare them to open-loop manufacturing processes. We then close the loop by discussing metabolism-repair systems and describe the rationality of the self-referential equation f = f (f). This relationship is derived from some boundary conditions that, in molecular systems biology, can be stated as the cardinality of the following molecular sets must be about equal: metabolome, genome, proteome. We show that this conjecture is not likely correct so the problem of self-referential mappings for describing the boundary between living and nonliving systems remains an open question. We calculate a lower and upper bound for the number of edges in the molecular interaction network (the interactome) for two cellular organisms and for two manufacturomes for CMOS integrated circuit manufacturing. Conclusions We show that the relevant mapping relations may not be Abelian, and that these problems cannot yet be resolved because the interactomes and manufacturomes are incomplete. PMID:21689427

  2. Biological regeneration of phenol-loaded activated carbon (up flow system)

    International Nuclear Information System (INIS)

    Durrani, M.A.Q.J.; Mirajuddin; Martin, R.J.

    1995-01-01

    This paper represents the report on the biological regeneration of totally activated carbon following the experimental studies carried out at the University of Birmingham, U.K. Biological regeneration is one of several methods that may be used to restore the adsorptive capacity of exhausted granular activated carbon. This study deals with in situ biological regeneration on a pilot scale. The principal objective of this research was to ascertain whether biological regeneration of GAC could occur under conditions typical of water treatment. The important parameters which may have the greatest impact on bio regeneration for a given adsorbate were studied. The research investigated the extent of bio regeneration for phenol of concentration 50 mg/l. Bio regeneration in the total exhaustion system was evaluated in terms of regeneration efficiency and the substrate removal. A three mode procedure was followed for each bio regeneration run. The prepared carbon was initialing exhausted with an adsorbate; it was then bio regenerated with a mixed culture of bacteria, and lastly the carbon was saturated. In the totally exhausted GAC system, the bio regeneration was enhanced by increasing the duration of regeneration for a fixed initial biomass content of the bioreactor. The regenerated phenol loaded GAC bed had nearly gained its original adsorption after the 5-day period of regeneration. Bacterial counts in the effluents of regenerated GAC columns were significantly more than those of fresh carbon effluents. (author)

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

    Science.gov (United States)

    Jalili, Mahdi

    2018-03-01

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

  4. Systems of organic farming in spring vetch I: Biological response of sucking insect pests

    Directory of Open Access Journals (Sweden)

    Ivelina Nikolova

    2015-04-01

    Full Text Available Four systems of organic farming and a conventional farming system were studied over the period 2012-2014. The organic system trial variants included: I – an organic farming system without any biological products used (growth under natural soil fertility – Control; II – an organic farming system involving the use of a biological foliar fertilizer and a biological plant growth regulator (Polyversum+Biofa; III – an organic farming system in which a biological insecticide (NeemAzal T/S was used; IV – an organic farming system including a combination of three organic products: the foliar fertilizer, the plant growth regulator and the bioinsecticide (Polyversum+Biofa+NeemAzal T/S. Variant V represented a conventional farming system in which synthetic products were used in combination (foliar fertilizer, plant growth regulator and insecticide: Masterblend+Flordimex 420+Nurelle D. Treatment of vetch plants with the biological insecticide NeemAzal in combination with Biofa and Polyversum resulted in the lowest density of sucking pests, compared to all other organic farming methods tested (i.e. without NeemAzal, with NeemAzal alone, and its combination with Biofa and Polyversum. The greatest reduction in pest numbers during the vegetation period in that variant was observed in species of the order Thysanoptera (36.0-41.4%, followed by Hemiptera, and the families Aphididae (31.6-40.3% and Cicadellidae (27.3-28.6%. This combination showed an efficient synergistic interaction and an increase in biological efficacy as compared to individual application of NeemAzal. The highest toxic impact was found against Thrips tabaci, followed by Acyrthosiphon pisum. An analysis of variance regarding the efficacy against the species A. pisum, E. pteridis and T. tabaci showed that type of treatment had the most dominant influence and statistically significant impact.

  5. A Chado case study: an ontology-based modular schema for representing genome-associated biological information.

    Science.gov (United States)

    Mungall, Christopher J; Emmert, David B

    2007-07-01

    A few years ago, FlyBase undertook to design a new database schema to store Drosophila data. It would fully integrate genomic sequence and annotation data with bibliographic, genetic, phenotypic and molecular data from the literature representing a distillation of the first 100 years of research on this major animal model system. In developing this new integrated schema, FlyBase also made a commitment to ensure that its design was generic, extensible and available as open source, so that it could be employed as the core schema of any model organism data repository, thereby avoiding redundant software development and potentially increasing interoperability. Our question was whether we could create a relational database schema that would be successfully reused. Chado is a relational database schema now being used to manage biological knowledge for a wide variety of organisms, from human to pathogens, especially the classes of information that directly or indirectly can be associated with genome sequences or the primary RNA and protein products encoded by a genome. Biological databases that conform to this schema can interoperate with one another, and with application software from the Generic Model Organism Database (GMOD) toolkit. Chado is distinctive because its design is driven by ontologies. The use of ontologies (or controlled vocabularies) is ubiquitous across the schema, as they are used as a means of typing entities. The Chado schema is partitioned into integrated subschemas (modules), each encapsulating a different biological domain, and each described using representations in appropriate ontologies. To illustrate this methodology, we describe here the Chado modules used for describing genomic sequences. GMOD is a collaboration of several model organism database groups, including FlyBase, to develop a set of open-source software for managing model organism data. The Chado schema is freely distributed under the terms of the Artistic License (http

  6. Integrative radiation systems biology

    International Nuclear Information System (INIS)

    Unger, Kristian

    2014-01-01

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

  7. Animal protein production modules in biological life support systems: Novel combined aquaculture techniques based on the closed equilibrated biological aquatic system (C.E.B.A.S.)

    Science.gov (United States)

    Blüm, V.; Andriske, M.; Kreuzberg, K.; Schreibman, M. P.

    Based on the experiences made with the Closed Equilibrated Biological Aquatic System (C.E.B.A.S.) which was primarily deveoloped for long-term and multi-generation experiments with aquatic animals and plants in a space station highly effective fresh water recycling modules were elaborated utilizing a combination of ammonia oxidizing bacteria filters and higher plants. These exhibit a high effectivity to eliminate phosphate and anorganic nitrogen compounds and arc. in addidition. able to contribute to the oxygen supply of the aquatic animals. The C.E.B.A.S. filter system is able to keep a closed artificial aquatic ecosystem containing teleost fishes and water snails biologically stable for several month and to eliminate waste products deriving from degraded dead fishes without a decrease of the oxygen concentration down to less than 3.5 mg/l at 25 °C. More advanced C.E.B.A.S. filter systems, the BIOCURE filters, were also developed for utilization in semiintensive and intensive aquaculture systems for fishes. In fact such combined animal-plant aquaculture systems represent highly effective productions sites for human food if proper plant and fish species are selected The present papers elucidates ways to novel aquaculture systems in which herbivorous fishes are raised by feeding them with plant biomass produced in the BIOCURE filters and presents the scheme of a modification which utilizes a plant species suitable also for human nutrition. Special attention is paid to the benefits of closed aquaculture system modules which may be integrated into bioregenerative life support systems of a higher complexity for, e. g.. lunar or planetary bases including some psychologiccal aspects of the introduction of animal protein production into plant-based life support systems. Moreover, the basic reproductive biological problems of aquatic animal breeding under reduced gravity are explained leading to a disposition of essential research programs in this context.

  8. Efficient Bayesian estimates for discrimination among topologically different systems biology models.

    Science.gov (United States)

    Hagen, David R; Tidor, Bruce

    2015-02-01

    A major effort in systems biology is the development of mathematical models that describe complex biological systems at multiple scales and levels of abstraction. Determining the topology-the set of interactions-of a biological system from observations of the system's behavior is an important and difficult problem. Here we present and demonstrate new methodology for efficiently computing the probability distribution over a set of topologies based on consistency with existing measurements. Key features of the new approach include derivation in a Bayesian framework, incorporation of prior probability distributions of topologies and parameters, and use of an analytically integrable linearization based on the Fisher information matrix that is responsible for large gains in efficiency. The new method was demonstrated on a collection of four biological topologies representing a kinase and phosphatase that operate in opposition to each other with either processive or distributive kinetics, giving 8-12 parameters for each topology. The linearization produced an approximate result very rapidly (CPU minutes) that was highly accurate on its own, as compared to a Monte Carlo method guaranteed to converge to the correct answer but at greater cost (CPU weeks). The Monte Carlo method developed and applied here used the linearization method as a starting point and importance sampling to approach the Bayesian answer in acceptable time. Other inexpensive methods to estimate probabilities produced poor approximations for this system, with likelihood estimation showing its well-known bias toward topologies with more parameters and the Akaike and Schwarz Information Criteria showing a strong bias toward topologies with fewer parameters. These results suggest that this linear approximation may be an effective compromise, providing an answer whose accuracy is near the true Bayesian answer, but at a cost near the common heuristics.

  9. 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...

  10. Metabolomics: Definitions and Significance in Systems Biology.

    Science.gov (United States)

    Klassen, Aline; Faccio, Andréa Tedesco; Canuto, Gisele André Baptista; da Cruz, Pedro Luis Rocha; Ribeiro, Henrique Caracho; Tavares, Marina Franco Maggi; Sussulini, Alessandra

    2017-01-01

    Nowadays, there is a growing interest in deeply understanding biological mechanisms not only at the molecular level (biological components) but also the effects of an ongoing biological process in the organism as a whole (biological functionality), as established by the concept of systems biology. Within this context, metabolomics is one of the most powerful bioanalytical strategies that allow obtaining a picture of the metabolites of an organism in the course of a biological process, being considered as a phenotyping tool. Briefly, metabolomics approach consists in identifying and determining the set of metabolites (or specific metabolites) in biological samples (tissues, cells, fluids, or organisms) under normal conditions in comparison with altered states promoted by disease, drug treatment, dietary intervention, or environmental modulation. The aim of this chapter is to review the fundamentals and definitions used in the metabolomics field, as well as to emphasize its importance in systems biology and clinical studies.

  11. 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.

  12. Sensitivity analysis approaches applied to systems biology models.

    Science.gov (United States)

    Zi, Z

    2011-11-01

    With the rising application of systems biology, sensitivity analysis methods have been widely applied to study the biological systems, including metabolic networks, signalling pathways and genetic circuits. Sensitivity analysis can provide valuable insights about how robust the biological responses are with respect to the changes of biological parameters and which model inputs are the key factors that affect the model outputs. In addition, sensitivity analysis is valuable for guiding experimental analysis, model reduction and parameter estimation. Local and global sensitivity analysis approaches are the two types of sensitivity analysis that are commonly applied in systems biology. Local sensitivity analysis is a classic method that studies the impact of small perturbations on the model outputs. On the other hand, global sensitivity analysis approaches have been applied to understand how the model outputs are affected by large variations of the model input parameters. In this review, the author introduces the basic concepts of sensitivity analysis approaches applied to systems biology models. Moreover, the author discusses the advantages and disadvantages of different sensitivity analysis methods, how to choose a proper sensitivity analysis approach, the available sensitivity analysis tools for systems biology models and the caveats in the interpretation of sensitivity analysis results.

  13. Impact of Thermodynamic Principles in Systems Biology

    NARCIS (Netherlands)

    Heijnen, J.J.

    2010-01-01

    It is shown that properties of biological systems which are relevant for systems biology motivated mathematical modelling are strongly shaped by general thermodynamic principles such as osmotic limit, Gibbs energy dissipation, near equilibria and thermodynamic driving force. Each of these aspects

  14. Systems Biology of Metabolism: Annual Review of Biochemistry

    DEFF Research Database (Denmark)

    Nielsen, Jens

    2017-01-01

    Metabolism is highly complex and involves thousands of different connected reactions; it is therefore necessary to use mathematical models for holistic studies. The use of mathematical models in biology is referred to as systems biology. In this review, the principles of systems biology are descr...

  15. Systems biology of stored blood cells: can it help to extend the expiration date?

    Science.gov (United States)

    Paglia, Giuseppe; Palsson, Bernhard Ø; Sigurjonsson, Olafur E

    2012-12-05

    With increasingly stringent regulations regarding deferral and elimination of blood donors it will become increasingly important to extend the expiration date of blood components beyond the current allowed storage periods. One reason for the storage time limit for blood components is that platelets and red blood cells develop a condition called storage lesions during their storage in plastic blood containers. Systems biology provides comprehensive bio-chemical descriptions of organisms through quantitative measurements and data integration in mathematical models. The biological knowledge for a target organism can be translated in a mathematical format and used to compute physiological properties. The use of systems biology represents a concrete solution in the study of blood cell storage lesions, and it may open up new avenues towards developing better storage methods and better storage media, thereby extending the storage period of blood components. This article is part of a Special Issue entitled: Integrated omics. Copyright © 2012 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2017-07-05

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

  17. Plant Systems Biology at the Single-Cell Level.

    Science.gov (United States)

    Libault, Marc; Pingault, Lise; Zogli, Prince; Schiefelbein, John

    2017-11-01

    Our understanding of plant biology is increasingly being built upon studies using 'omics and system biology approaches performed at the level of the entire plant, organ, or tissue. Although these approaches open new avenues to better understand plant biology, they suffer from the cellular complexity of the analyzed sample. Recent methodological advances now allow plant scientists to overcome this limitation and enable biological analyses of single-cells or single-cell-types. Coupled with the development of bioinformatics and functional genomics resources, these studies provide opportunities for high-resolution systems analyses of plant phenomena. In this review, we describe the recent advances, current challenges, and future directions in exploring the biology of single-cells and single-cell-types to enhance our understanding of plant biology as a system. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. On the interplay between mathematics and biology: hallmarks toward a new systems biology.

    Science.gov (United States)

    Bellomo, Nicola; Elaiw, Ahmed; Althiabi, Abdullah M; Alghamdi, Mohammed Ali

    2015-03-01

    This paper proposes a critical analysis of the existing literature on mathematical tools developed toward systems biology approaches and, out of this overview, develops a new approach whose main features can be briefly summarized as follows: derivation of mathematical structures suitable to capture the complexity of biological, hence living, systems, modeling, by appropriate mathematical tools, Darwinian type dynamics, namely mutations followed by selection and evolution. Moreover, multiscale methods to move from genes to cells, and from cells to tissue are analyzed in view of a new systems biology approach. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. General method to find the attractors of discrete dynamic models of biological systems

    Science.gov (United States)

    Gan, Xiao; Albert, Réka

    2018-04-01

    Analyzing the long-term behaviors (attractors) of dynamic models of biological networks can provide valuable insight. We propose a general method that can find the attractors of multilevel discrete dynamical systems by extending a method that finds the attractors of a Boolean network model. The previous method is based on finding stable motifs, subgraphs whose nodes' states can stabilize on their own. We extend the framework from binary states to any finite discrete levels by creating a virtual node for each level of a multilevel node, and describing each virtual node with a quasi-Boolean function. We then create an expanded representation of the multilevel network, find multilevel stable motifs and oscillating motifs, and identify attractors by successive network reduction. In this way, we find both fixed point attractors and complex attractors. We implemented an algorithm, which we test and validate on representative synthetic networks and on published multilevel models of biological networks. Despite its primary motivation to analyze biological networks, our motif-based method is general and can be applied to any finite discrete dynamical system.

  20. General method to find the attractors of discrete dynamic models of biological systems.

    Science.gov (United States)

    Gan, Xiao; Albert, Réka

    2018-04-01

    Analyzing the long-term behaviors (attractors) of dynamic models of biological networks can provide valuable insight. We propose a general method that can find the attractors of multilevel discrete dynamical systems by extending a method that finds the attractors of a Boolean network model. The previous method is based on finding stable motifs, subgraphs whose nodes' states can stabilize on their own. We extend the framework from binary states to any finite discrete levels by creating a virtual node for each level of a multilevel node, and describing each virtual node with a quasi-Boolean function. We then create an expanded representation of the multilevel network, find multilevel stable motifs and oscillating motifs, and identify attractors by successive network reduction. In this way, we find both fixed point attractors and complex attractors. We implemented an algorithm, which we test and validate on representative synthetic networks and on published multilevel models of biological networks. Despite its primary motivation to analyze biological networks, our motif-based method is general and can be applied to any finite discrete dynamical system.

  1. Computational Modeling of Biological Systems From Molecules to Pathways

    CERN Document Server

    2012-01-01

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

  2. 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.

  3. JSBML 1.0: providing a smorgasbord of options to encode systems biology models

    DEFF Research Database (Denmark)

    Rodriguez, Nicolas; Thomas, Alex; Watanabe, Leandro

    2015-01-01

    JSBML, the official pure Java programming library for the Systems Biology Markup Language (SBML) format, has evolved with the advent of different modeling formalisms in systems biology and their ability to be exchanged and represented via extensions of SBML. JSBML has matured into a major, active...... open-source project with contributions from a growing, international team of developers who not only maintain compatibility with SBML, but also drive steady improvements to the Java interface and promote ease-of-use with end users. Source code, binaries and documentation for JSBML can be freely...... obtained under the terms of the LGPL 2.1 from the website http://sbml.org/Software/JSBML. More information about JSBML can be found in the user guide at http://sbml.org/Software/JSBML/docs/. jsbml-development@googlegroups.com or andraeger@eng.ucsd.edu Supplementary data are available at Bioinformatics...

  4. Systems Biology and Stem Cell Pluripotency

    DEFF Research Database (Denmark)

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

    2016-01-01

    Recent breakthroughs in stem cell biology have accelerated research in the area of regenerative medicine. Over the past years, it has become possible to derive patient-specific stem cells which can be used to generate different cell populations for potential cell therapy. Systems biological...... 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...

  5. 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. © 2015 Wiley Periodicals, Inc.

  6. Optoelectronic system and apparatus for connection to biological systems

    Science.gov (United States)

    Okandan, Murat; Nielson, Gregory N.

    2018-03-06

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

  7. 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.

  8. A system for success: BMC Systems Biology, a new open access journal

    OpenAIRE

    Webb Penelope A; Hodgkinson Matt J

    2007-01-01

    Abstract BMC Systems Biology is the first open access journal spanning the growing field of systems biology from molecules up to ecosystems. The journal has launched as more and more institutes are founded that are similarly dedicated to this new approach. BMC Systems Biology builds on the ongoing success of the BMC series, providing a venue for all sound research in the systems-level analysis of biology.

  9. 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. These stu......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....... These studies have identified a plethora of novel effector proteins stored in the granules of neutrophils. In addition, these studies provide evidence that neutrophil differentiation and immune response are governed by a highly coordinated transcriptional programme that regulates cellular fate and function...

  10. Biological Potential in Serpentinizing Systems

    Science.gov (United States)

    Hoehler, Tori M.

    2016-01-01

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

  11. On the limitations of standard statistical modeling in biological systems: a full Bayesian approach for biology.

    Science.gov (United States)

    Gomez-Ramirez, Jaime; Sanz, Ricardo

    2013-09-01

    One of the most important scientific challenges today is the quantitative and predictive understanding of biological function. Classical mathematical and computational approaches have been enormously successful in modeling inert matter, but they may be inadequate to address inherent features of biological systems. We address the conceptual and methodological obstacles that lie in the inverse problem in biological systems modeling. We introduce a full Bayesian approach (FBA), a theoretical framework to study biological function, in which probability distributions are conditional on biophysical information that physically resides in the biological system that is studied by the scientist. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. 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’.

  13. BetaWB - A language for modular representation of biological systems

    DEFF Research Database (Denmark)

    Ihekwaba, Adoha; Larcher, Roberto; Mardare, Radu Iulian

    2007-01-01

    A. Ihekwaba, R. Larcher, R. Mardare, C. Priami. BetaWB - A language for modular representation of biological systems. In Proc. of International Conference on Systems Biology (ICSB), 2007......A. Ihekwaba, R. Larcher, R. Mardare, C. Priami. BetaWB - A language for modular representation of biological systems. In Proc. of International Conference on Systems Biology (ICSB), 2007...

  14. Synthetic Biology and the U.S. Biotechnology Regulatory System: Challenges and Options

    Energy Technology Data Exchange (ETDEWEB)

    Carter, Sarah R. [J. Craig Venter Inst., Rockville, MD (United States); Rodemeyer, Michael [Univ. of Virginia, Charlottesville, VA (United States); Garfinkel, Michele S. [EMBO, Heidelberg (Germany); Friedman, Robert M. [J. Craig Venter Inst., Rockville, MD (United States)

    2014-05-01

    Synthetic Biology and the U.S. Biotechnology Regulatory System: Challenges and Options Sarah R. Carter, Ph.D., J. Craig Venter Institute; Michael Rodemeyer, J.D., University of Virginia; Michele S. Garfinkel, Ph.D., EMBO; Robert M. Friedman, Ph.D., J. Craig Venter Institute In recent years, a range of genetic engineering techniques referred to as “synthetic biology” has significantly expanded the tool kit available to scientists and engineers, providing them with far greater capabilities to engineer organisms than previous techniques allowed. The field of synthetic biology includes the relatively new ability to synthesize long pieces of DNA from chemicals, as well as improved methods for genetic manipulation and design of genetic pathways to achieve more precise control of biological systems. These advances will help usher in a new generation of genetically engineered microbes, plants, and animals. The JCVI Policy Center team, along with researchers at the University of Virginia and EMBO, examined how well the current U.S. regulatory system for genetically engineered products will handle the near-term introduction of organisms engineered using synthetic biology. In particular, the focus was on those organisms intended to be used or grown directly in the environment, outside of a contained facility. The study concludes that the U.S. regulatory agencies have adequate legal authority to address most, but not all, potential environmental, health and safety concerns posed by these organisms. Such near-term products are likely to represent incremental changes rather than a marked departure from previous genetically engineered organisms. However, the study also identified two key challenges for the regulatory system, which are detailed in the report. First, USDA’s authority over genetically engineered plants depends on the use of an older engineering technique that is no longer necessary for many applications. The shift to synthetic biology and other newer genetic

  15. "Life-bearing molecules" versus "life-embodying systems": Two contrasting views on the what-is-life (WIL) problem persisting from the early days of molecular biology to the post-genomic cell- and organism-level biology.

    Science.gov (United States)

    Sato, Naoki

    2018-05-01

    "What is life?" is an ultimate biological quest for the principle that makes organisms alive. This 'WIL problem' is not, however, a simple one that we have a straightforward strategy to attack. From the beginning, molecular biology tried to identify molecules that bear the essence of life: the double helical DNA represented replication, and enzymes were micro-actuators of biological activities. A dominating idea behind these mainstream biological studies relies on the identification of life-bearing molecules, which themselves are models of life. Another, prevalent idea emphasizes that life resides in the whole system of an organism, but not in some particular molecules. The behavior of a complex system may be considered to embody the essence of life. The thermodynamic view of life system in the early 20th century was remodeled as physics of complex systems and systems biology. The two views contrast with each other, but they are no longer heritage of the historical dualism in biology, such as mechanism/materialism versus vitalism, or reductionism versus holism. These two views are both materialistic and mechanistic, and act as driving forces of modern biology. In reality, molecules function in a context of systems, whereas systems presuppose functional molecules. A key notion to reconcile this conflict is that subjects of biological studies are given before we start to study them. Cell- or organism-level biology is destined to the dialectic of molecules and systems, but this antagonism can be resolved by dynamic thinking involving biological evolution. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Yeast systems biology to unravel the network of life

    DEFF Research Database (Denmark)

    Mustacchi, Roberta; Hohmann, S; Nielsen, Jens

    2006-01-01

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

  17. 3S - Systematic, systemic, and systems biology and toxicology.

    Science.gov (United States)

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

    2018-01-01

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

  18. A dedicated database system for handling multi-level data in systems biology.

    Science.gov (United States)

    Pornputtapong, Natapol; Wanichthanarak, Kwanjeera; Nilsson, Avlant; Nookaew, Intawat; Nielsen, Jens

    2014-01-01

    Advances in high-throughput technologies have enabled extensive generation of multi-level omics data. These data are crucial for systems biology research, though they are complex, heterogeneous, highly dynamic, incomplete and distributed among public databases. This leads to difficulties in data accessibility and often results in errors when data are merged and integrated from varied resources. Therefore, integration and management of systems biological data remain very challenging. To overcome this, we designed and developed a dedicated database system that can serve and solve the vital issues in data management and hereby facilitate data integration, modeling and analysis in systems biology within a sole database. In addition, a yeast data repository was implemented as an integrated database environment which is operated by the database system. Two applications were implemented to demonstrate extensibility and utilization of the system. Both illustrate how the user can access the database via the web query function and implemented scripts. These scripts are specific for two sample cases: 1) Detecting the pheromone pathway in protein interaction networks; and 2) Finding metabolic reactions regulated by Snf1 kinase. In this study we present the design of database system which offers an extensible environment to efficiently capture the majority of biological entities and relations encountered in systems biology. Critical functions and control processes were designed and implemented to ensure consistent, efficient, secure and reliable transactions. The two sample cases on the yeast integrated data clearly demonstrate the value of a sole database environment for systems biology research.

  19. Strategies for structuring interdisciplinary education in Systems Biology

    DEFF Research Database (Denmark)

    Cvijovic, Marija; Höfer, Thomas; Aćimović, Jure

    2016-01-01

    function by employing experimental data, mathematical models and computational simulations. As Systems Biology is inherently multidisciplinary, education within this field meets numerous hurdles including departmental barriers, availability of all required expertise locally, appropriate teaching material...... and example curricula. As university education at the Bachelor’s level is traditionally built upon disciplinary degrees, we believe that the most effective way to implement education in Systems Biology would be at the Master’s level, as it offers a more flexible framework. Our team of experts and active...... performers of Systems Biology education suggest here (i) a definition of the skills that students should acquire within a Master’s programme in Systems Biology, (ii) a possible basic educational curriculum with flexibility to adjust to different application areas and local research strengths, (iii...

  20. The Systems Biology Markup Language (SBML): Language Specification for Level 3 Version 1 Core.

    Science.gov (United States)

    Hucka, Michael; Bergmann, Frank T; Hoops, Stefan; Keating, Sarah M; Sahle, Sven; Schaff, James C; Smith, Lucian P; Wilkinson, Darren J

    2015-09-04

    Computational models can help researchers to interpret data, understand biological function, and make quantitative predictions. The Systems Biology Markup Language (SBML) is a file format for representing computational models in a declarative form that can be exchanged between different software systems. SBML is oriented towards describing biological processes of the sort common in research on a number of topics, including metabolic pathways, cell signaling pathways, and many others. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. This document provides the specification for Version 1 of SBML Level 3 Core. The specification defines the data structures prescribed by SBML as well as their encoding in XML, the eXtensible Markup Language. This specification also defines validation rules that determine the validity of an SBML document, and provides many examples of models in SBML form. Other materials and software are available from the SBML project web site, http://sbml.org/.

  1. Redefining plant systems biology: from cell to ecosystem

    NARCIS (Netherlands)

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

    2011-01-01

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

  2. Microgravity Fluids for Biology, Workshop

    Science.gov (United States)

    Griffin, DeVon; Kohl, Fred; Massa, Gioia D.; Motil, Brian; Parsons-Wingerter, Patricia; Quincy, Charles; Sato, Kevin; Singh, Bhim; Smith, Jeffrey D.; Wheeler, Raymond M.

    2013-01-01

    Microgravity Fluids for Biology represents an intersection of biology and fluid physics that present exciting research challenges to the Space Life and Physical Sciences Division. Solving and managing the transport processes and fluid mechanics in physiological and biological systems and processes are essential for future space exploration and colonization of space by humans. Adequate understanding of the underlying fluid physics and transport mechanisms will provide new, necessary insights and technologies for analyzing and designing biological systems critical to NASAs mission. To enable this mission, the fluid physics discipline needs to work to enhance the understanding of the influence of gravity on the scales and types of fluids (i.e., non-Newtonian) important to biology and life sciences. In turn, biomimetic, bio-inspired and synthetic biology applications based on physiology and biology can enrich the fluid mechanics and transport phenomena capabilities of the microgravity fluid physics community.

  3. Electromagnetic fields in biological systems

    National Research Council Canada - National Science Library

    Lin, James C

    2012-01-01

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

  4. 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...

  5. 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...... 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...

  6. Synthetic Biology: Engineering Living Systems from Biophysical Principles.

    Science.gov (United States)

    Bartley, Bryan A; Kim, Kyung; Medley, J Kyle; Sauro, Herbert M

    2017-03-28

    Synthetic biology was founded as a biophysical discipline that sought explanations for the origins of life from chemical and physical first principles. Modern synthetic biology has been reinvented as an engineering discipline to design new organisms as well as to better understand fundamental biological mechanisms. However, success is still largely limited to the laboratory and transformative applications of synthetic biology are still in their infancy. Here, we review six principles of living systems and how they compare and contrast with engineered systems. We cite specific examples from the synthetic biology literature that illustrate these principles and speculate on their implications for further study. To fully realize the promise of synthetic biology, we must be aware of life's unique properties. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  7. Two sides of the same coin? The (techno)epistemic cultures of systems and synthetic biology.

    Science.gov (United States)

    Kastenhofer, Karen

    2013-06-01

    Systems and synthetic biology both emerged around the turn of this century as labels for new research approaches. Although their disciplinary status as well as their relation to each other is rarely discussed in depth, now and again the idea is invoked that both approaches represent 'two sides of the same coin'. The following paper focuses on this general notion and compares it with empirical findings concerning the epistemic cultures prevalent in the two contexts. Drawing on interviews with researchers from both fields, on participatory observation in conferences and courses and on documentary analysis, this paper delineates differences and similarities, incompatibilities and blurred boundaries. By reconstructing systems and synthetic biology's epistemic cultures, this paper argues that they represent two 'communities of vision', encompassing heterogeneous practices. Understanding the relation of the respective visions of understanding nature and engineering life is seen as indispensible for the characterisation of (techno)science in more general terms. Depending on the conceptualisation of understanding and construction (or: science and engineering), related practices such as in silico modelling for enhancing understanding or enabling engineering can either be seen as incommensurable or 'two sides of one coin'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Biological data warehousing system for identifying transcriptional regulatory sites from gene expressions of microarray data.

    Science.gov (United States)

    Tsou, Ann-Ping; Sun, Yi-Ming; Liu, Chia-Lin; Huang, Hsien-Da; Horng, Jorng-Tzong; Tsai, Meng-Feng; Liu, Baw-Juine

    2006-07-01

    Identification of transcriptional regulatory sites plays an important role in the investigation of gene regulation. For this propose, we designed and implemented a data warehouse to integrate multiple heterogeneous biological data sources with data types such as text-file, XML, image, MySQL database model, and Oracle database model. The utility of the biological data warehouse in predicting transcriptional regulatory sites of coregulated genes was explored using a synexpression group derived from a microarray study. Both of the binding sites of known transcription factors and predicted over-represented (OR) oligonucleotides were demonstrated for the gene group. The potential biological roles of both known nucleotides and one OR nucleotide were demonstrated using bioassays. Therefore, the results from the wet-lab experiments reinforce the power and utility of the data warehouse as an approach to the genome-wide search for important transcription regulatory elements that are the key to many complex biological systems.

  9. Structure, function, and behaviour of computational models in systems biology.

    Science.gov (United States)

    Knüpfer, Christian; Beckstein, Clemens; Dittrich, Peter; Le Novère, Nicolas

    2013-05-31

    Systems Biology develops computational models in order to understand biological phenomena. The increasing number and complexity of such "bio-models" necessitate computer support for the overall modelling task. Computer-aided modelling has to be based on a formal semantic description of bio-models. But, even if computational bio-models themselves are represented precisely in terms of mathematical expressions their full meaning is not yet formally specified and only described in natural language. We present a conceptual framework - the meaning facets - which can be used to rigorously specify the semantics of bio-models. A bio-model has a dual interpretation: On the one hand it is a mathematical expression which can be used in computational simulations (intrinsic meaning). On the other hand the model is related to the biological reality (extrinsic meaning). We show that in both cases this interpretation should be performed from three perspectives: the meaning of the model's components (structure), the meaning of the model's intended use (function), and the meaning of the model's dynamics (behaviour). In order to demonstrate the strengths of the meaning facets framework we apply it to two semantically related models of the cell cycle. Thereby, we make use of existing approaches for computer representation of bio-models as much as possible and sketch the missing pieces. The meaning facets framework provides a systematic in-depth approach to the semantics of bio-models. It can serve two important purposes: First, it specifies and structures the information which biologists have to take into account if they build, use and exchange models. Secondly, because it can be formalised, the framework is a solid foundation for any sort of computer support in bio-modelling. The proposed conceptual framework establishes a new methodology for modelling in Systems Biology and constitutes a basis for computer-aided collaborative research.

  10. The aims of systems biology: between molecules and organisms.

    Science.gov (United States)

    Noble, D

    2011-05-01

    The systems approach to biology has a long history. Its recent rapid resurgence at the turn of the century reflects the problems encountered in interpreting the sequencing of the genome and the failure of that immense achievement to provide rapid and direct solutions to major multi-factorial diseases. This paper argues that systems biology is necessarily multilevel and that there is no privileged level of causality in biological systems. It is an approach rather than a separate discipline. Functionality arises from biological networks that interact with the genome, the environment and the phenotype. This view of biology is very different from the gene-centred views of neo-Darwinism and molecular biology. In neuroscience, the systems approach leads naturally to 2 important conclusions: first, that the idea of 'programs' in the brain is confusing, and second, that the self is better interpreted as a process than as an object. © Georg Thieme Verlag KG Stuttgart · New York.

  11. Bridging the gap between clinicians and systems biologists: from network biology to translational biomedical research.

    Science.gov (United States)

    Jinawath, Natini; Bunbanjerdsuk, Sacarin; Chayanupatkul, Maneerat; Ngamphaiboon, Nuttapong; Asavapanumas, Nithi; Svasti, Jisnuson; Charoensawan, Varodom

    2016-11-22

    With the wealth of data accumulated from completely sequenced genomes and other high-throughput experiments, global studies of biological systems, by simultaneously investigating multiple biological entities (e.g. genes, transcripts, proteins), has become a routine. Network representation is frequently used to capture the presence of these molecules as well as their relationship. Network biology has been widely used in molecular biology and genetics, where several network properties have been shown to be functionally important. Here, we discuss how such methodology can be useful to translational biomedical research, where scientists traditionally focus on one or a small set of genes, diseases, and drug candidates at any one time. We first give an overview of network representation frequently used in biology: what nodes and edges represent, and review its application in preclinical research to date. Using cancer as an example, we review how network biology can facilitate system-wide approaches to identify targeted small molecule inhibitors. These types of inhibitors have the potential to be more specific, resulting in high efficacy treatments with less side effects, compared to the conventional treatments such as chemotherapy. Global analysis may provide better insight into the overall picture of human diseases, as well as identify previously overlooked problems, leading to rapid advances in medicine. From the clinicians' point of view, it is necessary to bridge the gap between theoretical network biology and practical biomedical research, in order to improve the diagnosis, prevention, and treatment of the world's major diseases.

  12. Representative elements: A step to large-scale fracture system simulation

    International Nuclear Information System (INIS)

    Clemo, T.M.

    1987-01-01

    Large-scale simulation of flow and transport in fractured media requires the development of a technique to represent the effect of a large number of fractures. Representative elements are used as a tool to model a subset of a fracture system as a single distributed entity. Representative elements are part of a modeling concept called dual permeability. Dual permeability modeling combines discrete fracture simulation of the most important fractures with the distributed modeling of the less important fracture of a fracture system. This study investigates the use of stochastic analysis to determine properties of representative elements. Given an assumption of fully developed laminar flow, the net fracture conductivities and hence flow velocities can be determined from descriptive statistics of fracture spacing, orientation, aperture, and extent. The distribution of physical characteristics about their mean leads to a distribution of the associated conductivities. The variance of hydraulic conductivity induces dispersion into the transport process. Simple fracture systems are treated to demonstrate the usefulness of stochastic analysis. Explicit equations for conductivity of an element are developed and the dispersion characteristics are shown. Explicit formulation of the hydraulic conductivity and transport dispersion reveals the dependence of these important characteristics on the parameters used to describe the fracture system. Understanding these dependencies will help to focus efforts to identify the characteristics of fracture systems. Simulations of stochastically generated fracture sets do not provide this explicit functional dependence on the fracture system parameters. 12 refs., 6 figs

  13. The capacity of Australia's protected-area system to represent threatened species.

    Science.gov (United States)

    Watson, James E M; Evans, Megan C; Carwardine, Josie; Fuller, Richard A; Joseph, Liana N; Segan, Dan B; Taylor, Martin F J; Fensham, R J; Possingham, Hugh P

    2011-04-01

    The acquisition or designation of new protected areas is usually based on criteria for representation of different ecosystems or land-cover classes, and it is unclear how well-threatened species are conserved within protected-area networks. Here, we assessed how Australia's terrestrial protected-area system (89 million ha, 11.6% of the continent) overlaps with the geographic distributions of threatened species and compared this overlap against a model that randomly placed protected areas across the continent and a spatially efficient model that placed protected areas across the continent to maximize threatened species' representation within the protected-area estate. We defined the minimum area needed to conserve each species on the basis of the species' range size. We found that although the current configuration of protected areas met targets for representation of a given percentage of species' ranges better than a random selection of areas, 166 (12.6%) threatened species occurred entirely outside protected areas and target levels of protection were met for only 259 (19.6%) species. Critically endangered species were among those with the least protection; 12 (21.1%) species occurred entirely outside protected areas. Reptiles and plants were the most poorly represented taxonomic groups, and amphibians the best represented. Spatial prioritization analyses revealed that an efficient protected-area system of the same size as the current protected-area system (11.6% of the area of Australia) could meet representation targets for 1272 (93.3%) threatened species. Moreover, the results of these prioritization analyses showed that by protecting 17.8% of Australia, all threatened species could reach target levels of representation, assuming all current protected areas are retained. Although this amount of area theoretically could be protected, existing land uses and the finite resources available for conservation mean land acquisition may not be possible or even effective

  14. 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…

  15. Mathematical methods in systems biology.

    Science.gov (United States)

    Kashdan, Eugene; Duncan, Dominique; Parnell, Andrew; Schattler, Heinz

    2016-12-01

    The editors of this Special Issue of Mathematical Biosciences and Engineering were the organizers for the Third International Workshop "Mathematical Methods in System Biology" that took place on June 15-18, 2015 at the University College Dublin in Ireland. As stated in the workshop goals, we managed to attract a good mix of mathematicians and statisticians working on biological and medical applications with biologists and clinicians interested in presenting their challenging problems and looking to find mathematical and statistical tools for their solutions.

  16. 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

  17. Biological drugs for the treatment of psoriasis in a public health system

    Directory of Open Access Journals (Sweden)

    Luciane Cruz Lopes

    2014-08-01

    Full Text Available OBJECTIVE To analyze the access and utilization profile of biological medications for psoriasis provided by the judicial system in Brazil. METHODS This is a cross-sectional study. We interviewed a total of 203 patients with psoriasis who were on biological medications obtained by the judicial system of the State of Sao Paulo, from 2004 to 2010. Sociodemographics, medical, and political-administrative characteristics were complemented with data obtained from dispensation orders that included biological medications to treat psoriasis and the legal actions involved. The data was analyzed using an electronic data base and shown as simple variable frequencies. The prescriptions contained in the lawsuits were analyzed according to legal provisions. RESULTS A total of 190 lawsuits requesting several biological drugs (adalimumab, efalizumab, etanercept, and infliximab were analyzed. Patients obtained these medications as a result of injunctions (59.5% or without having ever demanded biological medication from any health institution (86.2%, i.e., public or private health services. They used the prerogative of free legal aid (72.6%, even though they were represented by private lawyers (91.1% and treated in private facilities (69.5%. Most of the patients used a biological medication for more than 13 months (66.0%, and some patients were undergoing treatment with this medication when interviewed (44.9%. Approximately one third of the patients discontinued treatment due to worsening of their illness (26.6%, adverse drug reactions (20.5%, lack of efficacy, or because the doctor discontinued this medication (13.8%. None of the analyzed medical prescriptions matched the legal prescribing requirements. Clinical monitoring results showed that 70.3% of the patients had not undergone laboratory examinations (blood work, liver and kidney function tests for treatment control purposes. CONCLUSIONS The plaintiffs resorted to legal action to get access to biological

  18. Biological drugs for the treatment of psoriasis in a public health system

    Science.gov (United States)

    Lopes, Luciane Cruz; Silveira, Miriam Sanches do Nascimento; de Camargo, Iara Alves; Barberato, Silvio; Del Fiol, Fernando de Sá; Osorio-de-Castro, Claudia Garcia Serpa

    2014-01-01

    OBJECTIVE To analyze the access and utilization profile of biological medications for psoriasis provided by the judicial system in Brazil. METHODS This is a cross-sectional study. We interviewed a total of 203 patients with psoriasis who were on biological medications obtained by the judicial system of the State of Sao Paulo, from 2004 to 2010. Sociodemographics, medical, and political-administrative characteristics were complemented with data obtained from dispensation orders that included biological medications to treat psoriasis and the legal actions involved. The data was analyzed using an electronic data base and shown as simple variable frequencies. The prescriptions contained in the lawsuits were analyzed according to legal provisions. RESULTS A total of 190 lawsuits requesting several biological drugs (adalimumab, efalizumab, etanercept, and infliximab) were analyzed. Patients obtained these medications as a result of injunctions (59.5%) or without having ever demanded biological medication from any health institution (86.2%), i.e., public or private health services. They used the prerogative of free legal aid (72.6%), even though they were represented by private lawyers (91.1%) and treated in private facilities (69.5%). Most of the patients used a biological medication for more than 13 months (66.0%), and some patients were undergoing treatment with this medication when interviewed (44.9%). Approximately one third of the patients discontinued treatment due to worsening of their illness (26.6%), adverse drug reactions (20.5%), lack of efficacy, or because the doctor discontinued this medication (13.8%). None of the analyzed medical prescriptions matched the legal prescribing requirements. Clinical monitoring results showed that 70.3% of the patients had not undergone laboratory examinations (blood work, liver and kidney function tests) for treatment control purposes. CONCLUSIONS The plaintiffs resorted to legal action to get access to biological medications

  19. The bottom-up approach to defining life : deciphering the functional organization of biological cells via multi-objective representation of biological complexity from molecules to cells

    Directory of Open Access Journals (Sweden)

    Sathish ePeriyasamy

    2013-12-01

    Full Text Available In silico representation of cellular systems needs to represent the adaptive dynamics of biological cells, recognizing a cell’s multi-objective topology formed by spatially and temporally cohesive intracellular structures. The design of these models needs to address the hierarchical and concurrent nature of cellular functions and incorporate the ability to self-organise in response to transitions between healthy and pathological phases, and adapt accordingly. The functions of biological systems are constantly evolving, due to the ever changing demands of their environment. Biological systems meet these demands by pursuing objectives, aided by their constituents, giving rise to biological functions. A biological cell is organised into an objective/task hierarchy. These objective hierarchy corresponds to the nested nature of temporally cohesive structures and representing them will facilitate in studying pleiotropy and polygeny by modeling causalities propagating across multiple interconnected intracellular processes. Although biological adaptations occur in physiological, developmental and reproductive timescales, the paper is focused on adaptations that occur within physiological timescales, where the biomolecular activities contributing to functional organisation, play a key role in cellular physiology. The paper proposes a multi-scale and multi-objective modelling approach from the bottom-up by representing temporally cohesive structures for multi-tasking of intracellular processes. Further the paper characterises the properties and constraints that are consequential to the organisational and adaptive dynamics in biological cells.

  20. 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.

  1. 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.

  2. Modeling of Biological Intelligence for SCM System Optimization

    Science.gov (United States)

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

    2012-01-01

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

  3. Systems biology at work

    NARCIS (Netherlands)

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

    2010-01-01

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

  4. Advances in Structural Biology and the Application to Biological Filament Systems.

    Science.gov (United States)

    Popp, David; Koh, Fujiet; Scipion, Clement P M; Ghoshdastider, Umesh; Narita, Akihiro; Holmes, Kenneth C; Robinson, Robert C

    2018-04-01

    Structural biology has experienced several transformative technological advances in recent years. These include: development of extremely bright X-ray sources (microfocus synchrotron beamlines and free electron lasers) and the use of electrons to extend protein crystallography to ever decreasing crystal sizes; and an increase in the resolution attainable by cryo-electron microscopy. Here we discuss the use of these techniques in general terms and highlight their application for biological filament systems, an area that is severely underrepresented in atomic resolution structures. We assemble a model of a capped tropomyosin-actin minifilament to demonstrate the utility of combining structures determined by different techniques. Finally, we survey the methods that attempt to transform high resolution structural biology into more physiological environments, such as the cell. Together these techniques promise a compelling decade for structural biology and, more importantly, they will provide exciting discoveries in understanding the designs and purposes of biological machines. © 2018 The Authors. BioEssays Published by WILEY Periodicals, Inc.

  5. Systems biology for molecular life sciences and its impact in biomedicine.

    Science.gov (United States)

    Medina, Miguel Ángel

    2013-03-01

    Modern systems biology is already contributing to a radical transformation of molecular life sciences and biomedicine, and it is expected to have a real impact in the clinical setting in the next years. In this review, the emergence of systems biology is contextualized with a historic overview, and its present state is depicted. The present and expected future contribution of systems biology to the development of molecular medicine is underscored. Concerning the present situation, this review includes a reflection on the "inflation" of biological data and the urgent need for tools and procedures to make hidden information emerge. Descriptions of the impact of networks and models and the available resources and tools for applying them in systems biology approaches to molecular medicine are provided as well. The actual current impact of systems biology in molecular medicine is illustrated, reviewing two cases, namely, those of systems pharmacology and cancer systems biology. Finally, some of the expected contributions of systems biology to the immediate future of molecular medicine are commented.

  6. 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 ‘‘...

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

    Science.gov (United States)

    De Domenico, Manlio

    2018-03-01

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

  8. Application of vascular aquatic plants for pollution removal, energy and food production in a biological system

    Science.gov (United States)

    Wolverton, B. C.; Barlow, R. M.; Mcdonald, R. C.

    1975-01-01

    Vascular aquatic plants such as water hyacinths (Eichhornia crassipes) (Mart.) Solms and alligator weeds (Alternanthera philoxeroides) (Mart.) Griesb., when utilized in a controlled biological system (including a regular program of harvesting to achieve maximum growth and pollution removal efficiency), may represent a remarkably efficient and inexpensive filtration and disposal system for toxic materials and sewage released into waters near urban and industrial areas. The harvested and processed plant materials are sources of energy, fertilizer, animal feed, and human food. Such a system has industrial, municipal, and agricultural applications.

  9. Systems biology solutions for biochemical production challenges.

    Science.gov (United States)

    Hansen, Anne Sofie Lærke; Lennen, Rebecca M; Sonnenschein, Nikolaus; Herrgård, Markus J

    2017-06-01

    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 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 for biofuels and -chemicals. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    Indian Academy of Sciences (India)

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

  11. Advancing metabolic engineering through systems biology of industrial microorganisms

    DEFF Research Database (Denmark)

    Dai, Zongjie; Nielsen, Jens

    2015-01-01

    resources. The objective of systems biology is to gain a comprehensive and quantitative understanding of living cells and can hereby enhance our ability to characterize and predict cellular behavior. Systems biology of industrial microorganisms is therefore valuable for metabolic engineering. Here we review......Development of sustainable processes to produce bio-based compounds is necessary due to the severe environmental problems caused by the use of fossil resources. Metabolic engineering can facilitate the development of highly efficient cell factories to produce these compounds from renewable...... the application of systems biology tools for the identification of metabolic engineering targets which may lead to reduced development time for efficient cell factories. Finally, we present some perspectives of systems biology for advancing metabolic engineering further....

  12. Systems Biology Markup Language (SBML) Level 2 Version 5: Structures and Facilities for Model Definitions.

    Science.gov (United States)

    Hucka, Michael; Bergmann, Frank T; Dräger, Andreas; Hoops, Stefan; Keating, Sarah M; Le Novère, Nicolas; Myers, Chris J; Olivier, Brett G; Sahle, Sven; Schaff, James C; Smith, Lucian P; Waltemath, Dagmar; Wilkinson, Darren J

    2015-09-04

    Computational models can help researchers to interpret data, understand biological function, and make quantitative predictions. The Systems Biology Markup Language (SBML) is a file format for representing computational models in a declarative form that can be exchanged between different software systems. SBML is oriented towards describing biological processes of the sort common in research on a number of topics, including metabolic pathways, cell signaling pathways, and many others. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. This document provides the specification for Version 5 of SBML Level 2. The specification defines the data structures prescribed by SBML as well as their encoding in XML, the eXtensible Markup Language. This specification also defines validation rules that determine the validity of an SBML document, and provides many examples of models in SBML form. Other materials and software are available from the SBML project web site, http://sbml.org.

  13. Systems Biology Markup Language (SBML Level 2 Version 5: Structures and Facilities for Model Definitions

    Directory of Open Access Journals (Sweden)

    Hucka Michael

    2015-06-01

    Full Text Available Computational models can help researchers to interpret data, understand biological function, and make quantitative predictions. The Systems Biology Markup Language (SBML is a file format for representing computational models in a declarative form that can be exchanged between different software systems. SBML is oriented towards describing biological processes of the sort common in research on a number of topics, including metabolic pathways, cell signaling pathways, and many others. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. This document provides the specification for Version 5 of SBML Level 2. The specification defines the data structures prescribed by SBML as well as their encoding in XML, the eXtensible Markup Language. This specification also defines validation rules that determine the validity of an SBML document, and provides many examples of models in SBML form. Other materials and software are available from the SBML project web site, http://sbml.org/.

  14. Dietary antioxidant synergy in chemical and biological systems.

    Science.gov (United States)

    Wang, Sunan; Zhu, Fan

    2017-07-24

    Antioxidant (AOX) synergies have been much reported in chemical ("test-tube" based assays focusing on pure chemicals), biological (tissue culture, animal and clinical models), and food systems during the past decade. Tentative synergies differ from each other due to the composition of AOX and the quantification methods. Regeneration mechanism responsible for synergy in chemical systems has been discussed. Solvent effects could contribute to the artifacts of synergy observed in the chemical models. Synergy in chemical models may hardly be relevant to biological systems that have been much less studied. Apparent discrepancies exist in understanding the molecular mechanisms in both chemical and biological systems. This review discusses diverse variables associated with AOX synergy and molecular scenarios for explanation. Future research to better utilize the synergy is suggested.

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

    Science.gov (United States)

    2010-01-01

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  17. Interactive analysis of systems biology molecular expression data

    Directory of Open Access Journals (Sweden)

    Prabhakar Sunil

    2008-02-01

    Full Text Available Abstract Background Systems biology aims to understand biological systems on a comprehensive scale, such that the components that make up the whole are connected to one another and work through dependent interactions. Molecular correlations and comparative studies of molecular expression are crucial to establishing interdependent connections in systems biology. The existing software packages provide limited data mining capability. The user must first generate visualization data with a preferred data mining algorithm and then upload the resulting data into the visualization package for graphic visualization of molecular relations. Results Presented is a novel interactive visual data mining application, SysNet that provides an interactive environment for the analysis of high data volume molecular expression information of most any type from biological systems. It integrates interactive graphic visualization and statistical data mining into a single package. SysNet interactively presents intermolecular correlation information with circular and heatmap layouts. It is also applicable to comparative analysis of molecular expression data, such as time course data. Conclusion The SysNet program has been utilized to analyze elemental profile changes in response to an increasing concentration of iron (Fe in growth media (an ionomics dataset. This study case demonstrates that the SysNet software is an effective platform for interactive analysis of molecular expression information in systems biology.

  18. Tracing organizing principles: Learning from the history of systems biology

    DEFF Research Database (Denmark)

    Green, Sara; Wolkenhauer, Olaf

    2014-01-01

    on this historical background in order to increase the understanding of the motivation behind the search for general principles and to clarify different epistemic aims within systems biology. We pinpoint key aspects of earlier approaches that also underlie the current practice. These are i) the focus on relational......With the emergence of systems biology, the identification of organizing principles is being highlighted as a key research aim. Researchers attempt to “reverse engineer” the functional organization of biological systems using methodologies from mathematics, engineering and computer science while...... taking advantage of data produced by new experimental techniques. While systems biology is a relatively new approach, the quest for general principles of biological organization dates back to systems theoretic approaches in early and mid-twentieth century. The aim of this paper is to draw...

  19. The Systems Biology Markup Language (SBML): Language Specification for Level 3 Version 2 Core.

    Science.gov (United States)

    Hucka, Michael; Bergmann, Frank T; Dräger, Andreas; Hoops, Stefan; Keating, Sarah M; Le Novère, Nicolas; Myers, Chris J; Olivier, Brett G; Sahle, Sven; Schaff, James C; Smith, Lucian P; Waltemath, Dagmar; Wilkinson, Darren J

    2018-03-09

    Computational models can help researchers to interpret data, understand biological functions, and make quantitative predictions. The Systems Biology Markup Language (SBML) is a file format for representing computational models in a declarative form that different software systems can exchange. SBML is oriented towards describing biological processes of the sort common in research on a number of topics, including metabolic pathways, cell signaling pathways, and many others. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. This document provides the specification for Version 2 of SBML Level 3 Core. The specification defines the data structures prescribed by SBML, their encoding in XML (the eXtensible Markup Language), validation rules that determine the validity of an SBML document, and examples of models in SBML form. The design of Version 2 differs from Version 1 principally in allowing new MathML constructs, making more child elements optional, and adding identifiers to all SBML elements instead of only selected elements. Other materials and software are available from the SBML project website at http://sbml.org/.

  20. An online model composition tool for system biology models.

    Science.gov (United States)

    Coskun, Sarp A; Cicek, A Ercument; Lai, Nicola; Dash, Ranjan K; Ozsoyoglu, Z Meral; Ozsoyoglu, Gultekin

    2013-09-05

    There are multiple representation formats for Systems Biology computational models, and the Systems Biology Markup Language (SBML) is one of the most widely used. SBML is used to capture, store, and distribute computational models by Systems Biology data sources (e.g., the BioModels Database) and researchers. Therefore, there is a need for all-in-one web-based solutions that support advance SBML functionalities such as uploading, editing, composing, visualizing, simulating, querying, and browsing computational models. We present the design and implementation of the Model Composition Tool (Interface) within the PathCase-SB (PathCase Systems Biology) web portal. The tool helps users compose systems biology models to facilitate the complex process of merging systems biology models. We also present three tools that support the model composition tool, namely, (1) Model Simulation Interface that generates a visual plot of the simulation according to user's input, (2) iModel Tool as a platform for users to upload their own models to compose, and (3) SimCom Tool that provides a side by side comparison of models being composed in the same pathway. Finally, we provide a web site that hosts BioModels Database models and a separate web site that hosts SBML Test Suite models. Model composition tool (and the other three tools) can be used with little or no knowledge of the SBML document structure. For this reason, students or anyone who wants to learn about systems biology will benefit from the described functionalities. SBML Test Suite models will be a nice starting point for beginners. And, for more advanced purposes, users will able to access and employ models of the BioModels Database as well.

  1. SEEK: a systems biology data and model management platform.

    Science.gov (United States)

    Wolstencroft, Katherine; Owen, Stuart; Krebs, Olga; Nguyen, Quyen; Stanford, Natalie J; Golebiewski, Martin; Weidemann, Andreas; Bittkowski, Meik; An, Lihua; Shockley, David; Snoep, Jacky L; Mueller, Wolfgang; Goble, Carole

    2015-07-11

    Systems biology research typically involves the integration and analysis of heterogeneous data types in order to model and predict biological processes. Researchers therefore require tools and resources to facilitate the sharing and integration of data, and for linking of data to systems biology models. There are a large number of public repositories for storing biological data of a particular type, for example transcriptomics or proteomics, and there are several model repositories. However, this silo-type storage of data and models is not conducive to systems biology investigations. Interdependencies between multiple omics datasets and between datasets and models are essential. Researchers require an environment that will allow the management and sharing of heterogeneous data and models in the context of the experiments which created them. The SEEK is a suite of tools to support the management, sharing and exploration of data and models in systems biology. The SEEK platform provides an access-controlled, web-based environment for scientists to share and exchange data and models for day-to-day collaboration and for public dissemination. A plug-in architecture allows the linking of experiments, their protocols, data, models and results in a configurable system that is available 'off the shelf'. Tools to run model simulations, plot experimental data and assist with data annotation and standardisation combine to produce a collection of resources that support analysis as well as sharing. Underlying semantic web resources additionally extract and serve SEEK metadata in RDF (Resource Description Format). SEEK RDF enables rich semantic queries, both within SEEK and between related resources in the web of Linked Open Data. The SEEK platform has been adopted by many systems biology consortia across Europe. It is a data management environment that has a low barrier of uptake and provides rich resources for collaboration. This paper provides an update on the functions and

  2. Advancing metabolic engineering through systems biology of industrial microorganisms.

    Science.gov (United States)

    Dai, Zongjie; Nielsen, Jens

    2015-12-01

    Development of sustainable processes to produce bio-based compounds is necessary due to the severe environmental problems caused by the use of fossil resources. Metabolic engineering can facilitate the development of highly efficient cell factories to produce these compounds from renewable resources. The objective of systems biology is to gain a comprehensive and quantitative understanding of living cells and can hereby enhance our ability to characterize and predict cellular behavior. Systems biology of industrial microorganisms is therefore valuable for metabolic engineering. Here we review the application of systems biology tools for the identification of metabolic engineering targets which may lead to reduced development time for efficient cell factories. Finally, we present some perspectives of systems biology for advancing metabolic engineering further. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. 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.

  4. 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

  5. An Augmented γ-Spray System to Visualize Biological Effects for Human Body

    Science.gov (United States)

    Manabe, Seiya; Tenzou, Hideki; Kasuga, Takaaki; Iwakura, Yukiko; Johnston, Robert

    2017-09-01

    The purpose of this study was to develop a new educational system with an easy-to-use interface in order to support comprehension of the biological effects of radiation on the human body within a short period of time. A paint spray-gun was used as a gamma rays source mock-up for the system. The application screen shows the figure of a human body for radiation deposition using the γ-Sprayer, a virtual radiation source, as well as equivalent dosage and a panel for setting the irradiation conditions. While the learner stands in front of the PC monitor, the virtual radiation source is used to deposit radiation on the graphic of the human body that is displayed. Tissue damage is calculated using an interpolation method from the data calculated by the PHITS simulation code in advance while the learner is pulling the trigger with respect to the irradiation time, incident position, and distance from the screen. It was confirmed that the damage was well represented by the interpolation method. The augmented ?-Spray system was assessed by questionnaire. Pre-post questionnaire was taken for our 41 students in National Institute of Technology, Kagawa College. It was also confirmed that the system has a capability of teaching the basic radiation protection concept, quantitative feeling of the radiation dose, and the biological effects

  6. Advances in the use of biologic agents for the treatment of systemic vasculitis

    Science.gov (United States)

    Chung, Sharon A.; Seo, Philip

    2010-01-01

    Purpose of review Due to the well-known toxicities of cyclophosphamide, substantial interest exists in finding other therapies to treat primary systemic vasculitis. Biologic agents have been proposed as an alternative to cyclophosphamide for these disorders because of their recent success in treating other rheumatic diseases. This article reviews the current state-of-the-art with regards to the use of biologic agents as a treatment for systemic vasculitis. Recent findings The greatest amount of experience with these agents for the treatment of systemic vasculitis is with anti-tumor necrosis factor agents, pooled intravenous immunoglobulin, and anti-B cell therapies such as rituximab. Intravenous immunoglobulin is already a standard therapy for Kawasaki's disease, but should also be considered for the treatment of ANCA-associated vasculitis when standard therapies are either ineffective or contraindicated. Early experience with tumor necrosis factor inhibitors indicates that they may be effective for the treatment of Takayasu's arteritis, but their role in the treatment of other forms of vasculitis remains controversial. Early experience with rituximab for the treatment of several forms of vasculitis has been quite promising, but must be confirmed by ongoing randomized clinical trials. Summary Biologic agents represent the next evolution in treatment for the primary systemic vasculitides. Greater understanding of these diseases has allowed use to move further away from non-specific, highly toxic therapies towards a more directed approach. As our experience with these agents increases, they will likely form the keystone of treatment in the near future. PMID:19077713

  7. 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. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  8. The biological effects of ozone on representative members of five groups of animal viruses

    Energy Technology Data Exchange (ETDEWEB)

    Bolton, D.C.; Zee, Y.C.; Osebold, J.W.

    1982-04-01

    In an effort to establish the biological relevance of the reactions of ozone with soluble proteins and lipid bilayer membrane systems, representative viruses from five major virus groups were exposed to moderate concentrations of ozone. The virus suspensions were exposed at 37/sup 0/C to 0.00, 0.16, and 0.64 ppm ozone in the gas phase. The ozone reacted with the virus suspensions as a thin film of fluid on the surface of a rotating culture bottle as the gas was drawn through the bottle at a flow rate of 2 liters/min. The three enveloped viruses tested exhibited different susceptibilities to ozone inactivation which correlated with their thermolability in the absence of ozone. The order of susceptibility to ozone inactivation of the enveloped viruses was vesicular stomatitis virus (VSV) (Rhabdoviridae) > influenza A virus (WSN strain) (Orthomyxoviridae) > infectious bovine rhinotracheitis virus (IBRV) (Herpesviridae). The inactivation reactions of the enveloped viruses with ozone showed pseudo-first-order kinetics. A simple reaction model was used to derive a reaction rate expression from which rate constrants and reaction stoichiometry were estimated. In contrast to the enveloped viruses, the two nonenveloped viruses examined were relatively resistant to ozone inactivation. Polio virus type I (Picornaviridae) was found to be completely resistant to ozone inactivation after 60 hr exposure to either ozone concentration, while infectious canine hepatitis virus (Adenoviridae) showed only slight inactivation after exposure to 0.64 ppm ozone for 66 hr. The significance of these results with regard to the reactions of ozone with cell membranes and other components is discussed.

  9. Generating Systems Biology Markup Language Models from the Synthetic Biology Open Language.

    Science.gov (United States)

    Roehner, Nicholas; Zhang, Zhen; Nguyen, Tramy; Myers, Chris J

    2015-08-21

    In the context of synthetic biology, model generation is the automated process of constructing biochemical models based on genetic designs. This paper discusses the use cases for model generation in genetic design automation (GDA) software tools and introduces the foundational concepts of standards and model annotation that make this process useful. Finally, this paper presents an implementation of model generation in the GDA software tool iBioSim and provides an example of generating a Systems Biology Markup Language (SBML) model from a design of a 4-input AND sensor written in the Synthetic Biology Open Language (SBOL).

  10. Noninvasive biological sensor system for detection of drunk driving.

    Science.gov (United States)

    Murata, Kohji; Fujita, Etsunori; Kojima, Shigeyuki; Maeda, Shinitirou; Ogura, Yumi; Kamei, Tsutomu; Tsuji, Toshio; Kaneko, Shigehiko; Yoshizumi, Masao; Suzuki, Nobutaka

    2011-01-01

    Systems capable of monitoring the biological condition of a driver and issuing warnings during instances of drowsiness have recently been studied. Moreover, many researchers have reported that biological signals, such as brain waves, pulsation waves, and heart rate, are different between people who have and have not consumed alcohol. Currently, we are developing a noninvasive system to detect individuals driving under the influence of alcohol by measuring biological signals. We used the frequency time series analysis to attempt to distinguish between normal and intoxicated states of a person as the basis of the sensing system.

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

    Science.gov (United States)

    Pezzulo, Giovanni; Levin, Michael

    2016-11-01

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

  12. 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

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

    Science.gov (United States)

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

    2014-11-01

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

  14. SEEK: a systems biology data and model management platform.

    NARCIS (Netherlands)

    Wolstencroft, K.J.; Owen, S.; Krebs, O.; Nguyen, Q.; Stanford, N.J.; Golebiewski, M.; Weidemann, A.; Bittkowski, M.; An, L.; Shockley, D.; Snoep, J.L.; Mueller, W.; Goble, C.

    2015-01-01

    Background: Systems biology research typically involves the integration and analysis of heterogeneous data types in order to model and predict biological processes. Researchers therefore require tools and resources to facilitate the sharing and integration of data, and for linking of data to systems

  15. From Fertilization to Birth: Representing Development in High School Biology Textbooks

    Science.gov (United States)

    Wellner, Karen L.

    Biology textbooks are everybody's business. In accepting the view that texts are created with specific social goals in mind, I examined 127 twentieth-century high school biology textbooks for representations of animal development. Paragraphs and visual representations were coded and placed in one of four scientific literacy categories: descriptive, investigative, nature of science, and human embryos, technology, and society (HETS). I then interpreted how embryos and fetuses have been socially constructed for students. I also examined the use of Haeckel's embryo drawings to support recapitulation and evolutionary theory. Textbooks revealed that publication of Haeckel's drawings was influenced by evolutionists and anti-evolutionists in the 1930s, 1960s, and the 1990s. Haeckel's embryos continue to persist in textbooks because they "safely" illustrate similarities between embryos and are rarely discussed in enough detail to understand comparative embryology's role in the support of evolution. Certain events coincided with changes in how embryos were presented: (a) the growth of the American Medical Association (AMA) and an increase in birth rates (1950s); (b) the Biological Sciences Curriculum Study (BSCS) and public acceptance of birth control methods (1960s); (c) Roe vs. Wade (1973); (d) in vitro fertilization and Lennart Nilsson's photographs (1970s); (e) prenatal technology and fetocentrism (1980s); and (f) genetic engineering and Science-Technology-Society (STS) curriculum (1980s and 1990s). By the end of the twentieth century, changing conceptions, research practices, and technologies all combined to transform the nature of biological development. Human embryos went from a highly descriptive, static, and private object to that of sometimes contentious public figure. I contend that an ignored source for helping move embryos into the public realm is schoolbooks. Throughout the 1900s, authors and publishers accomplished this by placing biology textbook embryos and

  16. Modeling of nonlinear biological phenomena modeled by S-systems.

    Science.gov (United States)

    Mansouri, Majdi M; Nounou, Hazem N; Nounou, Mohamed N; Datta, Aniruddha A

    2014-03-01

    A central challenge in computational modeling of biological systems is the determination of the model parameters. In such cases, estimating these variables or parameters from other easily obtained measurements can be extremely useful. For example, time-series dynamic genomic data can be used to develop models representing dynamic genetic regulatory networks, which can be used to design intervention strategies to cure major diseases and to better understand the behavior of biological systems. Unfortunately, biological measurements are usually highly infected by errors that hide the important characteristics in the data. Therefore, these noisy measurements need to be filtered to enhance their usefulness in practice. This paper addresses the problem of state and parameter estimation of biological phenomena modeled by S-systems using Bayesian approaches, where the nonlinear observed system is assumed to progress according to a probabilistic state space model. The performances of various conventional and state-of-the-art state estimation techniques are compared. These techniques include the extended Kalman filter (EKF), unscented Kalman filter (UKF), particle filter (PF), and the developed variational Bayesian filter (VBF). Specifically, two comparative studies are performed. In the first comparative study, the state variables (the enzyme CadA, the model cadBA, the cadaverine Cadav and the lysine Lys for a model of the Cad System in Escherichia coli (CSEC)) are estimated from noisy measurements of these variables, and the various estimation techniques are compared by computing the estimation root mean square error (RMSE) with respect to the noise-free data. In the second comparative study, the state variables as well as the model parameters are simultaneously estimated. In this case, in addition to comparing the performances of the various state estimation techniques, the effect of the number of estimated model parameters on the accuracy and convergence of these

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

    Science.gov (United States)

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

    2018-01-02

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

  18. The role of mechanics in biological and bio-inspired systems.

    Science.gov (United States)

    Egan, Paul; Sinko, Robert; LeDuc, Philip R; Keten, Sinan

    2015-07-06

    Natural systems frequently exploit intricate multiscale and multiphasic structures to achieve functionalities beyond those of man-made systems. Although understanding the chemical make-up of these systems is essential, the passive and active mechanics within biological systems are crucial when considering the many natural systems that achieve advanced properties, such as high strength-to-weight ratios and stimuli-responsive adaptability. Discovering how and why biological systems attain these desirable mechanical functionalities often reveals principles that inform new synthetic designs based on biological systems. Such approaches have traditionally found success in medical applications, and are now informing breakthroughs in diverse frontiers of science and engineering.

  19. 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

  20. Holarchical Systems and Emotional Holons : Biologically-Inspired System Designs for Control of Autonomous Aerial Vehicles

    Science.gov (United States)

    Ippolito, Corey; Plice, Laura; Pisanich, Greg

    2003-01-01

    The BEES (Bio-inspired Engineering for Exploration Systems) for Mars project at NASA Ames Research Center has the goal of developing bio-inspired flight control strategies to enable aerial explorers for Mars scientific investigations. This paper presents a summary of our ongoing research into biologically inspired system designs for control of unmanned autonomous aerial vehicle communities for Mars exploration. First, we present cooperative design considerations for robotic explorers based on the holarchical nature of biological systems and communities. Second, an outline of an architecture for cognitive decision making and control of individual robotic explorers is presented, modeled after the emotional nervous system of cognitive biological systems. Keywords: Holarchy, Biologically Inspired, Emotional UAV Flight Control

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

    Science.gov (United States)

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

    2017-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Sorokin Anatoly

    2015-06-01

    Full Text Available 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.

  3. Biological information systems: Evolution as cognition-based information management.

    Science.gov (United States)

    Miller, William B

    2018-05-01

    An alternative biological synthesis is presented that conceptualizes evolutionary biology as an epiphenomenon of integrated self-referential information management. Since all biological information has inherent ambiguity, the systematic assessment of information is required by living organisms to maintain self-identity and homeostatic equipoise in confrontation with environmental challenges. Through their self-referential attachment to information space, cells are the cornerstone of biological action. That individualized assessment of information space permits self-referential, self-organizing niche construction. That deployment of information and its subsequent selection enacted the dominant stable unicellular informational architectures whose biological expressions are the prokaryotic, archaeal, and eukaryotic unicellular forms. Multicellularity represents the collective appraisal of equivocal environmental information through a shared information space. This concerted action can be viewed as systematized information management to improve information quality for the maintenance of preferred homeostatic boundaries among the varied participants. When reiterated in successive scales, this same collaborative exchange of information yields macroscopic organisms as obligatory multicellular holobionts. Cognition-Based Evolution (CBE) upholds that assessment of information precedes biological action, and the deployment of information through integrative self-referential niche construction and natural cellular engineering antecedes selection. Therefore, evolutionary biology can be framed as a complex reciprocating interactome that consists of the assessment, communication, deployment and management of information by self-referential organisms at multiple scales in continuous confrontation with environmental stresses. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    DEFF Research Database (Denmark)

    Nielsen, Jens; Jewett, Michael Christopher

    2008-01-01

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

  5. EURASIP journal on bioinformatics & systems biology

    National Research Council Canada - National Science Library

    2006-01-01

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

  6. Agent-Based Modeling in Molecular Systems Biology.

    Science.gov (United States)

    Soheilypour, Mohammad; Mofrad, Mohammad R K

    2018-06-08

    Molecular systems orchestrating the biology of the cell typically involve a complex web of interactions among various components and span a vast range of spatial and temporal scales. Computational methods have advanced our understanding of the behavior of molecular systems by enabling us to test assumptions and hypotheses, explore the effect of different parameters on the outcome, and eventually guide experiments. While several different mathematical and computational methods are developed to study molecular systems at different spatiotemporal scales, there is still a need for methods that bridge the gap between spatially-detailed and computationally-efficient approaches. In this review, we summarize the capabilities of agent-based modeling (ABM) as an emerging molecular systems biology technique that provides researchers with a new tool in exploring the dynamics of molecular systems/pathways in health and disease. © 2018 WILEY Periodicals, Inc.

  7. Marine biological data and information management system

    Digital Repository Service at National Institute of Oceanography (India)

    Sarupria, J.S.

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

  8. Predictive modelling of complex agronomic and biological systems.

    Science.gov (United States)

    Keurentjes, Joost J B; Molenaar, Jaap; Zwaan, Bas J

    2013-09-01

    Biological systems are tremendously complex in their functioning and regulation. Studying the multifaceted behaviour and describing the performance of such complexity has challenged the scientific community for years. The reduction of real-world intricacy into simple descriptive models has therefore convinced many researchers of the usefulness of introducing mathematics into biological sciences. Predictive modelling takes such an approach another step further in that it takes advantage of existing knowledge to project the performance of a system in alternating scenarios. The ever growing amounts of available data generated by assessing biological systems at increasingly higher detail provide unique opportunities for future modelling and experiment design. Here we aim to provide an overview of the progress made in modelling over time and the currently prevalent approaches for iterative modelling cycles in modern biology. We will further argue for the importance of versatility in modelling approaches, including parameter estimation, model reduction and network reconstruction. Finally, we will discuss the difficulties in overcoming the mathematical interpretation of in vivo complexity and address some of the future challenges lying ahead. © 2013 John Wiley & Sons Ltd.

  9. The Systems Biology Markup Language (SBML: Language Specification for Level 3 Version 2 Core

    Directory of Open Access Journals (Sweden)

    Hucka Michael

    2018-03-01

    Full Text Available Computational models can help researchers to interpret data, understand biological functions, and make quantitative predictions. The Systems Biology Markup Language (SBML is a file format for representing computational models in a declarative form that different software systems can exchange. SBML is oriented towards describing biological processes of the sort common in research on a number of topics, including metabolic pathways, cell signaling pathways, and many others. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. This document provides the specification for Version 2 of SBML Level 3 Core. The specification defines the data structures prescribed by SBML, their encoding in XML (the eXtensible Markup Language, validation rules that determine the validity of an SBML document, and examples of models in SBML form. The design of Version 2 differs from Version 1 principally in allowing new MathML constructs, making more child elements optional, and adding identifiers to all SBML elements instead of only selected elements. Other materials and software are available from the SBML project website at http://sbml.org/.

  10. The Systems Biology Markup Language (SBML: Language Specification for Level 3 Version 1 Core

    Directory of Open Access Journals (Sweden)

    Hucka Michael

    2018-04-01

    Full Text Available Computational models can help researchers to interpret data, understand biological functions, and make quantitative predictions. The Systems Biology Markup Language (SBML is a file format for representing computational models in a declarative form that different software systems can exchange. SBML is oriented towards describing biological processes of the sort common in research on a number of topics, including metabolic pathways, cell signaling pathways, and many others. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. This document provides the specification for Release 2 of Version 1 of SBML Level 3 Core. The specification defines the data structures prescribed by SBML, their encoding in XML (the eXtensible Markup Language, validation rules that determine the validity of an SBML document, and examples of models in SBML form. No design changes have been made to the description of models between Release 1 and Release 2; changes are restricted to the format of annotations, the correction of errata and the addition of clarifications. Other materials and software are available from the SBML project website at http://sbml.org/.

  11. 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)

  12. Systems Biology of the Fluxome

    Directory of Open Access Journals (Sweden)

    Miguel A. Aon

    2015-07-01

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

  13. Carbon nanomaterials in biological systems

    International Nuclear Information System (INIS)

    Pu Chun Ke; Qiao Rui

    2007-01-01

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

  14. Quantitative computational models of molecular self-assembly in systems biology.

    Science.gov (United States)

    Thomas, Marcus; Schwartz, Russell

    2017-05-23

    Molecular self-assembly is the dominant form of chemical reaction in living systems, yet efforts at systems biology modeling are only beginning to appreciate the need for and challenges to accurate quantitative modeling of self-assembly. Self-assembly reactions are essential to nearly every important process in cell and molecular biology and handling them is thus a necessary step in building comprehensive models of complex cellular systems. They present exceptional challenges, however, to standard methods for simulating complex systems. While the general systems biology world is just beginning to deal with these challenges, there is an extensive literature dealing with them for more specialized self-assembly modeling. This review will examine the challenges of self-assembly modeling, nascent efforts to deal with these challenges in the systems modeling community, and some of the solutions offered in prior work on self-assembly specifically. The review concludes with some consideration of the likely role of self-assembly in the future of complex biological system models more generally.

  15. Programming with models: modularity and abstraction provide powerful capabilities for systems biology.

    Science.gov (United States)

    Mallavarapu, Aneil; Thomson, Matthew; Ullian, Benjamin; Gunawardena, Jeremy

    2009-03-06

    Mathematical models are increasingly used to understand how phenotypes emerge from systems of molecular interactions. However, their current construction as monolithic sets of equations presents a fundamental barrier to progress. Overcoming this requires modularity, enabling sub-systems to be specified independently and combined incrementally, and abstraction, enabling generic properties of biological processes to be specified independently of specific instances. These, in turn, require models to be represented as programs rather than as datatypes. Programmable modularity and abstraction enables libraries of modules to be created, which can be instantiated and reused repeatedly in different contexts with different components. We have developed a computational infrastructure that accomplishes this. We show here why such capabilities are needed, what is required to implement them and what can be accomplished with them that could not be done previously.

  16. Vibrational resonances in biological systems at microwave frequencies.

    Science.gov (United States)

    Adair, Robert K

    2002-03-01

    Many biological systems can be expected to exhibit resonance behavior involving the mechanical vibration of system elements. The natural frequencies of such resonances will, generally, be in the microwave frequency range. Some of these systems will be coupled to the electromagnetic field by the charge distributions they carry, thus admitting the possibility that microwave exposures may generate physiological effects in man and other species. However, such microwave excitable resonances are expected to be strongly damped by interaction with their aqueous biological environment. Although those dissipation mechanisms have been studied, the limitations on energy transfers that follow from the limited coupling of these resonances to the electromagnetic field have not generally been considered. We show that this coupling must generally be very small and thus the absorbed energy is so strongly limited that such resonances cannot affect biology significantly even if the systems are much less strongly damped than expected from basic dissipation models.

  17. Building gene co-expression networks using transcriptomics data for systems biology investigations

    DEFF Research Database (Denmark)

    Kadarmideen, Haja; Watson-Haigh, Nathan S.

    2012-01-01

    Gene co-expression networks (GCN), built using high-throughput gene expression data are fundamental aspects of systems biology. The main aims of this study were to compare two popular approaches to building and analysing GCN. We use real ovine microarray transcriptomics datasets representing four......) is connected within a network. The two GCN construction methods used were, Weighted Gene Co-expression Network Analysis (WGCNA) and Partial Correlation and Information Theory (PCIT) methods. Nodes were ranked based on their connectivity measures in each of the four different networks created by WGCNA and PCIT...... (with > 20000 genes) access to large computer clusters, particularly those with larger amounts of shared memory is recommended....

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

    Science.gov (United States)

    Guzzi, Rodolfo; Colombo, Teresa; Paci, Paola

    2018-01-01

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

  19. 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.

  20. Systems-biology dissection of eukaryotic cell growth

    Directory of Open Access Journals (Sweden)

    Andrews Justen

    2010-05-01

    Full Text Available Abstract A recent article in BMC Biology illustrates the use of a systems-biology approach to integrate data across the transcriptome, proteome and metabolome of budding yeast in order to dissect the relationship between nutrient conditions and cell growth. See research article http://jbiol.com/content/6/2/4 and http://www.biomedcentral.com/1741-7007/8/68

  1. It’s the System, Stupid: How Systems Biology Is Transforming

    Science.gov (United States)

    2010-01-01

    So far, little is known about systems biology and its potential for changing how we diagnose and treat disease. That will change soon, say the systems experts, who advise payers to begin learning now about how it could make healthcare efficient. PMID:22478806

  2. A dedicated database system for handling multi-level data in systems biology

    OpenAIRE

    Pornputtapong, Natapol; Wanichthanarak, Kwanjeera; Nilsson, Avlant; Nookaew, Intawat; Nielsen, Jens

    2014-01-01

    Background Advances in high-throughput technologies have enabled extensive generation of multi-level omics data. These data are crucial for systems biology research, though they are complex, heterogeneous, highly dynamic, incomplete and distributed among public databases. This leads to difficulties in data accessibility and often results in errors when data are merged and integrated from varied resources. Therefore, integration and management of systems biological data remain very challenging...

  3. Partial differential equations for self-organization in cellular and developmental biology

    International Nuclear Information System (INIS)

    Baker, R E; Gaffney, E A; Maini, P K

    2008-01-01

    Understanding the mechanisms governing and regulating the emergence of structure and heterogeneity within cellular systems, such as the developing embryo, represents a multiscale challenge typifying current integrative biology research, namely, explaining the macroscale behaviour of a system from microscale dynamics. This review will focus upon modelling how cell-based dynamics orchestrate the emergence of higher level structure. After surveying representative biological examples and the models used to describe them, we will assess how developments at the scale of molecular biology have impacted on current theoretical frameworks, and the new modelling opportunities that are emerging as a result. We shall restrict our survey of mathematical approaches to partial differential equations and the tools required for their analysis. We will discuss the gap between the modelling abstraction and biological reality, the challenges this presents and highlight some open problems in the field. (invited article)

  4. Systems Biology of Saccharomyces cerevisiae Physiology and its DNA Damage Response

    DEFF Research Database (Denmark)

    Fazio, Alessandro

    The yeast Saccharomyces cerevisiae is a model organism in biology, being widely used in fundamental research, the first eukaryotic organism to be fully sequenced and the platform for the development of many genomics techniques. Therefore, it is not surprising that S. cerevisiae has also been widely...... used in the field of systems biology during the last decade. This thesis investigates S. cerevisiae growth physiology and DNA damage response by using a systems biology approach. Elucidation of the relationship between growth rate and gene expression is important to understand the mechanisms regulating...... set of growth dependent genes by using a multi-factorial experimental design. Moreover, new insights into the metabolic response and transcriptional regulation of these genes have been provided by using systems biology tools (Chapter 3). One of the prerequisite of systems biology should...

  5. PathSys: integrating molecular interaction graphs for systems biology

    Directory of Open Access Journals (Sweden)

    Raval Alpan

    2006-02-01

    Full Text Available Abstract Background The goal of information integration in systems biology is to combine information from a number of databases and data sets, which are obtained from both high and low throughput experiments, under one data management scheme such that the cumulative information provides greater biological insight than is possible with individual information sources considered separately. Results Here we present PathSys, a graph-based system for creating a combined database of networks of interaction for generating integrated view of biological mechanisms. We used PathSys to integrate over 14 curated and publicly contributed data sources for the budding yeast (S. cerevisiae and Gene Ontology. A number of exploratory questions were formulated as a combination of relational and graph-based queries to the integrated database. Thus, PathSys is a general-purpose, scalable, graph-data warehouse of biological information, complete with a graph manipulation and a query language, a storage mechanism and a generic data-importing mechanism through schema-mapping. Conclusion Results from several test studies demonstrate the effectiveness of the approach in retrieving biologically interesting relations between genes and proteins, the networks connecting them, and of the utility of PathSys as a scalable graph-based warehouse for interaction-network integration and a hypothesis generator system. The PathSys's client software, named BiologicalNetworks, developed for navigation and analyses of molecular networks, is available as a Java Web Start application at http://brak.sdsc.edu/pub/BiologicalNetworks.

  6. Echinococcus as a model system: biology and epidemiology.

    Science.gov (United States)

    Thompson, R C A; Jenkins, D J

    2014-10-15

    The introduction of Echinococcus to Australia over 200 years ago and its establishment in sheep rearing areas of the country inflicted a serious medical and economic burden on the country. This resulted in an investment in both basic and applied research aimed at learning more about the biology and life cycle of Echinococcus. This research served to illustrate the uniqueness of the parasite in terms of developmental biology and ecology, and the value of Echinococcus as a model system in a broad range of research, from fundamental biology to theoretical control systems. These studies formed the foundation for an international, diverse and ongoing research effort on the hydatid organisms encompassing stem cell biology, gene regulation, strain variation, wildlife diseases and models of transmission dynamics. We describe the development, nature and diversity of this research, and how it was initiated in Australia but subsequently has stimulated much international and collaborative research on Echinococcus. Copyright © 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

  7. Thermostability of biological systems: fundamentals, challenges, and quantification.

    Science.gov (United States)

    He, Xiaoming

    2011-01-01

    This review examines the fundamentals and challenges in engineering/understanding the thermostability of biological systems over a wide temperature range (from the cryogenic to hyperthermic regimen). Applications of the bio-thermostability engineering to either destroy unwanted or stabilize useful biologicals for the treatment of diseases in modern medicine are first introduced. Studies on the biological responses to cryogenic and hyperthermic temperatures for the various applications are reviewed to understand the mechanism of thermal (both cryo and hyperthermic) injury and its quantification at the molecular, cellular and tissue/organ levels. Methods for quantifying the thermophysical processes of the various applications are then summarized accounting for the effect of blood perfusion, metabolism, water transport across cell plasma membrane, and phase transition (both equilibrium and non-equilibrium such as ice formation and glass transition) of water. The review concludes with a summary of the status quo and future perspectives in engineering the thermostability of biological systems.

  8. Biological Macro and Micro Systems Co-existing in the “Fountain of the Two Dragons”, Palermo

    Directory of Open Access Journals (Sweden)

    Enza Di Carlo

    2017-06-01

    Full Text Available Stone works of art located outdoors are exposed to natural deterioration, due to several physical, chemical and biological factors. Biological macro- and micro-systems (e.g. weeds, insects, algae, mosses, fungi and bacteria may induce the biodeterioration of stone materials. In February 2014, the state of conservation of the Fountain of the two Dragons in Palermo was examined, during which time biological colonization in some areas of the fountain and statues, was also detected. The monument represents an excellent substrate for the development and growth of microrganisms and organisms that need a continuous supply of water. Direct solar irradiance promotes the development of photoautotrophic organisms, bryophyte flora, in addition to several microbial genera, responsible for pigmentation, discoloring, efflorescence. After autotrophic colonization, some organisms find an ideal habitat also during wintertime, including two species of gastropods and two species of Hemiptera, omnivorous, a species of Collembola, mostly fungivorous. This interdisciplinary study has enabled the detection and identification of different biological communities, providing information for a subsequent project of preventive conservation of the fountain and its surroundings.

  9. 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...

  10. Systems Biology-Based Platforms to Accelerate Research of Emerging Infectious Diseases.

    Science.gov (United States)

    Oh, Soo Jin; Choi, Young Ki; Shin, Ok Sarah

    2018-03-01

    Emerging infectious diseases (EIDs) pose a major threat to public health and security. Given the dynamic nature and significant impact of EIDs, the most effective way to prevent and protect against them is to develop vaccines in advance. Systems biology approaches provide an integrative way to understand the complex immune response to pathogens. They can lead to a greater understanding of EID pathogenesis and facilitate the evaluation of newly developed vaccine-induced immunity in a timely manner. In recent years, advances in high throughput technologies have enabled researchers to successfully apply systems biology methods to analyze immune responses to a variety of pathogens and vaccines. Despite recent advances, computational and biological challenges impede wider application of systems biology approaches. This review highlights recent advances in the fields of systems immunology and vaccinology, and presents ways that systems biology-based platforms can be applied to accelerate a deeper understanding of the molecular mechanisms of immunity against EIDs. © Copyright: Yonsei University College of Medicine 2018.

  11. 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.

  12. Anion binding in biological systems

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  13. 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.

  14. Continuous time Boolean modeling for biological signaling: application of Gillespie algorithm.

    OpenAIRE

    Stoll, Gautier; Viara, Eric; Barillot, Emmanuel; Calzone, Laurence

    2012-01-01

    Abstract Mathematical modeling is used as a Systems Biology tool to answer biological questions, and more precisely, to validate a network that describes biological observations and predict the effect of perturbations. This article presents an algorithm for modeling biological networks in a discrete framework with continuous time. Background There exist two major types of mathematical modeling approaches: (1) quantitative modeling, representing various chemical species concentrations by real...

  15. Systems Biology Graphical Notation: Activity Flow language Level 1 Version 1.2

    Directory of Open Access Journals (Sweden)

    Mi Huaiyu

    2015-06-01

    Full Text Available 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.

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

    Science.gov (United States)

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

    2017-12-05

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

  17. High energy fast neutrons from the Harwell variable energy cyclotron. II. Biologic studies in mammalian systems

    International Nuclear Information System (INIS)

    Berry, R.J.; Bance, D.A.; Barnes, D.W.H.; Cox, R.; Goodhead, D.T.; Sansom, J.M.; Thacker, J.

    1977-01-01

    A high energy fast neutron beam potentially suitable for radiotherapy has been described in a companion paper. Its biologic effects have been studied in the following experimental systems: clonal survival and mutation induction after irradiation in vitro in Chinese hamster cells and human diploid fibroblasts; survival of reproductive capacity in vivo of murine hemopoietic colony-forming cells and murine intestinal crypts after irradiation in vivo; survival of reproductive capacity in vivo after irradiation in vitro or in vivo of murine lymphocytic leukemia cells; acute intestinal death following total body irradiation of mice and guinea pigs; and hemopoietic death following total body irradiation of mice and guinea pigs. The relative biologic effectiveness of these high energy neutrons varied among the different biologic systems, and in several cases varied with the size of the radiation dose. The oxygen enhancement ratio was studied in murine lymphocytic leukemia cells irradiated under aerobic or hypoxic conditions in vitro and assayed for survival of reproductive capacity in vivo. Compared with x-rays, the potential therapeutic gain factor for these neutrons was about 1.5. This work represents a ''radiobiologic calibration'' program which it is suggested should be undertaken before new and unknown fast neutron spectra are used for experimental radiotherapy. The results are compared with biologic studies carried out at high energy fast neutron generators in the United States

  18. Applications of dynamical systems in biology and medicine

    CERN Document Server

    Radunskaya, Ami

    2015-01-01

    This volume highlights problems from a range of biological and medical applications that can be interpreted as questions about system behavior or control.  Topics include drug resistance in cancer and malaria, biological fluid dynamics, auto-regulation in the kidney, anti-coagulation therapy, evolutionary diversification and photo-transduction.  Mathematical techniques used to describe and investigate these biological and medical problems include ordinary, partial and stochastic differentiation equations, hybrid discrete-continuous approaches, as well as 2 and 3D numerical simulation. .

  19. Radiological/biological/aerosol removal system

    Science.gov (United States)

    Haslam, Jeffery J

    2015-03-17

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

  20. Advantages and Pitfalls of Mass Spectrometry Based Metabolome Profiling in Systems Biology

    Directory of Open Access Journals (Sweden)

    Ina Aretz

    2016-04-01

    Full Text Available Mass spectrometry-based metabolome profiling became the method of choice in systems biology approaches and aims to enhance biological understanding of complex biological systems. Genomics, transcriptomics, and proteomics are well established technologies and are commonly used by many scientists. In comparison, metabolomics is an emerging field and has not reached such high-throughput, routine and coverage than other omics technologies. Nevertheless, substantial improvements were achieved during the last years. Integrated data derived from multi-omics approaches will provide a deeper understanding of entire biological systems. Metabolome profiling is mainly hampered by its diversity, variation of metabolite concentration by several orders of magnitude and biological data interpretation. Thus, multiple approaches are required to cover most of the metabolites. No software tool is capable of comprehensively translating all the data into a biologically meaningful context yet. In this review, we discuss the advantages of metabolome profiling and main obstacles limiting progress in systems biology.

  1. Advantages and Pitfalls of Mass Spectrometry Based Metabolome Profiling in Systems Biology.

    Science.gov (United States)

    Aretz, Ina; Meierhofer, David

    2016-04-27

    Mass spectrometry-based metabolome profiling became the method of choice in systems biology approaches and aims to enhance biological understanding of complex biological systems. Genomics, transcriptomics, and proteomics are well established technologies and are commonly used by many scientists. In comparison, metabolomics is an emerging field and has not reached such high-throughput, routine and coverage than other omics technologies. Nevertheless, substantial improvements were achieved during the last years. Integrated data derived from multi-omics approaches will provide a deeper understanding of entire biological systems. Metabolome profiling is mainly hampered by its diversity, variation of metabolite concentration by several orders of magnitude and biological data interpretation. Thus, multiple approaches are required to cover most of the metabolites. No software tool is capable of comprehensively translating all the data into a biologically meaningful context yet. In this review, we discuss the advantages of metabolome profiling and main obstacles limiting progress in systems biology.

  2. Specifications of Standards in Systems and Synthetic Biology.

    Science.gov (United States)

    Schreiber, Falk; Bader, Gary D; Golebiewski, Martin; Hucka, Michael; Kormeier, Benjamin; Le Novère, Nicolas; Myers, Chris; Nickerson, David; Sommer, Björn; Waltemath, Dagmar; Weise, Stephan

    2015-09-04

    Standards shape our everyday life. From nuts and bolts to electronic devices and technological processes, standardised products and processes are all around us. Standards have technological and economic benefits, such as making information exchange, production, and services more efficient. However, novel, innovative areas often either lack proper standards, or documents about standards in these areas are not available from a centralised platform or formal body (such as the International Standardisation Organisation). Systems and synthetic biology is a relatively novel area, and it is only in the last decade that the standardisation of data, information, and models related to systems and synthetic biology has become a community-wide effort. Several open standards have been established and are under continuous development as a community initiative. COMBINE, the ‘COmputational Modeling in BIology’ NEtwork has been established as an umbrella initiative to coordinate and promote the development of the various community standards and formats for computational models. There are yearly two meeting, HARMONY (Hackathons on Resources for Modeling in Biology), Hackathon-type meetings with a focus on development of the support for standards, and COMBINE forums, workshop-style events with oral presentations, discussion, poster, and breakout sessions for further developing the standards. For more information see http://co.mbine.org/. So far the different standards were published and made accessible through the standards’ web- pages or preprint services. The aim of this special issue is to provide a single, easily accessible and citable platform for the publication of standards in systems and synthetic biology. This special issue is intended to serve as a central access point to standards and related initiatives in systems and synthetic biology, it will be published annually to provide an opportunity for standard development groups to communicate updated specifications.

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

    Science.gov (United States)

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

    2018-03-01

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

  4. Quantitative, high-resolution proteomics for data-driven systems biology

    DEFF Research Database (Denmark)

    Cox, J.; Mann, M.

    2011-01-01

    Systems biology requires comprehensive data at all molecular levels. Mass spectrometry (MS)-based proteomics has emerged as a powerful and universal method for the global measurement of proteins. In the most widespread format, it uses liquid chromatography (LC) coupled to high-resolution tandem...... primary structure of proteins including posttranslational modifications, to localize proteins to organelles, and to determine protein interactions. Here, we describe the principles of analysis and the areas of biology where proteomics can make unique contributions. The large-scale nature of proteomics...... data and its high accuracy pose special opportunities as well as challenges in systems biology that have been largely untapped so far....

  5. Power Laws, Scale-Free Networks and Genome Biology

    CERN Document Server

    Koonin, Eugene V; Karev, Georgy P

    2006-01-01

    Power Laws, Scale-free Networks and Genome Biology deals with crucial aspects of the theoretical foundations of systems biology, namely power law distributions and scale-free networks which have emerged as the hallmarks of biological organization in the post-genomic era. The chapters in the book not only describe the interesting mathematical properties of biological networks but moves beyond phenomenology, toward models of evolution capable of explaining the emergence of these features. The collection of chapters, contributed by both physicists and biologists, strives to address the problems in this field in a rigorous but not excessively mathematical manner and to represent different viewpoints, which is crucial in this emerging discipline. Each chapter includes, in addition to technical descriptions of properties of biological networks and evolutionary models, a more general and accessible introduction to the respective problems. Most chapters emphasize the potential of theoretical systems biology for disco...

  6. Tritium fractionation in biological systems and in analytical procedures

    International Nuclear Information System (INIS)

    Kim, M.A.; Baumgaertner, F.

    1991-01-01

    The organically bound tritium (OBT) is evaluated in biological systems by measuring the tritium distribution ratio (R-value), i.e. tritium concentrations in organic substance to tissue water. The determination of the R-value is found to involve always isotope fractionation in applied analytical procedures and hence the evaluation of the true OBT-value in a given biological system appears more complicated than hitherto known in the literature. The present work concentrates on the tritium isotope fraction in the tissue water separation and on the resulting effects on the R-value. The analytical procedures examined are vacuum freeze drying under equilibrium and non-equilibrium conditions and azeotropic distillation. The vaporization isotope effects are determined separately in the phase transition of solid or liquid to gas in pure water systems as well as in real biological systems, e.g. maize plant. The results are systematically analysed and the influence of isotope effects on the R-value is rigorously quantified. (orig.)

  7. Systematic integration of experimental data and models in systems biology.

    Science.gov (United States)

    Li, Peter; Dada, Joseph O; Jameson, Daniel; Spasic, Irena; Swainston, Neil; Carroll, Kathleen; Dunn, Warwick; Khan, Farid; Malys, Naglis; Messiha, Hanan L; Simeonidis, Evangelos; Weichart, Dieter; Winder, Catherine; Wishart, Jill; Broomhead, David S; Goble, Carole A; Gaskell, Simon J; Kell, Douglas B; Westerhoff, Hans V; Mendes, Pedro; Paton, Norman W

    2010-11-29

    The behaviour of biological systems can be deduced from their mathematical models. However, multiple sources of data in diverse forms are required in the construction of a model in order to define its components and their biochemical reactions, and corresponding parameters. Automating the assembly and use of systems biology models is dependent upon data integration processes involving the interoperation of data and analytical resources. Taverna workflows have been developed for the automated assembly of quantitative parameterised metabolic networks in the Systems Biology Markup Language (SBML). A SBML model is built in a systematic fashion by the workflows which starts with the construction of a qualitative network using data from a MIRIAM-compliant genome-scale model of yeast metabolism. This is followed by parameterisation of the SBML model with experimental data from two repositories, the SABIO-RK enzyme kinetics database and a database of quantitative experimental results. The models are then calibrated and simulated in workflows that call out to COPASIWS, the web service interface to the COPASI software application for analysing biochemical networks. These systems biology workflows were evaluated for their ability to construct a parameterised model of yeast glycolysis. Distributed information about metabolic reactions that have been described to MIRIAM standards enables the automated assembly of quantitative systems biology models of metabolic networks based on user-defined criteria. Such data integration processes can be implemented as Taverna workflows to provide a rapid overview of the components and their relationships within a biochemical system.

  8. Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering

    NARCIS (Netherlands)

    He, F.; Murabito, E.; Westerhoff, H.V.

    2016-01-01

    Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out throughin silicotheoretical studies with the aim to guide and complement furtherin vitroandin vivoexperimental

  9. A day of systems and synthetic biology for non-experts: reflections on day 1 of the EMBL/EMBO joint conference on Science and Society.

    Science.gov (United States)

    Moore, Andrew

    2009-01-01

    From understanding ageing to the creation of artificial membrane-bounded 'organisms', systems biology and synthetic biology are seen as the latest revolutions in the life sciences. They certainly represent a major change of gear, but paradigm shifts? This is open to debate, to say the least. For scientists they open up exciting ways of studying living systems, of formulating the 'laws of life', and the relationship between the origin of life, evolution and artificial biological systems. However, the ethical and societal considerations are probably indistinguishable from those of human genetics and genetically modified organisms. There are some tangible developments just around the corner for society, and as ever, our ability to understand the consequences of, and manage, our own progress lags far behind our technological abilities. Furthermore our educational systems are doing a bad job of preparing the next generation of scientists and non-scientists.

  10. EPR spectroscopy of complex biological iron-sulfur systems.

    Science.gov (United States)

    Hagen, Wilfred R

    2018-02-21

    From the very first discovery of biological iron-sulfur clusters with EPR, the spectroscopy has been used to study not only purified proteins but also complex systems such as respiratory complexes, membrane particles and, later, whole cells. In recent times, the emphasis of iron-sulfur biochemistry has moved from characterization of individual proteins to the systems biology of iron-sulfur biosynthesis, regulation, degradation, and implications for human health. Although this move would suggest a blossoming of System-EPR as a specific, non-invasive monitor of Fe/S (dys)homeostasis in whole cells, a review of the literature reveals limited success possibly due to technical difficulties in adherence to EPR spectroscopic and biochemical standards. In an attempt to boost application of System-EPR the required boundary conditions and their practical applications are explicitly and comprehensively formulated.

  11. Guidelines for Developing Successful Short Advanced Courses in Systems Medicine and Systems Biology

    KAUST Repository

    Gomez-Cabrero, David

    2017-08-23

    Summary Systems medicine and systems biology have inherent educational challenges. These have largely been addressed either by providing new masters programs or by redesigning undergraduate programs. In contrast, short courses can respond to a different need: they can provide condensed updates for professionals across academia, the clinic, and industry. These courses have received less attention. Here, we share our experiences in developing and providing such courses to current and future leaders in systems biology and systems medicine. We present guidelines for how to reproduce our courses, and we offer suggestions for how to select students who will nurture an interdisciplinary learning environment and thrive there.

  12. Guidelines for Developing Successful Short Advanced Courses in Systems Medicine and Systems Biology

    KAUST Repository

    Gomez-Cabrero, David; Marabita, Francesco; Tarazona, Sonia; Cano, Isaac; Roca, Josep; Conesa, Ana; Sabatier, Philippe; Tegner, Jesper

    2017-01-01

    Summary Systems medicine and systems biology have inherent educational challenges. These have largely been addressed either by providing new masters programs or by redesigning undergraduate programs. In contrast, short courses can respond to a different need: they can provide condensed updates for professionals across academia, the clinic, and industry. These courses have received less attention. Here, we share our experiences in developing and providing such courses to current and future leaders in systems biology and systems medicine. We present guidelines for how to reproduce our courses, and we offer suggestions for how to select students who will nurture an interdisciplinary learning environment and thrive there.

  13. Strategies for structuring interdisciplinary education in Systems Biology: an European perspective

    NARCIS (Netherlands)

    Cvijovic, Marija; Höfer, Thomas; Acimovic, Jure; Alberghina, Lilia; Almaas, Eivind; Besozzi, Daniela; Blomberg, Anders; Bretschneider, Till; Cascante, Marta; Collin, Olivier; Atauri, de Pedro; Depner, Cornelia; Dickinson, Robert; Dobrzynski, Maciej; Fleck, C.; Garcia-Ojalvo, Jordi; Gonze, Didier; Hahn, Jens; Hess, Heide Marie; Hollmann, Susanne; Krantz, Marcus; Kummer, Ursula; Lundh, Torbjörn; Martial, Gifta; Martins dos Santos, V.A.P.; Mauer-Oberthür, Angela; Regierer, Babette; Skene, Barbara; Stalidzans, Egils; Stelling, Jörg; Teusink, Bas; Workman, Christopher T.; Hohmann, Stefan

    2016-01-01

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

  14. 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....

  15. Systems biology and biomarker discovery

    Energy Technology Data Exchange (ETDEWEB)

    Rodland, Karin D.

    2010-12-01

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

  16. 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.

  17. Function of dynamic models in systems biology: linking structure to behaviour.

    Science.gov (United States)

    Knüpfer, Christian; Beckstein, Clemens

    2013-10-08

    Dynamic models in Systems Biology are used in computational simulation experiments for addressing biological questions. The complexity of the modelled biological systems and the growing number and size of the models calls for computer support for modelling and simulation in Systems Biology. This computer support has to be based on formal representations of relevant knowledge fragments. In this paper we describe different functional aspects of dynamic models. This description is conceptually embedded in our "meaning facets" framework which systematises the interpretation of dynamic models in structural, functional and behavioural facets. Here we focus on how function links the structure and the behaviour of a model. Models play a specific role (teleological function) in the scientific process of finding explanations for dynamic phenomena. In order to fulfil this role a model has to be used in simulation experiments (pragmatical function). A simulation experiment always refers to a specific situation and a state of the model and the modelled system (conditional function). We claim that the function of dynamic models refers to both the simulation experiment executed by software (intrinsic function) and the biological experiment which produces the phenomena under investigation (extrinsic function). We use the presented conceptual framework for the function of dynamic models to review formal accounts for functional aspects of models in Systems Biology, such as checklists, ontologies, and formal languages. Furthermore, we identify missing formal accounts for some of the functional aspects. In order to fill one of these gaps we propose an ontology for the teleological function of models. We have thoroughly analysed the role and use of models in Systems Biology. The resulting conceptual framework for the function of models is an important first step towards a comprehensive formal representation of the functional knowledge involved in the modelling and simulation process

  18. Glycoengineering in CHO cells: Advances in systems biology

    DEFF Research Database (Denmark)

    Tejwani, Vijay; Andersen, Mikael Rørdam; Nam, Jong Hyun

    2018-01-01

    are not well understood. A systems biology approach combining different technologies is needed for complete understanding of the molecular processes accounting for this variability and to open up new venues in cell line development. In this review, we describe several advances in genetic manipulation, modeling......For several decades, glycoprotein biologics have been successfully produced from Chinese hamster ovary (CHO) cells. The therapeutic efficacy and potency of glycoprotein biologics are often dictated by their post translational modifications, particularly glycosylation, which unlike protein synthesis....... Recently, CHO cells have also been explored for production of therapeutic glycosaminoglycans (e.g. heparin), which presents similar challenges as producing glycoproteins biologics. Approaches to controlling heterogeneity in CHO cells and directing the biosynthetic process toward desired glycoforms...

  19. Enterprise Systems Implementations: Organizational Influence Processes for Corporate User Representatives

    DEFF Research Database (Denmark)

    Nielsen, Peter Axel; Nordheim, Stig

    2008-01-01

    -depth, interpretive study from the oil industry, where we analyze a case of innovative integration of an ECM system with collaboration technologies. The data collection has been longitudinal. The data analysis has been performed through the perspective of organizational influence processes. The main finding concerns...... an organizational role as corporate user representative to deal with the scale and complexities of implementation. A single person was particularly influential in the role. At the outset a user representative had to perform upward influence processes from a lower formal position. This is impeding...

  20. The Histochemistry and Cell Biology omnium-gatherum: the year 2015 in review.

    Science.gov (United States)

    Taatjes, Douglas J; Roth, Jürgen

    2016-03-01

    We provide here our annual review/synopsis of all of the articles published in Histochemistry and Cell Biology (HCB) for the preceding year. In 2015, HCB published 102 articles, representing a wide variety of topics and methodologies. For ease of access to these differing topics, we have created categories, as determined by the types of articles presented to provide a quick index representing the general areas covered. This year, these categories include: (1) advances in methodologies; (2) molecules in health and disease; (3) organelles, subcellular structures, and compartments; (4) the nucleus; (5) stem cells and tissue engineering; (6) cell cultures: properties and capabilities; (7) connective tissues and extracellular matrix; (8) developmental biology; (9) nervous system; (10) musculoskeletal system; (11) respiratory and cardiovascular system; (12) liver and gastrointestinal tract; and (13) male and female reproductive systems. Of note, the categories proceed from methods development, to molecules, intracellular compartments, stem cells and cell culture, extracellular matrix, developmental biology, and finishing with various organ systems, hopefully presenting a logical journey from methods to organismal molecules, cells, and whole tissue systems.

  1. Design of fluidized-bed, biological denitrification systems

    International Nuclear Information System (INIS)

    Patton, B.D.; Hancher, C.W.; Pitt, W.W.; Walker, J.F.

    1982-01-01

    Many commercial processes yield nitrate-containing wastewaters that are being discharged to the environment because traditional recovery or disposal methods are economically unacceptable. The anticipated discharge limits (i.e., 10 to 20 g (NO 3 - )/m 3 ) being considered by many states will not allow continued release of these wastewaters. The new discharge standards can be met economically by use of the fluidizied-bed, biological denitrification process. Research and development studies were conducted with 0.05-, 0.10-, 0.20-, and 0.50-m-diam fluidized-bed bioreactor systems. Feed nitrate concentrations were in the 0 to 10,000 g (NO 3 - )/m 3 range. Using the data from these studies, rate expressions were developed for the destruction of nitrate as a function of nitrate concentration. Methods were also developed for sizing bioreactors and biomass control systems. The sizing methods for fluidized-bed denitrification systems are described, and support systems such as sampling and analysis, instrumentation and controls, utilities, and bacteria storage are discussed. Operation of the process is also briefly discussed to aid the designer. Using the methods presented in this report, fluidized-bed, biological denitrification systems can be designed to treat nitrate wastewater streams

  2. Stochastic chemical kinetics theory and (mostly) systems biological applications

    CERN Document Server

    Érdi, Péter; Lente, Gabor

    2014-01-01

    This volume reviews the theory and simulation methods of stochastic kinetics by integrating historical and recent perspectives, presents applications, mostly in the context of systems biology and also in combustion theory. In recent years, due to the development in experimental techniques, such as optical imaging, single cell analysis, and fluorescence spectroscopy, biochemical kinetic data inside single living cells have increasingly been available. The emergence of systems biology brought renaissance in the application of stochastic kinetic methods.

  3. Biological and geophysical feedbacks with fire in the Earth system

    Science.gov (United States)

    Archibald, S.; Lehmann, C. E. R.; Belcher, C. M.; Bond, W. J.; Bradstock, R. A.; Daniau, A.-L.; Dexter, K. G.; Forrestel, E. J.; Greve, M.; He, T.; Higgins, S. I.; Hoffmann, W. A.; Lamont, B. B.; McGlinn, D. J.; Moncrieff, G. R.; Osborne, C. P.; Pausas, J. G.; Price, O.; Ripley, B. S.; Rogers, B. M.; Schwilk, D. W.; Simon, M. F.; Turetsky, M. R.; Van der Werf, G. R.; Zanne, A. E.

    2018-03-01

    Roughly 3% of the Earth’s land surface burns annually, representing a critical exchange of energy and matter between the land and atmosphere via combustion. Fires range from slow smouldering peat fires, to low-intensity surface fires, to intense crown fires, depending on vegetation structure, fuel moisture, prevailing climate, and weather conditions. While the links between biogeochemistry, climate and fire are widely studied within Earth system science, these relationships are also mediated by fuels—namely plants and their litter—that are the product of evolutionary and ecological processes. Fire is a powerful selective force and, over their evolutionary history, plants have evolved traits that both tolerate and promote fire numerous times and across diverse clades. Here we outline a conceptual framework of how plant traits determine the flammability of ecosystems and interact with climate and weather to influence fire regimes. We explore how these evolutionary and ecological processes scale to impact biogeochemical and Earth system processes. Finally, we outline several research challenges that, when resolved, will improve our understanding of the role of plant evolution in mediating the fire feedbacks driving Earth system processes. Understanding current patterns of fire and vegetation, as well as patterns of fire over geological time, requires research that incorporates evolutionary biology, ecology, biogeography, and the biogeosciences.

  4. Learning (from) the errors of a systems biology model.

    Science.gov (United States)

    Engelhardt, Benjamin; Frőhlich, Holger; Kschischo, Maik

    2016-02-11

    Mathematical modelling is a labour intensive process involving several iterations of testing on real data and manual model modifications. In biology, the domain knowledge guiding model development is in many cases itself incomplete and uncertain. A major problem in this context is that biological systems are open. Missed or unknown external influences as well as erroneous interactions in the model could thus lead to severely misleading results. Here we introduce the dynamic elastic-net, a data driven mathematical method which automatically detects such model errors in ordinary differential equation (ODE) models. We demonstrate for real and simulated data, how the dynamic elastic-net approach can be used to automatically (i) reconstruct the error signal, (ii) identify the target variables of model error, and (iii) reconstruct the true system state even for incomplete or preliminary models. Our work provides a systematic computational method facilitating modelling of open biological systems under uncertain knowledge.

  5. Investigating cholesterol metabolism and ageing using a systems biology approach.

    Science.gov (United States)

    Morgan, A E; Mooney, K M; Wilkinson, S J; Pickles, N A; Mc Auley, M T

    2017-08-01

    CVD accounted for 27 % of all deaths in the UK in 2014, and was responsible for 1·7 million hospital admissions in 2013/2014. This condition becomes increasingly prevalent with age, affecting 34·1 and 29·8 % of males and females over 75 years of age respectively in 2011. The dysregulation of cholesterol metabolism with age, often observed as a rise in LDL-cholesterol, has been associated with the pathogenesis of CVD. To compound this problem, it is estimated by 2050, 22 % of the world's population will be over 60 years of age, in culmination with a growing resistance and intolerance to pre-existing cholesterol regulating drugs such as statins. Therefore, it is apparent research into additional therapies for hypercholesterolaemia and CVD prevention is a growing necessity. However, it is also imperative to recognise this complex biological system cannot be studied using a reductionist approach; rather its biological uniqueness necessitates a more integrated methodology, such as that offered by systems biology. In this review, we firstly discuss cholesterol metabolism and how it is affected by diet and the ageing process. Next, we describe therapeutic strategies for hypercholesterolaemia, and finally how the systems biology paradigm can be utilised to investigate how ageing interacts with complex systems such as cholesterol metabolism. We conclude by emphasising the need for nutritionists to work in parallel with the systems biology community, to develop novel approaches to studying cholesterol metabolism and its interaction with ageing.

  6. Causal biological network database: a comprehensive platform of causal biological network models focused on the pulmonary and vascular systems.

    Science.gov (United States)

    Boué, Stéphanie; Talikka, Marja; Westra, Jurjen Willem; Hayes, William; Di Fabio, Anselmo; Park, Jennifer; Schlage, Walter K; Sewer, Alain; Fields, Brett; Ansari, Sam; Martin, Florian; Veljkovic, Emilija; Kenney, Renee; Peitsch, Manuel C; Hoeng, Julia

    2015-01-01

    With the wealth of publications and data available, powerful and transparent computational approaches are required to represent measured data and scientific knowledge in a computable and searchable format. We developed a set of biological network models, scripted in the Biological Expression Language, that reflect causal signaling pathways across a wide range of biological processes, including cell fate, cell stress, cell proliferation, inflammation, tissue repair and angiogenesis in the pulmonary and cardiovascular context. This comprehensive collection of networks is now freely available to the scientific community in a centralized web-based repository, the Causal Biological Network database, which is composed of over 120 manually curated and well annotated biological network models and can be accessed at http://causalbionet.com. The website accesses a MongoDB, which stores all versions of the networks as JSON objects and allows users to search for genes, proteins, biological processes, small molecules and keywords in the network descriptions to retrieve biological networks of interest. The content of the networks can be visualized and browsed. Nodes and edges can be filtered and all supporting evidence for the edges can be browsed and is linked to the original articles in PubMed. Moreover, networks may be downloaded for further visualization and evaluation. Database URL: http://causalbionet.com © The Author(s) 2015. Published by Oxford University Press.

  7. KiMoSys: a web-based repository of experimental data for KInetic MOdels of biological SYStems.

    Science.gov (United States)

    Costa, Rafael S; Veríssimo, André; Vinga, Susana

    2014-08-13

    The kinetic modeling of biological systems is mainly composed of three steps that proceed iteratively: model building, simulation and analysis. In the first step, it is usually required to set initial metabolite concentrations, and to assign kinetic rate laws, along with estimating parameter values using kinetic data through optimization when these are not known. Although the rapid development of high-throughput methods has generated much omics data, experimentalists present only a summary of obtained results for publication, the experimental data files are not usually submitted to any public repository, or simply not available at all. In order to automatize as much as possible the steps of building kinetic models, there is a growing requirement in the systems biology community for easily exchanging data in combination with models, which represents the main motivation of KiMoSys development. KiMoSys is a user-friendly platform that includes a public data repository of published experimental data, containing concentration data of metabolites and enzymes and flux data. It was designed to ensure data management, storage and sharing for a wider systems biology community. This community repository offers a web-based interface and upload facility to turn available data into publicly accessible, centralized and structured-format data files. Moreover, it compiles and integrates available kinetic models associated with the data.KiMoSys also integrates some tools to facilitate the kinetic model construction process of large-scale metabolic networks, especially when the systems biologists perform computational research. KiMoSys is a web-based system that integrates a public data and associated model(s) repository with computational tools, providing the systems biology community with a novel application facilitating data storage and sharing, thus supporting construction of ODE-based kinetic models and collaborative research projects.The web application implemented using Ruby

  8. Systems Biology of Meridians, Acupoints, and Chinese Herbs in Disease

    Directory of Open Access Journals (Sweden)

    Li-Ling Lin

    2012-01-01

    Full Text Available Meridians, acupoints, and Chinese herbs are important components of traditional Chinese medicine (TCM. They have been used for disease treatment and prevention and as alternative and complementary therapies. Systems biology integrates omics data, such as transcriptional, proteomic, and metabolomics data, in order to obtain a more global and complete picture of biological activity. To further understand the existence and functions of the three components above, we reviewed relevant research in the systems biology literature and found many recent studies that indicate the value of acupuncture and Chinese herbs. Acupuncture is useful in pain moderation and relieves various symptoms arising from acute spinal cord injury and acute ischemic stroke. Moreover, Chinese herbal extracts have been linked to wound repair, the alleviation of postmenopausal osteoporosis severity, and anti-tumor effects, among others. Different acupoints, variations in treatment duration, and herbal extracts can be used to alleviate various symptoms and conditions and to regulate biological pathways by altering gene and protein expression. Our paper demonstrates how systems biology has helped to establish a platform for investigating the efficacy of TCM in treating different diseases and improving treatment strategies.

  9. Simultaneous biological nutrient removal: evaluation of autotrophic denitrification, heterotrophic nitrification, and biological phosphorus removal in full-scale systems.

    Science.gov (United States)

    Littleton, Helen X; Daigger, Glen T; Strom, Peter F; Cowan, Robert A

    2003-01-01

    Simultaneous biological nutrient removal (SBNR) is the biological removal of nitrogen and phosphorus in excess of that required for biomass synthesis in a biological wastewater treatment system without defined anaerobic or anoxic zones. Evidence is growing that significant SBNR can occur in many systems, including the aerobic zone of systems already configured for biological nutrient removal. Although SBNR systems offer several potential advantages, they cannot be fully realized until the mechanisms responsible for SBNR are better understood. Consequently, a research program was initiated with the basic hypothesis that three mechanisms might be responsible for SBNR: the reactor macroenvironment, the floc microenvironment, and novel microorganisms. Previously, the nutrient removal capabilities of seven full-scale, staged, closed-loop bioreactors known as Orbal oxidation ditches were evaluated. Chemical analysis and microbiological observations suggested that SBNR occurred in these systems. Three of these plants were further examined in this research to evaluate the importance of novel microorganisms, especially for nitrogen removal. A screening tool was developed to determine the relative significance of the activities of microorganisms capable of autotrophic denitrification and heterotrophic nitrification-aerobic denitrification in biological nutrient removal systems. The results indicated that novel microorganisms were not substantial contributors to SBNR in the plants studied. Phosphorus metabolism (anaerobic release, aerobic uptake) was also tested in one of the plants. Activity within the mixed liquor that was consistent with current theories for phosphorus-accumulating organisms (PAOs) was observed. Along with other observations, this suggests the presence of PAOs in the facilities studied.

  10. Separating intrinsic from extrinsic fluctuations in dynamic biological systems.

    Science.gov (United States)

    Hilfinger, Andreas; Paulsson, Johan

    2011-07-19

    From molecules in cells to organisms in ecosystems, biological populations fluctuate due to the intrinsic randomness of individual events and the extrinsic influence of changing environments. The combined effect is often too complex for effective analysis, and many studies therefore make simplifying assumptions, for example ignoring either intrinsic or extrinsic effects to reduce the number of model assumptions. Here we mathematically demonstrate how two identical and independent reporters embedded in a shared fluctuating environment can be used to identify intrinsic and extrinsic noise terms, but also how these contributions are qualitatively and quantitatively different from what has been previously reported. Furthermore, we show for which classes of biological systems the noise contributions identified by dual-reporter methods correspond to the noise contributions predicted by correct stochastic models of either intrinsic or extrinsic mechanisms. We find that for broad classes of systems, the extrinsic noise from the dual-reporter method can be rigorously analyzed using models that ignore intrinsic stochasticity. In contrast, the intrinsic noise can be rigorously analyzed using models that ignore extrinsic stochasticity only under very special conditions that rarely hold in biology. Testing whether the conditions are met is rarely possible and the dual-reporter method may thus produce flawed conclusions about the properties of the system, particularly about the intrinsic noise. Our results contribute toward establishing a rigorous framework to analyze dynamically fluctuating biological systems.

  11. Two faces of entropy and information in biological systems.

    Science.gov (United States)

    Mitrokhin, Yuriy

    2014-10-21

    The article attempts to overcome the well-known paradox of contradictions between the emerging biological organization and entropy production in biological systems. It is assumed that quality, speculative correlation between entropy and antientropy processes taking place both in the past and today in the metabolic and genetic cellular systems may be perfectly authorized for adequate description of the evolution of biological organization. So far as thermodynamic entropy itself cannot compensate for the high degree of organization which exists in the cell, we discuss the mode of conjunction of positive entropy events (mutations) in the genetic systems of the past generations and the formation of organized structures of current cells. We argue that only the information which is generated in the conditions of the information entropy production (mutations and other genome reorganization) in genetic systems of the past generations provides the physical conjunction of entropy and antientropy processes separated from each other in time generations. It is readily apparent from the requirements of the Second law of thermodynamics. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Integrating phosphoproteomics in systems biology

    Directory of Open Access Journals (Sweden)

    Yu Liu

    2014-07-01

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

  13. 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.

  14. 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...

  15. Radical production in biological systems

    International Nuclear Information System (INIS)

    Johnson, J.R.; Akabani, G.

    1994-10-01

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

  16. Promoting Systems Thinking through Biology Lessons

    Science.gov (United States)

    Riess, Werner; Mischo, Christoph

    2010-01-01

    This study's goal was to analyze various teaching approaches within the context of natural science lessons, especially in biology. The main focus of the paper lies on the effectiveness of different teaching methods in promoting systems thinking in the field of Education for Sustainable Development. The following methods were incorporated into the…

  17. Systems Biology of Immune Response to Live and Inactivated Dengue Virus Vaccines

    Science.gov (United States)

    2017-09-01

    AWARD NUMBER: W81XWH-16-2-0032 TITLE: Systems Biology of Immune Response to Live and Inactivated Dengue Virus Vaccines PRINCIPAL INVESTIGATOR...CONTRACT NUMBER Systems Biology of Immune Response to Live and Inactivated Dengue Virus Vaccines 5b. GRANT NUMBER W81XWH-16-2-0032 5c. PROGRAM ELEMENT...cell) responses will be measured using molecular and cellular approaches and the data analyzed using a systems biology approach. During the first

  18. Availability, uptake and translocation of plutonium within biological systems: a review of the significant literature. Final report

    International Nuclear Information System (INIS)

    Mullen, A.A.; Mosley, R.E.

    1976-04-01

    The report is a selective review of the literature on the availability of plutonium in the environment and its cycling throughout representative biological systems ranging from large biomes covering hundreds of miles to the molecular transformations within individual cells. No attempt was made to develop a comprehensive bibliography. Rather, references were selected for inclusion as representative documentation for the vast spectrum of material that is available on the subject. Important general references are listed separately. Thereafter the literature is described in essay form on a subject basis. References cited by number in the text are listed in complete bibliographic form at the end of the report together with an author index. The majority of the material reviewed is limited to relatively recent publications

  19. What it takes to understand and cure a living system: computational systems biology and a systems biology-driven pharmacokinetics-pharmacodynamics platform

    NARCIS (Netherlands)

    Swat, Maciej; Kiełbasa, Szymon M.; Polak, Sebastian; Olivier, Brett; Bruggeman, Frank J.; Tulloch, Mark Quinton; Snoep, Jacky L.; Verhoeven, Arthur J.; Westerhoff, Hans V.

    2011-01-01

    The utility of model repositories is discussed in the context of systems biology (SB). It is shown how such repositories, and in particular their live versions, can be used for computational SB: we calculate the robustness of the yeast glycolytic network with respect to perturbations of one of its

  20. Integrative systems and synthetic biology of cell-matrix adhesion sites.

    Science.gov (United States)

    Zamir, Eli

    2016-09-02

    The complexity of cell-matrix adhesion convolves its roles in the development and functioning of multicellular organisms and their evolutionary tinkering. Cell-matrix adhesion is mediated by sites along the plasma membrane that anchor the actin cytoskeleton to the matrix via a large number of proteins, collectively called the integrin adhesome. Fundamental challenges for understanding how cell-matrix adhesion sites assemble and function arise from their multi-functionality, rapid dynamics, large number of components and molecular diversity. Systems biology faces these challenges in its strive to understand how the integrin adhesome gives rise to functional adhesion sites. Synthetic biology enables engineering intracellular modules and circuits with properties of interest. In this review I discuss some of the fundamental questions in systems biology of cell-matrix adhesion and how synthetic biology can help addressing them.

  1. Boolean modeling in systems biology: an overview of methodology and applications

    International Nuclear Information System (INIS)

    Wang, Rui-Sheng; Albert, Réka; Saadatpour, Assieh

    2012-01-01

    Mathematical modeling of biological processes provides deep insights into complex cellular systems. While quantitative and continuous models such as differential equations have been widely used, their use is obstructed in systems wherein the knowledge of mechanistic details and kinetic parameters is scarce. On the other hand, a wealth of molecular level qualitative data on individual components and interactions can be obtained from the experimental literature and high-throughput technologies, making qualitative approaches such as Boolean network modeling extremely useful. In this paper, we build on our research to provide a methodology overview of Boolean modeling in systems biology, including Boolean dynamic modeling of cellular networks, attractor analysis of Boolean dynamic models, as well as inferring biological regulatory mechanisms from high-throughput data using Boolean models. We finally demonstrate how Boolean models can be applied to perform the structural analysis of cellular networks. This overview aims to acquaint life science researchers with the basic steps of Boolean modeling and its applications in several areas of systems biology. (paper)

  2. Converting differential-equation models of biological systems to membrane computing.

    Science.gov (United States)

    Muniyandi, Ravie Chandren; Zin, Abdullah Mohd; Sanders, J W

    2013-12-01

    This paper presents a method to convert the deterministic, continuous representation of a biological system by ordinary differential equations into a non-deterministic, discrete membrane computation. The dynamics of the membrane computation is governed by rewrite rules operating at certain rates. That has the advantage of applying accurately to small systems, and to expressing rates of change that are determined locally, by region, but not necessary globally. Such spatial information augments the standard differentiable approach to provide a more realistic model. A biological case study of the ligand-receptor network of protein TGF-β is used to validate the effectiveness of the conversion method. It demonstrates the sense in which the behaviours and properties of the system are better preserved in the membrane computing model, suggesting that the proposed conversion method may prove useful for biological systems in particular. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  3. Quantum mechanical simulation methods for studying biological systems

    International Nuclear Information System (INIS)

    Bicout, D.; Field, M.

    1996-01-01

    Most known biological mechanisms can be explained using fundamental laws of physics and chemistry and a full understanding of biological processes requires a multidisciplinary approach in which all the tools of biology, chemistry and physics are employed. An area of research becoming increasingly important is the theoretical study of biological macromolecules where numerical experimentation plays a double role of establishing a link between theoretical models and predictions and allowing a quantitative comparison between experiments and models. This workshop brought researchers working on different aspects of the development and application of quantum mechanical simulation together, assessed the state-of-the-art in the field and highlighted directions for future research. Fourteen lectures (theoretical courses and specialized seminars) deal with following themes: 1) quantum mechanical calculations of large systems, 2) ab initio molecular dynamics where the calculation of the wavefunction and hence the energy and forces on the atoms for a system at a single nuclear configuration are combined with classical molecular dynamics algorithms in order to perform simulations which use a quantum mechanical potential energy surface, 3) quantum dynamical simulations, electron and proton transfer processes in proteins and in solutions and finally, 4) free seminars that helped to enlarge the scope of the workshop. (N.T.)

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

    African Journals Online (AJOL)

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

  5. Multiway modeling and analysis in stem cell systems biology

    Directory of Open Access Journals (Sweden)

    Vandenberg Scott L

    2008-07-01

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

  6. Tritium isotope fractionation in biological systems and in analytical procedures

    International Nuclear Information System (INIS)

    Kim, M.A.; Baumgaertner, Franz

    1989-01-01

    The organically bound tritium (OBT) is evaluated in biological systems by determining the tritium distribution ratio (R-value), i.e. tritium concentrations in organic substance to cell water. The determination of the R-value always involves isotope fractionation is applied analytical procedures and hence the evaluation of the true OBT -value in a given biological system appears more complicated than hitherto known in the literature. The present work concentrates on the tritium isotope fractionation in the cell water separation and on the resulting effects on the R-value. The analytical procedures examined are vacuum freeze drying under equilibrium and non-equilibrium conditions and azeotropic distillation. The vaporization isotope effects are determined separately in the phase transition of solid or liquid to gas in pure tritium water systems as well as in real biological systems, e.g. corn plant. The results are systematically analyzed and the influence of isotope effects on the R-value is rigorously quantified

  7. Biochemical Space: A Framework for Systemic Annotation of Biological Models

    Czech Academy of Sciences Publication Activity Database

    Klement, M.; Děd, T.; Šafránek, D.; Červený, Jan; Müller, Stefan; Steuer, Ralf

    2014-01-01

    Roč. 306, JUL (2014), s. 31-44 ISSN 1571-0661 R&D Projects: GA MŠk(CZ) EE2.3.20.0256 Institutional support: RVO:67179843 Keywords : biological models * model annotation * systems biology * cyanobacteria Subject RIV: EH - Ecology, Behaviour

  8. Review of "Stochastic Modelling for Systems Biology" by Darren Wilkinson

    Directory of Open Access Journals (Sweden)

    Bullinger Eric

    2006-12-01

    Full Text Available Abstract "Stochastic Modelling for Systems Biology" by Darren Wilkinson introduces the peculiarities of stochastic modelling in biology. This book is particularly suited to as a textbook or for self-study, and for readers with a theoretical background.

  9. C.E.B.A.S., a closed equilibrated biological aquatic system as a possible precursor for a long-term life support system?

    Science.gov (United States)

    Blüm, V.

    C.E.B.A.S.-AQUARACK is a long-term multi-generation experimental device for aquatic organisms which is disposed for utlizitation in a space station. It results from the basic idea of a space aquarium for maintaining aquatic animals for longer periods integrated in a AQUARACK which consists of a modular animal holding tank, a semi-biological/physical water recycling system and an electronical control unit. The basic idea to replace a part of the water recycling system by a continuous culture of unicellular algae primarily leads to a second system for experiments with algae, a botanical AQUARACK consisting of an algal reactor, a water recycling and the electronical control unit. The combination of the zoological part, and the botanical part with a common control system in the AQUARACK, however, results in a ``Closed Equilibrated Biological Aquatic System'' (C.E.B.A.S.) representing an closed artificial ecosystem. Although this is disposed primarily as an experimental device for basic zoological, botanical and interdisciplinary research it opens the theoretical possibility to adapt it for combined production of animal and plant biomass on ground or in space. The paper explains the basic conception of the hardware construction of the zoological part of the system, the corresponding scientific frame program including the choice of the experimental animals and gives some selected examples of the hardware-related resrearch. It furtheron discusses the practical and economical relevance of the system in the development of a controlled aquatical life support system in general.

  10. A Generic Language for Biological Systems based on Bigraphs

    DEFF Research Database (Denmark)

    Damgaard, Troels Christoffer; Krivine, Jean

    Several efforts have shown that process calculi developed for reasoning about concurrent and mobile systems may be employed for modelling biological systems at the molecular level. In this paper, we initiate investigation of the meta-language framework bigraphical reactive systems, due to Milner et...

  11. Metabolomics for functional genomics, systems biology, and biotechnology.

    Science.gov (United States)

    Saito, Kazuki; Matsuda, Fumio

    2010-01-01

    Metabolomics now plays a significant role in fundamental plant biology and applied biotechnology. Plants collectively produce a huge array of chemicals, far more than are produced by most other organisms; hence, metabolomics is of great importance in plant biology. Although substantial improvements have been made in the field of metabolomics, the uniform annotation of metabolite signals in databases and informatics through international standardization efforts remains a challenge, as does the development of new fields such as fluxome analysis and single cell analysis. The principle of transcript and metabolite cooccurrence, particularly transcriptome coexpression network analysis, is a powerful tool for decoding the function of genes in Arabidopsis thaliana. This strategy can now be used for the identification of genes involved in specific pathways in crops and medicinal plants. Metabolomics has gained importance in biotechnology applications, as exemplified by quantitative loci analysis, prediction of food quality, and evaluation of genetically modified crops. Systems biology driven by metabolome data will aid in deciphering the secrets of plant cell systems and their application to biotechnology.

  12. Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering.

    Science.gov (United States)

    He, Fei; Murabito, Ettore; Westerhoff, Hans V

    2016-04-01

    Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out through in silico theoretical studies with the aim to guide and complement further in vitro and in vivo experimental efforts. Clearly, what counts is the result in vivo, not only in terms of maximal productivity but also robustness against environmental perturbations. Engineering an organism towards an increased production flux, however, often compromises that robustness. In this contribution, we review and investigate how various analytical approaches used in metabolic engineering and synthetic biology are related to concepts developed by systems and control engineering. While trade-offs between production optimality and cellular robustness have already been studied diagnostically and statically, the dynamics also matter. Integration of the dynamic design aspects of control engineering with the more diagnostic aspects of metabolic, hierarchical control and regulation analysis is leading to the new, conceptual and operational framework required for the design of robust and productive dynamic pathways. © 2016 The Author(s).

  13. Data management and data enrichment for systems biology projects.

    Science.gov (United States)

    Wittig, Ulrike; Rey, Maja; Weidemann, Andreas; Müller, Wolfgang

    2017-11-10

    Collecting, curating, interlinking, and sharing high quality data are central to de.NBI-SysBio, the systems biology data management service center within the de.NBI network (German Network for Bioinformatics Infrastructure). The work of the center is guided by the FAIR principles for scientific data management and stewardship. FAIR stands for the four foundational principles Findability, Accessibility, Interoperability, and Reusability which were established to enhance the ability of machines to automatically find, access, exchange and use data. Within this overview paper we describe three tools (SABIO-RK, Excemplify, SEEK) that exemplify the contribution of de.NBI-SysBio services to FAIR data, models, and experimental methods storage and exchange. The interconnectivity of the tools and the data workflow within systems biology projects will be explained. For many years we are the German partner in the FAIRDOM initiative (http://fair-dom.org) to establish a European data and model management service facility for systems biology. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Systems configured to distribute a telephone call, communication systems, communication methods and methods of routing a telephone call to a service representative

    Science.gov (United States)

    Harris, Scott H.; Johnson, Joel A.; Neiswanger, Jeffery R.; Twitchell, Kevin E.

    2004-03-09

    The present invention includes systems configured to distribute a telephone call, communication systems, communication methods and methods of routing a telephone call to a customer service representative. In one embodiment of the invention, a system configured to distribute a telephone call within a network includes a distributor adapted to connect with a telephone system, the distributor being configured to connect a telephone call using the telephone system and output the telephone call and associated data of the telephone call; and a plurality of customer service representative terminals connected with the distributor and a selected customer service representative terminal being configured to receive the telephone call and the associated data, the distributor and the selected customer service representative terminal being configured to synchronize, application of the telephone call and associated data from the distributor to the selected customer service representative terminal.

  15. Biological restoration of central nervous system architecture and function: part 3-stem cell- and cell-based applications and realities in the biological management of central nervous system disorders: traumatic, vascular, and epilepsy disorders.

    Science.gov (United States)

    Farin, Azadeh; Liu, Charles Y; Langmoen, Iver A; Apuzzo, Michael L J

    2009-11-01

    STEM CELL THERAPY has emerged as a promising novel therapeutic endeavor for traumatic brain injury, spinal cord injury, stroke, and epilepsy in experimental studies. A few preliminary clinical trials have further supported its safety and early efficacy after transplantation into humans. Although not yet clinically available for central nervous system disorders, stem cell technology is expected to evolve into one of the most powerful tools in the biological management of complex central nervous system disorders, many of which currently have limited treatment modalities. The identification of stem cells, discovery of neurogenesis, and application of stem cells to treat central nervous system disorders represent a dramatic evolution and expansion of the neurosurgeon's capabilities into the neurorestoration and neuroregeneration realms. In Part 3 of a 5-part series on stem cells, we discuss the theory, experimental evidence, and clinical data pertaining to the use of stem cells for the treatment of traumatic, vascular, and epileptic disorders.

  16. Construction of a Linux based chemical and biological information system.

    Science.gov (United States)

    Molnár, László; Vágó, István; Fehér, András

    2003-01-01

    A chemical and biological information system with a Web-based easy-to-use interface and corresponding databases has been developed. The constructed system incorporates all chemical, numerical and textual data related to the chemical compounds, including numerical biological screen results. Users can search the database by traditional textual/numerical and/or substructure or similarity queries through the web interface. To build our chemical database management system, we utilized existing IT components such as ORACLE or Tripos SYBYL for database management and Zope application server for the web interface. We chose Linux as the main platform, however, almost every component can be used under various operating systems.

  17. Reference materials and representative test materials: the nanotechnology case

    International Nuclear Information System (INIS)

    Roebben, G.; Rasmussen, K.; Kestens, V.; Linsinger, T. P. J.; Rauscher, H.; Emons, H.; Stamm, H.

    2013-01-01

    An increasing number of chemical, physical and biological tests are performed on manufactured nanomaterials for scientific and regulatory purposes. Existing test guidelines and measurement methods are not always directly applicable to or relevant for nanomaterials. Therefore, it is necessary to verify the use of the existing methods with nanomaterials, thereby identifying where modifications are needed, and where new methods need to be developed and validated. Efforts for verification, development and validation of methods as well as quality assurance of (routine) test results significantly benefit from the availability of suitable test and reference materials. This paper provides an overview of the existing types of reference materials and introduces a new class of test materials for which the term ‘representative test material’ is proposed. The three generic concepts of certified reference material, reference material(non-certified) and representative test material constitute a comprehensive system of benchmarks that can be used by all measurement and testing communities, regardless of their specific discipline. This paper illustrates this system with examples from the field of nanomaterials, including reference materials and representative test materials developed at the European Commission’s Joint Research Centre, in particular at the Institute for Reference Materials and Measurements (IRMM), and at the Institute for Health and Consumer Protection (IHCP).

  18. Synthetic and systems biology for microbial production of commodity chemicals.

    Science.gov (United States)

    Chubukov, Victor; Mukhopadhyay, Aindrila; Petzold, Christopher J; Keasling, Jay D; Martín, Héctor García

    2016-01-01

    The combination of synthetic and systems biology is a powerful framework to study fundamental questions in biology and produce chemicals of immediate practical application such as biofuels, polymers, or therapeutics. However, we cannot yet engineer biological systems as easily and precisely as we engineer physical systems. In this review, we describe the path from the choice of target molecule to scaling production up to commercial volumes. We present and explain some of the current challenges and gaps in our knowledge that must be overcome in order to bring our bioengineering capabilities to the level of other engineering disciplines. Challenges start at molecule selection, where a difficult balance between economic potential and biological feasibility must be struck. Pathway design and construction have recently been revolutionized by next-generation sequencing and exponentially improving DNA synthesis capabilities. Although pathway optimization can be significantly aided by enzyme expression characterization through proteomics, choosing optimal relative protein expression levels for maximum production is still the subject of heuristic, non-systematic approaches. Toxic metabolic intermediates and proteins can significantly affect production, and dynamic pathway regulation emerges as a powerful but yet immature tool to prevent it. Host engineering arises as a much needed complement to pathway engineering for high bioproduct yields; and systems biology approaches such as stoichiometric modeling or growth coupling strategies are required. A final, and often underestimated, challenge is the successful scale up of processes to commercial volumes. Sustained efforts in improving reproducibility and predictability are needed for further development of bioengineering.

  19. Creating biological nanomaterials using synthetic biology

    International Nuclear Information System (INIS)

    Rice, MaryJoe K; Ruder, Warren C

    2014-01-01

    Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. These signaling networks are especially important in fields such as biomedicine and biochemical engineering. Additionally, biological networks can also be critical to the production of naturally occurring biological nanomaterials, and as a result, synthetic biology holds tremendous potential in creating new materials. This review introduces the field of synthetic biology, discusses how biological systems naturally produce materials, and then presents examples and strategies for incorporating synthetic biology approaches in the development of new materials. In particular, strategies for using synthetic biology to produce both organic and inorganic nanomaterials are discussed. Ultimately, synthetic biology holds the potential to dramatically impact biological materials science with significant potential applications in medical systems. (review)

  20. Creating biological nanomaterials using synthetic biology.

    Science.gov (United States)

    Rice, MaryJoe K; Ruder, Warren C

    2014-02-01

    Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. These signaling networks are especially important in fields such as biomedicine and biochemical engineering. Additionally, biological networks can also be critical to the production of naturally occurring biological nanomaterials, and as a result, synthetic biology holds tremendous potential in creating new materials. This review introduces the field of synthetic biology, discusses how biological systems naturally produce materials, and then presents examples and strategies for incorporating synthetic biology approaches in the development of new materials. In particular, strategies for using synthetic biology to produce both organic and inorganic nanomaterials are discussed. Ultimately, synthetic biology holds the potential to dramatically impact biological materials science with significant potential applications in medical systems.

  1. Gradient matching methods for computational inference in mechanistic models for systems biology: a review and comparative analysis

    Directory of Open Access Journals (Sweden)

    Benn eMacdonald

    2015-11-01

    Full Text Available Parameter inference in mathematical models of biological pathways, expressed as coupled ordinary differential equations (ODEs, is a challenging problem in contemporary systems biology. Conventional methods involve repeatedly solving the ODEs by numerical integration, which is computationally onerous and does not scale up to complex systems. Aimed at reducing the computational costs, new concepts based on gradient matching have recently been proposed in the computational statistics and machine learning literature. In a preliminary smoothing step, the time series data are interpolated; then, in a second step, the parameters of the ODEs are optimised so as to minimise some metric measuring the difference between the slopes of the tangents to the interpolants, and the time derivatives from the ODEs. In this way, the ODEs never have to be solved explicitly. This review provides a concise methodological overview of the current state-of-the-art methods for gradient matching in ODEs, followed by an empirical comparative evaluation based on a set of widely used and representative benchmark data.

  2. Optical sensors and their applications for probing biological systems

    DEFF Research Database (Denmark)

    Palanco, Marta Espina

    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 and mammal......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...... of a trapped cell. The project could provide new insights into the desired biosensor for future membrane-protein cell studies....

  3. Continuous time Boolean modeling for biological signaling: application of Gillespie algorithm.

    Science.gov (United States)

    Stoll, Gautier; Viara, Eric; Barillot, Emmanuel; Calzone, Laurence

    2012-08-29

    Mathematical modeling is used as a Systems Biology tool to answer biological questions, and more precisely, to validate a network that describes biological observations and predict the effect of perturbations. This article presents an algorithm for modeling biological networks in a discrete framework with continuous time. There exist two major types of mathematical modeling approaches: (1) quantitative modeling, representing various chemical species concentrations by real numbers, mainly based on differential equations and chemical kinetics formalism; (2) and qualitative modeling, representing chemical species concentrations or activities by a finite set of discrete values. Both approaches answer particular (and often different) biological questions. Qualitative modeling approach permits a simple and less detailed description of the biological systems, efficiently describes stable state identification but remains inconvenient in describing the transient kinetics leading to these states. In this context, time is represented by discrete steps. Quantitative modeling, on the other hand, can describe more accurately the dynamical behavior of biological processes as it follows the evolution of concentration or activities of chemical species as a function of time, but requires an important amount of information on the parameters difficult to find in the literature. Here, we propose a modeling framework based on a qualitative approach that is intrinsically continuous in time. The algorithm presented in this article fills the gap between qualitative and quantitative modeling. It is based on continuous time Markov process applied on a Boolean state space. In order to describe the temporal evolution of the biological process we wish to model, we explicitly specify the transition rates for each node. For that purpose, we built a language that can be seen as a generalization of Boolean equations. Mathematically, this approach can be translated in a set of ordinary differential

  4. Continuum analysis of biological systems conserved quantities, fluxes and forces

    CERN Document Server

    Suraishkumar, G K

    2014-01-01

    This book addresses the analysis, in the continuum regime, of biological systems at various scales, from the cellular level to the industrial one. It presents both fundamental conservation principles (mass, charge, momentum and energy) and relevant fluxes resulting from appropriate driving forces, which are important for the analysis, design and operation of biological systems. It includes the concept of charge conservation, an important principle for biological systems that is not explicitly covered in any other book of this kind. The book is organized in five parts: mass conservation; charge conservation; momentum conservation; energy conservation; and multiple conservations simultaneously applied. All mathematical aspects are presented step by step, allowing any reader with a basic mathematical background (calculus, differential equations, linear algebra, etc.) to follow the text with ease. The book promotes an intuitive understanding of all the relevant principles and in so doing facilitates their applica...

  5. Next-generation mammalian genetics toward organism-level systems biology.

    Science.gov (United States)

    Susaki, Etsuo A; Ukai, Hideki; Ueda, Hiroki R

    2017-01-01

    Organism-level systems biology in mammals aims to identify, analyze, control, and design molecular and cellular networks executing various biological functions in mammals. In particular, system-level identification and analysis of molecular and cellular networks can be accelerated by next-generation mammalian genetics. Mammalian genetics without crossing, where all production and phenotyping studies of genome-edited animals are completed within a single generation drastically reduce the time, space, and effort of conducting the systems research. Next-generation mammalian genetics is based on recent technological advancements in genome editing and developmental engineering. The process begins with introduction of double-strand breaks into genomic DNA by using site-specific endonucleases, which results in highly efficient genome editing in mammalian zygotes or embryonic stem cells. By using nuclease-mediated genome editing in zygotes, or ~100% embryonic stem cell-derived mouse technology, whole-body knock-out and knock-in mice can be produced within a single generation. These emerging technologies allow us to produce multiple knock-out or knock-in strains in high-throughput manner. In this review, we discuss the basic concepts and related technologies as well as current challenges and future opportunities for next-generation mammalian genetics in organism-level systems biology.

  6. 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...

  7. A Checklist for Successful Quantitative Live Cell Imaging in Systems Biology

    Science.gov (United States)

    Sung, Myong-Hee

    2013-01-01

    Mathematical modeling of signaling and gene regulatory networks has provided unique insights about systems behaviors for many cell biological problems of medical importance. Quantitative single cell monitoring has a crucial role in advancing systems modeling of molecular networks. However, due to the multidisciplinary techniques that are necessary for adaptation of such systems biology approaches, dissemination to a wide research community has been relatively slow. In this essay, I focus on some technical aspects that are often under-appreciated, yet critical in harnessing live cell imaging methods to achieve single-cell-level understanding and quantitative modeling of molecular networks. The importance of these technical considerations will be elaborated with examples of successes and shortcomings. Future efforts will benefit by avoiding some pitfalls and by utilizing the lessons collectively learned from recent applications of imaging in systems biology. PMID:24709701

  8. Biological diversity in the patent system.

    Directory of Open Access Journals (Sweden)

    Paul Oldham

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

  9. cellPACK: a virtual mesoscope to model and visualize structural systems biology.

    Science.gov (United States)

    Johnson, Graham T; Autin, Ludovic; Al-Alusi, Mostafa; Goodsell, David S; Sanner, Michel F; Olson, Arthur J

    2015-01-01

    cellPACK assembles computational models of the biological mesoscale, an intermediate scale (10-100 nm) between molecular and cellular biology scales. cellPACK's modular architecture unites existing and novel packing algorithms to generate, visualize and analyze comprehensive three-dimensional models of complex biological environments that integrate data from multiple experimental systems biology and structural biology sources. cellPACK is available as open-source code, with tools for validation of models and with 'recipes' and models for five biological systems: blood plasma, cytoplasm, synaptic vesicles, HIV and a mycoplasma cell. We have applied cellPACK to model distributions of HIV envelope protein to test several hypotheses for consistency with experimental observations. Biologists, educators and outreach specialists can interact with cellPACK models, develop new recipes and perform packing experiments through scripting and graphical user interfaces at http://cellPACK.org/.

  10. Review and application of group theory to molecular systems biology.

    Science.gov (United States)

    Rietman, Edward A; Karp, Robert L; Tuszynski, Jack A

    2011-06-22

    In this paper we provide a review of selected mathematical ideas that can help us better understand the boundary between living and non-living systems. We focus on group theory and abstract algebra applied to molecular systems biology. Throughout this paper we briefly describe possible open problems. In connection with the genetic code we propose that it may be possible to use perturbation theory to explore the adjacent possibilities in the 64-dimensional space-time manifold of the evolving genome. With regards to algebraic graph theory, there are several minor open problems we discuss. In relation to network dynamics and groupoid formalism we suggest that the network graph might not be the main focus for understanding the phenotype but rather the phase space of the network dynamics. We show a simple case of a C6 network and its phase space network. We envision that the molecular network of a cell is actually a complex network of hypercycles and feedback circuits that could be better represented in a higher-dimensional space. We conjecture that targeting nodes in the molecular network that have key roles in the phase space, as revealed by analysis of the automorphism decomposition, might be a better way to drug discovery and treatment of cancer.

  11. System as metaphor in the psychology and biology of shame.

    Science.gov (United States)

    Maunder, R

    1996-01-01

    Biological theories of brain and psychological theories of mind are two systems of explanation that seem related to one another. The nature of the relationship is problematic and constitutes the age-old mind-body problem. The most prominent solutions currently are variations of materialism. While psychological theories can be consistent with materialism, there remains a difficulty in comprehending nonphysical (social, psychological) causes of physical effects. This difficulty is an obstacle to integration in psychiatry, where we routinely assume that illnesses that include or depend on biological dysfunction are caused multifactorially by causal agents such as perceived parental warmth, parental loss, stressful life events, genetics, and personality (Hammen et al. 1992; Kendler et al. 1993). Unity theory adopts the stance that neurobiological theories and psychological theories are essentially disparate explanations of the same psychobiological events; thus the relationship of mind to brain is one of shared reference (Goodman 1991; Maunder 1995). In Goodman's model the gap between biological and psychological systems is not bridgeable. Different conceptual categories refer to the same referents but cannot interact with each other. Stepping into the breach, systems theory has been presented as offering a language that can bridge the gap between psychological and biological theories of causation (Schwartz 1981; Weiner 1989). Thus, there is a controversy about the applicability of systems theory for integration in psychiatry.

  12. Carcinogenesis: alterations in reciprocal interactions of normal functional structure of biologic systems.

    Science.gov (United States)

    Davydyan, Garri

    2015-12-01

    The evolution of biologic systems (BS) includes functional mechanisms that in some conditions may lead to the development of cancer. Using mathematical group theory and matrix analysis, previously, it was shown that normally functioning BS are steady functional structures regulated by three basis regulatory components: reciprocal links (RL), negative feedback (NFB) and positive feedback (PFB). Together, they form an integrative unit maintaining system's autonomy and functional stability. It is proposed that phylogenetic development of different species is implemented by the splitting of "rudimentary" characters into two relatively independent functional parts that become encoded in chromosomes. The functional correlate of splitting mechanisms is RL. Inversion of phylogenetic mechanisms during ontogenetic development leads cell differentiation until cells reach mature states. Deterioration of reciprocal structure in the genome during ontogenesis gives rise of pathological conditions characterized by unsteadiness of the system. Uncontrollable cell proliferation and invasive cell growth are the leading features of the functional outcomes of malfunctioning systems. The regulatory element responsible for these changes is RL. In matrix language, pathological regulation is represented by matrices having positive values of diagonal elements ( TrA  > 0) and also positive values of matrix determinant ( detA  > 0). Regulatory structures of that kind can be obtained if the negative entry of the matrix corresponding to RL is replaced with the positive one. To describe not only normal but also pathological states of BS, a unit matrix should be added to the basis matrices representing RL, NFB and PFB. A mathematical structure corresponding to the set of these four basis functional patterns (matrices) is a split quaternion (coquaternion). The structure and specific role of basis elements comprising four-dimensional linear space of split quaternions help to understand what

  13. Networks as a Privileged Way to Develop Mesoscopic Level Approaches in Systems Biology

    OpenAIRE

    Alessandro Giuliani

    2014-01-01

    The methodologies advocated in computational biology are in many cases proper system-level approaches. These methodologies are variously connected to the notion of “mesosystem” and thus on the focus on relational structures that are at the basis of biological regulation. Here, I describe how the formalization of biological systems by means of graph theory constitutes an extremely fruitful approach to biology. I suggest the epistemological relevance of the notion of graph resides in its multil...

  14. Quantum Information Biology: From Information Interpretation of Quantum Mechanics to Applications in Molecular Biology and Cognitive Psychology

    Science.gov (United States)

    Asano, Masanari; Basieva, Irina; Khrennikov, Andrei; Ohya, Masanori; Tanaka, Yoshiharu; Yamato, Ichiro

    2015-10-01

    We discuss foundational issues of quantum information biology (QIB)—one of the most successful applications of the quantum formalism outside of physics. QIB provides a multi-scale model of information processing in bio-systems: from proteins and cells to cognitive and social systems. This theory has to be sharply distinguished from "traditional quantum biophysics". The latter is about quantum bio-physical processes, e.g., in cells or brains. QIB models the dynamics of information states of bio-systems. We argue that the information interpretation of quantum mechanics (its various forms were elaborated by Zeilinger and Brukner, Fuchs and Mermin, and D' Ariano) is the most natural interpretation of QIB. Biologically QIB is based on two principles: (a) adaptivity; (b) openness (bio-systems are fundamentally open). These principles are mathematically represented in the framework of a novel formalism— quantum adaptive dynamics which, in particular, contains the standard theory of open quantum systems.

  15. When one model is not enough: Combining epistemic tools in systems biology

    DEFF Research Database (Denmark)

    Green, Sara

    2013-01-01

    . The conceptual repertoire of Rheinberger’s historical epistemology offers important insights for an analysis of the modelling practice. I illustrate this with a case study on network modeling in systems biology where engineering approaches are applied to the study of biological systems. I shall argue...

  16. A two-way interface between limited Systems Biology Markup Language and R

    Directory of Open Access Journals (Sweden)

    Radivoyevitch Tomas

    2004-12-01

    Full Text Available Abstract Background Systems Biology Markup Language (SBML is gaining broad usage as a standard for representing dynamical systems as data structures. The open source statistical programming environment R is widely used by biostatisticians involved in microarray analyses. An interface between SBML and R does not exist, though one might be useful to R users interested in SBML, and SBML users interested in R. Results A model structure that parallels SBML to a limited degree is defined in R. An interface between this structure and SBML is provided through two function definitions: write.SBML( which maps this R model structure to SBML level 2, and read.SBML( which maps a limited range of SBML level 2 files back to R. A published model of purine metabolism is provided in this SBML-like format and used to test the interface. The model reproduces published time course responses before and after its mapping through SBML. Conclusions List infrastructure preexisting in R makes it well-suited for manipulating SBML models. Further developments of this SBML-R interface seem to be warranted.

  17. A two-way interface between limited Systems Biology Markup Language and R.

    Science.gov (United States)

    Radivoyevitch, Tomas

    2004-12-07

    Systems Biology Markup Language (SBML) is gaining broad usage as a standard for representing dynamical systems as data structures. The open source statistical programming environment R is widely used by biostatisticians involved in microarray analyses. An interface between SBML and R does not exist, though one might be useful to R users interested in SBML, and SBML users interested in R. A model structure that parallels SBML to a limited degree is defined in R. An interface between this structure and SBML is provided through two function definitions: write.SBML() which maps this R model structure to SBML level 2, and read.SBML() which maps a limited range of SBML level 2 files back to R. A published model of purine metabolism is provided in this SBML-like format and used to test the interface. The model reproduces published time course responses before and after its mapping through SBML. List infrastructure preexisting in R makes it well-suited for manipulating SBML models. Further developments of this SBML-R interface seem to be warranted.

  18. A distributed approach for parameters estimation in System Biology models

    International Nuclear Information System (INIS)

    Mosca, E.; Merelli, I.; Alfieri, R.; Milanesi, L.

    2009-01-01

    Due to the lack of experimental measurements, biological variability and experimental errors, the value of many parameters of the systems biology mathematical models is yet unknown or uncertain. A possible computational solution is the parameter estimation, that is the identification of the parameter values that determine the best model fitting respect to experimental data. We have developed an environment to distribute each run of the parameter estimation algorithm on a different computational resource. The key feature of the implementation is a relational database that allows the user to swap the candidate solutions among the working nodes during the computations. The comparison of the distributed implementation with the parallel one showed that the presented approach enables a faster and better parameter estimation of systems biology models.

  19. 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.

  20. Ion beam induced fluorescence imaging in biological systems

    International Nuclear Information System (INIS)

    Bettiol, Andrew A.; Mi, Zhaohong; Vanga, Sudheer Kumar; Chen, Ce-belle; Tao, Ye; Watt, Frank

    2015-01-01

    Imaging fluorescence generated by MeV ions in biological systems such as cells and tissue sections requires a high resolution beam (<100 nm), a sensitive detection system and a fluorescent probe that has a high quantum efficiency and low bleaching rate. For cutting edge applications in bioimaging, the fluorescence imaging technique needs to break the optical diffraction limit allowing for sub-cellular structure to be visualized, leading to a better understanding of cellular function. In a nuclear microprobe this resolution requirement can be readily achieved utilizing low beam current techniques such as Scanning Transmission Ion Microscopy (STIM). In recent times, we have been able to extend this capability to fluorescence imaging through the development of a new high efficiency fluorescence detection system, and through the use of new novel fluorescent probes that are resistant to ion beam damage (bleaching). In this paper we demonstrate ion beam induced fluorescence imaging in several biological samples, highlighting the advantages and challenges associated with using this technique

  1. StrateGene: object-oriented programming in molecular biology.

    Science.gov (United States)

    Carhart, R E; Cash, H D; Moore, J F

    1988-03-01

    This paper describes some of the ways that object-oriented programming methodologies have been used to represent and manipulate biological information in a working application. When running on a Xerox 1100 series computer, StrateGene functions as a genetic engineering workstation for the management of information about cloning experiments. It represents biological molecules, enzymes, fragments, and methods as classes, subclasses, and members in a hierarchy of objects. These objects may have various attributes, which themselves can be defined and classified. The attributes and their values can be passed from the classes of objects down to the subclasses and members. The user can modify the objects and their attributes while using them. New knowledge and changes to the system can be incorporated relatively easily. The operations on the biological objects are associated with the objects themselves. This makes it easier to invoke them correctly and allows generic operations to be customized for the particular object.

  2. 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.

  3. Systems Biology of the Immune Response to Live and Inactivated Dengue Virus Vaccines

    Science.gov (United States)

    2017-09-01

    AWARD NUMBER: W81XWH-16-2-0031 TITLE: Systems Biology of the Immune Response to Live and Inactivated Dengue Virus Vaccines PRINCIPAL...SUBTITLE 5a. CONTRACT NUMBER Systems Biology of the Immune Response to Live and Inactivated Dengue Virus Vaccines 5b. GRANT NUMBER W81XWH-16-2-0031 5c...adaptive (T and B cell) responses will be measured using molecular and cellular approaches and the data analyzed using a systems biology approach

  4. Interactions of nanomaterials and biological systems: implications to personalized nanomedicine☆

    Science.gov (United States)

    Zhang, Xue-Qing; Xu, Xiaoyang; Bertrand, Nicolas; Pridgen, Eric; Swami, Archana; Farokhzad, Omid C.

    2012-01-01

    The application of nanotechnology to personalized medicine provides an unprecedented opportunity to improve the treatment of many diseases. Nanomaterials offer several advantages as therapeutic and diagnostic tools due to design flexibility, small sizes, large surface-to-volume ratio, and ease of surface modification with multivalent ligands to increase avidity for target molecules. Nanomaterials can be engineered to interact with specific biological components, allowing them to benefit from the insights provided by personalized medicine techniques. To tailor these interactions, a comprehensive knowledge of how nanomaterials interact with biological systems is critical. Herein, we discuss how the interactions of nanomaterials with biological systems can guide their design for diagnostic, imaging and drug delivery purposes. A general overview of nanomaterials under investigation is provided with an emphasis on systems that have reached clinical trials. Finally, considerations for the development of personalized nanomedicines are summarized such as the potential toxicity, scientific and technical challenges in fabricating them, and regulatory and ethical issues raised by the utilization of nanomaterials. PMID:22917779

  5. Biological Detection System Technologies Technology and Industrial Base Study. A Primer on Biological Detection Technologies

    National Research Council Canada - National Science Library

    2001-01-01

    .... and Canadian military personnel. In light of these concerns both defense departments have increased efforts to develop and field biological agent detection systems to help protect their military forces and fixed assets...

  6. Synthetic Biology Outside the Cell: Linking Computational Tools to Cell-Free Systems

    International Nuclear Information System (INIS)

    Lewis, Daniel D.; Villarreal, Fernando D.; Wu, Fan; Tan, Cheemeng

    2014-01-01

    As mathematical models become more commonly integrated into the study of biology, a common language for describing biological processes is manifesting. Many tools have emerged for the simulation of in vivo synthetic biological systems, with only a few examples of prominent work done on predicting the dynamics of cell-free synthetic systems. At the same time, experimental biologists have begun to study dynamics of in vitro systems encapsulated by amphiphilic molecules, opening the door for the development of a new generation of biomimetic systems. In this review, we explore both in vivo and in vitro models of biochemical networks with a special focus on tools that could be applied to the construction of cell-free expression systems. We believe that quantitative studies of complex cellular mechanisms and pathways in synthetic systems can yield important insights into what makes cells different from conventional chemical systems.

  7. Synthetic Biology Outside the Cell: Linking Computational Tools to Cell-Free Systems

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, Daniel D. [Integrative Genetics and Genomics, University of California Davis, Davis, CA (United States); Department of Biomedical Engineering, University of California Davis, Davis, CA (United States); Villarreal, Fernando D.; Wu, Fan; Tan, Cheemeng, E-mail: cmtan@ucdavis.edu [Department of Biomedical Engineering, University of California Davis, Davis, CA (United States)

    2014-12-09

    As mathematical models become more commonly integrated into the study of biology, a common language for describing biological processes is manifesting. Many tools have emerged for the simulation of in vivo synthetic biological systems, with only a few examples of prominent work done on predicting the dynamics of cell-free synthetic systems. At the same time, experimental biologists have begun to study dynamics of in vitro systems encapsulated by amphiphilic molecules, opening the door for the development of a new generation of biomimetic systems. In this review, we explore both in vivo and in vitro models of biochemical networks with a special focus on tools that could be applied to the construction of cell-free expression systems. We believe that quantitative studies of complex cellular mechanisms and pathways in synthetic systems can yield important insights into what makes cells different from conventional chemical systems.

  8. An Ocean Biology-induced Negative Feedback on ENSO in the Tropical Pacific Climate System

    Science.gov (United States)

    Zhang, R. H.

    2016-02-01

    Biological conditions in the tropical Pacific Ocean (e.g., phytoplankton biomass) are strongly regulated by physical changes associated with the El Niño-Southern Oscillation (ENSO). The existence and variation of phytoplankton biomass, in turn, act to modulate the vertical penetration of the incoming sunlight in the upper ocean, presenting an ocean biology-induced heating (OBH) effect on the climate system. Previously, a penetration depth of solar radiation in the upper ocean (Hp) is defined to describe the related bio-climate connections. Parameterized in terms of its relationship with the sea surface temperature (SST) in the tropical Pacific, an empirical model for interannual Hp variability has been derived from remotely sensed ocean color data, which is incorporated into a hybrid coupled model (HCM) to represent OBH effects. In this paper, various HCM experiments are performed to demonstrate the bio-feedback onto ENSO, including a climatological Hp run (in which Hp is prescribed as seasonally varying only), interannual Hp runs (with different intensities of interannually varying OBH effects), and a run in which the sign of the OBH effect is artificially reversed. Significant modulating impacts on interannual variability are found in the HCM, characterized by a negative feedback between ocean biology and the climate system in the tropical Pacific: the stronger the OBH feedback, the weaker the interannual variability. Processes involved in the feedback are analyzed; it is illustrated that the SST is modulated indirectly by ocean dynamical processes induced by OBH. The significance and implication of the OBH effects are discussed for their roles in ENSO variability and model biases in the tropical Pacific.

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

    Science.gov (United States)

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

    2018-01-01

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

  10. Notions of radiation chemistry in biological systems

    International Nuclear Information System (INIS)

    Mastro, N.L. del.

    1989-10-01

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

  11. Biological regeneration of humic acid-loaded partially exhausted activated carbon (down flow system)

    International Nuclear Information System (INIS)

    Durrani, M.A.Q.J.; Martin, R.J.; Khaliq, F.

    1995-01-01

    This paper represents the report on the biological regeneration of partially exhausted (down flow) activated carbon following the experimental studies carried out at the university of Birmingham, UK. The Research investigated the extent of bio regeneration of humic acid of concentration 100 mg/l. Bio regeneration in the partial exhaustion system (down flow) was evaluated in terms of substrate removal. Bacterial counts in the effluents of regenerated GAC columns were significantly more than those of fresh carbon effluents. The regeneration performance of the bio regeneration, partially exhausted (with humic acid) carbon increased during initial cycles, later on, it deteriorated significantly with each successive regeneration cycle. Microbial fouling of the carbon, especially at the bottom of the carbon bed was found to produce a substantial deterioration of the bio regeneration performance. (author)

  12. Characteristics of microbial community functional structure of a biological coking wastewater treatment system.

    Science.gov (United States)

    Joshi, Dev Raj; Zhang, Yu; Zhang, Hong; Gao, Yingxin; Yang, Min

    2018-01-01

    Nitrogenous heterocyclic compounds are key pollutants in coking wastewater; however, the functional potential of microbial communities for biodegradation of such contaminants during biological treatment is still elusive. Herein, a high throughput functional gene array (GeoChip 5.0) in combination with Illumina HiSeq2500 sequencing was used to compare and characterize the microbial community functional structure in a long run (500days) bench scale bioreactor treating coking wastewater, with a control system treating synthetic wastewater. Despite the inhibitory toxic pollutants, GeoChip 5.0 detected almost all key functional gene (average 61,940 genes) categories in the coking wastewater sludge. With higher abundance, aromatic ring cleavage dioxygenase genes including multi ring1,2diox; one ring2,3diox; catechol represented significant functional potential for degradation of aromatic pollutants which was further confirmed by Illumina HiSeq2500 analysis results. Response ratio analysis revealed that three nitrogenous compound degrading genes- nbzA (nitro-aromatics), tdnB (aniline), and scnABC (thiocyanate) were unique for coking wastewater treatment, which might be strong cause to increase ammonia level during the aerobic process. Additionally, HiSeq2500 elucidated carbozole and isoquinoline degradation genes in the system. These findings expanded our understanding on functional potential of microbial communities to remove organic nitrogenous pollutants; hence it will be useful in optimization strategies for biological treatment of coking wastewater. Copyright © 2017. Published by Elsevier B.V.

  13. Towards a system level understanding of non-model organisms sampled from the environment: a network biology approach.

    Science.gov (United States)

    Williams, Tim D; Turan, Nil; Diab, Amer M; Wu, Huifeng; Mackenzie, Carolynn; Bartie, Katie L; Hrydziuszko, Olga; Lyons, Brett P; Stentiford, Grant D; Herbert, John M; Abraham, Joseph K; Katsiadaki, Ioanna; Leaver, Michael J; Taggart, John B; George, Stephen G; Viant, Mark R; Chipman, Kevin J; Falciani, Francesco

    2011-08-01

    The acquisition and analysis of datasets including multi-level omics and physiology from non-model species, sampled from field populations, is a formidable challenge, which so far has prevented the application of systems biology approaches. If successful, these could contribute enormously to improving our understanding of how populations of living organisms adapt to environmental stressors relating to, for example, pollution and climate. Here we describe the first application of a network inference approach integrating transcriptional, metabolic and phenotypic information representative of wild populations of the European flounder fish, sampled at seven estuarine locations in northern Europe with different degrees and profiles of chemical contaminants. We identified network modules, whose activity was predictive of environmental exposure and represented a link between molecular and morphometric indices. These sub-networks represented both known and candidate novel adverse outcome pathways representative of several aspects of human liver pathophysiology such as liver hyperplasia, fibrosis, and hepatocellular carcinoma. At the molecular level these pathways were linked to TNF alpha, TGF beta, PDGF, AGT and VEGF signalling. More generally, this pioneering study has important implications as it can be applied to model molecular mechanisms of compensatory adaptation to a wide range of scenarios in wild populations.

  14. Biomimicry, Biofabrication, and Biohybrid Systems: The Emergence and Evolution of Biological Design.

    Science.gov (United States)

    Raman, Ritu; Bashir, Rashid

    2017-10-01

    The discipline of biological design has a relatively short history, but has undergone very rapid expansion and development over that time. This Progress Report outlines the evolution of this field from biomimicry to biofabrication to biohybrid systems' design, showcasing how each subfield incorporates bioinspired dynamic adaptation into engineered systems. Ethical implications of biological design are discussed, with an emphasis on establishing responsible practices for engineering non-natural or hypernatural functional behaviors in biohybrid systems. This report concludes with recommendations for implementing biological design into educational curricula, ensuring effective and responsible practices for the next generation of engineers and scientists. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Creation of computer system for simulation nanoparticles interaction with biological objects concept

    International Nuclear Information System (INIS)

    Sarana, Yu.V.; Smol'nik, N.S.; Mel'nov, S.B.

    2014-01-01

    Main problem of nanotoxicology is that biological effects of most nanoparticles are unknown. So creation of system predictioning nanoparticles biological activity spectra is a great challenge. Here we give a concept of such system creation; it includes 6 stages realization of which help to implement nanotechnology most safely and effectively. (authors)

  16. Synthetic Biology: Applications in the Food Sector.

    Science.gov (United States)

    Tyagi, Ashish; Kumar, Ashwani; Aparna, S V; Mallappa, Rashmi H; Grover, Sunita; Batish, Virender Kumar

    2016-08-17

    Synthetic biology also termed as "genomic alchemy" represents a powerful area of science that is based on the convergence of biological sciences with systems engineering. It has been fittingly described as "moving from reading the genetic code to writing it" as it focuses on building, modeling, designing and fabricating novel biological systems using customized gene components that result in artificially created genetic circuitry. The scientifically compelling idea of the technological manipulation of life has been advocated since long time. Realization of this idea has gained momentum with development of high speed automation and the falling cost of gene sequencing and synthesis following the completion of the human genome project. Synthetic biology will certainly be instrumental in shaping the development of varying areas ranging from biomedicine, biopharmaceuticals, chemical production, food and dairy quality monitoring, packaging, and storage of food and dairy products, bioremediation and bioenergy production, etc. However, potential dangers of using synthetic life forms have to be acknowledged and adoption of policies by the scientific community to ensure safe practice while making important advancements in the ever expanding field of synthetic biology is to be fully supported and implemented.

  17. A generic algorithm for layout of biological networks.

    Science.gov (United States)

    Schreiber, Falk; Dwyer, Tim; Marriott, Kim; Wybrow, Michael

    2009-11-12

    Biological networks are widely used to represent processes in biological systems and to capture interactions and dependencies between biological entities. Their size and complexity is steadily increasing due to the ongoing growth of knowledge in the life sciences. To aid understanding of biological networks several algorithms for laying out and graphically representing networks and network analysis results have been developed. However, current algorithms are specialized to particular layout styles and therefore different algorithms are required for each kind of network and/or style of layout. This increases implementation effort and means that new algorithms must be developed for new layout styles. Furthermore, additional effort is necessary to compose different layout conventions in the same diagram. Also the user cannot usually customize the placement of nodes to tailor the layout to their particular need or task and there is little support for interactive network exploration. We present a novel algorithm to visualize different biological networks and network analysis results in meaningful ways depending on network types and analysis outcome. Our method is based on constrained graph layout and we demonstrate how it can handle the drawing conventions used in biological networks. The presented algorithm offers the ability to produce many of the fundamental popular drawing styles while allowing the exibility of constraints to further tailor these layouts.

  18. Recent advances in modeling languages for pathway maps and computable biological networks.

    Science.gov (United States)

    Slater, Ted

    2014-02-01

    As our theories of systems biology grow more sophisticated, the models we use to represent them become larger and more complex. Languages necessarily have the expressivity and flexibility required to represent these models in ways that support high-resolution annotation, and provide for simulation and analysis that are sophisticated enough to allow researchers to master their data in the proper context. These languages also need to facilitate model sharing and collaboration, which is currently best done by using uniform data structures (such as graphs) and language standards. In this brief review, we discuss three of the most recent systems biology modeling languages to appear: BEL, PySB and BCML, and examine how they meet these needs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. 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.

  20. Applications of membrane computing in systems and synthetic biology

    CERN Document Server

    Gheorghe, Marian; Pérez-Jiménez, Mario

    2014-01-01

    Membrane Computing was introduced as a computational paradigm in Natural Computing. The models introduced, called Membrane (or P) Systems, provide a coherent platform to describe and study living cells as computational systems. Membrane Systems have been investigated for their computational aspects and employed to model problems in other fields, like: Computer Science, Linguistics, Biology, Economy, Computer Graphics, Robotics, etc. Their inherent parallelism, heterogeneity and intrinsic versatility allow them to model a broad range of processes and phenomena, being also an efficient means to solve and analyze problems in a novel way. Membrane Computing has been used to model biological systems, becoming with time a thorough modeling paradigm comparable, in its modeling and predicting capabilities, to more established models in this area. This book is the result of the need to collect, in an organic way, different facets of this paradigm. The chapters of this book, together with the web pages accompanying th...

  1. Degradation characteristics of 2,4-dichlorophenoxyacetic acid in electro-biological system

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, JingLi, E-mail: jinglizhangczp@126.com [Tianjin Key Laboratory of Aquatic Science and Technology, Tianjin Institute of Urban Construction, Tianjin 300384 (China); Cao, ZhanPing; Zhang, HongWei [School of Environmental and Chemical Engineering, Tianjin Polytechnic University, Tianjin 300387 (China); Zhao, LianMei [Tianjin Key Laboratory of Aquatic Science and Technology, Tianjin Institute of Urban Construction, Tianjin 300384 (China); Sun, XuDong; Mei, Feng [School of Environmental and Chemical Engineering, Tianjin Polytechnic University, Tianjin 300387 (China)

    2013-11-15

    Highlights: • The 2,4-D reductive degradation was studied in an electro-biological system. • The electric auxiliary accelerates 2,4-D microbial degradation. • A electron transfer is achieved between the electrode, bacteria and the pollutants. • The paper provides a promising way for the degradation of persistent organics. -- Abstract: The reductive degradation of 2,4-dichlorophenoxyacetic acid (2,4-D) was studied in an electro-biological system, a biological system and an electric catalytic system, respectively. Electrochemical characteristics were monitored by cyclic voltammetry and the intermediate products of 2,4-D degradation were determined by high speed liquid chromatography (HPLC). The results showed that all 2,4-D degradations in the three systems conformed to the kinetics characteristics of one-order reaction, and the degradation kinetics constants were 28.74 × 10{sup −2} h{sup −1}, 19.73 × 10{sup −2} h{sup −1} and 3.54 × 10{sup −2} h{sup −1}, respectively. The kinetics constant in the electro-biological system was higher than the sum in the other two systems by 19%. The electrochemical assistance provided the electrons and accelerated the electron transfer rate in the microbial degradation of 2,4-D. The degradation resulted from the microbial reduction strengthened by the electrochemical assistance. The electron transfer existed between the electrode, cytochrome, NAD and the pollutants. A long-range electron transfer process could be achieved on the multi-phase interfaces between the electrode, bacteria and the pollutants.

  2. Uncovering the underlying physical mechanisms of biological systems via quantification of landscape and flux

    International Nuclear Information System (INIS)

    Xu Li; Chu Xiakun; Yan Zhiqiang; Zheng Xiliang; Zhang Kun; Zhang Feng; Yan Han; Wu Wei; Wang Jin

    2016-01-01

    In this review, we explore the physical mechanisms of biological processes such as protein folding and recognition, ligand binding, and systems biology, including cell cycle, stem cell, cancer, evolution, ecology, and neural networks. Our approach is based on the landscape and flux theory for nonequilibrium dynamical systems. This theory provides a unifying principle and foundation for investigating the underlying mechanisms and physical quantification of biological systems. (topical review)

  3. 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.

  4. Dynamical systems in population biology

    CERN Document Server

    Zhao, Xiao-Qiang

    2017-01-01

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

  5. Dynamic optimization of distributed biological systems using robust and efficient numerical techniques.

    Science.gov (United States)

    Vilas, Carlos; Balsa-Canto, Eva; García, Maria-Sonia G; Banga, Julio R; Alonso, Antonio A

    2012-07-02

    Systems biology allows the analysis of biological systems behavior under different conditions through in silico experimentation. The possibility of perturbing biological systems in different manners calls for the design of perturbations to achieve particular goals. Examples would include, the design of a chemical stimulation to maximize the amplitude of a given cellular signal or to achieve a desired pattern in pattern formation systems, etc. Such design problems can be mathematically formulated as dynamic optimization problems which are particularly challenging when the system is described by partial differential equations.This work addresses the numerical solution of such dynamic optimization problems for spatially distributed biological systems. The usual nonlinear and large scale nature of the mathematical models related to this class of systems and the presence of constraints on the optimization problems, impose a number of difficulties, such as the presence of suboptimal solutions, which call for robust and efficient numerical techniques. Here, the use of a control vector parameterization approach combined with efficient and robust hybrid global optimization methods and a reduced order model methodology is proposed. The capabilities of this strategy are illustrated considering the solution of a two challenging problems: bacterial chemotaxis and the FitzHugh-Nagumo model. In the process of chemotaxis the objective was to efficiently compute the time-varying optimal concentration of chemotractant in one of the spatial boundaries in order to achieve predefined cell distribution profiles. Results are in agreement with those previously published in the literature. The FitzHugh-Nagumo problem is also efficiently solved and it illustrates very well how dynamic optimization may be used to force a system to evolve from an undesired to a desired pattern with a reduced number of actuators. The presented methodology can be used for the efficient dynamic optimization of

  6. Predicting in vivo effect levels for repeat-dose systemic toxicity using chemical, biological, kinetic and study covariates.

    Science.gov (United States)

    Truong, Lisa; Ouedraogo, Gladys; Pham, LyLy; Clouzeau, Jacques; Loisel-Joubert, Sophie; Blanchet, Delphine; Noçairi, Hicham; Setzer, Woodrow; Judson, Richard; Grulke, Chris; Mansouri, Kamel; Martin, Matthew

    2018-02-01

    In an effort to address a major challenge in chemical safety assessment, alternative approaches for characterizing systemic effect levels, a predictive model was developed. Systemic effect levels were curated from ToxRefDB, HESS-DB and COSMOS-DB from numerous study types totaling 4379 in vivo studies for 1247 chemicals. Observed systemic effects in mammalian models are a complex function of chemical dynamics, kinetics, and inter- and intra-individual variability. To address this complex problem, systemic effect levels were modeled at the study-level by leveraging study covariates (e.g., study type, strain, administration route) in addition to multiple descriptor sets, including chemical (ToxPrint, PaDEL, and Physchem), biological (ToxCast), and kinetic descriptors. Using random forest modeling with cross-validation and external validation procedures, study-level covariates alone accounted for approximately 15% of the variance reducing the root mean squared error (RMSE) from 0.96 log 10 to 0.85 log 10  mg/kg/day, providing a baseline performance metric (lower expectation of model performance). A consensus model developed using a combination of study-level covariates, chemical, biological, and kinetic descriptors explained a total of 43% of the variance with an RMSE of 0.69 log 10  mg/kg/day. A benchmark model (upper expectation of model performance) was also developed with an RMSE of 0.5 log 10  mg/kg/day by incorporating study-level covariates and the mean effect level per chemical. To achieve a representative chemical-level prediction, the minimum study-level predicted and observed effect level per chemical were compared reducing the RMSE from 1.0 to 0.73 log 10  mg/kg/day, equivalent to 87% of predictions falling within an order-of-magnitude of the observed value. Although biological descriptors did not improve model performance, the final model was enriched for biological descriptors that indicated xenobiotic metabolism gene expression, oxidative stress, and

  7. Semantic Data Integration and Knowledge Management to Represent Biological Network Associations.

    Science.gov (United States)

    Losko, Sascha; Heumann, Klaus

    2017-01-01

    The vast quantities of information generated by academic and industrial research groups are reflected in a rapidly growing body of scientific literature and exponentially expanding resources of formalized data, including experimental data, originating from a multitude of "-omics" platforms, phenotype information, and clinical data. For bioinformatics, the challenge remains to structure this information so that scientists can identify relevant information, to integrate this information as specific "knowledge bases," and to formalize this knowledge across multiple scientific domains to facilitate hypothesis generation and validation. Here we report on progress made in building a generic knowledge management environment capable of representing and mining both explicit and implicit knowledge and, thus, generating new knowledge. Risk management in drug discovery and clinical research is used as a typical example to illustrate this approach. In this chapter we introduce techniques and concepts (such as ontologies, semantic objects, typed relationships, contexts, graphs, and information layers) that are used to represent complex biomedical networks. The BioXM™ Knowledge Management Environment is used as an example to demonstrate how a domain such as oncology is represented and how this representation is utilized for research.

  8. Systems Biology of Glucocorticoids in Muscle Disease

    Science.gov (United States)

    2010-10-01

    Introduction Duchenne muscular dystrophy (DMD) is the most common and incurable muscular dystrophy of childhood. Muscle regeneration fails with...SUBJECT TERMS Duchenne Muscular dystrophy , Glucocorticoids, Systems biology, Drug mechanism 16. SECURITY CLASSIFICATION OF: U 17. LIMITATION...better targeted and more effective therapies for Duchenne muscular dystrophy dynamically. This MDA grant proposal is led by Dr. Eric Hoffman, and it

  9. Development of a Prototype System for Archiving Integrative/Hybrid Structure Models of Biological Macromolecules.

    Science.gov (United States)

    Vallat, Brinda; Webb, Benjamin; Westbrook, John D; Sali, Andrej; Berman, Helen M

    2018-04-09

    Essential processes in biology are carried out by large macromolecular assemblies, whose structures are often difficult to determine by traditional methods. Increasingly, researchers combine measured data and computed information from several complementary methods to obtain "hybrid" or "integrative" structural models of macromolecules and their assemblies. These integrative/hybrid (I/H) models are not archived in the PDB because of the absence of standard data representations and processing mechanisms. Here we present the development of data standards and a prototype system for archiving I/H models. The data standards provide the definitions required for representing I/H models that span multiple spatiotemporal scales and conformational states, as well as spatial restraints derived from different experimental techniques. Based on these data definitions, we have built a prototype system called PDB-Dev, which provides the infrastructure necessary to archive I/H structural models. PDB-Dev is now accepting structures and is open to the community for new submissions. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. Pragmatic turn in biology: From biological molecules to genetic content operators.

    Science.gov (United States)

    Witzany, Guenther

    2014-08-26

    Erwin Schrödinger's question "What is life?" received the answer for decades of "physics + chemistry". The concepts of Alain Turing and John von Neumann introduced a third term: "information". This led to the understanding of nucleic acid sequences as a natural code. Manfred Eigen adapted the concept of Hammings "sequence space". Similar to Hilbert space, in which every ontological entity could be defined by an unequivocal point in a mathematical axiomatic system, in the abstract "sequence space" concept each point represents a unique syntactic structure and the value of their separation represents their dissimilarity. In this concept molecular features of the genetic code evolve by means of self-organisation of matter. Biological selection determines the fittest types among varieties of replication errors of quasi-species. The quasi-species concept dominated evolution theory for many decades. In contrast to this, recent empirical data on the evolution of DNA and its forerunners, the RNA-world and viruses indicate cooperative agent-based interactions. Group behaviour of quasi-species consortia constitute de novo and arrange available genetic content for adaptational purposes within real-life contexts that determine epigenetic markings. This review focuses on some fundamental changes in biology, discarding its traditional status as a subdiscipline of physics and chemistry.

  11. ADAM: analysis of discrete models of biological systems using computer algebra.

    Science.gov (United States)

    Hinkelmann, Franziska; Brandon, Madison; Guang, Bonny; McNeill, Rustin; Blekherman, Grigoriy; Veliz-Cuba, Alan; Laubenbacher, Reinhard

    2011-07-20

    Many biological systems are modeled qualitatively with discrete models, such as probabilistic Boolean networks, logical models, Petri nets, and agent-based models, to gain a better understanding of them. The computational complexity to analyze the complete dynamics of these models grows exponentially in the number of variables, which impedes working with complex models. There exist software tools to analyze discrete models, but they either lack the algorithmic functionality to analyze complex models deterministically or they are inaccessible to many users as they require understanding the underlying algorithm and implementation, do not have a graphical user interface, or are hard to install. Efficient analysis methods that are accessible to modelers and easy to use are needed. We propose a method for efficiently identifying attractors and introduce the web-based tool Analysis of Dynamic Algebraic Models (ADAM), which provides this and other analysis methods for discrete models. ADAM converts several discrete model types automatically into polynomial dynamical systems and analyzes their dynamics using tools from computer algebra. Specifically, we propose a method to identify attractors of a discrete model that is equivalent to solving a system of polynomial equations, a long-studied problem in computer algebra. Based on extensive experimentation with both discrete models arising in systems biology and randomly generated networks, we found that the algebraic algorithms presented in this manuscript are fast for systems with the structure maintained by most biological systems, namely sparseness and robustness. For a large set of published complex discrete models, ADAM identified the attractors in less than one second. Discrete modeling techniques are a useful tool for analyzing complex biological systems and there is a need in the biological community for accessible efficient analysis tools. ADAM provides analysis methods based on mathematical algorithms as a web

  12. A Friendly-Biological Reactor SIMulator (BioReSIM for studying biological processes in wastewater treatment processes

    Directory of Open Access Journals (Sweden)

    Raul Molina

    2014-12-01

    Full Text Available Biological processes for wastewater treatments are inherently dynamic systems because of the large variations in the influent wastewater flow rate, concentration composition and the adaptive behavior of the involved microorganisms. Moreover, the sludge retention time (SRT is a critical factor to understand the bioreactor performances when changes in the influent or in the operation conditions take place. Since SRT are usually in the range of 10-30 days, the performance of biological reactors needs a long time to be monitored in a regular laboratory demonstration, limiting the knowledge that can be obtained in the experimental lab practice. In order to overcome this lack, mathematical models and computer simulations are useful tools to describe biochemical processes and predict the overall performance of bioreactors under different working operation conditions and variations of the inlet wastewater composition. The mathematical solution of the model could be difficult as numerous biochemical processes can be considered. Additionally, biological reactors description (mass balance, etc. needs models represented by partial or/and ordinary differential equations associated to algebraic expressions, that require complex computational codes to obtain the numerical solutions. Different kind of software for mathematical modeling can be used, from large degree of freedom simulators capable of free models definition (as AQUASIM, to closed predefined model structure programs (as BIOWIN. The first ones usually require long learning curves, whereas the second ones could be excessively rigid for specific wastewater treatment systems. As alternative, we present Biological Reactor SIMulator (BioReSIM, a MATLAB code for the simulation of sequencing batch reactors (SBR and rotating biological contactors (RBC as biological systems of suspended and attached biomass for wastewater treatment, respectively. This BioReSIM allows the evaluation of simple and complex

  13. In vivo biology and toxicology of fullerenes and their derivatives

    DEFF Research Database (Denmark)

    Nielsen, Gunnar Damgård; Roursgaard, Martin; Jensen, Keld Alstrup

    2008-01-01

    Fullerenes represent a group of nanoparticles discovered in 1985. They are spherical molecules consisting entirely of carbon atoms (C(x)) to which side chains can be added, furnishing compounds with widely different properties. Fullerenes interact with biological systems, for example, by enzyme i...

  14. STOCHSIMGPU: parallel stochastic simulation for the Systems Biology Toolbox 2 for MATLAB

    KAUST Repository

    Klingbeil, G.

    2011-02-25

    Motivation: The importance of stochasticity in biological systems is becoming increasingly recognized and the computational cost of biologically realistic stochastic simulations urgently requires development of efficient software. We present a new software tool STOCHSIMGPU that exploits graphics processing units (GPUs) for parallel stochastic simulations of biological/chemical reaction systems and show that significant gains in efficiency can be made. It is integrated into MATLAB and works with the Systems Biology Toolbox 2 (SBTOOLBOX2) for MATLAB. Results: The GPU-based parallel implementation of the Gillespie stochastic simulation algorithm (SSA), the logarithmic direct method (LDM) and the next reaction method (NRM) is approximately 85 times faster than the sequential implementation of the NRM on a central processing unit (CPU). Using our software does not require any changes to the user\\'s models, since it acts as a direct replacement of the stochastic simulation software of the SBTOOLBOX2. © The Author 2011. Published by Oxford University Press. All rights reserved.

  15. STOCHSIMGPU: parallel stochastic simulation for the Systems Biology Toolbox 2 for MATLAB

    KAUST Repository

    Klingbeil, G.; Erban, R.; Giles, M.; Maini, P. K.

    2011-01-01

    Motivation: The importance of stochasticity in biological systems is becoming increasingly recognized and the computational cost of biologically realistic stochastic simulations urgently requires development of efficient software. We present a new

  16. Quantum Dynamics in Biological Systems

    Science.gov (United States)

    Shim, Sangwoo

    In the first part of this dissertation, recent efforts to understand quantum mechanical effects in biological systems are discussed. Especially, long-lived quantum coherences observed during the electronic energy transfer process in the Fenna-Matthews-Olson complex at physiological condition are studied extensively using theories of open quantum systems. In addition to the usual master equation based approaches, the effect of the protein structure is investigated in atomistic detail through the combined application of quantum chemistry and molecular dynamics simulations. To evaluate the thermalized reduced density matrix, a path-integral Monte Carlo method with a novel importance sampling approach is developed for excitons coupled to an arbitrary phonon bath at a finite temperature. In the second part of the thesis, simulations of molecular systems and applications to vibrational spectra are discussed. First, the quantum dynamics of a molecule is simulated by combining semiclassical initial value representation and density funcitonal theory with analytic derivatives. A computationally-tractable approximation to the sum-of-states formalism of Raman spectra is subsequently discussed.

  17. 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...

  18. An Integrated Biological Control System At Hanford

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  19. AN INTEGRATED BIOLOGICAL CONTROL SYSTEM AT HANFORD

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-02-11

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

  20. Metabolic engineering with systems biology tools to optimize production of prokaryotic secondary metabolites

    DEFF Research Database (Denmark)

    Kim, Hyun Uk; Charusanti, Pep; Lee, Sang Yup

    2016-01-01

    Metabolic engineering using systems biology tools is increasingly applied to overproduce secondary metabolites for their potential industrial production. In this Highlight, recent relevant metabolic engineering studies are analyzed with emphasis on host selection and engineering approaches...... for the optimal production of various prokaryotic secondary metabolites: native versus heterologous hosts (e.g., Escherichia coli) and rational versus random approaches. This comparative analysis is followed by discussions on systems biology tools deployed in optimizing the production of secondary metabolites....... The potential contributions of additional systems biology tools are also discussed in the context of current challenges encountered during optimization of secondary metabolite production....

  1. From immunology to MRI data anlysis: Problems in mathematical biology

    Science.gov (United States)

    Waters, Ryan Samuel

    This thesis represents a collection of four distinct biological projects rising from immunology and metabolomics that required unique and creative mathematical approaches. One project focuses on understanding the role IL-2 plays in immune response regulation and exploring how these effects can be altered. We developed several dynamic models of the receptor signaling network which we analyze analytically and numerically. In a second project focused also on MS, we sought to create a system for grading magnetic resonance images (MRI) with good correlation with disability. The goal is for these MRI scores to provide a better standard for large-scale clinical drug trials, which limits the bias associated with differences in available MRI technology and general grader/participant variability. The third project involves the study of the CRISPR adaptive immune system in bacteria. Bacterial cells recognize and acquire snippets of exogenous genetic material, which they incorporate into their DNA. In this project we explore the optimal design for the CRISPR system given a viral distribution to maximize its probability of survival. The final project involves the study of the benefits for colocalization of coupled enzymes in metabolic pathways. The hypothesized kinetic advantage, known as `channeling', of putting coupled enzymes closer together has been used as justification for the colocalization of coupled enzymes in biological systems. We developed and analyzed a simple partial differential equation of the diffusion of the intermediate substrate between coupled enzymes to explore the phenomena of channeling. The four projects of my thesis represent very distinct biological problems that required a variety of techniques from diverse areas of mathematics ranging from dynamical modeling to statistics, Fourier series and calculus of variations. In each case, quantitative techniques were used to address biological questions from a mathematical perspective ultimately providing

  2. Macroscopic Quantum-Type Potentials in Theoretical Systems Biology

    Directory of Open Access Journals (Sweden)

    Laurent Nottale

    2013-12-01

    Full Text Available We review in this paper the use of the theory of scale relativity and fractal space-time as a tool particularly well adapted to the possible development of a future genuine systems theoretical biology. We emphasize in particular the concept of quantum-type potentials, since, in many situations, the effect of the fractality of space—or of the underlying medium—can be reduced to the addition of such a potential energy to the classical equations of motion. Various equivalent representations—geodesic, quantum-like, fluid mechanical, stochastic—of these equations are given, as well as several forms of generalized quantum potentials. Examples of their possible intervention in high critical temperature superconductivity and in turbulence are also described, since some biological processes may be similar in some aspects to these physical phenomena. These potential extra energy contributions could have emerged in biology from the very fractal nature of the medium, or from an evolutive advantage, since they involve spontaneous properties of self-organization, morphogenesis, structuration and multi-scale integration. Finally, some examples of applications of the theory to actual biological-like processes and functions are also provided.

  3. Modular microfluidic system for biological sample preparation

    Science.gov (United States)

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

    2015-09-29

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

  4. Modelling, abstraction, and computation in systems biology: A view from computer science.

    Science.gov (United States)

    Melham, Tom

    2013-04-01

    Systems biology is centrally engaged with computational modelling across multiple scales and at many levels of abstraction. Formal modelling, precise and formalised abstraction relationships, and computation also lie at the heart of computer science--and over the past decade a growing number of computer scientists have been bringing their discipline's core intellectual and computational tools to bear on biology in fascinating new ways. This paper explores some of the apparent points of contact between the two fields, in the context of a multi-disciplinary discussion on conceptual foundations of systems biology. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Magnetic Actuation of Biological Systems

    Science.gov (United States)

    Lauback, Stephanie D.

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

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

    Science.gov (United States)

    Saks, Valdur; Monge, Claire; Guzun, Rita

    2009-01-01

    We live in times of paradigmatic changes for the biological sciences. Reductionism, that for the last six decades has been the philosophical basis of biochemistry and molecular biology, is being displaced by Systems Biology, which favors the study of integrated systems. Historically, Systems Biology - defined as the higher level analysis of complex biological systems - was pioneered by Claude Bernard in physiology, Norbert Wiener with the development of cybernetics, and Erwin Schrödinger in his thermodynamic approach to the living. Systems Biology applies methods inspired by cybernetics, network analysis, and non-equilibrium dynamics of open systems. These developments follow very precisely the dialectical principles of development from thesis to antithesis to synthesis discovered by Hegel. Systems Biology opens new perspectives for studies of the integrated processes of energy metabolism in different cells. These integrated systems acquire new, system-level properties due to interaction of cellular components, such as metabolic compartmentation, channeling and functional coupling mechanisms, which are central for regulation of the energy fluxes. State of the art of these studies in the new area of Molecular System Bioenergetics is analyzed. PMID:19399243

  7. Prostaglandins and their receptors in insect biology

    Directory of Open Access Journals (Sweden)

    David eStanley

    2011-12-01

    Full Text Available We treat the biological significance of prostaglandins (PGs and their known receptors in insect biology. PGs and related eicosanoids are oxygenated derivatives of arachidonic acid (AA and two other C20 polyunsaturated fatty acids. PGs are mostly appreciated in the context of biomedicine, but a growing body of literature indicates the biological significance of these compounds extends throughout the animal kingdom, and possibly beyond. PGs act in several crucial areas of insect biology. In reproduction, a specific PG, PGE2, releases oviposition behavior in most crickets and a few other insect species; PGs also mediate events in egg development in some species, which may represent all insects. PGs play major roles in modulating fluid secretion in Malpighian tubules, rectum and salivary glands, although, again, this has been studied in only a few insect species that may represent the Class. Insect immunity is a very complex defense system. PGs and other eicosanoids mediate a large number of immune reactions to infection and invasion. The actions of most PGs are mediated by specific receptors. Biomedical research has discovered a great deal of knowledge about PG receptors in mammals, including their structures, pharmacology, molecular biology and cellular locations. Studies of PG receptors in insects lag behind the biomedical background, however, recent results hold the promise of accelerated research in this area. A PG receptor has been identified in a class of lepidopteran hemocytes and experimentally linked to the release of prophenoloxidase. We conclude that research into PGs and their receptors in insects will lead to important advances in our understanding of insect biology.

  8. Growing trend of CE at the omics level: the frontier of systems biology.

    Science.gov (United States)

    Oh, Eulsik; Hasan, Md Nabiul; Jamshed, Muhammad; Park, Soo Hyun; Hong, Hye-Min; Song, Eun Joo; Yoo, Young Sook

    2010-01-01

    In a novel attempt to comprehend the complexity of life, systems biology has recently emerged as a state-of-the-art approach for biological research in contrast to the reductionist approaches that have been used in molecular cell biology since the 1950s. Because a massive amount of information is required in many systems biology studies of life processes, we have increasingly come to depend on techniques that provide high-throughput omics data. CE and CE coupled to MS have served as powerful analytical tools for providing qualitative and quantitative omics data. Recent systems biology studies have focused strongly on the diagnosis and treatment of diseases. The increasing number of clinical research papers on drug discovery and disease therapies reflects this growing interest among scientists. Since such clinical research reflects one of the ultimate purposes of bioscience, these trends will be sustained for a long time. Thus, this review mainly focuses on the application of CE and CE-MS in diagnosis as well as on the latest CE methods developed. Furthermore, we outline the new challenges that arose in 2008 and later in elucidating the system-level functions of the bioconstituents of living organisms.

  9. Biologically Inspired Micro-Flight Research

    Science.gov (United States)

    Raney, David L.; Waszak, Martin R.

    2003-01-01

    Natural fliers demonstrate a diverse array of flight capabilities, many of which are poorly understood. NASA has established a research project to explore and exploit flight technologies inspired by biological systems. One part of this project focuses on dynamic modeling and control of micro aerial vehicles that incorporate flexible wing structures inspired by natural fliers such as insects, hummingbirds and bats. With a vast number of potential civil and military applications, micro aerial vehicles represent an emerging sector of the aerospace market. This paper describes an ongoing research activity in which mechanization and control concepts for biologically inspired micro aerial vehicles are being explored. Research activities focusing on a flexible fixed- wing micro aerial vehicle design and a flapping-based micro aerial vehicle concept are presented.

  10. Notes on a PDE system for biological network formation

    KAUST Repository

    Haskovec, Jan

    2016-01-22

    We present new analytical and numerical results for the elliptic–parabolic system of partial differential equations proposed by Hu and Cai, which models the formation of biological transport networks. The model describes the pressure field using a Darcy’s type equation and the dynamics of the conductance network under pressure force effects. Randomness in the material structure is represented by a linear diffusion term and conductance relaxation by an algebraic decay term. The analytical part extends the results of Haskovec et al. (2015) regarding the existence of weak and mild solutions to the whole range of meaningful relaxation exponents. Moreover, we prove finite time extinction or break-down of solutions in the spatially one-dimensional setting for certain ranges of the relaxation exponent. We also construct stationary solutions for the case of vanishing diffusion and critical value of the relaxation exponent, using a variational formulation and a penalty method. The analytical part is complemented by extensive numerical simulations. We propose a discretization based on mixed finite elements and study the qualitative properties of network structures for various parameter values. Furthermore, we indicate numerically that some analytical results proved for the spatially one-dimensional setting are likely to be valid also in several space dimensions.

  11. Towards a system level understanding of non-model organisms sampled from the environment: a network biology approach.

    Directory of Open Access Journals (Sweden)

    Tim D Williams

    2011-08-01

    Full Text Available The acquisition and analysis of datasets including multi-level omics and physiology from non-model species, sampled from field populations, is a formidable challenge, which so far has prevented the application of systems biology approaches. If successful, these could contribute enormously to improving our understanding of how populations of living organisms adapt to environmental stressors relating to, for example, pollution and climate. Here we describe the first application of a network inference approach integrating transcriptional, metabolic and phenotypic information representative of wild populations of the European flounder fish, sampled at seven estuarine locations in northern Europe with different degrees and profiles of chemical contaminants. We identified network modules, whose activity was predictive of environmental exposure and represented a link between molecular and morphometric indices. These sub-networks represented both known and candidate novel adverse outcome pathways representative of several aspects of human liver pathophysiology such as liver hyperplasia, fibrosis, and hepatocellular carcinoma. At the molecular level these pathways were linked to TNF alpha, TGF beta, PDGF, AGT and VEGF signalling. More generally, this pioneering study has important implications as it can be applied to model molecular mechanisms of compensatory adaptation to a wide range of scenarios in wild populations.

  12. A Calculus for Modelling, Simulating and Analysing Compartmentalized Biological Systems

    DEFF Research Database (Denmark)

    Mardare, Radu Iulian; Ihekwaba, Adoha

    2007-01-01

    A. Ihekwaba, R. Mardare. A Calculus for Modelling, Simulating and Analysing Compartmentalized Biological Systems. Case study: NFkB system. In Proc. of International Conference of Computational Methods in Sciences and Engineering (ICCMSE), American Institute of Physics, AIP Proceedings, N 2...

  13. 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

  14. Approaches to Quality Risk Management When Using Single-Use Systems in the Manufacture of Biologics.

    Science.gov (United States)

    Ishii-Watabe, Akiko; Hirose, Akihiko; Katori, Noriko; Hashii, Norikata; Arai, Susumu; Awatsu, Hirotoshi; Eiza, Akira; Hara, Yoshiaki; Hattori, Hideshi; Inoue, Tomomi; Isono, Tetsuya; Iwakura, Masahiro; Kajihara, Daisuke; Kasahara, Nobuo; Matsuda, Hiroyuki; Murakami, Sei; Nakagawa, Taishiro; Okumura, Takehiro; Omasa, Takeshi; Takuma, Shinya; Terashima, Iyo; Tsukahara, Masayoshi; Tsutsui, Maiko; Yano, Takahiro; Kawasaki, Nana

    2015-10-01

    Biologics manufacturing technology has made great progress in the last decade. One of the most promising new technologies is the single-use system, which has improved the efficiency of biologics manufacturing processes. To ensure safety of biologics when employing such single-use systems in the manufacturing process, various issues need to be considered including possible extractables/leachables and particles arising from the components used in single-use systems. Japanese pharmaceutical manufacturers, together with single-use suppliers, members of the academia and regulatory authorities have discussed the risks of using single-use systems and established control strategies for the quality assurance of biologics. In this study, we describe approaches for quality risk management when employing single-use systems in the manufacturing of biologics. We consider the potential impact of impurities related to single-use components on drug safety and the potential impact of the single-use system on other critical quality attributes as well as the stable supply of biologics. We also suggest a risk-mitigating strategy combining multiple control methods which includes the selection of appropriate single-use components, their inspections upon receipt and before releasing for use and qualification of single-use systems. Communication between suppliers of single-use systems and the users, as well as change controls in the facilities both of suppliers and users, are also important in risk-mitigating strategies. Implementing these control strategies can mitigate the risks attributed to the use of single-use systems. This study will be useful in promoting the development of biologics as well as in ensuring their safety, quality and stable supply.

  15. Iterative Systems Biology for Medicine – time for advancing from network signature to mechanistic equations

    KAUST Repository

    Gomez-Cabrero, David

    2017-05-09

    The rise and growth of Systems Biology following the sequencing of the human genome has been astounding. Early on, an iterative wet-dry methodology was formulated which turned out as a successful approach in deciphering biological complexity. Such type of analysis effectively identified and associated molecular network signatures operative in biological processes across different systems. Yet, it has proven difficult to distinguish between causes and consequences, thus making it challenging to attack medical questions where we require precise causative drug targets and disease mechanisms beyond a web of associated markers. Here we review principal advances with regard to identification of structure, dynamics, control, and design of biological systems, following the structure in the visionary review from 2002 by Dr. Kitano. Yet, here we find that the underlying challenge of finding the governing mechanistic system equations enabling precision medicine remains open thus rendering clinical translation of systems biology arduous. However, stunning advances in raw computational power, generation of high-precision multi-faceted biological data, combined with powerful algorithms hold promise to set the stage for data-driven identification of equations implicating a fundamental understanding of living systems during health and disease.

  16. Growing trend of CE at the omics level: the frontier of systems biology--an update.

    Science.gov (United States)

    Ban, Eunmi; Park, Soo Hyun; Kang, Min-Jung; Lee, Hyun-Jung; Song, Eun Joo; Yoo, Young Sook

    2012-01-01

    Omics is the study of proteins, peptides, genes, and metabolites in living organisms. Systems biology aims to understand the system through the study of the relationship between elements such as genes and proteins in biological system. Recently, systems biology emerged as the result of the advanced development of high-throughput analysis technologies such as DNA sequencers, DNA arrays, and mass spectrometry for omics studies. Among a number of analytical tools and technologies, CE and CE coupled to MS are promising and relatively rapidly developing tools with the potential to provide qualitative and quantitative analyses of biological molecules. With an emphasis on CE for systems biology, this review summarizes the method developments and applications of CE for the genomic, transcriptomic, proteomic, and metabolomic studies focusing on the drug discovery and disease diagnosis and therapies since 2009. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. [Habitability and biological life support systems for man].

    Science.gov (United States)

    Gazenko, O G; Grigor'ev, A I; Meleshko, G I; Shepelev, E Ia

    1990-01-01

    This paper discusses general concepts and specific details of the habitability of space stations and planetary bases completely isolated from the Earth for long periods of time. It emphasizes inadequacy of the present-day knowledge about natural conditions that provide a biologically acceptable environment on the Earth as well as lack of information about life support systems as a source of consumables (oxygen, water, food) and a tool for waste management. The habitability of advanced space vehicles is closely related to closed bioregenerative systems used as life support systems.

  18. 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.

  19. 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. PMID:23170064

  20. Systems biology approaches and tools for analysis of interactomes and multi-target drugs.

    Science.gov (United States)

    Schrattenholz, André; Groebe, Karlfried; Soskic, Vukic

    2010-01-01

    Systems biology is essentially a proteomic and epigenetic exercise because the relatively condensed information of genomes unfolds on the level of proteins. The flexibility of cellular architectures is not only mediated by a dazzling number of proteinaceous species but moreover by the kinetics of their molecular changes: The time scales of posttranslational modifications range from milliseconds to years. The genetic framework of an organism only provides the blue print of protein embodiments which are constantly shaped by external input. Indeed, posttranslational modifications of proteins represent the scope and velocity of these inputs and fulfil the requirements of integration of external spatiotemporal signal transduction inside an organism. The optimization of biochemical networks for this type of information processing and storage results in chemically extremely fine tuned molecular entities. The huge dynamic range of concentrations, the chemical diversity and the necessity of synchronisation of complex protein expression patterns pose the major challenge of systemic analysis of biological models. One further message is that many of the key reactions in living systems are essentially based on interactions of moderate affinities and moderate selectivities. This principle is responsible for the enormous flexibility and redundancy of cellular circuitries. In complex disorders such as cancer or neurodegenerative diseases, which initially appear to be rooted in relatively subtle dysfunctions of multimodal physiologic pathways, drug discovery programs based on the concept of high affinity/high specificity compounds ("one-target, one-disease"), which has been dominating the pharmaceutical industry for a long time, increasingly turn out to be unsuccessful. Despite improvements in rational drug design and high throughput screening methods, the number of novel, single-target drugs fell much behind expectations during the past decade, and the treatment of "complex

  1. Roles of Nicotinamide Adenine Dinucleotide (NAD+ in Biological Systems

    Directory of Open Access Journals (Sweden)

    Palmiro Poltronieri

    2018-01-01

    Full Text Available NAD+ has emerged as a crucial element in both bioenergetic and signaling pathways since it acts as a key regulator of cellular and organism homeostasis. NAD+ is a coenzyme in redox reactions, a donor of adenosine diphosphate-ribose (ADPr moieties in ADP-ribosylation reactions, a substrate for sirtuins, a group of histone deacetylase enzymes that use NAD+ to remove acetyl groups from proteins; NAD+ is also a precursor of cyclic ADP-ribose, a second messenger in Ca++ release and signaling, and of diadenosine tetraphosphate (Ap4A and oligoadenylates (oligo2′-5′A, two immune response activating compounds. In the biological systems considered in this review, NAD+ is mostly consumed in ADP-ribose (ADPr transfer reactions. In this review the roles of these chemical products are discussed in biological systems, such as in animals, plants, fungi and bacteria. In the review, two types of ADP-ribosylating enzymes are introduced as well as the pathways to restore the NAD+ pools in these systems.

  2. Quantification of layered patterns with structural anisotropy: a comparison of biological and geological systems

    Directory of Open Access Journals (Sweden)

    I. Smolyar

    2016-03-01

    Full Text Available Large-scale patterns evident from satellite images of aeolian landforms on Earth and other planets; those of intermediate scale in marine and terrestrial sand ripples and sediment profiles; and small-scale patterns such as lamellae in the bones of vertebrates and annuli in fish scales are each represented by layers of different thicknesses and lengths. Layered patterns are important because they form a record of the state of internal and external factors that regulate pattern formation in these geological and biological systems. It is therefore potentially possible to recognize trends, periodicities, and events in the history of the formation of these systems among the incremental sequences. Though the structures and sizes of these 2-D patterns are typically scale-free, they are also characteristically anisotropic; that is, the number of layers and their absolute thicknesses vary significantly during formation. The aim of the present work is to quantify the structure of layered patterns and to reveal similarities and differences in the processing and interpretation of layered landforms and biological systems. To reach this goal we used N-partite graph and Boolean functions to quantify the structure of layers and plot charts for “layer thickness vs. layer number” and “layer area vs. layer number”. These charts serve as a source of information about events in the history of formation of layered systems. The concept of synchronization of layer formation across a 2-D plane is introduced to develop the procedure for plotting “layer thickness vs. layer number” and “layer area vs. layer number”, which takes into account the structural anisotropy of layered patterns and increase signal-to-noise ratio in charts. Examples include landforms on Mars and Earth and incremental layers in human and iguana bones.

  3. CASTOR BEAN AND SUNFLOWER INTERCROPPING SYSTEMS IN ROW ARRANGEMENT: BIOLOGICAL EFFICIENCY

    Directory of Open Access Journals (Sweden)

    Ciro de Miranda Pinto

    2012-07-01

    Full Text Available An experiment field was carried in the agricultural seasons 2008, 2009 and 2010, with aim of studying the response of castorbean (Ricinus communis L. intercropping with sunflower (Helianthus annus L. in row arrangement in the dryland farming conditions. In addition, it was evaluated the biological efficiency of plants in intercropping systems.The design used in the experiment was randomized block with seven treatement and four replications. The treatments were represented by rows of castor oil (Ma and sunflower (Gi listed below: 1Ma:1Gi; 1Ma:2Gi; 1Ma:3Gi; 2Ma:2Gi; 2Ma:3Gi; castor and sunflower in the monoculture. The efficiency of intercropping was measured by LER, ATER, LEC, average between LER and ATER, SPI and CoR. The grain yield of castor bean and sunflower were reduced in intercropped row arrangements. The row arrangement 1Ma:2Gi showed the smallest reduction of average productivity of castor beans and sunflower in the evaluation period of the experiment. The castor bean was the dominant crop in relation to sunflower.

  4. Using systems and structure biology tools to dissect cellular phenotypes.

    Science.gov (United States)

    Floratos, Aris; Honig, Barry; Pe'er, Dana; Califano, Andrea

    2012-01-01

    The Center for the Multiscale Analysis of Genetic Networks (MAGNet, http://magnet.c2b2.columbia.edu) was established in 2005, with the mission of providing the biomedical research community with Structural and Systems Biology algorithms and software tools for the dissection of molecular interactions and for the interaction-based elucidation of cellular phenotypes. Over the last 7 years, MAGNet investigators have developed many novel analysis methodologies, which have led to important biological discoveries, including understanding the role of the DNA shape in protein-DNA binding specificity and the discovery of genes causally related to the presentation of malignant phenotypes, including lymphoma, glioma, and melanoma. Software tools implementing these methodologies have been broadly adopted by the research community and are made freely available through geWorkbench, the Center's integrated analysis platform. Additionally, MAGNet has been instrumental in organizing and developing key conferences and meetings focused on the emerging field of systems biology and regulatory genomics, with special focus on cancer-related research.

  5. Structural Systems Biology Evaluation of Metabolic Thermotolerance in Escherichia coli

    DEFF Research Database (Denmark)

    Chang, Roger L.; Andrews, Kathleen; Kim, Donghyuk

    2013-01-01

    Improve the System A "systems biology" approach may clarify, for example, how particular proteins determine sensitivity of bacteria to extremes of temperature. Chang et al. (p. 1220) integrated information on protein structure with a model of metabolism, thus associating the protein structure of ...

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

    Directory of Open Access Journals (Sweden)

    Valdur Saks

    2009-03-01

    Full Text Available We live in times of paradigmatic changes for the biological sciences. Reductionism, that for the last six decades has been the philosophical basis of biochemistry and molecular biology, is being displaced by Systems Biology, which favors the study of integrated systems. Historically, Systems Biology - defined as the higher level analysis of complex biological systems - was pioneered by Claude Bernard in physiology, Norbert Wiener with the development of cybernetics, and Erwin Schrödinger in his thermodynamic approach to the living. Systems Biology applies methods inspired by cybernetics, network analysis, and non-equilibrium dynamics of open systems. These developments follow very precisely the dialectical principles of development from thesis to antithesis to synthesis discovered by Hegel. Systems Biology opens new perspectives for studies of the integrated processes of energy metabolism in different cells. These integrated systems acquire new, system-level properties due to interaction of cellular components, such as metabolic compartmentation, channeling and functional coupling mechanisms, which are central for regulation of the energy fluxes. State of the art of these studies in the new area of Molecular System Bioenergetics is analyzed.

  7. Using semantics for representing experimental protocols.

    Science.gov (United States)

    Giraldo, Olga; García, Alexander; López, Federico; Corcho, Oscar

    2017-11-13

    An experimental protocol is a sequence of tasks and operations executed to perform experimental research in biological and biomedical areas, e.g. biology, genetics, immunology, neurosciences, virology. Protocols often include references to equipment, reagents, descriptions of critical steps, troubleshooting and tips, as well as any other information that researchers deem important for facilitating the reusability of the protocol. Although experimental protocols are central to reproducibility, the descriptions are often cursory. There is the need for a unified framework with respect to the syntactic structure and the semantics for representing experimental protocols. In this paper we present "SMART Protocols ontology", an ontology for representing experimental protocols. Our ontology represents the protocol as a workflow with domain specific knowledge embedded within a document. We also present the S ample I nstrument R eagent O bjective (SIRO) model, which represents the minimal common information shared across experimental protocols. SIRO was conceived in the same realm as the Patient Intervention Comparison Outcome (PICO) model that supports search, retrieval and classification purposes in evidence based medicine. We evaluate our approach against a set of competency questions modeled as SPARQL queries and processed against a set of published and unpublished protocols modeled with the SP Ontology and the SIRO model. Our approach makes it possible to answer queries such as Which protocols use tumor tissue as a sample. Improving reporting structures for experimental protocols requires collective efforts from authors, peer reviewers, editors and funding bodies. The SP Ontology is a contribution towards this goal. We build upon previous experiences and bringing together the view of researchers managing protocols in their laboratory work. Website: https://smartprotocols.github.io/ .

  8. 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.

  9. Ordinary differential equations with applications in molecular biology.

    Science.gov (United States)

    Ilea, M; Turnea, M; Rotariu, M

    2012-01-01

    Differential equations are of basic importance in molecular biology mathematics because many biological laws and relations appear mathematically in the form of a differential equation. In this article we presented some applications of mathematical models represented by ordinary differential equations in molecular biology. The vast majority of quantitative models in cell and molecular biology are formulated in terms of ordinary differential equations for the time evolution of concentrations of molecular species. Assuming that the diffusion in the cell is high enough to make the spatial distribution of molecules homogenous, these equations describe systems with many participating molecules of each kind. We propose an original mathematical model with small parameter for biological phospholipid pathway. All the equations system includes small parameter epsilon. The smallness of epsilon is relative to the size of the solution domain. If we reduce the size of the solution region the same small epsilon will result in a different condition number. It is clear that the solution for a smaller region is less difficult. We introduce the mathematical technique known as boundary function method for singular perturbation system. In this system, the small parameter is an asymptotic variable, different from the independent variable. In general, the solutions of such equations exhibit multiscale phenomena. Singularly perturbed problems form a special class of problems containing a small parameter which may tend to zero. Many molecular biology processes can be quantitatively characterized by ordinary differential equations. Mathematical cell biology is a very active and fast growing interdisciplinary area in which mathematical concepts, techniques, and models are applied to a variety of problems in developmental medicine and bioengineering. Among the different modeling approaches, ordinary differential equations (ODE) are particularly important and have led to significant advances

  10. 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.

  11. The Systems Biology Research Tool: evolvable open-source software

    OpenAIRE

    Wright, J; Wagner, A

    2008-01-01

    Abstract Background Research in the field of systems biology requires software for a variety of purposes. Software must be used to store, retrieve, analyze, and sometimes even to collect the data obtained from system-level (often high-throughput) experiments. Software must also be used to implement mathematical models and algorithms required for simulation and theoretical predictions on the system-level. Results We introduce a free, easy-to-use, open-source, integrated software platform calle...

  12. Biological indicators for monitoring water quality of MTF canals system

    Science.gov (United States)

    Sethi, S. L.

    1975-01-01

    Biological models, diversity indexes, were developed to predict environmental effects of NASA's Mississippi test facility (MTF) chemical operations on canal systems in the area. To predict the effects on local streams, a physical model of unpolluted streams was established. The model is fed by artesian well water free of background levels of pollutants. The species diversity and biota composition of unpolluted MTF stream was determined; resulting information will be used to form baseline data for future comparisons. Biological modeling was accomplished by adding controlled quantities or kinds of chemical pollutants and evaluating the effects of these chemicals on the biological life of the stream.

  13. Discovering biological progression underlying microarray samples.

    Directory of Open Access Journals (Sweden)

    Peng Qiu

    2011-04-01

    Full Text Available In biological systems that undergo processes such as differentiation, a clear concept of progression exists. We present a novel computational approach, called Sample Progression Discovery (SPD, to discover patterns of biological progression underlying microarray gene expression data. SPD assumes that individual samples of a microarray dataset are related by an unknown biological process (i.e., differentiation, development, cell cycle, disease progression, and that each sample represents one unknown point along the progression of that process. SPD aims to organize the samples in a manner that reveals the underlying progression and to simultaneously identify subsets of genes that are responsible for that progression. We demonstrate the performance of SPD on a variety of microarray datasets that were generated by sampling a biological process at different points along its progression, without providing SPD any information of the underlying process. When applied to a cell cycle time series microarray dataset, SPD was not provided any prior knowledge of samples' time order or of which genes are cell-cycle regulated, yet SPD recovered the correct time order and identified many genes that have been associated with the cell cycle. When applied to B-cell differentiation data, SPD recovered the correct order of stages of normal B-cell differentiation and the linkage between preB-ALL tumor cells with their cell origin preB. When applied to mouse embryonic stem cell differentiation data, SPD uncovered a landscape of ESC differentiation into various lineages and genes that represent both generic and lineage specific processes. When applied to a prostate cancer microarray dataset, SPD identified gene modules that reflect a progression consistent with disease stages. SPD may be best viewed as a novel tool for synthesizing biological hypotheses because it provides a likely biological progression underlying a microarray dataset and, perhaps more importantly, the

  14. Macro to microfluidics system for biological environmental monitoring.

    Science.gov (United States)

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

    2012-01-01

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

  15. Co-culture systems and technologies: taking synthetic biology to the next level.

    Science.gov (United States)

    Goers, Lisa; Freemont, Paul; Polizzi, Karen M

    2014-07-06

    Co-culture techniques find myriad applications in biology for studying natural or synthetic interactions between cell populations. Such techniques are of great importance in synthetic biology, as multi-species cell consortia and other natural or synthetic ecology systems are widely seen to hold enormous potential for foundational research as well as novel industrial, medical and environmental applications with many proof-of-principle studies in recent years. What is needed for co-cultures to fulfil their potential? Cell-cell interactions in co-cultures are strongly influenced by the extracellular environment, which is determined by the experimental set-up, which therefore needs to be given careful consideration. An overview of existing experimental and theoretical co-culture set-ups in synthetic biology and adjacent fields is given here, and challenges and opportunities involved in such experiments are discussed. Greater focus on foundational technology developments for co-cultures is needed for many synthetic biology systems to realize their potential in both applications and answering biological questions. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  16. Organizing principles as tools for bridging the gap between system theory and biological experimentation.

    Science.gov (United States)

    Mekios, Constantinos

    2016-04-01

    Twentieth-century theoretical efforts towards the articulation of general system properties came short of having the significant impact on biological practice that their proponents envisioned. Although the latter did arrive at preliminary mathematical formulations of such properties, they had little success in showing how these could be productively incorporated into the research agenda of biologists. Consequently, the gap that kept system-theoretic principles cut-off from biological experimentation persisted. More recently, however, simple theoretical tools have proved readily applicable within the context of systems biology. In particular, examples reviewed in this paper suggest that rigorous mathematical expressions of design principles, imported primarily from engineering, could produce experimentally confirmable predictions of the regulatory properties of small biological networks. But this is not enough for contemporary systems biologists who adopt the holistic aspirations of early systemologists, seeking high-level organizing principles that could provide insights into problems of biological complexity at the whole-system level. While the presented evidence is not conclusive about whether this strategy could lead to the realization of the lofty goal of a comprehensive explanatory integration, it suggests that the ongoing quest for organizing principles is pragmatically advantageous for systems biologists. The formalisms postulated in the course of this process can serve as bridges between system-theoretic concepts and the results of molecular experimentation: they constitute theoretical tools for generalizing molecular data, thus producing increasingly accurate explanations of system-wide phenomena.

  17. 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.

  18. The quest for a new modelling framework in mathematical biology. Comment on "On the interplay between mathematics and biology: Hallmarks towards a new systems biology" by N. Bellomo et al.

    Science.gov (United States)

    Eftimie, Raluca

    2015-03-01

    One of the main unsolved problems of modern physics is finding a "theory of everything" - a theory that can explain, with the help of mathematics, all physical aspects of the universe. While the laws of physics could explain some aspects of the biology of living systems (e.g., the phenomenological interpretation of movement of cells and animals), there are other aspects specific to biology that cannot be captured by physics models. For example, it is generally accepted that the evolution of a cell-based system is influenced by the activation state of cells (e.g., only activated and functional immune cells can fight diseases); on the other hand, the evolution of an animal-based system can be influenced by the psychological state (e.g., distress) of animals. Therefore, the last 10-20 years have seen also a quest for a "theory of everything"-approach extended to biology, with researchers trying to propose mathematical modelling frameworks that can explain various biological phenomena ranging from ecology to developmental biology and medicine [1,2,6]. The basic idea behind this approach can be found in a few reviews on ecology and cell biology [6,7,9-11], where researchers suggested that due to the parallel between the micro-scale dynamics and the emerging macro-scale phenomena in both cell biology and in ecology, many mathematical methods used for ecological processes could be adapted to cancer modelling [7,9] or to modelling in immunology [11]. However, this approach generally involved the use of different models to describe different biological aspects (e.g., models for cell and animal movement, models for competition between cells or animals, etc.).

  19. The SEEK: a platform for sharing data and models in systems biology.

    Science.gov (United States)

    Wolstencroft, Katy; Owen, Stuart; du Preez, Franco; Krebs, Olga; Mueller, Wolfgang; Goble, Carole; Snoep, Jacky L

    2011-01-01

    Systems biology research is typically performed by multidisciplinary groups of scientists, often in large consortia and in distributed locations. The data generated in these projects tend to be heterogeneous and often involves high-throughput "omics" analyses. Models are developed iteratively from data generated in the projects and from the literature. Consequently, there is a growing requirement for exchanging experimental data, mathematical models, and scientific protocols between consortium members and a necessity to record and share the outcomes of experiments and the links between data and models. The overall output of a research consortium is also a valuable commodity in its own right. The research and associated data and models should eventually be available to the whole community for reuse and future analysis. The SEEK is an open-source, Web-based platform designed for the management and exchange of systems biology data and models. The SEEK was originally developed for the SysMO (systems biology of microorganisms) consortia, but the principles and objectives are applicable to any systems biology project. The SEEK provides an index of consortium resources and acts as gateway to other tools and services commonly used in the community. For example, the model simulation tool, JWS Online, has been integrated into the SEEK, and a plug-in to PubMed allows publications to be linked to supporting data and author profiles in the SEEK. The SEEK is a pragmatic solution to data management which encourages, but does not force, researchers to share and disseminate their data to community standard formats. It provides tools to assist with management and annotation as well as incentives and added value for following these recommendations. Data exchange and reuse rely on sufficient annotation, consistent metadata descriptions, and the use of standard exchange formats for models, data, and the experiments they are derived from. In this chapter, we present the SEEK platform

  20. Understanding genetic variation - the value of systems biology.

    Science.gov (United States)

    Hütt, Marc-Thorsten

    2014-04-01

    Pharmacology is currently transformed by the vast amounts of genome-associated information available for system-level interpretation. Here I review the potential of systems biology to facilitate this interpretation, thus paving the way for the emerging field of systems pharmacology. In particular, I will show how gene regulatory and metabolic networks can serve as a framework for interpreting high throughput data and as an interface to detailed dynamical models. In addition to the established connectivity analyses of effective networks, I suggest here to also analyze higher order architectural properties of effective networks. © 2013 The British Pharmacological Society.

  1. Cell illustrator 4.0: a computational platform for systems biology.

    Science.gov (United States)

    Nagasaki, Masao; Saito, Ayumu; Jeong, Euna; Li, Chen; Kojima, Kaname; Ikeda, Emi; Miyano, Satoru

    2011-01-01

    Cell Illustrator is a software platform for Systems Biology that uses the concept of Petri net for modeling and simulating biopathways. It is intended for biological scientists working at bench. The latest version of Cell Illustrator 4.0 uses Java Web Start technology and is enhanced with new capabilities, including: automatic graph grid layout algorithms using ontology information; tools using Cell System Markup Language (CSML) 3.0 and Cell System Ontology 3.0; parameter search module; high-performance simulation module; CSML database management system; conversion from CSML model to programming languages (FORTRAN, C, C++, Java, Python and Perl); import from SBML, CellML, and BioPAX; and, export to SVG and HTML. Cell Illustrator employs an extension of hybrid Petri net in an object-oriented style so that biopathway models can include objects such as DNA sequence, molecular density, 3D localization information, transcription with frame-shift, translation with codon table, as well as biochemical reactions.

  2. Interactions between physical, chemical and biological processes in aquatic systems - impacts on receiving waters with different contents of treated wastewater

    International Nuclear Information System (INIS)

    Kreuzinger, N.

    2000-08-01

    Two scenarios have be chosen within this PhD Thesis to describe the integrative key-significance of interactions between most relevant physical, chemical and biological processes in aquatic systems. These two case studies are used to illustrate and describe the importance of a detailed synthesis of biological, physical and chemical interactions in aquatic systems in order to provide relevant protection of water resources and to perform a sound water management. Methods are described to allow a detailed assessment of particular aspects within the complexity of the overall integration and therefore serve as a basis to determine the eventual necessity of proposed water management measures. Regarding the anthropogenic influence of treated wastewater on aquatic systems, one case study focuses on the interactions between emitted waters from a wastewater treatment plant and the resulting immission situation of its receiving water (The receiving water is quantitatively influenced by the treated wastewater by 95 %). This thesis proves that the effluent of wastewater treatment plants operated by best available technology meets the quality standards of running waters for the nutrients nitrogen and phosphorus, carbon-parameters, oxygen-regime and ecotoxicology. Within the second case study the focus is put on interactions between immissions and water usage. The general importance of biological phosphorus precipitation on the trophic situation of aquatic systems is described. Nevertheless, this generally known but within the field of applied limnology so far unrespected process of immobilization of phosphorus could be shown to represent a significant and major impact on phytoplannctotic development and eutrification. (author)

  3. Evaluation of impedance on biological Tissues using automatic control measurement system

    Energy Technology Data Exchange (ETDEWEB)

    Kil, Sang Hyeong; Shin, Dong Hoon; Lee, Seong Mo [Pusan National University, Yangsan (Korea, Republic of); Lee, Moo Seok; Kim, Sang Sik [Pusan National University, Busan (Korea, Republic of); Kim, Gun FDo; Lee, Jong Kyu [Pukyung National University, Busan (Korea, Republic of)

    2015-08-15

    Each biological tissue has endemic electrical characteristics owing to various differences such as those in cellular arrangement or organization form. The endemic electrical characteristics change when any biological change occurs. This work is a preliminary study surveying the changes in the electrical characteristics of biological tissue caused by radiation exposure. For protection against radiation hazards, therefore the electrical characteristics of living tissue were evaluated after development of the automatic control measurement system using LabVIEW. No alteration of biological tissues was observed before and after measurement of the electrical characteristics, and the biological tissues exhibited similar patterns. Through repeated measurements using the impedance/gain-phase analyzer, the coefficient of variation was determined as within 10%. The reproducibility impedance phase difference in electrical characteristics of the biological tissue did not change, and the tissue had resistance. The absolute value of impedance decreased constantly in proportion to the frequency. It has become possible to understand the electrical characteristics of biological tissues through the measurements made possible by the use of the developed.

  4. Evaluation of impedance on biological Tissues using automatic control measurement system

    International Nuclear Information System (INIS)

    Kil, Sang Hyeong; Shin, Dong Hoon; Lee, Seong Mo; Lee, Moo Seok; Kim, Sang Sik; Kim, Gun FDo; Lee, Jong Kyu

    2015-01-01

    Each biological tissue has endemic electrical characteristics owing to various differences such as those in cellular arrangement or organization form. The endemic electrical characteristics change when any biological change occurs. This work is a preliminary study surveying the changes in the electrical characteristics of biological tissue caused by radiation exposure. For protection against radiation hazards, therefore the electrical characteristics of living tissue were evaluated after development of the automatic control measurement system using LabVIEW. No alteration of biological tissues was observed before and after measurement of the electrical characteristics, and the biological tissues exhibited similar patterns. Through repeated measurements using the impedance/gain-phase analyzer, the coefficient of variation was determined as within 10%. The reproducibility impedance phase difference in electrical characteristics of the biological tissue did not change, and the tissue had resistance. The absolute value of impedance decreased constantly in proportion to the frequency. It has become possible to understand the electrical characteristics of biological tissues through the measurements made possible by the use of the developed.

  5. How causal analysis can reveal autonomy in models of biological systems

    Science.gov (United States)

    Marshall, William; Kim, Hyunju; Walker, Sara I.; Tononi, Giulio; Albantakis, Larissa

    2017-11-01

    Standard techniques for studying biological systems largely focus on their dynamical or, more recently, their informational properties, usually taking either a reductionist or holistic perspective. Yet, studying only individual system elements or the dynamics of the system as a whole disregards the organizational structure of the system-whether there are subsets of elements with joint causes or effects, and whether the system is strongly integrated or composed of several loosely interacting components. Integrated information theory offers a theoretical framework to (1) investigate the compositional cause-effect structure of a system and to (2) identify causal borders of highly integrated elements comprising local maxima of intrinsic cause-effect power. Here we apply this comprehensive causal analysis to a Boolean network model of the fission yeast (Schizosaccharomyces pombe) cell cycle. We demonstrate that this biological model features a non-trivial causal architecture, whose discovery may provide insights about the real cell cycle that could not be gained from holistic or reductionist approaches. We also show how some specific properties of this underlying causal architecture relate to the biological notion of autonomy. Ultimately, we suggest that analysing the causal organization of a system, including key features like intrinsic control and stable causal borders, should prove relevant for distinguishing life from non-life, and thus could also illuminate the origin of life problem. This article is part of the themed issue 'Reconceptualizing the origins of life'.

  6. Systems biology approaches to the study of cardiovascular drugs

    NARCIS (Netherlands)

    Nikolsky, Y.; Kleemann, R.

    2010-01-01

    Atherogenic lipids and chronic inflammation drive the development of cardiovascular disorders such as atherosclerosis. Many cardiovascular drugs target the liver which is involved in the formation of lipid and inflammatory risk factors. With robust systems biology tools and comprehensive

  7. BIOZON: a system for unification, management and analysis of heterogeneous biological data

    Directory of Open Access Journals (Sweden)

    Yona Golan

    2006-02-01

    Full Text Available Abstract Background Integration of heterogeneous data types is a challenging problem, especially in biology, where the number of databases and data types increase rapidly. Amongst the problems that one has to face are integrity, consistency, redundancy, connectivity, expressiveness and updatability. Description Here we present a system (Biozon that addresses these problems, and offers biologists a new knowledge resource to navigate through and explore. Biozon unifies multiple biological databases consisting of a variety of data types (such as DNA sequences, proteins, interactions and cellular pathways. It is fundamentally different from previous efforts as it uses a single extensive and tightly connected graph schema wrapped with hierarchical ontology of documents and relations. Beyond warehousing existing data, Biozon computes and stores novel derived data, such as similarity relationships and functional predictions. The integration of similarity data allows propagation of knowledge through inference and fuzzy searches. Sophisticated methods of query that span multiple data types were implemented and first-of-a-kind biological ranking systems were explored and integrated. Conclusion The Biozon system is an extensive knowledge resource of heterogeneous biological data. Currently, it holds more than 100 million biological documents and 6.5 billion relations between them. The database is accessible through an advanced web interface that supports complex queries, "fuzzy" searches, data materialization and more, online at http://biozon.org.

  8. Neuroproteomics and Systems Biology Approach to Identify Temporal Biomarker Changes Post Experimental Traumatic Brain Injury in Rats

    Directory of Open Access Journals (Sweden)

    Firas H Kobeissy

    2016-11-01

    Full Text Available Traumatic brain injury (TBI represents a critical health problem of which diagnosis, management and treatment remain challenging. TBI is a contributing factor in approximately 1/3 of all injury-related deaths in the United States. The Centers for Disease Control and Prevention (CDC estimate that 1.7 million TBI people suffer a TBI in the United States annually. Efforts continue to focus on elucidating the complex molecular mechanisms underlying TBI pathophysiology and defining sensitive and specific biomarkers that can aid in improving patient management and care. Recently, the area of neuroproteomics-systems biology is proving to be a prominent tool in biomarker discovery for central nervous system (CNS injury and other neurological diseases. In this work, we employed the controlled cortical impact (CCI model of experimental TBI in rat model to assess the temporal-global proteome changes after acute (1 day and for the first time, subacute (7 days, post-injury time frame using the established CAX-PAGE LC-MS/MS platform for protein separation combined with discrete systems biology analyses to identify temporal biomarker changes related to this rat TBI model. Rather than focusing on any one individual molecular entities, we used in silico systems biology approach to understand the global dynamics that govern proteins that are differentially altered post-injury. In addition, gene ontology analysis of the proteomic data was conducted in order to categorize the proteins by molecular function, biological process, and cellular localization. Results show alterations in several proteins related to inflammatory responses and oxidative stress in both acute (1 day and subacute (7 days periods post TBI. Moreover, results suggest a differential upregulation of neuroprotective proteins at 7-days post-CCI involved in cellular functions such as neurite growth, regeneration, and axonal guidance. Our study is amongst the first to assess temporal neuroproteome

  9. Reducing and verifying haloacetic acids in treated drinking water using a biological filter system.

    Science.gov (United States)

    Lou, Jie C; Chan, Hung Y; Yang, Chih Y; Tseng, Wei B; Han, Jia Y

    2014-01-01

    This study focused on reducing the haloacetic acid (HAA) concentrations in treated drinking water. HAA has been thought to be one possible nutrient supporting heterotrophic bacteria regrowth in drinking water. In this study, experiments were conducted using a pilot-scale system to evaluate the efficiency of biological filters (BF) for reducing excess HAA concentrations in water. The BF system reduced the total HAA concentration and the concentrations of five HAA species in the water. Dichloroacetic acid (DCAA), monobromoacetic acid (MBAA) and dibromoacetic acid (DBAA) were the three main HAA5 species that were present in the treated drinking water in this investigation. Combined, these three species represent approximately 77% of the HAA5 in the finished water after BF. The verification of the empirical HAA equation for the outlet in the BF system indicated linear relationships with high correlation coefficients. The empirical equation for the HAA5 concentrations in the finished water was established by examining other nutrients (e.g., dissolved organic carbon (DOC), ultraviolet absorbance at 254 nm wavelength (UV254), and ammonia nitrogen) that can reduce pathogenic contamination. These findings may be useful for designing advanced processes for conventional water treatment plants or for managing water treatment and distribution systems for providing high-quality drinking water.

  10. A data integration approach for cell cycle analysis oriented to model simulation in systems biology

    Directory of Open Access Journals (Sweden)

    Mosca Ettore

    2007-08-01

    Full Text Available Abstract Background The cell cycle is one of the biological processes most frequently investigated in systems biology studies and it involves the knowledge of a large number of genes and networks of protein interactions. A deep knowledge of the molecular aspect of this biological process can contribute to making cancer research more accurate and innovative. In this context the mathematical modelling of the cell cycle has a relevant role to quantify the behaviour of each component of the systems. The mathematical modelling of a biological process such as the cell cycle allows a systemic description that helps to highlight some features such as emergent properties which could be hidden when the analysis is performed only from a reductionism point of view. Moreover, in modelling complex systems, a complete annotation of all the components is equally important to understand the interaction mechanism inside the network: for this reason data integration of the model components has high relevance in systems biology studies. Description In this work, we present a resource, the Cell Cycle Database, intended to support systems biology analysis on the Cell Cycle process, based on two organisms, yeast and mammalian. The database integrates information about genes and proteins involved in the cell cycle process, stores complete models of the interaction networks and allows the mathematical simulation over time of the quantitative behaviour of each component. To accomplish this task, we developed, a web interface for browsing information related to cell cycle genes, proteins and mathematical models. In this framework, we have implemented a pipeline which allows users to deal with the mathematical part of the models, in order to solve, using different variables, the ordinary differential equation systems that describe the biological process. Conclusion This integrated system is freely available in order to support systems biology research on the cell cycle and

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

    KAUST Repository

    Nielsen, Jens

    2016-01-01

    . 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

  12. Evolving cell models for systems and synthetic biology.

    Science.gov (United States)

    Cao, Hongqing; Romero-Campero, Francisco J; Heeb, Stephan; Cámara, Miguel; Krasnogor, Natalio

    2010-03-01

    This paper proposes a new methodology for the automated design of cell models for systems and synthetic biology. Our modelling framework is based on P systems, a discrete, stochastic and modular formal modelling language. The automated design of biological models comprising the optimization of the model structure and its stochastic kinetic constants is performed using an evolutionary algorithm. The evolutionary algorithm evolves model structures by combining different modules taken from a predefined module library and then it fine-tunes the associated stochastic kinetic constants. We investigate four alternative objective functions for the fitness calculation within the evolutionary algorithm: (1) equally weighted sum method, (2) normalization method, (3) randomly weighted sum method, and (4) equally weighted product method. The effectiveness of the methodology is tested on four case studies of increasing complexity including negative and positive autoregulation as well as two gene networks implementing a pulse generator and a bandwidth detector. We provide a systematic analysis of the evolutionary algorithm's results as well as of the resulting evolved cell models.

  13. Improvements in algal lipid production: a systems biology and gene editing approach.

    Science.gov (United States)

    Banerjee, Avik; Banerjee, Chiranjib; Negi, Sangeeta; Chang, Jo-Shu; Shukla, Pratyoosh

    2018-05-01

    In the wake of rising energy demands, microalgae have emerged as potential sources of sustainable and renewable carbon-neutral fuels, such as bio-hydrogen and bio-oil. For rational metabolic engineering, the elucidation of metabolic pathways in fine detail and their manipulation according to requirements is the key to exploiting the use of microalgae. Emergence of site-specific nucleases have revolutionized applied research leading to biotechnological gains. Genome engineering as well as modulation of the endogenous genome with high precision using CRISPR systems is being gradually employed in microalgal research. Further, to optimize and produce better algal platforms, use of systems biology network analysis and integration of omics data is required. This review discusses two important approaches: systems biology and gene editing strategies used on microalgal systems with a focus on biofuel production and sustainable solutions. It also emphasizes that the integration of such systems would contribute and compliment applied research on microalgae. Recent advances in microalgae are discussed, including systems biology, gene editing approaches in lipid bio-synthesis, and antenna engineering. Lastly, it has been attempted here to showcase how CRISPR/Cas systems are a better editing tool than existing techniques that can be utilized for gene modulation and engineering during biofuel production.

  14. Recent developments in systems biology and metabolic engineering of plant microbe interactions

    Directory of Open Access Journals (Sweden)

    Vishal Kumar

    2016-09-01

    Full Text Available Microorganisms play a crucial role in the sustainability of the various ecosystems. The characterization of various interactions between microorganisms and other biotic factors is a necessary footstep to understand the association and functions of microbial communities. Among the different microbial interactions in an ecosystem, plant-microbe interaction plays an important role to balance the ecosystem. The present review explores plant microbe interactions using gene editing and system biology tools towards the comprehension in improvement of plant traits. Further, system biology tools like FBA, OptKnock and constrain based modeling helps in understanding such interactions as a whole. In addition, various gene editing tools have been summarized and a strategy has been hypothesized for the development of disease free plants. Furthermore, we have tried to summarize the predictions through data retrieved from various types of sources such as high throughput sequencing data (e.g. single nucleotide polymorphism (SNP detection, RNA-seq, proteomics and metabolic models have been reconstructed from such sequences for species communities. It is well known fact that systems biology approaches and modeling of biological networks will enable us to learn the insight of such network and will also help further in understanding these interactions.

  15. STOCHSIMGPU: parallel stochastic simulation for the Systems Biology Toolbox 2 for MATLAB.

    Science.gov (United States)

    Klingbeil, Guido; Erban, Radek; Giles, Mike; Maini, Philip K

    2011-04-15

    The importance of stochasticity in biological systems is becoming increasingly recognized and the computational cost of biologically realistic stochastic simulations urgently requires development of efficient software. We present a new software tool STOCHSIMGPU that exploits graphics processing units (GPUs) for parallel stochastic simulations of biological/chemical reaction systems and show that significant gains in efficiency can be made. It is integrated into MATLAB and works with the Systems Biology Toolbox 2 (SBTOOLBOX2) for MATLAB. The GPU-based parallel implementation of the Gillespie stochastic simulation algorithm (SSA), the logarithmic direct method (LDM) and the next reaction method (NRM) is approximately 85 times faster than the sequential implementation of the NRM on a central processing unit (CPU). Using our software does not require any changes to the user's models, since it acts as a direct replacement of the stochastic simulation software of the SBTOOLBOX2. The software is open source under the GPL v3 and available at http://www.maths.ox.ac.uk/cmb/STOCHSIMGPU. The web site also contains supplementary information. klingbeil@maths.ox.ac.uk Supplementary data are available at Bioinformatics online.

  16. Systems Biology Approaches to Discerning Striated Muscle Pathologies

    OpenAIRE

    Mukund, Kavitha

    2016-01-01

    The human muscular system represents nearly 75% of the body mass and encompasses two major muscle forms- striated and smooth. Striated muscle, composed broadly of myofibers, accompanying membrane systems, cytoskeletal networks together with the metabolic and regulatory machinery, have revealed complexities in composition, structure and function. A disruption to any component within this complex system of interactions lead to disorders of the muscle, typically characterized by muscle fiber los...

  17. Casual Games and Casual Learning About Human Biological Systems

    Science.gov (United States)

    Price, C. Aaron; Gean, Katherine; Christensen, Claire G.; Beheshti, Elham; Pernot, Bryn; Segovia, Gloria; Person, Halcyon; Beasley, Steven; Ward, Patricia

    2016-02-01

    Casual games are everywhere. People play them throughout life to pass the time, to engage in social interactions, and to learn. However, their simplicity and use in distraction-heavy environments can attenuate their potential for learning. This experimental study explored the effects playing an online, casual game has on awareness of human biological systems. Two hundred and forty-two children were given pretests at a Museum and posttests at home after playing either a treatment or control game. Also, 41 children were interviewed to explore deeper meanings behind the test results. Results show modest improvement in scientific attitudes, ability to identify human biological systems and in the children's ability to describe how those systems work together in real-world scenarios. Interviews reveal that children drew upon their prior school learning as they played the game. Also, on the surface they perceived the game as mainly entertainment but were easily able to discern learning outcomes when prompted. Implications for the design of casual games and how they can be used to enhance transfer of knowledge from the classroom to everyday life are discussed.

  18. Allostatic load and biological anthropology.

    Science.gov (United States)

    Edes, Ashley N; Crews, Douglas E

    2017-01-01

    Multiple stressors affect developing and adult organisms, thereby partly structuring their phenotypes. Determining how stressors influence health, well-being, and longevity in human and nonhuman primate populations are major foci within biological anthropology. Although much effort has been devoted to examining responses to multiple environmental and sociocultural stressors, no holistic metric to measure stress-related physiological dysfunction has been widely applied within biological anthropology. Researchers from disciplines outside anthropology are using allostatic load indices (ALIs) to estimate such dysregulation and examine life-long outcomes of stressor exposures, including morbidity and mortality. Following allostasis theory, allostatic load represents accumulated physiological and somatic damage secondary to stressors and senescent processes experienced over the lifespan. ALIs estimate this wear-and-tear using a composite of biomarkers representing neuroendocrine, cardiovascular, metabolic, and immune systems. Across samples, ALIs are associated significantly with multiple individual characteristics (e.g., age, sex, education, DNA variation) of interest within biological anthropology. They also predict future outcomes, including aspects of life history variation (e.g., survival, lifespan), mental and physical health, morbidity and mortality, and likely health disparities between groups, by stressor exposures, ethnicity, occupations, and degree of departure from local indigenous life ways and integration into external and commodified ones. ALIs also may be applied to similar stress-related research areas among nonhuman primates. Given the reports from multiple research endeavors, here we propose ALIs may be useful for assessing stressors, stress responses, and stress-related dysfunction, current and long-term cognitive function, health and well-being, and risk of early mortality across many research programs within biological anthropology. © 2017 American

  19. A systems biology approach for miRNA-mRNA expression patterns analysis in non-small cell lung cancer.

    Science.gov (United States)

    Najafi, Ali; Tavallaei, Mahmood; Hosseini, Sayed Mostafa

    2016-01-01

    Non-small cell lung cancers (NSCLCs) is a prevalent and heterogeneous subtype of lung cancer accounting for 85 percent of patients. MicroRNAs (miRNAs), a class of small endogenous non-coding RNAs, incorporate into regulation of gene expression post-transcriptionally. Therefore, deregulation of miRNAs' expression has provided further layers of complexity to the molecular etiology and pathogenesis of different diseases and malignancies. Although, until now considerable number of studies has been carried out to illuminate this complexity in NSCLC, they have remained less effective in their goal due to lack of a holistic and integrative systems biology approach which considers all natural elaborations of miRNAs' function. It is able to reliably nominate most affected signaling pathways and therapeutic target genes by deregulated miRNAs during a particular pathological condition. Herein, we utilized a holistic systems biology approach, based on appropriate re-analyses of microarray datasets followed by reliable data filtering, to analyze integrative and combinatorial deregulated miRNA-mRNA interaction network in NSCLC, aiming to ascertain miRNA-dysregulated signaling pathway and potential therapeutic miRNAs and mRNAs which represent a lion' share during various aspects of NSCLC's pathogenesis. Our systems biology approach introduced and nominated 1) important deregulated miRNAs in NSCLCs compared with normal tissue 2) significant and confident deregulated mRNAs which were anti-correlatively targeted by deregulated miRNA in NSCLCs and 3) dysregulated signaling pathways in association with deregulated miRNA-mRNAs interactions in NSCLCs. These results introduce possible mechanism of function of deregulated miRNAs and mRNAs in NSCLC that could be used as potential therapeutic targets.

  20. Study of the effects of radon in three biological systems

    International Nuclear Information System (INIS)

    Tavera, L.; Balcazar, M.; Lopez, A.; Brena, M.; Rosa, M.E. De la; Villalobos P, R.

    2002-01-01

    The radon and its decay products are responsible of the 3/4 parts of the exposure of the persons to the environmental radiation. The discovery at the end of XIX Century of the illnesses, mainly of cancer, which appeared in the presence of radon, lead to an accelerated growing of the radon studies: monitoring, dosimetry, effects on the persons, etc. Several epidemiological studies of radon in miners and population in general have been realized; advancing in the knowledge about the concentration-lung cancer risk relationship, but with discrepancies in the results depending on the concentration levels. Therefor, studies which consuming time, efforts and money go on doing. The research of the radon effects in biological systems different to human, allows to realize studies in less time, in controlled conditions and generally at lower cost, generating information about the alpha radiation effects in the cellular field. Therefor it was decided to study the response of three biological systems exposed to radon: an unicellular bacteria Escherichia Coli which was exposed directly to alpha particles from an electrodeposited source for determining the sensitivity limit of the chose technique. A plant, Tradescantia, for studying the cytogenetic effect of the system exposed to controlled concentrations of radon. An insect, Drosophila Melanogaster, for studying the genetic effects and the accumulated effects in several generations exposed to radon. In this work the experimental settlements are presented for the expositions of the systems and the biological results commenting the importance of these. (Author)

  1. An overview of bioinformatics methods for modeling biological pathways in yeast.

    Science.gov (United States)

    Hou, Jie; Acharya, Lipi; Zhu, Dongxiao; Cheng, Jianlin

    2016-03-01

    The advent of high-throughput genomics techniques, along with the completion of genome sequencing projects, identification of protein-protein interactions and reconstruction of genome-scale pathways, has accelerated the development of systems biology research in the yeast organism Saccharomyces cerevisiae In particular, discovery of biological pathways in yeast has become an important forefront in systems biology, which aims to understand the interactions among molecules within a cell leading to certain cellular processes in response to a specific environment. While the existing theoretical and experimental approaches enable the investigation of well-known pathways involved in metabolism, gene regulation and signal transduction, bioinformatics methods offer new insights into computational modeling of biological pathways. A wide range of computational approaches has been proposed in the past for reconstructing biological pathways from high-throughput datasets. Here we review selected bioinformatics approaches for modeling biological pathways inS. cerevisiae, including metabolic pathways, gene-regulatory pathways and signaling pathways. We start with reviewing the research on biological pathways followed by discussing key biological databases. In addition, several representative computational approaches for modeling biological pathways in yeast are discussed. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  2. Biological removal of algae in an integrated pond system

    CSIR Research Space (South Africa)

    Meiring, PGJ

    1995-01-01

    Full Text Available A system of oxidation ponds in series with a biological trickling filter is described. It was known that this arrangement was incapable of reducing effectively the levels of algae present in the pond liquid even though nitrification was effected...

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

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. GPSR: A Resource for Genomics Proteomics and Systems Biology. Small programs as building unit. Why PERL? Why not BioPerl? Why not PERL modules? Advantage of independent programs. Language independent; Can be run independently.

  4. The role of analytical sciences in medical systems biology

    NARCIS (Netherlands)

    Greef, J. van der; Stroobant, P.; Heijden, R. van der

    2004-01-01

    Medical systems biology has generated widespread interest because of its bold conception and exciting potential, but the field is still in its infancy. Although there has been tremendous progress achieved recently in generating, integrating and analysing data in the medical and pharmaceutical field,

  5. Evolutionary systems biology: historical and philosophical perspectives on an emerging synthesis.

    Science.gov (United States)

    O'Malley, Maureen A

    2012-01-01

    Systems biology (SB) is at least a decade old now and maturing rapidly. A more recent field, evolutionary systems biology (ESB), is in the process of further developing system-level approaches through the expansion of their explanatory and potentially predictive scope. This chapter will outline the varieties of ESB existing today by tracing the diverse roots and fusions that make up this integrative project. My approach is philosophical and historical. As well as examining the recent origins of ESB, I will reflect on its central features and the different clusters of research it comprises. In its broadest interpretation, ESB consists of five overlapping approaches: comparative and correlational ESB; network architecture ESB; network property ESB; population genetics ESB; and finally, standard evolutionary questions answered with SB methods. After outlining each approach with examples, I will examine some strong general claims about ESB, particularly that it can be viewed as the next step toward a fuller modern synthesis of evolutionary biology (EB), and that it is also the way forward for evolutionary and systems medicine. I will conclude with a discussion of whether the emerging field of ESB has the capacity to combine an even broader scope of research aims and efforts than it presently does.

  6. Metabolic adaptation of a human pathogen during chronic infections - a systems biology approach

    DEFF Research Database (Denmark)

    Thøgersen, Juliane Charlotte

    modeling to uncover how human pathogens adapt to the human host. Pseudomonas aeruginosa infections in cystic fibrosis patients are used as a model system for under-­‐ standing these adaptation processes. The exploratory systems biology approach facilitates identification of important phenotypes...... by classical molecular biology approaches where genes and reactions typically are investigated in a one to one relationship. This thesis is an example of how mathematical approaches and modeling can facilitate new biologi-­‐ cal understanding and provide new surprising ideas to important biological processes....... and metabolic pathways that are necessary or related to establishment of chronic infections. Archetypal analysis showed to be successful in extracting relevant phenotypes from global gene expression da-­‐ ta. Furthermore, genome-­‐scale metabolic modeling showed to be useful in connecting the genotype...

  7. Heavy water effects on the structure, functions and behavior of biological systems

    International Nuclear Information System (INIS)

    Buzgariu, Wanda; Caloianu, Maria; Moldovan, Lucia; Titescu, G.

    2003-01-01

    The H 2 O substitution for D 2 O either in environment or in the culture medium of the living systems generates changes in their main functions and composition. In this paper some of the heavy water effects in biological systems such as structural and functional changes were reviewed: normal cell architecture alterations, cell division and membrane functions disturbance, muscular contractility and the perturbations of biological oscillators such as circadian rhythm, heart rate, respiratory cycle, tidal and ultradian rhythm. (authors)

  8. Autonomy and the Ambiguity of Biological Rationalities: Systems Theory, ADHD and Kant

    Science.gov (United States)

    Haye, Andrés; Matus, Claudia; Cottet, Pablo; Niño, Sebastián

    2018-01-01

    We present a theoretical review of notions of autonomy to show how they organize discourses within social sciences around the biological reality of ideal self-regulating individuals. First, we reconstruct key meanings of autonomy in biological theory, focusing on theories of autopoietic systems and their connections to constructivist…

  9. On the Interplay between the Evolvability and Network Robustness in an Evolutionary Biological Network: A Systems Biology Approach

    Science.gov (United States)

    Chen, Bor-Sen; Lin, Ying-Po

    2011-01-01

    In the evolutionary process, the random transmission and mutation of genes provide biological diversities for natural selection. In order to preserve functional phenotypes between generations, gene networks need to evolve robustly under the influence of random perturbations. Therefore, the robustness of the phenotype, in the evolutionary process, exerts a selection force on gene networks to keep network functions. However, gene networks need to adjust, by variations in genetic content, to generate phenotypes for new challenges in the network’s evolution, ie, the evolvability. Hence, there should be some interplay between the evolvability and network robustness in evolutionary gene networks. In this study, the interplay between the evolvability and network robustness of a gene network and a biochemical network is discussed from a nonlinear stochastic system point of view. It was found that if the genetic robustness plus environmental robustness is less than the network robustness, the phenotype of the biological network is robust in evolution. The tradeoff between the genetic robustness and environmental robustness in evolution is discussed from the stochastic stability robustness and sensitivity of the nonlinear stochastic biological network, which may be relevant to the statistical tradeoff between bias and variance, the so-called bias/variance dilemma. Further, the tradeoff could be considered as an antagonistic pleiotropic action of a gene network and discussed from the systems biology perspective. PMID:22084563

  10. Representing culture in interstellar messages

    Science.gov (United States)

    Vakoch, Douglas A.

    2008-09-01

    As scholars involved with the Search for Extraterrestrial Intelligence (SETI) have contemplated how we might portray humankind in any messages sent to civilizations beyond Earth, one of the challenges they face is adequately representing the diversity of human cultures. For example, in a 2003 workshop in Paris sponsored by the SETI Institute, the International Academy of Astronautics (IAA) SETI Permanent Study Group, the International Society for the Arts, Sciences and Technology (ISAST), and the John Templeton Foundation, a varied group of artists, scientists, and scholars from the humanities considered how to encode notions of altruism in interstellar messages . Though the group represented 10 countries, most were from Europe and North America, leading to the group's recommendation that subsequent discussions on the topic should include more globally representative perspectives. As a result, the IAA Study Group on Interstellar Message Construction and the SETI Institute sponsored a follow-up workshop in Santa Fe, New Mexico, USA in February 2005. The Santa Fe workshop brought together scholars from a range of disciplines including anthropology, archaeology, chemistry, communication science, philosophy, and psychology. Participants included scholars familiar with interstellar message design as well as specialists in cross-cultural research who had participated in the Symposium on Altruism in Cross-cultural Perspective, held just prior to the workshop during the annual conference of the Society for Cross-cultural Research . The workshop included discussion of how cultural understandings of altruism can complement and critique the more biologically based models of altruism proposed for interstellar messages at the 2003 Paris workshop. This paper, written by the chair of both the Paris and Santa Fe workshops, will explore the challenges of communicating concepts of altruism that draw on both biological and cultural models.

  11. A consensus yeast metabolic network reconstruction obtained from a community approach to systems biology

    DEFF Research Database (Denmark)

    Herrgard, Markus; Swainston, Neil; Dobson, Paul

    2008-01-01

    and in a manner that permits automated reasoning. The reconstruction is readily available via a publicly accessible database and in the Systems Biology Markup Language (http://www.comp-sys-bio.org/yeastnet). It can be maintained as a resource that serves as a common denominator for studying the systems biology...

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

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. GPSR: A Resource for Genomics Proteomics and Systems Biology. A journey from simple computer programs to drug/vaccine informatics. Limitations of existing web services. History repeats (Web to Standalone); Graphics vs command mode. General purpose ...

  13. The Representatives of Amelanchier Medik. Genus in Ukraine

    Directory of Open Access Journals (Sweden)

    Opalko Anatoliy Ivanovich

    2015-04-01

    Full Text Available The information on fruit and decorative value, honey and medicinal properties of the genus Amelanchier Medik. is generalized. Their biological characteristics, chemical composition and palatability traits of the fruit, the ways of consumption and processing, including drying, preparing juices, syrups, jams, candied fruit jellies, confiture, and fruit wine are specified. The environmental adaptability and effectiveness of using juneberry for phytomelioration are mentioned. Several versions of the origin of the genus Amelanchier name and interpretation of its specific epithets are described. The controversial issues of the genus Amelanchier system were discussed from the classical and molecular genetic approaches. The attention is focused on two main aspects of views on the place of the genus Amelanchier representatives of the family Rosaceae Juss. within the particular subfamily, namely the subfamily Pyroideae Burnett (Maloideae S. Weber or the subfamily Amygdaloideae Arn., which indicates the necessity for further comparative morphological and molecular genetic studies of the family Rosaceae. The directions of evolution, habitat and invasive ability of some species of the genus Amelanchier are characterised. The list of the genus Amelanchier representatives cultivated in Ukraine is given.

  14. Biological impact of music and software-based auditory training

    Science.gov (United States)

    Kraus, Nina

    2012-01-01

    Auditory-based communication skills are developed at a young age and are maintained throughout our lives. However, some individuals – both young and old – encounter difficulties in achieving or maintaining communication proficiency. Biological signals arising from hearing sounds relate to real-life communication skills such as listening to speech in noisy environments and reading, pointing to an intersection between hearing and cognition. Musical experience, amplification, and software-based training can improve these biological signals. These findings of biological plasticity, in a variety of subject populations, relate to attention and auditory memory, and represent an integrated auditory system influenced by both sensation and cognition. Learning outcomes The reader will (1) understand that the auditory system is malleable to experience and training, (2) learn the ingredients necessary for auditory learning to successfully be applied to communication, (3) learn that the auditory brainstem response to complex sounds (cABR) is a window into the integrated auditory system, and (4) see examples of how cABR can be used to track the outcome of experience and training. PMID:22789822

  15. Universally sloppy parameter sensitivities in systems biology models.

    Directory of Open Access Journals (Sweden)

    Ryan N Gutenkunst

    2007-10-01

    Full Text Available Quantitative computational models play an increasingly important role in modern biology. Such models typically involve many free parameters, and assigning their values is often a substantial obstacle to model development. Directly measuring in vivo biochemical parameters is difficult, and collectively fitting them to other experimental data often yields large parameter uncertainties. Nevertheless, in earlier work we showed in a growth-factor-signaling model that collective fitting could yield well-constrained predictions, even when it left individual parameters very poorly constrained. We also showed that the model had a "sloppy" spectrum of parameter sensitivities, with eigenvalues roughly evenly distributed over many decades. Here we use a collection of models from the literature to test whether such sloppy spectra are common in systems biology. Strikingly, we find that every model we examine has a sloppy spectrum of sensitivities. We also test several consequences of this sloppiness for building predictive models. In particular, sloppiness suggests that collective fits to even large amounts of ideal time-series data will often leave many parameters poorly constrained. Tests over our model collection are consistent with this suggestion. This difficulty with collective fits may seem to argue for direct parameter measurements, but sloppiness also implies that such measurements must be formidably precise and complete to usefully constrain many model predictions. We confirm this implication in our growth-factor-signaling model. Our results suggest that sloppy sensitivity spectra are universal in systems biology models. The prevalence of sloppiness highlights the power of collective fits and suggests that modelers should focus on predictions rather than on parameters.

  16. Universally sloppy parameter sensitivities in systems biology models.

    Science.gov (United States)

    Gutenkunst, Ryan N; Waterfall, Joshua J; Casey, Fergal P; Brown, Kevin S; Myers, Christopher R; Sethna, James P

    2007-10-01

    Quantitative computational models play an increasingly important role in modern biology. Such models typically involve many free parameters, and assigning their values is often a substantial obstacle to model development. Directly measuring in vivo biochemical parameters is difficult, and collectively fitting them to other experimental data often yields large parameter uncertainties. Nevertheless, in earlier work we showed in a growth-factor-signaling model that collective fitting could yield well-constrained predictions, even when it left individual parameters very poorly constrained. We also showed that the model had a "sloppy" spectrum of parameter sensitivities, with eigenvalues roughly evenly distributed over many decades. Here we use a collection of models from the literature to test whether such sloppy spectra are common in systems biology. Strikingly, we find that every model we examine has a sloppy spectrum of sensitivities. We also test several consequences of this sloppiness for building predictive models. In particular, sloppiness suggests that collective fits to even large amounts of ideal time-series data will often leave many parameters poorly constrained. Tests over our model collection are consistent with this suggestion. This difficulty with collective fits may seem to argue for direct parameter measurements, but sloppiness also implies that such measurements must be formidably precise and complete to usefully constrain many model predictions. We confirm this implication in our growth-factor-signaling model. Our results suggest that sloppy sensitivity spectra are universal in systems biology models. The prevalence of sloppiness highlights the power of collective fits and suggests that modelers should focus on predictions rather than on parameters.

  17. Feasibility of using the Omaha System to represent public health nurse manager interventions.

    Science.gov (United States)

    Monsen, Karen A; Newsom, Eric T

    2011-01-01

    To test the feasibility of representing public health nurse (PHN) manager interventions using a recognized standardized nursing terminology. A nurse manager in a Midwest local public health agency documented nurse manager interventions using the Omaha System for 5 months. ANALYTIC STRATEGY: The data were analyzed and the results were compared with the results from a parallel analysis of existing PHN intervention data. Interventions for 79 "clients" (projects, teams, or individuals) captured 76% of recorded work hours, and addressed 43% of Omaha System problems. Most problems were addressed at the "community" level (87.1%) versus the "individual" level (12.9%). Nursing practice differed between the 2 knowledge domains of public health family home visiting nursing and public health nursing management. Standardized nursing terminologies have the potential to represent, describe, and quantify nurse manager interventions for future evaluation and research. © 2011 Wiley Periodicals, Inc.

  18. Improving integrative searching of systems chemical biology data using semantic annotation.

    Science.gov (United States)

    Chen, Bin; Ding, Ying; Wild, David J

    2012-03-08

    Systems chemical biology and chemogenomics are considered critical, integrative disciplines in modern biomedical research, but require data mining of large, integrated, heterogeneous datasets from chemistry and biology. We previously developed an RDF-based resource called Chem2Bio2RDF that enabled querying of such data using the SPARQL query language. Whilst this work has proved useful in its own right as one of the first major resources in these disciplines, its utility could be greatly improved by the application of an ontology for annotation of the nodes and edges in the RDF graph, enabling a much richer range of semantic queries to be issued. We developed a generalized chemogenomics and systems chemical biology OWL ontology called Chem2Bio2OWL that describes the semantics of chemical compounds, drugs, protein targets, pathways, genes, diseases and side-effects, and the relationships between them. The ontology also includes data provenance. We used it to annotate our Chem2Bio2RDF dataset, making it a rich semantic resource. Through a series of scientific case studies we demonstrate how this (i) simplifies the process of building SPARQL queries, (ii) enables useful new kinds of queries on the data and (iii) makes possible intelligent reasoning and semantic graph mining in chemogenomics and systems chemical biology. Chem2Bio2OWL is available at http://chem2bio2rdf.org/owl. The document is available at http://chem2bio2owl.wikispaces.com.

  19. Data warehousing in molecular biology.

    Science.gov (United States)

    Schönbach, C; Kowalski-Saunders, P; Brusic, V

    2000-05-01

    In the business and healthcare sectors data warehousing has provided effective solutions for information usage and knowledge discovery from databases. However, data warehousing applications in the biological research and development (R&D) sector are lagging far behind. The fuzziness and complexity of biological data represent a major challenge in data warehousing for molecular biology. By combining experiences in other domains with our findings from building a model database, we have defined the requirements for data warehousing in molecular biology.

  20. CINRG: Systems Biology of Glucocorticoids in Muscle Disease

    Science.gov (United States)

    2013-10-01

    Contract W81XWH-09-1-0726 SYSTEMS BIOLOGY OF GLUCOCORTICOIDS IN MUSCLE DISEASE Introduction Duchenne muscular dystrophy (DMD) is the most... muscle and enable the development of better targeted and more effective therapies for Duchenne muscular dystrophy dynamically. This MDA grant...common and incurable muscular dystrophy of childhood. Muscle regeneration fails with advancing age, leading to considerable fibrosis. Corticosteroid

  1. Systems biology technologies enable personalized traditional Chinese medicine: a systematic review.

    Science.gov (United States)

    Wang, Xijun; Zhang, Aihua; Sun, Hui; Wang, Ping

    2012-01-01

    Traditional Chinese medicine (TCM), an alternative medicine, focuses on the treatment of human disease via the integrity of the close relationship between body and syndrome analysis. It remains a form of primary care in most Asian countries and its characteristics showcase the great advantages of personalized medicine. Although this approach to disease diagnosis, prognosis and treatment has served the medical establishment well for thousands of years, it has serious shortcomings in the era of modern medicine that stem from its reliance on reductionist principles of experimentation and analysis. In this way, systems biology offers the potential to personalize medicine, facilitating the provision of the right care to the right patient at the right time. We expect that systems biology will have a major impact on future personalized therapeutic approaches which herald the future of medicine. Here we summarize current trends and critically review the potential limitations and future prospects of such treatments. Some characteristic examples are presented to highlight the application of this groundbreaking platform to personalized TCM as well as some of the necessary milestones for moving systems biology of a state-of-the-art nature into mainstream health care.

  2. A second inheritance system: the extension of biology through culture.

    Science.gov (United States)

    Whiten, Andrew

    2017-10-06

    By the mid-twentieth century (thus following the 'Modern Synthesis' in evolutionary biology), the behavioural sciences offered only the sketchy beginnings of a scientific literature documenting evidence for cultural inheritance in animals-the transmission of traditional behaviours via learning from others (social learning). By contrast, recent decades have seen a massive growth in the documentation of such cultural phenomena, driven by long-term field studies and complementary laboratory experiments. Here, I review the burgeoning scope of discoveries in this field, which increasingly suggest that this 'second inheritance system', built on the shoulders of the primary genetic inheritance system, occurs widely among vertebrates and possibly in invertebrates too. Its novel characteristics suggest significant implications for our understanding of evolutionary biology. I assess the extent to which this second system extends the scope of evolution, both by echoing principal properties of the primary, organic evolutionary system, and going beyond it in significant ways. This is well established in human cultural evolution; here, I address animal cultures more generally. The further major, and related, question concerns the extent to which the consequences of widespread animal cultural transmission interact with the primary, genetically based inheritance systems, shaping organic evolution.

  3. A systems biology approach to study systemic inflammation.

    Science.gov (United States)

    Chen, Bor-Sen; Wu, Chia-Chou

    2014-01-01

    Systemic inflammation needs a precise control on the sequence and magnitude of occurring events. The high throughput data on the host-pathogen interactions gives us an opportunity to have a glimpse on the systemic inflammation. In this article, a dynamic Candida albicans-zebrafish interactive infectious network is built as an example to demonstrate how systems biology approach can be used to study systematic inflammation. In particular, based on microarray data of C. albicans and zebrafish during infection, the hyphal growth, zebrafish, and host-pathogen intercellular PPI networks were combined to form an integrated infectious PPI network that helps us understand the systematic mechanisms underlying the pathogenicity of C. albicans and the immune response of the host. The signaling pathways for morphogenesis and hyphal growth of C. albicans were 2 significant interactions found in the intercellular PPI network. Two cellular networks were also developed corresponding to the different infection stages (adhesion and invasion), and then compared with each other to identify proteins to gain more insight into the pathogenic role of hyphal development in the C. albicans infection process. Important defense-related proteins in zebrafish were predicted using the same approach. This integrated network consisting of intercellular invasion and cellular defense processes during infection can improve medical therapies and facilitate development of new antifungal drugs.

  4. Advances in reproductive biology and seed production systems of ...

    African Journals Online (AJOL)

    Eucalyptus globulus is the main eucalypt species grown in Australian plantations. The focus on seedling deployment systems, coupled with exploitation of large, open-pollinated base populations for breeding purposes over the last two decades, has required a detailed understanding of the reproductive biology of this ...

  5. Synthetic Biology Outside the Cell: Linking Computational Tools to Cell-Free Systems

    Directory of Open Access Journals (Sweden)

    Daniel eLewis

    2014-12-01

    Full Text Available As mathematical models become more commonly integrated into the study of biology, a common language for describing biological processes is manifesting. Many tools have emerged for the simulation of in vivo systems, with only a few examples of prominent work done on predicting the dynamics of cell-free systems. At the same time, experimental biologists have begun to study dynamics of in vitro systems encapsulated by amphiphilic molecules, opening the door for the development of a new generation of biomimetic systems. In this review, we explore both in vivo and in vitro models of biochemical networks with a special focus on tools that could be applied to the construction of cell-free expression systems. We believe that quantitative studies of complex cellular mechanisms and pathways in synthetic systems can yield important insights into what makes cells different from conventional chemical systems.

  6. Mathematical computer simulation of the process of ultrasound interaction with biological medium

    International Nuclear Information System (INIS)

    Yakovleva, T.; Nassiri, D.; Ciantar, D.

    1996-01-01

    The aim of the paper is to study theoretically the interaction of ultrasound irradiation with biological medium and the peculiarities of ultrasound scattering by inhomogeneities of biological tissue, which can be represented by fractal structures. This investigation has been used for the construction of the computer model of three-dimensional ultrasonic imaging system what gives the possibility to define more accurately the pathological changes in such a tissue by means of its image analysis. Poster 180. (author)

  7. Aging in a Relativistic Biological Space-Time

    Directory of Open Access Journals (Sweden)

    Davide Maestrini

    2018-05-01

    Full Text Available Here we present a theoretical and mathematical perspective on the process of aging. We extend the concepts of physical space and time to an abstract, mathematically-defined space, which we associate with a concept of “biological space-time” in which biological dynamics may be represented. We hypothesize that biological dynamics, represented as trajectories in biological space-time, may be used to model and study different rates of biological aging. As a consequence of this hypothesis, we show how dilation or contraction of time analogous to relativistic corrections of physical time resulting from accelerated or decelerated biological dynamics may be used to study precipitous or protracted aging. We show specific examples of how these principles may be used to model different rates of aging, with an emphasis on cancer in aging. We discuss how this theory may be tested or falsified, as well as novel concepts and implications of this theory that may improve our interpretation of biological aging.

  8. Workshop Introduction: Systems Biology and Biological Models

    Science.gov (United States)

    As we consider the future of toxicity testing, the importance of applying biological models to this problem is clear. Modeling efforts exist along a continuum with respect to the level of organization (e.g. cell, tissue, organism) linked to the resolution of the model. Generally,...

  9. Ionic interactions in biological and physical systems: a variational treatment.

    Science.gov (United States)

    Eisenberg, Bob

    2013-01-01

    Chemistry is about chemical reactions. Chemistry is about electrons changing their configurations as atoms and molecules react. Chemistry has for more than a century studied reactions as if they occurred in ideal conditions of infinitely dilute solutions. But most reactions occur in salt solutions that are not ideal. In those solutions everything (charged) interacts with everything else (charged) through the electric field, which is short and long range extending to the boundaries of the system. Mathematics has recently been developed to deal with interacting systems of this sort. The variational theory of complex fluids has spawned the theory of liquid crystals (or vice versa). In my view, ionic solutions should be viewed as complex fluids, particularly in the biological and engineering context. In both biology and electrochemistry ionic solutions are mixtures highly concentrated (to approximately 10 M) where they are most important, near electrodes, nucleic ids, proteins, active sites of enzymes, and ionic channels. Ca2+ is always involved in biological solutions because the concentration (really free energy per mole) of Ca2+ in a particular location is the signal that controls many biological functions. Such interacting systems are not simple fluids, and it is no wonder that analysis of interactions, such as the Hofmeister series, rooted in that tradition has not succeeded as one would hope. Here, we present a variational treatment of ard spheres in a frictional dielectric with the hope that such a treatment of an lectrolyte as a complex fluid will be productive. The theory automatically extends to spatially nonuniform boundary conditions and the nonequilibrium systems and flows they produce. The theory is unavoidably self-consistent since differential equations are derived (not assumed) from models of (Helmholtz free) nergy and dissipation of the electrolyte. The origin of the Hofmeister series is (in my view) an inverse problem that becomes well posed when

  10. A geometric initial guess for localized electronic orbitals in modular biological systems

    Energy Technology Data Exchange (ETDEWEB)

    Beckman, P. G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Univ. of Chicago, IL (United States); Fattebert, J. L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Lau, E. Y. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Osei-Kuffuor, D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2017-09-11

    Recent first-principles molecular dynamics algorithms using localized electronic orbitals have achieved O(N) complexity and controlled accuracy in simulating systems with finite band gaps. However, accurately deter- mining the centers of these localized orbitals during simulation setup may require O(N3) operations, which is computationally infeasible for many biological systems. We present an O(N) approach for approximating orbital centers in proteins, DNA, and RNA which uses non-localized solutions for a set of fixed-size subproblems to create a set of geometric maps applicable to larger systems. This scalable approach, used as an initial guess in the O(N) first-principles molecular dynamics code MGmol, facilitates first-principles simulations in biological systems of sizes which were previously impossible.

  11. MODELLING OF RADIONUCLIDE MIGRATION IN THE SYSTEM OF NUCLEAR POWER PLANT BIOLOGICAL PONDS

    Directory of Open Access Journals (Sweden)

    Ю. Кутлахмедов

    2011-04-01

    Full Text Available Migration of radionuclide coming from nuclear power plant into the system of biological pondsand then into the water reservoir-cooler is considered in the article. The theme of the work ismodeling of radionuclide migration process in the system of biological ponds on the example of thePivdennoukrainska nuclear power plant using chamber models method. Typical water ecosystemconsisting of three chambers (chamber-water, chamber-biota and chamber-bed silt was the basistaken by the authors. Application of chamber models method allowed authors to develop thedynamic chamber model of radionuclide migration in nuclear power plant biological ponds. Thismodel allows to forecast values and dynamics of radioactive water pollution based on limitedecosystem monitoring data. Thus, parameters of radioactive capacity of nuclear power plantbiological ponds system and water reservoir-cooler were modeled by authors, the estimation andprognosis of radionuclide distribution and accumulation in the system of nuclear power plantbiological ponds were done. Authors also explain the roles of basin water, biomass and bed silt inradionuclide deposition

  12. Systems biology-embedded target validation: improving efficacy in drug discovery.

    Science.gov (United States)

    Vandamme, Drieke; Minke, Benedikt A; Fitzmaurice, William; Kholodenko, Boris N; Kolch, Walter

    2014-01-01

    The pharmaceutical industry is faced with a range of challenges with the ever-escalating costs of drug development and a drying out of drug pipelines. By harnessing advances in -omics technologies and moving away from the standard, reductionist model of drug discovery, there is significant potential to reduce costs and improve efficacy. Embedding systems biology approaches in drug discovery, which seek to investigate underlying molecular mechanisms of potential drug targets in a network context, will reduce attrition rates by earlier target validation and the introduction of novel targets into the currently stagnant market. Systems biology approaches also have the potential to assist in the design of multidrug treatments and repositioning of existing drugs, while stratifying patients to give a greater personalization of medical treatment. © 2013 Wiley Periodicals, Inc.

  13. Data management strategies for multinational large-scale systems biology projects.

    Science.gov (United States)

    Wruck, Wasco; Peuker, Martin; Regenbrecht, Christian R A

    2014-01-01

    Good accessibility of publicly funded research data is essential to secure an open scientific system and eventually becomes mandatory [Wellcome Trust will Penalise Scientists Who Don't Embrace Open Access. The Guardian 2012]. By the use of high-throughput methods in many research areas from physics to systems biology, large data collections are increasingly important as raw material for research. Here, we present strategies worked out by international and national institutions targeting open access to publicly funded research data via incentives or obligations to share data. Funding organizations such as the British Wellcome Trust therefore have developed data sharing policies and request commitment to data management and sharing in grant applications. Increased citation rates are a profound argument for sharing publication data. Pre-publication sharing might be rewarded by a data citation credit system via digital object identifiers (DOIs) which have initially been in use for data objects. Besides policies and incentives, good practice in data management is indispensable. However, appropriate systems for data management of large-scale projects for example in systems biology are hard to find. Here, we give an overview of a selection of open-source data management systems proved to be employed successfully in large-scale projects.

  14. Developmental biology, the stem cell of biological disciplines

    OpenAIRE

    Gilbert, Scott F.

    2017-01-01

    Developmental biology (including embryology) is proposed as "the stem cell of biological disciplines.” Genetics, cell biology, oncology, immunology, evolutionary mechanisms, neurobiology, and systems biology each has its ancestry in developmental biology. Moreover, developmental biology continues to roll on, budding off more disciplines, while retaining its own identity. While its descendant disciplines differentiate into sciences with a restricted set of paradigms, examples, and techniques, ...

  15. What does systems biology mean for drug development?

    Science.gov (United States)

    Schrattenholz, André; Soskić, Vukić

    2008-01-01

    The complexity and flexibility of cellular architectures is increasingly recognized by impressive progress on the side of molecular analytics, i.e. proteomics, genomics and metabolomics. One of the messages from systems biology is that the number of molecular species in cellular networks is orders of magnitude bigger than anticipated by genomic analysis, in particular by fast posttranslational modifications of proteins. The requirements to manage external signals, integrate spatiotemporal signal transduction inside an organism and at the same time optimizing networks of biochemical and chemical reactions result in chemically extremely fine tuned molecular entities. Chemical side reactions of enzymatic activity, like e.g. random oxidative damage of proteins by free radicals during aging constantly introduce epigenetic alterations of protein targets. These events gradually and on an individual stochastic scale, keep modifying activities of these targets, and their affinities and selectivities towards biological and pharmacological ligands. One further message is that many of the key reactions in living systems are essentially based on interactions of low affinities and even low selectivities. This principle is responsible for the enormous flexibility and redundancy of cellular circuitries. So, in complex disorders like cancer or neurodegenerative diseases, which are rooted in relatively subtle and multimodal dysfunction of important physiologic pathways, drug discovery programs based on the concept of high affinity/high specificity compounds ("one-target, one-disease"), which still dominate the pharmaceutical industry increasingly turn out to be unsuccessful. Despite improvements in rational drug design and high throughput screening methods, the number of novel, single-target drugs fell much behind expectations during the past decade and the treatment of "complex diseases" remains a most pressing medical need. Currently a change of paradigm can be observed with

  16. Fabrication, Characterization, and Biological Activity of Avermectin Nano-delivery Systems with Different Particle Sizes

    Science.gov (United States)

    Wang, Anqi; Wang, Yan; Sun, Changjiao; Wang, Chunxin; Cui, Bo; Zhao, Xiang; Zeng, Zhanghua; Yao, Junwei; Yang, Dongsheng; Liu, Guoqiang; Cui, Haixin

    2018-01-01

    Nano-delivery systems for the active ingredients of pesticides can improve the utilization rates of pesticides and prolong their control effects. This is due to the nanocarrier envelope and controlled release function. However, particles containing active ingredients in controlled release pesticide formulations are generally large and have wide size distributions. There have been limited studies about the effect of particle size on the controlled release properties and biological activities of pesticide delivery systems. In the current study, avermectin (Av) nano-delivery systems were constructed with different particle sizes and their performances were evaluated. The Av release rate in the nano-delivery system could be effectively controlled by changing the particle size. The biological activity increased with decreasing particle size. These results suggest that Av nano-delivery systems can significantly improve the controllable release, photostability, and biological activity, which will improve efficiency and reduce pesticide residues.

  17. Automated parameter estimation for biological models using Bayesian statistical model checking.

    Science.gov (United States)

    Hussain, Faraz; Langmead, Christopher J; Mi, Qi; Dutta-Moscato, Joyeeta; Vodovotz, Yoram; Jha, Sumit K

    2015-01-01

    Probabilistic models have gained widespread acceptance in the systems biology community as a useful way to represent complex biological systems. Such models are developed using existing knowledge of the structure and dynamics of the system, experimental observations, and inferences drawn from statistical analysis of empirical data. A key bottleneck in building such models is that some system variables cannot be measured experimentally. These variables are incorporated into the model as numerical parameters. Determining values of these parameters that justify existing experiments and provide reliable predictions when model simulations are performed is a key research problem. Using an agent-based model of the dynamics of acute inflammation, we demonstrate a novel parameter estimation algorithm by discovering the amount and schedule of doses of bacterial lipopolysaccharide that guarantee a set of observed clinical outcomes with high probability. We synthesized values of twenty-eight unknown parameters such that the parameterized model instantiated with these parameter values satisfies four specifications describing the dynamic behavior of the model. We have developed a new algorithmic technique for discovering parameters in complex stochastic models of biological systems given behavioral specifications written in a formal mathematical logic. Our algorithm uses Bayesian model checking, sequential hypothesis testing, and stochastic optimization to automatically synthesize parameters of probabilistic biological models.

  18. Teleology and its constitutive role for biology as the science of organized systems in nature.

    Science.gov (United States)

    Toepfer, Georg

    2012-03-01

    'Nothing in biology makes sense, except in the light of teleology'. This could be the first sentence in a textbook about the methodology of biology. The fundamental concepts in biology, e.g. 'organism' and 'ecosystem', are only intelligible given a teleological framework. Since early modern times, teleology has often been considered methodologically unscientific. With the acceptance of evolutionary theory, one popular strategy for accommodating teleological reasoning was to explain it by reference to selection in the past: functions were reconstructed as 'selected effects'. But the theory of evolution obviously presupposes the existence of organisms as organized and regulated, i.e. functional systems. Therefore, evolutionary theory cannot provide the foundation for teleology. The underlying reason for the central methodological role of teleology in biology is not its potential to offer particular forms of (evolutionary) explanations for the presence of parts, but rather an ontological one: organisms and other basic biological entities do not exist as physical bodies do, as amounts of matter with a definite form. Rather, they are dynamic systems in stable equilibrium; despite changes of their matter and form (in metabolism and metamorphosis) they maintain their identity. What remains constant in these kinds of systems is their 'organization', i.e. the causal pattern of interdependence of parts with certain effects of each part being relevant for the working of the system. Teleological analysis consists in the identification of these system-relevant effects and at the same time of the system as a whole. Therefore, the identity of biological systems cannot be specified without teleological reasoning. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Physics and biology

    International Nuclear Information System (INIS)

    Frauenfelder, H.

    1988-01-01

    The author points out that the coupling between physics and biology is becoming closer as time goes on. He tries to show that physical studies on biological systems not only yield insight into biology but also provide results of interest to physics. Biological systems are extremly complex system. Ideally one would like to understand the behavior of such systems in terms of the behavior of its constituent atoms. Since in small organisms this may be 10 20 atoms, it is clear these are not simple many-body systems. He reviews the basic elements of cells and then considers the broader questions of structure, complexity, and function, which must be looked at on levels from the cell to the organism. Despite the vast amount of observational material already in existence, biophysics and biological physics are only at a beginning. We can expect that physics will continue to interact strongly with biology. Actually, the connection also includes chemistry and mathematics. New tools that become available in physics will continue to be applied to biological problems. We can expect that the flow of information will not be one way; biological systems will provide new information on many old and new parts of physics, from reaction theory and transport phenomena to complexity, cooperativity, and nonlinear processes

  20. Interaction of biological systems with static and ELF electric and magnetic fields

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, L.E.; Kelman, B.J.; Weigel, R.J. (eds.)

    1987-01-01

    Although background levels of atmospheric electric and geomagnetic field levels are extremely low, over the past several decades, human beings and other life forms on this planet have been subjected to a dramatically changing electromagnetic milieu. An exponential increase in exposure to electromagnetic fields has occurred, largely because of such technological advances as the growth of electrical power generation and transmission systems, the increased use of wireless communications, and the use of radar. In addition, electromagnetic field generating devices have proliferated in industrial plants, office buildings, homes, public transportation systems, and elsewhere. Although significant increases have occurred in electromagnetic field strenghths spanning all frequency ranges, this symposium addresses only the impact of these fields at static and extremely low frequencies (ELF), primarily 50 and 60 Hz. This volume contains the proceedings of the symposium entitled /open quotes/Interaction of biological systems with static and ELF electric and magnetic fields/close quotes/. The purpose of the symposium was to provide a forum for discussions of all aspects of research on the interaction of static and ELF electromagnetic fields with biological systems. These systems include simple biophysical models, cell and organ preparations, whole animals, and man. Dosimetry, exposure system design, and artifacts in ELF bioeffects research were also addressed, along with current investigations that examine fundamental mechanisms of interactions between the fields and biological processes. Papers are indexed separately.

  1. Human visual system automatically represents large-scale sequential regularities.

    Science.gov (United States)

    Kimura, Motohiro; Widmann, Andreas; Schröger, Erich

    2010-03-04

    Our brain recordings reveal that large-scale sequential regularities defined across non-adjacent stimuli can be automatically represented in visual sensory memory. To show that, we adopted an auditory paradigm developed by Sussman, E., Ritter, W., and Vaughan, H. G. Jr. (1998). Predictability of stimulus deviance and the mismatch negativity. NeuroReport, 9, 4167-4170, Sussman, E., and Gumenyuk, V. (2005). Organization of sequential sounds in auditory memory. NeuroReport, 16, 1519-1523 to the visual domain by presenting task-irrelevant infrequent luminance-deviant stimuli (D, 20%) inserted among task-irrelevant frequent stimuli being of standard luminance (S, 80%) in randomized (randomized condition, SSSDSSSSSDSSSSD...) and fixed manners (fixed condition, SSSSDSSSSDSSSSD...). Comparing the visual mismatch negativity (visual MMN), an event-related brain potential (ERP) index of memory-mismatch processes in human visual sensory system, revealed that visual MMN elicited by deviant stimuli was reduced in the fixed compared to the randomized condition. Thus, the large-scale sequential regularity being present in the fixed condition (SSSSD) must have been represented in visual sensory memory. Interestingly, this effect did not occur in conditions with stimulus-onset asynchronies (SOAs) of 480 and 800 ms but was confined to the 160-ms SOA condition supporting the hypothesis that large-scale regularity extraction was based on perceptual grouping of the five successive stimuli defining the regularity. 2010 Elsevier B.V. All rights reserved.

  2. Quantum Information Biology: From Theory of Open Quantum Systems to Adaptive Dynamics

    Science.gov (United States)

    Asano, Masanari; Basieva, Irina; Khrennikov, Andrei; Ohya, Masanori; Tanaka, Yoshiharu; Yamato, Ichiro

    This chapter reviews quantum(-like) information biology (QIB). Here biology is treated widely as even covering cognition and its derivatives: psychology and decision making, sociology, and behavioral economics and finances. QIB provides an integrative description of information processing by bio-systems at all scales of life: from proteins and cells to cognition, ecological and social systems. Mathematically QIB is based on the theory of adaptive quantum systems (which covers also open quantum systems). Ideologically QIB is based on the quantum-like (QL) paradigm: complex bio-systems process information in accordance with the laws of quantum information and probability. This paradigm is supported by plenty of statistical bio-data collected at all bio-scales. QIB re ects the two fundamental principles: a) adaptivity; and, b) openness (bio-systems are fundamentally open). In addition, quantum adaptive dynamics provides the most generally possible mathematical representation of these principles.

  3. Comparative systems biology between human and animal models based on next-generation sequencing methods.

    Science.gov (United States)

    Zhao, Yu-Qi; Li, Gong-Hua; Huang, Jing-Fei

    2013-04-01

    Animal models provide myriad benefits to both experimental and clinical research. Unfortunately, in many situations, they fall short of expected results or provide contradictory results. In part, this can be the result of traditional molecular biological approaches that are relatively inefficient in elucidating underlying molecular mechanism. To improve the efficacy of animal models, a technological breakthrough is required. The growing availability and application of the high-throughput methods make systematic comparisons between human and animal models easier to perform. In the present study, we introduce the concept of the comparative systems biology, which we define as "comparisons of biological systems in different states or species used to achieve an integrated understanding of life forms with all their characteristic complexity of interactions at multiple levels". Furthermore, we discuss the applications of RNA-seq and ChIP-seq technologies to comparative systems biology between human and animal models and assess the potential applications for this approach in the future studies.

  4. Cardiovascular safety of biologic therapies for the treatment of RA.

    Science.gov (United States)

    Greenberg, Jeffrey D; Furer, Victoria; Farkouh, Michael E

    2011-11-15

    Cardiovascular disease represents a major source of extra-articular comorbidity in patients with rheumatoid arthritis (RA). A combination of traditional cardiovascular risk factors and RA-related factors accounts for the excess risk in RA. Among RA-related factors, chronic systemic inflammation has been implicated in the pathogenesis and progression of atherosclerosis. A growing body of evidence--mainly derived from observational databases and registries--suggests that specific RA therapies, including methotrexate and anti-TNF biologic agents, can reduce the risk of future cardiovascular events in patients with RA. The cardiovascular profile of other biologic therapies for the treatment of RA has not been adequately studied, including of investigational drugs that improve systemic inflammation but alter traditional cardiovascular risk factors. In the absence of large clinical trials adequately powered to detect differences in cardiovascular events between biologic drugs in RA, deriving firm conclusions on cardiovascular safety is challenging. Nevertheless, observational research using large registries has emerged as a promising approach to study the cardiovascular risk of emerging RA biologic therapies.

  5. Novel approaches to the integration and analysis of systems biology data

    OpenAIRE

    Ramírez, Fidel

    2011-01-01

    The opportunity to investigate whole cellular systems using experimental and computational high-throughput methods leads to the generation of unprecedented amounts of data. Processing of these data often results in large lists of genes or proteins that need to be analyzed and interpreted in the context of all other biological information that is already available. To support such analyses, repositories aggregating and merging the biological information contained in different databases are req...

  6. Biological standards for the Knowledge-Based BioEconomy: What is at stake.

    Science.gov (United States)

    de Lorenzo, Víctor; Schmidt, Markus

    2018-01-25

    The contribution of life sciences to the Knowledge-Based Bioeconomy (KBBE) asks for the transition of contemporary, gene-based biotechnology from being a trial-and-error endeavour to becoming an authentic branch of engineering. One requisite to this end is the need for standards to measure and represent accurately biological functions, along with languages for data description and exchange. However, the inherent complexity of biological systems and the lack of quantitative tradition in the field have largely curbed this enterprise. Fortunately, the onset of systems and synthetic biology has emphasized the need for standards not only to manage omics data, but also to increase reproducibility and provide the means of engineering living systems in earnest. Some domains of biotechnology can be easily standardized (e.g. physical composition of DNA sequences, tools for genome editing, languages to encode workflows), while others might be standardized with some dedicated research (e.g. biological metrology, operative systems for bio-programming cells) and finally others will require a considerable effort, e.g. defining the rules that allow functional composition of biological activities. Despite difficulties, these are worthy attempts, as the history of technology shows that those who set/adopt standards gain a competitive advantage over those who do not. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Improving integrative searching of systems chemical biology data using semantic annotation

    Directory of Open Access Journals (Sweden)

    Chen Bin

    2012-03-01

    Full Text Available Abstract Background Systems chemical biology and chemogenomics are considered critical, integrative disciplines in modern biomedical research, but require data mining of large, integrated, heterogeneous datasets from chemistry and biology. We previously developed an RDF-based resource called Chem2Bio2RDF that enabled querying of such data using the SPARQL query language. Whilst this work has proved useful in its own right as one of the first major resources in these disciplines, its utility could be greatly improved by the application of an ontology for annotation of the nodes and edges in the RDF graph, enabling a much richer range of semantic queries to be issued. Results We developed a generalized chemogenomics and systems chemical biology OWL ontology called Chem2Bio2OWL that describes the semantics of chemical compounds, drugs, protein targets, pathways, genes, diseases and side-effects, and the relationships between them. The ontology also includes data provenance. We used it to annotate our Chem2Bio2RDF dataset, making it a rich semantic resource. Through a series of scientific case studies we demonstrate how this (i simplifies the process of building SPARQL queries, (ii enables useful new kinds of queries on the data and (iii makes possible intelligent reasoning and semantic graph mining in chemogenomics and systems chemical biology. Availability Chem2Bio2OWL is available at http://chem2bio2rdf.org/owl. The document is available at http://chem2bio2owl.wikispaces.com.

  8. System for determining sizes of biological macromolecules

    International Nuclear Information System (INIS)

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

    1987-01-01

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

  9. From Biology to Quality (BQ)

    DEFF Research Database (Denmark)

    Nielsen, Michael Engelbrecht; Ingerslev, Hans-Christian

    2011-01-01

    “Quality is never an accident; it is always the result of high intention, sincere effort, intelligent direction and skilful execution; it represents the wise choice of many alternatives.” (William A. Foster) The quality of fish meat is dependent upon a wide range of biological and non-biological ...

  10. Comparatives of Expressive Activities of Junior High School Students with Different Types of Representative Systems

    Directory of Open Access Journals (Sweden)

    Geydebrekht N.A.

    2017-08-01

    Full Text Available The article presents data from a study of drawings of children of primary school age to identify the сcomparative diagnostic parameters that allow to define the leading representative system in the child. 164 drawings of 51 persons under test of the two grades of primary school were analyzed. The observation and modified in relation to primary school age version of the method «Representational systems bias test» (Lewis A., Puselik R., 2012 were used as elements of the diagnostic unit. Based on these results it is concluded that the drawings of children of primary school age with different types of representative systems have differences, sufficient to justify their diagnostic informative value. The results of the study make comparative profiles of children of primary school age with different types of representational systems to facilitate the diagnostic part of the work with children's drawings.

  11. Network Reconstruction of Dynamic Biological Systems

    OpenAIRE

    Asadi, Behrang

    2013-01-01

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

  12. Leaf LIMS: A Flexible Laboratory Information Management System with a Synthetic Biology Focus.

    Science.gov (United States)

    Craig, Thomas; Holland, Richard; D'Amore, Rosalinda; Johnson, James R; McCue, Hannah V; West, Anthony; Zulkower, Valentin; Tekotte, Hille; Cai, Yizhi; Swan, Daniel; Davey, Robert P; Hertz-Fowler, Christiane; Hall, Anthony; Caddick, Mark

    2017-12-15

    This paper presents Leaf LIMS, a flexible laboratory information management system (LIMS) designed to address the complexity of synthetic biology workflows. At the project's inception there was a lack of a LIMS designed specifically to address synthetic biology processes, with most systems focused on either next generation sequencing or biobanks and clinical sample handling. Leaf LIMS implements integrated project, item, and laboratory stock tracking, offering complete sample and construct genealogy, materials and lot tracking, and modular assay data capture. Hence, it enables highly configurable task-based workflows and supports data capture from project inception to completion. As such, in addition to it supporting synthetic biology it is ideal for many laboratory environments with multiple projects and users. The system is deployed as a web application through Docker and is provided under a permissive MIT license. It is freely available for download at https://leaflims.github.io .

  13. Developmental biology, the stem cell of biological disciplines.

    Science.gov (United States)

    Gilbert, Scott F

    2017-12-01

    Developmental biology (including embryology) is proposed as "the stem cell of biological disciplines." Genetics, cell biology, oncology, immunology, evolutionary mechanisms, neurobiology, and systems biology each has its ancestry in developmental biology. Moreover, developmental biology continues to roll on, budding off more disciplines, while retaining its own identity. While its descendant disciplines differentiate into sciences with a restricted set of paradigms, examples, and techniques, developmental biology remains vigorous, pluripotent, and relatively undifferentiated. In many disciplines, especially in evolutionary biology and oncology, the developmental perspective is being reasserted as an important research program.

  14. Hydrogen production from biomass by biological systems

    International Nuclear Information System (INIS)

    Sharifan, H.R.; Qader, S.

    2009-01-01

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

  15. Update on the use of systemic biologic agents in the treatment of noninfectious uveitis

    Directory of Open Access Journals (Sweden)

    Pasadhika S

    2014-02-01

    Full Text Available Sirichai Pasadhika,1 James T Rosenbaum2 1Department of Ophthalmology, Southern Arizona Veterans Administration Health Care System, Tucson, AZ, USA; 2Legacy Devers Eye Institute, Portland, OR, USA Abstract: Uveitis is one of the leading causes of blindness worldwide. Noninfectious uveitis may be associated with other systemic conditions, such as human leukocyte antigen B27-related spondyloarthropathies, inflammatory bowel disease, juvenile idiopathic arthritis, Behçet's disease, and sarcoidosis. Conventional therapy with corticosteroids and immunosuppressive agents (such as methotrexate, azathioprine, mycophenolate mofetil, and cyclosporine may not be sufficient to control ocular inflammation or prevent non-ophthalmic complications in refractory patients. Off-label use of biologic response modifiers has been studied as primary and secondary therapeutic agents. They are very useful when conventional immunosuppressive therapy has failed or has been poorly tolerated, or to treat concomitant ophthalmic and systemic inflammation that might benefit from these medications. Biologic therapy, primarily infliximab, and adalimumab, have been shown to be rapidly effective for the treatment of various subtypes of refractory uveitis and retinal vasculitis, especially Behçet's disease-related eye conditions and the uveitis associated with juvenile idiopathic arthritis. Other agents such as golimumab, abatacept, canakinumab, gevokizumab, tocilizumab, and alemtuzumab may have great future promise for the treatment of uveitis. It has been shown that with proper monitoring, biologic therapy can significantly improve quality of life in patients with uveitis, particularly those with concurrent systemic symptoms. However, given high cost as well as the limited long-term safety data, we do not routinely recommend biologics as first-line therapy for noninfectious uveitis in most patients. These agents should be used with caution by experienced clinicians. The present

  16. A comprehensive patient-derived xenograft collection representing the heterogeneity of melanoma

    OpenAIRE

    Krepler, Clemens; Sproesser, Katrin; Brafford, Patricia; Beqiri, Marilda; Garman, Bradley; Xiao, Min; Shannan, Batool; Watters, Andrea; Perego, Michela; Zhang, Gao; Vultur, Adina; Yin, Xiangfan; Liu, Qin; Anastopoulos, Ioannis N; Wubbenhorst, Bradley

    2017-01-01

    Summary: Therapy of advanced melanoma is changing dramatically. Following mutational and biological subclassification of this heterogeneous cancer, several targeted and immune therapies were approved and increased survival significantly. To facilitate further advancements through pre-clinical in vivo modeling, we have established 459 patient-derived xenografts (PDX) and live tissue samples from 384 patients representing the full spectrum of clinical, therapeutic, mutational, and biological he...

  17. Aluminum-Induced Entropy in Biological Systems: Implications for Neurological Disease

    Directory of Open Access Journals (Sweden)

    Christopher A. Shaw

    2014-01-01

    Full Text Available Over the last 200 years, mining, smelting, and refining of aluminum (Al in various forms have increasingly exposed living species to this naturally abundant metal. Because of its prevalence in the earth’s crust, prior to its recent uses it was regarded as inert and therefore harmless. However, Al is invariably toxic to living systems and has no known beneficial role in any biological systems. Humans are increasingly exposed to Al from food, water, medicinals, vaccines, and cosmetics, as well as from industrial occupational exposure. Al disrupts biological self-ordering, energy transduction, and signaling systems, thus increasing biosemiotic entropy. Beginning with the biophysics of water, disruption progresses through the macromolecules that are crucial to living processes (DNAs, RNAs, proteoglycans, and proteins. It injures cells, circuits, and subsystems and can cause catastrophic failures ending in death. Al forms toxic complexes with other elements, such as fluorine, and interacts negatively with mercury, lead, and glyphosate. Al negatively impacts the central nervous system in all species that have been studied, including humans. Because of the global impacts of Al on water dynamics and biosemiotic systems, CNS disorders in humans are sensitive indicators of the Al toxicants to which we are being exposed.

  18. Structural Identifiability of Dynamic Systems Biology Models.

    Science.gov (United States)

    Villaverde, Alejandro F; Barreiro, Antonio; Papachristodoulou, Antonis

    2016-10-01

    A powerful way of gaining insight into biological systems is by creating a nonlinear differential equation model, which usually contains many unknown parameters. Such a model is called structurally identifiable if it is possible to determine the values of its parameters from measurements of the model outputs. Structural identifiability is a prerequisite for parameter estimation, and should be assessed before exploiting a model. However, this analysis is seldom performed due to the high computational cost involved in the necessary symbolic calculations, which quickly becomes prohibitive as the problem size increases. In this paper we show how to analyse the structural identifiability of a very general class of nonlinear models by extending methods originally developed for studying observability. We present results about models whose identifiability had not been previously determined, report unidentifiabilities that had not been found before, and show how to modify those unidentifiable models to make them identifiable. This method helps prevent problems caused by lack of identifiability analysis, which can compromise the success of tasks such as experiment design, parameter estimation, and model-based optimization. The procedure is called STRIKE-GOLDD (STRuctural Identifiability taKen as Extended-Generalized Observability with Lie Derivatives and Decomposition), and it is implemented in a MATLAB toolbox which is available as open source software. The broad applicability of this approach facilitates the analysis of the increasingly complex models used in systems biology and other areas.

  19. Biology and Medicine Division annual report, 1987

    International Nuclear Information System (INIS)

    1988-04-01

    Modern biology is characterized by rapid change. The development of new tools and the results derived from their application to various biological systems require significant shifts in our concepts and the strategies that are adopted to analyze and elucidate mechanisms. In parallel with exciting new scientific developments our organizational structure and programmatic emphases have altered. These changes and developments have enabled the life sciences at LBL to be better positioned to create and respond to new opportunities. The work summarized in this annual report reflects a vital multifaceted research program that is in the vanguard of the areas represented. We are committed to justifying the confidence expressed by LBL through the new mission statement and reorganizational changes designed to give greater prominence to the life sciences

  20. Biology and Medicine Division annual report, 1987

    Energy Technology Data Exchange (ETDEWEB)

    1988-04-01

    Modern biology is characterized by rapid change. The development of new tools and the results derived from their application to various biological systems require significant shifts in our concepts and the strategies that are adopted to analyze and elucidate mechanisms. In parallel with exciting new scientific developments our organizational structure and programmatic emphases have altered. These changes and developments have enabled the life sciences at LBL to be better positioned to create and respond to new opportunities. The work summarized in this annual report reflects a vital multifaceted research program that is in the vanguard of the areas represented. We are committed to justifying the confidence expressed by LBL through the new mission statement and reorganizational changes designed to give greater prominence to the life sciences.

  1. Macroscopic Theory for Evolving Biological Systems Akin to Thermodynamics.

    Science.gov (United States)

    Kaneko, Kunihiko; Furusawa, Chikara

    2018-05-20

    We present a macroscopic theory to characterize the plasticity, robustness, and evolvability of biological responses and their fluctuations. First, linear approximation in intracellular reaction dynamics is used to demonstrate proportional changes in the expression of all cellular components in response to a given environmental stress, with the proportion coefficient determined by the change in growth rate as a consequence of the steady growth of cells. We further demonstrate that this relationship is supported through adaptation experiments of bacteria, perhaps too well as this proportionality is held even across cultures of different types of conditions. On the basis of simulations of cell models, we further show that this global proportionality is a consequence of evolution in which expression changes in response to environmental or genetic perturbations are constrained along a unique one-dimensional curve, which is a result of evolutionary robustness. It then follows that the expression changes induced by environmental changes are proportionally reduced across different components of a cell by evolution, which is akin to the Le Chatelier thermodynamics principle. Finally, with the aid of a fluctuation-response relationship, this proportionality is shown to hold between fluctuations caused by genetic changes and those caused by noise. Overall, these results and support from the theoretical and experimental literature suggest a formulation of cellular systems akin to thermodynamics, in which a macroscopic potential is given by the growth rate (or fitness) represented as a function of environmental and evolutionary changes.

  2. Measurement of sexual health in the U.S.: an inventory of nationally representative surveys and surveillance systems.

    Science.gov (United States)

    Ivankovich, Megan B; Leichliter, Jami S; Douglas, John M

    2013-01-01

    To identify opportunities within nationally representative surveys and surveillance systems to measure indicators of sexual health, we reviewed and inventoried existing data systems that include variables relevant to sexual health. We searched for U.S. nationally representative surveys and surveillance systems that provided individual-level sexual health data. We assessed the methods of each data system and catalogued them by their measurement of the following domains of sexual health: knowledge, communication, attitudes, service access and utilization, sexual behaviors, relationships, and adverse health outcomes. We identified 18 U.S.-focused, nationally representative data systems: six assessing the general population, seven focused on special populations, and five addressing health outcomes. While these data systems provide a rich repository of information from which to assess national measures of sexual health, they present several limitations. Most importantly, apart from data on service utilization, routinely gathered, national data are currently focused primarily on negative aspects of sexual health (e.g., risk behaviors and adverse health outcomes) rather than more positive attributes (e.g., healthy communication and attitudes, and relationship quality). Nationally representative data systems provide opportunities to measure a broad array of domains of sexual health. However, current measurement gaps indicate the need to modify existing surveys, where feasible and appropriate, and develop new tools to include additional indicators that address positive domains of sexual health of the U.S. population across the life span. Such data can inform the development of effective policy actions, services, prevention programs, and resource allocation to advance sexual health.

  3. Representing vision and blindness.

    Science.gov (United States)

    Ray, Patrick L; Cox, Alexander P; Jensen, Mark; Allen, Travis; Duncan, William; Diehl, Alexander D

    2016-01-01

    There have been relatively few attempts to represent vision or blindness ontologically. This is unsurprising as the related phenomena of sight and blindness are difficult to represent ontologically for a variety of reasons. Blindness has escaped ontological capture at least in part because: blindness or the employment of the term 'blindness' seems to vary from context to context, blindness can present in a myriad of types and degrees, and there is no precedent for representing complex phenomena such as blindness. We explore current attempts to represent vision or blindness, and show how these attempts fail at representing subtypes of blindness (viz., color blindness, flash blindness, and inattentional blindness). We examine the results found through a review of current attempts and identify where they have failed. By analyzing our test cases of different types of blindness along with the strengths and weaknesses of previous attempts, we have identified the general features of blindness and vision. We propose an ontological solution to represent vision and blindness, which capitalizes on resources afforded to one who utilizes the Basic Formal Ontology as an upper-level ontology. The solution we propose here involves specifying the trigger conditions of a disposition as well as the processes that realize that disposition. Once these are specified we can characterize vision as a function that is realized by certain (in this case) biological processes under a range of triggering conditions. When the range of conditions under which the processes can be realized are reduced beyond a certain threshold, we are able to say that blindness is present. We characterize vision as a function that is realized as a seeing process and blindness as a reduction in the conditions under which the sight function is realized. This solution is desirable because it leverages current features of a major upper-level ontology, accurately captures the phenomenon of blindness, and can be

  4. A system for the obtention and analysis of diffuse reflection spectra from biological tissue

    International Nuclear Information System (INIS)

    La Cadena, A. de; La Rosa, J. de; Stolik, S.

    2012-01-01

    The diffuse reflection spectroscopy is a technique with is possible to study biological tissue. In the field of the biomedical applications is useful for diagnostic purposes, since is possible to analyze biological tissue in a non invasive way. also, can be used with therapeutical purposes, for example in photodynamic therapy or laser surgery because with this technique it can be determined the biological effects produced by these treatments. In this paper is shown the development of a system to obtain and analyze diffuse reflection spectra of biological tissues, using a LED as a light source, that emits light between 400-700nm. The system has an interface for the regulation of the emittance of the LED. For diffuse reflectance spectra analysis, we use an HR4000CG-UV-NIR spectrometer. (Author)

  5. Synthetic Biology and Microbial Fuel Cells: Towards Self-Sustaining Life Support Systems

    Science.gov (United States)

    Hogan, John Andrew

    2014-01-01

    NASA ARC and the J. Craig Venter Institute (JCVI) collaborated to investigate the development of advanced microbial fuels cells (MFCs) for biological wastewater treatment and electricity production (electrogenesis). Synthetic biology techniques and integrated hardware advances were investigated to increase system efficiency and robustness, with the intent of increasing power self-sufficiency and potential product formation from carbon dioxide. MFCs possess numerous advantages for space missions, including rapid processing, reduced biomass and effective removal of organics, nitrogen and phosphorus. Project efforts include developing space-based MFC concepts, integration analyses, increasing energy efficiency, and investigating novel bioelectrochemical system applications

  6. Nuclear magnetic resonance applications in biological systems

    International Nuclear Information System (INIS)

    Jiang Ling; Liu Maili

    2011-01-01

    Nuclear magnetic resonance (NMR) spectroscopy is a state-of-the-art technology which has been widely applied in biological systems over the past decades. It is a powerful tool for macromolecular structure determination in solution, and has the unique advantage of being capable of elucidating the structure and dynamic behavior of proteins during vital biomedical processes. In this review, we introduce the recent progress in NMR techniques for studying the structure, interaction and dynamics of proteins. The methods for NMR based drug discovery and metabonomics are also briefly introduced. (authors)

  7. A model of heavy ion detection in physical and biological systems

    International Nuclear Information System (INIS)

    Waligorski, M.P.R.

    1988-01-01

    Track structure theory (the Katz model) and its application to the detection of heavy ions in physical and biological systems are reviewed. Following the use of a new corrected formula describing the radial distribution of average dose around the path of a heavy ion, based on results of Monte Carlo calculations and on results of experimental measurements, better agreement is achieved between model calculations and experimentally measured relative effectiveness, for enzymatic and viral systems, for the Fricke dosemeter and for alanine and thermoluminescent (TDL-700) dosemeters irradiated with beams of heavy charged particles. From experimentally measured RBE dependences for survival and frequency of neoplastic transformations in a mammalian cell culture irradiated with beams of energetic heavy ions, values of model parameters for these biological endpoints have been extracted, and a model extrapolation to the low-dose region performed. Results of model calculations are then compared with evaluations of the lung cancer hazard in populations exposed to radon and its progeny. The model can be applied to practical phenomenological analysis of radiation damage in solid-state systems and to dosimetry of charged particle and fast neutron beams using a variety of detectors. The model can also serve as a guide in building more basic models of the action of ionizing radiation with physical and biological systems and guide of development of models of radiation risk more relevant than that used presently. 185 refs., 31 figs., 3 tabs. (author)

  8. A survey of chemicals inducing lipid peroxidation in biological systems.

    Science.gov (United States)

    Kappus, H

    1987-01-01

    A great number of drugs and chemicals are reviewed which have been shown to stimulate lipid peroxidation in any biological system. The underlying mechanisms, as far as known, are also dealt with. Lipid peroxidation induced by iron ions, organic hydroperoxides, halogenated hydrocarbons, redox cycling drugs, glutathione depleting chemicals, ethanol, heavy metals, ozone, nitrogen dioxide and a number of miscellaneous compounds, e.g. hydrazines, pesticides, antibiotics, are mentioned. It is shown that lipid peroxidation is stimulated by many of these compounds. However, quantitative estimates cannot be given yet and it is still impossible to judge the biological relevance of chemical-induced lipid peroxidation.

  9. Sulfur K-edge absorption spectroscopy on selected biological systems

    International Nuclear Information System (INIS)

    Lichtenberg, Henning

    2008-07-01

    Sulfur is an essential element in organisms. In this thesis investigations of sulfur compounds in selected biological systems by XANES (X-ray Absorption Near Edge Structure) spectroscopy are reported. XANES spectroscopy at the sulfur K-edge provides an excellent tool to gain information about the local environments of sulfur atoms in intact biological samples - no extraction processes are required. Spatially resolved measurements using a Kirkpatrick-Baez mirror focusing system were carried out to investigate the infection of wheat leaves by rust fungi. The results give information about changes in the sulfur metabolism of the host induced by the parasite and about the extension of the infection into visibly uninfected plant tissue. Furthermore, XANES spectra of microbial mats from sulfidic caves were measured. These mats are dominated by microbial groups involved in cycling sulfur. Additionally, the influence of sulfate deprivation and H 2 S exposure on sulfur compounds in onion was investigated. To gain an insight into the thermal degradation of organic material the influence of roasting of sulfur compounds in coffee beans was studied. (orig.)

  10. Neural network models: from biology to many - body phenomenology

    International Nuclear Information System (INIS)

    Clark, J.W.

    1993-01-01

    Theoretical work in neural networks has a strange feel for most physicists. In some cases the aspect of design becomes paramount. More comfortable ground at least for many body theorists may be found in realistic biological simulation, although the complexity of most problems is so awesome that incisive results will be hard won. It has also shown the impressive capabilities of artificial networks in pattern recognition and classification may be exploited to solve management problems in experimental physics and for discovery of radically new theoretical description of physical systems. This advance represents an important step towards the ultimate goal of neuro biological paradigm. (A.B.)

  11. 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.

  12. Modeling systems-level dynamics: Understanding without mechanistic explanation in integrative systems biology.

    Science.gov (United States)

    MacLeod, Miles; Nersessian, Nancy J

    2015-02-01

    In this paper we draw upon rich ethnographic data of two systems biology labs to explore the roles of explanation and understanding in large-scale systems modeling. We illustrate practices that depart from the goal of dynamic mechanistic explanation for the sake of more limited modeling goals. These processes use abstract mathematical formulations of bio-molecular interactions and data fitting techniques which we call top-down abstraction to trade away accurate mechanistic accounts of large-scale systems for specific information about aspects of those systems. We characterize these practices as pragmatic responses to the constraints many modelers of large-scale systems face, which in turn generate more limited pragmatic non-mechanistic forms of understanding of systems. These forms aim at knowledge of how to predict system responses in order to manipulate and control some aspects of them. We propose that this analysis of understanding provides a way to interpret what many systems biologists are aiming for in practice when they talk about the objective of a "systems-level understanding." Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Tav4SB: integrating tools for analysis of kinetic models of biological systems.

    Science.gov (United States)

    Rybiński, Mikołaj; Lula, Michał; Banasik, Paweł; Lasota, Sławomir; Gambin, Anna

    2012-04-05

    Progress in the modeling of biological systems strongly relies on the availability of specialized computer-aided tools. To that end, the Taverna Workbench eases integration of software tools for life science research and provides a common workflow-based framework for computational experiments in Biology. The Taverna services for Systems Biology (Tav4SB) project provides a set of new Web service operations, which extend the functionality of the Taverna Workbench in a domain of systems biology. Tav4SB operations allow you to perform numerical simulations or model checking of, respectively, deterministic or stochastic semantics of biological models. On top of this functionality, Tav4SB enables the construction of high-level experiments. As an illustration of possibilities offered by our project we apply the multi-parameter sensitivity analysis. To visualize the results of model analysis a flexible plotting operation is provided as well. Tav4SB operations are executed in a simple grid environment, integrating heterogeneous software such as Mathematica, PRISM and SBML ODE Solver. The user guide, contact information, full documentation of available Web service operations, workflows and other additional resources can be found at the Tav4SB project's Web page: http://bioputer.mimuw.edu.pl/tav4sb/. The Tav4SB Web service provides a set of integrated tools in the domain for which Web-based applications are still not as widely available as for other areas of computational biology. Moreover, we extend the dedicated hardware base for computationally expensive task of simulating cellular models. Finally, we promote the standardization of models and experiments as well as accessibility and usability of remote services.

  14. 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

  15. Integration of Proteomics, Bioinformatics, and Systems Biology in Traumatic Brain Injury Biomarker Discovery

    Science.gov (United States)

    Guingab-Cagmat, J.D.; Cagmat, E.B.; Hayes, R.L.; Anagli, J.

    2013-01-01

    Traumatic brain injury (TBI) is a major medical crisis without any FDA-approved pharmacological therapies that have been demonstrated to improve functional outcomes. It has been argued that discovery of disease-relevant biomarkers might help to guide successful clinical trials for TBI. Major advances in mass spectrometry (MS) have revolutionized the field of proteomic biomarker discovery and facilitated the identification of several candidate markers that are being further evaluated for their efficacy as TBI biomarkers. However, several hurdles have to be overcome even during the discovery phase which is only the first step in the long process of biomarker development. The high-throughput nature of MS-based proteomic experiments generates a massive amount of mass spectral data presenting great challenges in downstream interpretation. Currently, different bioinformatics platforms are available for functional analysis and data mining of MS-generated proteomic data. These tools provide a way to convert data sets to biologically interpretable results and functional outcomes. A strategy that has promise in advancing biomarker development involves the triad of proteomics, bioinformatics, and systems biology. In this review, a brief overview of how bioinformatics and systems biology tools analyze, transform, and interpret complex MS datasets into biologically relevant results is discussed. In addition, challenges and limitations of proteomics, bioinformatics, and systems biology in TBI biomarker discovery are presented. A brief survey of researches that utilized these three overlapping disciplines in TBI biomarker discovery is also presented. Finally, examples of TBI biomarkers and their applications are discussed. PMID:23750150

  16. Numerical study on a canonized Hamiltonian system representing reduced magnetohydrodynamics and its comparison with two-dimensional Euler system

    OpenAIRE

    Kaneko, Yuta; Yoshida, Zensho

    2014-01-01

    Introducing a Clebsch-like parameterization, we have formulated a canonical Hamiltonian system on a symplectic leaf of reduced magnetohydrodynamics. An interesting structure of the equations is in that the Lorentz-force, which is a quadratic nonlinear term in the conventional formulation, appears as a linear term -{\\Delta}Q, just representing the current density (Q is a Clebsch variable, and {\\Delta} is the two-dimensional Laplacian); omitting this term reduces the system into the two-dimensi...

  17. The Spectrum Prize: A simple algorithm to evaluate the relative sensitivity of γ-ray spectra, representative of detection systems

    Energy Technology Data Exchange (ETDEWEB)

    Spolaore, P.

    2016-03-11

    A simple analysis of gamma spectra selected to represent the performance of different detection systems, or, for one same system, different operation modes or states of progress of the system development, allows to compare the relative average-sensitivities of the represented systems themselves, as operated in the selected cases. The obtained SP figure-of-merit takes into account and correlates the main parameters commonly used to estimate the performance of a system. An example of application is given.

  18. MATHEMATICAL MODEL OF AUTOMATED REHABILITATION SYSTEM WITH BIOLOGICAL FEEDBACK FOR REHABILITATION AND DEVELOPMENT OF MUSCULOSKELETAL SYSTEM

    Directory of Open Access Journals (Sweden)

    Kirill A. Kalyashin

    2013-01-01

    Full Text Available In order to increase the efficiency and safety of rehabilitation of musculoskeletal system, the model and the algorithm for patient interaction with automated rehabilitation system with biological feedback was developed, based on registration and management of the second functional parameter, which prevents risks of overwork while intensive exercises.

  19. [Avifauna in silvopastoral systems in the Mesoamerican Biological Corridor, Tabasco, México].

    Science.gov (United States)

    González-Valdivia, Noel; Barba-Macías, Everardo; Hernández-Daumás, Salvador; Ochoa-Gaona, Susana

    2014-09-01

    Silvopastoral systems support local ecological and economical features as they enhance conservation of floral and faunal communities. As other animal communities, avifauna may be a good representative of habitat alterations, both as the species and functional levels. In order to attend the initiative of Mesoamerican Biological Corridor initiative (CBM) in the state of Tabasco, we studied the diversity of birds in two silvopastoral systems: scattered trees in pastures (ADP), and trees in boundary-hedgerows (AL). For this, we applied the fixed radius counting point method in three priority sites in Tabasco's CBM during the dry and wet season of 2011, and a total of 56, 60 and 62 points were evaluated in Huimanguillo, Tenosique and Tacotalpa, respectively. We observed 2 084 individuals of 154 species (79-89% of expected diversity) and 36 bird families. We detected 92, 87 and 85 species in Huimanguillo, Tenosique and Tacotalpa, respectively, including 35 protected species, of which 23, 19 and 16 in each locality, respectively. All sites showed high diversity (H' ≥ 3.20), low species dominance (D ≥ 0.08) and high equitability (J ≥ 0.77). Species composition showed differences between sites, being most similar Tacotalpa and Tenosique. Ten species were considered characteristic for sites. Although the silvopastoral system did contain protected species, the low diversity and the early successional character of the arboreal components were not attractive to frugivorous bird species. Diversification with native trees can improve the systems to create a complementary habitat and to increase landscape connectivity. The management of silvopastoral practices on cattle dominated landscapes in Tabasco could improve its ecological quality, and thus achieve the CBM's objectives ofbiodiversity conservation combined with human economic activities.

  20. Thermodynamic Optimality criteria for biological systems in linear irreversible thermodynamics

    International Nuclear Information System (INIS)

    Chimal, J C; Sánchez, N; Ramírez, PR

    2017-01-01

    In this paper the methodology of the so-called Linear Irreversible Thermodynamics (LIT) is applied; although traditionally used locally to study general systems in non-equilibrium states in which it is consider both internal and external contributions to the entropy increments in order to analyze the efficiency of two coupled processes with generalized fluxes J 1 , J 2 and their corresponding forces X 1 , X 2 . We extend the former analysis to takes into account two different operating regimes namely: Omega Function and Efficient Power criterion, respectively. Results show analogies in the optimal performance between and we can say that there exist a criteria of optimization which can be used specially for biological systems where a good design of the biological parameters made by nature at maximum efficient power conditions lead to more efficient engines than those at the maximum power conditions or ecological conditions. (paper)