WorldWideScience

Sample records for cellular systems biology

  1. The evolution of early cellular systems viewed through the lens of biological interactions

    Directory of Open Access Journals (Sweden)

    Anthony M Poole

    2015-10-01

    Full Text Available The minimal cell concept represents a pragmatic approach to the question of how few genes are required to run a cell. This is a helpful way to build a parts-list, and has been more successful than attempts to deduce a minimal gene set for life by inferring the gene repertoire of the Last Universal Common Ancestor, as few genes trace back to this hypothetical ancestral state. However, the study of minimal cellular systems is the study of biological outliers where, by practical necessity, coevolutionary interactions are minimised or ignored. In this paper, we consider the biological context from which minimal genomes have been removed. For instance, some of the most reduced genomes are from endosymbionts and are the result of coevolutionary interactions with a host; few such organisms are ‘free-living’. As few, if any, biological systems exist in complete isolation, we expect that, as with modern life, early biological systems were part of an ecosystem, replete with organismal interactions. We favour refocusing discussions of the evolution of cellular systems on processes rather than gene counts. We therefore draw a distinction between a pragmatic minimal cell (an interesting engineering problem, a distributed genome (a system resulting from an evolutionary transition involving more than one cell and the looser coevolutionary interactions that are ubiquitous in ecosystems. Finally, we consider the distributed genome and coevolutionary interactions between genomic entities in the context of early evolution.

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

    Science.gov (United States)

    Watanabe, Leandro; Myers, Chris J

    2016-08-19

    The Systems Biology Markup Language (SBML) has been widely used for modeling biological systems. Although SBML has been successful in representing a wide variety of biochemical models, the core standard lacks the structure for representing large complex regular systems in a standard way, such as whole-cell and cellular population models. These models require a large number of variables to represent certain aspects of these types of models, such as the chromosome in the whole-cell model and the many identical cell models in a cellular population. While SBML core is not designed to handle these types of models efficiently, the proposed SBML arrays package can represent such regular structures more easily. However, in order to take full advantage of the package, analysis needs to be aware of the arrays structure. When expanding the array constructs within a model, some of the advantages of using arrays are lost. This paper describes a more efficient way to simulate arrayed models. To illustrate the proposed method, this paper uses a population of repressilator and genetic toggle switch circuits as examples. Results show that there are memory benefits using this approach with a modest cost in runtime. PMID:26912276

  3. Microfluidics-Based in Vivo Mimetic Systems for the Study of Cellular Biology

    OpenAIRE

    Kim, Donghyuk; Wu, Xiaojie; Young, Ashlyn T.; Haynes, Christy L.

    2014-01-01

    Conspectus The human body is a complex network of molecules, organelles, cells, tissues, and organs: an uncountable number of interactions and transformations interconnect all the system’s components. In addition to these biochemical components, biophysical components, such as pressure, flow, and morphology, and the location of all of these interactions play an important role in the human body. Technical difficulties have frequently limited researchers from observing cellular biology as it oc...

  4. Space experiment "Cellular Responses to Radiation in Space (CellRad)": Hardware and biological system tests.

    Science.gov (United States)

    Hellweg, Christine E; Dilruba, Shahana; Adrian, Astrid; Feles, Sebastian; Schmitz, Claudia; Berger, Thomas; Przybyla, Bartos; Briganti, Luca; Franz, Markus; Segerer, Jürgen; Spitta, Luis F; Henschenmacher, Bernd; Konda, Bikash; Diegeler, Sebastian; Baumstark-Khan, Christa; Panitz, Corinna; Reitz, Günther

    2015-11-01

    One factor contributing to the high uncertainty in radiation risk assessment for long-term space missions is the insufficient knowledge about possible interactions of radiation with other spaceflight environmental factors. Such factors, e.g. microgravity, have to be considered as possibly additive or even synergistic factors in cancerogenesis. Regarding the effects of microgravity on signal transduction, it cannot be excluded that microgravity alters the cellular response to cosmic radiation, which comprises a complex network of signaling pathways. The purpose of the experiment "Cellular Responses to Radiation in Space" (CellRad, formerly CERASP) is to study the effects of combined exposure to microgravity, radiation and general space flight conditions on mammalian cells, in particular Human Embryonic Kidney (HEK) cells that are stably transfected with different plasmids allowing monitoring of proliferation and the Nuclear Factor κB (NF-κB) pathway by means of fluorescent proteins. The cells will be seeded on ground in multiwell plate units (MPUs), transported to the ISS, and irradiated by an artificial radiation source after an adaptation period at 0 × g and 1 × g. After different incubation periods, the cells will be fixed by pumping a formaldehyde solution into the MPUs. Ground control samples will be treated in the same way. For implementation of CellRad in the Biolab on the International Space Station (ISS), tests of the hardware and the biological systems were performed. The sequence of different steps in MPU fabrication (cutting, drilling, cleaning, growth surface coating, and sterilization) was optimized in order to reach full biocompatibility. Different coatings of the foil used as growth surface revealed that coating with 0.1 mg/ml poly-D-lysine supports cell attachment better than collagen type I. The tests of prototype hardware (Science Model) proved its full functionality for automated medium change, irradiation and fixation of cells. Exposure of

  5. Cellular and molecular biology group

    International Nuclear Information System (INIS)

    Model DNA polymers have been employed to measure physico-chemical effects of X-irradiation and the influence of known base sequences on the transcription by RNA polymerases. These experiments allow quantitative estimates of the fidelity of transcription in the presence of physical and chemical agents. Cells in culture provide the basic system for studying radiation effects on DNA synthesis, organization of DNA in the nucleus, effects of pollutants on genetic information transfer and gene expression, nucleic acid structure, proliferation capacity, histone phosphorylation, and chromatin structure and function. Mathematical models of the immune response have been formulated, and the biochemical properties of the cell surface have been characterized. The use of flow systems to provide rapid karyotype analysis has been established for relatively simple karyotypes, and a series of cell-cycle-dependent, temperature-sensitive mutant mammalian cell lines have been derived and appear useful for cycle progression and mutagenesis studies

  6. Cellular respiration: replicating in vivo systems biology for in vitro exploration of human exposome, microbiome, and disease pathogenesis biomarkers

    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 ex...

  7. Imaging cellular and molecular biological functions

    Energy Technology Data Exchange (ETDEWEB)

    Shorte, S.L. [Institut Pasteur, 75 - Paris (France). Plateforme d' Imagerie Dynamique PFID-Imagopole; Frischknecht, F. (eds.) [Heidelberg Univ. Medical School (Germany). Dept. of Parasitology

    2007-07-01

    'Imaging cellular and molecular biological function' provides a unique selection of essays by leading experts, aiming at scientist and student alike who are interested in all aspects of modern imaging, from its application and up-scaling to its development. Indeed the philosophy of this volume is to provide student, researcher, PI, professional or provost the means to enter this applications field with confidence, and to construct the means to answer their own specific questions. (orig.)

  8. Cellular Biology in Terms of Stochastic Nonlinear Biochemical Dynamics: Emergent Properties, Isogenetic Variations and Chemical System Inheritability

    Science.gov (United States)

    Qian, Hong

    2010-12-01

    Based on a stochastic, nonlinear, open biochemical reaction system perspective, we present an analytical theory for cellular biochemical processes. The chemical master equation (CME) approach provides a unifying mathematical framework for cellular modeling. We apply this theory to both self-regulating gene networks and phosphorylation-dephosphorylation signaling modules with feedbacks. Two types of bistability are illustrated in mesoscopic biochemical systems: one that has a macroscopic, deterministic counterpart and another that does not. In certain cases, the latter stochastic bistability is shown to be a "ghost" of the extinction phenomenon. We argue the thermal fluctuations inherent in molecular processes do not disappear in mesoscopic cell-sized nonlinear systems; rather they manifest themselves as isogenetic variations on a different time scale. Isogenetic biochemical variations in terms of the stochastic attractors can have extremely long lifetime. Transitions among discrete stochastic attractors spend most of the time in "waiting", exhibit punctuated equilibria. It can be naturally passed to "daughter cells" via a simple growth and division process. The CME system follows a set of nonequilibrium thermodynamic laws that include non-increasing free energy F( t) with external energy drive Q hk ≥0, and total entropy production rate e p =- dF/ dt+ Q hk ≥0. In the thermodynamic limit, with a system's size being infinitely large, the nonlinear bistability in the CME exhibits many of the characteristics of macroscopic equilibrium phase transition.

  9. Nano-jewels in biology. Gold and platinum on diamond nanoparticles as antioxidant systems against cellular oxidative stress.

    Science.gov (United States)

    Martín, Roberto; Menchón, Cristina; Apostolova, Nadezda; Victor, Victor M; Alvaro, Mercedes; Herance, José Raúl; García, Hermenegildo

    2010-11-23

    Diamond nanoparticles (DNPs) obtained by explosive detonation have become commercially available. These commercial DNPs can be treated under Fenton conditions (FeSO(4) and H(2)O(2) at acidic pH) to obtain purer DNP samples with a small average particle size (4 nm) and a large population of surface OH groups (HO-DNPs). These Fenton-treated HO-DNPs have been used as a support of gold and platinum nanoparticles (≤2 nm average size). The resulting materials (Au/HO-DNP and Pt/HO-DNP) exhibit a high antioxidant activity against reactive oxygen species induced in a hepatoma cell line. In addition to presenting good biocompatibility, Au/HO- and Pt/HO-DNP exhibit about a two-fold higher antioxidant activity than glutathione, one of the reference antioxidant systems. The most active material against cellular oxidative stress was Au/HO-DNP. PMID:20939514

  10. The regeneration of epidermal cells of Saintpaulia leaves as a new plant-tissue system for cellular radiation biology.

    Science.gov (United States)

    Engels, F M; van der Laan, F M; Leenhouts, H P; Chadwick, K H

    1980-09-01

    Investigation of the nucleus of epidermal cells of the petioles of Saintpaulia leaves by cytofluorimetry revealed that all cells are in a non-cycling pre DNA synthesis phase. Cultivation of dissected leaves results in a synchronous regeneration process of a defined number of cells. Five days after onset of cultivation the cells reach the first mitosis. The nuclear development during the regeneration process is described. Irradiation of the leaves results in a directly visible inhibition of this regenerating capability which is used to quantify cell survival in a tissue. The data show that the radiation response has a similar shape to that of the survival of single cells in culture. This response can be observed before the first mitosis of the cells and its application as a new plant tissue system for cellular radiation research is discussed. PMID:7012060

  11. Integrated cellular systems

    Science.gov (United States)

    Harper, Jason C.

    integrate cells and direct their behaviors. This process permits, for the first time, the selection and in situ isolation of a single target cell from a population of cells with mixed phenotypes, and the subsequent monitoring of its behavior, and that of its progeny, under well defined conditions. These techniques promise a new means to integrate biomolecules with nanostructures and macroscale systems, and to manipulate cellular behavior at the individual cell level, having significant implications towards development of practical and robust integrated cellular systems.

  12. Synthetic Biology: Tools to Design, Build, and Optimize Cellular Processes

    Directory of Open Access Journals (Sweden)

    Eric Young

    2010-01-01

    Full Text Available The general central dogma frames the emergent properties of life, which make biology both necessary and difficult to engineer. In a process engineering paradigm, each biological process stream and process unit is heavily influenced by regulatory interactions and interactions with the surrounding environment. Synthetic biology is developing the tools and methods that will increase control over these interactions, eventually resulting in an integrative synthetic biology that will allow ground-up cellular optimization. In this review, we attempt to contextualize the areas of synthetic biology into three tiers: (1 the process units and associated streams of the central dogma, (2 the intrinsic regulatory mechanisms, and (3 the extrinsic physical and chemical environment. Efforts at each of these three tiers attempt to control cellular systems and take advantage of emerging tools and approaches. Ultimately, it will be possible to integrate these approaches and realize the vision of integrative synthetic biology when cells are completely rewired for biotechnological goals. This review will highlight progress towards this goal as well as areas requiring further research.

  13. From Cellular Mechanotransduction to Biologically Inspired Engineering

    Science.gov (United States)

    Ingber, Donald E.

    2010-01-01

    This article is based on a lecture I presented as the recipient of the 2009 Pritzker Distinguished Lecturer Award at the Biomedical Engineering Society annual meeting in October 2009. Here, I review more than thirty years of research from my laboratory, beginning with studies designed to test the theory that cells use tensegrity (tensional integrity) architecture to stabilize their shape and sense mechanical signals, which I believed to be critical for control of cell function and tissue development. Although I was trained as a cell biologist, I found that the tools I had at my disposal were insufficient to experimentally test these theories, and thus I ventured into engineering to find critical solutions. This path has been extremely fruitful as it has led to confirmation of the critical role that physical forces play in developmental control, as well as how cells sense and respond to mechanical signals at the molecular level through a process known as cellular mechanotransduction. Many of the predictions of the cellular tensegrity model relating to cell mechanical behaviors have been shown to be valid, and this vision of cell structure led to discovery of the central role that transmembrane adhesion receptors, such as integrins, and the cytoskeleton play in mechanosensing and mechanochemical conversion. In addition, these fundamental studies have led to significant unexpected technology fallout, including development of micromagnetic actuators for non-invasive control of cellular signaling, microfluidic systems as therapeutic extracorporeal devices for sepsis therapy, and new DNA-based nanobiotechnology approaches that permit construction of artificial tensegrities that mimic properties of living materials for applications in tissue engineering and regenerative medicine. PMID:20140519

  14. Biological dosimetry: biochemical and cellular parameters

    International Nuclear Information System (INIS)

    Early after the beginning of radiobiology studies, biochemistry has led to research of a biological dosimeter. From an extensive literature review, methods were selected that might be suitable for dose assessment via biochemical indicators. By now, research both in laboratory animals and in therapeutic or accidental human exposures, do not allow to retain a biochemical parameter alone for the purpose of diagnosis or prognosis. Several enzymatic activities have been precociously studied after irradiation: from these studies, it seems that analysis of four enzymatic activities in serum (serum glutamic oxaloacetic transaminase, amylase, lactic dehydrogenase, alkaline phosphatase) could be the most useful dosimetry system for mass sorting. Detection of DNA damage or methods for measuring somatic mutations are currently advancing and provide important new opportunities for biological dosimetry of low doses

  15. Modeling formalisms in Systems Biology

    OpenAIRE

    Machado, C. D.; Costa, Rafael S.; Rocha, Miguel; Ferreira, E. C.; Tidor, Bruce; Rocha, I.

    2011-01-01

    Systems Biology has taken advantage of computational tools and high-throughput experimental data to model several biological processes. These include signaling, gene regulatory, and metabolic networks. However, most of these models are specific to each kind of network. Their interconnection demands a whole-cell modeling framework for a complete understanding of cellular systems. We describe the features required by an integrated framework for modeling, analyzing and simulating biological proc...

  16. Semantic annotation of biological concepts interplaying microbial cellular responses

    Directory of Open Access Journals (Sweden)

    Carreira Rafael

    2011-11-01

    Full Text Available Abstract Background Automated extraction systems have become a time saving necessity in Systems Biology. Considerable human effort is needed to model, analyse and simulate biological networks. Thus, one of the challenges posed to Biomedical Text Mining tools is that of learning to recognise a wide variety of biological concepts with different functional roles to assist in these processes. Results Here, we present a novel corpus concerning the integrated cellular responses to nutrient starvation in the model-organism Escherichia coli. Our corpus is a unique resource in that it annotates biomedical concepts that play a functional role in expression, regulation and metabolism. Namely, it includes annotations for genetic information carriers (genes and DNA, RNA molecules, proteins (transcription factors, enzymes and transporters, small metabolites, physiological states and laboratory techniques. The corpus consists of 130 full-text papers with a total of 59043 annotations for 3649 different biomedical concepts; the two dominant classes are genes (highest number of unique concepts and compounds (most frequently annotated concepts, whereas other important cellular concepts such as proteins account for no more than 10% of the annotated concepts. Conclusions To the best of our knowledge, a corpus that details such a wide range of biological concepts has never been presented to the text mining community. The inter-annotator agreement statistics provide evidence of the importance of a consolidated background when dealing with such complex descriptions, the ambiguities naturally arising from the terminology and their impact for modelling purposes. Availability is granted for the full-text corpora of 130 freely accessible documents, the annotation scheme and the annotation guidelines. Also, we include a corpus of 340 abstracts.

  17. The cellular and molecular biology of medulloblastoma

    NARCIS (Netherlands)

    Peringa, A; Fung, KM; Muragaki, Y; Trojanowski, JQ

    1995-01-01

    Medulloblastomas are prototypical of primitive neuroectodermal tumors which are some of the most frequent malignant brain tumors of childhood. The cell biology of medulloblastomas is still poorly understood, but recent studies of the expression of trophic factors and their receptors in medulloblasto

  18. Cellular-based preemption system

    Science.gov (United States)

    Bachelder, Aaron D. (Inventor)

    2011-01-01

    A cellular-based preemption system that uses existing cellular infrastructure to transmit preemption related data to allow safe passage of emergency vehicles through one or more intersections. A cellular unit in an emergency vehicle is used to generate position reports that are transmitted to the one or more intersections during an emergency response. Based on this position data, the one or more intersections calculate an estimated time of arrival (ETA) of the emergency vehicle, and transmit preemption commands to traffic signals at the intersections based on the calculated ETA. Additional techniques may be used for refining the position reports, ETA calculations, and the like. Such techniques include, without limitation, statistical preemption, map-matching, dead-reckoning, augmented navigation, and/or preemption optimization techniques, all of which are described in further detail in the above-referenced patent applications.

  19. Biological (molecular and cellular) markers of toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Shugart, L.R.; D' Surney, S.J.; Gettys-Hull, C.; Greeley, M.S. Jr.

    1991-12-15

    Several molecular and cellular markers of genotoxicity were adapted for measurement in the Medaka (Oryzias latipes), and were used to describe the effects of treatment of the organism with diethylnitrosamine (DEN). NO{sup 6}-ethyl guanine adducts were detected, and a slight statistically significant, increase in DNA strand breaks was observed. These results are consistent with the hypothesis that prolonged exposure to high levels of DEN induced alkyltransferase activity which enzymatically removes any O{sup 6}-ethyl guanine adducts but does not result in strand breaks or hypomethylation of the DNA such as might be expected from excision repair of chemically modified DNA. Following a five week continuous DEN exposure with 100 percent renewal of DEN-water every third day, the F values (DNA double strandedness) increased considerably and to similar extent in fish exposed to 25, 50, and 100 ppM DEN. This has been observed also in medaka exposed to BaP.

  20. Biological (molecular and cellular) markers of toxicity

    International Nuclear Information System (INIS)

    Several molecular and cellular markers of genotoxicity were adapted for measurement in the Medaka (Oryzias latipes), and were used to describe the effects of treatment of the organism with diethylnitrosamine (DEN). NO6-ethyl guanine adducts were detected, and a slight statistically significant, increase in DNA strand breaks was observed. These results are consistent with the hypothesis that prolonged exposure to high levels of DEN induced alkyltransferase activity which enzymatically removes any O6-ethyl guanine adducts but does not result in strand breaks or hypomethylation of the DNA such as might be expected from excision repair of chemically modified DNA. Following a five week continuous DEN exposure with 100 percent renewal of DEN-water every third day, the F values (DNA double strandedness) increased considerably and to similar extent in fish exposed to 25, 50, and 100 ppM DEN. This has been observed also in medaka exposed to BaP

  1. Analysis of cellular manufacturing systems

    OpenAIRE

    Heragu, Sunderesh; Meng, Gang; Zijm, Henk; Ommeren, van, J.C.

    2001-01-01

    In this paper, we present an open queuing network modeling approach to estimate performance measures of a cellular manufacturing layout. It is assumed a layout and production data for a planning period of specified length are available. The production data takes into account, processing and handling set-up times as well as transfer and process batch size information of multiple products that flow through the system. It is assumed that two sets of discrete material handling devices are used fo...

  2. 2012 CELLULAR & MOLECULAR FUNGAL BIOLOGY GORDON RESEARCH CONFERENCE, JUNE 17 - 22, 2012

    Energy Technology Data Exchange (ETDEWEB)

    Judith Berman

    2012-06-22

    The Gordon Research Conference on CELLULAR & MOLECULAR FUNGAL BIOLOGY was held at Holderness School, Holderness New Hampshire, June 17 - 22, 2012. The 2012 Gordon Conference on Cellular and Molecular Fungal Biology (CMFB) will present the latest, cutting-edge research on the exciting and growing field of molecular and cellular aspects of fungal biology. Topics will range from yeast to filamentous fungi, from model systems to economically important organisms, and from saprophytes and commensals to pathogens of plants and animals. The CMFB conference will feature a wide range of topics including systems biology, cell biology and morphogenesis, organismal interactions, genome organisation and regulation, pathogenesis, energy metabolism, biomass production and population genomics. The Conference was well-attended with 136 participants. Gordon Research Conferences does not permit publication of meeting proceedings.

  3. The extracellular matrix of plants: Molecular, cellular and developmental biology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-31

    A symposium entitled ``The Extracellular Matrix of Plants: Molecular, Cellular and Developmental Biology was held in Tamarron, Colorado, March 15--21, 1996. The following topics were explored in addresses by 43 speakers: structure and biochemistry of cell walls; biochemistry, molecular biology and biosynthesis of lignin; secretory pathway and synthesis of glycoproteins; biosynthesis of matrix polysaccharides, callose and cellulose; role of the extracellular matrix in plant growth and development; plant cell walls in symbiosis and pathogenesis.

  4. Fluorescence microscopy of single autofluorescent proteins for cellular biology

    OpenAIRE

    Cognet, Laurent; Coussen, Françoise; Choquet, Daniel; Lounis, Brahim

    2002-01-01

    International audience In this paper we review the applicability of autofluorescent proteins for single-molecule imaging in biology. The photophysical characteristics of several mutants of the Green Fluorescent Protein (GFP) and those of DsRed are compared and critically discussed for their use in cellular biology. The alternative use of two-photon excitation at the single-molecule level or Fluorescence Correlation Spectroscopy is envisaged for the study of individual autofluorescent prote...

  5. Estimation in Cellular Radio Systems

    OpenAIRE

    Blom, Jonas; Gunnarsson, Fredrik; Gustafsson, Fredrik

    1999-01-01

    The problem to track time-varying parameters in cellular radio systems is studied, and the focus is on estimation based only on the signals that are readily available. Previous work have demonstrated very good performance, but were relying on analog measurement that are not available. Most of the information is lost due to quantization and sampling at a rate that might be as low as 2 Hz (GSM case). For that matter a maximum likelihood estimator have been designed and exemplified in the case o...

  6. Cellular energy allocation in zebra mussels exposed along a pollution gradient: linking cellular effects to higher levels of biological organization

    International Nuclear Information System (INIS)

    Organisms exposed to suboptimal environments incur a cost of dealing with stress in terms of metabolic resources. The total amount of energy available for maintenance, growth and reproduction, based on the biochemical analysis of the energy budget, may provide a sensitive measure of stress in an organism. While the concept is clear, linking cellular or biochemical responses to the individual and population or community level remains difficult. The aim of this study was to validate, under field conditions, using cellular energy budgets [i.e. changes in glycogen-, lipid- and protein-content and mitochondrial electron transport system (ETS)] as an ecologically relevant measurement of stress by comparing these responses to physiological and organismal endpoints. Therefore, a 28-day in situ bioassay with zebra mussels (Dreissena polymorpha) was performed in an effluent-dominated stream. Five locations were selected along the pollution gradient and compared with a nearby (reference) site. Cellular Energy Allocation (CEA) served as a biomarker of cellular energetics, while Scope for Growth (SFG) indicated effects on a physiological level and Tissue Condition Index and wet tissue weight/dry tissue weight ratio were used as endpoints of organismal effects. Results indicated that energy budgets at a cellular level of biological organization provided the fastest and most sensitive response and energy budgets are a relevant currency to extrapolate cellular effects to higher levels of biological organization within the exposed mussels. - Exposure of zebra mussels along a pollution gradient has adverse effects on the cellular energy allocation, and results can be linked with higher levels of biological organization

  7. 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.

  8. 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).

  9. Systems interface biology

    OpenAIRE

    Francis J Doyle; Stelling, Jörg

    2006-01-01

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

  10. Modeling evolution and immune system by cellular automata

    Energy Technology Data Exchange (ETDEWEB)

    Bezzi, M. [Scuola Internazionale Superiore di Studi Avanzati, Trieste (Italy); Istituto Nazionale di Fisica della Materia, Florence (Italy)

    2001-07-01

    In this review the behavior of two different biological systems is investigated using cellular automata. Starting from this spatially extended approach it is also tried, in some cases, to reduce the complexity of the system introducing mean-field approximation, and solving (or trying to solve) these simplified systems. It is discussed the biological meaning of the results, the comparison with experimental data (if available) and the different features between spatially extended and mean-field versions. The biological systems considered in this review are the following: Darwinian evolution in simple ecosystems and immune system response. In the first section the main features of molecular evolution are introduced, giving a short survey of genetics for physicists and discussing some models for prebiotic systems and simple ecosystems. It is also introduced a cellular automaton model for studying a set of evolving individuals in a general fitness landscape, considering also the effects of co-evolution. In particular the process of species formation (speciation) is described in sect. 5. The second part deals with immune system modeling. The biological features of immune response are discussed, as well as it is introduced the concept of shape space and of idiotypic network. More detailed reviews which deal with immune system models (mainly focused on idiotypic network models) can be found. Other themes here discussed: the applications of CA to immune system modeling, two complex cellular automata for humoral and cellular immune response. Finally, it is discussed the biological data and the general conclusions are drawn in the last section.

  11. Modeling evolution and immune system by cellular automata

    International Nuclear Information System (INIS)

    In this review the behavior of two different biological systems is investigated using cellular automata. Starting from this spatially extended approach it is also tried, in some cases, to reduce the complexity of the system introducing mean-field approximation, and solving (or trying to solve) these simplified systems. It is discussed the biological meaning of the results, the comparison with experimental data (if available) and the different features between spatially extended and mean-field versions. The biological systems considered in this review are the following: Darwinian evolution in simple ecosystems and immune system response. In the first section the main features of molecular evolution are introduced, giving a short survey of genetics for physicists and discussing some models for prebiotic systems and simple ecosystems. It is also introduced a cellular automaton model for studying a set of evolving individuals in a general fitness landscape, considering also the effects of co-evolution. In particular the process of species formation (speciation) is described in sect. 5. The second part deals with immune system modeling. The biological features of immune response are discussed, as well as it is introduced the concept of shape space and of idiotypic network. More detailed reviews which deal with immune system models (mainly focused on idiotypic network models) can be found. Other themes here discussed: the applications of CA to immune system modeling, two complex cellular automata for humoral and cellular immune response. Finally, it is discussed the biological data and the general conclusions are drawn in the last section

  12. 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.

  13. 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’.

  14. Cellular structure in system of interacting particles

    OpenAIRE

    Lev, Bohdan

    2008-01-01

    The general description of formation the cellular structure in the system of interacting particles is proposed. Interactions between particles are presumably well-understood and the phase transition in which can be studied in the scale of particle resolution. We presented analytical results of possible cellular structures for suspension of colloidal particles, in system particles immersed in liquid crystal and gravitational system. We have shown that cellular structure formation can occur in ...

  15. Biological Augmentation of Flexor Tendon Repair: A Challenging Cellular Landscape.

    Science.gov (United States)

    Loiselle, Alayna E; Kelly, Meghan; Hammert, Warren C

    2016-01-01

    Advances in surgical technique and rehabilitation have transformed zone II flexor tendon injuries from an inoperable no-man's land to a standard surgical procedure. Despite these advances, many patients develop substantial range of motion-limiting adhesions after primary flexor tendon repair. These suboptimal outcomes may benefit from biologic augmentation or intervention during the flexor tendon healing process. However, there is no consensus biological approach to promote satisfactory flexor tendon healing; we propose that insufficient understanding of the complex cellular milieu in the healing tendon has hindered the development of successful therapies. This article reviews recent advances in our understanding of the cellular components of flexor tendon healing and adhesion formation, including resident tendon cells, synovial sheath, macrophages, and bone marrow-derived cells. In addition, it examines molecular approaches that have been used in translational animal models to improve flexor tendon healing and gliding function, with a specific focus on progress made using murine models of healing. This information highlights the importance of understanding and potentially exploiting the heterogeneity of the cellular environment during flexor tendon healing, to define rational therapeutic approaches to improve healing outcomes. PMID:26652792

  16. Recent development of cellular manufacturing systems

    Indian Academy of Sciences (India)

    P K Arora; A Haleem; M K Singh

    2013-06-01

    Cellular manufacturing system has been proved a vital approach for batch and job shop production systems. Group technology has been an essential tool for developing a cellular manufacturing system. The paper aims to discuss various cell formation techniques and highlights the significant research work done in past over the years and attempts to points out the gap in research.

  17. Analysis of cellular manufacturing systems

    NARCIS (Netherlands)

    Heragu, Sunderesh; Meng, Gang; Zijm, Henk; Ommeren, van Jan-Kees

    2001-01-01

    In this paper, we present an open queuing network modeling approach to estimate performance measures of a cellular manufacturing layout. It is assumed a layout and production data for a planning period of specified length are available. The production data takes into account, processing and handli

  18. Fluorescence microscopy of single autofluorescent proteins for cellular biology

    CERN Document Server

    Cognet, Laurent; Choquet, Daniel; Lounis, Brahim

    2002-01-01

    In this paper we review the applicability of autofluorescent proteins for single-molecule imaging in biology. The photophysical characteristics of several mutants of the Green Fluorescent Protein (GFP) and those of DsRed are compared and critically discussed for their use in cellular biology. The alternative use of two-photon excitation at the single-molecule level or Fluorescence Correlation Spectroscopy is envisaged for the study of individual autofluorescent proteins. Single-molecule experiments performed in live cells using eGFP and preferably eYFP fusion proteins are reviewed. Finally, the first use at the single-molecule level of citrine, a more photostable variant of the eYFP is reported when fused to a receptor for neurotransmitter in live cells.

  19. Cellular and Molecular Biological Approaches to Interpreting Ancient Biomarkers

    Science.gov (United States)

    Newman, Dianne K.; Neubauer, Cajetan; Ricci, Jessica N.; Wu, Chia-Hung; Pearson, Ann

    2016-06-01

    Our ability to read the molecular fossil record has advanced significantly in the past decade. Improvements in biomarker sampling and quantification methods, expansion of molecular sequence databases, and the application of genetic and cellular biological tools to problems in biomarker research have enabled much of this progress. By way of example, we review how attempts to understand the biological function of 2-methylhopanoids in modern bacteria have changed our interpretation of what their molecular fossils tell us about the early history of life. They were once thought to be biomarkers of cyanobacteria and hence the evolution of oxygenic photosynthesis, but we now believe that 2-methylhopanoid biosynthetic capacity originated in the Alphaproteobacteria, that 2-methylhopanoids are regulated in response to stress, and that hopanoid 2-methylation enhances membrane rigidity. We present a new interpretation of 2-methylhopanes that bridges the gap between studies of the functions of 2-methylhopanoids and their patterns of occurrence in the rock record.

  20. The Universe as a Cellular System

    CERN Document Server

    Aragón-Calvo, Miguel A

    2014-01-01

    Cellular systems are observed everywhere in nature, from crystal domains in metals, soap froth and cucumber cells to the network of cosmological voids. Surprisingly, despite their disparate scale and origin all cellular systems follow certain scaling laws relating their geometry, topology and dynamics. Using a cosmological N-body simulation we found that the Cosmic Web, the largest known cellular system, follows the same scaling relations seen elsewhere in nature. Our results extend the validity of scaling relations in cellular systems by over 30 orders of magnitude in scale with respect to previous studies. The dynamics of cellular systems can be used to interpret local observations such as the local velocity anomaly as the result of a collapsing void in our cosmic backyard. Moreover, scaling relations depend on the curvature of space, providing an independent measure of geometry.

  1. p53: Biology and role for cellular radiosensitivity

    International Nuclear Information System (INIS)

    Purpose: p53 is the most commonly mutated gene in human tumors with large impact on cellular biology and response to radiation. Many excellent reviews are available on various aspects but for several years none about the role of p53 for radiosensitivity. The latter is the aim of the present paper. Methods: Review of the literature. Results: p53 is a regulator of apoptosis mainly in hematopoetic tissue. In normal tissue and solid tumors presumably other functions have more impact on the cellular response. p53 controls cell-cycle progression after irradiation and also DNA-repair, namely homologous and non-homologous recombination. Mutations of p53 alter these functions which may be responsible for an enhanced cellular and tumor radioresistance. At present only few reports were able to show that under tightly controlled conditions loss of p53 wild-type function leads to enhanced radioresistance. A general proof is still lacking. Conclusion: The emerging picture in the year 2000 shows p53 as a central protein in a multi-enzyme multi-function network which is far from being fully understood. Although p53 appears to be a major regulator it is certainly not the unreplacable component the loss of which uniformly determines radioresistance. Only further understanding of modifiers and cooperators in the cell and in the specific tissue context will elucidate p53's role for radiosensitivity and radiotherapy. (orig.)

  2. Engineering scalable biological systems

    OpenAIRE

    Lu, Timothy K.

    2010-01-01

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

  3. MILLIMETER-WAVE EMISSIVITY OF CELLULAR SYSTEMS

    Science.gov (United States)

    A general analysis has been presented of the millimeter-wave and farinfrared spectroscopic properties of in vivo cellular systems, and of the boson radiative equilibrium with steady-state nonequilibrium molecular systems. The frequency threshhold of spectroscopic properties assoc...

  4. 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.

  5. Redefining plant systems biology: from cell to ecosystem

    NARCIS (Netherlands)

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

    2011-01-01

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

  6. Inverse problems in systems biology

    International Nuclear Information System (INIS)

    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)

  7. Beyond the Cell: Using Multiscalar Topics to Bring Interdisciplinarity into Undergraduate Cellular Biology Courses.

    Science.gov (United States)

    Weber, Carolyn F

    2016-01-01

    Western science has grown increasingly reductionistic and, in parallel, the undergraduate life sciences curriculum has become disciplinarily fragmented. While reductionistic approaches have led to landmark discoveries, many of the most exciting scientific advances in the late 20th century have occurred at disciplinary interfaces; work at these interfaces is necessary to manage the world's looming problems, particularly those that are rooted in cellular-level processes but have ecosystem- and even global-scale ramifications (e.g., nonsustainable agriculture, emerging infectious diseases). Managing such problems requires comprehending whole scenarios and their emergent properties as sums of their multiple facets and complex interrelationships, which usually integrate several disciplines across multiple scales (e.g., time, organization, space). This essay discusses bringing interdisciplinarity into undergraduate cellular biology courses through the use of multiscalar topics. Discussing how cellular-level processes impact large-scale phenomena makes them relevant to everyday life and unites diverse disciplines (e.g., sociology, cell biology, physics) as facets of a single system or problem, emphasizing their connections to core concepts in biology. I provide specific examples of multiscalar topics and discuss preliminary evidence that using such topics may increase students' understanding of the cell's position within an ecosystem and how cellular biology interfaces with other disciplines. PMID:27146162

  8. Beyond the Cell: Using Multiscalar Topics to Bring Interdisciplinarity into Undergraduate Cellular Biology Courses

    Science.gov (United States)

    Weber, Carolyn F.

    2016-01-01

    Western science has grown increasingly reductionistic and, in parallel, the undergraduate life sciences curriculum has become disciplinarily fragmented. While reductionistic approaches have led to landmark discoveries, many of the most exciting scientific advances in the late 20th century have occurred at disciplinary interfaces; work at these interfaces is necessary to manage the world’s looming problems, particularly those that are rooted in cellular-level processes but have ecosystem- and even global-scale ramifications (e.g., nonsustainable agriculture, emerging infectious diseases). Managing such problems requires comprehending whole scenarios and their emergent properties as sums of their multiple facets and complex interrelationships, which usually integrate several disciplines across multiple scales (e.g., time, organization, space). This essay discusses bringing interdisciplinarity into undergraduate cellular biology courses through the use of multiscalar topics. Discussing how cellular-level processes impact large-scale phenomena makes them relevant to everyday life and unites diverse disciplines (e.g., sociology, cell biology, physics) as facets of a single system or problem, emphasizing their connections to core concepts in biology. I provide specific examples of multiscalar topics and discuss preliminary evidence that using such topics may increase students’ understanding of the cell’s position within an ecosystem and how cellular biology interfaces with other disciplines. PMID:27146162

  9. 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.

  10. Quantitative Redox Biology: An approach to understanding the role of reactive species in defining the cellular redox environment

    OpenAIRE

    Buettner, Garry R.; Wagner, Brett A.; Victor G J Rodgers

    2013-01-01

    Systems biology is now recognized as a needed approach to understand the dynamics of inter- and intra-cellular processes. Redox processes are at the foundation of nearly all aspects of biology. Free radicals, related oxidants, and antioxidants are central to the basic functioning of cells and tissues. They set the cellular redox environment and therefore are key to regulation of biochemical pathways and networks, thereby influencing organism health. To understand how short-lived, quasi-stable...

  11. Weighted Centroid Correction Localization in Cellular Systems

    Directory of Open Access Journals (Sweden)

    Rong-Zheng Li

    2011-01-01

    Full Text Available Problem statement: There is a large demand for wireless Location-Based Service (LBS and it is provided by many wireless cellular systems. In process of positioning a Mobile Station (MS, the computing speed is as important as the positioning accuracy and the algorithm should also be resistant to environmental influences. Approach: A new positioning method based on Weighted Centroid Correction Localization (WCCL for wireless cellular systems is introduced in this article. Firstly, referring to the receiving-state of an MS in cellular systems, it computes a weighted centroid of surrounding Base Stations (BSs as a rough approximate position of the MS. Then, according to the distances between the MS and the BSs being less or bigger than the computed distances between the BSs and the weighted centroid, it corrects the coordinate of the weighted centroid towards the directions of the BSs by moving it closer or farther in turn. Results: According to our experiments, WCCL improves the positioning accuracy, as well as to provide a better resistance to environmental influences. Conclusion: As a modified centroid-based localization algorithm, WCCL obtains weighting factors from the receiving-state of MS in multi-cells structured cellular systems and obtains a better positioning result in cellular systems without updating the network equipment. Therefore, for the cellular positioning problem, WCCL algorithm can be an alternate solution.

  12. Hyper bio assembler for 3D cellular systems

    CERN Document Server

    Arai, Fumihito; Yamato, Masayuki

    2015-01-01

    Hyper Bio Assembler for Cellular Systems is the first book to present a new methodology for measuring and separating target cells at high speed and constructing 3D cellular systems in vitro. This book represents a valuable resource for biologists, biophysicists and robotic engineers, as well as researchers interested in this new frontier area, offering a better understanding of the measurement, separation, assembly, analysis and synthesis of complex biological tissue, and of the medical applications of these technologies. This book is the outcome of the new academic fields of the Ministry of Education, Culture, Sports, Science and Technology’s Grant-in-Aid for Scientific Research in Japan.

  13. INVITED ARTICLE: Partial differential equations for self-organization in cellular and developmental biology

    Science.gov (United States)

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

    2008-11-01

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

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

    International Nuclear Information System (INIS)

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

  15. Monte Carlo simulation in systems biology

    OpenAIRE

    Schellenberger, Jan

    2010-01-01

    Constraint Based Reconstruction and Analysis (COBRA) is a framework within the field of Systems Biology which aims to understand cellular metabolism through the analysis of large scale metabolic models. These models are based on meticulously curated reconstructions of all chemical reactions in an organism. Instead of attempting to predict the exact state of the biological system, COBRA describes the physiological constraints that the system must satisfy and studies the range of solutions sati...

  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. 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.

  18. Cellular computation using classifier systems

    OpenAIRE

    Kelly, Ciaran; Decraene, James, Lobo, Victor; Mitchell, George G.; McMullin, Barry; O'Brien, Darragh

    2006-01-01

    The EU FP6 Integrated Project PACE ('Programmable Artificial Cell Evolution') is investigating the creation, de novo, of chemical 'protocells'. These will be minimal 'wetware' chemical systems integrating molecular information carriers, primitive energy conversion (metabolism) and containment (membrane). Ultimately they should be capable of autonomous reproduction, and be 'programmable' to realise specific desired function. A key objective of PACE is to explore the application of such pro...

  19. 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...

  20. Consistency Principle in Biological Dynamical Systems

    OpenAIRE

    Kaneko, Kunihiko; Furusawa, Chikara

    2008-01-01

    We propose a principle of consistency between different hierarchical levels of biological systems. Given a consistency between molecule replication and cell reproduction, universal statistical laws on cellular chemical abundances are derived and confirmed experimentally. They include a power law distribution of gene expressions, a lognormal distribution of cellular chemical abundances over cells, and embedding of the power law into the network connectivity distribution. Second, given a consis...

  1. A systems biology approach uncovers cellular strategies used by Methylobacterium extorquens AM1 during the switch from multi- to single-carbon growth.

    Directory of Open Access Journals (Sweden)

    Elizabeth Skovran

    Full Text Available BACKGROUND: When organisms experience environmental change, how does their metabolic network reset and adapt to the new condition? Methylobacterium extorquens is a bacterium capable of growth on both multi- and single-carbon compounds. These different modes of growth utilize dramatically different central metabolic pathways with limited pathway overlap. METHODOLOGY/PRINCIPAL FINDINGS: This study focused on the mechanisms of metabolic adaptation occurring during the transition from succinate growth (predicted to be energy-limited to methanol growth (predicted to be reducing-power-limited, analyzing changes in carbon flux, gene expression, metabolites and enzymatic activities over time. Initially, cells experienced metabolic imbalance with excretion of metabolites, changes in nucleotide levels and cessation of cell growth. Though assimilatory pathways were induced rapidly, a transient block in carbon flow to biomass synthesis occurred, and enzymatic assays suggested methylene tetrahydrofolate dehydrogenase as one control point. This "downstream priming" mechanism ensures that significant carbon flux through these pathways does not occur until they are fully induced, precluding the buildup of toxic intermediates. Most metabolites that are required for growth on both carbon sources did not change significantly, even though transcripts and enzymatic activities required for their production changed radically, underscoring the concept of metabolic setpoints. CONCLUSIONS/SIGNIFICANCE: This multi-level approach has resulted in new insights into the metabolic strategies carried out to effect this shift between two dramatically different modes of growth and identified a number of potential flux control and regulatory check points as a further step toward understanding metabolic adaptation and the cellular strategies employed to maintain metabolic setpoints.

  2. p53: Biology and role for cellular radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Dahm-Daphi, J. [Hamburg Univ. (Germany). Abt. fuer Strahlentherapie und Onkologie

    2000-06-01

    Purpose: p53 is the most commonly mutated gene in human tumors with large impact on cellular biology and response to radiation. Many excellent reviews are available on various aspects but for several years none about the role of p53 for radiosensitivity. The latter is the aim of the present paper. Methods: Review of the literature. Results: p53 is a regulator of apoptosis mainly in hematopoetic tissue. In normal tissue and solid tumors presumably other functions have more impact on the cellular response. p53 controls cell-cycle progression after irradiation and also DNA-repair, namely homologous and non-homologous recombination. Mutations of p53 alter these functions which may be responsible for an enhanced cellular and tumor radioresistance. At present only few reports were able to show that under tightly controlled conditions loss of p53 wild-type function leads to enhanced radioresistance. A general proof is still lacking. Conclusion: The emerging picture in the year 2000 shows p53 as a central protein in a multi-enzyme multi-function network which is far from being fully understood. Although p53 appears to be a major regulator it is certainly not the unreplacable component the loss of which uniformly determines radioresistance. Only further understanding of modifiers and cooperators in the cell and in the specific tissue context will elucidate p53's role for radiosensitivity and radiotherapy. (orig.) [German] Hintergrund: p53 ist das am haeufigsten mutierte Gen in menschlichen Tumoren mit grossem Einfluss auf die zellulaere Biologie und Strahlenantwort. Viele ausgezeichnete Uebersichten sind verfuegbar, aber seit Jahren keine, die die Rolle von p53 fuer die Strahlenempfindlichkeit beleuchtet. Dies ist das Ziel der vorliegenden Arbeit. Methode: Literaturuebersicht. Ergebnis: p53 ist ein Regulator der Apoptose in haematopoetischen Gewerben. Im uebrigen Normalgewebe und in soliden Tumoren haben andere Funktionen groessere Bedeutung fuer die Zellantwort. Nach

  3. Systems Biology Analysis of Heterocellular Signaling.

    Science.gov (United States)

    Tape, Christopher J

    2016-08-01

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

  4. Hierarchical Cellular Structures in High-Capacity Cellular Communication Systems

    CERN Document Server

    Jain, R K; Agrawal, N K

    2011-01-01

    In the prevailing cellular environment, it is important to provide the resources for the fluctuating traffic demand exactly in the place and at the time where and when they are needed. In this paper, we explored the ability of hierarchical cellular structures with inter layer reuse to increase the capacity of mobile communication network by applying total frequency hopping (T-FH) and adaptive frequency allocation (AFA) as a strategy to reuse the macro and micro cell resources without frequency planning in indoor pico cells [11]. The practical aspects for designing macro- micro cellular overlays in the existing big urban areas are also explained [4]. Femto cells are inducted in macro / micro / pico cells hierarchical structure to achieve the required QoS cost effectively.

  5. 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 ‘‘...

  6. Experimental genomics: The application of DNA microarrays in cellular and molecular biology studies

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The genome sequence information in combination with DNA microarrays promises to revolutionize the way of cellular and molecular biological research by allowing complex mixtures of RNA and DNA to interrogated in a parallel and quant itative fashion. DNA microarrays can be used to measure levels of gene expressio n for tens of thousands of gene simultaneously and take advantage of all availab le sequence information for experimental design and data interpretation in pursu it of biological understanding. Recent progress in experimental genomics allows DNA microarrays not simply to provide a catalogue of all the genes and informati on about their function, but to understand how the components work together to comprise functioning cells and organisms. This brief review gives a survey of DNA microarrays technology and its applications in genome and gene function analysis, gene expression studies, biological signal and defense system, cell cyclereg ulation, mechanism of transcriptional regulation, proteomics, and the functional ity of food component.

  7. 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."

  8. Literature Review on Dynamic Cellular Manufacturing System

    Science.gov (United States)

    Nouri Houshyar, A.; Leman, Z.; Pakzad Moghadam, H.; Ariffin, M. K. A. M.; Ismail, N.; Iranmanesh, H.

    2014-06-01

    In previous decades, manufacturers faced a lot of challenges because of globalization and high competition in markets. These problems arise from shortening product life cycle, rapid variation in demand of products, and also rapid changes in manufcaturing technologies. Nowadays most manufacturing companies expend considerable attention for improving flexibility and responsiveness in order to overcome these kinds of problems and also meet customer's needs. By considering the trend toward the shorter product life cycle, the manufacturing environment is towards manufacturing a wide variety of parts in small batches [1]. One of the major techniques which are applied for improving manufacturing competitiveness is Cellular Manufacturing System (CMS). CMS is type of manufacturing system which tries to combine flexibility of job shop and also productivity of flow shop. In addition, Dynamic cellular manufacturing system which considers different time periods for the manufacturing system becomes an important topic and attracts a lot of attention to itself. Therefore, this paper made attempt to have a brief review on this issue and focused on all published paper on this subject. Although, this topic gains a lot of attention to itself during these years, none of previous researchers focused on reviewing the literature of that which can be helpful and useful for other researchers who intend to do the research on this topic. Therefore, this paper is the first study which has focused and reviewed the literature of dynamic cellular manufacturing system.

  9. Quantum Biology at the Cellular Level - elements of the research program

    OpenAIRE

    Bordonaro, Michael; Ogryzko, Vasily

    2013-01-01

    Quantum Biology is emerging as a new field at the intersection between fundamental physics and biology, promising novel insights into the nature and origin of biological order. We discuss several elements of QBCL (Quantum Biology at Cellular Level), a research program designed to extend the reach of quantum concepts to higher than molecular levels of biological organization. Key words. decoherence, macroscopic superpositions, basis-dependence, formal superposition, non-classical correlations,...

  10. Integrative radiation systems biology.

    Science.gov (United States)

    Unger, Kristian

    2014-01-01

    Maximisation of the ratio of normal tissue preservation and tumour cell reduction is the main concept of radiotherapy alone or combined with chemo-, immuno- or biologically targeted therapy. The foremost parameter influencing this ratio is radiation sensitivity and its modulation towards a more efficient killing of tumour cells and a better preservation of normal tissue at the same time is the overall aim of modern therapy schemas. Nevertheless, this requires a deep understanding of the molecular mechanisms of radiation sensitivity in order to identify its key players as potential therapeutic targets. Moreover, the success of conventional approaches that tried to statistically associate altered radiation sensitivity with any molecular phenotype such as gene expression proofed to be somewhat limited since the number of clinically used targets is rather sparse. However, currently a paradigm shift is taking place from pure frequentistic association analysis to the rather holistic systems biology approach that seeks to mathematically model the system to be investigated and to allow the prediction of an altered phenotype as the function of one single or a signature of biomarkers. Integrative systems biology also considers the data from different molecular levels such as the genome, transcriptome or proteome in order to partially or fully comprehend the causal chain of molecular mechanisms. An example for the application of this concept currently carried out at the Clinical Cooperation Group "Personalized Radiotherapy in Head and Neck Cancer" of the Helmholtz-Zentrum München and the LMU Munich is described. This review article strives for providing a compact overview on the state of the art of systems biology, its actual challenges, potential applications, chances and limitations in radiation oncology research working towards improved personalised therapy concepts using this relatively new methodology. PMID:24411063

  11. Integrative radiation systems biology

    International Nuclear Information System (INIS)

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

  12. A framework for understanding cellular manufacturing systems

    OpenAIRE

    Silva, Sílvio Carmo; Alves, Anabela Carvalho

    2002-01-01

    Many practical benefits, such as superior quality of products and short manufacturing lead times, are usually associated with Cellular Manufacturing. These and other benefits can lead to important competitive advantages of companies. However, to fully achieve these benefits there is a need for an evolution from the traditional concept of CM to the more comprehensive one, which we call Product Oriented Manufacturing. Here systems are dynamically reconfigured for total manufac...

  13. Spectrum sharing for future mobile cellular systems

    OpenAIRE

    Bennis, M

    2009-01-01

    Abstract Spectrum sharing has become a high priority research area over the past few years. The motivation behind this lies in the fact that the limited spectrum is currently inefficiently utilized. As recognized by the World radio communication conference (WRC)-07, the amount of identified spectrum is not large enough to support large bandwidths for a substantial number of operators. Therefore, it is paramount for future mobile cellular systems to share the frequency spectrum and coexist ...

  14. Dynamic Channel Allocation in Sectored Cellular Systems

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    It is known that dynamic channel assignment(DCA) strategy outperforms the fixed channel assignment(FCA) strategy in omni-directional antenna cellular systems. One of the most important methods used in DCA was channel borrowing. But with the emergence of cell sectorization and spatial division multiple access(SDMA) which are used to increase the capacity of cellular systems, the channel assignment faces a series of new problems. In this paper, a dynamic channel allocation scheme based on sectored cellular systems is proposed. By introducing intra-cell channel borrowing (borrowing channels from neighboring sectors) and inter-cell channel borrowing (borrowing channels from neighboring cells) methods, previous DCA strategies, including compact pattern based channel borrowing(CPCB) and greedy based dynamic channel assignment(GDCA) schemes proposed by the author, are improved significantly. The computer simulation shows that either intra-cell borrowing scheme or inter-cell borrowing scheme is efficient enough to uniform and non-uniform traffic service distributions.

  15. Immunoisolation Patch System for Cellular Transplantation

    Science.gov (United States)

    Wang, Taylor G. (Inventor)

    2014-01-01

    An immunoisolation patch system, and particularly a patch system comprising multiple immunoisolation microcapsules, each encapsulating biological material such as cells for transplantation, which can be used in the prophylactic and therapeutic treatment of disease in large animals and humans without the need for immunosuppression.

  16. 47 CFR 22.923 - Cellular system configuration.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular system configuration. 22.923 Section... MOBILE SERVICES Cellular Radiotelephone Service § 22.923 Cellular system configuration. Mobile stations... directly or through cellular repeaters. Auxiliary test stations may communicate with base or...

  17. Systems biology of fungal infection

    Directory of Open Access Journals (Sweden)

    Fabian eHorn

    2012-04-01

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

  18. 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....

  19. Traffic Engineering of Cellular Wireless Communication Systems

    DEFF Research Database (Denmark)

    Iversen, Villy Bæk

    2002-01-01

    In mobile communications an efficient utilisation of the channels is of great importance. In this paper we describe the basic principles for obtaining the maximum utilisation and study strategies for obtaining these limits. In general a high degree of sharing is efficient, but requires service...... protection mechanisms to guarantee the Quality of Service for all services. We study cellular systems with hierarchical cells, and the effect of overlapping cells, and we show that by call packing we obtain a very high utilisation. The models are generalisations of the Erlang-B formula, and include general...

  20. Protein microarrays for systems biology

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

  1. Novel chlorinated dibenzofurans isolated from the cellular slime mold, Polysphondylium filamentosum, and their biological activities.

    Science.gov (United States)

    Kikuchi, Haruhisa; Kubohara, Yuzuru; Nguyen, Van Hai; Katou, Yasuhiro; Oshima, Yoshiteru

    2013-08-01

    Cellular slime molds are expected to have the huge potential for producing secondary metabolites including polyketides, and we have studied the diversity of secondary metabolites of cellular slime molds for their potential utilization as new biological resources for natural product chemistry. From the methanol extract of fruiting bodies of Polysphondylium filamentosum, we obtained new chlorinated benzofurans Pf-1 (4) and Pf-2 (5) which display multiple biological activities; these include stalk cell differentiation-inducing activity in the well-studied cellular slime mold, Dictyostelium discoideum, and inhibitory activities on cell proliferation in mammalian cells and gene expression in Drosophila melanogaster. PMID:23746784

  2. Influence of physical and biological factors in cellular radiosensitivity

    International Nuclear Information System (INIS)

    The use of therapeutic radiopharmaceuticals is associated with radiation damage, and this at-nuclear physical properties of radionuclides used and the characteristics of the irradiated cells. The work deals with the damage caused by radiation to DNA, factors that condition and tools that can be used to measure it. It presents current concepts of death and cellular radiosensitivity, based on the pioneering work in this field. Enter the neighborhood effect and adaptive response and evaluates the influence of the same in the paradigms of classical radiobiology. (author)

  3. Interferon-γ: biological function and application for study of cellular immune response

    Directory of Open Access Journals (Sweden)

    A. A. Lutckii

    2015-01-01

    Full Text Available Cellular immune response plays a central role in control of intracellular pathogens like viruses, some bacteria and parasites. Evaluation of presence, specificity and strength of cellular immune response can be done by investigation of reaction of immune cells to specific stimulus, like antigen. The major cellular reactions to antigen stimulation are production of cytokines, proliferation and cytotoxicity. This review is focused on interferon-gamma as one of the central Th1 cytokines: its biology, immunological role and application as marker of cellular immune response.

  4. 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.

  5. Systems Biology from a Yeast Omics Perspective

    OpenAIRE

    Snyder, Michael; Gallagher, Jennifer E.G.

    2009-01-01

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

  6. 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.

  7. Simulating Complex Systems by Cellular Automata

    CERN Document Server

    Kroc, Jiri; Hoekstra, Alfons G

    2010-01-01

    Deeply rooted in fundamental research in Mathematics and Computer Science, Cellular Automata (CA) are recognized as an intuitive modeling paradigm for Complex Systems. Already very basic CA, with extremely simple micro dynamics such as the Game of Life, show an almost endless display of complex emergent behavior. Conversely, CA can also be designed to produce a desired emergent behavior, using either theoretical methodologies or evolutionary techniques. Meanwhile, beyond the original realm of applications - Physics, Computer Science, and Mathematics – CA have also become work horses in very different disciplines such as epidemiology, immunology, sociology, and finance. In this context of fast and impressive progress, spurred further by the enormous attraction these topics have on students, this book emerges as a welcome overview of the field for its practitioners, as well as a good starting point for detailed study on the graduate and post-graduate level. The book contains three parts, two major parts on th...

  8. Mnk kinase pathway: Cellular functions and biological outcomes

    Institute of Scientific and Technical Information of China (English)

    Sonali; Joshi; Leonidas; C; Platanias

    2014-01-01

    The mitogen-activated protein kinase(MAPK) interacting protein kinases 1 and 2(Mnk1 and Mnk2) play important roles in controlling signals involved in mRNA translation. In addition to the MAPKs(p38 or Erk), multiple studies suggest that the Mnk kinases can be regulated by other known kinases such as Pak2 and/or other unidentified kinases by phosphorylation of residues distinct from the sites phosphorylated by the MAPKs. Several studies have established multiple Mnk protein targets, including PSF, heterogenous nuclear ribonucleoprotein A1, Sprouty 2 and have lead to the identification of distinct biological functions and substrate specificity for the Mnk kinases. In this review we discuss the pathways regulating the Mnk kinases, their known substrates as well as the functional consequences of engagement of pathways controlled by Mnk kinases. These kinases play an important role in mRNA translation via their regulation of eukaryotic initiation factor 4E(eIF4E) and their functions have important implications in tumor biology as well as the regulation of drug resistance to anti-oncogenic therapies. Other studies have identified a role for the Mnk kinases in cap-independent mRNA translation, suggesting that the Mnk kinases can exert important functional effects independently of the phosphorylation of eIF4 E. The role of Mnk kinases in inflammation and inflammationinduced malignancies is also discussed.

  9. Optimization of Inter Cellular Movement of Parts in Cellular Manufacturing System Using Genetic Algorithm

    OpenAIRE

    Siva Prasad Darla; C.D. Naiju; Polu Vidya Sagar; B. Venkat Likhit

    2014-01-01

    In the modern manufacturing environment, Cellular Manufacturing Systems (CMS) have gained greater importance in job shop or batch-type production to gain economic advantage similar to those of mass production. Successful implementation of CMS highly depends on the determination of part families; machine cells and minimizing inter cellular movement. This study considers machine component grouping problems namely inter-cellular movement and cell load variation by developing a mathematical model...

  10. Optimization of Inter Cellular Movement of Parts in Cellular Manufacturing System Using Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Siva Prasad Darla

    2014-01-01

    Full Text Available In the modern manufacturing environment, Cellular Manufacturing Systems (CMS have gained greater importance in job shop or batch-type production to gain economic advantage similar to those of mass production. Successful implementation of CMS highly depends on the determination of part families; machine cells and minimizing inter cellular movement. This study considers machine component grouping problems namely inter-cellular movement and cell load variation by developing a mathematical model and optimizing the solution using Genetic Algorithm to arrive at a cell formation to minimize the inter-cellular movement and cell load variation. The results are presented with a numerical example.

  11. Computer algebra in systems biology

    CERN Document Server

    Laubenbacher, Reinhard

    2007-01-01

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

  12. Telemetry System of Biological Parameters

    Directory of Open Access Journals (Sweden)

    Jan Spisak

    2005-01-01

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

  13. 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 ...

  14. Telemetry System of Biological Parameters

    OpenAIRE

    2005-01-01

    The mobile telemetry system of biological parameters serves for reading and wireless data transfer of measured values of selected biological parameters to an outlying computer. It concerns basically long time monitoring of vital function of car pilot.The goal of this projects is to propose mobile telemetry system for reading, wireless transfer and processing of biological parameters of car pilot during physical and psychical stress. It has to be made with respect to minimal consum...

  15. Computational Systems Biology Analysis of Cell Reprogramming and Activation Dynamics

    OpenAIRE

    Fu, Yan

    2012-01-01

    In the past two decades, molecular cell biology has transitioned from a traditional descriptive science into a quantitative science that systematically measures cellular dynamics on different levels of genome, transcriptome and proteome. Along with this transition emerges the interdisciplinary field of systems biology, which aims to unravel complex interactions in biological systems through integrating experimental data into qualitative or quantitative models and computer simulations. In th...

  16. 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....

  17. Promoting inter/multidisciplinary education and research in bioinformatics, systems biology and intelligent computing.

    Science.gov (United States)

    Yang, Mary Qu; Niemierko, Andrzej; Yang, Jack Y; Jin, Yufang

    2009-01-01

    Bioinformatics and systems biology are two booming research areas studying live organisms. Though having different focuses, bioinformatics and systems biology often share same or similar engineering and computer science methods to elucidate the mechanisms of multi-level biological systems. Regulatory mechanisms underlying biological processes involve interactions at cellular, sub-cellular, genomic and genetic levels. Accordingly, we need to bridge the gaps of biomedical researches at different levels of studies and foster the interdisciplinary and multidisciplinary research between both bioinformatics and systems biology domains. The synergic research on integrating bioinformatics and systems biology facilitates the advances in biology and medicine. PMID:20090160

  18. Cellular toxicity (High-Throughput Cellular Assays for Modeling Toxicity in the Fish Reproductive System)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The purpose of this project is to adapt cellular in vitro assay systems of the rainbow trout pituitary, liver and ovary for high-throughput screening (HTS) of...

  19. 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.

  20. 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),...

  1. Cellular burdens and biological effects on tissue level caused by inhaled radon progenies

    CERN Document Server

    Madas, Balázs G; Farkas, Árpád; Szőke, István

    2014-01-01

    In the case of radon exposure, the spatial distribution of deposited radioactive particles is highly inhomogeneous in the central airways. The objective of this research is to investigate the consequences of this heterogeneity regarding cellular burdens in the bronchial epithelium and to study the possible biological effects on tissue level. Applying a computational fluid dynamics program, the deposition distribution of inhaled radon daughters has been determined in a bronchial airway model for 23 minutes of work in the New Mexico uranium mine corresponding to 0.0129 WLM exposure. A numerical epithelium model based on experimental data has been utilized in order to quantify cellular hits and doses. Finally, a carcinogenesis model considering cell death induced cell cycle shortening has been applied to assess the biological responses. Computations present, that cellular dose may reach 1.5 Gy, which is several orders of magnitude higher than tissue dose. The results are in agreement with the histological findin...

  2. Molecular Biology, Biochemistry and Cellular Physiology of Cysteine Metabolism in Arabidopsis thaliana

    Science.gov (United States)

    Hell, Rüdiger; Wirtz, Markus

    2011-01-01

    Cysteine is one of the most versatile molecules in biology, taking over such different functions as catalysis, structure, regulation and electron transport during evolution. Research on Arabidopsis has contributed decisively to the understanding of cysteine synthesis and its role in the assimilatory pathways of S, N and C in plants. The multimeric cysteine synthase complex is present in the cytosol, plastids and mitochondria and forms the centre of a unique metabolic sensing and signaling system. Its association is reversible, rendering the first enzyme of cysteine synthesis active and the second one inactive, and vice-versa. Complex formation is triggered by the reaction intermediates of cysteine synthesis in response to supply and demand and gives rise to regulation of genes of sulfur metabolism to adjust cellular sulfur homeostasis. Combinations of biochemistry, forward and reverse genetics, structural- and cell-biology approaches using Arabidopsis have revealed new enzyme functions and the unique pattern of spatial distribution of cysteine metabolism in plant cells. These findings place the synthesis of cysteine in the centre of the network of primary metabolism. PMID:22303278

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

    Science.gov (United States)

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

    2014-01-01

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

  4. Machine Learning in Systems Biology

    OpenAIRE

    d'Alché-Buc Florence; Wehenkel Louis

    2008-01-01

    Abstract This supplement contains extended versions of a selected subset of papers presented at the workshop MLSB 2007, Machine Learning in Systems Biology, Evry, France, from September 24 to 25, 2007.

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

    OpenAIRE

    Wayne Materi; Wishart, David S.

    2007-01-01

    In recent years it has become clear that carcinogenesis is a complex process, both at the molecular and cellular levels. Understanding the origins, growth and spread of cancer, therefore requires an integrated or system-wide approach. Computational systems biology is an emerging sub-discipline in systems biology that utilizes the wealth of data from genomic, proteomic and metabolomic studies to build computer simulations of intra and intercellular processes. Several useful descriptive and pre...

  6. Modelling coordination in biological systems

    OpenAIRE

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

    2004-01-01

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

  7. Optimization in computational systems biology

    OpenAIRE

    Banga Julio R

    2008-01-01

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

  8. A Decade of Systems Biology

    OpenAIRE

    Chuang, Han-Yu; Hofree, Matan; Ideker, Trey

    2010-01-01

    Systems biology provides a framework for assembling models of biological systems from systematic measurements. Since the field was first introduced a decade ago, considerable progress has been made in technologies for global cell measurement and in computational analyses of these data to map and model cell function. It has also greatly expanded into the translational sciences, with approaches pioneered in yeast now being applied to elucidate human development and disease. Here, we review the ...

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

    OpenAIRE

    Smolke, Christina D.; Silver, Pamela A.

    2011-01-01

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

  10. Ten questions about systems biology

    DEFF Research Database (Denmark)

    Joyner, Michael J; Pedersen, Bente K

    2011-01-01

    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. 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...

  12. Molecular biophysics: detection and characterization of damage in molecular, cellular, and physiological systems

    International Nuclear Information System (INIS)

    This section contains summaries of research on the detection and characterization of damage in molecular, cellular, and physiological systems. Projects under investigation in this section include: chemical synthesis of nucleic acid derivatives; structural and conformational properties of biological molecules in solution; crystallographic and chemical studies of immunoglobulin structure; instrument design and development for x-ray and neutron scattering studies of biological molecules; and chromobiology and circadian regulation

  13. Dynamic production scheduling in virtual cellular manufacturing systems

    OpenAIRE

    马俊; Ma, Jun

    2012-01-01

    Manufacturing companies must constantly improve productivity to respond to dynamic changes in customer demand in order to maintain their competitiveness and marketshares. This requires manufacturers to adopt more efficient methodologies to design and control their manufacturing systems. In recent decades, virtual cellular manufacturing (VCM), as an advanced manufacturing concept, has attracted increasing attention in the research community, because traditional cellular manufacturing is inadeq...

  14. A study of the biological effects of rare earth elements at cellular level using nuclear techniques

    International Nuclear Information System (INIS)

    Objective: To investigate the biological effects and the effecting mechanisms of rare earth elements La, Gd and Ce on cultured rat cells. Methods: The biological effects of La3+ on cultured rat cells and the subcellular distribution of La and Gd and Ce, and the inflow of 45Ca2+ into the cells and total cellular calcium were measured by isotopic tracing, Proton Induced X Ray Emission Analysis (PIXE) and the techniques of biochemistry and cellular biology. Results: La3+ at the concentration of 10-10(or 10-9) - 10-6 mol/L significantly increased quantity of incorporation of 3H-TdR into DNA, total cellular protein and the activity of succinic dehydrogenase of mitochondria. The cell cycle analysis showed that the proportions of cells in S phase were accordingly increased acted by La3+ at above range of concentration. But these values were significantly decreased when concentration of La3+ raised to 10-4 - 10-3 mol/L. It was further discovered that La, Gd and Ce distributed mostly in the nuclei, and then in membranes. Gd and Ce also promoted the inflow of 45Ca2+ into the cells and increased the total calcium content in cells. Conclusions: 1) La3+ at a wide concentration range of 10-10( or 10-9) - 10-6 mol/L promotes proliferation of cultured rat cells, but at even higher concentration (10-4 - 10-3 mol/L) shows cellular toxicity, and there is a striking dose-effect relationship. 2) La, Gd and Ce can enter the cells and mainly distribute in the nuclei. 3) Gd and Ce can promote the inflow of extracellular Ca2+ into the cells and increase total cellular calcium

  15. Stochastic narrow escape in molecular and cellular biology analysis and applications

    CERN Document Server

    Holcman, David

    2015-01-01

    This book covers recent developments in the non-standard asymptotics of the mathematical narrow escape problem in stochastic theory, as well as applications of the narrow escape problem in cell biology. The first part of the book concentrates on mathematical methods, including advanced asymptotic methods in partial equations, and is aimed primarily at applied mathematicians and theoretical physicists who are interested in biological applications. The second part of the book is intended for computational biologists, theoretical chemists, biochemists, biophysicists, and physiologists. It includes a summary of output formulas from the mathematical portion of the book and concentrates on their applications in modeling specific problems in theoretical molecular and cellular biology. Critical biological processes, such as synaptic plasticity and transmission, activation of genes by transcription factors, or double-strained DNA break repair, are controlled by diffusion in structures that have both large and small sp...

  16. Towards systems thinking in cell biology education

    OpenAIRE

    Verhoeff, Roald Pieter

    2003-01-01

    Students are taught a large variety of life structures and processes at the cellular level. The concepts used to describe them are mainly drawn from the sub-cellular level, but this knowledge seems to be fragmentary if its integration at the cellular and organismic level remains undone. As a consequence, many students fail to acquire coherent conceptual understanding of the cell as a basic and functional unit of the organism. To enhance the coherence in students’ cell biological knowledge we ...

  17. Systems biology and cancer, [Editorial

    OpenAIRE

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

    2011-01-01

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

  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. Hormesis and adaptive cellular control systems

    Science.gov (United States)

    Hormetic dose response occurs for many endpoints associated with exposures of biological organisms to environmental stressors. Cell-based U- or inverted U-shaped responses may derive from common processes involved in activation of adaptive responses required to protect cells from...

  20. Spectral efficiency of cellular land mobile radio systems

    OpenAIRE

    Hammuda, H; McGeehan, JP; Bateman, A.

    1988-01-01

    A rigorous and comprehensive approach to the definition and evaluation of spectral efficiency of cellular land mobile radio systems is presented. The method accounts for all pertinent system parameters within a cellular land mobile radio network. Subjective tests to evaluate the protection ratio for various systems is thought to be imperative to the evaluation of spectral efficiency. A comparison is made of a number of current and proposed mobile radio schemes based on the spectral efficiency...

  1. BioXyce: an engineering platform for the study of cellular systems.

    Science.gov (United States)

    May, E E; Schiek, R L

    2009-03-01

    Researchers use constructs from the field of electrical engineering for the modelling and analysis of biological systems, but few exploit parallels between electrical and biological circuits for simulation purposes. The authors discuss the development of BioXyce, a circuit-based biological simulation platform that uses Xyce, a large-scale electrical circuit simulator, as its simulation engine. BioXyce is capable of simulating whole-cell and multicellular systems. Simulation results for the central metabolism in Escherichia coli K12 and cellular differentiation in Drosophila sp. are presented. PMID:19292562

  2. Iterative Cellular Screening System for Nanoparticle Safety Testing

    Directory of Open Access Journals (Sweden)

    Franziska Sambale

    2015-01-01

    Full Text Available Nanoparticles have the potential to exhibit risks to human beings and to the environment; due to the wide applications of nanoproducts, extensive risk management must not be neglected. Therefore, we have constructed a cell-based, iterative screening system to examine a variety of nanoproducts concerning their toxicity during development. The sensitivity and application of various cell-based methods were discussed and proven by applying the screening to two different nanoparticles: zinc oxide and titanium dioxide nanoparticles. They were used as benchmarks to set up our methods and to examine their effects on mammalian cell lines. Different biological processes such as cell viability, gene expression of interleukin-8 and heat shock protein 70, as well as morphology changes were investigated. Within our screening system, both nanoparticle suspensions and coatings can be tested. Electric cell impedance measurements revealed to be a good method for online monitoring of cellular behavior. The implementation of three-dimensional cell culture is essential to better mimic in vivo conditions. In conclusion, our screening system is highly efficient, cost minimizing, and reduces the need for animal studies.

  3. Cellular Particle Dynamics simulation of biomechanical relaxation processes of multi-cellular systems

    Science.gov (United States)

    McCune, Matthew; Kosztin, Ioan

    2013-03-01

    Cellular Particle Dynamics (CPD) is a theoretical-computational-experimental framework for describing and predicting the time evolution of biomechanical relaxation processes of multi-cellular systems, such as fusion, sorting and compression. In CPD, cells are modeled as an ensemble of cellular particles (CPs) that interact via short range contact interactions, characterized by an attractive (adhesive interaction) and a repulsive (excluded volume interaction) component. The time evolution of the spatial conformation of the multicellular system is determined by following the trajectories of all CPs through numerical integration of their equations of motion. Here we present CPD simulation results for the fusion of both spherical and cylindrical multi-cellular aggregates. First, we calibrate the relevant CPD model parameters for a given cell type by comparing the CPD simulation results for the fusion of two spherical aggregates to the corresponding experimental results. Next, CPD simulations are used to predict the time evolution of the fusion of cylindrical aggregates. The latter is relevant for the formation of tubular multi-cellular structures (i.e., primitive blood vessels) created by the novel bioprinting technology. Work supported by NSF [PHY-0957914]. Computer time provided by the University of Missouri Bioinformatics Consortium.

  4. Bridging the gap between systems biology and synthetic biology

    OpenAIRE

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

    2013-01-01

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

  5. 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

  6. Interference cancellation technique under imperfect synchronization in cellular systems

    Institute of Scientific and Technical Information of China (English)

    WANG; Xin; WU; Zhuo

    2009-01-01

    In this paper, an asynchronous cooperative cellular system applied with space-time block coding(STBC)is investigated. A signal detector is proposed based on parallel interference cancellation(PIC), to cancel the inter-symbol interference(ISI)caused by the imperfect synchronization. Simulation results show that the proposed PIC detector can effectively suppress the ISI, but there is still a comparatively high error floor, due to the co-channel interference(CCI)of the cellular system.

  7. Magnetic effects in cellular and molecular systems

    International Nuclear Information System (INIS)

    Brief discussions are presented of six aspects of the phenomenon. Individual topics discussed include: (1) mechanisms of magnetic field interactions with retinal rods; (2) orientation of biological membranes and cells in magnetic fields; (3) enzyme-substrate reactions in high magnetic fields; (4) effects on cell function resulting from exposure to strong magnetic fields at 40K; (5) effects of a transverse magnetic field on the dose distribution of high energy electrons and in the responses of mammalian cells in vitro to x rays; and (6) effect of magnetic fields on the drug-induced contractility of the ciliate Spirostomum

  8. Modelling Cellular Processes using Membrane Systems with Peripheral and Integral Proteins

    OpenAIRE

    Cavaliere, Matteo; Sedwards, Sean

    2006-01-01

    Membrane systems were introduced as models of computation inspired by the structure and functioning of biological cells. Recently, membrane systems have also been shown to be suitable to model cellular processes. We introduce a new model called Membrane Systems with Peripheral and Integral Proteins. The model has compartments enclosed by membranes, floating objects, objects associated to the internal and external surfaces of the membranes and also objects integral to the membranes. The floati...

  9. Modelling coordination in biological systems

    NARCIS (Netherlands)

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

    2004-01-01

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

  10. Tunable promoters in systems biology

    DEFF Research Database (Denmark)

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

    2005-01-01

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

  11. The brittleness model of complex system based on cellular automata

    Institute of Scientific and Technical Information of China (English)

    LIN De-ming; JIN Hong-zhang; LI Qi; WU Hong-mei

    2004-01-01

    Now the research on the complex system is a hot spot. Brittleness is one of the basic characteristics of a complex system. In a complex system, after one of subsystems is struck to be collapsed, the whole system will collapse. Meanwhile, cellular automata is a discrete dynamic system. When the rule is given, the cellular automata could be defined. Then it can imitate the complex action. Cellular automata is used to simulate the brittleness action in this study. Entropy was used to analyze the action and get the rule. Then,three normal brittleness models were given. The result shows that the brittleness of complex system is existent and in addition some important behavior mode of complex system brittleness has been achieved.

  12. A differential genome-wide transcriptome analysis: impact of cellular copper on complex biological processes like aging and development.

    Directory of Open Access Journals (Sweden)

    Jörg Servos

    Full Text Available The regulation of cellular copper homeostasis is crucial in biology. Impairments lead to severe dysfunctions and are known to affect aging and development. Previously, a loss-of-function mutation in the gene encoding the copper-sensing and copper-regulated transcription factor GRISEA of the filamentous fungus Podospora anserina was reported to lead to cellular copper depletion and a pleiotropic phenotype with hypopigmentation of the mycelium and the ascospores, affected fertility and increased lifespan by approximately 60% when compared to the wild type. This phenotype is linked to a switch from a copper-dependent standard to an alternative respiration leading to both a reduced generation of reactive oxygen species (ROS and of adenosine triphosphate (ATP. We performed a genome-wide comparative transcriptome analysis of a wild-type strain and the copper-depleted grisea mutant. We unambiguously assigned 9,700 sequences of the transcriptome in both strains to the more than 10,600 predicted and annotated open reading frames of the P. anserina genome indicating 90% coverage of the transcriptome. 4,752 of the transcripts differed significantly in abundance with 1,156 transcripts differing at least 3-fold. Selected genes were investigated by qRT-PCR analyses. Apart from this general characterization we analyzed the data with special emphasis on molecular pathways related to the grisea mutation taking advantage of the available complete genomic sequence of P. anserina. This analysis verified but also corrected conclusions from earlier data obtained by single gene analysis, identified new candidates of factors as part of the cellular copper homeostasis system including target genes of transcription factor GRISEA, and provides a rich reference source of quantitative data for further in detail investigations. Overall, the present study demonstrates the importance of systems biology approaches also in cases were mutations in single genes are analyzed to

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

    DEFF Research Database (Denmark)

    Andersen, Mikael Rørdam

    2008-01-01

    The recent dawn of the new biological mindset called systems biology has put forth a new way of analyzing and understanding biology. Carried by the notion that no element of a cell is an island, systems biology takes a holistic approach, and attempts to understand life as systems that have co...... 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 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...

  14. Bridging the gap between systems biology and synthetic biology

    Directory of Open Access Journals (Sweden)

    FuzhongZhang

    2013-07-01

    Full Text Available Systems biology is an inter-disciplinary science that studies the complex interactions and the collective behavior of a cell or an organism. Synthetic biology, as a technological subject, combines biological science and engineering, allowing the design and manipulation of a system for certain applications. Both systems and synthetic biology have played important roles in the recent development of microbial platforms for energy, materials, and environmental applications. More importantly, systems biology provides the knowledge necessary for the development of synthetic biology tools, which in turn facilitates the manipulation and understanding of complex biological systems. Thus, the combination of systems and synthetic biology has huge potential for studying and engineering microbes, especially to perform advanced tasks, such as producing biofuels. Although there have been very few studies in integrating systems and synthetic biology, existing examples have demonstrated great power in extending microbiological capabilities. This review focuses on recent efforts in microbiological genomics, transcriptomics, proteomics and metabolomics, aiming to fill the gap between systems and synthetic biology.

  15. Performance evaluation of cellular layouts : extension to DRC system contexts

    NARCIS (Netherlands)

    Suresh, NC; Gaalman, GJC

    2000-01-01

    This study involves a comparison of the performance of functional layouts (FL) and cellular manufacturing (CM) systems in a dual-resource-constrained( DRC) system context. Past studies of FL and CM have been based mostly on single-resource-constrained( SRC) systems. Recent studies have included labo

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

    OpenAIRE

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

    2011-01-01

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

  17. A cellular imaging CDIO project for 2nd semester students in engineering biology

    OpenAIRE

    Wetterö, Jonas; Pettersson, Sofia; Holmgren Peterson, Kajsa

    2006-01-01

    The demand for exact engineering within the life sciences is growing and the Engineering Biology programme at Linköping University, Linköping, Sweden, prepares students for a career at this interface. Conceive – Design – Implement – Operate (CDIO) was recently pioneered in an introductory project course. Groups of six to seven students apply a LIPS scalable project model from traditional engineering educational environments on, for example, a cellular imaging task in a hospital setting, prior...

  18. Just Working with the Cellular Machine: A High School Game for Teaching Molecular Biology

    Science.gov (United States)

    Cardoso, Fernanda Serpa; Dumpel, Renata; Gomes da Silva, Luisa B.; Rodrigues, Carlos R.; Santos, Dilvani O.; Cabral, Lucio Mendes; Castro, Helena C.

    2008-01-01

    Molecular biology is a difficult comprehension subject due to its high complexity, thus requiring new teaching approaches. Herein, we developed an interdisciplinary board game involving the human immune system response against a bacterial infection for teaching molecular biology at high school. Initially, we created a database with several…

  19. Traffic Engineering of Cellular Wireless Communication Systems

    DEFF Research Database (Denmark)

    Iversen, Villy Bæk

    2002-01-01

    In mobile communications an efficient utilisation of the channels is of great importance. In this paper we describe the basic principles for obtaining the maximum utilisation and study strategies for obtaining these limits. In general a high degree of sharing is efficient, but requires service pr...... arrival processes, and multi-rate (multi-media) traffic for third generation systems....

  20. Bridging the gaps in systems biology

    OpenAIRE

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

    2014-01-01

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

  1. Cross-Layer Energy Optimization in Cooperative Cellular Systems

    Directory of Open Access Journals (Sweden)

    M.Sushanth Babu

    2012-10-01

    Full Text Available Cooperative networking is currently under standardization for future wireless cellular systems. This paper considers energy efficient transmission schemes in cooperative cellular transceiver systems. In which, we analyze how to minimize energy consumption per information bit in single link. Further, Target bit error probability, Packet length, Retransmission and Transmission distance for both coded and un coded system are considered as the performance metrics for the optimization of energy. The simulation results illustrate the effect of energy efficient modulation schemes for variable distances and fixed bit error probability.

  2. Systems Approaches for Synthetic Biology: A Pathway Toward Mammalian Design

    Directory of Open Access Journals (Sweden)

    RahulRekhi

    2013-10-01

    Full Text Available We review methods of understanding cellular interactions through computation in order to guide the synthetic design of mammalian cells for translational applications, such as regenerative medicine and cancer therapies. In doing so, we argue that the challenges of engineering mammalian cells provide a prime opportunity to leverage advances in computational systems biology. We support this claim systematically, by addressing each of the principal challenges to existing synthetic bioengineering approaches—stochasticity, complexity, and scale—with specific methods and paradigms in systems biology. Moreover, we characterize a key set of diverse computational techniques, including agent-based modeling, Bayesian network analysis, graph theory, and Gillespie simulations, with specific utility towards synthetic biology. Lastly, we examine the mammalian applications of synthetic biology for medicine and health, and how computational systems biology can aid in the continued development of these applications.

  3. 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.

  4. 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.

  5. Systems Biology of Asthma and Allergic Diseases: A Multiscale Approach

    OpenAIRE

    Bunyavanich, Supinda; Schadt, Eric E.

    2014-01-01

    Systems biology is an approach to understanding living systems that focuses on modeling diverse types of high-dimensional interactions to develop a more comprehensive understanding of complex phenotypes manifested by the system. High throughput molecular, cellular, and physiologic profiling of populations is coupled with bioinformatic and computational techniques to identify new functional roles for genes, regulatory elements, and metabolites in the context of the molecular networks that defi...

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

    OpenAIRE

    Bor-Sen Chen; Chia-Chou Wu

    2013-01-01

    Systems biology aims at achieving a system-level understanding of living organisms and applying this knowledge to various fields such as synthetic biology, metabolic engineering, and medicine. System-level understanding of living organisms can be derived from insight into: (i) system structure and the mechanism of biological networks such as gene regulation, protein interactions, signaling, and metabolic pathways; (ii) system dynamics of biological networks, which provides an understanding of...

  7. General Chemistry and Cellular and Molecular Biology: An Experiment in Curricular Symbiosis

    Science.gov (United States)

    Truman Schwartz, A.; Serie, Jan

    2001-11-01

    During the 1998-99 academic year, with the support of the Howard Hughes Medical Institute, we co-taught integrated courses in general chemistry and cell biology to 23 first-year students. The double course was organized around six units: I. Energetics: Harvesting (Bio)Chemical Energy; II. The Regulation of Biological Processes: Chemical Kinetics and Equilibrium; III. Membranes and Electrochemical Gradients; IV. Acids and Bases and the Regulation of pH; V. Intracellular Compartments and Transport; and VI. Cellular Communication. The chemistry and biology were both taught in a manner meant to enhance understanding of these major themes and to emphasize the relationships between the two disciplines. Both of us were present for all class sessions and shared teaching responsibilities. The examinations, which corresponded to the units, also stressed the interdependence of biology and chemistry. The laboratory components were not integrated; rather the students were dispersed among laboratory sections shared with students from more traditional lecture sections. The paper reports on this experiment in curricular symbiosis, which proved to be a challenging and rewarding learning experience for both the students and us.

  8. 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...

  9. Evolution of Cellular Automata using Lindenmayer Systems and Fourier Transforms

    OpenAIRE

    Berg, Sivert

    2013-01-01

    Cellular automata (CAs) are a class of highly parallel computing systems consisting of many simple computing elements called cells. The cells can only communicate with neighboring cells, meaning there is no global communication in the system. Programming such a system to solve complex problems can be a daunting task, and indirect methods are often applied to make it easier. In this thesis we use evolutionary algorithms (EAs) to evolve CAs. We also look at the possibility of employing L-system...

  10. Using a Virtual Tissue Culture System to Assist Students in Understanding Life at the Cellular Level

    Science.gov (United States)

    McLauglin, Jacqueline S.; Seaquist, Stephen B.

    2008-01-01

    In every biology course ever taught in the nation's classrooms, and in every biology book ever published, students are taught about the "cell." The cell is as fundamental to biology as the atom is to chemistry. Truly, everything an organism does occurs fundamentally at the cellular level. Beyond memorizing the cellular definition, students are not…

  11. Challenges in Characterizing and Controlling Complex Cellular Systems

    Science.gov (United States)

    Wikswo, John

    2011-03-01

    Multicellular dynamic biological processes such as developmental differentiation, wound repair, disease, aging, and even homeostasis can be represented by trajectories through a phase space whose extent reflects the genetic, post-translational, and metabolic complexity of the process - easily extending to tens of thousands of dimensions. Intra- and inter-cellular sensing and regulatory systems and their nested, redundant, and non-linear feed-forward and feed-back controls create high-dimensioned attractors in this phase space. Metabolism provides free energy to drive non-equilibrium processes and dynamically reconfigure attractors. Studies of single molecules and cells provide only minimalist projections onto a small number of axes. It may be difficult to infer larger-scale emergent behavior from linearized experiments that perform only small amplitude perturbations on a limited number of the dimensions. Complete characterization may succeed for bounded component problems, such as an individual cell cycle or signaling cascade, but larger systems problems will require a coarse-grained approach. Hence a new experimental and analytical framework is needed. Possibly one could utilize high-amplitude, multi-variable driving of the system to infer coarse-grained, effective models, which in turn can be tested by their ability to control systems behavior. Navigation at will between attractors in a high-dimensioned dynamical system will provide not only detailed knowledge of the shape of attractor basins, but also measures of underlying stochastic events such as noise in gene expression or receptor binding and how both affect system stability and robustness. Needed for this are wide-bandwidth methods to sense and actuate large numbers of intracellular and extracellular variables and automatically and rapidly infer dynamic control models. The success of this approach may be determined by how broadly the sensors and actuators can span the full dimensionality of the phase space

  12. 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...... 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.......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...

  13. Yeast systems biology to unravel the network of life

    DEFF Research Database (Denmark)

    Mustacchi, Roberta; Hohmann, S; Nielsen, Jens

    2006-01-01

    Systems biology focuses on obtaining a quantitative description of complete biological systems, even complete cellular function. In this way, it will be possible to perform computer-guided design of novel drugs, advanced therapies for treatment of complex diseases, and to perform in silico design...... of advanced cell factories for production of fuels, chemicals, food ingredients and pharmaceuticals. The yeast Saccharomyces cerevisiae represents an excellent model system; the density of biological information available on this organism allows it to serve as a eukaryotic model for studying human...... diseases. Furthermore, it serves as an industrial workhorse for production of a wide range of chemicals and pharmaceuticals. Systems biology involves the combination of novel experimental techniques from different disciplines as well as functional genomics, bioinformatics and mathematical modelling, and...

  14. Control of Directional Macromolecular Trafficking Across Specific Cellular Boundaries: A Key to Integrative Plant Biology

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    There is now solid evidence that cell-to-cell trafficking of certain proteins and RNAs plays a critical role in trans-cellular regulation of gene expression to coordinate cellular differentiation and development. Such trafficking also is critical for viral infection and plant defense. The mechanisms of trafficking remain poorly understood. Although some proteins may move between cells by diffusion, many proteins and RNAs move in a highly regulated fashion. Regulation is likely achieved through interactions between distinct protein or RNA motifs and cellular factors. Some motifs and factors have been identified. One of the major focuses for future studies is to identify all motifs and their cognate factors and further elucidate their roles in trafficking between specific cells. With increasing information from such studies, we should be able to develop an understanding of the mechanisms that regulate trafficking of various proteins and RNAs across all and specific cellular boundaries. On the basis of such mechanistic knowledge, we can further investigate how the trafficking machinery has evolved to regulate developmental and physiological processes in a plant, how pathogens have co-evolved to use this machinery for systemic spread in a plant, and how plants use this machinery for counterdefense.

  15. A Novel Mathematical Model Describing Adaptive Cellular Drug Metabolism and Toxicity in the Chemoimmune System

    OpenAIRE

    Tóth, Attila; Brózik, Anna; Szakács, Gergely; Sarkadi, Balázs; Hegedüs, Tamás

    2015-01-01

    Cells cope with the threat of xenobiotic stress by activating a complex molecular network that recognizes and eliminates chemically diverse toxic compounds. This “chemoimmune system” consists of cellular Phase I and Phase II metabolic enzymes, Phase 0 and Phase III ATP Binding Cassette (ABC) membrane transporters, and nuclear receptors regulating these components. In order to provide a systems biology characterization of the chemoimmune network, we designed a reaction kinetic model based on d...

  16. 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

  17. 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.

  18. Controlled vocabularies and semantics in systems biology

    OpenAIRE

    Courtot, Mélanie; Juty, Nick; Knüpfer, Christian; Waltemath, Dagmar; Zhukova, Anna; Dräger, Andreas; Dumontier, Michel; Finney, Andrew; Golebiewski, Martin; Hastings, Janna; Hoops, Stefan; Keating, Sarah; Douglas B. Kell; Kerrien, Samuel; Lawson, James

    2011-01-01

    The use of computational modeling to describe and analyze biological systems is at the heart of systems biology. This Perspective discusses the development and use of ontologies that are designed to add semantic information to computational models and simulations.

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

    OpenAIRE

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

    2014-01-01

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

  20. Answering biological questions: querying a systems biology database for nutrigenomics

    OpenAIRE

    Evelo, Chris T.; van Bochove, Kees; Saito, Jahn-Takeshi

    2010-01-01

    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 particularly urgent objective in coping with the data avalanche is making biologically meaningful information accessible to the researcher. This contribution describes how we intend to meet this objective ...

  1. Towards a continuum theory of movement in interacting cellular systems

    Science.gov (United States)

    Newman, Timothy

    2003-10-01

    Interacting cellular systems form the basis of all higher organisms, and are fundamental to the understanding of embryogenesis, organ function, and neoplasms. I will describe a stochastic model of cell interactions which can be applied to these problems, and present some of our recent results on chemotactic response.

  2. Survey of Engineering Models for Systems Biology

    OpenAIRE

    Reeves, Gregory T.; Hrischuk, Curtis E.

    2016-01-01

    In recent years, the field of systems biology has emerged from a confluence of an increase both in molecular biotechnology and in computing storage and power. As a discipline, systems biology shares many characteristics with engineering. However, before the benefits of engineering-based modeling formalisms and analysis tools can be applied to systems biology, the engineering discipline(s) most related to systems biology must be identified. In this paper, we identify the cell as an embedded co...

  3. Radical production in biological systems

    International Nuclear Information System (INIS)

    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

  4. In Silico Modeling of the Immune System: Cellular and Molecular Scale Approaches

    Directory of Open Access Journals (Sweden)

    Mariagrazia Belfiore

    2014-01-01

    Full Text Available The revolutions in biotechnology and information technology have produced clinical data, which complement biological data. These data enable detailed descriptions of various healthy and diseased states and responses to therapies. For the investigation of the physiology and pathology of the immune responses, computer and mathematical models have been used in the last decades, enabling the representation of biological processes. In this modeling effort, a major issue is represented by the communication between models that work at cellular and molecular level, that is, multiscale representation. Here we sketch some attempts to model immune system dynamics at both levels.

  5. Whole-Organism Cellular Pathology: A Systems Approach to Phenomics.

    Science.gov (United States)

    Cheng, K C; Katz, S R; Lin, A Y; Xin, X; Ding, Y

    2016-01-01

    Phenotype is defined as the state of an organism resulting from interactions between genes, environment, disease, molecular mechanisms, and chance. The purpose of the emerging field of phenomics is to systematically determine and measure phenotypes across biology for the sake of understanding. Phenotypes can affect more than one cell type and life stage, so ideal phenotyping would include the state of every cell type within the context of both tissue architecture and the whole organism at each life stage. In medicine, high-resolution anatomic assessment of phenotype is obtained from histology. Histology's interpretative power, codified by Virchow as cellular pathology, is derived from its ability to discern diagnostic and characteristic cellular changes in diseased tissues. Cellular pathology is observed in every major human disease and relies on the ability of histology to detect cellular change in any cell type due to unbiased pan-cellular staining, even in optically opaque tissues. Our laboratory has shown that histology is far more sensitive than stereomicroscopy for detecting phenotypes in zebrafish mutants. Those studies have also shown that more complete sampling, greater consistency in sample orientation, and the inclusion of phenotypes extending over longer length scales would provide greater coverage of common phenotypes. We are developing technical approaches to achieve an ideal detection of cellular pathology using an improved form of X-ray microtomography that retains the strengths and addresses the weaknesses of histology as a screening tool. We are using zebrafish as a vertebrate model based on the overlaps between zebrafish and mammalian tissue architecture, and a body size small enough to allow whole-organism, volumetric imaging at cellular resolution. Automation of whole-organism phenotyping would greatly increase the value of phenomics. Potential societal benefits would include reduction in the cost of drug development, a reduction in the

  6. Ion beam induced fluorescence imaging in biological systems

    Science.gov (United States)

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

    2015-04-01

    Imaging fluorescence generated by MeV ions in biological systems such as cells and tissue sections requires a high resolution beam (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.

  7. Signal processing for molecular and cellular biological physics: an emerging field

    Science.gov (United States)

    Little, Max A.; Jones, Nick S.

    2013-01-01

    Recent advances in our ability to watch the molecular and cellular processes of life in action—such as atomic force microscopy, optical tweezers and Forster fluorescence resonance energy transfer—raise challenges for digital signal processing (DSP) of the resulting experimental data. This article explores the unique properties of such biophysical time series that set them apart from other signals, such as the prevalence of abrupt jumps and steps, multi-modal distributions and autocorrelated noise. It exposes the problems with classical linear DSP algorithms applied to this kind of data, and describes new nonlinear and non-Gaussian algorithms that are able to extract information that is of direct relevance to biological physicists. It is argued that these new methods applied in this context typify the nascent field of biophysical DSP. Practical experimental examples are supplied. PMID:23277603

  8. Cellular and Developmental Biology of TRPM7 Channel-Kinase: Implicated Roles in Cancer

    Directory of Open Access Journals (Sweden)

    Nelson S. Yee

    2014-07-01

    Full Text Available The transient receptor potential melastatin-subfamily member 7 (TRPM7 is a ubiquitously expressed cation-permeable ion channel with intrinsic kinase activity that plays important roles in various physiological functions. Biochemical and electrophysiological studies, in combination with molecular analyses of TRPM7, have generated insights into its functions as a cellular sensor and transducer of physicochemical stimuli. Accumulating evidence indicates that TRPM7 channel-kinase is essential for cellular processes, such as proliferation, survival, differentiation, growth, and migration. Experimental studies in model organisms, such as zebrafish, mouse, and frog, have begun to elucidate the pleiotropic roles of TRPM7 during embryonic development from gastrulation to organogenesis. Aberrant expression and/or activity of the TRPM7 channel-kinase have been implicated in human diseases including a variety of cancer. Studying the functional roles of TRPM7 and the underlying mechanisms in normal cells and developmental processes is expected to help understand how TRPM7 channel-kinase contributes to pathogenesis, such as malignant neoplasia. On the other hand, studies of TRPM7 in diseases, particularly cancer, will help shed new light in the normal functions of TRPM7 under physiological conditions. In this article, we will provide an updated review of the structural features and biological functions of TRPM7, present a summary of current knowledge of its roles in development and cancer, and discuss the potential of TRPM7 as a clinical biomarker and therapeutic target in malignant diseases.

  9. The Tumorigenic Roles of the Cellular REDOX Regulatory Systems

    OpenAIRE

    Stéphanie Anaís Castaldo; Joana Raquel Freitas; Nadine Vasconcelos Conchinha; Patrícia Alexandra Madureira

    2016-01-01

    The cellular REDOX regulatory systems play a central role in maintaining REDOX homeostasis that is crucial for cell integrity, survival, and proliferation. To date, a substantial amount of data has demonstrated that cancer cells typically undergo increasing oxidative stress as the tumor develops, upregulating these important antioxidant systems in order to survive, proliferate, and metastasize under these extreme oxidative stress conditions. Since a large number of chemotherapeutic agents cur...

  10. Analyzing the Biology on the System Level

    Institute of Scientific and Technical Information of China (English)

    Wei Tong

    2004-01-01

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

  11. Quantum Effects in Biological Systems

    Science.gov (United States)

    Roy, Sisir

    2014-07-01

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

  12. BiologicalNetworks: visualization and analysis tool for systems biology

    OpenAIRE

    Baitaluk, Michael; Sedova, Mayya; Ray, Animesh; Gupta, Amarnath

    2006-01-01

    Systems level investigation of genomic scale information requires the development of truly integrated databases dealing with heterogeneous data, which can be queried for simple properties of genes or other database objects as well as for complex network level properties, for the analysis and modelling of complex biological processes. Towards that goal, we recently constructed PathSys, a data integration platform for systems biology, which provides dynamic integration over a diverse set of dat...

  13. Modeling biological systems with Answer Set Programming

    OpenAIRE

    Thiele, Sven

    2012-01-01

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

  14. Bayesian approaches to reverse engineer cellular systems: a simulation study on nonlinear Gaussian networks

    Directory of Open Access Journals (Sweden)

    Ramoni Marco F

    2007-05-01

    Full Text Available Abstract Background Reverse engineering cellular networks is currently one of the most challenging problems in systems biology. Dynamic Bayesian networks (DBNs seem to be particularly suitable for inferring relationships between cellular variables from the analysis of time series measurements of mRNA or protein concentrations. As evaluating inference results on a real dataset is controversial, the use of simulated data has been proposed. However, DBN approaches that use continuous variables, thus avoiding the information loss associated with discretization, have not yet been extensively assessed, and most of the proposed approaches have dealt with linear Gaussian models. Results We propose a generalization of dynamic Gaussian networks to accommodate nonlinear dependencies between variables. As a benchmark dataset to test the new approach, we used data from a mathematical model of cell cycle control in budding yeast that realistically reproduces the complexity of a cellular system. We evaluated the ability of the networks to describe the dynamics of cellular systems and their precision in reconstructing the true underlying causal relationships between variables. We also tested the robustness of the results by analyzing the effect of noise on the data, and the impact of a different sampling time. Conclusion The results confirmed that DBNs with Gaussian models can be effectively exploited for a first level analysis of data from complex cellular systems. The inferred models are parsimonious and have a satisfying goodness of fit. Furthermore, the networks not only offer a phenomenological description of the dynamics of cellular systems, but are also able to suggest hypotheses concerning the causal interactions between variables. The proposed nonlinear generalization of Gaussian models yielded models characterized by a slightly lower goodness of fit than the linear model, but a better ability to recover the true underlying connections between

  15. Principles of Systems Biology, No. 8.

    Science.gov (United States)

    2016-08-01

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

  16. Just working with the cellular machine: A high school game for teaching molecular biology.

    Science.gov (United States)

    Cardoso, Fernanda Serpa; Dumpel, Renata; da Silva, Luisa B Gomes; Rodrigues, Carlos R; Santos, Dilvani O; Cabral, Lucio Mendes; Castro, Helena C

    2008-03-01

    Molecular biology is a difficult comprehension subject due to its high complexity, thus requiring new teaching approaches. Herein, we developed an interdisciplinary board game involving the human immune system response against a bacterial infection for teaching molecular biology at high school. Initially, we created a database with several questions and a game story that invites the students for helping the human immunological system to produce antibodies (IgG) and fight back a pathogenic bacterium second-time invasion. The game involves answering questions completing the game board in which the antibodies "are synthesized" through the molecular biology process. At the end, a problem-based learning approach is used, and a last question is raised about proteins. Biology teachers and high school students evaluated the game and considered it an easy and interesting tool for teaching the theme. An increase of about 5-30% in answering molecular biology questions revealed that the game improves learning and induced a more engaged and proactive learning profile in the high school students. PMID:21591175

  17. Tensegrity, cellular biophysics, and the mechanics of living systems

    Science.gov (United States)

    Ingber, Donald E.; Wang, Ning; Stamenović, Dimitrije

    2014-01-01

    The recent convergence between physics and biology has led many physicists to enter the fields of cell and developmental biology. One of the most exciting areas of interest has been the emerging field of mechanobiology that centers on how cells control their mechanical properties, and how physical forces regulate cellular biochemical responses, a process that is known as mechanotransduction. In this article, we review the central role that tensegrity (tensional integrity) architecture, which depends on tensile prestress for its mechanical stability, plays in biology. We describe how tensional prestress is a critical governor of cell mechanics and function, and how use of tensegrity by cells contributes to mechanotransduction. Theoretical tensegrity models are also described that predict both quantitative and qualitative behaviors of living cells, and these theoretical descriptions are placed in context of other physical models of the cell. In addition, we describe how tensegrity is used at multiple size scales in the hierarchy of life — from individual molecules to whole living organisms — to both stabilize three-dimensional form and to channel forces from the macroscale to the nanoscale, thereby facilitating mechanochemical conversion at the molecular level. PMID:24695087

  18. Tensegrity, cellular biophysics, and the mechanics of living systems

    Science.gov (United States)

    Ingber, Donald E.; Wang, Ning; Stamenović, Dimitrije

    2014-04-01

    The recent convergence between physics and biology has led many physicists to enter the fields of cell and developmental biology. One of the most exciting areas of interest has been the emerging field of mechanobiology that centers on how cells control their mechanical properties, and how physical forces regulate cellular biochemical responses, a process that is known as mechanotransduction. In this article, we review the central role that tensegrity (tensional integrity) architecture, which depends on tensile prestress for its mechanical stability, plays in biology. We describe how tensional prestress is a critical governor of cell mechanics and function, and how use of tensegrity by cells contributes to mechanotransduction. Theoretical tensegrity models are also described that predict both quantitative and qualitative behaviors of living cells, and these theoretical descriptions are placed in context of other physical models of the cell. In addition, we describe how tensegrity is used at multiple size scales in the hierarchy of life—from individual molecules to whole living organisms—to both stabilize three-dimensional form and to channel forces from the macroscale to the nanoscale, thereby facilitating mechanochemical conversion at the molecular level.

  19. Tensegrity, cellular biophysics, and the mechanics of living systems

    International Nuclear Information System (INIS)

    The recent convergence between physics and biology has led many physicists to enter the fields of cell and developmental biology. One of the most exciting areas of interest has been the emerging field of mechanobiology that centers on how cells control their mechanical properties, and how physical forces regulate cellular biochemical responses, a process that is known as mechanotransduction. In this article, we review the central role that tensegrity (tensional integrity) architecture, which depends on tensile prestress for its mechanical stability, plays in biology. We describe how tensional prestress is a critical governor of cell mechanics and function, and how use of tensegrity by cells contributes to mechanotransduction. Theoretical tensegrity models are also described that predict both quantitative and qualitative behaviors of living cells, and these theoretical descriptions are placed in context of other physical models of the cell. In addition, we describe how tensegrity is used at multiple size scales in the hierarchy of life—from individual molecules to whole living organisms—to both stabilize three-dimensional form and to channel forces from the macroscale to the nanoscale, thereby facilitating mechanochemical conversion at the molecular level. (review article)

  20. Uplink Channel Dependent Scheduling for Future Cellular Systems

    OpenAIRE

    Jersenius, Kristina

    2007-01-01

    One goal in the development of future cellular systems is to increase performance. Channel dependent scheduling can possibly contribute to a performance enhancement. It requires channel qualityinformation and uplink channel knowledge is often incomplete. This master thesis work compares channel dependent scheduling and channel independent scheduling for a Single Carrier Frequency Division Multiple Access-based uplink in time domain and time and frequencydomain assuming continuous channel qual...

  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. 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...

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

    DEFF Research Database (Denmark)

    Nielsen, Jens; Jewett, Michael Christopher

    2008-01-01

    Industrial biotechnology is a rapidly growing field. With the increasing shift towards a bio-based economy, there is rising demand for developing efficient cell factories that can produce fuels, chemicals, pharmaceuticals, materials, nutraceuticals, and even food ingredients. The yeast Saccharomy...... 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.......Industrial biotechnology is a rapidly growing field. With the increasing shift towards a bio-based economy, there is rising demand for developing efficient cell factories that can produce fuels, chemicals, pharmaceuticals, materials, nutraceuticals, and even food ingredients. The yeast...... 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...

  4. Biologically erodable microspheres as potential oral drug delivery systems

    Science.gov (United States)

    Mathiowitz, Edith; Jacob, Jules S.; Jong, Yong S.; Carino, Gerardo P.; Chickering, Donald E.; Chaturvedi, Pravin; Santos, Camilla A.; Vijayaraghavan, Kavita; Montgomery, Sean; Bassett, Michael; Morrell, Craig

    1997-03-01

    Biologically adhesive delivery systems offer important advantages1-5 over conventional drug delivery systems6. Here we show that engineered polymer microspheres made of biologically erodable polymers, which display strong adhesive interactions with gastrointestinal mucus and cellular linings, can traverse both the mucosal absorptive epithelium and the follicle-associated epithelium covering the lymphoid tissue of Peyer's patches. The polymers maintain contact with intestinal epithelium for extended periods of time and actually penetrate it, through and between cells. Thus, once loaded with compounds of pharmacological interest, the microspheres could be developed as delivery systems to transfer biologically active molecules to the circulation. We show that these microspheres increase the absorption of three model substances of widely different molecular size: dicumarol, insulin and plasmid DNA.

  5. Cellular structure of detonation utilized in propulsion system

    Science.gov (United States)

    Zhang, XuDong; Fan, BaoChun; Gui, MingYue; Pan, ZhenHua

    2012-10-01

    How to confine a detonation in a combustor is a key issue of detonation applications in propulsion systems. Based on achieving schemes, detonations applied in the combustor, including pulse detonation wave (PDW), oblique detonation wave (ODW) and rotating detonation wave (RDW), are different from that described by the classic CJ theory in fine structures and its self-sustaining mechanisms. In this work, the cellular structures and flow fields of ODW and RDW were obtained numerically, and the fundamental characteristics and self-sustaining mechanisms of the detonations were analyzed and discussed. ODW front consists of three parts: the ZND-like front, the single-headed triple point front and the dual-headed triple point front. Cellular structures of RDW are heterogeneous, and the cell size near the outer wall is smaller than that near the inner wall.

  6. Towards Engineering Biological Systems in a Broader Context.

    Science.gov (United States)

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

    2016-02-27

    Significant advances have been made in synthetic biology to program information processing capabilities in cells. While these designs can function predictably in controlled laboratory environments, the reliability of these devices in complex, temporally changing environments has not yet been characterized. As human society faces global challenges in agriculture, human health and energy, synthetic biology should develop predictive design principles for biological systems operating in complex environments. Natural biological systems have evolved mechanisms to overcome innumerable and diverse environmental challenges. Evolutionary design rules should be extracted and adapted to engineer stable and predictable ecological function. We highlight examples of natural biological responses spanning the cellular, population and microbial community levels that show promise in synthetic biology contexts. We argue that synthetic circuits embedded in host organisms or designed ecologies informed by suitable measurement of biotic and abiotic environmental parameters could be used as engineering substrates to achieve target functions in complex environments. Successful implementation of these methods will broaden the context in which synthetic biological systems can be applied to solve important problems. PMID:26546279

  7. Green light radiation effects on free radicals inhibition in cellular and chemical systems.

    Science.gov (United States)

    Comorosan, Sorin; Polosan, Silviu; Jipa, Silviu; Popescu, Irinel; Marton, George; Ionescu, Elena; Cristache, Ligia; Badila, Dumitru; Mitrica, Radu

    2011-01-10

    Free radicals generation is inhibited through green light (GL) irradiation in cellular systems and in chemical reactions. Standard melanocyte cultures were UV-irradiated and the induced cellular reactive oxygen species (ROS) were quantified by the fluorescence technique. The same cell cultures, previously protected by a 24h GL exposure, displayed a significantly lower ROS production. A simple chemical reaction is subsequently chosen, in which the production of free radicals is well defined. Paraffin wax and mineral oil were GL irradiated during thermal degradation and the oxidation products checked by chemiluminescence [CL] and Fourier transform infrared spectra [FT-IR]. The same clear inhibition of the radical oxidation of alkanes is recorded. A quantum chemistry modeling of these results is performed and a mechanism involving a new type of Rydberg macromolecular systems with implications for biology and medicine is suggested. PMID:20934350

  8. Multiuser Scheduling on the Downlink of an LTE Cellular System

    Directory of Open Access Journals (Sweden)

    Raymond Kwan

    2008-01-01

    Full Text Available The challenge of scheduling user transmissions on the downlink of a long-term evolution (LTE cellular communication system is addressed. In particular, a novel optimalmultiuser scheduler is proposed. Numerical results show that the system performance improves with increasing correlation among OFDMA subcarriers. It is found that only a limited amount of feedback information is needed to achieve relatively good performance. A suboptimal reduced-complexity scheduler is also proposed and shown to provide good performance. The suboptimal scheme is especially attractive when the number of users is large, in which case the complexity of the optimal scheme is high.

  9. DNA-controlled dynamic colloidal nanoparticle systems for mediating cellular interaction

    Science.gov (United States)

    Ohta, Seiichi; Glancy, Dylan; Chan, Warren C. W.

    2016-02-01

    Precise control of biosystems requires development of materials that can dynamically change physicochemical properties. Inspired by the ability of proteins to alter their conformation to mediate function, we explored the use of DNA as molecular keys to assemble and transform colloidal nanoparticle systems. The systems consist of a core nanoparticle surrounded by small satellites, the conformation of which can be transformed in response to DNA via a toe-hold displacement mechanism. The conformational changes can alter the optical properties and biological interactions of the assembled nanosystem. Photoluminescent signal is altered by changes in fluorophore-modified particle distance, whereas cellular targeting efficiency is increased 2.5 times by changing the surface display of targeting ligands. These concepts provide strategies for engineering dynamic nanotechnology systems for navigating complex biological environments.

  10. Integrating phosphoproteomics in systems biology

    OpenAIRE

    Yu Liu; Chance, Mark R.

    2014-01-01

    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 fundam...

  11. Tritium Exchange in Biological Systems

    International Nuclear Information System (INIS)

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

  12. Network systems biology for targeted cancer therapies

    Institute of Scientific and Technical Information of China (English)

    Ting-Ting Zhou

    2012-01-01

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

  13. Systems biology and mechanics of growth.

    Science.gov (United States)

    Eskandari, Mona; Kuhl, Ellen

    2015-01-01

    In contrast to inert systems, living biological systems have the advantage to adapt to their environment through growth and evolution. This transfiguration is evident during embryonic development, when the predisposed need to grow allows form to follow function. Alterations in the equilibrium state of biological systems breed disease and mutation in response to environmental triggers. The need to characterize the growth of biological systems to better understand these phenomena has motivated the continuum theory of growth and stimulated the development of computational tools in systems biology. Biological growth in development and disease is increasingly studied using the framework of morphoelasticity. Here, we demonstrate the potential for morphoelastic simulations through examples of volume, area, and length growth, inspired by tumor expansion, chronic bronchitis, brain development, intestine formation, plant shape, and myopia. We review the systems biology of living systems in light of biochemical and optical stimuli and classify different types of growth to facilitate the design of growth models for various biological systems within this generic framework. Exploring the systems biology of growth introduces a new venue to control and manipulate embryonic development, disease progression, and clinical intervention. PMID:26352286

  14. Perturbation Biology: inferring signaling networks in cellular systems

    OpenAIRE

    Molinelli, Evan J.; Korkut, Anil; Wang, Weiqing; Miller, Martin L; Gauthier, Nicholas P.; Jing, Xiaohong; Kaushik, Poorvi; He, Qin; Mills, Gordon; Solit, David B.; Pratilas, Christine A.; Weigt, Martin; Braunstein, Alfredo; Pagnani, Andrea; Zecchina, Riccardo

    2013-01-01

    Author Summary Drugs that target specific effects of signaling proteins are promising agents for treating cancer. One of the many obstacles facing optimal drug design is inadequate quantitative understanding of the coordinated interactions between signaling proteins. De novo model inference of network or pathway models refers to the algorithmic construction of mathematical predictive models from experimental data without dependence on prior knowledge. De novo inference is difficult because of...

  15. A Mean Field Game Approach to Scheduling in Cellular Systems

    OpenAIRE

    Manjrekar, Mayank; Ramaswamy, Vinod; Shakkottai, Srinivas

    2013-01-01

    We study auction-theoretic scheduling in cellular networks using the idea of mean field equilibrium (MFE). Here, agents model their opponents through a distribution over their action spaces and play the best response. The system is at an MFE if this action is itself a sample drawn from the assumed distribution. In our setting, the agents are smart phone apps that generate service requests, experience waiting costs, and bid for service from base stations. We show that if we conduct a second-pr...

  16. Optimal channel utilization and service protection in cellular communication systems

    DEFF Research Database (Denmark)

    Iversen, Villy Bæk

    In mobile communications an efficient utilization of the channels is of great importance.In this paper we consider the basic principles for obtaining the maximum utilization, and we study strategies for obtaining these limits.In general a high degree of sharing is efficient, but requires service...... protection mechanisms for protecting services and subscriber groups.We study cellular systems with overlaid cells, and the effect of overlapping cells, and we show that by dynamic channel allocation we obtain a high utilization.The models are generalizations of the Erlang-B formula, and can be evaluated...

  17. Modeling and simulation for train control system using cellular automata

    Institute of Scientific and Technical Information of China (English)

    LI; KePing; GAO; ZiYou; YANG; LiXing

    2007-01-01

    Train control system plays a key role in railway traffic. Its function is to manage and control the train movement on railway networks. In our previous works, based on the cellular automata (CA) model, we proposed several models and algorithms for simulating the train movement under different control system conditions. However, these models are only suitable for some simple traffic conditions. Some basic factors, which are important for train movement, are not considered. In this paper, we extend these models and algorithms and give a unified formula. Using the proposed method, we analyze and discuss the space-time diagram of railway traffic flow and the trajectories of the train movement. The numerical simulation and analytical results demonstrate that the unified CA model is an effective tool for simulating the train control system.

  18. Method for analyzing signaling networks in complex cellular systems.

    Science.gov (United States)

    Plavec, Ivan; Sirenko, Oksana; Privat, Sylvie; Wang, Yuker; Dajee, Maya; Melrose, Jennifer; Nakao, Brian; Hytopoulos, Evangelos; Berg, Ellen L; Butcher, Eugene C

    2004-02-01

    Now that the human genome has been sequenced, the challenge of assigning function to human genes has become acute. Existing approaches using microarrays or proteomics frequently generate very large volumes of data not directly related to biological function, making interpretation difficult. Here, we describe a technique for integrative systems biology in which: (i) primary cells are cultured under biologically meaningful conditions; (ii) a limited number of biologically meaningful readouts are measured; and (iii) the results obtained under several different conditions are combined for analysis. Studies of human endothelial cells overexpressing different signaling molecules under multiple inflammatory conditions show that this system can capture a remarkable range of functions by a relatively small number of simple measurements. In particular, measurement of seven different protein levels by ELISA under four different conditions is capable of reconstructing pathway associations of 25 different proteins representing four known signaling pathways, implicating additional participants in the NF-kappaBorRAS/mitogen-activated protein kinase pathways and defining additional interactions between these pathways. PMID:14745015

  19. 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.

  20. The emergence of modularity in biological systems

    Science.gov (United States)

    Lorenz, Dirk M.; Jeng, Alice; Deem, Michael W.

    2011-06-01

    In this review, we discuss modularity and hierarchy in biological systems. We review examples from protein structure, genetics, and biological networks of modular partitioning of the geometry of biological space. We review theories to explain modular organization of biology, with a focus on explaining how biology may spontaneously organize to a structured form. That is, we seek to explain how biology nucleated from among the many possibilities in chemistry. The emergence of modular organization of biological structure will be described as a symmetry-breaking phase transition, with modularity as the order parameter. Experimental support for this description will be reviewed. Examples will be presented from pathogen structure, metabolic networks, gene networks, and protein-protein interaction networks. Additional examples will be presented from ecological food networks, developmental pathways, physiology, and social networks.

  1. SELF-ADAPTIVE CONTROLS OF A COMPLEX CELLULAR SIGNALING TRANSDUCTION SYSTEM

    Institute of Scientific and Technical Information of China (English)

    LI Hong; ZHOU Zhiyuan; DAI Rongyang; LUO Bo; ZHENG Xiaoli; YANG Wenli; HE Tao; WU Minglu

    2004-01-01

    In cells, the interactions of distinct signaling transduction pathways originating from cross-talkings between signaling molecules give rise to the formation of signaling transduction networks, which contributes to the changes (emergency) of kinetic behaviors of signaling system compared with single molecule or pathway. Depending on the known experimental data, we have constructed a model for complex cellular signaling transduction system, which is derived from signaling transduction of epidermal growth factor receptor in neuron. By the computational simulating methods, the self-adaptive controls of this system have been investigated. We find that this model exhibits a relatively stable selfadaptive system, especially to over-stimulation of agonist, and the amplitude and duration of signaling intermediates in it could be controlled by multiple self-adaptive effects, such as "signal scattering", "positive feedback", "negative feedback" and "B-Raf shunt". Our results provide an approach to understanding the dynamic behaviors of complex biological systems.

  2. Coarse-grained cellular automaton for traffic systems

    CERN Document Server

    Krawczyk, Malgorzata J

    2012-01-01

    A coarse-grained cellular automaton is proposed to simulate traffic systems. There, cells represent road sections. A cell can be in two states: jammed or passable. Numerical calculations are performed for a piece of square lattice with open boundary conditions, for the same piece with some cells removed and for a map of a small city. The results indicate the presence of a phase transition in the parameter space, between two macroscopic phases: passable and jammed. The results are supplemented by exact calculations of the stationary probabilities of states for the related Kripke structure constructed for the traffic system. There, the symmetry-based reduction of the state space allows to partially reduce the computational limitations of the numerical method.

  3. A MULTI CRITERIA APPROACH TO DESIGNING THE CELLULAR MANUFACTURING SYSTEM

    Directory of Open Access Journals (Sweden)

    Rika Ampuh Hadiguna

    2005-01-01

    Full Text Available Cellular manufacturing system design problems such as design framework, manufacturing cells layout and layout evaluation. The research objective is developing the framework to designing manufacturing cells with considering the organization and management aspects in shopfloor. In this research have compared the existing layout with proposed layout which applied the multi criteria approach. The proposed method is combining Analytical Hierarchy Process (AHP, Clustering and heuristic approach. The result has show that grouping with Single Linkage Clustering (SLC to be selected as manufacturing cells. The comparison of clustering weight is 0,567, 0,245 and 0,188 for SLC, Complete Linkage Clustering (CLC and Average Linkage Clustering (ALC, respectively. This result shows that generating layout by using grouping result from SLC. The evaluation result shows that types of manufacturing cells better than process layout which used the existing system.

  4. Genomes, phylogeny, and evolutionary systems biology

    OpenAIRE

    Medina, Monica

    2005-01-01

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

  5. Biological control in greenhouse systems.

    Science.gov (United States)

    Paulitz, T C; Bélanger, R R

    2001-01-01

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

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

    OpenAIRE

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

    2015-01-01

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

  7. Developmental systems biology flourishing on new technologies

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

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

  8. Developmental systems biology flourishing on new technologies.

    Science.gov (United States)

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

    2008-10-01

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

  9. Performance Analysis of Handoff in CDMA Cellular System

    Directory of Open Access Journals (Sweden)

    Dr. Dalveer Kaur

    2013-07-01

    Full Text Available Handoff mechanism is extremely important in cellular network because of the cellular architecture employed to maximize spectrum utilization. This unique feature has driven the rapid growth in the mobile network industry, changing it from a new technology into a massive industry within less than two decades. Handoff is the essential functionality for dealing with the mobility of the mobile users. This paper shows the soft handoff effects on the uplink direction of IS-95 CDMA networks is carried out, leading to optimize soft handoff for capacity under perfect power control approach. In practical systems, there is a nonzero handoff completion delay and soft handoff provides the required robustness to delays, although it comes at the expense of additional network resources. Thus, there is a tradeoff between the extent of soft handoff required and the handoff execution delay. This paper presents an analytical framework to study this tradeoff and also discuss simulation results simulated with the help of Matlab. For this, handoff dropping probability is minimized up to 0.1%.

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

    Science.gov (United States)

    Tribe, Michael; Pritchard, Alan J.

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

  11. Feeding Behaviors in Cellular Slime Molds: A Microbial System To Study Competition.

    Science.gov (United States)

    Bozzone, Donna M.

    1997-01-01

    Describes a laboratory project for first-year biology students that examines competition among various cellular slime molds. After a brief introduction to the topic of competition and basic life history information about cellular slime molds, students choose a question and design original experiments to seek an answer. (Author/AIM)

  12. Multi-Scale Continuum Modeling of Biological Processes: From Molecular Electro-Diffusion to Sub-Cellular Signaling Transduction

    OpenAIRE

    Cheng, Y; Kekenes-Huskey, P; Hake, JE; Holst, MJ; McCammon, JA; Michailova, AP

    2012-01-01

    This article provides a brief review of multi-scale modeling at the molecular to cellular scale, with new results for heart muscle cells. A finite element-based simulation package (SMOL) was used to investigate the signaling transduction at molecular and sub-cellular scales (http://mccammon.ucsd.edu/smol/, http://FETK.org) by numerical solution of time-dependent Smoluchowski equations and a reaction-diffusion system. At the molecular scale, SMOL has yielded experimentally-validated estimates ...

  13. Wireless Secrecy in Cellular Systems with Infrastructure--Aided Cooperation

    CERN Document Server

    Popovski, Petar

    2008-01-01

    In cellular systems, confidentiality of uplink transmission with respect to eavesdropping terminals can be ensured by creating intentional inteference via scheduling of concurrent downlink transmissions. In this paper, this basic idea is explored from an information-theoretic standpoint by focusing on a two-cell scenario where the involved base stations are connected via a finite-capacity backbone link. A number of transmission strategies are considered that aim at improving uplink confidentiality under constraints on the downlink rate that acts as an interfering signal. The strategies differ mainly in the way the backbone link is exploited by the cooperating downlink- to the uplink-operated base stations. Achievable rates are derived for both the Gaussian (unfaded) and the fading cases, under different assumptions on the channel state information available at different nodes. Numerical results are also provided to corroborate the analysis. Overall, the analysis reveals that a combination of scheduling and ba...

  14. Cellular Manufacturing System with Dynamic Lot Size Material Handling

    Science.gov (United States)

    Khannan, M. S. A.; Maruf, A.; Wangsaputra, R.; Sutrisno, S.; Wibawa, T.

    2016-02-01

    Material Handling take as important role in Cellular Manufacturing System (CMS) design. In several study at CMS design material handling was assumed per pieces or with constant lot size. In real industrial practice, lot size may change during rolling period to cope with demand changes. This study develops CMS Model with Dynamic Lot Size Material Handling. Integer Linear Programming is used to solve the problem. Objective function of this model is minimizing total expected cost consisting machinery depreciation cost, operating costs, inter-cell material handling cost, intra-cell material handling cost, machine relocation costs, setup costs, and production planning cost. This model determines optimum cell formation and optimum lot size. Numerical examples are elaborated in the paper to ilustrate the characterictic of the model.

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

    Energy Technology Data Exchange (ETDEWEB)

    Cannon, William R.; Baxter, Douglas J.

    2012-08-15

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

  16. Cellular mechanisms underlying the interaction between cannabinoid and opioid system.

    Science.gov (United States)

    Parolaro, D; Rubino, T; Viganò, D; Massi, P; Guidali, C; Realini, N

    2010-04-01

    Recently, the presence of functional interaction between the opioid and cannabinoid system has been shown in various pharmacological responses. Although there is an increasing interest for the feasible therapeutic application of a co-administration of cannabinoids and opioids in some disorders (i.e. to manage pain, to modulate immune system and emotions) and the combined use of the two drugs by drug abusers is becoming largely diffuse, only few papers focused on cellular and molecular mechanisms underlying this interaction. This review updates the biochemical and molecular underpinnings of opioid and cannabinoid interaction, both within the central nervous system and periphery. The most convincing theory for the explanation of this reciprocal interaction involves (i) the release of opioid peptides by cannabinoids or endocannabinoids by opioids, (ii) the existence of a direct receptor-receptor interaction when the receptors are co-expressed in the same cells, and (iii) the interaction of their intracellular pathways. Finally, the cannabinoid/opioid interaction might be different in the brain rewarding networks and in those accounting for other pharmacological effects (antinociception, modulation of emotionality and cognitive behavior), as well as between the central nervous system and periphery. Further insights about the cannabinoid/opioid interaction could pave the way for new and promising therapeutic approaches. PMID:20017730

  17. Using hybrid concurrent constraint programming to model dynamic biological systems

    OpenAIRE

    Bockmayr, Alexander; Courtois, Arnaud

    2002-01-01

    Systems biology is a new area in biology that aims at achieving a systems-level understanding of biological systems. While current genome projects provide a huge amount of data on genes or proteins, lots of research is still necessary to understand how the different parts of a biological system interact in order to perform complex biological functions. Computational models that help to analyze, explain or predict the behavior of biological systems play a crucial role in systems biology. The g...

  18. Controlled vocabularies and semantics in systems biology

    OpenAIRE

    Courtot, Mélanie; Hucka, Michael

    2011-01-01

    The use of computational modeling to describe and analyze biological systems is at the heart of systems biology. Model structures, simulation descriptions and numerical results can be encoded in structured formats, but there is an increasing need to provide an additional semantic layer. Semantic information adds meaning to components of structured descriptions to help identify and interpret them unambiguously. Ontologies are one of the tools frequently used for this purpose. We describe here ...

  19. Model Systems for Cardiovascular Regenerative Biology

    OpenAIRE

    Garbern, Jessica C.; Mummery, Christine L.; Lee, Richard T.

    2013-01-01

    There is an urgent clinical need to develop new therapeutic approaches to treat heart failure, but the biology of cardiovascular regeneration is complex. Model systems are required to advance our understanding of biological mechanisms of cardiac regeneration as well as to test therapeutic approaches to regenerate tissue and restore cardiac function following injury. An ideal model system should be inexpensive, easily manipulated, easily reproducible, physiologically representative of human di...

  20. Caenorhabditis elegans - A model system for space biology studies

    Science.gov (United States)

    Johnson, Thomas E.; Nelson, Gregory A.

    1991-01-01

    The utility of the nematode Caenorhabditis elegans in studies spanning aspects of development, aging, and radiobiology is reviewed. These topics are interrelated via cellular and DNA repair processes especially in the context of oxidative stress and free-radical metabolism. The relevance of these research topics to problems in space biology is discussed and properties of the space environment are outlined. Exposure to the space-flight environment can induce rapid changes in living systems that are similar to changes occurring during aging; manipulation of these environmental parameters may represent an experimental strategy for studies of development and senescence. The current and future opportunities for such space-flight experimentation are presented.

  1. Bioferroelectricity and optical properties of biological systems

    Science.gov (United States)

    Bystrov, Vladimir; Bystrova, Natalia

    2003-08-01

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

  2. Research Progression of Cellular Autophagy in Liver System Diseases

    Directory of Open Access Journals (Sweden)

    Chunyun Liu

    2013-09-01

    Full Text Available Autophagy is a basic biological phenomenon widely existed in eukaryotic cells and an important mechanism for cells to adjust to the surrounding environment, prevent invasion of pathogenic micro-organisms and maintain homeostasis, whose activity changes evidently in multiple liver system diseases, suggesting that there is close association between autophagy and the generation and development of liver system diseases. It is also reported that autophagy develops and exerts an important function in many liver-related diseases, such as hepatic carcinoma, non-alcoholic fatty liver disease, alcoholic liver disease, viral liver disease and acute liver injury. Therefore, this study aimed to summarize the relationship between autophagy and multiple liver diseases, hoping to explore the effect of autophagy in liver system diseases and further study the regulative effect of autophagy so as to provide new thoughts for their treatment.

  3. The Tumorigenic Roles of the Cellular REDOX Regulatory Systems

    Science.gov (United States)

    Castaldo, Stéphanie Anaís; Freitas, Joana Raquel; Conchinha, Nadine Vasconcelos; Madureira, Patrícia Alexandra

    2016-01-01

    The cellular REDOX regulatory systems play a central role in maintaining REDOX homeostasis that is crucial for cell integrity, survival, and proliferation. To date, a substantial amount of data has demonstrated that cancer cells typically undergo increasing oxidative stress as the tumor develops, upregulating these important antioxidant systems in order to survive, proliferate, and metastasize under these extreme oxidative stress conditions. Since a large number of chemotherapeutic agents currently used in the clinic rely on the induction of ROS overload or change of ROS quality to kill the tumor, the cancer cell REDOX adaptation represents a significant obstacle to conventional chemotherapy. In this review we will first examine the different factors that contribute to the enhanced oxidative stress generally observed within the tumor microenvironment. We will then make a comprehensive assessment of the current literature regarding the main antioxidant proteins and systems that have been shown to be positively associated with tumor progression and chemoresistance. Finally we will make an analysis of commonly used chemotherapeutic drugs that induce ROS. The current knowledge of cancer cell REDOX adaptation raises the issue of developing novel and more effective therapies for these tumors that are usually resistant to conventional ROS inducing chemotherapy. PMID:26682014

  4. The Tumorigenic Roles of the Cellular REDOX Regulatory Systems.

    Science.gov (United States)

    Castaldo, Stéphanie Anaís; Freitas, Joana Raquel; Conchinha, Nadine Vasconcelos; Madureira, Patrícia Alexandra

    2016-01-01

    The cellular REDOX regulatory systems play a central role in maintaining REDOX homeostasis that is crucial for cell integrity, survival, and proliferation. To date, a substantial amount of data has demonstrated that cancer cells typically undergo increasing oxidative stress as the tumor develops, upregulating these important antioxidant systems in order to survive, proliferate, and metastasize under these extreme oxidative stress conditions. Since a large number of chemotherapeutic agents currently used in the clinic rely on the induction of ROS overload or change of ROS quality to kill the tumor, the cancer cell REDOX adaptation represents a significant obstacle to conventional chemotherapy. In this review we will first examine the different factors that contribute to the enhanced oxidative stress generally observed within the tumor microenvironment. We will then make a comprehensive assessment of the current literature regarding the main antioxidant proteins and systems that have been shown to be positively associated with tumor progression and chemoresistance. Finally we will make an analysis of commonly used chemotherapeutic drugs that induce ROS. The current knowledge of cancer cell REDOX adaptation raises the issue of developing novel and more effective therapies for these tumors that are usually resistant to conventional ROS inducing chemotherapy. PMID:26682014

  5. The Tumorigenic Roles of the Cellular REDOX Regulatory Systems

    Directory of Open Access Journals (Sweden)

    Stéphanie Anaís Castaldo

    2016-01-01

    Full Text Available The cellular REDOX regulatory systems play a central role in maintaining REDOX homeostasis that is crucial for cell integrity, survival, and proliferation. To date, a substantial amount of data has demonstrated that cancer cells typically undergo increasing oxidative stress as the tumor develops, upregulating these important antioxidant systems in order to survive, proliferate, and metastasize under these extreme oxidative stress conditions. Since a large number of chemotherapeutic agents currently used in the clinic rely on the induction of ROS overload or change of ROS quality to kill the tumor, the cancer cell REDOX adaptation represents a significant obstacle to conventional chemotherapy. In this review we will first examine the different factors that contribute to the enhanced oxidative stress generally observed within the tumor microenvironment. We will then make a comprehensive assessment of the current literature regarding the main antioxidant proteins and systems that have been shown to be positively associated with tumor progression and chemoresistance. Finally we will make an analysis of commonly used chemotherapeutic drugs that induce ROS. The current knowledge of cancer cell REDOX adaptation raises the issue of developing novel and more effective therapies for these tumors that are usually resistant to conventional ROS inducing chemotherapy.

  6. 47 CFR 90.672 - Unacceptable interference to non-cellular 800 MHz licensees from 800 MHz cellular systems or part...

    Science.gov (United States)

    2010-10-01

    ... Business/Industrial Land Transportation Pool. (a) Definition. Except as provided in 47 CFR 90.617(k... 47 Telecommunication 5 2010-10-01 2010-10-01 false Unacceptable interference to non-cellular 800 MHz licensees from 800 MHz cellular systems or part 22 Cellular Radiotelephone systems, and within...

  7. 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. PMID:26783720

  8. Carbon-13 NMR spectroscopy of biological systems

    CERN Document Server

    Beckmann, Nicolau

    1995-01-01

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

  9. Ion beam induced fluorescence imaging in biological systems

    International Nuclear Information System (INIS)

    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

  10. Python Unleashed on Systems Biology

    OpenAIRE

    Christopher R Myers; Gutenkunst, Ryan N.; Sethna, James P.

    2007-01-01

    We have built an open-source software system for the modeling of biomolecular reaction networks, SloppyCell, which is written in Python and makes substantial use of third-party libraries for numerics, visualization, and parallel programming. We highlight here some of the powerful features that Python provides that enable SloppyCell to do dynamic code synthesis, symbolic manipulation, and parallel exploration of complex parameter spaces.

  11. Towards Systems Biology of Human Pulmonary Fibrosis

    OpenAIRE

    Studer, Sean M.; Kaminski, Naftali

    2007-01-01

    The integrated effect of multiple pathways, molecules, genetic polymorphisms, environmental stimuli, and possible infection determines the lung phenotype in idiopathic pulmonary fibrosis (IPF), a chronic progressive and often lethal lung disease. Systems biology approaches aim to provide a systemwide view of biological process using computational tools and high-throughput technologies. Although much of the analysis of genome-level transcriptional high-resolution profiles of IPF was reductioni...

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

    OpenAIRE

    Bor-Sen Chen; Wei-Sheng Wu

    2007-01-01

    Systems biology is a rapidly expanding field that integrates diverse areas of science such as physics, engineering, computer science, mathematics, and biology toward the goal of elucidating the underlying principles of hierarchical metabolic and regulatory systems in the cell, and ultimately leading to predictive understanding of cellular response to perturbations. Because post-genomics research is taking place throughout the tree of life, comparative approaches offer a way for combining data...

  13. RNase-L control of cellular mRNAs: roles in biologic functions and mechanisms of substrate targeting.

    Science.gov (United States)

    Brennan-Laun, Sarah E; Ezelle, Heather J; Li, Xiao-Ling; Hassel, Bret A

    2014-04-01

    RNase-L is a mediator of type 1 interferon-induced antiviral activity that has diverse and critical cellular roles, including the regulation of cell proliferation, differentiation, senescence and apoptosis, tumorigenesis, and the control of the innate immune response. Although RNase-L was originally shown to mediate the endonucleolytic cleavage of both viral and ribosomal RNAs in response to infection, more recent evidence indicates that RNase-L also functions in the regulation of cellular mRNAs as an important mechanism by which it exerts its diverse biological functions. Despite this growing body of work, many questions remain regarding the roles of mRNAs as RNase-L substrates. This review will survey known and putative mRNA substrates of RNase-L, propose mechanisms by which it may selectively cleave these transcripts, and postulate future clinical applications. PMID:24697205

  14. Synchronization, TIGoRS, and Information Flow in Complex Systems: Dispositional Cellular Automata.

    Science.gov (United States)

    Sulis, William H

    2016-04-01

    Synchronization has a long history in physics where it refers to the phase matching of two identical oscillators. This notion has been extensively studied in physics as well as in biology, where it has been applied to such widely varying phenomena as the flashing of fireflies and firing of neurons in the brain. Human behavior, however, may be recurrent but it is not oscillatory even though many physiological systems do exhibit oscillatory tendencies. Moreover, much of human behaviour is collaborative and cooperative, where the individual behaviours may be distinct yet contemporaneous (if not simultaneous) and taken collectively express some functionality. In the context of behaviour, the important aspect is the repeated co-occurrence in time of behaviours that facilitate the propagation of information or of functionality, regardless of whether or not these behaviours are similar or identical. An example of this weaker notion of synchronization is transient induced global response synchronization (TIGoRS). Previous work has shown that TIGoRS is a ubiquitous phenomenon among complex systems, enabling them to stably parse environmental transients into salient units to which they stably respond. This leads to the notion of Sulis machines, which emergently generate a primitive linguistic structure through their dynamics. This article reviews the notion of TIGoRS and its expression in several complex systems models including tempered neural networks, driven cellular automata and cocktail party automata. The emergent linguistics of Sulis machines are discussed. A new class of complex systems model, the dispositional cellular automaton is introduced. A new metric for TIGoRS, the excess synchronization, is introduced and applied to the study of TIGoRS in dispositional cellular automata. It is shown that these automata exhibit a nonlinear synchronization response to certain perturbing transients. PMID:27033136

  15. Hydrodynamic Interactions in Colloidal and Biological Systems

    OpenAIRE

    Reichert, Michael

    2006-01-01

    Colloids are widely considered as model systems to elucidate fundamental processes in atomic systems. However, there is one feature truly specific to colloidal suspensions that distinguishes them fundamentally from atomic systems: hydrodynamic interactions, which can lead to fascinating collective behavior.In this thesis, we present analytical work and simulation results for several micron-scale colloidal and biological systems where the dynamics is predominantly governed by hydrodynamic inte...

  16. Tensegrity I. Cell structure and hierarchical systems biology

    Science.gov (United States)

    Ingber, Donald E.

    2003-01-01

    In 1993, a Commentary in this journal described how a simple mechanical model of cell structure based on tensegrity architecture can help to explain how cell shape, movement and cytoskeletal mechanics are controlled, as well as how cells sense and respond to mechanical forces (J. Cell Sci. 104, 613-627). The cellular tensegrity model can now be revisited and placed in context of new advances in our understanding of cell structure, biological networks and mechanoregulation that have been made over the past decade. Recent work provides strong evidence to support the use of tensegrity by cells, and mathematical formulations of the model predict many aspects of cell behavior. In addition, development of the tensegrity theory and its translation into mathematical terms are beginning to allow us to define the relationship between mechanics and biochemistry at the molecular level and to attack the larger problem of biological complexity. Part I of this two-part article covers the evidence for cellular tensegrity at the molecular level and describes how this building system may provide a structural basis for the hierarchical organization of living systems--from molecule to organism. Part II, which focuses on how these structural networks influence information processing networks, appears in the next issue.

  17. Photosynthetic system as a biological functional element

    International Nuclear Information System (INIS)

    Photosynthetic apparatus of high plants and photosynthetic bacteria is essentially autonomic system in terms of genetics and structural -functional properties located in specific medium, a bio-membrane. Processes of light absorption and exciton migration in light harvesting antenna, separation and further transfer of charges in reaction centers have specific features, which may be used for application of these objects as key elements in construction of future biological functional elements. Progress in study and genetic modification of photosynthetic membranes achieved during the last decade opens great prospects in development biological functional elements and systems. The main characteristics of photosynthetic system for these purposes are: (i) energy conversion processes in the first light phase of the photosynthesis have very short periods, up to picoseconds, which indicates possibility of creation of ultrafast functional elements on their basis; (ii) characteristics sizes of photosynthetic units, 10-100 nm, and possibility to arrange regularly disposed elements in relevant membranes could be prospective point for creation of nano structures and on their basis relevant biologic functional elements; (iii) elements based on modified photosynthetic apparatus and bio-membranes might be efficiently created by methods of gene engineering and manipulation, that open huge opportunities for development of read biological functional systems. In the paper structural-functional properties and characteristics of high plants and purple photosynthetic bacteria, which may be useful for creation of future biological functional elements are considered. (author)

  18. 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.

  19. Stochastic Physics, Complex Systems and Biology

    CERN Document Server

    Qian, Hong

    2012-01-01

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

  20. A novel mathematical model describing adaptive cellular drug metabolism and toxicity in the chemoimmune system.

    Directory of Open Access Journals (Sweden)

    Attila Tóth

    Full Text Available Cells cope with the threat of xenobiotic stress by activating a complex molecular network that recognizes and eliminates chemically diverse toxic compounds. This "chemoimmune system" consists of cellular Phase I and Phase II metabolic enzymes, Phase 0 and Phase III ATP Binding Cassette (ABC membrane transporters, and nuclear receptors regulating these components. In order to provide a systems biology characterization of the chemoimmune network, we designed a reaction kinetic model based on differential equations describing Phase 0-III participants and regulatory elements, and characterized cellular fitness to evaluate toxicity. In spite of the simplifications, the model recapitulates changes associated with acquired drug resistance and allows toxicity predictions under variable protein expression and xenobiotic exposure conditions. Our simulations suggest that multidrug ABC transporters at Phase 0 significantly facilitate the defense function of successive network members by lowering intracellular drug concentrations. The model was extended with a novel toxicity framework which opened the possibility of performing in silico cytotoxicity assays. The alterations of the in silico cytotoxicity curves show good agreement with in vitro cell killing experiments. The behavior of the simplified kinetic model suggests that it can serve as a basis for more complex models to efficiently predict xenobiotic and drug metabolism for human medical applications.

  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. Discovery of Chemical Toxicity via Biological Networks and Systems Biology

    Energy Technology Data Exchange (ETDEWEB)

    Perkins, Edward; Habib, Tanwir; Guan, Xin; Escalon, Barbara; Falciani, Francesco; Chipman, J.K.; Antczak, Philipp; Edwards, Stephen; Taylor, Ronald C.; Vulpe, Chris; Loguinov, Alexandre; Van Aggelen, Graham; Villeneuve, Daniel L.; Garcia-Reyero, Natalia

    2010-09-30

    Both soldiers and animals are exposed to many chemicals as the result of military activities. Tools are needed to understand the hazards and risks that chemicals and new materials pose to soldiers and the environment. We have investigated the potential of global gene regulatory networks in understanding the impact of chemicals on reproduction. We characterized effects of chemicals on ovaries of the model animal system, the Fathead minnow (Pimopheles promelas) connecting chemical impacts on gene expression to circulating blood levels of the hormones testosterone and estradiol in addition to the egg yolk protein vitellogenin. We describe the application of reverse engineering complex interaction networks from high dimensional gene expression data to characterize chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis that governs reproduction in fathead minnows. The construction of global gene regulatory networks provides deep insights into how drugs and chemicals effect key organs and biological pathways.

  3. 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

  4. 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.

  5. The similia principle: results obtained in a cellular model system.

    Science.gov (United States)

    Wiegant, Fred; Van Wijk, Roeland

    2010-01-01

    This paper describes the results of a research program focused on the beneficial effect of low dose stress conditions that were applied according to the similia principle to cells previously disturbed by more severe stress conditions. In first instance, we discuss criteria for research on the similia principle at the cellular level. Then, the homologous ('isopathic') approach is reviewed, in which the initial (high dose) stress used to disturb cellular physiology and the subsequent (low dose) stress are identical. Beneficial effects of low dose stress are described in terms of increased cellular survival capacity and at the molecular level as an increase in the synthesis of heat shock proteins (hsps). Both phenomena reflect a stimulation of the endogenous cellular self-recovery capacity. Low dose stress conditions applied in a homologous approach stimulate the synthesis of hsps and enhance survival in comparison with stressed cells that were incubated in the absence of low dose stress conditions. Thirdly, the specificity of the low dose stress condition is described where the initial (high dose) stress is different in nature from the subsequently applied (low dose) stress; the heterologous or 'heteropathic' approach. The results support the similia principle at the cellular level and add to understanding of how low dose stress conditions influence the regulatory processes underlying self-recovery. In addition, the phenomenon of 'symptom aggravation' which is also observed at the cellular level, is discussed in the context of self-recovery. Finally, the difference in efficiency between the homologous and the heterologous approach is discussed; a perspective is indicated for further research; and the relationship between studies on the similia principle and the recently introduced concept of 'postconditioning hormesis' is emphasized. PMID:20129172

  6. Nutritional Systems Biology: Definitions and Approaches

    DEFF Research Database (Denmark)

    Panagiotou, Gianni; Nielsen, Jens

    2009-01-01

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

  7. Studies on Semantic Systems Chemical Biology

    Science.gov (United States)

    Chen, Bin

    2012-01-01

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

  8. 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…

  9. Notions of radiation chemistry in biological systems

    International Nuclear Information System (INIS)

    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)

  10. Modular microfluidic system for biological sample preparation

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-09-29

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

  11. Microbial Stress Tolerance for Biofuels: Systems Biology

    Science.gov (United States)

    This book provides comprehensive up-to-date understanding and frontier research addressing mechanisms of microbial stress tolerance involved in biofuels using a systems biology approach. It ties closely with the cutting edge technology with a focus on the challenging subject of biofuels. The develo...

  12. On the biological basis for competing macroscopic dose descriptors for kilovoltage dosimetry: cellular dosimetry for brachytherapy and diagnostic radiology

    Science.gov (United States)

    Thomson, R. M.; Carlsson Tedgren, Å.; Williamson, J. F.

    2013-02-01

    The purpose of this work is to investigate how alternative macroscopic dose descriptors track absorbed dose to biologically relevant subcellular targets via Monte Carlo (MC) analysis of cellular models for a variety of cancerous and normal soft tissues for kilovoltage radiation. The relative mass distributions of water, light inorganic elements, and protein components of nuclear and cytoplasm compartments for various tissues are determined from a literature review. These data are used to develop representative cell models to demonstrate the range of mass elemental compositions of these subcellular structures encountered in the literature from which radiological quantities (energy absorption and attenuation coefficients; stopping powers) are computed. Using representative models of cell clusters, doses to subcellular targets are computed using MC simulation for photon sources of energies between 20 and 370 keV and are compared to bulk medium dose descriptors. It is found that cells contain significant and varying mass fractions of protein and inorganic elements, leading to variations in mass energy absorption coefficients for cytoplasm and nuclear media as large as 10% compared to water for sub-50 keV photons. Doses to subcellular structures vary by as much as 23% compared to doses to the corresponding average bulk medium or to small water cavities embedded in the bulk medium. Relationships between cellular target doses and doses to the bulk medium or to a small water cavity embedded in the bulk medium are sensitive to source energy and cell morphology, particularly for lower energy sources, e.g., low energy brachytherapy (water or the corresponding average bulk tissue. For kilovoltage photon sources, neither dose to bulk medium nor dose to water quantitatively tracks energy imparted to biologically relevant subcellular targets for the range of cellular morphologies and tissues considered.

  13. Language Based Techniques for Systems Biology

    DEFF Research Database (Denmark)

    Pilegaard, Henrik

    calculi have similarly been used for the study of bio-chemical reactive systems. In this dissertation it is argued that techniques rooted in the theory and practice of programming languages, language based techniques if you will, constitute a strong basis for the investigation of models of biological......Process calculus is the common denominator for a class of compact, idealised, domain-specific formalisms normally associated with the study of reactive concurrent systems within Computer Science. With the rise of the interactioncentred science of Systems Biology a number of bio-inspired process...... systems as formalised in a process calculus. In particular it is argued that Static Program Analysis provides a useful approach to the study of qualitative properties of such models. In support of this claim a number of static program analyses are developed for Regev’s BioAmbients – a bio-inspired variant...

  14. Multi-scale continuum modeling of biological processes: from molecular electro-diffusion to sub-cellular signaling transduction

    Science.gov (United States)

    Cheng, Y.; Kekenes-Huskey, P.; Hake, J. E.; Holst, M. J.; McCammon, J. A.; Michailova, A. P.

    2012-01-01

    This paper presents a brief review of multi-scale modeling at the molecular to cellular scale, with new results for heart muscle cells. A finite element-based simulation package (SMOL) was used to investigate the signaling transduction at molecular and sub-cellular scales (http://mccammon.ucsd.edu/smol/, http://FETK.org) by numerical solution of the time-dependent Smoluchowski equations and a reaction-diffusion system. At the molecular scale, SMOL has yielded experimentally validated estimates of the diffusion-limited association rates for the binding of acetylcholine to mouse acetylcholinesterase using crystallographic structural data. The predicted rate constants exhibit increasingly delayed steady-state times, with increasing ionic strength, and demonstrate the role of an enzyme's electrostatic potential in influencing ligand binding. At the sub-cellular scale, an extension of SMOL solves a nonlinear, reaction-diffusion system describing Ca2+ ligand buffering and diffusion in experimentally derived rodent ventricular myocyte geometries. Results reveal the important role of mobile and stationary Ca2+ buffers, including Ca2+ indicator dye. We found that alterations in Ca2+-binding and dissociation rates of troponin C (TnC) and total TnC concentration modulate sub-cellular Ca2+ signals. The model predicts that reduced off-rate in the whole troponin complex (TnC, TnI, TnT) versus reconstructed thin filaments (Tn, Tm, actin) alters cytosolic Ca2+ dynamics under control conditions or in disease-linked TnC mutations. The ultimate goal of these studies is to develop scalable methods and theories for the integration of molecular-scale information into simulations of cellular-scale systems.

  15. Multi-scale continuum modeling of biological processes: from molecular electro-diffusion to sub-cellular signaling transduction

    International Nuclear Information System (INIS)

    This paper presents a brief review of multi-scale modeling at the molecular to cellular scale, with new results for heart muscle cells. A finite element-based simulation package (SMOL) was used to investigate the signaling transduction at molecular and sub-cellular scales (http://mccammon.ucsd.edu/smol/, http://FETK.org) by numerical solution of the time-dependent Smoluchowski equations and a reaction-diffusion system. At the molecular scale, SMOL has yielded experimentally validated estimates of the diffusion-limited association rates for the binding of acetylcholine to mouse acetylcholinesterase using crystallographic structural data. The predicted rate constants exhibit increasingly delayed steady-state times, with increasing ionic strength, and demonstrate the role of an enzyme's electrostatic potential in influencing ligand binding. At the sub-cellular scale, an extension of SMOL solves a nonlinear, reaction-diffusion system describing Ca2+ ligand buffering and diffusion in experimentally derived rodent ventricular myocyte geometries. Results reveal the important role of mobile and stationary Ca2+ buffers, including Ca2+ indicator dye. We found that alterations in Ca2+-binding and dissociation rates of troponin C (TnC) and total TnC concentration modulate sub-cellular Ca2+ signals. The model predicts that reduced off-rate in the whole troponin complex (TnC, TnI, TnT) versus reconstructed thin filaments (Tn, Tm, actin) alters cytosolic Ca2+ dynamics under control conditions or in disease-linked TnC mutations. The ultimate goal of these studies is to develop scalable methods and theories for the integration of molecular-scale information into simulations of cellular-scale systems.

  16. Novel approaches to the integration and analysis of systems biology data

    OpenAIRE

    Ramírez, Fidel

    2011-01-01

    The opportunity to investigate whole cellular systems using experimental and computational high-throughput methods leads to the generation of unprecedented amounts of data. Processing of these data often results in large lists of genes or proteins that need to be analyzed and interpreted in the context of all other biological information that is already available. To support such analyses, repositories aggregating and merging the biological information contained in different databases are req...

  17. Infobiotics : computer-aided synthetic systems biology

    OpenAIRE

    Blakes, Jonathan

    2013-01-01

    Until very recently Systems Biology has, despite its stated goals, been too reductive in terms of the models being constructed and the methods used have been, on the one hand, unsuited for large scale adoption or integration of knowledge across scales, and on the other hand, too fragmented. The thesis of this dissertation is that better computational languages and seamlessly integrated tools are required by systems and synthetic biologists to enable them to meet the significant challenges inv...

  18. Translocation Biosensors – Cellular System Integrators to Dissect CRM1-Dependent Nuclear Export by Chemicogenomics

    Directory of Open Access Journals (Sweden)

    Roland H. Stauber

    2009-07-01

    Full Text Available Fluorescent protein biosensors are powerful cellular systems biology tools for dissecting the complexity of cellular processes with high spatial and temporal resolution. As regulated nucleo-cytoplasmic transport is crucial for the modulation of numerous (pathophysiological cellular responses, a detailed understanding of its molecular mechanism would open up novel options for a rational manipulation of the cell. In contrast to genetic approaches, we here established and employed high-content cellular translocation biosensors applicable for dissecting nuclear export by chemicogenomics. A431 cell lines, stably expressing a translocation biosensor composed of glutathione S-transferase, GFP and a rational combination of nuclear import and export signals, were engineered by antibiotic selection and flow cytometry sorting. Using an optimized nuclear translocation algorithm, the translocation response could be robustly quantified on the Cellomics Arrayscan® VTI platform. Subsequent to assay optimization, the assay was developed into a higher density 384-well format high-content assay and employed for the screening of the 17K ChemBioNet compound collection. This library was selected on the basis of a genetic algorithm used to identify maximum common chemical substructures in a database of annotated bioactive molecules and hence, is well-placed in the chemical space covered by bioactive compounds. Automated multiparameter data analysis combined with visual inspection allowed us to identify and to rationally discriminate true export inhibitors from false positives, which included fluorescent compounds or cytotoxic substances that dramatically affected the cellular morphology. A total of 120 potential hit compounds were selected for Cellomics Arrayscan® VTI based rescreening. The export inhibitory activity of 20 compounds effective at concentrations < 25 μM were confirmed by fluorescence microscopy in several cell lines. Interestingly, kinetic analysis

  19. Cellular Interactions and Biological Responses to Titanium Dioxide Nanoparticles in HepG2 and BEAS-2B Cells: Role of Cell Culture Media

    Science.gov (United States)

    ABSTRACT We have shown previously that the composition of the biological medium used in vitro can affect the cellular interaction and biological response of titanium dioxide nanoparticles (nano-TiO2) in human lung epithelial cells. However, it is unclear if these effects are co...

  20. Fröhlich systems in cellular physiology

    Czech Academy of Sciences Publication Activity Database

    Šrobár, Fedor

    2012-01-01

    Roč. 113, č. 2 (2012), s. 95-104. ISSN 1214-6994 R&D Projects: GA ČR(CZ) GAP102/11/0649 Institutional support: RVO:67985882 Keywords : Biophysics * Cellular Physiology Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering

  1. Effects of industrial chemicals and radioactive materials in biological systems

    International Nuclear Information System (INIS)

    Much has been written on the effects of radiation and toxic chemicals on biological systems. In this communication general considerations regarding these topics will be discussed very briefly; the major emphasis will be focused on the effects of chemicals, namely ethyl methane sulfonate (EMS) on Amoeba, Advantages to the use of amoeba for studying the effects of radiation and chemicals include the following: large mononucleate unicellular organisms having a long generation time; opportunity to study cellular organelles and biochemical and genetic alterations in a single cell system; and a long cell cycle, the stages of which can be synchronized without resorting to chemical treatment or temperature shock and thereby readily permitting study at defined stages of the cell's life cycle. This, in turn, is discussed in light of current disposal methods for this type of waste and how it might be safely disposed of

  2. Integrated multilaboratory systems biology reveals differences in protein metabolism between two reference yeast strains

    DEFF Research Database (Denmark)

    Canelas, Andre B.; Harrison, Nicola; Fazio, Alessandro;

    2010-01-01

    The field of systems biology is often held back by difficulties in obtaining comprehensive, high-quality, quantitative data sets. In this paper, we undertook an interlaboratory effort to generate such a data set for a very large number of cellular components in the yeast Saccharomyces cerevisiae,...

  3. Microbial community changes in biological phosphate-removal systems on altering sludge phosphorus content

    NARCIS (Netherlands)

    Liu, WT; Linning, KD; Nakamura, K; Mino, T; Matsuo, T; Forney, LJ

    2000-01-01

    Biomarkers (respiratory quinones and cellular fatty acids) and denaturing gradient gel electrophoresis (DGGE) of PCR-amplified 16S rRNA genes were used to characterize the microbial community structure of lab-scale enhanced biological phosphate-removal (EBPR) systems in response to altering sludge p

  4. Analyzing Defects in the "Caenorhabditis Elegans" Nervous System Using Organismal and Cell Biological Approaches

    Science.gov (United States)

    Guziewicz, Megan; Vitullo, Toni; Simmons, Bethany; Kohn, Rebecca Eustance

    2002-01-01

    The goal of this laboratory exercise is to increase student understanding of the impact of nervous system function at both the organismal and cellular levels. This inquiry-based exercise is designed for an undergraduate course examining principles of cell biology. After observing the movement of "Caenorhabditis elegans" with defects in their…

  5. Green light effects on biological systems: a new biophysical phenomenon.

    Science.gov (United States)

    Comorosan, Sorin; Kappel, Wilhelm; Constantinescu, Ileana; Gheorghe, Marin; Ionescu, Elena; Pîrvu, Cristian; Cinca, Sabin; Cristache, Ligia

    2009-08-01

    This paper reports a new phenomenon connected with the influence of green light (GL) on biological systems. Our experiments have revealed an antioxidant effect of GL on cells subjected to lethal doses of UV at the cellular level and a protective effect of GL on DNA denatured by UV, coupled with a structural modification of DNA macromolecules under GL irradiation, at the molecular level. Mouse melanocyte cultures are subjected to UV irradiations with L(50) fluxes of 16.0 J m(-2) s(-1). GL is obtained from a strontium aluminate pigment, which emits GL under UV activation. Cells grown in GL, prior to UV irradiation, present a clear surprising protective effect with surviving values close to the controls. A GL antioxidant effect is suggested to be mediated through GL influence on cellular water cluster dynamics. To test this hypothesis, reactive oxygen species (ROS) are determined in cell cultures. The results revealed a decrease of cellular ROS generation in the UV-irradiated samples protected by a previous 24 h of GL irradiation. At the DNA level, the same type of GL protection against UV damage is recorded by gel electrophoresis and by UV spectroscopy of the irradiated DNA molecules. Two physical methods, impedance spectroscopy and chronoamperometry, have revealed at the level of GL-irradiated DNA molecules spectral modifications that correlate with the UV spectroscopy results. The interaction between the chargeless photons and the field of water molecules from the cellular compartments is discussed in relation with the new field of macroscopic quantum coherence phenomena. PMID:19669578

  6. Eukaryotic Systems Broaden the Scope of Synthetic Biology

    OpenAIRE

    Haynes, Karmella A.; Silver, Pamela A.

    2009-01-01

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

  7. Molecular Biology, Biochemistry and Cellular Physiology of Cysteine Metabolism in Arabidopsis thaliana

    OpenAIRE

    Hell, Rüdiger; Wirtz, Markus

    2011-01-01

    Cysteine is one of the most versatile molecules in biology, taking over such different functions as catalysis, structure, regulation and electron transport during evolution. Research on Arabidopsis has contributed decisively to the understanding of cysteine synthesis and its role in the assimilatory pathways of S, N and C in plants. The multimeric cysteine synthase complex is present in the cytosol, plastids and mitochondria and forms the centre of a unique metabolic sensing and signaling sys...

  8. Chemical biology of mutagenesis and DNA repair: cellular responses to DNA alkylation

    OpenAIRE

    Shrivastav, Nidhi; Li, Deyu; Essigmann, John M.

    2009-01-01

    The reaction of DNA-damaging agents with the genome results in a plethora of lesions, commonly referred to as adducts. Adducts may cause DNA to mutate, they may represent the chemical precursors of lethal events and they can disrupt expression of genes. Determination of which adduct is responsible for each of these biological endpoints is difficult, but this task has been accomplished for some carcinogenic DNA-damaging agents. Here, we describe the respective contributions of specific DNA les...

  9. Molecular and cellular biology of the senescent hypertrophied and failing heart.

    Science.gov (United States)

    Swynghedauw, B; Besse, S; Assayag, P; Carré, F; Chevalier, B; Charlemagne, D; Delcayre, C; Hardouin, S; Heymes, C; Moalic, J M

    1995-11-01

    During aging, experimental studies have revealed various cellular changes, principal among which is myocyte hypertrophy, which compensates for the loss of myocytes and is associated with fibrosis. The expression of alpha-myosin heavy chain is replaced by that of the isogene beta-myosin, which leads to decreased myosin adenosine triphosphatase (ATPase) activity. In consequence, contraction is slower and more energetically economical. The Ca(2+)-ATPase of the sarcoplasmic reticulum and Na+/Ca2+ exchange activity are decreased, which probably explains the reduced velocity of relaxation. Membrane receptors are also modified, since the density of both the total beta-adrenergic and muscarinic receptors is decreased. The senescent heart is able to hypertrophy in response to overload and to adapt to the new requirements. Similar alterations are observed both in the senescent heart and in the overloaded heart, in clinical as well as in experimental studies; however, differences do exist, especially in terms of fibrosis and arrhythmias. PMID:7495213

  10. Biological (molecular and cellular) markers of toxicity. Final report, September 15, 1988--September 14, 1991

    Energy Technology Data Exchange (ETDEWEB)

    Shugart, L.R.; D`Surney, S.J.; Gettys-Hull, C.; Greeley, M.S. Jr.

    1991-12-15

    Several molecular and cellular markers of genotoxicity were adapted for measurement in the Medaka (Oryzias latipes), and were used to describe the effects of treatment of the organism with diethylnitrosamine (DEN). NO{sup 6}-ethyl guanine adducts were detected, and a slight statistically significant, increase in DNA strand breaks was observed. These results are consistent with the hypothesis that prolonged exposure to high levels of DEN induced alkyltransferase activity which enzymatically removes any O{sup 6}-ethyl guanine adducts but does not result in strand breaks or hypomethylation of the DNA such as might be expected from excision repair of chemically modified DNA. Following a five week continuous DEN exposure with 100 percent renewal of DEN-water every third day, the F values (DNA double strandedness) increased considerably and to similar extent in fish exposed to 25, 50, and 100 ppM DEN. This has been observed also in medaka exposed to BaP.

  11. 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 throughin silicotheoretical studies with the aim to guide and complement furtherin vitroandin vivoexperimental efforts. Clearly, what counts is the resultin vivo, not only in terms of maximal productivity but also robustness against environmental perturbations. Engineering an organism towards an increased production flux, however, often compromises that robustness. In this contribution, we review and investigate how various analytical approaches used in metabolic engineering and synthetic biology are related to concepts developed by systems and control engineering. While trade-offs between production optimality and cellular robustness have already been studied diagnostically and statically, the dynamics also matter. Integration of the dynamic design aspects of control engineering with the more diagnostic aspects of metabolic, hierarchical control and regulation analysis is leading to the new, conceptual and operational framework required for the design of robust and productive dynamic pathways. PMID:27075000

  12. Station Model for Rail Transit System Using Cellular Automata

    Institute of Scientific and Technical Information of China (English)

    XUN Jing; NING Bin; LI Ke-Ping

    2009-01-01

    In this paper, we propose a new cellular automata model to simulate the railway traffic at station.Based on NaSch model, the proposed station model is composed of the main track and the siding track.Two different schemes for trains passing through station are considered.One is the scheme of "pass by the main track, start and stop by the siding track".The other is the scheme of "two tracks play the same role".We simulate the train movement using the proposed model and analyze the traffic flow at station.The simulation results demonstrate that the proposed cellular automata model can be successfully used for the simulations of railway traffic.Some characteristic behaviors of railway traffic flow can be reproduced.Moreover, the simulation values of the minimum headway are close to the theoretical values.This result demonstrates the dependability and availability of the proposed model.

  13. Cellular Manufacturing Systems: Organization, Trends And Innovative Methods

    OpenAIRE

    İŞLİER, Attila

    2015-01-01

    Interchangeability is the distinguishing feature of modern manufacturing. A huge production capacity to satisfy the people is reached thanks to that concept. Yet that prospect brought up a dilemma too. Efficient but inflexible flow lines for very limited product types on one side and unproductive flexible batch production for numerous diverse parts on the other side. The remedy is thought of as Cellular Manufacturing (CM). That seemed a brilliant idea but the proliferation of CM has never rea...

  14. LRRK2 Kinase Activity and Biology are Not Uniformly Predicted by its Autophosphorylation and Cellular Phosphorylation Site Status

    Directory of Open Access Journals (Sweden)

    April Reynolds

    2014-06-01

    Full Text Available Missense mutations in the Leucine Rich Repeat protein Kinase 2 (LRRK2 gene are the most common genetic predisposition to develop Parkinson’s disease (PD LRRK2 is a large multi-domain phosphoprotein with a GTPase domain and a serine/threonine protein kinase domain whose activity is implicated in neuronal toxicity; however the precise mechanism is unknown. LRRK2 autophosphorylates on several serine/threonine residues across the enzyme and is found constitutively phosphorylated on Ser910, Ser935, Ser955 and Ser973, which are proposed to be regulated by upstream kinases. Here we investigate the phosphoregulation at these sites by analyzing the effects of disease-associated mutations Arg1441Cys, Arg1441Gly, Ala1442Pro, Tyr1699Cys, Ile2012Thr, Gly2019Ser, and Ile2020Thr. We also studied alanine substitutions of phosphosite serines 910, 935, 955 and 973 and specific LRRK2 inhibition on autophosphorylation of LRRK2 Ser1292, Thr1491, Thr2483 and phosphorylation at the cellular sites. We found that mutants in the Roc-COR domains, including Arg1441Cys, Arg1441His, Ala1442Pro and Tyr1699Cys, can positively enhance LRRK2 kinase activity while concomitantly inducing the dephosphorylation of the cellular sites. Mutation of the cellular sites individually did not affect LRRK2 intrinsic kinase activity; however, Ser910/935/955/973Ala mutations trended toward increased kinase activity of LRRK2. Increased cAMP levels did not lead to increased LRRK2 cellular site phosphorylation, 14-3-3 binding or kinase activity. In cells, inhibition of LRRK2 kinase activity leads to dephosphorylation of Ser1292 by Calyculin A and okadaic acid sensitive phosphatases, while the cellular sites are dephosphorylated by Calyculin A sensitive phosphatases. These findings indicate that comparative analysis of both Ser1292 and Ser910/935/955/973 phosphorylation sites will provide important and distinct measures of LRRK2 kinase and biological activity in vitro and in vivo.

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

    Science.gov (United States)

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

    2016-06-17

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

  16. Effects of Pesticides on Biological Systems

    Directory of Open Access Journals (Sweden)

    Ergul Belge Kurutas

    2003-06-01

    Full Text Available The use of pesticid both in Turkey and other contries is widespread in order to combat against many pests which cause economical damages. However, pesticides in human pass through skin, respiratory or digestive systems and is metabolized by monooxygenase system dependent upon cytocrome P450 in liver. They also give rise to severe decreases cytochrome P450 and amount of "hem" enzyme activites of glucose-6-phosphatase, pyrophosphatase by stimulating lipid peroxidation on hepatic microsomes. In this study effects of pesticides on biological systems will be presented in genaral terms. [Archives Medical Review Journal 2003; 12(3.000: 215-228

  17. Systems Biology: The take, input, vision, concerns and hopes

    OpenAIRE

    Graeme Tucker

    2009-01-01

    Systems Biology is a relatively new branch of biology that brings together an interdisciplinary team of scientist, computer engineers and mathematicians. Biomedicine can gain much from the input of Systems Biology. The object and aims of this article centre on clarification and direction for Systems Biology, notably in regard to human health and disease.

  18. Evolutionary systems biology of amino acid biosynthetic cost in yeast.

    Directory of Open Access Journals (Sweden)

    Michael D Barton

    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

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

    OpenAIRE

    Moškon, Miha

    2012-01-01

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

  20. Assessment of beta-emitter radionuclides in biological samples using liquid scintillation counting. Application to the study of internal doses in molecular and cellular biology techniques

    International Nuclear Information System (INIS)

    The radioisotopic techniques used in Molecular and Cellular Biology involve external and internal irradiation risk. It is necessary to control the possible internal contamination associated to the development of these techniques. The internal contamination risk can be due to physical and chemical properties of the labelled compounds, aerosols generated during the performance technique. The aim of this work was to estimate the possible intake of specific beta emitters during the technique development and to propose the required criterions to perform Individual Monitoring. The most representative radioisotopic techniques were selected attending their potential risk of internal contamination. Techniques were analysed applying IAEA methodology according to the used activity in each technique. It was necessary to identify the worker groups that would require individual monitoring on the base of their specific risk. Different measurement procedures were applied to study the possible intake in group risk and more than 160 persons were measured by in vitro bioassay. (Author) 96 refs

  1. Interaction of heavy ions with nuclear chromatin: Spatiotemporal investigations of biological responses in a cellular environment

    International Nuclear Information System (INIS)

    Ion beams offer the possibility to generate strictly localized DNA lesions within subregions of a cell nucleus. The distribution of the ion-induced damage can be indirectly visualized by immunocytochemical detection of repair-related proteins as radiation-induced foci. The proteins analyzed here were the double-strand break marker γ-H2AX, the excision repair and replication protein PCNA and the cell cycle regulator CDKN1A. A newly developed adjustable sample holder is now used to apply an irradiation geometry characterized by a small angle between the plane of the cellular monolayer and the incoming ion beam. This allows the spatial analysis of protein accumulations along ion trajectories, revealing an unexpected clustering after irradiation with low-energy zinc ions. The patterns of protein aggregation observed show considerable intrinsic variability, but similar patterns of protein clustering were obtained for functionally different proteins irrespective of the type of ion beam applied, confirming previous observations for lower and higher LET beams. Foci sizes within ion tracks were found to be larger for γ-H2AX foci in comparison to CDKN1A foci, in agreement with the known histone H2AX phosphorylation response. The results suggest that not the pattern of dose deposition but the underlying chromatin structure determines the distribution of protein clusters along tracks. Therefore, the requirement of time-lapse studies using live cells is emphasized for future studies on chromatin movement as a potential component of the DNA damage response

  2. Biological Properties of Iron Oxide Nanoparticles for Cellular and Molecular Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Claus-Christian Glüer

    2010-12-01

    Full Text Available Superparamagnetic iron-oxide particles (SPIO are used in different ways as contrast agents for magnetic resonance imaging (MRI: Particles with high nonspecific uptake are required for unspecific labeling of phagocytic cells whereas those that target specific molecules need to have very low unspecific cellular uptake. We compared iron-oxide particles with different core materials (magnetite, maghemite, different coatings (none, dextran, carboxydextran, polystyrene and different hydrodynamic diameters (20–850 nm for internalization kinetics, release of internalized particles, toxicity, localization of particles and ability to generate contrast in MRI. Particle uptake was investigated with U118 glioma cells und human umbilical vein endothelial cells (HUVEC, which exhibit different phagocytic properties. In both cell types, the contrast agents Resovist, B102, non-coated Fe3O4 particles and microspheres were better internalized than dextran-coated Nanomag particles. SPIO uptake into the cells increased with particle/iron concentrations. Maximum intracellular accumulation of iron particles was observed between 24 h to 36 h of exposure. Most particles were retained in the cells for at least two weeks, were deeply internalized, and only few remained adsorbed at the cell surface. Internalized particles clustered in the cytosol of the cells. Furthermore, all particles showed a low toxicity. By MRI, monolayers consisting of 5000 Resovist-labeled cells could easily be visualized. Thus, for unspecific cell labeling, Resovist and microspheres show the highest potential, whereas Nanomag particles are promising contrast agents for target-specific labeling.

  3. Applicability of Computational Systems Biology in Toxicology

    DEFF Research Database (Denmark)

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

    2014-01-01

    and databases are used to model and predict effects of chemicals on, for instance, human health. In toxicology, computational systems biology enables identification of important pathways and molecules from large data sets; tasks that can be extremely laborious when performed by a classical literature search....... However, computational systems biology offers more advantages than providing a high-throughput literature search; it may form the basis for establishment of hypotheses on potential links between environmental chemicals and human diseases, which would be very difficult to establish experimentally....... This is possible due to the existence of comprehensive databases containing information on networks of human protein–protein interactions and protein–disease associations. Experimentally determined targets of the specific chemical of interest can be fed into these networks to obtain additional information that can...

  4. Diversity and Multiplexing Tradeoff in the Uplink of Cellular Systems with Linear MMSE Receiver

    CERN Document Server

    Song, Xiaoshi; Liu, Danpu

    2011-01-01

    In this paper, we extend the diversity and multiplexing tradeoff (DMT) analysis from point-to-point channels to cellular systems to evaluate the impact of inter-cell interference on the system reliability and efficiency. Fundamental tradeoff among diversity order, multiplexing gain and inter-cell interference intensity is characterized to reveal the capability of multiple antennas in cellular systems. And the detrimental effects of the inter-cell interference on the system performance of diversity and multiplexing is presented and analyzed.

  5. Graphical Modelling in Genetics and Systems Biology

    OpenAIRE

    Scutari, Marco

    2012-01-01

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

  6. Standards and Ontologies in Computational Systems Biology

    OpenAIRE

    Sauro, Herbert M; Bergmann, Frank

    2008-01-01

    With the growing importance of computational models in systems biology there has been much interest in recent years to develop standard model interchange languages that permit biologists to easily exchange models between different software tools. In this chapter two chief model exchange standards, SBML and CellML are described. In addition, other related features including visual layout initiatives, ontologies and best practices for model annotation are discussed. Software tools such as devel...

  7. 电磁辐射的细胞生物学效应研究进展%Progress in biological effects on the cellular level of electromagnetic radiation

    Institute of Scientific and Technical Information of China (English)

    丁真; 李劲涛; 吴水才; 曾毅

    2015-01-01

    With the rapid development of communication industry, the man⁃made electromagnetic pollution which was mainly caused by convenient electronic appliances has been a worldwide concern� Studies indicated that electromagnetic radiation ( EMR) could be harmful to human health, by affecting the nervous system, immune system, genital system and cardiocerebral vascular system� However, the cellular and molecular mechanisms were still unclear� The EMR impacts on cell viability, apoptosis, cell membrane function, cell receptor, cell signal transduction and genetic expression were illustrated and discussed here� The biological effects on the cellular level caused by EMR were summarized to provide evidences for further study on biological mechanism of EMR.%随着工业、信息行业的飞速发展,各种电子产品在给人类日常生活带来巨大便利的同时,产生的电磁污染也引起了人们的广泛关注。已有大量研究表明电磁辐射能从神经系统、免疫系统、生殖系统以及心脑血管系统等各个方面对人体产生不良影响,但具体微观作用机制还不能确定。本文综述了电磁辐射对细胞增殖、凋亡、细胞膜、受体分子、跨膜信号转导以及基因表达等方面的影响,详细介绍了细胞水平上电磁辐射的生物学效应,以期进一步对电磁辐射生物效应机制进行详细深入的研究。

  8. Applications of space-electrophoresis in medicine. [for cellular separations in molecular biology

    Science.gov (United States)

    Bier, M.

    1976-01-01

    The nature of electrophoresis is reviewed and potential advances realizable in the field of biology and medicine from a space electrophoresis facility are examined. The ground-based applications of electrophoresis: (1) characterization of an ionized species; (2) determination of the quantitative composition of a complex mixture; and (3) isolation of the components of a mixture, separation achieved on the basis of the difference in transport rates is reviewed. The electrophoresis of living cells is considered, touching upon the following areas: the separation of T and B lymphocytes; the genetic influence on mouse lymphocyte mobilities; the abnormal production of specific and monoclonal immunoproteins; and the study of cancer. Schematic diagrams are presented of three types of electrophoresis apparatus: the column assembly for the static electrophoresis experiment on the Apollo-Soyuz mission, the continuous flow apparatus used in the same mission and a miniaturized electrophoresis apparatus.

  9. Influence of Pichia pastoris cellular material on polymerase chain reaction performance as a synthetic biology standard for genome monitoring.

    Science.gov (United States)

    Templar, Alexander; Woodhouse, Stefan; Keshavarz-Moore, Eli; Nesbeth, Darren N

    2016-08-01

    Advances in synthetic genomics are now well underway in yeasts due to the low cost of synthetic DNA. These new capabilities also bring greater need for quantitating the presence, loss and rearrangement of loci within synthetic yeast genomes. Methods for achieving this will ideally; i) be robust to industrial settings, ii) adhere to a global standard and iii) be sufficiently rapid to enable at-line monitoring during cell growth. The methylotrophic yeast Pichia pastoris (P. pastoris) is increasingly used for industrial production of biotherapeutic proteins so we sought to answer the following questions for this particular yeast species. Is time-consuming DNA purification necessary to obtain accurate end-point polymerase chain reaction (e-pPCR) and quantitative PCR (qPCR) data? Can the novel linear regression of efficiency qPCR method (LRE qPCR), which has properties desirable in a synthetic biology standard, match the accuracy of conventional qPCR? Does cell cultivation scale influence PCR performance? To answer these questions we performed e-pPCR and qPCR in the presence and absence of cellular material disrupted by a mild 30s sonication procedure. The e-pPCR limit of detection (LOD) for a genomic target locus was 50pg (4.91×10(3) copies) of purified genomic DNA (gDNA) but the presence of cellular material reduced this sensitivity sixfold to 300pg gDNA (2.95×10(4) copies). LRE qPCR matched the accuracy of a conventional standard curve qPCR method. The presence of material from bioreactor cultivation of up to OD600=80 did not significantly compromise the accuracy of LRE qPCR. We conclude that a simple and rapid cell disruption step is sufficient to render P. pastoris samples of up to OD600=80 amenable to analysis using LRE qPCR which we propose as a synthetic biology standard. PMID:27211507

  10. The role of time delay in adaptive cellular negative feedback systems.

    Science.gov (United States)

    Lapytsko, Anastasiya; Schaber, Jörg

    2016-06-01

    Adaptation in cellular systems is often mediated by negative feedbacks, which usually come with certain time delays causing several characteristic response patterns including an overdamped response, damped or sustained oscillations. Here, we analyse generic two-dimensional delay differential equations with delayed negative feedback describing the dynamics of biochemical adaptive signal-response networks. We derive explicit thresholds and boundaries showing how time delay determines characteristic response patterns of these networks. Applying our theoretical analyses to concrete data we show that adaptation to osmotic stress in yeast is optimal in the sense of minimizing adaptation time without causing oscillatory behaviour, i.e., a critically damped response. In addition, our framework demonstrates that a slight increase of time delay in the NF-κB system might induce a switch from damped to sustained oscillatory behaviour. Thus, we demonstrate how delay differential equations can be used to explicitly study the delay in biochemical negative feedback systems. Our analysis also provides insight into how time delay may tune biological signal-response patterns and control the systems behaviour. PMID:26995333

  11. Analyzing Defects in the Caenorhabditis elegans Nervous System Using Organismal and Cell Biological Approaches

    OpenAIRE

    Guziewicz, Megan; Vitullo, Toni; Simmons, Bethany; Kohn, Rebecca Eustance

    2002-01-01

    The goal of this laboratory exercise is to increase student understanding of the impact of nervous system function at both the organismal and cellular levels. This inquiry-based exercise is designed for an undergraduate course examining principles of cell biology. After observing the movement of Caenorhabditis elegans with defects in their nervous system, students examine the structure of the nervous system to categorize the type of defect. They distinguish between defects in synaptic vesicle...

  12. Mitochondria in mesenchymal stem cell biology and cell therapy: From cellular differentiation to mitochondrial transfer.

    Science.gov (United States)

    Hsu, Yi-Chao; Wu, Yu-Ting; Yu, Ting-Hsien; Wei, Yau-Huei

    2016-04-01

    Mesenchymal stem cells (MSCs) are characterized to have the capacity of self-renewal and the potential to differentiate into mesoderm, ectoderm-like and endoderm-like cells. MSCs hold great promise for cell therapies due to their multipotency in vitro and therapeutic advantage of hypo-immunogenicity and lower tumorigenicity. Moreover, it has been shown that MSCs can serve as a vehicle to transfer mitochondria into cells after cell transplantation. Mitochondria produce most of the energy through oxidative phosphorylation in differentiated cells. It has been increasingly clear that the switch of energy supply from glycolysis to aerobic metabolism is essential for successful differentiation of MSCs. Post-translational modifications of proteins have been established to regulate mitochondrial function and metabolic shift during MSCs differentiation. In this article, we review and provide an integrated view on the roles of different protein kinases and sirtuins in the maintenance and differentiation of MSCs. Importantly, we provide evidence to suggest that alteration in the expression of Sirt3 and Sirt5 and relative changes in the acylation levels of mitochondrial proteins might be involved in the activation of mitochondrial function and adipogenic differentiation of adipose-derived MSCs. We summarize their roles in the regulation of mitochondrial biogenesis and metabolism, oxidative responses and differentiation of MSCs. On the other hand, we discuss recent advances in the study of mitochondrial dynamics and mitochondrial transfer as well as their roles in the differentiation and therapeutic application of MSCs to improve cell function in vitro and in animal models. Accumulating evidence has substantiated that the therapeutic potential of MSCs is conferred not only by cell replacement and paracrine effects but also by transferring mitochondria into injured tissues or cells to modulate the cellular metabolism in situ. Therefore, elucidation of the underlying mechanisms

  13. Kinetic Monte Carlo and Cellular Particle Dynamics Simulations of Multicellular Systems

    CERN Document Server

    Flenner, Elijah; Barz, Bogdan; Neagu, Adrian; Forgacs, Gabor; Kosztin, Ioan

    2011-01-01

    Computer modeling of multicellular systems has been a valuable tool for interpreting and guiding in vitro experiments relevant to embryonic morphogenesis, tumor growth, angiogenesis and, lately, structure formation following the printing of cell aggregates as bioink particles. Computer simulations based on Metropolis Monte Carlo (MMC) algorithms were successful in explaining and predicting the resulting stationary structures (corresponding to the lowest adhesion energy state). Here we introduce two alternatives to the MMC approach for modeling cellular motion and self-assembly: (1) a kinetic Monte Carlo (KMC), and (2) a cellular particle dynamics (CPD) method. Unlike MMC, both KMC and CPD methods are capable of simulating the dynamics of the cellular system in real time. In the KMC approach a transition rate is associated with possible rearrangements of the cellular system, and the corresponding time evolution is expressed in terms of these rates. In the CPD approach cells are modeled as interacting cellular ...

  14. Modeling chemical systems using cellular automata a textbook and laboratory manual

    CERN Document Server

    Kier, Lemont B; Cheng, Chao-Kun

    2006-01-01

    Provides a practical introduction to an exciting modeling paradigm for complex systems. This book discusses the nature of scientific inquiry using models and simulations, and describes the nature of cellular automata models. It gives descriptions of how cellular automata models can be used in the study of a variety of phenomena.

  15. A unique cellular scaling rule in the avian auditory system.

    Science.gov (United States)

    Corfield, Jeremy R; Long, Brendan; Krilow, Justin M; Wylie, Douglas R; Iwaniuk, Andrew N

    2016-06-01

    Although it is clear that neural structures scale with body size, the mechanisms of this relationship are not well understood. Several recent studies have shown that the relationship between neuron numbers and brain (or brain region) size are not only different across mammalian orders, but also across auditory and visual regions within the same brains. Among birds, similar cellular scaling rules have not been examined in any detail. Here, we examine the scaling of auditory structures in birds and show that the scaling rules that have been established in the mammalian auditory pathway do not necessarily apply to birds. In galliforms, neuronal densities decrease with increasing brain size, suggesting that auditory brainstem structures increase in size faster than neurons are added; smaller brains have relatively more neurons than larger brains. The cellular scaling rules that apply to auditory brainstem structures in galliforms are, therefore, different to that found in primate auditory pathway. It is likely that the factors driving this difference are associated with the anatomical specializations required for sound perception in birds, although there is a decoupling of neuron numbers in brain structures and hair cell numbers in the basilar papilla. This study provides significant insight into the allometric scaling of neural structures in birds and improves our understanding of the rules that govern neural scaling across vertebrates. PMID:26002617

  16. Review on the Effects Research of Microgravity Cellular and Molecular Biology.%微重力细胞分子生物学效应研究进展

    Institute of Scientific and Technical Information of China (English)

    李英贤; 李琦; 王晓刚; 李莹辉

    2011-01-01

    Space cellular and molecular biology is to study the mechanism of changes affecting astronaut health such as bone loss and muscle dystrophy, heart and lung disorder, immunity system inhibition and alteration in motor sensory system. The aim ia to disclose intracellular changes under space environment. In this paper, we review the progress in this field from the view of cellular structure and morphology, cellular proliferation and differentiation, cell signaling pathway and the changes in gene expression,protein translation and epigenetics.%空间细胞分子生物学针对空间条件下肌肉与骨骼代谢失调、心肺功能紊乱、免疫及感觉运动系统变化等影响航天员身体健康的因素,深入分子内部探索细胞内各种分子事件的变化,揭示细胞对空间环境变化的响应机制.本文主要就微重力条件下细胞形态结构的变化、细胞的增殖与分化、胞内信号转导途径的改变以及由此导致的基因表达与蛋白翻译的改变和表观遗传学变化等方面的研究进展进行了综述.

  17. Engineering biological systems toward a sustainable bioeconomy.

    Science.gov (United States)

    Lopes, Mateus Schreiner Garcez

    2015-06-01

    The nature of our major global risks calls for sustainable innovations to decouple economic growth from greenhouse gases emission. The development of sustainable technologies has been negatively impacted by several factors including sugar production costs, production scale, economic crises, hydraulic fracking development and the market inability to capture externality costs. However, advances in engineering of biological systems allow bridging the gap between exponential growth of knowledge about biology and the creation of sustainable value chains for a broad range of economic sectors. Additionally, industrial symbiosis of different biobased technologies can increase competitiveness and sustainability, leading to the development of eco-industrial parks. Reliable policies for carbon pricing and revenue reinvestments in disruptive technologies and in the deployment of eco-industrial parks could boost the welfare while addressing our major global risks toward the transition from a fossil to a biobased economy. PMID:25845304

  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. Tracking the Dynamic Relationship between Cellular Systems and Extracellular Subproteomes in Pseudomonas aeruginosa Biofilms.

    Science.gov (United States)

    Park, Amber J; Murphy, Kathleen; Surette, Matthew D; Bandoro, Christopher; Krieger, Jonathan R; Taylor, Paul; Khursigara, Cezar M

    2015-11-01

    The transition of the opportunistic pathogen Pseudomonas aeruginosa from free-living bacteria into surface-associated biofilm communities represents a viable target for the prevention and treatment of chronic infectious disease. We have established a proteomics platform that identified 2443 and 1142 high-confidence proteins in P. aeruginosa whole cells and outer-membrane vesicles (OMVs), respectively, at three time points during biofilm development (ProteomeXchange identifier PXD002605). The analysis of cellular systems, specifically the phenazine biosynthetic pathway, demonstrates that whole-cell protein abundance correlates to end product (i.e., pyocyanin) concentrations in biofilm but not in planktonic cultures. Furthermore, increased cellular protein abundance in this pathway results in quantifiable pyocyanin in early biofilm OMVs and OMVs from both growth modes isolated at later time points. Overall, our data indicate that the OMVs being released from the surface of the biofilm whole cells have unique proteomes in comparison to their planktonic counterparts. The relative abundance of OMV proteins from various subcellular sources showed considerable differences between the two growth modes over time, supporting the existence and preferential activation of multiple OMV biogenesis mechanisms under different conditions. The consistent detection of cytoplasmic proteins in all of the OMV subproteomes challenges the notion that OMVs are composed of outer membrane and periplasmic proteins alone. Direct comparisons of outer-membrane protein abundance levels between OMVs and whole cells shows ratios that vary greatly from 1:1 and supports previous studies that advocate the specific inclusion, or "packaging", of proteins into OMVs. The quantitative analysis of packaged protein groups suggests biogenesis mechanisms that involve untethered, rather than absent, peptidoglycan-binding proteins. Collectively, individual protein and biological system analyses of biofilm OMVs

  20. Arabidopsis thaliana as a Model Organism in Systems Biology

    OpenAIRE

    Van Norman, Jaimie M.; Benfey, Philip N

    2009-01-01

    Significant progress has been made in identification of genes and gene networks involved in key biological processes. Yet, how these genes and networks are coordinated over increasing levels of biological complexity, from cells to tissues to organs, remains unclear. To address complex biological questions, biologists are increasingly using high-throughput tools and systems biology approaches to examine complex biological systems at a global scale. A system is a network of interacting and inte...

  1. CRM1 is a cellular target of curcumin: new insights for the myriad of biological effects of an ancient spice.

    Science.gov (United States)

    Niu, Mingshan; Wu, Sijin; Mao, Lei; Yang, Yongliang

    2013-10-01

    Curcumin is the major constituent of turmeric plant, an ancient spice widely used in Indian cuisine and traditional herbal medicine. Recently, the potential medical use of curcumin as anti-cancer and anti-inflammatory agent has set off an upsurge in research into the mechanism for its broad biological effects. We showed that CRM1, an important nuclear exportin, is a cellular target of curcumin by serious experimental and theoretical investigation. Using a nuclear export functional assay, we observed a clear and rapid shift of cargo proteins from a cytoplasmic localization to the nucleus when treated with curcumin or its structural analogue dibenzylideneacetone (DBA). We demonstrated that curcumin could specifically target the conserved Cys(528) of CRM1 through mass spectrometric analysis and in vivo experiments. Furthermore, computational modeling has revealed that curcumin could be correctly docked into the hydrophobic pocket of CRM1 judged from shape complementarity and putative molecular interactions. The Michael acceptor moiety on curcumin is within the appropriate distance to enable Michael reaction with Cys residue of CRM1. More importantly, we showed that nuclear retention of FOXO1 could be observed in the presence of Leptomycin B (LMB) or curcumin whereas in cells expressing the CRM1-Cys(528) mutant, only a cytoplasmic localization was observed. The inhibition of nuclear traffic by curcumin may account for its myriad of biological effects, particularly for its therapeutic properties in cancer and inflammatory diseases. Our findings may have important implications for further clinical investigation of curcumin. PMID:23829533

  2. A Free Energy Principle for Biological Systems

    Directory of Open Access Journals (Sweden)

    Friston Karl

    2012-10-01

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

  3. 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.

  4. 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…

  5. Statistical analysis of nanoparticle dosing in a dynamic cellular system

    Science.gov (United States)

    Summers, Huw D.; Rees, Paul; Holton, Mark D.; Rowan Brown, M.; Chappell, Sally C.; Smith, Paul J.; Errington, Rachel J.

    2011-03-01

    The delivery of nanoparticles into cells is important in therapeutic applications and in nanotoxicology. Nanoparticles are generally targeted to receptors on the surfaces of cells and internalized into endosomes by endocytosis, but the kinetics of the process and the way in which cell division redistributes the particles remain unclear. Here we show that the chance of success or failure of nanoparticle uptake and inheritance is random. Statistical analysis of nanoparticle-loaded endosomes indicates that particle capture is described by an over-dispersed Poisson probability distribution that is consistent with heterogeneous adsorption and internalization. Partitioning of nanoparticles in cell division is random and asymmetric, following a binomial distribution with mean probability of 0.52-0.72. These results show that cellular targeting of nanoparticles is inherently imprecise due to the randomness of nature at the molecular scale, and the statistical framework offers a way to predict nanoparticle dosage for therapy and for the study of nanotoxins.

  6. Validity of the Cauchy-Born rule applied to discrete cellular-scale models of biological tissues

    KAUST Repository

    Davit, Y.

    2013-04-30

    The development of new models of biological tissues that consider cells in a discrete manner is becoming increasingly popular as an alternative to continuum methods based on partial differential equations, although formal relationships between the discrete and continuum frameworks remain to be established. For crystal mechanics, the discrete-to-continuum bridge is often made by assuming that local atom displacements can be mapped homogeneously from the mesoscale deformation gradient, an assumption known as the Cauchy-Born rule (CBR). Although the CBR does not hold exactly for noncrystalline materials, it may still be used as a first-order approximation for analytic calculations of effective stresses or strain energies. In this work, our goal is to investigate numerically the applicability of the CBR to two-dimensional cellular-scale models by assessing the mechanical behavior of model biological tissues, including crystalline (honeycomb) and noncrystalline reference states. The numerical procedure involves applying an affine deformation to the boundary cells and computing the quasistatic position of internal cells. The position of internal cells is then compared with the prediction of the CBR and an average deviation is calculated in the strain domain. For center-based cell models, we show that the CBR holds exactly when the deformation gradient is relatively small and the reference stress-free configuration is defined by a honeycomb lattice. We show further that the CBR may be used approximately when the reference state is perturbed from the honeycomb configuration. By contrast, for vertex-based cell models, a similar analysis reveals that the CBR does not provide a good representation of the tissue mechanics, even when the reference configuration is defined by a honeycomb lattice. The paper concludes with a discussion of the implications of these results for concurrent discrete and continuous modeling, adaptation of atom-to-continuum techniques to biological

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

    International Nuclear Information System (INIS)

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

  8. The emerging role of skeletal muscle oxidative metabolism as a biological target and cellular regulator of cancer-induced muscle wasting.

    Science.gov (United States)

    Carson, James A; Hardee, Justin P; VanderVeen, Brandon N

    2016-06-01

    While skeletal muscle mass is an established primary outcome related to understanding cancer cachexia mechanisms, considerable gaps exist in our understanding of muscle biochemical and functional properties that have recognized roles in systemic health. Skeletal muscle quality is a classification beyond mass, and is aligned with muscle's metabolic capacity and substrate utilization flexibility. This supplies an additional role for the mitochondria in cancer-induced muscle wasting. While the historical assessment of mitochondria content and function during cancer-induced muscle loss was closely aligned with energy flux and wasting susceptibility, this understanding has expanded to link mitochondria dysfunction to cellular processes regulating myofiber wasting. The primary objective of this article is to highlight muscle mitochondria and oxidative metabolism as a biological target of cancer cachexia and also as a cellular regulator of cancer-induced muscle wasting. Initially, we examine the role of muscle metabolic phenotype and mitochondria content in cancer-induced wasting susceptibility. We then assess the evidence for cancer-induced regulation of skeletal muscle mitochondrial biogenesis, dynamics, mitophagy, and oxidative stress. In addition, we discuss environments associated with cancer cachexia that can impact the regulation of skeletal muscle oxidative metabolism. The article also examines the role of cytokine-mediated regulation of mitochondria function, followed by the potential role of cancer-induced hypogonadism. Lastly, a role for decreased muscle use in cancer-induced mitochondrial dysfunction is reviewed. PMID:26593326

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

    Science.gov (United States)

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

    2014-01-01

    As mathematical models become more commonly integrated into the study of biology, a common language for describing biological processes is manifesting. Many tools have emerged for the simulation of in vivo synthetic biological systems, with only a few examples of prominent work done on predicting the dynamics of cell-free synthetic systems. At the same time, experimental biologists have begun to study dynamics of in vitro systems encapsulated by amphiphilic molecules, opening the door for the development of a new generation of biomimetic systems. In this review, we explore both in vivo and in vitro models of biochemical networks with a special focus on tools that could be applied to the construction of cell-free expression systems. We believe that quantitative studies of complex cellular mechanisms and pathways in synthetic systems can yield important insights into what makes cells different from conventional chemical systems. PMID:25538941

  10. Integration of peroxisomes into an endomembrane system that governs cellular aging

    Directory of Open Access Journals (Sweden)

    Adam eBeach

    2012-07-01

    Full Text Available The peroxisome is an organelle that has long been known for its essential roles in oxidation of fatty acids, maintenance of reactive oxygen species (ROS homeostasis and anaplerotic replenishment of tricarboxylic acid (TCA cycle intermediates destined for mitochondria. Growing evidence supports the view that these peroxisome-confined metabolic processes play an essential role in defining the replicative and chronological age of a eukaryotic cell. Much progress has recently been made in defining molecular mechanisms that link cellular aging to fatty acid oxidation, ROS turnover and anaplerotic metabolism in peroxisomes. Emergent studies have revealed that these organelles not only house longevity-defining metabolic reactions but can also regulate cellular aging via their dynamic communication with other cellular compartments. Peroxisomes communicate with other organelles by establishing extensive physical contact with lipid bodies, maintaining an endoplasmic reticulum (ER to peroxisome connectivity system, exchanging certain metabolites, and being involved in the bidirectional flow of some of their protein and lipid constituents. The scope of this review is to summarize the evidence that peroxisomes are dynamically integrated into an endomembrane system that governs cellular aging. We discuss recent progress in understanding how communications between peroxisomes and other cellular compartments within this system influence the development of a pro- or anti-aging cellular pattern. We also propose a model for the integration of peroxisomes into the endomembrane system governing cellular aging and critically evaluate several molecular mechanisms underlying such integration.

  11. 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

  12. 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...... binding domain (LBD) has been associated with EDCs, a significant number of EDCs do not appear to influence the LBDs of these receptors. Therefore, we evaluated the potential biological effects of EDCs in humans with the aim to rationalize the etiology of certain disorders associated with the reproductive...

  13. Integrative Systems Biology: Elucidating Complex Traits

    DEFF Research Database (Denmark)

    Pers, Tune Hannes

    human traits and disease. e esis is structured as follows. Chapter  presents a few introductory remarks to integrative systems biology, and Chapter  gives a brief description of human genetic variation and GWA analysis. Chapters - present the main topics in the esis (integrative methodologies for...... body-mass index associated gene products coalesce onto distinct protein complexes, and show that these putative risk modules incriminate novel candidate obesitysusceptibility genes. e last overall line of research presented here, provides examples on how networks of human metabolism may serve as a...

  14. A new method for decreasing cell-load variation in dynamic cellular manufacturing systems

    OpenAIRE

    Aidin Delgoshaei; Mohd Khairol Mohd Ariffin,; Btht Hang Tuah Bin Baharudin; Zulkiflle Leman

    2016-01-01

    Cell load variation is considered a significant shortcoming in scheduling of cellular manufacturing systems. In this article, a new method is proposed for scheduling dynamic cellular manufacturing systems in the presence of bottleneck and parallel machines. The aim of this method is to control cell load variation during the process of determining the best trading off values between in-house manufacturing and outsourcing. A genetic algorithm (GA) is developed because of the high potential of t...

  15. Exploring the cellular and tissue uptake of nanomaterials in a range of biological samples using multimodal nonlinear optical microscopy

    Science.gov (United States)

    Johnston, Helinor J.; Mouras, Rabah; Brown, David M.; Elfick, Alistair; Stone, Vicki

    2015-12-01

    The uptake of nanomaterials (NMs) by cells is critical in determining their potential biological impact, whether beneficial or detrimental. Thus, investigation of NM internalization by cells is a common consideration in hazard and efficacy studies. There are currently a number of approaches that are routinely used to investigate NM-cell interactions, each of which have their own advantages and limitations. Ideally, imaging modalities used to investigate NM uptake by cells should not require the NM to be labelled (e.g. with fluorophores) to facilitate its detection. We present a multimodal imaging approach employing a combination of label-free microscopies that can be used to investigate NM-cell interactions. Coherent anti-Stokes Raman scattering microscopy was used in combination with either two-photon photoluminescence or four-wave mixing (FWM) to visualize the uptake of gold or titanium dioxide NMs respectively. Live and fixed cell imaging revealed that NMs were internalized by J774 macrophage and C3A hepatocyte cell lines (15-31 μg ml-1). Sprague Dawley rats were exposed to NMs (intratracheal instillation, 62 μg) and NMs were detected in blood and lung leucocytes, lung and liver tissue, demonstrating that NMs could translocate from the exposure site. Obtained data illustrate that multimodal nonlinear optical microscopy may help overcome current challenges in the assessment of NM cellular uptake and biodistribution. It is therefore a powerful tool that can be used to investigate unlabelled NM cellular and tissue uptake in three dimensions, requires minimal sample preparation, and is applicable to live and fixed cells.

  16. Model checking biological systems described using ambient calculus

    DEFF Research Database (Denmark)

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

    2005-01-01

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

  17. An Integrated Biological Control System At Hanford

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Albert A de Graaf

    2009-11-01

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

  2. Ultrasensitive Force Detection and Applications to Biological Systems

    Science.gov (United States)

    Kenny, Thomas

    2001-03-01

    For many years, researchers have developed a variety of micromechanical devices for a range of applications. The majority of these devices are based on micromechanical force transducers to convert external physical signals into electrical signals. The force sensing capabilities of these devices are remarkable - it is possible to design devices with force resolution ranging from milli-N to atto-N within this technology. In addition to the conventional applications for MEMS devices, it is possible to tailor these designs to allow interesting scientific measurements on biological systems. For example, there are active research communities investigating cellular adhesion, protein folding, and animal locomotion. In all of these cases, the basic questions are mechanical in nature, and direct force measurements can provide new insight. This talk will review some ongoing biological research that makes use of MEMS devices, and discuss opportunities for new directions. Collaborators on this research include : Yiching Liang, Robert Rudnitsky, Michael Bartsch, Robert Full, Kellar Autumn, James Nelson, Jim Spudich, and Mark Cutkosky This work is funded by NSF (XYZ on a Chip) and ONR MURI (Biomimetic Robots).

  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. Rerouting Cellular Electron Flux To Increase the Rate of Biological Methane Production.

    Science.gov (United States)

    Catlett, Jennie L; Ortiz, Alicia M; Buan, Nicole R

    2015-10-01

    Methanogens are anaerobic archaea that grow by producing methane, a gas that is both an efficient renewable fuel and a potent greenhouse gas. We observed that overexpression of the cytoplasmic heterodisulfide reductase enzyme HdrABC increased the rate of methane production from methanol by 30% without affecting the growth rate relative to the parent strain. Hdr enzymes are essential in all known methane-producing archaea. They function as the terminal oxidases in the methanogen electron transport system by reducing the coenzyme M (2-mercaptoethane sulfonate) and coenzyme B (7-mercaptoheptanoylthreonine sulfonate) heterodisulfide, CoM-S-S-CoB, to regenerate the thiol-coenzymes for reuse. In Methanosarcina acetivorans, HdrABC expression caused an increased rate of methanogenesis and a decrease in metabolic efficiency on methylotrophic substrates. When acetate was the sole carbon and energy source, neither deletion nor overexpression of HdrABC had an effect on growth or methane production rates. These results suggest that in cells grown on methylated substrates, the cell compensates for energy losses due to expression of HdrABC with an increased rate of substrate turnover and that HdrABC lacks the appropriate electron donor in acetate-grown cells. PMID:26162885

  5. 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

  6. Spatial Structures and Regulation in Biological Systems

    DEFF Research Database (Denmark)

    Yde, Pernille

    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...... environmental conditions are different pH and calcium concentrations. We construct a mathematical model for the aggregation process, and fit the model to an array of experimental data. The model reproduces the dynamics of the aggregation process and predicts final size distributions of the aggregates, which...... conditions of the cell. We then construct a multicellular 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...

  7. Biological Systems for Hydrogen Photoproduction (Presentation)

    Energy Technology Data Exchange (ETDEWEB)

    Ghirardi, M. L.

    2012-05-01

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

  8. Developing integrated TOF-SIMS/MALDI IMS system in studying biological systems

    Science.gov (United States)

    Wu, Ligang

    Using imaging mass spectrometry (IMS) techniques (including TOF-SIMS and MALDI IMS) to study biological systems is a relatively new concept and quickly gained popularity in recent years. Imaging mass spectrometry is a discovery technology that utilizes a focused ion beam or laser beam to desorb ions from sample surface. By detecting the desorbed ions, the chemical distributions and biological changes of a sample surface can be analyzed. These techniques offer a new analytical imaging approach to investigate biological processes at the cellular and tissue level. In this research, a novel integrated TOF-SIMS/MALDI IMS system as well as IMS based biological-sample-preparation techniques and data-reduction methods are developed. We then demonstrate the power of these techniques in studying different biological systems, including monosaccharides isomers, human breast cancer cell lines, mouse embryo tissues and mouse kidney sections. Using TOF-SIMS and statistical analysis methods, seven monosaccharide isomers are fully differentiated by analyzing their characteristic spectral pattern. In addition, a deep understanding of the fragmentation pathway of these isomers under ion bombardment is gained. In an application of TOF-SIMS to the differentiation of three human breast cancer cell lines, MCF-7, T47D, and MDA-MB-231, we show that principal component analysis (PCA) data reduction of TOF-SIMS spectra can differentiate cellular compartments (cytosol, nuclear and particulate) within the cell types, as well as homogenates from among the three cell lines. In a tissue-specific application, we extend the analytical capabilities of TOF-SIMS and PCA by imaging and differentiating Formalin-fixed paraffin-embedded (FFPE) mouse embryo tissues. We demonstrate reproducible differentiation of six tissue types based on the remaining small molecules after paraffin-embedding and the fragments of the cellular proteins. In a unique study of fresh frozen mouse kidney tissues, both TOF

  9. A Simple Scheme for Improved Performance of Fixed Outage Rate Cellular System

    Directory of Open Access Journals (Sweden)

    Hussein M.A. Basi

    2004-01-01

    Full Text Available The traffic characteristic of mobile cellular systems is rather distinct from that of a fixed telephone network. However the system planning and design are still carried out with the tools of conventional traffic theory. In the recent days much work is being done in the performance evaluation of mobile or cellular communication systems in order to develop a system with greater efficiency. The useful parameters to estimate the performance of the system are voice quality, frequency spectrum efficiency and Grade of Service (GOS. The grade of service will be affected due to outage of channels. In this study, a new scheme is proposed to reduce lost calls due to channel outage in the fixed rate outage cellular system. In this proposed scheme the call will never dropped but may be delayed. The system performance is evaluated for different conditions and the results are discussed.

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

    Science.gov (United States)

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

    2016-01-01

    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. PMID:27311441

  11. Large-scale violation of detailed balance in biological systems

    Science.gov (United States)

    Broedersz, Chase; Battle, Christopher; Fakhri, Nikta; Mackintosh, Fred; Schmidt, Christopher

    2015-03-01

    Living systems are out of equilibrium. A fundamental manifestation of non-equilibrium dynamics in biological systems is the violation of detailed balance: at the microscopic level, enzymatic processes such as kinetic proofreading or molecular motor activity clearly violate detailed balance. We study how such non-equilibrium dynamics emerge at macroscopic scales in cellular assemblies. We measure the steady-state dynamics of two systems, beating flagella of Chlamydomonas reinhardtii and mechanosensitive primary cilia protruding from epithelial kidney cells. The flagellum exhibits clear non-equilibrium driving, whereas fluctuations in the primary cilium are difficult to differentiate from Brownian motion. We parameterize the shapes of the flagellum and primary cilium using a low-dimensional representation of their configuration phase space, and use the measured dynamics to infer the steady-state probability distributions and probability currents. For both the flagellum and the primary cilium we find significant, coherent circulating probability currents, demonstrating that these systems violate detailed balance at the mesoscopic scale.

  12. Multiparametric imaging of biological systems by force-distance curve-based AFM.

    Science.gov (United States)

    Dufrêne, Yves F; Martínez-Martín, David; Medalsy, Izhar; Alsteens, David; Müller, Daniel J

    2013-09-01

    A current challenge in the life sciences is to understand how biological systems change their structural, biophysical and chemical properties to adjust functionality. Addressing this issue has been severely hampered by the lack of methods capable of imaging biosystems at high resolution while simultaneously mapping their multiple properties. Recent developments in force-distance (FD) curve-based atomic force microscopy (AFM) now enable researchers to combine (sub)molecular imaging with quantitative mapping of physical, chemical and biological interactions. Here we discuss the principles and applications of advanced FD-based AFM tools for the quantitative multiparametric characterization of complex cellular and biomolecular systems under physiological conditions. PMID:23985731

  13. Robert Feulgen Prize Lecture 1993. The journey of the insulin receptor into the cell: from cellular biology to pathophysiology.

    Science.gov (United States)

    Carpentier, J L

    1993-09-01

    The data that we have reviewed indicate that insulin binds to a specific cell-surface receptor. The complex then becomes involved in a series of steps which lead the insulin-receptor complex to be internalized and rapidly delivered to endosomes. From this sorting station, the hormone is targeted to lysosomes to be degraded while the receptor is recycled back to the cell surface. This sequence of events presents two degrees of ligand specificity: (a) The first step is ligand-dependent and requires insulin-induced receptor phosphorylation of specific tyrosine residues. It consists in the surface redistribution of the receptor from microvilli where it preferentially localizes in its unoccupied form. (b) The second step is more general and consists in the association with clathrin-coated pits which represents the internalization gate common to many receptors. This sequence of events participates in the regulation of the biological action of the hormone and can thus be implicated in the pathophysiology of diabetes mellitus and various extreme insulin resistance syndromes, including type A extreme insulin resistance, leprechaunism, and Rabson-Mendehall syndrome. Alterations of the internalization process can result either from intrinsic abnormalities of the receptor or from more general alteration of the plasma membrane or of the cell metabolism. Type I diabetes is an example of the latter possibility, since general impairment of endocytosis could contribute to extracellular matrix accumulation and to an increase in blood cholesterol. Thus, better characterization of the molecular and cellular biology of the insulin receptor and of its journey inside the cell definitely leads to better understanding of disease states, including diabetes. PMID:8244769

  14. From cellular mechanotransduction to biologically inspired engineering: 2009 Pritzker Award Lecture, BMES Annual Meeting October 10, 2009.

    Science.gov (United States)

    Ingber, Donald E

    2010-03-01

    This article is based on a lecture I presented as the recipient of the 2009 Pritzker Distinguished Lecturer Award at the Biomedical Engineering Society annual meeting in October 2009. Here, I review more than thirty years of research from my laboratory, beginning with studies designed to test the theory that cells use tensegrity (tensional integrity) architecture to stabilize their shape and sense mechanical signals, which I believed to be critical for control of cell function and tissue development. Although I was trained as a cell biologist, I found that the tools I had at my disposal were insufficient to experimentally test these theories, and thus I ventured into engineering to find critical solutions. This path has been extremely fruitful as it has led to confirmation of the critical role that physical forces play in developmental control, as well as how cells sense and respond to mechanical signals at the molecular level through a process known as cellular mechanotransduction. Many of the predictions of the cellular tensegrity model relating to cell mechanical behaviors have been shown to be valid, and this vision of cell structure led to discovery of the central role that transmembrane adhesion receptors, such as integrins, and the cytoskeleton play in mechanosensing and mechanochemical conversion. In addition, these fundamental studies have led to significant unexpected technology fallout, including development of micromagnetic actuators for non-invasive control of cellular signaling, microfluidic systems as therapeutic extracorporeal devices for sepsis therapy, and new DNA-based nanobiotechnology approaches that permit construction of artificial tensegrities that mimic properties of living materials for applications in tissue engineering and regenerative medicine. PMID:20140519

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

    OpenAIRE

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

    2014-01-01

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

  16. Computational Fluid Dynamic Approach for Biological System Modeling

    OpenAIRE

    Huang, Weidong; Wu, Chundu; Xiao, Bingjia; Xia, Weidong

    2005-01-01

    Various biological system models have been proposed in systems biology, which are based on the complex biological reactions kinetic of various components. These models are not practical because we lack of kinetic information. In this paper, it is found that the enzymatic reaction and multi-order reaction rate is often controlled by the transport of the reactants in biological systems. A Computational Fluid Dynamic (CFD) approach, which is based on transport of the components and kinetics of b...

  17. The effect of an autologous cellular gel-matrix integrated implant system on wound healing

    Directory of Open Access Journals (Sweden)

    Morales Patricio

    2010-06-01

    Full Text Available Abstract Background This manuscript reports the production and preclinical studies to examine the tolerance and efficacy of an autologous cellular gel-matrix integrated implant system (IIS aimed to treat full-thickness skin lesions. Methods The best concentration of fibrinogen and thrombin was experimentally determined by employing 28 formula ratios of thrombin and fibrinogen and checking clot formation and apparent stability. IIS was formed by integrating skin cells by means of the in situ gelification of fibrin into a porous crosslinked scaffold composed of chitosan, gelatin and hyaluronic acid. The in vitro cell proliferation within the IIS was examined by the MTT assay and PCNA expression. An experimental rabbit model consisting of six circular lesions was utilized to test each of the components of the IIS. Then, the IIS was utilized in an animal model to cover a 35% body surface full thickness lesion. Results The preclinical assays in rabbits demonstrated that the IIS was well tolerated and also that IIS-treated rabbit with lesions of 35% of their body surface, exhibited a better survival rate (p = 0,06. Conclusion IIS should be further studied as a new wound dressing which shows promising properties, being the most remarkable its good biological tolerance and cell growth promotion properties.

  18. 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.

  19. Quantifying electron transfer reactions in biological systems

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  20. Quantum integrable systems. Quantitative methods in biology

    CERN Document Server

    Feverati, Giovanni

    2011-01-01

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

  1. Integrative Systems Biology Applied to Toxicology

    DEFF Research Database (Denmark)

    Kongsbak, Kristine Grønning

    that were in concordance with their effects in experimental animals. In project II, I profiled the effects on rat liver gene expression levels following exposure to a 14-chemical mixture ± the presence of an endocrine disrupting chemical. This project helped us shed light on the mechanism of action of......Humans are exposed to various chemical agents through food, cosmetics, pharmaceuticals and other sources. Exposure to chemicals is suspected of playing a main role in the development of some adverse health effects in humans. Additionally, European regulatory authorities have recognized the risk...... 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...

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  3. Building Biologically-Inspired Self-Adapting Systems

    OpenAIRE

    Brun, Yuriy

    2008-01-01

    Biological systems are far more complex than systems we design and build today. The human body alone has orders of magnitude more complexity than our most-intricate designed systems. Further, biological systems are decentralized in such a way that allows them to benefit from built-in error-correction, fault tolerance, and scalability. It follows that if we can extract certain properties of biological systems and inject them into our software design process, we may be able to build complex ...

  4. Proceedings Second International Workshop on Hybrid Systems and Biology

    OpenAIRE

    Dang, Thao; Piazza, Carla

    2013-01-01

    This volume contains the proceedings of the Second International Workshop Hybrid Systems and Biology (HSB 2013) held in Taormina (Italy), on September 2th, 2013. The workshop is affiliated to the 12th European Conference on Artificial Life (ECAL 2013). Systems biology aims at providing a system-level understanding of biological systems by unveiling their structure, dynamics and control methods. Due to the intrinsic multi-scale nature of these systems in space, in organization levels and in ti...

  5. Systems Biology and Ecology of Streamlined Bacterioplankton

    Science.gov (United States)

    Giovannoni, S. J.

    2014-12-01

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

  6. Radiating Frohlich system as a model of cellular electromagnetism

    Czech Academy of Sciences Publication Activity Database

    Šrobár, Fedor

    2015-01-01

    Roč. 34, č. 4 (2015), s. 355-360. ISSN 1536-8378 Institutional support: RVO:67985882 Keywords : electromagnetic radiation * Fröhlich systems * cell physiology Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 1.194, year: 2014

  7. Four-Way Relaying in Wireless Cellular Systems

    DEFF Research Database (Denmark)

    Liu, Huaping; Popovski, Petar; De Carvalho, Elisabeth; Zhao, Yuping; Sun, Fan

    2013-01-01

    Two-way relaying in wireless systems has initiated a large research effort during the past few years. Nevertheless, it represents only a specific traffic pattern and it is of interest to investigate other traffic patterns where such a simultaneous processing of information flows can bring...

  8. Expert systems guide biological phosphorus removal

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-10-01

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

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

    Directory of Open Access Journals (Sweden)

    James Michael Whitacre

    2012-05-01

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

  10. Workshop Day on Dynamical Systems in Biology 2008

    OpenAIRE

    2009-01-01

    Workshop on mathematical modelling of biological systems, held in conjunction with the Board meeting of the European Society on Mathematical and Theoretical Biology (held in Évora, Portugal, March 2008)

  11. In Vitro Testing of Biomaterials for Neural Repair: Focus on Cellular Systems and High-Content Analysis.

    Science.gov (United States)

    Baldassarro, Vito Antonio; Dolci, Luisa Stella; Mangano, Chiara; Giardino, Luciana; Gualandi, Chiara; Focarete, Maria Letizia; Calzà, Laura

    2016-01-01

    Biomimetic materials are designed to stimulate specific cellular responses at the molecular level. To improve the soundness of in vitro testing of the biological impact of new materials, appropriate cell systems and technologies must be standardized also taking regulatory issues into consideration. In this study, the biological and molecular effects of different scaffolds on three neural systems, that is, the neural cell line SH-SY5Y, primary cortical neurons, and neural stem cells, were compared. The effect of poly(L-lactic acid) scaffolds having different surface geometry (conventional two-dimensional seeding flat surface, random or aligned fibers as semi3D structure) and chemical functionalization (laminin or ECM extract) were studied. The endpoints were defined for efficacy (i.e., neural differentiation and neurite elongation) and for safety (i.e., cell death/survival) using high-content analysis. It is demonstrated that (i) the definition of the biological properties of biomaterials is profoundly influenced by the test system used; (ii) the definition of the in vitro safety profile of biomaterials for neural repair is also influenced by the test system; (iii) cell-based high-content screening may well be successfully used to characterize both the efficacy and safety of novel biomaterials, thus speeding up and improving the soundness of this critical step in material science having medical applications. PMID:27588220

  12. PhosphoPep—a phosphoproteome resource for systems biology research in Drosophila Kc167 cells

    OpenAIRE

    Bodenmiller, Bernd; Malmstrom, Johan; Gerrits, Bertran; Campbell, David; Lam, Henry; Schmidt, Alexander; Rinner, Oliver; Mueller, Lukas N.; Shannon, Paul T.; Pedrioli, Patrick G.; Panse, Christian; Lee, Hoo-Keun; Schlapbach, Ralph; Aebersold, Ruedi

    2007-01-01

    The ability to analyze and understand the mechanisms by which cells process information is a key question of systems biology research. Such mechanisms critically depend on reversible phosphorylation of cellular proteins, a process that is catalyzed by protein kinases and phosphatases. Here, we present PhosphoPep, a database containing more than 10 000 unique high-confidence phosphorylation sites mapping to nearly 3500 gene models and 4600 distinct phosphoproteins of the Drosophila melanogaste...

  13. Iterative Cellular Screening System for Nanoparticle Safety Testing

    OpenAIRE

    Franziska Sambale; Frank Stahl; Ferdinand Rüdinger; Dror Seliktar; Cornelia Kasper; Detlef Bahnemann; Thomas Scheper

    2015-01-01

    Nanoparticles have the potential to exhibit risks to human beings and to the environment; due to the wide applications of nanoproducts, extensive risk management must not be neglected. Therefore, we have constructed a cell-based, iterative screening system to examine a variety of nanoproducts concerning their toxicity during development. The sensitivity and application of various cell-based methods were discussed and proven by applying the screening to two different nanoparticles: zinc oxide ...

  14. Knowledge discovery for stochastic models of biological systems

    OpenAIRE

    Forlin, Michele

    2010-01-01

    Biology is the science of life and living organisms. Empowered by the deployment of several automated experimental frameworks, this discipline has seen a tremendous growth during the last decades. Recently, the focus towards studying biological systems holistically, has lead to biology converging with other disciplines. In particular, computer science is playing an increasingly important role in biology, because of its ability to disentangle complex system level issues. This increasing inter...

  15. The cellular composition of the human immune system is shaped by age and cohabitation.

    Science.gov (United States)

    Carr, Edward J; Dooley, James; Garcia-Perez, Josselyn E; Lagou, Vasiliki; Lee, James C; Wouters, Carine; Meyts, Isabelle; Goris, An; Boeckxstaens, Guy; Linterman, Michelle A; Liston, Adrian

    2016-04-01

    Detailed population-level description of the human immune system has recently become achievable. We used a 'systems-level' approach to establish a resource of cellular immune profiles of 670 healthy individuals. We report a high level of interindividual variation, with low longitudinal variation, at the level of cellular subset composition of the immune system. Despite the profound effects of antigen exposure on individual antigen-specific clones, the cellular subset structure proved highly elastic, with transient vaccination-induced changes followed by a return to the individual's unique baseline. Notably, the largest influence on immunological variation identified was cohabitation, with 50% less immunological variation between individuals who share an environment (as parents) than between people in the wider population. These results identify local environmental conditions as a key factor in shaping the human immune system. PMID:26878114

  16. Analytical Results to Improve the Capacity of A Cellular System In Frequency Selective Rayleigh Fading Channel

    Directory of Open Access Journals (Sweden)

    Pravindra Kumar

    2010-10-01

    Full Text Available One of the biggest draw back of wireless environment is the limited bandwidth. However, the users sharing this limited bandwidth have been increased considerably by using SDMA technique that can enhancethe capacity of communication system. There are some techniques that can increase the capacity of the cellular system, these are- Spreading Technique, Error Control Coding Technique, Multipath Diversity Technique ( i.e. Rake Receiver, Smart Antenna Technique. In this paper we have used all these technique and examined how thecapacity of cellular system vary with varying the different parameters such as- the value of spreading factor, the number of Rake fingers, the number of interfering cells, value of directivity of Adaptive Antenna at base station. In the results we find that the capacity of a cellular system is varying with these parameters.

  17. Design of mobile telemedicine systems using GSM and IS-54 cellular telephone standards.

    Science.gov (United States)

    Istepanian, R H; Woodward, B; Gorilas, E; Balos, P A

    1998-01-01

    This paper presents an overview of the design of mobile telemedical systems using cellular telephone channels. A mobile telemedicine communication system was studied using both the GSM and the IS-54 standards, which are the most widely used commercial cellular telephone systems in Europe and North America, respectively. A simulation using a photoplethesmography signal showed successful transmission of data with bit error rates of less than 10(-7) at the receiver for the IS-54 standard and less than 10(-5) for the GSM standard, depending on the mobile channel conditions used. PMID:9640747

  18. 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 ...

  19. Nervous system disease associated with dominant cellular radiosensitivity

    International Nuclear Information System (INIS)

    Ionizing radiation sensitivity has been demonstrated in the following neurological diseases: sporadic and familial Alzheimer's disease, familial non-specific dementia, amyotrophic lateral sclerosis and Parkinsonism dementia of Guam, Huntington's disease, multiple sclerosis. Family studies in many cases give data consistent with dominant genetics, as does cell fusion analysis in the one disease so studied. In no case was there an absolute association between radiosensitivity and a given neurological disease. It is proposed that the underlying mutations are in genes controlling facets of nervous or immune system differentiation and development. 15 references, 2 tables

  20. Cellular automata

    CERN Document Server

    Codd, E F

    1968-01-01

    Cellular Automata presents the fundamental principles of homogeneous cellular systems. This book discusses the possibility of biochemical computers with self-reproducing capability.Organized into eight chapters, this book begins with an overview of some theorems dealing with conditions under which universal computation and construction can be exhibited in cellular spaces. This text then presents a design for a machine embedded in a cellular space or a machine that can compute all computable functions and construct a replica of itself in any accessible and sufficiently large region of t

  1. Ecological and biological systems under extreme conditions

    International Nuclear Information System (INIS)

    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

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

    OpenAIRE

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

    2012-01-01

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

  3. Multiway modeling and analysis in stem cell systems biology

    OpenAIRE

    Vandenberg Scott L; Bennett Kristin; Aguis Pheadra; Acar Evrim; Yener Bülent; Plopper George E

    2008-01-01

    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 deterministi...

  4. Multicompartmentalized polymeric systems: towards biomimetic cellular structure and function.

    Science.gov (United States)

    Marguet, Maïté; Bonduelle, Colin; Lecommandoux, Sébastien

    2013-01-21

    The cell is certainly one of the most complex and exciting systems in Nature that scientists are still trying to fully understand. Such a challenge pushes material scientists to seek to reproduce its perfection by building biomimetic materials with high-added value and previously unmatched properties. Thanks to their versatility, their robustness and the current state of polymer chemistry science, we believe polymer-based materials to constitute or represent ideal candidates when addressing the challenge of biomimicry, which defines the focus of this review. The first step consists in mimicking the structure of the cell: its inner compartments, the organelles, with a multicompartmentalized structure, and the rest, i.e. the cytoplasm minus the organelles (mainly cytoskeleton/cytosol) with gels or particular solutions (highly concentrated for example) in one compartment, and finally the combination of both. Achieving this first structural step enables us to considerably widen the gap of possibilities in drug delivery systems. Another powerful property of the cell lies in its metabolic function. The second step is therefore to achieve enzymatic reactions in a compartment, as occurs in the organelles, in a highly controlled, selective and efficient manner. We classify the most exciting polymersome nanoreactors reported in our opinion into two different subsections, depending on their very final concept or purpose of design. We also highlight in a thorough table the experimental sections crucial to such work. Finally, after achieving control over these prerequisites, scientists are able to combine them and push the frontiers of biomimicry further: from cell structure mimics towards a controlled biofunctionality. Such a biomimetic approach in material design and the future research it will stimulate, are believed to bring considerable enrichments to the fields of drug delivery, (bio)sensors, (bio)catalysis and (bio)technology. PMID:23073077

  5. Design mobile satellite system architecture as an integral part of the cellular access digital network

    Science.gov (United States)

    Chien, E. S. K.; Marinho, J. A.; Russell, J. E., Sr.

    1988-01-01

    The Cellular Access Digital Network (CADN) is the access vehicle through which cellular technology is brought into the mainstream of the evolving integrated telecommunications network. Beyond the integrated end-to-end digital access and per call network services provisioning of the Integrated Services Digital Network (ISDN), the CADN engenders the added capability of mobility freedom via wireless access. One key element of the CADN network architecture is the standard user to network interface that is independent of RF transmission technology. Since the Mobile Satellite System (MSS) is envisioned to not only complement but also enhance the capabilities of the terrestrial cellular telecommunications network, compatibility and interoperability between terrestrial cellular and mobile satellite systems are vitally important to provide an integrated moving telecommunications network of the future. From a network standpoint, there exist very strong commonalities between the terrestrial cellular system and the mobile satellite system. Therefore, the MSS architecture should be designed as an integral part of the CADN. This paper describes the concept of the CADN, the functional architecture of the MSS, and the user-network interface signaling protocols.

  6. BioModel Engineering: Its role in Systems Biology and Synthetic Biology

    OpenAIRE

    Gilbert, David Roger; Breitling, Rainer; Heiner, Monika

    2009-01-01

    BioModel Engineering takes place at the interface of computing science, mathematics, engineering and biology, and provides a systematic approach for designing, constructing and analyzing computational models of biological systems. Some of its central concepts are inspired by efficient software engineering strategies. BioModel Engineering does not aim at engineering biological systems per se, but rather aims at describing their structure and behavior, in particular at the le...

  7. 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.

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

    Science.gov (United States)

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

    2014-01-01

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

  9. Molecular and cellular designs of insect taste receptor system

    Directory of Open Access Journals (Sweden)

    Kunio Isono

    2010-06-01

    Full Text Available The insect gustatory receptors (GRs are members of a large G-protein coupled receptor family distantly related to the insect olfactory receptors. They are phylogenetically different from taste receptors of most other animals. GRs are often coexpressed with other GRs in single receptor neurons. Taste receptors other than GRs are also expressed in some neurons. Recent molecular studies in the fruitfly Drosophila revealed that the insect taste receptor system not only covers a wide ligand spectrum of sugars, bitter substances or salts that are common to mammals but also includes reception of pheromone and somatosensory stimulants. However, the central mechanism to perceive and discriminate taste information is not yet elucidated. Analysis of the primary projection of taste neurons to the brain shows that the projection profiles depend basically on the peripheral locations of the neurons as well as the GRs that they express. These results suggest that both peripheral and central design principles of insect taste perception are different from those of olfactory perception.

  10. 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.

  11. 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. PMID:26734603

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

    CERN Document Server

    Auger, P

    2013-01-01

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

  13. Application of spectral hole burning to the study of in vitro cellular systems

    Energy Technology Data Exchange (ETDEWEB)

    Milanovich, Nebojsa

    1999-11-08

    Chapter 1 of this thesis describes the various stages of tumor development and a multitude of diagnostic techniques used to detect cancer. Chapter 2 gives an overview of the aspects of hole burning spectroscopy important for its application to the study of cellular systems. Chapter 3 gives general descriptions of cellular organelles, structures, and physical properties that can serve as possible markers for the differentiation of normal and cancerous cells. Also described in Chapter 3 are the principles of cryobiology important for low temperature spectroscopy of cells, characterization of MCF-10F (normal) and MCF-7 (cancer) cells lines which will serve as model systems, and cellular characteristics of aluminum phthalocyanine tetrasulfonate (APT), which was used as the test probe. Chapters 4 and 5 are previously published papers by the author pertaining to the results obtained from the application of hole burning to the study of cellular systems. Chapter 4 presents the first results obtained by spectral hole burning of cellular systems and Chapter 5 gives results for the differentiation of MCF-10F and MCF-7 cells stained with APT by an external applied electric (Stark) field. A general conclusion is presented in Chapter 6. Appendices A and B provide additional characterization of the cell/probe model systems. Appendix A describes the uptake and subcellular distribution of APT in MCF-10F and MCF-7 cells and Appendix B compares the hole burning characteristics of APT in cells when the cells are in suspension and when they are examined while adhering to a glass coverslip. Appendix C presents preliminary results for a novel probe molecule, referred to as a molecular thumbtack, designed by the authors for use in future hole burning applications to cellular systems.

  14. Modeling and Simulation Tools: From Systems Biology to Systems Medicine.

    Science.gov (United States)

    Olivier, Brett G; Swat, Maciej J; Moné, Martijn J

    2016-01-01

    Modeling is an integral component of modern biology. In this chapter we look into the role of the model, as it pertains to Systems Medicine, and the software that is required to instantiate and run it. We do this by comparing the development, implementation, and characteristics of tools that have been developed to work with two divergent methodologies: Systems Biology and Pharmacometrics. From the Systems Biology perspective we consider the concept of "Software as a Medical Device" and what this may imply for the migration of research-oriented, simulation software into the domain of human health.In our second perspective, we see how in practice hundreds of computational tools already accompany drug discovery and development at every stage of the process. Standardized exchange formats are required to streamline the model exchange between tools, which would minimize translation errors and reduce the required time. With the emergence, almost 15 years ago, of the SBML standard, a large part of the domain of interest is already covered and models can be shared and passed from software to software without recoding them. Until recently the last stage of the process, the pharmacometric analysis used in clinical studies carried out on subject populations, lacked such an exchange medium. We describe a new emerging exchange format in Pharmacometrics which covers the non-linear mixed effects models, the standard statistical model type used in this area. By interfacing these two formats the entire domain can be covered by complementary standards and subsequently the according tools. PMID:26677194

  15. Soft particle analysis of electrokinetics of biological cells and their model systems

    Energy Technology Data Exchange (ETDEWEB)

    Makino, Kimiko; Ohshima, Hiroyuki, E-mail: makino@rs.noda.tus.ac.jp, E-mail: ohshima@rs.noda.tus.ac.jp [Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510 (Japan)

    2011-03-15

    In this article, we review the applications of a novel theory (Ohshima 2009 Sci. Technol. Adv. Mater. 10 063001) to the analysis of electrokinetic data for various soft particles, that is, particles covered with an ion-permeable surface layer of polyelectrolytes. Soft particles discussed in this review include various biological cells and hydrogel-coated particles as a model of biological cells. Cellular transformations increase the concentration of sialic acid of glycoproteins and are associated with blocked biosynthesis of glycolipids and aberrant expression of the developmentally programmed biosynthetic pathway. The change in shape or biological function of cells may affect their surface properties and can be detected by electrokinetic measurements. The experimental results were analyzed with Ohshima's electrokinetic formula for soft particles and soft surfaces. As a model system, hydrogel surfaces that mimic biological surfaces were also prepared and their surface properties were studied. (topical review)

  16. Teaching Systems Biology: An Active-Learning Approach

    Science.gov (United States)

    Kumar, Anuj

    2005-01-01

    With genomics well established in modern molecular biology, recent studies have sought to further the discipline by integrating complementary methodologies into a holistic depiction of the molecular mechanisms underpinning cell function. This genomic subdiscipline, loosely termed "systems biology," presents the biology educator with both…

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

    OpenAIRE

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

    2009-01-01

    The use of computational modeling and simulation has increased in many biological fields, but despite their potential these techniques are only marginally applied in nutritional sciences. Nevertheless, recent applications of modeling have been instrumental in answering important nutritional questions from the cellular up to the physiological levels. Capturing the complexity of today's important nutritional research questions poses a challenge for modeling to become truly integrative in the co...

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

    OpenAIRE

    de Graaf, A A; Freidig, A.P.; Roos, B.; Jamshidi, N.; M. Heinemann; Rullmann, J.A.C.; Hall, K. D.; Adiels, M.; Ommen, B. van

    2009-01-01

    The use of computational modeling and simulation has increased in many biological fields, but despite their potential these techniques are only marginally applied in nutritional sciences. Nevertheless, recent applications of modeling have been instrumental in answering important nutritional questions from the cellular up to the physiological levels. Capturing the complexity of today's important nutritional research questions poses a challenge for modeling to become truly integrative in the co...

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

    OpenAIRE

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

    2009-01-01

    The use of computational modeling and simulation has increased in many biological fields, but despite their potential these techniques are only marginally applied in nutritional sciences. Nevertheless, recent applications of modeling have been instrumental in answering important nutritional questions from the cellular up to the physiological levels. Capturing the complexity of today’s important nutritional research questions poses a challenge for modeling to become truly integrative in the co...

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

    OpenAIRE

    Guo, Q. Max; Zakhari, Sam

    2008-01-01

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

  1. 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...... 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...

  2. Interactive analysis of systems biology molecular expression data

    OpenAIRE

    Prabhakar Sunil; Salt David E; Kane Michael D; Stephenson Alan; Ouyang Qi; Zhang Mingwu; Burgner John; Buck Charles; Zhang Xiang

    2008-01-01

    Abstract Background Systems biology aims to understand biological systems on a comprehensive scale, such that the components that make up the whole are connected to one another and work through dependent interactions. Molecular correlations and comparative studies of molecular expression are crucial to establishing interdependent connections in systems biology. The existing software packages provide limited data mining capability. The user must first generate visualization data with a preferr...

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

    OpenAIRE

    Tsivunchyk, Olga S.

    2004-01-01

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

  4. Multiscale Spatial Computational Systems Biology (Dagstuhl Seminar 14481)

    OpenAIRE

    Gilbert, David; Heiner, Monika; TAKAHASHI, Koichi; Uhrmacher, Adelinde M.

    2015-01-01

    This report documents the program and the outcomes of Dagstuhl Seminar 14481 "Multiscale Spatial Computational Systems Biology". This seminar explored challenges arising from the need to model and analyse complex biological systems at multiple scales (spatial and temporal), which falls within the general remit of Computational Systems Biology. A distinguishing factor of the seminar was the modelling exercise -- where teams explored different modelling paradigms, in order to better understand...

  5. An online model composition tool for system biology models

    OpenAIRE

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

    2013-01-01

    Background There are multiple representation formats for Systems Biology computational models, and the Systems Biology Markup Language (SBML) is one of the most widely used. SBML is used to capture, store, and distribute computational models by Systems Biology data sources (e.g., the BioModels Database) and researchers. Therefore, there is a need for all-in-one web-based solutions that support advance SBML functionalities such as uploading, editing, composing, visualizing, simulating, queryin...

  6. MMBSM: A Meta Model for Biological System Modeling

    OpenAIRE

    Touraj Banirostam; Mehdi N. Fesharaki

    2012-01-01

    Increasing the complexity and interactions, network centric organizations would become less effective and it seems that getting pattern of biological system might represent an appropriate approach to this problem. Based on Capra Cognitive Framework, basic parameters in a biological system and the whole role of these parameters will be evaluated and then again according to the mentioned framework, a model of biological- social systems and their effective elements will get analyzed in this pape...

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

    OpenAIRE

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

    2013-01-01

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

  8. RDFScape: Semantic Web meets Systems Biology

    Science.gov (United States)

    Splendiani, Andrea

    2008-01-01

    Background The recent availability of high-throughput data in molecular biology has increased the need for a formal representation of this knowledge domain. New ontologies are being developed to formalize knowledge, e.g. about the functions of proteins. As the Semantic Web is being introduced into the Life Sciences, the basis for a distributed knowledge-base that can foster biological data analysis is laid. However, there still is a dichotomy, in tools and methodologies, between the use of ontologies in biological investigation, that is, in relation to experimental observations, and their use as a knowledge-base. Results RDFScape is a plugin that has been developed to extend a software oriented to biological analysis with support for reasoning on ontologies in the semantic web framework. We show with this plugin how the use of ontological knowledge in biological analysis can be extended through the use of inference. In particular, we present two examples relative to ontologies representing biological pathways: we demonstrate how these can be abstracted and visualized as interaction networks, and how reasoning on causal dependencies within elements of pathways can be implemented. Conclusions The use of ontologies for the interpretation of high-throughput biological data can be improved through the use of inference. This allows the use of ontologies not only as annotations, but as a knowledge-base from which new information relevant for specific analysis can be derived. PMID:18460179

  9. Cellular Automata based Encrypted ECG-hash Code Generation: An Application in Inter-human Biometric Authentication System

    Directory of Open Access Journals (Sweden)

    Subrata Nandi

    2014-10-01

    Full Text Available In this modern era, biometrics incorporate various mechanisms to recognize inimitable features of human beings by utilizing their biological and evident features. This paper proposes a novel technique for constructing a resilient and secure biometric recognition system. In this paper, an ECG-hash code of two distinct individuals has been formed by taking dot product of electrocardiogram (ECG feature matrices of two persons located at two different sites at respective databases. The validity of the system increases as samples from both persons, between whom the transmission takes place, are essential. Besides, electrocardiogram is such a unique feature of an individual that could not be compromised at any circumstance as contradictory to other features like fingerprints, face recognition etc. Moreover, the ECG-hash code is encrypted using rule vector of cellular automata that gives better security in terms of randomness of generated cipher text.

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

    OpenAIRE

    Nicola Bernabò; Barbara Barboni; Mauro Maccarrone

    2014-01-01

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

  11. A guide to numerical modelling in systems biology

    CERN Document Server

    Deuflhard, Peter

    2015-01-01

    This book is intended for students of computational systems biology with only a limited background in mathematics. Typical books on systems biology merely mention algorithmic approaches, but without offering a deeper understanding. On the other hand, mathematical books are typically unreadable for computational biologists. The authors of the present book have worked hard to fill this gap. The result is not a book on systems biology, but on computational methods in systems biology. This book originated from courses taught by the authors at Freie Universität Berlin. The guiding idea of the courses was to convey those mathematical insights that are indispensable for systems biology, teaching the necessary mathematical prerequisites by means of many illustrative examples and without any theorems. The three chapters cover the mathematical modelling of biochemical and physiological processes, numerical simulation of the dynamics of biological networks, and identification of model parameters by means of comparisons...

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

    Science.gov (United States)

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

    2013-12-01

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

  13. Radiation, nitric oxide and cellular death

    International Nuclear Information System (INIS)

    The mechanisms of radiation induced cellular death constitute an objective of research ever since the first biological effects of radiation were first observed. The explosion of information produced in the last 20 years calls for a careful analysis due to the apparent contradictory data related to the cellular system studied and the range of doses used. This review focuses on the role of the active oxygen species, in particular the nitric oxides, in its relevance as potential mediator of radiation induced cellular death

  14. Quantifying electron transfer reactions in biological systems: what interactions play the major role?

    Science.gov (United States)

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

    2015-12-01

    Various biological processes involve the conversion of energy into forms that are usable for chemical transformations and are quantum mechanical in nature. Such processes involve light absorption, excited electronic states formation, excitation energy transfer, electrons and protons tunnelling which for example occur in photosynthesis, cellular respiration, DNA repair, and possibly magnetic field sensing. Quantum biology uses computation to model biological interactions in light of quantum mechanical effects and has primarily developed over the past decade as a result of convergence between quantum physics and biology. In this paper we consider electron transfer in biological processes, from a theoretical view-point; namely in terms of quantum mechanical and semi-classical models. We systematically characterize the interactions between the moving electron and its biological environment to deduce the driving force for the electron transfer reaction and to establish those interactions that play the major role in propelling the electron. The suggested approach is seen as a general recipe to treat electron transfer events in biological systems computationally, and we utilize it to describe specifically the electron transfer reactions in Arabidopsis thaliana cryptochrome-a signaling photoreceptor protein that became attractive recently due to its possible function as a biological magnetoreceptor.

  15. RDFScape: Semantic Web meets Systems Biology

    OpenAIRE

    Splendiani Andrea

    2008-01-01

    Abstract Background The recent availability of high-throughput data in molecular biology has increased the need for a formal representation of this knowledge domain. New ontologies are being developed to formalize knowledge, e.g. about the functions of proteins. As the Semantic Web is being introduced into the Life Sciences, the basis for a distributed knowledge-base that can foster biological data analysis is laid. However, there still is a dichotomy, in tools and methodologies, between the ...

  16. Mimo radar waveform design for spectrum sharing with cellular systems a Matlab based approach

    CERN Document Server

    Khawar, Awais; Clancy, T Charles

    2016-01-01

    This book discusses spectrum sharing between cellular systems and radars. The book addresses a novel way to design radar waveforms that can enable spectrum sharing between radars and communication systems, without causing interference to communication systems, and at the same time achieving radar objectives of target detection, estimation, and tracking. The book includes a MATLAB-based approach, which provides reader with a way to learn, experiment, compare, and build on top of existing algorithms.

  17. The use of global transcriptional analysis to reveal the biological and cellular events involved in distinct development phases of Trichophyton rubrum conidial germination

    Directory of Open Access Journals (Sweden)

    Ding Guohui

    2007-04-01

    Full Text Available Abstract Background Conidia are considered to be the primary cause of infections by Trichophyton rubrum. Results We have developed a cDNA microarray containing 10250 ESTs to monitor the transcriptional strategy of conidial germination. A total of 1561 genes that had their expression levels specially altered in the process were obtained and hierarchically clustered with respect to their expression profiles. By functional analysis, we provided a global view of an important biological system related to conidial germination, including characterization of the pattern of gene expression at sequential developmental phases, and changes of gene expression profiles corresponding to morphological transitions. We matched the EST sequences to GO terms in the Saccharomyces Genome Database (SGD. A number of homologues of Saccharomyces cerevisiae genes related to signalling pathways and some important cellular processes were found to be involved in T. rubrum germination. These genes and signalling pathways may play roles in distinct steps, such as activating conidial germination, maintenance of isotropic growth, establishment of cell polarity and morphological transitions. Conclusion Our results may provide insights into molecular mechanisms of conidial germination at the cell level, and may enhance our understanding of regulation of gene expression related to the morphological construction of T. rubrum.

  18. Specificity of pH sensitive Tc(V)-DMS for acidophilic osteoclastic bone cells: biological and cellular studies

    International Nuclear Information System (INIS)

    Bone scintigraphy is a sensitive imaging method for detecting skeletal metastases but the low specificity has decreased its oncological use. Bone scintigraphy has relied on Tc-bisphosphonate (Tc-BP) agents with affinity for the mineral phase. However, bio-functional Tc(V)-DMS agent, sensitive to acid pH of tumoral tissue has shown osteotrophic properties, in adult bone pathologies. Objectives: Basis for understanding the osteotropic character of the pH sensitive Tc(V)-DMS in bone metastasis. Methods: Studies on differential Tc(V)-DMS and Tc-BP accumulation response were carried out by acidophilic osteoclast (OC) and basophilic osteoblast (OB) cells subjected to variable pH incubation media (HEPES, 370C) and by bone tissue of Ehrlich Ascites Tumor (EAT) bearing mice, exposed to systemic NH4Cl or glucose mediated acidification (GmAc). Agents injected into tail vein and bone radioactivity analyzed. Bone metabolism markers measured in blood and urine (pH, Pi, Ca , Alp, Dpd). Acid-base regulation effect at cellular level, analyzed by using bafilomycin, amiloride, DIDS and acetazolamide inhibitors. Results: Lack of any OB response to acidification or alkalinization detected with either Tc(V)-DMS or Tc-BP agent. However, OC cells were highly sensitivity to acidification only in the presence of Tc(V)-DMS showing great radioactivity increase as the pH was lowered. This specificity also detected, in EAT bearing mice; increased bone tissue accumulation in response to systemic acidification was clearly detected upon administration of Tc(V)-DMS only under GmAc, an experimental model showing high urine excretion of deoxypyridinoline, a bone resorption marker. Conclusion: Peculiarity of multi nucleated OC cells sensitive to the environment pH and their activation in acid pH has been well known. Tc-BP agent showed lack of affinity for OC or OB cells. Specific affinity of OC cells for Tc(V)-DMS and its increased bone accumulation with the systemic pH lowering reflect the p

  19. Animal models of human disease. Pathology and molecular biology of spontaneous neoplasms occurring in transgenic mice carrying and expressing activated cellular oncogenes.

    OpenAIRE

    Pattengale, P K; Stewart, T A; Leder, A; Sinn, E; Muller, W.; Tepler, I; Schmidt, E.; Leder, P

    1989-01-01

    This present review focuses on spontaneous neoplasms occurring in transgenic mice carrying and expressing activated cellular oncogenes. The historical development of transgenic mice as in vivo disease models is briefly traced, followed by a brief description of the actual technology in such systems. Additional emphasis is placed on the concept of targeting activated cellular oncogenes to specific tissues in transgenic mice. Cumulative experience with activated (Vmyc, ras, and neu (erb-B2] onc...

  20. An integrated approach for the cell formation and layout design in cellular manufacturing systems

    NARCIS (Netherlands)

    Javadi, Babak; Jolai, Fariborz; Slomp, Jannes; Rabbani, Masoud; Tavakkoli-Moghaddam, Reza

    2013-01-01

    In this paper, a comprehensive model is presented for cell formation and layout design in cellular manufacturing systems (CMS). The proposed model incorporates an extensive coverage of important operational features and especially layout design aspects to determine optimal cell configuration and Int

  1. 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.

  2. A Magnetic Sensor System for Biological Detection

    KAUST Repository

    Li, Fuquan

    2015-05-01

    Magnetic biosensors detect biological targets through sensing the stray field of magnetic beads which label the targets. Commonly, magnetic biosensors employ the “sandwich” method to immobilize biological targets, i.e., the targets are sandwiched between a bio-functionalized sensor surface and bio-functionalized magnetic beads. This method has been used very successfully in different application, but its execution requires a rather elaborate procedure including several washing and incubation steps. This dissertation investigates a new magnetic biosensor concept, which enables a simple and effective detection of biological targets. The biosensor takes advantage of the size difference between bare magnetic beads and compounds of magnetic beads and biological targets. First, the detection of super-paramagnetic beads via magnetic tunnel junction (MTJ) sensors is implemented. Frequency modulation is used to enhance the signal-to-noise ratio, enabling the detection of a single magnetic bead. Second, the concept of the magnetic biosensor is investigated theoretically. The biosensor consists of an MTJ sensor, which detects the stray field of magnetic beads inside of a trap on top of the MTJ. A microwire between the trap and the MTJ is used to attract magnetic beads to the trapping well by applying a current to it. The MTJ sensor’s output depends on the number of beads inside the trap. If biological targets are in the sample solution, the beads will form bead compounds consisting of beads linked to the biological targets. Since bead compounds are larger than bare beads, the number of beads inside the trapping well will depend on the presence of biological targets. Hence, the output of the MTJ sensor will depend on the biological targets. The dependences of sensor signals on the sizes of the MTJ sensor, magnetic beads and biological targets are studied to find the optimum constellations for the detection of specific biological targets. The optimization is demonstrated

  3. A preliminary study on estimating extra-cellular nitrate reductase activities in estuarine systems

    OpenAIRE

    Pant H. K.

    2009-01-01

    Enzymes catalyzing ammonium (NH4+)/nitrate (NO3–) into nitrous oxide (N2O)/molecular nitrogen (N2), play critical roles in water quality management. The objective of this paper was to investigate the role of extra-cellular enzymes in cycling of nitrogen (N) in aquatic systems. It appears that N in estuaries, salt marshes, etc., does not stay long enough to be available for uptake, thus, creating N limited conditions. This study showed that indigenous extra-cellular nitrate reductase along wit...

  4. Impact of Underlaid Multi-antenna D2D on Cellular Downlink in Massive MIMO Systems

    OpenAIRE

    Agarwal, Amit; Mukherjee, Sudarshan; Mohammed, Saif Khan

    2015-01-01

    In this paper, we consider a massive multiple-input multiple-output (MIMO) downlink system underlaid with a network of multi-antenna D2D user equipments (UEs). Each D2D transmitter (Tx) uses all its antennas to beamform information towards its desired D2D receiver, which uses only a single antenna for reception. While beamforming at the D2D Tx reduces D2D interference to the neighbouring cellular UEs (CUEs), the cellular-to-D2D interference is also negligible due to highly directional beamfor...

  5. 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.

  6. Dynamics and kinetics of model biological systems

    Science.gov (United States)

    Mirigian, Stephen

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

  7. Biologic

    CERN Document Server

    Kauffman, L H

    2002-01-01

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

  8. Building momentum for systems and synthetic biology in India

    OpenAIRE

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

    2010-01-01

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

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

    OpenAIRE

    Bartocci, Ezio; Lió, Pietro

    2016-01-01

    As the amount of biological data in the public domain grows, so does the range of modeling and analysis techniques employed in systems biology. In recent years, a number of theoretical computer science developments have enabled modeling methodology to keep pace. The growing interest in systems biology in executable models and their analysis has necessitated the borrowing of terms and methods from computer science, such as formal analysis, model checking, static analysis, and runtime verificat...

  10. Moving Towards Interpretable Mechanisms in Human Systems Biology

    OpenAIRE

    Thomas, Alex

    2015-01-01

    A detailed understanding of biomolecular mechanisms enables predictive modeling in biological systems. In the late 1990's, whole-genome sequencing and the development of various high-throughput technologies led to the emergence of systems biology, primarily in simple model organisms such as bacteria and yeast. Mechanisms between biological components and processes were cataloged and placed in mathematical frameworks to explain the role of genotype and environmental factors on phenotypes. Some...

  11. Systems biology approaches to dissect mammalian innate immunity

    OpenAIRE

    Shapira, Sagi D.; Hacohen, Nir

    2010-01-01

    Advances in experimental tools have allowed for the systematic identification of components and biological processes as well quantification of their activities over time. Together with computational analysis, these measurement and perturbation technologies have given rise to the field of systems biology, which seeks to discover, analyze and model the interactions of physical components in a biological system. Although in its infancy, recent application of this approach has resulted in novel i...

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

    OpenAIRE

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

    2012-01-01

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

  13. RNase-L Control of Cellular mRNAs: Roles in Biologic Functions and Mechanisms of Substrate Targeting

    OpenAIRE

    Brennan-Laun, Sarah E.; Ezelle, Heather J.; Li, Xiao-Ling; Hassel, Bret A.

    2014-01-01

    RNase-L is a mediator of type 1 interferon-induced antiviral activity that has diverse and critical cellular roles, including the regulation of cell proliferation, differentiation, senescence and apoptosis, tumorigenesis, and the control of the innate immune response. Although RNase-L was originally shown to mediate the endonucleolytic cleavage of both viral and ribosomal RNAs in response to infection, more recent evidence indicates that RNase-L also functions in the regulation of cellular mR...

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

    Science.gov (United States)

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

    2012-11-01

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

  15. Approximate bayesian parameter inference for dynamical systems in systems biology

    International Nuclear Information System (INIS)

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

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

    DEFF Research Database (Denmark)

    Green, Sara; Wolkenhauer, Olaf

    2014-01-01

    With the emergence of systems biology, the identification of organizing principles is being highlighted as a key research aim. Researchers attempt to “reverse engineer” the functional organization of biological systems using methodologies from mathematics, engineering and computer science while...

  17. 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...

  18. REVIEWS OF TOPICAL PROBLEMS: Study of spatially extended dynamical systems using probabilistic cellular automata

    Science.gov (United States)

    Vanag, Vladimir K.

    1999-05-01

    Spatially extended dynamical systems are ubiquitous and include such things as insect and animal populations; complex chemical, technological, and geochemical processes; humanity itself, and much more. It is clearly desirable to have a certain universal tool with which the highly complex behaviour of nonlinear dynamical systems can be analyzed and modelled. For this purpose, cellular automata seem to be good candidates. In the present review, emphasis is placed on the possibilities that various types of probabilistic cellular automata (PCA), such as DSMC (direct simulation Monte Carlo) and LGCA (lattice-gas cellular automata), offer. The methods are primarily designed for modelling spatially extended dynamical systems with inner fluctuations accounted for. For the Willamowskii-Roessler and Oregonator models, PCA applications to the following problems are illustrated: the effect of fluctuations on the dynamics of nonlinear systems; Turing structure formation; the effect of hydrodynamic modes on the behaviour of nonlinear chemical systems (stirring effects); bifurcation changes in the dynamical regimes of complex systems with restricted geometry or low spatial dimension; and the description of chemical systems in microemulsions.

  19. The Current State and Perspectives of Systems Biology

    Institute of Scientific and Technical Information of China (English)

    Tielui Shi; Yixue Li

    2006-01-01

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

  20. Cooperative joint precoding in a downlink cellular system with shared relay: Design and performance evaluation

    KAUST Repository

    Kwon, JaeWoo

    2012-10-01

    In this paper, we investigate a relay enhanced cellular system, where a relay station is located in the overlap area served by two base stations. We propose cooperative joint precoding schemes for the downlink transmission of such relay enhanced cellular system to maximize the system capacity while minimizing the interference at both the relay station and the mobile stations. We formulate the optimization problems to maximize the system capacity and design the multiuser precoding vectors at each base station and the relay station. We quantify the ergodic rate performance of the proposed multiuser precoding schemes through statistical analysis. The extensively derived ergodic expressions will facilitate the accurate performance evaluation of the proposed transmission schemes. Numerical results show that the proposed schemes can effectively cancel the interference and improve the sum rate and the outage performance for cell edge users. © 2002-2012 IEEE.

  1. Role of Multi Agent System for Qos Guarantee in Cellular Networks

    OpenAIRE

    Nupur Giri; Shrikant Bodhe

    2012-01-01

    The paper highlights the benefits of Multi Agent System for maintaining QoS in cellular network by evaluating various multi agent based call admission control strategies for different traffic conditions. It establishes the effect of degree of distribution of agents on system performance by comparing the two service architectures, namely centralized and distributed, for reactivity, responsiveness, utilization of resources, communication overhead, sustainability, scalability, robustness and mo...

  2. Cellular and subcellular localization of protein I in the peripheral nervous system.

    OpenAIRE

    Fried, G.; Nestler, E J; De Camilli, P; Stjärne, L; Olson, L; Lundberg, J M; Hökfelt, T; Ouimet, C C; Greengard, P

    1982-01-01

    The cellular and subcellular distribution of protein I, a major brain phosphoprotein, has been studied in the peripheral nervous system. The levels of protein I in various peripheral nerves and innervated peripheral tissues were determined by radioimmunoassay and radioimmunolabeling of polyacrylamide gels. The results indicated tha protein I is present throughout the peripheral nervous system. Denervation studies of adrenal medulla and iris suggested that the protein I contained in peripheral...

  3. Phase transition in the economically modeled growth of a cellular nervous system

    OpenAIRE

    Nicosia V.; Vertes P.E.; Schafer W.R.; Latora V.; Bullmore E.T.

    2013-01-01

    Spatially embedded complex networks, such as nervous systems, the Internet, and transportation networks, generally have nontrivial topological patterns of connections combined with nearly minimal wiring costs. However, the growth rules shaping these economical tradeoffs between cost and topology are not well understood. Here, we study the cellular nervous system of the nematode worm Caenorhabditis elegans, together with information on the birth times of neurons and on their spatial locations....

  4. Development Of An Agent Based Simulation For The Cellular Transport System And Scenario Based Performance Analysis

    Directory of Open Access Journals (Sweden)

    Elif Karakaya

    2016-01-01

    Full Text Available Intralogistics Systems, in the rapidly increasing global business environment, are becoming more complex to analyze and more challenging to manage. In order to achieve the highest possible performance of warehouse operations, demanded by today’s modern businesses, intralogistics systems should be agile and flexible. With this objective in mind, the Cellular Transport System (CTS was developed as an alternative intralogistics system by Fraunhofer Institute for Material Flow and Logistics. This study investigates novel intralogistics system, the CTS, and proposes an integrated simulation tool in order to systematically anticipate change drivers and take optimum measures for the CTS.

  5. A Systems Biology Approach in Therapeutic Response Study for Different Dosing Regimens—a Modeling Study of Drug Effects on Tumor Growth using Hybrid Systems

    OpenAIRE

    Xiangfang Li; Lijun Qian; Bittner, Michale L.; Dougherty, Edward R.

    2012-01-01

    Motivated by the frustration of translation of research advances in the molecular and cellular biology of cancer into treatment, this study calls for cross-disciplinary efforts and proposes a methodology of incorporating drug pharmacology information into drug therapeutic response modeling using a computational systems biology approach. The objectives are two fold. The first one is to involve effective mathematical modeling in the drug development stage to incorporate preclinical and clinical...

  6. Biological Therapy-Induced Systemic Vasculitis.

    Science.gov (United States)

    Gutiérrez-González, Luis Arturo

    2016-07-01

    The use of biologics has been associated with the paradoxical development of biologics-induced autoimmune diseases. The purpose of this review was to describe the key immunopathogenic mechanisms involved in the development of these conditions, and to discuss the clinical and laboratory characteristics usually described in the medical literature, reviewing case reports as well as records on national biologic therapies (BIOGEAS, RABBIT, BSRBR-RA, BIOBADAVEN). More than 200 cases have so far been reported, all of them diagnosed on the basis of the histopathology or meeting the ACR/Chapel Hill criteria. Over 75 % of the cases were females with a mean age of 48 ± 5 years. More than 50 % had rheumatoid arthritis. Most of the biologics-associated vasculitis developed in 90 ± 31 days. Complete resolution in almost 75 % of the cases was observed upon treatment discontinuation; however, steroid therapy was indicated for all patients and one death was recorded. The use of cyclophosphamide, rituximab or plasma exchange was reserved for the most severe cases. PMID:27165496

  7. Physics and Size in Biological Systems.

    Science.gov (United States)

    Barnes, George

    1989-01-01

    Described is the subject of biological scaling for physics teachers including examples and in-depth reading. Topics are elements of scaling, terminal velocities, Lilliputian and Brobdingnagian, brain evolution, dolphin echolocation, surface tension, gravity change, food and oxygen, and seeing. Ten references on physics and size, and ten questions…

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-08-15

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

  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. Machine learning in systems biology at different scales : from molecular biology to ecology

    OpenAIRE

    Aderhold, Andrej

    2015-01-01

    Machine learning has been a source for continuous methodological advances in the field of computational learning from data. Systems biology has profited in various ways from machine learning techniques but in particular from network inference, i.e. the learning of interactions given observed quantities of the involved components or data that stem from interventional experiments. Originally this domain of system biology was confined to the inference of gene regulation networks but ...

  11. Cellular and molecular mechanisms of sexual differentiation in the mammalian nervous system.

    Science.gov (United States)

    Forger, Nancy G; Strahan, J Alex; Castillo-Ruiz, Alexandra

    2016-01-01

    Neuroscientists are likely to discover new sex differences in the coming years, spurred by the National Institutes of Health initiative to include both sexes in preclinical studies. This review summarizes the current state of knowledge of the cellular and molecular mechanisms underlying sex differences in the mammalian nervous system, based primarily on work in rodents. Cellular mechanisms examined include neurogenesis, migration, the differentiation of neurochemical and morphological cell phenotype, and cell death. At the molecular level we discuss evolving roles for epigenetics, sex chromosome complement, the immune system, and newly identified cell signaling pathways. We review recent findings on the role of the environment, as well as genome-wide studies with some surprising results, causing us to re-think often-used models of sexual differentiation. We end by pointing to future directions, including an increased awareness of the important contributions of tissues outside of the nervous system to sexual differentiation of the brain. PMID:26790970

  12. A preliminary study on estimating extra-cellular nitrate reductase activities in estuarine systems

    Directory of Open Access Journals (Sweden)

    Pant H. K.

    2009-07-01

    Full Text Available Enzymes catalyzing ammonium (NH4+/nitrate (NO3– into nitrous oxide (N2O/molecular nitrogen (N2, play critical roles in water quality management. The objective of this paper was to investigate the role of extra-cellular enzymes in cycling of nitrogen (N in aquatic systems. It appears that N in estuaries, salt marshes, etc., does not stay long enough to be available for uptake, thus, creating N limited conditions. This study showed that indigenous extra-cellular nitrate reductase along with others involved in N transformations in the waters/sediments of estuarine systems can cause complete removal of NH4+ and NO3– from the waters and available NH4+ and NO3– from the sediments. These results indicate that due to high extra-cellular nitrate reductase and other enzymes associated with N transformations in sediments/waters, substantial amounts of NH4+ and NO3– can be quickly lost from the systems as N2O and/or nitric oxide (NO, in turn, creating N limited conditions in estuarine systems. Such high activities of indigenous nitrate reductase and others are useful in removing readily bioavailable N from the systems, thereby avoidance of eutrophic conditions. However, they might contribute in increasing the N2O, a potent greenhouse gas with global warming potential (GWP of 296, in the atmosphere.

  13. 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.

  14. Molecular recognition in chemical and biological systems.

    Science.gov (United States)

    Persch, Elke; Dumele, Oliver; Diederich, François

    2015-03-01

    Structure-based ligand design in medicinal chemistry and crop protection relies on the identification and quantification of weak noncovalent interactions and understanding the role of water. Small-molecule and protein structural database searches are important tools to retrieve existing knowledge. Thermodynamic profiling, combined with X-ray structural and computational studies, is the key to elucidate the energetics of the replacement of water by ligands. Biological receptor sites vary greatly in shape, conformational dynamics, and polarity, and require different ligand-design strategies, as shown for various case studies. Interactions between dipoles have become a central theme of molecular recognition. Orthogonal interactions, halogen bonding, and amide⋅⋅⋅π stacking provide new tools for innovative lead optimization. The combination of synthetic models and biological complexation studies is required to gather reliable information on weak noncovalent interactions and the role of water. PMID:25630692

  15. Universally Sloppy Parameter Sensitivities in Systems Biology

    OpenAIRE

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

    2007-01-01

    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...

  16. Measuring cell identity in noisy biological systems

    OpenAIRE

    Birnbaum, Kenneth D; Kussell, Edo

    2011-01-01

    Global gene expression measurements are increasingly obtained as a function of cell type, spatial position within a tissue and other biologically meaningful coordinates. Such data should enable quantitative analysis of the cell-type specificity of gene expression, but such analyses can often be confounded by the presence of noise. We introduce a specificity measure Spec that quantifies the information in a gene's complete expression profile regarding any given cell type, and an uncertainty me...

  17. A Stream Control Transmission Protocol Based OAM System of 3G Cellular Network

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    OAM (Operations, Administration and Maintenance) system is a very important component of 3G cellular network. In order to acquire overall management, fast response and steady operation, an SCTP (Stream Control Transmission Protocol) based OAM, i. e. , SOAM system was proposed. SOAM implements new characters of SCTP such as multi-stream, enforced SACK and heartbeat mechanism on its transport layer. These characters help SOAM decrease the message transmission delay and accelerate the link failure detection. Besides, a new component named SOAM agent was introduced to improve the operation efficiency of SOAM. The experimental results prove the proposed SOAM system achieves better performance on signaling transmission compared with conventional TCP based OAM system.

  18. Systems for Detection and Identification of Biological Aerosols (Review Paper)

    OpenAIRE

    Eva Švabenska

    2012-01-01

    Easy and inexpensive manufacturing of biological weapons, their complicated detection, expensive protection, difficult treating of affected individuals, selective impact only for people, animals or plants, are all factors making an effective defense against biological warfare agents very difficult. The aim of this study is an introduction to the systems for the detection and identification of biological aerosols containing dangerous bioagents. The basic techniques used for detection and ident...

  19. "Sickle Cell Anemia: Tracking down a Mutation": An Interactive Learning Laboratory That Communicates Basic Principles of Genetics and Cellular Biology

    Science.gov (United States)

    Jarrett, Kevin; Williams, Mary; Horn, Spencer; Radford, David; Wyss, J. Michael

    2016-01-01

    "Sickle cell anemia: tracking down a mutation" is a full-day, inquiry-based, biology experience for high school students enrolled in genetics or advanced biology courses. In the experience, students use restriction endonuclease digestion, cellulose acetate gel electrophoresis, and microscopy to discover which of three putative patients…

  20. Systems biology of cisplatin resistance: past, present and future.

    Science.gov (United States)

    Galluzzi, L; Vitale, I; Michels, J; Brenner, C; Szabadkai, G; Harel-Bellan, A; Castedo, M; Kroemer, G

    2014-01-01

    The platinum derivative cis-diamminedichloroplatinum(II), best known as cisplatin, is currently employed for the clinical management of patients affected by testicular, ovarian, head and neck, colorectal, bladder and lung cancers. For a long time, the antineoplastic effects of cisplatin have been fully ascribed to its ability to generate unrepairable DNA lesions, hence inducing either a permanent proliferative arrest known as cellular senescence or the mitochondrial pathway of apoptosis. Accumulating evidence now suggests that the cytostatic and cytotoxic activity of cisplatin involves both a nuclear and a cytoplasmic component. Despite the unresolved issues regarding its mechanism of action, the administration of cisplatin is generally associated with high rates of clinical responses. However, in the vast majority of cases, malignant cells exposed to cisplatin activate a multipronged adaptive response that renders them less susceptible to the antiproliferative and cytotoxic effects of the drug, and eventually resume proliferation. Thus, a large fraction of cisplatin-treated patients is destined to experience therapeutic failure and tumor recurrence. Throughout the last four decades great efforts have been devoted to the characterization of the molecular mechanisms whereby neoplastic cells progressively lose their sensitivity to cisplatin. The advent of high-content and high-throughput screening technologies has accelerated the discovery of cell-intrinsic and cell-extrinsic pathways that may be targeted to prevent or reverse cisplatin resistance in cancer patients. Still, the multifactorial and redundant nature of this phenomenon poses a significant barrier against the identification of effective chemosensitization strategies. Here, we discuss recent systems biology studies aimed at deconvoluting the complex circuitries that underpin cisplatin resistance, and how their findings might drive the development of rational approaches to tackle this clinically relevant

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

    OpenAIRE

    Pablo Szekely; Hila Sheftel; Avi Mayo; Uri Alon

    2013-01-01

    Biological regulatory systems face a fundamental tradeoff: they must be effective but at the same time also economical. For example, regulatory systems that are designed to repair damage must be effective in reducing damage, but economical in not making too many repair proteins because making excessive proteins carries a fitness cost to the cell, called protein burden. In order to see how biological systems compromise between the two tasks of effectiveness and economy, we applied an approach ...

  2. Systems approaches to biology and disease enable translational systems medicine.

    Science.gov (United States)

    Hood, Leroy; Tian, Qiang

    2012-08-01

    The development and application of systems strategies to biology and disease are transforming medical research and clinical practice in an unprecedented rate. In the foreseeable future, clinicians, medical researchers, and ultimately the consumers and patients will be increasingly equipped with a deluge of personal health information, e.g., whole genome sequences, molecular profiling of diseased tissues, and periodic multi-analyte blood testing of biomarker panels for disease and wellness. The convergence of these practices will enable accurate prediction of disease susceptibility and early diagnosis for actionable preventive schema and personalized treatment regimes tailored to each individual. It will also entail proactive participation from all major stakeholders in the health care system. We are at the dawn of predictive, preventive, personalized, and participatory (P4) medicine, the fully implementation of which requires marrying basic and clinical researches through advanced systems thinking and the employment of high-throughput technologies in genomics, proteomics, nanofluidics, single-cell analysis, and computation strategies in a highly-orchestrated discipline we termed translational systems medicine. PMID:23084773

  3. 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.

  4. Suitability of the cellular viability technique as a control tool of the chlorine dosage on the activated sludge of a biological process affected by bulking

    International Nuclear Information System (INIS)

    This work demonstrates the suitability of the cellular viability technique as a control tool of the chlorine dosage on the activated sludge of a biological process affected by the overabundance of the filamentous bacteria (Thiothrix-021N). This technique was used to establish the chlorine dosage according to the observed damages on cellular membranes of both, floc-forming bacteria as well as filamentous bacteria. To identify the filamentous bacteria responsible for the macro-structural alteration of the flocs, several criteria were, met, including morphologic characteristics as well as conventional microbiological stains: Gram, Neisser and polyhydroxy alkanoates. FISH was used to confirm the obtained results, providing a definitive identification of the filamentous bacteria responsible for the alteration. (Author) 11 refs

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

    Directory of Open Access Journals (Sweden)

    Yona Golan

    2006-02-01

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

  6. Redox Homeostasis and Cellular Antioxidant Systems: Crucial Players in Cancer Growth and Therapy

    Directory of Open Access Journals (Sweden)

    Barbara Marengo

    2016-01-01

    Full Text Available Reactive oxygen species (ROS and their products are components of cell signaling pathways and play important roles in cellular physiology and pathophysiology. Under physiological conditions, cells control ROS levels by the use of scavenging systems such as superoxide dismutases, peroxiredoxins, and glutathione that balance ROS generation and elimination. Under oxidative stress conditions, excessive ROS can damage cellular proteins, lipids, and DNA, leading to cell damage that may contribute to carcinogenesis. Several studies have shown that cancer cells display an adaptive response to oxidative stress by increasing expression of antioxidant enzymes and molecules. As a double-edged sword, ROS influence signaling pathways determining beneficial or detrimental outcomes in cancer therapy. In this review, we address the role of redox homeostasis in cancer growth and therapy and examine the current literature regarding the redox regulatory systems that become upregulated in cancer and their role in promoting tumor progression and resistance to chemotherapy.

  7. The CRISPR-Cas immune system : Biology, mechanisms and applications

    OpenAIRE

    Rath, Devashish; Amlinger, Lina; Rath, Archana; Lundgren, Magnus

    2015-01-01

    Viruses are a common threat to cellular life, not the least to bacteria and archaea who constitute the majority of life on Earth. Consequently, a variety of mechanisms to resist virus infection has evolved. A recent discovery is the adaptive immune system in prokaryotes, a type of system previously thought to be present only in vertebrates. The system, called CRISPR-Cas, provide sequence-specific adaptive immunity and fundamentally affect our understanding of virus host interaction. CRISPR-ba...

  8. 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

  9. Ion irradiation and the biological effect of immune system

    International Nuclear Information System (INIS)

    Ion irradiation exists broadly in the people's life. It can induce a series of the biological effect in body depending on the different type and dose of ionization. This article expound the effect of ion irradiation on the biological function of immune system, affording the theorial guide in the appreciation, precaution and treatment of irradiation injury. (authors)

  10. Systems-biology dissection of eukaryotic cell growth

    OpenAIRE

    Andrews Justen; Przytycka Teresa M

    2010-01-01

    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

  11. RF and ELF Exposures from Cellular Phone Handsets: TDMA and CDMA Systems (invited paper)

    International Nuclear Information System (INIS)

    The future digital systems for personal communications have now been partially standardised, so it is possible to get a good idea of the exposure power levels and time variation of the power, which may be assumed to be the two biologically relevant parameters. Using GSM and the coming UMTS system the relevant details are discussed, where the main difference is between the highly periodic TDMA (Time Division Multiple Access) power variation and the more smooth, slowly varying CDMA signal (Code Division Multiple Access). Epidemiological and biological studies must reflect the intricate details of the various systems. (author)

  12. Improved Analysis of Co-Channel Interference in Cellular Communications Systems

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zu-fan; DU Hui-ping; ZHU Wei-le

    2005-01-01

    In terms of the carrier-to-interference-ratio, the performance of co-channel interference in cellular communications systems is studied. The approach is based on an improved analysis, which allows to take into account some area in the desired sector may not be interfered by some co-channel sectors with exact geometrical analysis, instead of the entire sector interfered by some co-channel sectors. Other features, such as power control and the number of interferences are also included.

  13. Investigation of Vehicles as Probes Using Global Positioning System and Cellular Phone Tracking: Field Operational Test

    OpenAIRE

    Yim, Y. B. Youngbin; Cayford, Randall

    2001-01-01

    This paper reports on the first phase of the location technology evaluation for probe vehicles. Two technologies were evaluated, Global Positioning Systems (GPS) and the cellular phone tracking technology developed by US Wireless. Although GPS has shown great potential for vehicle probes, much of the previous research is theoretical in nature. Very little work has been done in the areas of experimental research, implementation or deployment. Most of the field tests were anecdotal; a systemati...

  14. Stochastic Ordering based Carrier-to-Interference Ratio Analysis for the Shotgun Cellular Systems

    CERN Document Server

    Madhusudhanan, Prasanna; Youjian,; Liu,; Brown, Timothy X; Baker, Kenneth R

    2011-01-01

    A simple analytical tool based on stochastic ordering is developed to compare the distributions of carrier-to-interference ratio at the mobile station of two cellular systems where the base stations are distributed randomly according to certain non-homogeneous Poisson point processes. The comparison is conveniently done by studying only the base station densities without having to solve for the distributions of the carrier-to-interference ratio, that are often hard to obtain.

  15. An Exact Path-Loss Density Model for Mobiles in a Cellular System

    OpenAIRE

    Abdulla, Mouhamed; Shayan, Yousef R.

    2013-01-01

    In trying to emulate the spatial position of wireless nodes for purpose of analysis, we rely on stochastic simulation. And, it is customary, for mobile systems, to consider a base-station radiation coverage by an ideal cell shape. For cellular analysis, a hexagon contour is always preferred mainly because of its tessellating nature. Despite this fact, largely due to its intrinsic simplicity, in literature only random dispersion model for a circular shape is known. However, if considered, this...

  16. Site-specific recombinatorics: in situ cellular barcoding with the Cre Lox system

    OpenAIRE

    Weber, Tom S.; Dukes, Mark; Miles, Denise; Glaser, Stefan; Naik, Shalin; Duffy, Ken R.

    2016-01-01

    Cellular barcoding is a significant, recently developed, biotechnology tool that enables the familial identification of progeny of individual cells in vivo. Most existing approaches rely on ex vivo viral transduction of cells with barcodes, followed by adoptive transfer into an animal, which works well for some systems, but precludes barcoding cells in their native environment, such as those inside solid tissues. With a view to overcoming this limitation, we propose a new design for a genetic...

  17. Mobile Radio Communications: Second and Third Generation Cellular and WATM Systems: 2nd

    OpenAIRE

    Steele, R; Hanzo, L

    1999-01-01

    This comprehensive all-in-one reference work covers the fundamental physical aspects of mobile communications and explains the latest techniques employed in second and third generation digital cellular mobile radio systems. Mobile radio communications technology has progressed rapidly and it is now capable of the transmission of voice, data and image signals. This new edition reflects the current state-of-the-art by featuring: * Expanded and updated sections on voice compression techniques, i...

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

    Science.gov (United States)

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

    2016-06-01

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

  19. Generalized Carrier to Interference Ratio Analysis for the Shotgun Cellular System

    CERN Document Server

    Madhusudhanan, Prasanna; Liu, Youjian; Brown, Timothy X; Baker, Kenneth

    2010-01-01

    In this paper, the performance of cellular systems in which the base-stations (BS) are randomly placed (so-called shotgun cellular system, SCS) is studied. Previous results for a uniform 2-dimensional distribution of BS are generalized to non-uniform placement of BS in any dimension. The carrier-to-interference ratio (CIR) and the carrier-to-interference-plus-noise ratio (CINR) are analyzed for dense and sparse BS density cellular systems, respectively. A semi-analytical expression for the tail probability of the CIR is derived. Additionally, a tool for comparing the CIR performances of two SCSs based on BS densities is presented. With these results, we completely characterize the performance of a SCS with an arbitrary BS density function. Next, a SCS affected by random shadow fading is shown to be equivalent to another SCS without shadow fading and a different BS density function, and hence the performance of a uniform l-D SCS is independent of shadow fading. Thus, for a sparse uniform l-D SCS, the effect of...

  20. Managing complexity of cellular systems: theoretical tools for dynamic modeling of metabolic reaction networks

    NARCIS (Netherlands)

    Nikerel, I.E.

    2009-01-01

    The study on biological systems attracts more and more interest since these systems offer interesting solutions to problems in diverse areas ranging from sustainable production of chemicals and fuels, environmental problems to medical questions. This thesis is concerned with the effort of improvin

  1. Core Principles for Talent Management System and its Impact on Competitive Advantage "Applied Study Cellular Communications Companies in Jordan"

    OpenAIRE

    Mohammad Fathi Almaaitah; Yoshifumi Harada; Mohd Foad Bin Sakdan

    2015-01-01

    The aim of this study is to measure the core principles of talent management system and its impact on competitive advantage in Cellular communications companies in Jordan, The population of the study consisted of Three cellular telecom companies operating in the Jordanian market, the study sample was selected a random sample of employees in administrative levels: top management and middle management and supervisors in cellular communications companies operating in Jordan, and around include (...

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    Webb Penelope A

    2007-09-01

    Full Text Available 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.

  4. 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

  5. Cognitive Cellular Systems: A New Challenge on the RF Analog Frontend

    Science.gov (United States)

    Varga, Gabor; Schrey, Moritz; Subbiah, Iyappan; Ashok, Arun; Heinen, Stefan

    2016-07-01

    Cognitive Cellular Systems are seen today as one of the most promising ways of moving forward solving or at least easing the still worsening situation of congested spectrum caused by the growing number of users and the expectation of higher data transfer rates. As the intelligence of a Cognitive Radio system is located in the digital domain - the Cognitive Engine and associated layers - extensive research has been ongoing in that domain since Mitola published his idea in 1999. Since, a big progress has been made in the domain of architectures and algorithms making systems more efficient and highly flexible. The pace of this progress, however, is going to be impeded by hard requirements on the received and transmitted signal quality, introducing ultimate challenges on the performance of the RF analog frontend, such as in-band local oscillator harmonics, ultra low sensitivity and ultra high linearity. The RF frontend is thus likely to become the limiting technical factor in the true realization of a Cognitive Cellular System. Based on short recapitulations of the most crucial issues in RF analog design for Cognitive Systems, this article will point out why those mechanisms become responsible for the limitation of the overall performance particularly in a broadband Cognitive Cellular System. Furthermore, as part of a possible solution to ease the situation, system design of a high intermediate frequency (IF) to UHF frequency converter for cognitive radios is discussed and the performance of such a converter analyzed as a proof of concept. In addition to successfully tackling some of the challenges, such a high-IF converter enables white space operation for existing commercial devices by acting as frequency converter. From detailed measurements, the capabilities in both physical layer and application layer performance of a high-IF frontend developed out of off-the-shelf components is explained and is shown to provide negligible degradation to the commercial device

  6. Probabilistic modeling and machine learning in structural and systems biology

    OpenAIRE

    2007-01-01

    This supplement contains extended versions of a selected subset of papers presented at the workshop PMSB 2007, Probabilistic Modeling and Machine Learning in Structural and Systems Biology, Tuusula, Finland, from June 17 to 18, 2006.

  7. Evaluation models for contaminated sites – biological system at risk

    OpenAIRE

    Golomeova, Mirjana; Krstev, Boris; Golomeov, Blagoj; Zendelska, Afrodita; Krstev, Aleksandar

    2009-01-01

    The paper presents the different methods that can be used correspond to three types of approaches, testing, monitoring, and modeling: experimental models, in situ indicators and mathematical models, and choice of model for contaminated sites – biological system at risk.

  8. A Structure of Biological System and Functionality using Artificial Neural Networks

    Directory of Open Access Journals (Sweden)

    Khaled Mohammed Beer Gamal

    2014-07-01

    Full Text Available Artificial neural networks have, as initial motivation, the structure of biological systems, and constitute an alternative computability paradigm. For that reason we will review some aspects of the way in which biological systems perform information processing. The fascination which still pervades this research field has much to do with the points of contact with the surprisingly elegant methods used by neurons in order to process information at the cellular level. Several million years of evolution have led to very sophisticated solutions to the problem of dealing with an uncertain environment. In this chapter we will discuss some elements of these strategies in order to determine what features we want to adopt in our abstract models of neural networks.

  9. Systems biology solutions to challenges in marine biotechnology

    OpenAIRE

    Gov, Esra; Arga, Kazim Y

    2014-01-01

    Marine biotechnology can be considered as the use of marine bioresources as the target or source of biotechnological applications. Despite many successes have been achieved in marine biotechnology, still many gaps remain to be filled in our basic knowledge on marine science before it could be fully exploited. Systems biology focuses on complex interactions within biological systems, using a holistic approach instead of the traditional reductionism. Marine ecosystems, with different levels of ...

  10. Data management in systems biology I - Overview and bibliography

    OpenAIRE

    Mayer, Gerhard

    2009-01-01

    Large systems biology projects can encompass several workgroups often located in different countries. An overview about existing data standards in systems biology and the management, storage, exchange and integration of the generated data in large distributed research projects is given, the pros and cons of the different approaches are illustrated from a practical point of view, the existing software - open source as well as commercial - and the relevant literature is extensively overview, so...

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

    OpenAIRE

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

    2011-01-01

    Abstract The natural environment for plants is composed of a complex set of abiotic stresses and biotic stresses. Plant responses to these stresses are equally complex. Systems biology approaches facilitate a multi-targeted approach by allowing one to identify regulatory hubs in complex networks. Systems biology takes the molecular parts (transcripts, proteins and metabolites) of an organism and attempts to fit them into functional networks or models designed to describe and predict the dynam...

  12. Parameter estimation in systems biology models using spline approximation

    OpenAIRE

    Yeung Lam F; Zhan Choujun

    2011-01-01

    Abstract Background Mathematical models for revealing the dynamics and interactions properties of biological systems play an important role in computational systems biology. The inference of model parameter values from time-course data can be considered as a "reverse engineering" process and is still one of the most challenging tasks. Many parameter estimation methods have been developed but none of these methods is effective for all cases and can overwhelm all other approaches. Instead, vari...

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

    CERN Document Server

    Érdi, Péter

    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.

  14. Systems biology driven software design for the research enterprise

    OpenAIRE

    Killcoyne Sarah; Cavnor Christopher; Boyle John; Shmulevich Ilya

    2008-01-01

    Abstract Background In systems biology, and many other areas of research, there is a need for the interoperability of tools and data sources that were not originally designed to be integrated. Due to the interdisciplinary nature of systems biology, and its association with high throughput experimental platforms, there is an additional need to continually integrate new technologies. As scientists work in isolated groups, integration with other groups is rarely a consideration when building the...

  15. A Geometrical-Based Model for Cochannel Interference Analysis and Capacity Estimation of CDMA Cellular Systems

    Directory of Open Access Journals (Sweden)

    Konstantinos B. Baltzis

    2008-10-01

    Full Text Available A common assumption in cellular communications is the circular-cell approximation. In this paper, an alternative analysis based on the hexagonal shape of the cells is presented. A geometrical-based stochastic model is proposed to describe the angle of arrival of the interfering signals in the reverse link of a cellular system. Explicit closed form expressions are derived, and simulations performed exhibit the characteristics and validate the accuracy of the proposed model. Applications in the capacity estimation of WCDMA cellular networks are presented. Dependence of system capacity of the sectorization of the cells and the base station antenna radiation pattern is explored. Comparisons with data in literature validate the accuracy of the proposed model. The degree of error of the hexagonal and the circular-cell approaches has been investigated indicating the validity of the proposed model. Results have also shown that, in many cases, the two approaches give similar results when the radius of the circle equals to the hexagon inradius. A brief discussion on how the proposed technique may be applied to broadband access networks is finally made.

  16. Automaton based detection of affected cells in three dimensional biological system

    OpenAIRE

    Dundas, Jitesh

    2011-01-01

    The aim of this research review is to propose the logic and search mechanism for the development of an artificially intelligent automaton (AIA) that can find affected cells in a 3-dimensional biological system. Research on the possible application of such automatons to detect and control cancer cells in the human body are greatly focused MRI and PET scans finds the affected regions at the tissue level even as we can find the affected regions at the cellular level using the framework. The AIA ...

  17. Mathematical aspects of pattern formation in biological systems

    CERN Document Server

    Wei, Juncheng

    2013-01-01

    This monograph is concerned with the mathematical analysis of patterns which are encountered in biological systems. It summarises, expands and relates results obtained in the field during the last fifteen years. It also links the results to biological applications and highlights their relevance to phenomena in nature. Of particular concern are large-amplitude patterns far from equilibrium in biologically relevant models.The approach adopted in the monograph is based on the following paradigms:• Examine the existence of spiky steady states in reaction-diffusion systems and select as observabl

  18. Dynamic mapping of flood boundaries: current possibilities offered by Earth Observation System and Cellular Automata

    Directory of Open Access Journals (Sweden)

    A. Gerardi

    2014-01-01

    Full Text Available Flooding is an ongoing and complex problem in Italy. Very large floods caused inundation of the closest areas to the city centre in Rome in 1937, 1976, 1992, 2005 and most recently in 2008. Rome is located at the bottom of the Tiber River catchment, which cover an area of 16 000 km2. Intense precipitations struck the Tyrrhenian Sea side of the peninsula inducing a flood event on the Tiber and Aniene's (Tiber's tributary basins – which captured the attention of the national and international media. Actually there is no validated model in operation for real-time flood forecasting. This research aims at comparing the Cellular Model CAESAR (Cellular Automation Evolutionary Slope And River application on a reach of the Aniene River with Earth Observation Systems. The main result expected is the prediction of future channel dynamics on short and medium time scale.

  19. A Pedestrian Navigation System Using Cellular Phone Video-Conferencing Functions

    Directory of Open Access Journals (Sweden)

    Akihiko Sugiura

    2012-01-01

    Full Text Available A user’s position-specific field has been developed using the Global Positioning System (GPS technology. To determine the position using cellular phones, a device was developed, in which a pedestrian navigation unit carries the GPS. However, GPS cannot specify a position in a subterranean environment or indoors, which is beyond the reach of transmitted signals. In addition, the position-specification precision of GPS, that is, its resolution, is on the order of several meters, which is deemed insufficient for pedestrians. In this study, we proposed and evaluated a technique for locating a user’s 3D position by setting up a marker in the navigation space detected in the image of a cellular phone. By experiment, we verified the effectiveness and accuracy of the proposed method. Additionally, we improved the positional precision because we measured the position distance using numerous markers.

  20. Systems Biology Approaches to Understand Natural Products Biosynthesis

    Science.gov (United States)

    Licona-Cassani, Cuauhtemoc; Cruz-Morales, Pablo; Manteca, Angel; Barona-Gomez, Francisco; Nielsen, Lars K.; Marcellin, Esteban

    2015-01-01

    Actinomycetes populate soils and aquatic sediments that impose biotic and abiotic challenges for their survival. As a result, actinomycetes metabolism and genomes have evolved to produce an overwhelming diversity of specialized molecules. Polyketides, non-ribosomal peptides, post-translationally modified peptides, lactams, and terpenes are well-known bioactive natural products with enormous industrial potential. Accessing such biological diversity has proven difficult due to the complex regulation of cellular metabolism in actinomycetes and to the sparse knowledge of their physiology. The past decade, however, has seen the development of omics technologies that have significantly contributed to our better understanding of their biology. Key observations have contributed toward a shift in the exploitation of actinomycete’s biology, such as using their full genomic potential, activating entire pathways through key metabolic elicitors and pathway engineering to improve biosynthesis. Here, we review recent efforts devoted to achieving enhanced discovery, activation, and manipulation of natural product biosynthetic pathways in model actinomycetes using genome-scale biological datasets. PMID:26697425

  1. Systems biology approaches to understand natural products biosynthesis

    Directory of Open Access Journals (Sweden)

    Cuauhtemoc eLicona-Cassani

    2015-12-01

    Full Text Available Actinomycetes populate soils and aquatic sediments which impose biotic and abiotic challenges for their survival. As a result, actinomycetes metabolism and genomes have evolved to produce an overwhelming diversity of specialized molecules. Polyketides, non-ribosomal peptides, post-translationally modified peptides, lactams and terpenes are well known bioactive natural products with enormous industrial potential. Accessing such biological diversity has proven difficult due to the complex regulation of cellular metabolism in actinomycetes and to the sparse knowledge of their physiology. The past decade, however, has seen the development of omics technologies that have significantly contributed to our better understanding of their biology. Key observations have contributed towards a shift in the exploitation of actinomycetes biology, such as using their full genomic potential, activating entire pathways through key metabolic elicitors and pathway engineering to improve biosynthesis. Here, we review recent efforts devoted to achieving enhanced discovery, activation and manipulation of natural product biosynthetic pathways in model actinomycetes using genome-scale biological datasets.

  2. Insects as test systems for assessing the potential role of microgravity in biological development and evolution

    Science.gov (United States)

    Vernós, I.; Carratalá, M.; González-Jurado, J.; Valverde, J. R.; Calleja, M.; Domingo, A.; Vinós, J.; Cervera, M.; Marco, R.

    Gravity and radiation are undoubtedly the two major environmental factors altered in space. Gravity is a weak force, which creates a permanent potential field acting on the mass of biological systems and their cellular components, strongly reduced in space flights. Developmental systems, particularly at very early stages, provide the larger cellular compartments known, where the effects of alterations in the size of the gravity vector on living organisms can be more effectively tested. The insects, one of the more highly evolved classes of animals in which early development occurs in a syncytial embryo, are systems particularly well suited to test these effects and the specific developmental mechanisms affected. Furthermore, they share some basic features such as small size, short life cycles, relatively high radio-resistance, etc. and show a diversity of developmental strategies and tempos advantageous in experiments of this type in space. Drosophila melanogaster, the current biological paradigm to study development, with so much genetic and evolutionary background available, is clearly the reference organism for these studies. The current evidence on the effects of the physical parameters altered in space flights on insect development indicate a surprising correlation between effects seen on the fast developing and relatively small Drosophila embryo and the more slowly developing and large Carausius morosus system. In relation to the issue of the importance of developmental and environmental constraints in biological evolution, still the missing link in current evolutionary thinking, insects and space facilities for long-term experiments could provide useful experimental settings where to critically assess how development and evolution may be interconnected. Finally, it has to be pointed out that since there are experimental data indicating a possible synergism between microgravity and space radiation, possible effects of space radiation should be taken into

  3. Estimation of the Carrier-to-Interference Ratio in Cellular Radio Systems

    OpenAIRE

    Gunnarsson, Fredrik; Blom, Jonas; Gustafsson, Fredrik

    1999-01-01

    The problem to track time-varying parameters in cellular radio systems is studied. The focus is on estimation based only on the signals that are readily available. Previous work has demonstrated very good performance relying on analog measurement. In a real system most of the information is lost due to quantization and sampling at a rate that might be as low as 2 Hz (GSM case). Therefore a different approach is required and for that matter a maximum likelihood estimator has been designed and ...

  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. An asynchronous communication system based on the hyperchaotic system of 6th-order cellular neural network

    Science.gov (United States)

    Wang, Xingyuan; Xu, Bing; Luo, Chao

    2012-11-01

    This paper proposes a novel asynchronous communication scheme. Based on this scheme, a model using the hyperchaotic system of 6th-order Cellular Neural Network (CNN) is designed. This scheme enhances the security of asynchronous communication compared to the conventional ones. It is noteworthy that the proposed communication scheme does not depend on synchronization, and almost all chaotic systems can be involved in this scheme. Numerical simulations show the effectiveness of this scheme.

  6. Application of Bioinformatics and Systems Biology in Medicinal Plant Studies

    Institute of Scientific and Technical Information of China (English)

    DENG You-ping; AI Jun-mei; XIAO Pei-gen

    2010-01-01

    One important purpose to investigate medicinal plants is to understand genes and enzymes that govern the biological metabolic process to produce bioactive compounds.Genome wide high throughput technologies such as genomics,transcriptomics,proteomics and metabolomics can help reach that goal.Such technologies can produce a vast amount of data which desperately need bioinformatics and systems biology to process,manage,distribute and understand these data.By dealing with the"omics"data,bioinformatics and systems biology can also help improve the quality of traditional medicinal materials,develop new approaches for the classification and authentication of medicinal plants,identify new active compounds,and cultivate medicinal plant species that tolerate harsh environmental conditions.In this review,the application of bioinformatics and systems biology in medicinal plants is briefly introduced.

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

    Directory of Open Access Journals (Sweden)

    Ezio Bartocci

    2016-01-01

    Full Text Available As the amount of biological data in the public domain grows, so does the range of modeling and analysis techniques employed in systems biology. In recent years, a number of theoretical computer science developments have enabled modeling methodology to keep pace. The growing interest in systems biology in executable models and their analysis has necessitated the borrowing of terms and methods from computer science, such as formal analysis, model checking, static analysis, and runtime verification. Here, we discuss the most important and exciting computational methods and tools currently available to systems biologists. We believe that a deeper understanding of the concepts and theory highlighted in this review will produce better software practice, improved investigation of complex biological processes, and even new ideas and better feedback into computer science.

  8. Virtual Tissues and Developmental Systems Biology

    Science.gov (United States)

    Computational modeling of embryonic systems to analyze how 'core development processes' are wired together. Has the potential to address environmental and human health factors with broad scientific and economic impacts.

  9. 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...

  10. 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.

  11. Effects of Pesticides on Biological Systems

    OpenAIRE

    Ergul Belge Kurutas; Metin Kilinc

    2003-01-01

    The use of pesticid both in Turkey and other contries is widespread in order to combat against many pests which cause economical damages. However, pesticides in human pass through skin, respiratory or digestive systems and is metabolized by monooxygenase system dependent upon cytocrome P450 in liver. They also give rise to severe decreases cytochrome P450 and amount of "hem" enzyme activites of glucose-6-phosphatase, pyrophosphatase by stimulating lipid peroxidation on hepatic microsomes. In ...

  12. AN EFFICIENT RADIO RESOURCE MANAGEMENT STRATEGY FOR ADAPTIVE OFDM CELLULAR SYSTEMS

    Institute of Scientific and Technical Information of China (English)

    Yu Guanding; Zhang Zhaoyang; Qiu Peiliang

    2006-01-01

    This paper presents an efficient Radio Resource Management (RRM) strategy for adaptive Orthogonal Frequency Division Multiplexing (OFDM) cellular systems. In the proposed strategy, only those users who have the same distance from their base stations can reuse a same subcarrier. This can guarantee the received Carrier-to-Interference ratio (C/I) of each subcarrier to be acceptable as required by system planning. Then by employing different modulation scheme on each subcarrier according to its received C/I, system spectral efficiency can be gracefully increased. Analytical and simulation results show that the spectral efficiency is improved by 40% without sacrificing the Bit Error Rate (BER) performance and call blocking probability and system capacity of the proposed strategy is better than conventional systems.

  13. DNA Mismatch Repair System: Repercussions in Cellular Homeostasis and Relationship with Aging

    Directory of Open Access Journals (Sweden)

    Juan Cristóbal Conde-Pérezprina

    2012-01-01

    Full Text Available The mechanisms that concern DNA repair have been studied in the last years due to their consequences in cellular homeostasis. The diverse and damaging stimuli that affect DNA integrity, such as changes in the genetic sequence and modifications in gene expression, can disrupt the steady state of the cell and have serious repercussions to pathways that regulate apoptosis, senescence, and cancer. These altered pathways not only modify cellular and organism longevity, but quality of life (“health-span”. The DNA mismatch repair system (MMR is highly conserved between species; its role is paramount in the preservation of DNA integrity, placing it as a necessary focal point in the study of pathways that prolong lifespan, aging, and disease. Here, we review different insights concerning the malfunction or absence of the DNA-MMR and its impact on cellular homeostasis. In particular, we will focus on DNA-MMR mechanisms regulated by known repair proteins MSH2, MSH6, PMS2, and MHL1, among others.

  14. Biologically-Inspired Water Propulsion System

    Institute of Scientific and Technical Information of China (English)

    Andrzej Sioma

    2013-01-01

    Most propulsion systems of vehicles travelling in the aquatic environment are equipped with propellers.Observations of nature,however,show that the absolute majority of organisms travel through water using wave motion,paddling or using water jet power.Inspired by these observations of nature,an innovative propulsion system working in aquatic environment was developed.This paper presents the design of the water propulsion system.Particular attention was paid to the use of paddling techniques and water jet power.A group of organisms that use those mechanisms to travel through water was selected and analysed.The results of research were used in the design of a propulsion system modelled simultaneously on two methods of movement in the aquatic environment.A method for modelling a propulsion system using a combination of the two solutions and the result were described.A conceptual design and a prototype constructed based on the solution were presented.With respect to the solution developed,studies and analyses of selected parameters of the prototype were described.

  15. Systems-Biology Approaches to Discover Anti-Viral Effectors of the Human Innate Immune Response

    Directory of Open Access Journals (Sweden)

    Andreas F.R. Sommer

    2011-07-01

    Full Text Available Virus infections elicit an immediate innate response involving antiviral factors. The activities of some of these factors are, in turn, blocked by viral countermeasures. The ensuing battle between the host and the viruses is crucial for determining whether the virus establishes a foothold and/or induces adaptive immune responses. A comprehensive systems-level understanding of the repertoire of anti-viral effectors in the context of these immediate virus-host responses would provide significant advantages in devising novel strategies to interfere with the initial establishment of infections. Recent efforts to identify cellular factors in a comprehensive and unbiased manner, using genome-wide siRNA screens and other systems biology “omics” methodologies, have revealed several potential anti-viral effectors for viruses like Human immunodeficiency virus type 1 (HIV-1, Hepatitis C virus (HCV, West Nile virus (WNV, and influenza virus. This review describes the discovery of novel viral restriction factors and discusses how the integration of different methods in systems biology can be used to more comprehensively identify the intimate interactions of viruses and the cellular innate resistance.

  16. Amoxicillin in a biological water recovery system

    International Nuclear Information System (INIS)

    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 NO3- and NO2- 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 wastewater

  17. Amoxicillin in a biological water recovery system

    Energy Technology Data Exchange (ETDEWEB)

    Morse, A.; Jackson, A.; Rainwater, K. [Texas Tech Univ., Water Resources Center, Lubbock, Texas (United States); Pickering, K. [Johnson Space Center, NASA, Houston, Texas (United States)

    2002-06-15

    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{sub 3}{sup -} and NO{sub 2}{sup -} as the e{sup -} 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

  18. Potential role of atomic force microscopy in systems biology.

    Science.gov (United States)

    Ramachandran, Srinivasan; Teran Arce, Fernando; Lal, Ratnesh

    2011-01-01

    Systems biology is a quantitative approach for understanding a biological system at its global level through systematic perturbation and integrated analysis of all its components. Simultaneous acquisition of information data sets pertaining to the system components (e.g., genome, proteome) is essential to implement this approach. There are limitations to such an approach in measuring gene expression levels and accounting for all proteins in the system. The success of genomic studies is critically dependent on polymerase chain reaction (PCR) for its amplification, but PCR is very uneven in amplifying the samples, ineffective in scarce samples and unreliable in low copy number transcripts. On the other hand, lack of amplifying techniques for proteins critically limits their identification to only a small fraction of high concentration proteins. Atomic force microscopy (AFM), AFM cantilever sensors, and AFM force spectroscopy in particular, could address these issues directly. In this article, we reviewed and assessed their potential role in systems biology. PMID:21766465

  19. MMBSM: A Meta Model for Biological System Modeling

    Directory of Open Access Journals (Sweden)

    Touraj Banirostam

    2012-09-01

    Full Text Available Increasing the complexity and interactions, network centric organizations would become less effective and it seems that getting pattern of biological system might represent an appropriate approach to this problem. Based on Capra Cognitive Framework, basic parameters in a biological system and the whole role of these parameters will be evaluated and then again according to the mentioned framework, a model of biological- social systems and their effective elements will get analyzed in this paper. Moreover, the relations between existed elements in noticed model will be assessed and their impacts on each other will get presented. The proposed model (MMBSM will be considered through looking at the functionality of the Immune System and after that, its approach will get evaluated based on existed elements in the Immune System and the way they operate.

  20. Temporal order of evolution of DNA replication systems inferred by comparison of cellular and viral DNA polymerases

    Directory of Open Access Journals (Sweden)

    Koonin Eugene V

    2006-12-01

    Full Text Available Abstract Background The core enzymes of the DNA replication systems show striking diversity among cellular life forms and more so among viruses. In particular, and counter-intuitively, given the central role of DNA in all cells and the mechanistic uniformity of replication, the core enzymes of the replication systems of bacteria and archaea (as well as eukaryotes are unrelated or extremely distantly related. Viruses and plasmids, in addition, possess at least two unique DNA replication systems, namely, the protein-primed and rolling circle modalities of replication. This unexpected diversity makes the origin and evolution of DNA replication systems a particularly challenging and intriguing problem in evolutionary biology. Results I propose a specific succession for the emergence of different DNA replication systems, drawing argument from the differences in their representation among viruses and other selfish replicating elements. In a striking pattern, the DNA replication systems of viruses infecting bacteria and eukaryotes are dominated by the archaeal-type B-family DNA polymerase (PolB whereas the bacterial replicative DNA polymerase (PolC is present only in a handful of bacteriophage genomes. There is no apparent mechanistic impediment to the involvement of the bacterial-type replication machinery in viral DNA replication. Therefore, I hypothesize that the observed, markedly unequal distribution of the replicative DNA polymerases among the known cellular and viral replication systems has a historical explanation. I propose that, among the two types of DNA replication machineries that are found in extant life forms, the archaeal-type, PolB-based system evolved first and had already given rise to a variety of diverse viruses and other selfish elements before the advent of the bacterial, PolC-based machinery. Conceivably, at that stage of evolution, the niches for DNA-viral reproduction have been already filled with viruses replicating with the