WorldWideScience

Sample records for biological timing system

  1. Circadian systems biology: When time matters

    Directory of Open Access Journals (Sweden)

    Luise Fuhr

    2015-01-01

    In this manuscript we review the combination of experimental methodologies, bioinformatics and theoretical models that have been essential to explore this remarkable timing-system. Such an integrative and interdisciplinary approach may provide new strategies with regard to chronotherapeutic treatment and new insights concerning the restoration of the circadian timing in clock-associated diseases.

  2. Elucidation of time-dependent systems biology cell response patterns with time course network enrichment

    DEFF Research Database (Denmark)

    Wiwie, Christian; Rauch, Alexander; Haakonsson, Anders

    2018-01-01

    , no methods exist to integrate time series data with networks, thus preventing the identification of time-dependent systems biology responses. We close this gap with Time Course Network Enrichment (TiCoNE). It combines a new kind of human-augmented clustering with a novel approach to network enrichment...

  3. Time-ordered product expansions for computational stochastic system biology

    International Nuclear Information System (INIS)

    Mjolsness, Eric

    2013-01-01

    The time-ordered product framework of quantum field theory can also be used to understand salient phenomena in stochastic biochemical networks. It is used here to derive Gillespie’s stochastic simulation algorithm (SSA) for chemical reaction networks; consequently, the SSA can be interpreted in terms of Feynman diagrams. It is also used here to derive other, more general simulation and parameter-learning algorithms including simulation algorithms for networks of stochastic reaction-like processes operating on parameterized objects, and also hybrid stochastic reaction/differential equation models in which systems of ordinary differential equations evolve the parameters of objects that can also undergo stochastic reactions. Thus, the time-ordered product expansion can be used systematically to derive simulation and parameter-fitting algorithms for stochastic systems. (paper)

  4. Systems Biology

    Indian Academy of Sciences (India)

    IAS Admin

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

  5. Computational Systems Chemical Biology

    OpenAIRE

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

    2011-01-01

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

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

    KAUST Repository

    Gomez-Cabrero, David; Tegner, Jesper

    2017-01-01

    The rise and growth of Systems Biology following the sequencing of the human genome has been astounding. Early on, an iterative wet-dry methodology was formulated which turned out as a successful approach in deciphering biological complexity

  7. Imaging systems and algorithms to analyze biological samples in real-time using mobile phone microscopy.

    Science.gov (United States)

    Shanmugam, Akshaya; Usmani, Mohammad; Mayberry, Addison; Perkins, David L; Holcomb, Daniel E

    2018-01-01

    Miniaturized imaging devices have pushed the boundaries of point-of-care imaging, but existing mobile-phone-based imaging systems do not exploit the full potential of smart phones. This work demonstrates the use of simple imaging configurations to deliver superior image quality and the ability to handle a wide range of biological samples. Results presented in this work are from analysis of fluorescent beads under fluorescence imaging, as well as helminth eggs and freshwater mussel larvae under white light imaging. To demonstrate versatility of the systems, real time analysis and post-processing results of the sample count and sample size are presented in both still images and videos of flowing samples.

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

    KAUST Repository

    Gomez-Cabrero, David

    2017-05-09

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

  9. Center of cancer systems biology second annual workshop--tumor metronomics: timing and dose level dynamics.

    Science.gov (United States)

    Hahnfeldt, Philip; Hlatky, Lynn; Klement, Giannoula Lakka

    2013-05-15

    Metronomic chemotherapy, the delivery of doses in a low, regular manner so as to avoid toxic side effects, was introduced over 12 years ago in the face of substantial clinical and preclinical evidence supporting its tumor-suppressive capability. It constituted a marked departure from the classic maximum-tolerated dose (MTD) strategy, which, given its goal of rapid eradication, uses dosing sufficiently intense to require rest periods between cycles to limit toxicity. Even so, upfront tumor eradication is frequently not achieved with MTD, whereupon a de facto goal of longer-term tumor control is often pursued. As metronomic dosing has shown tumor control capability, even for cancers that have become resistant to the same drug delivered under MTD, the question arises whether it may be a preferable alternative dosing approach from the outset. To date, however, our knowledge of the coupled dynamics underlying metronomic dosing is neither sufficiently well developed nor widely enough disseminated to establish its actual potential. Meeting organizers thus felt the time was right, armed with new quantitative approaches, to call a workshop on "Tumor Metronomics: Timing and Dose Level Dynamics" to explore prospects for gaining a deeper, systems-level appreciation of the metronomics concept. The workshop proved to be a forum in which experts from the clinical, biologic, mathematical, and computational realms could work together to clarify the principles and underpinnings of metronomics. Among other things, the need for significant shifts in thinking regarding endpoints to be used as clinical standards of therapeutic progress was recognized. ©2013 AACR.

  10. Arena3D: visualizing time-driven phenotypic differences in biological systems

    Directory of Open Access Journals (Sweden)

    Secrier Maria

    2012-03-01

    Full Text Available Abstract Background Elucidating the genotype-phenotype connection is one of the big challenges of modern molecular biology. To fully understand this connection, it is necessary to consider the underlying networks and the time factor. In this context of data deluge and heterogeneous information, visualization plays an essential role in interpreting complex and dynamic topologies. Thus, software that is able to bring the network, phenotypic and temporal information together is needed. Arena3D has been previously introduced as a tool that facilitates link discovery between processes. It uses a layered display to separate different levels of information while emphasizing the connections between them. We present novel developments of the tool for the visualization and analysis of dynamic genotype-phenotype landscapes. Results Version 2.0 introduces novel features that allow handling time course data in a phenotypic context. Gene expression levels or other measures can be loaded and visualized at different time points and phenotypic comparison is facilitated through clustering and correlation display or highlighting of impacting changes through time. Similarity scoring allows the identification of global patterns in dynamic heterogeneous data. In this paper we demonstrate the utility of the tool on two distinct biological problems of different scales. First, we analyze a medium scale dataset that looks at perturbation effects of the pluripotency regulator Nanog in murine embryonic stem cells. Dynamic cluster analysis suggests alternative indirect links between Nanog and other proteins in the core stem cell network. Moreover, recurrent correlations from the epigenetic to the translational level are identified. Second, we investigate a large scale dataset consisting of genome-wide knockdown screens for human genes essential in the mitotic process. Here, a potential new role for the gene lsm14a in cytokinesis is suggested. We also show how phenotypic

  11. Bioremediation 3.0: Engineering pollutant-removing bacteria in the times of systemic biology

    DEFF Research Database (Denmark)

    Dvořák, Pavel; Nikel, Pablo Ivan; Damborskýc, Jiří

    2017-01-01

    pollutants with no external intervention, the onset of genetic engineering in the 1980s allowed the possibility of rational design of bacteria to catabolize specific compounds, which could eventually be released into the environment as bioremediation agents. The complexity of this endeavour and the lack...... of fundamental knowledge nonetheless led to the virtual abandonment of such a recombinant DNA-based bioremediation only a decade later. In a twist of events, the last few years have witnessed the emergence of new systemic fields (including systems and synthetic biology, and metabolic engineering) that allow....... In this article, we analyze how contemporary systemic biology is helping to take the design of bioremediation agents back to the core of environmental biotechnology. We inspect a number of recent strategies for catabolic pathway construction and optimization and we bring them together by proposing an engineering...

  12. Systems Biology and Ratio-Based, Real-Time Disease Surveillance.

    Science.gov (United States)

    Fair, J M; Rivas, A L

    2015-08-01

    Most infectious disease surveillance methods are not well fit for early detection. To address such limitation, here we evaluated a ratio- and Systems Biology-based method that does not require prior knowledge on the identity of an infective agent. Using a reference group of birds experimentally infected with West Nile virus (WNV) and a problem group of unknown health status (except that they were WNV-negative and displayed inflammation), both groups were followed over 22 days and tested with a system that analyses blood leucocyte ratios. To test the ability of the method to discriminate small data sets, both the reference group (n = 5) and the problem group (n = 4) were small. The questions of interest were as follows: (i) whether individuals presenting inflammation (disease-positive or D+) can be distinguished from non-inflamed (disease-negative or D-) birds, (ii) whether two or more D+ stages can be detected and (iii) whether sample size influences detection. Within the problem group, the ratio-based method distinguished the following: (i) three (one D- and two D+) data classes; (ii) two (early and late) inflammatory stages; (iii) fast versus regular or slow responders; and (iv) individuals that recovered from those that remained inflamed. Because ratios differed in larger magnitudes (up to 48 times larger) than percentages, it is suggested that data patterns are likely to be recognized when disease surveillance methods are designed to measure inflammation and utilize ratios. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

  13. Time-evolution of the entropy of fluctuations in some biological systems as investigated by NMR

    International Nuclear Information System (INIS)

    Lenk, R.

    1979-01-01

    A simple expression for the entropy of fluctuations has been developed, using the tunnelling-effect model. This gives the possibility to estimate the changes and evolution of entropy in non-crystalline and biological samples by NMR investigations. On the other hand, the oscillatory character of the time-evolution of some properties, experimentally found in the investigated samples of plants, is interpreted in terms of the generalized master equation with an exponential memory function. (Auth.)

  14. Bioremediation 3.0: Engineering pollutant-removing bacteria in the times of systemic biology.

    Science.gov (United States)

    Dvořák, Pavel; Nikel, Pablo I; Damborský, Jiří; de Lorenzo, Víctor

    2017-11-15

    Elimination or mitigation of the toxic effects of chemical waste released to the environment by industrial and urban activities relies largely on the catalytic activities of microorganisms-specifically bacteria. Given their capacity to evolve rapidly, they have the biochemical power to tackle a large number of molecules mobilized from their geological repositories through human action (e.g., hydrocarbons, heavy metals) or generated through chemical synthesis (e.g., xenobiotic compounds). Whereas naturally occurring microbes already have considerable ability to remove many environmental pollutants with no external intervention, the onset of genetic engineering in the 1980s allowed the possibility of rational design of bacteria to catabolize specific compounds, which could eventually be released into the environment as bioremediation agents. The complexity of this endeavour and the lack of fundamental knowledge nonetheless led to the virtual abandonment of such a recombinant DNA-based bioremediation only a decade later. In a twist of events, the last few years have witnessed the emergence of new systemic fields (including systems and synthetic biology, and metabolic engineering) that allow revisiting the same environmental pollution challenges through fresh and far more powerful approaches. The focus on contaminated sites and chemicals has been broadened by the phenomenal problems of anthropogenic emissions of greenhouse gases and the accumulation of plastic waste on a global scale. In this article, we analyze how contemporary systemic biology is helping to take the design of bioremediation agents back to the core of environmental biotechnology. We inspect a number of recent strategies for catabolic pathway construction and optimization and we bring them together by proposing an engineering workflow. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Biological conversion system

    Science.gov (United States)

    Scott, C.D.

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

  16. 31P spin-lattice relaxation time measurements in biological systems

    International Nuclear Information System (INIS)

    Suzuki, Eiji; Maeda, Munehiro; Kuki, Satoru; Tsukamoto, Kenji; Kawakami, Tsuyoshi; Seo, Yoshiteru; Murakami, Masataka; Watari, Hiroshi

    1989-01-01

    Spin-lattice relaxation time (T 1 ) of phosphorus compounds in the perfused heart, liver, kidney and erythrocytes of rats were measured by the DESPOT (Driven-equilibrium single-pulse observation of T 1 ) method at 8.45 T. This method is a rapid and accurate technique for the measurement of T 1 values. T 1 values of phosphomonoesters (PME), 2, 3-diphosphoglycerate (DPG), inorganic phosphate (Pi), phosphodiesters (PDE), phosphocreatine (PCr) and three phosphates of ATP were ranged from 0.15±0.02 sec (β-ATP in the liver) to 8.5±1.6 sec (PDE in the kidney). T 1 value of β-ATP in the liver was 1/4-1/5 of those in the mandibular gland, heart, erythrocytes and kidney. T 1 values obtained from biological materials are useful for selecting the optimal pulse repetition times and pulse angles to maximize the signal-to-noise ratio of 13 P spectra, and for correcting distortions of signal intensities in the spectra. (author)

  17. Integrative radiation systems biology

    International Nuclear Information System (INIS)

    Unger, Kristian

    2014-01-01

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

  18. Mapping biological systems to network systems

    CERN Document Server

    Rathore, Heena

    2016-01-01

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

  19. Telemetry System of Biological Parameters

    Directory of Open Access Journals (Sweden)

    Jan Spisak

    2005-01-01

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

  20. A real-time measurement system for parameters of live biology metabolism process with fiber optics

    Science.gov (United States)

    Tao, Wei; Zhao, Hui; Liu, Zemin; Cheng, Jinke; Cai, Rong

    2010-08-01

    Energy metabolism is one of the basic life activities of cellular in which lactate, O2 and CO2 will be released into the extracellular environment. By monitoring the quantity of these parameters, the mitochondrial performance will be got. A continuous measurement system for the concentration of O2, CO2 and PH value is introduced in this paper. The system is made up of several small-sized fiber optics biosensors corresponding to the container. The setup of the system and the principle of measurement of several parameters are explained. The setup of the fiber PH sensor based on principle of light absorption is also introduced in detail and some experimental results are given. From the results we can see that the system can measure the PH value precisely suitable for cell cultivation. The linear and repeatable accuracies are 3.6% and 6.7% respectively, which can fulfill the measurement task.

  1. Quantum Effects in Biological Systems

    CERN Document Server

    2016-01-01

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

  2. Systems Biology and Health Systems Complexity in;

    NARCIS (Netherlands)

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

    2016-01-01

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

  3. Nutritional Systems Biology

    DEFF Research Database (Denmark)

    Jensen, Kasper

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

  4. Time in physics and biology

    Directory of Open Access Journals (Sweden)

    BRUNO GÜNTHER

    2004-01-01

    Full Text Available In contrast with classical physics, particularly with Sir Isaac Newton, where time is a continuous function, generally valid, eternally and evenly flowing as an absolute time dimension, in the biological sciences, time is in essence of cyclical nature (physiological periodicities, where future passes to past through an infinitely thin boundary, the present. In addition, the duration of the present (DP leads to the so-called 'granulation of time' in living beings, so that by the fusion of two successive pictures of the world, which are not entirely similar, they attain the perception of 'movement,' both in the real world as well as in the sham-movement in the mass media (TV.

  5. Effect of sludge retention time on continuous-flow system with enhanced biological phosphorus removal granules at different COD loading.

    Science.gov (United States)

    Li, Dong; Lv, Yufeng; Zeng, Huiping; Zhang, Jie

    2016-11-01

    The effect of sludge retention time (SRT) on the continuous-flow system with enhanced biological phosphorus removal (EBPR) granules at different COD loading was investigated during the operation of more than 220days. And the results showed that when the system operated at long SRT (30days) and low COD loading (200mg·L(-1)), it could maintain excellent performance. However, long SRT and high COD loading (300mg·L(-1)) deteriorated the settling ability of granules and the performance of system and resulted in the overgrowth of filamentous bacteria. Meanwhile, the transformation of poly-β-hydroxyalkanoates (PHAs) and glycogen in metabolism process was inhibited. Moreover, the results of pyrosequencing indicated that filamentous bacteria had a competitive advantage over polyphosphate-accumulating organisms (PAOs) at high COD loading and long SRT. The PAOs specious of Candidatus_Accumlibater and system performance increased obviously when the SRT was reduced to 20days at high COD loading. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Systems biology at work

    NARCIS (Netherlands)

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

    2010-01-01

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

  7. Plant Systems Biology (editorial)

    Science.gov (United States)

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

  8. Time lags in biological models

    CERN Document Server

    MacDonald, Norman

    1978-01-01

    In many biological models it is necessary to allow the rates of change of the variables to depend on the past history, rather than only the current values, of the variables. The models may require discrete lags, with the use of delay-differential equations, or distributed lags, with the use of integro-differential equations. In these lecture notes I discuss the reasons for including lags, especially distributed lags, in biological models. These reasons may be inherent in the system studied, or may be the result of simplifying assumptions made in the model used. I examine some of the techniques available for studying the solution of the equations. A large proportion of the material presented relates to a special method that can be applied to a particular class of distributed lags. This method uses an extended set of ordinary differential equations. I examine the local stability of equilibrium points, and the existence and frequency of periodic solutions. I discuss the qualitative effects of lags, and how these...

  9. Biophysics and systems biology.

    Science.gov (United States)

    Noble, Denis

    2010-03-13

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

  10. 7th Annual Systems Biology Symposium: Systems Biology and Engineering

    Energy Technology Data Exchange (ETDEWEB)

    Galitski, Timothy P.

    2008-04-01

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

  11. Inverse problems in systems biology

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  12. Biological mechanisms, one molecule at a time

    Science.gov (United States)

    Tinoco, Ignacio; Gonzalez, Ruben L.

    2011-01-01

    The last 15 years have witnessed the development of tools that allow the observation and manipulation of single molecules. The rapidly expanding application of these technologies for investigating biological systems of ever-increasing complexity is revolutionizing our ability to probe the mechanisms of biological reactions. Here, we compare the mechanistic information available from single-molecule experiments with the information typically obtained from ensemble studies and show how these two experimental approaches interface with each other. We next present a basic overview of the toolkit for observing and manipulating biology one molecule at a time. We close by presenting a case study demonstrating the impact that single-molecule approaches have had on our understanding of one of life's most fundamental biochemical reactions: the translation of a messenger RNA into its encoded protein by the ribosome. PMID:21685361

  13. Logical analysis of biological systems

    DEFF Research Database (Denmark)

    Mardare, Radu Iulian

    2005-01-01

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

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

    Science.gov (United States)

    Wolkenhauer, O

    2001-09-01

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

  15. Mapping of courses on vector biology and vector-borne diseases systems: time for a worldwide effort

    Science.gov (United States)

    Casas, Jérôme; Lazzari, Claudio; Insausti, Teresita; Launois, Pascal; Fouque, Florence

    2016-01-01

    Major emergency efforts are being mounted for each vector-borne disease epidemiological crisis anew, while knowledge about the biology of arthropods vectors is dwindling slowly but continuously, as is the number of field entomologists. The discrepancy between the rates of production of knowledge and its use and need for solving crises is widening, in particular due to the highly differing time spans of the two concurrent processes. A worldwide web based search using multiple key words and search engines of onsite and online courses in English, Spanish, Portuguese, French, Italian and German concerned with the biology of vectors identified over 140 courses. They are geographically and thematically scattered, the vast majority of them are on-site, with very few courses using the latest massive open online course (MOOC) powerfulness. Over two third of them is given in English and Western Africa is particularity poorly represented. The taxonomic groups covered are highly unbalanced towards mosquitoes. A worldwide unique portal to guide students of all grades and levels of expertise, in particular those in remote locations, is badly needed. This is the objective a new activity supported by the Special Programme for Research and Training in Tropical Diseases (TDR). PMID:27759770

  16. Systems Biology of the Fluxome

    Directory of Open Access Journals (Sweden)

    Miguel A. Aon

    2015-07-01

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

  17. Beam-time for biology

    CERN Multimedia

    Jordan Juras

    2010-01-01

    There's no question that playing with mercury or handling radioactive cadmium with your bare hands is a risky business. But understanding how these and other toxic metals interact with biomolecules within the body is a challenging feat; one for which the ISOLDE IS488 collaboration hopes to provide valuable insight.   General view of the ISOLDE experimental area. Unlike most of the facilities at CERN's accelerator complex, ISOLDE is not targeted mainly at particle physics. Rather, it produces radioactive nuclei during proton bombardment to study, among other things, physical and biological chemistry. At ISOLDE, the 1.4 GeV proton beam of the PS Booster (an early stage in CERN's accelerator complex) produces nuclear reactions in a thick target, creating a large variety of radioactive nuclei, which are mass-separated for use in experiments. In the case of the IS488 collaboration, the ion beam is directed into ice. "We implant radioactive metal ions into ice", explains Monika Stac...

  18. Mammalian Synthetic Biology: Engineering Biological Systems.

    Science.gov (United States)

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

    2017-06-21

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

  19. Electromagnetic fields in biological systems

    National Research Council Canada - National Science Library

    Lin, James C

    2012-01-01

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

  20. Excited states in biological systems

    International Nuclear Information System (INIS)

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

    1979-01-01

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

  1. Static Analysis for Systems Biology

    DEFF Research Database (Denmark)

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

    2004-01-01

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

  2. Systems biology and medicine

    Indian Academy of Sciences (India)

    work could potentially provide us with ways to identify drug ... appropriately balance cause, effect, and context of a given clinical ... would not provide answers/solutions to multitude of tasks that were ... a major challenge of contemporary biology is to embark on an ... nificantly govern the life and responsiveness of cells.

  3. The order axiom and the biological space time

    International Nuclear Information System (INIS)

    Vu Huu Nhu

    2014-01-01

    This work focuses on the field of Biological Space - Time. In fact the conception of Biological Space - Time is connected with order character of sets. Because the illustration of order axioms is very important for searching order systems. In this work, the new form of order axioms has been illustrated in the form of (a,b) ≠ (b.a). It is a common form of Descartes product. Based on this we suggest the following formation of order lemma (a.b) ≠(b.a)↔ a Φ b. In this case Φ is an order relation. From the new form of order axiom, we determine the order system as follows: If S = (a,b) the set of two elements and the order axiom (a.b) ≠ (b.a) is satisfied. So that, in this case, S is called an order system. The life system are the most important order systems. We could illustrate the biological system as: S = (A, T, G, C). In this set, A, T, G, C are the elements of the genetic code and the order axiom is satisfied. As we know, for example, in genetic code: (AUG) ≠ (UGA) ≠ (UAG). The order biological system induces an order relation and it is the origin of the conception of Biological Space Time. The students of Physics and Biology could use this book as basic course for studies of Biological Space Time. (author)

  4. Heuristic Strategies in Systems Biology

    Directory of Open Access Journals (Sweden)

    Fridolin Gross

    2016-06-01

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

  5. Systems biology of fungal infection

    Directory of Open Access Journals (Sweden)

    Fabian eHorn

    2012-04-01

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

  6. Systems biology and biomarker discovery

    Energy Technology Data Exchange (ETDEWEB)

    Rodland, Karin D.

    2010-12-01

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

  7. Time-resolved and steady-state studies of biologically and chemically relevant systems using laser, absorption, and fluorescence spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Barnes, Charles Ashley [Iowa State Univ., Ames, IA (United States)

    2014-12-20

    In Chapter 2 several experimental and data analysis methods used in this thesis are described. In Chapter 3 steady-state fluorescence spectroscopy was used to determine the concentration of the efflux pump inhibitors (EPIs), pheophorbide a and pyropheophorbide a, in the feces of animals and it was found that their levels far exceed those reported to be inhibitory to efflux pumps. In Chapter 4 the solvation dynamics of 6-Propionyl-2-(N,Ndimethyl) aminonaphthalene (PRODAN) was studied in reverse micelles. The two fluorescent states of PRODAN solvate on different time scales and as such care must be exercised in solvation dynamic studies involving it and its analogs. In Chapter 5 we studied the experimental and theoretical solvation dynamics of coumarin 153 (C153) in wild-type (WT) and modified myoglobins. Based on the nuclear magnetic resonance (NMR) spectroscopy and time-resolved fluorescence studies, we have concluded that it is important to thoroughly characterize the structure of a protein and probe system before comparing the theoretical and experimental results. In Chapter 6 the photophysical and spectral properties of a derivative of the medically relevant compound curcumin called cyclocurcumin was studied. Based on NMR, fluorescence, and absorption studies, the ground- and excited-states of cyclocurcumin are complicated by the existence of multiple structural isomers. In Chapter 7 the hydrolysis of cellulose by a pure form of cellulase in an ionic liquid, HEMA, and its aqueous mixtures at various temperatures were studied with the goal of increasing the cellulose to glucose conversion for biofuel production. It was found that HEMA imparts an additional stability to cellulase and can allow for faster conversion of cellulose to glucose using a pre-treatment step in comparison to only buffer.

  8. Compartmental study of biological systems

    International Nuclear Information System (INIS)

    Moretti, J.L.

    1975-01-01

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

  9. Ten questions about systems biology

    DEFF Research Database (Denmark)

    Joyner, Michael J; Pedersen, Bente K

    2011-01-01

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

  10. Ten questions about systems biology

    DEFF Research Database (Denmark)

    Joyner, Michael J; Pedersen, Bente K

    2011-01-01

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

  11. Real-Time Tracking the Synthesis and Degradation of Albumin in Complex Biological Systems with a near-Infrared Fluorescent Probe.

    Science.gov (United States)

    Jin, Qiang; Feng, Lei; Zhang, Shui-Jun; Wang, Dan-Dan; Wang, Fang-Jun; Zhang, Yi; Cui, Jing-Nan; Guo, Wen-Zhi; Ge, Guang-Bo; Yang, Ling

    2017-09-19

    In this study, a novel fluorescent detection system for biological sensing of human albumin (HA) was developed on the basis of the pseudoesterase activity and substrate preference of HA. The designed near-infrared (NIR) fluorescent probe (DDAP) could be effectively hydrolyzed by HA, accompanied by significant changes in both color and fluorescence spectrum. The sensing mechanism was fully investigated by fluorescence spectroscopy, NMR, and mass spectra. DDAP exhibited excellent selectivity and sensitivity toward HA over a variety of human plasma proteins, hydrolases, and abundant biomolecules found in human body. The probe has been successfully applied to measure native HA in diluted plasma samples and the secreted HA in the hepatocyte culture supernatant. DDAP has also been used for fluorescence imaging of HA reabsorption in living renal cells, and the results show that the probe exhibits good cell permeability, low cytotoxicity and high imaging resolution. Furthermore, DDAP has been successfully used for real-time tracking the uptaking and degradation of albumin in ex vivo mouse kidney models for the first time. All these results clearly demonstrated that DDAP-based assay held great promise for real-time sensing and tracking HA in complex biological systems, which would be very useful for basic researches and clinical diagnosis of HA-associated diseases.

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

    Science.gov (United States)

    Smolke, Christina D; Silver, Pamela A

    2011-03-18

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

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

    International Nuclear Information System (INIS)

    Min Rui

    2010-01-01

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

  14. From systems biology to systems biomedicine.

    Science.gov (United States)

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

    2012-08-01

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

  15. Improving the Timed Automata Approach to Biological Pathway Dynamics

    NARCIS (Netherlands)

    Langerak, R.; Pol, Jaco van de; Post, Janine N.; Schivo, Stefano; Aceto, Luca; Bacci, Giorgio; Bacci, Giovanni; Ingólfsdóttir, Anna; Legay, Axel; Mardare, Radu

    2017-01-01

    Biological systems such as regulatory or gene networks can be seen as a particular type of distributed systems, and for this reason they can be modeled within the Timed Automata paradigm, which was developed in the computer science context. However, tools designed to model distributed systems often

  16. Biological repair with time-dependent irradiation

    International Nuclear Information System (INIS)

    Broyles, A.A.; Shapiro, C.S.

    1985-01-01

    Recent experiments have provided new data that explore the effectiveness of biological repair in assessing damage due to exposures from ionizing radiation. These data are mainly from experiments conducted at constant dose rates, to study the effectiveness per unit dose of different dose rates. Here, we develop new formulae to estimate the effectiveness of an arbitrary time-dependent dose rate exposure

  17. Magnetic Actuation of Biological Systems

    Science.gov (United States)

    Lauback, Stephanie D.

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

  18. Nanoscale technology in biological systems

    CERN Document Server

    Greco, Ralph S; Smith, R Lane

    2004-01-01

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

  19. Using simulation to interpret a discrete time survival model in a complex biological system: fertility and lameness in dairy cows.

    Directory of Open Access Journals (Sweden)

    Christopher D Hudson

    Full Text Available The ever-growing volume of data routinely collected and stored in everyday life presents researchers with a number of opportunities to gain insight and make predictions. This study aimed to demonstrate the usefulness in a specific clinical context of a simulation-based technique called probabilistic sensitivity analysis (PSA in interpreting the results of a discrete time survival model based on a large dataset of routinely collected dairy herd management data. Data from 12,515 dairy cows (from 39 herds were used to construct a multilevel discrete time survival model in which the outcome was the probability of a cow becoming pregnant during a given two day period of risk, and presence or absence of a recorded lameness event during various time frames relative to the risk period amongst the potential explanatory variables. A separate simulation model was then constructed to evaluate the wider clinical implications of the model results (i.e. the potential for a herd's incidence rate of lameness to influence its overall reproductive performance using PSA. Although the discrete time survival analysis revealed some relatively large associations between lameness events and risk of pregnancy (for example, occurrence of a lameness case within 14 days of a risk period was associated with a 25% reduction in the risk of the cow becoming pregnant during that risk period, PSA revealed that, when viewed in the context of a realistic clinical situation, a herd's lameness incidence rate is highly unlikely to influence its overall reproductive performance to a meaningful extent in the vast majority of situations. Construction of a simulation model within a PSA framework proved to be a very useful additional step to aid contextualisation of the results from a discrete time survival model, especially where the research is designed to guide on-farm management decisions at population (i.e. herd rather than individual level.

  20. Workshop Introduction: Systems Biology and Biological Models

    Science.gov (United States)

    As we consider the future of toxicity testing, the importance of applying biological models to this problem is clear. Modeling efforts exist along a continuum with respect to the level of organization (e.g. cell, tissue, organism) linked to the resolution of the model. Generally,...

  1. Systems biology approach to bioremediation

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-06-01

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

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

    Science.gov (United States)

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

    2017-09-01

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

  3. Tunable promoters in systems biology

    DEFF Research Database (Denmark)

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

    2005-01-01

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

  4. Systems Biology of Industrial Microorganisms

    Science.gov (United States)

    Papini, Marta; Salazar, Margarita; Nielsen, Jens

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

  5. Systems Biology-an interdisciplinary approach.

    Science.gov (United States)

    Friboulet, Alain; Thomas, Daniel

    2005-06-15

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

  6. Mathematical methods in systems biology.

    Science.gov (United States)

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

    2016-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Bor-Sen Chen

    2013-10-01

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

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

    Science.gov (United States)

    Chen, Bor-Sen; Wu, Chia-Chou

    2013-01-01

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

  9. Tunable promoters in synthetic and systems biology

    DEFF Research Database (Denmark)

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

    2012-01-01

    in synthetic biology. A number of tools exist to manipulate the steps in between gene sequence and functional protein in living cells, but out of these the most straight-forward approach is to alter the gene expression level by manipulating the promoter sequence. Some of the promoter tuning tools available......Synthetic and systems biologists need standardized, modular and orthogonal tools yielding predictable functions in vivo. In systems biology such tools are needed to quantitatively analyze the behavior of biological systems while the efficient engineering of artificial gene networks is central...... for accomplishing such altered gene expression levels are discussed here along with examples of their use, and ideas for new tools are described. The road ahead looks very promising for synthetic and systems biologists as tools to achieve just about anything in terms of tuning and timing multiple gene expression...

  10. Carbon nanomaterials in biological systems

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-09-19

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

  11. Carbon nanomaterials in biological systems

    International Nuclear Information System (INIS)

    Pu Chun Ke; Qiao Rui

    2007-01-01

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

  12. Analyzing the Biology on the System Level

    OpenAIRE

    Tong, Wei

    2016-01-01

    Although various genome projects have provided us enormous static sequence information, understanding of the sophisticated biology continues to require integrating the computational modeling, system analysis, technology development for experiments, and quantitative experiments all together to analyze the biology architecture on various levels, which is just the origin of systems biology subject. This review discusses the object, its characteristics, and research attentions in systems biology,...

  13. Biological Potential in Serpentinizing Systems

    Science.gov (United States)

    Hoehler, Tori M.

    2016-01-01

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

  14. Anion binding in biological systems

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-11-15

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

  15. Anion binding in biological systems

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  16. Anion binding in biological systems

    Science.gov (United States)

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

    2009-11-01

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

  17. Nonlinear dynamics in biological systems

    CERN Document Server

    Carballido-Landeira, Jorge

    2016-01-01

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

  18. Concurrent systems and time synchronization

    Science.gov (United States)

    Burgin, Mark; Grathoff, Annette

    2018-05-01

    In the majority of scientific fields, system dynamics is described assuming existence of unique time for the whole system. However, it is established theoretically, for example, in relativity theory or in the system theory of time, and validated experimentally that there are different times and time scales in a variety of real systems - physical, chemical, biological, social, etc. In spite of this, there are no wide-ranging scientific approaches to exploration of such systems. Therefore, the goal of this paper is to study systems with this property. We call them concurrent systems because processes in them can go, events can happen and actions can be performed in different time scales. The problem of time synchronization is specifically explored.

  19. Real-time systems

    OpenAIRE

    Badr, Salah M.; Bruztman, Donald P.; Nelson, Michael L.; Byrnes, Ronald Benton

    1992-01-01

    This paper presents an introduction to the basic issues involved in real-time systems. Both real-time operating sys and real-time programming languages are explored. Concurrent programming and process synchronization and communication are also discussed. The real-time requirements of the Naval Postgraduate School Autonomous Under Vehicle (AUV) are then examined. Autonomous underwater vehicle (AUV), hard real-time system, real-time operating system, real-time programming language, real-time sy...

  20. Computational Modeling of Biological Systems From Molecules to Pathways

    CERN Document Server

    2012-01-01

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

  1. [Network structures in biological systems].

    Science.gov (United States)

    Oleskin, A V

    2013-01-01

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

  2. Systems biology of Microbial Communities

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-04-11

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

  3. Modeling biological pathway dynamics with timed automata.

    Science.gov (United States)

    Schivo, Stefano; Scholma, Jetse; Wanders, Brend; Urquidi Camacho, Ricardo A; van der Vet, Paul E; Karperien, Marcel; Langerak, Rom; van de Pol, Jaco; Post, Janine N

    2014-05-01

    Living cells are constantly subjected to a plethora of environmental stimuli that require integration into an appropriate cellular response. This integration takes place through signal transduction events that form tightly interconnected networks. The understanding of these networks requires capturing their dynamics through computational support and models. ANIMO (analysis of Networks with Interactive Modeling) is a tool that enables the construction and exploration of executable models of biological networks, helping to derive hypotheses and to plan wet-lab experiments. The tool is based on the formalism of Timed Automata, which can be analyzed via the UPPAAL model checker. Thanks to Timed Automata, we can provide a formal semantics for the domain-specific language used to represent signaling networks. This enforces precision and uniformity in the definition of signaling pathways, contributing to the integration of isolated signaling events into complex network models. We propose an approach to discretization of reaction kinetics that allows us to efficiently use UPPAAL as the computational engine to explore the dynamic behavior of the network of interest. A user-friendly interface hides the use of Timed Automata from the user, while keeping the expressive power intact. Abstraction to single-parameter kinetics speeds up construction of models that remain faithful enough to provide meaningful insight. The resulting dynamic behavior of the network components is displayed graphically, allowing for an intuitive and interactive modeling experience.

  4. Radical production in biological systems

    International Nuclear Information System (INIS)

    Johnson, J.R.; Akabani, G.

    1994-10-01

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

  5. Set membership experimental design for biological systems

    Directory of Open Access Journals (Sweden)

    Marvel Skylar W

    2012-03-01

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

  6. Integrating phosphoproteomics in systems biology

    Directory of Open Access Journals (Sweden)

    Yu Liu

    2014-07-01

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

  7. Dynamical systems in population biology

    CERN Document Server

    Zhao, Xiao-Qiang

    2017-01-01

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

  8. Institute for Genomics and Systems Biology

    Science.gov (United States)

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

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  10. Fostering synergy between cell biology and systems biology.

    Science.gov (United States)

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

    2015-08-01

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

  11. Mammalian Synthetic Biology: Time for Big MACs.

    Science.gov (United States)

    Martella, Andrea; Pollard, Steven M; Dai, Junbiao; Cai, Yizhi

    2016-10-21

    The enabling technologies of synthetic biology are opening up new opportunities for engineering and enhancement of mammalian cells. This will stimulate diverse applications in many life science sectors such as regenerative medicine, development of biosensing cell lines, therapeutic protein production, and generation of new synthetic genetic regulatory circuits. Harnessing the full potential of these new engineering-based approaches requires the design and assembly of large DNA constructs-potentially up to chromosome scale-and the effective delivery of these large DNA payloads to the host cell. Random integration of large transgenes, encoding therapeutic proteins or genetic circuits into host chromosomes, has several drawbacks such as risks of insertional mutagenesis, lack of control over transgene copy-number and position-specific effects; these can compromise the intended functioning of genetic circuits. The development of a system orthogonal to the endogenous genome is therefore beneficial. Mammalian artificial chromosomes (MACs) are functional, add-on chromosomal elements, which behave as normal chromosomes-being replicating and portioned to daughter cells at each cell division. They are deployed as useful gene expression vectors as they remain independent from the host genome. MACs are maintained as a single-copy and can accommodate multiple gene expression cassettes of, in theory, unlimited DNA size (MACs up to 10 megabases have been constructed). MACs therefore enabled control over ectopic gene expression and represent an excellent platform to rapidly prototype and characterize novel synthetic gene circuits without recourse to engineering the host genome. This review describes the obstacles synthetic biologists face when working with mammalian systems and how the development of improved MACs can overcome these-particularly given the spectacular advances in DNA synthesis and assembly that are fuelling this research area.

  12. Quantum Dynamics in Biological Systems

    Science.gov (United States)

    Shim, Sangwoo

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

  13. Editorial overview : Systems biology for biotechnology

    NARCIS (Netherlands)

    Heinemann, Matthias; Pilpel, Yitzhak

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

  14. Integrating systems biology models and biomedical ontologies.

    Science.gov (United States)

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

    2011-08-11

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

  15. Applicability of Computational Systems Biology in Toxicology

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  16. Metabolomics: Definitions and Significance in Systems Biology.

    Science.gov (United States)

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

    2017-01-01

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

  17. Timing system for PLS

    International Nuclear Information System (INIS)

    Chang, S.S.; Kim, M.S.; Won, S.C.; Choi, S.J.

    1991-01-01

    The PLS timing system consists of a master oscillator, a repetition rate pulse generator, a storage ring rf synchronizing system, and a rf driver and kicker trigger system composed of a fixed delay module and variable delay modules. All the timing modules are installed in the VME crates and controlled by the 32 bit microprocessors, and communicating with the Host computer via Ethernet. This paper describes the architectural design of this system as well as the requirements of performance

  18. Biological Therapy in Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Mariana Postal

    2012-01-01

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

  19. Systems biology of personalized nutrition

    NARCIS (Netherlands)

    Ommen, B. van; Broek, T. van den; Hoogh, I. de; Erk, M. van; Someren, E. van; Rouhani-Rankouhi, T.; Anthony, J.C.; Hogenelst, K.; Pasman, W.; Boorsma, A.; Wopereis, S.

    2017-01-01

    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

  20. Philosophy of Systems and Synthetic Biology

    DEFF Research Database (Denmark)

    Green, Sara

    2017-01-01

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

  1. Real time expert systems

    International Nuclear Information System (INIS)

    Asami, Tohru; Hashimoto, Kazuo; Yamamoto, Seiichi

    1992-01-01

    Recently, aiming at the application to the plant control for nuclear reactors and traffic and communication control, the research and the practical use of the expert system suitable to real time processing have become conspicuous. In this report, the condition for the required function to control the object that dynamically changes within a limited time is presented, and the technical difference between the real time expert system developed so as to satisfy it and the expert system of conventional type is explained with the actual examples and from theoretical aspect. The expert system of conventional type has the technical base in the problem-solving equipment originating in STRIPS. The real time expert system is applied to the fields accompanied by surveillance and control, to which conventional expert system is hard to be applied. The requirement for the real time expert system, the example of the real time expert system, and as the techniques of realizing real time processing, the realization of interruption processing, dispersion processing, and the mechanism of maintaining the consistency of knowledge are explained. (K.I.)

  2. Micro-separation toward systems biology.

    Science.gov (United States)

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

    2006-02-17

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

  3. The TRISTAN timing system

    International Nuclear Information System (INIS)

    Urakawa, Junji; Ishii, Kazuhiro; Kadokura, Eiichi; Kawamoto, Takashi; Kikuchi, Mitsuo; Kikutani, Eiji

    1990-01-01

    The TRISTAN accelerator complex comprises four accelerators: a 200 MeV electron linac for positron production, a 2.5 GeV linac, an 8 GeV accumulation ring (AR) and a 30 GeV main ring (MR). The TRISTAN timing system is divided into fast and slow timing systems. The fast timing system supplies timing signals (fast timing) for devices whose operation is synchronized with bunched beams from either the linac or the AR. These signals are also used in various beam monitors and beam feedback systems. The slow timing system generates trigger signals (slow timing) in order to achieve synchronization between the magnetic field and the rf accelerating voltage of the AR or MR. These triggers are also used for the automatic operation of machines. The TRISTAN timing system fulfills the following features with the required flexibility and extensibility while in the operation mode: (1) the linac gun trigger signals and the AR revolution clock are synchronized within ≅ 100 ps in timing accuracy, and a short pulse (≅ 1.5 ns) from the linac is injected and accumulated into an arbitrarily selected bucket of AR for a long time; (2) bucket matching between the AR and MR is achieved within ±6 ps in timing accuracy and a single bunched beam from the AR is injected into an arbitrarily selected bucket of the MR; (3) the slow timing system manages the operation mode of the AR and MR with both flexibility and extensibility; (4) the synchronization signals are transmitted through coaxial cables over a circumference of 3 km from the main control room. (orig.)

  4. Biological Systems Thinking for Control Engineering Design

    Directory of Open Access Journals (Sweden)

    D. J. Murray-Smith

    2004-01-01

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

  5. Impact of Thermodynamic Principles in Systems Biology

    NARCIS (Netherlands)

    Heijnen, J.J.

    2010-01-01

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

  6. Aspergilli: Systems biology and industrial applications

    DEFF Research Database (Denmark)

    Knuf, Christoph; Nielsen, Jens

    2012-01-01

    possible to implement systems biology tools to advance metabolic engineering. These tools include genome-wide transcription analysis and genome-scale metabolic models. Herein, we review achievements in the field and highlight the impact of Aspergillus systems biology on industrial biotechnology....

  7. Systems biology in critical-care nursing.

    Science.gov (United States)

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

    2011-01-01

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

  8. Marine biological data and information management system

    Digital Repository Service at National Institute of Oceanography (India)

    Sarupria, J.S.

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

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

    Science.gov (United States)

    Wolkenhauer, Olaf; Mesarovic, Mihajlo

    2005-05-01

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

  10. Accelerator-timing system

    International Nuclear Information System (INIS)

    Timmer, E.; Heine, E.

    1985-01-01

    Along the NIKHEF accelerator in Amsterdam (Netherlands), at several places a signal is needed for the sychronisation of all devices with the acceleration process. In this report, basic principles and arrangements of this timing system are described

  11. Genomes, Phylogeny, and Evolutionary Systems Biology

    Energy Technology Data Exchange (ETDEWEB)

    Medina, Monica

    2005-03-25

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

  12. Biological timing and the clock metaphor: oscillatory and hourglass mechanisms.

    Science.gov (United States)

    Rensing, L; Meyer-Grahle, U; Ruoff, P

    2001-05-01

    Living organisms have developed a multitude of timing mechanisms--"biological clocks." Their mechanisms are based on either oscillations (oscillatory clocks) or unidirectional processes (hourglass clocks). Oscillatory clocks comprise circatidal, circalunidian, circadian, circalunar, and circannual oscillations--which keep time with environmental periodicities--as well as ultradian oscillations, ovarian cycles, and oscillations in development and in the brain, which keep time with biological timescales. These clocks mainly determine time points at specific phases of their oscillations. Hourglass clocks are predominantly found in development and aging and also in the brain. They determine time intervals (duration). More complex timing systems combine oscillatory and hourglass mechanisms, such as the case for cell cycle, sleep initiation, or brain clocks, whereas others combine external and internal periodicities (photoperiodism, seasonal reproduction). A definition of a biological clock may be derived from its control of functions external to its own processes and its use in determining temporal order (sequences of events) or durations. Biological and chemical oscillators are characterized by positive and negative feedback (or feedforward) mechanisms. During evolution, living organisms made use of the many existing oscillations for signal transmission, movement, and pump mechanisms, as well as for clocks. Some clocks, such as the circadian clock, that time with environmental periodicities are usually compensated (stabilized) against temperature, whereas other clocks, such as the cell cycle, that keep time with an organismic timescale are not compensated. This difference may be related to the predominance of negative feedback in the first class of clocks and a predominance of positive feedback (autocatalytic amplification) in the second class. The present knowledge of a compensated clock (the circadian oscillator) and an uncompensated clock (the cell cycle), as well

  13. Magnetic Nanotweezers for Interrogating Biological Processes in Space and Time.

    Science.gov (United States)

    Kim, Ji-Wook; Jeong, Hee-Kyung; Southard, Kaden M; Jun, Young-Wook; Cheon, Jinwoo

    2018-04-17

    The ability to sense and manipulate the state of biological systems has been extensively advanced during the past decade with the help of recent developments in physical tools. Unlike standard genetic and pharmacological perturbation techniques-knockdown, overexpression, small molecule inhibition-that provide a basic on/off switching capability, these physical tools provide the capacity to control the spatial, temporal, and mechanical properties of the biological targets. Among the various physical cues, magnetism offers distinct advantages over light or electricity. Magnetic fields freely penetrate biological tissues and are already used for clinical applications. As one of the unique features, magnetic fields can be transformed into mechanical stimuli which can serve as a cue in regulating biological processes. However, their biological applications have been limited due to a lack of high-performance magnetism-to-mechanical force transducers with advanced spatiotemporal capabilities. In this Account, we present recent developments in magnetic nanotweezers (MNTs) as a useful tool for interrogating the spatiotemporal control of cells in living tissue. MNTs are composed of force-generating magnetic nanoparticles and field generators. Through proper design and the integration of individual components, MNTs deliver controlled mechanical stimulation to targeted biomolecules at any desired space and time. We first discuss about MNT configuration with different force-stimulation modes. By modulating geometry of the magnetic field generator, MNTs exert pulling, dipole-dipole attraction, and rotational forces to the target specifically and quantitatively. We discuss the key physical parameters determining force magnitude, which include magnetic field strength, magnetic field gradient, magnetic moment of the magnetic particle, as well as distance between the field generator and the particle. MNTs also can be used over a wide range of biological time scales. By simply

  14. Discrete-Time Systems

    Indian Academy of Sciences (India)

    We also describe discrete-time systems in terms of difference ... A more modern alternative, especially for larger systems, is to convert ... In other words, ..... picture?) State-variable equations are also called state-space equations because the ...

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

    OpenAIRE

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

    2012-01-01

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

  16. An engineering design approach to systems biology.

    Science.gov (United States)

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

    2017-07-17

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

  17. Multisensor Instrument for Real-Time Biological Monitoring

    Science.gov (United States)

    Zhang, Sean (Zhanxiang); Xu, Guoda; Qiu, Wei; Lin, Freddie

    2004-01-01

    The figure schematically depicts an instrumentation system, called a fiber optic-based integration system (FOBIS), that is undergoing development to enable real-time monitoring of fluid cell cultures, bioprocess flows, and the like. The FOBIS design combines a micro flow cytometer (MFC), a microphotometer (MP), and a fluorescence-spectrum- or binding-force-measuring micro-sensor (MS) in a single instrument that is capable of measuring multiple biological parameters simultaneously or sequentially. The fiber-optic-based integration system is so named because the MFC, the MP, and the MS are integrated into a single optical system that is coupled to light sources and photometric equipment via optical fibers. The optical coupling components also include a wavelength-division multiplexer and diffractive optical elements. The FOBIS includes a laserdiode- and fiber-optic-based optical trapping subsystem (optical tweezers ) with microphotometric and micro-sensing capabilities for noninvasive confinement and optical measurement of relevant parameters of a single cell or other particle. Some of the measurement techniques implemented together by the FOBIS have long been used separately to obtain basic understanding of the optical properties of individual cells and other organisms, the optical properties of populations of organisms, and the interrelationships among these properties, physiology of the organisms, and physical processes that govern the media that surround the organisms. For example, flow cytometry yields information on numerical concentrations, cross-sectional areas, and types of cells or other particles. Micro-sensing can be used to measure pH and concentrations of oxygen, carbon dioxide, glucose, metabolites, calcium, and antigens in a cell-culture fluid, thereby providing feedback that can be helpful in improving control over a bioprocess. Microphotometry (including measurements of scattering and fluorescence) can yield further information about optically

  18. BioCichlid: central dogma-based 3D visualization system of time-course microarray data on a hierarchical biological network.

    Science.gov (United States)

    Ishiwata, Ryosuke R; Morioka, Masaki S; Ogishima, Soichi; Tanaka, Hiroshi

    2009-02-15

    BioCichlid is a 3D visualization system of time-course microarray data on molecular networks, aiming at interpretation of gene expression data by transcriptional relationships based on the central dogma with physical and genetic interactions. BioCichlid visualizes both physical (protein) and genetic (regulatory) network layers, and provides animation of time-course gene expression data on the genetic network layer. Transcriptional regulations are represented to bridge the physical network (transcription factors) and genetic network (regulated genes) layers, thus integrating promoter analysis into the pathway mapping. BioCichlid enhances the interpretation of microarray data and allows for revealing the underlying mechanisms causing differential gene expressions. BioCichlid is freely available and can be accessed at http://newton.tmd.ac.jp/. Source codes for both biocichlid server and client are also available.

  19. Real-Time Agent-Based Modeling Simulation with in-situ Visualization of Complex Biological Systems: A Case Study on Vocal Fold Inflammation and Healing.

    Science.gov (United States)

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

    2016-05-01

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

  20. EURASIP journal on bioinformatics & systems biology

    National Research Council Canada - National Science Library

    2006-01-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

  2. Time reversal communication system

    Science.gov (United States)

    Candy, James V.; Meyer, Alan W.

    2008-12-02

    A system of transmitting a signal through a channel medium comprises digitizing the signal, time-reversing the digitized signal, and transmitting the signal through the channel medium. The channel medium may be air, earth, water, tissue, metal, and/or non-metal.

  3. Dynamics of Nonlinear Time-Delay Systems

    CERN Document Server

    Lakshmanan, Muthusamy

    2010-01-01

    Synchronization of chaotic systems, a patently nonlinear phenomenon, has emerged as a highly active interdisciplinary research topic at the interface of physics, biology, applied mathematics and engineering sciences. In this connection, time-delay systems described by delay differential equations have developed as particularly suitable tools for modeling specific dynamical systems. Indeed, time-delay is ubiquitous in many physical systems, for example due to finite switching speeds of amplifiers in electronic circuits, finite lengths of vehicles in traffic flows, finite signal propagation times in biological networks and circuits, and quite generally whenever memory effects are relevant. This monograph presents the basics of chaotic time-delay systems and their synchronization with an emphasis on the effects of time-delay feedback which give rise to new collective dynamics. Special attention is devoted to scalar chaotic/hyperchaotic time-delay systems, and some higher order models, occurring in different bran...

  4. Hydrogen production from biomass by biological systems

    International Nuclear Information System (INIS)

    Sharifan, H.R.; Qader, S.

    2009-01-01

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

  5. Omics/systems biology and cancer cachexia.

    Science.gov (United States)

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

    2016-06-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  7. Decision Making in Biological Systems

    DEFF Research Database (Denmark)

    Tian, Chengzhe

    This thesis consists of five projects in three topics with a shared theme of understanding cellular decision-making processes with mathematical modeling. In the first topic, we address the possible interaction between bacterial Toxin-Antitoxin (TA) systems and stringent response alarmone guanosin...

  8. Aging in a Relativistic Biological Space-Time

    Directory of Open Access Journals (Sweden)

    Davide Maestrini

    2018-05-01

    Full Text Available Here we present a theoretical and mathematical perspective on the process of aging. We extend the concepts of physical space and time to an abstract, mathematically-defined space, which we associate with a concept of “biological space-time” in which biological dynamics may be represented. We hypothesize that biological dynamics, represented as trajectories in biological space-time, may be used to model and study different rates of biological aging. As a consequence of this hypothesis, we show how dilation or contraction of time analogous to relativistic corrections of physical time resulting from accelerated or decelerated biological dynamics may be used to study precipitous or protracted aging. We show specific examples of how these principles may be used to model different rates of aging, with an emphasis on cancer in aging. We discuss how this theory may be tested or falsified, as well as novel concepts and implications of this theory that may improve our interpretation of biological aging.

  9. Carbon-13 NMR spectroscopy of biological systems

    CERN Document Server

    Beckmann, Nicolau

    1995-01-01

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

  10. JKJ accelerator timing system

    International Nuclear Information System (INIS)

    Ohmori, C.; Mori, Y.; Yoshii, M.; Yamamoto, M.

    2001-01-01

    The JKJ (JAERl-KEK Joint Project) accelerator complex consists of the linear accelerator, 3 GeV and 50 GeV synchrotrons. To minimize the beam loss during the beam transfer from the 3 GeV synchrotron to the 50 GeV one, the synchronization of the two RF system of the rings is very important. To reduce the background from the high and low momentum neutron, the neutron beam chopper will be employed. The 3 GeV RF will be also synchronized to the chopper timing when the beam goes to the neutron facility. The whole timing control system of these accelerators and chopper will be described. (author)

  11. Memorized discrete systems and time-delay

    CERN Document Server

    Luo, Albert C J

    2017-01-01

    This book examines discrete dynamical systems with memory—nonlinear systems that exist extensively in biological organisms and financial and economic organizations, and time-delay systems that can be discretized into the memorized, discrete dynamical systems. It book further discusses stability and bifurcations of time-delay dynamical systems that can be investigated through memorized dynamical systems as well as bifurcations of memorized nonlinear dynamical systems, discretization methods of time-delay systems, and periodic motions to chaos in nonlinear time-delay systems. The book helps readers find analytical solutions of MDS, change traditional perturbation analysis in time-delay systems, detect motion complexity and singularity in MDS; and determine stability, bifurcation, and chaos in any time-delay system.

  12. Systems Biology and Stem Cell Pluripotency

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    Science.gov (United States)

    Dai, Zongjie; Nielsen, Jens

    2015-12-01

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

  14. Advancing metabolic engineering through systems biology of industrial microorganisms

    DEFF Research Database (Denmark)

    Dai, Zongjie; Nielsen, Jens

    2015-01-01

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

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

    Science.gov (United States)

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

    2010-03-01

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

  16. Systems biology solutions for biochemical production challenges

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  17. Systems biology solutions for biochemical production challenges.

    Science.gov (United States)

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

    2017-06-01

    There is an urgent need to significantly accelerate the development of microbial cell factories to produce fuels and chemicals from renewable feedstocks in order to facilitate the transition to a biobased society. Methods commonly used within the field of systems biology including omics characterization, genome-scale metabolic modeling, and adaptive laboratory evolution can be readily deployed in metabolic engineering projects. However, high performance strains usually carry tens of genetic modifications and need to operate in challenging environmental conditions. This additional complexity compared to basic science research requires pushing systems biology strategies to their limits and often spurs innovative developments that benefit fields outside metabolic engineering. Here we survey recent advanced applications of systems biology methods in engineering microbial production strains for biofuels and -chemicals. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Drawing inspiration from biological optical systems

    Science.gov (United States)

    Wolpert, H. D.

    2009-08-01

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

  19. Synthetic Biology: Advancing Biological Frontiers by Building Synthetic Systems

    OpenAIRE

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

    2012-01-01

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

  20. Role of time in symbiotic systems

    Energy Technology Data Exchange (ETDEWEB)

    Agrawala, A.K. [Univ. of Maryland, College Park, MD (United States)

    1996-12-31

    All systems have a dynamics which reflects the changes in the system in time and, therefore, have to maintain a notion of time, either explicitly or implicitly. Traditionally, the notion of time in constructed systems has been implicitly specified at design time through rigid structures such as sampled data systems which operate with a fixed time tick, feedback systems which are designed reflecting a fixed time scale for the dynamics of the system as well as the controller responses, etc. In biological systems, the sense of time is a key element but it is not rigidly structured, even though all such systems have a clear notion of time. We define the notion of time in systems in terms of temporal locality, time scale and time horizon. Temporal locality gives the notion of the accuracy with which the system knows about the current time. Time scale reflects the scale indicating the smallest and the largest granularity considered. It also reflects the reaction time. The time horizon indicates the time beyond which the system considers to be distant future and may not take it into account in its actions. Note that the temporal locality, time scale and the time horizon may be different for different types of actions of a system, thereby permitting the system to use multiple notions of time concurrently. In multi agent systems each subsystem may have its own notion of time but when intentions take place a coordination is necessary. Such coordination requires that the notions of time for different agents of the system be consistent. Clearly, the consistency requirement in this case does not mean exactly identical but implies that different agents can coordinate their actions which must take place in time. When the actions only require a determinate ordering the required coordination is much less severe than the case requiring actions to take place at the same time.

  1. Systems Biology — the Broader Perspective

    Directory of Open Access Journals (Sweden)

    Jonathan Bard

    2013-06-01

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

  2. The time slice system

    International Nuclear Information System (INIS)

    DeWitt, J.

    1990-01-01

    We have designed a fast readout system for silicon microstrip detectors which could be used at HERA, LHC, and SSC. The system consists of an analog amplifier-comparator chip (AACC) and a digital time slice chip (DTSC). The analog ship is designed in dielectric isolated bipolar technology for low noise and potential radiation hardness. The DTSC is built in CMOS for low power use and high circuit density. The main implementation aims are low power consumption and compactness. The architectural goal is automatic data reduction, and ease of external interface. The pipelining of event information is done digitally in the DTSC. It has a 64 word deep level 1 buffer acting as a FIFO, and a 16 word deep level 2 buffer acting as a dequeue. The DTSC also includes an asynchronous bus interface. We are first building a scaled up (100 μm instead of 25 μm pitch) and slower (10 MHz instead of 60 MHz) version in 2 μm CMOS and plan to test the principle of operation of this system in the Leading Proton Spectrometer (LPS) of the ZEUS detector at HERA. Another very important development will be tested there: the radiation hardening of the chips. We have started a collaboration with a rad-hard foundry and with Los Alamos National Laboratories to test and evaluate rad-hard processes and the final rad-hard product. Initial data are very promising, because radiation resistance of up to many Mrad have been achieved. (orig.)

  3. Systems Biology for Organotypic Cell Cultures

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-08-04

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

  4. Promoting Systems Thinking through Biology Lessons

    Science.gov (United States)

    Riess, Werner; Mischo, Christoph

    2010-01-01

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

  5. Systems Biology of Glucocorticoids in Muscle Disease

    Science.gov (United States)

    2010-10-01

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

  6. Modular microfluidic system for biological sample preparation

    Science.gov (United States)

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

    2015-09-29

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

  7. Radiological/biological/aerosol removal system

    Science.gov (United States)

    Haslam, Jeffery J

    2015-03-17

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

  8. Notions of radiation chemistry in biological systems

    International Nuclear Information System (INIS)

    Mastro, N.L. del.

    1989-10-01

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

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

    Science.gov (United States)

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

    2014-11-01

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

  10. Integrative Systems Biology Applied to Toxicology

    DEFF Research Database (Denmark)

    Kongsbak, Kristine Grønning

    associated with combined exposure to multiple chemicals. Testing all possible combinations of the tens of thousands environmental chemicals is impractical. This PhD project was launched to apply existing computational systems biology methods to toxicological research. In this thesis, I present in three...... of a system thereby suggesting new ways of thinking specific toxicological endpoints. Furthermore, computational methods can serve as valuable input for the hypothesis generating phase of the preparations of a research project....

  11. Toward mechanical systems biology in bone.

    Science.gov (United States)

    Trüssel, Andreas; Müller, Ralph; Webster, Duncan

    2012-11-01

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

  12. A Magnetic Sensor System for Biological Detection

    KAUST Repository

    Li, Fuquan

    2015-05-01

    for the detection of E. coli, and similar optimization processes can be performed for the detection of other biological targets. Third, we demonstrate the new magnetic biosensor concept using a mechanical trap capable of detecting nucleic acids via the size difference between bare magnetic beads and bead compounds. The bead compounds are formed through linking nonmagnetic beads of 1 µm in diameter and magnetic beads of 2.8 µm in diameter by the target nucleic acids. The purpose of the nonmagnetic beads is to increase the size of the compounds, since the nucleic acid is very small compared to the magnetic beads. Alternatively, smaller magnetic beads could be used but their detection would be more challenging. Finally, an enhanced version of the magnetic biosensor concept is developed using an electromagnetic trap for the detection of E. coli. The trap is formed by a current-carrying microwire that attracts magnetic beads into a virtual sensing space. As in the case of the mechanical trap, the sensor signal depends on the number of beads inside of the sensing space. The distance which magnetic beads can be detected from by the MTJ sensor defines the sensing space. The results showed that the output signal depends on the concentration of E. coli in the sample solution and that individual E. coli bacterium inside the sensing space could be detected using super-paramagnetic beads that are 2.8 µm in diameter. In summary, this dissertation investigates a new magnetic biosensor concept, which detects biological targets via the size difference between bare magnetic beads and compounds of magnetic beads and biological targets. The new method is extremely simple and enables the detection of biological targets in two simple steps and within a short time. The concept is demonstrated for the detection of nucleic acid and E. coli.

  13. Timing system observations

    International Nuclear Information System (INIS)

    Winans, J.

    1994-01-01

    The purpose of this document is to augment Synchronized Time Stamp Support authored by Jim Kowalkowski. This document provides additional documentation to clarify and explain software involved in timing operations of the accelerator

  14. Radionuclide Imaging Technologies for Biological Systems

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-05-14

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

  15. Optoelectronic system and apparatus for connection to biological systems

    Science.gov (United States)

    Okandan, Murat; Nielson, Gregory N.

    2018-03-06

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

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

    Science.gov (United States)

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

    2016-06-17

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

  17. Real Time Systems

    DEFF Research Database (Denmark)

    Christensen, Knud Smed

    2000-01-01

    Describes fundamentals of parallel programming and a kernel for that. Describes methods for modelling and checking parallel problems. Real time problems.......Describes fundamentals of parallel programming and a kernel for that. Describes methods for modelling and checking parallel problems. Real time problems....

  18. Interactive analysis of systems biology molecular expression data

    Directory of Open Access Journals (Sweden)

    Prabhakar Sunil

    2008-02-01

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

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

    Indian Academy of Sciences (India)

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

  20. Complex biological and bio-inspired systems

    Energy Technology Data Exchange (ETDEWEB)

    Ecke, Robert E [Los Alamos National Laboratory

    2009-01-01

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

  1. Life: An Introduction to Complex Systems Biology

    CERN Document Server

    Kaneko, Kunihiko

    2006-01-01

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

  2. System biology and the project Encode

    Directory of Open Access Journals (Sweden)

    M. Yu. Obolenskaya

    2014-08-01

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

  3. Engineering biological systems toward a sustainable bioeconomy.

    Science.gov (United States)

    Lopes, Mateus Schreiner Garcez

    2015-06-01

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

  4. Adaptable data management for systems biology investigations

    Directory of Open Access Journals (Sweden)

    Burdick David

    2009-03-01

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

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

    Science.gov (United States)

    2010-01-01

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

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

    Science.gov (United States)

    Simpson, Melanie Rae

    2016-01-01

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

  7. The Feasibility of Systems Thinking in Biology Education

    Science.gov (United States)

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

    2011-01-01

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

  8. Optical Biosensors to Explore Biological Systems

    DEFF Research Database (Denmark)

    Palanco, Marta Espina; Mogensen, Klaus Bo; Andersen, Nils H. Skovgaard

    2016-01-01

    their capability to work in biosensor devices. For example, Raman spectroscopy can be non-invasive and can provide 1 μm of spatial resolution in 1 second of collection time, well suited for sensing. Moreover, it may give information at the single cell and even approaching the single molecule scale. Here we present...... protein may be used as an efficient sensor in an organic environment via a biomimetic membrane model. The combination of both biomimetic membranes and protein membranes as a signal transduction medium has interesting applications in biology and medicine. It is crucial that the matrix where a protein...

  9. The LCLS Timing Event System

    Energy Technology Data Exchange (ETDEWEB)

    Dusatko, John; Allison, S.; Browne, M.; Krejcik, P.; /SLAC

    2012-07-23

    The Linac Coherent Light Source requires precision timing trigger signals for various accelerator diagnostics and controls at SLAC-NAL. A new timing system has been developed that meets these requirements. This system is based on COTS hardware with a mixture of custom-designed units. An added challenge has been the requirement that the LCLS Timing System must co-exist and 'know' about the existing SLC Timing System. This paper describes the architecture, construction and performance of the LCLS timing event system.

  10. Biological diversity in the patent system.

    Directory of Open Access Journals (Sweden)

    Paul Oldham

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

  11. A Biological Perspective on the Meaning of Time

    Science.gov (United States)

    Rothschild, Lynn J.

    2014-01-01

    We have become impatient waiting for a web page to load, but the first member of our species evolved about 150,000 years ago - a geological instant as brief and as transitory as a text message. The shortest generation time of a bacterium is a sprint at under ten minutes, whereas a 200-year old whale, turtle or tree is not unknown. Life is a phenomenon that integrates processes ranging from the near instantaneous reactions of photosynthesis to the more stately pace of evolution. Here I will elucidate these processes with radically different time scales that go to creating and maintaining the diversity of life on earth, the clocks that nature uses to time them, and how modern biology is being used to alter the natural time scales.

  12. Time rescaling and pattern formation in biological evolution.

    Science.gov (United States)

    Igamberdiev, Abir U

    2014-09-01

    Biological evolution is analyzed as a process of continuous measurement in which biosystems interpret themselves in the environment resulting in changes of both. This leads to rescaling of internal time (heterochrony) followed by spatial reconstructions of morphology (heterotopy). The logical precondition of evolution is the incompleteness of biosystem's internal description, while the physical precondition is the uncertainty of quantum measurement. The process of evolution is based on perpetual changes in interpretation of information in the changing world. In this interpretation the external biospheric gradients are used for establishment of new features of organization. It is concluded that biological evolution involves the anticipatory epigenetic changes in the interpretation of genetic symbolism which cannot generally be forecasted but can provide canalization of structural transformations defined by the existing organization and leading to predictable patterns of form generation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Nuclear magnetic resonance applications in biological systems

    International Nuclear Information System (INIS)

    Jiang Ling; Liu Maili

    2011-01-01

    Nuclear magnetic resonance (NMR) spectroscopy is a state-of-the-art technology which has been widely applied in biological systems over the past decades. It is a powerful tool for macromolecular structure determination in solution, and has the unique advantage of being capable of elucidating the structure and dynamic behavior of proteins during vital biomedical processes. In this review, we introduce the recent progress in NMR techniques for studying the structure, interaction and dynamics of proteins. The methods for NMR based drug discovery and metabonomics are also briefly introduced. (authors)

  14. System for determining sizes of biological macromolecules

    International Nuclear Information System (INIS)

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

    1987-01-01

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

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

    CERN Document Server

    Feldman, Yuri

    2015-01-01

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

  16. Redefining plant systems biology: from cell to ecosystem

    NARCIS (Netherlands)

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

    2011-01-01

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

  17. An Integrated Biological Control System At Hanford

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  18. AN INTEGRATED BIOLOGICAL CONTROL SYSTEM AT HANFORD

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-02-11

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

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

    Science.gov (United States)

    Hagen, Wilfred R

    2018-02-21

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

  20. Applications of membrane computing in systems and synthetic biology

    CERN Document Server

    Gheorghe, Marian; Pérez-Jiménez, Mario

    2014-01-01

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

  1. Prototyping real-time systems

    OpenAIRE

    Clynch, Gary

    1994-01-01

    The traditional software development paradigm, the waterfall life cycle model, is defective when used for developing real-time systems. This thesis puts forward an executable prototyping approach for the development of real-time systems. A prototyping system is proposed which uses ESML (Extended Systems Modelling Language) as a prototype specification language. The prototyping system advocates the translation of non-executable ESML specifications into executable LOOPN (Language of Object ...

  2. Structural Identifiability of Dynamic Systems Biology Models.

    Science.gov (United States)

    Villaverde, Alejandro F; Barreiro, Antonio; Papachristodoulou, Antonis

    2016-10-01

    A powerful way of gaining insight into biological systems is by creating a nonlinear differential equation model, which usually contains many unknown parameters. Such a model is called structurally identifiable if it is possible to determine the values of its parameters from measurements of the model outputs. Structural identifiability is a prerequisite for parameter estimation, and should be assessed before exploiting a model. However, this analysis is seldom performed due to the high computational cost involved in the necessary symbolic calculations, which quickly becomes prohibitive as the problem size increases. In this paper we show how to analyse the structural identifiability of a very general class of nonlinear models by extending methods originally developed for studying observability. We present results about models whose identifiability had not been previously determined, report unidentifiabilities that had not been found before, and show how to modify those unidentifiable models to make them identifiable. This method helps prevent problems caused by lack of identifiability analysis, which can compromise the success of tasks such as experiment design, parameter estimation, and model-based optimization. The procedure is called STRIKE-GOLDD (STRuctural Identifiability taKen as Extended-Generalized Observability with Lie Derivatives and Decomposition), and it is implemented in a MATLAB toolbox which is available as open source software. The broad applicability of this approach facilitates the analysis of the increasingly complex models used in systems biology and other areas.

  3. Stochastic transport processes in discrete biological systems

    CERN Document Server

    Frehland, Eckart

    1982-01-01

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

  4. Model checking biological systems described using ambient calculus

    DEFF Research Database (Denmark)

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

    2005-01-01

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

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

    Science.gov (United States)

    Calvert, Jane; Fujimura, Joan H

    2011-06-01

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

  6. Implied Movement in Static Images Reveals Biological Timing Processing

    Directory of Open Access Journals (Sweden)

    Francisco Carlos Nather

    2015-08-01

    Full Text Available Visual perception is adapted toward a better understanding of our own movements than those of non-conspecifics. The present study determined whether time perception is affected by pictures of different species by considering the evolutionary scale. Static (“S” and implied movement (“M” images of a dog, cheetah, chimpanzee, and man were presented to undergraduate students. S and M images of the same species were presented in random order or one after the other (S-M or M-S for two groups of participants. Movement, Velocity, and Arousal semantic scales were used to characterize some properties of the images. Implied movement affected time perception, in which M images were overestimated. The results are discussed in terms of visual motion perception related to biological timing processing that could be established early in terms of the adaptation of humankind to the environment.

  7. Time scale of diffusion in molecular and cellular biology

    International Nuclear Information System (INIS)

    Holcman, D; Schuss, Z

    2014-01-01

    Diffusion is the driver of critical biological processes in cellular and molecular biology. The diverse temporal scales of cellular function are determined by vastly diverse spatial scales in most biophysical processes. The latter are due, among others, to small binding sites inside or on the cell membrane or to narrow passages between large cellular compartments. The great disparity in scales is at the root of the difficulty in quantifying cell function from molecular dynamics and from simulations. The coarse-grained time scale of cellular function is determined from molecular diffusion by the mean first passage time of molecular Brownian motion to a small targets or through narrow passages. The narrow escape theory (NET) concerns this issue. The NET is ubiquitous in molecular and cellular biology and is manifested, among others, in chemical reactions, in the calculation of the effective diffusion coefficient of receptors diffusing on a neuronal cell membrane strewn with obstacles, in the quantification of the early steps of viral trafficking, in the regulation of diffusion between the mother and daughter cells during cell division, and many other cases. Brownian trajectories can represent the motion of a molecule, a protein, an ion in solution, a receptor in a cell or on its membrane, and many other biochemical processes. The small target can represent a binding site or an ionic channel, a hidden active site embedded in a complex protein structure, a receptor for a neurotransmitter on the membrane of a neuron, and so on. The mean time to attach to a receptor or activator determines diffusion fluxes that are key regulators of cell function. This review describes physical models of various subcellular microdomains, in which the NET coarse-grains the molecular scale to a higher cellular-level, thus clarifying the role of cell geometry in determining subcellular function. (topical review)

  8. Time scale of diffusion in molecular and cellular biology

    Science.gov (United States)

    Holcman, D.; Schuss, Z.

    2014-05-01

    Diffusion is the driver of critical biological processes in cellular and molecular biology. The diverse temporal scales of cellular function are determined by vastly diverse spatial scales in most biophysical processes. The latter are due, among others, to small binding sites inside or on the cell membrane or to narrow passages between large cellular compartments. The great disparity in scales is at the root of the difficulty in quantifying cell function from molecular dynamics and from simulations. The coarse-grained time scale of cellular function is determined from molecular diffusion by the mean first passage time of molecular Brownian motion to a small targets or through narrow passages. The narrow escape theory (NET) concerns this issue. The NET is ubiquitous in molecular and cellular biology and is manifested, among others, in chemical reactions, in the calculation of the effective diffusion coefficient of receptors diffusing on a neuronal cell membrane strewn with obstacles, in the quantification of the early steps of viral trafficking, in the regulation of diffusion between the mother and daughter cells during cell division, and many other cases. Brownian trajectories can represent the motion of a molecule, a protein, an ion in solution, a receptor in a cell or on its membrane, and many other biochemical processes. The small target can represent a binding site or an ionic channel, a hidden active site embedded in a complex protein structure, a receptor for a neurotransmitter on the membrane of a neuron, and so on. The mean time to attach to a receptor or activator determines diffusion fluxes that are key regulators of cell function. This review describes physical models of various subcellular microdomains, in which the NET coarse-grains the molecular scale to a higher cellular-level, thus clarifying the role of cell geometry in determining subcellular function.

  9. Microbial stress tolerance for biofuels. Systems biology

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-07-01

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

  10. Spatial Structures and Regulation in Biological Systems

    DEFF Research Database (Denmark)

    Yde, Pernille

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

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

    Science.gov (United States)

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

    2016-06-16

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

  12. Behaviors of tritium in terrestrial biological system

    International Nuclear Information System (INIS)

    Inomata, Tsuyako

    1983-01-01

    The in vivo behaviors of HTO- 3 H in food chain models in experimental animals were described. Of pregnant mice that had ingested HTO and drinking water alone for 19 days, the total 3 H content in the tissue/wet weight was greater by 20% in fetuses and newborns than in mothers, and the proportion of tissue-bound 3 H was 8-24% in mothers and 3% in fetuses. The mean 3 H concentration in the free water in tissues was about 36% of ingested HTO. When only 3 H foods were ingested for 18 days, the total 3 H content in the tissue/wet weight showed no marked difference among the mother, fetuses and newborns, nor did the bound 3 H level show great differences. With respect to the tissue distribution of 3 H, only the incorporation rate by the mother's brain from HTO was satisfactory, whereas in other organs, the mother, fetuses and newborns showed higher incorporation rates from 3 H foods. The ratio of specific radioactivity of soft tissue 3 H in mothers to HTO in drinking water exceeded 1 only for the spleen, but other tissues showed no biological concentration. Again, no biological concentration was observed with 3 H foods. Environmental HTO did not result in biological concentration of 3 H in mother mice that had ingested 3 H foods, but 3 H was rather diluted. Tissues other than the spleen showed similar values of 3 H ingestion from environmental HTO through all routes. However, the proportion of bound 3 H in the total 3 H in the soft tissue was about 1.4-1.6 times that on ingestion of HTO alone. (Chiba, N.)

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

    Science.gov (United States)

    De Domenico, Manlio

    2018-03-01

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

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

    Science.gov (United States)

    Gomez-Ramirez, Jaime; Sanz, Ricardo

    2013-09-01

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

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

    Science.gov (United States)

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

    2017-09-01

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

  16. Dependable Real-Time Systems

    Science.gov (United States)

    1991-09-30

    0196 or 413 545-0720 PI E-mail Address: krithi@nirvan.cs.umass.edu, stankovic(ocs.umass.edu Grant or Contract Title: Dependable Real - Time Systems Grant...Dependable Real - Time Systems " Grant or Contract Number: N00014-85-k-0398 L " Reporting Period: 1 Oct 87 - 30 Sep 91 , 2. Summary of Accomplishments ’ 2.1 Our...in developing a sound approach to scheduling tasks in complex real - time systems , (2) developed a real-time operating system kernel, a preliminary

  17. Official Union Time Tracking System

    Data.gov (United States)

    Social Security Administration — Official Union Time Tracking System captures the reporting and accounting of the representational activity for all American Federation of Government Employees (AFGE)...

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

    Science.gov (United States)

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

    1990-01-01

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

  19. Notions of similarity for systems biology models.

    Science.gov (United States)

    Henkel, Ron; Hoehndorf, Robert; Kacprowski, Tim; Knüpfer, Christian; Liebermeister, Wolfram; Waltemath, Dagmar

    2018-01-01

    Systems biology models are rapidly increasing in complexity, size and numbers. When building large models, researchers rely on software tools for the retrieval, comparison, combination and merging of models, as well as for version control. These tools need to be able to quantify the differences and similarities between computational models. However, depending on the specific application, the notion of 'similarity' may greatly vary. A general notion of model similarity, applicable to various types of models, is still missing. Here we survey existing methods for the comparison of models, introduce quantitative measures for model similarity, and discuss potential applications of combined similarity measures. To frame model comparison as a general problem, we describe a theoretical approach to defining and computing similarities based on a combination of different model aspects. The six aspects that we define as potentially relevant for similarity are underlying encoding, references to biological entities, quantitative behaviour, qualitative behaviour, mathematical equations and parameters and network structure. We argue that future similarity measures will benefit from combining these model aspects in flexible, problem-specific ways to mimic users' intuition about model similarity, and to support complex model searches in databases. © The Author 2016. Published by Oxford University Press.

  20. 3S - Systematic, systemic, and systems biology and toxicology.

    Science.gov (United States)

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

    2018-01-01

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

  1. A Magnetic Sensor System for Biological Detection

    KAUST Repository

    Li, Fuquan

    2015-01-01

    Magnetic biosensors detect biological targets through sensing the stray field of magnetic beads which label the targets. Commonly, magnetic biosensors employ the “sandwich” method to immobilize biological targets, i.e., the targets are sandwiched

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

    International Nuclear Information System (INIS)

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

    2002-01-01

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

  3. Heliborne time domain electromagnetic system

    International Nuclear Information System (INIS)

    Bhattacharya, S.

    2009-01-01

    Atomic Minerals Directorate (AMD), are using heliborne and ground time domain electromagnetic (TDEM) system for the exploration of deep seated unconformity type uranium deposits. Uranium has been explored in various parts of the world like Athabasca basin using time domain electromagnetic system. AMD has identified some areas in India where such deposits are available. Apart from uranium exploration, the TDEM systems are used for the exploration of deep seated minerals like diamonds. Bhabha Atomic Research Centre (BARC) is involved in the indigenous design of the heliborne time domain system since this system is useful for DAE and also it has a scope of wide application. In this paper we discuss about the principle of time domain electromagnetic systems, their capabilities and the development and problems of such system for various other mineral exploration. (author)

  4. Hologenomics: Systems-Level Host Biology.

    Science.gov (United States)

    Theis, Kevin R

    2018-01-01

    The hologenome concept of evolution is a hypothesis explaining host evolution in the context of the host microbiomes. As a hypothesis, it needs to be evaluated, especially with respect to the extent of fidelity of transgenerational coassociation of host and microbial lineages and the relative fitness consequences of repeated associations within natural holobiont populations. Behavioral ecologists are in a prime position to test these predictions because they typically focus on animal phenotypes that are quantifiable, conduct studies over multiple generations within natural animal populations, and collect metadata on genetic relatedness and relative reproductive success within these populations. Regardless of the conclusion on the hologenome concept as an evolutionary hypothesis, a hologenomic perspective has applied value as a systems-level framework for host biology, including in medicine. Specifically, it emphasizes investigating the multivarious and dynamic interactions between patient genomes and the genomes of their diverse microbiota when attempting to elucidate etiologies of complex, noninfectious diseases.

  5. Predictive modelling of complex agronomic and biological systems.

    Science.gov (United States)

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

    2013-09-01

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

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

    Science.gov (United States)

    Guzzi, Rodolfo; Colombo, Teresa; Paci, Paola

    2018-01-01

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

  7. Biomarkers of Nanoparticles Impact on Biological Systems

    Science.gov (United States)

    Mikhailenko, V.; Ieleiko, L.; Glavin, A.; Sorochinska, J.

    Studies of nanoscale mineral fibers have demonstrated that the toxic and carcinogenic effects are related to the surface area and surface activity of inhaled particles. Particle surface characteristics are considered to be key factors in the generation of free radicals and reactive oxygen species and are related to the development of apoptosis or cancer. Existing physico-chemical methods do not always allow estimation of the nanoparticles impact on organismal and cellular levels. The aim of this study was to develop marker system for evaluation the toxic and carcinogenic effects of nanoparticles on cells. The markers are designed with respect to important nanoparticles characteristics for specific and sensitive assessment of their impact on biological system. We have studied DNA damage, the activity of xanthine oxidoreductase influencing the level of free radicals, bioenergetic status, phospholipids profile and formation of 1H-NMR-visible mobile lipid domains in Ehrlich carcinoma cells. The efficiency of the proposed marker system was tested in vivo and in vitro with the use of C60 fullerene nanoparticles and multiwalled carbon nanotubes. Our data suggest that multiwalled carbon nanotubes and fullerene C60 may pose genotoxic effect, change energy metabolism and membrane structure, alter free radical level via xanthine oxidase activation and cause mobile lipid domains formation as determined in vivo and in vitro studies on Ehrlich carcinoma cells.

  8. DTW4Omics: comparing patterns in biological time series.

    Directory of Open Access Journals (Sweden)

    Rachel Cavill

    Full Text Available When studying time courses of biological measurements and comparing these to other measurements eg. gene expression and phenotypic endpoints, the analysis is complicated by the fact that although the associated elements may show the same patterns of behaviour, the changes do not occur simultaneously. In these cases standard correlation-based measures of similarity will fail to find significant associations. Dynamic time warping (DTW is a technique which can be used in these situations to find the optimal match between two time courses, which may then be assessed for its significance. We implement DTW4Omics, a tool for performing DTW in R. This tool extends existing R scripts for DTW making them applicable for "omics" datasets where thousands entities may need to be compared with a range of markers and endpoints. It includes facilities to estimate the significance of the matches between the supplied data, and provides a set of plots to enable the user to easily visualise the output. We illustrate the utility of this approach using a dataset linking the exposure of the colon carcinoma Caco-2 cell line to oxidative stress by hydrogen peroxide (H2O2 and menadione across 9 timepoints and show that on average 85% of the genes found are not obtained from a standard correlation analysis between the genes and the measured phenotypic endpoints. We then show that when we analyse the genes identified by DTW4Omics as significantly associated with a marker for oxidative DNA damage (8-oxodG, through over-representation, an Oxidative Stress pathway is identified as the most over-represented pathway demonstrating that the genes found by DTW4Omics are biologically relevant. In contrast, when the positively correlated genes were similarly analysed, no pathways were found. The tool is implemented as an R Package and is available, along with a user guide from http://web.tgx.unimaas.nl/svn/public/dtw/.

  9. Systems Biology of Metabolism: Annual Review of Biochemistry

    DEFF Research Database (Denmark)

    Nielsen, Jens

    2017-01-01

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

  10. Statistical Model Checking for Biological Systems

    DEFF Research Database (Denmark)

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

    2014-01-01

    Statistical Model Checking (SMC) is a highly scalable simulation-based verification approach for testing and estimating the probability that a stochastic system satisfies a given linear temporal property. The technique has been applied to (discrete and continuous time) Markov chains, stochastic...

  11. A SYSTEMIC VISION OF BIOLOGY: OVERCOMING LINEARITY

    Directory of Open Access Journals (Sweden)

    M. Mayer

    2005-07-01

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

  12. Time trends in biological fertility in Western Europe

    DEFF Research Database (Denmark)

    Joffe, Michael; Holmes, Jane; Jensen, Tina Kold

    2013-01-01

    analyses demonstrated that this rise was visible as a male cohort effect for both TTP and contraceptive failure. On the other hand, the female birth cohort effect showed a slight fall in the first half of the study period for both TTP and contraceptive failure. As a period effect, fertility remained...... of which are calculated to be small. The declining female fertility accords with a falling dizygotic twinning rate during the same period.......We investigated trends in biological fertility in a comprehensive analysis of 5 major European data sets with data on time to pregnancy (TTP) and proportion of contraceptive failures. In particular, we distinguished a period effect from a birth cohort effect (lifelong tendency) in both sexes...

  13. Advancing cell biology through proteomics in space and time (PROSPECTS)

    DEFF Research Database (Denmark)

    Lamond, A.I.; Uhlen, M.; Horning, S.

    2012-01-01

    a range of sensitive and quantitative approaches for measuring protein structures and dynamics that promise to revolutionize our understanding of cell biology and molecular mechanisms in both human cells and model organisms. The Proteomics Specification in Time and Space (PROSPECTS) Network is a unique EU......-funded project that brings together leading European research groups, spanning from instrumentation to biomedicine, in a collaborative five year initiative to develop new methods and applications for the functional analysis of cellular proteins. This special issue of Molecular and Cellular Proteomics presents 16...... quantification of protein levels. Manuscripts in this issue exemplify approaches for performing quantitative measurements of cell proteomes and for studying their dynamic responses to perturbation, both during normal cellular responses and in disease mechanisms. Here we present a perspective on how...

  14. Ecological and biological systems under extreme conditions

    Energy Technology Data Exchange (ETDEWEB)

    Zlobin, V S; Nenishkiene, V B

    1989-01-01

    The behaviour of biological and ecological systems under extreme conditions (high and low temperatures, electromagnetic fields of different frequencies, ultraviolet. X-ray and gamma radiation) is analyzed. The ecosystems of macro- and microalgae living in salt, brackinsh and fresh waters are considered in the evolutional aspect basing on their chemical and biochemical composition taking into account the mechanism of radionuclide uptake by water plant cells, osmotic regulation, water and ice structures, combined water in a living organism. The problems of life-support in cosmic flights and of mastering the planets of the Solar system, for instance Mars and Venus, utilizing some microalgae and bacteria with high adaptive properties are discussed. Abnormal water points and their role in the metabolism of a water plant cell are estimated. The 'life niches' are determined at the temperatures exceeding 100 deg C and the possibility of existence for living organisms in high pressure and temperature is grounded. Attempts are made to change the metabolism of the plant and animal cell by subjecting it to the action of electromagnetic and thermal fields, heavy water, chemical and pharmocological substances changing the structure of bound water. 333 refs.; 79 tabs.

  15. Complexity, Analysis and Control of Singular Biological Systems

    CERN Document Server

    Zhang, Qingling; Zhang, Xue

    2012-01-01

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

  16. Network Reconstruction of Dynamic Biological Systems

    OpenAIRE

    Asadi, Behrang

    2013-01-01

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

  17. The Advanced LIGO timing system

    International Nuclear Information System (INIS)

    Bartos, Imre; Factourovich, Maxim; Marka, Szabolcs; Marka, Zsuzsa; Raics, Zoltan; Bork, Rolf; Heefner, Jay; Schwinberg, Paul; Sigg, Daniel

    2010-01-01

    Gravitational wave detection using a network of detectors relies upon the precise time stamping of gravitational wave signals. The relative arrival times between detectors are crucial, e.g. in recovering the source direction, an essential step in using gravitational waves for multi-messenger astronomy. Due to the large size of gravitational wave detectors, timing at different parts of a given detector also needs to be highly synchronized. In general, the requirement toward the precision of timing is determined such that, upon detection, the deduced (astro-) physical results should not be limited by the precision of timing. The Advanced LIGO optical timing distribution system is designed to provide UTC-synchronized timing information for the Advanced LIGO detectors that satisfies the above criterium. The Advanced LIGO timing system has modular structure, enabling quick and easy adaptation to the detector frame as well as possible changes or additions of components. It also includes a self-diagnostics system that enables the remote monitoring of the status of timing. After the description of the Advanced LIGO timing system, several tests are presented that demonstrate its precision and robustness.

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

    Science.gov (United States)

    Mitrokhin, Yuriy

    2014-10-21

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

  19. Systems biology of microbial exopolysaccharides production

    Directory of Open Access Journals (Sweden)

    Ozlem eAtes

    2015-12-01

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

  20. Systems Biology of Microbial Exopolysaccharides Production.

    Science.gov (United States)

    Ates, Ozlem

    2015-01-01

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

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

    Science.gov (United States)

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

    2012-08-29

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

  2. Integrating external biological knowledge in the construction of regulatory networks from time-series expression data

    Directory of Open Access Journals (Sweden)

    Lo Kenneth

    2012-08-01

    Full Text Available Abstract Background Inference about regulatory networks from high-throughput genomics data is of great interest in systems biology. We present a Bayesian approach to infer gene regulatory networks from time series expression data by integrating various types of biological knowledge. Results We formulate network construction as a series of variable selection problems and use linear regression to model the data. Our method summarizes additional data sources with an informative prior probability distribution over candidate regression models. We extend the Bayesian model averaging (BMA variable selection method to select regulators in the regression framework. We summarize the external biological knowledge by an informative prior probability distribution over the candidate regression models. Conclusions We demonstrate our method on simulated data and a set of time-series microarray experiments measuring the effect of a drug perturbation on gene expression levels, and show that it outperforms leading regression-based methods in the literature.

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

    Science.gov (United States)

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

    2017-07-05

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

  4. Primary energy-transformations in biological systems

    Energy Technology Data Exchange (ETDEWEB)

    Lehninger, A.L.

    1980-10-01

    In this paper I shall review the main outlines of current research on the molecular aspects of the primary energy-coupling mechanisms in cells, those carried out by energy-transducing membranes. They include the capture of solar energy by the chloroplast membranes of green plants, used to generate carbohydrates and molecular oxygen from carbon dioxide and water, and the counterpart of photosynthesis, the process of respiration in heterotrophic organisms, in which reduced organic products generated by photosynthesis are oxidized at the expense of dioxygen to form carbon dioxide and water. Although the cycling of dioxygen, carbon dioxide, and organic matter between the plant and animal worlds is well known, it is not generally appreciated that the magnitude of biological energy flux in these cycles is huge compared to the total energy flux in man-made devices. A major consequence is that the concentration of carbon dioxide in the atmosphere has been increasing at a significant rate, at a time when there is also a decrease, at least in some parts of the world, in the counterbalancing utilization of CO/sub 2/ by green plants, due to deforestation. The greenhouse effect of increased atmospheric CO/sub 2/ may not only change the earth's climate, but also may influence the rate of photosynthesis. It is also not generally appreciated that energy flow in the biosphere leads to production of enormous amounts of organic matter potentially useful in furnishing man's energy requirements.

  5. Quantifying electron transfer reactions in biological systems

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  6. Systems biology: properties of reconstructed networks

    National Research Council Canada - National Science Library

    Palsson, Bernhard

    2006-01-01

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

  7. Precision medicine driven by cancer systems biology.

    Science.gov (United States)

    Filipp, Fabian V

    2017-03-01

    Molecular insights from genome and systems biology are influencing how cancer is diagnosed and treated. We critically evaluate big data challenges in precision medicine. The melanoma research community has identified distinct subtypes involving chronic sun-induced damage and the mitogen-activated protein kinase driver pathway. In addition, despite low mutation burden, non-genomic mitogen-activated protein kinase melanoma drivers are found in membrane receptors, metabolism, or epigenetic signaling with the ability to bypass central mitogen-activated protein kinase molecules and activating a similar program of mitogenic effectors. Mutation hotspots, structural modeling, UV signature, and genomic as well as non-genomic mechanisms of disease initiation and progression are taken into consideration to identify resistance mutations and novel drug targets. A comprehensive precision medicine profile of a malignant melanoma patient illustrates future rational drug targeting strategies. Network analysis emphasizes an important role of epigenetic and metabolic master regulators in oncogenesis. Co-occurrence of driver mutations in signaling, metabolic, and epigenetic factors highlights how cumulative alterations of our genomes and epigenomes progressively lead to uncontrolled cell proliferation. Precision insights have the ability to identify independent molecular pathways suitable for drug targeting. Synergistic treatment combinations of orthogonal modalities including immunotherapy, mitogen-activated protein kinase inhibitors, epigenetic inhibitors, and metabolic inhibitors have the potential to overcome immune evasion, side effects, and drug resistance.

  8. Isotopic fractionation of tritium in biological systems.

    Science.gov (United States)

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

    2014-04-01

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

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

    Science.gov (United States)

    2011-01-01

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

  10. Real-time vision systems

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, R.; Hernandez, J.E.; Lu, Shin-yee [Lawrence Livermore National Lab., CA (United States)

    1994-11-15

    Many industrial and defence applications require an ability to make instantaneous decisions based on sensor input of a time varying process. Such systems are referred to as `real-time systems` because they process and act on data as it occurs in time. When a vision sensor is used in a real-time system, the processing demands can be quite substantial, with typical data rates of 10-20 million samples per second. A real-time Machine Vision Laboratory (MVL) was established in FY94 to extend our years of experience in developing computer vision algorithms to include the development and implementation of real-time vision systems. The laboratory is equipped with a variety of hardware components, including Datacube image acquisition and processing boards, a Sun workstation, and several different types of CCD cameras, including monochrome and color area cameras and analog and digital line-scan cameras. The equipment is reconfigurable for prototyping different applications. This facility has been used to support several programs at LLNL, including O Division`s Peacemaker and Deadeye Projects as well as the CRADA with the U.S. Textile Industry, CAFE (Computer Aided Fabric Inspection). To date, we have successfully demonstrated several real-time applications: bullet tracking, stereo tracking and ranging, and web inspection. This work has been documented in the ongoing development of a real-time software library.

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

    Science.gov (United States)

    Degrazio, Dominick

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

  12. The People's Time Sharing System

    NARCIS (Netherlands)

    Tanenbaum, A.S.; Benson, W.H.

    1973-01-01

    A set of programs running under a multiprogramming batch operating system on the CDC 6600 which provide remote users with a time sharing service is described. The basis for the system is the ability of a user program to create job control statements during execution, thereby tricking the operating

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

    KAUST Repository

    Nielsen, Jens

    2016-01-25

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

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

    DEFF Research Database (Denmark)

    Nielsen, Jens; Jewett, Michael Christopher

    2008-01-01

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

  15. Macroscopic Quantum-Type Potentials in Theoretical Systems Biology

    Directory of Open Access Journals (Sweden)

    Laurent Nottale

    2013-12-01

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

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

    DEFF Research Database (Denmark)

    Green, Sara; Serban, Maria; Scholl, Raphael

    2018-01-01

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    African Journals Online (AJOL)

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

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

    Indian Academy of Sciences (India)

    B J Rao

    2018-02-13

    Feb 13, 2018 ... Lorencova 2016), sociology, physics, computer science, economics and even biology ... dynamic complexity associated with them at multiple levels? .... Social anthropology and the science of chaos (Oxford: Berghahn Books).

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

    Science.gov (United States)

    Fletcher, Eugene; Krivoruchko, Anastasia; Nielsen, Jens

    2016-06-01

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

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

    DEFF Research Database (Denmark)

    Fletcher, Eugene; Krivoruchko, Anastasia; Nielsen, Jens

    2016-01-01

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

  2. Main injector synchronous timing system

    International Nuclear Information System (INIS)

    Blokland, W.; Steimel, J.

    1998-01-01

    The Synchronous Timing System is designed to provide sub-nanosecond timing to instrumentation during the acceleration of particles in the Main Injector. Increased energy of the beam particles leads to a small but significant increase in speed, reducing the time it takes to complete a full turn of the ring by 61 nanoseconds (or more than 3 rf buckets). In contrast, the reference signal, used to trigger instrumentation and transmitted over a cable, has a constant group delay. This difference leads to a phase slip during the ramp and prevents instrumentation such as dampers from properly operating without additional measures. The Synchronous Timing System corrects for this phase slip as well as signal propagation time changes due to temperature variations. A module at the LLRF system uses a 1.2 Gbit/s G-Link chip to transmit the rf clock and digital data (e.g. the current frequency) over a single mode fiber around the ring. Fiber optic couplers at service buildings split off part of this signal for a local module which reconstructs a synchronous beam reference signal. This paper describes the background, design and expected performance of the Synchronous Timing System. copyright 1998 American Institute of Physics

  3. Main injector synchronous timing system

    International Nuclear Information System (INIS)

    Blokland, Willem; Steimel, James

    1998-01-01

    The Synchronous Timing System is designed to provide sub-nanosecond timing to instrumentation during the acceleration of particles in the Main Injector. Increased energy of the beam particles leads to a small but significant increase in speed, reducing the time it takes to complete a full turn of the ring by 61 nanoseconds (or more than 3 rf buckets). In contrast, the reference signal, used to trigger instrumentation and transmitted over a cable, has a constant group delay. This difference leads to a phase slip during the ramp and prevents instrumentation such as dampers from properly operating without additional measures. The Synchronous Timing System corrects for this phase slip as well as signal propagation time changes due to temperature variations. A module at the LLRF system uses a 1.2 Gbit/s G-Link chip to transmit the rf clock and digital data (e.g. the current frequency) over a single mode fiber around the ring. Fiber optic couplers at service buildings split off part of this signal for a local module which reconstructs a synchronous beam reference signal. This paper describes the background, design and expected performance of the Synchronous Timing System

  4. Reaction times to weak test lights. [psychophysics biological model

    Science.gov (United States)

    Wandell, B. A.; Ahumada, P.; Welsh, D.

    1984-01-01

    Maloney and Wandell (1984) describe a model of the response of a single visual channel to weak test lights. The initial channel response is a linearly filtered version of the stimulus. The filter output is randomly sampled over time. Each time a sample occurs there is some probability increasing with the magnitude of the sampled response - that a discrete detection event is generated. Maloney and Wandell derive the statistics of the detection events. In this paper a test is conducted of the hypothesis that the reaction time responses to the presence of a weak test light are initiated at the first detection event. This makes it possible to extend the application of the model to lights that are slightly above threshold, but still within the linear operating range of the visual system. A parameter-free prediction of the model proposed by Maloney and Wandell for lights detected by this statistic is tested. The data are in agreement with the prediction.

  5. Evaluation of a commercial biologically based IMRT treatment planning system

    International Nuclear Information System (INIS)

    Semenenko, Vladimir A.; Reitz, Bodo; Day, Ellen; Qi, X. Sharon; Miften, Moyed; Li, X. Allen

    2008-01-01

    A new inverse treatment planning system (TPS) for external beam radiation therapy with high energy photons is commercially available that utilizes both dose-volume-based cost functions and a selection of cost functions which are based on biological models. The purpose of this work is to evaluate quality of intensity-modulated radiation therapy (IMRT) plans resulting from the use of biological cost functions in comparison to plans designed using a traditional TPS employing dose-volume-based optimization. Treatment planning was performed independently at two institutions. For six cancer patients, including head and neck (one case from each institution), prostate, brain, liver, and rectal cases, segmental multileaf collimator IMRT plans were designed using biological cost functions and compared with clinically used dose-based plans for the same patients. Dose-volume histograms and dosimetric indices, such as minimum, maximum, and mean dose, were extracted and compared between the two types of treatment plans. Comparisons of the generalized equivalent uniform dose (EUD), a previously proposed plan quality index (fEUD), target conformity and heterogeneity indices, and the number of segments and monitor units were also performed. The most prominent feature of the biologically based plans was better sparing of organs at risk (OARs). When all plans from both institutions were combined, the biologically based plans resulted in smaller EUD values for 26 out of 33 OARs by an average of 5.6 Gy (range 0.24 to 15 Gy). Owing to more efficient beam segmentation and leaf sequencing tools implemented in the biologically based TPS compared to the dose-based TPS, an estimated treatment delivery time was shorter in most (five out of six) cases with some plans showing up to 50% reduction. The biologically based plans were generally characterized by a smaller conformity index, but greater heterogeneity index compared to the dose-based plans. Overall, compared to plans based on dose

  6. Versatile timing system for MFTF

    International Nuclear Information System (INIS)

    Lau, N.H.C.

    1981-01-01

    This System consists of the Master Timing Transmitter and the Local Timing Receivers. The Master Timing Transmitter located in the control room initiates timing messages, abort messages and precise delay messages. A sync message is sent when one of the other three is not being sent. The Local Timing Receiver, located in the equipment area, decodes the incoming messages and generates 6 MHz, 3MHz and 1 MHz continuous clocks. A 250 KHz sync clock is derived from the sync messages, to which all pulse outputs are synchronized. The Local Timing Receiver also provides two ON-OFF delay counters of 64 bits each, and one OFF delay counter of 32 bits. Detection of abort messages and an out-of-sync signal will automatically disable all outputs

  7. From experimental systems to evolutionary biology: an impossible journey?

    Science.gov (United States)

    Morange, Michel

    2013-01-01

    The historical approach to the sciences has undergone a sea change during recent decades. Maybe the major contribution of Hans-Jörg Rheinberger to this movement was his demonstration of the importance of experimental systems, and of their transformations, in the development of the sciences. To describe these transformations, Hans-Jörg borrows metaphors from evolutionary biology. I want to argue that evolutionary biologists can find in these recent historical studies plenty of models and concepts to address unresolved issues in their discipline. At a time when transdisciplinarity is highly praised, it is useful to provide a precise description of the obstacles that have so far prevented this exchange.

  8. Mean Transit Time and Mean Residence Time for Linear Diffusion–Convection–Reaction Transport System

    Directory of Open Access Journals (Sweden)

    Jacek Waniewski

    2007-01-01

    Full Text Available Characteristic times for transport processes in biological systems may be evaluated as mean transit times (MTTs (for transit states or mean residence times (MRT (for steady states. It is shown in a general framework of a (linear reaction–diffusion–convection equation that these two times are related. Analytical formulas are also derived to calculate moments of exit time distribution using solutions for a stationary state of the system.

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

    Science.gov (United States)

    Noble, D

    2011-05-01

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

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

    CERN Document Server

    Noji, Sumihare; Ueno, Naoto; Maini, Philip

    2003-01-01

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

  11. A review of imaging techniques for systems biology

    Directory of Open Access Journals (Sweden)

    Po Ming J

    2008-08-01

    Full Text Available Abstract This paper presents a review of imaging techniques and of their utility in system biology. During the last decade systems biology has matured into a distinct field and imaging has been increasingly used to enable the interplay of experimental and theoretical biology. In this review, we describe and compare the roles of microscopy, ultrasound, CT (Computed Tomography, MRI (Magnetic Resonance Imaging, PET (Positron Emission Tomography, and molecular probes such as quantum dots and nanoshells in systems biology. As a unified application area among these different imaging techniques, examples in cancer targeting are highlighted.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2015-03-01

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

  14. Biological oceanography of the red oceanic system

    Science.gov (United States)

    Theil, Hjalmar; Weikert, Horst

    1. In 1977, 1979 and 1980-81, investigations were carried out which aimed at evaluating the potential risks from mining metalliferous muds precipating in the Atlantis II Deep of the central Red Sea. This environmental research was initiated by the Saudi Sudanese Red Sea Joint Commission in order to avoid any danger for the Red Sea ecosystem. The broad environmental research programme coherent studies in physical, chemical, biological, and geological oceanography as well as toxicological investigations in the oceanic and in reef zones. We summarise the results from our biological fiels studies in the open sea. 2. The biological investigations were concentrated on the area of the Atlantis II Deep. Benthos was sampled between 700-2000m. For comparison a few samples were also taken further north in the central Red Sea, and to east and west along the flanking deep terraces (500-1000m). Plankton studies covered the total water column above the Deep, and were extended along the axial through to north and south. 3. Benthos sampling was carried out using a heavy closing trawl, a large box grab (box size 50 × 50 cm), Van Veen grabs and traps; photographic surveys were made a phototrap and a photosled. Community respiration was measured with a ship-board method using grab subsamples. Nutrient concentrations, seston and phytoplankton standing stocks as well as in situ primary production were determined from hydrocast samples. Data on zooplankton and micronekton composition and standing stock were obtained from samples collected using different multiple opening-and-closing nets equipped with 100 μm, 300 μm, and 1000 μm mesh sizes. Daily and ontogenetical vertical migration patterns were studied by comparisons of data from midday and midnight tows. 4. Throughout the whole area the sediment is a pteropod ooze containing low contentrations of organic matter; measured organic carbon and nitrogen contents were 0.5 and 0.05% respectively, and chloroplastic pigment equivalents

  15. Multiway modeling and analysis in stem cell systems biology

    Directory of Open Access Journals (Sweden)

    Vandenberg Scott L

    2008-07-01

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

  16. Programming Morphogenesis through Systems and Synthetic Biology.

    Science.gov (United States)

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

    2018-04-01

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

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

    Science.gov (United States)

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

    2018-03-01

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  19. Mining biological information from 3D short time-series gene expression data: the OPTricluster algorithm.

    Science.gov (United States)

    Tchagang, Alain B; Phan, Sieu; Famili, Fazel; Shearer, Heather; Fobert, Pierre; Huang, Yi; Zou, Jitao; Huang, Daiqing; Cutler, Adrian; Liu, Ziying; Pan, Youlian

    2012-04-04

    Nowadays, it is possible to collect expression levels of a set of genes from a set of biological samples during a series of time points. Such data have three dimensions: gene-sample-time (GST). Thus they are called 3D microarray gene expression data. To take advantage of the 3D data collected, and to fully understand the biological knowledge hidden in the GST data, novel subspace clustering algorithms have to be developed to effectively address the biological problem in the corresponding space. We developed a subspace clustering algorithm called Order Preserving Triclustering (OPTricluster), for 3D short time-series data mining. OPTricluster is able to identify 3D clusters with coherent evolution from a given 3D dataset using a combinatorial approach on the sample dimension, and the order preserving (OP) concept on the time dimension. The fusion of the two methodologies allows one to study similarities and differences between samples in terms of their temporal expression profile. OPTricluster has been successfully applied to four case studies: immune response in mice infected by malaria (Plasmodium chabaudi), systemic acquired resistance in Arabidopsis thaliana, similarities and differences between inner and outer cotyledon in Brassica napus during seed development, and to Brassica napus whole seed development. These studies showed that OPTricluster is robust to noise and is able to detect the similarities and differences between biological samples. Our analysis showed that OPTricluster generally outperforms other well known clustering algorithms such as the TRICLUSTER, gTRICLUSTER and K-means; it is robust to noise and can effectively mine the biological knowledge hidden in the 3D short time-series gene expression data.

  20. Nuclear magnetic resonance studies of biological systems

    International Nuclear Information System (INIS)

    Antypas, W.G. Jr.

    1988-01-01

    The difference between intracellular and extracellular proton relaxation rates provides the basis for the determination of the mean hemoglobin concentration (MHC) in red blood cells. The observed water T 1 relaxation data from red blood cell samples under various conditions were fit to the complete equation for the time-dependent decay of magnetization for a two-compartment system including chemical exchange. The MHC for each sample was calculated from the hematocrit and the intracellular water fraction as determined by NMR. The binding of the phosphorylcholine (PC) analogue, 2-(trimethylphosphonio)-ethylphosphate (phosphoryl-phosphocholine, PPC) to the PC binding myeloma proteins TEPC-15, McPC 603, and MOPC 167 was studied by 31 P NMR

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

    Science.gov (United States)

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

    2017-11-01

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

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

    DEFF Research Database (Denmark)

    Green, Sara; Wolkenhauer, Olaf

    2014-01-01

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

  3. Yeast systems biology to unravel the network of life

    DEFF Research Database (Denmark)

    Mustacchi, Roberta; Hohmann, S; Nielsen, Jens

    2006-01-01

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

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

    Science.gov (United States)

    Jalili, Mahdi

    2018-03-01

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

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

    NARCIS (Netherlands)

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

    2016-01-01

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

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

    National Research Council Canada - National Science Library

    2001-01-01

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

  7. Automated Bayesian model development for frequency detection in biological time series

    Directory of Open Access Journals (Sweden)

    Oldroyd Giles ED

    2011-06-01

    Full Text Available Abstract Background A first step in building a mathematical model of a biological system is often the analysis of the temporal behaviour of key quantities. Mathematical relationships between the time and frequency domain, such as Fourier Transforms and wavelets, are commonly used to extract information about the underlying signal from a given time series. This one-to-one mapping from time points to frequencies inherently assumes that both domains contain the complete knowledge of the system. However, for truncated, noisy time series with background trends this unique mapping breaks down and the question reduces to an inference problem of identifying the most probable frequencies. Results In this paper we build on the method of Bayesian Spectrum Analysis and demonstrate its advantages over conventional methods by applying it to a number of test cases, including two types of biological time series. Firstly, oscillations of calcium in plant root cells in response to microbial symbionts are non-stationary and noisy, posing challenges to data analysis. Secondly, circadian rhythms in gene expression measured over only two cycles highlights the problem of time series with limited length. The results show that the Bayesian frequency detection approach can provide useful results in specific areas where Fourier analysis can be uninformative or misleading. We demonstrate further benefits of the Bayesian approach for time series analysis, such as direct comparison of different hypotheses, inherent estimation of noise levels and parameter precision, and a flexible framework for modelling the data without pre-processing. Conclusions Modelling in systems biology often builds on the study of time-dependent phenomena. Fourier Transforms are a convenient tool for analysing the frequency domain of time series. However, there are well-known limitations of this method, such as the introduction of spurious frequencies when handling short and noisy time series, and

  8. Automated Bayesian model development for frequency detection in biological time series.

    Science.gov (United States)

    Granqvist, Emma; Oldroyd, Giles E D; Morris, Richard J

    2011-06-24

    A first step in building a mathematical model of a biological system is often the analysis of the temporal behaviour of key quantities. Mathematical relationships between the time and frequency domain, such as Fourier Transforms and wavelets, are commonly used to extract information about the underlying signal from a given time series. This one-to-one mapping from time points to frequencies inherently assumes that both domains contain the complete knowledge of the system. However, for truncated, noisy time series with background trends this unique mapping breaks down and the question reduces to an inference problem of identifying the most probable frequencies. In this paper we build on the method of Bayesian Spectrum Analysis and demonstrate its advantages over conventional methods by applying it to a number of test cases, including two types of biological time series. Firstly, oscillations of calcium in plant root cells in response to microbial symbionts are non-stationary and noisy, posing challenges to data analysis. Secondly, circadian rhythms in gene expression measured over only two cycles highlights the problem of time series with limited length. The results show that the Bayesian frequency detection approach can provide useful results in specific areas where Fourier analysis can be uninformative or misleading. We demonstrate further benefits of the Bayesian approach for time series analysis, such as direct comparison of different hypotheses, inherent estimation of noise levels and parameter precision, and a flexible framework for modelling the data without pre-processing. Modelling in systems biology often builds on the study of time-dependent phenomena. Fourier Transforms are a convenient tool for analysing the frequency domain of time series. However, there are well-known limitations of this method, such as the introduction of spurious frequencies when handling short and noisy time series, and the requirement for uniformly sampled data. Biological time

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

    Directory of Open Access Journals (Sweden)

    Wright Jeremiah

    2008-06-01

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

  10. Scaling for Dynamical Systems in Biology.

    Science.gov (United States)

    Ledder, Glenn

    2017-11-01

    Asymptotic methods can greatly simplify the analysis of all but the simplest mathematical models and should therefore be commonplace in such biological areas as ecology and epidemiology. One essential difficulty that limits their use is that they can only be applied to a suitably scaled dimensionless version of the original dimensional model. Many books discuss nondimensionalization, but with little attention given to the problem of choosing the right scales and dimensionless parameters. In this paper, we illustrate the value of using asymptotics on a properly scaled dimensionless model, develop a set of guidelines that can be used to make good scaling choices, and offer advice for teaching these topics in differential equations or mathematical biology courses.

  11. Magnetic biosensor system to detect biological targets

    KAUST Repository

    Li, Fuquan

    2012-09-01

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

  12. Casual Games and Casual Learning About Human Biological Systems

    Science.gov (United States)

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

    2016-02-01

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

  13. Ion beam induced fluorescence imaging in biological systems

    International Nuclear Information System (INIS)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2017-03-28

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

  15. Systems biology and p4 medicine: past, present, and future.

    Science.gov (United States)

    Hood, Leroy

    2013-04-01

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

  16. Coinduction in concurrent timed systems

    Czech Academy of Sciences Publication Activity Database

    Komenda, Jan

    2010-01-01

    Roč. 264, č. 2 (2010), s. 177-197 ISSN 1571-0661 Grant - others:EU Projekt(XE) EU.ICT.DISC 224498 Institutional research plan: CEZ:AV0Z10190503 Keywords : timed discrete-event systems * partial Mealy automata * functional stream calculus * synchronous composition Subject RIV: BA - General Mathematics http://www.sciencedirect.com/science/article/pii/S1571066110000794

  17. The time is right: proteome biology of stem cells.

    NARCIS (Netherlands)

    Whetton, A.D.; Williamson, A.J.K.; Krijgsveld, J.; Lee, B.H.; Lemischka, I.; Oh, S.; Pera, M.; Mummery, C.L.; Heck, A.J.R.

    2008-01-01

    In stem cell biology, there is a growing need for advanced technologies that may help to unravel the molecular mechanisms of self-renewal and differentiation. Proteomics, the comprehensive analysis of proteins, is such an emerging technique. To facilitate interactions between specialists in

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

    Science.gov (United States)

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

    2014-03-01

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

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

    Science.gov (United States)

    Transtrum, Mark K; Qiu, Peng

    2016-05-01

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

  20. Fermi Timing and Synchronization System

    International Nuclear Information System (INIS)

    Wilcox, R.; Staples, J.; Doolittle, L.; Byrd, J.; Ratti, A.; Kaertner, F.X.; Kim, J.; Chen, J.; Ilday, F.O.; Ludwig, F.; Winter, A.; Ferianis, M.; Danailov, M.; D'Auria, G.

    2006-01-01

    The Fermi FEL will depend critically on precise timing of its RF, laser and diagnostic subsystems. The timing subsystem to coordinate these functions will need to reliably maintain sub-100fs synchronicity between distant points up to 300m apart in the Fermi facility. The technology to do this is not commercially available, and has not been experimentally demonstrated in a working facility. Therefore, new technology must be developed to meet these needs. Two approaches have been researched by different groups working with the Fermi staff. At MIT, a pulse transmission scheme has been developed for synchronization of RF and laser devices. And at LBL, a CW transmission scheme has been developed for RF and laser synchronization. These respective schemes have advantages and disadvantages that will become better understood in coming years. This document presents the work done by both teams, and suggests a possible system design which integrates them both. The integrated system design provides an example of how choices can be made between the different approaches without significantly changing the basic infrastructure of the system. Overall system issues common to any synchronization scheme are also discussed

  1. Fermi Timing and Synchronization System

    Energy Technology Data Exchange (ETDEWEB)

    Wilcox, R.; Staples, J.; Doolittle, L.; Byrd, J.; Ratti, A.; Kaertner, F.X.; Kim, J.; Chen, J.; Ilday, F.O.; Ludwig, F.; Winter, A.; Ferianis, M.; Danailov, M.; D' Auria, G.

    2006-07-19

    The Fermi FEL will depend critically on precise timing of its RF, laser and diagnostic subsystems. The timing subsystem to coordinate these functions will need to reliably maintain sub-100fs synchronicity between distant points up to 300m apart in the Fermi facility. The technology to do this is not commercially available, and has not been experimentally demonstrated in a working facility. Therefore, new technology must be developed to meet these needs. Two approaches have been researched by different groups working with the Fermi staff. At MIT, a pulse transmission scheme has been developed for synchronization of RF and laser devices. And at LBL, a CW transmission scheme has been developed for RF and laser synchronization. These respective schemes have advantages and disadvantages that will become better understood in coming years. This document presents the work done by both teams, and suggests a possible system design which integrates them both. The integrated system design provides an example of how choices can be made between the different approaches without significantly changing the basic infrastructure of the system. Overall system issues common to any synchronization scheme are also discussed.

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

    Directory of Open Access Journals (Sweden)

    Leroy Hood

    2013-04-01

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

  3. Dense time discretization technique for verification of real time systems

    International Nuclear Information System (INIS)

    Makackas, Dalius; Miseviciene, Regina

    2016-01-01

    Verifying the real-time system there are two different models to control the time: discrete and dense time based models. This paper argues a novel verification technique, which calculates discrete time intervals from dense time in order to create all the system states that can be reached from the initial system state. The technique is designed for real-time systems specified by a piece-linear aggregate approach. Key words: real-time system, dense time, verification, model checking, piece-linear aggregate

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

    Czech Academy of Sciences Publication Activity Database

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Bullinger Eric

    2006-12-01

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

  6. A systems biology approach to study systemic inflammation.

    Science.gov (United States)

    Chen, Bor-Sen; Wu, Chia-Chou

    2014-01-01

    Systemic inflammation needs a precise control on the sequence and magnitude of occurring events. The high throughput data on the host-pathogen interactions gives us an opportunity to have a glimpse on the systemic inflammation. In this article, a dynamic Candida albicans-zebrafish interactive infectious network is built as an example to demonstrate how systems biology approach can be used to study systematic inflammation. In particular, based on microarray data of C. albicans and zebrafish during infection, the hyphal growth, zebrafish, and host-pathogen intercellular PPI networks were combined to form an integrated infectious PPI network that helps us understand the systematic mechanisms underlying the pathogenicity of C. albicans and the immune response of the host. The signaling pathways for morphogenesis and hyphal growth of C. albicans were 2 significant interactions found in the intercellular PPI network. Two cellular networks were also developed corresponding to the different infection stages (adhesion and invasion), and then compared with each other to identify proteins to gain more insight into the pathogenic role of hyphal development in the C. albicans infection process. Important defense-related proteins in zebrafish were predicted using the same approach. This integrated network consisting of intercellular invasion and cellular defense processes during infection can improve medical therapies and facilitate development of new antifungal drugs.

  7. Mobile real time radiography system

    Energy Technology Data Exchange (ETDEWEB)

    Vigil, J.; Taggart, D.; Betts, S. [Los Alamos National Lab., NM (United States)] [and others

    1997-11-01

    A 450-keV Mobile Real Time Radiography (RTR) System was delivered to Los Alamos National Laboratory (LANL) in January 1996. It was purchased to inspect containers of radioactive waste produced at (LANL). Since its delivery it has been used to radiograph more than 600 drums of radioactive waste at various LANL sites. It has the capability of inspecting waste containers of various sizes from <1-gal. buckets up to standard waste boxes (SWB, dimensions 54.5 in. x 71 in. x 37 in.). It has three independent x-ray acquisition formats. The primary system used is a 12- in. image intensifier, the second is a 36-in. linear diode array (LDA) and the last is an open system. It is fully self contained with on board generator, HVAC, and a fire suppression system. It is on a 53-ft long x 8-ft. wide x 14-ft. high trailer that can be moved over any highway requiring only an easily obtainable overweight permit because it weights {approximately}38 tons. It was built to conform to industry standards for a cabinet system which does not require an exclusion zone. The fact that this unit is mobile has allowed us to operate where the waste is stored, rather than having to move the waste to a fixed facility.

  8. Space-Time Reference Systems

    CERN Document Server

    Soffel, Michael

    2013-01-01

    The high accuracy of modern astronomical spatial-temporal reference systems has made them considerably complex. This book offers a comprehensive overview of such systems. It begins with a discussion of ‘The Problem of Time’, including recent developments in the art of clock making (e.g., optical clocks) and various time scales. The authors address  the definitions and realization of spatial coordinates by reference to remote celestial objects such as quasars. After an extensive treatment of classical equinox-based coordinates, new paradigms for setting up a celestial reference system are introduced that no longer refer to the translational and rotational motion of the Earth. The role of relativity in the definition and realization of such systems is clarified. The topics presented in this book are complemented by exercises (with solutions). The authors offer a series of files, written in Maple, a standard computer algebra system, to help readers get a feel for the various models and orders of magnitude. ...

  9. Mobile real time radiography system

    International Nuclear Information System (INIS)

    Vigil, J.; Taggart, D.; Betts, S.

    1997-01-01

    A 450-keV Mobile Real Time Radiography (RTR) System was delivered to Los Alamos National Laboratory (LANL) in January 1996. It was purchased to inspect containers of radioactive waste produced at (LANL). Since its delivery it has been used to radiograph more than 600 drums of radioactive waste at various LANL sites. It has the capability of inspecting waste containers of various sizes from <1-gal. buckets up to standard waste boxes (SWB, dimensions 54.5 in. x 71 in. x 37 in.). It has three independent x-ray acquisition formats. The primary system used is a 12- in. image intensifier, the second is a 36-in. linear diode array (LDA) and the last is an open system. It is fully self contained with on board generator, HVAC, and a fire suppression system. It is on a 53-ft long x 8-ft. wide x 14-ft. high trailer that can be moved over any highway requiring only an easily obtainable overweight permit because it weights ∼38 tons. It was built to conform to industry standards for a cabinet system which does not require an exclusion zone. The fact that this unit is mobile has allowed us to operate where the waste is stored, rather than having to move the waste to a fixed facility

  10. A real time monitoring system

    International Nuclear Information System (INIS)

    Fontanini, Horacio; Galdoz, Erwin

    1989-01-01

    A real time monitoring system is described. It was initially developed to be used as a man-machine interface between a basic principles simulator of the Embalse Nuclear Power Plant and the operators. This simulator is under construction at the Bariloche Atomic Center's Process Control Division. Due to great design flexibility, this system can also be used in real plants. The system is designed to be run on a PC XT or AT personal computer with high resolution graphics capabilities. Three interrelated programs compose the system: 1) Graphics Editor, to build static image to be used as a reference frame where to show dynamically updated data. 2) Data acquisition and storage module. It is a memory resident module to acquire and store data in background. Data can be acquired and stored without interference with the operating system, via serial port or through analog-to-digital converter attached to the personal computer. 3) Display module. It shows the acquired data according to commands received from configuration files prepared by the operator. (Author) [es

  11. Race in an epigenetic time: thinking biology in the plural.

    Science.gov (United States)

    Meloni, Maurizio

    2017-09-01

    The notion that biological memories of environmental experiences can be embedded in the human genome and even transmitted transgenerationally is increasingly relevant in the postgenomic world, particularly in molecular epigenetics, where the genome is conceptualized as porous to environmental signals. In this article I discuss the current rethinking of race in epigenetic rather than genetic terms, emphasizing some of its paradoxical implications, especially for public policy. I claim in particular that: (i) if sociologists want to investigate race in a postgenomic world they should pay more attention to this novel plastic and biosocial view of race; and (ii) there are no reasons to believe that an epigenetic view will extinguish race, or that soft-inheritance claims will produce a less exclusionary discourse than genetics (hard heredity). Quite the opposite, the ground for a re-racialization of social debates and the reinforcement of biological boundaries between groups are highlighted in the article. © London School of Economics and Political Science 2017.

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

    Science.gov (United States)

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

    2015-08-21

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

  13. Universally sloppy parameter sensitivities in systems biology models.

    Directory of Open Access Journals (Sweden)

    Ryan N Gutenkunst

    2007-10-01

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

  14. Universally sloppy parameter sensitivities in systems biology models.

    Science.gov (United States)

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

    2007-10-01

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

  15. Relational time in anyonic systems

    Science.gov (United States)

    Nikolova, A.; Brennen, G. K.; Osborne, T. J.; Milburn, G. J.; Stace, T. M.

    2018-03-01

    In a seminal paper [Phys. Rev. D 27, 2885 (1983), 10.1103/PhysRevD.27.2885], Page and Wootters suggest that time evolution could be described solely in terms of correlations between systems and clocks, as a means of dealing with the "problem of time" stemming from vanishing Hamiltonian dynamics in many theories of quantum gravity. Their approach seeks to identify relational dynamics given a Hamiltonian constraint on the physical states. Here we present a "state-centric" reformulation of the Page and Wootters model better suited to cases where the Hamiltonian constraint is satisfied, such as anyons emerging in Chern-Simons theories. We describe relational time by encoding logical "clock" qubits into topologically protected anyonic degrees of freedom. The minimum temporal increment of such anyonic clocks is determined by the universality of the anyonic braid group, with nonuniversal models naturally exhibiting discrete time. We exemplify this approach by using SU (2) 2 anyons and discuss generalizations to other states and models.

  16. Optical Time-of-Flight and Absorbance Imaging of Biologic Media

    Science.gov (United States)

    Benaron, David A.; Stevenson, David K.

    1993-03-01

    Imaging the interior of living bodies with light may assist in the diagnosis and treatment of a number of clinical problems, which include the early detection of tumors and hypoxic cerebral injury. An existing picosecond time-of-flight and absorbance (TOFA) optical system has been used to image a model biologic system and a rat. Model measurements confirmed TOFA principles in systems with a high degree of photon scattering; rat images, which were constructed from the variable time delays experienced by a fixed fraction of early-arriving transmitted photons, revealed identifiable internal structure. A combination of light-based quantitative measurement and TOFA localization may have applications in continuous, noninvasive monitoring for structural imaging and spatial chemometric analysis in humans.

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

    Science.gov (United States)

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

    2014-01-01

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

  18. Sensitivity analysis approaches applied to systems biology models.

    Science.gov (United States)

    Zi, Z

    2011-11-01

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

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

    OpenAIRE

    Webb Penelope A; Hodgkinson Matt J

    2007-01-01

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

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

    Science.gov (United States)

    Hodgkinson, Matt J; Webb, Penelope A

    2007-09-04

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

  1. Systems biology of neutrophil differentiation and immune response

    DEFF Research Database (Denmark)

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

    2005-01-01

    Systems biology has emerged as a new scientific field, which aims at investigating biological processes at the genomic and proteomic levels. Recent studies have unravelled aspects of neutrophil differentiation and immune responses at the systems level using high-throughput technologies. These stu......Systems biology has emerged as a new scientific field, which aims at investigating biological processes at the genomic and proteomic levels. Recent studies have unravelled aspects of neutrophil differentiation and immune responses at the systems level using high-throughput technologies....... These studies have identified a plethora of novel effector proteins stored in the granules of neutrophils. In addition, these studies provide evidence that neutrophil differentiation and immune response are governed by a highly coordinated transcriptional programme that regulates cellular fate and function...

  2. Systems biology approaches to the study of cardiovascular drugs

    NARCIS (Netherlands)

    Nikolsky, Y.; Kleemann, R.

    2010-01-01

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

  3. Strategies for structuring interdisciplinary education in Systems Biology

    DEFF Research Database (Denmark)

    Cvijovic, Marija; Höfer, Thomas; Aćimović, Jure

    2016-01-01

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

  4. Time delay systems theory, numerics, applications, and experiments

    CERN Document Server

    Ersal, Tulga; Orosz, Gábor

    2017-01-01

    This volume collects contributions related to selected presentations from the 12th IFAC Workshop on Time Delay Systems, Ann Arbor, June 28-30, 2015. The included papers present novel techniques and new results of delayed dynamical systems. The topical spectrum covers control theory, numerical analysis, engineering and biological applications as well as experiments and case studies. The target audience primarily comprises research experts in the field of time delay systems, but the book may also be beneficial for graduate students alike. .

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

    OpenAIRE

    I. C. Baianu

    2012-01-01

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

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

    CERN Document Server

    Érdi, Péter; Lente, Gabor

    2014-01-01

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

  7. Complex systems of biological interest stability under ionising radiations

    International Nuclear Information System (INIS)

    Maclot, Sylvain

    2014-01-01

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

  8. Biological causal links on physiological and evolutionary time scales.

    Science.gov (United States)

    Karmon, Amit; Pilpel, Yitzhak

    2016-04-26

    Correlation does not imply causation. If two variables, say A and B, are correlated, it could be because A causes B, or that B causes A, or because a third factor affects them both. We suggest that in many cases in biology, the causal link might be bi-directional: A causes B through a fast-acting physiological process, while B causes A through a slowly accumulating evolutionary process. Furthermore, many trained biologists tend to consistently focus at first on the fast-acting direction, and overlook the slower process in the opposite direction. We analyse several examples from modern biology that demonstrate this bias (codon usage optimality and gene expression, gene duplication and genetic dispensability, stem cell division and cancer risk, and the microbiome and host metabolism) and also discuss an example from linguistics. These examples demonstrate mutual effects between the fast physiological processes and the slow evolutionary ones. We believe that building awareness of inference biases among biologists who tend to prefer one causal direction over another could improve scientific reasoning.

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

    Science.gov (United States)

    Fletcher, Liz; Rosser, Susan; Elfick, Alistair

    2016-06-15

    The Centre for Synthetic and Systems Biology ('SynthSys') was originally established in 2007 as the Centre for Integrative Systems Biology, funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Engineering and Physical Sciences Research Council (EPSRC). Today, SynthSys embraces an extensive multidisciplinary community of more than 200 researchers from across the University with a common interest in synthetic and systems biology. Our research is broad and deep, addressing a diversity of scientific questions, with wide ranging impact. We bring together the power of synthetic biology and systems approaches to focus on three core thematic areas: industrial biotechnology, agriculture and the environment, and medicine and healthcare. In October 2015, we opened a newly refurbished building as a physical hub for our new U.K. Centre for Mammalian Synthetic Biology funded by the BBSRC/EPSRC/MRC as part of the U.K. Research Councils' Synthetic Biology for Growth programme. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  10. Fast removal of oxygen from biological systems

    International Nuclear Information System (INIS)

    Dewey, D.L.; Michael, B.D.

    1975-01-01

    Reference is made to the fact that if radiation is given at a high enough dose rate, the biological effect of oxygen is less than at low dose rates. Examples are given of 'break-point' experiments showing the effect. It is stated that the rapid removal of a substance by radiation is not confined to oxygen: the only criterion required to demonstrate the effect is that the chemical causes a measurable sensitization or protection at a concentration small enough so that it can be depleted at a relatively low dose of radiation. Sufficient confidence is now placed in the effect that it can be used the other way round; that is, to measure the position of the break-point and from this measurement determine the oxygen concentration at the target site at the instant before irradiation. Examples are given of the use of the high dose rate technique for measuring the oxygen concentration inside mammalian cells (Chinese hamster cells). The effects of partial pressures of inert gases, and the effect of elevated gas pressures, are discussed. (U.K.)

  11. What does systems biology mean for drug development?

    Science.gov (United States)

    Schrattenholz, André; Soskić, Vukić

    2008-01-01

    The complexity and flexibility of cellular architectures is increasingly recognized by impressive progress on the side of molecular analytics, i.e. proteomics, genomics and metabolomics. One of the messages from systems biology is that the number of molecular species in cellular networks is orders of magnitude bigger than anticipated by genomic analysis, in particular by fast posttranslational modifications of proteins. The requirements to manage external signals, integrate spatiotemporal signal transduction inside an organism and at the same time optimizing networks of biochemical and chemical reactions result in chemically extremely fine tuned molecular entities. Chemical side reactions of enzymatic activity, like e.g. random oxidative damage of proteins by free radicals during aging constantly introduce epigenetic alterations of protein targets. These events gradually and on an individual stochastic scale, keep modifying activities of these targets, and their affinities and selectivities towards biological and pharmacological ligands. One further message is that many of the key reactions in living systems are essentially based on interactions of low affinities and even low selectivities. This principle is responsible for the enormous flexibility and redundancy of cellular circuitries. So, in complex disorders like cancer or neurodegenerative diseases, which are rooted in relatively subtle and multimodal dysfunction of important physiologic pathways, drug discovery programs based on the concept of high affinity/high specificity compounds ("one-target, one-disease"), which still dominate the pharmaceutical industry increasingly turn out to be unsuccessful. Despite improvements in rational drug design and high throughput screening methods, the number of novel, single-target drugs fell much behind expectations during the past decade and the treatment of "complex diseases" remains a most pressing medical need. Currently a change of paradigm can be observed with

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

    Science.gov (United States)

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

    2018-03-01

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

  13. System chemical biology studies of endocrine disruptors

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Oprea, Tudor I.

    Endocrine disrupting chemicals (EDCs) alter hormonal balance and other physiological systems through inappropriate developmental or adult exposure, perturbing the reproductive function of further generations. While disruption of key receptors (e.g., estrogen, androgen, and thyroid) at the ligand...

  14. A Generic Language for Biological Systems based on Bigraphs

    DEFF Research Database (Denmark)

    Damgaard, Troels Christoffer; Krivine, Jean

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

  15. Modeling life the mathematics of biological systems

    CERN Document Server

    Garfinkel, Alan; Guo, Yina

    2017-01-01

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

  16. Biologically inspired collision avoidance system for unmanned vehicles

    Science.gov (United States)

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

    2009-05-01

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

  17. Amoxicillin in a biological water recovery system

    International Nuclear Information System (INIS)

    Morse, A.; Jackson, A.; Rainwater, K.; Pickering, K.

    2002-01-01

    Pharmaceuticals are new contaminants of concern in the aquatic environment, having been identified in groundwater, surface water, and residential tap water. Possible sources of pharmaceuticals include household wastewaters, runoff from feedlots, or waste discharges from pharmaceutical manufacturing plants. When surface water or groundwater supplies impacted by pharmaceuticals are used in drinking water production, the contaminants may reduce drinking water quality. Many pharmaceuticals, such as amoxicillin, pass through the body largely unmetabolized and directly enter wastewater collection systems. Pharmaceuticals are designed to persist in the body long enough to have the desired therapeutic effect. Therefore, they may also have the ability to persist in the environment (Seiler et al, 1999). The purpose of this work is to determine the overall transformation potential of a candidate pharmaceutical in wastewater treatment with specific emphasis on recycle systems. Amoxicillin is the selected pharmaceutical agent, an orally absorbed broad-spectrum antibiotic with a variety of clinical uses including ear, nose, and throat infections and lower respiratory tract infections. Experiments were conducted using an anaerobic reactor (with NO 3 - and NO 2 - as the e - acceptors) followed by a two-phase nitrifying tubular reactor. Influent composed of water, urine and surfactant was spiked with amoxicillin and fed into the wastewater recycle system. The concentration of amoxicillin in the feed and effluent was quantified using an HPLC. Results from this study include potential for long-term buildup in recycled systems, accumulation of breakdown products and possible transfer of antibiotic resistance to microorganisms in the system effluent. In addition, the results of this study may provide information on contamination potential for communities that are considering supplementing drinking water supplies with recovered wastewater or for entities considering a closed loop

  18. PathSys: integrating molecular interaction graphs for systems biology

    Directory of Open Access Journals (Sweden)

    Raval Alpan

    2006-02-01

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

  19. Single molecule tools for enzymology, structural biology, systems biology and nanotechnology: an update

    Science.gov (United States)

    Widom, Julia R.; Dhakal, Soma; Heinicke, Laurie A.; Walter, Nils G.

    2015-01-01

    Toxicology is the highly interdisciplinary field studying the adverse effects of chemicals on living organisms. It requires sensitive tools to detect such effects. After their initial implementation during the 1990s, single-molecule fluorescence detection tools were quickly recognized for their potential to contribute greatly to many different areas of scientific inquiry. In the intervening time, technical advances in the field have generated ever-improving spatial and temporal resolution, and have enabled the application of single-molecule fluorescence to increasingly complex systems, such as live cells. In this review, we give an overview of the optical components necessary to implement the most common versions of single-molecule fluorescence detection. We then discuss current applications to enzymology and structural studies, systems biology, and nanotechnology, presenting the technical considerations that are unique to each area of study, along with noteworthy recent results. We also highlight future directions that have the potential to revolutionize these areas of study by further exploiting the capabilities of single-molecule fluorescence microscopy. PMID:25212907

  20. Geological Time, Biological Events and the Learning Transfer Problem

    Science.gov (United States)

    Johnson, Claudia C.; Middendorf, Joan; Rehrey, George; Dalkilic, Mehmet M.; Cassidy, Keely

    2014-01-01

    Comprehension of geologic time does not come easily, especially for students who are studying the earth sciences for the first time. This project investigated the potential success of two teaching interventions that were designed to help non-science majors enrolled in an introductory geology class gain a richer conceptual understanding of the…

  1. Time Error Analysis of SOE System Using Network Time Protocol

    International Nuclear Information System (INIS)

    Keum, Jong Yong; Park, Geun Ok; Park, Heui Youn

    2005-01-01

    To find the accuracy of time in the fully digitalized SOE (Sequence of Events) system, we used a formal specification of the Network Time Protocol (NTP) Version 3, which is used to synchronize time keeping among a set of distributed computers. Through constructing a simple experimental environments and experimenting internet time synchronization, we analyzed the time errors of local clocks of SOE system synchronized with a time server via computer networks

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

    Science.gov (United States)

    Molnár, László; Vágó, István; Fehér, András

    2003-01-01

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

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

    Science.gov (United States)

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

    2013-09-05

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

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

    Science.gov (United States)

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

    2010-11-29

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

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

    Science.gov (United States)

    He, Xiaoming

    2011-01-01

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  7. Applications of dynamical systems in biology and medicine

    CERN Document Server

    Radunskaya, Ami

    2015-01-01

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

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

    Science.gov (United States)

    Sethi, S. L.

    1975-01-01

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

  9. Quantum and classical dynamics in biologically inspired systems

    International Nuclear Information System (INIS)

    Guerreschi, G.

    2012-01-01

    Quantum biology is an emerging field in which traditional believes and paradigms are under examination. Typically, quantum effects are witnessed inside quantum optics or atomic physics laboratories in systems which are kept under control and isolated from any noise source by means of very advanced technology. Biological systems exhibit opposite characteristics: They are usually constituted of macromolecules continuously exposed to a warm and wet environment, well beyond our control; but at the same time, they operate far away from equilibrium. Recently, the experimental observation of excitonic coherence in photosynthetic complexes has con firmed that, in non-equilibrium scenarios, quantum phenomena can survive even in presence of a noisy environment. The challenge faced by the ongoing research is twofold: On one side, considering biological molecules as effective nanomachines, one has to address questions of principle regarding their design and functioning; on the other side, one has to investigate real systems which are experimentally accessible and identify such features in these concrete scenarios. The present thesis contributes to both of these aspects. In Part I, we demonstrate how entanglement can be persistently generated even under unfavorable environmental conditions. The physical mechanism is modeled after the idea of conformational changes, and it relies on the interplay of classical oscillations of large structures with the quantum dynamics of a few interacting degrees of freedom. In a similar context, we show that the transfer of an excitation through a linear chain of sites can be enhanced when the inter-site distances oscillate periodically. This enhancement is present even in comparison with the static con figuration which is optimal in the classical case and, therefore, it constitutes a clear signature of the underlying quantum dynamics. In Part II of this thesis, we study the radical pair mechanism from the perspective of quantum control and

  10. Biological effects of particles from the paris subway system.

    Science.gov (United States)

    Bachoual, Rafik; Boczkowski, Jorge; Goven, Delphine; Amara, Nadia; Tabet, Lyes; On, Dinhill; Leçon-Malas, Véronique; Aubier, Michel; Lanone, Sophie

    2007-10-01

    Particulate matter (PM) from atmospheric pollution can easily deposit in the lungs and induce recruitment of inflammatory cells, a source of inflammatory cytokines, oxidants, and matrix metalloproteases (MMPs), which are important players in lung structural homeostasis. In many large cities, the subway system is a potent source of PM emission, but little is known about the biological effects of PM from this source. We performed a comprehensive study to evaluate the biological effects of PM sampled at two sites (RER and Metro) in the Paris subway system. Murine macrophages (RAW 264.7) and C57Bl/6 mice, respectively, were exposed to 0.01-10 microg/cm2 and 5-100 microg/mouse subway PM or reference materials [carbon black (CB), titanium dioxide (TiO2), or diesel exhaust particles (DEPs)]. We analyzed cell viability, production of cellular and lung proinflammatory cytokines [tumor necrosis factor alpha (TNFalpha), macrophage inflammatory protein (MIP-2), KC (the murin analog of interleukin-8), and granulocyte macrophage-colony stimulating factor (GM-CSF)], and mRNA or protein expression of MMP-2, -9, and -12 and heme oxygenase-1 (HO-1). Deferoxamine and polymixin B were used to evaluate the roles of iron and endotoxin, respectively. Noncytotoxic concentrations of subway PM (but not CB, TiO2, or DEPs) induced a time- and dose-dependent increase in TNFalpha and MIP-2 production by RAW 264.7 cells, in a manner involving, at least in part, PM iron content (34% inhibition of TNF production 8 h after stimulation of RAW 264.7 cells with 10 microg/cm2 RER particles pretreated with deferoxamine). Similar increased cytokine production was transiently observed in vivo in mice and was accompanied by an increased neutrophil cellularity of bronchoalveolar lavage (84.83+/-0.98% of polymorphonuclear neutrophils for RER-treated mice after 24 h vs 7.33+/-0.99% for vehicle-treated animals). Subway PM induced an increased expression of MMP-12 and HO-1 both in vitro and in vivo. PM from the

  11. Systems-biology dissection of eukaryotic cell growth

    Directory of Open Access Journals (Sweden)

    Andrews Justen

    2010-05-01

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

  12. Modeling of biological intelligence for SCM system optimization.

    Science.gov (United States)

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

    2012-01-01

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

  13. Dietary antioxidant synergy in chemical and biological systems.

    Science.gov (United States)

    Wang, Sunan; Zhu, Fan

    2017-07-24

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

  14. Modeling of Biological Intelligence for SCM System Optimization

    Directory of Open Access Journals (Sweden)

    Shengyong Chen

    2012-01-01

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

  15. Modeling of Biological Intelligence for SCM System Optimization

    Science.gov (United States)

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

    2012-01-01

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

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

    International Nuclear Information System (INIS)

    Kim, M.A.; Baumgaertner, Franz

    1989-01-01

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

  17. Vibrational resonances in biological systems at microwave frequencies.

    Science.gov (United States)

    Adair, Robert K

    2002-03-01

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

  18. Upshot of the ripening time on biological activities, phenol content ...

    African Journals Online (AJOL)

    Anis

    2013-10-02

    Oct 2, 2013 ... ripening time, seed count and ability to reflow (Wessels,. 1988; Pimienta, 1990 .... at 50°C for 120 min, and the absorbance was measured using a model EAR 400 micro .... regenerate the ''active” reduced antioxidant. Iron reducing .... adsorption to cell membranes, interaction with enzymes, substrate and ...

  19. A New Data Management System for Biological and Chemical Oceanography

    Science.gov (United States)

    Groman, R. C.; Chandler, C.; Allison, D.; Glover, D. M.; Wiebe, P. H.

    2007-12-01

    The Biological and Chemical Oceanography Data Management Office (BCO-DMO) was created to serve PIs principally funded by NSF to conduct marine chemical and ecological research. The new office is dedicated to providing open access to data and information developed in the course of scientific research on short and intermediate time-frames. The data management system developed in support of U.S. JGOFS and U.S. GLOBEC programs is being modified to support the larger scope of the BCO-DMO effort, which includes ultimately providing a way to exchange data with other data systems. The open access system is based on a philosophy of data stewardship, support for existing and evolving data standards, and use of public domain software. The DMO staff work closely with originating PIs to manage data gathered as part of their individual programs. In the new BCO-DMO data system, project and data set metadata records designed to support re-use of the data are stored in a relational database (MySQL) and the data are stored in or made accessible by the JGOFS/GLOBEC object- oriented, relational, data management system. Data access will be provided via any standard Web browser client user interface through a GIS application (Open Source, OGC-compliant MapServer), a directory listing from the data holdings catalog, or a custom search engine that facilitates data discovery. In an effort to maximize data system interoperability, data will also be available via Web Services; and data set descriptions will be generated to comply with a variety of metadata content standards. The office is located at the Woods Hole Oceanographic Institution and web access is via http://www.bco-dmo.org.

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

    Science.gov (United States)

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

    2017-08-01

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

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

    DEFF Research Database (Denmark)

    Mardare, Radu Iulian; Ihekwaba, Adoha

    2007-01-01

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  3. Hepatocellular carcinoma: a systems biology perspective

    Directory of Open Access Journals (Sweden)

    Lorenza Alice D'alessandro

    2013-02-01

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

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

    Science.gov (United States)

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

    2015-07-11

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-12-09

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

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  7. Systems, Shocks and Time Bombs

    Science.gov (United States)

    Winder, Nick

    The following sections are included: * Introduction * Modelling strategies * Are time-bomb phenomena important? * Heuristic approaches to time-bomb phenomena * Three rational approaches to TBP * Two irrational approaches * Conclusions * References

  8. Time Warp Operating System (TWOS)

    Science.gov (United States)

    Bellenot, Steven F.

    1993-01-01

    Designed to support parallel discrete-event simulation, TWOS is complete implementation of Time Warp mechanism - distributed protocol for virtual time synchronization based on process rollback and message annihilation.

  9. Astrobiology Extends Biology into Deep Time and Space

    Science.gov (United States)

    Desmarais, David

    2003-01-01

    To understand our own origins and to search for biospheres beyond Earth, we need a more robust concept of life itself. We must learn how to discriminate between attributes that are fundamental to all living systems versus those that represent principally local outcomes of long-term survival on Earth. We should identify the most basic environmental needs of life, chart the distribution of other habitable worlds, and understand the factors that created their distribution. Studies of microbial communities and the geologic record will be summarized that offer clues about the early evolution of our own biosphere as well as the signatures of life that we might find in the heavens.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    CERN Document Server

    Suraishkumar, G K

    2014-01-01

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

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

    Science.gov (United States)

    Engelhardt, Benjamin; Frőhlich, Holger; Kschischo, Maik

    2016-02-11

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

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

    Science.gov (United States)

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

    2018-04-01

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

  14. Glycoengineering in CHO cells: Advances in systems biology

    DEFF Research Database (Denmark)

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

    2018-01-01

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

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

    Science.gov (United States)

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

    2011-06-22

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

  16. Optical sensors and their applications for probing biological systems

    DEFF Research Database (Denmark)

    Palanco, Marta Espina

    There is a great interest in exploring and developing new optical sensitive methodologies for probing complex biological systems. In this project we developed non-invasive and sensitive biosensor strategies for studying physiologically relevant chemical and physical properties of plant and mammal......There is a great interest in exploring and developing new optical sensitive methodologies for probing complex biological systems. In this project we developed non-invasive and sensitive biosensor strategies for studying physiologically relevant chemical and physical properties of plant...... of a trapped cell. The project could provide new insights into the desired biosensor for future membrane-protein cell studies....

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

    OpenAIRE

    Wright, J; Wagner, A

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Li-Ling Lin

    2012-01-01

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

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

    KAUST Repository

    Klingbeil, G.

    2011-02-25

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

  20. Agent-Based Modeling in Molecular Systems Biology.

    Science.gov (United States)

    Soheilypour, Mohammad; Mofrad, Mohammad R K

    2018-06-08

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

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

    Science.gov (United States)

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

    2018-05-09

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

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  3. Formal Modeling and Analysis of Timed Systems

    DEFF Research Database (Denmark)

    Larsen, Kim Guldstrand; Niebert, Peter

    This book constitutes the thoroughly refereed post-proceedings of the First International Workshop on Formal Modeling and Analysis of Timed Systems, FORMATS 2003, held in Marseille, France in September 2003. The 19 revised full papers presented together with an invited paper and the abstracts of ...... systems, discrete time systems, timed languages, and real-time operating systems....... of two invited talks were carefully selected from 36 submissions during two rounds of reviewing and improvement. All current aspects of formal method for modeling and analyzing timed systems are addressed; among the timed systems dealt with are timed automata, timed Petri nets, max-plus algebras, real-time......This book constitutes the thoroughly refereed post-proceedings of the First International Workshop on Formal Modeling and Analysis of Timed Systems, FORMATS 2003, held in Marseille, France in September 2003. The 19 revised full papers presented together with an invited paper and the abstracts...

  4. Real Time Advanced Clustering System

    Directory of Open Access Journals (Sweden)

    Giuseppe Spampinato

    2017-05-01

    Full Text Available This paper describes a system to gather information from a stationary camera to identify moving objects. The proposed solution makes only use of motion vectors between adjacent frames, obtained from any algorithm. Starting from them, the system is able to retrieve clusters of moving objects in a scene acquired by an image sensor device. Since all the system is only based on optical flow, it is really simple and fast, to be easily integrated directly in low cost cameras. The experimental results show fast and robust performance of our method. The ANSI-C code has been tested on the ARM Cortex A15 CPU @2.32GHz, obtaining an impressive fps, about 3000 fps, excluding optical flow computation and I/O. Moreover, the system has been tested for different applications, cross traffic alert and video surveillance, in different conditions, indoor and outdoor, and with different lenses.

  5. Real-time systems architectures

    International Nuclear Information System (INIS)

    Sendall, D.M.

    1986-01-01

    The aim of this paper is to explore some of the design issues in online data acquisition and monitoring systems for high-energy physics experiments. In particular it concentrates on the multi-processor aspects of the design of existing and planned experiments. The central problem to be solved by these systems is the readout and checking of the apparatus, and the recording and perhaps some processing of the data. (Auth.)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-12-29

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

  7. Request for Travel Funds for Systems Radiation Biology Workshop

    Energy Technology Data Exchange (ETDEWEB)

    Barcellos-Hoff, Mary Helen [NYU School of Medicine

    2014-03-22

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

  8. Biological removal of algae in an integrated pond system

    CSIR Research Space (South Africa)

    Meiring, PGJ

    1995-01-01

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

  9. The role of analytical sciences in medical systems biology

    NARCIS (Netherlands)

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

    2004-01-01

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

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

    KAUST Repository

    Nielsen, Jens

    2016-01-01

    . Besides its wide industrial use, S. cerevisiae serves as an eukaryal model organism, and many systems biology tools have therefore been developed for this organism. Among these genome-scale metabolic models have shown to be most successful as they easy

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

    Science.gov (United States)

    Hilfinger, Andreas; Paulsson, Johan

    2011-07-19

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

  12. CINRG: Systems Biology of Glucocorticoids in Muscle Disease

    Science.gov (United States)

    2013-10-01

    Contract W81XWH-09-1-0726 SYSTEMS BIOLOGY OF GLUCOCORTICOIDS IN MUSCLE DISEASE Introduction Duchenne muscular dystrophy (DMD) is the most... muscle and enable the development of better targeted and more effective therapies for Duchenne muscular dystrophy dynamically. This MDA grant...common and incurable muscular dystrophy of childhood. Muscle regeneration fails with advancing age, leading to considerable fibrosis. Corticosteroid

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

    Science.gov (United States)

    Maunder, R

    1996-01-01

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

  14. FIELD INVESTIGATION OF BIOLOGICAL TOILET SYSTEMS AND GREY WATER TREATMENT

    Science.gov (United States)

    The objective of the field program was to determine the operational characteristics and overall acceptability of popular models of biological toilets and a few select grey water systems. A field observation scheme was devised to take advantage of in-use sites throughout the State...

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

    Indian Academy of Sciences (India)

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

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

    Indian Academy of Sciences (India)

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

  17. Advances in reproductive biology and seed production systems of ...

    African Journals Online (AJOL)

    Eucalyptus globulus is the main eucalypt species grown in Australian plantations. The focus on seedling deployment systems, coupled with exploitation of large, open-pollinated base populations for breeding purposes over the last two decades, has required a detailed understanding of the reproductive biology of this ...

  18. Systems biology perspectives on minimal and simpler cells.

    Science.gov (United States)

    Xavier, Joana C; Patil, Kiran Raosaheb; Rocha, Isabel

    2014-09-01

    The concept of the minimal cell has fascinated scientists for a long time, from both fundamental and applied points of view. This broad concept encompasses extreme reductions of genomes, the last universal common ancestor (LUCA), the creation of semiartificial cells, and the design of protocells and chassis cells. Here we review these different areas of research and identify common and complementary aspects of each one. We focus on systems biology, a discipline that is greatly facilitating the classical top-down and bottom-up approaches toward minimal cells. In addition, we also review the so-called middle-out approach and its contributions to the field with mathematical and computational models. Owing to the advances in genomics technologies, much of the work in this area has been centered on minimal genomes, or rather minimal gene sets, required to sustain life. Nevertheless, a fundamental expansion has been taking place in the last few years wherein the minimal gene set is viewed as a backbone of a more complex system. Complementing genomics, progress is being made in understanding the system-wide properties at the levels of the transcriptome, proteome, and metabolome. Network modeling approaches are enabling the integration of these different omics data sets toward an understanding of the complex molecular pathways connecting genotype to phenotype. We review key concepts central to the mapping and modeling of this complexity, which is at the heart of research on minimal cells. Finally, we discuss the distinction between minimizing the number of cellular components and minimizing cellular complexity, toward an improved understanding and utilization of minimal and simpler cells. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  19. Systems Biology Perspectives on Minimal and Simpler Cells

    Science.gov (United States)

    Xavier, Joana C.; Patil, Kiran Raosaheb

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Maranas Costas D

    2008-01-01

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

  1. Notes on a PDE system for biological network formation

    KAUST Repository

    Haskovec, Jan

    2016-01-22

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

  2. A survey of chemicals inducing lipid peroxidation in biological systems.

    Science.gov (United States)

    Kappus, H

    1987-01-01

    A great number of drugs and chemicals are reviewed which have been shown to stimulate lipid peroxidation in any biological system. The underlying mechanisms, as far as known, are also dealt with. Lipid peroxidation induced by iron ions, organic hydroperoxides, halogenated hydrocarbons, redox cycling drugs, glutathione depleting chemicals, ethanol, heavy metals, ozone, nitrogen dioxide and a number of miscellaneous compounds, e.g. hydrazines, pesticides, antibiotics, are mentioned. It is shown that lipid peroxidation is stimulated by many of these compounds. However, quantitative estimates cannot be given yet and it is still impossible to judge the biological relevance of chemical-induced lipid peroxidation.

  3. Neural network models for biological waste-gas treatment systems.

    Science.gov (United States)

    Rene, Eldon R; Estefanía López, M; Veiga, María C; Kennes, Christian

    2011-12-15

    This paper outlines the procedure for developing artificial neural network (ANN) based models for three bioreactor configurations used for waste-gas treatment. The three bioreactor configurations chosen for this modelling work were: biofilter (BF), continuous stirred tank bioreactor (CSTB) and monolith bioreactor (MB). Using styrene as the model pollutant, this paper also serves as a general database of information pertaining to the bioreactor operation and important factors affecting gas-phase styrene removal in these biological systems. Biological waste-gas treatment systems are considered to be both advantageous and economically effective in treating a stream of polluted air containing low to moderate concentrations of the target contaminant, over a rather wide range of gas-flow rates. The bioreactors were inoculated with the fungus Sporothrix variecibatus, and their performances were evaluated at different empty bed residence times (EBRT), and at different inlet styrene concentrations (C(i)). The experimental data from these bioreactors were modelled to predict the bioreactors performance in terms of their removal efficiency (RE, %), by adequate training and testing of a three-layered back propagation neural network (input layer-hidden layer-output layer). Two models (BIOF1 and BIOF2) were developed for the BF with different combinations of easily measurable BF parameters as the inputs, that is concentration (gm(-3)), unit flow (h(-1)) and pressure drop (cm of H(2)O). The model developed for the CSTB used two inputs (concentration and unit flow), while the model for the MB had three inputs (concentration, G/L (gas/liquid) ratio, and pressure drop). Sensitivity analysis in the form of absolute average sensitivity (AAS) was performed for all the developed ANN models to ascertain the importance of the different input parameters, and to assess their direct effect on the bioreactors performance. The performance of the models was estimated by the regression

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  5. Two classes of bipartite networks: nested biological and social systems.

    Science.gov (United States)

    Burgos, Enrique; Ceva, Horacio; Hernández, Laura; Perazzo, R P J; Devoto, Mariano; Medan, Diego

    2008-10-01

    Bipartite graphs have received some attention in the study of social networks and of biological mutualistic systems. A generalization of a previous model is presented, that evolves the topology of the graph in order to optimally account for a given contact preference rule between the two guilds of the network. As a result, social and biological graphs are classified as belonging to two clearly different classes. Projected graphs, linking the agents of only one guild, are obtained from the original bipartite graph. The corresponding evolution of its statistical properties is also studied. An example of a biological mutualistic network is analyzed in detail, and it is found that the model provides a very good fitting of all the main statistical features. The model also provides a proper qualitative description of the same features observed in social webs, suggesting the possible reasons underlying the difference in the organization of these two kinds of bipartite networks.

  6. Specifications of Standards in Systems and Synthetic Biology.

    Science.gov (United States)

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

    2015-09-04

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

  7. Polynomial algebra of discrete models in systems biology.

    Science.gov (United States)

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

    2010-07-01

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

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

    CERN Document Server

    2015-01-01

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

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

    Science.gov (United States)

    Liu, Ying; Li, Hongxia; Xiao, Kai

    2016-01-01

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

  10. Sirius PSB: a generic system for analysis of biological sequences.

    Science.gov (United States)

    Koh, Chuan Hock; Lin, Sharene; Jedd, Gregory; Wong, Limsoon

    2009-12-01

    Computational tools are essential components of modern biological research. For example, BLAST searches can be used to identify related proteins based on sequence homology, or when a new genome is sequenced, prediction models can be used to annotate functional sites such as transcription start sites, translation initiation sites and polyadenylation sites and to predict protein localization. Here we present Sirius Prediction Systems Builder (PSB), a new computational tool for sequence analysis, classification and searching. Sirius PSB has four main operations: (1) Building a classifier, (2) Deploying a classifier, (3) Search for proteins similar to query proteins, (4) Preliminary and post-prediction analysis. Sirius PSB supports all these operations via a simple and interactive graphical user interface. Besides being a convenient tool, Sirius PSB has also introduced two novelties in sequence analysis. Firstly, genetic algorithm is used to identify interesting features in the feature space. Secondly, instead of the conventional method of searching for similar proteins via sequence similarity, we introduced searching via features' similarity. To demonstrate the capabilities of Sirius PSB, we have built two prediction models - one for the recognition of Arabidopsis polyadenylation sites and another for the subcellular localization of proteins. Both systems are competitive against current state-of-the-art models based on evaluation of public datasets. More notably, the time and effort required to build each model is greatly reduced with the assistance of Sirius PSB. Furthermore, we show that under certain conditions when BLAST is unable to find related proteins, Sirius PSB can identify functionally related proteins based on their biophysical similarities. Sirius PSB and its related supplements are available at: http://compbio.ddns.comp.nus.edu.sg/~sirius.

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

    Directory of Open Access Journals (Sweden)

    Mosca Ettore

    2007-08-01

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

  12. A 'Universal Time' system for ASDEX upgrade

    International Nuclear Information System (INIS)

    Raupp, Gerhard; Cole, R.; Behler, K.; Fitzek, M.; Heimann, P.; Lohs, A.; Lueddecke, K.; Neu, G.; Schacht, J.; Treutterer, W.; Zasche, D.; Zehetbauer, Th.; Zilker, M.

    2003-01-01

    For the new generation of intelligent controllers for plasma diagnostics, discharge control and long-pulse experiment control a new time system supporting steady state real-time operation has been devised. A central unit counts time at nanosecond resolution, covering more than the experiment lifetime. The broadcast time information serves local units to perform application functions such as current time readout, trigger generation and sample time measurement. Time is treated as a precisely measured quantity like other physical quantities. Tagging all detected events and sampled values with measured times as [value; time]-entities facilitates real-time data analysis, steady state protocolling and time-sorted archiving

  13. Quantum mechanical simulation methods for studying biological systems

    International Nuclear Information System (INIS)

    Bicout, D.; Field, M.

    1996-01-01

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

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

    Science.gov (United States)

    Thompson, R C A; Jenkins, D J

    2014-10-15

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

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

    Science.gov (United States)

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

    2017-12-05

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

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

    Science.gov (United States)

    Hütt, Marc-Thorsten

    2014-04-01

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

  17. From globally coupled maps to complex-systems biology

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-09-15

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

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

    Science.gov (United States)

    Bittner, Michael L.; Dougherty, Edward R.

    2012-01-01

    For science, theoretical or applied, to significantly advance, researchers must use the most appropriate mathematical methods. A century and a half elapsed between Newton’s development of the calculus and Laplace’s development of celestial mechanics. One cannot imagine the latter without the former. Today, more than three-quarters of a century has elapsed since the birth of stochastic systems theory. This article provides a perspective on the utilization of systems theory as the proper vehicle for the development of systems biology and its application to complex regulatory diseases such as cancer. PMID:23170064

  19. Tritium fractionation in biological systems and in analytical procedures

    International Nuclear Information System (INIS)

    Kim, M.A.; Baumgaertner, F.

    1991-01-01

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

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

    Science.gov (United States)

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

    2016-11-22

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-03-01

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

  2. The OME Framework for genome-scale systems biology

    Energy Technology Data Exchange (ETDEWEB)

    Palsson, Bernhard O. [Univ. of California, San Diego, CA (United States); Ebrahim, Ali [Univ. of California, San Diego, CA (United States); Federowicz, Steve [Univ. of California, San Diego, CA (United States)

    2014-12-19

    The life sciences are undergoing continuous and accelerating integration with computational and engineering sciences. The biology that many in the field have been trained on may be hardly recognizable in ten to twenty years. One of the major drivers for this transformation is the blistering pace of advancements in DNA sequencing and synthesis. These advances have resulted in unprecedented amounts of new data, information, and knowledge. Many software tools have been developed to deal with aspects of this transformation and each is sorely needed [1-3]. However, few of these tools have been forced to deal with the full complexity of genome-scale models along with high throughput genome- scale data. This particular situation represents a unique challenge, as it is simultaneously necessary to deal with the vast breadth of genome-scale models and the dizzying depth of high-throughput datasets. It has been observed time and again that as the pace of data generation continues to accelerate, the pace of analysis significantly lags behind [4]. It is also evident that, given the plethora of databases and software efforts [5-12], it is still a significant challenge to work with genome-scale metabolic models, let alone next-generation whole cell models [13-15]. We work at the forefront of model creation and systems scale data generation [16-18]. The OME Framework was borne out of a practical need to enable genome-scale modeling and data analysis under a unified framework to drive the next generation of genome-scale biological models. Here we present the OME Framework. It exists as a set of Python classes. However, we want to emphasize the importance of the underlying design as an addition to the discussions on specifications of a digital cell. A great deal of work and valuable progress has been made by a number of communities [13, 19-24] towards interchange formats and implementations designed to achieve similar goals. While many software tools exist for handling genome

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

    Directory of Open Access Journals (Sweden)

    Daniel eLewis

    2014-12-01

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

  4. Research in Distributed Real-Time Systems

    Science.gov (United States)

    Mukkamala, R.

    1997-01-01

    This document summarizes the progress we have made on our study of issues concerning the schedulability of real-time systems. Our study has produced several results in the scalability issues of distributed real-time systems. In particular, we have used our techniques to resolve schedulability issues in distributed systems with end-to-end requirements. During the next year (1997-98), we propose to extend the current work to address the modeling and workload characterization issues in distributed real-time systems. In particular, we propose to investigate the effect of different workload models and component models on the design and the subsequent performance of distributed real-time systems.

  5. Thermodynamic Optimality criteria for biological systems in linear irreversible thermodynamics

    International Nuclear Information System (INIS)

    Chimal, J C; Sánchez, N; Ramírez, PR

    2017-01-01

    In this paper the methodology of the so-called Linear Irreversible Thermodynamics (LIT) is applied; although traditionally used locally to study general systems in non-equilibrium states in which it is consider both internal and external contributions to the entropy increments in order to analyze the efficiency of two coupled processes with generalized fluxes J 1 , J 2 and their corresponding forces X 1 , X 2 . We extend the former analysis to takes into account two different operating regimes namely: Omega Function and Efficient Power criterion, respectively. Results show analogies in the optimal performance between and we can say that there exist a criteria of optimization which can be used specially for biological systems where a good design of the biological parameters made by nature at maximum efficient power conditions lead to more efficient engines than those at the maximum power conditions or ecological conditions. (paper)

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

    Science.gov (United States)

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

    2013-12-06

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

  7. Teleology and its constitutive role for biology as the science of organized systems in nature.

    Science.gov (United States)

    Toepfer, Georg

    2012-03-01

    'Nothing in biology makes sense, except in the light of teleology'. This could be the first sentence in a textbook about the methodology of biology. The fundamental concepts in biology, e.g. 'organism' and 'ecosystem', are only intelligible given a teleological framework. Since early modern times, teleology has often been considered methodologically unscientific. With the acceptance of evolutionary theory, one popular strategy for accommodating teleological reasoning was to explain it by reference to selection in the past: functions were reconstructed as 'selected effects'. But the theory of evolution obviously presupposes the existence of organisms as organized and regulated, i.e. functional systems. Therefore, evolutionary theory cannot provide the foundation for teleology. The underlying reason for the central methodological role of teleology in biology is not its potential to offer particular forms of (evolutionary) explanations for the presence of parts, but rather an ontological one: organisms and other basic biological entities do not exist as physical bodies do, as amounts of matter with a definite form. Rather, they are dynamic systems in stable equilibrium; despite changes of their matter and form (in metabolism and metamorphosis) they maintain their identity. What remains constant in these kinds of systems is their 'organization', i.e. the causal pattern of interdependence of parts with certain effects of each part being relevant for the working of the system. Teleological analysis consists in the identification of these system-relevant effects and at the same time of the system as a whole. Therefore, the identity of biological systems cannot be specified without teleological reasoning. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Radioprotection by dimethyl sulfoxide on two biological system

    International Nuclear Information System (INIS)

    Bernardes, D.M.L.; Villavicencio, A.L.C.H.; Del Mastro, N.L.

    1990-01-01

    The effects of dimethyl sulfoxide treatment on two biological systems are examined: a) In vivo, the level of albinic mouse survive from IPEN, when irradiated with 9 Gy of 60 Co., 1 hour after the injection ip of DMSO 0,025M. b) In vivo, molecular level, when DMSO 1M, is added 10 min. before the irradiation with 25.000 Gy of 60 Co, from an aqueous solution of proteins from crystalline bovine. (C.G.C.) [pt

  9. Ionic interactions in biological and physical systems: a variational treatment.

    Science.gov (United States)

    Eisenberg, Bob

    2013-01-01

    Chemistry is about chemical reactions. Chemistry is about electrons changing their configurations as atoms and molecules react. Chemistry has for more than a century studied reactions as if they occurred in ideal conditions of infinitely dilute solutions. But most reactions occur in salt solutions that are not ideal. In those solutions everything (charged) interacts with everything else (charged) through the electric field, which is short and long range extending to the boundaries of the system. Mathematics has recently been developed to deal with interacting systems of this sort. The variational theory of complex fluids has spawned the theory of liquid crystals (or vice versa). In my view, ionic solutions should be viewed as complex fluids, particularly in the biological and engineering context. In both biology and electrochemistry ionic solutions are mixtures highly concentrated (to approximately 10 M) where they are most important, near electrodes, nucleic ids, proteins, active sites of enzymes, and ionic channels. Ca2+ is always involved in biological solutions because the concentration (really free energy per mole) of Ca2+ in a particular location is the signal that controls many biological functions. Such interacting systems are not simple fluids, and it is no wonder that analysis of interactions, such as the Hofmeister series, rooted in that tradition has not succeeded as one would hope. Here, we present a variational treatment of ard spheres in a frictional dielectric with the hope that such a treatment of an lectrolyte as a complex fluid will be productive. The theory automatically extends to spatially nonuniform boundary conditions and the nonequilibrium systems and flows they produce. The theory is unavoidably self-consistent since differential equations are derived (not assumed) from models of (Helmholtz free) nergy and dissipation of the electrolyte. The origin of the Hofmeister series is (in my view) an inverse problem that becomes well posed when

  10. Making real-time reactive systems reliable

    Science.gov (United States)

    Marzullo, Keith; Wood, Mark

    1990-01-01

    A reactive system is characterized by a control program that interacts with an environment (or controlled program). The control program monitors the environment and reacts to significant events by sending commands to the environment. This structure is quite general. Not only are most embedded real time systems reactive systems, but so are monitoring and debugging systems and distributed application management systems. Since reactive systems are usually long running and may control physical equipment, fault tolerance is vital. The research tries to understand the principal issues of fault tolerance in real time reactive systems and to build tools that allow a programmer to design reliable, real time reactive systems. In order to make real time reactive systems reliable, several issues must be addressed: (1) How can a control program be built to tolerate failures of sensors and actuators. To achieve this, a methodology was developed for transforming a control program that references physical value into one that tolerates sensors that can fail and can return inaccurate values; (2) How can the real time reactive system be built to tolerate failures of the control program. Towards this goal, whether the techniques presented can be extended to real time reactive systems is investigated; and (3) How can the environment be specified in a way that is useful for writing a control program. Towards this goal, whether a system with real time constraints can be expressed as an equivalent system without such constraints is also investigated.

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

    Science.gov (United States)

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

    2017-11-10

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

    Raman, Ritu; Bashir, Rashid

    2017-10-01

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

  14. A Systems Biology Approach to Infectious Disease Research: Innovating the Pathogen-Host Research Paradigm

    Energy Technology Data Exchange (ETDEWEB)

    Aderem, Alan; Adkins, Joshua N.; Ansong, Charles; Galagan, James; Kaiser, Shari; Korth, Marcus J.; Law, G. L.; McDermott, Jason E.; Proll, Sean; Rosenberger, Carrie; Schoolnik, Gary; Katze, Michael G.

    2011-02-01

    The 20th century was marked by extraordinary advances in our understanding of microbes and infectious disease, but pandemics remain, food and water borne illnesses are frequent, multi-drug resistant microbes are on the rise, and the needed drugs and vaccines have not been developed. The scientific approaches of the past—including the intense focus on individual genes and proteins typical of molecular biology—have not been sufficient to address these challenges. The first decade of the 21st century has seen remarkable innovations in technology and computational methods. These new tools provide nearly comprehensive views of complex biological systems and can provide a correspondingly deeper understanding of pathogen-host interactions. To take full advantage of these innovations, the National Institute of Allergy and Infectious Diseases recently initiated the Systems Biology Program for Infectious Disease Research. As participants of the Systems Biology Program we think that the time is at hand to redefine the pathogen-host research paradigm.

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

    Science.gov (United States)

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

    2018-03-01

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

  16. Real-Time Operating Systems for Multicore Embedded Systems

    OpenAIRE

    Tomiyama, Hiroyuki; Honda, Shinya; Takada, Hiroaki

    2008-01-01

    Multicore systems-on-chip have become popular inthe design of embedded systems in order to simultaneously achieve high performance and low power consumption. On the software side, real-time operating systems are necessary in orderto handle growing complexity of embedded software. This paper describes requirements, design principles and implementation techniques for real-time operating systems to be used inasymmetric multicore systems.

  17. Archtecture of distributed real-time systems

    OpenAIRE

    Wing Leung, Cheuk

    2013-01-01

    CRAFTERS (Constraint and Application Driven Framework for Tailoring Embedded Real-time System) project aims to address the problem of uncertainty and heterogeneity in a distributed system by providing seamless, portable connectivity and middleware. This thesis contributes to the project by investigating the techniques that can be used in a distributed real-time embedded system. The conclusion is that, there is a list of specifications to be meet in order to provide a transparent and real-time...

  18. Research Directions in Real-Time Systems.

    Science.gov (United States)

    1996-09-01

    This report summarizes a survey of published research in real time systems . Material is presented that provides an overview of the topic, focusing on...communications protocols and scheduling techniques. It is noted that real - time systems deserve special attention separate from other areas because of...formal tools for design and analysis of real - time systems . The early work on applications as well as notable theoretical advances are summarized

  19. A Real-Time Systems Symposium Preprint.

    Science.gov (United States)

    1983-09-01

    Real - Time Systems Symposium Preprint Interim Tech...estimate of the occurence of the error. Unclassii ledSECUqITY CLASSIF’ICA T" NO MI*IA If’ inDI /’rrd erter for~~ble. ’Corrputnqg A REAL - TIME SYSTEMS SYMPOSIUM...ABSTRACT This technical report contains a preprint of a paper accepted for presentation at the REAL - TIME SYSTEMS SYMPOSIUM, Arlington,

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

    Science.gov (United States)

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

    2016-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Atsushi eFukushima

    2014-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Zlatogor Minchev

    2005-12-01

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

  3. Wearable System for Acquisition and Monitoring of Biological Signals

    Science.gov (United States)

    Piccinini, D. J.; Andino, N. B.; Ponce, S. D.; Roberti, MA; López, y. N.

    2016-04-01

    This paper presents a modular, wearable system for acquisition and wireless transmission of biological signals. Configurable slaves for different signals (such as ECG, EMG, inertial sensors, and temperature) based in the ADS1294 Medical Analog Front End are connected to a Master, based in the CC3200 microcontroller, both from Texas Instruments. The slaves are configurable according to the specific application, providing versatility to the wearable system. The battery consumption is reduced, through a couple of Li-ion batteries and the circuit has also a battery charger. A custom made box was designed and fabricated in a 3D printer, preserving the requirements of low cost, low weight and safety recommendations.

  4. Systems biology of lactic acid bacteria: a critical review.

    Science.gov (United States)

    Teusink, Bas; Bachmann, Herwig; Molenaar, Douwe

    2011-08-30

    Understanding the properties of a system as emerging from the interaction of well described parts is the most important goal of Systems Biology. Although in the practice of Lactic Acid Bacteria (LAB) physiology we most often think of the parts as the proteins and metabolites, a wider interpretation of what a part is can be useful. For example, different strains or species can be the parts of a community, or we could study only the chemical reactions as the parts of metabolism (and forgetting about the enzymes that catalyze them), as is done in flux balance analysis. As long as we have some understanding of the properties of these parts, we can investigate whether their interaction leads to novel or unanticipated behaviour of the system that they constitute. There has been a tendency in the Systems Biology community to think that the collection and integration of data should continue ad infinitum, or that we will otherwise not be able to understand the systems that we study in their details. However, it may sometimes be useful to take a step back and consider whether the knowledge that we already have may not explain the system behaviour that we find so intriguing. Reasoning about systems can be difficult, and may require the application of mathematical techniques. The reward is sometimes the realization of unexpected conclusions, or in the worst case, that we still do not know enough details of the parts, or of the interactions between them. We will discuss a number of cases, with a focus on LAB-related work, where a typical systems approach has brought new knowledge or perspective, often counterintuitive, and clashing with conclusions from simpler approaches. Also novel types of testable hypotheses may be generated by the systems approach, which we will illustrate. Finally we will give an outlook on the fields of research where the systems approach may point the way for the near future.

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

    NARCIS (Netherlands)

    Yin, X.; Struik, P.C.

    2010-01-01

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

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

    Science.gov (United States)

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

    2004-06-01

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

  7. The Advanced Photon Source injection timing system

    International Nuclear Information System (INIS)

    Lenkszus, F.R.; Laird, R.

    1995-01-01

    The Advanced Photon Source consists of five accelerators. The injection timing system provides the signals required to cause a bunch emitted from the electron gun to navigate through intermediate accelerators to a specific bucket (1 out of 1296) within the storage ring. Two linacs and a positron accumulator ring operate at 60Hz while a booster synchrotron ramps and injects into the storage ring at 2Hz. The distributed, modular VME/VXI-based injection timing system is controlled by two EPICS-based input/output controllers (IOCs). Over 40 VME/VXI cards have been developed to implement the system. Card types range from 352MHz VXI timing modules to VME-based fiber optic fanouts and logic translators/drivers. All timing is distributed with fiber optics. Timing references are derived directly from machine low-level rf of 9.77MHz and 352MHz. The timing references provide triggers to programmable delay generators. Three grades of timing are provided. Precision timing is derived from commercial digital delay generators, intermediate precision timing is obtained from VXI 8-channel digital delay generators which provide timing with 25ns peak-to-peak jitter, and modest precision timing is provided by the APS event system. The timing system is fully integrated into the APS EPICS-based control system

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

    Directory of Open Access Journals (Sweden)

    Sudin eBhattacharya

    2012-12-01

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

  9. A second inheritance system: the extension of biology through culture.

    Science.gov (United States)

    Whiten, Andrew

    2017-10-06

    By the mid-twentieth century (thus following the 'Modern Synthesis' in evolutionary biology), the behavioural sciences offered only the sketchy beginnings of a scientific literature documenting evidence for cultural inheritance in animals-the transmission of traditional behaviours via learning from others (social learning). By contrast, recent decades have seen a massive growth in the documentation of such cultural phenomena, driven by long-term field studies and complementary laboratory experiments. Here, I review the burgeoning scope of discoveries in this field, which increasingly suggest that this 'second inheritance system', built on the shoulders of the primary genetic inheritance system, occurs widely among vertebrates and possibly in invertebrates too. Its novel characteristics suggest significant implications for our understanding of evolutionary biology. I assess the extent to which this second system extends the scope of evolution, both by echoing principal properties of the primary, organic evolutionary system, and going beyond it in significant ways. This is well established in human cultural evolution; here, I address animal cultures more generally. The further major, and related, question concerns the extent to which the consequences of widespread animal cultural transmission interact with the primary, genetically based inheritance systems, shaping organic evolution.

  10. Design of fluidized-bed, biological denitrification systems

    International Nuclear Information System (INIS)

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

    1982-01-01

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

  11. A flexible time recording and time correlation analysis system

    International Nuclear Information System (INIS)

    Shenhav, N.J.; Leiferman, G.; Segal, Y.; Notea, A.

    1983-01-01

    A system was developed to digitize and record the time intervals between detection event pulses, feed to its input channels from a detection device. The accumulated data is transferred continuously in real time to a disc through a PDP 11/34 minicomputer. Even though the system was designed for a specific scope, i.e., the comparative study of passive neutron nondestructive assay methods, it can be characterized by its features as a general purpose time series recorder. The time correlation analysis is performed by software after completion of the data accumulation. The digitizing clock period is selectable and any value, larger than a minimum of 100 ns, may be selected. Bursts of up to 128 events with a frequency up to 10 MHz may be recorded. With the present recorder-minicomputer combination, the maximal average recording frequency is 40 kHz. (orig.)

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

    Saito, Kazuki; Matsuda, Fumio

    2010-01-01

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

  14. Multiprocessor scheduling for real-time systems

    CERN Document Server

    Baruah, Sanjoy; Buttazzo, Giorgio

    2015-01-01

    This book provides a comprehensive overview of both theoretical and pragmatic aspects of resource-allocation and scheduling in multiprocessor and multicore hard-real-time systems.  The authors derive new, abstract models of real-time tasks that capture accurately the salient features of real application systems that are to be implemented on multiprocessor platforms, and identify rules for mapping application systems onto the most appropriate models.  New run-time multiprocessor scheduling algorithms are presented, which are demonstrably better than those currently used, both in terms of run-time efficiency and tractability of off-line analysis.  Readers will benefit from a new design and analysis framework for multiprocessor real-time systems, which will translate into a significantly enhanced ability to provide formally verified, safety-critical real-time systems at a significantly lower cost.

  15. Horn Clauses for Communicating Timed Systems

    Directory of Open Access Journals (Sweden)

    Hossein Hojjat

    2014-12-01

    Full Text Available Languages based on the theory of timed automata are a well established approach for modelling and analysing real-time systems, with many applications both in industrial and academic context. Model checking for timed automata has been studied extensively during the last two decades; however, even now industrial-grade model checkers are available only for few timed automata dialects (in particular Uppaal timed automata, exhibit limited scalability for systems with large discrete state space, or cannot handle parametrised systems. We explore the use of Horn constraints and off-the-shelf model checkers for analysis of networks of timed automata. The resulting analysis method is fully symbolic and applicable to systems with large or infinite discrete state space, and can be extended to include various language features, for instance Uppaal-style communication/broadcast channels and BIP-style interactions, and systems with infinite parallelism. Experiments demonstrate the feasibility of the method.

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

    Science.gov (United States)

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

    2014-01-01

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

  17. The TdeV timing system

    International Nuclear Information System (INIS)

    deVillers, P.; Lliev, B.; Larsen, J.M.; Strong, C.

    1992-01-01

    This paper reports on the timing system that provides the clock and trigger signals used to synchronize power supplies, waveforms, gas injection, plasma control, diagnostic equipments and data-acquisition systems on TdeV (Tokamak de Varennes). The two major components of the timing system are the MPB Encoder and Decoder CAMAC modules which are linked via ta fibre optic cable (timing highway) carrying a 1 MHz master clock and timing events. The Decoders generate the synchronization signals with a resolution of 1 μs upon recognition of timing events encoded on the timing highway by the Encoder modules. The integration of these programmable CAMAC modules, developed to meet the requirements of TdeV, allows the design of a distributed timing system with a simple but flexible architecture

  18. Review of neutron radiographic applications in industrial and biological systems

    International Nuclear Information System (INIS)

    Ashraf, M.M.; Khan, A.R.

    1992-10-01

    Neutron radiography is a non-destructive testing technique and is being used worldwide for the design and the development of reactor fuels for research and power reactors. It is also being used for non-destructive examination of nuclear industrial products. In addition to its explosives and other industrial sectors. In addition to its applications in industrial sectors, the technique is widely used for research and development activities in biological systems. A review of technical applications of neutron radiography in different fields particularly in nuclear fuel management, aerospace industry, explosives and biology is presented. The methodology of neutron radiography is also discussed in detail along with the advantages of the technique. In addition, the potential of the neutron radiography facility at PINSTECH has been described. (author)

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

    DEFF Research Database (Denmark)

    Audouze, Karine Marie Laure; Grandjean, Philippe

    2011-01-01

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

  20. Application of enriched stable isotopes as tracers in biological systems

    DEFF Research Database (Denmark)

    Stürup, Stefan; Hansen, Helle Rüsz; Gammelgaard, Bente

    2008-01-01

    The application of enriched stable isotopes of minerals and trace elements as tracers in biological systems is a rapidly growing research field that benefits from the many new developments in inorganic mass spectrometric instrumentation, primarily within inductively coupled plasma mass spectrometry...... (ICP-MS) instrumentation, such as reaction/collision cell ICP-MS and multicollector ICP-MS with improved isotope ratio measurement and interference removal capabilities. Adaptation and refinement of radioisotope tracer experiment methodologies for enriched stable isotope experiments......, and the development of new methodologies coupled with more advanced compartmental and mathematical models for the distribution of elements in living organisms has enabled a broader use of enriched stable isotope experiments in the biological sciences. This review discusses the current and future uses of enriched...

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

    Science.gov (United States)

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2013-05-31

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

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

    Science.gov (United States)

    Volk, Tyler; Rummel, John D.

    1987-01-01

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

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

    Science.gov (United States)

    Ippolito, Corey; Plice, Laura; Pisanich, Greg

    2003-01-01

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

  5. A methodology to annotate systems biology markup language models with the synthetic biology open language.

    Science.gov (United States)

    Roehner, Nicholas; Myers, Chris J

    2014-02-21

    Recently, we have begun to witness the potential of synthetic biology, noted here in the form of bacteria and yeast that have been genetically engineered to produce biofuels, manufacture drug precursors, and even invade tumor cells. The success of these projects, however, has often failed in translation and application to new projects, a problem exacerbated by a lack of engineering standards that combine descriptions of the structure and function of DNA. To address this need, this paper describes a methodology to connect the systems biology markup language (SBML) to the synthetic biology open language (SBOL), existing standards that describe biochemical models and DNA components, respectively. Our methodology involves first annotating SBML model elements such as species and reactions with SBOL DNA components. A graph is then constructed from the model, with vertices corresponding to elements within the model and edges corresponding to the cause-and-effect relationships between these elements. Lastly, the graph is traversed to assemble the annotating DNA components into a composite DNA component, which is used to annotate the model itself and can be referenced by other composite models and DNA components. In this way, our methodology can be used to build up a hierarchical library of models annotated with DNA components. Such a library is a useful input to any future genetic technology mapping algorithm that would automate the process of composing DNA components to satisfy a behavioral specification. Our methodology for SBML-to-SBOL annotation is implemented in the latest version of our genetic design automation (GDA) software tool, iBioSim.

  6. Modulation of radiosensitivity of biological systems by medicinal herbs

    International Nuclear Information System (INIS)

    Goyal, P.K.

    2012-01-01

    The global environmental pollution is responsible for the exposure of living beings to the influence of various technogenic factors, including ionizing radiation. Exposure to such radiation represents a genuine, increasing threat to mankind and our environment. The steadily increasing applications of radiation in clinical practice, industrial and agricultural activities, residual radio-activity resulting from nuclear test explosions, have a measurable impact contributing to significant radiation hazards in humans. Further, the proliferation of terrorism and asymmetric warfare in the 21st century has rendered the modern world a dangerous place to live and work. With the realization of deleterious effects of ionizing radiation, a need was felt to protect human beings against these harmful effects by using physical and/or chemical means. Many chemical compounds have been tested for radio protective action but their practical applicability remained limited owing to their inherent toxicity at the optimum dose level. Various plants have been used for various ailments in humans since time immemorial, and herbal preparations have usually been considered safe and less toxic than the synthetic compounds. Therefore, screening of natural products present a major avenue for the discovery of new radio protective drugs and such products have drawn the attention of investigators during the last two decades. The Indian system of medicine employs a large number of plants and some of these herbals viz. The extracts of certain medicinal plant like Amla (Emblica officinalis), Rosemary (Rosemary officinalis), Methi (Trigonella foenum graecum) sapthaparna (Alstonia scholaris), Bael (Aegle inarmelos), Bhumi amla (Phyllanthus niruri), Jamun (Syzgium cumini), Gloe (Tinospora cordifolia) have been trialed in this laboratory for their radio protective action in various biological systems of mammals. The extracts of various parts of such plants have appreciable DRF on the basis of survival

  7. Modulation of radiosensitivity of biological systems by medicinal herbs

    Energy Technology Data Exchange (ETDEWEB)

    Goyal, P.K., E-mail: pkgoyal2002@gmail.com [Radiation and Cancer Biology Laboratory, Department of Zoology, University of Rajasthan, Jaipur (India)

    2012-07-01

    The global environmental pollution is responsible for the exposure of living beings to the influence of various technogenic factors, including ionizing radiation. Exposure to such radiation represents a genuine, increasing threat to mankind and our environment. The steadily increasing applications of radiation in clinical practice, industrial and agricultural activities, residual radio-activity resulting from nuclear test explosions, have a measurable impact contributing to significant radiation hazards in humans. Further, the proliferation of terrorism and asymmetric warfare in the 21st century has rendered the modern world a dangerous place to live and work. With the realization of deleterious effects of ionizing radiation, a need was felt to protect human beings against these harmful effects by using physical and/or chemical means. Many chemical compounds have been tested for radio protective action but their practical applicability remained limited owing to their inherent toxicity at the optimum dose level. Various plants have been used for various ailments in humans since time immemorial, and herbal preparations have usually been considered safe and less toxic than the synthetic compounds. Therefore, screening of natural products present a major avenue for the discovery of new radio protective drugs and such products have drawn the attention of investigators during the last two decades. The Indian system of medicine employs a large number of plants and some of these herbals viz. The extracts of certain medicinal plant like Amla (Emblica officinalis), Rosemary (Rosemary officinalis), Methi (Trigonella foenum graecum) sapthaparna (Alstonia scholaris), Bael (Aegle inarmelos), Bhumi amla (Phyllanthus niruri), Jamun (Syzgium cumini), Gloe (Tinospora cordifolia) have been trialed in this laboratory for their radio protective action in various biological systems of mammals. The extracts of various parts of such plants have appreciable DRF on the basis of survival

  8. Macro to microfluidics system for biological environmental monitoring.

    Science.gov (United States)

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

    2012-01-01

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

  9. Verifying duration properties of timed transition systems

    DEFF Research Database (Denmark)

    Liu, Zhiming; Ravn, Anders P.; Li, Xiaoshan

    1998-01-01

    This paper proposes a method for formal real-time systems development:Requirements and high level design decisions are time interval properties and are therefore specified in the Duration Calculus (DC), while implementations are described bytimed transition systems (TTS). A link from implementati...

  10. Heterogeneous Embedded Real-Time Systems Environment

    Science.gov (United States)

    2003-12-01

    AFRL-IF-RS-TR-2003-290 Final Technical Report December 2003 HETEROGENEOUS EMBEDDED REAL - TIME SYSTEMS ENVIRONMENT Integrated...HETEROGENEOUS EMBEDDED REAL - TIME SYSTEMS ENVIRONMENT 6. AUTHOR(S) Cosmo Castellano and James Graham 5. FUNDING NUMBERS C - F30602-97-C-0259

  11. Synchronization of timing systems on TFTR

    International Nuclear Information System (INIS)

    Montague, J.; Sichta, P.

    1992-01-01

    This paper reports on the TOKAMAK Fusion Test Reactor (TFTR) facility clock system which has four related timing subsystems: the TFTR shot clock, the Neutral Beams clocks, the Ion Cyclotron Range of Frequencies (ICRF) system clock, and the Disruption Trigger System. These systems have been integrated to support increasingly fast sampling rates in data acquisition and greater accuracy in the firing of the Neutral Beams and ICRF systems during TFTR shots

  12. Resource-Parameterized Timing Analysis of Real-Time Systems

    DEFF Research Database (Denmark)

    Kim, Jin Hyun; Legay, Axel; Larsen, Kim Guldstrand

    2015-01-01

    on a specic platform. For the same reason, a configuration of platforms cannot be independent from applications in most cases. This paper proposes a new analysis framework of real-time systems where an application and a platform can be analyzed in a fully independent way such that not only the application...

  13. Army Secure Operating System: Information Security for Real Time Systems

    National Research Council Canada - National Science Library

    Anderson, Eric

    1984-01-01

    The Army Secure Operating System (ASOS) project, under the management of the U.S. Army CECOM organization, will provide real time systems software necessary for fielding modern Battlefield Automation Systems...

  14. Time Optimal Control Laws for Bilinear Systems

    Directory of Open Access Journals (Sweden)

    Salim Bichiou

    2018-01-01

    Full Text Available The aim of this paper is to determine the feedforward and state feedback suboptimal time control for a subset of bilinear systems, namely, the control sequence and reaching time. This paper proposes a method that uses Block pulse functions as an orthogonal base. The bilinear system is projected along that base. The mathematical integration is transformed into a product of matrices. An algebraic system of equations is obtained. This system together with specified constraints is treated as an optimization problem. The parameters to determine are the final time, the control sequence, and the states trajectories. The obtained results via the newly proposed method are compared to known analytical solutions.

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

    Science.gov (United States)

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

    2012-12-05

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

  16. Biological, chemical, physical and time series data collected from station WQB04 by University of Hawai'i at Hilo and assembled by Pacific Islands Ocean Observing System (PacIOOS) in the North Pacific Ocean from 2010-10-23 to 2016-12-31 (NCEI Accession 0161523)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NCEI Accession 0161523 contains biological, chemical, physical and time series data in netCDF formatted files, which follow the Climate and Forecast metadata...

  17. The Meaning of Time. An Introduction into Philosophical, Biological and Physical Aspects of Time

    Science.gov (United States)

    1991-01-15

    mentioned already Plato (428-347BC) as the originator of the essential quasistatic view of time and history. He was preceded by Parmenides (540BC and Zeno...after. * Being and Entities: Being is the most universal concept. It was 31 discovered by Parmenides (- 500 B.C.), who saw that of all the diversity of

  18. An USB-based time measurement system

    International Nuclear Information System (INIS)

    Qin Xi; Liu Shubin; An Qi

    2010-01-01

    In this paper,we report the electronics of a timing measurement system of PTB(portable TDC board), which is a handy tool based on USB interface, customized for high precision time measurements without any crates. The time digitization is based on the High Performance TDC Chip (HPTDC). The real-time compensation for HPTDC outputs and the USB master logic are implemented in an ALTERA's Cyclone FPGA. The architecture design and logic design are described in detail. Test of the system showed a time resolution of 13.3 ps. (authors)

  19. Model Checking Real-Time Systems

    DEFF Research Database (Denmark)

    Bouyer, Patricia; Fahrenberg, Uli; Larsen, Kim Guldstrand

    2018-01-01

    This chapter surveys timed automata as a formalism for model checking real-time systems. We begin with introducing the model, as an extension of finite-state automata with real-valued variables for measuring time. We then present the main model-checking results in this framework, and give a hint...

  20. Modular specification of real-time systems

    DEFF Research Database (Denmark)

    Inal, Recep

    1994-01-01

    Duration Calculus, a real-time interval logic, has been embedded in the Z specification language to provide a notation for real-time systems that combines the modularisation and abstraction facilities of Z with a logic suitable for reasoning about real-time properties. In this article the notation...

  1. Cellular respiration: replicating in vivo systems biology for in ...

    Science.gov (United States)

    This editorial develops a philosophy for expanding the scope of Journal of Breath Research (JBR) into the realm of cellular level study, and links certain topics back to more traditional systemic research for understanding human health based on exhaled breath constituents. The express purpose is to provide a publication outlet for novel breath related research that includes in vitro studies, especially those that explore the biological origin and expression of compounds that may ultimately influence the constituents of exhaled breath. The new topics include all manner of methods and instrumentations for making in vivo and in vitro measurements, the use of different biological media (blood, urine saliva, swabs) including human and microbial cell-lines, in vitro kinetic studies of metabolism, and advances in ex vivo methods for maintaining metabolic competency and viability of biological samples. Traditionally, JBR has published articles on human breath analysis for diagnosing disease, tracking health state, assessing the dose and effect of exogenous chemicals, and contributions of malodorous compounds from the oral/nasal cavity. These have also included research describing novel sampling and analytical technologies, most notably those implementing mass spectrometry, chemical sensors and optical measurement instrumentation (Amann and Smith 2013). The journal’s original scope has also embraced animal models as surrogates for human sampling, new mathematical and

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

    Science.gov (United States)

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

    2012-07-02

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

  3. A large-scale cryoelectronic system for biological sample banking

    Science.gov (United States)

    Shirley, Stephen G.; Durst, Christopher H. P.; Fuchs, Christian C.; Zimmermann, Heiko; Ihmig, Frank R.

    2009-11-01

    We describe a polymorphic electronic infrastructure for managing biological samples stored over liquid nitrogen. As part of this system we have developed new cryocontainers and carrier plates attached to Flash memory chips to have a redundant and portable set of data at each sample. Our experimental investigations show that basic Flash operation and endurance is adequate for the application down to liquid nitrogen temperatures. This identification technology can provide the best sample identification, documentation and tracking that brings added value to each sample. The first application of the system is in a worldwide collaborative research towards the production of an AIDS vaccine. The functionality and versatility of the system can lead to an essential optimization of sample and data exchange for global clinical studies.

  4. The Treatment of Geological Time & the History of Life on Earth in High School Biology Textbooks

    Science.gov (United States)

    Summers, Gerald; Decker, Todd; Barrow, Lloyd

    2007-01-01

    In spite of the importance of geological time in evolutionary biology, misconceptions about historical events in the history of life on Earth are common. Glenn (1990) has documented a decline from 1960 to 1989 in the amount of space devoted to the history of life in high school earth science textbooks, but we are aware of no similar study in…

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

    Directory of Open Access Journals (Sweden)

    Palmiro Poltronieri

    2018-01-01

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

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

    Science.gov (United States)

    Saks, Valdur; Monge, Claire; Guzun, Rita

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Valdur Saks

    2009-03-01

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

  8. Aspergilli: Models for systems biology in filamentous fungi

    DEFF Research Database (Denmark)

    Brandl, Julian; Andersen, Mikael Rørdam

    2017-01-01

    and proteomics where outstanding contributions are highlighted. From past developments it becomes apparent that CRISPR technology will speed up genetic research in the Aspergillus field. This speed up will allow for an increase in systems biology targeted research by accelerating data generation. The increase......Aspergillus is a diverse genus of filamentous fungi including common house hold mold as well as human pathogens. More than 350 species are currently part of this genus and all their genomes are soon to be sequenced. The availability of this vast amount of data will allow for more in...

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

    OpenAIRE

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jeffrey W Prichard

    2015-01-01

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

  11. The First Time Ever I Saw Your Feet: Inversion Effect in Newborns' Sensitivity to Biological Motion

    Science.gov (United States)

    Bardi, Lara; Regolin, Lucia; Simion, Francesca

    2014-01-01

    Inversion effect in biological motion perception has been recently attributed to an innate sensitivity of the visual system to the gravity-dependent dynamic of the motion. However, the specific cues that determine the inversion effect in naïve subjects were never investigated. In the present study, we have assessed the contribution of the local…

  12. Tensegrity I. Cell structure and hierarchical systems biology

    Science.gov (United States)

    Ingber, Donald E.

    2003-01-01

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

  13. Sulfur K-edge absorption spectroscopy on selected biological systems

    International Nuclear Information System (INIS)

    Lichtenberg, Henning

    2008-07-01

    Sulfur is an essential element in organisms. In this thesis investigations of sulfur compounds in selected biological systems by XANES (X-ray Absorption Near Edge Structure) spectroscopy are reported. XANES spectroscopy at the sulfur K-edge provides an excellent tool to gain information about the local environments of sulfur atoms in intact biological samples - no extraction processes are required. Spatially resolved measurements using a Kirkpatrick-Baez mirror focusing system were carried out to investigate the infection of wheat leaves by rust fungi. The results give information about changes in the sulfur metabolism of the host induced by the parasite and about the extension of the infection into visibly uninfected plant tissue. Furthermore, XANES spectra of microbial mats from sulfidic caves were measured. These mats are dominated by microbial groups involved in cycling sulfur. Additionally, the influence of sulfate deprivation and H 2 S exposure on sulfur compounds in onion was investigated. To gain an insight into the thermal degradation of organic material the influence of roasting of sulfur compounds in coffee beans was studied. (orig.)

  14. Strategies for the reduction of Legionella in biological treatment systems.

    Science.gov (United States)

    Nogueira, R; Utecht, K-U; Exner, M; Verstraete, W; Rosenwinkel, K-H

    A community-wide outbreak of Legionnaire's disease occurred in Warstein, Germany, in August 2013. The epidemic strain, Legionella pneumophila Serogruppe 1, was isolated from an industrial wastewater stream entering the municipal wastewater treatment plant (WWTP) in Wartein, the WWTP itself, the river Wäster and air/water samples from an industrial cooling system 3 km downstream of the WWTP. The present study investigated the effect of physical-chemical disinfection methods on the reduction of the concentration of Legionella in the biological treatment and in the treated effluent entering the river Wäster. Additionally, to gain insight into the factors that promote the growth of Legionella in biological systems, growth experiments were made with different substrates and temperatures. The dosage rates of silver micro-particles, hydrogen peroxide, chlorine dioxide and ozone and pH stress to the activated sludge were not able to decrease the number of culturable Legionella spp. in the effluent. Nevertheless, the UV treatment of secondary treated effluent reduced Legionella spp. on average by 1.6-3.4 log units. Laboratory-scale experiments and full-scale measurements suggested that the aerobic treatment of warm wastewater (30-35 °C) rich in organic nitrogen (protein) is a possible source of Legionella infection.

  15. SYSTEMS BIOLOGY AND METABOLIC ENGINEERING OF ARTHROSPIRA CELL FACTORIES

    Directory of Open Access Journals (Sweden)

    Amornpan Klanchui

    2012-10-01

    Full Text Available Arthrospira are attractive candidates to serve as cell factories for production of many valuable compounds useful for food, feed, fuel and pharmaceutical industries. In connection with the development of sustainable bioprocessing, it is a challenge to design and develop efficient Arthrospira cell factories which can certify effective conversion from the raw materials (i.e. CO2 and sun light into desired products. With the current availability of the genome sequences and metabolic models of Arthrospira, the development of Arthrospira factories can now be accelerated by means of systems biology and the metabolic engineering approach. Here, we review recent research involving the use of Arthrospira cell factories for industrial applications, as well as the exploitation of systems biology and the metabolic engineering approach for studying Arthrospira. The current status of genomics and proteomics through the development of the genome-scale metabolic model of Arthrospira, as well as the use of mathematical modeling to simulate the phenotypes resulting from the different metabolic engineering strategies are discussed. At the end, the perspective and future direction on Arthrospira cell factories for industrial biotechnology are presented.

  16. MIDAS: A Modular DNA Assembly System for Synthetic Biology.

    Science.gov (United States)

    van Dolleweerd, Craig J; Kessans, Sarah A; Van de Bittner, Kyle C; Bustamante, Leyla Y; Bundela, Rudranuj; Scott, Barry; Nicholson, Matthew J; Parker, Emily J

    2018-04-20

    A modular and hierarchical DNA assembly platform for synthetic biology based on Golden Gate (Type IIS restriction enzyme) cloning is described. This enabling technology, termed MIDAS (for Modular Idempotent DNA Assembly System), can be used to precisely assemble multiple DNA fragments in a single reaction using a standardized assembly design. It can be used to build genes from libraries of sequence-verified, reusable parts and to assemble multiple genes in a single vector, with full user control over gene order and orientation, as well as control of the direction of growth (polarity) of the multigene assembly, a feature that allows genes to be nested between other genes or genetic elements. We describe the detailed design and use of MIDAS, exemplified by the reconstruction, in the filamentous fungus Penicillium paxilli, of the metabolic pathway for production of paspaline and paxilline, key intermediates in the biosynthesis of a range of indole diterpenes-a class of secondary metabolites produced by several species of filamentous fungi. MIDAS was used to efficiently assemble a 25.2 kb plasmid from 21 different modules (seven genes, each composed of three basic parts). By using a parts library-based system for construction of complex assemblies, and a unique set of vectors, MIDAS can provide a flexible route to assembling tailored combinations of genes and other genetic elements, thereby supporting synthetic biology applications in a wide range of expression hosts.

  17. Evolving cell models for systems and synthetic biology.

    Science.gov (United States)

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

    2010-03-01

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

  18. Complex Time-Delay Systems Theory and Applications

    CERN Document Server

    Atay, Fatihcan M

    2010-01-01

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

  19. Work at Aldermaston on plutonium binding with biological systems

    International Nuclear Information System (INIS)

    Popplewell, D.S.

    1976-01-01

    Over a number of years, the Chemistry Division of AWRE, Aldermaston, studied the nature of plutonium in various biological systems. The object of the work was to identify those natural products of the body which play a part in the transport and deposition of accidental intakes of plutonium. These results should be of value in formulating more effective therapeutic measures for plutonium removal from the body. The paper reviews the work at AWRE on the interaction of plutonium with serum and rat liver. Experiments on the uptake of plutonium into cell cultures are described. The aim of these experiments was to see whether a model system could be set up for testing the efficacy by which chelating agents could remove plutonium from within cells. A simple hypothesis is presented for the mode of transport of plutonium within animals. (author)

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

    DEFF Research Database (Denmark)

    Andersen, Mikael Rørdam

    2008-01-01

    sequenced Aspergilli are a known human pathogen (Aspergillus fumigatus), a model organism for cellular mechanisms (Aspergillus nidulans) and two industrial workhorses (Aspergillus niger and Aspergillus oryzae). In the presented work, new analytical and computational tools have been designed and a systems......-evolved and not as a haphazardly compiled list of parts. This has been made possible by the socalled genomic revolution — the sequencing of the genomic DNA of a rapidly increasing number of organisms — and the “omic” tecniques following in the wake of the genome projects: metabolomic, proteomic, and transcriptomic to mention...... a few. The recent publication of the genome sequences of several filamentous fungi of the Aspergillus species (Aspergilli), has, along with the accumulation of years of reductionist studies, been a catalyst for the application of systems biology to this interesting group of fungi. Among the genome...

  1. Biological elements carry out optical tasks in coherent imaging systems

    Science.gov (United States)

    Ferraro, P.; Bianco, V.; Paturzo, M.; Miccio, L.; Memmolo, P.; Merola, F.; Marchesano, V.

    2016-03-01

    We show how biological elements, like live bacteria species and Red Blood Cells (RBCs) can accomplish optical functionalities in DH systems. Turbid media allow coherent microscopy despite the strong light scattering these provoke, acting on light just as moving diffusers. Furthermore, a turbid medium can have positive effects on a coherent imaging system, providing resolution enhancement and mimicking the action of noise decorrelation devices, thus yielding an image quality significantly higher than the quality achievable through a transparent medium in similar recording conditions. Besides, suspended RBCs are demonstrated to behave as controllable liquid micro-lenses, opening new possibilities in biophotonics for endoscopy imaging purposes, as well as telemedicine for point-of-care diagnostics in developing countries and low-resource settings.

  2. Theoretical discussion for quantum computation in biological systems

    Science.gov (United States)

    Baer, Wolfgang

    2010-04-01

    Analysis of the brain as a physical system, that has the capacity of generating a display of every day observed experiences and contains some knowledge of the physical reality which stimulates those experiences, suggests the brain executes a self-measurement process described by quantum theory. Assuming physical reality is a universe of interacting self-measurement loops, we present a model of space as a field of cells executing such self-measurement activities. Empty space is the observable associated with the measurement of this field when the mass and charge density defining the material aspect of the cells satisfy the least action principle. Content is the observable associated with the measurement of the quantum wave function ψ interpreted as mass-charge displacements. The illusion of space and its content incorporated into cognitive biological systems is evidence of self-measurement activity that can be associated with quantum operations.

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

    KAUST Repository

    Gomez-Cabrero, David

    2017-08-23

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

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

    KAUST Repository

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

    2017-01-01

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

  5. System for monitoring an industrial or biological process

    Science.gov (United States)

    Gross, Kenneth C.; Wegerich, Stephan W.; Vilim, Rick B.; White, Andrew M.

    1998-01-01

    A method and apparatus for monitoring and responding to conditions of an industrial process. Industrial process signals, such as repetitive manufacturing, testing and operational machine signals, are generated by a system. Sensor signals characteristic of the process are generated over a time length and compared to reference signals over the time length. The industrial signals are adjusted over the time length relative to the reference signals, the phase shift of the industrial signals is optimized to the reference signals and the resulting signals output for analysis by systems such as SPRT.

  6. Scala for Real-Time Systems?

    DEFF Research Database (Denmark)

    Schoeberl, Martin

    2015-01-01

    Java served well as a general-purpose language. However, during its two decades of constant change it has gotten some weight and legacy in the language syntax and the libraries. Furthermore, Java's success for real-time systems is mediocre. Scala is a modern object-oriented and functional language...... with interesting new features. Although a new language, it executes on a Java virtual machine, reusing that technology. This paper explores Scala as language for future real-time systems....

  7. Failure analysis of real-time systems

    International Nuclear Information System (INIS)

    Jalashgar, A.; Stoelen, K.

    1998-01-01

    This paper highlights essential aspects of real-time software systems that are strongly related to the failures and their course of propagation. The significant influence of means-oriented and goal-oriented system views in the description, understanding and analysing of those aspects is elaborated. The importance of performing failure analysis prior to reliability analysis of real-time systems is equally addressed. Problems of software reliability growth models taking the properties of such systems into account are discussed. Finally, the paper presents a preliminary study of a goal-oriented approach to model the static and dynamic characteristics of real-time systems, so that the corresponding analysis can be based on a more descriptive and informative picture of failures, their effects and the possibility of their occurrence. (author)

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  9. Testing Real-Time Systems Using UPPAAL

    DEFF Research Database (Denmark)

    Hessel, Anders; Larsen, Kim Guldstrand; Mikucionis, Marius

    2008-01-01

    This chapter presents principles and techniques for model-based black-box conformance testing of real-time systems using the Uppaal model-checking tool-suite. The basis for testing is given as a network of concurrent timed automata specified by the test engineer. Relativized input...

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

    Science.gov (United States)

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

    2009-10-15

    Mechanistic models are becoming more and more popular in Systems Biology; identification and control of models underlying biochemical pathways of interest in oncology is a primary goal in this field. Unfortunately the scarce availability of data still limits our understanding of the intrinsic characteristics of complex pathologies like cancer: acquiring information for a system understanding of complex reaction networks is time consuming and expensive. Stimulus response experiments (SRE) have been used to gain a deeper insight into the details of biochemical mechanisms underlying cell life and functioning. Optimisation of the input time-profile, however, still remains a major area of research due to the complexity of the problem and its relevance for the task of information retrieval in systems biology-related experiments. We have addressed the problem of quantifying the information associated to an experiment using the Fisher Information Matrix and we have proposed an optimal experimental design strategy based on evolutionary algorithm to cope with the problem of information gathering in Systems Biology. On the basis of the theoretical results obtained in the field of control systems theory, we have studied the dynamical properties of the signals to be used in cell stimulation. The results of this study have been used to develop a microfluidic device for the automation of the process of cell stimulation for system identification. We have applied the proposed approach to the Epidermal Growth Factor Receptor pathway and we observed that it minimises the amount of parametric uncertainty associated to the identified model. A statistical framework based on Monte-Carlo estimations of the uncertainty ellipsoid confirmed the superiority of optimally designed experiments over canonical inputs. The proposed approach can be easily extended to multiobjective formulations that can also take advantage of identifiability analysis. Moreover, the availability of fully automated

  11. Fermion systems in discrete space-time

    International Nuclear Information System (INIS)

    Finster, Felix

    2007-01-01

    Fermion systems in discrete space-time are introduced as a model for physics on the Planck scale. We set up a variational principle which describes a non-local interaction of all fermions. This variational principle is symmetric under permutations of the discrete space-time points. We explain how for minimizers of the variational principle, the fermions spontaneously break this permutation symmetry and induce on space-time a discrete causal structure

  12. Fermion systems in discrete space-time

    Energy Technology Data Exchange (ETDEWEB)

    Finster, Felix [NWF I - Mathematik, Universitaet Regensburg, 93040 Regensburg (Germany)

    2007-05-15

    Fermion systems in discrete space-time are introduced as a model for physics on the Planck scale. We set up a variational principle which describes a non-local interaction of all fermions. This variational principle is symmetric under permutations of the discrete space-time points. We explain how for minimizers of the variational principle, the fermions spontaneously break this permutation symmetry and induce on space-time a discrete causal structure.

  13. Fermion Systems in Discrete Space-Time

    OpenAIRE

    Finster, Felix

    2006-01-01

    Fermion systems in discrete space-time are introduced as a model for physics on the Planck scale. We set up a variational principle which describes a non-local interaction of all fermions. This variational principle is symmetric under permutations of the discrete space-time points. We explain how for minimizers of the variational principle, the fermions spontaneously break this permutation symmetry and induce on space-time a discrete causal structure.

  14. Fermion systems in discrete space-time

    Science.gov (United States)

    Finster, Felix

    2007-05-01

    Fermion systems in discrete space-time are introduced as a model for physics on the Planck scale. We set up a variational principle which describes a non-local interaction of all fermions. This variational principle is symmetric under permutations of the discrete space-time points. We explain how for minimizers of the variational principle, the fermions spontaneously break this permutation symmetry and induce on space-time a discrete causal structure.

  15. Advances in Real-Time Systems

    CERN Document Server

    Chakraborty, Samarjit

    2012-01-01

    This volume contains the lectures given in honor to Georg Farber as tribute to his contributions in the area of real-time and embedded systems. The chapters of many leading scientists cover a wide range of aspects, like robot or automotive vision systems or medical aspects.

  16. uncertain dynamic systems on time scales

    Directory of Open Access Journals (Sweden)

    V. Lakshmikantham

    1995-01-01

    Full Text Available A basic feedback control problem is that of obtaining some desired stability property from a system which contains uncertainties due to unknown inputs into the system. Despite such imperfect knowledge in the selected mathematical model, we often seek to devise controllers that will steer the system in a certain required fashion. Various classes of controllers whose design is based on the method of Lyapunov are known for both discrete [4], [10], [15], and continuous [3–9], [11] models described by difference and differential equations, respectively. Recently, a theory for what is known as dynamic systems on time scales has been built which incorporates both continuous and discrete times, namely, time as an arbitrary closed sets of reals, and allows us to handle both systems simultaneously [1], [2], [12], [13]. This theory permits one to get some insight into and better understanding of the subtle differences between discrete and continuous systems. We shall, in this paper, utilize the framework of the theory of dynamic systems on time scales to investigate the stability properties of conditionally invariant sets which are then applied to discuss controlled systems with uncertain elements. For the notion of conditionally invariant set and its stability properties, see [14]. Our results offer a new approach to the problem in question.

  17. Real-time systems design and analysis

    CERN Document Server

    Laplante, Phillip A

    2004-01-01

    "Real-Time Systems Design and Analysis, Third Edition is essential for students and practicing software engineers who want improved designs, faster computation, and ultimate cost savings. Chapters discuss hardware considerations and software requirements, software systems design, the software production process, performance estimation and optimization, and engineering considerations."--Jacket.

  18. Embedded and real-time operating systems

    CERN Document Server

    Wang, K C

    2017-01-01

    This book covers the basic concepts and principles of operating systems, showing how to apply them to the design and implementation of complete operating systems for embedded and real-time systems. It includes all the foundational and background information on ARM architecture, ARM instructions and programming, toolchain for developing programs, virtual machines for software implementation and testing, program execution image, function call conventions, run-time stack usage and link C programs with assembly code. It describes the design and implementation of a complete OS for embedded systems in incremental steps, explaining the design principles and implementation techniques. For Symmetric Multiprocessing (SMP) embedded systems, the author examines the ARM MPcore processors, which include the SCU and GIC for interrupts routing and interprocessor communication and synchronization by Software Generated Interrupts (SGIs). Throughout the book, complete working sample systems demonstrate the design principles and...

  19. Evolutionary systems biology of amino acid biosynthetic cost in yeast.

    Directory of Open Access Journals (Sweden)

    Michael D Barton

    2010-08-01

    Full Text Available Every protein has a biosynthetic cost to the cell based on the synthesis of its constituent amino acids. In order to optimise growth and reproduction, natural selection is expected, where possible, to favour the use of proteins whose constituents are cheaper to produce, as reduced biosynthetic cost may confer a fitness advantage to the organism. Quantifying the cost of amino acid biosynthesis presents challenges, since energetic requirements may change across different cellular and environmental conditions. We developed a systems biology approach to estimate the cost of amino acid synthesis based on genome-scale metabolic models and investigated the effects of the cost of amino acid synthesis on Saccharomyces cerevisiae gene expression and protein evolution. First, we used our two new and six previously reported measures of amino acid cost in conjunction with codon usage bias, tRNA gene number and atomic composition to identify which of these factors best predict transcript and protein levels. Second, we compared amino acid cost with rates of amino acid substitution across four species in the genus Saccharomyces. Regardless of which cost measure is used, amino acid biosynthetic cost is weakly associated with transcript and protein levels. In contrast, we find that biosynthetic cost and amino acid substitution rates show a negative correlation, but for only a subset of cost measures. In the economy of the yeast cell, we find that the cost of amino acid synthesis plays a limited role in shaping transcript and protein expression levels compared to that of translational optimisation. Biosynthetic cost does, however, appear to affect rates of amino acid evolution in Saccharomyces, suggesting that expensive amino acids may only be used when they have specific structural or functional roles in protein sequences. However, as there appears to be no single currency to compute the cost of amino acid synthesis across all cellular and environmental

  20. Temporal logics and real time expert systems.

    Science.gov (United States)

    Blom, J A

    1996-10-01

    This paper introduces temporal logics. Due to the eternal compromise between expressive adequacy and reasoning efficiency that must decided upon in any application, full (first order logic or modal logic based) temporal logics are frequently not suitable. This is especially true in real time expert systems, where a fixed (and usually small) response time must be guaranteed. One such expert system, Fagan's VM, is reviewed, and a delineation is given of how to formally describe and reason with time in medical protocols. It is shown that Petri net theory is a useful tool to check the correctness of formalised protocols.