Science.gov

Sample records for actual biological systems

  1. Gauging triple stores with actual biological data

    PubMed Central

    2012-01-01

    Background Semantic Web technologies have been developed to overcome the limitations of the current Web and conventional data integration solutions. The Semantic Web is expected to link all the data present on the Internet instead of linking just documents. One of the foundations of the Semantic Web technologies is the knowledge representation language Resource Description Framework (RDF). Knowledge expressed in RDF is typically stored in so-called triple stores (also known as RDF stores), from which it can be retrieved with SPARQL, a language designed for querying RDF-based models. The Semantic Web technologies should allow federated queries over multiple triple stores. In this paper we compare the efficiency of a set of biologically relevant queries as applied to a number of different triple store implementations. Results Previously we developed a library of queries to guide the use of our knowledge base Cell Cycle Ontology implemented as a triple store. We have now compared the performance of these queries on five non-commercial triple stores: OpenLink Virtuoso (Open-Source Edition), Jena SDB, Jena TDB, SwiftOWLIM and 4Store. We examined three performance aspects: the data uploading time, the query execution time and the scalability. The queries we had chosen addressed diverse ontological or biological questions, and we found that individual store performance was quite query-specific. We identified three groups of queries displaying similar behaviour across the different stores: 1) relatively short response time queries, 2) moderate response time queries and 3) relatively long response time queries. SwiftOWLIM proved to be a winner in the first group, 4Store in the second one and Virtuoso in the third one. Conclusions Our analysis showed that some queries behaved idiosyncratically, in a triple store specific manner, mainly with SwiftOWLIM and 4Store. Virtuoso, as expected, displayed a very balanced performance - its load time and its response time for all the

  2. What is Systems Biology?

    PubMed Central

    Breitling, Rainer

    2010-01-01

    Systems biology is increasingly popular, but to many biologists it remains unclear what this new discipline actually encompasses. This brief personal perspective starts by outlining the asthetic qualities that motivate systems biologists, discusses which activities do not belong to the core of systems biology, and finally explores the crucial link with synthetic biology. It concludes by attempting to define systems biology as the research endeavor that aims at providing the scientific foundation for successful synthetic biology. PMID:21423352

  3. Systems Biology

    SciTech Connect

    Wiley, H S.

    2006-06-01

    The biology revolution over the last 50 years has been driven by the ascendancy of molecular biology. This was enthusiastically embraced by most biologists because it took us into increasingly familiar territory. It took mysterious processes, such as the replication of genetic material and assigned them parts that could be readily understood by the human mind. When we think of ''molecular machines'' as being the underlying basis of life, we are using a paradigm derived from everyday experience. However, the price that we paid was a relentless drive towards reductionism and the attendant balkanization of biology. Now along comes ''systems biology'' that promises us a solution to the problem of ''knowing more and more about less and less''. Unlike molecular biology, systems biology appears to be taking us into unfamiliar intellectual territory, such as statistics, mathematics and computer modeling. Not surprisingly, systems biology has met with widespread skepticism and resistance. Why do we need systems biology anyway and how does this new area of research promise to change the face of biology in the next couple of decades?

  4. Biological Sex, Sex-Role, and Self-Actualization of College Students.

    ERIC Educational Resources Information Center

    Guyot, Gary W.; Vollemaere, Erik

    Self-actualization, which involves the ultimate development of one's abilities regardless of external influences, is the basis for many personality theories. To assess the relationship between biological sex, sex role, and self-actualization, the Bem Sex Role Inventory (BSRI) and the Personal Orientation Inventory (POI) were administered to 129…

  5. Systems interface biology

    PubMed Central

    Doyle, Francis J; Stelling, Jörg

    2006-01-01

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

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

    ERIC Educational Resources Information Center

    Bandyopadhyay, Aditi

    2013-01-01

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

  7. Perceived and actual similarities in biological and adoptive families: does perceived similarity bias genetic inferences?

    PubMed

    Scarr, S; Scarf, E; Weinberg, R A

    1980-09-01

    Critics of the adoption method to estimate the relative effects of genetic and environmental differences on behavioral development claim that important biases are created by the knowledge of biological relatedness or adoptive status. Since the 1950s, agency policy has led to nearly all adopted children knowing that they are adopted. To test the hypothesis that knowledge of biological or adoptive status influences actual similarity, we correlated absolute differences in objective test scores with ratings of similarity by adolescents and their parents in adoptive and biological families. Although biological family members see themselves as more similar than adoptive family members, there are also important generational and gender differences in perceived similarity that cut across family type. There is moderate agreement among family members on the degree of perceived similarity, but there is no correlation between perceived and actual similarity in intelligence or temperament. However, family members are more accurate about shared social attitudes. Knowledge of adoptive or biological relatedness is related to the degree of perceived similarity, but perceptions of similarity are not related to objective similarities and thus do not constitute a bias in comparisons of measured differences in intelligence or temperament in adoptive and biological families.

  8. Biological conversion system

    DOEpatents

    Scott, C.D.

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

  9. Computational systems chemical biology.

    PubMed

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

    2011-01-01

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

  10. Metabonomics and systems biology.

    PubMed

    De Preter, Vicky

    2015-01-01

    Systems biology represents an integrative research strategy that studies the interactions between DNA, mRNA, protein, and metabolite level in an organism, thereby including the interactions with the physical environment and other organisms. The application of metabonomics, or the quantitative study of metabolites in biological systems, in systems biology is currently an emerging area of research, which can contribute to the discovery of (disease) signatures, drug targeting and design, and the further elucidation of basic and more complex biochemical principles. This chapter covers the contribution of metabonomics in advancing our understanding in systems biology.

  11. Power Delivery from an Actual Thermoelectric Generation System

    NASA Astrophysics Data System (ADS)

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

    2014-06-01

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

  12. Engineering scalable biological systems

    PubMed Central

    2010-01-01

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

  13. [Systems biology of cancer].

    PubMed

    Barillot, Emmanuel; Calzone, Laurence; Zinovyev, Andrei

    2009-01-01

    Cancer Systems Biology is now accepted and recognized as a promising field both in biological and clinical research. It relies on a rigorous formalization of regulation networks into precise and unambiguous languages. It provides both detailed and modular views of the complex biological system of interest (which in cancer research is typically an interaction network governing essential cellular events such as proliferation, differentiation, cell death...) in order to facilitate the interpretation of molecular profiles of tumors. The translation of these networks into mathematical models allows prediction of the evolution of the system in time and under certain perturbations. As a result, it can not only propose specific target points for pharmaceutical purposes, but also anticipate the evolution of tumors as well as their classifications. These characteristics emphasize the important role of Systems Biology of Cancer in the future of biomedical research.

  14. Dimensions of systems biology.

    PubMed

    Huang, S; Wikswo, J

    2006-01-01

    Systems biology, possibly the latest sub-discipline of biology, has arisen as a result of the shockwave of genomic and proteomic data that has appeared in the past few years. However, despite ubiquitous initiatives that carry this label, there is no precise definition of systems biology other than the implication of a new, all-encompassing, multidisciplinary endeavor. Here we propose that systems biology is more than the integration of biology with methods of the physical and computational sciences, and also more than the expansion of the single-pathway approach to embracing genome-scale networks. It is the discipline that specifically addresses the fundamental properties of the complexity that living systems represent. To facilitate the discussion, we dissect and project the multifaceted systems complexity of living organisms into five dimensions: (1) molecular complexity; (2) structural complexity; (3) temporal complexity; (4) abstraction and emergence; and (5) algorithmic complexity. This "five-dimensional space" may provide a framework for comparing, classifying, and complementing the vast diversity of existing systems biology programs and their goals, and will also give a glimpse of the magnitude of the scientific problems associated with unraveling the ultimate mysteries of life.

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

    USGS Publications Warehouse

    Stephenson, N.L.

    1998-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

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

  17. Systems cell biology.

    PubMed

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

    2014-09-15

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

  18. Systems cell biology

    PubMed Central

    Mast, Fred D.; Ratushny, Alexander V.

    2014-01-01

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

  19. Computational Systems Biology

    SciTech Connect

    McDermott, Jason E.; Samudrala, Ram; Bumgarner, Roger E.; Montogomery, Kristina; Ireton, Renee

    2009-05-01

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

  20. Plant Systems Biology (editorial)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ‘‘...

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

    PubMed

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

    2000-01-01

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

  2. Biophysics and systems biology

    PubMed Central

    Noble, Denis

    2010-01-01

    Biophysics at the systems level, as distinct from molecular biophysics, acquired its most famous paradigm in the work of Hodgkin and Huxley, who integrated their equations for the nerve impulse in 1952. Their approach has since been extended to other organs of the body, notably including the heart. The modern field of computational biology has expanded rapidly during the first decade of the twenty-first century and, through its contribution to what is now called systems biology, it is set to revise many of the fundamental principles of biology, including the relations between genotypes and phenotypes. Evolutionary theory, in particular, will require re-assessment. To succeed in this, computational and systems biology will need to develop the theoretical framework required to deal with multilevel interactions. While computational power is necessary, and is forthcoming, it is not sufficient. We will also require mathematical insight, perhaps of a nature we have not yet identified. This article is therefore also a challenge to mathematicians to develop such insights. PMID:20123750

  3. 7th Annual Systems Biology Symposium: Systems Biology and Engineering

    SciTech Connect

    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."

  4. A Comparison of the Actual and Preferred Classroom Learning Environment in Biology and Chemistry as Perceived by High School Students.

    ERIC Educational Resources Information Center

    Hofstein, Avi; Lazarowitz, Reuven

    1986-01-01

    The actual and preferred students' perception of classroom learning environment was measured using a modified Hebrew version of the Learning Environment Inventory (LEI). This (validated and analyzed for reliability) was given to chemistry (N=1080) and biology (N=400) students. Results and implications are discussed. (Author/JN)

  5. Systems biology, emergence and antireductionism.

    PubMed

    Kesić, Srdjan

    2016-09-01

    This study explores the conceptual history of systems biology and its impact on philosophical and scientific conceptions of reductionism, antireductionism and emergence. Development of systems biology at the beginning of 21st century transformed biological science. Systems biology is a new holistic approach or strategy how to research biological organisms, developed through three phases. The first phase was completed when molecular biology transformed into systems molecular biology. Prior to the second phase, convergence between applied general systems theory and nonlinear dynamics took place, hence allowing the formation of systems mathematical biology. The second phase happened when systems molecular biology and systems mathematical biology, together, were applied for analysis of biological data. Finally, after successful application in science, medicine and biotechnology, the process of the formation of modern systems biology was completed. Systems and molecular reductionist views on organisms were completely opposed to each other. Implications of systems and molecular biology on reductionist-antireductionist debate were quite different. The analysis of reductionism, antireductionism and emergence issues, in the era of systems biology, revealed the hierarchy between methodological, epistemological and ontological antireductionism. Primarily, methodological antireductionism followed from the systems biology. Only after, epistemological and ontological antireductionism could be supported. PMID:27579007

  6. Systems biology, emergence and antireductionism.

    PubMed

    Kesić, Srdjan

    2016-09-01

    This study explores the conceptual history of systems biology and its impact on philosophical and scientific conceptions of reductionism, antireductionism and emergence. Development of systems biology at the beginning of 21st century transformed biological science. Systems biology is a new holistic approach or strategy how to research biological organisms, developed through three phases. The first phase was completed when molecular biology transformed into systems molecular biology. Prior to the second phase, convergence between applied general systems theory and nonlinear dynamics took place, hence allowing the formation of systems mathematical biology. The second phase happened when systems molecular biology and systems mathematical biology, together, were applied for analysis of biological data. Finally, after successful application in science, medicine and biotechnology, the process of the formation of modern systems biology was completed. Systems and molecular reductionist views on organisms were completely opposed to each other. Implications of systems and molecular biology on reductionist-antireductionist debate were quite different. The analysis of reductionism, antireductionism and emergence issues, in the era of systems biology, revealed the hierarchy between methodological, epistemological and ontological antireductionism. Primarily, methodological antireductionism followed from the systems biology. Only after, epistemological and ontological antireductionism could be supported.

  7. Biological life-support systems

    NASA Technical Reports Server (NTRS)

    Shepelev, Y. Y.

    1975-01-01

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

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

    ERIC Educational Resources Information Center

    Sheppard, Keith; Robbins, Dennis M.

    2007-01-01

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

  9. Virtual vision system with actual flavor by olfactory display

    NASA Astrophysics Data System (ADS)

    Sakamoto, Kunio; Kanazawa, Fumihiro

    2010-11-01

    The authors have researched multimedia system and support system for nursing studies on and practices of reminiscence therapy and life review therapy. The concept of the life review is presented by Butler in 1963. The process of thinking back on one's life and communicating about one's life to another person is called life review. There is a famous episode concerning the memory. It is called as Proustian effects. This effect is mentioned on the Proust's novel as an episode that a story teller reminds his old memory when he dipped a madeleine in tea. So many scientists research why smells trigger the memory. The authors pay attention to the relation between smells and memory although the reason is not evident yet. Then we have tried to add an olfactory display to the multimedia system so that the smells become a trigger of reminding buried memories. An olfactory display is a device that delivers smells to the nose. It provides us with special effects, for example to emit smell as if you were there or to give a trigger for reminding us of memories. The authors have developed a tabletop display system connected with the olfactory display. For delivering a flavor to user's nose, the system needs to recognition and measure positions of user's face and nose. In this paper, the authors describe an olfactory display which enables to detect the nose position for an effective delivery.

  10. Actualizing sustainability: environmental policy for resilience in ecological systems

    EPA Science Inventory

    Society benefits from ecological systems in many ways. These benefits are often referred to as ecosystem services (MA 2005). Because these services matter to humans, they are critical to sustainability. Sustainability has many definitions, but for this chapter, we link our defi...

  11. Systems biology: a biologist's viewpoint.

    PubMed

    Bose, Biplab

    2013-12-01

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

  12. Systems biology: a biologist's viewpoint.

    PubMed

    Bose, Biplab

    2013-12-01

    The debate over reductionism and antireductionism in biology is very old. Even the systems approach in biology is more than five decades old. However, mainstream biology, particularly experimental biology, has broadly sidestepped those debates and ideas. Post-genome data explosion and development of high-throughput techniques led to resurfacing of those ideas and debates as a new incarnation called Systems Biology. Though experimental biologists have co-opted systems biology and hailed it as a paradigm shift, it is practiced in different shades and understood with divergent meanings. Biology has certain questions linked with organization of multiple components and processes. Often such questions involve multilevel systems. Here in this essay we argue that systems theory provides required framework and abstractions to explore those questions. We argue that systems biology should follow the logical and mathematical approach of systems theory and transmogrification of systems biology to mere collection of higher dimensional data must be avoided. Therefore, the questions that we ask and the priority of those questions should also change. Systems biology should focus on system-level properties and investigate complexity without shying away from it. PMID:23872085

  13. Biological carbon fixation: A study of Isochrysis sp. growth under actual coal-fired power plant's flue gas

    NASA Astrophysics Data System (ADS)

    >Liyana Yahya, Muhammad Nazry Chik, Mohd Asyraf Mohd Azmir Pang,

    2013-06-01

    Preliminary study on the growth of marine microalgae Isochrysis sp. was carried out using actual flue gas from a coal-fired power station. The species was cultured using a 2×10-L customized bubble column photobioreactor skid under specified culture conditions. With an initial culture density of 0.459 Abs (optical density at 560 nm wavelength), the species was found able to survive - observed by increases in optical densities, number of cells and weights - in the presence of actual coal-fired flue gas containing on average 4.08 % O2, 200.21 mg/m3 SO2, 212.29 mg/m3 NOx, 4.73 % CO2 and 50.72 mg/m3 CO. Results thus add value to the potential and capability of microalgae, especially for Isochrysis sp., to be the biological carbon fixer in neutralizing carbon emissions from power plants.

  14. Computational representation of biological systems

    SciTech Connect

    Frazier, Zach; McDermott, Jason E.; Guerquin, Michal; Samudrala, Ram

    2009-04-20

    Integration of large and diverse biological data sets is a daunting problem facing systems biology researchers. Exploring the complex issues of data validation, integration, and representation, we present a systematic approach for the management and analysis of large biological data sets based on data warehouses. Our system has been implemented in the Bioverse, a framework combining diverse protein information from a variety of knowledge areas such as molecular interactions, pathway localization, protein structure, and protein function.

  15. Systems biology of innate immunity

    PubMed Central

    Zak, Daniel E.; Aderem, Alan

    2009-01-01

    Summary Systems biology is the comprehensive and quantitative analysis of the interactions between all of the components of biological systems over time. Systems biology involves an iterative cycle, in which emerging biological problems drive the development of new technologies and computational tools. These technologies and tools then open new frontiers that revolutionize biology. Innate immunity is well suited for systems analysis, because the relevant cells can be isolated in various functional states and their interactions can be reconstituted in a biologically meaningful manner. Application of the tools of systems biology to the innate immune system will enable comprehensive analysis of the complex interactions that maintain the difficult balance between host defense and inflammatory disease. In this review, we discuss innate immunity in the context of the systems biology concepts, emergence, robustness, and modularity, and we describe emerging technologies we are applying in our systems-level analyses. These technologies include genomics, proteomics, computational analysis, forward genetics screens, and analyses that link human genetic polymorphisms to disease resistance. PMID:19120490

  16. Pervasive robustness in biological systems.

    PubMed

    Félix, Marie-Anne; Barkoulas, Michalis

    2015-08-01

    Robustness is characterized by the invariant expression of a phenotype in the face of a genetic and/or environmental perturbation. Although phenotypic variance is a central measure in the mapping of the genotype and environment to the phenotype in quantitative evolutionary genetics, robustness is also a key feature in systems biology, resulting from nonlinearities in quantitative relationships between upstream and downstream components. In this Review, we provide a synthesis of these two lines of investigation, converging on understanding how variation propagates across biological systems. We critically assess the recent proliferation of studies identifying robustness-conferring genes in the context of the nonlinearity in biological systems. PMID:26184598

  17. Aging and computational systems biology.

    PubMed

    Mooney, Kathleen M; Morgan, Amy E; Mc Auley, Mark T

    2016-01-01

    Aging research is undergoing a paradigm shift, which has led to new and innovative methods of exploring this complex phenomenon. The systems biology approach endeavors to understand biological systems in a holistic manner, by taking account of intrinsic interactions, while also attempting to account for the impact of external inputs, such as diet. A key technique employed in systems biology is computational modeling, which involves mathematically describing and simulating the dynamics of biological systems. Although a large number of computational models have been developed in recent years, these models have focused on various discrete components of the aging process, and to date no model has succeeded in completely representing the full scope of aging. Combining existing models or developing new models may help to address this need and in so doing could help achieve an improved understanding of the intrinsic mechanisms which underpin aging.

  18. Imaging methodologies for systems biology.

    PubMed

    Smith, Sarah E; Slaughter, Brian D; Unruh, Jay R

    2014-01-01

    Systems biology has recently achieved significant success in the understanding of complex interconnected phenomena such as cell polarity and migration. In this context, the definition of systems biology has come to encompass the integration of quantitative measurements with sophisticated modeling approaches. This article will review recent progress in live cell imaging technologies that have expanded the possibilities of quantitative in vivo measurements, particularly in regards to molecule counting and quantitative measurements of protein concentration and dynamics. These methods have gained and continue to gain popularity with the biological community. In general, we will discuss three broad categories: protein interactions, protein quantitation, and protein dynamics. PMID:25482526

  19. Biological Life Support Systems

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Session MP2 includes short reports on: (1) Crew Regenerative Life Support in Long Duration Space Missions; (2) Bioconversion Systems for Food and Water on Long Term Space Missions; (3) Novel Laboratory Approaches to Multi-purpose Aquatic Biogenerative Closed-Loop Food Production Systems; and (4) Artificial Neural Network Derived Plant Growth Models.

  20. Teaching Biological Systems.

    ERIC Educational Resources Information Center

    Walters, Julia

    1988-01-01

    Described is an activity which allows the investigation of human body systems using textbooks to enhance research skills and providing an opportunity for collaboration between pupils. Discussed are the purpose, materials, method, and results of this teaching method. Reported are some of the advantages of using this activity in teaching systems.…

  1. Proteomics technology in systems biology.

    PubMed

    Smith, Jeffrey C; Figeys, Daniel

    2006-08-01

    It has now become apparent that a full understanding of a biological process (e.g. a disease state) is only possible if all biomolecular interactions are taken into account. Systems biology works towards understanding the intricacies of cellular life through the collaborative efforts of biologists, chemists, mathematicians and computer scientists and recently, a number of laboratories around the world have embarked upon such research agendas. The fields of genomics and proteomics are foundational in systems biology studies and a great deal of research is currently being conducted in each worldwide. Moreover, many technological advances (particularly in mass spectrometry) have led to a dramatic rise in the number of proteomic studies over the past two decades. This short review summarizes a selection of technological innovations in proteomics that contribute to systems biology studies. PMID:16880956

  2. Modeling formalisms in Systems Biology

    PubMed Central

    2011-01-01

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

  3. Modeling formalisms in Systems Biology.

    PubMed

    Machado, Daniel; Costa, Rafael S; Rocha, Miguel; Ferreira, Eugénio C; Tidor, Bruce; Rocha, Isabel

    2011-01-01

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

  4. Systems Biology and immune aging.

    PubMed

    O'Connor, José-Enrique; Herrera, Guadalupe; Martínez-Romero, Alicia; de Oyanguren, Francisco Sala; Díaz, Laura; Gomes, Angela; Balaguer, Susana; Callaghan, Robert C

    2014-11-01

    Many alterations of innate and adaptive immunity are common in the aging population, which reflect a deterioration of the immune system, and have lead to the terms "immune aging" or "immunosenescence". Systems Biology aims to the comprehensive knowledge of the structure, dynamics, control and design that define a given biological system. Systems Biology benefits from the continuous advances in the omics sciences, based on high-throughput and high-content technologies, as well as on bioinformatic tools for data mining and integration. The Systems Biology approach is becoming gradually used to propose and to test comprehensive models of aging, both at the level of the immune system and the whole organism. In this way, immune aging may be described by a dynamic view of the states and interactions of every individual cell and molecule of the immune system and their role in the context of aging and longevity. This mini-review presents a panoramics of the current strategies, tools and challenges for applying Systems Biology to immune aging.

  5. Kinetic Modeling of Biological Systems

    PubMed Central

    Petzold, Linda; Pettigrew, Michel F.

    2010-01-01

    The dynamics of how the constituent components of a natural system interact defines the spatio-temporal response of the system to stimuli. Modeling the kinetics of the processes that represent a biophysical system has long been pursued with the aim of improving our understanding of the studied system. Due to the unique properties of biological systems, in addition to the usual difficulties faced in modeling the dynamics of physical or chemical systems, biological simulations encounter difficulties that result from intrinsic multiscale and stochastic nature of the biological processes. This chapter discusses the implications for simulation of models involving interacting species with very low copy numbers, which often occur in biological systems and give rise to significant relative fluctuations. The conditions necessitating the use of stochastic kinetic simulation methods and the mathematical foundations of the stochastic simulation algorithms are presented. How the well-organized structural hierarchies often seen in biological systems can lead to multiscale problems, and possible ways to address the encountered computational difficulties are discussed. We present the details of the existing kinetic simulation methods, and discuss their strengths and shortcomings. A list of the publicly available kinetic simulation tools and our reflections for future prospects are also provided. PMID:19381542

  6. Circadian systems biology in Metazoa.

    PubMed

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

    2015-11-01

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

  7. Reaction chemistry of nitrogen species in hydrothermal systems: Simple reactions, waste simulants, and actual wastes

    SciTech Connect

    Dell`Orco, P.; Luan, L.; Proesmans, P.; Wilmanns, E.

    1995-02-01

    Results are presented from hydrothermal reaction systems containing organic components, nitrogen components, and an oxidant. Reaction chemistry observed in simple systems and in simple waste simulants is used to develop a model which presents global nitrogen chemistry in these reactive systems. The global reaction path suggested is then compared with results obtained for the treatment of an actual waste stream containing only C-N-0-H species.

  8. The Systems Biology Graphical Notation.

    PubMed

    Le Novère, Nicolas; Hucka, Michael; Mi, Huaiyu; Moodie, Stuart; Schreiber, Falk; Sorokin, Anatoly; Demir, Emek; Wegner, Katja; Aladjem, Mirit I; Wimalaratne, Sarala M; Bergman, Frank T; Gauges, Ralph; Ghazal, Peter; Kawaji, Hideya; Li, Lu; Matsuoka, Yukiko; Villéger, Alice; Boyd, Sarah E; Calzone, Laurence; Courtot, Melanie; Dogrusoz, Ugur; Freeman, Tom C; Funahashi, Akira; Ghosh, Samik; Jouraku, Akiya; Kim, Sohyoung; Kolpakov, Fedor; Luna, Augustin; Sahle, Sven; Schmidt, Esther; Watterson, Steven; Wu, Guanming; Goryanin, Igor; Kell, Douglas B; Sander, Chris; Sauro, Herbert; Snoep, Jacky L; Kohn, Kurt; Kitano, Hiroaki

    2009-08-01

    Circuit diagrams and Unified Modeling Language diagrams are just two examples of standard visual languages that help accelerate work by promoting regularity, removing ambiguity and enabling software tool support for communication of complex information. Ironically, despite having one of the highest ratios of graphical to textual information, biology still lacks standard graphical notations. The recent deluge of biological knowledge makes addressing this deficit a pressing concern. Toward this goal, we present the Systems Biology Graphical Notation (SBGN), a visual language developed by a community of biochemists, modelers and computer scientists. SBGN consists of three complementary languages: process diagram, entity relationship diagram and activity flow diagram. Together they enable scientists to represent networks of biochemical interactions in a standard, unambiguous way. We believe that SBGN will foster efficient and accurate representation, visualization, storage, exchange and reuse of information on all kinds of biological knowledge, from gene regulation, to metabolism, to cellular signaling.

  9. Workshop Introduction: Systems Biology and Biological Models

    EPA Science Inventory

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

  10. Systems biology approach to bioremediation

    SciTech Connect

    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’.

  11. Systems Biology of Industrial Microorganisms

    NASA Astrophysics Data System (ADS)

    Papini, Marta; Salazar, Margarita; Nielsen, Jens

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

  12. Leak Locating Experiment for Actual Underground Water Supply Pipelines with a Novel Locating System

    NASA Astrophysics Data System (ADS)

    Lee, Young-Sup; Yoon, Dong-Jin; Kang, Seokhoon; Jun, Kyungkoo; Choi, Byoungjo

    This paper presents a novel leak locating system to identify precise position of leak spots of underground water supply pipelines. The system has been studied and developed upon excellent foundation with modern mobile communication technology and the internet. However, the leak locating algorithm in the new system requires knowing the exact acoustical wave speed inside water-filled pipelines and the accurate time arrival difference between sensors to detect precise leak location. Especially the time difference is calculated with optimal maximum likelihood method. For the demonstration of the new system, an intensive experiment performed with 315 m long actual underground water supply pipelines showed an excellent detection capability.

  13. Biologically inspired dynamic material systems.

    PubMed

    Studart, André R

    2015-03-01

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

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

    PubMed Central

    Chen, Bor-Sen; Wu, Chia-Chou

    2013-01-01

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

  15. Bridging the gap between systems biology and synthetic biology

    PubMed Central

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

    2013-01-01

    Systems biology is an inter-disciplinary science that studies the complex interactions and the collective behavior of a cell or an organism. Synthetic biology, as a technological subject, combines biological science and engineering, allowing the design and manipulation of a system for certain applications. Both systems and synthetic biology have played important roles in the recent development of microbial platforms for energy, materials, and environmental applications. More importantly, systems biology provides the knowledge necessary for the development of synthetic biology tools, which in turn facilitates the manipulation and understanding of complex biological systems. Thus, the combination of systems and synthetic biology has huge potential for studying and engineering microbes, especially to perform advanced tasks, such as producing biofuels. Although there have been very few studies in integrating systems and synthetic biology, existing examples have demonstrated great power in extending microbiological capabilities. This review focuses on recent efforts in microbiological genomics, transcriptomics, proteomics, and metabolomics, aiming to fill the gap between systems and synthetic biology. PMID:23898328

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

    PubMed

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

    2013-01-01

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

  17. System biology of gene regulation.

    PubMed

    Baitaluk, Michael

    2009-01-01

    ) questions of biological relevance. Thus systems biology could be treated as such a socioscientific phenomenon and a new approach to both experiments and theory that is defined by the strategy of pursuing integration of complex data about the interactions in biological systems from diverse experimental sources using interdisciplinary tools and personnel. PMID:19623486

  18. Mining literature for systems biology.

    PubMed

    Roberts, Phoebe M

    2006-12-01

    Currently, literature is integrated in systems biology studies in three ways. Hand-curated pathways have been sufficient for assembling models in numerous studies. Second, literature is frequently accessed in a derived form, such as the concepts represented by the Medical Subject Headings (MeSH) and Gene Ontologies (GO), or functional relationships captured in protein-protein interaction (PPI) databases; both of these are convenient, consistent reductions of more complex concepts expressed as free text in the literature. Moreover, their contents are easily integrated into computational processes required for dealing with large data sets. Last, mining text directly for specific types of information is on the rise as text analytics methods become more accurate and accessible. These uses of literature, specifically manual curation, derived concepts captured in ontologies and databases, and indirect and direct application of text mining, will be discussed as they pertain to systems biology.

  19. Systems biology of diuretic resistance

    PubMed Central

    Knepper, Mark A.

    2015-01-01

    Diuretics are commonly used to treat hypertension and extracellular fluid volume expansion. However, the development of compensatory responses in the kidney limits the benefit of this class of drugs. In this issue of the JCI, Grimm and colleagues use a systems biology approach in mice lacking the kinase SPAK and unravel a complex mechanism that explains thiazide diuretic resistance. The overall process involves interactions among six different cell types in the kidney. PMID:25893597

  20. Anion binding in biological systems

    NASA Astrophysics Data System (ADS)

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

    2009-11-01

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

  1. Optimum Design of a Passive Suspension System of a Vehicle Subjected to Actual Random Road Excitations

    NASA Astrophysics Data System (ADS)

    Tamboli, J. A.; Joshi, S. G.

    1999-01-01

    Vehicles are subjected to random excitation due to road unevenness and variable velocity. In most research work reported earlier, the response analysis for Mean Square Acceleration Response (MSAR) has been carried out by considering the power spectral density (PSD) of the road excitation as white noise, and the velocity of the vehicle as constant. However, in the present paper the PSD of the actual road excitation has been found to follow an approximately exponentially decreasing curve. Also the change in vehicle velocity has a significant effect on the values of Root Mean Square Acceleration Response (RMSAR). Therefore, in this work, the RMSAR of a vehicle dynamic system subjected to actual random road excitations is obtained so as to account for the effect of the actual PSD of road excitation and the frequent changes in vehicle velocity. The RMSAR of the vehicle is calculated for actual field excitation using the Fast Fourier Transformation (FFT) technique to obtain the PSD, by recording observations at the rear wheel. The effect of time lag due to wheelbase on the RMSAR of the vehicle is studied. For this purpose, a new ratio α(τ) has been introduced. The relationship between α(τ) and the autocorrelation has been formulated. This ratio is useful for considering the effect of time lag due to wheelbase on RMSAR. Similarly, the effect of vehicle velocity on the RMSAR is obtained.Further, from a ride comfort point of view, the values of the design variables like spring stiffness and viscous damping coefficient of the front and rear suspensions have been obtained, by minimising the RMSAR using the desired boundary values of the vertical RMSAR as specified in the chart of ISO 2631, 1985(E) [1].

  2. Autonomous Biological System (ABS) experiments.

    PubMed

    MacCallum, T K; Anderson, G A; Poynter, J E; Stodieck, L S; Klaus, D M

    1998-12-01

    Three space flight experiments have been conducted to test and demonstrate the use of a passively controlled, materially closed, bioregenerative life support system in space. The Autonomous Biological System (ABS) provides an experimental environment for long term growth and breeding of aquatic plants and animals. The ABS is completely materially closed, isolated from human life support systems and cabin atmosphere contaminants, and requires little need for astronaut intervention. Testing of the ABS marked several firsts: the first aquatic angiosperms to be grown in space; the first higher organisms (aquatic invertebrate animals) to complete their life cycles in space; the first completely bioregenerative life support system in space; and, among the first gravitational ecology experiments. As an introduction this paper describes the ABS, its flight performance, advantages and disadvantages.

  3. Systems biology of the microvasculature.

    PubMed

    Clegg, Lindsay E; Mac Gabhann, Feilim

    2015-05-01

    The vascular network carries blood throughout the body, delivering oxygen to tissues and providing a pathway for communication between distant organs. The network is hierarchical and structured, but also dynamic, especially at the smaller scales. Remodeling of the microvasculature occurs in response to local changes in oxygen, gene expression, cell-cell communication, and chemical and mechanical stimuli from the microenvironment. These local changes occur as a result of physiological processes such as growth and exercise, as well as acute and chronic diseases including stroke, cancer, and diabetes, and pharmacological intervention. While the vasculature is an important therapeutic target in many diseases, drugs designed to inhibit vascular growth have achieved only limited success, and no drug has yet been approved to promote therapeutic vascular remodeling. This highlights the challenges involved in identifying appropriate therapeutic targets in a system as complex as the vasculature. Systems biology approaches provide a means to bridge current understanding of the vascular system, from detailed signaling dynamics measured in vitro and pre-clinical animal models of vascular disease, to a more complete picture of vascular regulation in vivo. This will translate to an improved ability to identify multi-component biomarkers for diagnosis, prognosis, and monitoring of therapy that are easy to measure in vivo, as well as better drug targets for specific disease states. In this review, we summarize systems biology approaches that have advanced our understanding of vascular function and dysfunction in vivo, with a focus on computational modeling.

  4. Biological diversity in the patent system.

    PubMed

    Oldham, Paul; Hall, Stephen; Forero, Oscar

    2013-01-01

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

  5. Biological Diversity in the Patent System

    PubMed Central

    Oldham, Paul; Hall, Stephen; Forero, Oscar

    2013-01-01

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

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

    PubMed Central

    Cazier, Joseph A; Medlin, B. Dawn

    2006-01-01

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

  7. [Network structures in biological systems].

    PubMed

    Oleskin, A V

    2013-01-01

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

  8. Systems biology of neurodegenerative diseases.

    PubMed

    Wood, Levi B; Winslow, Ashley R; Strasser, Samantha Dale

    2015-07-01

    Neurodegenerative diseases (NDs) collectively afflict more than 40 million people worldwide. The majority of these diseases lack therapies to slow or stop progression due in large part to the challenge of disentangling the simultaneous presentation of broad, multifaceted pathophysiologic changes. Present technologies and computational capabilities suggest an optimistic future for deconvolving these changes to identify novel mechanisms driving ND onset and progression. In particular, integration of highly multi-dimensional omic analytical techniques (e.g., microarray, mass spectrometry) with computational systems biology approaches provides a systematic methodology to elucidate new mechanisms driving NDs. In this review, we begin by summarizing the complex pathophysiology of NDs associated with protein aggregation, emphasizing the shared complex dysregulation found in all of these diseases, and discuss available experimental ND models. Next, we provide an overview of technological and computational techniques used in systems biology that are applicable to studying NDs. We conclude by reviewing prior studies that have applied these approaches to NDs and comment on the necessity of combining analysis from both human tissues and model systems to identify driving mechanisms. We envision that the integration of computational approaches with multiple omic analyses of human tissues, and mouse and in vitro models, will enable the discovery of new therapeutic strategies for these devastating diseases.

  9. Systems biology of Microbial Communities

    SciTech Connect

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

    2008-04-11

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

  10. The primary test of measuremental system for the actual emittance of relativistic electron beams

    SciTech Connect

    Liang Fu; Tai-bin Du; Xin Chen

    1995-12-31

    Recent, a new measuremental system has been established basically in Tsinghua University PRA. This system is able to measure the lower emittance of the electron beams from the RF accelerators for the FEL. It consists of a scanning magnetic field, a slit, a fluorescent screen, and a TV camera, an image processing system, a CAD 386 computer. Using it an actual phase diagram is obtained for 4-10 Mev electron beams, The principle and structure of the facility were reported in the Proceeding of the 15th FEL Conference. This paper describes the performance of the main components and the results of first measurement for the electron gun and 4Mev standing wave LINAC, Some new suggests are related too.

  11. Mass spectrometry in systems biology an introduction.

    PubMed

    Dunn, Warwick B

    2011-01-01

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

  12. Systems biology and biomarker discovery

    SciTech Connect

    Rodland, Karin D.

    2010-12-01

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

  13. Systems Biology of Fungal Infection

    PubMed Central

    Horn, Fabian; Heinekamp, Thorsten; Kniemeyer, Olaf; Pollmächer, Johannes; Valiante, Vito; Brakhage, Axel A.

    2012-01-01

    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 behaviors 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 modeling 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. PMID:22485108

  14. Magnetic heterogeneity of biological systems.

    PubMed

    Piruzyan, L A; Kuznetsov, A A; Chikov, V M

    1980-01-01

    In biological systems nonuniformity of magnetic susceptibility, magnetic heterogeneity, is a reflection of their physical-chemical and morphological heterogeneity, A characteristic value of heterogeneity is delta K approximately 10(-6)-10(-7) CGS units, a quantitative measurement of susceptibility of cells and other small objects, may give qualitatively new information about their life processes. Patterns and features of movement of small biological objects and liquids affected by magnetic forces were studied. A method was developed for measuring magnetic susceptibility of single microobjects based on observation of movement of the objects in a strong heterogeneous field with parameters (formula: see text) grad H2/2 approximately 10(9)-10(10) Oe2/cm. This method does not require knowing the distribution of the field along the path of movement of the particles, and does not require preliminary calibration. Movement of human erythrocytes, rat hepatocytes, and starch granules in liquids at a point of entry into a gap with the field was observed experimentally. With sufficiently large fields Ho approximately (1-2) x 10(4) Oe, the value of the magnetic force was enough to change the rate of sedimentation movement of the objects appreciably (up to stopping it). This made it possible to compute the value delta K for cells approximately 10(-7)-10(-8) CGS units and to obtain the value of K for starch granules (-0.80 x 10(-6) cGS units). In connection with the fact that sensitivity to gravity in plants is coupled with a disturbance of the intracellular starch granules under the influence of gravity, certain problems of stimulating the effect of gravity on plants by magnetic forces were studied. Noncontact force effect on magnetically heterogeneous biological objects is a promising instrument for biophysical studies.

  15. Quantum Effects in Biological Systems

    NASA Astrophysics Data System (ADS)

    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.

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

    NASA Technical Reports Server (NTRS)

    McCloud, Peter L.

    2010-01-01

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

  17. Fostering synergy between cell biology and systems biology.

    PubMed

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

    2015-08-01

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

  18. Fostering synergy between cell biology and systems biology

    PubMed Central

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

    2015-01-01

    In the shared pursuit of elucidating detailed mechanisms of cell function, systems biology presents a natural complement to ongoing efforts in cell biology. Systems biology aims to characterize biological systems through integrated and quantitative modeling of cellular information. The process of model building and analysis provides value through synthesizing and cataloging information about cells and molecules; predicting mechanisms and identifying generalizable themes; generating hypotheses and guiding experimental design; and highlighting knowledge gaps and refining understanding. In turn, incorporating domain expertise and experimental data is critical for building towards whole cell models. An iterative cycle of interaction between cell and systems biologists advances the goals of both fields and establishes a framework for mechanistic understanding of the genome-to-phenome relationship. PMID:26013981

  19. Principles of Systems Biology, No. 8.

    PubMed

    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

  20. Actual versus design performance of solar systems in the National Solar Data Network

    NASA Astrophysics Data System (ADS)

    Logee, T. L.; Kendall, P. W.

    1984-09-01

    Field measured performance were compared to the designer predicted performance. The field measured data were collected by the National Solar Data Network (NSDN) over a period of 6 years. Data from 25 solar systems were selected from a data pool of some 170 solar systems. Several concerns arose which can be partially allayed by study of the NSDN data. These are: what types of failures occurred and why; how good was the design versus actual performance; why was predicted performance not achieved in the field; and which components should be integrated with a system type for good performance. The measured results were also compared to f-chart 5.1 results. This comparison is a type of normalization in that all systems are modeled with the same process. An added benefit of this normalization is a further validation of the f-Chart model on a fairly large scale. The systems are modeled using equipment design parameters, measured loads, and f-Chart weather data from nearby cities.

  1. Proving Stabilization of Biological Systems

    NASA Astrophysics Data System (ADS)

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

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

  2. A SYSTEMS BIOLOGY APPROACH TO DEVELOPMENTAL TOXICOLOGY

    EPA Science Inventory

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

  3. INTERNATIONAL CONFERENCE ON INTELLIGENT SYSTEMS FOR MOLECULAR BIOLOGY (ISMB)

    SciTech Connect

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

    2009-12-29

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

  4. Biologically erodable microspheres as potential oral drug delivery systems

    NASA Astrophysics Data System (ADS)

    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. Spatial Aspects in Biological System Simulations

    PubMed Central

    Resat, Haluk; Costa, Michelle N.; Shankaran, Harish

    2012-01-01

    Mathematical models of the dynamical properties of biological systems aim to improve our understanding of the studied system with the ultimate goal of being able to predict system responses in the absence of experimentation. Despite the enormous advances that have been made in biological modeling and simulation, the inherently multiscale character of biological systems and the stochasticity of biological processes continue to present significant computational and conceptual challenges. Biological systems often consist of well-organized structural hierarchies, which inevitably lead to multiscale problems. This chapter introduces and discusses the advantages and shortcomings of several simulation methods that are being used by the scientific community to investigate the spatiotemporal properties of model biological systems. We first describe the foundations of the methods and then describe their relevance and possible application areas with illustrative examples from our own research. Possible ways to address the encountered computational difficulties are also discussed. PMID:21187236

  6. Introducing systems biology for nursing science.

    PubMed

    Founds, Sandra A

    2009-07-01

    Systems biology expands on general systems theory as the "omics'' era rapidly progresses. Although systems biology has been institutionalized as an interdisciplinary framework in the biosciences, it is not yet apparent in nursing. This article introduces systems biology for nursing science by presenting an overview of the theory. This framework for the study of organisms from molecular to environmental levels includes iterations of computational modeling, experimentation, and theory building. Synthesis of complex biological processes as whole systems rather than isolated parts is emphasized. Pros and cons of systems biology are discussed, and relevance of systems biology to nursing is described. Nursing research involving molecular, physiological, or biobehavioral questions may be guided by and contribute to the developing science of systems biology. Nurse scientists can proactively incorporate systems biology into their investigations as a framework for advancing the interdisciplinary science of human health care. Systems biology has the potential to advance the research and practice goals of the National Institute for Nursing Research in the National Institutes of Health Roadmap initiative. PMID:19221104

  7. Systems biology approaches in aging research.

    PubMed

    Chauhan, Anuradha; Liebal, Ulf W; Vera, Julio; Baltrusch, Simone; Junghanß, Christian; Tiedge, Markus; Fuellen, Georg; Wolkenhauer, Olaf; Köhling, Rüdiger

    2015-01-01

    Aging is a systemic process which progressively manifests itself at multiple levels of structural and functional organization from molecular reactions and cell-cell interactions in tissues to the physiology of an entire organ. There is ever increasing data on biomedical relevant network interactions for the aging process at different scales of time and space. To connect the aging process at different structural, temporal and spatial scales, extensive systems biological approaches need to be deployed. Systems biological approaches can not only systematically handle the large-scale datasets (like high-throughput data) and the complexity of interactions (feedback loops, cross talk), but also can delve into nonlinear behaviors exhibited by several biological processes which are beyond intuitive reasoning. Several public-funded agencies have identified the synergistic role of systems biology in aging research. Using one of the notable public-funded programs (GERONTOSYS), we discuss how systems biological approaches are helping the scientists to find new frontiers in aging research. We elaborate on some systems biological approaches deployed in one of the projects of the consortium (ROSage). The systems biology field in aging research is at its infancy. It is open to adapt existing systems biological methodologies from other research fields and devise new aging-specific systems biological methodologies.

  8. Systems biology and cardiac arrhythmias

    PubMed Central

    Grace, Andrew A; Roden, Dan M

    2013-01-01

    During the past few years, the development of effective, empirical technologies for treatment of cardiac arrhythmias has exceeded the pace at which detailed knowledge of the underlying biology has accumulated. As a result, although some clinical arrhythmias can be cured with techniques such as catheter ablation, drug treatment and prediction of the risk of sudden death remain fairly primitive. The identification of key candidate genes for monogenic arrhythmia syndromes shows that to bring basic biology to the clinic is a powerful approach. Increasingly sophisticated experimental models and methods of measurement, including stem cell-based models of human cardiac arrhythmias, are being deployed to study how perturbations in several biologic pathways can result in an arrhythmia-prone heart. The biology of arrhythmia is largely quantifiable, which allows for systematic analysis that could transform treatment strategies that are often still empirical into management based on molecular evidence. PMID:23101717

  9. Systems biology and cardiac arrhythmias.

    PubMed

    Grace, Andrew A; Roden, Dan M

    2012-10-27

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

  10. Systems biology and mechanics of growth.

    PubMed

    Eskandari, Mona; Kuhl, Ellen

    2015-01-01

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

  11. Method of measurement in biological systems

    DOEpatents

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

    1993-05-11

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

  12. Genomes, Phylogeny, and Evolutionary Systems Biology

    SciTech Connect

    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.

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

    PubMed

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

    2009-12-20

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

  14. Developmental systems biology flourishing on new technologies.

    PubMed

    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

  15. Applicability of computational systems biology in toxicology.

    PubMed

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

    2014-07-01

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

  16. Soil water availability as controlling factor for actual evapotranspiration in urban soil-vegetation-systems

    NASA Astrophysics Data System (ADS)

    Thomsen, Simon; Reisdorff, Christoph; Gröngröft, Alexander; Jensen, Kai; Eschenbach, Annette

    2015-04-01

    The City of Hamburg is characterized by a large number of greens, parks and roadside trees: 600.000 trees cover about 14% of the city area, and moreover, 245.000 roadside trees can be found here. Urban vegetation is generally known to positively contribute to the urban micro-climate via cooling by evapotranspiration (ET). The water for ET is predominantly stored in the urban soils. Hence, the actual evapotranspiration (ETa) is - beside atmospheric drivers - determined by soil water availability at the soil surface and in the rooting zones of the respective vegetation. The overall aim of this study is to characterize soil water availability as a regulative factor for ETa in urban soil-vegetation systems. The specific questions addressed are: i) What is the spatio-temporal variation in soil water availability at the study sites? ii) Which soil depths are predominantly used for water uptake by the vegetation forms investigated? and iii) Which are the threshold values of soil water tension and soil water content (Θ), respectively, that limit ETa under dry conditions on both grass-dominated and tree-dominated sites? Three study areas were established in the urban region of Hamburg, Germany. We selected areas featuring both single tree stands and grass-dominated sites, both representing typical vegetation forms in Hamburg. The areas are characterized by relatively dry soil conditions. However, they differ in regard to soil water availability. At each area we selected one site dominated by Common Oak (Quercus ruber L.) with ages from 40 to 120 years, and paired each oak tree site with a neighboring grass-dominated site. All field measurements were performed during the years 2013 and 2014. At each site, we continuously measured soil water tension and Θ up to 160 cm depth, and xylem sap flux of each of three oak trees per site in a 15 min-resolution. Furthermore, we measured soil hydraulic properties as pF-curve, saturated and unsaturated conductivity at all sites

  17. Systems Biology Analysis of Heterocellular Signaling.

    PubMed

    Tape, Christopher J

    2016-08-01

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

  18. Bridging the gaps in systems biology.

    PubMed

    Cvijovic, Marija; Almquist, Joachim; Hagmar, Jonas; Hohmann, Stefan; Kaltenbach, Hans-Michael; Klipp, Edda; Krantz, Marcus; Mendes, Pedro; Nelander, Sven; Nielsen, Jens; Pagnani, Andrea; Przulj, Natasa; Raue, Andreas; Stelling, Jörg; Stoma, Szymon; Tobin, Frank; Wodke, Judith A H; Zecchina, Riccardo; Jirstrand, Mats

    2014-10-01

    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 our understanding of many cellular processes. However, given the massive amount of qualitative and quantitative data currently produced and number of burning questions in health care and biotechnology needed to be solved is still in its early phases. The field requires novel approaches for abstraction, for modeling bioprocesses that follow different biochemical and biophysical rules, and for combining different modules into larger models that still allow realistic simulation with the computational power available today. We have identified and discussed currently most prominent problems in systems biology: (1) how to bridge different scales of modeling abstraction, (2) how to bridge the gap between topological and mechanistic modeling, and (3) how to bridge the wet and dry laboratory gap. The future success of systems biology largely depends on bridging the recognized gaps.

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

    ERIC Educational Resources Information Center

    Tribe, Michael; Pritchard, Alan J.

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

  20. A formal language for computational systems biology.

    PubMed

    Errampalli, Daniel D; Priami, Corrado; Quaglia, Paola

    2004-01-01

    The post-genomic era has opened new insights into the complex biochemical reaction systems present in the cell and has generated huge amount of information. The biological systems are highly complex and can overwhelm the numerically computable models. Therefore, models employing symbolical techniques might provide a faster insight. This paper presents some preliminary results and recent trends in the above direction. Specifically, it presents an overview of the main features of some formalisms and techniques from the field of specification languages for concurrency and mobility, which have been proposed to model and simulate the dynamics of the interaction of complex biological systems. The ultimate goal of these symbolic approaches is the modeling, analysis, simulation, and hopefully prediction of the behavior of biological systems (vs. biological components).

  1. Functional Translational Readthrough: A Systems Biology Perspective

    PubMed Central

    Schueren, Fabian

    2016-01-01

    Translational readthrough (TR) has come into renewed focus because systems biology approaches have identified the first human genes undergoing functional translational readthrough (FTR). FTR creates functional extensions to proteins by continuing translation of the mRNA downstream of the stop codon. Here we review recent developments in TR research with a focus on the identification of FTR in humans and the systems biology methods that have spurred these discoveries. PMID:27490485

  2. A framework for evolutionary systems biology

    PubMed Central

    Loewe, Laurence

    2009-01-01

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

  3. Functional Translational Readthrough: A Systems Biology Perspective.

    PubMed

    Schueren, Fabian; Thoms, Sven

    2016-08-01

    Translational readthrough (TR) has come into renewed focus because systems biology approaches have identified the first human genes undergoing functional translational readthrough (FTR). FTR creates functional extensions to proteins by continuing translation of the mRNA downstream of the stop codon. Here we review recent developments in TR research with a focus on the identification of FTR in humans and the systems biology methods that have spurred these discoveries. PMID:27490485

  4. Controlled vocabularies and semantics in systems biology

    PubMed Central

    Courtot, Mélanie; Juty, Nick; Knüpfer, Christian; Waltemath, Dagmar; Zhukova, Anna; Dräger, Andreas; Dumontier, Michel; Finney, Andrew; Golebiewski, Martin; Hastings, Janna; Hoops, Stefan; Keating, Sarah; Kell, Douglas B; Kerrien, Samuel; Lawson, James; Lister, Allyson; Lu, James; Machne, Rainer; Mendes, Pedro; Pocock, Matthew; Rodriguez, Nicolas; Villeger, Alice; Wilkinson, Darren J; Wimalaratne, Sarala; Laibe, Camille; Hucka, Michael; Le Novère, Nicolas

    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 three ontologies created specifically to address the needs of the systems biology community. The Systems Biology Ontology (SBO) provides semantic information about the model components. The Kinetic Simulation Algorithm Ontology (KiSAO) supplies information about existing algorithms available for the simulation of systems biology models, their characterization and interrelationships. The Terminology for the Description of Dynamics (TEDDY) categorizes dynamical features of the simulation results and general systems behavior. The provision of semantic information extends a model's longevity and facilitates its reuse. It provides useful insight into the biology of modeled processes, and may be used to make informed decisions on subsequent simulation experiments. PMID:22027554

  5. A Philosophical Perspective on Evolutionary Systems Biology

    PubMed Central

    Soyer, Orkun S.; Siegal, Mark L.

    2015-01-01

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

  6. Multiscale Computational Models of Complex Biological Systems

    PubMed Central

    Walpole, Joseph; Papin, Jason A.; Peirce, Shayn M.

    2014-01-01

    Integration of data across spatial, temporal, and functional scales is a primary focus of biomedical engineering efforts. The advent of powerful computing platforms, coupled with quantitative data from high-throughput experimental platforms, has allowed multiscale modeling to expand as a means to more comprehensively investigate biological phenomena in experimentally relevant ways. This review aims to highlight recently published multiscale models of biological systems while using their successes to propose the best practices for future model development. We demonstrate that coupling continuous and discrete systems best captures biological information across spatial scales by selecting modeling techniques that are suited to the task. Further, we suggest how to best leverage these multiscale models to gain insight into biological systems using quantitative, biomedical engineering methods to analyze data in non-intuitive ways. These topics are discussed with a focus on the future of the field, the current challenges encountered, and opportunities yet to be realized. PMID:23642247

  7. Omics/systems biology and cancer cachexia.

    PubMed

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

    2016-06-01

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

  8. Translational Systems Biology and Voice Pathophysiology

    PubMed Central

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

    2011-01-01

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

  9. Nonequilibrium Thermodynamics in Biological Systems

    NASA Astrophysics Data System (ADS)

    Aoki, I.

    2005-12-01

    1. Respiration Oxygen-uptake by respiration in organisms decomposes macromolecules such as carbohydrate, protein and lipid and liberates chemical energy of high quality, which is then used to chemical reactions and motions of matter in organisms to support lively order in structure and function in organisms. Finally, this chemical energy becomes heat energy of low quality and is discarded to the outside (dissipation function). Accompanying this heat energy, entropy production which inevitably occurs by irreversibility also is discarded to the outside. Dissipation function and entropy production are estimated from data of respiration. 2. Human body From the observed data of respiration (oxygen absorption), the entropy production in human body can be estimated. Entropy production from 0 to 75 years old human has been obtained, and extrapolated to fertilized egg (beginning of human life) and to 120 years old (maximum period of human life). Entropy production show characteristic behavior in human life span : early rapid increase in short growing phase and later slow decrease in long aging phase. It is proposed that this tendency is ubiquitous and constitutes a Principle of Organization in complex biotic systems. 3. Ecological communities From the data of respiration of eighteen aquatic communities, specific (i.e. per biomass) entropy productions are obtained. They show two phase character with respect to trophic diversity : early increase and later decrease with the increase of trophic diversity. The trophic diversity in these aquatic ecosystems is shown to be positively correlated with the degree of eutrophication, and the degree of eutrophication is an "arrow of time" in the hierarchy of aquatic ecosystems. Hence specific entropy production has the two phase: early increase and later decrease with time. 4. Entropy principle for living systems The Second Law of Thermodynamics has been expressed as follows. 1) In isolated systems, entropy increases with time and

  10. Systems biology: leading the revolution in ecotoxicology.

    PubMed

    Garcia-Reyero, Natàlia; Perkins, Edward J

    2011-02-01

    The rapid development of new technologies such as transcriptomics, proteomics, and metabolomics (Omics) are changing the way ecotoxicology is practiced. The data deluge has begun with genomes of over 65 different aquatic species that are currently being sequenced, and many times that number with at least some level of transcriptome sequencing. Integrating these top-down methodologies is an essential task in the field of systems biology. Systems biology is a biology-based interdisciplinary field that focuses on complex interactions in biological systems, with the intent to model and discover emergent properties of the system. Recent studies demonstrate that Omics technologies provide valuable insight into ecotoxicity, both in laboratory exposures with model organisms and with animals exposed in the field. However, these approaches require a context of the whole animal and population to be relevant. Powerful approaches using reverse engineering to determine interacting networks of genes, proteins, or biochemical reactions are uncovering unique responses to toxicants. Modeling efforts in aquatic animals are evolving to interrelate the interacting networks of a system and the flow of information linking these elements. Just as is happening in medicine, systems biology approaches that allow the integration of many different scales of interaction and information are already driving a revolution in understanding the impacts of pollutants on aquatic systems.

  11. Method of measurement in biological systems

    DOEpatents

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

    1994-01-01

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

  12. Method of measurement in biological systems

    DOEpatents

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

    1993-05-11

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

  13. Method of measurement in biological systems

    DOEpatents

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

    1994-12-27

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

  14. TOPICAL REVIEW: Inverse problems in systems biology

    NASA Astrophysics Data System (ADS)

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

    2009-12-01

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

  15. Ultrafast optics: Imaging and manipulating biological systems

    NASA Astrophysics Data System (ADS)

    Sheetz, Kraig E.; Squier, Jeff

    2009-03-01

    The rapid evolution of ultrafast optics technology over the past two decades has opened the window to a broad range of applications in biology and medicine. Compact, reliable, and turn-key ultrafast laser systems are enabling cutting-edge science to take place in everyday laboratories and clinics. Led by the discovery of two-photon excitation fluorescence microscopy nearly 20 years ago, the biological imaging community is exploring unique image contrast mechanisms and pushing spatial and temporal resolution to new limits. Concurrent with advancements in imaging are developments in the precision application of extremely high peak intensities available in ultrashort pulses for disrupting or manipulating targeted locations in biological systems on the submicron scale while leaving surrounding tissue healthy. The ability for scientists to selectively discriminate structures of interest at the cellular and subcellular levels under relevant physiological conditions shows tremendous promise for accelerating the path to understanding biological functions at the most fundamental level.

  16. New biologic therapy for systemic lupus erythematosus.

    PubMed

    Ding, Hui Jen; Gordon, Caroline

    2013-06-01

    Systemic lupus erythematosus (SLE) is a heterogenous multi-systemic autoimmune disease that is associated with considerable morbidity and mortality. Rituximab is one of the earliest biologic therapies used in SLE. It performed well in off-label studies but failed to demonstrate efficacy in randomised controlled trials. Abatacept is a biologic developed for inflammatory arthritis but has shown promise in SLE. Belimumab is the first biologically approved therapy in fifty years for treatment of SLE. The development of biological therapies for SLE parallels the increasing understanding of the immunopathogenesis of SLE and looks promising. New drugs in development are those targeting the co-stimulatory modulation, cytokines and the B and T cells. Of interest are epratuzumab, the interferon antagonists and peptide-based therapies.

  17. Natural production of biological optical systems

    NASA Astrophysics Data System (ADS)

    Choi, Seung Ho; Kim, Young L.

    2015-03-01

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

  18. Computational systems biology in cancer brain metastasis.

    PubMed

    Peng, Huiming; Tan, Hua; Zhao, Weiling; Jin, Guangxu; Sharma, Sambad; Xing, Fei; Watabe, Kounosuke; Zhou, Xiaobo

    2016-01-01

    Brain metastases occur in 20-40% of patients with advanced malignancies. A better understanding of the mechanism of this disease will help us to identify novel therapeutic strategies. In this review, we will discuss the systems biology approaches used in this area, including bioinformatics and mathematical modeling. Bioinformatics has been used for identifying the molecular mechanisms driving brain metastasis and mathematical modeling methods for analyzing dynamics of a system and predicting optimal therapeutic strategies. We will illustrate the strategies, procedures, and computational techniques used for studying systems biology in cancer brain metastases. We will give examples on how to use a systems biology approach to analyze a complex disease. Some of the approaches used to identify relevant networks, pathways, and possibly biomarkers in metastasis will be reviewed into details. Finally, certain challenges and possible future directions in this area will also be discussed.

  19. A Systems Biology Approach to Iron Metabolism

    PubMed Central

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

    2015-01-01

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

  20. Aquaporin Biology and Nervous System

    PubMed Central

    Barbara, Buffoli

    2010-01-01

    Our understanding of the movement of water through cell membranes has been greatly advanced by the discovery of a family of water-specific, membrane-channel proteins: the Aquaporins (AQPs). These proteins are present in organisms at all levels of life, and their unique permeability characteristics and distribution in numerous tissues indicate diverse roles in the regulation of water homeostasis. Phenotype analysis of AQP knock-out mice has confirmed the predicted role of AQPs in osmotically driven transepithelial fluid transport, as occurs in the urinary concentrating mechanism and glandular fluid secretion. Regarding their expression in nervous system, there are evidences suggesting that AQPs are differentially expressed in the peripheral versus central nervous system and that channel-mediated water transport mechanisms may be involved in cerebrospinal fluid formation, neuronal signal transduction and information processing. Moreover, a number of recent studies have revealed the importance of mammalian AQPs in both physiological and pathophysiological mechanisms and have suggested that pharmacological modulation of AQP expression and activity may provide new tools for the treatment of variety of human disorders in which water and small solute transport may be involved. For all the AQPs, new contributions to physiological functions are likely to be discovered with ongoing work in this rapidly expanding field of research. PMID:21119880

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

    PubMed

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

    2010-03-01

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

  2. Current advances in systems and integrative biology

    PubMed Central

    Robinson, Scott W.; Fernandes, Marco; Husi, Holger

    2014-01-01

    Systems biology has gained a tremendous amount of interest in the last few years. This is partly due to the realization that traditional approaches focusing only on a few molecules at a time cannot describe the impact of aberrant or modulated molecular environments across a whole system. Furthermore, a hypothesis-driven study aims to prove or disprove its postulations, whereas a hypothesis-free systems approach can yield an unbiased and novel testable hypothesis as an end-result. This latter approach foregoes assumptions which predict how a biological system should react to an altered microenvironment within a cellular context, across a tissue or impacting on distant organs. Additionally, re-use of existing data by systematic data mining and re-stratification, one of the cornerstones of integrative systems biology, is also gaining attention. While tremendous efforts using a systems methodology have already yielded excellent results, it is apparent that a lack of suitable analytic tools and purpose-built databases poses a major bottleneck in applying a systematic workflow. This review addresses the current approaches used in systems analysis and obstacles often encountered in large-scale data analysis and integration which tend to go unnoticed, but have a direct impact on the final outcome of a systems approach. Its wide applicability, ranging from basic research, disease descriptors, pharmacological studies, to personalized medicine, makes this emerging approach well suited to address biological and medical questions where conventional methods are not ideal. PMID:25379142

  3. Biodegradation of polyacrylamide by anaerobic digestion under mesophilic condition and its performance in actual dewatered sludge system.

    PubMed

    Dai, Xiaohu; Luo, Fan; Yi, Jing; He, Qunbiao; Dong, Bin

    2014-02-01

    Polyacrylamide (PAM) used in sludge dewatering widely exists in high-solid anaerobic digestion. Degradation of polyacrylamide accompanied with accumulation of its toxic monomer is important to disposition of biogas residues. The potential of anaerobic digestion activity in microbial utilization of PAM was investigated in this study. The results indicated that the utilization rate of PAM (as nitrogen source) was influenced by accumulation of ammonia, while cumulative removal of amide group was accorded with zeroth order reaction in actual dewatered system. The adjoining amide group can combined into ether group after biodegradation. PAM can be broken down in different position of its carbon chain backbone. In actual sludge system, the hydrolytic PAM was liable to combined tyrosine-rich protein to form colloid complex, and then consumed as carbon source to form monomer when easily degradable organics were exhausted. The accumulation of acrylamide was leveled off ultimately, accompanied with the yield of methane.

  4. Systems Biology Approaches to New Vaccine Development

    PubMed Central

    Oberg, Ann L.; Kennedy, Richard B.; Li, Peter; Ovsyannikova, Inna G.; Poland, Gregory A.

    2011-01-01

    Summary The current “isolate, inactivate, inject” vaccine development strategy has served the field of vaccinology well, and such empirical vaccine candidate development has even led to the eradication of smallpox. However, such an approach suffers from limitations, and as an empirical approach, does not fully utilize our knowledge of immunology and genetics. A more complete understanding of the biological processes culminating in disease resistance is needed. The advent of high-dimensional assay technology and “systems biology” along with a vaccinomics approach [1;2] is spawning a new era in the science of vaccine development. Here we review recent developments in systems biology and strategies for applying this approach and its resulting data to expand our knowledge base and drive directed development of new vaccines. We also provide applied examples and point out new directions for the field in order to illustrate the power of systems biology. PMID:21570272

  5. Systems medicine: evolution of systems biology from bench to bedside.

    PubMed

    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 pathways and regulatory networks rather than individual failing components. Systems biology not only facilitates basic biological research but also provides new avenues through which to understand human diseases, identify diagnostic biomarkers, and develop disease treatments. At the same time, systems biology seeks to assist in drug discovery, drug optimization, drug combinations, and drug repositioning by investigating the molecular mechanisms of action of drugs at a system's level. Indeed, systems biology is evolving to systems medicine as a new discipline that aims to offer new approaches for addressing the diagnosis and treatment of major human diseases uniquely, effectively, and with personalized precision.

  6. Systems Biology Approach to Developing “Systems Therapeutics”

    PubMed Central

    2014-01-01

    The standard drug development model uses reductionist approaches to discover small molecules targeting one pathway. Although systems biology analyzes multiple pathways, the approach is often used to develop a small molecule interacting at only one pathway in the system. Similar to that in physics where a departure from the old reductionist “Copenhagen View” of quantum physics to a new and predictive systems based, collective model has emerged yielding new breakthroughs such as the LASER, a new model is emerging in biology where systems biology is used to develop a new technology acting at multiple pathways called “systems therapeutics.” PMID:24900858

  7. Complexity in cancer biology: is systems biology the answer?

    PubMed Central

    Koutsogiannouli, Evangelia; Papavassiliou, Athanasios G; Papanikolaou, Nikolaos A

    2013-01-01

    Complex phenotypes emerge from the interactions of thousands of macromolecules that are organized in multimolecular complexes and interacting functional modules. In turn, modules form functional networks in health and disease. Omics approaches collect data on changes for all genes and proteins and statistical analysis attempts to uncover the functional modules that perform the functions that characterize higher levels of biological organization. Systems biology attempts to transcend the study of individual genes/proteins and to integrate them into higher order information. Cancer cells exhibit defective genetic and epigenetic networks formed by altered complexes and network modules arising in different parts of tumor tissues that sustain autonomous cell behavior which ultimately lead tumor growth. We suggest that an understanding of tumor behavior must address not only molecular but also, and more importantly, tumor cell heterogeneity, by considering cancer tissue genetic and epigenetic networks, by characterizing changes in the types, composition, and interactions of complexes and networks in the different parts of tumor tissues, and by identifying critical hubs that connect them in time and space. PMID:23634284

  8. Standards and Ontologies in Computational Systems Biology

    PubMed Central

    Sauro, Herbert M.; Bergmann, Frank

    2009-01-01

    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 developer libraries and basic editing tools are also introduced together with a discussion on the future of modeling languages and visualization tools in systems biology. PMID:18793134

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

    PubMed Central

    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 pathways and regulatory networks rather than individual failing components. Systems biology not only facilitates basic biological research, but also provides new avenues through which to understand human diseases, identify diagnostic biomarkers, and develop disease treatments. At the same time, systems biology seeks to assist in drug discovery, drug optimization, drug combinations, and drug repositioning by investigating the molecular mechanisms of action of drugs at a system’s level. Indeed, systems biology is evolving to systems medicine as a new discipline that aims to offer new approaches for addressing the diagnosis and treatment of major human diseases uniquely, effectively, and with personalized precision. PMID:25891169

  10. Towards systems biology of mycotoxin regulation.

    PubMed

    Subramaniam, Rajagopal; Rampitsch, Christof

    2013-04-01

    Systems biology is a scientific approach that integrates many scientific disciplines to develop a comprehensive understanding of biological phenomena, thus allowing the prediction and accurate simulation of complex biological behaviors. It may be presumptuous to write about toxin regulation at the level of systems biology, but the last decade of research is leading us closer than ever to this approach. Past research has delineated multiple levels of regulation in the pathways leading to the biosynthesis of secondary metabolites, including mycotoxins. At the top of this hierarchy, the global or master transcriptional regulators perceive various environmental cues such as climatic conditions, the availability of nutrients, and the developmental stages of the organism. Information accumulated from various inputs is integrated through a complex web of signalling networks to generate the eventual outcome. This review will focus on adapting techniques such as chemical and other genetic tools available in the model system Saccharomyces cerevisiae, to disentangle the various biological networks involved in the biosynthesis of mycotoxins in the Fusarium spp.

  11. Semantic Annotation for Biological Information Retrieval System

    PubMed Central

    Oshaiba, Mohamed Marouf Z.; El Houby, Enas M. F.; Salah, Akram

    2015-01-01

    Online literatures are increasing in a tremendous rate. Biological domain is one of the fast growing domains. Biological researchers face a problem finding what they are searching for effectively and efficiently. The aim of this research is to find documents that contain any combination of biological process and/or molecular function and/or cellular component. This research proposes a framework that helps researchers to retrieve meaningful documents related to their asserted terms based on gene ontology (GO). The system utilizes GO by semantically decomposing it into three subontologies (cellular component, biological process, and molecular function). Researcher has the flexibility to choose searching terms from any combination of the three subontologies. Document annotation is taking a place in this research to create an index of biological terms in documents to speed the searching process. Query expansion is used to infer semantically related terms to asserted terms. It increases the search meaningful results using the term synonyms and term relationships. The system uses a ranking method to order the retrieved documents based on the ranking weights. The proposed system achieves researchers' needs to find documents that fit the asserted terms semantically. PMID:25737720

  12. Systems Biology — the Broader Perspective

    PubMed Central

    Bard, Jonathan

    2013-01-01

    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. PMID:24709708

  13. Semantic annotation for biological information retrieval system.

    PubMed

    Oshaiba, Mohamed Marouf Z; El Houby, Enas M F; Salah, Akram

    2015-01-01

    Online literatures are increasing in a tremendous rate. Biological domain is one of the fast growing domains. Biological researchers face a problem finding what they are searching for effectively and efficiently. The aim of this research is to find documents that contain any combination of biological process and/or molecular function and/or cellular component. This research proposes a framework that helps researchers to retrieve meaningful documents related to their asserted terms based on gene ontology (GO). The system utilizes GO by semantically decomposing it into three subontologies (cellular component, biological process, and molecular function). Researcher has the flexibility to choose searching terms from any combination of the three subontologies. Document annotation is taking a place in this research to create an index of biological terms in documents to speed the searching process. Query expansion is used to infer semantically related terms to asserted terms. It increases the search meaningful results using the term synonyms and term relationships. The system uses a ranking method to order the retrieved documents based on the ranking weights. The proposed system achieves researchers' needs to find documents that fit the asserted terms semantically.

  14. Self Organizing Systems and the Research Implications for Biological Systems

    NASA Astrophysics Data System (ADS)

    Denkins-Taffe, Lauren R.; Alfred, Marcus; Lindesay, James

    2008-03-01

    The knowledge gained from the human genome project, has provided an added opportunity to study the dynamical relationships within biological systems and can lead to an increased knowledge of diseases and subsequent drug discovery. Through computation, methods in which to rebuild these systems are being studied. These methods, which have first been applied to simpler systems: predator-prey, and self sustaining ecosystems can be applied to the study of microscopic biological systems.

  15. Discovery of Chemical Toxicity via Biological Networks and Systems Biology

    SciTech Connect

    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.

  16. Systems biology and physical biology of clathrin-mediated endocytosis.

    PubMed

    Ramanan, Vyas; Agrawal, Neeraj J; Liu, Jin; Engles, Sean; Toy, Randall; Radhakrishnan, Ravi

    2011-08-01

    In this review, we describe the application of experimental data and modeling of intracellular endocytic trafficking mechanisms with a focus on the process of clathrin-mediated endocytosis. A detailed parts-list for the protein-protein interactions in clathrin-mediated endocytosis has been available for some time. However, recent experimental, theoretical, and computational tools have proved to be critical in establishing a sequence of events, cooperative dynamics, and energetics of the intracellular process. On the experimental front, total internal reflection fluorescence microscopy, photo-activated localization microscopy, and spinning-disk confocal microscopy have focused on assembly and patterning of endocytic proteins at the membrane, while on the theory front, minimal theoretical models for clathrin nucleation, biophysical models for membrane curvature and bending elasticity, as well as methods from computational structural and systems biology, have proved insightful in describing membrane topologies, curvature mechanisms, and energetics.

  17. The Actual (Un)usefulness of the Bologna System in Medical Education

    PubMed Central

    Masic, Izet; Begic, Edin

    2016-01-01

    Introduction: Faculty of Medicine, University of Sarajevo has officially started working on 22.11.1944, and is the oldest faculty in the medical field in Bosnia and Herzegovina. At the same time there are two systems of organization of the teaching process, the old system and the Bologna system. Aim: To analyze the implementation of the Bologna system, and making an overview of its justification. Material and methods: Answers from questionnaires from total of 459 students were analyzed (197 who had studied under the old system and 262 who studied under the Bologna system), so total of four generations of the Bologna system. They filled out a questionnaire in which they evaluated the teaching process. Student’s opinion about quality of medical education was measured by modified Lickert scale. Results: Students of old system are older than students of the Bologna process, whose average age is increasing from generation to generation, given the growing number of students who repeat a year. All students of old system repeated an academic year once or several times (p <0.05). Analysis of average grades showed statistically significant difference (p <0.05), where students in the Bologna system had higher averages than students who were studying under the old system. The presence of large number of female students, in both systems is significant (p <0.05). Out of 33 questions about satisfaction of class, 15 were answered with better average grade from students of the Bologna system. A slight improvement in the Bologna system is in terms of the evaluation of the quality of the educational process (teachers, methods, effects). The only significant progress has been proven in terms of rating the degree of computerization of the educational process–general records on enrolled students (old system vs Bologna system–3,44 vs 3,63), record of attendance (3,47 vs 3,73), obtaining certificates (3,08 vs 3,84), method of registration of exam (2,98 vs 3,71), method of practical

  18. Cadmium and zinc interactions and their transfer in soil-crop system under actual field conditions.

    PubMed

    Nan, Zhongren; Li, Jijun; Zhang, Jianming; Cheng, Guodong

    2002-02-21

    The transfer of Cd and Zn from calcareous soils nearby a non-ferrous mining and smelting bases to the spring wheat (Triticum aestivum L.) and corn (Zea mays L.) tissues and the interactions between the two metals concerned were investigated under actual field conditions. Samples of soils and entire crops were randomly collected during harvest time in 1998 in the Baiyin region. The soil metal contents showed that the furrows had been polluted (mean values: 3.16 mg kg(-1) for Cd; 146.78 mg kg(-1) for Zn) and the significant spatial variation of the soil contamination existed here (ranges, Cd: 0.14-19.3 mg kg(-1); Zn: 43.5-565.0 mg kg(-1)). The translocation ratios of the two metals from soil to crop parts in the region studied were relatively lower and the order of the element transfer in different plant tissues was root > stem > grain. The transfer ratio of element Cd was lower than that of element Zn. Cd and Zn uptake by the crop structures could be best described by four models (P < 0.01): linear; exponential; quadratic; and cubic. Apart from a linear relationship between the element Cd in the corn grains and soils, models were generally non-lincar. An analysis of Cd-Zn interaction mechanism led to the conclusion that the effects of the two metals were synergistic to each other under field conditions, in which increasing Cd and Zn contents in soils could increase the accumulations of Zn or Cd in the two crops.

  19. Meeting report: Signal transduction meets systems biology

    PubMed Central

    2012-01-01

    In the 21st century, systems-wide analyses of biological processes are getting more and more realistic. Especially for the in depth analysis of signal transduction pathways and networks, various approaches of systems biology are now successfully used. The EU FP7 large integrated project SYBILLA (Systems Biology of T-cell Activation in Health and Disease) coordinates such an endeavor. By using a combination of experimental data sets and computational modelling, the consortium strives for gaining a detailed and mechanistic understanding of signal transduction processes that govern T-cell activation. In order to foster the interaction between systems biologists and experimentally working groups, SYBILLA co-organized the 15th meeting “Signal Transduction: Receptors, Mediators and Genes” together with the Signal Transduction Society (STS). Thus, the annual STS conference, held from November 7 to 9, 2011 in Weimar, Germany, provided an interdisciplinary forum for research on signal transduction with a major focus on systems biology addressing signalling events in T-cells. Here we report on a selection of ongoing projects of SYBILLA and how they were discussed at this interdisciplinary conference. PMID:22546078

  20. Systems biology data analysis methodology in pharmacogenomics

    PubMed Central

    Rodin, Andrei S; Gogoshin, Grigoriy; Boerwinkle, Eric

    2012-01-01

    Pharmacogenetics aims to elucidate the genetic factors underlying the individual’s response to pharmacotherapy. Coupled with the recent (and ongoing) progress in high-throughput genotyping, sequencing and other genomic technologies, pharmacogenetics is rapidly transforming into pharmacogenomics, while pursuing the primary goals of identifying and studying the genetic contribution to drug therapy response and adverse effects, and existing drug characterization and new drug discovery. Accomplishment of both of these goals hinges on gaining a better understanding of the underlying biological systems; however, reverse-engineering biological system models from the massive datasets generated by the large-scale genetic epidemiology studies presents a formidable data analysis challenge. In this article, we review the recent progress made in developing such data analysis methodology within the paradigm of systems biology research that broadly aims to gain a ‘holistic’, or ‘mechanistic’ understanding of biological systems by attempting to capture the entirety of interactions between the components (genetic and otherwise) of the system. PMID:21919609

  1. Macroscopic Quantum-Type Potentials in Theoretical Systems Biology

    PubMed Central

    Nottale, Laurent

    2014-01-01

    We review in this paper the use of the theory of scale relativity and fractal space-time as a tool particularly well adapted to the possible development of a future genuine systems theoretical biology. We emphasize in particular the concept of quantum-type potentials, since, in many situations, the effect of the fractality of space—or of the underlying medium—can be reduced to the addition of such a potential energy to the classical equations of motion. Various equivalent representations—geodesic, quantum-like, fluid mechanical, stochastic—of these equations are given, as well as several forms of generalized quantum potentials. Examples of their possible intervention in high critical temperature superconductivity and in turbulence are also described, since some biological processes may be similar in some aspects to these physical phenomena. These potential extra energy contributions could have emerged in biology from the very fractal nature of the medium, or from an evolutive advantage, since they involve spontaneous properties of self-organization, morphogenesis, structuration and multi-scale integration. Finally, some examples of applications of the theory to actual biological-like processes and functions are also provided. PMID:24709901

  2. Macroscopic quantum-type potentials in theoretical systems biology.

    PubMed

    Nottale, Laurent

    2013-01-01

    We review in this paper the use of the theory of scale relativity and fractal space-time as a tool particularly well adapted to the possible development of a future genuine systems theoretical biology. We emphasize in particular the concept of quantum-type potentials, since, in many situations, the effect of the fractality of space-or of the underlying medium-can be reduced to the addition of such a potential energy to the classical equations of motion. Various equivalent representations-geodesic, quantum-like, fluid mechanical, stochastic-of these equations are given, as well as several forms of generalized quantum potentials. Examples of their possible intervention in high critical temperature superconductivity and in turbulence are also described, since some biological processes may be similar in some aspects to these physical phenomena. These potential extra energy contributions could have emerged in biology from the very fractal nature of the medium, or from an evolutive advantage, since they involve spontaneous properties of self-organization, morphogenesis, structuration and multi-scale integration. Finally, some examples of applications of the theory to actual biological-like processes and functions are also provided. PMID:24709901

  3. Biological pathways as communicating computer systems.

    PubMed

    Kwiatkowska, Marta Z; Heath, John K

    2009-08-15

    Time and cost are the enemies of cell biology. The number of experiments required to rigorously dissect and comprehend a pathway of even modest complexity is daunting. Methods are needed to formulate biological pathways in a machine-analysable fashion, which would automate the process of considering all possible experiments in a complex pathway and identify those that command attention. In this Essay, we describe a method that is based on the exploitation of computational tools that were originally developed to analyse reactive communicating computer systems such as mobile phones and web browsers. In this approach, the biological process is articulated as an executable computer program that can be interrogated using methods that were developed to analyse complex software systems. Using case studies of the FGF, MAPK and Delta/Notch pathways, we show that the application of this technology can yield interesting insights into the behaviour of signalling pathways, which have subsequently been corroborated by experimental data. PMID:19657015

  4. Modular microfluidic system for biological sample preparation

    DOEpatents

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

    2015-09-29

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

  5. Radiological/biological/aerosol removal system

    DOEpatents

    Haslam, Jeffery J

    2015-03-17

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

  6. Studies on Semantic Systems Chemical Biology

    ERIC Educational Resources Information Center

    Chen, Bin

    2012-01-01

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

  7. Microbial Stress Tolerance for Biofuels: Systems Biology

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  8. Promoting Systems Thinking through Biology Lessons

    ERIC Educational Resources Information Center

    Riess, Werner; Mischo, Christoph

    2010-01-01

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

  9. Diagnostic opto-electronic system for measuring physical and biological characteristics of the skin in vivo

    NASA Astrophysics Data System (ADS)

    Makara, Ivanna V.; Kozhukhar, Oleksander T.; Komada, Pawel; Dussembayeva, Shynar

    2015-12-01

    Actuality development of optoelectronic rapid diagnostic system for measuring physical and biological characteristics of the skin in vivo with radiation of electromagnetic radiation in the optical range to obtain objective information on the spatial distribution of biochemical and morphological and anatomical components are different for state standards and pathology.

  10. Evaluation of the interactive chemistry of coal-petroleum systems using model and actual reactants

    SciTech Connect

    Curtis, C.W.; Chung, Wook Jin )

    1988-01-01

    The coprocessing of coal with petroleum residuum simultaneously liquefies coal and upgrades petroleum residuum into higher value products. However, coal and petroleum residuum manifest very different chemical properties with coal being more aromatic with a H/C ratio of 0.6 - 0.8 and petroleum residuum more aliphatic with a H/C ratio of 1.4 to 1.6. Although a number of studies have demonstrated the feasibility of coprocessing on the basis of product selectivity and metals reduction, the interactive chemistry involved between the coal and petroleum materials during coprocessing has not yet been determined. In this study, the interactive chemistry between coal and petroleum molecules has been examined: first by using model compound types representative of coal and residuum and then by combining the model systems with Illinois No. 6 coal and Maya topped long residuum (TLR). The model systems, composed of naphthalene (NAPH) representing aromatics, 1,4-dimethylcyclohexane (DMC) representing saturated compounds, phenol (PN) representing phenolics, benzothiophene (BZT) representing sulfur compounds, and quinoline (QN) representing nitrogen compounds, were reacted thermally and catalytically using a Shell 324 NiMo/Al{sub 2}O{sub 3} catalyst. The model systems were reacted individually and then combined together to ascertain the effect of the different components on the thermal and catalytic reactions of the different model systems. Illinois No. 6 coal and Maya TLR were each, respectively, added to the model compound systems and reacted thermally and catalytically.

  11. Evaluation of the interactive chemistry of coal-petroleum systems using model and actual reactants

    SciTech Connect

    Curtis, C.W.; Chung, W.J. )

    1988-06-01

    The coprocessing of coal with petroleum residuum simultaneously liquefies coal and upgrades petroleum residuum into higher value products. However, coal and petroleum residuum manifest very different chemical properties with coal being more aromatic with a H/C ratio of 0.6 - 0.8 and petroleum residuum more aliphatic with a H/C ratio of 1.4 to 1.6. Although a number of studies have demonstrated the feasibility of coprocessing on the basis of product selectivity and metals reduction (1-8), the interactive chemistry involved between the coal and petroleum materials during coprocessing has not yet been determined. In this study, the interactive chemistry between coal and petroleum molecules have been examined: first by using model compound types representative of coal and residuum and then by combining the model systems will Illinois No. 6 coal and Maya topped long residuum (TLR). The model systems, composed of napthalene (NAPH) representing aromatics, 1,4- dimethylcyclohexane (DMC) representing saturated compounds, phenol (PN) representing phenolics, benzothiophene (BZT) representing suflur compounds, and quinoline (QN) representing nitrogen compounds, were reacted thermally and catalytically using a Shell 324 NiMo/Al/sub 2/O/sub 3/ catalyst. The model systems were reacted individually and then combined together to ascertain the effect of the different components on the thermal and catalytic reactions of the different model systems. Illinois No. 6 coal and Maya TLR were each, respectively, added to the model compound systems and reacted thermally and catalytically.

  12. Modeling and testing of fractionation effects with refrigerant blends in an actual residential heat pump system

    SciTech Connect

    Biancardi, F.R.; Pandy, D.R.; Sienel, T.H.; Michels, H.H.

    1997-12-31

    The heating, ventilating, and air-conditioning (HVAC) industry is actively evaluating and testing hydrofluorocarbon (HFC) refrigerant blends as a means of complying with current and impending national and international environmental regulations restricting the use and disposal of conventional chlorofluorocarbon (CFC) and hydrochlorofluorocarbon (HCFC) refrigerants that contribute to the global ozone-depletion effects. While analyses and system performance tools have shown that HFC refrigerant blends offer certain performance, capacity, and operational advantages, there are significant possible service and operational issues that are raised by the use of blends. Many of these issues occur due to the fractionation of the blends. Therefore, the objective of this program was to conduct analyses and experimental tests aimed at understanding these issues, develop approaches or techniques to predict these effects, and convey to the industry safe and reliable approaches. As a result, analytical models verified by laboratory data have been developed that predict the fractionation effects of HFC refrigerant blends (1) when exposed to selected POE lubricants, (2) during the system charging process from large liquid containers, and (3) during system start-up, operation, and shutdown within various system components (where two-phase refrigerant exists) and during selected system and component leakage scenarios. Model predictions and experimental results are presented for HFC refrigerant blends containing R-32, R-134a, and R-125 and the data are generalized for various operating conditions and scenarios.

  13. Whom Do Employers Actually Hire? The Educating Systems Librarian Research Project Report 2.

    ERIC Educational Resources Information Center

    Xu, Hong; Chen, Hsin-liang

    2000-01-01

    This follow-up report of 133 job advertisements for systems librarians in "American Libraries" during 1996-97 compares results of a content analysis of advertisements and a survey of employers and newly hired librarians. Results show gaps in regard to education requirements, work experience, job responsibilities, and areas of knowledge and skills.…

  14. A tuberculosis ontology for host systems biology.

    PubMed

    Levine, David M; Dutta, Noton K; Eckels, Josh; Scanga, Charles; Stein, Catherine; Mehra, Smriti; Kaushal, Deepak; Karakousis, Petros C; Salamon, Hugh

    2015-09-01

    A major hurdle facing tuberculosis (TB) investigators who want to utilize a rapidly growing body of data from both systems biology approaches and omics technologies is the lack of a standard vocabulary for data annotation and reporting. Lacking a means to readily compare samples from different research groups, a significant quantity of potentially informative data is largely ignored by researchers. To facilitate standardizing data across studies, a simple ontology of TB terms was developed to provide a common vocabulary for annotating data sets. New terminology was developed to address animal models and experimental systems, and existing clinically focused terminology was modified and adapted. This ontology can be used to annotate host TB data in public databases and collaborations, thereby standardizing database searches and allowing researchers to more easily compare results. To demonstrate the utility of a standard TB ontology for host systems biology, a web application was developed to annotate and compare human and animal model gene expression data sets.

  15. A Tuberculosis Ontology for Host Systems Biology

    PubMed Central

    Levine, David M.; Dutta, Noton K.; Eckels, Josh; Scanga, Charles; Stein, Catherine; Mehra, Smriti; Kaushal, Deepak; Karakousis, Petros C.; Salamon, Hugh

    2015-01-01

    Summary A major hurdle facing tuberculosis (TB) investigators who want to utilize a rapidly growing body of data from both systems biology approaches and omics technologies is the lack of a standard vocabulary for data annotation and reporting. Lacking a means to readily compare samples from different research groups, a significant quantity of potentially informative data is largely ignored by researchers. To facilitate standardizing data across studies, a simple ontology of TB terms was developed to provide a common vocabulary for annotating data sets. New terminology was developed to address animal models and experimental systems, and existing clinically focused terminology was modified and adapted. This ontology can be used to annotate host TB data in public databases and collaborations, thereby standardizing database searches and allowing researchers to more easily compare results. To demonstrate the utility of a standard TB ontology for host systems biology, a web application was developed to annotate and compare human and animal model gene expression data sets. PMID:26190839

  16. Computational systems biology for aging research.

    PubMed

    Mc Auley, Mark T; Mooney, Kathleen M

    2015-01-01

    Computational modelling is a key component of systems biology and integrates with the other techniques discussed thus far in this book by utilizing a myriad of data that are being generated to quantitatively represent and simulate biological systems. This chapter will describe what computational modelling involves; the rationale for using it, and the appropriateness of modelling for investigating the aging process. How a model is assembled and the different theoretical frameworks that can be used to build a model are also discussed. In addition, the chapter will describe several models which demonstrate the effectiveness of each computational approach for investigating the constituents of a healthy aging trajectory. Specifically, a number of models will be showcased which focus on the complex age-related disorders associated with unhealthy aging. To conclude, we discuss the future applications of computational systems modelling to aging research.

  17. Complexity and Stability in Biological Systems

    NASA Astrophysics Data System (ADS)

    Demongeot, Jacques; Demetrius, Lloyd A.

    2015-06-01

    The hypothesis that a positive correlation exists between the complexity of a biological system, as described by its connectance, and its stability, as measured by its ability to recover from disturbance, derives from the investigations of the physiologists, Bernard and Cannon, and the ecologist Elton. Studies based on the ergodic theory of dynamical systems and the theory of large deviations have furnished an analytic support for this hypothesis. Complexity in this context is described by the mathematical object evolutionary entropy, stability is characterized by the rate at which the system returns to its stable conditions (steady state or periodic attractor) after a random perturbation of its robustness. This article reviews the analytical basis of the entropy — robustness theorem — and invokes studies of genetic regulatory networks to provide empirical support for the correlation between complexity and stability. Earlier investigations based on numerical studies of random matrix models and the notion of local stability have led to the claim that complex ecosystems tend to be more dynamically fragile. This article elucidates the basis for this claim which is largely inconsistent with the empirical observations of Bernard, Cannon and Elton. Our analysis thus resolves a long standing controversy regarding the relation between complex biological systems and their capacity to recover from perturbations. The entropy-robustness principle is a mathematical proposition with implications for understanding the basis for the large variations in stability observed in biological systems having evolved under different environmental conditions.

  18. The Alpha Project, a model system for systems biology research

    PubMed Central

    Yu, Richard C.; Resnekov, Orna; Abola, A. Pia; Andrews, Steve S.; Benjamin, Kirsten R.; Bruck, Jehoshua; Burbulis, Ian; Colman-Lerner, Alejandro; Endy, Drew; Gordon, Andrew; Holl, Mark; Lok, Larry; Pesce, Gustavo; Serra, Eduard; Smith, Richard D.; Thomson, Ty M.; Tsong, Annie E.; Brent, Roger

    2009-01-01

    One goal of systems biology is to understand how genome-encoded parts interact to produce quantitative phenotypes. The Alpha Project is a medium-scale, interdisciplinary systems biology effort that aims to achieve this goal by understanding fundamental quantitative behaviors of a prototypic signal transduction pathway, the yeast pheromone response system from Saccharomyces cerevisiae. The Alpha Project distinguishes itself from many other systems biology projects by studying a tightly-bounded and well-characterized system that is easily modified by genetic means, and by focusing on deep understanding of a discrete number of important and accessible quantitative behaviors. During the project, we have developed tools to measure the appropriate data and develop models at appropriate levels of detail for studying a number of these quantitative behaviors. We also have developed transportable experimental tools and conceptual frameworks for understanding other signaling systems. In particular, we have begun to interpret system behaviors and their underlying molecular mechanisms through the lens of information transmission, a principal function of signaling systems. The Alpha Project demonstrates that interdisciplinary studies that identify key quantitative behaviors and measure important quantities, in the context of well-articulated abstractions of system function and appropriate analytical frameworks, can lead to deeper biological understanding. Our experience may provide a productive template for system biology investigations of other cellular systems. PMID:19045818

  19. Treatment of an actual slaughterhouse wastewater by integration of biological and advanced oxidation processes: Modeling, optimization, and cost-effectiveness analysis.

    PubMed

    Bustillo-Lecompte, Ciro Fernando; Mehrvar, Mehrab

    2016-11-01

    Biological and advanced oxidation processes are combined to treat an actual slaughterhouse wastewater (SWW) by a sequence of an anaerobic baffled reactor, an aerobic activated sludge reactor, and a UV/H2O2 photoreactor with recycle in continuous mode at laboratory scale. In the first part of this study, quadratic modeling along with response surface methodology are used for the statistical analysis and optimization of the combined process. The effects of the influent total organic carbon (TOC) concentration, the flow rate, the pH, the inlet H2O2 concentration, and their interaction on the overall treatment efficiency, CH4 yield, and H2O2 residual in the effluent of the photoreactor are investigated. The models are validated at different operating conditions using experimental data. Maximum TOC and total nitrogen (TN) removals of 91.29 and 86.05%, respectively, maximum CH4 yield of 55.72%, and minimum H2O2 residual of 1.45% in the photoreactor effluent were found at optimal operating conditions. In the second part of this study, continuous distribution kinetics is applied to establish a mathematical model for the degradation of SWW as a function of time. The agreement between model predictions and experimental values indicates that the proposed model could describe the performance of the combined anaerobic-aerobic-UV/H2O2 processes for the treatment of SWW. In the final part of the study, the optimized combined anaerobic-aerobic-UV/H2O2 processes with recycle were evaluated using a cost-effectiveness analysis to minimize the retention time, the electrical energy consumption, and the overall incurred treatment costs required for the efficient treatment of slaughterhouse wastewater effluents. PMID:27568982

  20. Integrative systems biology visualization with MAYDAY.

    PubMed

    Symons, Stephan; Zipplies, Christian; Battke, Florian; Nieselt, Kay

    2010-03-25

    Visualization is pivotal for gaining insight in systems biology data. As the size and complexity of datasets and supplemental information increases, an efficient, integrated framework for general and specialized views is necessary. MAYDAY is an application for analysis and visualization of general 'omics' data. It follows a trifold approach for data visualization, consisting of flexible data preprocessing, highly customizable data perspective plots for general purpose visualization and systems based plots. Here, we introduce two new systems biology visualization tools for MAYDAY. Efficiently implemented genomic viewers allow the display of variables associated with genomic locations. Multiple variables can be viewed using our new track-based ChromeTracks tool. A functional perspective is provided by visualizing metabolic pathways either in KEGG or BioPax format. Multiple options of displaying pathway components are available, including Systems Biology Graphical Notation (SBGN) glyphs. Furthermore, pathways can be viewed together with gene expression data either as heatmaps or profiles. We apply our tools to two 'omics' datasets of Pseudomonas aeruginosa. The general analysis and visualization tools of MAYDAY as well as our ChromeTracks viewer are applied to a transcriptome dataset. We furthermore integrate this dataset with a metabolome dataset and compare the activity of amino acid degradation pathways between these two datasets, by visually enhancing the pathway diagrams produced by MAYDAY.

  1. Image-based systems biology of infection.

    PubMed

    Medyukhina, Anna; Timme, Sandra; Mokhtari, Zeinab; Figge, Marc Thilo

    2015-06-01

    The successful treatment of infectious diseases requires interdisciplinary studies of all aspects of infection processes. The overarching combination of experimental research and theoretical analysis in a systems biology approach can unravel mechanisms of complex interactions between pathogens and the human immune system. Taking into account spatial information is especially important in the context of infection, since the migratory behavior and spatial interactions of cells are often decisive for the outcome of the immune response. Spatial information is provided by image and video data that are acquired in microscopy experiments and that are at the heart of an image-based systems biology approach. This review demonstrates how image-based systems biology improves our understanding of infection processes. We discuss the three main steps of this approach--imaging, quantitative characterization, and modeling--and consider the application of these steps in the context of studying infection processes. After summarizing the most relevant microscopy and image analysis approaches, we discuss ways to quantify infection processes, and address a number of modeling techniques that exploit image-derived data to simulate host-pathogen interactions in silico.

  2. Set membership experimental design for biological systems

    PubMed Central

    2012-01-01

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

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

    PubMed

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

    2016-06-17

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

  4. Unmanned Aircraft Systems complement biologging in spatial ecology studies.

    PubMed

    Mulero-Pázmány, Margarita; Barasona, Jose Ángel; Acevedo, Pelayo; Vicente, Joaquín; Negro, Juan José

    2015-11-01

    The knowledge about the spatial ecology and distribution of organisms is important for both basic and applied science. Biologging is one of the most popular methods for obtaining information about spatial distribution of animals, but requires capturing the animals and is often limited by costs and data retrieval. Unmanned Aircraft Systems (UAS) have proven their efficacy for wildlife surveillance and habitat monitoring, but their potential contribution to the prediction of animal distribution patterns and abundance has not been thoroughly evaluated. In this study, we assess the usefulness of UAS overflights to (1) get data to model the distribution of free-ranging cattle for a comparison with results obtained from biologged (GPS-GSM collared) cattle and (2) predict species densities for a comparison with actual density in a protected area. UAS and biologging derived data models provided similar distribution patterns. Predictions from the UAS model overestimated cattle densities, which may be associated with higher aggregated distributions of this species. Overall, while the particular researcher interests and species characteristics will influence the method of choice for each study, we demonstrate here that UAS constitute a noninvasive methodology able to provide accurate spatial data useful for ecological research, wildlife management and rangeland planning. PMID:26640661

  5. Image informatics in systems biology applications

    NASA Astrophysics Data System (ADS)

    Wong, Stephen T. C.

    2005-02-01

    Digital optical microscopy, coupled with parallel processing and a large arsenal of labeling techniques, offers tremendous values to localize, identify, and characterize cells and molecules. This generates many image informatics challenges in requiring new algorithms and tools to extract, classify, correlate, and model image features and content from massive amounts of cellular and molecular images acquired. Image informatics aims to fill this gap. Coupling automated microscopy and image analysis with biostatistical and data mining techniques to provide a system biologic approach in studying the cells, the basic unit of life, potentially leads to many exciting applications in life and health sciences. In this presentation, we describe certain new system biology applications enabled by image informatics technology.

  6. TOPICAL REVIEW: Carbon nanomaterials in biological systems

    NASA Astrophysics Data System (ADS)

    Ke, Pu Chun; Qiao, Rui

    2007-09-01

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

  7. [Experimental determination of bacterial decay characteristics in biological wastewater treatment system].

    PubMed

    Hao, Xiao-Di; Zhu, Jing-Yi; Cao, Xiu-Qin; Cao, Ya-Li

    2008-11-01

    The characteristics of cell decay in biological wastewater treatment systems were investigated under aerobic condition, by measuring the decay rate and by determining the death rate with LIVE/DEAD dyeing experiments. It was found that cell decay in biological wastewater treatment systems can be actually described as two parts: decay caused by cell death and decay derived from activity decrease. The experimental results revealed that 60% of cell decay in a nitrifying system was caused by activity decrease and 40% was caused by cell death. In a heterotrophic system, however, activity decrease was responsible for 80% of cell decay, and the other cell decay for 20% was caused by cell death.

  8. Endogenous Biologically Inspired Art of Complex Systems.

    PubMed

    Ji, Haru; Wakefield, Graham

    2016-01-01

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

  9. Probing biological systems with terahertz spectroscopy

    NASA Astrophysics Data System (ADS)

    Pickwell-MacPherson, Emma; Sun, Yiwen; Parrott, Edward P. J.

    2012-10-01

    Terahertz spectroscopy is able to probe several aspects of biological systems. Most well known is its sensitivity to water due to the strong water absorptions at terahertz frequencies. However an increasing number of studies have shown that it is not just water content that terahertz is sensitive to and that other factors such as tissue structure, molecular arrangement or even temperature can also affect the signal. Examples ranging from breast cancer spectroscopy to antibody protein spectroscopy will be presented and discussed.

  10. Predicting Dynamic Behavior of a Biological System Using ANNs

    NASA Astrophysics Data System (ADS)

    Osman, Mohd Haniff; Ibrahim, Ratnawati; Hashim, Ishak; Yeun, Liong Choong; Bakar, Azuraliza Abu; Hussein, Zeti Azura Mohamed

    2008-01-01

    In this paper, artificial neural networks (ANNs) are applied to predict protein concentrations of a biological system. The input data are generated from a nonlinear mathematical model of the protein concentration. The protein concentrations from CDC6 data with actual kinetic parameter are taken as the target output. The data are then trained using multilayer perceptron (MLP) neural network with a 6-6-6 configuration. The allocation of the data will be distributed into 3 categories that are 80% as training data, 10% as validation data, and 10% as test data. The learning rules used in this work to determine the best model are gradient descent, conjugate gradient, scaled conjugate gradient. It is found that the MLP with scaled conjugate gradient learning rule gives the best prediction rate.

  11. Systems biology of cancer biomarker detection.

    PubMed

    Mitra, Sanga; Das, Smarajit; Chakrabarti, Jayprokas

    2013-01-01

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

  12. The Emergence of Modularity in Biological Systems

    PubMed Central

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

    2015-01-01

    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. There once were two watchmakers, named Hora and Tempus, who manufactured very fine watches. Both of them were highly regarded, and the phones in their workshops rang frequently — new customers were constantly calling them. However, Hora prospered, while Tempus became poorer and poorer and finally lost his shop. What was the reason? The watches the men made consisted of about 1,000 parts each. Tempus had so constructed his that if he had one partly assembled and had to put it down — to answer the phone say— it immediately fell to pieces and had to be reassembled from the elements. The better the customers liked his watches, the more they phoned him, the more difficult it became for him to find enough uninterrupted time to finish a watch. The watches that Hora made were no less complex than those of Tempus. But he had designed them so that he could put together subassemblies of about ten elements each. Ten of these subassemblies, again, could be put together into a larger subassembly; and a system of ten of the latter sub

  13. Engineering simulations for cancer systems biology.

    PubMed

    Bown, James; Andrews, Paul S; Deeni, Yusuf; Goltsov, Alexey; Idowu, Michael; Polack, Fiona A C; Sampson, Adam T; Shovman, Mark; Stepney, Susan

    2012-11-01

    Computer simulation can be used to inform in vivo and in vitro experimentation, enabling rapid, low-cost hypothesis generation and directing experimental design in order to test those hypotheses. In this way, in silico models become a scientific instrument for investigation, and so should be developed to high standards, be carefully calibrated and their findings presented in such that they may be reproduced. Here, we outline a framework that supports developing simulations as scientific instruments, and we select cancer systems biology as an exemplar domain, with a particular focus on cellular signalling models. We consider the challenges of lack of data, incomplete knowledge and modelling in the context of a rapidly changing knowledge base. Our framework comprises a process to clearly separate scientific and engineering concerns in model and simulation development, and an argumentation approach to documenting models for rigorous way of recording assumptions and knowledge gaps. We propose interactive, dynamic visualisation tools to enable the biological community to interact with cellular signalling models directly for experimental design. There is a mismatch in scale between these cellular models and tissue structures that are affected by tumours, and bridging this gap requires substantial computational resource. We present concurrent programming as a technology to link scales without losing important details through model simplification. We discuss the value of combining this technology, interactive visualisation, argumentation and model separation to support development of multi-scale models that represent biologically plausible cells arranged in biologically plausible structures that model cell behaviour, interactions and response to therapeutic interventions. PMID:22974398

  14. Dynamic sensitivity analysis of biological systems

    PubMed Central

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

    2008-01-01

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

  15. Complex biological and bio-inspired systems

    SciTech Connect

    Ecke, Robert E

    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 accurately

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

    DOEpatents

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

    2000-08-01

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

  17. [Systems theory in medicine and biology].

    PubMed

    Feigl, W; Bonet, E M

    1989-03-15

    We try to determinate, that systems theory has to be introduced into modern medicine. The biological roots as well as the cybernetic ones are outlined. Among various concepts about systems theory the evaluation by Riedl seems to be the most efficient to explain medical procedures. His basic informations refer to von Bertalanffy, the additional introduction of a 4-cause-principle, Aristoteles, permits the explanation of complex relations. The examples of tumor and inflammation are used to demonstrate the basic idea of the formal cause as well as the final cause. The latter should also become an important fact in the solution of other medical problems.

  18. Systems biology of the vervet monkey.

    PubMed

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

    2013-01-01

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

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

    PubMed

    Medina, Miguel Ángel

    2013-03-01

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

  20. Engineering biological systems toward a sustainable bioeconomy.

    PubMed

    Lopes, Mateus Schreiner Garcez

    2015-06-01

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

  1. Engineering biological systems toward a sustainable bioeconomy.

    PubMed

    Lopes, Mateus Schreiner Garcez

    2015-06-01

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

  2. Recognition of metal cations by biological systems.

    PubMed

    Truter, M R

    1975-11-01

    Recognition of metal cations by biological systems can be compared with the geochemical criteria for isomorphous replacement. Biological systems are more highly selective and much more rapid. Methods of maintaining an optimum concentration, including storage and transfer for the essential trace elements, copper and iron, used in some organisms are in part reproducible by coordination chemists while other features have not been reporduced in models. Poisoning can result from a foreign metal taking part in a reaction irreversibly so that the recognition site or molecule is not released. For major nutrients, sodium, potassium, magnesium and calcium, there are similarities to the trace metals in selective uptake but differences qualitatively and quantitatively in biological activity. Compounds selective for potassium replace all the solvation sphere with a symmetrical arrangement of oxygen atoms; those selective for sodium give an asymmetrical environment with retention of a solvent molecule. Experiments with naturally occurring antibiotics and synthetic model compounds have shown that flexibility is an important feature of selectivity and that for transfer or carrier properties there is an optimum (as opposed to a maximum) metal-ligand stability constant. Thallium is taken up instead of potassium and will activate some enzymes; it is suggested that the poisonous characteristics arise because the thallium ion may bind more strongly than potassium to part of a site and then fail to bind additional atoms as required for the biological activity. Criteria for the design of selective complexing agents are given with indications of those which might transfer more than one metal at once. PMID:1815

  3. Adaptable data management for systems biology investigations

    PubMed Central

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

    2009-01-01

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

  4. The systems biology simulation core algorithm

    PubMed Central

    2013-01-01

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

  5. Chemical and Biological Applications of Turing Systems

    NASA Astrophysics Data System (ADS)

    Méndez, Vicenç; Fedotov, Sergei; Horsthemke, Werner

    Turing's paper on diffusion-driven instabilities in nonequilibrium reaction-diffusion systems as a means of biological pattern formation [440] attracted little attention for about two decades, as shown by the citation histogram in Fig. 12.1. One of the first scientists to be intrigued by Turing's ideas was Wardlaw, a botanist who thought about ways to test the mechanism experimentally [468, 470, 469]. By the early 1970s theoretical biologists and biomathematicians began to explore in earnest if Turing instabilities could explain spatial pattern formation in a variety of living systems and a considerable body of theoretical work was produced, see for example [157, 279, 231, 239, 182, 183, 264, 261, 308]. Morphogen-based pattern formation, where the long-range influence of signaling molecules induces structure, is a well-established phenomenon in developmental biology [26]. However, definitive evidence for a Turing mechanism of pattern formation within a morphogen system is still lacking. Several promising candidate systems exist and are discussed in Sect. 12.2.

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

    ERIC Educational Resources Information Center

    Simpson, Melanie Rae

    2016-01-01

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

  7. The Feasibility of Systems Thinking in Biology Education

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  8. Systems medicine: opportunities and challenges for systems biology approaches.

    PubMed

    Kolch, Walter; Kholodenko, Boris N

    2013-12-01

    Technological advance have not only dramatically accelerated progress in medical knowledge and practice, but also revealed the enormous complexity of diseases and pathogenetic mechanisms. Can systems biology approaches and computational modelling help defeat the challenge of exploding complexity? Four review articles discuss the challenges and opportunities for such systems level approaches in medicine, pathology and drug development.

  9. 6th Annual Systems Biology Symposium: Systems Biology and the Environment

    SciTech Connect

    Galitski, Timothy, P.

    2007-04-01

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

  10. [The Red Cross System for War Relief during the Second World War and Actual Conditions of Its Efforts in Burma].

    PubMed

    Kawahara, Yukari

    2015-12-01

    This paper aims to show the system for relief provided by the Japanese Red Cross relief units during the Second World War, as well as the actual activities of sixteen of its relief units dispatched to Burma. The Red Cross wartime relief efforts involved using personnel and funding prepared beforehand to provide aid to those injured in war, regardless of their status as ally or enemy. Thus they were able to receive support from the army in order to ensure safety and provide supplies. Nurses dispatched to Burma took care of many patients who suffered from malnutrition and physical injuries amidst the outbreak of infectious diseases typical of tropical areas, without sufficient replacement members. Base hospitals not meant for the front lines also came under attack, and the nurses' lives were thus in mortal danger. Of the 374 original members, 29 died or went missing in action.

  11. Actual versus predicted performance of an active solar heating system - A comparison using FCHART 4.0

    NASA Astrophysics Data System (ADS)

    Wetzel, P. E.

    1981-11-01

    The performance of an active solar heating system added to a house in Denver, CO was compared with predictions made by the FCHART 4.0 computer program. The house featured 43.23 sq m of collectors with an ethylene-glycol/water heat transfer fluid, and a 3.23 cu m storage tank. The house hot water was preheated in the storage tank, and home space heat was furnished whenever the storage water was above 32 C. Actual meteorological and heating demand data were used for the comparison, rather than long-term averages. Although monthly predictions by the FCHART program were found to diverge from measured data, the annual demand and supply predictions provided a good fit, i.e. within 9%, and were within 1% of the measured solar energy contributed to storage.

  12. AN INTEGRATED BIOLOGICAL CONTROL SYSTEM AT HANFORD

    SciTech Connect

    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.

  13. Systems biology of host-microbe metabolomics.

    PubMed

    Heinken, Almut; Thiele, Ines

    2015-01-01

    The human gut microbiota performs essential functions for host and well-being, but has also been linked to a variety of disease states, e.g., obesity and type 2 diabetes. The mammalian body fluid and tissue metabolomes are greatly influenced by the microbiota, with many health-relevant metabolites being considered 'mammalian-microbial co-metabolites'. To systematically investigate this complex host-microbial co-metabolism, a systems biology approach integrating high-throughput data and computational network models is required. Here, we review established top-down and bottom-up systems biology approaches that have successfully elucidated relationships between gut microbiota-derived metabolites and host health and disease. We focus particularly on the constraint-based modeling and analysis approach, which enables the prediction of mechanisms behind metabolic host-microbe interactions on the molecular level. We illustrate that constraint-based models are a useful tool for the contextualization of metabolomic measurements and can further our insight into host-microbe interactions, yielding, e.g., in potential novel drugs and biomarkers.

  14. Structural Identifiability of Dynamic Systems Biology Models

    PubMed Central

    Villaverde, Alejandro F.

    2016-01-01

    A powerful way of gaining insight into biological systems is by creating a nonlinear differential equation model, which usually contains many unknown parameters. Such a model is called structurally identifiable if it is possible to determine the values of its parameters from measurements of the model outputs. Structural identifiability is a prerequisite for parameter estimation, and should be assessed before exploiting a model. However, this analysis is seldom performed due to the high computational cost involved in the necessary symbolic calculations, which quickly becomes prohibitive as the problem size increases. In this paper we show how to analyse the structural identifiability of a very general class of nonlinear models by extending methods originally developed for studying observability. We present results about models whose identifiability had not been previously determined, report unidentifiabilities that had not been found before, and show how to modify those unidentifiable models to make them identifiable. This method helps prevent problems caused by lack of identifiability analysis, which can compromise the success of tasks such as experiment design, parameter estimation, and model-based optimization. The procedure is called STRIKE-GOLDD (STRuctural Identifiability taKen as Extended-Generalized Observability with Lie Derivatives and Decomposition), and it is implemented in a MATLAB toolbox which is available as open source software. The broad applicability of this approach facilitates the analysis of the increasingly complex models used in systems biology and other areas. PMID:27792726

  15. A Systems Biology View of Cancer

    PubMed Central

    Laubenbacher, Reinhard; Hower, Valerie; Jarrah, Abdul; Torti, Suzy V.; Shulaev, Vladimir; Mendes, Pedro; Torti, Frank M.; Akman, Steven

    2009-01-01

    SUMMARY In order to understand how a cancer cell is functionally different from a normal cell it is necessary to assess the complex network of pathways involving gene regulation, signaling, and cell metabolism, and the alterations in its dynamics caused by the several different types of mutations leading to malignancy. Since the network is typically complex, with multiple connections between pathways and important feedback loops, it is crucial to represent it in the form of a computational model that can be used for a rigorous analysis. This is the approach of systems biology, made possible by new –omics data generation technologies. The goal of this review is to illustrate this approach and its utility for our understanding of cancer. After a discussion of recent progress using a network-centric approach, three case studies related to diagnostics, therapy, and drug development are presented in detail. They focus on breast cancer, B cell lymphomas, and colorectal cancer. The discussion is centered on key mathematical and computational tools common to a systems biology approach. PMID:19505535

  16. Parallel stochastic systems biology in the cloud.

    PubMed

    Aldinucci, Marco; Torquati, Massimo; Spampinato, Concetto; Drocco, Maurizio; Misale, Claudia; Calcagno, Cristina; Coppo, Mario

    2014-09-01

    The stochastic modelling of biological systems, coupled with Monte Carlo simulation of models, is an increasingly popular technique in bioinformatics. The simulation-analysis workflow may result computationally expensive reducing the interactivity required in the model tuning. In this work, we advocate the high-level software design as a vehicle for building efficient and portable parallel simulators for the cloud. In particular, the Calculus of Wrapped Components (CWC) simulator for systems biology, which is designed according to the FastFlow pattern-based approach, is presented and discussed. Thanks to the FastFlow framework, the CWC simulator is designed as a high-level workflow that can simulate CWC models, merge simulation results and statistically analyse them in a single parallel workflow in the cloud. To improve interactivity, successive phases are pipelined in such a way that the workflow begins to output a stream of analysis results immediately after simulation is started. Performance and effectiveness of the CWC simulator are validated on the Amazon Elastic Compute Cloud.

  17. Biological Systems for Hydrogen Photoproduction (Presentation)

    SciTech Connect

    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.

  18. Modeling delayed processes in biological systems

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

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

  19. Are Biological Systems Poised at Criticality?

    NASA Astrophysics Data System (ADS)

    Mora, Thierry; Bialek, William

    2011-07-01

    Many of life's most fascinating phenomena emerge from interactions among many elements—many amino acids determine the structure of a single protein, many genes determine the fate of a cell, many neurons are involved in shaping our thoughts and memories. Physicists have long hoped that these collective behaviors could be described using the ideas and methods of statistical mechanics. In the past few years, new, larger scale experiments have made it possible to construct statistical mechanics models of biological systems directly from real data. We review the surprising successes of this "inverse" approach, using examples from families of proteins, networks of neurons, and flocks of birds. Remarkably, in all these cases the models that emerge from the data are poised near a very special point in their parameter space—a critical point. This suggests there may be some deeper theoretical principle behind the behavior of these diverse systems.

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

    PubMed

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

    2016-06-16

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

  1. Electromagnetic field interactions with biological systems

    SciTech Connect

    Frey, A.H. )

    1993-02-01

    This is a report on Symposia organized by the International Society for Bioelectricity and presented at the 1992 FASEB Meeting. The presentations summarized here were intended to provide a sampling of new and fruitful lines of research. The theme topics for the Symposia were cancer, neural function, cell signaling, pineal gland function, and immune system interactions. Living organisms are complex electrochemical systems that evolved over billions of years in a world with a relatively simple weak magnetic field and with few electromagnetic energy emitters. As is characteristic of living organisms, they interacted with and adapted to this environment of electric and magnetic fields. In recent years there has been a massive introduction of equipment that emits electromagnetic fields in an enormous range of new frequencies, modulations, and intensities. As living organisms have only recently found themselves immersed in this new and virtually ubiquitous environment, they have not had the opportunity to adapt to it. This gives biologists the opportunity to use these electromagnetic fields as probes to study the functioning of living systems. This is a significant opportunity, as new approaches to studying living systems so often provide the means to make great leaps in science. In recent years, a diversity of biologists have carried out experiments using electromagnetic fields to study the function of living cells and systems. This approach is now becoming quite fruitful and is yielding data that are advancing our knowledge in diverse areas of biology. 25 refs., 6 figs., 3 tabs.

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

    PubMed

    Gomez-Ramirez, Jaime; Sanz, Ricardo

    2013-09-01

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

  3. Lessons Learned from Eight Years' Experience of Actual Operation, and Future Prospects of JMA Earthquake Early Warning System

    NASA Astrophysics Data System (ADS)

    Hoshiba, M.; Nishimae, Y.

    2015-12-01

    Since 2007, experiences of actual operation of EEW have been gained by the Japan Meteorological Agency (JMA). During this period, we have learned lessons from many M6- and M7-class earthquakes, and the Mw9.0 Tohoku earthquake. During the Mw9.0 Tohoku earthquake, JMA system functioned well: it issued a warning message more than 15 s before strong ground shaking in the Tohoku district (relatively near distance from the epicenter). However, it was not perfect: in addition to the problem of large extent of fault rupture, some false warning messages were issued due to the confusion of the system because of simultaneous multiple aftershocks which occurred at the wide rupture area. To address the problems, JMA will introduce two new methods into the operational system this year to start their tests, aiming at practical operation within a couple of years. One is Integrated Particle Filter (IPF) method, which is an integrated algorithm of multiple hypocenter determination techniques with Bayesian estimation, in which amplitude information is also used for hypocenter determination. The other is Propagation of Local Undamped Motion (PLUM) method, in which warning message is issued when strong ground shaking is detected at nearby stations around the target site (e.g., within 30 km). Here, hypocenter and magnitude are not required in PLUM. Aiming at application for several years later, we are investigating a new approach, in which current wavefield is estimated in real time, and then future wavefield is predicted time evolutionally from the current situation using physics of wave propagation. Here, hypocenter and magnitude are not necessarily required, but real-time observation of ground shaking is necessary. JMA also plans to predict long period ground motion (up to 8 s) with the EEW system for earthquake damage mitigation in high-rise buildings. Its test will start using the operational system in the near future.

  4. Liquid crystal assemblies in biologically inspired systems

    PubMed Central

    Safinya, Cyrus R.; Deek, Joanna; Beck, Roy; Jones, Jayna B.; Leal, Cecilia; Ewert, Kai K.; Li, Youli

    2013-01-01

    In this paper, which is part of a collection in honor of Noel Clark's remarkable career on liquid crystal and soft matter research, we present examples of biologically inspired systems, which form liquid crystal (LC) phases with their LC nature impacting biological function in cells or being important in biomedical applications. One area focuses on understanding network and bundle formation of cytoskeletal polyampholytes (filamentous-actin, microtubules, and neurofilaments). Here, we describe studies on neurofilaments (NFs), the intermediate filaments of neurons, which form open network nematic liquid crystal hydrogels in axons. Synchrotron small-angle-x-ray scattering studies of NF-protein dilution experiments and NF hydrogels subjected to osmotic stress show that neurofilament networks are stabilized by competing long-range repulsion and attractions mediated by the neurofilament's polyampholytic sidearms. The attractions are present both at very large interfilament spacings, in the weak sidearm-interpenetrating regime, and at smaller interfilament spacings, in the strong sidearm-interpenetrating regime. A second series of experiments will describe the structure and properties of cationic liposomes (CLs) complexed with nucleic acids (NAs). CL-NA complexes form liquid crystalline phases, which interact in a structure-dependent manner with cellular membranes enabling the design of complexes for efficient delivery of nucleic acid (DNA, RNA) in therapeutic applications. PMID:24558293

  5. Mouse behavioural analysis in systems biology

    PubMed Central

    van Meer, Peter; Raber, Jacob

    2005-01-01

    Molecular techniques allowing in vivo modulation of gene expression have provided unique opportunities and challenges for behavioural studies aimed at understanding the function of particular genes or biological systems under physiological or pathological conditions. Although various animal models are available, the laboratory mouse (Mus musculus) has unique features and is therefore a preferred animal model. The mouse shares a remarkable genetic resemblance and aspects of behaviour with humans. In this review, first we describe common mouse models for behavioural analyses. As both genetic and environmental factors influence behavioural performance and need to be carefully evaluated in behavioural experiments, considerations for designing and interpretations of these experiments are subsequently discussed. Finally, common behavioural tests used to assess brain function are reviewed, and it is illustrated how behavioural tests are used to increase our understanding of the role of histaminergic neurotransmission in brain function. PMID:16035954

  6. Biosensors for antioxidant evaluation in biological systems.

    PubMed

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

    2013-02-01

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

  7. Systems biology of human benzene exposure

    PubMed Central

    Zhang, Luoping; McHale, Cliona M.; Rothman, Nathaniel; Li, Guilan; Ji, Zhiying; Vermeulen, Roel; Hubbard, Alan E.; Ren, Xuefeng; Shen, Min; Rappaport, Stephen M.; North, Matthew; Skibola, Christine F.; Yin, Songnian; Vulpe, Christopher; Chanock, Stephen J.; Smith, Martyn T.; Lan, Qing

    2010-01-01

    Toxicogenomic studies, including genome-wide analyses of susceptibility genes (genomics), gene expression (transcriptomics), protein expression (proteomics), and epigenetic modifications (epigenomics), of human populations exposed to benzene are crucial to understanding gene-environment interactions, providing the ability to develop biomarkers of exposure, early effect and susceptibility. Comprehensive analysis of these toxicogenomic and epigenomic profiles by bioinformatics in the context of phenotypic endpoints, comprises systems biology, which has the potential to comprehensively define the mechanisms by which benzene causes leukemia. We have applied this approach to a molecular epidemiology study of workers exposed to benzene. Hematotoxicity, a significant decrease in almost all blood cell counts, was identified as a phenotypic effect of benzene that occurred even below 1ppm benzene exposure. We found a significant decrease in the formation of progenitor colonies arising from bone marrow stem cells with increasing benzene exposure, showing that progenitor cells are more sensitive to the effects of benzene than mature blood cells, likely leading to the observed hematotoxicity. Analysis of transcriptomics by microarray in the peripheral blood mononuclear cells of exposed workers, identified genes and pathways (apoptosis, immune response, and inflammatory response) altered at high (>10ppm) and low (<1ppm) benzene levels. Serum proteomics by SELDI-TOF-MS revealed proteins consistently down-regulated in exposed workers. Preliminary epigenomics data showed effects of benzene on the DNA methylation of specific genes. Genomic screens for candidate genes involved in susceptibility to benzene toxicity are being undertaken in yeast, with subsequent confirmation by RNAi in human cells, to expand upon the findings from candidate gene analyses. Data on these and future biomarkers will be used to populate a large toxicogenomics database, to which we will apply bioinformatic

  8. Systems Biology and Ecology of Streamlined Bacterioplankton

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

    Whitacre, James Michael

    2012-01-01

    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. PMID:22593762

  10. Biological robustness: paradigms, mechanisms, and systems principles.

    PubMed

    Whitacre, James Michael

    2012-01-01

    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. PMID:22593762

  11. Expert systems guide biological phosphorus removal

    SciTech Connect

    Krichten, D.J.; Wilson, K.D.; Tracy, K.D. )

    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.

  12. Biomarkers of Nanoparticles Impact on Biological Systems

    NASA Astrophysics Data System (ADS)

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

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

  13. The Physics of a Volcanic System: What is the Actual Role Played by Tectonic Setting in Controlling Volcanic Activity?

    NASA Astrophysics Data System (ADS)

    Canon-Tapia, E.

    2005-12-01

    Modern text-books commonly explain volcanic activity as a direct consequence of plate tectonics, overlooking the different scales characteristic of both types of processes. By acknowledging such differences, however, it is possible to envisage a model of a volcanic system that is based in the same principles of hydrostatics established by Blaise Pascal over 300 yrs ago. Such principles allow us to estimate the local conditions required for the occurrence of volcanism at a given location highlighting the importance of the rock strength and the density difference between melt and its surroundings. This model shows that the minimum thickness of the zone of partial melting in the mantle (or seismically defined Low Velocity Zone) that is required to feed volcanic activity might range from 5 to over 100 km, but also that under certain circumstances a rock strength < 200 MPa may suffice to keep magma trapped at depth whereas in other cases a strength > 600 MPa will not suffice to stop magma ascent resulting in volcanic activity at the surface. Consequently, the model of volcanism developed here explains why is that a given LVZ may lead to volcanic activity in some places whereas a completely identical LVZ may not result in volcanic activity in a different location. Consequently, this model provides a general framework that allows us to better understand the actual role played by tectonic setting in controlling volcanism at a planetary scale.

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

    PubMed Central

    2011-01-01

    In this paper we provide a review of selected mathematical ideas that can help us better understand the boundary between living and non-living systems. We focus on group theory and abstract algebra applied to molecular systems biology. Throughout this paper we briefly describe possible open problems. In connection with the genetic code we propose that it may be possible to use perturbation theory to explore the adjacent possibilities in the 64-dimensional space-time manifold of the evolving genome. With regards to algebraic graph theory, there are several minor open problems we discuss. In relation to network dynamics and groupoid formalism we suggest that the network graph might not be the main focus for understanding the phenotype but rather the phase space of the network dynamics. We show a simple case of a C6 network and its phase space network. We envision that the molecular network of a cell is actually a complex network of hypercycles and feedback circuits that could be better represented in a higher-dimensional space. We conjecture that targeting nodes in the molecular network that have key roles in the phase space, as revealed by analysis of the automorphism decomposition, might be a better way to drug discovery and treatment of cancer. PMID:21696623

  15. Programmable temperature control system for biological materials

    NASA Technical Reports Server (NTRS)

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

    1982-01-01

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

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

    NASA Technical Reports Server (NTRS)

    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.

  17. [Application of systems biology and synthetic biology in strain improvement for biofuel production].

    PubMed

    Zhao, Xinqing; Bai, Fengwu; Li, Yin

    2010-07-01

    Biofuels are renewable and environmentally friendly, but high production cost makes them economically not competitive, and the development of robust strains is thus one of the prerequisites. In this article, strain improvement studies based on the information from systems biology studies are reviewed, with a focus on their applications on stress tolerance improvement. Furthermore, the contribution of systems biology, synthetic biology and metabolic engineering in strain development for biofuel production is discussed, with an expectation for developing more robust strains for biofuel production.

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

    PubMed Central

    Matsuoka, Yukiko; Ghosh, Samik; Kitano, Hiroaki

    2009-01-01

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

  19. Systems Biology of Microbial Exopolysaccharides Production

    PubMed Central

    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

  20. Systems Biology of Microbial Exopolysaccharides Production.

    PubMed

    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

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

    PubMed

    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.

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

    PubMed

    Fletcher, Liz; Rosser, Susan; Elfick, Alistair

    2016-06-15

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

  3. Cardiovascular Biology of the Incretin System

    PubMed Central

    Ussher, John R.; Drucker, Daniel J.

    2012-01-01

    Glucagon-like peptide-1 (GLP-1) is an incretin hormone that enhances glucose-stimulated insulin secretion and exerts direct and indirect actions on the cardiovascular system. GLP-1 and its related incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), are rapidly inactivated by the enzyme dipeptidyl peptidase 4 (DPP-4), a key determinant of incretin bioactivity. Two classes of medications that enhance incretin action, GLP-1R agonists and DPP-4 inhibitors, are used for the treatment of type 2 diabetes mellitus (T2DM). We review herein the cardiovascular biology of GLP-1R agonists and DPP-4 inhibitors, including direct and indirect effects on cardiomyocytes, blood vessels, adipocytes, the control of blood pressure and postprandial lipoprotein secretion. Both GLP-1R activation and DPP-4 inhibition exert multiple cardioprotective actions in preclinical models of cardiovascular dysfunction, and short term studies in human subjects appear to demonstrate modest yet beneficial actions on cardiac function in subjects with ischemic heart disease. Incretin-based agents control body weight, improve glycemic control with a low risk of hypoglycemia, decrease blood pressure, inhibit the secretion of intestinal chylomicrons, and reduce inflammation in preclinical studies. Nevertheless, there is limited information on the cardiovascular actions of these agents in patients with diabetes and established cardiovascular disease. Hence, a more complete understanding of the cardiovascular risk:benefit ratio of incretin-based therapies will require completion of long term cardiovascular outcome studies currently underway in patients with T2DM. PMID:22323472

  4. Learning from systems biology: An ``Omics'' approach to materials design

    NASA Astrophysics Data System (ADS)

    Rajan, Krishna

    2008-03-01

    An understanding of systems biology provides an excellent paradigm for the materials scientist. Ultimately one would like to take an “atoms-applications” approach to materials design. This paper describes how the concepts of genomics, proteomics, and other biological behavior which form the foundations of modern biology can be applied to materials design through materials informatics.

  5. Teaching Systems Biology: An Active-Learning Approach

    ERIC Educational Resources Information Center

    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…

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

    NASA Technical Reports Server (NTRS)

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

    2003-01-01

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

  7. RDFScape: Semantic Web meets Systems Biology

    PubMed Central

    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

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

    PubMed

    Schuldiner, Maya; Zalckvar, Einat

    2015-04-01

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

  9. Controlled ecological life support system - biological problems

    NASA Technical Reports Server (NTRS)

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

    1982-01-01

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

  10. Systems biology applied to heart failure with normal ejection fraction.

    PubMed

    Mesquita, Evandro Tinoco; Jorge, Antonio Jose Lagoeiro; Souza Junior, Celso Vale de; Cassino, João Paulo Pedroza

    2014-05-01

    Heart failure with normal ejection fraction (HFNEF) is currently the most prevalent clinical phenotype of heart failure. However, the treatments available have shown no reduction in mortality so far. Advances in the omics sciences and techniques of high data processing used in molecular biology have enabled the development of an integrating approach to HFNEF based on systems biology. This study aimed at presenting a systems-biology-based HFNEF model using the bottom-up and top-down approaches. A literature search was conducted for studies published between 1991 and 2013 regarding HFNEF pathophysiology, its biomarkers and systems biology. A conceptual model was developed using bottom-up and top-down approaches of systems biology. The use of systems-biology approaches for HFNEF, a complex clinical syndrome, can be useful to better understand its pathophysiology and to discover new therapeutic targets.

  11. Systems Biology Applied to Heart Failure With Normal Ejection Fraction

    PubMed Central

    Mesquita, Evandro Tinoco; Jorge, Antonio Jose Lagoeiro; de Souza, Celso Vale; Cassino, João Paulo Pedroza

    2014-01-01

    Heart failure with normal ejection fraction (HFNEF) is currently the most prevalent clinical phenotype of heart failure. However, the treatments available have shown no reduction in mortality so far. Advances in the omics sciences and techniques of high data processing used in molecular biology have enabled the development of an integrating approach to HFNEF based on systems biology. This study aimed at presenting a systems-biology-based HFNEF model using the bottom-up and top-down approaches. A literature search was conducted for studies published between 1991 and 2013 regarding HFNEF pathophysiology, its biomarkers and systems biology. A conceptual model was developed using bottom-up and top-down approaches of systems biology. The use of systems-biology approaches for HFNEF, a complex clinical syndrome, can be useful to better understand its pathophysiology and to discover new therapeutic targets. PMID:24918915

  12. Systems vaccinology: Enabling rational vaccine design with systems biological approaches.

    PubMed

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

    2015-09-29

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

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

    PubMed

    Fletcher, Eugene; Krivoruchko, Anastasia; Nielsen, Jens

    2016-06-01

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

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

    NASA Astrophysics Data System (ADS)

    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.

  15. The Simbios National Center: Systems Biology in Motion

    PubMed Central

    Schmidt, Jeanette P.; Delp, Scott L.; Sherman, Michael A.; Taylor, Charles A.; Pande, Vijay S.; Altman, Russ B.

    2010-01-01

    Physics-based simulation is needed to understand the function of biological structures and can be applied across a wide range of scales, from molecules to organisms. Simbios (the National Center for Physics-Based Simulation of Biological Structures, http://www.simbios.stanford.edu/) is one of seven NIH-supported National Centers for Biomedical Computation. This article provides an overview of the mission and achievements of Simbios, and describes its place within systems biology. Understanding the interactions between various parts of a biological system and integrating this information to understand how biological systems function is the goal of systems biology. Many important biological systems comprise complex structural systems whose components interact through the exchange of physical forces, and whose movement and function is dictated by those forces. In particular, systems that are made of multiple identifiable components that move relative to one another in a constrained manner are multibody systems. Simbios’ focus is creating methods for their simulation. Simbios is also investigating the biomechanical forces that govern fluid flow through deformable vessels, a central problem in cardiovascular dynamics. In this application, the system is governed by the interplay of classical forces, but the motion is distributed smoothly through the materials and fluids, requiring the use of continuum methods. In addition to the research aims, Simbios is working to disseminate information, software and other resources relevant to biological systems in motion. PMID:20107615

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

    PubMed

    Noble, D

    2011-05-01

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

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

    PubMed

    Yin, Xinyou; Struik, Paul C

    2010-05-01

    There is strong interplant competition in a crop stand for various limiting resources, resulting in complex compensation and regulation mechanisms along the developmental cascade of the whole crop. Despite decades-long use of principles in system dynamics (e.g. feedback control), current crop models often contain many empirical elements, and model parameters may have little biological meaning. Building on the experience in designing the relatively new model GECROS, we believe models can be made less empirical by employing existing physiological understanding and mathematical tools. In view of the potential added value of robust crop modelling to classical quantitative genetics, model input parameters are increasingly considered to represent 'genetic coefficients'. The advent of functional genomics and systems biology enables the elucidation of the molecular genetic basis of these coefficients. A number of case studies, in which the effects of quantitative trait loci or genes have been incorporated into existing ecophysiological models, have shown the promise of using models in analysing genotype-phenotype relationships of some crop traits. For further progress, crop models must be upgraded based on understanding at lower organizational levels for complicated phenomena such as sink formation in response to environmental cues, sink feedback on source activity, and photosynthetic acclimation to the prevailing environment. Within this context, the recently proposed 'crop systems biology', which combines modern genomics, traditional physiology and biochemistry, and advanced modelling, is believed ultimately to realize the expected roles of in silico modelling in narrowing genotype-phenotype gaps. This review summarizes recent findings and our opinions on perspectives for modelling genotype x environment interactions at crop level. PMID:20051352

  18. Pragmatic validity of the combined model of expert system for assessment and analysis of the actual quality overall structure of basketball players.

    PubMed

    Trninić, S; Dizdar, D; Dezman, B

    2002-06-01

    The authors presumed that it was possible to replace certain criteria of the expert system aimed at evaluating actual quality of basketball players, proposed by Trninić et al., with the corresponding indicators of situation-related efficiency (official statistics of the game). Hence, the aim of this study is to verify the potential of establishing such a combined model of expert system that would consist of both the evaluation criteria and certain number of objectively measurable aspects of actual quality (player's partial performance or playing efficiency) and to determine its pragmatic validity. To achieve the aim the sample comprised of 60 basketball players that were competing in the Croatian First Division League in the 1998/99 season was tested. The sample and their quality of play was described by the two different types of data: 1) the 13 situation-related efficiency data (FIBA statistics of the game) utilized to objectively assess performance or playing effectiveness of players, collected at 132 games played by 12 teams, and 2) the evaluation data, subjectively assessing actual quality of players, i.e. their perceived overall performance, collected at the end of the season from the 10 basketball trainers. On the basis of relatively high correlations within the 7 pairs of mutually equivalent variables (from 0.63 to 0.84) and the extremely high correlation (0.97) obtained between the perceived overall performance (actual quality), subjectively assessed with respect to the 19 criteria of the original expert evaluation system, and the overall performance (actual quality) assessed by the combined model (where the 8 evaluation criteria had been replaced by the 7 corresponding indicators ofplaying efficiency), it is feasible to consider the combined model of expert system as an acceptable tool for more objective and economical assessment of actual quality of basketball players.

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

    Hamon, Morgan; Hong, Jong Wook

    2013-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

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

    PubMed

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

    2015-03-01

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

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

    ERIC Educational Resources Information Center

    Kindig, Neal B.; Filley, Giles F.

    1983-01-01

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

  4. A Systems Approach to Biology (SAB).

    ERIC Educational Resources Information Center

    Bush, Kenneth H.; And Others

    This pupil's study guide is intended to be used with audio-taped biology modules. Each of the units (on laboratory techniques, plant and animal diversity, chemistry, cells, energy, microbiology, genetics, and development) contains an abstract providing an overview of the unit, the rationale and performance objectives for each module, questions to…

  5. Physics and Size in Biological Systems.

    ERIC Educational Resources Information Center

    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…

  6. Biological oceanography of the red oceanic system

    NASA Astrophysics Data System (ADS)

    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

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

    PubMed

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

    2016-08-26

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

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

    PubMed

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

    2016-01-01

    The 2015 International Conference on Intelligent Biology and Medicine (ICIBM 2015) was held on November 13-15, 2015 in Indianapolis, Indiana, USA. ICIBM 2015 included eight scientific sessions, three tutorial sessions, one poster session, and four keynote presentations that covered the frontier research in broad areas related to bioinformatics, systems biology, big data science, biomedical informatics, pharmacogenomics, and intelligent computing. Here, we present a summary of the 10 research articles that were selected from ICIBM 2015 and included in the supplement to BMC Systems Biology. PMID:27587087

  9. Integrative systems biology for data-driven knowledge discovery.

    PubMed

    Greene, Casey S; Troyanskaya, Olga G

    2010-09-01

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

  10. Integrative Systems Biology for Data Driven Knowledge Discovery

    PubMed Central

    Greene, Casey S.; Troyanskaya, Olga G.

    2015-01-01

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

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

    PubMed Central

    Alfieri, Roberta; Merelli, Ivan; Mosca, Ettore; Milanesi, Luciano

    2007-01-01

    resource for collecting all the information related to actual and future models of this network. The flexibility of the database allows the addition of mathematical data which are used for simulating the behavior of the cell cycle components in the different models. The resource deals with two relevant problems in systems biology: data integration and mathematical simulation of a crucial biological process related to cancer, such as the cell cycle. In this way the resource is useful both to retrieve information about cell cycle model components and to analyze their dynamical properties. The Cell Cycle Database can be used to find system-level properties, such as stable steady states and oscillations, by coupling structure and dynamical information about models. PMID:17678529

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

    PubMed

    Astakhov, Vadim

    2009-01-01

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

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

    PubMed

    Bagley, James R; Galpin, Andrew J

    2015-01-01

    Interdisciplinary exploration is vital to education in the 21st century. This manuscript outlines an innovative laboratory-based teaching method that combines elements of biochemistry/molecular biology, kinesiology/health science, computer science, and manufacturing engineering to give students the ability to better conceptualize complex biological systems. Here, we utilize technology available at most universities to print three-dimensional (3D) scale models of actual human muscle cells (myofibers) out of bioplastic materials. The same methodological approach could be applied to nearly any cell type or molecular structure. This advancement is significant because historically, two-dimensional (2D) myocellular images have proven insufficient for detailed analysis of organelle organization and morphology. 3D imaging fills this void by providing accurate and quantifiable myofiber structural data. Manipulating tangible 3D models combats 2D limitation and gives students new perspectives and alternative learning experiences that may assist their understanding. This approach also exposes learners to 1) human muscle cell extraction and isolation, 2) targeted fluorescence labeling, 3) confocal microscopy, 4) image processing (via open-source software), and 5) 3D printing bioplastic scale-models (×500 larger than the actual cells). Creating these physical models may further student's interest in the invisible world of molecular and cellular biology. Furthermore, this interdisciplinary laboratory project gives instructors of all biological disciplines a new teaching tool to foster integrative thinking. PMID:26345697

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

    PubMed

    Bagley, James R; Galpin, Andrew J

    2015-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Green, Sara; Wolkenhauer, Olaf

    2013-01-01

    With the emergence of systems biology, the identification of organizing principles is being highlighted as a key research aim. Researchers attempt to "reverse engineer" the functional organization of biological systems using methodologies from mathematics, engineering and computer science while taking advantage of data produced by new experimental techniques. While systems biology is a relatively new approach, the quest for general principles of biological organization dates back to systems theoretic approaches in early and mid-twentieth century. The aim of this paper is to draw on this historical background in order to increase the understanding of the motivation behind the search for general principles and to clarify different epistemic aims within systems biology. We pinpoint key aspects of earlier approaches that also underlie the current practice. These are i) the focus on relational and system-level properties, ii) the inherent critique of reductionism and fragmentation of knowledge resulting from overspecialization, and iii) the insight that the ideal of formulating abstract organizing principles is complementary to, rather than conflicting with, the aim of formulating detailed explanations of biological mechanisms. We argue that looking back not only helps us understand the current practice but also points to possible future directions for systems biology. PMID:24783672

  17. Systems approaches for synthetic biology: a pathway toward mammalian design

    PubMed Central

    Rekhi, Rahul; Qutub, Amina A.

    2013-01-01

    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 toward 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. PMID:24130532

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

    EPA Science Inventory

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

  19. In Vitro Electrochemistry of Biological Systems

    PubMed Central

    Adams, Kelly L.; Puchades, Maja; Ewing, Andrew G.

    2009-01-01

    This article reviews recent work involving electrochemical methods for in vitro analysis of biomolecules, with an emphasis on detection and manipulation at and of single cells and cultures of cells. The techniques discussed include constant potential amperometry, chronoamperometry, cellular electroporation, scanning electrochemical microscopy, and microfluidic platforms integrated with electrochemical detection. The principles of these methods are briefly described, followed in most cases with a short description of an analytical or biological application and its significance. The use of electrochemical methods to examine specific mechanistic issues in exocytosis is highlighted, as a great deal of recent work has been devoted to this application. PMID:20151038

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

    PubMed

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

    2016-06-01

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

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

    PubMed

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

    2004-06-01

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

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

    PubMed

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

    2004-06-01

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

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

    PubMed

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

    2015-08-21

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Poyatos, Juan F

    2012-01-01

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

  6. Integrated physiology and systems biology of PPARα.

    PubMed

    Kersten, Sander

    2014-07-01

    The Peroxisome Proliferator Activated Receptor alpha (PPARα) is a transcription factor that plays a major role in metabolic regulation. This review addresses the functional role of PPARα in intermediary metabolism and provides a detailed overview of metabolic genes targeted by PPARα, with a focus on liver. A distinction is made between the impact of PPARα on metabolism upon physiological, pharmacological, and nutritional activation. Low and high throughput gene expression analyses have allowed the creation of a comprehensive map illustrating the role of PPARα as master regulator of lipid metabolism via regulation of numerous genes. The map puts PPARα at the center of a regulatory hub impacting fatty acid uptake, fatty acid activation, intracellular fatty acid binding, mitochondrial and peroxisomal fatty acid oxidation, ketogenesis, triglyceride turnover, lipid droplet biology, gluconeogenesis, and bile synthesis/secretion. In addition, PPARα governs the expression of several secreted proteins that exert local and endocrine functions.

  7. Learning Delayed Influences of Biological Systems

    PubMed Central

    Ribeiro, Tony; Magnin, Morgan; Inoue, Katsumi; Sakama, Chiaki

    2015-01-01

    Boolean networks are widely used model to represent gene interactions and global dynamical behavior of gene regulatory networks. To understand the memory effect involved in some interactions between biological components, it is necessary to include delayed influences in the model. In this paper, we present a logical method to learn such models from sequences of gene expression data. This method analyzes each sequence one by one to iteratively construct a Boolean network that captures the dynamics of these observations. To illustrate the merits of this approach, we apply it to learning real data from bioinformatic literature. Using data from the yeast cell cycle, we give experimental results and show the scalability of the method. We show empirically that using this method we can handle millions of observations and successfully capture delayed influences of Boolean networks. PMID:25642421

  8. Network benchmarking: a happy marriage between systems and synthetic biology.

    PubMed

    Minty, Jeremy J; Varedi K, S Marjan; Nina Lin, Xiaoxia

    2009-03-27

    In their new Cell paper, Cantone et al. (2009) present exciting results on constructing and utilizing a small synthetic gene regulatory network in yeast that draws from two rapidly developing fields of systems and synthetic biology.

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

    PubMed

    Dai, Zongjie; Nielsen, Jens

    2015-12-01

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

  10. [Systems biology: from yesterday's concepts to tomorrow's discoveries].

    PubMed

    Carvunis, Anne-Ruxandra; Gomez, Elisa; Thierry-Mieg, Nicolas; Trilling, Laurent; Vidal, Marc

    2009-01-01

    The idea that genes and their products are the fundamental units of biology has profoundly influenced our scientific thinking during the second half of the past century. Today, this reductionism is challenged by a renaissance of a systems understanding of biology, focusing on the systems formed by interacting gene products rather than on individual gene products. This discipline, based on a complementary and more holistic approach, keeps expanding its scope thanks to biotechnological innovations as well as theoretical modeling. This review aims at showing how and why, since the beginning of the 21st century, in fundamental as well as biomedical research, systems biology is proving a promising paradigm for understanding emerging properties of complex biological systems.

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

    PubMed Central

    2013-01-01

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

  12. Renal systems biology of patients with systemic inflammatory response syndrome.

    PubMed

    Tsalik, Ephraim L; Willig, Laurel K; Rice, Brandon J; van Velkinburgh, Jennifer C; Mohney, Robert P; McDunn, Jonathan E; Dinwiddie, Darrell L; Miller, Neil A; Mayer, Eric S; Glickman, Seth W; Jaehne, Anja K; Glew, Robert H; Sopori, Mohan L; Otero, Ronny M; Harrod, Kevin S; Cairns, Charles B; Fowler, Vance G; Rivers, Emanuel P; Woods, Christopher W; Kingsmore, Stephen F; Langley, Raymond J

    2015-10-01

    A systems biology approach was used to comprehensively examine the impact of renal disease and hemodialysis (HD) on patient response during critical illness. To achieve this, we examined the metabolome, proteome, and transcriptome of 150 patients with critical illness, stratified by renal function. Quantification of plasma metabolites indicated greater change as renal function declined, with the greatest derangements in patients receiving chronic HD. Specifically, 6 uremic retention molecules, 17 other protein catabolites, 7 modified nucleosides, and 7 pentose phosphate sugars increased as renal function declined, consistent with decreased excretion or increased catabolism of amino acids and ribonucleotides. Similarly, the proteome showed increased levels of low-molecular-weight proteins and acute-phase reactants. The transcriptome revealed a broad-based decrease in mRNA levels among patients on HD. Systems integration revealed an unrecognized association between plasma RNASE1 and several RNA catabolites and modified nucleosides. Further, allantoin, N1-methyl-4-pyridone-3-carboxamide, and N-acetylaspartate were inversely correlated with the majority of significantly downregulated genes. Thus, renal function broadly affected the plasma metabolome, proteome, and peripheral blood transcriptome during critical illness; changes were not effectively mitigated by hemodialysis. These studies allude to several novel mechanisms whereby renal dysfunction contributes to critical illness.

  13. Renal systems biology of patients with systemic inflammatory response syndrome

    PubMed Central

    Tsalik, Ephraim L.; Willig, Laurel K.; Rice, Brandon J.; van Velkinburgh, Jennifer C.; Mohney, Robert P.; McDunn, Jonathan; Dinwiddie, Darrell L.; Miller, Neil A.; Mayer, Eric; Glickman, Seth W.; Jaehne, Anja K.; Glew, Robert H.; Sopori, Mohan L.; Otero, Ronny M.; Harrod, Kevin S.; Cairns, Charles B.; Fowler, Vance G.; Rivers, Emanuel P.; Woods, Christopher W.; Kingsmore, Stephen F.; Langley, Raymond J.

    2015-01-01

    A systems biology approach was used to comprehensively examine the impact of renal disease and hemodialysis (HD) on patient response during critical illness. To achieve this we examined the metabolome, proteome, and transcriptome of 150 patients with critical illness, stratified by renal function. Quantification of plasma metabolites indicated greater change as renal function declined, with the greatest derangements in patients receiving chronic HD. Specifically, 6 uremic retention molecules, 17 other protein catabolites, 7 modified nucleosides, and 7 pentose phosphate sugars increased as renal function declined, consistent with decreased excretion or increased catabolism of amino acids and ribonucleotides. Similarly, the proteome showed increased levels of low-molecular weight proteins and acute phase reactants. The transcriptome revealed a broad-based decrease in mRNA levels among patients on HD. Systems integration revealed an unrecognized association between plasma RNASE1 and several RNA catabolites and modified nucleosides. Further, allantoin, N1-methyl-4-pyridone-3-carboxamide, and n-acetylaspartate were inversely correlated with the majority of significantly down-regulated genes. Thus, renal function broadly affected the plasma metabolome, proteome, and peripheral blood transcriptome during critical illness; changes not effectively mitigated by hemodialysis. These studies allude to several novel mechanisms whereby renal dysfunction contributes to critical illness. PMID:25993322

  14. Renal systems biology of patients with systemic inflammatory response syndrome.

    PubMed

    Tsalik, Ephraim L; Willig, Laurel K; Rice, Brandon J; van Velkinburgh, Jennifer C; Mohney, Robert P; McDunn, Jonathan E; Dinwiddie, Darrell L; Miller, Neil A; Mayer, Eric S; Glickman, Seth W; Jaehne, Anja K; Glew, Robert H; Sopori, Mohan L; Otero, Ronny M; Harrod, Kevin S; Cairns, Charles B; Fowler, Vance G; Rivers, Emanuel P; Woods, Christopher W; Kingsmore, Stephen F; Langley, Raymond J

    2015-10-01

    A systems biology approach was used to comprehensively examine the impact of renal disease and hemodialysis (HD) on patient response during critical illness. To achieve this, we examined the metabolome, proteome, and transcriptome of 150 patients with critical illness, stratified by renal function. Quantification of plasma metabolites indicated greater change as renal function declined, with the greatest derangements in patients receiving chronic HD. Specifically, 6 uremic retention molecules, 17 other protein catabolites, 7 modified nucleosides, and 7 pentose phosphate sugars increased as renal function declined, consistent with decreased excretion or increased catabolism of amino acids and ribonucleotides. Similarly, the proteome showed increased levels of low-molecular-weight proteins and acute-phase reactants. The transcriptome revealed a broad-based decrease in mRNA levels among patients on HD. Systems integration revealed an unrecognized association between plasma RNASE1 and several RNA catabolites and modified nucleosides. Further, allantoin, N1-methyl-4-pyridone-3-carboxamide, and N-acetylaspartate were inversely correlated with the majority of significantly downregulated genes. Thus, renal function broadly affected the plasma metabolome, proteome, and peripheral blood transcriptome during critical illness; changes were not effectively mitigated by hemodialysis. These studies allude to several novel mechanisms whereby renal dysfunction contributes to critical illness. PMID:25993322

  15. Inspirations from biological optics for advanced photonic systems.

    PubMed

    Lee, Luke P; Szema, Robert

    2005-11-18

    Observing systems in nature has inspired humans to create technological tools that allow us to better understand and imitate biology. Biomimetics, in particular, owes much of its current development to advances in materials science and creative optical system designs. New investigational tools, such as those for microscopic imaging and chemical analyses, have added to our understanding of biological optics. Biologically inspired optical science has become the emerging topic among researchers and scientists. This is in part due to the availability of polymers with customizable optical properties and the ability to rapidly fabricate complex designs using soft lithography and three-dimensional microscale processing techniques.

  16. Chemical Biological Emergency Management Information System

    2004-06-15

    CB-EMIS is designed to provide information and analysis to transit system operators and emergency responders in the event of a chemical attack on a subway system. The software inforporates detector data, video images, train data, meteorological data, and above- and below-ground plume dispersion models, hight of the liquid level.

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

    PubMed Central

    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 define biological processes associated with system physiology. Given the complexity and heterogeneity of asthma and allergic diseases, a systems biology approach is attractive, as it has the potential to model the myriad connections and interdependencies between genetic predisposition, environmental perturbations, regulatory intermediaries, and molecular sequelae that ultimately lead to diverse disease phenotypes and treatment responses across individuals. The increasing availability of high-throughput technologies has enabled system-wide profiling of the genome, transcriptome, epigenome, microbiome, and metabolome, providing fodder for systems biology approaches to examine asthma and allergy at a more holistic level. In this article, we review the technologies and approaches for system-wide profiling as well as their more recent applications to asthma and allergy. We discuss approaches for integrating multiscale data through network analyses and provide perspective on how individually-captured health profiles will contribute to more accurate systems biology views of asthma and allergy. PMID:25468194

  18. Systems biology of asthma and allergic diseases: a multiscale approach.

    PubMed

    Bunyavanich, Supinda; Schadt, Eric E

    2015-01-01

    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 define biological processes associated with system physiology. Given the complexity and heterogeneity of asthma and allergic diseases, a systems biology approach is attractive, as it has the potential to model the myriad connections and interdependencies between genetic predisposition, environmental perturbations, regulatory intermediaries, and molecular sequelae that ultimately lead to diverse disease phenotypes and treatment responses across individuals. The increasing availability of high-throughput technologies has enabled system-wide profiling of the genome, transcriptome, epigenome, microbiome, and metabolome, providing fodder for systems biology approaches to examine asthma and allergy at a more holistic level. In this article we review the technologies and approaches for system-wide profiling, as well as their more recent applications to asthma and allergy. We discuss approaches for integrating multiscale data through network analyses and provide perspective on how individually captured health profiles will contribute to more accurate systems biology views of asthma and allergy.

  19. New approaches in data integration for systems chemical biology.

    PubMed

    Seoane, Jose A; López-Campos, Guillermo; Dorado, Julian; Martin-Sanchez, Fernando

    2013-01-01

    Advances done in "-Omics" technologies in the last 20 years have made available to the researches huge amounts of data spanning a wide variety of biological processes from gene sequences to the metabolites present in a cell at a particular time. The management, analysis and representation of these data have been facilitated by mean of the advances made by biomedical informatics in areas such as data architecture and integration systems. However, despite the efforts done by biologists in this area, research in drug design adds a new level of information by incorporating data related with small molecules, which increases the complexity of these integration systems. Current knowledge in molecular biology has shown that it is possible to use comprehensive and integrative approaches to understand the biological processes from a systems perspective and that pathological processes can be mapped into biological networks. Therefore, current strategies for drug design are focusing on how to interact with or modify those networks to achieve the desired effects on what is called systems chemical biology. In this review several approaches for data integration in systems chemical biology will be analysed and described. Furthermore, because of the increasing relevance of the development and use of nanomaterials and their expected impact in the near future, the requirements of integration systems that incorporate these new data types associated with nanomaterials will also be analysed.

  20. Impact of monitoring blood volume in the BD BACTEC™ FX blood culture system: virtual volume versus actual volume.

    PubMed

    Chang, Jeonghyun; Park, Jeong Su; Park, Sookja; Choi, Byeonghoo; Yoon, Nam Seop; Sung, Heungsup; Kim, Mi-Na

    2015-02-01

    The BACTEC™ FX (BD, USA) has been recently upgraded to measure virtual blood volume (VV) in batches of 25 PLUS Aerobic/F bottles. VVs were compared with manually measured actual volumes (AVs). The mean AV was larger in anaerobic bottles: 2.6±1.9mL in 2995 Aerobic/F bottles and 3.3±1.8mL in 3053 Lytic/10 Anaerobic/F bottles (P<0.001). The VV of Aerobic/F bottles was 2.4±1.4mL, and there was a significant correlation between the VVs and AVs of each department (P<0.001). The potential positivity in aerobic bottles increased 1.2-fold with a 1-mL increase in the AV (P<0.001). AV and VV were consistently less than adequate. Although the proportional effect of volume on positivity can be proven only with the AV, VVs are a reliable substitute for AVs to monitor the overall blood volumes and provide feedback to the individual departments or locations.

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

    NASA Technical Reports Server (NTRS)

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

    2012-01-01

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

  2. Biological and Physical Thresholds in Biogeomorphologically Self-organizing Systems.

    NASA Astrophysics Data System (ADS)

    Herman, P.; Bouma, T. J.; Van de Koppel, J.; Borsje, B.; van Belzen, J.; Balke, T.

    2012-12-01

    Many coastal and estuarine landscapes are formed as a consequence of biological-physical interactions. We review examples that we recently studied: coastal vegetations, microphytobenthos-stabilized mudflats, macrofauna-dominated sediments, sand wave formation influenced by animals. In these diverse ecosystems, self-organisation of the coupled landscape results from the existence of positive feedback loops between the physical and biological components. We focus on the question where, in space and/or in time, such feedback systems develop and what determines their persistence and their ability to shape the landscape. We hypothesize that an equilibrium of forces between physical and biological factors is necessary for a feedback loop to develop. This implies a scale match and a commensurate strength of the different factors. There are many examples of systems that are physically too dynamic for the development of biological populations that affect the landscape. We also show an example where biological influence, in the form of strong grazing pressure on microphytobenthos, disrupts a self-organized system on a mudflat. Thus, we define thresholds in parameter space which constrain the development of strongly interacting biogeomorphological systems. The hypothesis of commensurate physical and biological forces as a condition for the development of biogeomorphological systems has important consequences for the establishment and recruitment of such systems. Biological interactions and biological effects on the physical system develop in time with the recruitment and maturation of the biological system. Fully developed systems can therefore be in balance with stronger physical forces than immature, early recruiting phases. This represents a successional threshold that is difficult to overcome. We stress the importance of stochastic variability in physical conditions at a diversity of scales as a prerequisite for phase transitions from physically dominated to

  3. Caged oligonucleotides for studying biological systems

    PubMed Central

    Ruble, Brittani K.; Yeldell, Sean B.; Dmochowski, Ivan J.

    2015-01-01

    Light-activated (“caged”) compounds have been widely employed for studying biological processes with high spatial and temporal control. In the past decade, several new approaches for caging the structure and function of DNA and RNA oligonucleotides have been developed. This review focuses on caged oligonucleotides that incorporate site-specifically one or two photocleavable linkers, whose photolysis yields oligonucleotides with dramatic structural and functional changes. This technique has been employed by our laboratory and others to photoregulate gene expression in cells and living organisms, typically using near UV-activated organic chromophores. To improve capabilities for in vivo studies, we harnessed the rich inorganic photochemistry of ruthenium bipyridyl complexes to synthesize Ru-caged morpholino antisense oligonucleotides that remain inactive in zebrafish embryos until uncaged with visible light. Expanding into new caged oligonucleotide applications, our lab has developed Transcriptome In Vivo Analysis (TIVA) technology, which provides the first noninvasive, unbiased method for isolating mRNA from single neurons in brain tissues. TIVA-isolated mRNA can be amplified and then analyzed using next-generation sequencing (RNA-seq). PMID:25865001

  4. Magnetic resonances of ions in biological systems.

    PubMed

    Engström, Stefan; Bowman, Joseph D

    2004-12-01

    A magnetic field transduction mechanism based on an ion oscillator model is derived from an explicit quantum mechanical description. The governing equation prescribes how the electric dipole moment of an ion oscillating in a symmetric potential well evolves under the influence of an arbitrary magnetic field. The resulting equation is an analog of the Bloch equation, a well-studied model for magnetic resonances in atomic and molecular spectroscopy. The differential equation for this ion oscillator model is solved numerically for a few illustrative magnetic field exposures, showing when those resonances occur with single frequency, linearly polarized fields. Our formulation makes explicit the conditions that must be present for magnetic fields to produce observable biological effects under the ion oscillator model. The ion's potential well must have symmetry sufficient to produce a degenerate excited state, e.g., octahedral or trigonal bipyramid potentials. The impulse that excites the ion must be spatially correlated with the orientation of the detector that reads off the final state of the oscillator. The orientation between the static and oscillating magnetic fields that produces resonance is a complicated function of the field magnitudes and frequency. We suggest several classes of experiments that could critically test the validity of the model presented here.

  5. Virtual Tissues and Developmental Systems Biology

    EPA Science Inventory

    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.

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

    PubMed Central

    Bartocci, Ezio; Lió, Pietro

    2016-01-01

    As the amount of biological data in the public domain grows, so does the range of modeling and analysis techniques employed in systems biology. In recent years, a number of theoretical computer science developments have enabled modeling methodology to keep pace. The growing interest in systems biology in executable models and their analysis has necessitated the borrowing of terms and methods from computer science, such as formal analysis, model checking, static analysis, and runtime verification. Here, we discuss the most important and exciting computational methods and tools currently available to systems biologists. We believe that a deeper understanding of the concepts and theory highlighted in this review will produce better software practice, improved investigation of complex biological processes, and even new ideas and better feedback into computer science. PMID:26795950

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

    PubMed

    Bartocci, Ezio; Lió, Pietro

    2016-01-01

    As the amount of biological data in the public domain grows, so does the range of modeling and analysis techniques employed in systems biology. In recent years, a number of theoretical computer science developments have enabled modeling methodology to keep pace. The growing interest in systems biology in executable models and their analysis has necessitated the borrowing of terms and methods from computer science, such as formal analysis, model checking, static analysis, and runtime verification. Here, we discuss the most important and exciting computational methods and tools currently available to systems biologists. We believe that a deeper understanding of the concepts and theory highlighted in this review will produce better software practice, improved investigation of complex biological processes, and even new ideas and better feedback into computer science.

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

    PubMed Central

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

    2014-01-01

    Motivation: Biological system behaviors are often the outcome of complex interactions among a large number of cells and their biotic and abiotic environment. Computational biologists attempt to understand, predict and manipulate biological system behavior through mathematical modeling and computer simulation. Discrete agent-based modeling (in combination with high-resolution grids to model the extracellular environment) is a popular approach for building biological system models. However, the computational complexity of this approach forces computational biologists to resort to coarser resolution approaches to simulate large biological systems. High-performance parallel computers have the potential to address the computing challenge, but writing efficient software for parallel computers is difficult and time-consuming. Results: We have developed Biocellion, a high-performance software framework, to solve this computing challenge using parallel computers. To support a wide range of multicellular biological system models, Biocellion asks users to provide their model specifics by filling the function body of pre-defined model routines. Using Biocellion, modelers without parallel computing expertise can efficiently exploit parallel computers with less effort than writing sequential programs from scratch. We simulate cell sorting, microbial patterning and a bacterial system in soil aggregate as case studies. Availability and implementation: Biocellion runs on x86 compatible systems with the 64 bit Linux operating system and is freely available for academic use. Visit http://biocellion.com for additional information. Contact: seunghwa.kang@pnnl.gov PMID:25064572

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

    PubMed

    Mazzocchi, Fulvio

    2012-01-01

    Reductionism has largely influenced the development of science, culminating in its application to molecular biology. An increasing number of novel research findings have, however, shattered this view, showing how the molecular-reductionist approach cannot entirely handle the complexity of biological systems. Within this framework, the advent of systems biology as a new and more integrative field of research is described, along with the form which has taken on the debate of reductionism versus holism. Such an issue occupies a central position in systems biology, and nonetheless it is not always clearly delineated. This partly occurs because different dimensions (ontological, epistemological, methodological) are involved, and yet the concerned ones often remain unspecified. Besides, within systems biology different streams can be distinguished depending on the degree of commitment to embrace genuine systemic principles. Some useful insights into the future development of this discipline might be gained from the tradition of complexity and self-organization. This is especially true with regards the idea of self-reference, which incorporated into the organizational scheme is able to generate autonomy as an emergent property of the biological whole. PMID:22761024

  10. Towards Engineering Biological Systems in a Broader Context.

    PubMed

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

    2016-02-27

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

  11. Circadian systems biology: When time matters

    PubMed Central

    Fuhr, Luise; Abreu, Mónica; Pett, Patrick; Relógio, Angela

    2015-01-01

    The circadian clock is a powerful endogenous timing system, which allows organisms to fine-tune their physiology and behaviour to the geophysical time. The interplay of a distinct set of core-clock genes and proteins generates oscillations in expression of output target genes which temporally regulate numerous molecular and cellular processes. The study of the circadian timing at the organismal as well as at the cellular level outlines the field of chronobiology, which has been highly interdisciplinary ever since its origins. The development of high-throughput approaches enables the study of the clock at a systems level. In addition to experimental approaches, computational clock models exist which allow the analysis of rhythmic properties of the clock network. Such mathematical models aid mechanistic understanding and can be used to predict outcomes of distinct perturbations in clock components, thereby generating new hypotheses regarding the putative function of particular clock genes. Perturbations in the circadian timing system are linked to numerous molecular dysfunctions and may result in severe pathologies including cancer. A comprehensive knowledge regarding the mechanistic of the circadian system is crucial to develop new procedures to investigate pathologies associated with a deregulated clock. In this manuscript we review the combination of experimental methodologies, bioinformatics and theoretical models that have been essential to explore this remarkable timing-system. Such an integrative and interdisciplinary approach may provide new strategies with regard to chronotherapeutic treatment and new insights concerning the restoration of the circadian timing in clock-associated diseases. PMID:26288701

  12. Computational Proteomics: High-throughput Analysis for Systems Biology

    SciTech Connect

    Cannon, William R.; Webb-Robertson, Bobbie-Jo M.

    2007-01-03

    High-throughput (HTP) proteomics is a rapidly developing field that offers the global profiling of proteins from a biological system. The HTP technological advances are fueling a revolution in biology, enabling analyses at the scales of entire systems (e.g., whole cells, tumors, or environmental communities). However, simply identifying the proteins in a cell is insufficient for understanding the underlying complexity and operating mechanisms of the overall system. Systems level investigations are relying more and more on computational analyses, especially in the field of proteomics generating large-scale global data.

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

    PubMed

    Molnár, László; Vágó, István; Fehér, András

    2003-01-01

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

  14. Biologic Therapy in Inflammatory Immunomediated Systemic Diseases: Safety Profile.

    PubMed

    Moroncini, Gianluca; Albani, Lisa; Nobili, Lorenzo; Gabrielli, Armando

    2016-01-01

    The discovery of some key molecular mechanisms underlying the dysregulation of the immune system responsible for inflammatory systemic diseases as severe as Systemic Lupus Erythematosus (SLE), Systemic Sclerosis (SSc), and Systemic Vasculitides, led to the development and subsequent introduction into clinical practice of biological drugs which are significantly improving the management of such complex disorders. This novel molecular targeted therapeutics represents in fact a valid alternative or complementary treatment to conventional immunosuppressive strategies, characterized by broad, unspecific actions and severe adverse effects. Main advantages of the use of biologic drugs reside in their steroid-sparing effect and in the ability of inducing remission of refractory disease states or curing specific organ involvements. Aim of this article is to review and briefly discuss the scientific evidence supporting the use of biologics in these diseases, with a particular emphasis on their efficacy and safety profile compared to the canonical drugs.

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

    PubMed

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

    2004-07-01

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

  16. Applications of targeted proteomics in systems biology and translational medicine.

    PubMed

    Ebhardt, H Alexander; Root, Alex; Sander, Chris; Aebersold, Ruedi

    2015-09-01

    Biological systems are composed of numerous components of which proteins are of particularly high functional significance. Network models are useful abstractions for studying these components in context. Network representations display molecules as nodes and their interactions as edges. Because they are difficult to directly measure, functional edges are frequently inferred from suitably structured datasets consisting of the accurate and consistent quantification of network nodes under a multitude of perturbed conditions. For the precise quantification of a finite list of proteins across a wide range of samples, targeted proteomics exemplified by selected/multiple reaction monitoring (SRM, MRM) mass spectrometry has proven useful and has been applied to a variety of questions in systems biology and clinical studies. Here, we survey the literature of studies using SRM-MS in systems biology and clinical proteomics. Systems biology studies frequently examine fundamental questions in network biology, whereas clinical studies frequently focus on biomarker discovery and validation in a variety of diseases including cardiovascular disease and cancer. Targeted proteomics promises to advance our understanding of biological networks and the phenotypic significance of specific network states and to advance biomarkers into clinical use.

  17. Applications of targeted proteomics in systems biology and translational medicine

    PubMed Central

    Root, Alex; Sander, Chris; Aebersold, Ruedi

    2015-01-01

    Biological systems are composed of numerous components of which proteins are of particularly high functional significance. Network models are useful abstractions for studying these components in context. Network representations display molecules as nodes and their interactions as edges. Because they are difficult to directly measure, functional edges are frequently inferred from suitably structured datasets consisting of the accurate and consistent quantification of network nodes under a multitude of perturbed conditions. For the precise quantification of a finite list of proteins across a wide range of samples, targeted proteomics exemplified by selected/multiple reaction monitoring (SRM, MRM) mass spectrometry has proven useful and has been applied to a variety of questions in systems biology and clinical studies. Here, we survey the literature of studies using SRM‐MS in systems biology and clinical proteomics. Systems biology studies frequently examine fundamental questions in network biology, whereas clinical studies frequently focus on biomarker discovery and validation in a variety of diseases including cardiovascular disease and cancer. Targeted proteomics promises to advance our understanding of biological networks and the phenotypic significance of specific network states and to advance biomarkers into clinical use. PMID:26097198

  18. An online model composition tool for system biology models

    PubMed Central

    2013-01-01

    Background There are multiple representation formats for Systems Biology computational models, and the Systems Biology Markup Language (SBML) is one of the most widely used. SBML is used to capture, store, and distribute computational models by Systems Biology data sources (e.g., the BioModels Database) and researchers. Therefore, there is a need for all-in-one web-based solutions that support advance SBML functionalities such as uploading, editing, composing, visualizing, simulating, querying, and browsing computational models. Results We present the design and implementation of the Model Composition Tool (Interface) within the PathCase-SB (PathCase Systems Biology) web portal. The tool helps users compose systems biology models to facilitate the complex process of merging systems biology models. We also present three tools that support the model composition tool, namely, (1) Model Simulation Interface that generates a visual plot of the simulation according to user’s input, (2) iModel Tool as a platform for users to upload their own models to compose, and (3) SimCom Tool that provides a side by side comparison of models being composed in the same pathway. Finally, we provide a web site that hosts BioModels Database models and a separate web site that hosts SBML Test Suite models. Conclusions Model composition tool (and the other three tools) can be used with little or no knowledge of the SBML document structure. For this reason, students or anyone who wants to learn about systems biology will benefit from the described functionalities. SBML Test Suite models will be a nice starting point for beginners. And, for more advanced purposes, users will able to access and employ models of the BioModels Database as well. PMID:24006914

  19. EVOLUTIONARY BIOSCIENCE AS REGULATORY SYSTEMS BIOLOGY

    PubMed Central

    Davidson, Eric H.

    2011-01-01

    At present several entirely different explanatory approaches compete to illuminate the mechanisms by which animal body plans have evolved. Their respective relevance is briefly considered here in the light of modern knowledge of genomes and the regulatory processes by which development is controlled. Just as development is a system property of the regulatory genome, so causal explanation of evolutionary change in developmental process must be considered at a system level. Here I enumerate some mechanistic consequences that follow from the conclusion that evolution of the body plan has occurred by alteration of the structure of developmental gene regulatory networks. The hierarchy and multiple additional design features of these networks act to produce Boolean regulatory state specification functions at upstream phases of development of the body plan. These are created by the logic outputs of network subcircuits, and in modern animals these outputs are impervious to continuous adaptive variation unlike genes operating more peripherally in the network. PMID:21320483

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

    PubMed

    Thompson, R C A; Jenkins, D J

    2014-10-15

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

  1. Modeling and simulation of biological systems from image data

    PubMed Central

    Sbalzarini, Ivo F

    2013-01-01

    This essay provides an introduction to the terminology, concepts, methods, and challenges of image-based modeling in biology. Image-based modeling and simulation aims at using systematic, quantitative image data to build predictive models of biological systems that can be simulated with a computer. This allows one to disentangle molecular mechanisms from effects of shape and geometry. Questions like “what is the functional role of shape” or “how are biological shapes generated and regulated” can be addressed in the framework of image-based systems biology. The combination of image quantification, model building, and computer simulation is illustrated here using the example of diffusion in the endoplasmic reticulum. PMID:23533152

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

    PubMed Central

    He, Xiaoming

    2011-01-01

    This review examines the fundamentals and challenges in engineering/understanding the thermostability of biological systems over a wide temperature range (from the cryogenic to hyperthermic regimen). Applications of the bio-thermostability engineering to either destroy unwanted or stabilize useful biologicals for the treatment of diseases in modern medicine are first introduced. Studies on the biological responses to cryogenic and hyperthermic temperatures for the various applications are reviewed to understand the mechanism of thermal (both cryo and hyperthermic) injury and its quantification at the molecular, cellular and tissue/organ levels. Methods for quantifying the thermophysical processes of the various applications are then summarized accounting for the effect of blood perfusion, metabolism, water transport across cell plasma membrane, and phase transition (both equilibrium and non-equilibrium such as ice formation and glass transition) of water. The review concludes with a summary of the status quo and future perspectives in engineering the thermostability of biological systems. PMID:21769301

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

    NASA Technical Reports Server (NTRS)

    Sethi, S. L.

    1975-01-01

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

  4. Enterobacter aerogenes Needle Stick Leads to Improved Biological Management System

    SciTech Connect

    Johanson, Richard E.

    2004-08-01

    A laboratory worker who received a needle stick from a contaminated needle while working with a culture containing Enterobactor aerogenes developed a laboratory acquired infection. Although this organism has been shown to cause community and nosocomial infections, there have been no documented cases of a laboratory acquired infections. Lessons learned from the event led to corrective actions which included modification of lab procedures, development of a biological inventory tracking and risk identification system and the establishment of an effective biological safety program.

  5. Towards Environmental Systems Biology of Shewanella

    SciTech Connect

    Fredrickson, Jim K.; Romine, Margaret F.; Beliaev, Alex S.; Auchutung, Jennifer M.; Driscoll, Michael E.; Gardner, Timothy S.; Nealson, Kenneth H.; Osterman, Andrei L.; Pinchuk, Grigoriy E.; Reed, Jennifer L.; Rodionov, Dmitry; Rodrigues, Jorge L.M.; Saffarini, Daad; Serres, Margrethe H.; Spormann, Alfred M.; Zhulin, Igor B.; Tiedje, James M.

    2008-07-07

    Abstract: Shewanella are known for versatility in their electron accepting capacities, which allow them to couple decomposition of organic matter to reduction of the variety of terminal electron acceptors encountered in the stratified environments they inhabit. Due to their diverse metabolic capabilities, shewanellae play important roles in carbon cycling and have considerable potential for remediation of contaminated environments and use in microbial fuel cells. Systems-level analysis of the model species, S. oneidensis MR-1, and other members of this genus have provided significant insights into the signal transduction proteins, regulators, and metabolic and respiratory subsystems governing the remarkable versatility of the shewanellae.

  6. Towards environmental systems biology of Shewanella

    SciTech Connect

    Beliaev, Alexander S; Nealson, Kenneth H.; Pinchuk, Grigoriy; Rodrigues, Jorge L.M.; Saffarini, Daad; Serres, Margrethe H.; Zhulin, Igor B; Tiedje, James M

    2008-01-01

    Bacteria of the genus Shewanella are known for their versatile electron-accepting capacities, which allow them to couple the decomposition of organic matter to the reduction of the various terminal electron acceptors that they encounter in their stratified environments. Owing to their diverse metabolic capabilities, shewanellae are important for carbon cycling and have considerable potential for the remediation of contaminated environments and use in microbial fuel cells. Systems-level analysis of the model species Shewanella oneidensis MR-1 and other members of this genus has provided new insights into the signal-transduction proteins, regulators, and metabolic and respiratory subsystems that govern the remarkable versatility of the shewanellae.

  7. Metabolic syndrome: from epidemiology to systems biology

    PubMed Central

    Lusis, Aldons J.; Attie, Alan D.; Reue, Karen

    2010-01-01

    Metabolic syndrome (MetSyn) is a group of metabolic conditions that occur together and promote the development of cardiovascular disease (CVD) and diabetes. Recent genome-wide association studies have identified several novel susceptibility genes for MetSyn traits, and studies in rodent models have provided important molecular insights. However, as yet, only a small fraction of the genetic component is known. Systems-based approaches that integrate genomic, molecular and physiological data are complementing traditional genetic and biochemical approaches to more fully address the complexity of MetSyn. PMID:18852695

  8. Phase transitions in fluids and biological systems

    NASA Astrophysics Data System (ADS)

    Sipos, Maksim

    In this thesis, I consider systems from two seemingly different fields: fluid dynamics and microbial ecology. In these systems, the unifying features are the existences of global non-equilibrium steady states. I consider generic and statistical models for transitions between these global states, and I relate the model results with experimental data. A theme of this thesis is that these rather simple, minimal models are able to capture a lot of functional detail about complex dynamical systems. In Part I, I consider the transition between laminar and turbulent flow. I find that quantitative and qualitative features of pipe flow experiments, the superexponential lifetime and the splitting of turbulent puffs, and the growth rate of turbulent slugs, can all be explained by a coarse-grained, phenomenological model in the directed percolation universality class. To relate this critical phenomena approach closer to the fluid dynamics, I consider the transition to turbulence in the Burgers equation, a simplified model for Navier-Stokes equations. Via a transformation to a model of directed polymers in a random medium, I find that the transition to Burgers turbulence may also be in the directed percolation universality class. This evidence implies that the turbulent-to-laminar transition is statistical in nature and does not depend on details of the Navier-Stokes equations describing the fluid flow. In Part II, I consider the disparate subject of microbial ecology where the complex interactions within microbial ecosystems produce observable patterns in microbe abundance, diversity and genotype. In order to be able to study these patterns, I develop a bioinformatics pipeline to multiply align and quickly cluster large microbial metagenomics datasets. I also develop a novel metric that quantifies the degree of interactions underlying the assembly of a microbial ecosystem, particularly the transition between neutral (random) and niche (deterministic) assembly. I apply this

  9. Modeling of Biological Intelligence for SCM System Optimization

    PubMed Central

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

    2012-01-01

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

  10. Modeling of biological intelligence for SCM system optimization.

    PubMed

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

    2012-01-01

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

  11. BioModel engineering for multiscale Systems Biology.

    PubMed

    Heiner, Monika; Gilbert, David

    2013-04-01

    We discuss some motivational challenges arising from the need to model and analyse complex biological systems at multiple scales (spatial and temporal), and present a biomodel engineering framework to address some of these issues within the context of multiscale Systems Biology. Our methodology is based on a structured family of Petri net classes which enables the investigation of a given system using various modelling abstractions: qualitative, stochastic, continuous and hybrid, optionally in a spatial context. We illustrate our approach with case studies demonstrating hierarchical flattening, treatment of space, and hierarchical organisation of space.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  13. Reproducible quantitative proteotype data matrices for systems biology

    PubMed Central

    Röst, Hannes L.; Malmström, Lars; Aebersold, Ruedi

    2015-01-01

    Historically, many mass spectrometry–based proteomic studies have aimed at compiling an inventory of protein compounds present in a biological sample, with the long-term objective of creating a proteome map of a species. However, to answer fundamental questions about the behavior of biological systems at the protein level, accurate and unbiased quantitative data are required in addition to a list of all protein components. Fueled by advances in mass spectrometry, the proteomics field has thus recently shifted focus toward the reproducible quantification of proteins across a large number of biological samples. This provides the foundation to move away from pure enumeration of identified proteins toward quantitative matrices of many proteins measured across multiple samples. It is argued here that data matrices consisting of highly reproducible, quantitative, and unbiased proteomic measurements across a high number of conditions, referred to here as quantitative proteotype maps, will become the fundamental currency in the field and provide the starting point for downstream biological analysis. Such proteotype data matrices, for example, are generated by the measurement of large patient cohorts, time series, or multiple experimental perturbations. They are expected to have a large effect on systems biology and personalized medicine approaches that investigate the dynamic behavior of biological systems across multiple perturbations, time points, and individuals. PMID:26543201

  14. Reproducible quantitative proteotype data matrices for systems biology.

    PubMed

    Röst, Hannes L; Malmström, Lars; Aebersold, Ruedi

    2015-11-01

    Historically, many mass spectrometry-based proteomic studies have aimed at compiling an inventory of protein compounds present in a biological sample, with the long-term objective of creating a proteome map of a species. However, to answer fundamental questions about the behavior of biological systems at the protein level, accurate and unbiased quantitative data are required in addition to a list of all protein components. Fueled by advances in mass spectrometry, the proteomics field has thus recently shifted focus toward the reproducible quantification of proteins across a large number of biological samples. This provides the foundation to move away from pure enumeration of identified proteins toward quantitative matrices of many proteins measured across multiple samples. It is argued here that data matrices consisting of highly reproducible, quantitative, and unbiased proteomic measurements across a high number of conditions, referred to here as quantitative proteotype maps, will become the fundamental currency in the field and provide the starting point for downstream biological analysis. Such proteotype data matrices, for example, are generated by the measurement of large patient cohorts, time series, or multiple experimental perturbations. They are expected to have a large effect on systems biology and personalized medicine approaches that investigate the dynamic behavior of biological systems across multiple perturbations, time points, and individuals.

  15. Transport processes in biological systems: Tumoral cells and human brain

    NASA Astrophysics Data System (ADS)

    Lucia, Umberto

    2014-01-01

    The entropy generation approach has been developed for the analysis of complex systems, with particular regards to biological systems, in order to evaluate their stationary states. The entropy generation is related to the transport processes related to exergy flows. Moreover, cancer can be described as an open complex dynamic and self-organizing system. Consequently, it is used as an example useful to evaluate the different thermo-chemical quantities of the transport processes in normal and in tumoral cells systems.

  16. Interactive analysis of systems biology molecular expression data

    PubMed Central

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

    2008-01-01

    Background Systems biology aims to understand biological systems on a comprehensive scale, such that the components that make up the whole are connected to one another and work through dependent interactions. Molecular correlations and comparative studies of molecular expression are crucial to establishing interdependent connections in systems biology. The existing software packages provide limited data mining capability. The user must first generate visualization data with a preferred data mining algorithm and then upload the resulting data into the visualization package for graphic visualization of molecular relations. Results Presented is a novel interactive visual data mining application, SysNet that provides an interactive environment for the analysis of high data volume molecular expression information of most any type from biological systems. It integrates interactive graphic visualization and statistical data mining into a single package. SysNet interactively presents intermolecular correlation information with circular and heatmap layouts. It is also applicable to comparative analysis of molecular expression data, such as time course data. Conclusion The SysNet program has been utilized to analyze elemental profile changes in response to an increasing concentration of iron (Fe) in growth media (an ionomics dataset). This study case demonstrates that the SysNet software is an effective platform for interactive analysis of molecular expression information in systems biology. PMID:18312669

  17. Systems Biology and Mode of Action Based Risk Assessment

    EPA Science Inventory

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

  18. The Use of an Electronic Response System in Teaching Biology

    ERIC Educational Resources Information Center

    Bessler, William C.; Nisbet, Jerry J.

    1971-01-01

    An electronic student response system was used in teaching college biology to non-science students. Achievement of this treatment group was compared with that of the control group (not utilizing the response system). The only statistical significant difference found in an analysis of covariance was an interaction between treatment group and time…

  19. What's behind the Biological Classification System in Use Today?

    ERIC Educational Resources Information Center

    Robertson, William C.

    2010-01-01

    Whether students should memorize classification schemes (taxonomies) is a column in itself, but the author can address the role that this system plays in the study of biology. To that end, it will help to address how the system developed over time. And toward "that" end, you will do a simple activity to start. (Contains 3 figures.)

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

    EPA Science Inventory

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

  1. Actualizing panarchy within environmental policy: mechanisms for tweaking institutional hierarchies to mimic the social-ecological systems they manage

    EPA Science Inventory

    Environmental law plays a key role in shaping approaches to sustainability. In particular, the role of legal instruments, institutions, and the relationship of law to the inherent variability in social-ecological systems is critical. Sustainability likely must occur via the insti...

  2. Can Schools Be Autonomous in a Centralised Educational System?: On Formal and Actual School Autonomy in the Italian Context

    ERIC Educational Resources Information Center

    Agasisti, Tommaso; Catalano, Giuseppe; Sibiano, Piergiacomo

    2013-01-01

    Purpose: The purpose of this paper is to examine the difference between formal and real school autonomy in the Italian educational system. The Italian case is characterised by low levels of school autonomy. It is interesting to consider whether heterogeneity of patterns is possible in this context. A description of this heterogeneity is provided…

  3. An open system network for the biological sciences.

    PubMed Central

    Springer, G. K.; Loch, J. L.; Patrick, T. B.

    1991-01-01

    A description of an open system, distributed computing environment for the Biological Sciences is presented. This system utilizes a transparent interface in a computer network using NCS to implement an application system for molecular biologists to perform various processing activities from their local workstation. This system accepts requests for the services of a remote database server, located across the network, to perform all of the database searches needed to support the activities of the user. This database access is totally transparent to the user of the system and it appears, to the user, that all activities are being carried out on the local workstation. This system is a prototype for a much more extensive system being built to support the research efforts in the Biological Sciences at UMC. PMID:1807659

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

    PubMed

    Fong, Stephen S

    2014-08-01

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

  5. Effect of long-term actual spaceflight on the expression of key genes encoding serotonin and dopamine system

    NASA Astrophysics Data System (ADS)

    Popova, Nina; Shenkman, Boris; Naumenko, Vladimir; Kulikov, Alexander; Kondaurova, Elena; Tsybko, Anton; Kulikova, Elisabeth; Krasnov, I. B.; Bazhenova, Ekaterina; Sinyakova, Nadezhda

    The effect of long-term spaceflight on the central nervous system represents important but yet undeveloped problem. The aim of our work was to study the effect of 30-days spaceflight of mice on Russian biosatellite BION-M1 on the expression in the brain regions of key genes of a) serotonin (5-HT) system (main enzymes in 5-HT metabolism - tryptophan hydroxylase-2 (TPH-2), monoamine oxydase A (MAO A), 5-HT1A, 5-HT2A and 5-HT3 receptors); b) pivotal enzymes in DA metabolism (tyrosine hydroxylase, COMT, MAO A, MAO B) and D1, D2 receptors. Decreased expression of genes encoding the 5-HT catabolism (MAO A) and 5-HT2A receptor in some brain regions was shown. There were no differences between “spaceflight” and control mice in the expression of TPH-2 and 5-HT1A, 5-HT3 receptor genes. Significant changes were found in genetic control of DA system. Long-term spaceflight decreased the expression of genes encoding the enzyme in DA synthesis (tyrosine hydroxylase in s.nigra), DA metabolism (MAO B in the midbrain and COMT in the striatum), and D1 receptor in hypothalamus. These data suggested that 1) microgravity affected genetic control of 5-HT and especially the nigrostriatal DA system implicated in the central regulation of muscular tonus and movement, 2) the decrease in the expression of genes encoding key enzyme in DA synthesis, DA degradation and D1 receptor contributes to the movement impairment and dyskinesia produced by the spaceflight. The study was supported by Russian Foundation for Basic Research grant № 14-04-00173.

  6. Systems Biology Approaches to a Rational Drug Discovery Paradigm.

    PubMed

    Prathipati, Philip; Mizuguchi, Kenji

    2016-01-01

    Ligand- and structure-based drug design approaches complement phenotypic and target screens, respectively, and are the two major frameworks for guiding early-stage drug discovery efforts. Since the beginning of this century, the advent of the genomic era has presented researchers with a myriad of high throughput biological data (parts lists and their interaction networks) to address efficacy and toxicity, augmenting the traditional ligand- and structure-based approaches. This data rich era has also presented us with challenges related to integrating and analyzing these multi-platform and multi-dimensional datasets and translating them into viable hypotheses. Hence in the present paper, we review these existing approaches to drug discovery research and argue the case for a new systems biology based approach. We present the basic principles and the foundational arguments/underlying assumptions of the systems biology based approaches to drug design. Also discussed are systems biology data types (key entities, their attributes and their relationships with each other, and data models/representations), software and tools used for both retrospective and prospective analysis, and the hypotheses that can be inferred. In addition, we summarize some of the existing resources for a systems biology based drug discovery paradigm (open TG-GATEs, DrugMatrix, CMap and LINCs) in terms of their strengths and limitations. PMID:26306988

  7. Systems Biology Approaches to a Rational Drug Discovery Paradigm.

    PubMed

    Prathipati, Philip; Mizuguchi, Kenji

    2016-01-01

    Ligand- and structure-based drug design approaches complement phenotypic and target screens, respectively, and are the two major frameworks for guiding early-stage drug discovery efforts. Since the beginning of this century, the advent of the genomic era has presented researchers with a myriad of high throughput biological data (parts lists and their interaction networks) to address efficacy and toxicity, augmenting the traditional ligand- and structure-based approaches. This data rich era has also presented us with challenges related to integrating and analyzing these multi-platform and multi-dimensional datasets and translating them into viable hypotheses. Hence in the present paper, we review these existing approaches to drug discovery research and argue the case for a new systems biology based approach. We present the basic principles and the foundational arguments/underlying assumptions of the systems biology based approaches to drug design. Also discussed are systems biology data types (key entities, their attributes and their relationships with each other, and data models/representations), software and tools used for both retrospective and prospective analysis, and the hypotheses that can be inferred. In addition, we summarize some of the existing resources for a systems biology based drug discovery paradigm (open TG-GATEs, DrugMatrix, CMap and LINCs) in terms of their strengths and limitations.

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

    PubMed

    Engelhardt, Benjamin; Frőhlich, Holger; Kschischo, Maik

    2016-01-01

    Mathematical modelling is a labour intensive process involving several iterations of testing on real data and manual model modifications. In biology, the domain knowledge guiding model development is in many cases itself incomplete and uncertain. A major problem in this context is that biological systems are open. Missed or unknown external influences as well as erroneous interactions in the model could thus lead to severely misleading results. Here we introduce the dynamic elastic-net, a data driven mathematical method which automatically detects such model errors in ordinary differential equation (ODE) models. We demonstrate for real and simulated data, how the dynamic elastic-net approach can be used to automatically (i) reconstruct the error signal, (ii) identify the target variables of model error, and (iii) reconstruct the true system state even for incomplete or preliminary models. Our work provides a systematic computational method facilitating modelling of open biological systems under uncertain knowledge. PMID:26865316

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

    NASA Astrophysics Data System (ADS)

    Engelhardt, Benjamin; Frőhlich, Holger; Kschischo, Maik

    2016-02-01

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

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

    PubMed

    Engelhardt, Benjamin; Frőhlich, Holger; Kschischo, Maik

    2016-02-11

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

  11. Unravelling adverse reactions to NSAIDs using systems biology.

    PubMed

    Perkins, James R; Sanak, Marek; Canto, Gabriela; Blanca, Miguel; Cornejo-García, José Antonio

    2015-03-01

    We introduce the reader to systems biology, using adverse drug reactions (ADRs), specifically hypersensitivity reactions to multiple non-steroidal anti-inflammatory drugs (NSAIDs), as a model. To disentangle the different processes that contribute to these reactions - from drug intake to the appearance of symptoms - it will be necessary to create high-throughput datasets. Just as crucial will be the use of systems biology to integrate and make sense of them. We review previous work using systems biology to study related pathologies such as asthma/allergy, and NSAID metabolism. We show examples of their application to NSAIDs-hypersensitivity using current datasets. We describe breakthroughs in high-throughput technology and speculate on their use to improve our understanding of this and other drug-induced pathologies.

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

    PubMed Central

    Engelhardt, Benjamin; Frőhlich, Holger; Kschischo, Maik

    2016-01-01

    Mathematical modelling is a labour intensive process involving several iterations of testing on real data and manual model modifications. In biology, the domain knowledge guiding model development is in many cases itself incomplete and uncertain. A major problem in this context is that biological systems are open. Missed or unknown external influences as well as erroneous interactions in the model could thus lead to severely misleading results. Here we introduce the dynamic elastic-net, a data driven mathematical method which automatically detects such model errors in ordinary differential equation (ODE) models. We demonstrate for real and simulated data, how the dynamic elastic-net approach can be used to automatically (i) reconstruct the error signal, (ii) identify the target variables of model error, and (iii) reconstruct the true system state even for incomplete or preliminary models. Our work provides a systematic computational method facilitating modelling of open biological systems under uncertain knowledge. PMID:26865316

  13. Actual Condition Evaluation of Cogeneration System in an Urbanized Hotel, and Study of the Optimal Operation to Minimize the CO2 Emission

    NASA Astrophysics Data System (ADS)

    Katsuta, Masafumi; Kaneko, Akira; Yamamoto, Toru

    Recently, there is an important subject to reduce of the CO2 emission discharged from a building. A cogeneration system (CGS) is one of the effective facilities to reduce of the CO2 emission, but prudent consideration is required in design and operation. Because it is necessary to be matching electric demand and heat demand in order to obtain the high efficiency. In this paper, it is evaluated the power generation efficiency and heat recovery one of CGS in the actual urbanized hotel as measurement result. In addition, the optimal operation analysis is carried out in order to minimize CO2 emission in the present facility.

  14. Nervous System of Periplaneta americana Cockroach as a Model in Toxinological Studies: A Short Historical and Actual View.

    PubMed

    Stankiewicz, Maria; Dąbrowski, Marcin; de Lima, Maria Elena

    2012-01-01

    Nervous system of Periplaneta americana cockroach is used in a wide range of pharmacological studies, including electrophysiological techniques. This paper presents its role as a preparation in the development of toxinological studies in the following electrophysiological methods: double-oil-gap technique on isolated giant axon, patch-clamp on DUM (dorsal unpaired median) neurons, microelectrode technique in situ conditions on axon in connective and DUM neurons in ganglion, and single-fiber oil-gap technique on last abdominal ganglion synapse. At the end the application of cockroach synaptosomal preparation is mentioned. PMID:22666245

  15. Form and Actuality

    NASA Astrophysics Data System (ADS)

    Bitbol, Michel

    A basic choice underlies physics. It consists of banishing actual situations from theoretical descriptions, in order to reach a universal formal construct. Actualities are then thought of as mere local appearances of a transcendent reality supposedly described by the formal construct. Despite its impressive success, this method has left major loopholes in the foundations of science. In this paper, I document two of these loopholes. One is the problem of time asymmetry in statistical thermodynamics, and the other is the measurement problem of quantum mechanics. Then, adopting a broader philosophical standpoint, I try to turn the whole picture upside down. Here, full priority is given to actuality (construed as a mode of the immanent reality self-reflectively being itself) over formal constructs. The characteristic aporias of this variety of "Copernican revolution" are discussed.

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

    PubMed

    Jagers op Akkerhuis, Gerard A J M

    2008-02-01

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

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

    PubMed

    Jagers op Akkerhuis, Gerard A J M

    2008-02-01

    A structured approach is discussed for analysing hierarchy in the organization of biological and physical systems. The need for a structured approach follows from the observation that many hierarchies in the literature apply conflicting hierarchy rules and include ill-defined systems. As an alternative, we suggest a framework that is based on the following analytical steps: determination of the succession stage of the universe, identification of a specific system as part of the universe, specification of external influences on a system's creation and analysis of a system's internal organization. At the end, the paper discusses practical implications of the proposed method for the analysis of system organization and hierarchy in biology, ecology and physics. PMID:18211280

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

    PubMed Central

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

    2012-01-01

    Meridians, acupoints, and Chinese herbs are important components of traditional Chinese medicine (TCM). They have been used for disease treatment and prevention and as alternative and complementary therapies. Systems biology integrates omics data, such as transcriptional, proteomic, and metabolomics data, in order to obtain a more global and complete picture of biological activity. To further understand the existence and functions of the three components above, we reviewed relevant research in the systems biology literature and found many recent studies that indicate the value of acupuncture and Chinese herbs. Acupuncture is useful in pain moderation and relieves various symptoms arising from acute spinal cord injury and acute ischemic stroke. Moreover, Chinese herbal extracts have been linked to wound repair, the alleviation of postmenopausal osteoporosis severity, and anti-tumor effects, among others. Different acupoints, variations in treatment duration, and herbal extracts can be used to alleviate various symptoms and conditions and to regulate biological pathways by altering gene and protein expression. Our paper demonstrates how systems biology has helped to establish a platform for investigating the efficacy of TCM in treating different diseases and improving treatment strategies. PMID:23118787

  19. Controlled biological and biomimetic systems for landmine detection.

    PubMed

    Habib, Maki K

    2007-08-30

    Humanitarian demining requires to accurately detect, locate and deactivate every single landmine and other buried mine-like objects as safely and as quickly as possible, and in the most non-invasive manner. The quality of landmine detection affects directly the efficiency and safety of this process. Most of the available methods to detect explosives and landmines are limited by their sensitivity and/or operational complexities. All landmines leak with time small amounts of their explosives that can be found on surrounding ground and plant life. Hence, explosive signatures represent the robust primary indicator of landmines. Accordingly, developing innovative technologies and efficient techniques to identify in real-time explosives residue in mined areas represents an attractive and promising approach. Biological and biologically inspired detection technology has the potential to compete with or be used in conjunction with other artificial technology to complement performance strengths. Biological systems are sensitive to many different scents concurrently, a property that has proven difficult to replicate artificially. Understanding biological systems presents unique opportunities for developing new capabilities through direct use of trained bio-systems, integration of living and non-living components, or inspiring new design by mimicking biological capabilities. It is expected that controlled bio-systems, biotechnology and microbial techniques will contribute to the advancement of mine detection and other application domains. This paper provides directions, evaluation and analysis on the progress of controlled biological and biomimetic systems for landmine detection. It introduces and discusses different approaches developed, underlining their relative advantages and limitations, and highlighting trends, safety and ecology concern, and possible future directions. PMID:17662594

  20. Resentment of paternalism as system change sentiment: hostile sexism toward men and actual behavior in the 2008 U.S. presidential election.

    PubMed

    Tate, Charlotte Chuck

    2014-01-01

    Taking inspiration from Glick and colleagues (2004), this study tested the idea that resentment of paternalism (which is part of the hostile sexism toward men construct) might approximate desire for system change by correlating this variable with actual behavior associated with system change in a single culture. Specifically, voting behavior in the 2008 U.S. presidential election was predicted from political party affiliation, measures of hostile and benevolent sexism toward both women and men, and egalitarian racial attitudes using a U.S. college student sample. Results indicated that the only significant predictors of voting behavior were political party affiliation, resentment of paternalism, and egalitarian racial attitudes. Higher levels of resentment of paternalism were in fact associated with voting for the ticket that represented system change-holding the other predictors constant.

  1. Short-range biological standoff detection system (SR-BSDS)

    NASA Astrophysics Data System (ADS)

    Suliga, William; Burnham, Ralph L.; Deely, Timothy; Gavert, William; Pronko, Mark S.; Verdun, Gustavo; Verdun, Horacio R.; Cannaliato, V. James; Ginley, William J.; Hyttinen, Larry; Strawbridge, John B.

    1999-11-01

    Fibertek is currently under contract to the US Army Soldier and Biological Chemical Command (SBCCOM) at Aberdeen Proving Ground, MD to develop a multi-wavelength lidar system. Under this effort, Fibertek will deliver a system that is capable of detecting the presence of biological aerosols. The SR-BSDS has successfully demonstrated the ability to detect and track a biological aerosol cloud while discriminating between biological and non-biological aerosols and hard targets. The SR-BSDS is an active standoff detection system with both ultraviolet (UV) and infrared (IR) capability. The UV wavelengths can provide near real time detection and ranging of a particulate cloud with demonstrated discrimination capability. Recent enhancements to the IR capability extended the cloud detection range and acquisition capability as well as providing an autonomous operation mode of operation. The SR-BSDS can be operated in one of two modes, manual or autonomous. In the manual mode the operator selects the desired scan field of view, resolution, wavelength, and degree of pulse coadding, then instructs the system to start scanning. The system will monitor its own performance and display information to the operator to indicate proper operation. The system will monitor cloud data and warn the operator when the sensor is aimed at an aerosol of interest. If a biological cloud of interest is found, an audible alarm will sound, and the operator can examine cloud imagery while the system continues to automatically monitor and track all clouds in the field-of-view. The scanning parameters can also be changed easily upon aerosol detection, if desired. In the autonomous mode, the operator selects the desired scan field of view. The system automatically scans for aerosol clouds with the IR beam. This is accomplished in a rapid, single pulse laser firing mode. Once a cloud with specified characteristics is acquired, the system automatically switches over to an UV beam for discrimination

  2. The development of a test system for investigating the performances of personal aerosol samplers under actual workplace conditions.

    PubMed

    Botham, R A; Hughson, G W; Vincent, J H; Mark, D

    1991-10-01

    The performances of new "total" aerosol samplers for use in workplaces are required to match the inhalability criteria as contained in the latest recommendations of the International Standards Organization (ISO) and the American Conference of Governmental Industrial Hygienists (ACGIH). In the past, practical evaluations have been carried out under idealized conditions in wind tunnels, and there is now the need to extend these to more realistic workplace conditions. This paper describes a new test system that was designed and built for this purpose. It consisted of a life-size mannequin mounted on a trolley so that it can be taken to and wheeled around in workplaces. The mannequin itself incorporated a robotic arm so that, under joystick control, it can be made to simulate a range of worker movements, orientations, and attitudes. An electronically controlled, compact breathing machine provided a range of typical breathing parameters for the mannequin. The pump also provided air movement for a number of personal samplers that were mounted on the torso of the mannequin and tested in that position. Sampler performance should be assessed by comparing directly the aerosol collected by the sampler with that inhaled by the mannequin (and collected on filters inside the head).

  3. Role of Ubiquitin-Mediated Degradation System in Plant Biology

    PubMed Central

    Sharma, Bhaskar; Joshi, Deepti; Yadav, Pawan K.; Gupta, Aditya K.; Bhatt, Tarun K.

    2016-01-01

    Ubiquitin-mediated proteasomal degradation is an important mechanism to control protein load in the cells. Ubiquitin binds to a protein on lysine residue and usually promotes its degradation through 26S proteasome system. Abnormal proteins and regulators of many processes, are targeted for degradation by the ubiquitin-proteasome system. It allows cells to maintain the response to cellular level signals and altered environmental conditions. The ubiquitin-mediated proteasomal degradation system plays a key role in the plant biology, including abiotic stress, immunity, and hormonal signaling by interfering with key components of these pathways. The involvement of the ubiquitin system in many vital processes led scientists to explore more about the ubiquitin machinery and most importantly its targets. In this review, we have summarized recent discoveries of the plant ubiquitin system and its involvement in critical processes of plant biology. PMID:27375660

  4. Role of Ubiquitin-Mediated Degradation System in Plant Biology.

    PubMed

    Sharma, Bhaskar; Joshi, Deepti; Yadav, Pawan K; Gupta, Aditya K; Bhatt, Tarun K

    2016-01-01

    Ubiquitin-mediated proteasomal degradation is an important mechanism to control protein load in the cells. Ubiquitin binds to a protein on lysine residue and usually promotes its degradation through 26S proteasome system. Abnormal proteins and regulators of many processes, are targeted for degradation by the ubiquitin-proteasome system. It allows cells to maintain the response to cellular level signals and altered environmental conditions. The ubiquitin-mediated proteasomal degradation system plays a key role in the plant biology, including abiotic stress, immunity, and hormonal signaling by interfering with key components of these pathways. The involvement of the ubiquitin system in many vital processes led scientists to explore more about the ubiquitin machinery and most importantly its targets. In this review, we have summarized recent discoveries of the plant ubiquitin system and its involvement in critical processes of plant biology. PMID:27375660

  5. Agent-based models in translational systems biology

    PubMed Central

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

    2013-01-01

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

  6. Request for Travel Funds for Systems Radiation Biology Workshop

    SciTech Connect

    Barcellos-Hoff, Mary Helen

    2014-03-22

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

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

    PubMed

    Maunder, R

    1996-01-01

    Biological theories of brain and psychological theories of mind are two systems of explanation that seem related to one another. The nature of the relationship is problematic and constitutes the age-old mind-body problem. The most prominent solutions currently are variations of materialism. While psychological theories can be consistent with materialism, there remains a difficulty in comprehending nonphysical (social, psychological) causes of physical effects. This difficulty is an obstacle to integration in psychiatry, where we routinely assume that illnesses that include or depend on biological dysfunction are caused multifactorially by causal agents such as perceived parental warmth, parental loss, stressful life events, genetics, and personality (Hammen et al. 1992; Kendler et al. 1993). Unity theory adopts the stance that neurobiological theories and psychological theories are essentially disparate explanations of the same psychobiological events; thus the relationship of mind to brain is one of shared reference (Goodman 1991; Maunder 1995). In Goodman's model the gap between biological and psychological systems is not bridgeable. Different conceptual categories refer to the same referents but cannot interact with each other. Stepping into the breach, systems theory has been presented as offering a language that can bridge the gap between psychological and biological theories of causation (Schwartz 1981; Weiner 1989). Thus, there is a controversy about the applicability of systems theory for integration in psychiatry. PMID:8837180

  8. Integration of proteomics into systems biology of cancer.

    PubMed

    Hanash, S; Schliekelman, M; Zhang, Q; Taguchi, A

    2012-01-01

    Deciphering the complexity and heterogeneity of cancer, benefits from integration of proteomic level data into systems biology efforts. The opportunities available as a result of advances in proteomic technologies, the successes to date, and the challenges involved in integrating diverse datasets are addressed in this review.

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

    PubMed

    Maunder, R

    1996-01-01

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

  10. Systems Biology & Mode of Action Based Risk Assessment

    EPA Science Inventory

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

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  12. Integrating Computer Interfaced Videodisc Systems in Introductory College Biology.

    ERIC Educational Resources Information Center

    Ebert-Zawasky, Kathleen; Abegg, Gerald L.

    This study was designed as a systematic investigation of the feasibility and effectiveness of student authored videodisc presentations in a non-major introductory level college biology course. Students (n=66) used a quick-learn authoring system, the Macintosh computer, and videodisc player with color monitor. Results included: (1) students managed…

  13. Cancer systems biology: signal processing for cancer research.

    PubMed

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

    2011-04-01

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

  14. Can systems biology help to separate evolutionary analogies (convergent homoplasies) from homologies?

    PubMed

    Gordon, Malcolm S; Notar, Julia C

    2015-01-01

    Convergent evolutionary analogies (homoplasies) of many kinds occur in diverse phylogenetic clades/lineages on both the animal and plant branches of the Tree of Life. Living organisms whose last common ancestors lived millions to hundreds of millions of years ago have later converged morphologically, behaviorally or at other levels of functionality (from molecular genetics through biochemistry, physiology and other organismic processes) as a result of long term strong natural selection that has constrained and channeled evolutionary processes. This happens most often when organisms belonging to different clades occupy ecological niches, habitats or environments sharing major characteristics that select for a relatively narrow range of organismic properties. Systems biology, broadly defined, provides theoretical and methodological approaches that are beginning to make it possible to answer a perennial evolutionary biological question relating to convergent homoplasies: Are at least some of the apparent analogies actually unrecognized homologies? This review provides an overview of the current state of knowledge of important aspects of this topic area. It also provides a resource describing many homoplasies that may be fruitful subjects for systems biological research.

  15. The solar system: Importance of research to the biological sciences

    NASA Technical Reports Server (NTRS)

    Klein, Harold P.

    1992-01-01

    An attempt is made to describe the scope of scientific areas that comprise the current field of exobiology in the United States. From investigations of astrophysical phenomena that deal with the birth of stars and planetary systems to questions of molecular biology involving phylogenetic relationships among organisms, from attempts to simulate the synthesis of biological precursor molecules in the chemistry laboratory to making measurements of the organic constituents of Titan's atmosphere, these researches all converge toward a common objective--answering the question of how life came about in the universe.

  16. Neural fuzzy modeling of anaerobic biological wastewater treatment systems

    SciTech Connect

    Tay, J.H.; Zhang, X.

    1999-12-01

    Anaerobic biological wastewater treatment systems are difficult to model because their performance is complex and varies significantly with different reactor configurations, influent characteristics, and operational conditions. Instead of conventional kinetic modeling, advanced neural fuzzy technology was employed to develop a conceptual adaptive model for anaerobic treatment systems. The conceptual neural fuzzy model contains the robustness of fuzzy systems, the learning ability of neural networks, and can adapt to various situations. The conceptual model was used to simulate the daily performance of two high-rate anaerobic wastewater treatment systems with satisfactory results obtained.

  17. Link between truncated fractals and coupled oscillators in biological systems.

    PubMed

    Paar, V; Pavin, N; Rosandić, M

    2001-09-01

    This article aims at providing a new theoretical insight into the fundamental question of the origin of truncated fractals in biological systems. It is well known that fractal geometry is one of the characteristics of living organisms. However, contrary to mathematical fractals which are self-similar at all scales, the biological fractals are truncated, i.e. their self-similarity extends at most over a few orders of magnitude of separation. We show that nonlinear coupled oscillators, modeling one of the basic features of biological systems, may generate truncated fractals: a truncated fractal pattern for basin boundaries appears in a simple mathematical model of two coupled nonlinear oscillators with weak dissipation. This fractal pattern can be considered as a particular hidden fractal property. At the level of sufficiently fine precision technique the truncated fractality acts as a simple structure, leading to predictability, but at a lower level of precision it is effectively fractal, limiting the predictability of the long-term behavior of biological systems. We point out to the generic nature of our result.

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

    PubMed Central

    2010-01-01

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

  19. Specifications of Standards in Systems and Synthetic Biology.

    PubMed

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

    2015-09-04

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

  20. Specifications of Standards in Systems and Synthetic Biology.

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2016-01-01

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

  2. Using quantum mechanical approaches to study biological systems.

    PubMed

    Merz, Kenneth M

    2014-09-16

    Conspectus Quantum mechanics (QM) has revolutionized our understanding of the structure and reactivity of small molecular systems. Given the tremendous impact of QM in this research area, it is attractive to believe that this could also be brought into the biological realm where systems of a few thousand atoms and beyond are routine. Applying QM methods to biological problems brings an improved representation to these systems by the direct inclusion of inherently QM effects such as polarization and charge transfer. Because of the improved representation, novel insights can be gleaned from the application of QM tools to biomacromolecules in aqueous solution. To achieve this goal, the computational bottlenecks of QM methods had to be addressed. In semiempirical theory, matrix diagonalization is rate limiting, while in density functional theory or Hartree-Fock theory electron repulsion integral computation is rate-limiting. In this Account, we primarily focus on semiempirical models where the divide and conquer (D&C) approach linearizes the matrix diagonalization step with respect to the system size. Through the D&C approach, a number of applications to biological problems became tractable. Herein, we provide examples of QM studies on biological systems that focus on protein solvation as viewed by QM, QM enabled structure-based drug design, and NMR and X-ray biological structure refinement using QM derived restraints. Through the examples chosen, we show the power of QM to provide novel insights into biological systems, while also impacting practical applications such as structure refinement. While these methods can be more expensive than classical approaches, they make up for this deficiency by the more realistic modeling of the electronic nature of biological systems and in their ability to be broadly applied. Of the tools and applications discussed in this Account, X-ray structure refinement using QM models is now generally available to the community in the

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

    SciTech Connect

    Professor Andrew Murray

    2005-10-22

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

  4. Unraveling the mechanistic complexity of Alzheimer's disease through systems biology.

    PubMed

    Rollo, Jennifer L; Banihashemi, Nahid; Vafaee, Fatemeh; Crawford, John W; Kuncic, Zdenka; Holsinger, R M Damian

    2016-06-01

    Alzheimer's disease (AD) is a complex, multifactorial disease that has reached global epidemic proportions. The challenge remains to fully identify its underlying molecular mechanisms that will enable development of accurate diagnostic tools and therapeutics. Conventional experimental approaches that target individual or small sets of genes or proteins may overlook important parts of the regulatory network, which limits the opportunity of identifying multitarget interventions. Our perspective is that a more complete insight into potential treatment options for AD will only be made possible through studying the disease as a system. We propose an integrative systems biology approach that we argue has been largely untapped in AD research. We present key publications to demonstrate the value of this approach and discuss the potential to intensify research efforts in AD through transdisciplinary collaboration. We highlight challenges and opportunities for significant breakthroughs that could be made if a systems biology approach is fully exploited.

  5. Mode coupling in living systems: implications for biology and medicine.

    PubMed

    Swain, John

    2008-05-01

    Complex systems, and in particular biological ones, are characterized by large numbers of oscillations of widely differing frequencies. Various prejudices tend to lead to the assumption that such oscillators should generically be very weakly interacting. This paper reviews the basic ideas of linearity and nonlinearity as seen by a physicist, but with a view to biological systems. In particular, it is argued that large couplings between different oscillators of disparate frequencies are common, being present even in rather simple systems which are well-known in physics, although this issue is often glossed over. This suggests new experiments and investigations, as well as new approaches to therapies and human-environment interactions which, without the concepts described here, may otherwise seem unlikely to be interesting. The style of the paper is conversational with a minimum of mathematics, and no attempt at a complete list of references. PMID:18697625

  6. Modeling Functional Motions of Biological Systems by Customized Natural Moves.

    PubMed

    Demharter, Samuel; Knapp, Bernhard; Deane, Charlotte M; Minary, Peter

    2016-08-23

    Simulating the functional motions of biomolecular systems requires large computational resources. We introduce a computationally inexpensive protocol for the systematic testing of hypotheses regarding the dynamic behavior of proteins and nucleic acids. The protocol is based on natural move Monte Carlo, a highly efficient conformational sampling method with built-in customization capabilities that allows researchers to design and perform a large number of simulations to investigate functional motions in biological systems. We demonstrate the use of this protocol on both a protein and a DNA case study. Firstly, we investigate the plasticity of a class II major histocompatibility complex in the absence of a bound peptide. Secondly, we study the effects of the epigenetic mark 5-hydroxymethyl on cytosine on the structure of the Dickerson-Drew dodecamer. We show how our customized natural moves protocol can be used to investigate causal relationships of functional motions in biological systems. PMID:27558715

  7. Microbial Proteome Profiling and Systems Biology: Applications to Mycobacterium tuberculosis.

    PubMed

    Schubert, Olga T; Aebersold, Ruedi

    2015-01-01

    Each year, 1.3 million people die from tuberculosis, an infectious disease caused by Mycobacterium tuberculosis. Systems biology-based strategies might significantly contribute to the knowledge-guided development of more effective vaccines and drugs to prevent and cure infectious diseases. To build models simulating the behaviour of a system in response to internal or external stimuli and to identify potential targets for therapeutic intervention, systems biology approaches require the acquisition of quantitative molecular profiles on many perturbed states. Here we review the current state of proteomic analyses in Mycobacterium tuberculosis and discuss the potential of recently emerging targeting mass spectrometry-based techniques which enable fast, sensitive and accurate protein measurements.

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

    PubMed

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

    2016-01-01

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

  9. Physical methods for investigating structural colours in biological systems

    PubMed Central

    Vukusic, P.; Stavenga, D.G.

    2009-01-01

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

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

    PubMed

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

    2016-06-15

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

  11. Hierarchical Dynamical Information Systems With a Focus on Biology

    NASA Astrophysics Data System (ADS)

    Collier, John

    2003-06-01

    A system of a number of relatively stable units that can combine more or less freely to form somewhat less stable structures has a capacity to carry information in a more or less arbitrary way. I call such a system a physical information system if its properties are dynamically specified. All physical information systems have certain general dynamical properties. DNA can form such a system, but so can, to a lesser degree, RNA, proteins, cells and cellular subsystems, various immune system elements, organisms in populations and in ecosystems, as well as other higher-level phenomena. These systems are hierarchical structures with respect to the expression of lower level information at higher levels. This allows a distinction between macro and microstates within the system, with resulting statistical (entropy driven) dynamics, including the possibility of self-organization, system bifurcation, and the formation of higher levels of information expression. Although lower-level information is expressed in an information hierarchy, this in itself is not sufficient for reference, function, or meaning. Nonetheless, the expression of information is central to the realization of all of these. 'Biological information' is thus ambiguous between syntactic information in a hierarchical modular system, and functional information. However, the dynamics of hierarchical physical information systems is of interest to the study of how functional information might be embodied physically. I will address 1) how to tighten the relative terms in the characterizations of 'information system' and 'informational hierarchy' above, 2) how to distinguish between components of an information system combining to form more complex informational modules and the expression of information, 3) some aspects of the dynamics of such systems that are of biological interest, 4) why information expression in such systems is not sufficient for functional information, and 5) what further might be required for

  12. Improving collaboration by standardization efforts in systems biology.

    PubMed

    Dräger, Andreas; Palsson, Bernhard Ø

    2014-01-01

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

  13. Improving Collaboration by Standardization Efforts in Systems Biology

    PubMed Central

    Dräger, Andreas; Palsson, Bernhard Ø.

    2014-01-01

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

  14. From globally coupled maps to complex-systems biology.

    PubMed

    Kaneko, Kunihiko

    2015-09-01

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

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

    PubMed

    Bittner, Michael L; Dougherty, Edward R

    2012-01-01

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

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

    PubMed Central

    Bittner, Michael L.; Dougherty, Edward R.

    2012-01-01

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

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

    PubMed

    Bittner, Michael L; Dougherty, Edward R

    2012-01-01

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

  18. From globally coupled maps to complex-systems biology

    NASA Astrophysics Data System (ADS)

    Kaneko, Kunihiko

    2015-09-01

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

  19. Understanding genetic variation – the value of systems biology

    PubMed Central

    Hütt, Marc-Thorsten

    2014-01-01

    Pharmacology is currently transformed by the vast amounts of genome-associated information available for system-level interpretation. Here I review the potential of systems biology to facilitate this interpretation, thus paving the way for the emerging field of systems pharmacology. In particular, I will show how gene regulatory and metabolic networks can serve as a framework for interpreting high throughput data and as an interface to detailed dynamical models. In addition to the established connectivity analyses of effective networks, I suggest here to also analyze higher order architectural properties of effective networks. PMID:24725073

  20. From globally coupled maps to complex-systems biology

    SciTech Connect

    Kaneko, Kunihiko

    2015-09-15

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

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

    PubMed

    Mitrokhin, Yuriy

    2014-10-21

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

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

    PubMed

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

    2015-02-01

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

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

    SciTech Connect

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

    2009-03-01

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

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

    PubMed

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

    2007-12-01

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

  5. Investigating Bacterial Protein Synthesis Using Systems Biology Approaches.

    PubMed

    Gagarinova, Alla; Emili, Andrew

    2015-01-01

    Protein synthesis is essential for bacterial growth and survival. Its study in Escherichia coli helped uncover features conserved among bacteria as well as universally. The pattern of discovery and the identification of some of the longest-known components of the protein synthesis machinery, including the ribosome itself, tRNAs, and translation factors proceeded through many stages of successively more refined biochemical purifications, finally culminating in the isolation to homogeneity, identification, and mapping of the smallest unit required for performing the given function. These early studies produced a wealth of information. However, many unknowns remained. Systems biology approaches provide an opportunity to investigate protein synthesis from a global perspective, overcoming the limitations of earlier ad hoc methods to gain unprecedented insights. This chapter reviews innovative systems biology approaches, with an emphasis on those designed specifically for investigating the protein synthesis machinery in E. coli.

  6. The zebrafish: scalable in vivo modeling for systems biology

    PubMed Central

    Deo, Rahul C.; MacRae, Calum A.

    2011-01-01

    The zebrafish offers a scalable vertebrate model for many areas of biologic investigation. There is substantial conservation of genetic and genomic features and, at a higher order, conservation of intermolecular networks, as well as physiologic systems and phenotypes. We highlight recent work demonstrating the extent of this homology, and efforts to develop high-throughput phenotyping strategies suited to genetic or chemical screening on a scale compatible with in vivo validation for systems biology. We discuss the implications of these approaches for functional annotation of the genome, elucidation of multicellular processes in vivo, and mechanistic exploration of hypotheses generated by a broad range of ‘unbiased’ ‘omic technologies such as expression profiling and genome-wide association. Finally, we outline potential strategies for the application of the zebrafish to the systematic study of phenotypic architecture, disease heterogeneity and drug responses. PMID:20882534

  7. Systems Biology in Immunology – A Computational Modeling Perspective

    PubMed Central

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

    2011-01-01

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

  8. Systems biology of IL-6, IL-12 family cytokines.

    PubMed

    Dittrich, Anna; Hessenkemper, Wiebke; Schaper, Fred

    2015-10-01

    Interleukin-6-type cytokines play important roles in the communication between cells of multicellular organisms. They are involved in the regulation of complex cellular processes such as proliferation and differentiation and act as key player during inflammation and immune response. A major challenge is to understand how these complex non-linear processes are connected and regulated. Systems biology approaches are used to tackle this challenge in an iterative process of quantitative experimental and mathematical analyses. Here we review quantitative experimental studies and systems biology approaches dealing with the function of Interleukin-6-type cytokines in physiological and pathophysiological conditions. These approaches cover the analyses of signal transduction on a cellular level up to pharmacokinetic and pharmacodynamic studies on a whole organism level.

  9. A unifying view of 21st century systems biology.

    PubMed

    Vidal, Marc

    2009-12-17

    The idea that multi-scale dynamic complex systems formed by interacting macromolecules and metabolites, cells, organs and organisms underlie some of the most fundamental aspects of life was proposed by a few visionaries half a century ago. We are witnessing a powerful resurgence of this idea made possible by the availability of nearly complete genome sequences, ever improving gene annotations and interactome network maps, the development of sophisticated informatic and imaging tools, and importantly, the use of engineering and physics concepts such as control and graph theory. Alongside four other fundamental "great ideas" as suggested by Sir Paul Nurse, namely, the gene, the cell, the role of chemistry in biological processes, and evolution by natural selection, systems-level understanding of "What is Life" may materialize as one of the major ideas of biology.

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

    EPA Science Inventory

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

  11. Systems biology of tumor dormancy: linking biology and mathematics on multiple scales to improve cancer therapy.

    PubMed

    Enderling, Heiko; Hahnfeldt, Philip; Hlatky, Lynn; Almog, Nava

    2012-05-01

    For many decades, it has been appreciated that tumor progression is not monotonic, and development of a cancer cell does not equate to inevitable cancer presentation in the clinic. Tumor progression is challenged by numerous intrinsic and extrinsic bottlenecks that can hold the tumor in dormant stages for prolonged periods. Given the complex, multiscale nature of these bottlenecks, the Center of Cancer Systems Biology organized a workshop on critical issues of systems biology of tumor dormancy. The program for the meeting this past July, chaired by N. Almog and H. Enderling, included discussions and interactive breakout sessions on regulation of tumor dormancy by angiogenesis, tumor-immune system interactions, cancer stem cell kinetics, and cell signaling pathways. Three important conclusions emerged from the meeting. The first was the urgent need to differentiate between tumor cell and tumor population dormancy of the primary tumor and metastatic deposits, the second was the continued need for interdisciplinary dialogs, and the third was the need to bring cross-scale mechanistic thinking to the field to achieve a more robust understanding of tumor dormancy and its clinical implications. PMID:22414579

  12. So, you want to be a systems biologist? Determinants for creating graduate curricula in systems biology.

    PubMed

    Voit, E O; Kemp, M L

    2011-01-01

    Systems biology is uniquely situated at the interface of computing, mathematics, engineering and the biological sciences. This positioning creates unique challenges and opportunities over other interdisciplinary studies when developing academic curricula. Integrative systems biology attempts to span the field from observation to innovation, and thus requires successful students to gain skills from mining to manipulation. The authors outline examples of graduate program structures, as well as curricular aspects and assessment metrics that can be customised around the environmental niche of the academic institution towards the formalisation of effective educational opportunities in systems biology. Some of this material was presented at the 2009 Foundations of Systems Biology in Engineering (FOSBE 2009) Conference in Denver, August 2009. PMID:21261404

  13. Cell phone radiation exposure on brain and associated biological systems.

    PubMed

    Kesari, Kavindra Kumar; Siddiqui, Mohd Haris; Meena, Ramovatar; Verma, H N; Kumar, Shivendra

    2013-03-01

    Wireless technologies are ubiquitous today and the mobile phones are one of the prodigious output of this technology. Although the familiarization and dependency of mobile phones is growing at an alarming pace, the biological effects due to the exposure of radiations have become a subject of intense debate. The present evidence on mobile phone radiation exposure is based on scientific research and public policy initiative to give an overview of what is known of biological effects that occur at radiofrequency (RF)/ electromagnetic fields (EMFs) exposure. The conflict in conclusions is mainly because of difficulty in controlling the affecting parameters. Biological effects are dependent not only on the distance and size of the object (with respect to the object) but also on the environmental parameters. Health endpoints reported to be associated with RF include childhood leukemia, brain tumors, genotoxic effects, neurological effects and neurodegenerative diseases, immune system deregulation, allergic and inflammatory responses, infertility and some cardiovascular effects. Most of the reports conclude a reasonable suspicion of mobile phone risk that exists based on clear evidence of bio-effects which with prolonged exposures may reasonably be presumed to result in health impacts. The present study summarizes the public issue based on mobile phone radiation exposure and their biological effects. This review concludes that the regular and long term use of microwave devices (mobile phone, microwave oven) at domestic level can have negative impact upon biological system especially on brain. It also suggests that increased reactive oxygen species (ROS) play an important role by enhancing the effect of microwave radiations which may cause neurodegenerative diseases.

  14. Cell phone radiation exposure on brain and associated biological systems.

    PubMed

    Kesari, Kavindra Kumar; Siddiqui, Mohd Haris; Meena, Ramovatar; Verma, H N; Kumar, Shivendra

    2013-03-01

    Wireless technologies are ubiquitous today and the mobile phones are one of the prodigious output of this technology. Although the familiarization and dependency of mobile phones is growing at an alarming pace, the biological effects due to the exposure of radiations have become a subject of intense debate. The present evidence on mobile phone radiation exposure is based on scientific research and public policy initiative to give an overview of what is known of biological effects that occur at radiofrequency (RF)/ electromagnetic fields (EMFs) exposure. The conflict in conclusions is mainly because of difficulty in controlling the affecting parameters. Biological effects are dependent not only on the distance and size of the object (with respect to the object) but also on the environmental parameters. Health endpoints reported to be associated with RF include childhood leukemia, brain tumors, genotoxic effects, neurological effects and neurodegenerative diseases, immune system deregulation, allergic and inflammatory responses, infertility and some cardiovascular effects. Most of the reports conclude a reasonable suspicion of mobile phone risk that exists based on clear evidence of bio-effects which with prolonged exposures may reasonably be presumed to result in health impacts. The present study summarizes the public issue based on mobile phone radiation exposure and their biological effects. This review concludes that the regular and long term use of microwave devices (mobile phone, microwave oven) at domestic level can have negative impact upon biological system especially on brain. It also suggests that increased reactive oxygen species (ROS) play an important role by enhancing the effect of microwave radiations which may cause neurodegenerative diseases. PMID:23678539

  15. Systems biology as an approach for deciphering microbial interactions.

    PubMed

    Kumar Singh, Puneet; Shukla, Pratyoosh

    2015-03-01

    Different systems biology approaches may have a significant consequence in deciphering microbial interactions. Here, we endeavor to summarize, epigrammatic description of sophisticated techniques and software that provides an enhanced understanding of metagenomics data analysis. Apparently, such techniques are helpful to catalog various analysis categories and components that add appraisal to understand this approach. In addition, the constructions of metabolic networks of various genes present in human gut microbiome also give significant directions for determining the topological features of target enzymes.

  16. Microbiological evaluation of the mobile biological isolator system

    NASA Technical Reports Server (NTRS)

    Taylor, D. M.; Morelli, F.; Neiderheiser, W.; Tratz, W. M.

    1979-01-01

    Evaluations on critical components of the mobile biological isolation system were performed. High efficiency particulate air filter efficiency and suit integrity were found to withstand repeated ethylene oxide (ETO) sterilizations. The minimum ETO sterilization time required to inactivate all contaminant organisms was established at four hours. Two days of aerating at 120 F was found to dissipate all harmful ETO residuals from the suit. Donning and doffing procedures were clarified and written specifically for isolation rooms.

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

    PubMed

    Eisenberg, Bob

    2013-01-01

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

  18. Systems Biology of Polycystic Kidney Disease: a Critical Review

    PubMed Central

    Menezes, Luis Fernando; Germino, Gregory G

    2015-01-01

    The proliferation and diminishing costs of ‘omics’ approaches have finally opened the doors for small and medium laboratories to enter the ‘systems biology era’. This is a welcome evolution that requires a new framework to design, interpret and validate studies. Here we highlight some of the challenges, contributions, and prospects of the“cyst-ems biology” of polycystic kidney disease. PMID:25641951

  19. Evaluation of the Biolog automated microbial identification system

    NASA Technical Reports Server (NTRS)

    Klingler, J. M.; Stowe, R. P.; Obenhuber, D. C.; Groves, T. O.; Mishra, S. K.; Pierson, D. L.

    1992-01-01

    Biolog's identification system was used to identify 39 American Type Culture Collection reference taxa and 45 gram-negative isolates from water samples. Of the reference strains, 98% were identified to genus level and 76% to species level within 4 to 24 h. Identification of some authentic strains of Enterobacter, Klebsiella, and Serratia was unreliable. A total of 93% of the water isolates were identified.

  20. Cellular systems biology profiling applied to cellular models of disease.

    PubMed

    Giuliano, Kenneth A; Premkumar, Daniel R; Strock, Christopher J; Johnston, Patricia; Taylor, Lansing

    2009-11-01

    Building cellular models of disease based on the approach of Cellular Systems Biology (CSB) has the potential to improve the process of creating drugs as part of the continuum from early drug discovery through drug development and clinical trials and diagnostics. This paper focuses on the application of CSB to early drug discovery. We discuss the integration of protein-protein interaction biosensors with other multiplexed, functional biomarkers as an example in using CSB to optimize the identification of quality lead series compounds.

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

    PubMed Central

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

    2012-01-01

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

  2. Designing the Cloud-based DOE Systems Biology Knowledgebase

    SciTech Connect

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

    2011-09-01

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

  3. Reduction techniques for network validation in systems biology.

    PubMed

    Ackermann, J; Einloft, J; Nöthen, J; Koch, I

    2012-12-21

    The rapidly increasing amount of experimental biological data enables the development of large and complex, often genome-scale models of molecular systems. The simulation and analysis of these computer models of metabolism, signal transduction, and gene regulation are standard applications in systems biology, but size and complexity of the networks limit the feasibility of many methods. Reduction of networks provides a hierarchical view of complex networks and gives insight knowledge into their coarse-grained structural properties. Although network reduction has been extensively studied in computer science, adaptation and exploration of these concepts are still lacking for the analysis of biochemical reaction systems. Using the Petri net formalism, we describe two local network structures, common transition pairs and minimal transition invariants. We apply these two structural elements for network reduction. The reduction preserves the CTI-property (covered by transition invariants), which is an important feature for completeness of biological models. We demonstrate this concept for a selection of metabolic networks including a benchmark network of Saccharomyces cerevisiae whose straightforward treatment is not yet feasible even on modern supercomputers. PMID:22982289

  4. Synthetic fluorescent probes for studying copper in biological systems

    PubMed Central

    Cotruvo, Joseph A.; Aron, Allegra T.; Ramos-Torres, Karla M.; Chang, Christopher J.

    2015-01-01

    The potent redox activity of copper is required for sustaining life. Mismanagement of its cellular pools, however, can result in oxidative stress and damage connected to aging, neurodegenerative diseases, and metabolic disorders. Therefore, copper homeostasis is tightly regulated by cells and tissues. Whereas copper and other transition metal ions are commonly thought of as static cofactors buried within protein active sites, emerging data points to the presence of additional loosely bound, labile pools that can participate in dynamic signalling pathways. Against this backdrop, we review advances in sensing labile copper pools and understanding their functions using synthetic fluorescent indicators. Following brief introductions to cellular copper homeostasis and considerations in sensor design, we survey available fluorescent copper probes and evaluate their properties in the context of their utility as effective biological screening tools. We emphasize the need for combined chemical and biological evaluation of these reagents, as well as the value of complementing probe data with other techniques for characterizing the different pools of metal ions in biological systems. This holistic approach will maximize the exciting opportunities for these and related chemical technologies in the study and discovery of novel biology of metals. PMID:25692243

  5. From systems biology to analytic problems. Comment on the paper "On the interplay between mathematics and biology, hallmarks toward a new systems biology" by N. Bellomo et al.

    NASA Astrophysics Data System (ADS)

    Bellouquid, Abdelghani

    2015-03-01

    The new systems approach in biological sciences proposed in [1] is a constructive reply to the hints of the scientific community [2] and opens new research paths toward developments of new mathematical methods to model the living matter. This comment focuses on some analytic and modeling issues which are somewhat related to my personal scientific knowhow. I look forward to the answer to them as a critical analysis on the topics presented in the following might contribute to research activity in the field and, specifically, to the complex interplay between mathematics and biology. Therefore, after some introductory comment, I pose, for each issue, a specific question.

  6. On Mechanical Transitions in Biologically Motivated Soft Matter Systems

    NASA Astrophysics Data System (ADS)

    Fogle, Craig

    The notion of phase transitions as a characterization of a change in physical properties pervades modern physics. Such abrupt and fundamental changes in the behavior of physical systems are evident in condensed matter system and also occur in nuclear and subatomic settings. While this concept is less prevalent in the field of biology, recent advances have pointed to its relevance in a number of settings. Recent studies have modeled both the cell cycle and cancer as phase transition in physical systems. In this dissertation we construct simplified models for two biological systems. As described by those models, both systems exhibit phase transitions. The first model is inspired by the shape transition in the nuclei of neutrophils during differentiation. During differentiation the nucleus transitions from spherical to a shape often described as "beads on a string." As a simplified model of this system, we investigate the spherical-to-wrinkled transition in an elastic core bounded to a fluid shell system. We find that this model exhibits a first-order phase transition, and the shape that minimizes the energy of the system scales as (micror3/kappa). . The second system studied is motivated by the dynamics of globular proteins. These proteins may undergoes conformational changes with large displacements relative to their size. Transitions between conformational states are not possible if the dynamics are governed strictly by linear elasticity. We construct a model consisting of an predominantly elastic region near the energetic minimum of the system and a non-linear softening of the system at a critical displacement. We find that this simple model displays very rich dynamics include a sharp dynamical phase transition and driving-force-dependent symmetry breaking.

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

    EPA Science Inventory

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

  8. Algebraic Systems Biology: A Case Study for the Wnt Pathway.

    PubMed

    Gross, Elizabeth; Harrington, Heather A; Rosen, Zvi; Sturmfels, Bernd

    2016-01-01

    Steady-state analysis of dynamical systems for biological networks gives rise to algebraic varieties in high-dimensional spaces whose study is of interest in their own right. We demonstrate this for the shuttle model of the Wnt signaling pathway. Here, the variety is described by a polynomial system in 19 unknowns and 36 parameters. It has degree 9 over the parameter space. This case study explores multistationarity, model comparison, dynamics within regions of the state space, identifiability, and parameter estimation, from a geometric point of view. We employ current methods from computational algebraic geometry, polyhedral geometry, and combinatorics.

  9. Systemic treatment of early breast cancer--a biological perspective.

    PubMed

    Greenberg, Sally; Stopeck, Alison; Rugo, Hope S

    2011-05-01

    Breast cancer is the most common non-skin cancer affecting women worldwide. In the United States, over 90% of tumors are diagnosed as either in situ or localized to the breast or regional lymph nodes. Surgical treatment and adjuvant radiotherapy play an important role in loco-regional treatment of early stage breast cancer. Systemic adjuvant therapy is targeted towards isolated circulating and/or disseminated tumor cells to prevent systemic recurrence. This review will describe the diverse tumor biology of human breast cancer and how it influences decisions with regard to the use of adjuvant therapies. PMID:21480257

  10. Wearable System for Acquisition and Monitoring of Biological Signals

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

  11. Recent applications of Kirkwood-Buff theory to biological systems.

    PubMed

    Pierce, Veronica; Kang, Myungshim; Aburi, Mahalaxmi; Weerasinghe, Samantha; Smith, Paul E

    2008-01-01

    The effect of cosolvents on biomolecular equilibria has traditionally been rationalized using simple binding models. More recently, a renewed interest in the use of Kirkwood-Buff (KB) theory to analyze solution mixtures has provided new information on the effects of osmolytes and denaturants and their interactions with biomolecules. Here we review the status of KB theory as applied to biological systems. In particular, the existing models of denaturation are analyzed in terms of KB theory, and the use of KB theory to interpret computer simulation data for these systems is discussed.

  12. Integrated network analysis and effective tools in plant systems biology

    PubMed Central

    Fukushima, Atsushi; Kanaya, Shigehiko; Nishida, Kozo

    2014-01-01

    One of the ultimate goals in plant systems biology is to elucidate the genotype-phenotype relationship in plant cellular systems. Integrated network analysis that combines omics data with mathematical models has received particular attention. Here we focus on the latest cutting-edge computational advances that facilitate their combination. We highlight (1) network visualization tools, (2) pathway analyses, (3) genome-scale metabolic reconstruction, and (4) the integration of high-throughput experimental data and mathematical models. Multi-omics data that contain the genome, transcriptome, proteome, and metabolome and mathematical models are expected to integrate and expand our knowledge of complex plant metabolisms. PMID:25408696

  13. Mass balances for a biological life support system simulation model

    NASA Technical Reports Server (NTRS)

    Volk, Tyler; Rumel, John D.

    1987-01-01

    Design decisions to aid the development of future space-based biological life support systems (BLSS) can be made with simulation models. Here the biochemical stoichiometry is developed for: (1) protein, carbohydrate, fat, fiber, and lignin production in the edible and inedible parts of plants; (2) food consumption and production of organic solids in urine, feces, and wash water by the humans; and (3) operation of the waste processor. Flux values for all components are derived for a steady-state system with wheat as the sole food source.

  14. Algebraic Systems Biology: A Case Study for the Wnt Pathway.

    PubMed

    Gross, Elizabeth; Harrington, Heather A; Rosen, Zvi; Sturmfels, Bernd

    2016-01-01

    Steady-state analysis of dynamical systems for biological networks gives rise to algebraic varieties in high-dimensional spaces whose study is of interest in their own right. We demonstrate this for the shuttle model of the Wnt signaling pathway. Here, the variety is described by a polynomial system in 19 unknowns and 36 parameters. It has degree 9 over the parameter space. This case study explores multistationarity, model comparison, dynamics within regions of the state space, identifiability, and parameter estimation, from a geometric point of view. We employ current methods from computational algebraic geometry, polyhedral geometry, and combinatorics. PMID:26645985

  15. Recent Applications of Kirkwood-Buff Theory to Biological Systems

    PubMed Central

    Pierce, Veronica; Kang, Myungshim; Aburi, Mahalaxmi; Weerasinghe, Samantha; Smith, Paul E.

    2008-01-01

    The effect of cosolvents on biomolecular equilibria has traditionally been rationalized using simple binding models. More recently, a renewed interest in the use of Kirkwood-Buff (KB) theory to analyze solution mixtures has provided new information on the effects of osmolytes and denaturants and their interactions with biomolcules. Here we review the status of KB theory as applied to biological systems. In particular, the existing models of denaturation are analyzed in terms of KB theory, and the use of KB theory to interpret computer simulation data for these systems is discussed. PMID:18043873

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

    SciTech Connect

    Stenner, Robert D.; Hadley, Donald L.; Armstrong, Peter R.; Buck, John W.; Hoopes, Bonnie L.; Janus, Michael C.

    2001-03-01

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

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

    SciTech Connect

    Stenner, Robert D; Hadley, Donald L; Armstrong, Peter R; Buck, John W; Hoopes, Bonnie L

    2001-03-01

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

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

    PubMed Central

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

    2016-01-01

    Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out through in silico theoretical studies with the aim to guide and complement further in vitro and in vivo experimental efforts. Clearly, what counts is the result in vivo, not only in terms of maximal productivity but also robustness against environmental perturbations. Engineering an organism towards an increased production flux, however, often compromises that robustness. In this contribution, we review and investigate how various analytical approaches used in metabolic engineering and synthetic biology are related to concepts developed by systems and control engineering. While trade-offs between production optimality and cellular robustness have already been studied diagnostically and statically, the dynamics also matter. Integration of the dynamic design aspects of control engineering with the more diagnostic aspects of metabolic, hierarchical control and regulation analysis is leading to the new, conceptual and operational framework required for the design of robust and productive dynamic pathways. PMID:27075000

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

    PubMed

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

    2016-04-01

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

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

    PubMed

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

    2016-04-01

    Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out through in silico theoretical studies with the aim to guide and complement further in vitro and in vivo experimental efforts. Clearly, what counts is the result in vivo, not only in terms of maximal productivity but also robustness against environmental perturbations. Engineering an organism towards an increased production flux, however, often compromises that robustness. In this contribution, we review and investigate how various analytical approaches used in metabolic engineering and synthetic biology are related to concepts developed by systems and control engineering. While trade-offs between production optimality and cellular robustness have already been studied diagnostically and statically, the dynamics also matter. Integration of the dynamic design aspects of control engineering with the more diagnostic aspects of metabolic, hierarchical control and regulation analysis is leading to the new, conceptual and operational framework required for the design of robust and productive dynamic pathways. PMID:27075000

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  3. Systems analysis of biological networks in skeletal muscle function

    PubMed Central

    Smith, Lucas R.; Meyer, Gretchen; Lieber, Richard L.

    2014-01-01

    Skeletal muscle function depends on the efficient coordination among subcellular systems. These systems are composed of proteins encoded by a subset of genes, all of which are tightly regulated. In the cases where regulation is altered because of disease or injury, dysfunction occurs. To enable objective analysis of muscle gene expression profiles, we have defined nine biological networks whose coordination is critical to muscle function. We begin by describing the expression of proteins necessary for optimal neuromuscular junction function that results in the muscle cell action potential. That action potential is transmitted to proteins involved in excitation–contraction coupling enabling Ca2+ release. Ca2+ then activates contractile proteins supporting actin and myosin cross-bridge cycling. Force generated by cross-bridges is transmitted via cytoskeletal proteins through the sarcolemma and out to critical proteins that support the muscle extracellular matrix. Muscle contraction is fueled through many proteins that regulate energy metabolism. Inflammation is a common response to injury that can result in alteration of many pathways within muscle. Muscle also has multiple pathways that regulate size through atrophy or hypertrophy. Finally, the isoforms associated with fast muscle fibers and their corresponding isoforms in slow muscle fibers are delineated. These nine networks represent important biological systems that affect skeletal muscle function. Combining high-throughput systems analysis with advanced networking software will allow researchers to use these networks to objectively study skeletal muscle systems. PMID:23188744

  4. Scaling Reversible Adhesion in Synthetic and Biological Systems

    NASA Astrophysics Data System (ADS)

    Bartlett, Michael; Irschick, Duncan; Crosby, Alfred

    2013-03-01

    High capacity, easy release polymer adhesives, as demonstrated by a gecko's toe, present unique opportunities for synthetic design. However, without a framework that connects biological and synthetic adhesives from basic nanoscopic features to macroscopic systems, synthetic mimics have failed to perform favorably at large length scales. Starting from an energy balance, we develop a scaling approach to understand unstable interfacial fracture over multiple length scales. The simple theory reveals that reversibly adhesive polymers do not rely upon fibrillar features but require contradicting attributes: maximum compliance normal to the substrate and minimum compliance in the loading direction. We use this counterintuitive criterion to create reversible, easy release adhesives at macroscopic sizes (100 cm2) with unprecedented force capacities on the order of 3000 N. Importantly, we achieve this without fibrillar features, supporting our predictions and emphasizing the importance of subsurface anatomy in biological adhesive systems. Our theory describes adhesive force capacity as a function of material properties and geometry and is supported by over 1000 experiments, spanning both synthetic and biological adhesives, with agreement over 14 orders of magnitude in adhesive force.

  5. Performance of transdermal therapeutic systems: Effects of biological factors

    PubMed Central

    Singh, Inderjeet; Morris, Andrew Phillip

    2011-01-01

    Transdermal drug delivery (TDD) is a technique that is used to deliver a drug into the systemic circulation across the skin. This mechanism of drug delivery route has many advantages, including steady drug plasma concentrations, improved patient compliance, elimination of hepatic first pass, and degradation in the gastrointestinal tract. Over the last 30 years, many transdermal products have been launched in the market. Despite the inherent advantages of TDD and the growing list of transdermal products, one of the major drawbacks to TDD is the occurrence of inter- and intraindividual variation in the absorption of the drug across the skin. A majority of these variations are caused by biological factors, such as gender, age, ethnicity, and skin hydration and metabolism. These factors affect the integrity and the barrier qualities of the skin, which subsequently result in the variation in the amount of drug absorbed. The main objective of this review article is to provide a concise commentary on the biological factors that contribute to the variation in transdermal permeation of drugs across human skin and the available transdermal therapeutic systems that may reduce the variations caused by biological factors. PMID:23071913

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

    NASA Technical Reports Server (NTRS)

    Ippolito, Corey; Plice, Laura; Pisanich, Greg

    2003-01-01

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

  7. Biological tissue identification using a multispectral imaging system

    NASA Astrophysics Data System (ADS)

    Delporte, Céline; Sautrot, Sylvie; Ben Chouikha, Mohamed; Viénot, Françoise; Alquié, Georges

    2013-02-01

    A multispectral imaging system enabling biological tissue identifying and differentiation is presented. The measurement of β(λ) spectral radiance factor cube for four tissue types (beef muscle, pork muscle, turkey muscle and beef liver) present in the same scene was carried out. Three methods for tissue identification are proposed and their relevance evaluated. The first method correlates the scene spectral radiance factor with tissue database characteristics. This method gives detection rates ranging from 63.5 % to 85 %. The second method correlates the scene spectral radiance factor derivatives with a database of tissue β(λ) derivatives. This method is more efficient than the first one because it gives detection rates ranging from 79 % to 89 % with over-detection rates smaller than 0.2 %. The third method uses the biological tissue spectral signature. It enhances contrast in order to afford tissue differentiation and identification.

  8. TRIENNIAL LACTATION SYMPOSIUM: Nutrigenomics in livestock: Systems biology meets nutrition.

    PubMed

    Loor, J J; Vailati-Riboni, M; McCann, J C; Zhou, Z; Bionaz, M

    2015-12-01

    The advent of high-throughput technologies to study an animal's genome, proteome, and metabolome (i.e., "omics" tools) constituted a setback to the use of reductionism in livestock research. More recent development of "next-generation sequencing" tools was instrumental in allowing in-depth studies of the microbiome in the rumen and other sections of the gastrointestinal tract. Omics, along with bioinformatics, constitutes the foundation of modern systems biology, a field of study widely used in model organisms (e.g., rodents, yeast, humans) to enhance understanding of the complex biological interactions occurring within cells and tissues at the gene, protein, and metabolite level. Application of systems biology concepts is ideal for the study of interactions between nutrition and physiological state with tissue and cell metabolism and function during key life stages of livestock species, including the transition from pregnancy to lactation, in utero development, or postnatal growth. Modern bioinformatic tools capable of discerning functional outcomes and biologically meaningful networks complement the ever-increasing ability to generate large molecular, microbial, and metabolite data sets. Simultaneous visualization of the complex intertissue adaptations to physiological state and nutrition can now be discerned. Studies to understand the linkages between the microbiome and the absorptive epithelium using the integrative approach are emerging. We present examples of new knowledge generated through the application of functional analyses of transcriptomic, proteomic, and metabolomic data sets encompassing nutritional management of dairy cows, pigs, and poultry. Published work to date underscores that the integrative approach across and within tissues may prove useful for fine-tuning nutritional management of livestock. An important goal during this process is to uncover key molecular players involved in the organismal adaptations to nutrition. PMID:26641165

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

    PubMed Central

    2013-01-01

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

  10. Critical Assessment of Information Extraction Systems in Biology

    PubMed Central

    Hirschman, Lynette; Yeh, Alexander; Valencia, Alfonso

    2003-01-01

    An increasing number of groups are now working in the area of text mining, focusing on a wide range of problems and applying both statistical and linguistic approaches. However, it is not possible to compare the different approaches, because there are no common standards or evaluation criteria; in addition, the various groups are addressing different problems, often using private datasets. As a result, it is impossible to determine how well the existing systems perform, and particularly what performance level can be expected in real applications. This is similar to the situation in text processing in the late 1980s, prior to the Message Understanding Conferences (MUCs). With the introduction of a common evaluation and standardized evaluation metrics as part of these conferences, it became possible to compare approaches, to identify those techniques that did or did not work and to make progress. This progress has resulted in a common pipeline of processes and a set of shared tools available to the general research community. The field of biology is ripe for a similar experiment. Inspired by this example, the BioLINK group (Biological Literature, Information and Knowledge [1]) is organizing a CASP-like evaluation for the text data-mining community applied to biology. The two main tasks specifically address two major bottlenecks for text mining in biology: (1) the correct detection of gene and protein names in text; and (2) the extraction of functional information related to proteins based on the GO classification system. For further information and participation details, see http://www.pdg.cnb.uam.es/BioLink/BioCreative.eval.html PMID:18629031

  11. Process-based design of dynamical biological systems

    NASA Astrophysics Data System (ADS)

    Tanevski, Jovan; Todorovski, Ljupčo; Džeroski, Sašo

    2016-09-01

    The computational design of dynamical systems is an important emerging task in synthetic biology. Given desired properties of the behaviour of a dynamical system, the task of design is to build an in-silico model of a system whose simulated be- haviour meets these properties. We introduce a new, process-based, design methodology for addressing this task. The new methodology combines a flexible process-based formalism for specifying the space of candidate designs with multi-objective optimization approaches for selecting the most appropriate among these candidates. We demonstrate that the methodology is general enough to both formulate and solve tasks of designing deterministic and stochastic systems, successfully reproducing plausible designs reported in previous studies and proposing new designs that meet the design criteria, but have not been previously considered.

  12. Epigenomics and the concept of degeneracy in biological systems.

    PubMed

    Maleszka, Ryszard; Mason, Paul H; Barron, Andrew B

    2014-05-01

    Researchers in the field of epigenomics are developing more nuanced understandings of biological complexity, and exploring the multiple pathways that lead to phenotypic expression. The concept of degeneracy-referring to the multiple pathways that a system recruits to achieve functional plasticity-is an important conceptual accompaniment to the growing body of knowledge in epigenomics. Distinct from degradation, redundancy and dilapidation; degeneracy refers to the plasticity of traits whose function overlaps in some environments, but diverges in others. While a redundant system is composed of repeated identical elements performing the same function, a degenerate system is composed of different elements performing similar or overlapping functions. Here, we describe the degenerate structure of gene regulatory systems from the basic genetic code to flexible epigenomic modifications, and discuss how these structural features have contributed to organism complexity, robustness, plasticity and evolvability.

  13. Epigenomics and the concept of degeneracy in biological systems

    PubMed Central

    Mason, Paul H.; Barron, Andrew B.

    2014-01-01

    Researchers in the field of epigenomics are developing more nuanced understandings of biological complexity, and exploring the multiple pathways that lead to phenotypic expression. The concept of degeneracy—referring to the multiple pathways that a system recruits to achieve functional plasticity—is an important conceptual accompaniment to the growing body of knowledge in epigenomics. Distinct from degradation, redundancy and dilapidation; degeneracy refers to the plasticity of traits whose function overlaps in some environments, but diverges in others. While a redundant system is composed of repeated identical elements performing the same function, a degenerate system is composed of different elements performing similar or overlapping functions. Here, we describe the degenerate structure of gene regulatory systems from the basic genetic code to flexible epigenomic modifications, and discuss how these structural features have contributed to organism complexity, robustness, plasticity and evolvability. PMID:24335757

  14. Mass balances for a biological life support system simulation model

    NASA Technical Reports Server (NTRS)

    Volk, Tyler; Rummel, John D.

    1987-01-01

    Design decisions to aid the development of future space based biological life support systems (BLSS) can be made with simulation models. The biochemistry stoichiometry was developed for: (1) protein, carbohydrate, fat, fiber, and lignin production in the edible and inedible parts of plants; (2) food consumption and production of organic solids in urine, feces, and wash water by the humans; and (3) operation of the waste processor. Flux values for all components are derived for a steady state system with wheat as the sole food source. The large scale dynamics of a materially closed (BLSS) computer model is described in a companion paper. An extension of this methodology can explore multifood systems and more complex biochemical dynamics while maintaining whole system closure as a focus.

  15. Process-based design of dynamical biological systems

    PubMed Central

    Tanevski, Jovan; Todorovski, Ljupčo; Džeroski, Sašo

    2016-01-01

    The computational design of dynamical systems is an important emerging task in synthetic biology. Given desired properties of the behaviour of a dynamical system, the task of design is to build an in-silico model of a system whose simulated be- haviour meets these properties. We introduce a new, process-based, design methodology for addressing this task. The new methodology combines a flexible process-based formalism for specifying the space of candidate designs with multi-objective optimization approaches for selecting the most appropriate among these candidates. We demonstrate that the methodology is general enough to both formulate and solve tasks of designing deterministic and stochastic systems, successfully reproducing plausible designs reported in previous studies and proposing new designs that meet the design criteria, but have not been previously considered. PMID:27686219

  16. Systems biology of the autophagy-lysosomal pathway

    PubMed Central

    Jegga, Anil G; Schneider, Lonnie; Ouyang, Xiaosen

    2011-01-01

    The mechanisms of the control and activity of the autophagy-lysosomal protein degradation machinery are emerging as an important theme for neurodevelopment and neurodegeneration. However, the underlying regulatory and functional networks of known genes controlling autophagy and lysosomal function and their role in disease are relatively unexplored. We performed a systems biology-based integrative computational analysis to study the interactions between molecular components and to develop models for regulation and function of genes involved in autophagy and lysosomal function. Specifically, we analyzed transcriptional and microRNA-based post-transcriptional regulation of these genes and performed functional enrichment analyses to understand their involvement in nervous system-related diseases and phenotypes. Transcriptional regulatory network analysis showed that binding sites for transcription factors, SREBP1, USF, AP-1 and NFE2, are common among autophagy and lysosomal genes. MicroRNA enrichment analysis revealed miR-130, 98, 124, 204 and 142 as the putative post-transcriptional regulators of the autophagy-lysosomal pathway genes. Pathway enrichment analyses revealed that the mTOR and insulin signaling pathways are important in the regulation of genes involved in autophagy. In addition, we found that glycosaminoglycan and glycosphingolipid pathways also make a major contribution to lysosomal gene regulation. The analysis confirmed the known contribution of the autophagy-lysosomal genes to Alzheimer and Parkinson diseases and also revealed potential involvement in tuberous sclerosis, neuronal ceroidlipofuscinoses, sepsis and lung, liver and prostatic neoplasms. To further probe the impact of autophagy-lysosomal gene deficits on neurologically-linked phenotypes, we also mined the mouse knockout phenotype data for the autophagy-lysosomal genes and found them to be highly predictive of nervous system dysfunction. Overall this study demonstrates the utility of systems

  17. Laminated plastic microfluidic components for biological and chemical systems

    SciTech Connect

    Martin, P.M.; Matson, D.W.; Bennett, W.D.; Lin, Y.; Hammerstrom, D.J.

    1999-07-01

    Laminated plastic microfluidic components are being developed for biological testing systems and chemical sensors. Applications include a DNA thermal cycler, DNA analytical systems, electrophoretic flow systems, dialysis systems, and metal sensors for ground water. This article describes fabrication processes developed for these plastic microfluidic components, and the fabrication of a chromium metal sensor and a microdialysis device. Most of the components have a stacked architecture. Using this architecture, the fluid flows, or is pumped through, as many as nine laminated functional levels. Functions include pumping, mixing, reaction, detection, reservoirs, separations, and electronics. Polyimide, poly(methylmethacrylate) (PMMA), and polycarbonate materials with thicknesses between 25 and 125 {mu}m are used to construct the components. This makes the components low cost, inert to many biological fluids and chemicals, and disposable. The components are fabricated by excimer laser micromachining the microchannel patterns and microstructures in the various laminates. In some cases, micropumps are integrated into these components to move the fluids. Vias and interconnects are also cut by the laser and integrated with micropumps. The laminates are sealed and bonded by adhesive and thermal processes and are leak tight. The parts withstand pressures as high as 790 kPa. Typical channel widths are 50 to 100 {mu}m, with aspect ratios near 5. {copyright} {ital 1999 American Vacuum Society.}

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

    PubMed Central

    Materi, Wayne; Wishart, David S.

    2007-01-01

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

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

    PubMed

    Hood, Leroy

    2013-04-01

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

  20. Disciplinary baptisms: a comparison of the naming stories of genetics, molecular biology, genomics, and systems biology.

    PubMed

    Powell, Alexander; O'Malley, Maureen A; Müller-Wille, Staffan; Calvert, Jane; Dupré, John

    2007-01-01

    Understanding how scientific activities use naming stories to achieve disciplinary status is important not only for insight into the past, but for evaluating current claims that new disciplines are emerging. In order to gain a historical understanding of how new disciplines develop in relation to these baptismal narratives, we compare two recently formed disciplines, systems biology and genomics, with two earlier related life sciences, genetics and molecular biology. These four disciplines span the twentieth century, a period in which the processes of disciplinary demarcation fundamentally changed from those characteristic of the nineteenth century. We outline how the establishment of each discipline relies upon an interplay of factors that include paradigmatic achievements, technological innovation, and social formations. Our focus, however, is the baptism stories that give the new discipline a founding narrative and articulate core problems, general approaches and constitutive methods. The highly plastic process of achieving disciplinary identity is further marked by the openness of disciplinary definition, tension between technological possibilities and the ways in which scientific issues are conceived and approached, synthesis of reductive and integrative strategies, and complex social interactions. The importance--albeit highly variable--of naming stories in these four cases indicates the scope for future studies that focus on failed disciplines or competing names. Further attention to disciplinary histories could, we suggest, give us richer insight into scientific development. PMID:18411835

  1. Multimode lasers as analogs of complex biological systems (a survey)

    NASA Astrophysics Data System (ADS)

    Danilov, O. B.; Rosanov, N. N.; Solov'ev, N. A.; Soms, L. N.

    2016-04-01

    Simulating the activity of complex biological systems, in particular, the human brain, is a topical problem the solution of which is necessary both for understanding their functioning and for developing new classes of computational system based on operating principles of the brain. Some features and analogies that can be found in the operation of laser systems and brain and used for developing new generation computational systems are discussed. The appropriateness of such analogies is justified by the fact that both laser systems and the brain are open (interacting with the environment) dissipative spatially distributed nonlinear systems. Therefore, laser optical systems and, in particular, systems with dissipative optical solitons offer an opportunity to experimentally and theoretically model some important cognitive brain functions. One of particularities of the brain operation is the ability to manipulate images. Proceeding from this, in this work, problems related to generation and amplification with laser of spatial structures (images), as well as to amplification of signals coming to it from outside are discussed.

  2. Qualitative and quantitative analysis of systems and synthetic biology constructs using P systems.

    PubMed

    Konur, Savas; Gheorghe, Marian; Dragomir, Ciprian; Mierla, Laurentiu; Ipate, Florentin; Krasnogor, Natalio

    2015-01-16

    Computational models are perceived as an attractive alternative to mathematical models (e.g., ordinary differential equations). These models incorporate a set of methods for specifying, modeling, testing, and simulating biological systems. In addition, they can be analyzed using algorithmic techniques (e.g., formal verification). This paper shows how formal verification is utilized in systems and synthetic biology through qualitative vs quantitative analysis. Here, we choose two well-known case studies: quorum sensing in P. aeruginosas and pulse generator. The paper reports verification analysis of two systems carried out using some model checking tools, integrated to the Infobiotics Workbench platform, where system models are based on stochastic P systems.

  3. A large-scale cryoelectronic system for biological sample banking

    NASA Astrophysics Data System (ADS)

    Shirley, Stephen G.; Durst, Christopher H. P.; Fuchs, Christian C.; Zimmermann, Heiko; Ihmig, Frank R.

    2009-11-01

    We describe a polymorphic electronic infrastructure for managing biological samples stored over liquid nitrogen. As part of this system we have developed new cryocontainers and carrier plates attached to Flash memory chips to have a redundant and portable set of data at each sample. Our experimental investigations show that basic Flash operation and endurance is adequate for the application down to liquid nitrogen temperatures. This identification technology can provide the best sample identification, documentation and tracking that brings added value to each sample. The first application of the system is in a worldwide collaborative research towards the production of an AIDS vaccine. The functionality and versatility of the system can lead to an essential optimization of sample and data exchange for global clinical studies.

  4. Systems biology in 3D space--enter the morphome.

    PubMed

    Lucocq, John M; Mayhew, Terry M; Schwab, Yannick; Steyer, Anna M; Hacker, Christian

    2015-02-01

    Systems-based understanding of living organisms depends on acquiring huge datasets from arrays of genes, transcripts, proteins, and lipids. These data, referred to as 'omes', are assembled using 'omics' methodologies. Currently a comprehensive, quantitative view of cellular and organellar systems in 3D space at nanoscale/molecular resolution is missing. We introduce here the term 'morphome' for the distribution of living matter within a 3D biological system, and 'morphomics' for methods of collecting 3D data systematically and quantitatively. A sampling-based approach termed stereology currently provides rapid, precise, and minimally biased morphomics. We propose that stereology solves the 'big data' problem posed by emerging wide-scale electron microscopy (EM) and can establish quantitative links between the newer nanoimaging platforms such as electron tomography, cryo-EM, and correlative microscopy.

  5. Identification of dynamical biological systems based on random effects models.

    PubMed

    Batista, Levy; Bastogne, Thierry; Djermoune, El-Hadi

    2015-01-01

    System identification is a data-driven modeling approach more and more used in biology and biomedicine. In this application context, each assay is always repeated to estimate the response variability. The inference of the modeling conclusions to the whole population requires to account for the inter-individual variability within the modeling procedure. One solution consists in using random effects models but up to now no similar approach exists in the field of dynamical system identification. In this article, we propose a new solution based on an ARX (Auto Regressive model with eXternal inputs) structure using the EM (Expectation-Maximisation) algorithm for the estimation of the model parameters. Simulations show the relevance of this solution compared with a classical procedure of system identification repeated for each subject. PMID:26736981

  6. Systems biology driven software design for the research enterprise

    PubMed Central

    Boyle, John; Cavnor, Christopher; Killcoyne, Sarah; Shmulevich, Ilya

    2008-01-01

    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 required software tools. Results We illustrate an approach, through the discussion of a purpose built software architecture, which allows disparate groups to reuse tools and access data sources in a common manner. The architecture allows for: the rapid development of distributed applications; interoperability, so it can be used by a wide variety of developers and computational biologists; development using standard tools, so that it is easy to maintain and does not require a large development effort; extensibility, so that new technologies and data types can be incorporated; and non intrusive development, insofar as researchers need not to adhere to a pre-existing object model. Conclusion By using a relatively simple integration strategy, based upon a common identity system and dynamically discovered interoperable services, a light-weight software architecture can become the focal point through which scientists can both get access to and analyse the plethora of experimentally derived data. PMID:18578887

  7. Interactive threats of nanoparticles to the biological system.

    PubMed

    Roy, Ruchi; Kumar, Sandeep; Tripathi, Anurag; Das, Mukul; Dwivedi, Premendra D

    2014-01-01

    The use of nanoscale materials is growing exponentially, but concerns rise about the human hazards cannot be ignored. Nanotechnology has penetrated deep into our lives in diversified areas as engineering, information technology and diagnostics. Nonetheless owing to their peculiar properties these new materials also present new health risks upon interacting with biological systems. This is a typical case of technology preceding toxicity and therefore, various toxicological aspects for an array of nanomaterials are just beginning to be assessed. Several deleterious effects are being noticed, particularly in vitro situations as well as in mammalian system. Nanoparticles toxicity is compellingly related to oxidative stress, alteration of calcium homeostasis, gene expression, pro-inflammatory responses and cellular signalling events. It is therefore critical to understand the nature and origin of the toxicity imposed by nanomaterials. Keeping all these points in mind, the present review provides updated information on the various aspects such as sources of production, effect of different physical properties, interaction with biological system and mechanisms of engineered nanoparticles induced toxicities.

  8. Gene Therapy from the perspective of Systems Biology

    PubMed Central

    Mac Gabhann, Feilim; Annex, Brian H.

    2010-01-01

    Gene therapy research has expanded from its original concept of replacing absent or defective DNA with functional DNA for transcription. Genetic material may be delivered via multiple vectors, including naked plasmid DNA, viruses and even cells with the goal of increasing gene expression; and the targeting of specific tissues or cell types is aimed at decreasing risks of systemic or side effects. As with the development of any drug, there is an amount of empiricism in the choice of gene target, route of administration, dosing and in particular the scaling-up from pre-clinical models to clinical trials. Systems Biology, whose arsenal includes high-throughput experimental and computational studies that account for the complexities of host-disease-therapy interactions, holds significant promise in aiding the development and optimization of gene therapies, including personalized therapies and the identification of biomarkers for success of these strategies. In this review we describe some of the obstacles and successes in gene therapy, using the specific example of growth factor gene delivery to promote angiogenesis and blood vessel remodeling in ischemic diseases; we also make references to anti-angiogenic gene therapy in cancer. The opportunities for Systems Biology and in silico modeling to improve on current outcomes are highlighted. PMID:20886389

  9. Swimming simply: Minimal models and stroke optimization for biological systems

    NASA Astrophysics Data System (ADS)

    Burton, Lisa; Guasto, Jeffrey S.; Stocker, Roman; Hosoi, A. E.

    2012-11-01

    In this talk, we examine how to represent the kinematics of swimming biological systems. We present a new method of extracting optimal curvature-space basis modes from high-speed video microscopy images of motile spermatozoa by tracking their flagellar kinematics. Using as few as two basis modes to characterize the swimmer's shape, we apply resistive force theory to build a model and predict the swimming speed and net translational and rotational displacement of a sperm cell over any given stroke. This low-order representation of motility yields a complete visualization of the system dynamics. The visualization tools provide refined initialization and intuition for global stroke optimization and improve motion planning by taking advantage of symmetries in the shape space to design a stroke that produces a desired net motion. Comparing the predicted optimal strokes to those observed experimentally enables us to rationalize biological motion by identifying possible optimization goals of the organism. This approach is applicable to a wide array of systems at both low and high Reynolds numbers. Battelle Memorial Institute and NSF.

  10. Casual Games and Casual Learning About Human Biological Systems

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

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

  11. Computational Neuroscience: Modeling the Systems Biology of Synaptic Plasticity

    PubMed Central

    Kotaleski, Jeanette Hellgren; Blackwell, Kim T.

    2016-01-01

    Preface Synaptic plasticity is a mechanism proposed to underlie learning and memory. The complexity of the interactions between ion channels, enzymes, and genes involved in synaptic plasticity impedes a deep understanding of this phenomenon. Computer modeling is an approach to investigate the information processing that is performed by signaling pathways underlying synaptic plasticity. In the past few years, new software developments that blend computational neuroscience techniques with systems biology techniques have allowed large-scale, quantitative modeling of synaptic plasticity in neurons. We highlight significant advancements produced by these modeling efforts and introduce promising approaches that utilize advancements in live cell imaging. PMID:20300102

  12. Nodavirus-based biological container for targeted delivery system.

    PubMed

    Jariyapong, Pitchanee

    2015-01-01

    Biological containers such as virus-like particles (VLPs) have gained increasing interest in the fields of gene therapy and vaccine development. Several virus-based materials have been studied, but the toxicity, biodistribution, and immunology of these systems still require extensive investigation. The specific goal of this review is to provide information about nodaviruses, which are causative infectious agents of insects and aquatic animals, but not humans. By understanding the structure and biophysical properties of such viruses, further chemical or genetic modification for novel nanocarriers could be developed. Therefore, their application for therapeutic purposes, particularly in humans, is of great interest. PMID:24588230

  13. Systems Biology Approach for Cancer Vaccine Development and Evaluation.

    PubMed

    Circelli, Luisa; Petrizzo, Annacarmen; Tagliamonte, Maria; Tornesello, Maria Lina; Buonaguro, Franco M; Buonaguro, Luigi

    2015-07-14

    Therapeutic cancer vaccines do not hold promise yet as an effective anti-cancer treatment. Lack of efficacy or poor clinical outcomes are due to several antigenic and immunological aspects that need to be addressed in order to reverse such trends and significantly improve cancer vaccines' efficacy. The newly developed high throughput technologies and computational tools are instrumental to this aim allowing the identification of more specific antigens and the comprehensive analysis of the innate and adaptive immunities. Here, we review the potentiality of systems biology in providing novel insights in the mechanisms of the action of vaccines to improve their design and effectiveness.

  14. Yeast Systems Biology: Our Best Shot at Modeling a Cell

    PubMed Central

    Boone, Charles

    2014-01-01

    THE Genetics Society of America’s Edward Novitski Prize recognizes an extraordinary level of creativity and intellectual ingenuity in the solution of significant problems in genetics research. The 2014 recipient, Charles Boone, has risen to the top of the emergent discipline of postgenome systems biology by focusing on the global mapping of genetic interaction networks. Boone invented the synthetic genetic array (SGA) technology, which provides an automated method to cross thousands of strains carrying precise mutations and map large-scale yeast genetic interactions. These network maps offer researchers a functional wiring diagram of the cell, which clusters genes into specific pathways and reveals functional connections. PMID:25316779

  15. Text mining and its potential applications in systems biology.

    PubMed

    Ananiadou, Sophia; Kell, Douglas B; Tsujii, Jun-ichi

    2006-12-01

    With biomedical literature increasing at a rate of several thousand papers per week, it is impossible to keep abreast of all developments; therefore, automated means to manage the information overload are required. Text mining techniques, which involve the processes of information retrieval, information extraction and data mining, provide a means of solving this. By adding meaning to text, these techniques produce a more structured analysis of textual knowledge than simple word searches, and can provide powerful tools for the production and analysis of systems biology models. PMID:17045684

  16. Rigid Biological Systems as Models for Synthetic Composites

    NASA Astrophysics Data System (ADS)

    Mayer, George

    2005-11-01

    Advances that have been made in understanding the mechanisms underlying the mechanical behavior of a number of biological materials (namely mollusk shells and sponge spicules) are discussed here. Attempts at biomimicry of the structure of a nacreous layer of a mollusk shell have shown reasonable success. However, they have revealed additional issues that must be addressed if new synthetic composite materials that are based on natural systems are to be constructed. Some of the important advantages and limitations of copying from nature are also described here.

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

    NASA Technical Reports Server (NTRS)

    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.

  18. A complex systems approach to computational molecular biology

    SciTech Connect

    Lapedes, A. |

    1993-09-01

    We report on the containing research program at Santa Fe Institute that applies complex systems methodology to computational molecular biology. Two aspects are stressed here are the use of co-evolving adaptive neutral networks for determining predictable protein structure classifications, and the use of information theory to elucidate protein structure and function. A ``snapshot`` of the current state of research in these two topics is presented, representing the present state of two major research thrusts in the program of Genetic Data and Sequence Analysis at the Santa Fe Institute.

  19. The Search for Covalently Ligandable Proteins in Biological Systems.

    PubMed

    Badshah, Syed Lal; Mabkhot, Yahia Nasser

    2016-01-01

    This commentary highlights the recent article published in Nature, June 2016, titled: "Proteome-wide covalent ligand discovery in native biological systems". They screened the whole proteome of different human cell lines and cell lysates. Around 700 druggable cysteines in the whole proteome were found to bind the electrophilic fragments in both active and inactive states of the proteins. Their experiment and computational docking results agreed with one another. The usefulness of this study in terms of bringing a change in medicinal chemistry is highlighted here. PMID:27598117

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

    PubMed

    Morange, Michel

    2013-01-01

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

  1. TissueCypher™: A systems biology approach to anatomic pathology

    PubMed Central

    Prichard, Jeffrey W.; Davison, Jon M.; Campbell, Bruce B.; Repa, Kathleen A.; Reese, Lia M.; Nguyen, Xuan M.; Li, Jinhong; Foxwell, Tyler; Taylor, D. Lansing; Critchley-Thorne, Rebecca J.

    2015-01-01

    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 pathology in the

  2. Computational Systems Biology of Psoriasis: Are We Ready for the Age of Omics and Systems Biomarkers?

    PubMed

    Sevimoglu, Tuba; Arga, Kazim Yalcin

    2015-11-01

    Computational biology and 'omics' systems sciences are greatly impacting research on common diseases such as cancer. By contrast, dermatology covering an array of skin diseases with high prevalence in society, has received relatively less attention from 'omics' and computational biosciences. We are focusing on psoriasis, a common and debilitating autoimmune disease involving skin and joints. Using computational systems biology and reconstruction, topological, modular, and a novel correlational analyses (based on fold changes) of biological and transcriptional regulatory networks, we analyzed and integrated data from a total of twelve studies from the Gene Expression Omnibus (sample size = 534). Samples represented a comprehensive continuum from lesional and nonlesional skin, as well as bone marrow and dermal mesenchymal stem cells. We identified and propose here a JAK/STAT signaling pathway significant for psoriasis. Importantly, cytokines, interferon-stimulated genes, antimicrobial peptides, among other proteins, were involved in intrinsic parts of the proposed pathway. Several biomarker and therapeutic candidates such as SUB1 are discussed for future experimental studies. The integrative systems biology approach presented here illustrates a comprehensive perspective on the molecular basis of psoriasis. This also attests to the promise of systems biology research in skin diseases, with psoriasis as a systemic component. The present study reports, to the best of our knowledge, the largest set of microarray datasets on psoriasis, to offer new insights into the disease mechanisms with a proposal of a disease pathway. We call for greater computational systems biology research and analyses in dermatology and skin diseases in general.

  3. pH control in biological systems using calcium carbonate.

    PubMed

    Salek, S S; van Turnhout, A G; Kleerebezem, R; van Loosdrecht, M C M

    2015-05-01

    Due to its abundance, calcium carbonate (CaCO3) has high potentials as a source of alkalinity for biotechnological applications. The application of CaCO3 in biological systems as neutralizing agent is, however, limited due to potential difficulties in controlling the pH. The objective of the present study was to determine the dominant processes that control the pH in an acid-forming microbial process in the presence of CaCO3. To achieve that, a mathematical model was made with a minimum set of kinetically controlled and equilibrium reactions that was able to reproduce the experimental data of a batch fermentation experiment using finely powdered CaCO3. In the model, thermodynamic equilibrium was assumed for all speciation, complexation and precipitation reactions whereas, rate limited reactions were included for the biological fatty acid production, the mass transfer of CO2 from the liquid phase to the gas phase and the convective transport of CO2 out of the gas phase. The estimated pH-pattern strongly resembled the measured pH, suggesting that the chosen set of kinetically controlled and equilibrium reactions were establishing the experimental pH. A detailed analysis of the reaction system with the aid of the model revealed that the pH establishment was most sensitive to four factors: the mass transfer rate of CO2 to the gas phase, the biological acid production rate, the partial pressure of CO2 and the Ca(+2) concentration in the solution. Individual influences of these factors on the pH were investigated by extrapolating the model to a continuously stirred-tank reactor (CSTR) case. This case study indicates how the pH of a commonly used continuous biotechnological process could be manipulated and adjusted by altering these four factors. Achieving a better insight of the processes controlling the pH of a biological system using CaCO3 as its neutralizing agent can result in broader applications of CaCO3 in biotechnological industries.

  4. Systems biology applied to vaccine and immunotherapy development

    PubMed Central

    2011-01-01

    Immunotherapies, including vaccines, represent a potent tool to prevent or contain disease with high morbidity or mortality such as infections and cancer. However, despite their widespread use, we still have a limited understanding of the mechanisms underlying the induction of protective immune responses. Immunity is made of a multifaceted set of integrated responses involving a dynamic interaction of thousands of molecules; among those is a growing appreciation for the role the innate immunity (i.e. pathogen recognition receptors - PRRs) plays in determining the nature and duration (immune memory) of adaptive T and B cell immunity. The complex network of interactions between immune manipulation of the host (immunotherapy) on one side and innate and adaptive responses on the other might be fully understood only employing the global level of investigation provided by systems biology. In this framework, the advancement of high-throughput technologies, together with the extensive identification of new genes, proteins and other biomolecules in the "omics" era, facilitate large-scale biological measurements. Moreover, recent development of new computational tools enables the comprehensive and quantitative analysis of the interactions between all of the components of immunity over time. Here, we review recent progress in using systems biology to study and evaluate immunotherapy and vaccine strategies for infectious and neoplastic diseases. Multi-parametric data provide novel and often unsuspected mechanistic insights while enabling the identification of common immune signatures relevant to human investigation such as the prediction of immune responsiveness that could lead to the improvement of the design of future immunotherapy trials. Thus, the paradigm switch from "empirical" to "knowledge-based" conduct of medicine and immunotherapy in particular, leading to patient-tailored treatment. PMID:21933421

  5. Spin-glass structures in biological systems (abstract)

    NASA Astrophysics Data System (ADS)

    Tsapin, Alexandre I.; Blumenfeld, L. A.

    1994-05-01

    We have discovered spin-glass structures in different biological systems like animal and plant tissues, cells, chloroplasts, mitochondria, etc. These structures were detected by the ESR method. This work has been done using a synchronous culture of yeasts, saccharomyces cer. To detect spin-glass structures in a biological system, the sample must be cooled in the presence of a strong magnetic field, from 77 to 10 K. After such cooling, we recorded the ESR signal at g factor about 3.0 caused by spin-glass structures. The rotation of the sample at 10 K relative to the permanent magnetic field (always present in ESR experiments) leads to the significant change in the intensity of the ESR signal as well as in its shape. The curve of the dependence of the ESR signal intensity on the magnetic field in which the sample was cooled is S-shaped. The cooling of the same sample in zero magnetic field resulted in the absence of the ESR signal at g=3,0. It had been shown that the maximum ESR signal at g factor about 3,0 was reached 15 min before the beginning of mitosis. The study of the properties of the ESR signal at g=3,0 allowed us to make the conclusion that the paramagnetic centers responsible for this signal have been formed by Fe(II) ions localized at the chromosomes. Formed during mitosis, spin-glass structures which play a significant role in cell biology, can be detected only by the ESR method in field cooling experiments.

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

    PubMed

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

    2013-01-01

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

  7. Mathematical and Statistical Modeling in Cancer Systems Biology

    PubMed Central

    Blair, Rachael Hageman; Trichler, David L.; Gaille, Daniel P.

    2012-01-01

    Cancer is a major health problem with high mortality rates. In the post-genome era, investigators have access to massive amounts of rapidly accumulating high-throughput data in publicly available databases, some of which are exclusively devoted to housing Cancer data. However, data interpretation efforts have not kept pace with data collection, and gained knowledge is not necessarily translating into better diagnoses and treatments. A fundamental problem is to integrate and interpret data to further our understanding in Cancer Systems Biology. Viewing cancer as a network provides insights into the complex mechanisms underlying the disease. Mathematical and statistical models provide an avenue for cancer network modeling. In this article, we review two widely used modeling paradigms: deterministic metabolic models and statistical graphical models. The strength of these approaches lies in their flexibility and predictive power. Once a model has been validated, it can be used to make predictions and generate hypotheses. We describe a number of diverse applications to Cancer Biology, including, the system-wide effects of drug-treatments, disease prognosis, tumor classification, forecasting treatment outcomes, and survival predictions. PMID:22754537

  8. Tensegrity I. Cell structure and hierarchical systems biology

    NASA Technical Reports Server (NTRS)

    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.

  9. Systems biology perspectives on the carcinogenic potential of radiation

    PubMed Central

    Barcellos-Hoff, Mary Helen; Adams, Cassandra; Balmain, Allan; Costes, Sylvain V.; Demaria, Sandra; Illa-Bochaca, Irineu; Mao, Jian Hua; Ouyang, Haoxu; Sebastiano, Christopher; Tang, Jonathan

    2014-01-01

    This review focuses on recent experimental and modeling studies that attempt to define the physiological context in which high linear energy transfer (LET) radiation increases epithelial cancer risk and the efficiency with which it does so. Radiation carcinogenesis is a two-compartment problem: ionizing radiation can alter genomic sequence as a result of damage due to targeted effects (TE) from the interaction of energy and DNA; it can also alter phenotype and multicellular interactions that contribute to cancer by poorly understood non-targeted effects (NTE). Rather than being secondary to DNA damage and mutations that can initiate cancer, radiation NTE create the critical context in which to promote cancer. Systems biology modeling using comprehensive experimental data that integrates different levels of biological organization and time-scales is a means of identifying the key processes underlying the carcinogenic potential of high-LET radiation. We hypothesize that inflammation is a key process, and thus cancer susceptibility will depend on specific genetic predisposition to the type and duration of this response. Systems genetics using novel mouse models can be used to identify such determinants of susceptibility to cancer in radiation sensitive tissues following high-LET radiation. Improved understanding of radiation carcinogenesis achieved by defining the relative contribution of NTE carcinogenic effects and identifying the genetic determinants of the high-LET cancer susceptibility will help reduce uncertainties in radiation risk assessment.

  10. PAH Intermediates: Links between the Atmosphere and Biological Systems

    PubMed Central

    SIMONICH, STACI L. MASSEY; MOTORYKIN, OLEKSII; JARIYASOPIT, NARUMOL

    2010-01-01

    China is now the world's largest emitter of polycyclic aromatic hydrocarbons (PAHs). In addition, PAHs, and their reactive intermediates, undergo trans-Pacific atmospheric transport to the Western U.S. The objectives of our research are to predict, identify and quantify novel PAH intermediates in the atmosphere and biological systems, using computational methods, as well as laboratory and field experiments. Gaussian is used to predict the thermodynamic properties of parent structure PAHs, as well as the associated nitro-, oxy-, and hydroxy- PAH intermediates. Based on these predictions, state-of-the-art analytical chemistry techniques are used to identify and quantify these potential intermediates on Asian particulate matter before and after reaction in a continuous flow photochemical reactor. These same techniques are used to identify the relative proportion of PAH intermediates in PAH source regions (such as Beijing, China) and during long-range atmospheric transport to the Western U.S. PAH personal exposure studies in China and the Confederated Tribes of the Umatilla Indian Reservation in Oregon will be used to assess the similarities and differences in the PAH intermediates in biological systems relative to the atmosphere. PMID:20849837

  11. Strategies for the reduction of Legionella in biological treatment systems.

    PubMed

    Nogueira, R; Utecht, K-U; Exner, M; Verstraete, W; Rosenwinkel, K-H

    2016-01-01

    A community-wide outbreak of Legionnaire's disease occurred in Warstein, Germany, in August 2013. The epidemic strain, Legionella pneumophila Serogruppe 1, was isolated from an industrial wastewater stream entering the municipal wastewater treatment plant (WWTP) in Wartein, the WWTP itself, the river Wäster and air/water samples from an industrial cooling system 3 km downstream of the WWTP. The present study investigated the effect of physical-chemical disinfection methods on the reduction of the concentration of Legionella in the biological treatment and in the treated effluent entering the river Wäster. Additionally, to gain insight into the factors that promote the growth of Legionella in biological systems, growth experiments were made with different substrates and temperatures. The dosage rates of silver micro-particles, hydrogen peroxide, chlorine dioxide and ozone and pH stress to the activated sludge were not able to decrease the number of culturable Legionella spp. in the effluent. Nevertheless, the UV treatment of secondary treated effluent reduced Legionella spp. on average by 1.6-3.4 log units. Laboratory-scale experiments and full-scale measurements suggested that the aerobic treatment of warm wastewater (30-35 °C) rich in organic nitrogen (protein) is a possible source of Legionella infection. PMID:27533856

  12. Strategies for the reduction of Legionella in biological treatment systems.

    PubMed

    Nogueira, R; Utecht, K-U; Exner, M; Verstraete, W; Rosenwinkel, K-H

    2016-01-01

    A community-wide outbreak of Legionnaire's disease occurred in Warstein, Germany, in August 2013. The epidemic strain, Legionella pneumophila Serogruppe 1, was isolated from an industrial wastewater stream entering the municipal wastewater treatment plant (WWTP) in Wartein, the WWTP itself, the river Wäster and air/water samples from an industrial cooling system 3 km downstream of the WWTP. The present study investigated the effect of physical-chemical disinfection methods on the reduction of the concentration of Legionella in the biological treatment and in the treated effluent entering the river Wäster. Additionally, to gain insight into the factors that promote the growth of Legionella in biological systems, growth experiments were made with different substrates and temperatures. The dosage rates of silver micro-particles, hydrogen peroxide, chlorine dioxide and ozone and pH stress to the activated sludge were not able to decrease the number of culturable Legionella spp. in the effluent. Nevertheless, the UV treatment of secondary treated effluent reduced Legionella spp. on average by 1.6-3.4 log units. Laboratory-scale experiments and full-scale measurements suggested that the aerobic treatment of warm wastewater (30-35 °C) rich in organic nitrogen (protein) is a possible source of Legionella infection.

  13. On Having No Head: Cognition throughout Biological Systems.

    PubMed

    Baluška, František; Levin, Michael

    2016-01-01

    The central nervous system (CNS) underlies memory, perception, decision-making, and behavior in numerous organisms. However, neural networks have no monopoly on the signaling functions that implement these remarkable algorithms. It is often forgotten that neurons optimized cellular signaling modes that existed long before the CNS appeared during evolution, and were used by somatic cellular networks to orchestrate physiology, embryonic development, and behavior. Many of the key dynamics that enable information processing can, in fact, be implemented by different biological hardware. This is widely exploited by organisms throughout the tree of life. Here, we review data on memory, learning, and other aspects of cognition in a range of models, including single celled organisms, plants, and tissues in animal bodies. We discuss current knowledge of the molecular mechanisms at work in these systems, and suggest several hypotheses for future investigation. The study of cognitive processes implemented in aneural contexts is a fascinating, highly interdisciplinary topic that has many implications for evolution, cell biology, regenerative medicine, computer science, and synthetic bioengineering.

  14. On Having No Head: Cognition throughout Biological Systems.

    PubMed

    Baluška, František; Levin, Michael

    2016-01-01

    The central nervous system (CNS) underlies memory, perception, decision-making, and behavior in numerous organisms. However, neural networks have no monopoly on the signaling functions that implement these remarkable algorithms. It is often forgotten that neurons optimized cellular signaling modes that existed long before the CNS appeared during evolution, and were used by somatic cellular networks to orchestrate physiology, embryonic development, and behavior. Many of the key dynamics that enable information processing can, in fact, be implemented by different biological hardware. This is widely exploited by organisms throughout the tree of life. Here, we review data on memory, learning, and other aspects of cognition in a range of models, including single celled organisms, plants, and tissues in animal bodies. We discuss current knowledge of the molecular mechanisms at work in these systems, and suggest several hypotheses for future investigation. The study of cognitive processes implemented in aneural contexts is a fascinating, highly interdisciplinary topic that has many implications for evolution, cell biology, regenerative medicine, computer science, and synthetic bioengineering. PMID:27445884

  15. On Having No Head: Cognition throughout Biological Systems

    PubMed Central

    Baluška, František; Levin, Michael

    2016-01-01

    The central nervous system (CNS) underlies memory, perception, decision-making, and behavior in numerous organisms. However, neural networks have no monopoly on the signaling functions that implement these remarkable algorithms. It is often forgotten that neurons optimized cellular signaling modes that existed long before the CNS appeared during evolution, and were used by somatic cellular networks to orchestrate physiology, embryonic development, and behavior. Many of the key dynamics that enable information processing can, in fact, be implemented by different biological hardware. This is widely exploited by organisms throughout the tree of life. Here, we review data on memory, learning, and other aspects of cognition in a range of models, including single celled organisms, plants, and tissues in animal bodies. We discuss current knowledge of the molecular mechanisms at work in these systems, and suggest several hypotheses for future investigation. The study of cognitive processes implemented in aneural contexts is a fascinating, highly interdisciplinary topic that has many implications for evolution, cell biology, regenerative medicine, computer science, and synthetic bioengineering. PMID:27445884

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  17. What does systems biology mean for drug development?

    PubMed

    Schrattenholz, André; Soskić, Vukić

    2008-01-01

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

  18. Biological elements carry out optical tasks in coherent imaging systems

    NASA Astrophysics Data System (ADS)

    Ferraro, P.; Bianco, V.; Paturzo, M.; Miccio, L.; Memmolo, P.; Merola, F.; Marchesano, V.

    2016-03-01

    We show how biological elements, like live bacteria species and Red Blood Cells (RBCs) can accomplish optical functionalities in DH systems. Turbid media allow coherent microscopy despite the strong light scattering these provoke, acting on light just as moving diffusers. Furthermore, a turbid medium can have positive effects on a coherent imaging system, providing resolution enhancement and mimicking the action of noise decorrelation devices, thus yielding an image quality significantly higher than the quality achievable through a transparent medium in similar recording conditions. Besides, suspended RBCs are demonstrated to behave as controllable liquid micro-lenses, opening new possibilities in biophotonics for endoscopy imaging purposes, as well as telemedicine for point-of-care diagnostics in developing countries and low-resource settings.

  19. Standards, databases, and modeling tools in systems biology.

    PubMed

    Kohl, Michael

    2011-01-01

    Modeling is a means for integrating the results from Genomics, Transcriptomics, Proteomics, and Metabolomics experiments and for gaining insights into the interaction of the constituents of biological systems. However, sharing such large amounts of frequently heterogeneous and distributed experimental data needs both standard data formats and public repositories. Standardization and a public storage system are also important for modeling due to the possibility of sharing models irrespective of the used software tools. Furthermore, rapid model development strongly benefits from available software packages that relieve the modeler of recurring tasks like numerical integration of rate equations or parameter estimation. In this chapter, the most common standard formats used for model encoding and some of the major public databases in this scientific field are presented. The main features of currently available modeling software are discussed and proposals for the application of such tools are given.

  20. The role of coherence in emergent behavior of biological systems.

    PubMed

    Bertolaso, Marta; Capolupo, Antonio; Cherubini, Christian; Filippi, Simonetta; Gizzi, Alessio; Loppini, Alessandro; Vitiello, Giuseppe

    2015-01-01

    In his research activity, Emilio Del Giudice explored the possibility to move towards a unified view of some long-range dynamics in nature, ranging from quantum field theory in physics up to biology. Such a view is adopted in this contribution by discussing a mathematical model for synchronized electrical behavior of pancreatic beta cells. The stochasticity is a fundamental component of the physiological synchronized behavior of this system. On the contrary, in a pathological type I diabetes scenario, the cells are destroyed by the autoimmune system and their coherent behavior is lost. This phenomenology conceptually links to ideas of coherent dynamics in quantum physics. Possible implications both for physical sciences and for the epistemology of life sciences are outlined.

  1. Systems Biology of Recombinant Protein Production in Bacillus megaterium

    NASA Astrophysics Data System (ADS)

    Biedendieck, Rebekka; Bunk, Boyke; Fürch, Tobias; Franco-Lara, Ezequiel; Jahn, Martina; Jahn, Dieter

    Over the last two decades the Gram-positive bacterium Bacillus megaterium was systematically developed to a useful alternative protein production host. Multiple vector systems for high yield intra- and extracellular protein production were constructed. Strong inducible promoters were combined with DNA sequences for optimised ribosome binding sites, various leader peptides for protein export and N- as well as C-terminal affinity tags for affinity chromatographic purification of the desired protein. High cell density cultivation and recombinant protein production were successfully tested. For further system biology based control and optimisation of the production process the genomes of two B. megaterium strains were completely elucidated, DNA arrays designed, proteome, fluxome and metabolome analyses performed and all data integrated using the bioinformatics platform MEGABAC. Now, solid theoretical and experimental bases for primary modeling attempts of the production process are available.

  2. Hippocampal gene profiling: toward a systems biology of the hippocampus.

    PubMed

    Valor, Luis M; Barco, Angel

    2012-05-01

    Transcriptomics and proteomics approaches give a unique perspective for understanding brain and hippocampal functions but also pose unique challenges because of the singular complexity of the nervous system. The proliferation of genome-wide expression studies during the last decade has provided important insight into the molecular underpinnings of brain anatomy, neural plasticity, and neurological diseases. Microarray technology has dominated transcriptomics research, but this situation is rapidly changing with the recent technological advances in high-throughput sequencing. The full potential of transcriptomics in the neurosciences will be achieved as a result of its integration with other "-omics" disciplines as well as the development of novel analytical bioinformatics and systems biology tools for meta-analysis. Here, we review some of the most relevant advances in the gene profiling of the hippocampus, its relationship with proteomics approaches, and the promising perspectives for the future.

  3. Synthetic membranes and membrane processes with counterparts in biological systems

    NASA Astrophysics Data System (ADS)

    Matson, Stephen L.

    1996-02-01

    Conventional synthetic membranes, fashioned for the most part from rather unremarkable polymeric materials, are essentially passive structures that achieve various industrial and biomedical separations through simple and selective membrane permeation processes. Indeed, simplicity of membrane material, structure, and function has long been perceived as a virtue of membranes relative to other separation processes with which they compete. The passive membrane separation processes -- exemplified by micro- and ultrafiltration, dialysis, reverse osmosis, and gas permeation -- differ from one another primarily in terms of membrane morphology or structure (e.g., porous, gel-type, and nonporous) and the permeant transport mechanism and driving force (e.g., diffusion, convection, and 'solution/diffusion'). The passive membrane separation processes have in common the fact that interaction between permeant and membrane material is typically weak and physicochemical in nature; indeed, it is frequently an objective of membrane materials design to minimize interaction between permeant and membrane polymer, since such strategies can minimize membrane fouling. As a consequence, conventional membrane processes often provide only modest separation factors or permselectivities; that is, they are more useful in performing 'group separations' (i.e., the separation of different classes of material) than they are in fractionating species within a given class. It has long been recognized within the community of membrane technologists that biological membrane structures and their components are extraordinarily sophisticated and powerful as compared to their synthetic counterparts. Moreover, biomembranes and related biological systems have been 'designed' according to a very different paradigm -- one that frequently maximizes and capitalizes on extraordinarily strong and biochemically specific interactions between components of the membrane and species interacting with them. Thus, in recent

  4. Biological diversity of prokaryotic type IV secretion systems.

    PubMed

    Alvarez-Martinez, Cristina E; Christie, Peter J

    2009-12-01

    Type IV secretion systems (T4SS) translocate DNA and protein substrates across prokaryotic cell envelopes generally by a mechanism requiring direct contact with a target cell. Three types of T4SS have been described: (i) conjugation systems, operationally defined as machines that translocate DNA substrates intercellularly by a contact-dependent process; (ii) effector translocator systems, functioning to deliver proteins or other macromolecules to eukaryotic target cells; and (iii) DNA release/uptake systems, which translocate DNA to or from the extracellular milieu. Studies of a few paradigmatic systems, notably the conjugation systems of plasmids F, R388, RP4, and pKM101 and the Agrobacterium tumefaciens VirB/VirD4 system, have supplied important insights into the structure, function, and mechanism of action of type IV secretion machines. Information on these systems is updated, with emphasis on recent exciting structural advances. An underappreciated feature of T4SS, most notably of the conjugation subfamily, is that they are widely distributed among many species of gram-negative and -positive bacteria, wall-less bacteria, and the Archaea. Conjugation-mediated lateral gene transfer has shaped the genomes of most if not all prokaryotes over evolutionary time and also contributed in the short term to the dissemination of antibiotic resistance and other virulence traits among medically important pathogens. How have these machines adapted to function across envelopes of distantly related microorganisms? A survey of T4SS functioning in phylogenetically diverse species highlights the biological complexity of these translocation systems and identifies common mechanistic themes as well as novel adaptations for specialized purposes relating to the modulation of the donor-target cell interaction. PMID:19946141

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

    PubMed Central

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

    2015-01-01

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

  6. The systems perspective at the crossroads between chemistry and biology.

    PubMed

    de la Escosura, Andrés; Briones, Carlos; Ruiz-Mirazo, Kepa

    2015-09-21

    During the last century a number of authors pointed to the inherently systemic and dynamic nature of the living, yet their message was largely ignored by the mainstream of the scientific community. Tibor Ganti was one of those early pioneers, proposing a theoretical framework to understand the living principles in terms of chemical transformation cycles and their coupling. The turn of the century then brought with it a novel 'systems' paradigm, which shined light on all that previous work and carried many implications for the way we conceive of chemical and biological complexity today. In this article tribute is paid to some of those seminal contributions, highlighting the importance of adopting a systems view in present chemistry, particularly if plausible mechanisms of chemical evolution toward the first living entities want to be unraveled. We examine and put in perspective recent discoveries in the emerging subfield of 'prebiotic systems chemistry', reaching the conclusion that the functional coupling of protocellular subsystems (i.e., protometabolism, protogenome and membrane compartment) is the most challenging target to make qualitative advances in the problem of the origins of life. For the long-awaited goal of assembling an autonomous protocell from its most basic molecular building blocks, we further suggest that a systems integrative strategy should be considered from the earliest synthetic steps, already at the level of monomer precursors, opening the way to biogenesis. PMID:25983045

  7. Bridging Mechanistic and Phenomenological Models of Complex Biological Systems

    PubMed Central

    Transtrum, Mark K.; Qiu, Peng

    2016-01-01

    The inherent complexity of biological systems gives rise to complicated mechanistic models with a large number of parameters. On the other hand, the collective behavior of these systems can often be characterized by a relatively small number of phenomenological parameters. We use the Manifold Boundary Approximation Method (MBAM) as a tool for deriving simple phenomenological models from complicated mechanistic models. The resulting models are not black boxes, but remain expressed in terms of the microscopic parameters. In this way, we explicitly connect the macroscopic and microscopic descriptions, characterize the equivalence class of distinct systems exhibiting the same range of collective behavior, and identify the combinations of components that function as tunable control knobs for the behavior. We demonstrate the procedure for adaptation behavior exhibited by the EGFR pathway. From a 48 parameter mechanistic model, the system can be effectively described by a single adaptation parameter τ characterizing the ratio of time scales for the initial response and recovery time of the system which can in turn be expressed as a combination of microscopic reaction rates, Michaelis-Menten constants, and biochemical concentrations. The situation is not unlike modeling in physics in which microscopically complex processes can often be renormalized into simple phenomenological models with only a few effective parameters. The proposed method additionally provides a mechanistic explanation for non-universal features of the behavior. PMID:27187545

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

    PubMed

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

    2008-02-13

    Is the characterization of biological systems as complex systems in the mathematical sense a fruitful assertion? In this paper we argue in the affirmative, although obviously we do not attempt to confront all the issues raised by this question. We use the fly's visual system as an example and analyse our experimental results of one particular neuron in the fly's visual system from this point of view. We find that the motion-sensitive 'H1' neuron, which converts incoming signals into a sequence of identical pulses or 'spikes', encodes the information contained in the stimulus into an alphabet composed of a few letters. This encoding occurs on multilayered sets, one of the features attributed to complex systems. The conversion of intervals between consecutive occurrences of spikes into an alphabet requires us to construct a generating partition. This entails a one-to-one correspondence between sequences of spike intervals and words written in the alphabet. The alphabet dynamics is multifractal both with and without stimulus, though the multifractality increases with the stimulus entropy. This is in sharp contrast to models generating independent spike intervals, such as models using Poisson statistics, whose dynamics is monofractal. We embed the support of the probability measure, which describes the distribution of words written in this alphabet, in a two-dimensional space, whose topology can be reproduced by an M-shaped map. This map has positive Lyapunov exponents, indicating a chaotic-like encoding. PMID:17673416

  9. How People Actually Use Thermostats

    SciTech Connect

    Meier, Alan; Aragon, Cecilia; Hurwitz, Becky; Mujumdar, Dhawal; Peffer, Therese; Perry, Daniel; Pritoni, Marco

    2010-08-15

    Residential thermostats have been a key element in controlling heating and cooling systems for over sixty years. However, today's modern programmable thermostats (PTs) are complicated and difficult for users to understand, leading to errors in operation and wasted energy. Four separate tests of usability were conducted in preparation for a larger study. These tests included personal interviews, an on-line survey, photographing actual thermostat settings, and measurements of ability to accomplish four tasks related to effective use of a PT. The interviews revealed that many occupants used the PT as an on-off switch and most demonstrated little knowledge of how to operate it. The on-line survey found that 89% of the respondents rarely or never used the PT to set a weekday or weekend program. The photographic survey (in low income homes) found that only 30% of the PTs were actually programmed. In the usability test, we found that we could quantify the difference in usability of two PTs as measured in time to accomplish tasks. Users accomplished the tasks in consistently shorter times with the touchscreen unit than with buttons. None of these studies are representative of the entire population of users but, together, they illustrate the importance of improving user interfaces in PTs.

  10. Entity grammar systems: a grammatical tool for studying the hierarchical structures of biological systems.

    PubMed

    Wang, Yun

    2004-05-01

    The hierarchical structures of biological systems are the typical complex hierarchical dynamical structures in the physical world, the effective investigations on which could not be performed with the existing formal grammar systems. To meet the needs of the investigation on these kinds of systems, especially the emerging field of system biology, a grammatical tool was proposed in the present article. Because the grammatical tool mainly deals with the systems composed of structured entities, they are called entity grammar systems (EGSs). The structure of entities in EGSs have the general form of the objects in the physical world, which means EGSs could be used as a tool to study the complex system composed of many objects with different structures, just like the biological systems. The article contains the formal definition of EGSs and the hierarchy of EGSs, which is congruent with the Chomsky hierarchy. The relationship between EGSs and array grammar systems, graph grammar systems, tree grammar systems, multi-set grammar systems are discussed to show the generative power of EGSs. At the end of the present article, the steps to define new grammar systems with the form of EGS are provided and the possible applicable fields of EGSs are discussed. PMID:15006443

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

    PubMed

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

    2014-07-01

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

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

    PubMed

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

    2007-10-01

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

  13. Micrasterias as a Model System in Plant Cell Biology.

    PubMed

    Lütz-Meindl, Ursula

    2016-01-01

    The unicellular freshwater alga Micrasterias denticulata is an exceptional organism due to its complex star-shaped, highly symmetric morphology and has thus attracted the interest of researchers for many decades. As a member of the Streptophyta, Micrasterias is not only genetically closely related to higher land plants but shares common features with them in many physiological and cell biological aspects. These facts, together with its considerable cell size of about 200 μm, its modest cultivation conditions and the uncomplicated accessibility particularly to any microscopic techniques, make Micrasterias a very well suited cell biological plant model system. The review focuses particularly on cell wall formation and composition, dictyosomal structure and function, cytoskeleton control of growth and morphogenesis as well as on ionic regulation and signal transduction. It has been also shown in the recent years that Micrasterias is a highly sensitive indicator for environmental stress impact such as heavy metals, high salinity, oxidative stress or starvation. Stress induced organelle degradation, autophagy, adaption and detoxification mechanisms have moved in the center of interest and have been investigated with modern microscopic techniques such as 3-D- and analytical electron microscopy as well as with biochemical, physiological and molecular approaches. This review is intended to summarize and discuss the most important results obtained in Micrasterias in the last 20 years and to compare the results to similar processes in higher plant cells. PMID:27462330

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

    PubMed

    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

  15. Perturbation Biology: Inferring Signaling Networks in Cellular Systems

    PubMed Central

    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; Sander, Chris

    2013-01-01

    We present a powerful experimental-computational technology for inferring network models that predict the response of cells to perturbations, and that may be useful in the design of combinatorial therapy against cancer. The experiments are systematic series of perturbations of cancer cell lines by targeted drugs, singly or in combination. The response to perturbation is quantified in terms of relative changes in the measured levels of proteins, phospho-proteins and cellular phenotypes such as viability. Computational network models are derived de novo, i.e., without prior knowledge of signaling pathways, and are based on simple non-linear differential equations. The prohibitively large solution space of all possible network models is explored efficiently using a probabilistic algorithm, Belief Propagation (BP), which is three orders of magnitude faster than standard Monte Carlo methods. Explicit executable models are derived for a set of perturbation experiments in SKMEL-133 melanoma cell lines, which are resistant to the therapeutically important inhibitor of RAF kinase. The resulting network models reproduce and extend known pathway biology. They empower potential discoveries of new molecular interactions and predict efficacious novel drug perturbations, such as the inhibition of PLK1, which is verified experimentally. This technology is suitable for application to larger systems in diverse areas of molecular biology. PMID:24367245

  16. A data integration methodology for systems biology: Experimental verification

    PubMed Central

    Hwang, Daehee; Smith, Jennifer J.; Leslie, Deena M.; Weston, Andrea D.; Rust, Alistair G.; Ramsey, Stephen; de Atauri, Pedro; Siegel, Andrew F.; Bolouri, Hamid; Aitchison, John D.; Hood, Leroy

    2005-01-01

    The integration of data from multiple global assays is essential to understanding dynamic spatiotemporal interactions within cells. In a companion paper, we reported a data integration methodology, designated Pointillist, that can handle multiple data types from technologies with different noise characteristics. Here we demonstrate its application to the integration of 18 data sets relating to galactose utilization in yeast. These data include global changes in mRNA and protein abundance, genome-wide protein–DNA interaction data, database information, and computational predictions of protein–DNA and protein–protein interactions. We divided the integration task to determine three network components: key system elements (genes and proteins), protein–protein interactions, and protein–DNA interactions. Results indicate that the reconstructed network efficiently focuses on and recapitulates the known biology of galactose utilization. It also provided new insights, some of which were verified experimentally. The methodology described here, addresses a critical need across all domains of molecular and cell biology, to effectively integrate large and disparate data sets. PMID:16301536

  17. Systems biology approach for new target and biomarker identification.

    PubMed

    Wang, I-Ming; Stone, David J; Nickle, David; Loboda, Andrey; Puig, Oscar; Roberts, Christopher

    2013-01-01

    The pharmaceutical industry is spending increasingly large amounts of money on the discovery and development of novel medicines, but this investment is not adequately paying off in an increased rate of newly approved drugs by the FDA. The post-genomic era has provided a wealth of novel approaches for generating large, high-dimensional genetic and transcriptomic data sets from large cohorts of preclinical species as well as normal and diseased individuals. This systems biology approach to understanding disease-related biology is revolutionizing our understanding of the cellular pathways and gene networks underlying the onset of disease, and the mechanisms of pharmacological treatments that ameliorate disease phenotypes. In this article, we review a number of approaches being used by pharmaceutical and biotechnology companies, e.g., high-throughput DNA genotyping, sequencing, and genome-wide gene expression profiling, to enable drug discovery and development through the identification of new drug targets and biomarkers of disease progression, drug pharmacodynamics, and predictive markers for selecting the patients most likely to respond to therapy.

  18. Micrasterias as a Model System in Plant Cell Biology.

    PubMed

    Lütz-Meindl, Ursula

    2016-01-01

    The unicellular freshwater alga Micrasterias denticulata is an exceptional organism due to its complex star-shaped, highly symmetric morphology and has thus attracted the interest of researchers for many decades. As a member of the Streptophyta, Micrasterias is not only genetically closely related to higher land plants but shares common features with them in many physiological and cell biological aspects. These facts, together with its considerable cell size of about 200 μm, its modest cultivation conditions and the uncomplicated accessibility particularly to any microscopic techniques, make Micrasterias a very well suited cell biological plant model system. The review focuses particularly on cell wall formation and composition, dictyosomal structure and function, cytoskeleton control of growth and morphogenesis as well as on ionic regulation and signal transduction. It has been also shown in the recent years that Micrasterias is a highly sensitive indicator for environmental stress impact such as heavy metals, high salinity, oxidative stress or starvation. Stress induced organelle degradation, autophagy, adaption and detoxification mechanisms have moved in the center of interest and have been investigated with modern microscopic techniques such as 3-D- and analytical electron microscopy as well as with biochemical, physiological and molecular approaches. This review is intended to summarize and discuss the most important results obtained in Micrasterias in the last 20 years and to compare the results to similar processes in higher plant cells.

  19. Yeast prions: structure, biology, and prion-handling systems.

    PubMed

    Wickner, Reed B; Shewmaker, Frank P; Bateman, David A; Edskes, Herman K; Gorkovskiy, Anton; Dayani, Yaron; Bezsonov, Evgeny E

    2015-03-01

    A prion is an infectious protein horizontally transmitting a disease or trait without a required nucleic acid. Yeast and fungal prions are nonchromosomal genes composed of protein, generally an altered form of a protein that catalyzes the same alteration of the protein. Yeast prions are thus transmitted both vertically (as genes composed of protein) and horizontally (as infectious proteins, or prions). Formation of amyloids (linear ordered β-sheet-rich protein aggregates with β-strands perpendicular to the long axis of the filament) underlies most yeast and fungal prions, and a single prion protein can have any of several distinct self-propagating amyloid forms with different biological properties (prion variants). Here we review the mechanism of faithful templating of protein conformation, the biological roles of these prions, and their interactions with cellular chaperones, the Btn2 and Cur1 aggregate-handling systems, and other cellular factors governing prion generation and propagation. Human amyloidoses include the PrP-based prion conditions and many other, more common amyloid-based diseases, several of which show prion-like features. Yeast prions increasingly are serving as models for the understanding and treatment of many mammalian amyloidoses. Patients with different clinical pictures of the same amyloidosis may be the equivalent of yeasts with different prion variants.

  20. Micrasterias as a Model System in Plant Cell Biology

    PubMed Central

    Lütz-Meindl, Ursula

    2016-01-01

    The unicellular freshwater alga Micrasterias denticulata is an exceptional organism due to its complex star-shaped, highly symmetric morphology and has thus attracted the interest of researchers for many decades. As a member of the Streptophyta, Micrasterias is not only genetically closely related to higher land plants but shares common features with them in many physiological and cell biological aspects. These facts, together with its considerable cell size of about 200 μm, its modest cultivation conditions and the uncomplicated accessibility particularly to any microscopic techniques, make Micrasterias a very well suited cell biological plant model system. The review focuses particularly on cell wall formation and composition, dictyosomal structure and function, cytoskeleton control of growth and morphogenesis as well as on ionic regulation and signal transduction. It has been also shown in the recent years that Micrasterias is a highly sensitive indicator for environmental stress impact such as heavy metals, high salinity, oxidative stress or starvation. Stress induced organelle degradation, autophagy, adaption and detoxification mechanisms have moved in the center of interest and have been investigated with modern microscopic techniques such as 3-D- and analytical electron microscopy as well as with biochemical, physiological and molecular approaches. This review is intended to summarize and discuss the most important results obtained in Micrasterias in the last 20 years and to compare the results to similar processes in higher plant cells. PMID:27462330