Sample records for actual biological systems

  1. Biological system interactions.

    PubMed Central

    Adomian, G; Adomian, G E; Bellman, R E

    1984-01-01

    Mathematical modeling of cellular population growth, interconnected subsystems of the body, blood flow, and numerous other complex biological systems problems involves nonlinearities and generally randomness as well. Such problems have been dealt with by mathematical methods often changing the actual model to make it tractable. The method presented in this paper (and referenced works) allows much more physically realistic solutions. PMID:6585837

  2. Primary School Student Teachers' Perceived and Actual Knowledge in Biology

    ERIC Educational Resources Information Center

    Eija, Yli-Panula; Eila, Jeronen; Pongsakdi, Nonmanut

    2017-01-01

    Individuals' perceptions of their knowledge can have an important role in shaping their cognition and influencing their behaviour. However, there has been a scarcity of studies in biology on how perceived knowledge relates to actual knowledge. The focus of this article is on quantitative results analysing and interpreting student teachers'…

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

    PubMed

    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.

  4. Fact-finding survey of actual garbage discharged from dormitory and its biological anaerobic-aerobic treatment.

    PubMed

    Imai, T; Ukita, M; Sekine, M; Fukagawa, M; Nakanishi, H

    2000-01-01

    The objective of this study is to find a possibility of complete treatment of garbage and resource recovery (production of methane from available utility of carbon resource in garbage) by biological treatment process. As the first step, a fact-finding survey of actual garbage discharged from the dormitory of the Ube National College of Technology (equivalent to 300 population) was carried out. Second, the combined biological anaerobic-aerobic treatment, i.e. combination of upflow anaerobic sludge blanket (UASB) process and aerobic membrane bioreactor (AMB) process, was applied to the garbage treatment. The applicability and efficiency of this system were investigated in this study. The survey results showed that the composition and quantity of garbage from a student dormitory changed slightly during a week due to the change of the menu, however, they remained almost unchanged during the entire experimental period. The experimental results showed high biodegradability of the garbage, and demonstrated its suitability for methane production. The soluble nitrogen removal was high: over 97%. No excess sludge was wasted from the system. A high treatment efficiency of simultaneous organic carbon and nitrogen was obtained. The possibility of complete treatment of garbage with this process has been positively demonstrated by this study.

  5. How do biological systems discriminate among physically similar ions?

    PubMed

    Diamond, J M

    1975-10-01

    This paper reviews the history of understanding how biological systems can discriminate so strikingly among physically similar ions, especially alkali cations. Appreciation of qualitative regularities ("permitted sequences") and quantitative regularities ("selectivity isotherms") in ion selectivity grew first from studies of ion exchangers and glass electrodes, then of biological systems such as enzymes and cell membranes, and most recently of lipid bilayers doped with model pores and carriers. Discrimination of ions depends on both electrostatic and steric forces. "Black-box" studies on intact biological membranes have in some cases yielded molecular clues to the structure of the actual biological pores and carriers. Major current problems involve the extraction of these molecules; how to do it, what to do when it is achieved, and how (and if) it is relevant to the central problems of membrane function. Further advances are expected soon from studies of rate barriers within membranes, of voltage-dependent ("excitable") conducting channels, and of increasingly complex model systems and biological membranes.

  6. Measuring the Disparities between Biology Undergraduates' Perceptions and Their Actual Knowledge of Scientific Literature with Clickers

    ERIC Educational Resources Information Center

    Bandyopadhyay, Aditi

    2013-01-01

    This article demonstrates an innovative method used to determine the need for information literacy among science undergraduate students at Adelphi University. Using clickers technology, this study measured the disconnect between biology undergraduates' perceived and actual knowledge of scientific literature. The quantitative data collected in the…

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Goldberg, Debra; Hibbs, Matthew; Kall, Lukas

    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 hasmore » 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.« less

  8. Networks’ Characteristics Matter for Systems Biology

    PubMed Central

    Rider, Andrew K.; Milenković, Tijana; Siwo, Geoffrey H.; Pinapati, Richard S.; Emrich, Scott J.; Ferdig, Michael T.; Chawla, Nitesh V.

    2015-01-01

    A fundamental goal of systems biology is to create models that describe relationships between biological components. Networks are an increasingly popular approach to this problem. However, a scientist interested in modeling biological (e.g., gene expression) data as a network is quickly confounded by the fundamental problem: how to construct the network? It is fairly easy to construct a network, but is it the network for the problem being considered? This is an important problem with three fundamental issues: How to weight edges in the network in order to capture actual biological interactions? What is the effect of the type of biological experiment used to collect the data from which the network is constructed? How to prune the weighted edges (or what cut-off to apply)? Differences in the construction of networks could lead to different biological interpretations. Indeed, we find that there are statistically significant dissimilarities in the functional content and topology between gene co-expression networks constructed using different edge weighting methods, data types, and edge cut-offs. We show that different types of known interactions, such as those found through Affinity Capture-Luminescence or Synthetic Lethality experiments, appear in significantly varying amounts in networks constructed in different ways. Hence, we demonstrate that different biological questions may be answered by the different networks. Consequently, we posit that the approach taken to build a network can be matched to biological questions to get targeted answers. More study is required to understand the implications of different network inference approaches and to draw reliable conclusions from networks used in the field of systems biology. PMID:26500772

  9. 7th Annual Systems Biology Symposium: Systems Biology and Engineering

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    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 aremore » 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."« less

  10. Guidelines for Managing Suspected Chemical and Biological Agent Incidents in Rail Tunnel Systems

    DOT National Transportation Integrated Search

    2002-03-01

    These emergency management guidelines are designed to help transit managers (1) prepare and implement standard operating procedures (SOPs) for handling potential and actual chemical or biological agent attacks in their rail tunnel system and (2) unde...

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

    PubMed Central

    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.

    PubMed

    Chen, Bor-Sen; Wu, Chia-Chou

    2013-10-11

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

  13. Systems interface biology

    PubMed Central

    Doyle, Francis J; Stelling, Jörg

    2006-01-01

    The field of systems biology has attracted the attention of biologists, engineers, mathematicians, physicists, chemists and others in an endeavour to create systems-level understanding of complex biological networks. In particular, systems engineering methods are finding unique opportunities in characterizing the rich behaviour exhibited by biological systems. In the same manner, these new classes of biological problems are motivating novel developments in theoretical systems approaches. Hence, the interface between systems and biology is of mutual benefit to both disciplines. PMID:16971329

  14. Back to the biology in systems biology: what can we learn from biomolecular networks?

    PubMed

    Huang, Sui

    2004-02-01

    Genome-scale molecular networks, including protein interaction and gene regulatory networks, have taken centre stage in the investigation of the burgeoning disciplines of systems biology and biocomplexity. What do networks tell us? Some see in networks simply the comprehensive, detailed description of all cellular pathways, others seek in networks simple, higher-order qualities that emerge from the collective action of the individual pathways. This paper discusses networks from an encompassing category of thinking that will hopefully help readers to bridge the gap between these polarised viewpoints. Systems biology so far has emphasised the characterisation of large pathway maps. Now one has to ask: where is the actual biology in 'systems biology'? As structures midway between genome and phenome, and by serving as an 'extended genotype' or an 'elementary phenotype', molecular networks open a new window to the study of evolution and gene function in complex living systems. For the study of evolution, features in network topology offer a novel starting point for addressing the old debate on the relative contributions of natural selection versus intrinsic constraints to a particular trait. To study the function of genes, it is necessary not only to see them in the context of gene networks, but also to reach beyond describing network topology and to embrace the global dynamics of networks that will reveal higher-order, collective behaviour of the interacting genes. This will pave the way to understanding how the complexity of genome-wide molecular networks collapses to produce a robust whole-cell behaviour that manifests as tightly-regulated switching between distinct cell fates - the basis for multicellular life.

  15. Macroscopic Quantum-Type Potentials in Theoretical Systems Biology

    PubMed Central

    Nottale, Laurent

    2014-01-01

    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. PMID:24709901

  16. Computational systems chemical biology.

    PubMed

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

    2011-01-01

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

  17. Computational Systems Chemical Biology

    PubMed Central

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

    2013-01-01

    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). The overarching goal of computational SCB is to develop tools for integrated chemical-biological data acquisition, filtering and processing, by taking into account relevant information related to interactions between proteins and small molecules, possible metabolic transformations of small molecules, as well as associated information related to genes, networks, small molecules and, where applicable, mutants and variants of those proteins. There is yet an unmet need to develop an integrated in silico pharmacology / systems biology continuum that embeds drug-target-clinical outcome (DTCO) triplets, a capability that is vital to the future of chemical biology, pharmacology and systems biology. Through the development of the SCB approach, scientists will be able to start addressing, in an integrated simulation environment, questions that make the best use of our ever-growing chemical and biological data repositories at the system-wide level. This chapter reviews some of the major research concepts and describes key components that constitute the emerging area of computational systems chemical biology. PMID:20838980

  18. Biological life-support systems

    NASA Technical Reports Server (NTRS)

    Shepelev, Y. Y.

    1975-01-01

    The establishment of human living environments by biologic methods, utilizing the appropriate functions of autotrophic and heterotrophic organisms is examined. Natural biologic systems discussed in terms of modeling biologic life support systems (BLSS), the structure of biologic life support systems, and the development of individual functional links in biologic life support systems are among the factors considered. Experimental modeling of BLSS in order to determine functional characteristics, mechanisms by which stability is maintained, and principles underlying control and regulation is also discussed.

  19. [Cooperation with the electronic medical record and accounting system of an actual dose of drug given by a radiology information system].

    PubMed

    Yamamoto, Hideo; Yoneda, Tarou; Satou, Shuji; Ishikawa, Toru; Hara, Misako

    2009-12-20

    By input of the actual dose of a drug given into a radiology information system, the system converting with an accounting system into a cost of the drug from the actual dose in the electronic medical record was built. In the drug master, the first unit was set as the cost of the drug, and we set the second unit as the actual dose. The second unit in the radiology information system was received by the accounting system through electronic medical record. In the accounting system, the actual dose was changed into the cost of the drug using the dose of conversion to the first unit. The actual dose was recorded on a radiology information system and electronic medical record. The actual dose was indicated on the accounting system, and the cost for the drug was calculated. About the actual dose of drug, cooperation of the information in a radiology information system and electronic medical record were completed. It was possible to decide the volume of drug from the correct dose of drug at the previous inspection. If it is necessary for the patient to have another treatment of medicine, it is important to know the actual dose of drug given. Moreover, authenticity of electronic medical record based on a statute has also improved.

  20. Portable refrigerant charge meter and method for determining the actual refrigerant charge in HVAC systems

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gao, Zhiming; Abdelaziz, Omar; LaClair, Tim L.

    A refrigerant charge meter and a method for determining the actual refrigerant charge in HVAC systems are described. The meter includes means for determining an optimum refrigerant charge from system subcooling and system component parameters. The meter also includes means for determining the ratio of the actual refrigerant charge to the optimum refrigerant charge. Finally, the meter includes means for determining the actual refrigerant charge from the optimum refrigerant charge and the ratio of the actual refrigerant charge to the optimum refrigerant charge.

  1. From systems biology to systems biomedicine.

    PubMed

    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.

  2. Systems Biology-an interdisciplinary approach.

    PubMed

    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.

  3. Actual evapotranspiration and deficit: Biologically meaningful correlates of vegetation distribution across spatial scales

    USGS Publications Warehouse

    Stephenson, N.L.

    1998-01-01

    Correlative approaches to understanding the climatic controls of vegetation distribution have exhibited at least two important weaknesses: they have been conceptually divorced across spatial scales, and their climatic parameters have not necessarily represented aspects of climate of broad physiological importance to plants. Using examples from the literature and from the Sierra Nevada of California, I argue that two water balance parameters-actual evapotranspiration (AET) and deficit (D)-are biologically meaningful, are well correlated with the distribution of vegetation types, and exhibit these qualities over several orders of magnitude of spatial scale (continental to local). I reach four additional conclusions. (1) Some pairs of climatic parameters presently in use are functionally similar to AET and D; however, AET and D may be easier to interpret biologically. (2) Several well-known climatic parameters are biologically less meaningful or less important than AET and D, and consequently are poorer correlates of the distribution of vegetation types. Of particular interest, AET is a much better correlate of the distributions of coniferous and deciduous forests than minimum temperature. (3) The effects of evaporative demand and water availability on a site's water balance are intrinsically different. For example, the 'dry' experienced by plants on sunward slopes (high evaporative demand) is not comparable to the 'dry' experienced by plants on soils with low water-holding capacities (low water availability), and these differences are reflected in vegetation patterns. (4) Many traditional topographic moisture scalars-those that additively combine measures related to evaporative demand and water availability are not necessarily meaningful for describing site conditions as sensed by plants; the same holds for measured soil moisture. However, using AET and D in place of moisture scalars and measured soil moisture can solve these problems.

  4. Computational Systems Biology

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    McDermott, Jason E.; Samudrala, Ram; Bumgarner, Roger E.

    2009-05-01

    Computational systems biology is the term that we use to describe computational methods to identify, infer, model, and store relationships between the molecules, pathways, and cells (“systems”) involved in a living organism. Based on this definition, the field of computational systems biology has been in existence for some time. However, the recent confluence of high throughput methodology for biological data gathering, genome-scale sequencing and computational processing power has driven a reinvention and expansion of this field. The expansions include not only modeling of small metabolic{Ishii, 2004 #1129; Ekins, 2006 #1601; Lafaye, 2005 #1744} and signaling systems{Stevenson-Paulik, 2006 #1742; Lafaye, 2005more » #1744} but also modeling of the relationships between biological components in very large systems, incluyding whole cells and organisms {Ideker, 2001 #1124; Pe'er, 2001 #1172; Pilpel, 2001 #393; Ideker, 2002 #327; Kelley, 2003 #1117; Shannon, 2003 #1116; Ideker, 2004 #1111}{Schadt, 2003 #475; Schadt, 2006 #1661}{McDermott, 2002 #878; McDermott, 2005 #1271}. Generally these models provide a general overview of one or more aspects of these systems and leave the determination of details to experimentalists focused on smaller subsystems. The promise of such approaches is that they will elucidate patterns, relationships and general features that are not evident from examining specific components or subsystems. These predictions are either interesting in and of themselves (for example, the identification of an evolutionary pattern), or are interesting and valuable to researchers working on a particular problem (for example highlight a previously unknown functional pathway). Two events have occurred to bring about the field computational systems biology to the forefront. One is the advent of high throughput methods that have generated large amounts of information about particular systems in the form of genetic studies, gene expression analyses (both

  5. Biological conversion system

    DOEpatents

    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.

  6. Engineering scalable biological systems

    PubMed Central

    2010-01-01

    Synthetic biology is focused on engineering biological organisms to study natural systems and to provide new solutions for pressing medical, industrial and environmental problems. At the core of engineered organisms are synthetic biological circuits that execute the tasks of sensing inputs, processing logic and performing output functions. In the last decade, significant progress has been made in developing basic designs for a wide range of biological circuits in bacteria, yeast and mammalian systems. However, significant challenges in the construction, probing, modulation and debugging of synthetic biological systems must be addressed in order to achieve scalable higher-complexity biological circuits. Furthermore, concomitant efforts to evaluate the safety and biocontainment of engineered organisms and address public and regulatory concerns will be necessary to ensure that technological advances are translated into real-world solutions. PMID:21468204

  7. 6th Institute for Systems Biology International Symposium: Systems Biology and the Environment

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Galitski, Timothy P.

    2007-04-23

    Systems biology recognizes the complex multi-scale organization of biological systems, from molecules to ecosystems. The International Symposium on Systems Biology is an annual two-day event gathering the most influential researchers transforming biology into an integrative discipline investigating complex systems. In recognition of the fundamental similarity between the scientific problems addressed in environmental science and systems biology studies at the molecular, cellular, and organismal levels, the 2007 Symposium featured global leaders in “Systems Biology and the Environment.” The objective of the 2007 “Systems Biology and the Environment” International Symposium was to stimulate interdisciplinary thinking and research that spans systems biology andmore » environmental science. This Symposium was well aligned with the DOE’s Genomics: GTL program efforts to achieve scientific objectives for each of the three DOE missions: Develop biofuels as a major secure energy source for this century; Develop biological solutions for intractable environmental problems; Understand biosystems’ climate impacts and assess sequestration strategies. Our scientific program highlighted world-class research exemplifying these priorities. The Symposium featured 45 minute lectures from 12 researchers including: Penny/Sallie Chisholm of MIT gave the keynote address “Tiny Cells, Global Impact: What Prochlorococcus Can Teach Us About Systems Biology”, plus Jim Fredrickson of PNNL, Nitin Baliga of ISB, Steve Briggs of UCSD, David Cox of Perlegen Sciences, Antoine Danchin of Institut Pasteur, John Delaney of the U of Washington, John Groopman of Johns Hopkins, Ben Kerr of the U of Washington, Steve Koonin of BP, Elliott Meyerowitz of Caltech, and Ed Rubin of LBNL. The 2007 Symposium promoted DOE’s three mission areas among scientists from multiple disciplines representing academia, non-profit research institutions, and the private sector. As in all previous Symposia

  8. Fostering synergy between cell biology and systems biology.

    PubMed

    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.

  9. Biological Diversity in the Patent System

    PubMed Central

    Oldham, Paul; Hall, Stephen; Forero, Oscar

    2013-01-01

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

  10. Hierarchical structure of biological systems

    PubMed Central

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

    2014-01-01

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

  11. Plant systems biology: network matters.

    PubMed

    Lucas, Mikaël; Laplaze, Laurent; Bennett, Malcolm J

    2011-04-01

    Systems biology is all about networks. A recent trend has been to associate systems biology exclusively with the study of gene regulatory or protein-interaction networks. However, systems biology approaches can be applied at many other scales, from the subatomic to the ecosystem scales. In this review, we describe studies at the sub-cellular, tissue, whole plant and crop scales and highlight how these studies can be related to systems biology. We discuss the properties of system approaches at each scale as well as their current limits, and pinpoint in each case advances unique to the considered scale but representing potential for the other scales. We conclude by examining plant models bridging different scales and considering the future prospects of plant systems biology. © 2011 Blackwell Publishing Ltd.

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

    PubMed Central

    Smolke, Christina D.; Silver, Pamela A.

    2011-01-01

    Synthetic biology aims to make the engineering of biology faster and more predictable. In contrast, systems biology focuses on the interaction of myriad components and how these give rise to the dynamic and complex behavior of biological systems. Here, we examine the synergies between these two fields. PMID:21414477

  13. Micro-separation toward systems biology.

    PubMed

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

    2006-02-17

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

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

    PubMed

    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.

  15. The impact of biologic therapy in chronic plaque psoriasis from a societal perspective: an analysis based on Italian actual clinical practice.

    PubMed

    Polistena, B; Calzavara-Pinton, P; Altomare, G; Berardesca, E; Girolomoni, G; Martini, P; Peserico, A; Puglisi Guerra, A; Spandonaro, F; Vena Gino, A; Chimenti, S; Ayala, F

    2015-12-01

    Psoriasis is one of the most common forms of chronic dermatitis, affecting 2-3% of the worldwide population. It has a serious effect on the way patients perceive themselves and others, thereby prejudicing their quality of life and giving rise to a significant deterioration in their psycho-physical well-being; it also poses greater difficulties for them in leading a normal social life, including their ability to conduct a normal working life. All the above-mentioned issues imply a cost for the society. This study proposes to evaluate the impact on societal costs for the treatment of chronic plaque psoriasis with biologics (etanercept, infliximab and adalimumab) in the Italian clinical practice. A prospective observational study has been conducted in 12 specialized centres of the Psocare network, located throughout Italy. Direct and indirect costs (as well as the health-related quality of life of patients with plaque psoriasis undergoing biologic treatments) have been estimated, while the societal impact has been determined using a cost-utility approach. Non-medical and indirect costs account for as much as 44.97% of the total cost prior to treatment and to 6.59% after treatment, with an overall 71.38% decrease. Adopting a societal perspective in the actual clinical practice of the Italian participating centres, the ICER of biologic therapies for treating plaque psoriasis amounted to €18634.40 per QALY gained--a value far from the €28656.30 obtained by adopting a third-party payer perspective. Our study confirms that chronic psoriasis subjects patients to a considerable burden, together with their families and caregivers, stressing how important it is to take the societal perspective into consideration during the appraisal process. Besides, using data derived from Italian actual practice, treatment with biologics shows a noteworthy benefit in social terms. © 2015 European Academy of Dermatology and Venereology.

  16. SYSTEMS BIOLOGY MODEL DEVELOPMENT AND APPLICATION

    EPA Science Inventory

    System biology models holistically describe, in a quantitative fashion, the relationships between different levels of a biologic system. Relationships between individual components of a system are delineated. System biology models describe how the components of the system inter...

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

    DOEpatents

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

    2000-08-01

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

  18. Will Systems Biology Deliver Its Promise and Contribute to the Development of New or Improved Vaccines? What Really Constitutes the Study of "Systems Biology" and How Might Such an Approach Facilitate Vaccine Design.

    PubMed

    Germain, Ronald N

    2017-10-16

    A dichotomy exists in the field of vaccinology about the promise versus the hype associated with application of "systems biology" approaches to rational vaccine design. Some feel it is the only way to efficiently uncover currently unknown parameters controlling desired immune responses or discover what elements actually mediate these responses. Others feel that traditional experimental, often reductionist, methods for incrementally unraveling complex biology provide a more solid way forward, and that "systems" approaches are costly ways to collect data without gaining true insight. Here I argue that both views are inaccurate. This is largely because of confusion about what can be gained from classical experimentation versus statistical analysis of large data sets (bioinformatics) versus methods that quantitatively explain emergent properties of complex assemblies of biological components, with the latter reflecting what was previously called "physiology." Reductionist studies will remain essential for generating detailed insight into the functional attributes of specific elements of biological systems, but such analyses lack the power to provide a quantitative and predictive understanding of global system behavior. But by employing (1) large-scale screening methods for discovery of unknown components and connections in the immune system ( omics ), (2) statistical analysis of large data sets ( bioinformatics ), and (3) the capacity of quantitative computational methods to translate these individual components and connections into models of emergent behavior ( systems biology ), we will be able to better understand how the overall immune system functions and to determine with greater precision how to manipulate it to produce desired protective responses. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  19. Three-dimensional printing of human skeletal muscle cells: An interdisciplinary approach for studying biological systems.

    PubMed

    Bagley, James R; Galpin, Andrew J

    2015-01-01

    Interdisciplinary exploration is vital to education in the 21st century. This manuscript outlines an innovative laboratory-based teaching method that combines elements of biochemistry/molecular biology, kinesiology/health science, computer science, and manufacturing engineering to give students the ability to better conceptualize complex biological systems. Here, we utilize technology available at most universities to print three-dimensional (3D) scale models of actual human muscle cells (myofibers) out of bioplastic materials. The same methodological approach could be applied to nearly any cell type or molecular structure. This advancement is significant because historically, two-dimensional (2D) myocellular images have proven insufficient for detailed analysis of organelle organization and morphology. 3D imaging fills this void by providing accurate and quantifiable myofiber structural data. Manipulating tangible 3D models combats 2D limitation and gives students new perspectives and alternative learning experiences that may assist their understanding. This approach also exposes learners to 1) human muscle cell extraction and isolation, 2) targeted fluorescence labeling, 3) confocal microscopy, 4) image processing (via open-source software), and 5) 3D printing bioplastic scale-models (×500 larger than the actual cells). Creating these physical models may further student's interest in the invisible world of molecular and cellular biology. Furthermore, this interdisciplinary laboratory project gives instructors of all biological disciplines a new teaching tool to foster integrative thinking. © 2015 The International Union of Biochemistry and Molecular Biology.

  20. Systems biology and mechanics of growth.

    PubMed

    Eskandari, Mona; Kuhl, Ellen

    2015-01-01

    In contrast to inert systems, living biological systems have the advantage to adapt to their environment through growth and evolution. This transfiguration is evident during embryonic development, when the predisposed need to grow allows form to follow function. Alterations in the equilibrium state of biological systems breed disease and mutation in response to environmental triggers. The need to characterize the growth of biological systems to better understand these phenomena has motivated the continuum theory of growth and stimulated the development of computational tools in systems biology. Biological growth in development and disease is increasingly studied using the framework of morphoelasticity. Here, we demonstrate the potential for morphoelastic simulations through examples of volume, area, and length growth, inspired by tumor expansion, chronic bronchitis, brain development, intestine formation, plant shape, and myopia. We review the systems biology of living systems in light of biochemical and optical stimuli and classify different types of growth to facilitate the design of growth models for various biological systems within this generic framework. Exploring the systems biology of growth introduces a new venue to control and manipulate embryonic development, disease progression, and clinical intervention. © 2015 Wiley Periodicals, Inc.

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

    PubMed Central

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

    2011-01-01

    Artificial gene circuits have been proposed to be embedded into microbial cells that function as switches, timers, oscillators, and the Boolean logic gates. Building more complex systems from these basic gene circuit components is one key advance for biologic circuit design and synthetic biology. However, the behavior of bioengineered gene circuits remains unstable and uncertain. In this study, a nonlinear stochastic system is proposed to model the biological systems with intrinsic parameter fluctuations and environmental molecular noise from the cellular context in the host cell. Based on evolutionary systems biology algorithm, the design parameters of target gene circuits can evolve to specific values in order to robustly track a desired biologic function in spite of intrinsic and environmental noise. The fitness function is selected to be inversely proportional to the tracking error so that the evolutionary biological circuit can achieve the optimal tracking mimicking the evolutionary process of a gene circuit. Finally, several design examples are given in silico with the Monte Carlo simulation to illustrate the design procedure and to confirm the robust performance of the proposed design method. The result shows that the designed gene circuits can robustly track desired behaviors with minimal errors even with nontrivial intrinsic and external noise. PMID:22187523

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

    PubMed

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

    2011-01-01

    Artificial gene circuits have been proposed to be embedded into microbial cells that function as switches, timers, oscillators, and the Boolean logic gates. Building more complex systems from these basic gene circuit components is one key advance for biologic circuit design and synthetic biology. However, the behavior of bioengineered gene circuits remains unstable and uncertain. In this study, a nonlinear stochastic system is proposed to model the biological systems with intrinsic parameter fluctuations and environmental molecular noise from the cellular context in the host cell. Based on evolutionary systems biology algorithm, the design parameters of target gene circuits can evolve to specific values in order to robustly track a desired biologic function in spite of intrinsic and environmental noise. The fitness function is selected to be inversely proportional to the tracking error so that the evolutionary biological circuit can achieve the optimal tracking mimicking the evolutionary process of a gene circuit. Finally, several design examples are given in silico with the Monte Carlo simulation to illustrate the design procedure and to confirm the robust performance of the proposed design method. The result shows that the designed gene circuits can robustly track desired behaviors with minimal errors even with nontrivial intrinsic and external noise.

  3. Systems Approaches to Cancer Biology.

    PubMed

    Archer, Tenley C; Fertig, Elana J; Gosline, Sara J C; Hafner, Marc; Hughes, Shannon K; Joughin, Brian A; Meyer, Aaron S; Piccolo, Stephen R; Shajahan-Haq, Ayesha N

    2016-12-01

    Cancer systems biology aims to understand cancer as an integrated system of genes, proteins, networks, and interactions rather than an entity of isolated molecular and cellular components. The inaugural Systems Approaches to Cancer Biology Conference, cosponsored by the Association of Early Career Cancer Systems Biologists and the National Cancer Institute of the NIH, focused on the interdisciplinary field of cancer systems biology and the challenging cancer questions that are best addressed through the combination of experimental and computational analyses. Attendees found that elucidating the many molecular features of cancer inevitably reveals new forms of complexity and concluded that ensuring the reproducibility and impact of cancer systems biology studies will require widespread method and data sharing and, ultimately, the translation of important findings to the clinic. Cancer Res; 76(23); 6774-7. ©2016 AACR. ©2016 American Association for Cancer Research.

  4. Biophysics and systems biology.

    PubMed

    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.

  5. Biophysics and systems biology

    PubMed Central

    Noble, Denis

    2010-01-01

    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. PMID:20123750

  6. Institute for Genomics and Systems Biology

    Science.gov Websites

    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

  7. Integrating systems biology models and biomedical ontologies

    PubMed Central

    2011-01-01

    Background Systems biology is an approach to biology that emphasizes the structure and dynamic behavior of biological systems and the interactions that occur within them. To succeed, systems biology crucially depends on the accessibility and integration of data across domains and levels of granularity. Biomedical ontologies were developed to facilitate such an integration of data and are often used to annotate biosimulation models in systems biology. Results We provide a framework to integrate representations of in silico systems biology with those of in vivo biology as described by biomedical ontologies and demonstrate this framework using the Systems Biology Markup Language. We developed the SBML Harvester software that automatically converts annotated SBML models into OWL and we apply our software to those biosimulation models that are contained in the BioModels Database. We utilize the resulting knowledge base for complex biological queries that can bridge levels of granularity, verify models based on the biological phenomenon they represent and provide a means to establish a basic qualitative layer on which to express the semantics of biosimulation models. Conclusions We establish an information flow between biomedical ontologies and biosimulation models and we demonstrate that the integration of annotated biosimulation models and biomedical ontologies enables the verification of models as well as expressive queries. Establishing a bi-directional information flow between systems biology and biomedical ontologies has the potential to enable large-scale analyses of biological systems that span levels of granularity from molecules to organisms. PMID:21835028

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

    PubMed

    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.

  9. Power Delivery from an Actual Thermoelectric Generation System

    NASA Astrophysics Data System (ADS)

    Kaibe, Hiromasa; Kajihara, Takeshi; Nagano, Kouji; Makino, Kazuya; Hachiuma, Hirokuni; Natsuume, Daisuke

    2014-06-01

    Similar to photovoltaic (PV) and fuel cells, thermoelectric generators (TEGs) supply direct-current (DC) power, essentially requiring DC/alternating current (AC) conversion for delivery as electricity into the grid network. Use of PVs is already well established through power conditioning systems (PCSs) that enable DC/AC conversion with maximum-power-point tracking, which enables commercial use by customers. From the economic, legal, and regulatory perspectives, a commercial PCS for PVs should also be available for TEGs, preferably as is or with just simple adjustment. Herein, we report use of a PV PCS with an actual TEG. The results are analyzed, and proper application for TEGs is proposed.

  10. Systems biology of human atherosclerosis.

    PubMed

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

    2014-01-01

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

  11. Systems Biology Approach in Hypertension Research.

    PubMed

    Delles, Christian; Husi, Holger

    2017-01-01

    Systems biology is an approach to study all genes, gene transcripts, proteins, metabolites, and their interactions in specific cells, tissues, organs, or the whole organism. It is based on data derived from high-throughput analytical technologies and bioinformatics tools to analyze these data, and aims to understand the whole system rather than individual aspects of it. Systems biology can be applied to virtually all conditions and diseases and therefore also to hypertension and its underlying vascular disorders. Unlike other methods in this book there is no clear-cut protocol to explain a systems biology approach. We will instead outline some of the most important and common steps in the generation and analysis of systems biology data.

  12. Circadian systems biology in Metazoa.

    PubMed

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

    2015-11-01

    Systems biology, which can be defined as integrative biology, comprises multistage processes that can be used to understand components of complex biological systems of living organisms and provides hierarchical information to decoding life. Using systems biology approaches such as genomics, transcriptomics and proteomics, it is now possible to delineate more complicated interactions between circadian control systems and diseases. The circadian rhythm is a multiscale phenomenon existing within the body that influences numerous physiological activities such as changes in gene expression, protein turnover, metabolism and human behavior. In this review, we describe the relationships between the circadian control system and its related genes or proteins, and circadian rhythm disorders in systems biology studies. To maintain and modulate circadian oscillation, cells possess elaborative feedback loops composed of circadian core proteins that regulate the expression of other genes through their transcriptional activities. The disruption of these rhythms has been reported to be associated with diseases such as arrhythmia, obesity, insulin resistance, carcinogenesis and disruptions in natural oscillations in the control of cell growth. This review demonstrates that lifestyle is considered as a fundamental factor that modifies circadian rhythm, and the development of dysfunctions and diseases could be regulated by an underlying expression network with multiple circadian-associated signals. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  13. Modeling formalisms in Systems Biology

    PubMed Central

    2011-01-01

    Systems Biology has taken advantage of computational tools and high-throughput experimental data to model several biological processes. These include signaling, gene regulatory, and metabolic networks. However, most of these models are specific to each kind of network. Their interconnection demands a whole-cell modeling framework for a complete understanding of cellular systems. We describe the features required by an integrated framework for modeling, analyzing and simulating biological processes, and review several modeling formalisms that have been used in Systems Biology including Boolean networks, Bayesian networks, Petri nets, process algebras, constraint-based models, differential equations, rule-based models, interacting state machines, cellular automata, and agent-based models. We compare the features provided by different formalisms, and discuss recent approaches in the integration of these formalisms, as well as possible directions for the future. PMID:22141422

  14. Mammalian Synthetic Biology: Engineering Biological Systems.

    PubMed

    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.

  15. Metabolic systems biology: a brief primer.

    PubMed

    Edwards, Lindsay M

    2017-05-01

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

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

    ERIC Educational Resources Information Center

    Tribe, Michael; Pritchard, Alan J.

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

  17. Dynamics of biological systems: role of systems biology in medical research.

    PubMed

    Assmus, Heike E; Herwig, Ralf; Cho, Kwang-Hyun; Wolkenhauer, Olaf

    2006-11-01

    Cellular systems are networks of interacting components that change with time in response to external and internal events. Studying the dynamic behavior of these networks is the basis for an understanding of cellular functions and disease mechanisms. Quantitative time-series data leading to meaningful models can improve our knowledge of human physiology in health and disease, and aid the search for earlier diagnoses, better therapies and a healthier life. The advent of systems biology is about to take the leap into clinical research and medical applications. This review emphasizes the importance of a dynamic view and understanding of cell function. We discuss the potential for computer-aided mathematical modeling of biological systems in medical research with examples from some of the major therapeutic areas: cancer, cardiovascular, diabetic and neurodegenerative medicine.

  18. A framework for evolutionary systems biology

    PubMed Central

    Loewe, Laurence

    2009-01-01

    Background Many difficult problems in evolutionary genomics are related to mutations that have weak effects on fitness, as the consequences of mutations with large effects are often simple to predict. Current systems biology has accumulated much data on mutations with large effects and can predict the properties of knockout mutants in some systems. However experimental methods are too insensitive to observe small effects. Results Here I propose a novel framework that brings together evolutionary theory and current systems biology approaches in order to quantify small effects of mutations and their epistatic interactions in silico. Central to this approach is the definition of fitness correlates that can be computed in some current systems biology models employing the rigorous algorithms that are at the core of much work in computational systems biology. The framework exploits synergies between the realism of such models and the need to understand real systems in evolutionary theory. This framework can address many longstanding topics in evolutionary biology by defining various 'levels' of the adaptive landscape. Addressed topics include the distribution of mutational effects on fitness, as well as the nature of advantageous mutations, epistasis and robustness. Combining corresponding parameter estimates with population genetics models raises the possibility of testing evolutionary hypotheses at a new level of realism. Conclusion EvoSysBio is expected to lead to a more detailed understanding of the fundamental principles of life by combining knowledge about well-known biological systems from several disciplines. This will benefit both evolutionary theory and current systems biology. Understanding robustness by analysing distributions of mutational effects and epistasis is pivotal for drug design, cancer research, responsible genetic engineering in synthetic biology and many other practical applications. PMID:19239699

  19. High School Biology Today: What the Committee of Ten Actually Said

    PubMed Central

    2007-01-01

    This essay describes how in the 1890s the Committee of Ten arrived at their recommendations about the organization of the high school biological sciences and seeks to correct the frequently held, but erroneous view that the Committee of Ten was the initiator of the Biology-Chemistry-Physics order of teaching sciences prevalent in high schools today. The essay details the factors underlying the changing views of high school biology from its “natural history” origins, through its “zoology, botany, physiology” disciplinary phase to its eventual integration into a “general biology” course. The simultaneous parallel development of the “Carnegie Unit” for measuring coursework is highlighted as a significant contributor in the evolution of the present day high school biology course. The essay concludes with a discussion of the implications of the grade placement of the sciences for the future development of high school biology. PMID:17785402

  20. Omics/systems biology and cancer cachexia.

    PubMed

    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.

  1. Systems biology of personalized nutrition

    PubMed Central

    van Ommen, Ben; van den Broek, Tim; de Hoogh, Iris; van Erk, Marjan; van Someren, Eugene; Rouhani-Rankouhi, Tanja; Anthony, Joshua C; Hogenelst, Koen; Pasman, Wilrike; Boorsma, André; Wopereis, Suzan

    2017-01-01

    Abstract Personalized nutrition is fast becoming a reality due to a number of technological, scientific, and societal developments that complement and extend current public health nutrition recommendations. Personalized nutrition tailors dietary recommendations to specific biological requirements on the basis of a person’s health status and goals. The biology underpinning these recommendations is complex, and thus any recommendations must account for multiple biological processes and subprocesses occurring in various tissues and must be formed with an appreciation for how these processes interact with dietary nutrients and environmental factors. Therefore, a systems biology–based approach that considers the most relevant interacting biological mechanisms is necessary to formulate the best recommendations to help people meet their wellness goals. Here, the concept of “systems flexibility” is introduced to personalized nutrition biology. Systems flexibility allows the real-time evaluation of metabolism and other processes that maintain homeostasis following an environmental challenge, thereby enabling the formulation of personalized recommendations. Examples in the area of macro- and micronutrients are reviewed. Genetic variations and performance goals are integrated into this systems approach to provide a strategy for a balanced evaluation and an introduction to personalized nutrition. Finally, modeling approaches that combine personalized diagnosis and nutritional intervention into practice are reviewed. PMID:28969366

  2. Mass spectrometry in systems biology an introduction.

    PubMed

    Dunn, Warwick B

    2011-01-01

    The qualitative detection, quantification, and structural characterization of analytes in biological systems are important requirements for objectives to be fulfilled in systems biology research. One analytical tool applied to a multitude of systems biology studies is mass spectrometry, particularly for the study of proteins and metabolites. Here, the role of mass spectrometry in systems biology will be assessed, the advantages and disadvantages discussed, and the instrument configurations available described. Finally, general applications will be briefly reviewed. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Systems cell biology

    PubMed Central

    Mast, Fred D.; Ratushny, Alexander V.

    2014-01-01

    Systems cell biology melds high-throughput experimentation with quantitative analysis and modeling to understand many critical processes that contribute to cellular organization and dynamics. Recently, there have been several advances in technology and in the application of modeling approaches that enable the exploration of the dynamic properties of cells. Merging technology and computation offers an opportunity to objectively address unsolved cellular mechanisms, and has revealed emergent properties and helped to gain a more comprehensive and fundamental understanding of cell biology. PMID:25225336

  4. Application of hierarchical dissociated neural network in closed-loop hybrid system integrating biological and mechanical intelligence.

    PubMed

    Li, Yongcheng; Sun, Rong; Zhang, Bin; Wang, Yuechao; Li, Hongyi

    2015-01-01

    Neural networks are considered the origin of intelligence in organisms. In this paper, a new design of an intelligent system merging biological intelligence with artificial intelligence was created. It was based on a neural controller bidirectionally connected to an actual mobile robot to implement a novel vehicle. Two types of experimental preparations were utilized as the neural controller including 'random' and '4Q' (cultured neurons artificially divided into four interconnected parts) neural network. Compared to the random cultures, the '4Q' cultures presented absolutely different activities, and the robot controlled by the '4Q' network presented better capabilities in search tasks. Our results showed that neural cultures could be successfully employed to control an artificial agent; the robot performed better and better with the stimulus because of the short-term plasticity. A new framework is provided to investigate the bidirectional biological-artificial interface and develop new strategies for a future intelligent system using these simplified model systems.

  5. Application of Hierarchical Dissociated Neural Network in Closed-Loop Hybrid System Integrating Biological and Mechanical Intelligence

    PubMed Central

    Zhang, Bin; Wang, Yuechao; Li, Hongyi

    2015-01-01

    Neural networks are considered the origin of intelligence in organisms. In this paper, a new design of an intelligent system merging biological intelligence with artificial intelligence was created. It was based on a neural controller bidirectionally connected to an actual mobile robot to implement a novel vehicle. Two types of experimental preparations were utilized as the neural controller including ‘random’ and ‘4Q’ (cultured neurons artificially divided into four interconnected parts) neural network. Compared to the random cultures, the ‘4Q’ cultures presented absolutely different activities, and the robot controlled by the ‘4Q’ network presented better capabilities in search tasks. Our results showed that neural cultures could be successfully employed to control an artificial agent; the robot performed better and better with the stimulus because of the short-term plasticity. A new framework is provided to investigate the bidirectional biological-artificial interface and develop new strategies for a future intelligent system using these simplified model systems. PMID:25992579

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

    PubMed

    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.

  7. Theoretical aspects of Systems Biology.

    PubMed

    Bizzarri, Mariano; Palombo, Alessandro; Cucina, Alessandra

    2013-05-01

    The natural world consists of hierarchical levels of complexity that range from subatomic particles and molecules to ecosystems and beyond. This implies that, in order to explain the features and behavior of a whole system, a theory might be required that would operate at the corresponding hierarchical level, i.e. where self-organization processes take place. In the past, biological research has focused on questions that could be answered by a reductionist program of genetics. The organism (and its development) was considered an epiphenomenona of its genes. However, a profound rethinking of the biological paradigm is now underway and it is likely that such a process will lead to a conceptual revolution emerging from the ashes of reductionism. This revolution implies the search for general principles on which a cogent theory of biology might rely. Because much of the logic of living systems is located at higher levels, it is imperative to focus on them. Indeed, both evolution and physiology work on these levels. Thus, by no means Systems Biology could be considered a 'simple' 'gradual' extension of Molecular Biology. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Optimizing Nutrient Uptake in Biological Transport Networks

    NASA Astrophysics Data System (ADS)

    Ronellenfitsch, Henrik; Katifori, Eleni

    2013-03-01

    Many biological systems employ complex networks of vascular tubes to facilitate transport of solute nutrients, examples include the vascular system of plants (phloem), some fungi, and the slime-mold Physarum. It is believed that such networks are optimized through evolution for carrying out their designated task. We propose a set of hydrodynamic governing equations for solute transport in a complex network, and obtain the optimal network architecture for various classes of optimizing functionals. We finally discuss the topological properties and statistical mechanics of the resulting complex networks, and examine correspondence of the obtained networks to those found in actual biological systems.

  9. Systems cell biology.

    PubMed

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

    2014-09-15

    Systems cell biology melds high-throughput experimentation with quantitative analysis and modeling to understand many critical processes that contribute to cellular organization and dynamics. Recently, there have been several advances in technology and in the application of modeling approaches that enable the exploration of the dynamic properties of cells. Merging technology and computation offers an opportunity to objectively address unsolved cellular mechanisms, and has revealed emergent properties and helped to gain a more comprehensive and fundamental understanding of cell biology. © 2014 Mast et al.

  10. Radiation interactions with biological systems.

    PubMed

    Islam, Muhammad Torequl

    2017-05-01

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

  11. Biostack: A study of the biological effects on HZE galactic cosmic radiation

    NASA Technical Reports Server (NTRS)

    Buecker, H.

    1975-01-01

    The Biostack experiment designed to study the effect of individual heavy nucleii of the cosmic radiation environment upon biological systems during actual space flight is described. In each Biostack, several thousand biological objects were hit by an HZE particle. The response of the biological objects was studied. Results are discussed in terms of sensitivity to the hit.

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

    PubMed

    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.

  13. Focus issue: series on computational and systems biology.

    PubMed

    Gough, Nancy R

    2011-09-06

    The application of computational biology and systems biology is yielding quantitative insight into cellular regulatory phenomena. For the month of September, Science Signaling highlights research featuring computational approaches to understanding cell signaling and investigation of signaling networks, a series of Teaching Resources from a course in systems biology, and various other articles and resources relevant to the application of computational biology and systems biology to the study of signal transduction.

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

    PubMed

    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.

  15. Method of measurement in biological systems

    DOEpatents

    Turteltaub, K.W.; Vogel, J.S.; Felton, J.S.; Gledhill, B.L.; Davis, J.C.

    1994-12-27

    Disclosed is a method of quantifying molecules in biological substances comprising: a. selecting a biological host in which radioisotopes are present in concentrations equal to or less than those in the ambient biosphere, b. preparing a long-lived radioisotope labeled reactive chemical specie, c. administering the chemical specie to the biological host in doses sufficiently low to avoid significant overt damage to the biological system, d. allowing a period of time to elapse sufficient for dissemination and interaction of the chemical specie with the host throughout the biological system of the host, e. isolating a reacted fraction of the biological substance from the host in a manner sufficient to avoid contamination of the substance from extraneous sources, f. converting the fraction of biological substance by suitable means to a material which efficiently produces charged ions in at least one of several possible ion sources without introduction of significant isotopic fractionation, and, g. measuring the radioisotope concentration in the material by means of direct isotopic counting. 5 figures.

  16. Method of measurement in biological systems

    DOEpatents

    Turteltaub, K.W.; Vogel, J.S.; Felton, J.S.; Gledhill, B.L.: Davis, J.C.; Stanker, L.H.

    1993-05-11

    A method is disclosed of quantifying molecules in biological substances, comprising: selecting a biological host in which radioisotopes are present in concentrations equal to or less than those in the ambient biosphere; preparing a long-lived radioisotope labeled reactive chemical specie; administering the chemical specie to the biological host in doses sufficiently low to avoid significant overt damage to the biological system; allowing a period of time to elapse sufficient for dissemination and interaction of the chemical specie with the host throughout the biological system of the host; isolating a reacted fraction of the biological substance from the host in a manner sufficient to avoid contamination of the substance from extraneous sources; converting the fraction of biological substance by suitable means to a material which efficiently produces charged ions in at least one of several possible ion sources without introduction of significant isotopic fractionation; and measuring the radioisotope concentration in the material by means of direct isotopic counting.

  17. Method of measurement in biological systems

    DOEpatents

    Turteltaub, Kenneth W.; Vogel, John S.; Felton, James S.; Gledhill, Barton L.; Davis, Jay C.; Stanker, Larry H.

    1993-05-11

    Disclosed is a method of quantifying molecules in biological substances, comprising: a. selecting a biological host in which radioisotopes are present in concentrations equal to or less than those in the ambient biosphere, b. preparing a long-lived radioisotope labeled reactive chemical specie, c. administering said chemical specie to said biological host in doses sufficiently low to avoid significant overt damage to the biological system thereof, d. allowing a period of time to elapse sufficient for dissemination and interaction of said chemical specie with said host throughout said biological system of said host, e. isolating a reacted fraction of the biological substance from said host in a manner sufficient to avoid contamination of said substance from extraneous sources, f. converting said fraction of biological substance by suitable means to a material which efficiently produces charged ions in at least one of several possible ion sources without introduction of significant isotopic fractionation, and, g. measuring the radioisotope concentration in said material by means of direct isotopic counting.

  18. Method of measurement in biological systems

    DOEpatents

    Turteltaub, Kenneth W.; Vogel, John S.; Felton, James S.; Gledhill, Barton L.; Davis, Jay C.

    1994-01-01

    Disclosed is a method of quantifying molecules in biological substances comprising: a. selecting a biological host in which radioisotopes are present in concentrations equal to or less than those in the ambient biosphere, b. preparing a long-lived radioisotope labeled reactive chemical specie, c. administering said chemical specie to said biological host in doses sufficiently low to avoid significant overt damage to the biological system thereof, d. allowing a period of time to elapse sufficient for dissemination and interaction of said chemical specie with said host throughout said biological system of said host, e. isolating a reacted fraction of the biological substance from said host in a manner sufficient to avoid contamination of said substance from extraneous sources, f. converting said fraction of biological substance by suitable means to a material which efficiently produces charged ions in at least one of several possible ion sources without introduction of significant isotopic fractionation, and, g. measuring the radioisotope concentration in said material by means of direct isotopic counting.

  19. Translational Systems Biology and Voice Pathophysiology

    PubMed Central

    Li, Nicole Y. K.; Abbott, Katherine Verdolini; Rosen, Clark; An, Gary; Hebda, Patricia A.; Vodovotz, Yoram

    2011-01-01

    Objectives/Hypothesis Personalized medicine has been called upon to tailor healthcare to an individual's needs. Evidence-based medicine (EBM) has advocated using randomized clinical trials with large populations to evaluate treatment effects. However, due to large variations across patients, the results are likely not to apply to an individual patient. We suggest that a complementary, systems biology approach using computational modeling may help tackle biological complexity in order to improve ultimate patient care. The purpose of the article is: 1) to review the pros and cons of EBM, and 2) to discuss the alternative systems biology method and present its utility in clinical voice research. Study Design Tutorial Methods Literature review and discussion. Results We propose that translational systems biology can address many of the limitations of EBM pertinent to voice and other health care domains, and thus complement current health research models. In particular, recent work using mathematical modeling suggests that systems biology has the ability to quantify the highly complex biologic processes underlying voice pathophysiology. Recent data support the premise that this approach can be applied specifically in the case of phonotrauma and surgically induced vocal fold trauma, and may have particular power to address personalized medicine. Conclusions We propose that evidence around vocal health and disease be expanded beyond a population-based method to consider more fully issues of complexity and systems interactions, especially in implementing personalized medicine in voice care and beyond. PMID:20025041

  20. Autonomic nervous system activity during actual and mentally simulated preparation for movement.

    PubMed

    Bolliet, O; Collet, C; Dittmar, A

    2005-03-01

    The aim of this study was to compare actual versus mentally simulated preparation for a complex motor skill. Two behavioral periods are observed during weightlifting: (i) an initial phase in which the subject standing behind the bar is thought to focus his attention on forthcoming execution and (ii) a second phase between hands/bar contact and execution during which the subject is thought to increase activation. Such mental processes accompanying behavioral sequences are correlated with autonomic nervous system activity, phasic responses corresponding to allocation of attentional resources, and tonic variations related to increasing general activation. To study mental processes during preparation for action, 12 subjects performed actual and imagined preparation phases of execution. Six autonomic variables were measured continuously. Skin potential (chi2 = 0.16), skin temperature amplitude (Z = -0.66) and duration (Z = -1.78), skin blood flow amplitude (Z = -0.56) and duration (Z = -1.51), respiratory frequency amplitude (Z = -0.14) and duration (Z = -0.13), and duration of heart rate response (Z = -1.25) were shown to be comparable (p > .05), whatever the modality of preparation. However, during mentally simulated preparation, skin resistance response was shorter than in actual preparation (Z = -2.12, p < .05), thus attesting to a weaker load, whereas lower decrease in heart rate was elicited (Z = -1.96, p < .05). This may be explained by this particular experimental condition because mental preparation would not lead to actual action. Such autonomic variables could be used as feedback to improve performance.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    Louridas, George E; Lourida, Katerina G

    2017-02-21

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

  4. Applicability of computational systems biology in toxicology.

    PubMed

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

    2014-07-01

    Systems biology as a research field has emerged within the last few decades. Systems biology, often defined as the antithesis of the reductionist approach, integrates information about individual components of a biological system. In integrative systems biology, large data sets from various sources and databases are used to model and predict effects of chemicals on, for instance, human health. In toxicology, computational systems biology enables identification of important pathways and molecules from large data sets; tasks that can be extremely laborious when performed by a classical literature search. However, computational systems biology offers more advantages than providing a high-throughput literature search; it may form the basis for establishment of hypotheses on potential links between environmental chemicals and human diseases, which would be very difficult to establish experimentally. This is possible due to the existence of comprehensive databases containing information on networks of human protein-protein interactions and protein-disease associations. Experimentally determined targets of the specific chemical of interest can be fed into these networks to obtain additional information that can be used to establish hypotheses on links between the chemical and human diseases. Such information can also be applied for designing more intelligent animal/cell experiments that can test the established hypotheses. Here, we describe how and why to apply an integrative systems biology method in the hypothesis-generating phase of toxicological research. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  5. An engineering design approach to systems biology.

    PubMed

    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.

  6. The Feasibility of Systems Thinking in Biology Education

    ERIC Educational Resources Information Center

    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…

  7. New Tools and New Biology: Recent Miniaturized Systems for Molecular and Cellular Biology

    PubMed Central

    Hamon, Morgan; Hong, Jong Wook

    2013-01-01

    Recent advances in applied physics and chemistry have led to the development of novel microfluidic systems. Microfluidic systems allow minute amounts of reagents to be processed using μm-scale channels and offer several advantages over conventional analytical devices for use in biological sciences: faster, more accurate and more reproducible analytical performance, reduced cell and reagent consumption, portability, and integration of functional components in a single chip. In this review, we introduce how microfluidics has been applied to biological sciences. We first present an overview of the fabrication of microfluidic systems and describe the distinct technologies available for biological research. We then present examples of microsystems used in biological sciences, focusing on applications in molecular and cellular biology. PMID:24305843

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

    PubMed Central

    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

  9. High School Biology Today: What the Committee of Ten Actually Said

    ERIC Educational Resources Information Center

    Sheppard, Keith; Robbins, Dennis M.

    2007-01-01

    This essay describes how in the 1890s the Committee of Ten arrived at their recommendations about the organization of the high school biological sciences and seeks to correct the frequently held, but erroneous view that the Committee of Ten was the initiator of the Biology-Chemistry-Physics order of teaching sciences prevalent in high schools…

  10. Systems Biology Analysis of Heterocellular Signaling.

    PubMed

    Tape, Christopher J

    2016-08-01

    Tissues comprise multiple heterotypic cell types (e.g., epithelial, mesenchymal, and immune cells). Communication between heterotypic cell types is essential for biological cohesion and is frequently dysregulated in disease. Despite the importance of heterocellular communication, most systems biology techniques do not report cell-specific signaling data from mixtures of cells. As a result, our existing perspective of cellular behavior under-represents the influence of heterocellular signaling. Recent technical advances now permit the resolution of systems-level cell-specific signaling data. This review discusses how new physical, spatial, and isotopic resolving methods are facilitating unique systems biology studies of heterocellular communication. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Consistent design schematics for biological systems: standardization of representation in biological engineering

    PubMed Central

    Matsuoka, Yukiko; Ghosh, Samik; Kitano, Hiroaki

    2009-01-01

    The discovery by design paradigm driving research in synthetic biology entails the engineering of de novo biological constructs with well-characterized input–output behaviours and interfaces. The construction of biological circuits requires iterative phases of design, simulation and assembly, leading to the fabrication of a biological device. In order to represent engineered models in a consistent visual format and further simulating them in silico, standardization of representation and model formalism is imperative. In this article, we review different efforts for standardization, particularly standards for graphical visualization and simulation/annotation schemata adopted in systems biology. We identify the importance of integrating the different standardization efforts and provide insights into potential avenues for developing a common framework for model visualization, simulation and sharing across various tools. We envision that such a synergistic approach would lead to the development of global, standardized schemata in biology, empowering deeper understanding of molecular mechanisms as well as engineering of novel biological systems. PMID:19493898

  12. 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.

    NASA Astrophysics Data System (ADS)

    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.

  13. Indoor Air Nuclear, Biological, and Chemical Health Modeling and Assessment System

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Stenner, Robert D.; Hadley, Donald L.; Armstrong, Peter R.

    2001-03-01

    Indoor air quality effects on human health are of increasing concern to public health agencies and building owners. The prevention and treatment of 'sick building' syndrome and the spread of air-borne diseases in hospitals, for example, are well known priorities. However, increasing attention is being directed to the vulnerability of our public buildings/places, public security and national defense facilities to terrorist attack or the accidental release of air-borne biological pathogens, harmful chemicals, or radioactive contaminants. The Indoor Air Nuclear, Biological, and Chemical Health Modeling and Assessment System (IA-NBC-HMAS) was developed to serve as a health impact analysis tool for usemore » in addressing these concerns. The overall goal was to develop a user-friendly fully functional prototype Health Modeling and Assessment system, which will operate under the PNNL FRAMES system for ease of use and to maximize its integration with other modeling and assessment capabilities accessible within the FRAMES system (e.g., ambient air fate and transport models, water borne fate and transport models, Physiologically Based Pharmacokinetic models, etc.). The prototype IA-NBC-HMAS is designed to serve as a functional Health Modeling and Assessment system that can be easily tailored to meet specific building analysis needs of a customer. The prototype system was developed and tested using an actual building (i.e., the Churchville Building located at the Aberdeen Proving Ground) and release scenario (i.e., the release and measurement of tracer materials within the building) to ensure realism and practicality in the design and development of the prototype system. A user-friendly "demo" accompanies this report to allow the reader the opportunity for a "hands on" review of the prototype system's capability.« less

  14. Biologically inspired dynamic material systems.

    PubMed

    Studart, André R

    2015-03-09

    Numerous examples of material systems that dynamically interact with and adapt to the surrounding environment are found in nature, from hair-based mechanoreceptors in animals to self-shaping seed dispersal units in plants to remodeling bone in vertebrates. Inspired by such fascinating biological structures, a wide range of synthetic material systems have been created to replicate the design concepts of dynamic natural architectures. Examples of biological structures and their man-made counterparts are herein revisited to illustrate how dynamic and adaptive responses emerge from the intimate microscale combination of building blocks with intrinsic nanoscale properties. By using top-down photolithographic methods and bottom-up assembly approaches, biologically inspired dynamic material systems have been created 1) to sense liquid flow with hair-inspired microelectromechanical systems, 2) to autonomously change shape by utilizing plantlike heterogeneous architectures, 3) to homeostatically influence the surrounding environment through self-regulating adaptive surfaces, and 4) to spatially concentrate chemical species by using synthetic microcompartments. The ever-increasing complexity and remarkable functionalities of such synthetic systems offer an encouraging perspective to the rich set of dynamic and adaptive properties that can potentially be implemented in future man-made material systems. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. 40 CFR Appendix E to Part 63 - Monitoring Procedure for Nonthoroughly Mixed Open Biological Treatment Systems at Kraft Pulp...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... two separate components. The first data collection component demonstrates that the open biological... each zone of the open biological treatment unit. After the first two components of data collection are... determined using actual sampling data from the open biological treatment unit. This is done during the...

  16. 40 CFR Appendix E to Part 63 - Monitoring Procedure for Nonthoroughly Mixed Open Biological Treatment Systems at Kraft Pulp...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... two separate components. The first data collection component demonstrates that the open biological... each zone of the open biological treatment unit. After the first two components of data collection are... determined using actual sampling data from the open biological treatment unit. This is done during the...

  17. Metabolomics: Definitions and Significance in Systems Biology.

    PubMed

    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.

  18. Systems biology for organotypic cell cultures.

    PubMed

    Grego, Sonia; Dougherty, Edward R; Alexander, Francis J; Auerbach, Scott S; Berridge, Brian R; Bittner, Michael L; Casey, Warren; Cooley, Philip C; Dash, Ajit; Ferguson, Stephen S; Fennell, Timothy R; Hawkins, Brian T; Hickey, Anthony J; Kleensang, Andre; Liebman, Michael N J; Martin, Florian; Maull, Elizabeth A; Paragas, Jason; Qiao, Guilin Gary; Ramaiahgari, Sreenivasa; Sumner, Susan J; Yoon, Miyoung

    2017-01-01

    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.

  19. Stochastic simulation in systems biology

    PubMed Central

    Székely, Tamás; Burrage, Kevin

    2014-01-01

    Natural systems are, almost by definition, heterogeneous: this can be either a boon or an obstacle to be overcome, depending on the situation. Traditionally, when constructing mathematical models of these systems, heterogeneity has typically been ignored, despite its critical role. However, in recent years, stochastic computational methods have become commonplace in science. They are able to appropriately account for heterogeneity; indeed, they are based around the premise that systems inherently contain at least one source of heterogeneity (namely, intrinsic heterogeneity). In this mini-review, we give a brief introduction to theoretical modelling and simulation in systems biology and discuss the three different sources of heterogeneity in natural systems. Our main topic is an overview of stochastic simulation methods in systems biology. There are many different types of stochastic methods. We focus on one group that has become especially popular in systems biology, biochemistry, chemistry and physics. These discrete-state stochastic methods do not follow individuals over time; rather they track only total populations. They also assume that the volume of interest is spatially homogeneous. We give an overview of these methods, with a discussion of the advantages and disadvantages of each, and suggest when each is more appropriate to use. We also include references to software implementations of them, so that beginners can quickly start using stochastic methods for practical problems of interest. PMID:25505503

  20. Systems biology: the case for a systems science approach to diabetes.

    PubMed

    Petrasek, Danny

    2008-01-01

    The unprecedented accumulation of biological data in recent decades has underscored the need to organize and integrate the massive collection of information. In addition, there is rising agreement among biologists that a complete understanding of a single cell will not lead directly to a complete understanding of a system of cells. The success of a systems science approach in engineering and physics may be of great value in the evolution of biological science. This article reviews some examples that suggest the importance of a systems biology approach and, in addition, advance one specific systems science principle, the conservation of uncertainty, which may give insight into the emergent behavior of numerous biological and physiological phenomena.

  1. Applying differential dynamic logic to reconfigurable biological networks.

    PubMed

    Figueiredo, Daniel; Martins, Manuel A; Chaves, Madalena

    2017-09-01

    Qualitative and quantitative modeling frameworks are widely used for analysis of biological regulatory networks, the former giving a preliminary overview of the system's global dynamics and the latter providing more detailed solutions. Another approach is to model biological regulatory networks as hybrid systems, i.e., systems which can display both continuous and discrete dynamic behaviors. Actually, the development of synthetic biology has shown that this is a suitable way to think about biological systems, which can often be constructed as networks with discrete controllers, and present hybrid behaviors. In this paper we discuss this approach as a special case of the reconfigurability paradigm, well studied in Computer Science (CS). In CS there are well developed computational tools to reason about hybrid systems. We argue that it is worth applying such tools in a biological context. One interesting tool is differential dynamic logic (dL), which has recently been developed by Platzer and applied to many case-studies. In this paper we discuss some simple examples of biological regulatory networks to illustrate how dL can be used as an alternative, or also as a complement to methods already used. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Mathematical and Computational Modeling in Complex Biological Systems

    PubMed Central

    Li, Wenyang; Zhu, Xiaoliang

    2017-01-01

    The biological process and molecular functions involved in the cancer progression remain difficult to understand for biologists and clinical doctors. Recent developments in high-throughput technologies urge the systems biology to achieve more precise models for complex diseases. Computational and mathematical models are gradually being used to help us understand the omics data produced by high-throughput experimental techniques. The use of computational models in systems biology allows us to explore the pathogenesis of complex diseases, improve our understanding of the latent molecular mechanisms, and promote treatment strategy optimization and new drug discovery. Currently, it is urgent to bridge the gap between the developments of high-throughput technologies and systemic modeling of the biological process in cancer research. In this review, we firstly studied several typical mathematical modeling approaches of biological systems in different scales and deeply analyzed their characteristics, advantages, applications, and limitations. Next, three potential research directions in systems modeling were summarized. To conclude, this review provides an update of important solutions using computational modeling approaches in systems biology. PMID:28386558

  3. Mathematical and Computational Modeling in Complex Biological Systems.

    PubMed

    Ji, Zhiwei; Yan, Ke; Li, Wenyang; Hu, Haigen; Zhu, Xiaoliang

    2017-01-01

    The biological process and molecular functions involved in the cancer progression remain difficult to understand for biologists and clinical doctors. Recent developments in high-throughput technologies urge the systems biology to achieve more precise models for complex diseases. Computational and mathematical models are gradually being used to help us understand the omics data produced by high-throughput experimental techniques. The use of computational models in systems biology allows us to explore the pathogenesis of complex diseases, improve our understanding of the latent molecular mechanisms, and promote treatment strategy optimization and new drug discovery. Currently, it is urgent to bridge the gap between the developments of high-throughput technologies and systemic modeling of the biological process in cancer research. In this review, we firstly studied several typical mathematical modeling approaches of biological systems in different scales and deeply analyzed their characteristics, advantages, applications, and limitations. Next, three potential research directions in systems modeling were summarized. To conclude, this review provides an update of important solutions using computational modeling approaches in systems biology.

  4. Systems Biology of Industrial Microorganisms

    NASA Astrophysics Data System (ADS)

    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.

  5. Systems biology of industrial microorganisms.

    PubMed

    Papini, Marta; Salazar, Margarita; Nielsen, Jens

    2010-01-01

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

  6. On the interplay between mathematics and biology. Hallmarks toward a new systems biology

    NASA Astrophysics Data System (ADS)

    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.

  7. Integrative Systems Biology for Data Driven Knowledge Discovery

    PubMed Central

    Greene, Casey S.; Troyanskaya, Olga G.

    2015-01-01

    Integrative systems biology is an approach that brings together diverse high throughput experiments and databases to gain new insights into biological processes or systems at molecular through physiological levels. These approaches rely on diverse high-throughput experimental techniques that generate heterogeneous data by assaying varying aspects of complex biological processes. Computational approaches are necessary to provide an integrative view of these experimental results and enable data-driven knowledge discovery. Hypotheses generated from these approaches can direct definitive molecular experiments in a cost effective manner. Using integrative systems biology approaches, we can leverage existing biological knowledge and large-scale data to improve our understanding of yet unknown components of a system of interest and how its malfunction leads to disease. PMID:21044756

  8. Systems Biology for Organotypic Cell Cultures

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Grego, Sonia; Dougherty, Edward R.; Alexander, Francis J.

    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/genomicmore » 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

  9. CINRG: Systems Biology of Glucocorticoids in Muscle Disease

    DTIC Science & Technology

    2012-10-01

    Duchenne Muscular dystrophy , Glucocorticoids, Systems biology, Drug mechanism CINRG: Systems Biology of Glucocorticoids in Muscle Disease Zuyi Wang, Ph.D...2011-2012) for Contract W81XWH-09-1-0726 SYSTEMS BIOLOGY OF GLUCOCORTICOIDS IN MUSCLE DISEASE Introduction Duchenne muscular dystrophy ...DMD) is the most common and incurable muscular dystrophy of childhood. Muscle regeneration fails with advancing age, leading to considerable fibrosis

  10. Natural production of biological optical systems

    NASA Astrophysics Data System (ADS)

    Choi, Seung Ho; Kim, Young L.

    2015-03-01

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

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

    PubMed

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

    2004-06-01

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

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

    PubMed

    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.

  13. DAISY: a new software tool to test global identifiability of biological and physiological systems.

    PubMed

    Bellu, Giuseppina; Saccomani, Maria Pia; Audoly, Stefania; D'Angiò, Leontina

    2007-10-01

    A priori global identifiability is a structural property of biological and physiological models. It is considered a prerequisite for well-posed estimation, since it concerns the possibility of recovering uniquely the unknown model parameters from measured input-output data, under ideal conditions (noise-free observations and error-free model structure). Of course, determining if the parameters can be uniquely recovered from observed data is essential before investing resources, time and effort in performing actual biomedical experiments. Many interesting biological models are nonlinear but identifiability analysis for nonlinear system turns out to be a difficult mathematical problem. Different methods have been proposed in the literature to test identifiability of nonlinear models but, to the best of our knowledge, so far no software tools have been proposed for automatically checking identifiability of nonlinear models. In this paper, we describe a software tool implementing a differential algebra algorithm to perform parameter identifiability analysis for (linear and) nonlinear dynamic models described by polynomial or rational equations. Our goal is to provide the biological investigator a completely automatized software, requiring minimum prior knowledge of mathematical modelling and no in-depth understanding of the mathematical tools. The DAISY (Differential Algebra for Identifiability of SYstems) software will potentially be useful in biological modelling studies, especially in physiology and clinical medicine, where research experiments are particularly expensive and/or difficult to perform. Practical examples of use of the software tool DAISY are presented. DAISY is available at the web site http://www.dei.unipd.it/~pia/.

  14. DAISY: a new software tool to test global identifiability of biological and physiological systems

    PubMed Central

    Bellu, Giuseppina; Saccomani, Maria Pia; Audoly, Stefania; D’Angiò, Leontina

    2009-01-01

    A priori global identifiability is a structural property of biological and physiological models. It is considered a prerequisite for well-posed estimation, since it concerns the possibility of recovering uniquely the unknown model parameters from measured input-output data, under ideal conditions (noise-free observations and error-free model structure). Of course, determining if the parameters can be uniquely recovered from observed data is essential before investing resources, time and effort in performing actual biomedical experiments. Many interesting biological models are nonlinear but identifiability analysis for nonlinear system turns out to be a difficult mathematical problem. Different methods have been proposed in the literature to test identifiability of nonlinear models but, to the best of our knowledge, so far no software tools have been proposed for automatically checking identifiability of nonlinear models. In this paper, we describe a software tool implementing a differential algebra algorithm to perform parameter identifiability analysis for (linear and) nonlinear dynamic models described by polynomial or rational equations. Our goal is to provide the biological investigator a completely automatized software, requiring minimum prior knowledge of mathematical modelling and no in-depth understanding of the mathematical tools. The DAISY (Differential Algebra for Identifiability of SYstems) software will potentially be useful in biological modelling studies, especially in physiology and clinical medicine, where research experiments are particularly expensive and/or difficult to perform. Practical examples of use of the software tool DAISY are presented. DAISY is available at the web site http://www.dei.unipd.it/~pia/. PMID:17707944

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

    PubMed

    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.

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

    PubMed

    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.

  17. Dupuytren's: a systems biology disease

    PubMed Central

    2011-01-01

    Dupuytren's disease (DD) is an ill-defined fibroproliferative disorder of the palm of the hands leading to digital contracture. DD commonly occurs in individuals of northern European extraction. Cellular components and processes associated with DD pathogenesis include altered gene and protein expression of cytokines, growth factors, adhesion molecules, and extracellular matrix components. Histology has shown increased but varying levels of particular types of collagen, myofibroblasts and myoglobin proteins in DD tissue. Free radicals and localised ischaemia have been suggested to trigger the proliferation of DD tissue. Although the existing available biological information on DD may contain potentially valuable (though largely uninterpreted) information, the precise aetiology of DD remains unknown. Systems biology combines mechanistic modelling with quantitative experimentation in studies of networks and better understanding of the interaction of multiple components in disease processes. Adopting systems biology may be the ideal approach for future research in order to improve understanding of complex diseases of multifactorial origin. In this review, we propose that DD is a disease of several networks rather than of a single gene, and show that this accounts for the experimental observations obtained to date from a variety of sources. We outline how DD may be investigated more effectively by employing a systems biology approach that considers the disease network as a whole rather than focusing on any specific single molecule. PMID:21943049

  18. Systems Biology to Support Nanomaterial Grouping.

    PubMed

    Riebeling, Christian; Jungnickel, Harald; Luch, Andreas; Haase, Andrea

    2017-01-01

    The assessment of potential health risks of engineered nanomaterials (ENMs) is a challenging task due to the high number and great variety of already existing and newly emerging ENMs. Reliable grouping or categorization of ENMs with respect to hazards could help to facilitate prioritization and decision making for regulatory purposes. The development of grouping criteria, however, requires a broad and comprehensive data basis. A promising platform addressing this challenge is the systems biology approach. The different areas of systems biology, most prominently transcriptomics, proteomics and metabolomics, each of which provide a wealth of data that can be used to reveal novel biomarkers and biological pathways involved in the mode-of-action of ENMs. Combining such data with classical toxicological data would enable a more comprehensive understanding and hence might lead to more powerful and reliable prediction models. Physico-chemical data provide crucial information on the ENMs and need to be integrated, too. Overall statistical analysis should reveal robust grouping and categorization criteria and may ultimately help to identify meaningful biomarkers and biological pathways that sufficiently characterize the corresponding ENM subgroups. This chapter aims to give an overview on the different systems biology technologies and their current applications in the field of nanotoxicology, as well as to identify the existing challenges.

  19. Aerospace Medicine and Biology: A Continuing Bibliography. Supplement 483

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion.

  20. News from the Biological Stain Commission No. 11.

    PubMed

    Lyon, H O; Horobin, R W

    2012-01-01

    The 11th issue of News from the Biological Stain Commission (BSC) provides our first impressions of the REACH and ECHA programs. We intend to give a more thorough account of what these important programs actually mean in later editions of News from the Biological Stain Commission. Under the heading of Regulatory Affairs, the Biological Stain Commission's International Affairs Committee presents information from the opening session of the meeting of the International Standards Organization ISO/TC 212 Clinical laboratory testing and in vitro diagnostic test systems held on 2-4 June 2010 in Seoul, Republic of Korea.

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

    PubMed

    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.

  2. Optoelectronic system and apparatus for connection to biological systems

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Okandan, Murat; Nielson, Gregory N.

    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.

  3. Advances in systems biology: computational algorithms and applications.

    PubMed

    Huang, Yufei; Zhao, Zhongming; Xu, Hua; Shyr, Yu; Zhang, Bing

    2012-01-01

    The 2012 International Conference on Intelligent Biology and Medicine (ICIBM 2012) was held on April 22-24, 2012 in Nashville, Tennessee, USA. The conference featured six technical sessions, one tutorial session, one workshop, and 3 keynote presentations that covered state-of-the-art research activities in genomics, systems biology, and intelligent computing. In addition to a major emphasis on the next generation sequencing (NGS)-driven informatics, ICIBM 2012 aligned significant interests in systems biology and its applications in medicine. We highlight in this editorial the selected papers from the meeting that address the developments of novel algorithms and applications in systems biology.

  4. Hybrid semi-parametric mathematical systems: bridging the gap between systems biology and process engineering.

    PubMed

    Teixeira, Ana P; Carinhas, Nuno; Dias, João M L; Cruz, Pedro; Alves, Paula M; Carrondo, Manuel J T; Oliveira, Rui

    2007-12-01

    Systems biology is an integrative science that aims at the global characterization of biological systems. Huge amounts of data regarding gene expression, proteins activity and metabolite concentrations are collected by designing systematic genetic or environmental perturbations. Then the challenge is to integrate such data in a global model in order to provide a global picture of the cell. The analysis of these data is largely dominated by nonparametric modelling tools. In contrast, classical bioprocess engineering has been primarily founded on first principles models, but it has systematically overlooked the details of the embedded biological system. The full complexity of biological systems is currently assumed by systems biology and this knowledge can now be taken by engineers to decide how to optimally design and operate their processes. This paper discusses possible methodologies for the integration of systems biology and bioprocess engineering with emphasis on applications involving animal cell cultures. At the mathematical systems level, the discussion is focused on hybrid semi-parametric systems as a way to bridge systems biology and bioprocess engineering.

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

    PubMed

    Astakhov, Vadim

    2009-01-01

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

  6. Biological Potential in Serpentinizing Systems

    NASA Technical Reports Server (NTRS)

    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.

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

    PubMed

    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.

  8. Towards Engineering Biological Systems in a Broader Context.

    PubMed

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

    2016-02-27

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

  9. A Philosophical Perspective on Evolutionary Systems Biology

    PubMed Central

    Soyer, Orkun S.; Siegal, Mark L.

    2015-01-01

    Evolutionary systems biology (ESB) is an emerging hybrid approach that integrates methods, models, and data from evolutionary and systems biology. Drawing on themes that arose at a cross-disciplinary meeting on ESB in 2013, we discuss in detail some of the explanatory friction that arises in the interaction between evolutionary and systems biology. These tensions appear because of different modeling approaches, diverse explanatory aims and strategies, and divergent views about the scope of the evolutionary synthesis. We locate these discussions in the context of long-running philosophical deliberations on explanation, modeling, and theoretical synthesis. We show how many of the issues central to ESB’s progress can be understood as general philosophical problems. The benefits of addressing these philosophical issues feed back into philosophy too, because ESB provides excellent examples of scientific practice for the development of philosophy of science and philosophy of biology. PMID:26085823

  10. Towards Biological Inspiration in the Development of Complex Systems

    NASA Technical Reports Server (NTRS)

    Hinchey, Michael G.; Sterritt, Roy

    2006-01-01

    Greater understanding of biology in modem times has enabled significant breakthroughs in improving healthcare, quality of life, and eliminating many diseases and congenital illnesses. Simultaneously there is a move towards emulating nature and copying many of the wonders uncovered in biology, resulting in "biologically inspired" systems. Significant results have been reported in a wide range of areas, with systems inspired by nature enabling exploration, communication, and advances that were never dreamed possible just a few years ago. We warn, that as in many other fields of endeavor, we should be inspired by nature and biology, not engage in mimicry. We describe some results of biological inspiration that augur promise in terms of improving the safety and security of systems, and in developing self-managing systems, that we hope will ultimately lead to self-governing systems.

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

    PubMed

    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.

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

    PubMed

    Schuldiner, Maya; Zalckvar, Einat

    2015-04-01

    In recent years, high-throughput experimentation with quantitative analysis and modelling of cells, recently dubbed systems cell biology, has been harnessed to study the organisation and dynamics of simple biological systems. Here, we suggest that the peroxisome, a fascinating dynamic organelle, can be used as a good candidate for studying a complete biological system. We discuss several aspects of peroxisomes that can be studied using high-throughput systematic approaches and be integrated into a predictive model. Such approaches can be used in the future to study and understand how a more complex biological system, like a cell and maybe even ultimately a whole organism, works. © 2015 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

  13. Systems Biology-Based Investigation of Host-Plasmodium Interactions.

    PubMed

    Smith, Maren L; Styczynski, Mark P

    2018-05-18

    Malaria is a serious, complex disease caused by parasites of the genus Plasmodium. Plasmodium parasites affect multiple tissues as they evade immune responses, replicate, sexually reproduce, and transmit between vertebrate and invertebrate hosts. The explosion of omics technologies has enabled large-scale collection of Plasmodium infection data, revealing systems-scale patterns, mechanisms of pathogenesis, and the ways that host and pathogen affect each other. Here, we provide an overview of recent efforts using systems biology approaches to study host-Plasmodium interactions and the biological themes that have emerged from these efforts. We discuss some of the challenges in using systems biology for this goal, key research efforts needed to address those issues, and promising future malaria applications of systems biology. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Network dynamics and systems biology

    NASA Astrophysics Data System (ADS)

    Norrell, Johannes A.

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

  15. Thermal Protection System Cavity Heating for Simplified and Actual Geometries Using Computational Fluid Dynamics Simulations with Unstructured Grids

    NASA Technical Reports Server (NTRS)

    McCloud, Peter L.

    2010-01-01

    Thermal Protection System (TPS) Cavity Heating is predicted using Computational Fluid Dynamics (CFD) on unstructured grids for both simplified cavities and actual cavity geometries. Validation was performed using comparisons to wind tunnel experimental results and CFD predictions using structured grids. Full-scale predictions were made for simplified and actual geometry configurations on the Space Shuttle Orbiter in a mission support timeframe.

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

    NASA Technical Reports Server (NTRS)

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

    2014-01-01

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

  17. The common ground of genomics and systems biology

    PubMed Central

    2014-01-01

    The rise of systems biology is intertwined with that of genomics, yet their primordial relationship to one another is ill-defined. We discuss how the growth of genomics provided a critical boost to the popularity of systems biology. We describe the parts of genomics that share common areas of interest with systems biology today in the areas of gene expression, network inference, chromatin state analysis, pathway analysis, personalized medicine, and upcoming areas of synergy as genomics continues to expand its scope across all biomedical fields. PMID:25033072

  18. The emerging genomics and systems biology research lead to systems genomics studies.

    PubMed

    Yang, Mary Qu; Yoshigoe, Kenji; Yang, William; Tong, Weida; Qin, Xiang; Dunker, A; Chen, Zhongxue; Arbania, Hamid R; Liu, Jun S; Niemierko, Andrzej; Yang, Jack Y

    2014-01-01

    Synergistically integrating multi-layer genomic data at systems level not only can lead to deeper insights into the molecular mechanisms related to disease initiation and progression, but also can guide pathway-based biomarker and drug target identification. With the advent of high-throughput next-generation sequencing technologies, sequencing both DNA and RNA has generated multi-layer genomic data that can provide DNA polymorphism, non-coding RNA, messenger RNA, gene expression, isoform and alternative splicing information. Systems biology on the other hand studies complex biological systems, particularly systematic study of complex molecular interactions within specific cells or organisms. Genomics and molecular systems biology can be merged into the study of genomic profiles and implicated biological functions at cellular or organism level. The prospectively emerging field can be referred to as systems genomics or genomic systems biology. The Mid-South Bioinformatics Centre (MBC) and Joint Bioinformatics Ph.D. Program of University of Arkansas at Little Rock and University of Arkansas for Medical Sciences are particularly interested in promoting education and research advancement in this prospectively emerging field. Based on past investigations and research outcomes, MBC is further utilizing differential gene and isoform/exon expression from RNA-seq and co-regulation from the ChiP-seq specific for different phenotypes in combination with protein-protein interactions, and protein-DNA interactions to construct high-level gene networks for an integrative genome-phoneme investigation at systems biology level.

  19. Systems biology approach to bioremediation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    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 potentialmore » for making bioremediation breakthroughs and illuminating the ‘black box’.« less

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

    PubMed

    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.

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

    PubMed

    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.

  2. Modeling and simulation of biological systems using SPICE language

    PubMed Central

    Lallement, Christophe; Haiech, Jacques

    2017-01-01

    The article deals with BB-SPICE (SPICE for Biochemical and Biological Systems), an extension of the famous Simulation Program with Integrated Circuit Emphasis (SPICE). BB-SPICE environment is composed of three modules: a new textual and compact description formalism for biological systems, a converter that handles this description and generates the SPICE netlist of the equivalent electronic circuit and NGSPICE which is an open-source SPICE simulator. In addition, the environment provides back and forth interfaces with SBML (System Biology Markup Language), a very common description language used in systems biology. BB-SPICE has been developed in order to bridge the gap between the simulation of biological systems on the one hand and electronics circuits on the other hand. Thus, it is suitable for applications at the interface between both domains, such as development of design tools for synthetic biology and for the virtual prototyping of biosensors and lab-on-chip. Simulation results obtained with BB-SPICE and COPASI (an open-source software used for the simulation of biochemical systems) have been compared on a benchmark of models commonly used in systems biology. Results are in accordance from a quantitative viewpoint but BB-SPICE outclasses COPASI by 1 to 3 orders of magnitude regarding the computation time. Moreover, as our software is based on NGSPICE, it could take profit of incoming updates such as the GPU implementation, of the coupling with powerful analysis and verification tools or of the integration in design automation tools (synthetic biology). PMID:28787027

  3. Aerospace Medicine and Biology: A Continuing Bibliography With Indexes. Supplement 497

    NASA Technical Reports Server (NTRS)

    2000-01-01

    This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes (NASA/SP#2000-7011) lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention.

  4. System biology of gene regulation.

    PubMed

    Baitaluk, Michael

    2009-01-01

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

  5. Systems biology of cellular membranes: a convergence with biophysics.

    PubMed

    Chabanon, Morgan; Stachowiak, Jeanne C; Rangamani, Padmini

    2017-09-01

    Systems biology and systems medicine have played an important role in the last two decades in shaping our understanding of biological processes. While systems biology is synonymous with network maps and '-omics' approaches, it is not often associated with mechanical processes. Here, we make the case for considering the mechanical and geometrical aspects of biological membranes as a key step in pushing the frontiers of systems biology of cellular membranes forward. We begin by introducing the basic components of cellular membranes, and highlight their dynamical aspects. We then survey the functions of the plasma membrane and the endomembrane system in signaling, and discuss the role and origin of membrane curvature in these diverse cellular processes. We further give an overview of the experimental and modeling approaches to study membrane phenomena. We close with a perspective on the converging futures of systems biology and membrane biophysics, invoking the need to include physical variables such as location and geometry in the study of cellular membranes. WIREs Syst Biol Med 2017, 9:e1386. doi: 10.1002/wsbm.1386 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

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

    PubMed

    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.

  7. Realizing actual feedback control of complex network

    NASA Astrophysics Data System (ADS)

    Tu, Chengyi; Cheng, Yuhua

    2014-06-01

    In this paper, we present the concept of feedbackability and how to identify the Minimum Feedbackability Set of an arbitrary complex directed network. Furthermore, we design an estimator and a feedback controller accessing one MFS to realize actual feedback control, i.e. control the system to our desired state according to the estimated system internal state from the output of estimator. Last but not least, we perform numerical simulations of a small linear time-invariant dynamics network and a real simple food network to verify the theoretical results. The framework presented here could make an arbitrary complex directed network realize actual feedback control and deepen our understanding of complex systems.

  8. Underlying Principles of Natural Selection in Network Evolution: Systems Biology Approach

    PubMed Central

    Chen, Bor-Sen; Wu, Wei-Sheng

    2007-01-01

    Systems biology is a rapidly expanding field that integrates diverse areas of science such as physics, engineering, computer science, mathematics, and biology toward the goal of elucidating the underlying principles of hierarchical metabolic and regulatory systems in the cell, and ultimately leading to predictive understanding of cellular response to perturbations. Because post-genomics research is taking place throughout the tree of life, comparative approaches offer a way for combining data from many organisms to shed light on the evolution and function of biological networks from the gene to the organismal level. Therefore, systems biology can build on decades of theoretical work in evolutionary biology, and at the same time evolutionary biology can use the systems biology approach to go in new uncharted directions. In this study, we present a review of how the post-genomics era is adopting comparative approaches and dynamic system methods to understand the underlying design principles of network evolution and to shape the nascent field of evolutionary systems biology. Finally, the application of evolutionary systems biology to robust biological network designs is also discussed from the synthetic biology perspective. PMID:19468310

  9. Aerospace Medicine and Biology: A Continuing Bibliography. Supplement 475

    NASA Technical Reports Server (NTRS)

    1998-01-01

    This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion.

  10. Aerospace medicine and biology: A continuing bibliography with indexes, supplement

    NASA Technical Reports Server (NTRS)

    1972-01-01

    Subject coverage concentrates on the biological, physiological, psychological, and environmental effects to which man is subjected during and following simulated or actual flight in the earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Each entry consists of a standard citation accompanied by its abstract.

  11. Advancing Systems Biology in the International Conference on Intelligent Biology and Medicine (ICIBM) 2015.

    PubMed

    Zhao, Zhongming; Liu, Yunlong; Huang, Yufei; Huang, Kun; Ruan, Jianhua

    2016-08-26

    The 2015 International Conference on Intelligent Biology and Medicine (ICIBM 2015) was held on November 13-15, 2015 in Indianapolis, Indiana, USA. ICIBM 2015 included eight scientific sessions, three tutorial sessions, one poster session, and four keynote presentations that covered the frontier research in broad areas related to bioinformatics, systems biology, big data science, biomedical informatics, pharmacogenomics, and intelligent computing. Here, we present a summary of the 10 research articles that were selected from ICIBM 2015 and included in the supplement to BMC Systems Biology.

  12. Systems biology of the structural proteome.

    PubMed

    Brunk, Elizabeth; Mih, Nathan; Monk, Jonathan; Zhang, Zhen; O'Brien, Edward J; Bliven, Spencer E; Chen, Ke; Chang, Roger L; Bourne, Philip E; Palsson, Bernhard O

    2016-03-11

    The success of genome-scale models (GEMs) can be attributed to the high-quality, bottom-up reconstructions of metabolic, protein synthesis, and transcriptional regulatory networks on an organism-specific basis. Such reconstructions are biochemically, genetically, and genomically structured knowledge bases that can be converted into a mathematical format to enable a myriad of computational biological studies. In recent years, genome-scale reconstructions have been extended to include protein structural information, which has opened up new vistas in systems biology research and empowered applications in structural systems biology and systems pharmacology. Here, we present the generation, application, and dissemination of genome-scale models with protein structures (GEM-PRO) for Escherichia coli and Thermotoga maritima. We show the utility of integrating molecular scale analyses with systems biology approaches by discussing several comparative analyses on the temperature dependence of growth, the distribution of protein fold families, substrate specificity, and characteristic features of whole cell proteomes. Finally, to aid in the grand challenge of big data to knowledge, we provide several explicit tutorials of how protein-related information can be linked to genome-scale models in a public GitHub repository ( https://github.com/SBRG/GEMPro/tree/master/GEMPro_recon/). Translating genome-scale, protein-related information to structured data in the format of a GEM provides a direct mapping of gene to gene-product to protein structure to biochemical reaction to network states to phenotypic function. Integration of molecular-level details of individual proteins, such as their physical, chemical, and structural properties, further expands the description of biochemical network-level properties, and can ultimately influence how to model and predict whole cell phenotypes as well as perform comparative systems biology approaches to study differences between organisms. GEM

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

    ERIC Educational Resources Information Center

    Simpson, Melanie Rae

    2016-01-01

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

  14. Full Monte Carlo-Based Biologic Treatment Plan Optimization System for Intensity Modulated Carbon Ion Therapy on Graphics Processing Unit.

    PubMed

    Qin, Nan; Shen, Chenyang; Tsai, Min-Yu; Pinto, Marco; Tian, Zhen; Dedes, Georgios; Pompos, Arnold; Jiang, Steve B; Parodi, Katia; Jia, Xun

    2018-01-01

    One of the major benefits of carbon ion therapy is enhanced biological effectiveness at the Bragg peak region. For intensity modulated carbon ion therapy (IMCT), it is desirable to use Monte Carlo (MC) methods to compute the properties of each pencil beam spot for treatment planning, because of their accuracy in modeling physics processes and estimating biological effects. We previously developed goCMC, a graphics processing unit (GPU)-oriented MC engine for carbon ion therapy. The purpose of the present study was to build a biological treatment plan optimization system using goCMC. The repair-misrepair-fixation model was implemented to compute the spatial distribution of linear-quadratic model parameters for each spot. A treatment plan optimization module was developed to minimize the difference between the prescribed and actual biological effect. We used a gradient-based algorithm to solve the optimization problem. The system was embedded in the Varian Eclipse treatment planning system under a client-server architecture to achieve a user-friendly planning environment. We tested the system with a 1-dimensional homogeneous water case and 3 3-dimensional patient cases. Our system generated treatment plans with biological spread-out Bragg peaks covering the targeted regions and sparing critical structures. Using 4 NVidia GTX 1080 GPUs, the total computation time, including spot simulation, optimization, and final dose calculation, was 0.6 hour for the prostate case (8282 spots), 0.2 hour for the pancreas case (3795 spots), and 0.3 hour for the brain case (6724 spots). The computation time was dominated by MC spot simulation. We built a biological treatment plan optimization system for IMCT that performs simulations using a fast MC engine, goCMC. To the best of our knowledge, this is the first time that full MC-based IMCT inverse planning has been achieved in a clinically viable time frame. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Mathematical methods in systems biology.

    PubMed

    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. The Spring of Systems Biology-Driven Breeding.

    PubMed

    Lavarenne, Jérémy; Guyomarc'h, Soazig; Sallaud, Christophe; Gantet, Pascal; Lucas, Mikaël

    2018-05-12

    Genetics and molecular biology have contributed to the development of rationalized plant breeding programs. Recent developments in both high-throughput experimental analyses of biological systems and in silico data processing offer the possibility to address the whole gene regulatory network (GRN) controlling a given trait. GRN models can be applied to identify topological features helping to shortlist potential candidate genes for breeding purposes. Time-series data sets can be used to support dynamic modelling of the network. This will enable a deeper comprehension of network behaviour and the identification of the few elements to be genetically rewired to push the system towards a modified phenotype of interest. This paves the way to design more efficient, systems biology-based breeding strategies. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Modeling of biological intelligence for SCM system optimization.

    PubMed

    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.

  18. Modeling of Biological Intelligence for SCM System Optimization

    PubMed Central

    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

  19. Engineering plant metabolism into microbes: from systems biology to synthetic biology.

    PubMed

    Xu, Peng; Bhan, Namita; Koffas, Mattheos A G

    2013-04-01

    Plant metabolism represents an enormous repository of compounds that are of pharmaceutical and biotechnological importance. Engineering plant metabolism into microbes will provide sustainable solutions to produce pharmaceutical and fuel molecules that could one day replace substantial portions of the current fossil-fuel based economy. Metabolic engineering entails targeted manipulation of biosynthetic pathways to maximize yields of desired products. Recent advances in Systems Biology and the emergence of Synthetic Biology have accelerated our ability to design, construct and optimize cell factories for metabolic engineering applications. Progress in predicting and modeling genome-scale metabolic networks, versatile gene assembly platforms and delicate synthetic pathway optimization strategies has provided us exciting opportunities to exploit the full potential of cell metabolism. In this review, we will discuss how systems and synthetic biology tools can be integrated to create tailor-made cell factories for efficient production of natural products and fuel molecules in microorganisms. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2015-02-01

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

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

    PubMed

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

    2016-06-01

    Biotechnology applications require engineering complex multi-genic traits. The lack of knowledge on the genetic basis of complex phenotypes restricts our ability to rationally engineer them. However, complex phenotypes can be engineered at the systems level, utilizing directed evolution strategies that drive whole biological systems toward desired phenotypes without requiring prior knowledge of the genetic basis of the targeted trait. Recent developments in the synthetic biology field accelerates the directed evolution cycle, facilitating engineering of increasingly complex traits in biological systems. In this review, we summarize some of the most recent advances in directed evolution and synthetic biology that allows engineering of complex traits in microbial systems. Then, we discuss applications that can be achieved through engineering at the systems level. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    PubMed

    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.

  3. A SYSTEMS BIOLOGY APPROACH TO DEVELOPMENTAL TOXICOLOGY

    EPA Science Inventory

    Abstract
    Recent advances in developmental biology have yielded detailed models of gene regulatory networks (GRNs) involved in cell specification and other processes in embryonic differentiation. Such networks form the bedrock on which a systems biology approach to developme...

  4. Plant Systems Biology (editorial)

    USDA-ARS?s Scientific Manuscript database

    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 ‘‘...

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

    NASA Astrophysics Data System (ADS)

    De Domenico, Manlio

    2018-03-01

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

  6. Sixth International Conference on Systems Biology (ICSB 2005)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Professor Andrew Murray

    2005-10-22

    This grant supported the Sixth International Conference on Systems Biology (ICSB 2005), held in Boston, Massachusetts from October 19th to 22nd, 2005. The ICSB is the only major, annual, international conference focused exclusively on the important emerging field of systems biology. It draws together scientists with expertise in theoretical, computational and experimental approaches to understanding biological systems at many levels. Previous ICSB meetings have been held in Tokyo (2000), at Caltech (2001), at the Karolinska Institute (2002), at Washington University in St. Louis (2003), and in Heidelberg (2004). These conferences have been increasingly successful at bringing together the growing communitymore » of established and junior researchers with interests in this area. Boston is home to several groups that have shown leadership in the field and was therefore an ideal place to hold this conference . The executive committee for the conference comprised Jim Collins (Biomedical Engineering, Boston University), Marc Kirschner (chair of the new Department of Systems Biology at Harvard Medical School), Eric Lander (director of the Broad Institute of MIT and Harvard), Andrew Murray (director of Harvard’s Bauer Center for Genomics Research) and Peter Sorger (director of MIT’s Computational and Systems Biology Initiative). There are almost as many definitions of systems biology as there are systems biologists. We take a broad view of the field, and we succeeded in one of our major aims in organizing a conference that bridges two types of divide. The first is that between traditional academic disciplines: each of our sessions includes speakers from biology and from one or more physical or quantitative sciences. The second type includes those that separate experimental biologists from their colleagues who work on theory or computation. Here again, each session included representatives from at least two of these three categories; indeed, many of the speakers

  7. Actual Proliferating Index and p53 protein expression as prognostic marker in odontogenic cysts.

    PubMed

    Gadbail, A R; Chaudhary, M; Patil, S; Gawande, M

    2009-10-01

    The purpose of this study was to evaluate the biological aggressiveness of odontogenic keratocyst/keratocystic odontogenic tumour (KCOT), radicular cyst (RC) and dentigerous cyst (DC) by observing the actual proliferative activity of epithelium, and p53 protein expression. The actual proliferative activity was measured by Ki-67 Labelling Index and argyrophilic nucleolar organizing regions (AgNOR) count per nucleus. The p53 protein expression was also evaluated. Ki-67 positive cells were observed higher in suprabasal cell layers of KCOT with uniform distribution, a few of them were predominantly observed in basal cell layer in RC and DC. The AgNOR count was significantly higher in suprabasal cell layers of KCOT. The actual proliferative activity was noted to be higher in suprabasal cell layers of KCOT. The p53 immunolabelling was dense and scattered in basal and suprabasal cell layers in KCOT. The weakly stained p53 positive cells were observed diffusely distributed in KCOT, whereas they were mainly seen in basal cell layer of RC and DC. The quantitative and qualitative differences of the proliferative activity and the p53 protein expression in sporadic KCOT may be associated with intrinsic growth potential that could play a role in its development and explain locally aggressive biological behaviour. AgNOR count and p53 protein detection in odontogenic lesions can be of great consequence to predict the biological behaviour and prognosis.

  8. Systems biology solutions for biochemical production challenges.

    PubMed

    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.

  9. Transient Resetting: A Novel Mechanism for Synchrony and Its Biological Examples

    PubMed Central

    Li, Chunguang; Chen, Luonan; Aihara, Kazuyuki

    2006-01-01

    The study of synchronization in biological systems is essential for the understanding of the rhythmic phenomena of living organisms at both molecular and cellular levels. In this paper, by using simple dynamical systems theory, we present a novel mechanism, named transient resetting, for the synchronization of uncoupled biological oscillators with stimuli. This mechanism not only can unify and extend many existing results on (deterministic and stochastic) stimulus-induced synchrony, but also may actually play an important role in biological rhythms. We argue that transient resetting is a possible mechanism for the synchronization in many biological organisms, which might also be further used in the medical therapy of rhythmic disorders. Examples of the synchronization of neural and circadian oscillators as well as a chaotic neuron model are presented to verify our hypothesis. PMID:16933980

  10. Dietary antioxidant synergy in chemical and biological systems.

    PubMed

    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.

  11. Controlled biological and biomimetic systems for landmine detection.

    PubMed

    Habib, Maki K

    2007-08-30

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

  12. Tracing organizing principles: learning from the history of systems biology.

    PubMed

    Green, Sara; Wolkenhauer, Olaf

    2013-01-01

    With the emergence of systems biology, the identification of organizing principles is being highlighted as a key research aim. Researchers attempt to "reverse engineer" the functional organization of biological systems using methodologies from mathematics, engineering and computer science while taking advantage of data produced by new experimental techniques. While systems biology is a relatively new approach, the quest for general principles of biological organization dates back to systems theoretic approaches in early and mid-twentieth century. The aim of this paper is to draw on this historical background in order to increase the understanding of the motivation behind the search for general principles and to clarify different epistemic aims within systems biology. We pinpoint key aspects of earlier approaches that also underlie the current practice. These are i) the focus on relational and system-level properties, ii) the inherent critique of reductionism and fragmentation of knowledge resulting from overspecialization, and iii) the insight that the ideal of formulating abstract organizing principles is complementary to, rather than conflicting with, the aim of formulating detailed explanations of biological mechanisms. We argue that looking back not only helps us understand the current practice but also points to possible future directions for systems biology.

  13. Set membership experimental design for biological systems.

    PubMed

    Marvel, Skylar W; Williams, Cranos M

    2012-03-21

    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. 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. The practicability of our approach is illustrated with a case study. This study shows that our approach is able to 1) identify

  14. Set membership experimental design for biological systems

    PubMed Central

    2012-01-01

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

  15. Aerospace medicine and biology: A continuing bibliography with indexes, supplement 97

    NASA Technical Reports Server (NTRS)

    1972-01-01

    Subject coverage concentrates on the biological, physiological, psychological, and environmental effects to which man is subjected during and following simulated or actual flight in the earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Each entry consists of a standard citation accompanied by its abstract.

  16. Aerospace medicine and biology: A continuing bibliography with indexes (supplement 94)

    NASA Technical Reports Server (NTRS)

    1971-01-01

    Subject coverage concentrates on the biological, physiological, psychological, and environmental effects to which man is subjected during and following simulated or actual flight in the earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Each entry consists of a standard citation accompanied by its abstract.

  17. Aerospace medicine and biology: A continuing bibliography with indexes, supplement 96

    NASA Technical Reports Server (NTRS)

    1971-01-01

    Subject coverage concentrates on the biological, physiological, psychological, and environmental effects to which man is subjected during and following simulated or actual flight in the earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Each entry consists of a standard citation accompanied by its abstract.

  18. Aerospace medicine and biology: A continuing bibliography with indexes (supplement 100)

    NASA Technical Reports Server (NTRS)

    1972-01-01

    Subject coverage concentrates on the biological, physiological, psychological, and environmental effects to which man is subjected during and following simulated or actual flight in the earth's atmosphere or in interplanetary space. Reference describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Each entry consists of a standard citation accompanied by its abstract.

  19. Synthetic biology: advancing the design of diverse genetic systems

    PubMed Central

    Wang, Yen-Hsiang; Wei, Kathy Y.; Smolke, Christina D.

    2013-01-01

    A main objective of synthetic biology is to make the process of designing genetically-encoded biological systems more systematic, predictable, robust, scalable, and efficient. The examples of genetic systems in the field vary widely in terms of operating hosts, compositional approaches, and network complexity, ranging from a simple genetic switch to search-and-destroy systems. While significant advances in synthesis capabilities support the potential for the implementation of pathway- and genome-scale programs, several design challenges currently restrict the scale of systems that can be reasonably designed and implemented. Synthetic biology offers much promise in developing systems to address challenges faced in manufacturing, the environment and sustainability, and health and medicine, but the realization of this potential is currently limited by the diversity of available parts and effective design frameworks. As researchers make progress in bridging this design gap, advances in the field hint at ever more diverse applications for biological systems. PMID:23413816

  20. Aerospace Medicine and Biology: A Continuing Bibliography With Indexes

    NASA Technical Reports Server (NTRS)

    1997-01-01

    This issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes NASA SP-7O11 lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion.

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

    PubMed

    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.

    PubMed

    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. Genome Scale Modeling in Systems Biology: Algorithms and Resources

    PubMed Central

    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

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

    PubMed Central

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

    2014-01-01

    Motivation: 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. Results: 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. Availability and implementation: 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. Contact: seunghwa.kang@pnnl.gov PMID:25064572

  5. Apparatus and methods for manipulation and optimization of biological systems

    NASA Technical Reports Server (NTRS)

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

    2012-01-01

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

  6. Multiscale systems biology of trauma-induced coagulopathy.

    PubMed

    Tsiklidis, Evan; Sims, Carrie; Sinno, Talid; Diamond, Scott L

    2018-07-01

    Trauma with hypovolemic shock is an extreme pathological state that challenges the body to maintain blood pressure and oxygenation in the face of hemorrhagic blood loss. In conjunction with surgical actions and transfusion therapy, survival requires the patient's blood to maintain hemostasis to stop bleeding. The physics of the problem are multiscale: (a) the systemic circulation sets the global blood pressure in response to blood loss and resuscitation therapy, (b) local tissue perfusion is altered by localized vasoregulatory mechanisms and bleeding, and (c) altered blood and vessel biology resulting from the trauma as well as local hemodynamics control the assembly of clotting components at the site of injury. Building upon ongoing modeling efforts to simulate arterial or venous thrombosis in a diseased vasculature, computer simulation of trauma-induced coagulopathy is an emerging approach to understand patient risk and predict response. Despite uncertainties in quantifying the patient's dynamic injury burden, multiscale systems biology may help link blood biochemistry at the molecular level to multiorgan responses in the bleeding patient. As an important goal of systems modeling, establishing early metrics of a patient's high-dimensional trajectory may help guide transfusion therapy or warn of subsequent later stage bleeding or thrombotic risks. This article is categorized under: Analytical and Computational Methods > Computational Methods Biological Mechanisms > Regulatory Biology Models of Systems Properties and Processes > Mechanistic Models. © 2018 Wiley Periodicals, Inc.

  7. Agent-based models in translational systems biology

    PubMed Central

    An, Gary; Mi, Qi; Dutta-Moscato, Joyeeta; Vodovotz, Yoram

    2013-01-01

    Effective translational methodologies for knowledge representation are needed in order to make strides against the constellation of diseases that affect the world today. These diseases are defined by their mechanistic complexity, redundancy, and nonlinearity. Translational systems biology aims to harness the power of computational simulation to streamline drug/device design, simulate clinical trials, and eventually to predict the effects of drugs on individuals. The ability of agent-based modeling to encompass multiple scales of biological process as well as spatial considerations, coupled with an intuitive modeling paradigm, suggests that this modeling framework is well suited for translational systems biology. This review describes agent-based modeling and gives examples of its translational applications in the context of acute inflammation and wound healing. PMID:20835989

  8. An online model composition tool for system biology models

    PubMed Central

    2013-01-01

    Background 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. Results 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. Conclusions 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. PMID:24006914

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

    PubMed

    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.

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

    PubMed

    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).

  11. Modeling autism: a systems biology approach

    PubMed Central

    2012-01-01

    Autism is the fastest growing developmental disorder in the world today. The prevalence of autism in the US has risen from 1 in 2500 in 1970 to 1 in 88 children today. People with autism present with repetitive movements and with social and communication impairments. These impairments can range from mild to profound. The estimated total lifetime societal cost of caring for one individual with autism is $3.2 million US dollars. With the rapid growth in this disorder and the great expense of caring for those with autism, it is imperative for both individuals and society that techniques be developed to model and understand autism. There is increasing evidence that those individuals diagnosed with autism present with highly diverse set of abnormalities affecting multiple systems of the body. To this date, little to no work has been done using a whole body systems biology approach to model the characteristics of this disorder. Identification and modelling of these systems might lead to new and improved treatment protocols, better diagnosis and treatment of the affected systems, which might lead to improved quality of life by themselves, and, in addition, might also help the core symptoms of autism due to the potential interconnections between the brain and nervous system with all these other systems being modeled. This paper first reviews research which shows that autism impacts many systems in the body, including the metabolic, mitochondrial, immunological, gastrointestinal and the neurological. These systems interact in complex and highly interdependent ways. Many of these disturbances have effects in most of the systems of the body. In particular, clinical evidence exists for increased oxidative stress, inflammation, and immune and mitochondrial dysfunction which can affect almost every cell in the body. Three promising research areas are discussed, hierarchical, subgroup analysis and modeling over time. This paper reviews some of the systems disturbed in autism and

  12. A Systems Biology Approach to Iron Metabolism

    PubMed Central

    Chifman, J.; Laubenbacher, R.; Torti, S.V.

    2015-01-01

    Iron is critical to the survival of almost all living organisms. However, inappropriately low or high levels of iron are detrimental and contribute to a wide range of diseases. Recent advances in the study of iron metabolism have revealed multiple intricate pathways that are essential to the maintenance of iron homeostasis. Further, iron regulation involves processes at several scales, ranging from the subcellular to the organismal. This complexity makes a systems biology approach crucial, with its enabling technology of computational models based on a mathematical description of regulatory systems. Systems biology may represent a new strategy for understanding imbalances in iron metabolism and their underlying causes. PMID:25480643

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

    PubMed

    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. Determination of morphological parameters of biological cells by analysis of scattered-light distributions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Burger, D.E.

    1979-11-01

    The extraction of morphological parameters from biological cells by analysis of light-scatter patterns is described. A light-scattering measurement system has been designed and constructed that allows one to visually examine and photographically record biological cells or cell models and measure the light-scatter pattern of an individual cell or cell model. Using a laser or conventional illumination, the imaging system consists of a modified microscope with a 35 mm camera attached to record the cell image or light-scatter pattern. Models of biological cells were fabricated. The dynamic range and angular distributions of light scattered from these models was compared to calculatedmore » distributions. Spectrum analysis techniques applied on the light-scatter data give the sought after morphological cell parameters. These results compared favorably to shape parameters of the fabricated cell models confirming the mathematical model procedure. For nucleated biological material, correct nuclear and cell eccentricity as well as the nuclear and cytoplasmic diameters were determined. A method for comparing the flow equivalent of nuclear and cytoplasmic size to the actual dimensions is shown. This light-scattering experiment provides baseline information for automated cytology. In its present application, it involves correlating average size as measured in flow cytology to the actual dimensions determined from this technique. (ERB)« less

  15. Tutorial on Actual Space Environmental Hazards For Space Systems (Invited)

    NASA Astrophysics Data System (ADS)

    Mazur, J. E.; Fennell, J. F.; Guild, T. B.; O'Brien, T. P.

    2013-12-01

    It has become common in the space science community to conduct research on diverse physical phenomena because they are thought to contribute to space weather. However, satellites contend with only three primary environmental hazards: single event effects, vehicle charging, and total dose, and not every physical phenomenon that occurs in space contributes in substantial ways to create these hazards. One consequence of the mismatch between actual threats and all-encompassing research is the often-described gap between research and operations; another is the creation of forecasts that provide no actionable information for design engineers or spacecraft operators. An example of the latter is the physics of magnetic field emergence on the Sun; the phenomenon is relevant to the formation and launch of coronal mass ejections and is also causally related to the solar energetic particles that may get accelerated in the interplanetary shock. Unfortunately for the research community, the engineering community mitigates the space weather threat (single-event effects from heavy ions above ~50 MeV/nucleon) with a worst-case specification of the environment and not with a prediction. Worst-case definition requires data mining of past events, while predictions involve large-scale systems science from the Sun to the Earth that is compelling for scientists and their funding agencies but not actionable for design or for most operations. Differing priorities among different space-faring organizations only compounds the confusion over what science research is relevant. Solar particle impacts to human crew arise mainly from the total ionizing dose from the solar protons, so the priority for prediction in the human spaceflight community is therefore much different than in the unmanned satellite community, while both communities refer to the fundamental phenomenon as space weather. Our goal in this paper is the presentation of a brief tutorial on the primary space environmental phenomena

  16. Light microscopy applications in systems biology: opportunities and challenges

    PubMed Central

    2013-01-01

    Biological systems present multiple scales of complexity, ranging from molecules to entire populations. Light microscopy is one of the least invasive techniques used to access information from various biological scales in living cells. The combination of molecular biology and imaging provides a bottom-up tool for direct insight into how molecular processes work on a cellular scale. However, imaging can also be used as a top-down approach to study the behavior of a system without detailed prior knowledge about its underlying molecular mechanisms. In this review, we highlight the recent developments on microscopy-based systems analyses and discuss the complementary opportunities and different challenges with high-content screening and high-throughput imaging. Furthermore, we provide a comprehensive overview of the available platforms that can be used for image analysis, which enable community-driven efforts in the development of image-based systems biology. PMID:23578051

  17. Advanced systems biology methods in drug discovery and translational biomedicine.

    PubMed

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

    2013-01-01

    Systems biology is in an exponential development stage in recent years and has been widely utilized in biomedicine to better understand the molecular basis of human disease and the mechanism of drug action. Here, we discuss the fundamental concept of systems biology and its two computational methods that have been commonly used, that is, network analysis and dynamical modeling. The applications of systems biology in elucidating human disease are highlighted, consisting of human disease networks, treatment response prediction, investigation of disease mechanisms, and disease-associated gene prediction. In addition, important advances in drug discovery, to which systems biology makes significant contributions, are discussed, including drug-target networks, prediction of drug-target interactions, investigation of drug adverse effects, drug repositioning, and drug combination prediction. The systems biology methods and applications covered in this review provide a framework for addressing disease mechanism and approaching drug discovery, which will facilitate the translation of research findings into clinical benefits such as novel biomarkers and promising therapies.

  18. Cancer systems biology: signal processing for cancer research

    PubMed Central

    Yli-Harja, Olli; Ylipää, Antti; Nykter, Matti; Zhang, Wei

    2011-01-01

    In this editorial we introduce the research paradigms of signal processing in the era of systems biology. Signal processing is a field of science traditionally focused on modeling electronic and communications systems, but recently it has turned to biological applications with astounding results. The essence of signal processing is to describe the natural world by mathematical models and then, based on these models, develop efficient computational tools for solving engineering problems. Here, we underline, with examples, the endless possibilities which arise when the battle-hardened tools of engineering are applied to solve the problems that have tormented cancer researchers. Based on this approach, a new field has emerged, called cancer systems biology. Despite its short history, cancer systems biology has already produced several success stories tackling previously impracticable problems. Perhaps most importantly, it has been accepted as an integral part of the major endeavors of cancer research, such as analyzing the genomic and epigenomic data produced by The Cancer Genome Atlas (TCGA) project. Finally, we show that signal processing and cancer research, two fields that are seemingly distant from each other, have merged into a field that is indeed more than the sum of its parts. PMID:21439242

  19. Workshop Report: Systems Biology for Organotypic Cell Cultures

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Grego, Sonia; Dougherty, Edward R.; Alexander, Francis Joseph

    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/genomicmore » 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.« less

  20. Workshop Report: Systems Biology for Organotypic Cell Cultures

    DOE PAGES

    Grego, Sonia; Dougherty, Edward R.; Alexander, Francis Joseph; ...

    2016-11-14

    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/genomicmore » 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.« less

  1. The Self-Actualizing Case Method.

    ERIC Educational Resources Information Center

    Gunn, Bruce

    1980-01-01

    Presents a case procedure designed to assist trainees in perfecting their problem-solving skills. Elements of that procedure are the rationale behind this "self-actualizing" case method; the role that the instructor, case leaders, and participants play in its execution; and the closed-loop grading system used for peer evaluation. (CT)

  2. A Comparison of Biological and Adoptive Mothers and Fathers: The Relevance of Biological Kinship and Gendered Constructs of Parenthood.

    ERIC Educational Resources Information Center

    Miall, Charlene E.; March, Karen

    2003-01-01

    Used qualitative interviews to examine beliefs and values about biological and adoptive parents. Considered how biological kinship, gender, and actual parenting behavior affect the assessments respondents made of the emotional bonding between parents and children. Found that biological and adoptive parents viewed motherhood as instinctive and…

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

    PubMed

    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.

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

    NASA Technical Reports Server (NTRS)

    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

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

    PubMed

    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

  6. System approaches of Weiss and Bertalanffy and their relevance for systems biology today.

    PubMed

    Drack, Manfred; Wolkenhauer, Olaf

    2011-06-01

    System approaches in biology have a long history. We focus here on the thinking of Paul A. Weiss and Ludwig von Bertalanffy, who contributed a great deal towards making the system concept operable in biology in the early 20th century. To them, considering whole living systems, which includes their organisation or order, is equally important as the dynamics within systems and the interplay between different levels from molecules over cells to organisms. They also called for taking the intrinsic activity of living systems and the conservation of system states into account. We compare these notions with today's systems biology, which is often a bottom-up approach from molecular dynamics to cellular behaviour. We conclude that bringing together the early heuristics with recent formalisms and novel experimental set-ups can lead to fruitful results and understanding. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Agent-Based Modeling in Molecular Systems Biology.

    PubMed

    Soheilypour, Mohammad; Mofrad, Mohammad R K

    2018-07-01

    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.

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

    PubMed Central

    Thomas, Marcus; Schwartz, Russell

    2017-01-01

    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. PMID:28535149

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

    PubMed

    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.

  10. Modeling acclimatization by hybrid systems: condition changes alter biological system behavior models.

    PubMed

    Assar, Rodrigo; Montecino, Martín A; Maass, Alejandro; Sherman, David J

    2014-07-01

    In order to describe the dynamic behavior of a complex biological system, it is useful to combine models integrating processes at different levels and with temporal dependencies. Such combinations are necessary for modeling acclimatization, a phenomenon where changes in environmental conditions can induce drastic changes in the behavior of a biological system. In this article we formalize the use of hybrid systems as a tool to model this kind of biological behavior. A modeling scheme called strong switches is proposed. It allows one to take into account both minor adjustments to the coefficients of a continuous model, and, more interestingly, large-scale changes to the structure of the model. We illustrate the proposed methodology with two applications: acclimatization in wine fermentation kinetics, and acclimatization of osteo-adipo differentiation system linking stimulus signals to bone mass. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Aerospace medicine and biology: A continuing bibliography with indexes (supplement 368)

    NASA Technical Reports Server (NTRS)

    1992-01-01

    This bibliography lists 305 reports, articles, and other documents introduced into the NASA Scientific and Technical Information System during Sep. 1992. The subject coverage concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion.

  12. Aerospace medicine and biology: A continuing bibliography with indexes (supplement 366)

    NASA Technical Reports Server (NTRS)

    1992-01-01

    This bibliography lists 248 reports, articles, and other documents introduced into the NASA Scientific and Technical Information System during Aug. 1992. Subject coverage concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion.

  13. Dynamic sensitivity analysis of biological systems

    PubMed Central

    Wu, Wu Hsiung; Wang, Feng Sheng; Chang, Maw Shang

    2008-01-01

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

  14. Bio-Physics Manifesto -- for the Future of Physics and Biology

    NASA Astrophysics Data System (ADS)

    Oono, Y.

    2008-04-01

    The Newtonian revolution taught us how to dissect phenomena into contingencies (e.g., initial conditions) and fundamental laws (e.g., equations of motion). Since then, `fundamental physics' has been pursuing purer and leaner fundamental laws. Consequently, to explain real phenomena a lot of auxiliary conditions become required. Isn't it now the time to start studying `auxiliary conditions' seriously? The study of biological systems has a possibility of shedding light on this neglected side of phenomena in physics, because we organisms were constructed by our parents who supplied indispensable auxiliary conditions; we never self-organize. Thus, studying the systems lacking self-organizing capability (such as complex systems) may indicate new directions to physics and biology (biophysics). There have been attempts to construct a `general theoretical framework' of biology, but most of them never seriously looked at the actual biological world. Every serious natural science must start with establishing a phenomenological framework. Therefore, this must be the main part of bio-physics. However, this article is addressed mainly to theoretical physicists and discusses only certain theoretical aspects (with real illustrative examples).

  15. Vibrational resonances in biological systems at microwave frequencies.

    PubMed

    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.

  16. Virtual Tissues and Developmental Systems Biology (book chapter)

    EPA Science Inventory

    Virtual tissue (VT) models provide an in silico environment to simulate cross-scale properties in specific tissues or organs based on knowledge of the underlying biological networks. These integrative models capture the fundamental interactions in a biological system and enable ...

  17. Graphic Representation of Carbon Dioxide Equilibria in Biological Systems.

    ERIC Educational Resources Information Center

    Kindig, Neal B.; Filley, Giles F.

    1983-01-01

    The log C-pH diagram is a useful means of displaying quantitatively the many variables (including temperature) that determine acid-base equilibria in biological systems. Presents the diagram as extended to open/closed biological systems and derives a new water-ion balance method for determining equilibrium pH. (JN)

  18. Systems biology of eukaryotic superorganisms and the holobiont concept.

    PubMed

    Kutschera, Ulrich

    2018-06-14

    The founders of modern biology (Jean Lamarck, Charles Darwin, August Weismann etc.) were organismic life scientists who attempted to understand the morphology and evolution of living beings as a whole (i.e., the phenotype). However, with the emergence of the study of animal and plant physiology in the nineteenth century, this "holistic view" of the living world changed and was ultimately replaced by a reductionistic perspective. Here, I summarize the history of systems biology, i.e., the modern approach to understand living beings as integrative organisms, from genotype to phenotype. It is documented that the physiologists Claude Bernard and Julius Sachs, who studied humans and plants, respectively, were early pioneers of this discipline, which was formally founded 50 years ago. In 1968, two influential monographs, authored by Ludwig von Bertalanffy and Mihajlo D. Mesarović, were published, wherein a "systems theory of biology" was outlined. Definitions of systems biology are presented with reference to metabolic or cell signaling networks, analyzed via genomics, proteomics, and other methods, combined with computer simulations/mathematical modeling. Then, key insights of this discipline with respect to epiphytic microbes (Methylobacterium sp.) and simple bacteria (Mycoplasma sp.) are described. The principles of homeostasis, molecular systems energetics, gnotobiology, and holobionts (i.e., complexities of host-microbiota interactions) are outlined, and the significance of systems biology for evolutionary theories is addressed. Based on the microbe-Homo sapiens-symbiosis, it is concluded that human biology and health should be interpreted in light of a view of the biomedical sciences that is based on the holobiont concept.

  19. [Biological therapies in systemic lupus erythematosus].

    PubMed

    Cairoli, Ernesto; Espinosa, Gerard; Cervera, Ricard

    2010-07-01

    The immunosuppressive agents used in patients with systemic lupus erythematosus (SLE) have significantly improved prognosis. However, it is necessary to develop more specific immunosuppressive treatments with less toxicity. Better understanding of the mechanisms involved in the loss of tolerance in autoimmune diseases has contributed to the development of potential new treatments called biologic therapies. The targets of these biological therapies are directed toward the B cell depletion, interference in the co-stimulation signals and the blockade of cytokines. Therapies using anti-CD20 monoclonal antibodies have shown satisfactory results especially in patients with SLE refractory to conventional treatment. The biological therapies provide encouraging results that represent a possible option in the treatment of refractory patients as well as a potential therapy in the future management of SLE.

  20. Aerospace Medicine and Biology: A Continuing Bibliography with Indexes. Supplement 492

    NASA Technical Reports Server (NTRS)

    1999-01-01

    This report lists reports, articles and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion.

  1. Aerospace Medicine and Biology: A Continuing Bibliography With Indexes. Supplement 486

    NASA Technical Reports Server (NTRS)

    1999-01-01

    In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract.

  2. Specifications of Standards in Systems and Synthetic Biology.

    PubMed

    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

  3. Engineering biological systems using automated biofoundries

    PubMed Central

    Chao, Ran; Mishra, Shekhar; Si, Tong; Zhao, Huimin

    2017-01-01

    Engineered biological systems such as genetic circuits and microbial cell factories have promised to solve many challenges in the modern society. However, the artisanal processes of research and development are slow, expensive, and inconsistent, representing a major obstacle in biotechnology and bioengineering. In recent years, biological foundries or biofoundries have been developed to automate design-build-test engineering cycles in an effort to accelerate these processes. This review summarizes the enabling technologies for such biofoundries as well as their early successes and remaining challenges. PMID:28602523

  4. Formal reasoning about systems biology using theorem proving

    PubMed Central

    Hasan, Osman; Siddique, Umair; Tahar, Sofiène

    2017-01-01

    System biology provides the basis to understand the behavioral properties of complex biological organisms at different levels of abstraction. Traditionally, analysing systems biology based models of various diseases have been carried out by paper-and-pencil based proofs and simulations. However, these methods cannot provide an accurate analysis, which is a serious drawback for the safety-critical domain of human medicine. In order to overcome these limitations, we propose a framework to formally analyze biological networks and pathways. In particular, we formalize the notion of reaction kinetics in higher-order logic and formally verify some of the commonly used reaction based models of biological networks using the HOL Light theorem prover. Furthermore, we have ported our earlier formalization of Zsyntax, i.e., a deductive language for reasoning about biological networks and pathways, from HOL4 to the HOL Light theorem prover to make it compatible with the above-mentioned formalization of reaction kinetics. To illustrate the usefulness of the proposed framework, we present the formal analysis of three case studies, i.e., the pathway leading to TP53 Phosphorylation, the pathway leading to the death of cancer stem cells and the tumor growth based on cancer stem cells, which is used for the prognosis and future drug designs to treat cancer patients. PMID:28671950

  5. The Hospice Information System and its association with the congruence between the preferred and actual place of death.

    PubMed

    Lin, Huang-Ren; Wang, Jen-Hung; Hsieh, Jyh-Gang; Wang, Ying-Wei; Kao, Sheng-Lun

    2017-01-01

    A Hospice Information System (HIS) developed in eastern Taiwan in 2012 aimed to improve the quality of hospice care through an integrated system that provided telemetry-based vital sign records, online 24/7 consultations, online video interviews, and online health educations. The purpose of this study was to explore the congruence between the preferred and actual place of death (POD) among patients who received HIS services. A retrospective study was performed from January 2012 to August 2016. Data from patients enrolled in the HIS who died during this period were included. Data on basic characteristics and the actual and preferred POD were obtained from the HIS database. The primary outcome was the congruence between the preferred and actual POD. Secondary outcomes were comparisons between patients who did and did not achieve their preferred POD. Further comparisons between patients who did and did not achieve home death were also performed. In total, we enrolled 481 patients who received HIS services and died. Of them, 444 (92.3%) died at their preferred POD. Patients who preferred an inpatient hospice as their POD had higher achievement rate than those who wanted a home death. High-intensity HIS utilization was associated with a higher likelihood of home death than low-intensity HIS utilization. Patients living in areas distant from the medical center had lower achievement of home death than those living in local areas. This study suggested that patients enrolled in the HIS had high congruence between the actual and preferred POD.

  6. Aerospace Medicine and Biology: A Continuing Bibliography. Supplement 476

    NASA Technical Reports Server (NTRS)

    1998-01-01

    This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes (NASA/SP-1998-7011) lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract.

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

    PubMed

    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.

  8. Aerospace Medicine and Biology: A continuing bibliography with indexes, supplement 237

    NASA Technical Reports Server (NTRS)

    1982-01-01

    A bibliography is given on the biological, physiological, psychological, and environmental effects to which man is subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects of biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. In general, emphasis is placed on applied research, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion.

  9. Aerospace Medicine and Biology: A continuing bibliography with indexes, supplement 139

    NASA Technical Reports Server (NTRS)

    1975-01-01

    The biological, physiological, psychological, and environmental effects to which man is subjected during and following simulated or actual flight in the earth's atmosphere or in interplanetary space are referenced. Similar effects on biological organisms of lower order are also included. Related topics such as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors are discussed. Applied research is emphasized, but references to fundamental studies and theoretical principles related to experimental development are also included. A total of 242 reports, articles, and other documents are listed.

  10. Maps, books and other metaphors for systems biology.

    PubMed

    Ouzounis, Christos; Mazière, Pierre

    2006-07-01

    We briefly review the use of metaphors in science and progressively focus on fields from biology and molecular biology to genomics and bioinformatics. We discuss how metaphors are both a tool for scientific exploration and a medium for public communication of complex subjects, by various short examples. Finally, we propose a metaphor for systems biology that provides an illuminating perspective for the ambitious goals of this field and delimits its current agenda.

  11. Who is Self-Actualized?

    ERIC Educational Resources Information Center

    Roweton, William E.

    1981-01-01

    In an attempt to clarify Maslow's concept of self-actualization as it relates to human motivation, a class of educational psychology students wrote essays describing a self-actualized person and then attempted to decide whether public schools contribute to the production of self-actualized persons. Two-thirds of the students decided that schools…

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

    PubMed

    Somvanshi, Pramod Rajaram; Venkatesh, K V

    2014-03-01

    Human physiology is an ensemble of various biological processes spanning from intracellular molecular interactions to the whole body phenotypic response. Systems biology endures to decipher these multi-scale biological networks and bridge the link between genotype to phenotype. The structure and dynamic properties of these networks are responsible for controlling and deciding the phenotypic state of a cell. Several cells and various tissues coordinate together to generate an organ level response which further regulates the ultimate physiological state. The overall network embeds a hierarchical regulatory structure, which when unusually perturbed can lead to undesirable physiological state termed as disease. Here, we treat a disease diagnosis problem analogous to a fault diagnosis problem in engineering systems. Accordingly we review the application of engineering methodologies to address human diseases from systems biological perspective. The review highlights potential networks and modeling approaches used for analyzing human diseases. The application of such analysis is illustrated in the case of cancer and diabetes. We put forth a concept of cell-to-human framework comprising of five modules (data mining, networking, modeling, experimental and validation) for addressing human physiology and diseases based on a paradigm of system level analysis. The review overtly emphasizes on the importance of multi-scale biological networks and subsequent modeling and analysis for drug target identification and designing efficient therapies.

  13. Using the Unified Modelling Language (UML) to guide the systemic description of biological processes and systems.

    PubMed

    Roux-Rouquié, Magali; Caritey, Nicolas; Gaubert, Laurent; Rosenthal-Sabroux, Camille

    2004-07-01

    One of the main issues in Systems Biology is to deal with semantic data integration. Previously, we examined the requirements for a reference conceptual model to guide semantic integration based on the systemic principles. In the present paper, we examine the usefulness of the Unified Modelling Language (UML) to describe and specify biological systems and processes. This makes unambiguous representations of biological systems, which would be suitable for translation into mathematical and computational formalisms, enabling analysis, simulation and prediction of these systems behaviours.

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

    PubMed

    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.

  15. Thermostability of Biological Systems: Fundamentals, Challenges, and Quantification

    PubMed Central

    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. PMID:21769301

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

    PubMed

    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.

  17. Explanation in Biology: Reduction, Pluralism, and Explanatory Aims

    ERIC Educational Resources Information Center

    Brigandt, Ingo

    2013-01-01

    This essay analyzes and develops recent views about explanation in biology. Philosophers of biology have parted with the received deductive-nomological model of scientific explanation primarily by attempting to capture actual biological theorizing and practice. This includes an endorsement of different kinds of explanation (e.g., mathematical and…

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

    PubMed Central

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

    2015-01-01

    Sender–receiver (S–R) systems abound in biology, with communication systems sending information in various forms. Information theory provides a quantitative basis for analysing these processes and is being applied to study natural genetic, enzymatic and neural networks. Recent advances in synthetic biology are providing us with a wealth of artificial S–R systems, giving us quantitative control over networks with a finite number of well-characterised components. Combining the two approaches can help to predict how to maximise signalling robustness, and will allow us to make increasingly complex biological computers. Ultimately, pushing the boundaries of synthetic biology will require moving beyond engineering the flow of information and towards building more sophisticated circuits that interpret biological meaning. PMID:25282688

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

    PubMed Central

    2013-01-01

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

  20. ENFIN a network to enhance integrative systems biology.

    PubMed

    Kahlem, Pascal; Birney, Ewan

    2007-12-01

    Integration of biological data of various types and development of adapted bioinformatics tools represent critical objectives to enable research at the systems level. The European Network of Excellence ENFIN is engaged in developing both an adapted infrastructure to connect databases and platforms to enable the generation of new bioinformatics tools as well as the experimental validation of computational predictions. We will give an overview of the projects tackled within ENFIN and discuss the challenges associated with integration for systems biology.

  1. Systems biology of cancer biomarker detection.

    PubMed

    Mitra, Sanga; Das, Smarajit; Chakrabarti, Jayprokas

    2013-01-01

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

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

    PubMed

    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.

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

    PubMed Central

    2018-01-01

    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. PMID:29436184

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

    PubMed Central

    Cvijovic, Marija; Höfer, Thomas; Aćimović, Jure; Alberghina, Lilia; Almaas, Eivind; Besozzi, Daniela; Blomberg, Anders; Bretschneider, Till; Cascante, Marta; Collin, Olivier; de Atauri, Pedro; Depner, Cornelia; Dickinson, Robert; Dobrzynski, Maciej; Fleck, Christian; Garcia-Ojalvo, Jordi; Gonze, Didier; Hahn, Jens; Hess, Heide Marie; Hollmann, Susanne; Krantz, Marcus; Kummer, Ursula; Lundh, Torbjörn; Martial, Gifta; dos Santos, Vítor Martins; 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 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) a description of possible career paths for students who undergo such an education, (iv) conditions that should improve the recruitment of students to such programmes and (v) mechanisms for collaboration and excellence spreading among education professionals. With the growing interest of industry in applying Systems Biology approaches in their fields, a concerted action between academia and industry is needed to build this expertise. Here we present a reflection of the European situation and expertise, where most of the challenges we discuss are universal, anticipating that our suggestions will be useful internationally. We believe that one of the overriding goals of any Systems Biology education should be a student’s ability to phrase and communicate research questions in

  5. Anion binding in biological systems

    NASA Astrophysics Data System (ADS)

    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.

  6. Probing Gravitational Sensitivity in Biological Systems Using Magnetic Body Forces

    NASA Technical Reports Server (NTRS)

    Guevorkian, Karine; Wurzel, Sam; Mihalusova, Mariana; Valles, Jim

    2003-01-01

    At Brown University, we are developing the use of magnetic body forces as a means to simulate variable gravity body forces on biological systems. This tool promises new means to probe gravi-sensing and the gravi-response of biological systems. It also has the potential as a technique for screening future systems for space flight experiments.

  7. Demonstration Bulletin: Aqueous Biological Treatment System (Fixed-Film Biodegradation), Biotrol, Inc

    EPA Science Inventory

    This patented biological treatment system, called the BioTrol Aqueous Treatment System (BATS)., uses an amended microbial population to achieve biological degradation. The system is considered amended when a specific microorganism is added to the indigenous microbial population ...

  8. Review of stochastic hybrid systems with applications in biological systems modeling and analysis.

    PubMed

    Li, Xiangfang; Omotere, Oluwaseyi; Qian, Lijun; Dougherty, Edward R

    2017-12-01

    Stochastic hybrid systems (SHS) have attracted a lot of research interests in recent years. In this paper, we review some of the recent applications of SHS to biological systems modeling and analysis. Due to the nature of molecular interactions, many biological processes can be conveniently described as a mixture of continuous and discrete phenomena employing SHS models. With the advancement of SHS theory, it is expected that insights can be obtained about biological processes such as drug effects on gene regulation. Furthermore, combining with advanced experimental methods, in silico simulations using SHS modeling techniques can be carried out for massive and rapid verification or falsification of biological hypotheses. The hope is to substitute costly and time-consuming in vitro or in vivo experiments or provide guidance for those experiments and generate better hypotheses.

  9. A cumulative index to a continuing bibliography on aerospace medicine and biology, January 1972

    NASA Technical Reports Server (NTRS)

    1972-01-01

    Subject coverage concentrates on the biological, physiological, psychological, and environmental effects to which man is subjected during and following simulated or actual flight in the earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Each entry consists of a standard citation accompanied by its abstract.

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

    PubMed

    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.

  11. On the search for design principles in biological systems.

    PubMed

    Poyatos, Juan F

    2012-01-01

    The search for basic concepts and underlying principles was at the core of the systems approach to science and technology. This approach was somehow abandoned in mainstream biology after its initial proposal, due to the rise and success of molecular biology. This situation has changed. The accumulated knowledge of decades of molecular studies in combination with new technological advances, while further highlighting the intricacies of natural systems, is also bringing back the quest-for-principles research program. Here, I present two lessons that I derived from my own quest: the importance of studying biological information processing to identify common principles in seemingly unrelated contexts and the adequacy of using known design principles at one level of biological organization as a valuable tool to help recognizing principles at an alternative one. These and additional lessons should contribute to the ultimate goal of establishing principles able to integrate the many scales of biological complexity.

  12. Computational approaches to metabolic engineering utilizing systems biology and synthetic biology.

    PubMed

    Fong, Stephen S

    2014-08-01

    Metabolic engineering modifies cellular function to address various biochemical applications. Underlying metabolic engineering efforts are a host of tools and knowledge that are integrated to enable successful outcomes. Concurrent development of computational and experimental tools has enabled different approaches to metabolic engineering. One approach is to leverage knowledge and computational tools to prospectively predict designs to achieve the desired outcome. An alternative approach is to utilize combinatorial experimental tools to empirically explore the range of cellular function and to screen for desired traits. This mini-review focuses on computational systems biology and synthetic biology tools that can be used in combination for prospective in silico strain design.

  13. Engineering and Biology: Counsel for a Continued Relationship

    PubMed Central

    Levy, Arnon; Siegal, Mark L.; Soyer, Orkun S.; Wagner, Andreas

    2015-01-01

    Biologists frequently draw on ideas and terminology from engineering. Evolutionary systems biology—with its circuits, switches, and signal processing—is no exception. In parallel with the frequent links drawn between biology and engineering, there is ongoing criticism against this cross-fertilization, using the argument that over-simplistic metaphors from engineering are likely to mislead us as engineering is fundamentally different from biology. In this article, we clarify and reconfigure the link between biology and engineering, presenting it in a more favorable light. We do so by, first, arguing that critics operate with a narrow and incorrect notion of how engineering actually works, and of what the reliance on ideas from engineering entails. Second, we diagnose and diffuse one significant source of concern about appeals to engineering, namely that they are inherently and problematically metaphorical. We suggest that there is plenty of fertile ground left for a continued, healthy relationship between engineering and biology. PMID:26085824

  14. Engineering biological systems using automated biofoundries.

    PubMed

    Chao, Ran; Mishra, Shekhar; Si, Tong; Zhao, Huimin

    2017-07-01

    Engineered biological systems such as genetic circuits and microbial cell factories have promised to solve many challenges in the modern society. However, the artisanal processes of research and development are slow, expensive, and inconsistent, representing a major obstacle in biotechnology and bioengineering. In recent years, biological foundries or biofoundries have been developed to automate design-build-test engineering cycles in an effort to accelerate these processes. This review summarizes the enabling technologies for such biofoundries as well as their early successes and remaining challenges. Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  15. Radiological/biological/aerosol removal system

    DOEpatents

    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.

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

    PubMed

    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.

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

    PubMed Central

    Aretz, Ina; Meierhofer, David

    2016-01-01

    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. PMID:27128910

  18. How secure is your information system? An investigation into actual healthcare worker password practices.

    PubMed

    Cazier, Joseph A; Medlin, B Dawn

    2006-09-27

    For most healthcare information systems, passwords are the first line of defense in keeping patient and administrative records private and secure. However, this defense is only as strong as the passwords employees chose to use. A weak or easily guessed password is like an open door to the medical records room, allowing unauthorized access to sensitive information. In this paper, we present the results of a study of actual healthcare workers' password practices. In general, the vast majority of these passwords have significant security problems on several dimensions. Implications for healthcare professionals are discussed.

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

    NASA Astrophysics Data System (ADS)

    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

  20. Systems biology and livestock production.

    PubMed

    Headon, D

    2013-12-01

    The mapping of complete sets of genes, transcripts and proteins from many organisms has prompted the development of new '-omic' technologies for collecting and analysing very large amounts of data. Now that the tools to generate and interrogate such complete data sets are widely used, much of the focus of biological research has begun to turn towards understanding systems as a whole, rather than studying their components in isolation. This very broadly defined systems approach is being deployed across a range of problems and scales of organisation, including many aspects of the animal sciences. Here I review selected examples of this systems approach as applied to poultry and livestock production, product quality and welfare.

  1. Macro- and microscale fluid flow systems for endothelial cell biology.

    PubMed

    Young, Edmond W K; Simmons, Craig A

    2010-01-21

    Recent advances in microfluidics have brought forth new tools for studying flow-induced effects on mammalian cells, with important applications in cardiovascular, bone and cancer biology. The plethora of microscale systems developed to date demonstrate the flexibility of microfluidic designs, and showcase advantages of the microscale that are simply not available at the macroscale. However, the majority of these systems will likely not achieve widespread use in the biological laboratory due to their complexity and lack of user-friendliness. To gain widespread acceptance in the biological research community, microfluidics engineers must understand the needs of cell biologists, while biologists must be made aware of available technology. This review provides a critical evaluation of cell culture flow (CCF) systems used to study the effects of mechanical forces on endothelial cells (ECs) in vitro. To help understand the need for various designs of CCF systems, we first briefly summarize main properties of ECs and their native environments. Basic principles of various macro- and microscale systems are described and evaluated. New opportunities are uncovered for developing technologies that have potential to both improve efficiency of experimentation as well as answer important biological questions that otherwise cannot be tackled with existing systems. Finally, we discuss some of the unresolved issues related to microfluidic cell culture, suggest possible avenues of investigation that could resolve these issues, and provide an outlook for the future of microfluidics in biological research.

  2. Physical methods for investigating structural colours in biological systems

    PubMed Central

    Vukusic, P.; Stavenga, D.G.

    2009-01-01

    Many biological systems are known to use structural colour effects to generate aspects of their appearance and visibility. The study of these phenomena has informed an eclectic group of fields ranging, for example, from evolutionary processes in behavioural biology to micro-optical devices in technologically engineered systems. However, biological photonic systems are invariably structurally and often compositionally more elaborate than most synthetically fabricated photonic systems. For this reason, an appropriate gamut of physical methods and investigative techniques must be applied correctly so that the systems' photonic behaviour may be appropriately understood. Here, we survey a broad range of the most commonly implemented, successfully used and recently innovated physical methods. We discuss the costs and benefits of various spectrometric methods and instruments, namely scatterometers, microspectrophotometers, fibre-optic-connected photodiode array spectrometers and integrating spheres. We then discuss the role of the materials' refractive index and several of the more commonly used theoretical approaches. Finally, we describe the recent developments in the research field of photonic crystals and the implications for the further study of structural coloration in animals. PMID:19158009

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

    PubMed

    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.

  4. Reverse engineering and identification in systems biology: strategies, perspectives and challenges

    PubMed Central

    Villaverde, Alejandro F.; Banga, Julio R.

    2014-01-01

    The interplay of mathematical modelling with experiments is one of the central elements in systems biology. The aim of reverse engineering is to infer, analyse and understand, through this interplay, the functional and regulatory mechanisms of biological systems. Reverse engineering is not exclusive of systems biology and has been studied in different areas, such as inverse problem theory, machine learning, nonlinear physics, (bio)chemical kinetics, control theory and optimization, among others. However, it seems that many of these areas have been relatively closed to outsiders. In this contribution, we aim to compare and highlight the different perspectives and contributions from these fields, with emphasis on two key questions: (i) why are reverse engineering problems so hard to solve, and (ii) what methods are available for the particular problems arising from systems biology? PMID:24307566

  5. Reverse engineering and identification in systems biology: strategies, perspectives and challenges.

    PubMed

    Villaverde, Alejandro F; Banga, Julio R

    2014-02-06

    The interplay of mathematical modelling with experiments is one of the central elements in systems biology. The aim of reverse engineering is to infer, analyse and understand, through this interplay, the functional and regulatory mechanisms of biological systems. Reverse engineering is not exclusive of systems biology and has been studied in different areas, such as inverse problem theory, machine learning, nonlinear physics, (bio)chemical kinetics, control theory and optimization, among others. However, it seems that many of these areas have been relatively closed to outsiders. In this contribution, we aim to compare and highlight the different perspectives and contributions from these fields, with emphasis on two key questions: (i) why are reverse engineering problems so hard to solve, and (ii) what methods are available for the particular problems arising from systems biology?

  6. A benchmark for statistical microarray data analysis that preserves actual biological and technical variance.

    PubMed

    De Hertogh, Benoît; De Meulder, Bertrand; Berger, Fabrice; Pierre, Michael; Bareke, Eric; Gaigneaux, Anthoula; Depiereux, Eric

    2010-01-11

    Recent reanalysis of spike-in datasets underscored the need for new and more accurate benchmark datasets for statistical microarray analysis. We present here a fresh method using biologically-relevant data to evaluate the performance of statistical methods. Our novel method ranks the probesets from a dataset composed of publicly-available biological microarray data and extracts subset matrices with precise information/noise ratios. Our method can be used to determine the capability of different methods to better estimate variance for a given number of replicates. The mean-variance and mean-fold change relationships of the matrices revealed a closer approximation of biological reality. Performance analysis refined the results from benchmarks published previously.We show that the Shrinkage t test (close to Limma) was the best of the methods tested, except when two replicates were examined, where the Regularized t test and the Window t test performed slightly better. The R scripts used for the analysis are available at http://urbm-cluster.urbm.fundp.ac.be/~bdemeulder/.

  7. Improving Collaboration by Standardization Efforts in Systems Biology

    PubMed Central

    Dräger, Andreas; Palsson, Bernhard Ø.

    2014-01-01

    Collaborative genome-scale reconstruction endeavors of metabolic networks would not be possible without a common, standardized formal representation of these systems. The ability to precisely define biological building blocks together with their dynamic behavior has even been considered a prerequisite for upcoming synthetic biology approaches. Driven by the requirements of such ambitious research goals, standardization itself has become an active field of research on nearly all levels of granularity in biology. In addition to the originally envisaged exchange of computational models and tool interoperability, new standards have been suggested for an unambiguous graphical display of biological phenomena, to annotate, archive, as well as to rank models, and to describe execution and the outcomes of simulation experiments. The spectrum now even covers the interaction of entire neurons in the brain, three-dimensional motions, and the description of pharmacometric studies. Thereby, the mathematical description of systems and approaches for their (repeated) simulation are clearly separated from each other and also from their graphical representation. Minimum information definitions constitute guidelines and common operation protocols in order to ensure reproducibility of findings and a unified knowledge representation. Central database infrastructures have been established that provide the scientific community with persistent links from model annotations to online resources. A rich variety of open-source software tools thrives for all data formats, often supporting a multitude of programing languages. Regular meetings and workshops of developers and users lead to continuous improvement and ongoing development of these standardization efforts. This article gives a brief overview about the current state of the growing number of operation protocols, mark-up languages, graphical descriptions, and fundamental software support with relevance to systems biology. PMID:25538939

  8. Evolutionary game based control for biological systems with applications in drug delivery.

    PubMed

    Li, Xiaobo; Lenaghan, Scott C; Zhang, Mingjun

    2013-06-07

    Control engineering and analysis of biological systems have become increasingly important for systems and synthetic biology. Unfortunately, no widely accepted control framework is currently available for these systems, especially at the cell and molecular levels. This is partially due to the lack of appropriate mathematical models to describe the unique dynamics of biological systems, and the lack of implementation techniques, such as ultra-fast and ultra-small devices and corresponding control algorithms. This paper proposes a control framework for biological systems subject to dynamics that exhibit adaptive behavior under evolutionary pressures. The control framework was formulated based on evolutionary game based modeling, which integrates both the internal dynamics and the population dynamics. In the proposed control framework, the adaptive behavior was characterized as an internal dynamic, and the external environment was regarded as an external control input. The proposed open-interface control framework can be integrated with additional control algorithms for control of biological systems. To demonstrate the effectiveness of the proposed framework, an optimal control strategy was developed and validated for drug delivery using the pathogen Giardia lamblia as a test case. In principle, the proposed control framework can be applied to any biological system exhibiting adaptive behavior under evolutionary pressures. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Networking Omic Data to Envisage Systems Biological Regulation.

    PubMed

    Kalapanulak, Saowalak; Saithong, Treenut; Thammarongtham, Chinae

    To understand how biological processes work, it is necessary to explore the systematic regulation governing the behaviour of the processes. Not only driving the normal behavior of organisms, the systematic regulation evidently underlies the temporal responses to surrounding environments (dynamics) and long-term phenotypic adaptation (evolution). The systematic regulation is, in effect, formulated from the regulatory components which collaboratively work together as a network. In the drive to decipher such a code of lives, a spectrum of technologies has continuously been developed in the post-genomic era. With current advances, high-throughput sequencing technologies are tremendously powerful for facilitating genomics and systems biology studies in the attempt to understand system regulation inside the cells. The ability to explore relevant regulatory components which infer transcriptional and signaling regulation, driving core cellular processes, is thus enhanced. This chapter reviews high-throughput sequencing technologies, including second and third generation sequencing technologies, which support the investigation of genomics and transcriptomics data. Utilization of this high-throughput data to form the virtual network of systems regulation is explained, particularly transcriptional regulatory networks. Analysis of the resulting regulatory networks could lead to an understanding of cellular systems regulation at the mechanistic and dynamics levels. The great contribution of the biological networking approach to envisage systems regulation is finally demonstrated by a broad range of examples.

  10. Assessing actual evapotranspiration via surface energy balance aiming to optimize water and energy consumption in large scale pressurized irrigation systems

    NASA Astrophysics Data System (ADS)

    Awada, H.; Ciraolo, G.; Maltese, A.; Moreno Hidalgo, M. A.; Provenzano, G.; Còrcoles, J. I.

    2017-10-01

    Satellite imagery provides a dependable basis for computational models that aimed to determine actual evapotranspiration (ET) by surface energy balance. Satellite-based models enables quantifying ET over large areas for a wide range of applications, such as monitoring water distribution, managing irrigation and assessing irrigation systems' performance. With the aim to evaluate the energy and water consumption of a large scale on-turn pressurized irrigation system in the district of Aguas Nuevas, Albacete, Spain, the satellite-based image-processing model SEBAL was used for calculating actual ET. The model has been applied to quantify instantaneous, daily, and seasonal actual ET over high- resolution Landsat images for the peak water demand season (May to September) and for the years 2006 - 2008. The model provided a direct estimation of the distribution of main energy fluxes, at the instant when the satellite overpassed over each field of the district. The image acquisition day Evapotranspiration (ET24) was obtained from instantaneous values by assuming a constant evaporative fraction (Λ) for the entire day of acquisition; then, monthly and seasonal ET were estimated from the daily evapotranspiration (ETdaily) assuming that ET24 varies in proportion to reference ET (ETr) at the meteorological station, thus accounting for day to day variation in meteorological forcing. The comparison between the hydrants water consumption and the actual evapotranspiration, considering an irrigation efficiency of 85%, showed that a considerable amount of water and energy can be saved at district level.

  11. Biocharts: a visual formalism for complex biological systems

    PubMed Central

    Kugler, Hillel; Larjo, Antti; Harel, David

    2010-01-01

    We address one of the central issues in devising languages, methods and tools for the modelling and analysis of complex biological systems, that of linking high-level (e.g. intercellular) information with lower-level (e.g. intracellular) information. Adequate ways of dealing with this issue are crucial for understanding biological networks and pathways, which typically contain huge amounts of data that continue to grow as our knowledge and understanding of a system increases. Trying to comprehend such data using the standard methods currently in use is often virtually impossible. We propose a two-tier compound visual language, which we call Biocharts, that is geared towards building fully executable models of biological systems. One of the main goals of our approach is to enable biologists to actively participate in the computational modelling effort, in a natural way. The high-level part of our language is a version of statecharts, which have been shown to be extremely successful in software and systems engineering. The statecharts can be combined with any appropriately well-defined language (preferably a diagrammatic one) for specifying the low-level dynamics of the pathways and networks. We illustrate the language and our general modelling approach using the well-studied process of bacterial chemotaxis. PMID:20022895

  12. Parameter estimation using meta-heuristics in systems biology: a comprehensive review.

    PubMed

    Sun, Jianyong; Garibaldi, Jonathan M; Hodgman, Charlie

    2012-01-01

    This paper gives a comprehensive review of the application of meta-heuristics to optimization problems in systems biology, mainly focussing on the parameter estimation problem (also called the inverse problem or model calibration). It is intended for either the system biologist who wishes to learn more about the various optimization techniques available and/or the meta-heuristic optimizer who is interested in applying such techniques to problems in systems biology. First, the parameter estimation problems emerging from different areas of systems biology are described from the point of view of machine learning. Brief descriptions of various meta-heuristics developed for these problems follow, along with outlines of their advantages and disadvantages. Several important issues in applying meta-heuristics to the systems biology modelling problem are addressed, including the reliability and identifiability of model parameters, optimal design of experiments, and so on. Finally, we highlight some possible future research directions in this field.

  13. Aerospace medicine and biology: A continuing bibliography with indexes, supplement 107, October 1972

    NASA Technical Reports Server (NTRS)

    1972-01-01

    This Supplement of Aerospace Medicine and Biology lists 353 reports, articles, and other documents announced during September 1972 in Scientific and Technical Aerospace Reports or in International Aerospace Abstracts. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which man is subjected during and following simulated or actual flight in the earth's atmosphere or in interplanetary space. References describing similar effects of biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. In general, emphasis is placed on applied research, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion.

  14. How Secure Is Your Information System? An Investigation into Actual Healthcare Worker Password Practices

    PubMed Central

    Cazier, Joseph A; Medlin, B. Dawn

    2006-01-01

    For most healthcare information systems, passwords are the first line of defense in keeping patient and administrative records private and secure. However, this defense is only as strong as the passwords employees chose to use. A weak or easily guessed password is like an open door to the medical records room, allowing unauthorized access to sensitive information. In this paper, we present the results of a study of actual healthcare workers' password practices. In general, the vast majority of these passwords have significant security problems on several dimensions. Implications for healthcare professionals are discussed. PMID:18066366

  15. Aerospace Medicine and Biology: A Continuing Bibliography with Indexes. Supplement 488

    NASA Technical Reports Server (NTRS)

    1999-01-01

    This report lists reports, articles and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract.

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

    PubMed

    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.

  17. Systems Vaccinology: Enabling rational vaccine design with systems biological approaches

    PubMed Central

    Hagan, Thomas; Nakaya, Helder I.; Subramaniam, Shankar; Pulendran, Bali

    2015-01-01

    Vaccines have drastically reduced the mortality and morbidity of many diseases. However, vaccines have historically been developed empirically, and recent development of vaccines against current pandemics such as HIV and malaria has been met with difficulty. The advent of high-throughput technologies, coupled with systems biological methods of data analysis, has enabled researchers to interrogate the entire complement of a variety of molecular components within cells, and characterize the myriad interactions among them in order to model and understand the behavior of the system as a whole. In the context of vaccinology, these tools permit exploration of the molecular mechanisms by which vaccines induce protective immune responses. Here we review the recent advances, challenges, and potential of systems biological approaches in vaccinology. If the challenges facing this developing field can be overcome, systems vaccinology promises to empower the identification of early predictive signatures of vaccine response, as well as novel and robust correlates of protection from infection. Such discoveries, along with the improved understanding of immune responses to vaccination they impart, will play an instrumental role in development of the next generation of rationally designed vaccines. PMID:25858860

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

    PubMed

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

    2017-09-27

    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. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Systems biology of meridians, acupoints, and chinese herbs in disease.

    PubMed

    Lin, Li-Ling; Wang, Ya-Hui; Lai, Chi-Yu; Chau, Chan-Lao; Su, Guan-Chin; Yang, Chun-Yi; Lou, Shu-Ying; Chen, Szu-Kai; Hsu, Kuan-Hao; Lai, Yen-Ling; Wu, Wei-Ming; Huang, Jian-Long; Liao, Chih-Hsin; Juan, Hsueh-Fen

    2012-01-01

    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.

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

    PubMed

    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.

  1. Aerospace Medicine and Biology: A Continuing Bibliography with Indexes. Supplement 498

    NASA Technical Reports Server (NTRS)

    2000-01-01

    This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes (NASA/SP-1999-7011) lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract.

  2. Aerospace Medicine and Biology: A Continuing Bibliography with Indexes. Supplement 482

    NASA Technical Reports Server (NTRS)

    1999-01-01

    This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes (NASA/SP-1999-7011) lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract.

  3. Aerospace Medicine and Biology: A Continuing Bibliography with Indexes. Supplement 489

    NASA Technical Reports Server (NTRS)

    1999-01-01

    This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes (NASA/SP-1999-7011) lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract.

  4. Aerospace Medicine and Biology: A Continuing Bibliography with Indexes. Supplement 478

    NASA Technical Reports Server (NTRS)

    1998-01-01

    This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes (NASA/SP-1998-7011) lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract.

  5. Aerospace Medicine and Biology: A Continuing Bibliography with Indexes. Supplement 477

    NASA Technical Reports Server (NTRS)

    1998-01-01

    This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes (NASA/SP-1998-7011) lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract.

  6. Separating intrinsic from extrinsic fluctuations in dynamic biological systems

    PubMed Central

    Paulsson, Johan

    2011-01-01

    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. PMID:21730172

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

  10. Systems Biology Approaches for Host–Fungal Interactions: An Expanding Multi-Omics Frontier

    PubMed Central

    Culibrk, Luka; Croft, Carys A.

    2016-01-01

    Abstract Opportunistic fungal infections are an increasing threat for global health, and for immunocompromised patients in particular. These infections are characterized by interaction between fungal pathogen and host cells. The exact mechanisms and the attendant variability in host and fungal pathogen interaction remain to be fully elucidated. The field of systems biology aims to characterize a biological system, and utilize this knowledge to predict the system's response to stimuli such as fungal exposures. A multi-omics approach, for example, combining data from genomics, proteomics, metabolomics, would allow a more comprehensive and pan-optic “two systems” biology of both the host and the fungal pathogen. In this review and literature analysis, we present highly specialized and nascent methods for analysis of multiple -omes of biological systems, in addition to emerging single-molecule visualization techniques that may assist in determining biological relevance of multi-omics data. We provide an overview of computational methods for modeling of gene regulatory networks, including some that have been applied towards the study of an interacting host and pathogen. In sum, comprehensive characterizations of host–fungal pathogen systems are now possible, and utilization of these cutting-edge multi-omics strategies may yield advances in better understanding of both host biology and fungal pathogens at a systems scale. PMID:26885725

  11. Will systems biology offer new holistic paradigms to life sciences?

    PubMed Central

    Conti, Filippo; Valerio, Maria Cristina; Zbilut, Joseph P.

    2008-01-01

    A biological system, like any complex system, blends stochastic and deterministic features, displaying properties of both. In a certain sense, this blend is exactly what we perceive as the “essence of complexity” given we tend to consider as non-complex both an ideal gas (fully stochastic and understandable at the statistical level in the thermodynamic limit of a huge number of particles) and a frictionless pendulum (fully deterministic relative to its motion). In this commentary we make the statement that systems biology will have a relevant impact on nowadays biology if (and only if) will be able to capture the essential character of this blend that in our opinion is the generation of globally ordered collective modes supported by locally stochastic atomisms. PMID:19003440

  12. Promoting Systems Thinking through Biology Lessons

    ERIC Educational Resources Information Center

    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…

  13. Studies on Semantic Systems Chemical Biology

    ERIC Educational Resources Information Center

    Chen, Bin

    2012-01-01

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

  14. Algorithms in nature: the convergence of systems biology and computational thinking

    PubMed Central

    Navlakha, Saket; Bar-Joseph, Ziv

    2011-01-01

    Computer science and biology have enjoyed a long and fruitful relationship for decades. Biologists rely on computational methods to analyze and integrate large data sets, while several computational methods were inspired by the high-level design principles of biological systems. Recently, these two directions have been converging. In this review, we argue that thinking computationally about biological processes may lead to more accurate models, which in turn can be used to improve the design of algorithms. We discuss the similar mechanisms and requirements shared by computational and biological processes and then present several recent studies that apply this joint analysis strategy to problems related to coordination, network analysis, and tracking and vision. We also discuss additional biological processes that can be studied in a similar manner and link them to potential computational problems. With the rapid accumulation of data detailing the inner workings of biological systems, we expect this direction of coupling biological and computational studies to greatly expand in the future. PMID:22068329

  15. Learning Systems Biology: Conceptual Considerations toward a Web-Based Learning Platform

    ERIC Educational Resources Information Center

    Emmert-Streib, Frank; Dehmer, Matthias; Lyardet, Fernando

    2013-01-01

    Within recent years, there is an increasing need to train students, from biology and beyond, in quantitative methods that are relevant to cope with data-driven biology. Systems Biology is such a field that places a particular focus on the functional aspect of biology and molecular interacting processes. This paper deals with the conceptual design…

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

    PubMed

    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.

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

    PubMed

    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.

  18. Sensitivity analysis of dynamic biological systems with time-delays.

    PubMed

    Wu, Wu Hsiung; Wang, Feng Sheng; Chang, Maw Shang

    2010-10-15

    Mathematical modeling has been applied to the study and analysis of complex biological systems for a long time. Some processes in biological systems, such as the gene expression and feedback control in signal transduction networks, involve a time delay. These systems are represented as delay differential equation (DDE) models. Numerical sensitivity analysis of a DDE model by the direct method requires the solutions of model and sensitivity equations with time-delays. The major effort is the computation of Jacobian matrix when computing the solution of sensitivity equations. The computation of partial derivatives of complex equations either by the analytic method or by symbolic manipulation is time consuming, inconvenient, and prone to introduce human errors. To address this problem, an automatic approach to obtain the derivatives of complex functions efficiently and accurately is necessary. We have proposed an efficient algorithm with an adaptive step size control to compute the solution and dynamic sensitivities of biological systems described by ordinal differential equations (ODEs). The adaptive direct-decoupled algorithm is extended to solve the solution and dynamic sensitivities of time-delay systems describing by DDEs. To save the human effort and avoid the human errors in the computation of partial derivatives, an automatic differentiation technique is embedded in the extended algorithm to evaluate the Jacobian matrix. The extended algorithm is implemented and applied to two realistic models with time-delays: the cardiovascular control system and the TNF-α signal transduction network. The results show that the extended algorithm is a good tool for dynamic sensitivity analysis on DDE models with less user intervention. By comparing with direct-coupled methods in theory, the extended algorithm is efficient, accurate, and easy to use for end users without programming background to do dynamic sensitivity analysis on complex biological systems with time-delays.

  19. Systems biology, proteomics, and the future of health care: toward predictive, preventative, and personalized medicine.

    PubMed

    Weston, Andrea D; Hood, Leroy

    2004-01-01

    The emergence of systems biology is bringing forth a new set of challenges for advancing science and technology. Defining ways of studying biological systems on a global level, integrating large and disparate data types, and dealing with the infrastructural changes necessary to carry out systems biology, are just a few of the extraordinary tasks of this growing discipline. Despite these challenges, the impact of systems biology will be far-reaching, and significant progress has already been made. Moving forward, the issue of how to use systems biology to improve the health of individuals must be a priority. It is becoming increasingly apparent that the field of systems biology and one of its important disciplines, proteomics, will have a major role in creating a predictive, preventative, and personalized approach to medicine. In this review, we define systems biology, discuss the current capabilities of proteomics and highlight some of the necessary milestones for moving systems biology and proteomics into mainstream health care.

  20. Glucose Disappearance in Biological Treatment Systems

    PubMed Central

    Jeris, John S.; Cardenas, Raul R.

    1966-01-01

    Laboratory scale anaerobic and aerobic treatment units were conditioned with a daily slug-feed of glucose. After a period of acclimation and stabilization, glucose disappearance was monitored continuously after the slug feed. A continuous sampling apparatus is described. Mathematical analysis of the data indicate zero-order reactions for both biological treatment systems. PMID:16349685

  1. Evolutionary Tradeoffs between Economy and Effectiveness in Biological Homeostasis Systems

    PubMed Central

    Szekely, Pablo; Sheftel, Hila; Mayo, Avi; Alon, Uri

    2013-01-01

    Biological regulatory systems face a fundamental tradeoff: they must be effective but at the same time also economical. For example, regulatory systems that are designed to repair damage must be effective in reducing damage, but economical in not making too many repair proteins because making excessive proteins carries a fitness cost to the cell, called protein burden. In order to see how biological systems compromise between the two tasks of effectiveness and economy, we applied an approach from economics and engineering called Pareto optimality. This approach allows calculating the best-compromise systems that optimally combine the two tasks. We used a simple and general model for regulation, known as integral feedback, and showed that best-compromise systems have particular combinations of biochemical parameters that control the response rate and basal level. We find that the optimal systems fall on a curve in parameter space. Due to this feature, even if one is able to measure only a small fraction of the system's parameters, one can infer the rest. We applied this approach to estimate parameters in three biological systems: response to heat shock and response to DNA damage in bacteria, and calcium homeostasis in mammals. PMID:23950698

  2. Evolutionary tradeoffs between economy and effectiveness in biological homeostasis systems.

    PubMed

    Szekely, Pablo; Sheftel, Hila; Mayo, Avi; Alon, Uri

    2013-01-01

    Biological regulatory systems face a fundamental tradeoff: they must be effective but at the same time also economical. For example, regulatory systems that are designed to repair damage must be effective in reducing damage, but economical in not making too many repair proteins because making excessive proteins carries a fitness cost to the cell, called protein burden. In order to see how biological systems compromise between the two tasks of effectiveness and economy, we applied an approach from economics and engineering called Pareto optimality. This approach allows calculating the best-compromise systems that optimally combine the two tasks. We used a simple and general model for regulation, known as integral feedback, and showed that best-compromise systems have particular combinations of biochemical parameters that control the response rate and basal level. We find that the optimal systems fall on a curve in parameter space. Due to this feature, even if one is able to measure only a small fraction of the system's parameters, one can infer the rest. We applied this approach to estimate parameters in three biological systems: response to heat shock and response to DNA damage in bacteria, and calcium homeostasis in mammals.

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

    PubMed

    Bosl, William J

    2007-02-15

    Expert knowledge in journal articles is an important source of data for reconstructing biological pathways and creating new hypotheses. An important need for medical research is to integrate this data with high throughput sources to build useful models that span several scales. Researchers traditionally use mental models of pathways to integrate information and development new hypotheses. Unfortunately, the amount of information is often overwhelming and these are inadequate for predicting the dynamic response of complex pathways. Hierarchical computational models that allow exploration of semi-quantitative dynamics are useful systems biology tools for theoreticians, experimentalists and clinicians and may provide a means for cross-communication. A novel approach for biological pathway modeling based on hybrid intelligent systems or soft computing technologies is presented here. Intelligent hybrid systems, which refers to several related computing methods such as fuzzy logic, neural nets, genetic algorithms, and statistical analysis, has become ubiquitous in engineering applications for complex control system modeling and design. Biological pathways may be considered to be complex control systems, which medicine tries to manipulate to achieve desired results. Thus, hybrid intelligent systems may provide a useful tool for modeling biological system dynamics and computational exploration of new drug targets. A new modeling approach based on these methods is presented in the context of hedgehog regulation of the cell cycle in granule cells. Code and input files can be found at the Bionet website: www.chip.ord/~wbosl/Software/Bionet. This paper presents the algorithmic methods needed for modeling complicated biochemical dynamics using rule-based models to represent expert knowledge in the context of cell cycle regulation and tumor growth. A notable feature of this modeling approach is that it allows biologists to build complex models from their knowledge base without

  4. Electric and Magnetic Manipulation of Biological Systems

    NASA Astrophysics Data System (ADS)

    Lee, H.; Hunt, T. P.; Liu, Y.; Ham, D.; Westervelt, R. M.

    2005-06-01

    New types of biological cell manipulation systems, a micropost matrix, a microelectromagnet matrix, and a microcoil array, were developed. The micropost matrix consists of post-shaped electrodes embedded in an insulating layer. With a separate ac voltage applied to each electrode, the micropost matrix generates dielectrophoretic force to trap and move individual biological cells. The microelectromagnet matrix consists of two arrays of straight wires aligned perpendicular to each other, that are covered with insulating layers. By independently controlling the current in each wire, the microelectromagnet matrix creates versatile magnetic fields to manipulate individual biological cells attached to magnetic beads. The microcoil array is a set of coils implemented in a foundry using a standard silicon fabrication technology. Current sources to the coils, and control circuits are integrated on a single chip, making the device self-contained. Versatile manipulation of biological cells was demonstrated using these devices by generating optimized electric or magnetic field patterns. A single yeast cell was trapped and positioned with microscopic resolution, and multiple yeast cells were trapped and independently moved along the separate paths for cell-sorting.

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

    PubMed

    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.

  6. Proteomics and Systems Biology: Current and Future Applications in the Nutritional Sciences1

    PubMed Central

    Moore, J. Bernadette; Weeks, Mark E.

    2011-01-01

    In the last decade, advances in genomics, proteomics, and metabolomics have yielded large-scale datasets that have driven an interest in global analyses, with the objective of understanding biological systems as a whole. Systems biology integrates computational modeling and experimental biology to predict and characterize the dynamic properties of biological systems, which are viewed as complex signaling networks. Whereas the systems analysis of disease-perturbed networks holds promise for identification of drug targets for therapy, equally the identified critical network nodes may be targeted through nutritional intervention in either a preventative or therapeutic fashion. As such, in the context of the nutritional sciences, it is envisioned that systems analysis of normal and nutrient-perturbed signaling networks in combination with knowledge of underlying genetic polymorphisms will lead to a future in which the health of individuals will be improved through predictive and preventative nutrition. Although high-throughput transcriptomic microarray data were initially most readily available and amenable to systems analysis, recent technological and methodological advances in MS have contributed to a linear increase in proteomic investigations. It is now commonplace for combined proteomic technologies to generate complex, multi-faceted datasets, and these will be the keystone of future systems biology research. This review will define systems biology, outline current proteomic methodologies, highlight successful applications of proteomics in nutrition research, and discuss the challenges for future applications of systems biology approaches in the nutritional sciences. PMID:22332076

  7. Marine biology, intertidal ecology, and a new place for biology.

    PubMed

    Benson, Keith R

    2015-01-01

    At the present time, there is considerable interest for the physical setting of science, that is, its actual 'place' of practice. Among historians of biology, place has been considered to be a crucial component for the study of ecology. Other historians have noted the 'built' environments (laboratories) for the study of biology along the seashore, even referring to these places in terms more applicable to vacation sites. In this paper, I examine the place of intertidal ecology investigations, both in terms of the physical space and the built space. Part of the examination will investigate the aesthetic aspect of the Pacific Coast, part will evaluate the unique character of the intertidal zone, and part will consider the construction of natural laboratories and built laboratories as characteristic places for biology.

  8. The use of continuous culture in systems biology investigations.

    PubMed

    Winder, Catherine L; Lanthaler, Karin

    2011-01-01

    When acquiring data for systems biology studies, it is essential to perform the experiments in controlled and reproducible conditions. Advances in the fields of proteomics and metabolomics allow the quantitative analysis of the components of the biological cell. It is essential to include a method in the experimental pipeline to culture the biological system in controlled and reproducible conditions to facilitate the acquisition of high-quality data. The employment of continuous culture methods for the growth of microorganisms is an ideal tool to achieve these objectives. This chapter will review the continuous culture approaches which may be applied in such studies, outline the experimental options which should be considered, and describe the approach applied in the production of steady-state cultures of Saccharomyces cerevisiae. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. [Network structures in biological systems].

    PubMed

    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. Verification of Emmert's law in actual and virtual environments.

    PubMed

    Nakamizo, Sachio; Imamura, Mariko

    2004-11-01

    We examined Emmert's law by measuring the perceived size of an afterimage and the perceived distance of the surface on which the afterimage was projected in actual and virtual environments. The actual environment consisted of a corridor with ample cues as to distance and depth. The virtual environment was made from the CAVE of a virtual reality system. The afterimage, disc-shaped and one degree in diameter, was produced by flashing with an electric photoflash. The observers were asked to estimate the perceived distance to surfaces located at various physical distances (1 to 24 m) by the magnitude estimation method and to estimate the perceived size of the afterimage projected on the surfaces by a matching method. The results show that the perceived size of the afterimage was directly proportional to the perceived distance in both environments; thus, Emmert's law holds in virtual as well as actual environments. We suggest that Emmert's law is a specific case of a functional principle of distance scaling by the visual system.

  11. Method and apparatus to image biological interactions in plants

    DOEpatents

    Weisenberger, Andrew; Bonito, Gregory M.; Reid, Chantal D.; Smith, Mark Frederick

    2015-12-22

    A method to dynamically image the actual translocation of molecular compounds of interest in a plant root, root system, and rhizosphere without disturbing the root or the soil. The technique makes use of radioactive isotopes as tracers to label molecules of interest and to image their distribution in the plant and/or soil. The method allows for the study and imaging of various biological and biochemical interactions in the rhizosphere of a plant, including, but not limited to, mycorrhizal associations in such regions.

  12. Fuzzy Stochastic Petri Nets for Modeling Biological Systems with Uncertain Kinetic Parameters

    PubMed Central

    Liu, Fei; Heiner, Monika; Yang, Ming

    2016-01-01

    Stochastic Petri nets (SPNs) have been widely used to model randomness which is an inherent feature of biological systems. However, for many biological systems, some kinetic parameters may be uncertain due to incomplete, vague or missing kinetic data (often called fuzzy uncertainty), or naturally vary, e.g., between different individuals, experimental conditions, etc. (often called variability), which has prevented a wider application of SPNs that require accurate parameters. Considering the strength of fuzzy sets to deal with uncertain information, we apply a specific type of stochastic Petri nets, fuzzy stochastic Petri nets (FSPNs), to model and analyze biological systems with uncertain kinetic parameters. FSPNs combine SPNs and fuzzy sets, thereby taking into account both randomness and fuzziness of biological systems. For a biological system, SPNs model the randomness, while fuzzy sets model kinetic parameters with fuzzy uncertainty or variability by associating each parameter with a fuzzy number instead of a crisp real value. We introduce a simulation-based analysis method for FSPNs to explore the uncertainties of outputs resulting from the uncertainties associated with input parameters, which works equally well for bounded and unbounded models. We illustrate our approach using a yeast polarization model having an infinite state space, which shows the appropriateness of FSPNs in combination with simulation-based analysis for modeling and analyzing biological systems with uncertain information. PMID:26910830

  13. Revolution of Alzheimer Precision Neurology Passageway of Systems Biology and Neurophysiology.

    PubMed

    Hampel, Harald; Toschi, Nicola; Babiloni, Claudio; Baldacci, Filippo; Black, Keith L; Bokde, Arun L W; Bun, René S; Cacciola, Francesco; Cavedo, Enrica; Chiesa, Patrizia A; Colliot, Olivier; Coman, Cristina-Maria; Dubois, Bruno; Duggento, Andrea; Durrleman, Stanley; Ferretti, Maria-Teresa; George, Nathalie; Genthon, Remy; Habert, Marie-Odile; Herholz, Karl; Koronyo, Yosef; Koronyo-Hamaoui, Maya; Lamari, Foudil; Langevin, Todd; Lehéricy, Stéphane; Lorenceau, Jean; Neri, Christian; Nisticò, Robert; Nyasse-Messene, Francis; Ritchie, Craig; Rossi, Simone; Santarnecchi, Emiliano; Sporns, Olaf; Verdooner, Steven R; Vergallo, Andrea; Villain, Nicolas; Younesi, Erfan; Garaci, Francesco; Lista, Simone

    2018-03-16

    The Precision Neurology development process implements systems theory with system biology and neurophysiology in a parallel, bidirectional research path: a combined hypothesis-driven investigation of systems dysfunction within distinct molecular, cellular, and large-scale neural network systems in both animal models as well as through tests for the usefulness of these candidate dynamic systems biomarkers in different diseases and subgroups at different stages of pathophysiological progression. This translational research path is paralleled by an "omics"-based, hypothesis-free, exploratory research pathway, which will collect multimodal data from progressing asymptomatic, preclinical, and clinical neurodegenerative disease (ND) populations, within the wide continuous biological and clinical spectrum of ND, applying high-throughput and high-content technologies combined with powerful computational and statistical modeling tools, aimed at identifying novel dysfunctional systems and predictive marker signatures associated with ND. The goals are to identify common biological denominators or differentiating classifiers across the continuum of ND during detectable stages of pathophysiological progression, characterize systems-based intermediate endophenotypes, validate multi-modal novel diagnostic systems biomarkers, and advance clinical intervention trial designs by utilizing systems-based intermediate endophenotypes and candidate surrogate markers. Achieving these goals is key to the ultimate development of early and effective individualized treatment of ND, such as Alzheimer's disease. The Alzheimer Precision Medicine Initiative (APMI) and cohort program (APMI-CP), as well as the Paris based core of the Sorbonne University Clinical Research Group "Alzheimer Precision Medicine" (GRC-APM) were recently launched to facilitate the passageway from conventional clinical diagnostic and drug development toward breakthrough innovation based on the investigation of the

  14. Revolution of Alzheimer Precision Neurology: Passageway of Systems Biology and Neurophysiology

    PubMed Central

    Hampel, Harald; Toschi, Nicola; Babiloni, Claudio; Baldacci, Filippo; Black, Keith L.; Bokde, Arun L.W.; Bun, René S.; Cacciola, Francesco; Cavedo, Enrica; Chiesa, Patrizia A.; Colliot, Olivier; Coman, Cristina-Maria; Dubois, Bruno; Duggento, Andrea; Durrleman, Stanley; Ferretti, Maria-Teresa; George, Nathalie; Genthon, Remy; Habert, Marie-Odile; Herholz, Karl; Koronyo, Yosef; Koronyo-Hamaoui, Maya; Lamari, Foudil; Langevin, Todd; Lehéricy, Stéphane; Lorenceau, Jean; Neri, Christian; Nisticò, Robert; Nyasse-Messene, Francis; Ritchie, Craig; Rossi, Simone; Santarnecchi, Emiliano; Sporns, Olaf; Verdooner, Steven R.; Vergallo, Andrea; Villain, Nicolas; Younesi, Erfan; Garaci, Francesco; Lista, Simone

    2018-01-01

    The Precision Neurology development process implements systems theory with system biology and neurophysiology in a parallel, bidirectional research path: a combined hypothesis-driven investigation of systems dysfunction within distinct molecular, cellular and large-scale neural network systems in both animal models as well as through tests for the usefulness of these candidate dynamic systems biomarkers in different diseases and subgroups at different stages of pathophysiological progression. This translational research path is paralleled by an “omics”-based, hypothesis-free, exploratory research pathway, which will collect multimodal data from progressing asymptomatic, preclinical and clinical neurodegenerative disease (ND) populations, within the wide continuous biological and clinical spectrum of ND, applying high-throughput and high-content technologies combined with powerful computational and statistical modeling tools, aimed at identifying novel dysfunctional systems and predictive marker signatures associated with ND. The goals are to identify common biological denominators or differentiating classifiers across the continuum of ND during detectable stages of pathophysiological progression, characterize systems-based intermediate endophenotypes, validate multi-modal novel diagnostic systems biomarkers, and advance clinical intervention trial designs by utilizing systems-based intermediate endophenotypes and candidate surrogate markers. Achieving these goals is key to the ultimate development of early and effective individualized treatment of ND, such as Alzheimer’s disease (AD). The Alzheimer Precision Medicine Initiative (APMI) and cohort program (APMI-CP), as well as the Paris based core of the Sorbonne University Clinical Research Group “Alzheimer Precision Medicine” (GRC-APM) were recently launched to facilitate the passageway from conventional clinical diagnostic and drug development towards breakthrough innovation based on the investigation of

  15. Analysing hierarchy in the organization of biological and physical systems.

    PubMed

    Jagers op Akkerhuis, Gerard A J M

    2008-02-01

    A structured approach is discussed for analysing hierarchy in the organization of biological and physical systems. The need for a structured approach follows from the observation that many hierarchies in the literature apply conflicting hierarchy rules and include ill-defined systems. As an alternative, we suggest a framework that is based on the following analytical steps: determination of the succession stage of the universe, identification of a specific system as part of the universe, specification of external influences on a system's creation and analysis of a system's internal organization. At the end, the paper discusses practical implications of the proposed method for the analysis of system organization and hierarchy in biology, ecology and physics.

  16. From Diabetes Care to Diabetes Cure—The Integration of Systems Biology, eHealth, and Behavioral Change

    PubMed Central

    van Ommen, Ben; Wopereis, Suzan; van Empelen, Pepijn; van Keulen, Hilde M.; Otten, Wilma; Kasteleyn, Marise; Molema, Johanna J. W.; de Hoogh, Iris M.; Chavannes, Niels H.; Numans, Mattijs E.; Evers, Andrea W. M.; Pijl, Hanno

    2018-01-01

    From a biological view, most of the processes involved in insulin resistance, which drives the pathobiology of type 2 diabetes, are reversible. This theoretically makes the disease reversible and curable by changing dietary habits and physical activity, particularly when adopted early in the disease process. Yet, this is not fully implemented and exploited in health care due to numerous obstacles. This article reviews the state of the art in all areas involved in a diabetes cure-focused therapy and discusses the scientific and technological advancements that need to be integrated into a systems approach sustainable lifestyle-based healthcare system and economy. The implementation of lifestyle as cure necessitates personalized and sustained lifestyle adaptations, which can only be established by a systems approach, including all relevant aspects (personalized diagnosis and diet, physical activity and stress management, self-empowerment, motivation, participation and health literacy, all facilitated by blended care and ehealth). Introduction of such a systems approach in type 2 diabetes therapy not only requires a concerted action of many stakeholders but also a change in healthcare economy, with new winners and losers. A “call for action” is put forward to actually initiate this transition. The solution provided for type 2 diabetes is translatable to other lifestyle-related disorders. PMID:29403436

  17. From Diabetes Care to Diabetes Cure-The Integration of Systems Biology, eHealth, and Behavioral Change.

    PubMed

    van Ommen, Ben; Wopereis, Suzan; van Empelen, Pepijn; van Keulen, Hilde M; Otten, Wilma; Kasteleyn, Marise; Molema, Johanna J W; de Hoogh, Iris M; Chavannes, Niels H; Numans, Mattijs E; Evers, Andrea W M; Pijl, Hanno

    2017-01-01

    From a biological view, most of the processes involved in insulin resistance, which drives the pathobiology of type 2 diabetes, are reversible. This theoretically makes the disease reversible and curable by changing dietary habits and physical activity, particularly when adopted early in the disease process. Yet, this is not fully implemented and exploited in health care due to numerous obstacles. This article reviews the state of the art in all areas involved in a diabetes cure-focused therapy and discusses the scientific and technological advancements that need to be integrated into a systems approach sustainable lifestyle-based healthcare system and economy. The implementation of lifestyle as cure necessitates personalized and sustained lifestyle adaptations, which can only be established by a systems approach, including all relevant aspects (personalized diagnosis and diet, physical activity and stress management, self-empowerment, motivation, participation and health literacy, all facilitated by blended care and ehealth). Introduction of such a systems approach in type 2 diabetes therapy not only requires a concerted action of many stakeholders but also a change in healthcare economy, with new winners and losers. A "call for action" is put forward to actually initiate this transition. The solution provided for type 2 diabetes is translatable to other lifestyle-related disorders.

  18. Advances on plant-pathogen interactions from molecular toward systems biology perspectives.

    PubMed

    Peyraud, Rémi; Dubiella, Ullrich; Barbacci, Adelin; Genin, Stéphane; Raffaele, Sylvain; Roby, Dominique

    2017-05-01

    In the past 2 decades, progress in molecular analyses of the plant immune system has revealed key elements of a complex response network. Current paradigms depict the interaction of pathogen-secreted molecules with host target molecules leading to the activation of multiple plant response pathways. Further research will be required to fully understand how these responses are integrated in space and time, and exploit this knowledge in agriculture. In this review, we highlight systems biology as a promising approach to reveal properties of molecular plant-pathogen interactions and predict the outcome of such interactions. We first illustrate a few key concepts in plant immunity with a network and systems biology perspective. Next, we present some basic principles of systems biology and show how they allow integrating multiomics data and predict cell phenotypes. We identify challenges for systems biology of plant-pathogen interactions, including the reconstruction of multiscale mechanistic models and the connection of host and pathogen models. Finally, we outline studies on resistance durability through the robustness of immune system networks, the identification of trade-offs between immunity and growth and in silico plant-pathogen co-evolution as exciting perspectives in the field. We conclude that the development of sophisticated models of plant diseases incorporating plant, pathogen and climate properties represent a major challenge for agriculture in the future. © 2016 The Authors. The Plant Journal published by John Wiley & Sons Ltd and Society for Experimental Biology.

  19. Multiway modeling and analysis in stem cell systems biology

    PubMed Central

    2008-01-01

    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 collagen I substrate

  20. Quantitative Analysis of the Trends Exhibited by the Three Interdisciplinary Biological Sciences: Biophysics, Bioinformatics, and Systems Biology.

    PubMed

    Kang, Jonghoon; Park, Seyeon; Venkat, Aarya; Gopinath, Adarsh

    2015-12-01

    New interdisciplinary biological sciences like bioinformatics, biophysics, and systems biology have become increasingly relevant in modern science. Many papers have suggested the importance of adding these subjects, particularly bioinformatics, to an undergraduate curriculum; however, most of their assertions have relied on qualitative arguments. In this paper, we will show our metadata analysis of a scientific literature database (PubMed) that quantitatively describes the importance of the subjects of bioinformatics, systems biology, and biophysics as compared with a well-established interdisciplinary subject, biochemistry. Specifically, we found that the development of each subject assessed by its publication volume was well described by a set of simple nonlinear equations, allowing us to characterize them quantitatively. Bioinformatics, which had the highest ratio of publications produced, was predicted to grow between 77% and 93% by 2025 according to the model. Due to the large number of publications produced in bioinformatics, which nearly matches the number published in biochemistry, it can be inferred that bioinformatics is almost equal in significance to biochemistry. Based on our analysis, we suggest that bioinformatics be added to the standard biology undergraduate curriculum. Adding this course to an undergraduate curriculum will better prepare students for future research in biology.

  1. Aerospace Medicine and Biology: A continuing bibliography with indexes, supplement 143

    NASA Technical Reports Server (NTRS)

    1975-01-01

    This supplement to Aerospace Medicine and Biology (NASA SP-7011) lists 251 reports, articles and other documents announced during June 1975 in Scientific and Technical Aerospace Reports (STAR) or in International Aerospace Abstracts (IAA). The first issue of the bibliography was published in July 1964; since that time, monthly supplements have been issued. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, and environmental effects to which man is subjected during and following simulated or actual flight in the earth's atmosphere or in interplanetary space. References describing similar effects of biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. In general, emphasis is placed on applied research, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion.

  2. First Steps in Computational Systems Biology: A Practical Session in Metabolic Modeling and Simulation

    ERIC Educational Resources Information Center

    Reyes-Palomares, Armando; Sanchez-Jimenez, Francisca; Medina, Miguel Angel

    2009-01-01

    A comprehensive understanding of biological functions requires new systemic perspectives, such as those provided by systems biology. Systems biology approaches are hypothesis-driven and involve iterative rounds of model building, prediction, experimentation, model refinement, and development. Developments in computer science are allowing for ever…

  3. Biologically active chitosan systems for tissue engineering and regenerative medicine.

    PubMed

    Jiang, Tao; Kumbar, Sangamesh G; Nair, Lakshmi S; Laurencin, Cato T

    2008-01-01

    Biodegradable polymeric scaffolds are widely used as a temporary extracellular matrix in tissue engineering and regenerative medicine. By physical adsorption of biomolecules on scaffold surface, physical entrapment of biomolecules in polymer microspheres or hydrogels, and chemical immobilization of oligopeptides or proteins on biomaterials, biologically active biomaterials and scaffolds can be derived. These bioactive systems show great potential in tissue engineering in rendering bioactivity and/or specificity to scaffolds. This review highlights some of the biologically active chitosan systems for tissue engineering application and the associated strategies to develop such bioactive chitosan systems.

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

    PubMed Central

    He, Fei; Murabito, Ettore; Westerhoff, Hans 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 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. PMID:27075000

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

    PubMed

    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).

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

    PubMed

    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.

  7. MLCMS Actual Use, Perceived Use, and Experiences of Use

    ERIC Educational Resources Information Center

    Asiimwe, Edgar Napoleon; Grönlund, Åke

    2015-01-01

    Mobile learning involves use of mobile devices to participate in learning activities. Most e-learning activities are available to participants through learning systems such as learning content management systems (LCMS). Due to certain challenges, LCMS are not equally accessible on all mobile devices. This study investigates actual use, perceived…

  8. Information theory in systems biology. Part I: Gene regulatory and metabolic networks.

    PubMed

    Mousavian, Zaynab; Kavousi, Kaveh; Masoudi-Nejad, Ali

    2016-03-01

    "A Mathematical Theory of Communication", was published in 1948 by Claude Shannon to establish a framework that is now known as information theory. In recent decades, information theory has gained much attention in the area of systems biology. The aim of this paper is to provide a systematic review of those contributions that have applied information theory in inferring or understanding of biological systems. Based on the type of system components and the interactions between them, we classify the biological systems into 4 main classes: gene regulatory, metabolic, protein-protein interaction and signaling networks. In the first part of this review, we attempt to introduce most of the existing studies on two types of biological networks, including gene regulatory and metabolic networks, which are founded on the concepts of information theory. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    PubMed

    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.

  10. Polynomial algebra of discrete models in systems biology.

    PubMed

    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.

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

    PubMed

    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.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chubukov, Victor; Mukhopadhyay, Aindrila; Petzold, Christopher J.

    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 startmore » 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.« less

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

    DOE PAGES

    Chubukov, Victor; Mukhopadhyay, Aindrila; Petzold, Christopher J.; ...

    2016-04-07

    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 startmore » 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.« less

  14. Creating biological nanomaterials using synthetic biology.

    PubMed

    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.

  15. Actual and desired information provision after a stroke.

    PubMed

    Wachters-Kaufmann, Cresje; Schuling, Jan; The, Hauw; Meyboom-de Jong, Betty

    2005-02-01

    Stroke patients and caregivers have a substantial information need. The study investigates how information was actually provided to stroke patients and caregivers and how they prefer to be informed. The GP, neurologist and physiotherapist are both the actual and desired information providers. The actual and desired information correspond in terms of content, frequency, and method of presentation. However, patients and caregivers prefer to receive information within 24 h and to be informed about, and be given, relevant written information. The information given by the various professional stroke care-providers could be better co-ordinated. The role of the GP as an information provider lagged quite a long way behind. Recommendations for the provision of an improved information system is given. Most of the subjects are relatively young male patients with few disabilities and healthy caregivers. More attention should be paid to encouraging patients and caregivers to actively seek information to supplement the information given by professional stroke care-providers.

  16. Varieties of noise: analogical reasoning in synthetic biology.

    PubMed

    Knuuttila, Tarja; Loettgers, Andrea

    2014-12-01

    The picture of synthetic biology as a kind of engineering science has largely created the public understanding of this novel field, covering both its promises and risks. In this paper, we will argue that the actual situation is more nuanced and complex. Synthetic biology is a highly interdisciplinary field of research located at the interface of physics, chemistry, biology, and computational science. All of these fields provide concepts, metaphors, mathematical tools, and models, which are typically utilized by synthetic biologists by drawing analogies between the different fields of inquiry. We will study analogical reasoning in synthetic biology through the emergence of the functional meaning of noise, which marks an important shift in how engineering concepts are employed in this field. The notion of noise serves also to highlight the differences between the two branches of synthetic biology: the basic science-oriented branch and the engineering-oriented branch, which differ from each other in the way they draw analogies to various other fields of study. Moreover, we show that fixing the mapping between a source domain and the target domain seems not to be the goal of analogical reasoning in actual scientific practice.

  17. A Free Energy Principle for Biological Systems

    PubMed Central

    Karl, Friston

    2012-01-01

    This paper describes a free energy principle that tries to explain the ability of biological systems to resist a natural tendency to disorder. It appeals to circular causality of the sort found in synergetic formulations of self-organization (e.g., the slaving principle) and models of coupled dynamical systems, using nonlinear Fokker Planck equations. Here, circular causality is induced by separating the states of a random dynamical system into external and internal states, where external states are subject to random fluctuations and internal states are not. This reduces the problem to finding some (deterministic) dynamics of the internal states that ensure the system visits a limited number of external states; in other words, the measure of its (random) attracting set, or the Shannon entropy of the external states is small. We motivate a solution using a principle of least action based on variational free energy (from statistical physics) and establish the conditions under which it is formally equivalent to the information bottleneck method. This approach has proved useful in understanding the functional architecture of the brain. The generality of variational free energy minimisation and corresponding information theoretic formulations may speak to interesting applications beyond the neurosciences; e.g., in molecular or evolutionary biology. PMID:23204829

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

    PubMed

    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.

  19. Applications of systems biology towards microbial fuel production.

    PubMed

    Gowen, Christopher M; Fong, Stephen S

    2011-10-01

    Harnessing the immense natural diversity of biological functions for economical production of fuel has enormous potential benefits. Inevitably, however, the native capabilities for any given organism must be modified to increase the productivity or efficiency of a biofuel bioprocess. From a broad perspective, the challenge is to sufficiently understand the details of cellular functionality to be able to prospectively predict and modify the cellular function of a microorganism. Recent advances in experimental and computational systems biology approaches can be used to better understand cellular level function and guide future experiments. With pressure to quickly develop viable, renewable biofuel processes a balance must be maintained between obtaining depth of biological knowledge and applying that knowledge. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. The systems biology simulation core algorithm

    PubMed Central

    2013-01-01

    Background With the increasing availability of high dimensional time course data for metabolites, genes, and fluxes, the mathematical description of dynamical systems has become an essential aspect of research in systems biology. Models are often encoded in formats such as SBML, whose structure is very complex and difficult to evaluate due to many special cases. Results This article describes an efficient algorithm to solve SBML models that are interpreted in terms of ordinary differential equations. We begin our consideration with a formal representation of the mathematical form of the models and explain all parts of the algorithm in detail, including several preprocessing steps. We provide a flexible reference implementation as part of the Systems Biology Simulation Core Library, a community-driven project providing a large collection of numerical solvers and a sophisticated interface hierarchy for the definition of custom differential equation systems. To demonstrate the capabilities of the new algorithm, it has been tested with the entire SBML Test Suite and all models of BioModels Database. Conclusions The formal description of the mathematics behind the SBML format facilitates the implementation of the algorithm within specifically tailored programs. The reference implementation can be used as a simulation backend for Java™-based programs. Source code, binaries, and documentation can be freely obtained under the terms of the LGPL version 3 from http://simulation-core.sourceforge.net. Feature requests, bug reports, contributions, or any further discussion can be directed to the mailing list simulation-core-development@lists.sourceforge.net. PMID:23826941

  1. Insects as model systems in cell biology.

    PubMed

    Keil, Thomas A; Steinbrecht, R Alexander

    2010-01-01

    For almost 100 years, insects have been favorable "model systems" in biology. Just to mention a few examples: fruit flies in genetics and developmental biology; bugs and caterpillars in hormone research; houseflies, blowflies, and locusts in neurobiology; silk moths in pheromone research; honeybees and crickets in neuroethology. For more than 50 years the electron microscope (EM) has been a valuable tool in analyzing the structure of cells and organs of these creatures. However, progress in specimen preparation was relatively slow compared with mammalian material and, in 1970, it was taken for granted that insects were much more difficult to fix than mammals. Since then, methods have dramatically improved, and satisfactory results can now be obtained routinely with chemical as well as cryofixation. In this chapter we briefly demonstrate what can be achieved with insect material, and help the researcher to find the most appropriate method for her/his systems and scientific questions. Copyright © 2010 Elsevier Inc. All rights reserved.

  2. A systems biology analysis of autophagy in cancer therapy.

    PubMed

    Shi, Zheng; Li, Chun-yang; Zhao, Si; Yu, Yang; An, Na; Liu, Yong-xi; Wu, Chuan-fang; Yue, Bi-song; Bao, Jin-ku

    2013-09-01

    Autophagy, which degrades redundant or damaged cellular constituents, is intricately relevant to a variety of human diseases, most notably cancer. Autophagy exerts distinct effects on cancer initiation and progression, due to the intrinsic overlapping of autophagic and cancer signalling pathways. However, due to the complexity of cancer as a systemic disease, the fate of cancer cells is not decided by any one signalling pathway. Numerous autophagic inter-connectivity and cross-talk pathways need to be further clarified at a systems level. In this review, we propose a systems biology perspective for the comprehensive analysis of the autophagy-cancer network, focusing on systems biology analysis in autophagy and cancer therapy. Together, these analyses may not only improve our understanding on autophagy-cancer relationships, but also facilitate cancer drug discovery. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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

    PubMed Central

    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

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

    PubMed

    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.

  5. Social networks to biological networks: systems biology of Mycobacterium tuberculosis.

    PubMed

    Vashisht, Rohit; Bhardwaj, Anshu; Osdd Consortium; Brahmachari, Samir K

    2013-07-01

    Contextualizing relevant information to construct a network that represents a given biological process presents a fundamental challenge in the network science of biology. The quality of network for the organism of interest is critically dependent on the extent of functional annotation of its genome. Mostly the automated annotation pipelines do not account for unstructured information present in volumes of literature and hence large fraction of genome remains poorly annotated. However, if used, this information could substantially enhance the functional annotation of a genome, aiding the development of a more comprehensive network. Mining unstructured information buried in volumes of literature often requires manual intervention to a great extent and thus becomes a bottleneck for most of the automated pipelines. In this review, we discuss the potential of scientific social networking as a solution for systematic manual mining of data. Focusing on Mycobacterium tuberculosis, as a case study, we discuss our open innovative approach for the functional annotation of its genome. Furthermore, we highlight the strength of such collated structured data in the context of drug target prediction based on systems level analysis of pathogen.

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

    PubMed

    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.

  7. FAIRDOMHub: a repository and collaboration environment for sharing systems biology research.

    PubMed

    Wolstencroft, Katherine; Krebs, Olga; Snoep, Jacky L; Stanford, Natalie J; Bacall, Finn; Golebiewski, Martin; Kuzyakiv, Rostyk; Nguyen, Quyen; Owen, Stuart; Soiland-Reyes, Stian; Straszewski, Jakub; van Niekerk, David D; Williams, Alan R; Malmström, Lars; Rinn, Bernd; Müller, Wolfgang; Goble, Carole

    2017-01-04

    The FAIRDOMHub is a repository for publishing FAIR (Findable, Accessible, Interoperable and Reusable) Data, Operating procedures and Models (https://fairdomhub.org/) for the Systems Biology community. It is a web-accessible repository for storing and sharing systems biology research assets. It enables researchers to organize, share and publish data, models and protocols, interlink them in the context of the systems biology investigations that produced them, and to interrogate them via API interfaces. By using the FAIRDOMHub, researchers can achieve more effective exchange with geographically distributed collaborators during projects, ensure results are sustained and preserved and generate reproducible publications that adhere to the FAIR guiding principles of data stewardship. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. Evaluation of the Biolog MicroStation system for yeast identification

    NASA Technical Reports Server (NTRS)

    McGinnis, M. R.; Molina, T. C.; Pierson, D. L.; Mishra, S. K.

    1996-01-01

    One hundred and fifty-nine isolates representing 16 genera and 53 species of yeasts were processed with the Biolog MicroStation System for yeast identification. Thirteen genera and 38 species were included in the Biolog database. For these 129 isolates, correct identifications to the species level were 13.2, 39.5 and 48.8% after 24, 48 and 72 hours incubation at 30 degrees C, respectively. Three genera and 15 species which were not included in the Biolog database were also tested. Of the 30 isolates studied, 16.7, 53.3 and 56.7% of the isolates were given incorrect names from the system's database after 24,48 and 72 h incubation at 30 degrees C, respectively. The remaining isolates of this group were not identified.

  9. Glycoengineering in CHO Cells: Advances in Systems Biology.

    PubMed

    Tejwani, Vijay; Andersen, Mikael R; Nam, Jong Hyun; Sharfstein, Susan T

    2018-03-01

    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, is a non-templated process. Consequently, both native and recombinant glycoprotein production generate heterogeneous mixtures containing variable amounts of different glycoforms. Stability, potency, plasma half-life, and immunogenicity of the glycoprotein biologic are directly influenced by the glycoforms. 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 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, and glycan and glycoprotein analysis that together will provide new strategies for glycoengineering of CHO cells with desired or enhanced glycosylation capabilities. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    PubMed

    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.

  11. Systems Biology and Mode of Action Based Risk Assessment.

    EPA Science Inventory

    The application of systems biology approaches has greatly increased in the past decade largely as a consequence of the human genome project and technological advances in genomics and proteomics. Systems approaches have been used in the medical & pharmaceutical realm for diagnost...

  12. Flexible automated approach for quantitative liquid handling of complex biological samples.

    PubMed

    Palandra, Joe; Weller, David; Hudson, Gary; Li, Jeff; Osgood, Sarah; Hudson, Emily; Zhong, Min; Buchholz, Lisa; Cohen, Lucinda H

    2007-11-01

    A fully automated protein precipitation technique for biological sample preparation has been developed for the quantitation of drugs in various biological matrixes. All liquid handling during sample preparation was automated using a Hamilton MicroLab Star Robotic workstation, which included the preparation of standards and controls from a Watson laboratory information management system generated work list, shaking of 96-well plates, and vacuum application. Processing time is less than 30 s per sample or approximately 45 min per 96-well plate, which is then immediately ready for injection onto an LC-MS/MS system. An overview of the process workflow is discussed, including the software development. Validation data are also provided, including specific liquid class data as well as comparative data of automated vs manual preparation using both quality controls and actual sample data. The efficiencies gained from this automated approach are described.

  13. So what do we really mean when we say that systems biology is holistic?

    PubMed Central

    2010-01-01

    Background An old debate has undergone a resurgence in systems biology: that of reductionism versus holism. At least 35 articles in the systems biology literature since 2003 have touched on this issue. The histories of holism and reductionism in the philosophy of biology are reviewed, and the current debate in systems biology is placed in context. Results Inter-theoretic reductionism in the strict sense envisaged by its creators from the 1930s to the 1960s is largely impractical in biology, and was effectively abandoned by the early 1970s in favour of a more piecemeal approach using individual reductive explanations. Classical holism was a stillborn theory of the 1920s, but the term survived in several fields as a loose umbrella designation for various kinds of anti-reductionism which often differ markedly. Several of these different anti-reductionisms are on display in the holistic rhetoric of the recent systems biology literature. This debate also coincides with a time when interesting arguments are being proposed within the philosophy of biology for a new kind of reductionism. Conclusions Engaging more deeply with these issues should sharpen our ideas concerning the philosophy of systems biology and its future best methodology. As with previous decisive moments in the history of biology, only those theories that immediately suggest relatively easy experiments will be winners. PMID:20226033

  14. Systems biology, adverse outcome pathways, and ecotoxicology in the 21st century

    EPA Science Inventory

    While many definitions of systems biology exist, the majority of these contain most (if not all) of the following elements: global measurements of biological molecules to the extent technically feasible, dynamic measurements of key biological molecules to establish quantitative r...

  15. Aerospace Medicine and Biology: A Continuing Bibliography with Indexes. Supplement 490

    NASA Technical Reports Server (NTRS)

    1999-01-01

    This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes (NASA/SP-1999-7011) lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract. Two indexes-subject and author are included after the abstract section.

  16. Aerospace Medicine and Biology: A Continuing Bibliography with Indexes. Supplement 487

    NASA Technical Reports Server (NTRS)

    1999-01-01

    This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes (NASA/SP-1999-7011) lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract. Two indexes-subject and author are included after the abstract section.

  17. Aerospace Medicine and Biology: A Continuing Bibliography With Indexes. Supplement 502

    NASA Technical Reports Server (NTRS)

    2000-01-01

    This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes (NASA/SP-2000-7011) lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract. Two indexes-subject and author are included after the abstract section.

  18. Aerospace Medicine and Biology: A Continuing Bibliography with Indexes. Supplement 504

    NASA Technical Reports Server (NTRS)

    2000-01-01

    This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes (NASA/SP-2000-7011) lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract. Two indexes- subject and author are included after the abstract section.

  19. Aerospace Medicine and Biology: A Continuing Bibliography with Indexes. Supplement 494

    NASA Technical Reports Server (NTRS)

    1999-01-01

    This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract. The NASA CASI price code table, addresses of organizations, and document availability information are included before the abstract section. Two indexes--subject and author are included after the abstract section.

  20. Biologically-based signal processing system applied to noise removal for signal extraction

    DOEpatents

    Fu, Chi Yung; Petrich, Loren I.

    2004-07-13

    The method and system described herein use a biologically-based signal processing system for noise removal for signal extraction. A wavelet transform may be used in conjunction with a neural network to imitate a biological system. The neural network may be trained using ideal data derived from physical principles or noiseless signals to determine to remove noise from the signal.

  1. Chemical combination effects predict connectivity in biological systems

    PubMed Central

    Lehár, Joseph; Zimmermann, Grant R; Krueger, Andrew S; Molnar, Raymond A; Ledell, Jebediah T; Heilbut, Adrian M; Short, Glenn F; Giusti, Leanne C; Nolan, Garry P; Magid, Omar A; Lee, Margaret S; Borisy, Alexis A; Stockwell, Brent R; Keith, Curtis T

    2007-01-01

    Efforts to construct therapeutically useful models of biological systems require large and diverse sets of data on functional connections between their components. Here we show that cellular responses to combinations of chemicals reveal how their biological targets are connected. Simulations of pathways with pairs of inhibitors at varying doses predict distinct response surface shapes that are reproduced in a yeast experiment, with further support from a larger screen using human tumour cells. The response morphology yields detailed connectivity constraints between nearby targets, and synergy profiles across many combinations show relatedness between targets in the whole network. Constraints from chemical combinations complement genetic studies, because they probe different cellular components and can be applied to disease models that are not amenable to mutagenesis. Chemical probes also offer increased flexibility, as they can be continuously dosed, temporally controlled, and readily combined. After extending this initial study to cover a wider range of combination effects and pathway topologies, chemical combinations may be used to refine network models or to identify novel targets. This response surface methodology may even apply to non-biological systems where responses to targeted perturbations can be measured. PMID:17332758

  2. Systems biology impact on antiepileptic drug discovery.

    PubMed

    Margineanu, Doru Georg

    2012-02-01

    Systems biology (SB), a recent trend in bioscience research to consider the complex interactions in biological systems from a holistic perspective, sees the disease as a disturbed network of interactions, rather than alteration of single molecular component(s). SB-relying network pharmacology replaces the prevailing focus on specific drug-receptor interaction and the corollary of rational drug design of "magic bullets", by the search for multi-target drugs that would act on biological networks as "magic shotguns". Epilepsy being a multi-factorial, polygenic and dynamic pathology, SB approach appears particularly fit and promising for antiepileptic drug (AED) discovery. In fact, long before the advent of SB, AED discovery already involved some SB-like elements. A reported SB project aimed to find out new drug targets in epilepsy relies on a relational database that integrates clinical information, recordings from deep electrodes and 3D-brain imagery with histology and molecular biology data on modified expression of specific genes in the brain regions displaying spontaneous epileptic activity. Since hitting a single target does not treat complex diseases, a proper pharmacological promiscuity might impart on an AED the merit of being multi-potent. However, multi-target drug discovery entails the complicated task of optimizing multiple activities of compounds, while having to balance drug-like properties and to control unwanted effects. Specific design tools for this new approach in drug discovery barely emerge, but computational methods making reliable in silico predictions of poly-pharmacology did appear, and their progress might be quite rapid. The current move away from reductionism into network pharmacology allows expecting that a proper integration of the intrinsic complexity of epileptic pathology in AED discovery might result in literally anti-epileptic drugs. Copyright © 2011 Elsevier B.V. All rights reserved.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lewis, Daniel D.; Department of Biomedical Engineering, University of California Davis, Davis, CA; Villarreal, Fernando D.

    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 amore » 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.« less

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

    PubMed Central

    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. PMID:25538941

  5. Synthetic biology outside the cell: linking computational tools to cell-free systems.

    PubMed

    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.

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

    PubMed

    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.

  7. Systems Biology and Mode of Action Based Risk Assessment

    EPA Science Inventory

    The application of systems biology has increased in the past decade largely as a consequence of the human genome project and technological advances in genomics and proteomics. Systems approaches have been used in the medical & pharmaceutical realm for diagnostic purposes and targ...

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

    PubMed

    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

  9. cellPACK: A Virtual Mesoscope to Model and Visualize Structural Systems Biology

    PubMed Central

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

    2014-01-01

    cellPACK assembles computational models of the biological mesoscale, an intermediate scale (10−7–10−8m) between molecular and cellular biology. cellPACK’s modular architecture unites existing and novel packing algorithms to generate, visualize and analyze comprehensive 3D models of complex biological environments that integrate data from multiple experimental systems biology and structural biology sources. cellPACK is currently 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. PMID:25437435

  10. Evaluation and modeling of HIV based on communication theory in biological systems.

    PubMed

    Dong, Miaowu; Li, Wenrong; Xu, Xi

    2016-12-01

    Some forms of communication are used in biological systems such as HIV transmission in human beings. In this paper, we plan to get a unique insight into biological communication systems generally through the analogy between HIV infection and electrical communication system. The model established in this paper can be used to test and simulate various communication systems since it provides researchers with an opportunity. We interpret biological communication systems by using telecommunications exemplification from a layered communication protocol developed before and use the model to indicate HIV spreading. We also implement a simulation of HIV infection based on the layered communication protocol to predict the development of this disease and the results prove the validity of the model. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Internet-orientated Assessment of QOL and Actual Treatment Status in Japanese Patients with Inflammatory Bowel Disease: The 3I survey.

    PubMed

    Matsumoto, Takayuki; Yanai, Shunichi; Toya, Yosuke; Ueno, Masato; Nakamura, Shotaro

    2015-06-01

    This survey aimed to compare actual lifestyle factors and QOL between Japanese IBD patients and healthy Japanese controls, by questionnaire using an internet-web system. Through the internet-web system, we asked 464 patients with Crohn's disease [CD], 360 patients with ulcerative colitis [UC], and 4100 healthy controls to answer a questionnaire including an eight-item short-form health survey [SF-8]. The survey was conducted until data had been accumulated from the predetermined numbers of patients [120 patients each with CD and UC] and healthy controls [240 subjects]. QOL assessment by SF-8 revealed scores for six of the eight subscale items and the summary score for the mental component to be significantly lower in the CD and UC groups than in controls. There was a significant negative correlation between each SF-8 score and the degree of CD and UC symptoms. The marriage rate in adult patients was significantly lower in the CD than in the UC group or the controls. The mean annual income and the employment rate were significantly lower in the CD than in the UC group or the controls. CD patients receiving biologicals were more frequently satisfied with the efficacy of treatment than UC patients were with their treatment regimens [56% vs 29%]. Actual lifestyle factors and QOL appear to be impaired in Japanese patients with IBD, especially those with CD. The subjective efficacy of biologicals might be greater in CD than in UC. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  12. Synthetic biology: insights into biological computation.

    PubMed

    Manzoni, Romilde; Urrios, Arturo; Velazquez-Garcia, Silvia; de Nadal, Eulàlia; Posas, Francesc

    2016-04-18

    Organisms have evolved a broad array of complex signaling mechanisms that allow them to survive in a wide range of environmental conditions. They are able to sense external inputs and produce an output response by computing the information. Synthetic biology attempts to rationally engineer biological systems in order to perform desired functions. Our increasing understanding of biological systems guides this rational design, while the huge background in electronics for building circuits defines the methodology. In this context, biocomputation is the branch of synthetic biology aimed at implementing artificial computational devices using engineered biological motifs as building blocks. Biocomputational devices are defined as biological systems that are able to integrate inputs and return outputs following pre-determined rules. Over the last decade the number of available synthetic engineered devices has increased exponentially; simple and complex circuits have been built in bacteria, yeast and mammalian cells. These devices can manage and store information, take decisions based on past and present inputs, and even convert a transient signal into a sustained response. The field is experiencing a fast growth and every day it is easier to implement more complex biological functions. This is mainly due to advances in in vitro DNA synthesis, new genome editing tools, novel molecular cloning techniques, continuously growing part libraries as well as other technological advances. This allows that digital computation can now be engineered and implemented in biological systems. Simple logic gates can be implemented and connected to perform novel desired functions or to better understand and redesign biological processes. Synthetic biological digital circuits could lead to new therapeutic approaches, as well as new and efficient ways to produce complex molecules such as antibiotics, bioplastics or biofuels. Biological computation not only provides possible biomedical and

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

    PubMed

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

    2016-06-15

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

  14. Request for Travel Funds for Systems Radiation Biology Workshop

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Barcellos-Hoff, Mary Helen

    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 expensesmore » 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.« less

  15. Actualizing system benefits--Part II.

    PubMed

    Zinn, T K; DiGiulio, L W

    1988-05-01

    Do benefits impact the psychology of the information system buying decision? Is system success tied to achieving "promoted" benefits? Part II of this series reveals responses from a survey of some 3,000 executives about the importance of qualitative and quantitative benefits in the "buying process."

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

    PubMed

    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.

  17. A Unique Large-Scale Undergraduate Research Experience in Molecular Systems Biology for Non-Mathematics Majors

    ERIC Educational Resources Information Center

    Kappler, Ulrike; Rowland, Susan L.; Pedwell, Rhianna K.

    2017-01-01

    Systems biology is frequently taught with an emphasis on mathematical modeling approaches. This focus effectively excludes most biology, biochemistry, and molecular biology students, who are not mathematics majors. The mathematical focus can also present a misleading picture of systems biology, which is a multi-disciplinary pursuit requiring…

  18. Applying systems biology to biomedical research and health care: a précising definition of systems medicine.

    PubMed

    Schleidgen, Sebastian; Fernau, Sandra; Fleischer, Henrike; Schickhardt, Christoph; Oßa, Ann-Kristin; Winkler, Eva C

    2017-11-21

    Systems medicine has become a key word in biomedical research. Although it is often referred to as P4-(predictive, preventive, personalized and participatory)-medicine, it still lacks a clear definition and is open to interpretation. This conceptual lack of clarity complicates the scientific and public discourse on chances, risks and limits of Systems Medicine and may lead to unfounded hopes. Against this background, our goal was to develop a sufficiently precise and widely acceptable definition of Systems Medicine. In a first step, PubMed was searched using the keyword "systems medicine". A data extraction tabloid was developed putting forward a means/ends-division. Full-texts of articles containing Systems Medicine in title or abstract were screened for definitions. Definitions were extracted; their semantic elements were assigned as either means or ends. To reduce complexity of the resulting list, summary categories were developed inductively. In a second step, we applied six criteria for adequate definitions (necessity, non-circularity, non-redundancy, consistency, non-vagueness, and coherence) to these categories to derive a so-called précising definition of Systems Medicine. We identified 185 articles containing the term Systems Medicine in title or abstract. 67 contained at least one definition of Systems Medicine. In 98 definitions, we found 114 means and 132 ends. From these we derived the précising definition: Systems Medicine is an approach seeking to improve medical research (i.e. the understanding of complex processes occurring in diseases, pathologies and health states as well as innovative approaches to drug discovery) and health care (i.e. prevention, prediction, diagnosis and treatment) through stratification by means of Systems Biology (i.e. data integration, modeling, experimentation and bioinformatics). Our study also revealed the visionary character of Systems Medicine. Our insights, on the one hand, allow for a realistic identification of

  19. Analyzing Data for Systems Biology: Working at the Intersection of Thermodynamics and Data Analytics

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cannon, William R.; Baxter, Douglas J.

    2012-08-15

    Many challenges in systems biology have to do with analyzing data within the framework of molecular phenomena and cellular pathways. How does this relate to thermodynamics that we know govern the behavior of molecules? Making progress in relating data analysis to thermodynamics is essential in systems biology if we are to build predictive models that enable the field of synthetic biology. This report discusses work at the crossroads of thermodynamics and data analysis, and demonstrates that statistical mechanical free energy is a multinomial log likelihood. Applications to systems biology are presented.

  20. Marijuana and actual driving performance

    DOT National Transportation Integrated Search

    1993-11-01

    This report concerns the effects of marijuana smoking on actual driving performance. It presents the results of one pilot and three actual driving studies. The pilot study's major purpose was to establish the THC dose current marijuana users smoke to...

  1. Systems Biology of the Vervet Monkey

    PubMed Central

    Jasinska, Anna J.; Schmitt, Christopher A.; Service, Susan K.; Cantor, Rita M.; Dewar, Ken; Jentsch, James D.; Kaplan, Jay R.; Turner, Trudy R.; Warren, Wesley C.; Weinstock, George M.; Woods, Roger P.; Freimer, Nelson B.

    2013-01-01

    Nonhuman primates (NHP) provide crucial biomedical model systems intermediate between rodents and humans. The vervet monkey (also called the African green monkey) is a widely used NHP model that has unique value for genetic and genomic investigations of traits relevant to human diseases. This article describes the phylogeny and population history of the vervet monkey and summarizes the use of both captive and wild vervet monkeys in biomedical research. It also discusses the effort of an international collaboration to develop the vervet monkey as the most comprehensively phenotypically and genomically characterized NHP, a process that will enable the scientific community to employ this model for systems biology investigations. PMID:24174437

  2. Describing the complexity of systems: multivariable "set complexity" and the information basis of systems biology.

    PubMed

    Galas, David J; Sakhanenko, Nikita A; Skupin, Alexander; Ignac, Tomasz

    2014-02-01

    Context dependence is central to the description of complexity. Keying on the pairwise definition of "set complexity," we use an information theory approach to formulate general measures of systems complexity. We examine the properties of multivariable dependency starting with the concept of interaction information. We then present a new measure for unbiased detection of multivariable dependency, "differential interaction information." This quantity for two variables reduces to the pairwise "set complexity" previously proposed as a context-dependent measure of information in biological systems. We generalize it here to an arbitrary number of variables. Critical limiting properties of the "differential interaction information" are key to the generalization. This measure extends previous ideas about biological information and provides a more sophisticated basis for the study of complexity. The properties of "differential interaction information" also suggest new approaches to data analysis. Given a data set of system measurements, differential interaction information can provide a measure of collective dependence, which can be represented in hypergraphs describing complex system interaction patterns. We investigate this kind of analysis using simulated data sets. The conjoining of a generalized set complexity measure, multivariable dependency analysis, and hypergraphs is our central result. While our focus is on complex biological systems, our results are applicable to any complex system.

  3. 7 CFR 1437.101 - Actual production history.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Actual production history. 1437.101 Section 1437.101... Determining Yield Coverage Using Actual Production History § 1437.101 Actual production history. Actual production history (APH) is the unit's record of crop yield by crop year for the APH base period. The APH...

  4. 7 CFR 1437.101 - Actual production history.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Actual production history. 1437.101 Section 1437.101... Determining Yield Coverage Using Actual Production History § 1437.101 Actual production history. Actual production history (APH) is the unit's record of crop yield by crop year for the APH base period. The APH...

  5. 7 CFR 1437.101 - Actual production history.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Actual production history. 1437.101 Section 1437.101... Determining Yield Coverage Using Actual Production History § 1437.101 Actual production history. Actual production history (APH) is the unit's record of crop yield by crop year for the APH base period. The APH...

  6. 7 CFR 1437.101 - Actual production history.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Actual production history. 1437.101 Section 1437.101... Determining Yield Coverage Using Actual Production History § 1437.101 Actual production history. Actual production history (APH) is the unit's record of crop yield by crop year for the APH base period. The APH...

  7. 7 CFR 1437.101 - Actual production history.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Actual production history. 1437.101 Section 1437.101... Determining Yield Coverage Using Actual Production History § 1437.101 Actual production history. Actual production history (APH) is the unit's record of crop yield by crop year for the APH base period. The APH...

  8. Probing the biology of dry biological systems to address the basis of seed longevity

    USDA-ARS?s Scientific Manuscript database

    Drying cells reduces molecular mobility and slows chemical and physical reactions. As a result, dry biological systems deteriorate slowly. The time course of deterioration in a population of living cells often follows a sigmoidal pattern in which aging is occurring but no changes to viability are ...

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

    PubMed

    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

  10. Electromagnetic fields as structure-function zeitgebers in biological systems: environmental orchestrations of morphogenesis and consciousness.

    PubMed

    Rouleau, Nicolas; Dotta, Blake T

    2014-01-01

    Within a cell system structure dictates function. Any interaction between cells, or a cell and its environment, has the potential to have long term implications on the function of a given cell and emerging cell aggregates. The structure and function of cells are continuously subjected to modification by electrical and chemical stimuli. However, biological systems are also subjected to an ever-present influence: the electromagnetic (EM) environment. Biological systems have the potential to be influenced by subtle energies which are exchanged at atomic and subatomic scales as EM phenomena. These energy exchanges have the potential to manifest at higher orders of discourse and affect the output (behavior) of a biological system. Here we describe theoretical and experimental evidence of EM influence on cells and the integration of whole systems. Even weak interactions between EM energies and biological systems display the potential to affect a developing system. We suggest the growing literature of EM effects on biological systems has significant implications to the cell and its functional aggregates.

  11. Systems biology approaches for identifying adverse drug reactions and elucidating their underlying biological mechanisms.

    PubMed

    Boland, Mary Regina; Jacunski, Alexandra; Lorberbaum, Tal; Romano, Joseph D; Moskovitch, Robert; Tatonetti, Nicholas P

    2016-01-01

    Small molecules are indispensable to modern medical therapy. However, their use may lead to unintended, negative medical outcomes commonly referred to as adverse drug reactions (ADRs). These effects vary widely in mechanism, severity, and populations affected, making ADR prediction and identification important public health concerns. Current methods rely on clinical trials and postmarket surveillance programs to find novel ADRs; however, clinical trials are limited by small sample size, whereas postmarket surveillance methods may be biased and inherently leave patients at risk until sufficient clinical evidence has been gathered. Systems pharmacology, an emerging interdisciplinary field combining network and chemical biology, provides important tools to uncover and understand ADRs and may mitigate the drawbacks of traditional methods. In particular, network analysis allows researchers to integrate heterogeneous data sources and quantify the interactions between biological and chemical entities. Recent work in this area has combined chemical, biological, and large-scale observational health data to predict ADRs in both individual patients and global populations. In this review, we explore the rapid expansion of systems pharmacology in the study of ADRs. We enumerate the existing methods and strategies and illustrate progress in the field with a model framework that incorporates crucial data elements, such as diet and comorbidities, known to modulate ADR risk. Using this framework, we highlight avenues of research that may currently be underexplored, representing opportunities for future work. © 2015 Wiley Periodicals, Inc.

  12. Infrared Microtransmission And Microreflectance Of Biological Systems

    NASA Astrophysics Data System (ADS)

    Hill, Steve L.; Krishnan, K.; Powell, Jay R.

    1989-12-01

    The infrared microsampling technique has been successfully applied to a variety of biological systems. A microtomed tissue section may be prepared to permit both visual and infrared discrimination. Infrared structural information may be obtained for a single cell, and computer-enhanced images of tissue specimens may be calculated from spectral map data sets. An analysis of a tissue section anomaly may gg suest eitherprotein compositional differences or a localized concentration of foreign matterp. Opaque biological materials such as teeth, gallstones, and kidney stones may be analyzed by microreflectance spectroscop. Absorption anomalies due to specular dispersion are corrected with the Kraymers-Kronig transformation. Corrected microreflectance spectra may contribute to compositional analysis and correlate diseased-related spectral differences to visual specimen anomalies.

  13. The Metals in the Biological Periodic System of the Elements: Concepts and Conjectures

    PubMed Central

    Maret, Wolfgang

    2016-01-01

    A significant number of chemical elements are either essential for life with known functions, or present in organisms with poorly defined functional outcomes. We do not know all the essential elements with certainty and we know even less about the functions of apparently non-essential elements. In this article, I discuss a basis for a biological periodic system of the elements and that biochemistry should include the elements that are traditionally part of inorganic chemistry and not only those that are in the purview of organic chemistry. A biological periodic system of the elements needs to specify what “essential” means and to which biological species it refers. It represents a snapshot of our present knowledge and is expected to undergo further modifications in the future. An integrated approach of biometal sciences called metallomics is required to understand the interactions of metal ions, the biological functions that their chemical structures acquire in the biological system, and how their usage is fine-tuned in biological species and in populations of species with genetic variations (the variome). PMID:26742035

  14. Systems Biology of Glucocorticoids in Muscle Disease

    DTIC Science & Technology

    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

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

    PubMed

    Zhang, Jingli; Cao, Zhanping; Zhang, Hongwei; Zhao, Lianmei; Sun, Xudong; Mei, Feng

    2013-11-15

    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(-2) h(-1), 19.73 × 10(-2) h(-1) and 3.54 × 10(-2) h(-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. Copyright © 2013 Elsevier B.V. All rights reserved.

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

    PubMed Central

    Maier, Christopher W; Long, Jeffrey G; Hemminger, Bradley M; Giddings, Morgan C

    2009-01-01

    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 Ultra-Structure offers

  17. Traversing the conceptual divide between biological and statistical epistasis: systems biology and a more modern synthesis.

    PubMed

    Moore, Jason H; Williams, Scott M

    2005-06-01

    Epistasis plays an important role in the genetic architecture of common human diseases and can be viewed from two perspectives, biological and statistical, each derived from and leading to different assumptions and research strategies. Biological epistasis is the result of physical interactions among biomolecules within gene regulatory networks and biochemical pathways in an individual such that the effect of a gene on a phenotype is dependent on one or more other genes. In contrast, statistical epistasis is defined as deviation from additivity in a mathematical model summarizing the relationship between multilocus genotypes and phenotypic variation in a population. The goal of this essay is to review definitions and examples of biological and statistical epistasis and to explore the relationship between the two. Specifically, we present and discuss the following two questions in the context of human health and disease. First, when does statistical evidence of epistasis in human populations imply underlying biomolecular interactions in the etiology of disease? Second, when do biomolecular interactions produce patterns of statistical epistasis in human populations? Answers to these two reciprocal questions will provide an important framework for using genetic information to improve our ability to diagnose, prevent and treat common human diseases. We propose that systems biology will provide the necessary information for addressing these questions and that model systems such as bacteria, yeast and digital organisms will be a useful place to start.

  18. How Is the Body's Systemic Nature Manifested amongst High School Biology Students?

    ERIC Educational Resources Information Center

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

    2017-01-01

    This study follows two groups of students (67 in all) through the 3 years of their high school biology education and examines the development of their systems thinking--specifically their models of the human body as a system. Both groups were composed of biology majors, but the students in one group also participated in a PBLbased extension…

  19. Bioinformatics workflows and web services in systems biology made easy for experimentalists.

    PubMed

    Jimenez, Rafael C; Corpas, Manuel

    2013-01-01

    Workflows are useful to perform data analysis and integration in systems biology. Workflow management systems can help users create workflows without any previous knowledge in programming and web services. However the computational skills required to build such workflows are usually above the level most biological experimentalists are comfortable with. In this chapter we introduce workflow management systems that reuse existing workflows instead of creating them, making it easier for experimentalists to perform computational tasks.

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

    PubMed

    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

  1. ADAM: Analysis of Discrete Models of Biological Systems Using Computer Algebra

    PubMed Central

    2011-01-01

    Background 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. Results 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. Conclusions 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

  2. Adaptable data management for systems biology investigations.

    PubMed

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

    2009-03-06

    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. 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. 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.

  3. Adaptable data management for systems biology investigations

    PubMed Central

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

    2009-01-01

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

  4. A systems biology approach to understanding impacts of environmental contaminants on fish reproduction

    EPA Science Inventory

    Over the past decade, our research team at the US EPA Mid-Continent Ecology Division has employed systems biology approaches to examine and understand impacts of environmental contaminants on fish reproduction. Our systems biology approach is one in which iterations of model cons...

  5. Methods for improving simulations of biological systems: systemic computation and fractal proteins

    PubMed Central

    Bentley, Peter J.

    2009-01-01

    Modelling and simulation are becoming essential for new fields such as synthetic biology. Perhaps the most important aspect of modelling is to follow a clear design methodology that will help to highlight unwanted deficiencies. The use of tools designed to aid the modelling process can be of benefit in many situations. In this paper, the modelling approach called systemic computation (SC) is introduced. SC is an interaction-based language, which enables individual-based expression and modelling of biological systems, and the interactions between them. SC permits a precise description of a hypothetical mechanism to be written using an intuitive graph-based or a calculus-based notation. The same description can then be directly run as a simulation, merging the hypothetical mechanism and the simulation into the same entity. However, even when using well-designed modelling tools to produce good models, the best model is not always the most accurate one. Frequently, computational constraints or lack of data make it infeasible to model an aspect of biology. Simplification may provide one way forward, but with inevitable consequences of decreased accuracy. Instead of attempting to replace an element with a simpler approximation, it is sometimes possible to substitute the element with a different but functionally similar component. In the second part of this paper, this modelling approach is described and its advantages are summarized using an exemplar: the fractal protein model. Finally, the paper ends with a discussion of good biological modelling practice by presenting lessons learned from the use of SC and the fractal protein model. PMID:19324681

  6. ENFIN--A European network for integrative systems biology.

    PubMed

    Kahlem, Pascal; Clegg, Andrew; Reisinger, Florian; Xenarios, Ioannis; Hermjakob, Henning; Orengo, Christine; Birney, Ewan

    2009-11-01

    Integration of biological data of various types and the development of adapted bioinformatics tools represent critical objectives to enable research at the systems level. The European Network of Excellence ENFIN is engaged in developing an adapted infrastructure to connect databases, and platforms to enable both the generation of new bioinformatics tools and the experimental validation of computational predictions. With the aim of bridging the gap existing between standard wet laboratories and bioinformatics, the ENFIN Network runs integrative research projects to bring the latest computational techniques to bear directly on questions dedicated to systems biology in the wet laboratory environment. The Network maintains internally close collaboration between experimental and computational research, enabling a permanent cycling of experimental validation and improvement of computational prediction methods. The computational work includes the development of a database infrastructure (EnCORE), bioinformatics analysis methods and a novel platform for protein function analysis FuncNet.

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

    PubMed

    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. Quantum Dynamics in Biological Systems

    NASA Astrophysics Data System (ADS)

    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.

  9. Proving Stabilization of Biological Systems

    NASA Astrophysics Data System (ADS)

    Cook, Byron; Fisher, Jasmin; Krepska, Elzbieta; Piterman, Nir

    We describe an efficient procedure for proving stabilization of biological systems modeled as qualitative networks or genetic regulatory networks. For scalability, our procedure uses modular proof techniques, where state-space exploration is applied only locally to small pieces of the system rather than the entire system as a whole. Our procedure exploits the observation that, in practice, the form of modular proofs can be restricted to a very limited set. For completeness, our technique falls back on a non-compositional counterexample search. Using our new procedure, we have solved a number of challenging published examples, including: a 3-D model of the mammalian epidermis; a model of metabolic networks operating in type-2 diabetes; a model of fate determination of vulval precursor cells in the C. elegans worm; and a model of pair-rule regulation during segmentation in the Drosophila embryo. Our results show many orders of magnitude speedup in cases where previous stabilization proving techniques were known to succeed, and new results in cases where tools had previously failed.

  10. Web-based software tool for constraint-based design specification of synthetic biological systems.

    PubMed

    Oberortner, Ernst; Densmore, Douglas

    2015-06-19

    miniEugene provides computational support for solving combinatorial design problems, enabling users to specify and enumerate designs for novel biological systems based on sets of biological constraints. This technical note presents a brief tutorial for biologists and software engineers in the field of synthetic biology on how to use miniEugene. After reading this technical note, users should know which biological constraints are available in miniEugene, understand the syntax and semantics of these constraints, and be able to follow a step-by-step guide to specify the design of a classical synthetic biological system-the genetic toggle switch.1 We also provide links and references to more information on the miniEugene web application and the integration of the miniEugene software library into sophisticated Computer-Aided Design (CAD) tools for synthetic biology ( www.eugenecad.org ).

  11. Bipartite graphs in systems biology and medicine: a survey of methods and applications.

    PubMed

    Pavlopoulos, Georgios A; Kontou, Panagiota I; Pavlopoulou, Athanasia; Bouyioukos, Costas; Markou, Evripides; Bagos, Pantelis G

    2018-04-01

    The latest advances in high-throughput techniques during the past decade allowed the systems biology field to expand significantly. Today, the focus of biologists has shifted from the study of individual biological components to the study of complex biological systems and their dynamics at a larger scale. Through the discovery of novel bioentity relationships, researchers reveal new information about biological functions and processes. Graphs are widely used to represent bioentities such as proteins, genes, small molecules, ligands, and others such as nodes and their connections as edges within a network. In this review, special focus is given to the usability of bipartite graphs and their impact on the field of network biology and medicine. Furthermore, their topological properties and how these can be applied to certain biological case studies are discussed. Finally, available methodologies and software are presented, and useful insights on how bipartite graphs can shape the path toward the solution of challenging biological problems are provided.

  12. Network-based drug discovery by integrating systems biology and computational technologies

    PubMed Central

    Leung, Elaine L.; Cao, Zhi-Wei; Jiang, Zhi-Hong; Zhou, Hua

    2013-01-01

    Network-based intervention has been a trend of curing systemic diseases, but it relies on regimen optimization and valid multi-target actions of the drugs. The complex multi-component nature of medicinal herbs may serve as valuable resources for network-based multi-target drug discovery due to its potential treatment effects by synergy. Recently, robustness of multiple systems biology platforms shows powerful to uncover molecular mechanisms and connections between the drugs and their targeting dynamic network. However, optimization methods of drug combination are insufficient, owning to lacking of tighter integration across multiple ‘-omics’ databases. The newly developed algorithm- or network-based computational models can tightly integrate ‘-omics’ databases and optimize combinational regimens of drug development, which encourage using medicinal herbs to develop into new wave of network-based multi-target drugs. However, challenges on further integration across the databases of medicinal herbs with multiple system biology platforms for multi-target drug optimization remain to the uncertain reliability of individual data sets, width and depth and degree of standardization of herbal medicine. Standardization of the methodology and terminology of multiple system biology and herbal database would facilitate the integration. Enhance public accessible databases and the number of research using system biology platform on herbal medicine would be helpful. Further integration across various ‘-omics’ platforms and computational tools would accelerate development of network-based drug discovery and network medicine. PMID:22877768

  13. Multi-agent-based bio-network for systems biology: protein-protein interaction network as an example.

    PubMed

    Ren, Li-Hong; Ding, Yong-Sheng; Shen, Yi-Zhen; Zhang, Xiang-Feng

    2008-10-01

    Recently, a collective effort from multiple research areas has been made to understand biological systems at the system level. This research requires the ability to simulate particular biological systems as cells, organs, organisms, and communities. In this paper, a novel bio-network simulation platform is proposed for system biology studies by combining agent approaches. We consider a biological system as a set of active computational components interacting with each other and with an external environment. Then, we propose a bio-network platform for simulating the behaviors of biological systems and modelling them in terms of bio-entities and society-entities. As a demonstration, we discuss how a protein-protein interaction (PPI) network can be seen as a society of autonomous interactive components. From interactions among small PPI networks, a large PPI network can emerge that has a remarkable ability to accomplish a complex function or task. We also simulate the evolution of the PPI networks by using the bio-operators of the bio-entities. Based on the proposed approach, various simulators with different functions can be embedded in the simulation platform, and further research can be done from design to development, including complexity validation of the biological system.

  14. SBML-PET: a Systems Biology Markup Language-based parameter estimation tool.

    PubMed

    Zi, Zhike; Klipp, Edda

    2006-11-01

    The estimation of model parameters from experimental data remains a bottleneck for a major breakthrough in systems biology. We present a Systems Biology Markup Language (SBML) based Parameter Estimation Tool (SBML-PET). The tool is designed to enable parameter estimation for biological models including signaling pathways, gene regulation networks and metabolic pathways. SBML-PET supports import and export of the models in the SBML format. It can estimate the parameters by fitting a variety of experimental data from different experimental conditions. SBML-PET has a unique feature of supporting event definition in the SMBL model. SBML models can also be simulated in SBML-PET. Stochastic Ranking Evolution Strategy (SRES) is incorporated in SBML-PET for parameter estimation jobs. A classic ODE Solver called ODEPACK is used to solve the Ordinary Differential Equation (ODE) system. http://sysbio.molgen.mpg.de/SBML-PET/. The website also contains detailed documentation for SBML-PET.

  15. Integration of systems biology with bioprocess engineering: L: -threonine production by systems metabolic engineering of Escherichia coli.

    PubMed

    Lee, Sang Yup; Park, Jin Hwan

    2010-01-01

    Random mutation and selection or targeted metabolic engineering without consideration of its impact on the entire metabolic and regulatory networks can unintentionally cause genetic alterations in the region, which is not directly related to the target metabolite. This is one of the reasons why strategies for developing industrial strains are now shifted towards targeted metabolic engineering based on systems biology, which is termed systems metabolic engineering. Using systems metabolic engineering strategies, all the metabolic engineering works are conducted in systems biology framework, whereby entire metabolic and regulatory networks are thoroughly considered in an integrated manner. The targets for purposeful engineering are selected after all possible effects on the entire metabolic and regulatory networks are thoroughly considered. Finally, the strain, which is capable of producing the target metabolite to a high level close to the theoretical maximum value, can be constructed. Here we review strategies and applications of systems biology successfully implemented on bioprocess engineering, with particular focus on developing L: -threonine production strains of Escherichia coli.

  16. Modular microfluidic system for biological sample preparation

    DOEpatents

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

    2015-09-29

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

  17. Plant MetGenMAP: an integrative analysis system for plant systems biology

    USDA-ARS?s Scientific Manuscript database

    We have developed a web-based system, Plant MetGenMAP, which can identify significantly altered biochemical pathways and highly affected biological processes, predict functional roles of pathway genes, and potential pathway-related regulatory motifs from transcript and metabolite profile datasets. P...

  18. Magnetic Actuation of Biological Systems

    NASA Astrophysics Data System (ADS)

    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

  19. High performance computing in biology: multimillion atom simulations of nanoscale systems

    PubMed Central

    Sanbonmatsu, K. Y.; Tung, C.-S.

    2007-01-01

    Computational methods have been used in biology for sequence analysis (bioinformatics), all-atom simulation (molecular dynamics and quantum calculations), and more recently for modeling biological networks (systems biology). Of these three techniques, all-atom simulation is currently the most computationally demanding, in terms of compute load, communication speed, and memory load. Breakthroughs in electrostatic force calculation and dynamic load balancing have enabled molecular dynamics simulations of large biomolecular complexes. Here, we report simulation results for the ribosome, using approximately 2.64 million atoms, the largest all-atom biomolecular simulation published to date. Several other nanoscale systems with different numbers of atoms were studied to measure the performance of the NAMD molecular dynamics simulation program on the Los Alamos National Laboratory Q Machine. We demonstrate that multimillion atom systems represent a 'sweet spot' for the NAMD code on large supercomputers. NAMD displays an unprecedented 85% parallel scaling efficiency for the ribosome system on 1024 CPUs. We also review recent targeted molecular dynamics simulations of the ribosome that prove useful for studying conformational changes of this large biomolecular complex in atomic detail. PMID:17187988

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

    PubMed Central

    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

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

    PubMed

    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.

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

    PubMed Central

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

    2014-01-01

    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. PMID:24829281

  3. Computational Systems Biology in Cancer: Modeling Methods and Applications

    PubMed Central

    Materi, Wayne; Wishart, David S.

    2007-01-01

    In recent years it has become clear that carcinogenesis is a complex process, both at the molecular and cellular levels. Understanding the origins, growth and spread of cancer, therefore requires an integrated or system-wide approach. Computational systems biology is an emerging sub-discipline in systems biology that utilizes the wealth of data from genomic, proteomic and metabolomic studies to build computer simulations of intra and intercellular processes. Several useful descriptive and predictive models of the origin, growth and spread of cancers have been developed in an effort to better understand the disease and potential therapeutic approaches. In this review we describe and assess the practical and theoretical underpinnings of commonly-used modeling approaches, including ordinary and partial differential equations, petri nets, cellular automata, agent based models and hybrid systems. A number of computer-based formalisms have been implemented to improve the accessibility of the various approaches to researchers whose primary interest lies outside of model development. We discuss several of these and describe how they have led to novel insights into tumor genesis, growth, apoptosis, vascularization and therapy. PMID:19936081

  4. Systems Biology & Mode of Action Based Risk Assessment

    EPA Science Inventory

    The application of systems biology for risk assessment of environmental chemicals is a national extension of its use in pharmaceutical research. The basis for this is the concept of a key event network that builds on existing mode of action frameworks for risk assessment. The a...

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

    PubMed

    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.

  6. Fluorescence dynamics of biological systems using synchrotron radiation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gratton, E.; Mantulin, W.W.; Weber, G.

    1996-09-01

    A beamline for time-resolved fluorescence spectroscopy of biological systems is under construction at the Synchrotron Radiation Center. The fluorometer, operating in the frequency domain, will take advantage of the time structure of the synchrotron radiation light pulses to determine fluorescence lifetimes. Using frequency-domain techniques, the instrument can achieve an ultimate time resolution on the order of picoseconds. Preliminary experiments have shown that reducing the intensity of one of the fifteen electron bunches in the storage ring allows measurement of harmonic frequencies equivalent to the single-bunch mode. This mode of operation of the synchrotron significantly extends the range of lifetimes thatmore » can be measured. The wavelength range (encompassing the visible and ultraviolet), the range of measurable lifetimes, and the stability and reproducibility of the storage ring pulses should make this beamline a versatile tool for the investigation of the complex fluorescence decay of biological systems. {copyright} {ital 1996 American Institute of Physics.}« less

  7. Systems Biology and Biomechanical Model of Heart Failure

    PubMed Central

    Louridas, George E; Lourida, Katerina G

    2012-01-01

    Heart failure is seen as a complex disease caused by a combination of a mechanical disorder, cardiac remodeling and neurohormonal activation. To define heart failure the systems biology approach integrates genes and molecules, interprets the relationship of the molecular networks with modular functional units, and explains the interaction between mechanical dysfunction and cardiac remodeling. The biomechanical model of heart failure explains satisfactorily the progression of myocardial dysfunction and the development of clinical phenotypes. The earliest mechanical changes and stresses applied in myocardial cells and/or myocardial loss or dysfunction activate left ventricular cavity remodeling and other neurohormonal regulatory mechanisms such as early release of natriuretic peptides followed by SAS and RAAS mobilization. Eventually the neurohormonal activation and the left ventricular remodeling process are leading to clinical deterioration of heart failure towards a multi-organic damage. It is hypothesized that approaching heart failure with the methodology of systems biology we promote the elucidation of its complex pathophysiology and most probably we can invent new therapeutic strategies. PMID:22935019

  8. Biological Concepts. Student Manual. Biological Treatment Process Control.

    ERIC Educational Resources Information Center

    Carnegie, John W.

    This manual contains the textual material for a three-lesson unit which introduces students to the basic concepts applicable to all biological treatment systems. The general topic areas addressed in the lessons are: (1) the microorganisms found in biological systems; (2) the factors that affect the growth and health of biological systems; and (3)…

  9. Extracting biomarkers of commitment to cancer development: potential role of vibrational spectroscopy in systems biology.

    PubMed

    Theophilou, Georgios; Paraskevaidi, Maria; Lima, Kássio M G; Kyrgiou, Maria; Martin-Hirsch, Pierre L; Martin, Francis L

    2015-05-01

    The complex processes driving cancer have so far impeded the discovery of dichotomous biomarkers associated with its initiation and progression. Reductionist approaches utilizing 'omics' technologies have met some success in identifying molecular alterations associated with carcinogenesis. Systems biology is an emerging science that combines high-throughput investigation techniques to define the dynamic interplay between regulatory biological systems in response to internal and external cues. Vibrational spectroscopy has the potential to play an integral role within systems biology research approaches. It is capable of examining global models of carcinogenesis by scrutinizing chemical bond alterations within molecules. The application of infrared or Raman spectroscopic approaches coupled with computational analysis under the systems biology umbrella can assist the transition of biomarker research from the molecular level to the system level. The comprehensive representation of carcinogenesis as a multilevel biological process will inevitably revolutionize cancer-related healthcare by personalizing risk prediction and prevention.

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

    PubMed

    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.

  11. From globally coupled maps to complex-systems biology

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kaneko, Kunihiko, E-mail: kaneko@complex.c.u-tokyo.ac.jp

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

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

    PubMed

    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.

  13. Newton, Laplace, and The Epistemology of Systems Biology

    PubMed Central

    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

  14. Aerospace Medicine and Biology: A Continuing Bibliography with Indexes. Supplement 485

    NASA Technical Reports Server (NTRS)

    1999-01-01

    This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes (NASA/SP-1999-7011) lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract. The NASA CASI price code table, addresses of organizations, and document availability information are included before the abstract section. Two indexes-subject and author are included after the abstract section.

  15. Aerospace Medicine and Biology: A Continuing Bibliography With Indexes. Supplement 506

    NASA Technical Reports Server (NTRS)

    2000-01-01

    This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes (NASA/SP#2000-7011) lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth's atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract. The NASA CASI price code table, addresses of organizations, and document availability information are included before the abstract section. Two indexes- subject and author are included after the abstract section.

  16. Aerospace Medicine and Biology: A Continuing Bibliography with Indexes. Supplement 496

    NASA Technical Reports Server (NTRS)

    2000-01-01

    This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes (NASA/SP#2000-7011) lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth#s atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract. The NASA CASI price code table, addresses of organizations, and document availability information are included before the abstract section. Two indexes#subject and author are included after the abstract section.

  17. Aerospace Medicine and Biology: A Continuing Bibliography With Indexes. Supplement 499

    NASA Technical Reports Server (NTRS)

    2000-01-01

    This supplemental issue of Aerospace Medicine and Biology, A Continuing Bibliography with Indexes (NASA/SP#1999-7011) lists reports, articles, and other documents recently announced in the NASA STI Database. In its subject coverage, Aerospace Medicine and Biology concentrates on the biological, physiological, psychological, and environmental effects to which humans are subjected during and following simulated or actual flight in the Earth#s atmosphere or in interplanetary space. References describing similar effects on biological organisms of lower order are also included. Such related topics as sanitary problems, pharmacology, toxicology, safety and survival, life support systems, exobiology, and personnel factors receive appropriate attention. Applied research receives the most emphasis, but references to fundamental studies and theoretical principles related to experimental development also qualify for inclusion. Each entry in the publication consists of a standard bibliographic citation accompanied, in most cases, by an abstract. The NASA CASI price code table, addresses of organizations, and document availability information are included before the abstract section. Two indexes-subject and author are included after the abstract section.

  18. RNA Systems Biology for Cancer: From Diagnosis to Therapy.

    PubMed

    Amirkhah, Raheleh; Farazmand, Ali; Wolkenhauer, Olaf; Schmitz, Ulf

    2016-01-01

    It is due to the advances in high-throughput omics data generation that RNA species have re-entered the focus of biomedical research. International collaborate efforts, like the ENCODE and GENCODE projects, have spawned thousands of previously unknown functional non-coding RNAs (ncRNAs) with various but primarily regulatory roles. Many of these are linked to the emergence and progression of human diseases. In particular, interdisciplinary studies integrating bioinformatics, systems biology, and biotechnological approaches have successfully characterized the role of ncRNAs in different human cancers. These efforts led to the identification of a new tool-kit for cancer diagnosis, monitoring, and treatment, which is now starting to enter and impact on clinical practice. This chapter is to elaborate on the state of the art in RNA systems biology, including a review and perspective on clinical applications toward an integrative RNA systems medicine approach. The focus is on the role of ncRNAs in cancer.

  19. Interactions of platinum metals and their complexes in biological systems.

    PubMed Central

    LeRoy, A F

    1975-01-01

    Platinum-metal oxidation catalysts are to be introduced in exhaust systems of many 1975 model-year automobiles in the U.S. to meet Clean Air Act standards. Small quantities of finely divided catalyst have been found issuing from prototype systems; platinum and palladium compounds may be found also. Although platinum exhibits a remarkable resistance to oxidation and chemical attack, it reacts chemically under some conditions producing coordination complex compounds. Palladium reacts more readily than platinum. Some platinum-metal complexes interact with biological systems as bacteriostatic, bacteriocidal, viricidal, and immunosuppressive agents. Workers chronically exposed to platinum complexes often develop asthma-like respiratory distress and skin reactions called platinosis. Platinum complexes used alone and in combination therapy with other drugs have recently emerged as effective agents in cancer chemotherapy. Understanding toxic and favorable interactions of metal species with living organisms requires basic information on quantities and chemical characteristics of complexes at trace concentrations in biological materials. Some basic chemical kinetic and thermodynamic data are presented to characterize the chemical behavior of the complex cis-[Pt(NH3)2Cl2] used therapeutically. A brief discussion of platinum at manogram levels in biological tissue is discussed. PMID:50943

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

    PubMed

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

    2016-08-27

    Covering: 2012 to 2016Metabolic 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. Biological Systems for Hydrogen Photoproduction (Presentation)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ghirardi, M. L.

    2012-05-01

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

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

    PubMed

    Birkland, Aaron; Yona, Golan

    2006-02-15

    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. 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. 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.

  3. Systems Biology in Immunology – A Computational Modeling Perspective

    PubMed Central

    Germain, Ronald N.; Meier-Schellersheim, Martin; Nita-Lazar, Aleksandra; Fraser, Iain D. C.

    2011-01-01

    Systems biology is an emerging discipline that combines high-content, multiplexed measurements with informatic and computational modeling methods to better understand biological function at various scales. Here we present a detailed review of the methods used to create computational models and conduct simulations of immune function, We provide descriptions of the key data gathering techniques employed to generate the quantitative and qualitative data required for such modeling and simulation and summarize the progress to date in applying these tools and techniques to questions of immunological interest, including infectious disease. We include comments on what insights modeling can provide that complement information obtained from the more familiar experimental discovery methods used by most investigators and why quantitative methods are needed to eventually produce a better understanding of immune system operation in health and disease. PMID:21219182

  4. Cancer Systems Biology: a peak into the future of patient care?

    PubMed Central

    Werner, Henrica M. J.; Mills, Gordon B.; Ram, Prahlad T.

    2015-01-01

    Traditionally, scientific research has focused on studying individual events, such as single mutations, gene function or the effect of the manipulation of one protein on a biological phenotype. A range of technologies, combined with the ability to develop robust and predictive mathematical models, is beginning to provide information that will enable a holistic view of how the genomic and epigenetic aberrations in cancer cells can alter the homeostasis of signalling networks within these cells, between cancer cells and the local microenvironment, at the organ and organism level. This systems biology process needs to be integrated with an iterative approach wherein hypotheses and predictions that arise from modelling are refined and constrained by experimental evaluation. Systems biology approaches will be vital for developing and implementing effective strategies to deliver personalized cancer therapy. Specifically, these approaches will be important to select those patients most likely to benefit from targeted therapies as well as for the development and implementation of rational combinatorial therapies. Systems biology can help to increase therapy efficacy or bypass the emergence of resistance, thus converting the current (often short term) effects of targeted therapies into durable responses, ultimately to improve quality of life and provide a cure. PMID:24492837

  5. Conciliation biology: the eco-evolutionary management of permanently invaded biotic systems

    PubMed Central

    Carroll, Scott P

    2011-01-01

    Biotic invaders and similar anthropogenic novelties such as domesticates, transgenics, and cancers can alter ecology and evolution in environmental, agricultural, natural resource, public health, and medical systems. The resulting biological changes may either hinder or serve management objectives. For example, biological control and eradication programs are often defeated by unanticipated resistance evolution and by irreversibility of invader impacts. Moreover, eradication may be ill-advised when nonnatives introduce beneficial functions. Thus, contexts that appear to call for eradication may instead demand managed coexistence of natives with nonnatives, and yet applied biologists have not generally considered the need to manage the eco-evolutionary dynamics that commonly result from interactions of natives with nonnatives. Here, I advocate a conciliatory approach to managing systems where novel organisms cannot or should not be eradicated. Conciliatory strategies incorporate benefits of nonnatives to address many practical needs including slowing rates of resistance evolution, promoting evolution of indigenous biological control, cultivating replacement services and novel functions, and managing native–nonnative coevolution. Evolutionary links across disciplines foster cohesion essential for managing the broad impacts of novel biotic systems. Rather than signaling defeat, conciliation biology thus utilizes the predictive power of evolutionary theory to offer diverse and flexible pathways to more sustainable outcomes. PMID:25567967

  6. Systems biology for understanding and engineering of heterotrophic oleaginous microorganisms.

    PubMed

    Park, Beom Gi; Kim, Minsuk; Kim, Joonwon; Yoo, Heewang; Kim, Byung-Gee

    2017-01-01

    Heterotrophic oleaginous microorganisms continue to draw interest as they can accumulate a large amount of lipids which is a promising feedstock for the production of biofuels and oleochemicals. Nutrient limitation, especially nitrogen limitation, is known to effectively trigger the lipid production in these microorganisms. For the aim of developing improved strains, the mechanisms behind the lipid production have been studied for a long time. Nowadays, system-level understanding of their metabolism and associated metabolic switches is attainable with modern systems biology tools. This work reviews the systems biology studies, based on (i) top-down, large-scale 'omics' tools, and (ii) bottom-up, mathematical modeling methods, on the heterotrophic oleaginous microorganisms with an emphasis on further application to metabolic engineering. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Test operation of a real-time tsunami inundation forecast system using actual data observed by S-net

    NASA Astrophysics Data System (ADS)

    Suzuki, W.; Yamamoto, N.; Miyoshi, T.; Aoi, S.

    2017-12-01

    If the tsunami inundation information can be rapidly and stably forecast before the large tsunami attacks, the information would have effectively people realize the impeding danger and necessity of evacuation. Toward that goal, we have developed a prototype system to perform the real-time tsunami inundation forecast for Chiba prefecture, eastern Japan, using off-shore ocean bottom pressure data observed by the seafloor observation network for earthquakes and tsunamis along the Japan Trench (S-net) (Aoi et al., 2015, AGU). Because tsunami inundation simulation requires a large computation cost, we employ a database approach searching the pre-calculated tsunami scenarios that reasonably explain the observed S-net pressure data based on the multi-index method (Yamamoto et al., 2016, EPS). The scenario search is regularly repeated, not triggered by the occurrence of the tsunami event, and the forecast information is generated from the selected scenarios that meet the criterion. Test operation of the prototype system using the actual observation data started in April, 2017 and the performance and behavior of the system during non-tsunami event periods have been examined. It is found that the treatment of the noises affecting the observed data is the main issue to be solved toward the improvement of the system. Even if the observed pressure data are filtered to extract the tsunami signals, the noises in ordinary times or unusually large noises like high ocean waves due to storm affect the comparison between the observed and scenario data. Due to the noises, the tsunami scenarios are selected and the tsunami is forecast although any tsunami event does not actually occur. In most cases, the selected scenarios due to the noises have the fault models in the region along the Kurile or Izu-Bonin Trenches, far from the S-net region, or the fault models below the land. Based on the parallel operation of the forecast system with a different scenario search condition and

  8. Enhanced sampling techniques in molecular dynamics simulations of biological systems.

    PubMed

    Bernardi, Rafael C; Melo, Marcelo C R; Schulten, Klaus

    2015-05-01

    Molecular dynamics has emerged as an important research methodology covering systems to the level of millions of atoms. However, insufficient sampling often limits its application. The limitation is due to rough energy landscapes, with many local minima separated by high-energy barriers, which govern the biomolecular motion. In the past few decades methods have been developed that address the sampling problem, such as replica-exchange molecular dynamics, metadynamics and simulated annealing. Here we present an overview over theses sampling methods in an attempt to shed light on which should be selected depending on the type of system property studied. Enhanced sampling methods have been employed for a broad range of biological systems and the choice of a suitable method is connected to biological and physical characteristics of the system, in particular system size. While metadynamics and replica-exchange molecular dynamics are the most adopted sampling methods to study biomolecular dynamics, simulated annealing is well suited to characterize very flexible systems. The use of annealing methods for a long time was restricted to simulation of small proteins; however, a variant of the method, generalized simulated annealing, can be employed at a relatively low computational cost to large macromolecular complexes. Molecular dynamics trajectories frequently do not reach all relevant conformational substates, for example those connected with biological function, a problem that can be addressed by employing enhanced sampling algorithms. This article is part of a Special Issue entitled Recent developments of molecular dynamics. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Engineering biological systems toward a sustainable bioeconomy.

    PubMed

    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.

  10. Is synthetic biology mechanical biology?

    PubMed

    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.

  11. Systems biology: An emerging strategy for discovering novel pathogenetic mechanisms that promote cardiovascular disease.

    PubMed

    Maron, Bradley A; Leopold, Jane A

    2016-09-30

    Reductionist theory proposes that analyzing complex systems according to their most fundamental components is required for problem resolution, and has served as the cornerstone of scientific methodology for more than four centuries. However, technological gains in the current scientific era now allow for the generation of large datasets that profile the proteomic, genomic, and metabolomic signatures of biological systems across a range of conditions. The accessibility of data on such a vast scale has, in turn, highlighted the limitations of reductionism, which is not conducive to analyses that consider multiple and contemporaneous interactions between intermediates within a pathway or across constructs. Systems biology has emerged as an alternative approach to analyze complex biological systems. This methodology is based on the generation of scale-free networks and, thus, provides a quantitative assessment of relationships between multiple intermediates, such as protein-protein interactions, within and between pathways of interest. In this way, systems biology is well positioned to identify novel targets implicated in the pathogenesis or treatment of diseases. In this review, the historical root and fundamental basis of systems biology, as well as the potential applications of this methodology are discussed with particular emphasis on integration of these concepts to further understanding of cardiovascular disorders such as coronary artery disease and pulmonary hypertension.

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

    NASA Technical Reports Server (NTRS)

    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. Macro to microfluidics system for biological environmental monitoring.

    PubMed

    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.

  14. Understanding Water-Stress Responses in Soybean Using Hydroponics System-A Systems Biology Perspective.

    PubMed

    Tripathi, Prateek; Rabara, Roel C; Shulaev, Vladimir; Shen, Qingxi J; Rushton, Paul J

    2015-01-01

    The deleterious changes in environmental conditions such as water stress bring physiological and biochemical changes in plants, which results in crop loss. Thus, combating water stress is important for crop improvement to manage the needs of growing population. Utilization of hydroponics system in growing plants is questionable to some researchers, as it does not represent an actual field condition. However, trying to address a complex problem like water stress we have to utilize a simpler growing condition like the hydroponics system wherein every input given to the plants can be controlled. With the advent of high-throughput technologies, it is still challenging to address all levels of the genetic machinery whether a gene, protein, metabolite, and promoter. Thus, using a system of reduced complexity like hydroponics can certainly direct us toward the right candidates, if not completely help us to resolve the issue.

  15. Bi-Fi: an embedded sensor/system architecture for REMOTE biological monitoring.

    PubMed

    Farshchi, Shahin; Pesterev, Aleksey; Nuyujukian, Paul H; Mody, Istvan; Judy, Jack W

    2007-11-01

    Wireless-enabled processor modules intended for communicating low-frequency phenomena (i.e., temperature, humidity, and ambient light) have been enabled to acquire and transmit multiple biological signals in real time, which has been achieved by using computationally efficient data acquisition, filtering, and compression algorithms, and interfacing the modules with biological interface hardware. The sensor modules can acquire and transmit raw biological signals at a rate of 32 kb/s, which is near the hardware limit of the modules. Furthermore, onboard signal processing enables one channel, sampled at a rate of 4000 samples/s at 12-bit resolution, to be compressed via adaptive differential-pulse-code modulation (ADPCM) and transmitted in real time. In addition, the sensors can be configured to filter and transmit individual time-referenced "spike" waveforms, or to transmit the spike height and width for alleviating network traffic and increasing battery life. The system is capable of acquiring eight channels of analog signals as well as data via an asynchronous serial connection. A back-end server archives the biological data received via networked gateway sensors, and hosts them to a client application that enables users to browse recorded data. The system also acquires, filters, and transmits oxygen saturation and pulse rate via a commercial-off-the-shelf interface board. The system architecture can be configured for performing real-time nonobtrusive biological monitoring of humans or rodents. This paper demonstrates that low-power, computational, and bandwidth-constrained wireless-enabled platforms can indeed be leveraged for wireless biosignal monitoring.

  16. Endogenous Biologically Inspired Art of Complex Systems.

    PubMed

    Ji, Haru; Wakefield, Graham

    2016-01-01

    Since 2007, Graham Wakefield and Haru Ji have looked to nature for inspiration as they have created a series of "artificial natures," or interactive visualizations of biologically inspired complex systems that can evoke nature-like aesthetic experiences within mixed-reality art installations. This article describes how they have applied visualization, sonification, and interaction design in their work with artificial ecosystems and organisms using specific examples from their exhibited installations.

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

    PubMed

    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.

  18. A new organismal systems biology: how animals walk the tight rope between stability and change.

    PubMed

    Padilla, Dianna K; Tsukimura, Brian

    2014-07-01

    The amount of knowledge in the biological sciences is growing at an exponential rate. Simultaneously, the incorporation of new technologies in gathering scientific information has greatly accelerated our capacity to ask, and answer, new questions. How do we, as organismal biologists, meet these challenges, and develop research strategies that will allow us to address the grand challenge question: how do organisms walk the tightrope between stability and change? Organisms and organismal systems are complex, and multi-scale in both space and time. It is clear that addressing major questions about organismal biology will not come from "business as usual" approaches. Rather, we require the collaboration of a wide range of experts and integration of biological information with more quantitative approaches traditionally found in engineering and applied mathematics. Research programs designed to address grand challenge questions will require deep knowledge and expertise within subfields of organismal biology, collaboration and integration among otherwise disparate areas of research, and consideration of organisms as integrated systems. Our ability to predict which features of complex integrated systems provide the capacity to be robust in changing environments is poorly developed. A predictive organismal biology is needed, but will require more quantitative approaches than are typical in biology, including complex systems-modeling approaches common to engineering. This new organismal systems biology will have reciprocal benefits for biologists, engineers, and mathematicians who address similar questions, including those working on control theory and dynamical systems biology, and will develop the tools we need to address the grand challenge questions of the 21st century. © The Author 2014. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

  19. Photoacoustic tomography of foreign bodies in soft biological tissue.

    PubMed

    Cai, Xin; Kim, Chulhong; Pramanik, Manojit; Wang, Lihong V

    2011-04-01

    In detecting small foreign bodies in soft biological tissue, ultrasound imaging suffers from poor sensitivity (52.6%) and specificity (47.2%). Hence, alternative imaging methods are needed. Photoacoustic (PA) imaging takes advantage of strong optical absorption contrast and high ultrasonic resolution. A PA imaging system is employed to detect foreign bodies in biological tissues. To achieve deep penetration, we use near-infrared light ranging from 750 to 800 nm and a 5-MHz spherically focused ultrasonic transducer. PA images were obtained from various targets including glass, wood, cloth, plastic, and metal embedded more than 1 cm deep in chicken tissue. The locations and sizes of the targets from the PA images agreed well with those of the actual samples. Spectroscopic PA imaging was also performed on the objects. These results suggest that PA imaging can potentially be a useful intraoperative imaging tool to identify foreign bodies.

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

    PubMed

    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.

  1. 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.

    NASA Astrophysics Data System (ADS)

    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.).

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

    PubMed

    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.

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

    PubMed

    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.

  4. Cell Illustrator 4.0: a computational platform for systems biology.

    PubMed

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

    2010-01-01

    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.

  5. Morphomics: An integral part of systems biology of the human placenta.

    PubMed

    Mayhew, T M

    2015-04-01

    The placenta is a transient organ the functioning of which has health consequences far beyond the embryo/fetus. Understanding the biology of any system (organ, organism, single cell, etc) requires a comprehensive and inclusive approach which embraces all the biomedical disciplines and 'omic' technologies and then integrates information obtained from all of them. Among the latest 'omics' is morphomics. The terms morphome and morphomics have been applied incoherently in biology and biomedicine but, recently, they have been given clear and widescale definitions. Morphomics is placed in the context of other 'omics' and its pertinent technologies and tools for sampling and quantitation are reviewed. Emphasis is accorded to the importance of random sampling principles in systems biology and the value of combining 3D quantification with alternative imaging techniques to advance knowledge and understanding of the human placental morphome. By analogy to other 'omes', the morphome is the totality of morphological features within a system and morphomics is the systematic study of those structures. Information about structure is required at multiple levels of resolution in order to understand better the processes by which a given system alters with time, experimental treatment or environmental insult. Therefore, morphomics research includes all imaging techniques at all levels of achievable resolution from gross anatomy and medical imaging, via optical and electron microscopy, to molecular characterisation. Quantification is an important element of all 'omics' studies and, because biological systems exist and operate in 3-dimensional (3D) space, precise descriptions of form, content and spatial relationships require the quantification of structure in 3D. These considerations are relevant to future study contributions to the Human Placenta Project. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Yeast Immobilization Systems for Alcoholic Wine Fermentations: Actual Trends and Future Perspectives

    PubMed Central

    Moreno-García, Jaime; García-Martínez, Teresa; Mauricio, Juan C.; Moreno, Juan

    2018-01-01

    Yeast immobilization is defined as the physical confinement of intact cells to a region of space with conservation of biological activity. The use of these methodologies for alcoholic fermentation (AF) offers many advantages over the use of the conventional free yeast cell method and different immobilization systems have been proposed so far for different applications, like winemaking. The most studied methods for yeast immobilization include the use of natural supports (e.g., fruit pieces), organic supports (e.g., alginate), inorganic (e.g., porous ceramics), membrane systems, and multi-functional agents. Some advantages of the yeast-immobilization systems include: high cell densities, product yield improvement, lowered risk of microbial contamination, better control and reproducibility of the processes, as well as reuse of the immobilization system for batch fermentations and continuous fermentation technologies. However, these methods have some consequences on the behavior of the yeasts, affecting the final products of the fermentative metabolism. This review compiles current information about cell immobilizer requirements for winemaking purposes, the immobilization methods applied to the production of fermented beverages to date, and yeast physiological consequences of immobilization strategies. Finally, a recent inter-species immobilization methodology has been revised, where yeast cells are attached to the hyphae of a Generally Recognized As Safe fungus and remain adhered following loss of viability of the fungus. The bio-capsules formed with this method open new and promising strategies for alcoholic beverage production (wine and low ethanol content beverages). PMID:29497415

  7. Using Petri Net Tools to Study Properties and Dynamics of Biological Systems

    PubMed Central

    Peleg, Mor; Rubin, Daniel; Altman, Russ B.

    2005-01-01

    Petri Nets (PNs) and their extensions are promising methods for modeling and simulating biological systems. We surveyed PN formalisms and tools and compared them based on their mathematical capabilities as well as by their appropriateness to represent typical biological processes. We measured the ability of these tools to model specific features of biological systems and answer a set of biological questions that we defined. We found that different tools are required to provide all capabilities that we assessed. We created software to translate a generic PN model into most of the formalisms and tools discussed. We have also made available three models and suggest that a library of such models would catalyze progress in qualitative modeling via PNs. Development and wide adoption of common formats would enable researchers to share models and use different tools to analyze them without the need to convert to proprietary formats. PMID:15561791

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

    NASA Astrophysics Data System (ADS)

    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'.

  9. CEBS object model for systems biology data, SysBio-OM.

    PubMed

    Xirasagar, Sandhya; Gustafson, Scott; Merrick, B Alex; Tomer, Kenneth B; Stasiewicz, Stanley; Chan, Denny D; Yost, Kenneth J; Yates, John R; Sumner, Susan; Xiao, Nianqing; Waters, Michael D

    2004-09-01

    To promote a systems biology approach to understanding the biological effects of environmental stressors, the Chemical Effects in Biological Systems (CEBS) knowledge base is being developed to house data from multiple complex data streams in a systems friendly manner that will accommodate extensive querying from users. Unified data representation via a single object model will greatly aid in integrating data storage and management, and facilitate reuse of software to analyze and display data resulting from diverse differential expression or differential profile technologies. Data streams include, but are not limited to, gene expression analysis (transcriptomics), protein expression and protein-protein interaction analysis (proteomics) and changes in low molecular weight metabolite levels (metabolomics). To enable the integration of microarray gene expression, proteomics and metabolomics data in the CEBS system, we designed an object model, Systems Biology Object Model (SysBio-OM). The model is comprehensive and leverages other open source efforts, namely the MicroArray Gene Expression Object Model (MAGE-OM) and the Proteomics Experiment Data Repository (PEDRo) object model. SysBio-OM is designed by extending MAGE-OM to represent protein expression data elements (including those from PEDRo), protein-protein interaction and metabolomics data. SysBio-OM promotes the standardization of data representation and data quality by facilitating the capture of the minimum annotation required for an experiment. Such standardization refines the accuracy of data mining and interpretation. The open source SysBio-OM model, which can be implemented on varied computing platforms is presented here. A universal modeling language depiction of the entire SysBio-OM is available at http://cebs.niehs.nih.gov/SysBioOM/. The Rational Rose object model package is distributed under an open source license that permits unrestricted academic and commercial use and is available at http

  10. A unique large-scale undergraduate research experience in molecular systems biology for non-mathematics majors.

    PubMed

    Kappler, Ulrike; Rowland, Susan L; Pedwell, Rhianna K

    2017-05-01

    Systems biology is frequently taught with an emphasis on mathematical modeling approaches. This focus effectively excludes most biology, biochemistry, and molecular biology students, who are not mathematics majors. The mathematical focus can also present a misleading picture of systems biology, which is a multi-disciplinary pursuit requiring collaboration between biochemists, bioinformaticians, and mathematicians. This article describes an authentic large-scale undergraduate research experience (ALURE) in systems biology that incorporates proteomics, bacterial genomics, and bioinformatics in the one exercise. This project is designed to engage students who have a basic grounding in protein chemistry and metabolism and no mathematical modeling skills. The pedagogy around the research experience is designed to help students attack complex datasets and use their emergent metabolic knowledge to make meaning from large amounts of raw data. On completing the ALURE, participants reported a significant increase in their confidence around analyzing large datasets, while the majority of the cohort reported good or great gains in a variety of skills including "analysing data for patterns" and "conducting database or internet searches." An environmental scan shows that this ALURE is the only undergraduate-level system-biology research project offered on a large-scale in Australia; this speaks to the perceived difficulty of implementing such an opportunity for students. We argue however, that based on the student feedback, allowing undergraduate students to complete a systems-biology project is both feasible and desirable, even if the students are not maths and computing majors. © 2016 by The International Union of Biochemistry and Molecular Biology, 45(3):235-248, 2017. © 2016 The International Union of Biochemistry and Molecular Biology.

  11. Method for separating biological cells. [suspended in aqueous polymer systems

    NASA Technical Reports Server (NTRS)

    Brooks, D. E. (Inventor)

    1980-01-01

    A method for separating biological cells by suspending a mixed cell population in a two-phase polymer system is described. The polymer system consists of droplet phases with different surface potentials for which the cell populations exhibit different affinities. The system is subjected to an electrostatic field of sufficient intensity to cause migration of the droplets with an attendant separation of cells.

  12. The new car assessment program: does it predict the relative safety of vehicles in actual crashes?

    PubMed

    Nirula, Ram; Mock, Charles N; Nathens, Avery B; Grossman, David C

    2004-10-01

    Federal motor vehicle safety standards are based on crash test dummy analyses that estimate the relative risk of traumatic brain injury (TBI) and severe thoracic injury (STI) by quantifying head (Head Injury Criterion [HIC]) and chest (Chest Gravity Score [CGS]) acceleration. The New Car Assessment Program (NCAP) combines these probabilities to yield the vehicle's five-star rating. The validity of the NCAP system as it relates to an actual motor vehicle crash (MVC) remains undetermined. We therefore sought to determine whether HIC and CGS accurately predict TBI and STI in actual crashes, and compared the NCAP five-star rating system to the rates of TBI and/or STI in actual MVCs. We analyzed frontal crashes with restrained drivers from the 1994 to 1998 National Automotive Sampling System. The relationship of HIC and CGS to the probabilities of TBI and STI derived from crash tests were respectively compared with the HIC-TBI and CGS-STI risk relationships observed in actual crashes while controlling for covariates. Receiver operating characteristic curves determined the sensitivity and specificity of HIC and CGS as predictors of TBI and STI, respectively. Estimates of the likelihood of TBI and/or STI (in actual MVCs) were compared with the expected probabilities of TBI and STI (determined by crash test analysis), as they relate to NCAP ratings. The crash tests overestimate TBI likelihood at HIC scores >800 and underestimate it at scores <500. STI likelihood is overestimated when CGS exceeds 40 g. Receiver operating characteristic curves demonstrated poor sensitivity and specificity of HIC and CGS in predicting injury. The actual MVC injury probability estimates did not vary between vehicles of different NCAP rating. HIC and CGS are poor predictors of TBI and STI in actual MVCs. The NCAP five-star rating system is unable to differentiate vehicles of varying crashworthiness in actual MVCs. More sensitive parameters need to be developed and incorporated into vehicle

  13. Finding off-targets, biological pathways, and target diseases for chymase inhibitors via structure-based systems biology approach.

    PubMed

    Arooj, Mahreen; Sakkiah, Sugunadevi; Cao, Guang Ping; Kim, Songmi; Arulalapperumal, Venkatesh; Lee, Keun Woo

    2015-07-01

    Off-target binding connotes the binding of a small molecule of therapeutic significance to a protein target in addition to the primary target for which it was proposed. Progressively such off-targeting is emerging to be regular practice to reveal side effects. Chymase is an enzyme of hydrolase class that catalyzes hydrolysis of peptide bonds. A link between heart failure and chymase is ascribed, and a chymase inhibitor is in clinical phase II for treatment of heart failure. However, the underlying mechanisms of the off-target effects of human chymase inhibitors are still unclear. Here, we develop a robust computational strategy that is applicable to any enzyme system and that allows the prediction of drug effects on biological processes. Putative off-targets for chymase inhibitors were identified through various structural and functional similarity analyses along with molecular docking studies. Finally, literature survey was performed to incorporate these off-targets into biological pathways and to establish links between pathways and particular adverse effects. Off-targets of chymase inhibitors are linked to various biological pathways such as classical and lectin pathways of complement system, intrinsic and extrinsic pathways of coagulation cascade, and fibrinolytic system. Tissue kallikreins, granzyme M, neutrophil elastase, and mesotrypsin are also identified as off-targets. These off-targets and their associated pathways are elucidated for the effects of inflammation, cancer, hemorrhage, thrombosis, and central nervous system diseases (Alzheimer's disease). Prospectively, our approach is helpful not only to better understand the mechanisms of chymase inhibitors but also for drug repurposing exercises to find novel uses for these inhibitors. © 2014 Wiley Periodicals, Inc.

  14. Cell phone radiation exposure on brain and associated biological systems.

    PubMed

    Kesari, Kavindra Kumar; Siddiqui, Mohd Haris; Meena, Ramovatar; Verma, H N; Kumar, Shivendra

    2013-03-01

    Wireless technologies are ubiquitous today and the mobile phones are one of the prodigious output of this technology. Although the familiarization and dependency of mobile phones is growing at an alarming pace, the biological effects due to the exposure of radiations have become a subject of intense debate. The present evidence on mobile phone radiation exposure is based on scientific research and public policy initiative to give an overview of what is known of biological effects that occur at radiofrequency (RF)/ electromagnetic fields (EMFs) exposure. The conflict in conclusions is mainly because of difficulty in controlling the affecting parameters. Biological effects are dependent not only on the distance and size of the object (with respect to the object) but also on the environmental parameters. Health endpoints reported to be associated with RF include childhood leukemia, brain tumors, genotoxic effects, neurological effects and neurodegenerative diseases, immune system deregulation, allergic and inflammatory responses, infertility and some cardiovascular effects. Most of the reports conclude a reasonable suspicion of mobile phone risk that exists based on clear evidence of bio-effects which with prolonged exposures may reasonably be presumed to result in health impacts. The present study summarizes the public issue based on mobile phone radiation exposure and their biological effects. This review concludes that the regular and long term use of microwave devices (mobile phone, microwave oven) at domestic level can have negative impact upon biological system especially on brain. It also suggests that increased reactive oxygen species (ROS) play an important role by enhancing the effect of microwave radiations which may cause neurodegenerative diseases.

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

    PubMed

    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.

  16. Evolving cell models for systems and synthetic biology.

    PubMed

    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.

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

    PubMed

    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.

  18. Improvements in and actual performance of the Plant Experiment Unit onboard Kibo, the Japanese experiment module on the international space station

    NASA Astrophysics Data System (ADS)

    Yano, Sachiko; Kasahara, Haruo; Masuda, Daisuke; Tanigaki, Fumiaki; Shimazu, Toru; Suzuki, Hiromi; Karahara, Ichirou; Soga, Kouichi; Hoson, Takayuki; Tayama, Ichiro; Tsuchiya, Yoshikazu; Kamisaka, Seiichiro

    2013-03-01

    In 2004, Japan Aerospace Exploration Agency developed the engineered model of the Plant Experiment Unit and the Cell Biology Experiment Facility. The Plant Experiment Unit was designed to be installed in the Cell Biology Experiment Facility and to support the seed-to-seed life cycle experiment of Arabidopsis plants in space in the project named Space Seed. Ground-based experiments to test the Plant Experiment Unit showed that the unit needed further improvement of a system to control the water content of a seedbed using an infrared moisture analyzer and that it was difficult to keep the relative humidity inside the Plant Experiment Unit between 70 and 80% because the Cell Biology Experiment Facility had neither a ventilation system nor a dehumidifying system. Therefore, excess moisture inside the Cell Biology Experiment Facility was removed with desiccant bags containing calcium chloride. Eight flight models of the Plant Experiment Unit in which dry Arabidopsis seeds were fixed to the seedbed with gum arabic were launched to the International Space Station in the space shuttle STS-128 (17A) on August 28, 2009. Plant Experiment Unit were installed in the Cell Biology Experiment Facility with desiccant boxes, and then the Space Seed experiment was started in the Japanese Experiment Module, named Kibo, which was part of the International Space Station, on September 10, 2009 by watering the seedbed and terminated 2 months later on November 11, 2009. On April 19, 2010, the Arabidopsis plants harvested in Kibo were retrieved and brought back to Earth by the space shuttle mission STS-131 (19A). The present paper describes the Space Seed experiment with particular reference to the development of the Plant Experiment Unit and its actual performance in Kibo onboard the International Space Station. Downlinked images from Kibo showed that the seeds had started germinating 3 days after the initial watering. The plants continued growing, producing rosette leaves, inflorescence

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

    PubMed

    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.

  20. Casual Games and Casual Learning About Human Biological Systems

    NASA Astrophysics Data System (ADS)

    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.

  1. First-principles modeling of biological systems and structure-based drug-design.

    PubMed

    Sgrignani, Jacopo; Magistrato, Alessandra

    2013-03-01

    Molecular modeling techniques play a relevant role in drug design providing detailed information at atomistic level on the structural, dynamical, mechanistic and electronic properties of biological systems involved in diseases' onset, integrating and supporting commonly used experimental approaches. These information are often not accessible to the experimental techniques taken singularly, but are of crucial importance for drug design. Due to the enormous increase of the computer power in the last decades, quantum mechanical (QM) or first-principles-based methods have become often used to address biological issues of pharmaceutical relevance, providing relevant information for drug design. Due to their complexity and their size, biological systems are often investigated by means of a mixed quantum-classical (QM/MM) approach, which treats at an accurate QM level a limited chemically relevant portion of the system and at the molecular mechanics (MM) level the remaining of the biomolecule and its environment. This method provides a good compromise between computational cost and accuracy, allowing to characterize the properties of the biological system and the (free) energy landscape of the process in study with the accuracy of a QM description. In this review, after a brief introduction of QM and QM/MM methods, we will discuss few representative examples, taken from our work, of the application of these methods in the study of metallo-enzymes of pharmaceutical interest, of metal-containing anticancer drugs targeting the DNA as well as of neurodegenerative diseases. The information obtained from these studies may provide the basis for a rationale structure-based drug design of new and more efficient inhibitors or drugs.

  2. Comparison of simulated and actual wind shear radar data products

    NASA Technical Reports Server (NTRS)

    Britt, Charles L.; Crittenden, Lucille H.

    1992-01-01

    Prior to the development of the NASA experimental wind shear radar system, extensive computer simulations were conducted to determine the performance of the radar in combined weather and ground clutter environments. The simulation of the radar used analytical microburst models to determine weather returns and synthetic aperture radar (SAR) maps to determine ground clutter returns. These simulations were used to guide the development of hazard detection algorithms and to predict their performance. The structure of the radar simulation is reviewed. Actual flight data results from the Orlando and Denver tests are compared with simulated results. Areas of agreement and disagreement of actual and simulated results are shown.

  3. Nanoscale hybrid systems based on carbon nanotubes for biological sensing and control

    PubMed Central

    Cho, Youngtak; Shin, Narae; Kim, Daesan; Park, Jae Yeol

    2017-01-01

    This paper provides a concise review on the recent development of nanoscale hybrid systems based on carbon nanotubes (CNTs) for biological sensing and control. CNT-based hybrid systems have been intensively studied for versatile applications of biological interfaces such as sensing, cell therapy and tissue regeneration. Recent advances in nanobiotechnology not only enable the fabrication of highly sensitive biosensors at nanoscale but also allow the applications in the controls of cell growth and differentiation. This review describes the fabrication methods of such CNT-based hybrid systems and their applications in biosensing and cell controls. PMID:28188158

  4. Web-based applications for building, managing and analysing kinetic models of biological systems.

    PubMed

    Lee, Dong-Yup; Saha, Rajib; Yusufi, Faraaz Noor Khan; Park, Wonjun; Karimi, Iftekhar A

    2009-01-01

    Mathematical modelling and computational analysis play an essential role in improving our capability to elucidate the functions and characteristics of complex biological systems such as metabolic, regulatory and cell signalling pathways. The modelling and concomitant simulation render it possible to predict the cellular behaviour of systems under various genetically and/or environmentally perturbed conditions. This motivates systems biologists/bioengineers/bioinformaticians to develop new tools and applications, allowing non-experts to easily conduct such modelling and analysis. However, among a multitude of systems biology tools developed to date, only a handful of projects have adopted a web-based approach to kinetic modelling. In this report, we evaluate the capabilities and characteristics of current web-based tools in systems biology and identify desirable features, limitations and bottlenecks for further improvements in terms of usability and functionality. A short discussion on software architecture issues involved in web-based applications and the approaches taken by existing tools is included for those interested in developing their own simulation applications.

  5. A methodology for global-sensitivity analysis of time-dependent outputs in systems biology modelling.

    PubMed

    Sumner, T; Shephard, E; Bogle, I D L

    2012-09-07

    One of the main challenges in the development of mathematical and computational models of biological systems is the precise estimation of parameter values. Understanding the effects of uncertainties in parameter values on model behaviour is crucial to the successful use of these models. Global sensitivity analysis (SA) can be used to quantify the variability in model predictions resulting from the uncertainty in multiple parameters and to shed light on the biological mechanisms driving system behaviour. We present a new methodology for global SA in systems biology which is computationally efficient and can be used to identify the key parameters and their interactions which drive the dynamic behaviour of a complex biological model. The approach combines functional principal component analysis with established global SA techniques. The methodology is applied to a model of the insulin signalling pathway, defects of which are a major cause of type 2 diabetes and a number of key features of the system are identified.

  6. Autonomous biological system-an unique method of conducting long duration space flight experiments for pharmaceutical and gravitational biology research

    NASA Astrophysics Data System (ADS)

    Anderson, G. A.; MacCallum, T. K.; Poynter, J. E.; Klaus, D., Dr.

    1998-01-01

    Paragon Space Development Corporation (SDC) has developed an Autonomous Biological System (ABS) that can be flown in space to provide for long term growth and breeding of aquatic plants, animals, microbes and algae. The system functions autonomously and in isolation from the spacecraft life support systems and with no mandatory crew time required for function or observation. The ABS can also be used for long term plant and animal life support and breeding on a free flyer space craft. The ABS units are a research tool for both pharmaceutical and basic space biological sciences. Development flights in May of 1996 and September, 1996 through January, 1997 were largely successful, showing both that the hardware and life systems are performing with beneficial results, though some surprises were still found. The two space flights, plus the current flight now on Mir, are expected to result in both a scientific and commercially usable system for breeding and propagation of animals and plants in space.

  7. Industrial methodology for process verification in research (IMPROVER): toward systems biology verification

    PubMed Central

    Meyer, Pablo; Hoeng, Julia; Rice, J. Jeremy; Norel, Raquel; Sprengel, Jörg; Stolle, Katrin; Bonk, Thomas; Corthesy, Stephanie; Royyuru, Ajay; Peitsch, Manuel C.; Stolovitzky, Gustavo

    2012-01-01

    Motivation: Analyses and algorithmic predictions based on high-throughput data are essential for the success of systems biology in academic and industrial settings. Organizations, such as companies and academic consortia, conduct large multi-year scientific studies that entail the collection and analysis of thousands of individual experiments, often over many physical sites and with internal and outsourced components. To extract maximum value, the interested parties need to verify the accuracy and reproducibility of data and methods before the initiation of such large multi-year studies. However, systematic and well-established verification procedures do not exist for automated collection and analysis workflows in systems biology which could lead to inaccurate conclusions. Results: We present here, a review of the current state of systems biology verification and a detailed methodology to address its shortcomings. This methodology named ‘Industrial Methodology for Process Verification in Research’ or IMPROVER, consists on evaluating a research program by dividing a workflow into smaller building blocks that are individually verified. The verification of each building block can be done internally by members of the research program or externally by ‘crowd-sourcing’ to an interested community. www.sbvimprover.com Implementation: This methodology could become the preferred choice to verify systems biology research workflows that are becoming increasingly complex and sophisticated in industrial and academic settings. Contact: gustavo@us.ibm.com PMID:22423044

  8. Anxiety Symptoms in African American Youth: The Role of Puberty and Biological Sex

    ERIC Educational Resources Information Center

    Carter, Rona

    2015-01-01

    This study examined the effects of pubertal status, pubertal timing (actual and perceived), and youth biological sex on symptom dimensions of anxiety (i.e., social, separation, harm avoidance, physical) in African Americans (n = 252; ages 8-12). For girls, results indicated that pubertal status and timing (actual) exerted similar effects for some…

  9. Biological systems for human life support: Review of the research in the USSR

    NASA Technical Reports Server (NTRS)

    Shepelev, Y. Y.

    1979-01-01

    Various models of biological human life support systems are surveyed. Biological structures, dimensions, and functional parameters of man-chlorella-microorganism models are described. Significant observations and the results obtained from these models are reported.

  10. 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.)

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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.

  12. On Mechanical Transitions in Biologically Motivated Soft Matter Systems

    NASA Astrophysics Data System (ADS)

    Fogle, Craig

    The notion of phase transitions as a characterization of a change in physical properties pervades modern physics. Such abrupt and fundamental changes in the behavior of physical systems are evident in condensed matter system and also occur in nuclear and subatomic settings. While this concept is less prevalent in the field of biology, recent advances have pointed to its relevance in a number of settings. Recent studies have modeled both the cell cycle and cancer as phase transition in physical systems. In this dissertation we construct simplified models for two biological systems. As described by those models, both systems exhibit phase transitions. The first model is inspired by the shape transition in the nuclei of neutrophils during differentiation. During differentiation the nucleus transitions from spherical to a shape often described as "beads on a string." As a simplified model of this system, we investigate the spherical-to-wrinkled transition in an elastic core bounded to a fluid shell system. We find that this model exhibits a first-order phase transition, and the shape that minimizes the energy of the system scales as (micror3/kappa). . The second system studied is motivated by the dynamics of globular proteins. These proteins may undergoes conformational changes with large displacements relative to their size. Transitions between conformational states are not possible if the dynamics are governed strictly by linear elasticity. We construct a model consisting of an predominantly elastic region near the energetic minimum of the system and a non-linear softening of the system at a critical displacement. We find that this simple model displays very rich dynamics include a sharp dynamical phase transition and driving-force-dependent symmetry breaking.

  13. Computing the structural influence matrix for biological systems.

    PubMed

    Giordano, Giulia; Cuba Samaniego, Christian; Franco, Elisa; Blanchini, Franco

    2016-06-01

    We consider the problem of identifying structural influences of external inputs on steady-state outputs in a biological network model. We speak of a structural influence if, upon a perturbation due to a constant input, the ensuing variation of the steady-state output value has the same sign as the input (positive influence), the opposite sign (negative influence), or is zero (perfect adaptation), for any feasible choice of the model parameters. All these signs and zeros can constitute a structural influence matrix, whose (i, j) entry indicates the sign of steady-state influence of the jth system variable on the ith variable (the output caused by an external persistent input applied to the jth variable). Each entry is structurally determinate if the sign does not depend on the choice of the parameters, but is indeterminate otherwise. In principle, determining the influence matrix requires exhaustive testing of the system steady-state behaviour in the widest range of parameter values. Here we show that, in a broad class of biological networks, the influence matrix can be evaluated with an algorithm that tests the system steady-state behaviour only at a finite number of points. This algorithm also allows us to assess the structural effect of any perturbation, such as variations of relevant parameters. Our method is applied to nontrivial models of biochemical reaction networks and population dynamics drawn from the literature, providing a parameter-free insight into the system dynamics.

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

    ERIC Educational Resources Information Center

    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…

  15. Enterobacter aerogenes Needle Stick Leads to Improved Biological Management System

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Johanson, Richard E.

    2004-08-01

    A laboratory worker who received a needle stick from a contaminated needle while working with a culture containing Enterobactor aerogenes developed a laboratory acquired infection. Although this organism has been shown to cause community and nosocomial infections, there have been no documented cases of a laboratory acquired infections. Lessons learned from the event led to corrective actions which included modification of lab procedures, development of a biological inventory tracking and risk identification system and the establishment of an effective biological safety program.

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

    PubMed Central

    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

  17. Dissecting innate immune responses with the tools of systems biology.

    PubMed

    Smith, Kelly D; Bolouri, Hamid

    2005-02-01

    Systems biology strives to derive accurate predictive descriptions of complex systems such as innate immunity. The innate immune system is essential for host defense, yet the resulting inflammatory response must be tightly regulated. Current understanding indicates that this system is controlled by complex regulatory networks, which maintain homoeostasis while accurately distinguishing pathogenic infections from harmless exposures. Recent studies have used high throughput technologies and computational techniques that presage predictive models and will be the foundation of a systems level understanding of innate immunity.

  18. Network news: prime time for systems biology of the plant circadian clock.

    PubMed

    McClung, C Robertson; Gutiérrez, Rodrigo A

    2010-12-01

    Whole-transcriptome analyses have established that the plant circadian clock regulates virtually every plant biological process and most prominently hormonal and stress response pathways. Systems biology efforts have successfully modeled the plant central clock machinery and an iterative process of model refinement and experimental validation has contributed significantly to the current view of the central clock machinery. The challenge now is to connect this central clock to the output pathways for understanding how the plant circadian clock contributes to plant growth and fitness in a changing environment. Undoubtedly, systems approaches will be needed to integrate and model the vastly increased volume of experimental data in order to extract meaningful biological information. Thus, we have entered an era of systems modeling, experimental testing, and refinement. This approach, coupled with advances from the genetic and biochemical analyses of clock function, is accelerating our progress towards a comprehensive understanding of the plant circadian clock network. Copyright © 2010 Elsevier Ltd. All rights reserved.

  19. Synthetic fluorescent probes for studying copper in biological systems

    PubMed Central

    Cotruvo, Joseph A.; Aron, Allegra T.; Ramos-Torres, Karla M.; Chang, Christopher J.

    2015-01-01

    The potent redox activity of copper is required for sustaining life. Mismanagement of its cellular pools, however, can result in oxidative stress and damage connected to aging, neurodegenerative diseases, and metabolic disorders. Therefore, copper homeostasis is tightly regulated by cells and tissues. Whereas copper and other transition metal ions are commonly thought of as static cofactors buried within protein active sites, emerging data points to the presence of additional loosely bound, labile pools that can participate in dynamic signalling pathways. Against this backdrop, we review advances in sensing labile copper pools and understanding their functions using synthetic fluorescent indicators. Following brief introductions to cellular copper homeostasis and considerations in sensor design, we survey available fluorescent copper probes and evaluate their properties in the context of their utility as effective biological screening tools. We emphasize the need for combined chemical and biological evaluation of these reagents, as well as the value of complementing probe data with other techniques for characterizing the different pools of metal ions in biological systems. This holistic approach will maximize the exciting opportunities for these and related chemical technologies in the study and discovery of novel biology of metals. PMID:25692243

  20. Synthetic fluorescent probes for studying copper in biological systems.

    PubMed

    Cotruvo, Joseph A; Aron, Allegra T; Ramos-Torres, Karla M; Chang, Christopher J

    2015-07-07

    The potent redox activity of copper is required for sustaining life. Mismanagement of its cellular pools, however, can result in oxidative stress and damage connected to aging, neurodegenerative diseases, and metabolic disorders. Therefore, copper homeostasis is tightly regulated by cells and tissues. Whereas copper and other transition metal ions are commonly thought of as static cofactors buried within protein active sites, emerging data points to the presence of additional loosely bound, labile pools that can participate in dynamic signalling pathways. Against this backdrop, we review advances in sensing labile copper pools and understanding their functions using synthetic fluorescent indicators. Following brief introductions to cellular copper homeostasis and considerations in sensor design, we survey available fluorescent copper probes and evaluate their properties in the context of their utility as effective biological screening tools. We emphasize the need for combined chemical and biological evaluation of these reagents, as well as the value of complementing probe data with other techniques for characterizing the different pools of metal ions in biological systems. This holistic approach will maximize the exciting opportunities for these and related chemical technologies in the study and discovery of novel biology of metals.