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Sample records for integrated systems biology

  1. 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

  2. Systems biology as an integrated platform for bioinformatics, systems synthetic biology, and systems metabolic engineering.

    PubMed

    Chen, Bor-Sen; Wu, Chia-Chou

    2013-10-11

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

  3. 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

  4. 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.

  5. Implementation of integral feedback control in biological systems.

    PubMed

    Somvanshi, Pramod R; Patel, Anilkumar K; Bhartiya, Sharad; Venkatesh, K V

    2015-01-01

    Integral control design ensures that a key variable in a system is tightly maintained within acceptable levels. This approach has been widely used in engineering systems to ensure offset free operation in the presence of perturbations. Several biological systems employ such an integral control design to regulate cellular processes. An integral control design motif requires a negative feedback and an integrating process in the network loop. This review describes several biological systems, ranging from bacteria to higher organisms in which the presence of integral control principle has been hypothesized. The review highlights that in addition to the negative feedback, occurrence of zero-order kinetics in the process is a key element to realize the integral control strategy. Although the integral control motif is common to these systems, the mechanisms involved in achieving it are highly specific and can be incorporated at the level of signaling, metabolism, or at the phenotypic levels.

  6. 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

  7. Integrative system biology strategies for disease biomarker discovery.

    PubMed

    Zhang, Haiyuan; Hu, Hao; Deng, Cao; Chun, Yeona; Zhou, Shengtao; Huang, Fuqiang; Zhou, Qin

    2012-05-01

    Biomarkers are currently widely used to diagnose diseases, monitor treatments, and evaluate potential drug candidates. Research of differential Omics accelerate the advancements of biomarkers' discovery. By extracting biological knowledge from the 'omics' through integration, integrative system biology creates predictive models of cells, organs, biochemical processes and complete organisms, in addition to identifying human disease biomarkers. Recent development in high-throughput methods enables analysis of genome, transcriptome, proteome, and metabolome at an unprecedented scale, thus contributing to the deluge of experimental data in numerous public databases. Several integrative system biology approaches have been developed and applied to the discovery of disease biomarkers from databases. In this review, we highlight several of these approaches and identify future steps in the context of the field of integrative system biology.

  8. Integrating systems biology sources illuminates drug action

    PubMed Central

    Gottlieb, Assaf; Altman, Russ B.

    2014-01-01

    There are significant gaps in our understanding of the pathways by which drugs act. This incomplete knowledge limits our ability to use mechanistic molecular information rationally to repurpose drugs, understand their side effects, and predict their interactions with other drugs. Here we present DrugRouter: a novel method for generating drug-specific pathways of action by linking target genes, disease genes and pharmacogenes using gene interaction networks. We construct pathways for over a hundred drugs, and show that the genes included in our pathways (1) co-occur with the query drug in the literature, (2) significantly overlap or are adjacent to known drug-response pathways, and (3) are adjacent to genes that are hits in genome wide association studies assessing drug response. Finally, these computed pathways suggest novel drug repositioning opportunities (e.g., statins for follicular thyroid cancer), gene-side effect associations, and gene-drug interactions. Thus, DrugRouter generates hypotheses about drug actions using systems biology data. PMID:24577151

  9. 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.

  10. Software for systems biology: from tools to integrated platforms.

    PubMed

    Ghosh, Samik; Matsuoka, Yukiko; Asai, Yoshiyuki; Hsin, Kun-Yi; Kitano, Hiroaki

    2011-11-03

    Understanding complex biological systems requires extensive support from software tools. Such tools are needed at each step of a systems biology computational workflow, which typically consists of data handling, network inference, deep curation, dynamical simulation and model analysis. In addition, there are now efforts to develop integrated software platforms, so that tools that are used at different stages of the workflow and by different researchers can easily be used together. This Review describes the types of software tools that are required at different stages of systems biology research and the current options that are available for systems biology researchers. We also discuss the challenges and prospects for modelling the effects of genetic changes on physiology and the concept of an integrated platform.

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

    PubMed

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

    2014-03-24

    In the current era of large-scale biology, systems biology has evolved as a powerful approach to identify complex interactions within biological systems. In addition to high throughput identification and quantification techniques, methods based on high-quality mono-specific antibodies remain an essential element of the approach. To assist the large-scale design and production of peptide-directed antibodies for systems biology studies, we developed a fully integrated online application, AbDesigner (http://helixweb.nih.gov/AbDesigner/), to help researchers select optimal peptide immunogens for antibody generation against relatively disordered regions of target proteins. Here we describe AbDesigner in terms of its features, comparing it to other software tools, and use it to design three antibodies against kidney disease-related proteins in human, viz. nephrin, podocin, and apolipoprotein L1.

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

    PubMed Central

    2010-01-01

    Background The behaviour of biological systems can be deduced from their mathematical models. However, multiple sources of data in diverse forms are required in the construction of a model in order to define its components and their biochemical reactions, and corresponding parameters. Automating the assembly and use of systems biology models is dependent upon data integration processes involving the interoperation of data and analytical resources. Results Taverna workflows have been developed for the automated assembly of quantitative parameterised metabolic networks in the Systems Biology Markup Language (SBML). A SBML model is built in a systematic fashion by the workflows which starts with the construction of a qualitative network using data from a MIRIAM-compliant genome-scale model of yeast metabolism. This is followed by parameterisation of the SBML model with experimental data from two repositories, the SABIO-RK enzyme kinetics database and a database of quantitative experimental results. The models are then calibrated and simulated in workflows that call out to COPASIWS, the web service interface to the COPASI software application for analysing biochemical networks. These systems biology workflows were evaluated for their ability to construct a parameterised model of yeast glycolysis. Conclusions Distributed information about metabolic reactions that have been described to MIRIAM standards enables the automated assembly of quantitative systems biology models of metabolic networks based on user-defined criteria. Such data integration processes can be implemented as Taverna workflows to provide a rapid overview of the components and their relationships within a biochemical system. PMID:21114840

  13. DIPSBC - data integration platform for systems biology collaborations

    PubMed Central

    2012-01-01

    Background Modern biomedical research is often organized in collaborations involving labs worldwide. In particular in systems biology, complex molecular systems are analyzed that require the generation and interpretation of heterogeneous data for their explanation, for example ranging from gene expression studies and mass spectrometry measurements to experimental techniques for detecting molecular interactions and functional assays. XML has become the most prominent format for representing and exchanging these data. However, besides the development of standards there is still a fundamental lack of data integration systems that are able to utilize these exchange formats, organize the data in an integrative way and link it with applications for data interpretation and analysis. Results We have developed DIPSBC, an interactive data integration platform supporting collaborative research projects, based on Foswiki, Solr/Lucene, and specific helper applications. We describe the main features of the implementation and highlight the performance of the system with several use cases. All components of the system are platform independent and open-source developments and thus can be easily adopted by researchers. An exemplary installation of the platform which also provides several helper applications and detailed instructions for system usage and setup is available at http://dipsbc.molgen.mpg.de. Conclusions DIPSBC is a data integration platform for medium-scale collaboration projects that has been tested already within several research collaborations. Because of its modular design and the incorporation of XML data formats it is highly flexible and easy to use. PMID:22568834

  14. Meat science: From proteomics to integrated omics towards system biology.

    PubMed

    D'Alessandro, Angelo; Zolla, Lello

    2013-01-14

    Since the main ultimate goal of farm animal raising is the production of proteins for human consumption, research tools to investigate proteins play a major role in farm animal and meat science. Indeed, proteomics has been applied to the field of farm animal science to monitor in vivo performances of livestock animals (growth performances, fertility, milk quality etc.), but also to further our understanding of the molecular processes at the basis of meat quality, which are largely dependent on the post mortem biochemistry of the muscle, often in a species-specific way. Post mortem alterations to the muscle proteome reflect the biological complexity of the process of "muscle to meat conversion," a process that, despite decades of advancements, is all but fully understood. This is mainly due to the enormous amounts of variables affecting meat tenderness per se, including biological factors, such as animal species, breed specific-characteristic, muscle under investigation. However, it is rapidly emerging that the tender meat phenotype is not only tied to genetics (livestock breeding selection), but also to extrinsic factors, such as the rearing environment, feeding conditions, physical activity, administration of hormonal growth promotants, pre-slaughter handling and stress, post mortem handling. From this intricate scenario, biochemical approaches and systems-wide integrated investigations (metabolomics, transcriptomics, interactomics, phosphoproteomics, mathematical modeling), which have emerged as complementary tools to proteomics, have helped establishing a few milestones in our understanding of the events leading from muscle to meat conversion. The growing integration of omics disciplines in the field of systems biology will soon contribute to take further steps forward.

  15. Lean Big Data integration in systems biology and systems pharmacology.

    PubMed

    Ma'ayan, Avi; Rouillard, Andrew D; Clark, Neil R; Wang, Zichen; Duan, Qiaonan; Kou, Yan

    2014-09-01

    Data sets from recent large-scale projects can be integrated into one unified puzzle that can provide new insights into how drugs and genetic perturbations applied to human cells are linked to whole-organism phenotypes. Data that report how drugs affect the phenotype of human cell lines and how drugs induce changes in gene and protein expression in human cell lines can be combined with knowledge about human disease, side effects induced by drugs, and mouse phenotypes. Such data integration efforts can be achieved through the conversion of data from the various resources into single-node-type networks, gene-set libraries, or multipartite graphs. This approach can lead us to the identification of more relationships between genes, drugs, and phenotypes as well as benchmark computational and experimental methods. Overall, this lean 'Big Data' integration strategy will bring us closer toward the goal of realizing personalized medicine.

  16. Research on models of biological systems that can be integrated into mechatronic systems

    NASA Astrophysics Data System (ADS)

    Pop, P. P.; Pop-Vadean, A.; Barz, C.; Latinovic, T.; Chiver, O.

    2016-02-01

    The models of biological systems that we find on Earth can be the subject of research to develop a few mechatronic systems. Such models are offered by bees, ants, crows, cranes, etc. Article aims to investigate these models and their manifestations. Imitating this behavior and studied him offer ideas for develop models that can be integrated into mechatronic systems. They can be integrated into mechatronic system as algorithms for finding local optimum, to search, to detect an optimal way travel on a network, to find best decision, etc.

  17. [Systems biology is a bridge of integrated traditional Chinese and Western medicine].

    PubMed

    Chen, Hai-Bin; Cheng, Hai-Bo; Lu, Wei; Zhou, Hong-Guang; Wu, Mian-Hua

    2013-01-01

    The integration of Chinese medicine (CM) and Western medicine (WM) is the only way for the development of medicine, and it is the best form for unifying systems theory and reductionism. In this paper, systems biology and its application in medical research were discussed. The authors put forward that systems biology may possibly interpret the scientific connotation of the complex theoretic systems of CM, which will make WM to well know the human body and disease. We hold that systems biology is a bridge of integrated CM and WM.

  18. System integration and development for biological warfare agent surveillance

    NASA Astrophysics Data System (ADS)

    Mark, Jacob A.; Green, Lance D.; Deshpande, Alina; White, P. Scott

    2007-04-01

    A wide variety of technical needs exist for surveillance, monitoring, identifying, or detecting pathogens with potential use as biological terrorism or warfare agents. Because the needs vary greatly among diverse applications, tailored systems are needed that meet performance, information, and cost requirements. A systems perspective allows developers to identify chokepoints for each application, and focus R&D investments on the limiting factors. Surveillance and detection systems are comprised of three primary components: information (markers), chemistries (assays), and instrumentation for "readout". Careful consideration of these components within the context of each application will allow for increases in efficiency and performance not generally realized when researchers focus on a single component in isolation. In fact, many application requirements can be met with simple novel combinations of existing technologies, without the need for huge investments in basic research. Here we discuss some of the key parameters for surveillance, detection, and identification of biothreat agents, and provide examples of focused development that addresses key bottlenecks, and greatly improve system performance.

  19. Integrated Passive Biological Treatment System/ Mine Waste Technology Program Report #16

    EPA Science Inventory

    This report summarizes the results of the Mine Waste Technology Program (MWTP) Activity III, Project 16, Integrated, Passive Biological Treatment System, funded by the United States Environmental Protection Agency (EPA) and jointly administered by EPA and the United States Depar...

  20. 'Systems biology' in human exercise physiology: is it something different from integrative physiology?

    PubMed

    Greenhaff, Paul L; Hargreaves, Mark

    2011-03-01

    On first impression the 'whole-istic approach to understanding biology' that has been used to describe Systems Biology bears a striking resemblance to what many of us know as Integrative Physiology. However, closer scrutiny reveals that at the present time Systems Biology is rooted in processes operating at a cellular level ('the study of an organism, viewed as an integrated and interacting network of genes, proteins and biochemical reactions which give rise to life ultimately responsible for an organism's form and functions'; http://www.systemsbiology.org), and appears to have evolved as a direct result of advances in high throughput molecular biology platforms (and associated bioinformatics) over the past decade. The Systems Biology approach is in many ways laudable, but it will be immediately apparent to most exercise or integrative physiologists that the challenge of understanding the whole-animal response to exercise as a network of integrated and interacting genes, proteins and biochemical reactions is unlikely to be realized in the near future. This short review will attempt to clarify conceptual inconsistencies between the fields of Systems Biology and Integrative Physiology in the context of exercise science, and will attempt to identify the challenges to whole-body physiologists wishing to harness the tools of Systems Biology.

  1. Health as intra-systemic integrity: rethinking the foundations of systems biology and nanomedicine.

    PubMed

    Khushf, George

    2008-01-01

    In current research on systems biology and nanomedicine, we often find an ideal of a new science-based preventive medicine. I consider how disease, cause, explanation, diagnosis, and treatment are understood within this ideal, with special attention to the role of nanoscience and technology in elucidating the "circuit diagram" of a healthy system. I argue that the developmental systems theory that informed George Engel's biopsychosocial model addresses some deficiencies in the current systems ideal, but it needs to be integrated with an ethical analysis that is more attentive to the socioeconomic, cultural, and institutional factors that condition how we understand and manage disease. We also need a richer account of top-down causal paths if we are to appropriately understand diseases as disruptions of inter- and intra-systemic integrity.

  2. IntegromeDB: an integrated system and biological search engine

    PubMed Central

    2012-01-01

    Background With the growth of biological data in volume and heterogeneity, web search engines become key tools for researchers. However, general-purpose search engines are not specialized for the search of biological data. Description Here, we present an approach at developing a biological web search engine based on the Semantic Web technologies and demonstrate its implementation for retrieving gene- and protein-centered knowledge. The engine is available at http://www.integromedb.org. Conclusions The IntegromeDB search engine allows scanning data on gene regulation, gene expression, protein-protein interactions, pathways, metagenomics, mutations, diseases, and other gene- and protein-related data that are automatically retrieved from publicly available databases and web pages using biological ontologies. To perfect the resource design and usability, we welcome and encourage community feedback. PMID:22260095

  3. Circular causality in integrative multi-scale systems biology and its interaction with traditional medicine.

    PubMed

    Tasaki, Kazuyo Maria

    2013-04-01

    This paper discusses the concept of circular causality in "biological relativity" (Noble, Interface Focus. 2, 56-64, 2012) in the context of integrative and multi-scale systems approaches to biology. It also discusses the relationship between systems biology and traditional medicine (sometimes called scholarly medical traditions) mainly from East Asia and India. Systems biology helps illuminate circular processes identified in traditional medicine, while the systems concept of attractors in complex systems will also be important in analysing dynamic balance in the body processes that traditional medicine is concerned with. Ways of nudging disordered processes towards good attractors through the use of traditional medicines can lead to the development of new ways not only of curing disease but also of its prevention. Examples are given of cost-effective multi-component remedies that use integrative ideas derived from traditional medicine.

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

    PubMed

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

    2013-07-01

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

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

    PubMed Central

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

    2013-01-01

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

  6. Toward integration of systems biology formalism: the gene regulatory networks case.

    PubMed

    Gentilini, Raffaella

    2005-01-01

    We consider the problem of integrating different systems biology formalisms, namely, the process calculi based formalism, the modeling approach based on systems of differential equations, and the one relying on automata-like descriptions (and model checking). Specifically, we define automatic procedures for translating stochastic pi-calculus descriptions of gene regulatory networks to S-systems differential equations. Tools for extracting and reasoning on (approximate) solutions of S-systems have been recently developed in the literature, and can be exploited to establish a link with automata-based systems biology and model checking techniques.

  7. Making United States Integrated Ocean Observing System (U.S. IOOS) inclusive of marine biological resources

    USGS Publications Warehouse

    Moustahfid, H.; Potemra, J.; Goldstein, P.; Mendelssohn, R.; Desrochers, A.

    2011-01-01

    An important Data Management and Communication (DMAC) goal is to enable a multi-disciplinary view of the ocean environment by facilitating discovery and integration of data from various sources, projects and scientific domains. United States Integrated Ocean Observing System (U.S. IOOS) DMAC functional requirements are based upon guidelines for standardized data access services, data formats, metadata, controlled vocabularies, and other conventions. So far, the data integration effort has focused on geophysical U.S. IOOS core variables such as temperature, salinity, ocean currents, etc. The IOOS Biological Observations Project is addressing the DMAC requirements that pertain to biological observations standards and interoperability applicable to U.S. IOOS and to various observing systems. Biological observations are highly heterogeneous and the variety of formats, logical structures, and sampling methods create significant challenges. Here we describe an informatics framework for biological observing data (e.g. species presence/absence and abundance data) that will expand information content and reconcile standards for the representation and integration of these biological observations for users to maximize the value of these observing data. We further propose that the approach described can be applied to other datasets generated in scientific observing surveys and will provide a vehicle for wider dissemination of biological observing data. We propose to employ data definition conventions that are well understood in U.S. IOOS and to combine these with ratified terminologies, policies and guidelines. ?? 2011 MTS.

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

    NASA Astrophysics Data System (ADS)

    Wu, Ligang

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

  9. Systems biology and the integration of mechanistic explanation and mathematical explanation.

    PubMed

    Brigandt, Ingo

    2013-12-01

    The paper discusses how systems biology is working toward complex accounts that integrate explanation in terms of mechanisms and explanation by mathematical models-which some philosophers have viewed as rival models of explanation. Systems biology is an integrative approach, and it strongly relies on mathematical modeling. Philosophical accounts of mechanisms capture integrative in the sense of multilevel and multifield explanations, yet accounts of mechanistic explanation (as the analysis of a whole in terms of its structural parts and their qualitative interactions) have failed to address how a mathematical model could contribute to such explanations. I discuss how mathematical equations can be explanatorily relevant. Several cases from systems biology are discussed to illustrate the interplay between mechanistic research and mathematical modeling, and I point to questions about qualitative phenomena (rather than the explanation of quantitative details), where quantitative models are still indispensable to the explanation. Systems biology shows that a broader philosophical conception of mechanisms is needed, which takes into account functional-dynamical aspects, interaction in complex networks with feedback loops, system-wide functional properties such as distributed functionality and robustness, and a mechanism's ability to respond to perturbations (beyond its actual operation). I offer general conclusions for philosophical accounts of explanation.

  10. The role of bacillus-based biological control agents in integrated pest management systems: plant diseases.

    PubMed

    Jacobsen, B J; Zidack, N K; Larson, B J

    2004-11-01

    ABSTRACT Bacillus-based biological control agents (BCAs) have great potential in integrated pest management (IPM) systems; however, relatively little work has been published on integration with other IPM management tools. Unfortunately, most research has focused on BCAs as alternatives to synthetic chemical fungicides or bactericides and not as part of an integrated management system. IPM has had many definitions and this review will use the national coalition for IPM definition: "A sustainable approach to managing pests by combining biological, cultural, physical and chemical tools in a way that minimizes economic, health and environmental risks." This review will examine the integrated use of Bacillus-based BCAs with disease management tools, including resistant cultivars, fungicides or bactericides, or other BCAs. This integration is important because the consistency and degree of disease control by Bacillus-based BCAs is rarely equal to the control afforded by the best fungicides or bactericides. In theory, integration of several tools brings stability to disease management programs. Integration of BCAs with other disease management tools often provides broader crop adaptation and both more efficacious and consistent levels of disease control. This review will also discuss the use of Bacillus-based BCAs in fungicide resistance management. Work with Bacillus thuringiensis and insect pest management is the exception to the relative paucity of reports but will not be the focus of this review.

  11. Bioinformatics for transporter pharmacogenomics and systems biology: data integration and modeling with UML.

    PubMed

    Yan, Qing

    2010-01-01

    Bioinformatics is the rational study at an abstract level that can influence the way we understand biomedical facts and the way we apply the biomedical knowledge. Bioinformatics is facing challenges in helping with finding the relationships between genetic structures and functions, analyzing genotype-phenotype associations, and understanding gene-environment interactions at the systems level. One of the most important issues in bioinformatics is data integration. The data integration methods introduced here can be used to organize and integrate both public and in-house data. With the volume of data and the high complexity, computational decision support is essential for integrative transporter studies in pharmacogenomics, nutrigenomics, epigenetics, and systems biology. For the development of such a decision support system, object-oriented (OO) models can be constructed using the Unified Modeling Language (UML). A methodology is developed to build biomedical models at different system levels and construct corresponding UML diagrams, including use case diagrams, class diagrams, and sequence diagrams. By OO modeling using UML, the problems of transporter pharmacogenomics and systems biology can be approached from different angles with a more complete view, which may greatly enhance the efforts in effective drug discovery and development. Bioinformatics resources of membrane transporters and general bioinformatics databases and tools that are frequently used in transporter studies are also collected here. An informatics decision support system based on the models presented here is available at http://www.pharmtao.com/transporter . The methodology developed here can also be used for other biomedical fields.

  12. Data Integration for Dynamic and Sustainable Systems Biology Resources: Challenges and Lessons Learned

    PubMed Central

    Gabbard, Joseph L.; Shukla, Maulik; Sobral, Bruno

    2010-01-01

    Systems biology and infectious disease (host-pathogen-environment) research and development is becoming increasingly dependent on integrating data from diverse and dynamic sources. Maintaining integrated resources over long periods of time presents distinct challenges. This paper describes experiences and lessons learned from integrating data in two five-year projects focused on pathosystems biology: the Pathosystems Resource Integration Center (PATRIC, http://patric.vbi.vt.edu/), with a goal of developing bioinformatics resources for the research and countermeasures development communities based on genomics data, and the Resource Center for Biodefense Proteomics Research (RCBPR, http://www.proteomicsresource.org/), with a goal of developing resources based on the experiment data such as microarray and proteomics data from diverse sources and technologies. Some challenges include integrating genomic sequence and experiment data, data synchronization, data quality control, and usability engineering. We present examples of a variety of data integration problems drawn from our experiences with PATRIC and RBPRC, as well as open research questions related to long term sustainability, and describe the next steps to meeting these challenges. Novel contributions of this work include (1) an approach for addressing discrepancies between experiment results and interpreted results and (2) expanding the range of data integration techniques to include usability engineering at the presentation level. PMID:20491070

  13. Root Systems Biology: Integrative Modeling across Scales, from Gene Regulatory Networks to the Rhizosphere1

    PubMed Central

    Hill, Kristine; Porco, Silvana; Lobet, Guillaume; Zappala, Susan; Mooney, Sacha; Draye, Xavier; Bennett, Malcolm J.

    2013-01-01

    Genetic and genomic approaches in model organisms have advanced our understanding of root biology over the last decade. Recently, however, systems biology and modeling have emerged as important approaches, as our understanding of root regulatory pathways has become more complex and interpreting pathway outputs has become less intuitive. To relate root genotype to phenotype, we must move beyond the examination of interactions at the genetic network scale and employ multiscale modeling approaches to predict emergent properties at the tissue, organ, organism, and rhizosphere scales. Understanding the underlying biological mechanisms and the complex interplay between systems at these different scales requires an integrative approach. Here, we describe examples of such approaches and discuss the merits of developing models to span multiple scales, from network to population levels, and to address dynamic interactions between plants and their environment. PMID:24143806

  14. Integrated chemical and biological systems in nanowire structures towards nano-scale sensors

    NASA Astrophysics Data System (ADS)

    Hernandez, Rose M.

    Nanowires composed of metal and conducting polymers with integrated proteins and chemical systems have been investigated as building blocks for next-generation nano-scale sensors and assemblies. These nanowires were fabricated by combining chemical and electrochemical methods of synthesis of gold and conducting polymers in nanopores of anodized alumina membranes. Polymer nanowires were synthesized from buffer solutions as a mean to promote a biocompatible environment for the incorporation of proteins. A variety of proteins were incorporated into the polymer matrix by entrapment during polymerization that imparted the polymer material with biological functionality. Another class of composite nanowires containing electro-active conducting polymer junctions was developed for applications in chemical sensor arrays. The methodologies described in this thesis provide an inexpensive and straightforward approach to the synthesis of anisotropic nanoparticles incorporating a variety of biological and inorganic species that can be integrated to current microelectronic technologies for the development of nano-scale sensor arrays.

  15. Integrated Bio-Entity Network: A System for Biological Knowledge Discovery

    PubMed Central

    Bell, Lindsey; Chowdhary, Rajesh; Liu, Jun S.; Niu, Xufeng; Zhang, Jinfeng

    2011-01-01

    A significant part of our biological knowledge is centered on relationships between biological entities (bio-entities) such as proteins, genes, small molecules, pathways, gene ontology (GO) terms and diseases. Accumulated at an increasing speed, the information on bio-entity relationships is archived in different forms at scattered places. Most of such information is buried in scientific literature as unstructured text. Organizing heterogeneous information in a structured form not only facilitates study of biological systems using integrative approaches, but also allows discovery of new knowledge in an automatic and systematic way. In this study, we performed a large scale integration of bio-entity relationship information from both databases containing manually annotated, structured information and automatic information extraction of unstructured text in scientific literature. The relationship information we integrated in this study includes protein–protein interactions, protein/gene regulations, protein–small molecule interactions, protein–GO relationships, protein–pathway relationships, and pathway–disease relationships. The relationship information is organized in a graph data structure, named integrated bio-entity network (IBN), where the vertices are the bio-entities and edges represent their relationships. Under this framework, graph theoretic algorithms can be designed to perform various knowledge discovery tasks. We designed breadth-first search with pruning (BFSP) and most probable path (MPP) algorithms to automatically generate hypotheses—the indirect relationships with high probabilities in the network. We show that IBN can be used to generate plausible hypotheses, which not only help to better understand the complex interactions in biological systems, but also provide guidance for experimental designs. PMID:21738677

  16. Integrated biological-behavioural surveillance in pandemic-threat warning systems.

    PubMed

    Miller, Maureen; Hagan, Emily

    2017-01-01

    Economically and politically disruptive disease outbreaks are a hallmark of the 21st century. Although pandemics are driven by human behaviours, current surveillance systems for identifying pandemic threats are largely reliant on the monitoring of disease outcomes in clinical settings. Standardized integrated biological-behavioural surveillance could, and should, be used in community settings to complement such clinical monitoring. The usefulness of such an approach has already been demonstrated in studies on human immunodeficiency virus, where integrated surveillance contributed to a biologically based and quantifiable understanding of the behavioural risk factors associated with the transmission dynamics of the virus. When designed according to Strengthening the Reporting of Observational Studies in Epidemiology criteria, integrated surveillance requires that both behavioural risk factors - i.e. exposure variables - and disease-indicator outcome variables be measured in behavioural surveys. In the field of pandemic threats, biological outcome data could address the weaknesses of self-reported data collected in behavioural surveys. Data from serosurveys of viruses with pandemic potential, collected under non-outbreak conditions, indicate that serosurveillance could be used to predict future outbreaks. When conducted together, behavioural surveys and serosurveys could warn of future pandemics, potentially before the disease appears in clinical settings. Traditional disease-outcome surveillance must be frequent and ongoing to remain useful but behavioural surveillance remains informative even if conducted much less often, since behaviour change occurs slowly over time. Only through knowledge of specific behavioural risk factors can interventions and policies that can prevent the next pandemic be developed.

  17. Integration of transcriptomic and proteomic analysis towards understanding the systems biology of root hairs.

    PubMed

    Wang, Han; Lan, Ping; Shen, Ren Fang

    2016-03-01

    Plants and other multicellular organisms consist of many types of specialized cells. Systems-wide exploration of large-scale information from singe cell level is essential to understand how cell works. Root hairs, tubular-shaped outgrowths from root epidermal cells, play important roles in the acquisition of nutrients and water, in the interaction with microbe, and in plant anchorage, and represent an ideal model to study the biology of a single cell type. Single cell sampling combined with omics approaches has been applied to study plant root hairs. This review emphasizes the integration of omics approaches towards understanding the systems biology of root hairs, unraveling the common and plant species-specific properties of root hairs, as well as the concordance of protein and transcript abundance. Understanding plant root hair biology by mining the integrated omics data will provide a way to know how a single cell differentiates, elongates, and functions, which might help molecularly modify crops for developing sustainable agriculture practices.

  18. Anti-infectious drug repurposing using an integrated chemical genomics and structural systems biology approach.

    PubMed

    Ng, Clara; Hauptman, Ruth; Zhang, Yinliang; Bourne, Philip E; Xie, Lei

    2014-01-01

    The emergence of multi-drug and extensive drug resistance of microbes to antibiotics poses a great threat to human health. Although drug repurposing is a promising solution for accelerating the drug development process, its application to anti-infectious drug discovery is limited by the scope of existing phenotype-, ligand-, or target-based methods. In this paper we introduce a new computational strategy to determine the genome-wide molecular targets of bioactive compounds in both human and bacterial genomes. Our method is based on the use of a novel algorithm, ligand Enrichment of Network Topological Similarity (ligENTS), to map the chemical universe to its global pharmacological space. ligENTS outperforms the state-of-the-art algorithms in identifying novel drug-target relationships. Furthermore, we integrate ligENTS with our structural systems biology platform to identify drug repurposing opportunities via target similarity profiling. Using this integrated strategy, we have identified novel P. falciparum targets of drug-like active compounds from the Malaria Box, and suggest that a number of approved drugs may be active against malaria. This study demonstrates the potential of an integrative chemical genomics and structural systems biology approach to drug repurposing.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  20. A Neural Systems-Based Neurobiology and Neuropsychiatry Course: Integrating Biology, Psychodynamics, and Psychology in the Psychiatric Curriculum

    ERIC Educational Resources Information Center

    Lacy, Timothy; Hughes, John D.

    2006-01-01

    Objective: Psychotherapy and biological psychiatry remain divided in psychiatry residency curricula. Behavioral neurobiology and neuropsychiatry provide a systems-level framework that allows teachers to integrate biology, psychodynamics, and psychology. Method: The authors detail the underlying assumptions and outline of a neural systems-based…

  1. Hybrid integrated biological-solid-state system powered with adenosine triphosphate

    NASA Astrophysics Data System (ADS)

    Roseman, Jared M.; Lin, Jianxun; Ramakrishnan, Siddharth; Rosenstein, Jacob K.; Shepard, Kenneth L.

    2015-12-01

    There is enormous potential in combining the capabilities of the biological and the solid state to create hybrid engineered systems. While there have been recent efforts to harness power from naturally occurring potentials in living systems in plants and animals to power complementary metal-oxide-semiconductor integrated circuits, here we report the first successful effort to isolate the energetics of an electrogenic ion pump in an engineered in vitro environment to power such an artificial system. An integrated circuit is powered by adenosine triphosphate through the action of Na+/K+ adenosine triphosphatases in an integrated in vitro lipid bilayer membrane. The ion pumps (active in the membrane at numbers exceeding 2 × 106 mm-2) are able to sustain a short-circuit current of 32.6 pA mm-2 and an open-circuit voltage of 78 mV, providing for a maximum power transfer of 1.27 pW mm-2 from a single bilayer. Two series-stacked bilayers provide a voltage sufficient to operate an integrated circuit with a conversion efficiency of chemical to electrical energy of 14.9%.

  2. Meteorological Integration for the Biological Warning and Incident Characterization (BWIC) System: General Guidance for BWIC Cities

    SciTech Connect

    Shaw, William J.; Wang, Weiguo; Rutz, Frederick C.; Chapman, Elaine G.; Rishel, Jeremy P.; Xie, YuLong; Seiple, Timothy E.; Allwine, K Jerry

    2007-02-16

    The U.S. Department of Homeland Security (DHS) is responsible for developing systems to detect the release of aerosolized bioagents in urban environments. The system that accomplishes this, known as BioWatch, is a robust first-generation monitoring system. In conjunction with the BioWatch detection network, DHS has also developed a software tool for cities to use to assist in their response when a bioagent is detected. This tool, the Biological Warning and Incident Characterization (BWIC) System, will eventually be deployed to all BioWatch cities to aid in the interpretation of the public health significance of indicators from the BioWatch networks. BWIC consists of a set of integrated modules, including meteorological models, that estimate the effect of a biological agent on a city’s population once it has been detected. For the meteorological models in BWIC to successfully calculate the distribution of biological material, they must have as input accurate meteorological data, and wind fields in particular. The purpose of this document is to provide guidance for cities to use in identifying sources of good-quality local meteorological data that BWIC needs to function properly. This process of finding sources of local meteorological data, evaluating the data quality and gaps in coverage, and getting the data into BWIC, referred to as meteorological integration, is described. The good news for many cities is that meteorological measurement networks are becoming increasingly common. Most of these networks allow their data to be distributed in real time via the internet. Thus, cities will often only need to evaluate the quality of available measurements and perhaps add a modest number of stations where coverage is poor.

  3. Data integration and systems biology approaches for biomarker discovery: challenges and opportunities for multiple sclerosis.

    PubMed

    Villoslada, Pablo; Baranzini, Sergio

    2012-07-15

    New "omic" technologies and their application to systems biology approaches offer new opportunities for biomarker discovery in complex disorders, including multiple sclerosis (MS). Recent studies using massive genotyping, DNA arrays, antibody arrays, proteomics, glycomics, and metabolomics from different tissues (blood, cerebrospinal fluid, brain) have identified many molecules associated with MS, defining both susceptibility and functional targets (e.g., biomarkers). Such discoveries involve many different levels in the complex organizational hierarchy of humans (DNA, RNA, protein, etc.), and integrating these datasets into a coherent model with regard to MS pathogenesis would be a significant step forward. Given the dynamic and heterogeneous nature of MS, validating biomarkers is mandatory. To develop accurate markers of disease prognosis or therapeutic response that are clinically useful, combining molecular, clinical, and imaging data is necessary. Such an integrative approach would pave the way towards better patient care and more effective clinical trials that test new therapies, thus bringing the paradigm of personalized medicine in MS one step closer.

  4. Economic value of biological control in integrated pest management of managed plant systems.

    PubMed

    Naranjo, Steven E; Ellsworth, Peter C; Frisvold, George B

    2015-01-07

    Biological control is an underlying pillar of integrated pest management, yet little focus has been placed on assigning economic value to this key ecosystem service. Setting biological control on a firm economic foundation would help to broaden its utility and adoption for sustainable crop protection. Here we discuss approaches and methods available for valuation of biological control of arthropod pests by arthropod natural enemies and summarize economic evaluations in classical, augmentative, and conservation biological control. Emphasis is placed on valuation of conservation biological control, which has received little attention. We identify some of the challenges of and opportunities for applying economics to biological control to advance integrated pest management. Interaction among diverse scientists and stakeholders will be required to measure the direct and indirect costs and benefits of biological control that will allow farmers and others to internalize the benefits that incentivize and accelerate adoption for private and public good.

  5. Computational Systems Chemical Biology

    PubMed Central

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

    2013-01-01

    There is a critical need for improving the level of chemistry awareness in systems biology. The data and information related to modulation of genes and proteins by small molecules continue to accumulate at the same time as simulation tools in systems biology and whole body physiologically-based pharmacokinetics (PBPK) continue to evolve. We called this emerging area at the interface between chemical biology and systems biology systems chemical biology, SCB (Oprea et al., 2007). The overarching goal of computational SCB is to develop tools for integrated chemical-biological data acquisition, filtering and processing, by taking into account relevant information related to interactions between proteins and small molecules, possible metabolic transformations of small molecules, as well as associated information related to genes, networks, small molecules and, where applicable, mutants and variants of those proteins. There is yet an unmet need to develop an integrated in silico pharmacology / systems biology continuum that embeds drug-target-clinical outcome (DTCO) triplets, a capability that is vital to the future of chemical biology, pharmacology and systems biology. Through the development of the SCB approach, scientists will be able to start addressing, in an integrated simulation environment, questions that make the best use of our ever-growing chemical and biological data repositories at the system-wide level. This chapter reviews some of the major research concepts and describes key components that constitute the emerging area of computational systems chemical biology. PMID:20838980

  6. 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.

  7. Scale relativity theory and integrative systems biology: 1. Founding principles and scale laws.

    PubMed

    Auffray, Charles; Nottale, Laurent

    2008-05-01

    In these two companion papers, we provide an overview and a brief history of the multiple roots, current developments and recent advances of integrative systems biology and identify multiscale integration as its grand challenge. Then we introduce the fundamental principles and the successive steps that have been followed in the construction of the scale relativity theory, and discuss how scale laws of increasing complexity can be used to model and understand the behaviour of complex biological systems. In scale relativity theory, the geometry of space is considered to be continuous but non-differentiable, therefore fractal (i.e., explicitly scale-dependent). One writes the equations of motion in such a space as geodesics equations, under the constraint of the principle of relativity of all scales in nature. To this purpose, covariant derivatives are constructed that implement the various effects of the non-differentiable and fractal geometry. In this first review paper, the scale laws that describe the new dependence on resolutions of physical quantities are obtained as solutions of differential equations acting in the scale space. This leads to several possible levels of description for these laws, from the simplest scale invariant laws to generalized laws with variable fractal dimensions. Initial applications of these laws to the study of species evolution, embryogenesis and cell confinement are discussed.

  8. Scale relativity theory and integrative systems biology: 2. Macroscopic quantum-type mechanics.

    PubMed

    Nottale, Laurent; Auffray, Charles

    2008-05-01

    In these two companion papers, we provide an overview and a brief history of the multiple roots, current developments and recent advances of integrative systems biology and identify multiscale integration as its grand challenge. Then we introduce the fundamental principles and the successive steps that have been followed in the construction of the scale relativity theory, which aims at describing the effects of a non-differentiable and fractal (i.e., explicitly scale dependent) geometry of space-time. The first paper of this series was devoted, in this new framework, to the construction from first principles of scale laws of increasing complexity, and to the discussion of some tentative applications of these laws to biological systems. In this second review and perspective paper, we describe the effects induced by the internal fractal structures of trajectories on motion in standard space. Their main consequence is the transformation of classical dynamics into a generalized, quantum-like self-organized dynamics. A Schrödinger-type equation is derived as an integral of the geodesic equation in a fractal space. We then indicate how gauge fields can be constructed from a geometric re-interpretation of gauge transformations as scale transformations in fractal space-time. Finally, we introduce a new tentative development of the theory, in which quantum laws would hold also in scale space, introducing complexergy as a measure of organizational complexity. Initial possible applications of this extended framework to the processes of morphogenesis and the emergence of prokaryotic and eukaryotic cellular structures are discussed. Having founded elements of the evolutionary, developmental, biochemical and cellular theories on the first principles of scale relativity theory, we introduce proposals for the construction of an integrative theory of life and for the design and implementation of novel macroscopic quantum-type experiments and devices, and discuss their potential

  9. Economic value of biological control in integrated pest management of managed plant systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Biological control is an underlying pillar of integrated pest management, yet little focus has been placed on assigning economic value to this key ecosystem service. Setting biological control on a firm economic foundation would help to broaden its utility and adoption for sustainable crop protectio...

  10. Modeling systems-level dynamics: Understanding without mechanistic explanation in integrative systems biology.

    PubMed

    MacLeod, Miles; Nersessian, Nancy J

    2015-02-01

    In this paper we draw upon rich ethnographic data of two systems biology labs to explore the roles of explanation and understanding in large-scale systems modeling. We illustrate practices that depart from the goal of dynamic mechanistic explanation for the sake of more limited modeling goals. These processes use abstract mathematical formulations of bio-molecular interactions and data fitting techniques which we call top-down abstraction to trade away accurate mechanistic accounts of large-scale systems for specific information about aspects of those systems. We characterize these practices as pragmatic responses to the constraints many modelers of large-scale systems face, which in turn generate more limited pragmatic non-mechanistic forms of understanding of systems. These forms aim at knowledge of how to predict system responses in order to manipulate and control some aspects of them. We propose that this analysis of understanding provides a way to interpret what many systems biologists are aiming for in practice when they talk about the objective of a "systems-level understanding."

  11. Development of a Knowledgebase to Integrate, Analyze, Distribute, and Visualize Microbial Community Systems Biology Data

    SciTech Connect

    Banfield, Jillian

    2015-01-15

    We have developed a flexible knowledgebase system, ggKbase, (http://gg.berkeley.edu), to enable effective data analysis and knowledge generation from samples from which metagenomic and other ‘omics’ data are obtained. Within ggKbase, data can be interpreted, integrated and linked to other databases and services. Sequence information from complex metagenomic samples can be quickly and effectively resolved into genomes and biologically meaningful investigations of an organism’s metabolic potential can then be conducted. Critical features make analyses efficient, allowing analysis of hundreds of genomes at a time. The system is being used to support research in multiple DOE-relevant systems, including the LBNL SFA subsurface science biogeochemical cycling research at Rifle, Colorado. ggKbase is supporting the research of a rapidly growing group of users. It has enabled studies of carbon cycling in acid mine drainage ecosystems, biologically-mediated transformations in deep subsurface biomes sampled from mines and the north slope of Alaska, to study the human microbiome and for laboratory bioreactor-based remediation investigations.

  12. Development of an integrated system for rapid detection of biological agents

    NASA Astrophysics Data System (ADS)

    Terazono, Hideyuki; Takei, Hiroyuki; Hayashi, Masahito; Hattori, Akihiro; Yasuda, Kenji

    2010-04-01

    Weaponized biological agents are as great a threat as nuclear or chemical weapons. They must be detected at the earliest stage to prevent diffusion because once these agents are dispersed into the air, the rapidly decreasing concentration makes detection more of a challenge. Polymerase chain reaction (PCR) is a common method to create copies of a specific target region of a DNA sequence and to produce large quantities of DNA molecules. A few DNA molecules are rapidly amplified by PCR into billions of copies. While PCR is a powerful technique and is capable of countering new threats relatively easily, it is plagued by the number of processes necessary. Therefore, we have developed an integrated PCR system for rapid detection of biological agents captured from the air. Each processing function is performed by a dedicated module, and reduction in the process time has been made the top priority, without loss in the signal/noise ratio of the total system. Agents can be identified within 15 min from capture. A fully automated operation protects operators from exposure to potentially highly lethal samples.

  13. Integration of Telomere Length Dynamics into Systems Biology Framework: A Review

    PubMed Central

    Nersisyan, Lilit

    2016-01-01

    Telomere length dynamics plays a crucial role in regulation of cellular processes and cell fate. In contrast to epidemiological studies revealing the association of telomere length with age, age-related diseases, and cancers, the role of telomeres in regulation of transcriptome and epigenome and the role of genomic variations in telomere lengthening are not extensively analyzed. This is explained by the fact that experimental assays for telomere length measurement are resource consuming, and there are very few studies where high-throughput genomics, transcriptomics, and/or epigenomics experiments have been coupled with telomere length measurements. Recent development of computational approaches for assessment of telomere length from whole genome sequencing data pave a new perspective on integration of telomeres into high-throughput systems biology analysis framework. Herein, we review existing methodologies for telomere length measurement and compare them to computational approaches, as well as discuss their applications in large-scale studies on telomere length dynamics. PMID:27346946

  14. WebGestalt: an integrated system for exploring gene sets in various biological contexts

    PubMed Central

    Zhang, Bing; Kirov, Stefan; Snoddy, Jay

    2005-01-01

    High-throughput technologies have led to the rapid generation of large-scale datasets about genes and gene products. These technologies have also shifted our research focus from ‘single genes’ to ‘gene sets’. We have developed a web-based integrated data mining system, WebGestalt (), to help biologists in exploring large sets of genes. WebGestalt is composed of four modules: gene set management, information retrieval, organization/visualization, and statistics. The management module uploads, saves, retrieves and deletes gene sets, as well as performs Boolean operations to generate the unions, intersections or differences between different gene sets. The information retrieval module currently retrieves information for up to 20 attributes for all genes in a gene set. The organization/visualization module organizes and visualizes gene sets in various biological contexts, including Gene Ontology, tissue expression pattern, chromosome distribution, metabolic and signaling pathways, protein domain information and publications. The statistics module recommends and performs statistical tests to suggest biological areas that are important to a gene set and warrant further investigation. In order to demonstrate the use of WebGestalt, we have generated 48 gene sets with genes over-represented in various human tissue types. Exploration of all the 48 gene sets using WebGestalt is available for the public at . PMID:15980575

  15. WebGestalt: an integrated system for exploring gene sets in various biological contexts.

    PubMed

    Zhang, Bing; Kirov, Stefan; Snoddy, Jay

    2005-07-01

    High-throughput technologies have led to the rapid generation of large-scale datasets about genes and gene products. These technologies have also shifted our research focus from 'single genes' to 'gene sets'. We have developed a web-based integrated data mining system, WebGestalt (http://genereg.ornl.gov/webgestalt/), to help biologists in exploring large sets of genes. WebGestalt is composed of four modules: gene set management, information retrieval, organization/visualization, and statistics. The management module uploads, saves, retrieves and deletes gene sets, as well as performs Boolean operations to generate the unions, intersections or differences between different gene sets. The information retrieval module currently retrieves information for up to 20 attributes for all genes in a gene set. The organization/visualization module organizes and visualizes gene sets in various biological contexts, including Gene Ontology, tissue expression pattern, chromosome distribution, metabolic and signaling pathways, protein domain information and publications. The statistics module recommends and performs statistical tests to suggest biological areas that are important to a gene set and warrant further investigation. In order to demonstrate the use of WebGestalt, we have generated 48 gene sets with genes over-represented in various human tissue types. Exploration of all the 48 gene sets using WebGestalt is available for the public at http://genereg.ornl.gov/webgestalt/wg_enrich.php.

  16. Integrative biology of exercise.

    PubMed

    Hawley, John A; Hargreaves, Mark; Joyner, Michael J; Zierath, Juleen R

    2014-11-06

    Exercise represents a major challenge to whole-body homeostasis provoking widespread perturbations in numerous cells, tissues, and organs that are caused by or are a response to the increased metabolic activity of contracting skeletal muscles. To meet this challenge, multiple integrated and often redundant responses operate to blunt the homeostatic threats generated by exercise-induced increases in muscle energy and oxygen demand. The application of molecular techniques to exercise biology has provided greater understanding of the multiplicity and complexity of cellular networks involved in exercise responses, and recent discoveries offer perspectives on the mechanisms by which muscle "communicates" with other organs and mediates the beneficial effects of exercise on health and performance.

  17. Effective integration of systems biology, biomarkers, biosimulation and modelling in streamlining drug development.

    PubMed

    Krishna, Rajesh; Schaefer, Hans Guenter; Bjerrum, Ole J

    2007-05-01

    The European Federation of Pharmaceutical Sciences (EUFEPS) has long established itself as leaders in the field of interdisciplinary meetings to discuss issues that face drug development. It's ever popular and well attended "Optimizing Drug Development" series has tackled numerous issues, most recent of which have been drug interactions, getting the dose right, candidate selection, and biomarkers (Lesko et al., 2000; Rolan et al., 2003; Stanski et al., 2005; Tucker et al., 2001). Over a course of 3 productive days, the meeting on "Effective Integration of Systems Biology, Biomarkers, Biosimulation and Modelling in Streamlining Drug Development", held in Basel, Switzerland was jointly sponsored by EUFEPS, European Biosimulation Network of Excellence (BioSim), American College of Clinical Pharmacology (ACCP), European Centre of Pharmaceutical Medicine (ECPM), and Swiss Society of Pharmaceutical Sciences (SGRW). The meeting was focused on emerging aspects related to the quantitative understanding of underlying pathways in drug discovery and clinical development, i.e. moving from an empirical to a model-based, quantitative drug development process. The objectives of the meeting were: (1) to highlight the current state of the art on biomarkers (as they relate to quantitative fingerprinting of disease), systems biology, modelling and simulation; (2) to illustrate the applications of these emerging tools in increasing the efficiency and productivity of new drug development by case examples; (3) to understand the gaps in the technology and organizational implementations in governance, and (4) allow an opportunity for cross-disciplinary interaction, i.e., scientists with more theoretical and technical modelling and simulation expertise of the BioSim network and researchers experienced in applying modelling and simulation techniques in day-to-day drug development were drawn together. This report summarizes the outcome from this meeting.

  18. Integrating microRNAs into a system biology approach to acute lung injury.

    PubMed

    Zhou, Tong; Garcia, Joe G N; Zhang, Wei

    2011-04-01

    Acute lung injury (ALI), including the ventilator-induced lung injury (VILI) and the more severe acute respiratory distress syndrome (ARDS), are common and complex inflammatory lung diseases potentially affected by various genetic and nongenetic factors. Using the candidate gene approach, genetic variants associated with immune response and inflammatory pathways have been identified and implicated in ALI. Because gene expression is an intermediate phenotype that resides between the DNA sequence variation and the higher level cellular or whole-body phenotypes, the illustration of gene expression regulatory networks potentially could enhance understanding of disease susceptibility and the development of inflammatory lung syndromes. MicroRNAs (miRNAs) have emerged as a novel class of gene regulators that play critical roles in complex diseases including ALI. Comparisons of global miRNA profiles in animal models of ALI and VILI identified several miRNAs (eg, miR-146a and miR-155) previously implicated in immune response and inflammatory pathways. Therefore, via regulation of target genes in these biological processes and pathways, miRNAs potentially contribute to the development of ALI. Although this line of inquiry exists at a nascent stage, miRNAs have the potential to be critical components of a comprehensive model for inflammatory lung disease built by a systems biology approach that integrates genetic, genomic, proteomic, epigenetic as well as environmental stimuli information. Given their particularly recognized role in regulation of immune and inflammatory responses, miRNAs also serve as novel therapeutic targets and biomarkers for ALI/ARDS or VILI, thus facilitating the realization of personalized medicine for individuals with acute inflammatory lung disease.

  19. Development of Two Color Fluorescent Imager and Integrated Fluidic System for Nanosatellite Biology Applications

    NASA Technical Reports Server (NTRS)

    Wu, Diana Terri; Ricco, Antonio Joseph; Lera, Matthew P.; Timucin, Linda R.; Parra, Macarena P.

    2012-01-01

    Nanosatellites offer frequent, low-cost space access as secondary payloads on launches of larger conventional satellites. We summarize the payload science and technology of the Microsatellite in-situ Space Technologies (MisST) nanosatellite for conducting automated biological experiments. The payload (two fused 10-cm cubes) includes 1) an integrated fluidics system that maintains organism viability and supports growth and 2) a fixed-focus imager with fluorescence and scattered-light imaging capabilities. The payload monitors temperature, pressure and relative humidity, and actively controls temperature. C. elegans (nematode, 50 m diameter x 1 mm long) was selected as a model organism due to previous space science experience, its completely sequenced genome, size, hardiness, and the variety of strains available. Three strains were chosen: two green GFP-tagged strains and one red tdTomato-tagged strain that label intestinal, nerve, and pharyngeal cells, respectively. The integrated fluidics system includes bioanalytical and reservoir modules. The former consists of four 150 L culture wells and a 4x5 mm imaging zone the latter includes two 8 mL fluid reservoirs for reagent and waste storage. The fluidic system is fabricated using multilayer polymer rapid prototyping: laser cutting, precision machining, die cutting, and pressure-sensitive adhesives it also includes eight solenoid-operated valves and one mini peristaltic pump. Young larval-state (L2) nematodes are loaded in C. elegans Maintenance Media (CeMM) in the bioanalytical module during pre-launch assembly. By the time orbit is established, the worms have grown to sufficient density to be imaged and are fed fresh CeMM. The strains are pumped sequentially into the imaging area, imaged, then pumped into waste. Reagent storage utilizes polymer bags under slight pressure to prevent bubble formation in wells or channels. The optical system images green and red fluorescence bands by excitation with blue (473 nm peak

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

    PubMed Central

    Zamir, Eli

    2016-01-01

    ABSTRACT The complexity of cell-matrix adhesion convolves its roles in the development and functioning of multicellular organisms and their evolutionary tinkering. Cell-matrix adhesion is mediated by sites along the plasma membrane that anchor the actin cytoskeleton to the matrix via a large number of proteins, collectively called the integrin adhesome. Fundamental challenges for understanding how cell-matrix adhesion sites assemble and function arise from their multi-functionality, rapid dynamics, large number of components and molecular diversity. Systems biology faces these challenges in its strive to understand how the integrin adhesome gives rise to functional adhesion sites. Synthetic biology enables engineering intracellular modules and circuits with properties of interest. In this review I discuss some of the fundamental questions in systems biology of cell-matrix adhesion and how synthetic biology can help addressing them. PMID:26853318

  1. Integrated Biological Control

    SciTech Connect

    JOHNSON, A.R.

    2003-10-09

    Biological control is any activity taken to prevent, limit, clean up, or remediate potential environmental, health and safety, or workplace quality impacts from plants, animals, or microorganisms. At Hanford the principal emphasis of biological control is to prevent the transport of radioactive contamination by biological vectors (plants, animals, or microorganisms), and where necessary, control and clean up resulting contamination. Other aspects of biological control at Hanford include industrial weed control (e.g.; tumbleweeds), noxious weed control (invasive, non-native plant species), and pest control (undesirable animals such as rodents and stinging insects, and microorganisms such as molds that adversely affect the quality of the workplace environment). Biological control activities may be either preventive (a priori) or in response to existing contamination spread (a posteriori). Surveillance activities, including ground, vegetation, flying insect, and other surveys, and a priori control actions, such as herbicide spraying and placing biological barriers, are important in preventing radioactive contamination spread. If surveillance discovers that biological vectors have spread radioactive contamination, a posteriori control measures, such as fixing contamination, followed by cleanup and removal of the contamination to an approved disposal location are typical response functions. In some cases remediation following the contamination cleanup and removal is necessary. Biological control activities for industrial weeds, noxious weeds and pests have similar modes of prevention and response.

  2. Integrated Biological Control

    SciTech Connect

    JOHNSON, A.R.

    2002-09-01

    Biological control is any activity taken to prevent, limit, clean up, or remediate potential environmental, health and safety, or workplace quality impacts from plants, animals, or microorganisms. At Hanford the principal emphasis of biological control is to prevent the transport of radioactive contamination by biological vectors (plants, animals, or microorganisms), and where necessary, control and clean up resulting contamination. Other aspects of biological control at Hanford include industrial weed control (e.g.; tumbleweeds), noxious weed control (invasive, non-native plant species), and pest control (undesirable animals such as rodents and stinging insects; and microorganisms such as molds that adversely affect the quality of the workplace environment). Biological control activities may be either preventive (apriori) or in response to existing contamination spread (aposteriori). Surveillance activities, including ground, vegetation, flying insect, and other surveys, and apriori control actions, such as herbicide spraying and placing biological barriers, are important in preventing radioactive contamination spread. If surveillance discovers that biological vectors have spread radioactive contamination, aposteriori control measures, such as fixing contamination, followed by cleanup and removal of the contamination to an approved disposal location are typical response functions. In some cases remediation following the contamination cleanup and removal is necessary. Biological control activities for industrial weeds, noxious weeds and pests have similar modes of prevention and response.

  3. Integration of Proteomics, Bioinformatics, and Systems Biology in Traumatic Brain Injury Biomarker Discovery

    PubMed Central

    Guingab-Cagmat, J.D.; Cagmat, E.B.; Hayes, R.L.; Anagli, J.

    2013-01-01

    Traumatic brain injury (TBI) is a major medical crisis without any FDA-approved pharmacological therapies that have been demonstrated to improve functional outcomes. It has been argued that discovery of disease-relevant biomarkers might help to guide successful clinical trials for TBI. Major advances in mass spectrometry (MS) have revolutionized the field of proteomic biomarker discovery and facilitated the identification of several candidate markers that are being further evaluated for their efficacy as TBI biomarkers. However, several hurdles have to be overcome even during the discovery phase which is only the first step in the long process of biomarker development. The high-throughput nature of MS-based proteomic experiments generates a massive amount of mass spectral data presenting great challenges in downstream interpretation. Currently, different bioinformatics platforms are available for functional analysis and data mining of MS-generated proteomic data. These tools provide a way to convert data sets to biologically interpretable results and functional outcomes. A strategy that has promise in advancing biomarker development involves the triad of proteomics, bioinformatics, and systems biology. In this review, a brief overview of how bioinformatics and systems biology tools analyze, transform, and interpret complex MS datasets into biologically relevant results is discussed. In addition, challenges and limitations of proteomics, bioinformatics, and systems biology in TBI biomarker discovery are presented. A brief survey of researches that utilized these three overlapping disciplines in TBI biomarker discovery is also presented. Finally, examples of TBI biomarkers and their applications are discussed. PMID:23750150

  4. 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."

  5. How to integrate biological research into society and exclude errors in biomedical publications? Progress in theoretical and systems biology releases pressure on experimental research.

    PubMed

    Volkov, Vadim

    2014-01-01

    This brief opinion proposes measures to increase efficiency and exclude errors in biomedical research under the existing dynamic situation. Rapid changes in biology began with the description of the three dimensional structure of DNA 60 years ago; today biology has progressed by interacting with computer science and nanoscience together with the introduction of robotic stations for the acquisition of large-scale arrays of data. These changes have had an increasing influence on the entire research and scientific community. Future advance demands short-term measures to ensure error-proof and efficient development. They can include the fast publishing of negative results, publishing detailed methodical papers and excluding a strict connection between career progression and publication activity, especially for younger researchers. Further development of theoretical and systems biology together with the use of multiple experimental methods for biological experiments could also be helpful in the context of years and decades. With regards to the links between science and society, it is reasonable to compare both these systems, to find and describe specific features for biology and to integrate it into the existing stream of social life and financial fluxes. It will increase the level of scientific research and have mutual positive effects for both biology and society. Several examples are given for further discussion.

  6. An Integrative Computational Framework for Hypotheses-Driven Systems Biology Research in Proteomics and Genomics

    SciTech Connect

    Cannon, William R.; Webb-Robertson, Bobbie-Jo M.; Willse, Alan R.; Singhal, Mudita; McCue, Lee Ann; McDermott, Jason E.; Taylor, Ronald C.; Waters, Katrina M.; Oehmen, Christopher S.

    2009-04-01

    Systems biology research is sometimes categorized as either discovery science or hypothesis-driven science. However, we believe that hypotheses are always used regardless, and that explicit recognition that hypothesis testing underlies all high-throughput data analysis leads to better experimental designs, data analysis and interpretation of the data. We outline the current use of hypothesis testing for proteomics data analysis in systems biology research for several projects at the Pacific Northwest National Laboratory, and provide examples of where scientific principles can be used to formulate the hypotheses used to analyze the data. We additionally discuss the data infrastructure is required to (1) track the data from different projects and diverse assays, (2) pull the data together in a congruent manner, (3) analyze the data with respect to cellular networks, and (4) visualize the resulting networks and contrast those with information from bioinformatics databases.

  7. Teaching systems biology.

    PubMed

    Alves, R; Vilaprinyo, E; Sorribas, A

    2011-03-01

    Advances in systems biology are increasingly dependent upon the integration of various types of data and different methodologies to reconstruct how cells work at the systemic level. Thus, teams with a varied array of expertise and people with interdisciplinary training are needed. So far this training was thought to be more productive if aimed at the Masters or PhD level. At this level, multiple specialised and in-depth courses on the different subject matters of systems biology are taught to already well-prepared students. This approach is mostly based on the recognition that systems biology requires a wide background that is hard to find in undergraduate students. Nevertheless, and given the importance of the field, the authors argue that exposition of undergraduate students to the methods and paradigms of systems biology would be advantageous. Here they present and discuss a successful experiment in teaching systems biology to third year undergraduate biotechnology students at the University of Lleida in Spain. The authors' experience, together with that from others, argues for the adequateness of teaching systems biology at the undergraduate level. [Includes supplementary material].

  8. Integrative Biology of Diabetic Kidney Disease

    PubMed Central

    Harder, Jennifer L.; Hodgin, Jeffrey B.; Kretzler, Matthias

    2015-01-01

    Background The leading cause of end-stage renal disease in the US is diabetic kidney disease (DKD). Despite significant efforts to improve outcomes in DKD, the impact on disease progression has been disappointing. This has prompted clinicians and researchers to search for alternative approaches to identify persons at risk, and to search for more effective therapies to halt progression of DKD. The identification of novel therapies is critically dependent on a more comprehensive understanding of the pathophysiology of DKD, specifically at the molecular level. A more expansive and exploratory view of DKD is needed to complement more traditional research approaches that have focused on single molecules. Summary In recent years, sophisticated research methodologies have emerged within systems biology that should allow for a more comprehensive disease definition of DKD. Systems biology provides an interdisciplinary approach to describe complex interactions within biological systems, including how these interactions influence systems' functions and behaviors. Computational modeling of large, system-wide, quantitative data sets is used to generate molecular interaction pathways, such as metabolic and cell signaling networks. Key Messages Importantly, the interpretation of data generated by systems biology tools requires integration with enhanced clinical research data and validation using model systems. Such an integrative biological approach has already generated novel insights into pathways and molecules involved in DKD. In this review, we highlight recent examples of how combining systems biology with traditional clinical and model research efforts results in an integrative biology approach that significantly adds to the understanding of the complex pathophysiology of DKD. PMID:26929927

  9. A Systems Approach to Integrative Biology: An Overview of Statistical Methods to Elucidate Association and Architecture

    PubMed Central

    Ciaccio, Mark F.; Finkle, Justin D.; Xue, Albert Y.; Bagheri, Neda

    2014-01-01

    An organism’s ability to maintain a desired physiological response relies extensively on how cellular and molecular signaling networks interpret and react to environmental cues. The capacity to quantitatively predict how networks respond to a changing environment by modifying signaling regulation and phenotypic responses will help inform and predict the impact of a changing global enivronment on organisms and ecosystems. Many computational strategies have been developed to resolve cue–signal–response networks. However, selecting a strategy that answers a specific biological question requires knowledge both of the type of data being collected, and of the strengths and weaknesses of different computational regimes. We broadly explore several computational approaches, and we evaluate their accuracy in predicting a given response. Specifically, we describe how statistical algorithms can be used in the context of integrative and comparative biology to elucidate the genomic, proteomic, and/or cellular networks responsible for robust physiological response. As a case study, we apply this strategy to a dataset of quantitative levels of protein abundance from the mussel, Mytilus galloprovincialis, to uncover the temperature-dependent signaling network. PMID:24813462

  10. Scaling and systems biology for integrating multiple organs-on-a-chip.

    PubMed

    Wikswo, John P; Curtis, Erica L; Eagleton, Zachary E; Evans, Brian C; Kole, Ayeeshik; Hofmeister, Lucas H; Matloff, William J

    2013-09-21

    Coupled systems of in vitro microfabricated organs-on-a-chip containing small populations of human cells are being developed to address the formidable pharmacological and physiological gaps between monolayer cell cultures, animal models, and humans that severely limit the speed and efficiency of drug development. These gaps present challenges not only in tissue and microfluidic engineering, but also in systems biology: how does one model, test, and learn about the communication and control of biological systems with individual organs-on-chips that are one-thousandth or one-millionth of the size of adult organs, or even smaller, i.e., organs for a milliHuman (mHu) or microHuman (μHu)? Allometric scaling that describes inter-species variation of organ size and properties provides some guidance, but given the desire to utilize these systems to extend and validate human pharmacokinetic and pharmacodynamic (PK/PD) models in support of drug discovery and development, it is more appropriate to scale each organ functionally to ensure that it makes the suitable physiological contribution to the coupled system. The desire to recapitulate the complex organ-organ interactions that result from factors in the blood and lymph places a severe constraint on the total circulating fluid (~5 mL for a mHu and ~5 μL for a μHu) and hence on the pumps, valves, and analytical instruments required to maintain and study these systems. Scaling arguments also provide guidance on the design of a universal cell-culture medium, typically without red blood cells. This review presents several examples of scaling arguments and discusses steps that should ensure the success of this endeavour.

  11. Scaling and systems biology for integrating multiple organs-on-a-chip†

    PubMed Central

    Wikswo, John P.; Curtis, Erica L.; Eagleton, Zachary E.; Evans, Brian C.; Kole, Ayeeshik; Hofmeister, Lucas H.; Matloff, William J.

    2013-01-01

    Coupled systems of in vitro microfabricated organs-on-a-chip containing small populations of human cells are being developed to address the formidable pharmacological and physiological gaps between monolayer cell cultures, animal models, and humans that severely limit the speed and efficiency of drug development. These gaps present challenges not only in tissue and microfluidic engineering, but also in systems biology: how does one model, test, and learn about the communication and control of biological systems with individual organs-on-chips that are one-thousandth or one-millionth of the size of adult organs, or even smaller, i.e., organs for a milliHuman (mHu) or microHuman (μHu)? Allometric scaling that describes inter-species variation of organ size and properties provides some guidance, but given the desire to utilize these systems to extend and validate human pharmacokinetic and pharmacodynamic (PK/PD) models in support of drug discovery and development, it is more appropriate to scale each organ functionally to ensure that it makes the suitable physiological contribution to the coupled system. The desire to recapitulate the complex organorgan interactions that result from factors in the blood and lymph places a severe constraint on the total circulating fluid (~5 mL for a mHu and ~5 μL for a μHu) and hence on the pumps, valves, and analytical instruments required to maintain and study these systems. Scaling arguments also provide guidance on the design of a universal cell-culture medium, typically without red blood cells. This review presents several examples of scaling arguments and discusses steps that should ensure the success of this endeavour. PMID:23828456

  12. Semantic Web meets Integrative Biology: a survey.

    PubMed

    Chen, Huajun; Yu, Tong; Chen, Jake Y

    2013-01-01

    Integrative Biology (IB) uses experimental or computational quantitative technologies to characterize biological systems at the molecular, cellular, tissue and population levels. IB typically involves the integration of the data, knowledge and capabilities across disciplinary boundaries in order to solve complex problems. We identify a series of bioinformatics problems posed by interdisciplinary integration: (i) data integration that interconnects structured data across related biomedical domains; (ii) ontology integration that brings jargons, terminologies and taxonomies from various disciplines into a unified network of ontologies; (iii) knowledge integration that integrates disparate knowledge elements from multiple sources; (iv) service integration that build applications out of services provided by different vendors. We argue that IB can benefit significantly from the integration solutions enabled by Semantic Web (SW) technologies. The SW enables scientists to share content beyond the boundaries of applications and websites, resulting into a web of data that is meaningful and understandable to any computers. In this review, we provide insight into how SW technologies can be used to build open, standardized and interoperable solutions for interdisciplinary integration on a global basis. We present a rich set of case studies in system biology, integrative neuroscience, bio-pharmaceutics and translational medicine, to highlight the technical features and benefits of SW applications in IB.

  13. Knowledge-based fuzzy system for diagnosis and control of an integrated biological wastewater treatment process.

    PubMed

    Pires, O C; Palma, C; Costa, J C; Moita, I; Alves, M M; Ferreira, E C

    2006-01-01

    A supervisory expert system based on fuzzy logic rules was developed for diagnosis and control of a laboratory- scale plant comprising anaerobic digestion and anoxic/aerobic modules for combined high rate biological N and C removal. The design and implementation of a computational environment in LabVIEW for data acquisition, plant operation and distributed equipment control is described. A step increase in ammonia concentration from 20 to 60 mg N/L was applied during a trial period of 73 h. Recycle flow rate from the aerobic to the anoxic module and bypass flow rate from the influent directly to the anoxic reactor were the output variables of the fuzzy system. They were automatically changed (from 34 to 111 L/day and from 8 to 13 L/day, respectively), when new plant conditions were recognised by the expert system. Denitrification efficiency higher than 85% was achieved 30 h after the disturbance and 15 h after the system response at an HRT as low as 1.5 h. Nitrification efficiency gradually increased from 12 to 50% at an HRT of 3 h. The system proved to react properly in order to set adequate operating conditions that led to timely and efficient recovery of N and C removal rates.

  14. Integrated Omics in Systems Biology: The New Frontier for Environmental Biotechnology

    SciTech Connect

    Hazen, Terry C.

    2008-08-12

    Environmental biotechnology encompasses a wide range of characterization, monitoring and control for bioenergy and bioremediation technologies that are based on biological processes. Recent breakthroughs in our understanding of biogeochemical processes and genomics are leading to exciting new and cost effective ways to monitor and manipulate the environment and potentially produce bioenergy fuels as we also cleanup the environment. Indeed, our ability to sequence an entire microbial genome in just a few hours is leading to similar breakthroughs in characterizing proteomes, metabolomes, phenotypes, and fluxes for organisms, populations, and communities. Understanding and modeling functional microbial community structure and stress responses in subsurface environments has tremendous implications for our fundamental understanding of biogeochemistry and the potential for making biofuel breakthroughs. Monitoring techniques that inventory and monitor terminal electron acceptors and electron donors, enzyme probes that measure functional activity in the environment, functional genomic microarrays, phylogenetic microarrays, metabolomics, proteomics, and quantitative PCR are also being rapidly adapted for studies in environmental biotechnology. Integration of all of these new high throughput techniques using the latest advances in bioinformatics and modeling will enable break-through science in environmental biotechnology. A review of these techniques with examples from field studies and lab simulations will be discussed.

  15. Genomics and Integrated Systems Biology in Plasmodium falciparum: A Path to Malaria Control and Eradication

    PubMed Central

    Le Roch, Karine G.; Chung, Duk-Won D.; Ponts, Nadia

    2011-01-01

    The first draft of the human malaria parasite's genome was released in 2002. Since then, the malaria scientific community has witnessed a steady embrace of new and powerful functional genomic studies. Over the years, these approaches have slowly revolutionized malaria research and enabled the comprehensive, unbiased investigation of various aspects of the parasite's biology. These genome-wide analyses delivered a refined annotation of the parasite's genome, a better knowledge of its RNA, proteins, and metabolite derivatives, and fostered the discovery of new vaccine and drug targets. Despite the positive impacts of these genomic studies, most research and investment still focus on protein targets, drugs and vaccine candidates that were known before the publication of the parasite genome sequence. However, recent access to next-generation sequencing technologies, along with an increased number of genome-wide applications are expanding the impact of the parasite genome on biomedical research, contributing to a paradigm shift in research activities that may possibly lead to new optimized diagnosis and treatments. This review provides an update of Plasmodium falciparum genome sequences and an overview of the rapid development of genomics and system biology applications that have an immense potential of creating powerful tools for a successful malaria eradication campaign. PMID:21995286

  16. Complete Atomistic Model of a Bacterial Cytoplasm for Integrating Physics, Biochemistry, and Systems Biology

    PubMed Central

    Feig, Michael; Harada, Ryuhei; Mori, Takaharu; Yu, Isseki; Takahashi, Koichi; Sugita, Yuji

    2015-01-01

    A model for the cytoplasm of Mycoplasma genitalium is presented that integrates data from a variety of sources into a physically and biochemically consistent model. Based on gene annotations, core genes expected to be present in the cytoplasm were determined and a metabolic reaction network was reconstructed. The set of cytoplasmic genes and metabolites from the predicted reactions were assembled into a comprehensive atomistic model consisting of proteins with predicted structures, RNA, protein/RNA complexes, metabolites, ions, and solvent. The resulting model bridges between atomistic and cellular scales, between physical and biochemical aspects, and between structural and systems views of cellular systems and is meant as a starting point for a variety of simulation studies. PMID:25765281

  17. Computational Systems Biology

    SciTech Connect

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

    2009-05-01

    mRNA) and metabolomics. With such tools, research to consider systems as a whole are being conceived, planned and implemented experimentally on an ever more frequent and wider scale. The other is the growth of computational processing power and tools. Methods to analyze large data sets of this kind are often computationally demanding and, as is the case in other areas, the field has benefited from continuing improvements in computational hardware and methods. The field of computational biology is very much like a telescope with two sequential lenses: one lens represents the biological data and the other represents a computational and/or mathematical model of the data. Both lenses must be properly coordinated to yield an image that reflects biological reality. This means that the design parameters for both lenses must be designed in concert to create a system that yields a model of the organism that provides both predictive and mechanistic information. The chapters in this book describe the construction of subcomponents of such a system. Computational systems biology is a rapidly evolving field and no single group of investigators has yet developed a compete system that integrates both data generation and data analysis in such a way so as to allow full and accurate modeling of any single biological organism. However, the field is rapidly moving in that direction. The chapters in this book represent a snapshot of the current methods being developed and used in the area of computational systems biology. Each method or database described within represents one or more steps on the path to a complete description of a biological system. How these tools will evolve and ultimately be integrated is an area of intense research and interest. We hope that readers of this book will be motivated by the chapters within and become involved in this exciting area of research.

  18. toxoMine: an integrated omics data warehouse for Toxoplasma gondii systems biology research

    PubMed Central

    Rhee, David B.; Croken, Matthew McKnight; Shieh, Kevin R.; Sullivan, Julie; Micklem, Gos; Kim, Kami; Golden, Aaron

    2015-01-01

    Toxoplasma gondii (T. gondii) is an obligate intracellular parasite that must monitor for changes in the host environment and respond accordingly; however, it is still not fully known which genetic or epigenetic factors are involved in regulating virulence traits of T. gondii. There are on-going efforts to elucidate the mechanisms regulating the stage transition process via the application of high-throughput epigenomics, genomics and proteomics techniques. Given the range of experimental conditions and the typical yield from such high-throughput techniques, a new challenge arises: how to effectively collect, organize and disseminate the generated data for subsequent data analysis. Here, we describe toxoMine, which provides a powerful interface to support sophisticated integrative exploration of high-throughput experimental data and metadata, providing researchers with a more tractable means toward understanding how genetic and/or epigenetic factors play a coordinated role in determining pathogenicity of T. gondii. As a data warehouse, toxoMine allows integration of high-throughput data sets with public T. gondii data. toxoMine is also able to execute complex queries involving multiple data sets with straightforward user interaction. Furthermore, toxoMine allows users to define their own parameters during the search process that gives users near-limitless search and query capabilities. The interoperability feature also allows users to query and examine data available in other InterMine systems, which would effectively augment the search scope beyond what is available to toxoMine. toxoMine complements the major community database ToxoDB by providing a data warehouse that enables more extensive integrative studies for T. gondii. Given all these factors, we believe it will become an indispensable resource to the greater infectious disease research community. Database URL: http://toxomine.org PMID:26130662

  19. toxoMine: an integrated omics data warehouse for Toxoplasma gondii systems biology research.

    PubMed

    Rhee, David B; Croken, Matthew McKnight; Shieh, Kevin R; Sullivan, Julie; Micklem, Gos; Kim, Kami; Golden, Aaron

    2015-01-01

    Toxoplasma gondii (T. gondii) is an obligate intracellular parasite that must monitor for changes in the host environment and respond accordingly; however, it is still not fully known which genetic or epigenetic factors are involved in regulating virulence traits of T. gondii. There are on-going efforts to elucidate the mechanisms regulating the stage transition process via the application of high-throughput epigenomics, genomics and proteomics techniques. Given the range of experimental conditions and the typical yield from such high-throughput techniques, a new challenge arises: how to effectively collect, organize and disseminate the generated data for subsequent data analysis. Here, we describe toxoMine, which provides a powerful interface to support sophisticated integrative exploration of high-throughput experimental data and metadata, providing researchers with a more tractable means toward understanding how genetic and/or epigenetic factors play a coordinated role in determining pathogenicity of T. gondii. As a data warehouse, toxoMine allows integration of high-throughput data sets with public T. gondii data. toxoMine is also able to execute complex queries involving multiple data sets with straightforward user interaction. Furthermore, toxoMine allows users to define their own parameters during the search process that gives users near-limitless search and query capabilities. The interoperability feature also allows users to query and examine data available in other InterMine systems, which would effectively augment the search scope beyond what is available to toxoMine. toxoMine complements the major community database ToxoDB by providing a data warehouse that enables more extensive integrative studies for T. gondii. Given all these factors, we believe it will become an indispensable resource to the greater infectious disease research community.

  20. Linking childhood allergic asthma phenotypes with endotype through integrated systems biology: current evidence and research needs.

    PubMed

    Choi, Hyunok; Song, Won-Min; Zhang, Bin

    2017-03-01

    Asthma and other complex diseases results from a complex web of interactions involving inflammation, immunity, cell cycle, apoptosis, and metabolic perturbations across multiple organ systems. The extent to which various degrees of the age at onset, symptom severity, and the natural progression of the disease reflect multiple disease subtypes, influenced by unique process of development remains unknown. One of the most critical challenges to our understanding stems from incomplete understanding of the mechanisms. Within this review, we focus on the phenotypes of childhood allergic asthma as the basis to better understand the endotype for quantitative define subtypes of asthma. We highlight some of the known mechanistic pathways associated with the key hallmark events before the asthma onset. In particular, we examine how the recent advent of multiaxial -omics technologies and systems biology could help to clarify our current understanding of the pathway. We review how a large volume of molecular, genomic data generated by multiaxial technologies could be digested to identify cogent pathophysiologic molecular networks. We highlight some recent successes in application of these technologies within the context of other disease conditions for therapeutic interventions. We conclude by summarizing the research needs for the predictive value of preclinical biomarkers.

  1. 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

  2. Systems interface biology.

    PubMed

    Doyle, Francis J; Stelling, Jörg

    2006-10-22

    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.

  3. An integrated high-throughput data acquisition system for biological solution X-ray scattering studies.

    PubMed

    Martel, Anne; Liu, Ping; Weiss, Thomas M; Niebuhr, Marc; Tsuruta, Hiro

    2012-05-01

    A fully automated high-throughput solution X-ray scattering data collection system has been developed for protein structure studies at beamline 4-2 of the Stanford Synchrotron Radiation Lightsource. It is composed of a thin-wall quartz capillary cell, a syringe needle assembly on an XYZ positioning arm for sample delivery, a water-cooled sample rack and a computer-controlled fluid dispenser. It is controlled by a specifically developed software component built into the standard beamline control program Blu-Ice/DCS. The integrated system is intuitive and very simple to use, and enables experimenters to customize data collection strategy in a timely fashion in concert with an automated data processing program. The system also allows spectrophotometric determination of protein concentration for each sample aliquot in the beam via an in situ UV absorption spectrometer. A single set of solution scattering measurements requires a 20-30 µl sample aliquot and takes typically 3.5 min, including an extensive capillary cleaning cycle. Over 98.5% of measurements are valid and free from artefacts commonly caused by air-bubble contamination. The sample changer, which is compact and light, facilitates effortless switching with other sample-handling devices required for other types of non-crystalline X-ray scattering experiments.

  4. Finding Clarity by Fostering Confusion: Reflections on Teaching an Undergraduate Integrated Biological Systems Course

    ERIC Educational Resources Information Center

    Martin, Kirsten H.

    2015-01-01

    Undergraduate biology programs in smaller liberal arts colleges are increasingly becoming focused on health science fields. This narrowing of focus potentially decreases opportunities for these students to explore other sub-fields of biology. This perspectives article highlights how one small university in Connecticut decided to institute a…

  5. An inexpensive, temporally-integrated system for monitoring occurrence and biological effects of aquatic contaminants in the field

    EPA Science Inventory

    Assessment of potential ecological risks of complex contaminant mixtures in the environment requires integrated chemical and biological approaches. Instrumental analysis of environmental samples alone can identify contaminants, but provides only limited insights as to possible a...

  6. New opportunities for the integration of microorganisms into biological pest control systems in greenhouse crops.

    PubMed

    Gonzalez, Francisco; Tkaczuk, Cezary; Dinu, Mihaela Monica; Fiedler, Żaneta; Vidal, Stefan; Zchori-Fein, Einat; Messelink, Gerben J

    Biological pest control with mass-produced arthropod natural enemies is well developed in greenhouse crops and has often resulted in the evolution of complex ecosystems with persistent populations of multiple arthropod natural enemy species. However, there are cases where arthropod natural enemies are either not effective enough, not available, or their use is rather costly. For these reasons, biological control based on microorganisms, also referred to as 'microbials', represents a complementary strategy for further development. Although commercially available microbials have been around for quite some time, research on and the applied use of combinations of arthropod natural enemies and microbials have remained relatively under explored. Here, we review current uses of entomopathogenic fungi, bacteria and viruses, and their possible direct and indirect effects on arthropod natural enemies in European greenhouses. We discuss how microbials might be combined with arthropod natural enemies in the light of new methodologies and technologies such as conservation biological control, greenhouse climate management, and formulation and delivery. Furthermore, we explore the possibilities of using other microorganisms for biological control, such as endophytes, and the need to understand the effect of insect-associated microorganisms, or symbionts, on the success of biological control. Finally, we suggest future research directions to optimize the combined use of microbials and arthropod natural enemies in greenhouse production.

  7. Gene Selection Integrated with Biological Knowledge for Plant Stress Response Using Neighborhood System and Rough Set Theory.

    PubMed

    Meng, Jun; Zhang, Jing; Luan, Yushi

    2015-01-01

    Mining knowledge from gene expression data is a hot research topic and direction of bioinformatics. Gene selection and sample classification are significant research trends, due to the large amount of genes and small size of samples in gene expression data. Rough set theory has been successfully applied to gene selection, as it can select attributes without redundancy. To improve the interpretability of the selected genes, some researchers introduced biological knowledge. In this paper, we first employ neighborhood system to deal directly with the new information table formed by integrating gene expression data with biological knowledge, which can simultaneously present the information in multiple perspectives and do not weaken the information of individual gene for selection and classification. Then, we give a novel framework for gene selection and propose a significant gene selection method based on this framework by employing reduction algorithm in rough set theory. The proposed method is applied to the analysis of plant stress response. Experimental results on three data sets show that the proposed method is effective, as it can select significant gene subsets without redundancy and achieve high classification accuracy. Biological analysis for the results shows that the interpretability is well.

  8. Evaluation of microbial reduction of Fe(III)EDTA in a chemical absorption-biological reduction integrated NOx removal system

    SciTech Connect

    Wei Li; Cheng-Zhi Wu; Shi-Han Zhang; Ke Shao; Yao Shi

    2007-01-15

    A chemical absorption-biological reduction integrated process can be used to remove nitrogen oxides (NOx) from flue gas. In such a process, nitric oxide (NO) can be effectively absorbed by the ferrous chelate of ethylenediaminetetraacetate (Fe(II)EDTA) to form Fe(II)EDTA-NO, which can be biologically regenerated by denitrifying bacteria. However, in the course of these processes, part of the Fe(II)EDTA is also oxidized to Fe(III)EDTA. The reduction of Fe(III)EDTA to Fe(II)EDTA depends on the activity of iron-reducing bacteria in the system. Therefore, the effectiveness of the system relies on how to effectively bioreduce Fe(III)EDTA and Fe(II)EDTA-NO in the system. In this paper, a strain identified as Escherichia coli FR-2 (iron-reducing bacterium) was used to investigate the reduction rate of Fe(III)EDTA. The experimental results indicate that Fe(II)EDTA-NO and Fe(II)EDTA in the system can inhibit both the FR-2 cell growth and thus affect the Fe(III)EDTA reduction. The FR-2 cell growth rate and Fe(III)EDTA reduction rate decreased with increasing Fe(II)EDTA-NO and Fe(II)EDTA concentration in the solution. When the concentration of Fe(II)EDTA-NO reached 3.7 mM, the FR-2 cell growth almost stopped. A mathematical model was developed to explain the cell growth and inhibition kinetics. The predicted results are close to the experimental data and provide a preliminary evaluation of the kinetics of the biologically mediated reactions necessary to regenerate the spent scrubber solution. 33 refs., 7 figs., 2 tabs.

  9. Systems Biology of Embryogenesis

    PubMed Central

    Edelman, Lucas B.; Chandrasekaran, Sriram; Price, Nathan D.

    2010-01-01

    The development of a complete organism from a single cell involves extraordinarily complex orchestration of biological processes that vary intricately across space and time. Systems biology seeks to describe how all elements of a biological system interact in order to understand, model, and ultimately predict aspects of emergent biological processes. Embryogenesis represents an extraordinary opportunity – and challenge – for the application of systems biology. Systems approaches have already been used successfully to study various aspects of development, from complex intracellular networks to 4D models of organogenesis. Going forward, great advancements and discoveries can be expected from systems approaches applied to embryogenesis and developmental biology. PMID:20003850

  10. Integrative Biological Analysis For Neuropsychopharmacology

    PubMed Central

    Emmett, Mark R; Kroes, Roger A; Moskal, Joseph R; Conrad, Charles A; Priebe, Waldemar; Laezza, Fernanda; Meyer-Baese, Anke; Nilsson, Carol L

    2014-01-01

    Although advances in psychotherapy have been made in recent years, drug discovery for brain diseases such as schizophrenia and mood disorders has stagnated. The need for new biomarkers and validated therapeutic targets in the field of neuropsychopharmacology is widely unmet. The brain is the most complex part of human anatomy from the standpoint of number and types of cells, their interconnections, and circuitry. To better meet patient needs, improved methods to approach brain studies by understanding functional networks that interact with the genome are being developed. The integrated biological approaches—proteomics, transcriptomics, metabolomics, and glycomics—have a strong record in several areas of biomedicine, including neurochemistry and neuro-oncology. Published applications of an integrated approach to projects of neurological, psychiatric, and pharmacological natures are still few but show promise to provide deep biological knowledge derived from cells, animal models, and clinical materials. Future studes that yield insights based on integrated analyses promise to deliver new therapeutic targets and biomarkers for personalized medicine. PMID:23800968

  11. Integration of in silico methods and computational systems biology to explore endocrine-disrupting chemical binding with nuclear hormone receptors.

    PubMed

    Ruiz, P; Sack, A; Wampole, M; Bobst, S; Vracko, M

    2017-07-01

    Thousands of potential endocrine-disrupting chemicals present difficult regulatory challenges. Endocrine-disrupting chemicals can interfere with several nuclear hormone receptors associated with a variety of adverse health effects. The U.S. Environmental Protection Agency (U.S. EPA) has released its reviews of Tier 1 screening assay results for a set of pesticides in the Endocrine Disruptor Screening Program (EDSP), and recently, the Collaborative Estrogen Receptor Activity Prediction Project (CERAPP) data. In this study, the predictive ability of QSAR and docking approaches is evaluated using these data sets. This study also presents a computational systems biology approach using carbaryl (1-naphthyl methylcarbamate) as a case study. For estrogen receptor and androgen receptor binding predictions, two commercial and two open source QSAR tools were used, as was the publicly available docking tool Endocrine Disruptome. For estrogen receptor binding predictions, the ADMET Predictor, VEGA, and OCHEM models (specificity: 0.88, 0.88, and 0.86, and accuracy: 0.81, 0.84, and 0.88, respectively) were each more reliable than the MetaDrug™ model (specificity 0.81 and accuracy 0.77). For androgen receptor binding predictions, the Endocrine Disruptome and ADMET Predictor models (specificity: 0.94 and 0.8, and accuracy: 0.78 and 0.71, respectively) were more reliable than the MetaDrug™ model (specificity 0.33 and accuracy 0.4). A consensus approach is proposed that reaches general agreement among the models (specificity 0.94 and accuracy 0.89). This study integrates QSAR, docking, and systems biology approaches as a virtual screening tool for use in risk assessment. As such, this systems biology pathways and network analysis approach provides a means to more critically assess the potential effects of endocrine-disrupting chemicals.

  12. 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.

  13. An integrated systems biology approach to understanding the rules of keratinocyte colony formation.

    PubMed

    Sun, Tao; McMinn, Phil; Coakley, Simon; Holcombe, Mike; Smallwood, Rod; Macneil, Sheila

    2007-12-22

    Closely coupled in vitro and in virtuo models have been used to explore the self-organization of normal human keratinocytes (NHK). Although it can be observed experimentally, we lack the tools to explore many biological rules that govern NHK self-organization. An agent-based computational model was developed, based on rules derived from literature, which predicts the dynamic multicellular morphogenesis of NHK and of a keratinocyte cell line (HaCat cells) under varying extracellular Ca++ concentrations. The model enables in virtuo exploration of the relative importance of biological rules and was used to test hypotheses in virtuo which were subsequently examined in vitro. Results indicated that cell-cell and cell-substrate adhesions were critically important to NHK self-organization. In contrast, cell cycle length and the number of divisions that transit-amplifying cells could undergo proved non-critical to the final organization. Two further hypotheses, to explain the growth behaviour of HaCat cells, were explored in virtuo-an inability to differentiate and a differing sensitivity to extracellular calcium. In vitro experimentation provided some support for both hypotheses. For NHKs, the prediction was made that the position of stem cells would influence the pattern of cell migration post-wounding. This was then confirmed experimentally using a scratch wound model.

  14. Engineering challenges of BioNEMS: the integration of microfluidics, micro- and nanodevices, models and external control for systems biology.

    PubMed

    Wikswo, J P; Prokop, A; Baudenbacher, F; Cliffel, D; Csukas, B; Velkovsky, M

    2006-08-01

    Systems biology, i.e. quantitative, postgenomic, postproteomic, dynamic, multiscale physiology, addresses in an integrative, quantitative manner the shockwave of genetic and proteomic information using computer models that may eventually have 10(6) dynamic variables with non-linear interactions. Historically, single biological measurements are made over minutes, suggesting the challenge of specifying 10(6) model parameters. Except for fluorescence and micro-electrode recordings, most cellular measurements have inadequate bandwidth to discern the time course of critical intracellular biochemical events. Micro-array expression profiles of thousands of genes cannot determine quantitative dynamic cellular signalling and metabolic variables. Major gaps must be bridged between the computational vision and experimental reality. The analysis of cellular signalling dynamics and control requires, first, micro- and nano-instruments that measure simultaneously multiple extracellular and intracellular variables with sufficient bandwidth; secondly, the ability to open existing internal control and signalling loops; thirdly, external BioMEMS micro-actuators that provide high bandwidth feedback and externally addressable intracellular nano-actuators; and, fourthly, real-time, closed-loop, single-cell control algorithms. The unravelling of the nested and coupled nature of cellular control loops requires simultaneous recording of multiple single-cell signatures. Externally controlled nano-actuators, needed to effect changes in the biochemical, mechanical and electrical environment both outside and inside the cell, will provide a major impetus for nanoscience.

  15. TOWARD EFFICIENT RIPARIAN RESTORATION: INTEGRATING ECONOMIC, PHYSICAL, AND BIOLOGICAL MODELS

    EPA Science Inventory

    This paper integrates economic, biological, and physical models to determine the efficient combination and spatial allocation of conservation efforts for water quality protection and salmonid habitat enhancement in the Grande Ronde basin, Oregon. The integrated modeling system co...

  16. Atlas of Cancer Signalling Network: a systems biology resource for integrative analysis of cancer data with Google Maps

    PubMed Central

    Kuperstein, I; Bonnet, E; Nguyen, H-A; Cohen, D; Viara, E; Grieco, L; Fourquet, S; Calzone, L; Russo, C; Kondratova, M; Dutreix, M; Barillot, E; Zinovyev, A

    2015-01-01

    Cancerogenesis is driven by mutations leading to aberrant functioning of a complex network of molecular interactions and simultaneously affecting multiple cellular functions. Therefore, the successful application of bioinformatics and systems biology methods for analysis of high-throughput data in cancer research heavily depends on availability of global and detailed reconstructions of signalling networks amenable for computational analysis. We present here the Atlas of Cancer Signalling Network (ACSN), an interactive and comprehensive map of molecular mechanisms implicated in cancer. The resource includes tools for map navigation, visualization and analysis of molecular data in the context of signalling network maps. Constructing and updating ACSN involves careful manual curation of molecular biology literature and participation of experts in the corresponding fields. The cancer-oriented content of ACSN is completely original and covers major mechanisms involved in cancer progression, including DNA repair, cell survival, apoptosis, cell cycle, EMT and cell motility. Cell signalling mechanisms are depicted in detail, together creating a seamless ‘geographic-like' map of molecular interactions frequently deregulated in cancer. The map is browsable using NaviCell web interface using the Google Maps engine and semantic zooming principle. The associated web-blog provides a forum for commenting and curating the ACSN content. ACSN allows uploading heterogeneous omics data from users on top of the maps for visualization and performing functional analyses. We suggest several scenarios for ACSN application in cancer research, particularly for visualizing high-throughput data, starting from small interfering RNA-based screening results or mutation frequencies to innovative ways of exploring transcriptomes and phosphoproteomes. Integration and analysis of these data in the context of ACSN may help interpret their biological significance and formulate mechanistic hypotheses

  17. Systems biology of human atherosclerosis.

    PubMed

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

    2014-01-01

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

  18. Integrated systems biology analysis of KSHV latent infection reveals viral induction and reliance on peroxisome mediated lipid metabolism.

    PubMed

    Sychev, Zoi E; Hu, Alex; DiMaio, Terri A; Gitter, Anthony; Camp, Nathan D; Noble, William S; Wolf-Yadlin, Alejandro; Lagunoff, Michael

    2017-03-01

    Kaposi's Sarcoma associated Herpesvirus (KSHV), an oncogenic, human gamma-herpesvirus, is the etiological agent of Kaposi's Sarcoma the most common tumor of AIDS patients world-wide. KSHV is predominantly latent in the main KS tumor cell, the spindle cell, a cell of endothelial origin. KSHV modulates numerous host cell-signaling pathways to activate endothelial cells including major metabolic pathways involved in lipid metabolism. To identify the underlying cellular mechanisms of KSHV alteration of host signaling and endothelial cell activation, we identified changes in the host proteome, phosphoproteome and transcriptome landscape following KSHV infection of endothelial cells. A Steiner forest algorithm was used to integrate the global data sets and, together with transcriptome based predicted transcription factor activity, cellular networks altered by latent KSHV were predicted. Several interesting pathways were identified, including peroxisome biogenesis. To validate the predictions, we showed that KSHV latent infection increases the number of peroxisomes per cell. Additionally, proteins involved in peroxisomal lipid metabolism of very long chain fatty acids, including ABCD3 and ACOX1, are required for the survival of latently infected cells. In summary, novel cellular pathways altered during herpesvirus latency that could not be predicted by a single systems biology platform, were identified by integrated proteomics and transcriptomics data analysis and when correlated with our metabolomics data revealed that peroxisome lipid metabolism is essential for KSHV latent infection of endothelial cells.

  19. Integrated systems biology analysis of KSHV latent infection reveals viral induction and reliance on peroxisome mediated lipid metabolism

    PubMed Central

    Sychev, Zoi E.; Hu, Alex; Lagunoff, Michael

    2017-01-01

    Kaposi’s Sarcoma associated Herpesvirus (KSHV), an oncogenic, human gamma-herpesvirus, is the etiological agent of Kaposi’s Sarcoma the most common tumor of AIDS patients world-wide. KSHV is predominantly latent in the main KS tumor cell, the spindle cell, a cell of endothelial origin. KSHV modulates numerous host cell-signaling pathways to activate endothelial cells including major metabolic pathways involved in lipid metabolism. To identify the underlying cellular mechanisms of KSHV alteration of host signaling and endothelial cell activation, we identified changes in the host proteome, phosphoproteome and transcriptome landscape following KSHV infection of endothelial cells. A Steiner forest algorithm was used to integrate the global data sets and, together with transcriptome based predicted transcription factor activity, cellular networks altered by latent KSHV were predicted. Several interesting pathways were identified, including peroxisome biogenesis. To validate the predictions, we showed that KSHV latent infection increases the number of peroxisomes per cell. Additionally, proteins involved in peroxisomal lipid metabolism of very long chain fatty acids, including ABCD3 and ACOX1, are required for the survival of latently infected cells. In summary, novel cellular pathways altered during herpesvirus latency that could not be predicted by a single systems biology platform, were identified by integrated proteomics and transcriptomics data analysis and when correlated with our metabolomics data revealed that peroxisome lipid metabolism is essential for KSHV latent infection of endothelial cells. PMID:28257516

  20. Why is effective treatment of asthma so difficult? An integrated systems biology hypothesis of asthma

    PubMed Central

    Voelkel, Norbert F; Spiegel, Sarah

    2010-01-01

    A hypothesis is presented that asthma is not only an airway disease, but that the disease involves the entire lung, and that the chronicity of asthma and asthma exacerbations can perhaps be explained if one considers asthma as a systemic disease. Increased lung—not only airway—vascularity may be the result of the action of angiogenesis factors, such as vascular endothelial growth factor (VEGF) and sphingosine-1-phosphate (S1P). A bone-marrow lung axis can be postulated as one element of the systemic nature of the asthma syndrome, in which the inflamed lung emits chemotactic signals, which the bone marrow responds to by releasing cells that contribute to lung angiogenesis. A molecular model of the pathobiology of asthma can be built by connecting hypoxia-inducible transcription factor-1 alpha, VEGF S1P, and bone-marrow precursor cell mobilization and acknowledging that angiogenesis is part of the inflammatory response. PMID:19546879

  1. 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.

  2. Integrated assessment of biological invasions.

    PubMed

    Ibáñez, Ines; Diez, Jeffrey M; Miller, Luke P; Olden, Julian D; Sorte, Cascade J B; Blumenthal, Dana M; Bradley, Bethany A; D'Antonio, Carla M; Dukes, Jeffrey S; Early, Regan I; Grosholz, Edwin D; Lawler, Joshua J

    2014-01-01

    As the main witnesses of the ecological and economic impacts of invasions on ecosystems around the world, ecologists seek to provide the relevant science that informs managers about the potential for invasion of specific organisms in their region(s) of interest. Yet, the assorted literature that could inform such forecasts is rarely integrated to do so, and further, the diverse nature of the data available complicates synthesis and quantitative prediction. Here we present a set of analytical tools for synthesizing different levels of distributional and/or demographic data to produce meaningful assessments of invasion potential that can guide management at multiple phases of ongoing invasions, from dispersal to colonization to proliferation. We illustrate the utility of data-synthesis and data-model assimilation approaches with case studies of three well-known invasive species--a vine, a marine mussel, and a freshwater crayfish--under current and projected future climatic conditions. Results from the integrated assessments reflect the complexity of the invasion process and show that the most relevant climatic variables can have contrasting effects or operate at different intensities across habitat types. As a consequence, for two of the study species climate trends will increase the likelihood of invasion in some habitats and decrease it in others. Our results identified and quantified both bottlenecks and windows of opportunity for invasion, mainly related to the role of human uses of the landscape or to disruption of the flow of resources. The approach we describe has a high potential to enhance model realism, explanatory insight, and predictive capability, generating information that can inform management decisions and optimize phase-specific prevention and control efforts for a wide range of biological invasions.

  3. Designing integrated computational biology pipelines visually.

    PubMed

    Jamil, Hasan M

    2013-01-01

    The long-term cost of developing and maintaining a computational pipeline that depends upon data integration and sophisticated workflow logic is too high to even contemplate "what if" or ad hoc type queries. In this paper, we introduce a novel application building interface for computational biology research, called VizBuilder, by leveraging a recent query language called BioFlow for life sciences databases. Using VizBuilder, it is now possible to develop ad hoc complex computational biology applications at throw away costs. The underlying query language supports data integration and workflow construction almost transparently and fully automatically, using a best effort approach. Users express their application by drawing it with VizBuilder icons and connecting them in a meaningful way. Completed applications are compiled and translated as BioFlow queries for execution by the data management system LifeDB, for which VizBuilder serves as a front end. We discuss VizBuilder features and functionalities in the context of a real life application after we briefly introduce BioFlow. The architecture and design principles of VizBuilder are also discussed. Finally, we outline future extensions of VizBuilder. To our knowledge, VizBuilder is a unique system that allows visually designing computational biology pipelines involving distributed and heterogeneous resources in an ad hoc manner.

  4. WISB: Warwick Integrative Synthetic Biology Centre

    PubMed Central

    McCarthy, John

    2016-01-01

    Synthetic biology promises to create high-impact solutions to challenges in the areas of biotechnology, human/animal health, the environment, energy, materials and food security. Equally, synthetic biologists create tools and strategies that have the potential to help us answer important fundamental questions in biology. Warwick Integrative Synthetic Biology (WISB) pursues both of these mutually complementary ‘build to apply’ and ‘build to understand’ approaches. This is reflected in our research structure, in which a core theme on predictive biosystems engineering develops underpinning understanding as well as next-generation experimental/theoretical tools, and these are then incorporated into three applied themes in which we engineer biosynthetic pathways, microbial communities and microbial effector systems in plants. WISB takes a comprehensive approach to training, education and outreach. For example, WISB is a partner in the EPSRC/BBSRC-funded U.K. Doctoral Training Centre in synthetic biology, we have developed a new undergraduate module in the subject, and we have established five WISB Research Career Development Fellowships to support young group leaders. Research in Ethical, Legal and Societal Aspects (ELSA) of synthetic biology is embedded in our centre activities. WISB has been highly proactive in building an international research and training network that includes partners in Barcelona, Boston, Copenhagen, Madrid, Marburg, São Paulo, Tartu and Valencia. PMID:27284024

  5. SysBioCube: A Data Warehouse and Integrative Data Analysis Platform Facilitating Systems Biology Studies of Disorders of Military Relevance

    PubMed Central

    Chowbina, Sudhir; Hammamieh, Rasha; Kumar, Raina; Chakraborty, Nabarun; Yang, Ruoting; Mudunuri, Uma; Jett, Marti; Palma, Joseph M.; Stephens, Robert

    2013-01-01

    SysBioCube is an integrated data warehouse and analysis platform for experimental data relating to diseases of military relevance developed for the US Army Medical Research and Materiel Command Systems Biology Enterprise (SBE). It brings together, under a single database environment, pathophysio-, psychological, molecular and biochemical data from mouse models of post-traumatic stress disorder and (pre-) clinical data from human PTSD patients.. SysBioCube will organize, centralize and normalize this data and provide an access portal for subsequent analysis to the SBE. It provides new or expanded browsing, querying and visualization to provide better understanding of the systems biology of PTSD, all brought about through the integrated environment. We employ Oracle database technology to store the data using an integrated hierarchical database schema design. The web interface provides researchers with systematic information and option to interrogate the profiles of pan-omics component across different data types, experimental designs and other covariates. PMID:24303294

  6. SysBioCube: A Data Warehouse and Integrative Data Analysis Platform Facilitating Systems Biology Studies of Disorders of Military Relevance.

    PubMed

    Chowbina, Sudhir; Hammamieh, Rasha; Kumar, Raina; Chakraborty, Nabarun; Yang, Ruoting; Mudunuri, Uma; Jett, Marti; Palma, Joseph M; Stephens, Robert

    2013-01-01

    SysBioCube is an integrated data warehouse and analysis platform for experimental data relating to diseases of military relevance developed for the US Army Medical Research and Materiel Command Systems Biology Enterprise (SBE). It brings together, under a single database environment, pathophysio-, psychological, molecular and biochemical data from mouse models of post-traumatic stress disorder and (pre-) clinical data from human PTSD patients.. SysBioCube will organize, centralize and normalize this data and provide an access portal for subsequent analysis to the SBE. It provides new or expanded browsing, querying and visualization to provide better understanding of the systems biology of PTSD, all brought about through the integrated environment. We employ Oracle database technology to store the data using an integrated hierarchical database schema design. The web interface provides researchers with systematic information and option to interrogate the profiles of pan-omics component across different data types, experimental designs and other covariates.

  7. A linguistic integration of a biological database

    SciTech Connect

    Collado-Vides, J.

    1993-12-31

    One of the major theoretical concerns associated with the Human Genome Project is that of the methodology to decipher ``raw`` sequences of DNA. This work is concerned with a subsequent problem, the one of how huge amounts of already deciphered information that will emerge in the near future can be integrated in order to enhance their biological understanding. The formal foundations for a linguistic theory of the regulation of gene expression will be discussed. The linguistic analysis presented here is restricted to sequences with known biological function since: (1) there is no way to obtain, from DNA sequences alone, a regulatory representation of transcription units, and (2) the elements of substitution -- methodologically equivalent to phonemes -- are complete sequences of the binding sites of proteins. The authors have recently collected and analyzed the regulatory regions of a large number of E. coli promoters. The number of sigma 70 promoters studied may well represent the largest homogeneous body of knowledge of gene regulation at present. This collection is a data set for the construction of a grammar of the sigma 70 system of transcription and regulation. This grammatical model generates all the arrays of the collection, as well as novel combinations predicted to be consistent with the principles of the data set. This Grammar is testable, as well as expandable if the analysis of emerging data requires it. The elaboration of a linguistic methodology capable of integrating prokaryotic data constitutes a preliminary step towards the analysis and integration of the more complex eukaryotic systems of regulation.

  8. Bioregulatory systems medicine: an innovative approach to integrating the science of molecular networks, inflammation, and systems biology with the patient's autoregulatory capacity?

    PubMed Central

    Goldman, Alyssa W.; Burmeister, Yvonne; Cesnulevicius, Konstantin; Herbert, Martha; Kane, Mary; Lescheid, David; McCaffrey, Timothy; Schultz, Myron; Seilheimer, Bernd; Smit, Alta; St. Laurent, Georges; Berman, Brian

    2015-01-01

    Bioregulatory systems medicine (BrSM) is a paradigm that aims to advance current medical practices. The basic scientific and clinical tenets of this approach embrace an interconnected picture of human health, supported largely by recent advances in systems biology and genomics, and focus on the implications of multi-scale interconnectivity for improving therapeutic approaches to disease. This article introduces the formal incorporation of these scientific and clinical elements into a cohesive theoretical model of the BrSM approach. The authors review this integrated body of knowledge and discuss how the emergent conceptual model offers the medical field a new avenue for extending the armamentarium of current treatment and healthcare, with the ultimate goal of improving population health. PMID:26347656

  9. 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’.

  10. Systems Biology of Metabolism.

    PubMed

    Nielsen, Jens

    2017-03-08

    Metabolism is highly complex and involves thousands of different connected reactions; it is therefore necessary to use mathematical models for holistic studies. The use of mathematical models in biology is referred to as systems biology. In this review, the principles of systems biology are described, and two different types of mathematical models used for studying metabolism are discussed: kinetic models and genome-scale metabolic models. The use of different omics technologies, including transcriptomics, proteomics, metabolomics, and fluxomics, for studying metabolism is presented. Finally, the application of systems biology for analyzing global regulatory structures, engineering the metabolism of cell factories, and analyzing human diseases is discussed. Expected final online publication date for the Annual Review of Biochemistry Volume 86 is June 20, 2017. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  11. 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.

  12. ePlant and the 3D Data Display Initiative: Integrative Systems Biology on the World Wide Web

    PubMed Central

    Fucile, Geoffrey; Di Biase, David; Nahal, Hardeep; La, Garon; Khodabandeh, Shokoufeh; Chen, Yani; Easley, Kante; Christendat, Dinesh; Kelley, Lawrence; Provart, Nicholas J.

    2011-01-01

    Visualization tools for biological data are often limited in their ability to interactively integrate data at multiple scales. These computational tools are also typically limited by two-dimensional displays and programmatic implementations that require separate configurations for each of the user's computing devices and recompilation for functional expansion. Towards overcoming these limitations we have developed “ePlant” (http://bar.utoronto.ca/eplant) – a suite of open-source world wide web-based tools for the visualization of large-scale data sets from the model organism Arabidopsis thaliana. These tools display data spanning multiple biological scales on interactive three-dimensional models. Currently, ePlant consists of the following modules: a sequence conservation explorer that includes homology relationships and single nucleotide polymorphism data, a protein structure model explorer, a molecular interaction network explorer, a gene product subcellular localization explorer, and a gene expression pattern explorer. The ePlant's protein structure explorer module represents experimentally determined and theoretical structures covering >70% of the Arabidopsis proteome. The ePlant framework is accessed entirely through a web browser, and is therefore platform-independent. It can be applied to any model organism. To facilitate the development of three-dimensional displays of biological data on the world wide web we have established the “3D Data Display Initiative” (http://3ddi.org). PMID:21249219

  13. ePlant and the 3D data display initiative: integrative systems biology on the world wide web.

    PubMed

    Fucile, Geoffrey; Di Biase, David; Nahal, Hardeep; La, Garon; Khodabandeh, Shokoufeh; Chen, Yani; Easley, Kante; Christendat, Dinesh; Kelley, Lawrence; Provart, Nicholas J

    2011-01-10

    Visualization tools for biological data are often limited in their ability to interactively integrate data at multiple scales. These computational tools are also typically limited by two-dimensional displays and programmatic implementations that require separate configurations for each of the user's computing devices and recompilation for functional expansion. Towards overcoming these limitations we have developed "ePlant" (http://bar.utoronto.ca/eplant) - a suite of open-source world wide web-based tools for the visualization of large-scale data sets from the model organism Arabidopsis thaliana. These tools display data spanning multiple biological scales on interactive three-dimensional models. Currently, ePlant consists of the following modules: a sequence conservation explorer that includes homology relationships and single nucleotide polymorphism data, a protein structure model explorer, a molecular interaction network explorer, a gene product subcellular localization explorer, and a gene expression pattern explorer. The ePlant's protein structure explorer module represents experimentally determined and theoretical structures covering >70% of the Arabidopsis proteome. The ePlant framework is accessed entirely through a web browser, and is therefore platform-independent. It can be applied to any model organism. To facilitate the development of three-dimensional displays of biological data on the world wide web we have established the "3D Data Display Initiative" (http://3ddi.org).

  14. GPU computing for systems biology.

    PubMed

    Dematté, Lorenzo; Prandi, Davide

    2010-05-01

    The development of detailed, coherent, models of complex biological systems is recognized as a key requirement for integrating the increasing amount of experimental data. In addition, in-silico simulation of bio-chemical models provides an easy way to test different experimental conditions, helping in the discovery of the dynamics that regulate biological systems. However, the computational power required by these simulations often exceeds that available on common desktop computers and thus expensive high performance computing solutions are required. An emerging alternative is represented by general-purpose scientific computing on graphics processing units (GPGPU), which offers the power of a small computer cluster at a cost of approximately $400. Computing with a GPU requires the development of specific algorithms, since the programming paradigm substantially differs from traditional CPU-based computing. In this paper, we review some recent efforts in exploiting the processing power of GPUs for the simulation of biological systems.

  15. Integration of microfluidics into the synthetic biology design flow.

    PubMed

    Huang, Haiyao; Densmore, Douglas

    2014-09-21

    One goal of synthetic biology is to design and build genetic circuits in living cells for a range of applications. Major challenges in these efforts include increasing the scalability and robustness of engineered biological systems and streamlining and automating the synthetic biology workflow of specification-design-assembly-verification. We present here a summary of the advances in microfluidic technology, particularly microfluidic large scale integration, that can be used to address the challenges facing each step of the synthetic biology workflow. Microfluidic technologies allow precise control over the flow of biological content within microscale devices, and thus may provide more reliable and scalable construction of synthetic biological systems. The integration of microfluidics and synthetic biology has the capability to produce rapid prototyping platforms for characterization of genetic devices, testing of biotherapeutics, and development of biosensors.

  16. Modelling codependence in biological systems.

    PubMed

    Mandel, J J; Palfreyman, N M; Dubitzky, W

    2007-01-01

    A central aim of systems biology is to elucidate the complex dynamic structure of biological systems within which functioning and control occur. The success of this endeavour requires a dialogue between the two quite distinct disciplines of life science and systems theory, and so drives the need for graphical notations which facilitate this dialogue. Several methods have been developed for modelling and simulating biochemical networks, some of which provide notations for graphicall4y constructing a model. Such notations must support the full panoply of mechanisms of systems biology, including metabolic, regulatory, signalling and transport processes. Notations in systems biology tend to fall into two groups. The first group derives its orientation from conventional biochemical pathway diagrams, and so tends to ignore the role of information processing. The second group focuses on the processing of information, incorporating information-processing ideas from other systems-oriented disciplines, such as engineering and business. This, however, can lead to the two crucial and related difficulties of impedance mismatch and conceptual baggage. Impedance mismatch concerns the rift between non-biological notations and biological reality, which forces the researcher to employ awkward workarounds when modelling uniquely biological mechanisms. Conceptual baggage can arise when, for instance, an engineering notation is adapted to cater for these distinctively biological needs, since these adaptations will, typically, never completely free the notation of the conceptual structure of its original engineering motivation. A novel formalism, codependence modelling, which seeks to combine the needs of the biologist with the mathematical rigour required to support computer simulation of dynamics is proposed here. The notion of codependence encompasses the transformation of both chemical substance and information, thus integrating both metabolic and gene regulatory processes within a

  17. 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.

  18. Towards standards for data exchange and integration and their impact on a public database such as CEBS (Chemical Effects in Biological Systems)

    SciTech Connect

    Fostel, Jennifer M.

    2008-11-15

    Integration, re-use and meta-analysis of high content study data, typical of DNA microarray studies, can increase its scientific utility. Access to study data and design parameters would enhance the mining of data integrated across studies. However, without standards for which data to include in exchange, and common exchange formats, publication of high content data is time-consuming and often prohibitive. The MGED Society ( (www.mged.org)) was formed in response to the widespread publication of microarray data, and the recognition of the utility of data re-use for meta-analysis. The NIEHS has developed the Chemical Effects in Biological Systems (CEBS) database, which can manage and integrate study data and design from biological and biomedical studies. As community standards are developed for study data and metadata it will become increasingly straightforward to publish high content data in CEBS, where they will be available for meta-analysis. Different exchange formats for study data are being developed: Standard for Exchange of Nonclinical Data (SEND; (www.cdisc.org)); Tox-ML ( (www.Leadscope.com)) and Simple Investigation Formatted Text (SIFT) from the NIEHS. Data integration can be done at the level of conclusions about responsive genes and phenotypes, and this workflow is supported by CEBS. CEBS also integrates raw and preprocessed data within a given platform. The utility and a method for integrating data within and across DNA microarray studies is shown in an example analysis using DrugMatrix data deposited in CEBS by Iconix Pharmaceuticals.

  19. 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

  20. The Potato Systems Planner: Integrating Cropping System Impacts on Crop Yield and Quality, Soil Biology, Nutrient Cycling, Diseases, and Economics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Finding and developing profitable cropping systems is a high priority for the potato industry. Consequently, an interdisciplinary team of ARS scientists from the New England Plant, Soil, & Water Laboratory evaluated 14 different rotations for their impacts on crop yield and quality, nutrient availa...

  1. The `What is a system' reflection interview as a knowledge integration activity for high school students' understanding of complex systems in human biology

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

    This study examined the reflection interview as a tool for assessing and facilitating the use of 'systems language' amongst 11th grade students who have recently completed their first year of high school biology. Eighty-three students composed two concept maps in the 10th grade-one at the beginning of the school year and one at its end. The first part of the interview is dedicated to guiding the students through comparing their two concept maps and by means of both explicit and non-explicit teaching. Our study showed that the explicit guidance in comparing the two concept maps was more effective than the non-explicit, eliciting a variety of different, more specific, types of interactions and patterns (e.g. 'hierarchy', 'dynamism', 'homeostasis') in the students' descriptions of the human body system. The reflection interview as a knowledge integration activity was found to be an effective tool for assessing the subjects' conceptual models of 'system complexity', and for identifying those aspects of a system that are most commonly misunderstood.

  2. Recent trends in microdialysis sampling integrated with conventional and microanalytical systems for monitoring biological events: A review

    PubMed Central

    Nandi, Pradyot; Lunte, Susan M.

    2013-01-01

    Microdialysis (MD) is a sampling technique that can be employed to monitor biological events both in vivo and in vitro. When it is coupled to an analytical system, microdialysis can provide near realtime information on the time-dependent concentration changes of analytes in the extracellular space or other aqueous environments. Online systems for the analysis of microdialysis samples enable fast, selective and sensitive analysis while preserving the temporal information. Analytical methods employed for online analysis include liquid chromatography (LC), capillary (CE) and microchip electrophoresis and flow-through biosensor devices. This review article provides an overview of microdialysis sampling and online analysis systems with emphasis on in vivo analysis. Factors that affect the frequency of analysis and, hence, the temporal resolution of these systems are also discussed. PMID:19733728

  3. The Chernobyl Tissue Bank — A Repository for Biomaterial and Data Used in Integrative and Systems Biology Modeling the Human Response to Radiation

    PubMed Central

    Thomas, Geraldine; Unger, Kristian; Krznaric, Marko; Galpine, Angela; Bethel, Jackie; Tomlinson, Christopher; Woodbridge, Mark; Butcher, Sarah

    2012-01-01

    The only unequivocal radiological effect of the Chernobyl accident on human health is the increase in thyroid cancer in those exposed in childhood or early adolescence. In response to the scientific interest in studying the molecular biology of thyroid cancer post Chernobyl, the Chernobyl Tissue Bank (CTB: www.chernobyltissuebank.com) was established in 1998. Thus far it is has collected biological samples from 3,861 individuals, and provided 27 research projects with 11,254 samples. The CTB was designed from its outset as a resource to promote the integration of research and clinical data to facilitate a systems biology approach to radiation related thyroid cancer. The project has therefore developed as a multidisciplinary collaboration between clinicians, dosimetrists, molecular biologists and bioinformaticians and serves as a paradigm for tissue banking in the omics era. PMID:24704918

  4. Integration of Biological, Physical/Chemical and Energy Efficient Systems in the CELSS Antarctic Analog: Performance of Prototype Systems and Issues for Life Support

    NASA Technical Reports Server (NTRS)

    Bubenheim, David L.; Flynn, Michael T.; Lamparter, Richard; Bates, Maynard; Kliss, Mark (Technical Monitor)

    1998-01-01

    The Controlled Ecological Life Support System (CELSS) Antarctic Analog Project (CAAP) is a joint endeavor between the National Science Foundation, Office of Polar Programs (NSF-OPP), and the National Aeronautics and Space Administration (NASA). The fundamental objective is to develop, deploy, and operate a testbed of advanced life support technologies at the Amundsen-Scott South Pole Station that enable the objectives of both the NSF and NASA. The functions of food production, water purification, and waste treatment, recycle, and reduction provided by CAAP will improve the quality of life for the South Pole inhabitants, reduce logistics dependence, enhance safety, and minimize environmental impacts associated with human presence on the polar plateau. Because of the analogous technical, scientific, and mission features with Planetary missions, such as a mission to Mars, CAAP provides NASA with a method for validating technologies and overall approaches to supporting humans. Prototype systems for waste treatment, water recycle, resource recovery and crop production are being evaluated in a testbed at Ames Research Center. The combined performance of these biological and physical/chemical systems as an integrated function in support of the human habitat will be discussed. Overall system performance will be emphasized. The effectiveness and efficiency of component technologies will be discussed in the context of energy and mass flow within the system and contribution to achieving a mass and energy conservative system. Critical to the discussion are interfaces with habitat functions outside of the closed-loop life support: the ability of the system to satisfy the life support requirements of the habitat and the ability to define input requirements. The significance of analog functions in relation to future Mars habitats will be discussed.

  5. 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 ‘‘...

  6. Biological system interactions.

    PubMed Central

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

    1984-01-01

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

  7. Integrative Biology: A Capstone Course for an Introductory Biology Core

    ERIC Educational Resources Information Center

    Chaplin, Susan B.; Hartung, Nancy Z.

    2012-01-01

    A capstone to the biology introductory curriculum was developed with the specific goals of enhancing integration of course content, promoting development of oral presentation skills and critical reading and thinking skills, and introducing ecological principles omitted from the rest of the core. Classes of 12 to 16 students were team taught by…

  8. Systems biology of aging.

    PubMed

    Bolt, Kendra; Bergman, Aviv

    2015-01-01

    Human aging occurs at rates that vary widely between organisms and cell types. We hypothesize that in both cases, variation is due to differences in heat production, heat management and molecular susceptibility to heat-induced change. Metabolic rates have long been implored for their contributions to the aging process, with a negative correlation observed between basal metabolic rate and lifespan (Savage et al., Proc Natl Acad Sci U S A 104:4718–4723, 2007, Economos, Exp Gerontol 17:145–152, 1982, Keys et al., Metabolism 22:579–587, 1973, O’Connor et al., Comp Biochem Physiol Part A, Molr & Integr Physiol 133:835–842, 2002, Speakman, J Exp Biol 208:1717–1730, 2005, Poehlman, J Am Geriatrics Soc 41:552–559, 1993). Small amounts of heat are the well-known byproduct of metabolism and other biological processes, and despite their magnitude, are sufficient to elicit alterations in biomolecular characteristics (Somero, Ann Rev Physiol 57:43–68, 1995). Existing theories of aging suggest that damage occurs to the conformations or sequences of molecules, which only shifts focus onto the implied failure of repair mechanisms. Contrarily, heat-induced changes affect the behavioral characteristics of molecules and are thus able to persist “under the radar” of heat shock proteins and other canalizing mechanisms, which recognize only physical aberrancies (Rutherford and Lindquist, Nature 396:336–342, 1998, Siegal and Bergman, Proc Natl Acad Sci U S A 99:10528–10532, 2002, Waddington, Nature 150:563–565, 1942). According to our hypothesis, behavioral changes to the binding affinities, kinetics, motilities, and functionalities are dependent on minute energetic fields within and between molecules. Exposure to the thermal byproducts of metabolism cause heritable shifts in molecular interaction schemes and diminish the integrity of genetic and epigenetic networks. Restructured topologies alter the emergent properties of networks and are observed as the

  9. Equilibrium dialysis data and the relationships between preferential interaction parameters for biological systems in terms of Kirkwood-Buff integrals.

    PubMed

    Smith, Paul E

    2006-02-16

    Equilibrium dialysis data has provided valuable information concerning the preferential interaction of a cosolvent with a biomolecule in aqueous solutions. Here, we formulate the experimental data in terms of Kirkwood-Buff (KB) theory, resulting in equations that provide a simple physical picture of the dialysis experiment and thereby the interaction of a cosolvent with a biomolecule. These results are then used to establish exact relationships between preferential interaction coefficients, defined in different ensembles and/or using different concentration scales, in terms of KB integrals. It is then argued that the molality based equilibrium dialysis data represent the situation most relevant to computer simulations performed in either open or closed systems.

  10. A Novel Robot System Integrating Biological and Mechanical Intelligence Based on Dissociated Neural Network-Controlled Closed-Loop Environment

    PubMed Central

    Wang, Yuechao; Li, Hongyi; Zheng, Xiongfei

    2016-01-01

    We propose the architecture of a novel robot system merging biological and artificial intelligence based on a neural controller connected to an external agent. We initially built a framework that connected the dissociated neural network to a mobile robot system to implement a realistic vehicle. The mobile robot system characterized by a camera and two-wheeled robot was designed to execute the target-searching task. We modified a software architecture and developed a home-made stimulation generator to build a bi-directional connection between the biological and the artificial components via simple binomial coding/decoding schemes. In this paper, we utilized a specific hierarchical dissociated neural network for the first time as the neural controller. Based on our work, neural cultures were successfully employed to control an artificial agent resulting in high performance. Surprisingly, under the tetanus stimulus training, the robot performed better and better with the increasement of training cycle because of the short-term plasticity of neural network (a kind of reinforced learning). Comparing to the work previously reported, we adopted an effective experimental proposal (i.e. increasing the training cycle) to make sure of the occurrence of the short-term plasticity, and preliminarily demonstrated that the improvement of the robot’s performance could be caused independently by the plasticity development of dissociated neural network. This new framework may provide some possible solutions for the learning abilities of intelligent robots by the engineering application of the plasticity processing of neural networks, also for the development of theoretical inspiration for the next generation neuro-prostheses on the basis of the bi-directional exchange of information within the hierarchical neural networks. PMID:27806074

  11. A Novel Robot System Integrating Biological and Mechanical Intelligence Based on Dissociated Neural Network-Controlled Closed-Loop Environment.

    PubMed

    Li, Yongcheng; Sun, Rong; Wang, Yuechao; Li, Hongyi; Zheng, Xiongfei

    2016-01-01

    We propose the architecture of a novel robot system merging biological and artificial intelligence based on a neural controller connected to an external agent. We initially built a framework that connected the dissociated neural network to a mobile robot system to implement a realistic vehicle. The mobile robot system characterized by a camera and two-wheeled robot was designed to execute the target-searching task. We modified a software architecture and developed a home-made stimulation generator to build a bi-directional connection between the biological and the artificial components via simple binomial coding/decoding schemes. In this paper, we utilized a specific hierarchical dissociated neural network for the first time as the neural controller. Based on our work, neural cultures were successfully employed to control an artificial agent resulting in high performance. Surprisingly, under the tetanus stimulus training, the robot performed better and better with the increasement of training cycle because of the short-term plasticity of neural network (a kind of reinforced learning). Comparing to the work previously reported, we adopted an effective experimental proposal (i.e. increasing the training cycle) to make sure of the occurrence of the short-term plasticity, and preliminarily demonstrated that the improvement of the robot's performance could be caused independently by the plasticity development of dissociated neural network. This new framework may provide some possible solutions for the learning abilities of intelligent robots by the engineering application of the plasticity processing of neural networks, also for the development of theoretical inspiration for the next generation neuro-prostheses on the basis of the bi-directional exchange of information within the hierarchical neural networks.

  12. Plants in silico: why, why now and what?--an integrative platform for plant systems biology research.

    PubMed

    Zhu, Xin-Guang; Lynch, Jonathan P; LeBauer, David S; Millar, Andrew J; Stitt, Mark; Long, Stephen P

    2016-05-01

    A paradigm shift is needed and timely in moving plant modelling from largely isolated efforts to a connected community endeavour that can take full advantage of advances in computer science and in mechanistic understanding of plant processes. Plants in silico (Psi) envisions a digital representation of layered dynamic modules, linking from gene networks and metabolic pathways through to cellular organization, tissue, organ and whole plant development, together with resource capture and use efficiency in dynamic competitive environments, ultimately allowing a mechanistically rich simulation of the plant or of a community of plants in silico. The concept is to integrate models or modules from different layers of organization spanning from genome to phenome to ecosystem in a modular framework allowing the use of modules of varying mechanistic detail representing the same biological process. Developments in high-performance computing, functional knowledge of plants, the internet and open-source version controlled software make achieving the concept realistic. Open source will enhance collaboration and move towards testing and consensus on quantitative theoretical frameworks. Importantly, Psi provides a quantitative knowledge framework where the implications of a discovery at one level, for example, single gene function or developmental response, can be examined at the whole plant or even crop and natural ecosystem levels.

  13. Systems biology of kidney diseases.

    PubMed

    He, John Cijiang; Chuang, Peter Y; Ma'ayan, Avi; Iyengar, Ravi

    2012-01-01

    Kidney diseases manifest in progressive loss of renal function, which ultimately leads to complete kidney failure. The mechanisms underlying the origins and progression of kidney diseases are not fully understood. Multiple factors involved in the pathogenesis of kidney diseases have made the traditional candidate gene approach of limited value toward full understanding of the molecular mechanisms of these diseases. A systems biology approach that integrates computational modeling with large-scale data gathering of the molecular changes could be useful in identifying the multiple interacting genes and their products that drive kidney diseases. Advances in biotechnology now make it possible to gather large data sets to characterize the role of the genome, epigenome, transcriptome, proteome, and metabolome in kidney diseases. When combined with computational analyses, these experimental approaches will provide a comprehensive understanding of the underlying biological processes. Multiscale analysis that connects the molecular interactions and cell biology of different kidney cells to renal physiology and pathology can be utilized to identify modules of biological and clinical importance that are perturbed in disease processes. This integration of experimental approaches and computational modeling is expected to generate new knowledge that can help to identify marker sets to guide the diagnosis, monitor disease progression, and identify new therapeutic targets.

  14. Methods for biological data integration: perspectives and challenges

    PubMed Central

    Gligorijević, Vladimir; Pržulj, Nataša

    2015-01-01

    Rapid technological advances have led to the production of different types of biological data and enabled construction of complex networks with various types of interactions between diverse biological entities. Standard network data analysis methods were shown to be limited in dealing with such heterogeneous networked data and consequently, new methods for integrative data analyses have been proposed. The integrative methods can collectively mine multiple types of biological data and produce more holistic, systems-level biological insights. We survey recent methods for collective mining (integration) of various types of networked biological data. We compare different state-of-the-art methods for data integration and highlight their advantages and disadvantages in addressing important biological problems. We identify the important computational challenges of these methods and provide a general guideline for which methods are suited for specific biological problems, or specific data types. Moreover, we propose that recent non-negative matrix factorization-based approaches may become the integration methodology of choice, as they are well suited and accurate in dealing with heterogeneous data and have many opportunities for further development. PMID:26490630

  15. The GLOBE 3D Genome Platform - towards a novel system-biological paper tool to integrate the huge complexity of genome organization and function.

    PubMed

    Knoch, Tobias A; Lesnussa, Michael; Kepper, Nick; Eussen, Hubert B; Grosveld, Frank G

    2009-01-01

    Genomes are tremendous co-evolutionary holistic systems for molecular storage, processing and fabrication of information. Their system-biological complexity remains, however, still largely mysterious, despite immense sequencing achievements and huge advances in the understanding of the general sequential, three-dimensional and regulatory organization. Here, we present the GLOBE 3D Genome Platform a completely novel grid based virtual "paper" tool and in fact the first system-biological genome browser integrating the holistic complexity of genomes in a single easy comprehensible platform: Based on a detailed study of biophysical and IT requirements, every architectural level from sequence to morphology of one or several genomes can be approached in a real and in a symbolic representation simultaneously and navigated by continuous scale-free zooming within a unique three-dimensional OpenGL and grid driven environment. In principle an unlimited number of multi-dimensional data sets can be visualized, customized in terms of arrangement, shape, colour, and texture etc. as well as accessed and annotated individually or in groups using internal or external data bases/facilities. Any information can be searched and correlated by importing or calculating simple relations in real-time using grid resources. A general correlation and application platform for more complex correlative analysis and a front-end for system-biological simulations both using again the huge capabilities of grid infrastructures is currently under development. Hence, the GLOBE 3D Genome Platform is an example of a grid based approach towards a virtual desktop for genomic work combining the three fundamental distributed resources: i) visual data representation, ii) data access and management, and iii) data analysis and creation. Thus, the GLOBE 3D Genome Platform is the novel system-biology oriented information system urgently needed to access, present, annotate, and to simulate the holistic genome

  16. 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.

  17. Network biology methods integrating biological data for translational science.

    PubMed

    Bebek, Gurkan; Koyutürk, Mehmet; Price, Nathan D; Chance, Mark R

    2012-07-01

    The explosion of biomedical data, both on the genomic and proteomic side as well as clinical data, will require complex integration and analysis to provide new molecular variables to better understand the molecular basis of phenotype. Currently, much data exist in silos and is not analyzed in frameworks where all data are brought to bear in the development of biomarkers and novel functional targets. This is beginning to change. Network biology approaches, which emphasize the interactions between genes, proteins and metabolites provide a framework for data integration such that genome, proteome, metabolome and other -omics data can be jointly analyzed to understand and predict disease phenotypes. In this review, recent advances in network biology approaches and results are identified. A common theme is the potential for network analysis to provide multiplexed and functionally connected biomarkers for analyzing the molecular basis of disease, thus changing our approaches to analyzing and modeling genome- and proteome-wide data.

  18. 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.

  19. 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

  20. [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.

  1. 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.

  2. Industrial systems biology.

    PubMed

    Otero, José Manuel; Nielsen, Jens

    2010-02-15

    The chemical industry is currently undergoing a dramatic change driven by demand for developing more sustainable processes for the production of fuels, chemicals, and materials. In biotechnological processes different microorganisms can be exploited, and the large diversity of metabolic reactions represents a rich repository for the design of chemical conversion processes that lead to efficient production of desirable products. However, often microorganisms that produce a desirable product, either naturally or because they have been engineered through insertion of heterologous pathways, have low yields and productivities, and in order to establish an economically viable process it is necessary to improve the performance of the microorganism. Here metabolic engineering is the enabling technology. Through metabolic engineering the metabolic landscape of the microorganism is engineered such that there is an efficient conversion of the raw material, typically glucose, to the product of interest. This process may involve both insertion of new enzymes activities, deletion of existing enzyme activities, but often also deregulation of existing regulatory structures operating in the cell. In order to rapidly identify the optimal metabolic engineering strategy the industry is to an increasing extent looking into the use of tools from systems biology. This involves both x-ome technologies such as transcriptome, proteome, metabolome, and fluxome analysis, and advanced mathematical modeling tools such as genome-scale metabolic modeling. Here we look into the history of these different techniques and review how they find application in industrial biotechnology, which will lead to what we here define as industrial systems biology.

  3. MECHANISTIC INDICATORS OF CHILDHOOD ASTHMA (MICA): A SYSTEMS BIOLOGY APPROACH FOR THE INTEGRATION OF MULTIFACTORIAL EXPOSURE AND ENVIRONMENTAL HEALTH DATA

    EPA Science Inventory

    Modem methods in molecular biology and advanced computational tools show promise in elucidating complex interactions that occur between genes and environmental factors in diseases such as asthma. However, appropriately designed studies are critical for these methods to reach the...

  4. An inexpensive, temporally-integrated system for monitoring occurrence and biological effects of contaminants in the field (Poster)

    EPA Science Inventory

    Assessing potential biological impacts of complex mixtures of contaminants in aquatic environments is an ongoing challenge for ecotoxicologists. Instrumental analysis of site waters alone can identify contaminants but provides only limited insights as to possible adverse effects...

  5. An inexpensive, temporally-integrated system for monitoring occurrence and biological effects of contaminants in the field

    EPA Science Inventory

    Assessing potential biological impacts of complex mixtures of contaminants in aquatic environments is an ongoing challenge for ecotoxicologists. Instrumental analysis of site waters alone can identify contaminants but provides only limited insights as to possible adverse effects...

  6. The "What Is a System" Reflection Interview as a Knowledge Integration Activity for High School Students' Understanding of Complex Systems in Human Biology

    ERIC Educational Resources Information Center

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

    2016-01-01

    This study examined the reflection interview as a tool for assessing and facilitating the use of "systems language" amongst 11th grade students who have recently completed their first year of high school biology. Eighty-three students composed two concept maps in the 10th grade--one at the beginning of the school year and one at its end.…

  7. 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.

  8. The need for a biological registration system.

    PubMed

    Pihl, Todd D; Ribaudo, Randall K

    2010-06-01

    A biological registration system is capable of determining whether two complex biological molecules are the same or different, and can assign identifiers based on this determination. Although such systems are frequently employed by chemists, they are rarely used by biological scientists in the pharmaceutical industry. However, a biological registration system would have several enterprise-wide benefits, from R&D to IP to laboratory safety. Beyond these evident benefits, a biological registration system that integrates appropriately with other systems such as electronic laboratory notebooks and inventory databases could provide critical links to allow the integration of otherwise-siloed data and knowledge generated across global pharmaceutical companies and other large research institutions. Data and knowledge integration are widely recognized as critical yet elusive components of effective translational science and systems biology programs that would create greater efficiencies for drug discovery. However, determining the optimal construction of such systems remains a challenge. This feature review describes how a special interest group comprising several pharmaceutical companies and a software company was used to create a commercially viable and supportable system.

  9. From systems biology to photosynthesis and whole-plant physiology: a conceptual model for integrating multi-scale networks.

    PubMed

    Weston, David J; Hanson, Paul J; Norby, Richard J; Tuskan, Gerald A; Wullschleger, Stan D

    2012-02-01

    Network analysis is now a common statistical tool for molecular biologists. Network algorithms are readily used to model gene, protein and metabolic correlations providing insight into pathways driving biological phenomenon. One output from such an analysis is a candidate gene list that can be responsible, in part, for the biological process of interest. The question remains, however, as to whether molecular network analysis can be used to inform process models at higher levels of biological organization. In our previous work, transcriptional networks derived from three plant species were constructed, interrogated for orthology and then correlated with photosynthetic inhibition at elevated temperature. One unique aspect of that study was the link from co-expression networks to net photosynthesis. In this addendum, we propose a conceptual model where traditional network analysis can be linked to whole-plant models thereby informing predictions on key processes such as photosynthesis, nutrient uptake and assimilation, and C partitioning.

  10. BiologicalNetworks 2.0 - an integrative view of genome biology data

    PubMed Central

    2010-01-01

    Background A significant problem in the study of mechanisms of an organism's development is the elucidation of interrelated factors which are making an impact on the different levels of the organism, such as genes, biological molecules, cells, and cell systems. Numerous sources of heterogeneous data which exist for these subsystems are still not integrated sufficiently enough to give researchers a straightforward opportunity to analyze them together in the same frame of study. Systematic application of data integration methods is also hampered by a multitude of such factors as the orthogonal nature of the integrated data and naming problems. Results Here we report on a new version of BiologicalNetworks, a research environment for the integral visualization and analysis of heterogeneous biological data. BiologicalNetworks can be queried for properties of thousands of different types of biological entities (genes/proteins, promoters, COGs, pathways, binding sites, and other) and their relations (interactions, co-expression, co-citations, and other). The system includes the build-pathways infrastructure for molecular interactions/relations and module discovery in high-throughput experiments. Also implemented in BiologicalNetworks are the Integrated Genome Viewer and Comparative Genomics Browser applications, which allow for the search and analysis of gene regulatory regions and their conservation in multiple species in conjunction with molecular pathways/networks, experimental data and functional annotations. Conclusions The new release of BiologicalNetworks together with its back-end database introduces extensive functionality for a more efficient integrated multi-level analysis of microarray, sequence, regulatory, and other data. BiologicalNetworks is freely available at http://www.biologicalnetworks.org. PMID:21190573

  11. Metabolic Reconstruction of Setaria italica: A Systems Biology Approach for Integrating Tissue-Specific Omics and Pathway Analysis of Bioenergy Grasses

    PubMed Central

    de Oliveira Dal'Molin, Cristiana G.; Orellana, Camila; Gebbie, Leigh; Steen, Jennifer; Hodson, Mark P.; Chrysanthopoulos, Panagiotis; Plan, Manuel R.; McQualter, Richard; Palfreyman, Robin W.; Nielsen, Lars K.

    2016-01-01

    The urgent need for major gains in industrial crops productivity and in biofuel production from bioenergy grasses have reinforced attention on understanding C4 photosynthesis. Systems biology studies of C4 model plants may reveal important features of C4 metabolism. Here we chose foxtail millet (Setaria italica), as a C4 model plant and developed protocols to perform systems biology studies. As part of the systems approach, we have developed and used a genome-scale metabolic reconstruction in combination with the use of multi-omics technologies to gain more insights into the metabolism of S. italica. mRNA, protein, and metabolite abundances, were measured in mature and immature stem/leaf phytomers, and the multi-omics data were integrated into the metabolic reconstruction framework to capture key metabolic features in different developmental stages of the plant. RNA-Seq reads were mapped to the S. italica resulting for 83% coverage of the protein coding genes of S. italica. Besides revealing similarities and differences in central metabolism of mature and immature tissues, transcriptome analysis indicates significant gene expression of two malic enzyme isoforms (NADP- ME and NAD-ME). Although much greater expression levels of NADP-ME genes are observed and confirmed by the correspondent protein abundances in the samples, the expression of multiple genes combined to the significant abundance of metabolites that participates in C4 metabolism of NAD-ME and NADP-ME subtypes suggest that S. italica may use mixed decarboxylation modes of C4 photosynthetic pathways under different plant developmental stages. The overall analysis also indicates different levels of regulation in mature and immature tissues in carbon fixation, glycolysis, TCA cycle, amino acids, fatty acids, lignin, and cellulose syntheses. Altogether, the multi-omics analysis reveals different biological entities and their interrelation and regulation over plant development. With this study, we demonstrated

  12. Metabolic Reconstruction of Setaria italica: A Systems Biology Approach for Integrating Tissue-Specific Omics and Pathway Analysis of Bioenergy Grasses.

    PubMed

    de Oliveira Dal'Molin, Cristiana G; Orellana, Camila; Gebbie, Leigh; Steen, Jennifer; Hodson, Mark P; Chrysanthopoulos, Panagiotis; Plan, Manuel R; McQualter, Richard; Palfreyman, Robin W; Nielsen, Lars K

    2016-01-01

    The urgent need for major gains in industrial crops productivity and in biofuel production from bioenergy grasses have reinforced attention on understanding C4 photosynthesis. Systems biology studies of C4 model plants may reveal important features of C4 metabolism. Here we chose foxtail millet (Setaria italica), as a C4 model plant and developed protocols to perform systems biology studies. As part of the systems approach, we have developed and used a genome-scale metabolic reconstruction in combination with the use of multi-omics technologies to gain more insights into the metabolism of S. italica. mRNA, protein, and metabolite abundances, were measured in mature and immature stem/leaf phytomers, and the multi-omics data were integrated into the metabolic reconstruction framework to capture key metabolic features in different developmental stages of the plant. RNA-Seq reads were mapped to the S. italica resulting for 83% coverage of the protein coding genes of S. italica. Besides revealing similarities and differences in central metabolism of mature and immature tissues, transcriptome analysis indicates significant gene expression of two malic enzyme isoforms (NADP- ME and NAD-ME). Although much greater expression levels of NADP-ME genes are observed and confirmed by the correspondent protein abundances in the samples, the expression of multiple genes combined to the significant abundance of metabolites that participates in C4 metabolism of NAD-ME and NADP-ME subtypes suggest that S. italica may use mixed decarboxylation modes of C4 photosynthetic pathways under different plant developmental stages. The overall analysis also indicates different levels of regulation in mature and immature tissues in carbon fixation, glycolysis, TCA cycle, amino acids, fatty acids, lignin, and cellulose syntheses. Altogether, the multi-omics analysis reveals different biological entities and their interrelation and regulation over plant development. With this study, we demonstrated

  13. Intelligent test integration system

    NASA Technical Reports Server (NTRS)

    Sztipanovits, J.; Padalkar, S.; Rodriguez-Moscoso, J.; Kawamura, K.; Purves, B.; Williams, R.; Biglari, H.

    1988-01-01

    A new test technology is described which was developed for space system integration. The ultimate purpose of the system is to support the automatic generation of test systems in real time, distributed computing environments. The Intelligent Test Integration System (ITIS) is a knowledge based layer above the traditional test system components which can generate complex test configurations from the specification of test scenarios.

  14. Integration of pharmacokinetic and NRF2 system biology models to describe reactive oxygen species production and subsequent glutathione depletion in liver microfluidic biochips after flutamide exposure.

    PubMed

    Leclerc, Eric; Hamon, Jeremy; Legendre, Audrey; Bois, Frederic Y

    2014-10-01

    We present a systems biology analysis of rat primary hepatocytes response after exposure to 10 μM and 100 μM flutamide in liver microfluidic biochips. We coupled an in vitro pharmacokinetic (PK) model of flutamide to a system biology model of its reactive oxygen species (ROS) production and scavenging by the Nrf2 regulated glutathione production. The PK model was calibrated using data on flutamide kinetics, hydroxyflutamide and glutathione conjugates formation in microfluidic conditions. The parameters of Nrf2-related gene activities and the subsequent glutathione depletion were calibrated using microarray data from our microfluidic experiments and literature information. Following a 10 μM flutamide exposure, the model predicted a recovery time to baseline levels of glutathione (GSH) and ROS in agreement with our experimental observations. At 100 μM, the model predicted that metabolism saturation led to an important accumulation of flutamide in cells, a high ROS production and complete GSH depletion. The high levels of ROS predicted were consistent with the necrotic switch observed by transcriptomics, and the high cell mortality we had experimentally observed. The model predicted a transition between recoverable GSH depletion and deep GSH depletion at about 12.5 μM of flutamide (single perfusion exposure). Our work shows that in vitro biochip experiments can provide supporting information for complex in silico modeling including data from extra cellular and intra cellular levels. We believe that this approach can be an efficient strategy for a global integrated methodology in predictive toxicology.

  15. 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.

  16. Carbon Cycling and Biosequestration Integrating Biology and Climate Through Systems Science Report from the March 2008 Workshop

    SciTech Connect

    Graber, J.; Amthor, J.; Dahlman, R.; Drell, D.; Weatherwax, S.

    2008-12-01

    One of the most daunting challenges facing science in the 21st Century is to predict how Earth's ecosystems will respond to global climate change. The global carbon cycle plays a central role in regulating atmospheric carbon dioxide (CO{sub 2}) levels and thus Earth's climate, but our basic understanding of the myriad of tightly interlinked biological processes that drive the global carbon cycle remains limited at best. Whether terrestrial and ocean ecosystems will capture, store, or release carbon is highly dependent on how changing climate conditions affect processes performed by the organisms that form Earth's biosphere. Advancing our knowledge of biological components of the global carbon cycle is thus crucial to predicting potential climate change impacts, assessing the viability of climate change adaptation and mitigation strategies, and informing relevant policy decisions. Global carbon cycling is dominated by the paired biological processes of photosynthesis and respiration. Photosynthetic plants and microbes of Earth's land-masses and oceans use solar energy to transform atmospheric CO{sub 2} into organic carbon. The majority of this organic carbon is rapidly consumed by plants or microbial decomposers for respiration and returned to the atmosphere as CO{sub 2}. Coupling between the two processes results in a near equilibrium between photosynthesis and respiration at the global scale, but some fraction of organic carbon also remains in stabilized forms such as biomass, soil, and deep ocean sediments. This process, known as carbon biosequestration, temporarily removes carbon from active cycling and has thus far absorbed a substantial fraction of anthropogenic carbon emissions.

  17. Systems Biology of Coagulation

    PubMed Central

    Diamond, Scott L.

    2013-01-01

    Accurate computer simulation of blood function can inform drug target selection, patient-specific dosing, clinical trial design, biomedical device design, as well as the scoring of patient-specific disease risk and severity. These large-scale simulations rely on hundreds of independently measured physical parameters and kinetic rate constants. However, the models can be validated against large scale, patient-specific laboratory measurements. By validation with high dimensional data, modelling becomes a powerful tool to predict clinically complex scenarios. Currently, it is possible to accurately predict the clotting rate of plasma or blood in a tube as it is activated with a dose of tissue factor, even as numerous coagulation factors are altered by exogenous attenuation or potentiation. Similarly, the dynamics of platelet activation, as indicated by calcium mobilisation or inside-out signalling, can now be numerically simulated with accuracy in cases where platelets are exposed to combinations of agonists. Multiscale models have emerged to combine platelet function and coagulation kinetics into complete physics-based descriptions of thrombosis under flow. Blood flow controls platelet fluxes, delivery and removal of coagulation factors, adhesive bonding, and von Willebrand factor conformation. The field of Blood Systems Biology has now reached a stage that anticipates the inclusion of contact, complement, and fibrinolytic pathways along with models of neutrophil and endothelial activation. Along with “-omics” data sets, such advanced models seek to predict the multifactorial range of healthy responses and diverse bleeding and clotting scenarios, ultimately to understand and improve patient outcomes. PMID:23809126

  18. Biological Resource Centers and Systems Biology.

    PubMed

    Wang, Yufeng; Lilburn, Timothy G

    2009-02-11

    There are hundreds of Biological Resource Centers (BRCs) around the world, holding many little-studied microorganism. The proportion of bacterial strains that is well represented in the sequence and literature databases may be as low as 1%. This body of unexplored diversity represents an untapped source of useful strains and derived products. However, a modicum of phenotypic data is available for almost all the bacterial strains held by BRCs around the world. It is at the phenotypic level that our knowledge of the well-studied strains of bacteria and the many yet-to-be studied strains intersects. This suggests we might leverage the phenotypic data from the data-poor bacteria with the omics data from the data-rich bacteria, using our knowledge of their evolutionary relationships, to map the metabolic networks of the little-known bacteria. This systems biology-based approach is a new way to explore the diversity harbored in BRCs.

  19. 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

  20. System integration report

    NASA Technical Reports Server (NTRS)

    Badler, N. I.; Korein, J. D.; Meyer, C.; Manoochehri, K.; Rovins, J.; Beale, J.; Barr, B.

    1985-01-01

    Several areas that arise from the system integration issue were examined. Intersystem analysis is discussed as it relates to software development, shared data bases and interfaces between TEMPUS and PLAID, shaded graphics rendering systems, object design (BUILD), the TEMPUS animation system, anthropometric lab integration, ongoing TEMPUS support and maintenance, and the impact of UNIX and local workstations on the OSDS environment.

  1. Systems biology in neuroscience: bridging genes to cognition.

    PubMed

    Grant, Seth G N

    2003-10-01

    Systems biology is a new branch of biology aimed at understanding biological complexity. Genomic and proteomic methods integrated with cellular and organismal analyses allow modelling of physiological processes. Progress in understanding synapse composition and new experimental and bioinformatics methods indicate the synapse is an excellent starting point for global systems biology of the brain. A neuroscience systems biology programme, organized as a consortium, is proposed.

  2. Avionics systems integration technology

    NASA Technical Reports Server (NTRS)

    Stech, George; Williams, James R.

    1988-01-01

    A very dramatic and continuing explosion in digital electronics technology has been taking place in the last decade. The prudent and timely application of this technology will provide Army aviation the capability to prevail against a numerically superior enemy threat. The Army and NASA have exploited this technology explosion in the development and application of avionics systems integration technology for new and future aviation systems. A few selected Army avionics integration technology base efforts are discussed. Also discussed is the Avionics Integration Research Laboratory (AIRLAB) that NASA has established at Langley for research into the integration and validation of avionics systems, and evaluation of advanced technology in a total systems context.

  3. Carbon Nanotubes as Structural Elements in Integrated Biological Nanodevices

    NASA Astrophysics Data System (ADS)

    Prakash, Rohit; Cheney, Richard; Washburn, Sean; Superfine, Richard; Falvo, Michael

    2003-11-01

    Because of their unique mechanical, electrical, and spatial properties, Carbon Nanotubes (CNT) is an ideal candidate for nanometer scale electromechanical systems. An obstacle that arises immediately is the ability to produce substantial forces. Instead of following this course of miniaturization, it is possible integrate force-generating components that have been present for many years: biological motors. These protein complexes are responsible for muscle contractility and the intracellular transport of chromosomes and vesicles; they typically produce forces on a scale of piconewtons. We report progress toward attaching biological motor/filament complexes onto CNTs. We will also present results showing that individual carbon nanotubes (CNTs) can be visualized with fluorescence microscopy through non-covalent labeling with conventional fluorophores. These studies lend themselves not only to the integration of nano-scale objects into biological sciences, but also give us some understanding of the surface properties of CNTs.

  4. Hierarchical structure of biological systems

    PubMed Central

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

    2014-01-01

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

  5. From systems biology to systems biomedicine.

    PubMed

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

    2012-08-01

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

  6. How to integrate geology, biology, and modern wireless technologies to assess biotic-abiotic interactions on coastal dune systems: a new multidisciplinary approach

    NASA Astrophysics Data System (ADS)

    Sarti, Giovanni; Bertoni, Duccio; Bini, Monica; Ciccarelli, Daniela; Ribolini, Adriano; Ruocco, Matteo; Pozzebon, Alessandro; Alquini, Fernanda; Giaccari, Riccardo; Tordella, Stefano

    2014-05-01

    Coastal dune systems are arguably one of the most dynamic environments because their evolution is controlled by many factors, both natural and human-related. Hence, they are often exposed to processes leading to erosion, which in turn determine serious naturalistic and economic losses. Most recent studies carried out on different dune fields worldwide emphasized the notion that a better definition of this environment needs an approach that systematically involves several disciplines, striving to merge every data collected from any individual analyses. Therefore, a new multidisciplinary method to study coastal dune systems has been conceived in order to integrate geology, biology, and modern wireless technologies. The aim of the work is threefold: i) to check the reliability of this new approach; ii) to provide a dataset as complete as ever about the factors affecting the evolution of coastal dunes; and iii) to evaluate the influence of any biotic and abiotic factors on plant communities. The experimentation site is located along the Pisa coast within the Migliarino - S. Rossore - Massaciuccoli Regional Park, a protected area where human influence is low (Tuscany, Italy). A rectangle of 100 x 200 m containing 50 grids of 20 x 20 m was established along the coastal dune systems from the coastline to the pinewood at the landward end of the backdune area. Sampling from each grid determined grain-size analysis carried out on surface sediment samples such as geologic aspects; topographic surveys performed by means of DGPS-RTK instruments; geophysical surveys conducted with a GPR equipment, which will be matched with core drilling activities; digital image analysis of high definition pictures taken by means of a remote controlled aircraft drone flying over the study area; biological data obtained by percent cover of each vascular plant species recorded in the sampling unit. Along with geologic and biologic methodologies, this research implemented the use of informatics

  7. Analysis and Prediction of Pathways in HeLa Cells by Integrating Biological Levels of Organization with Systems-Biology Approaches

    PubMed Central

    Higareda-Almaraz, Juan Carlos; Valtierra-Gutiérrez, Ilse A.; Hernandez-Ortiz, Magdalena; Contreras, Sandra; Hernandez, Erika; Encarnacion, Sergio

    2013-01-01

    It has recently begun to be considered that cancer is a systemic disease and that it must be studied at every level of complexity using many of the currently available approaches, including high-throughput technologies and bioinformatics. To achieve such understanding in cervical cancer, we collected information on gene, protein and phosphoprotein expression of the HeLa cell line and performed a comprehensive analysis of the different signaling pathways, transcription networks and metabolic events in which they participate. A total expression analysis by RNA-Seq of the HeLa cell line showed that 19,974 genes were transcribed. Of these, 3,360 were over-expressed, and 2,129 under-expressed when compared to the NHEK cell line. A protein-protein interaction network was derived from the over-expressed genes and used to identify central elements and, together with the analysis of over-represented transcription factor motifs, to predict active signaling and regulatory pathways. This was further validated by Metal-Oxide Affinity Chromatography (MOAC) and Tandem Mass Spectrometry (MS/MS) assays which retrieved phosphorylated proteins. The 14-3-3 family members emerge as important regulators in carcinogenesis and as possible clinical targets. We observed that the different over- and under-regulated pathways in cervical cancer could be interrelated through elements that participate in crosstalks, therefore belong to what we term “meta-pathways”. Additionally, we highlighted the relations of each one of the differentially represented pathways to one or more of the ten hallmarks of cancer. These features could be maintained in many other types of cancer, regardless of mutations or genomic rearrangements, and favor their robustness, adaptations and the evasion of tissue control. Probably, this could explain why cancer cells are not eliminated by selective pressure and why therapy trials directed against molecular targets are not as effective as expected. PMID:23785426

  8. Systems Integration (Fact Sheet)

    SciTech Connect

    DOE Solar Energy Technologies Program

    2011-10-13

    The Systems Integration (SI) subprogram works closely with industry, universities, and the national laboratories to overcome technical barriers to the large-scale deployment of solar technologies. To support these goals, the subprogram invests primarily in four areas: grid integration, technology validation, solar resource assessment, and balance of system development.

  9. Systems Integration (Fact Sheet)

    SciTech Connect

    Not Available

    2011-10-01

    The Systems Integration (SI) subprogram works closely with industry, universities, and the national laboratories to overcome technical barriers to the large-scale deployment of solar technologies. To support these goals, the subprogram invests primarily in four areas: grid integration, technology validation, solar resource assessment, and balance of system development.

  10. Academic Research Integration System

    ERIC Educational Resources Information Center

    Surugiu, Iula; Velicano, Manole

    2008-01-01

    This paper comprises results concluding the research activity done so far regarding enhanced web services and system integration. The objective of the paper is to define the software architecture for a coherent framework and methodology for enhancing existing web services into an integrated system. This document presents the research work that has…

  11. [System biology and synthetic biology modify drug discovery and development].

    PubMed

    Haiech, Jacques; Ranjeva, Raoul; Kilhoffer, Marie-Claude

    2012-02-01

    Life Sciences are built on observations. Right now, a more systemic approach allowing to integrate the different organizational levels in Biology is emerging. Such an approach uses a set of technologies and strategies allowing to build models that appear to be more and more predictive (omics, bioinformatics, integrative biology, computational biology…). Those models accelerate the rational development of new therapies avoiding an engineering based only on trials and errors. This approach both holistic and predictive radically modifies the discovery and development modalities used today in health industries. Moreover, because of the apparition of new jobs at the interface of disciplines, of private and public sectors and of life sciences and engineering sciences, this implies to rethink the training programs in both their contents and their pedagogical tools.

  12. From Artificial Chemistries to Systems Biology

    NASA Astrophysics Data System (ADS)

    Kaleta, Christoph

    Artificial Chemistries abstract from real-world chemistries by reducing them to systems of interacting and reacting molecules. They have been used to study phenomena in a wide array of fields like social and ecological modelling, evolution or chemical computing. Artificial Chemistries are inherently difficult to study and, thus, methods have been proposed to analyze their complexity. This chapter outlines how the concept of chemical organization and software dedicated at their analysis can help to ease this task. The chemical organizations of a reaction network correspond to sets of molecules that can coexist over long periods of (simulation-) time. Thus, they can be used to study the full dynamic behavior a system can exhibit without the need to simulate it in every detail. Due to this appealing property, Chemical Organization Theory has been used in the study of a wide array of systems ranging from Artificial Chemistries to real-world chemistries and biological systems. Especially the analysis of biological systems motivated an integration of the tools dedicated to the study of chemical organizations into an application framework from Systems Biology. The benefit of this integration is that tools from Systems Biology can be used without much effort along with the tools for the computation of chemical organizations and vice versa. Thus, software for the analysis of chemical organizations seamlessly integrates into a framework covering almost any aspect of network design and analysis.

  13. Integrated Optic Chemical-Biological Sensors

    DTIC Science & Technology

    1999-02-26

    biomedical, and food safety applications that has the potential to fulfill many of the technical and performance demands. The sensor system is...within + 1 arc degree. Integrated interferometric based sensors have been developed to the prototype level for environmental, biomedical and food safety applications...system designed for food safety applications (exclusive of a flow cell) is shown in Figure 5. Dimensions of this package are approximately 2.5 x 3.0 x

  14. Use of a combination of methods of biological and physicochemical utilization of vegetative waste products and the human's exometabolites for creation of integrated life support systems

    NASA Astrophysics Data System (ADS)

    Zolotukhin, I. G.; Tikhomirov, A. A.; Kudenko, Y. A.; Gribovskaya, I. V.

    solution NaCl concentration was supported at a constant level and made up about 0,26 %. Distribution of total NaCl in the system components considered looked as follows: in roots - 0,7 %, in grain - 1,7 %, in straw - 2,9 %, in a nutrient solution - 16,3 % by the end of experiments. In the report the opportunities of use of the technologies considered for creation integrated biological-physicochemical LSS with a high degree of closure of internal mass exchange are discussed.

  15. A Systems Biology Approach to Reveal Putative Host-Derived Biomarkers of Periodontitis by Network Topology Characterization of MMP-REDOX/NO and Apoptosis Integrated Pathways.

    PubMed

    Zeidán-Chuliá, Fares; Gürsoy, Mervi; Neves de Oliveira, Ben-Hur; Özdemir, Vural; Könönen, Eija; Gürsoy, Ulvi K

    2015-01-01

    Periodontitis, a formidable global health burden, is a common chronic disease that destroys tooth-supporting tissues. Biomarkers of the early phase of this progressive disease are of utmost importance for global health. In this context, saliva represents a non-invasive biosample. By using systems biology tools, we aimed to (1) identify an integrated interactome between matrix metalloproteinase (MMP)-REDOX/nitric oxide (NO) and apoptosis upstream pathways of periodontal inflammation, and (2) characterize the attendant topological network properties to uncover putative biomarkers to be tested in saliva from patients with periodontitis. Hence, we first generated a protein-protein network model of interactions ("BIOMARK" interactome) by using the STRING 10 database, a search tool for the retrieval of interacting genes/proteins, with "Experiments" and "Databases" as input options and a confidence score of 0.400. Second, we determined the centrality values (closeness, stress, degree or connectivity, and betweenness) for the "BIOMARK" members by using the Cytoscape software. We found Ubiquitin C (UBC), Jun proto-oncogene (JUN), and matrix metalloproteinase-14 (MMP14) as the most central hub- and non-hub-bottlenecks among the 211 genes/proteins of the whole interactome. We conclude that UBC, JUN, and MMP14 are likely an optimal candidate group of host-derived biomarkers, in combination with oral pathogenic bacteria-derived proteins, for detecting periodontitis at its early phase by using salivary samples from patients. These findings therefore have broader relevance for systems medicine in global health as well.

  16. The nature of systems biology.

    PubMed

    Bruggeman, Frank J; Westerhoff, Hans V

    2007-01-01

    The advent of functional genomics has enabled the molecular biosciences to come a long way towards characterizing the molecular constituents of life. Yet, the challenge for biology overall is to understand how organisms function. By discovering how function arises in dynamic interactions, systems biology addresses the missing links between molecules and physiology. Top-down systems biology identifies molecular interaction networks on the basis of correlated molecular behavior observed in genome-wide "omics" studies. Bottom-up systems biology examines the mechanisms through which functional properties arise in the interactions of known components. Here, we outline the challenges faced by systems biology and discuss limitations of the top-down and bottom-up approaches, which, despite these limitations, have already led to the discovery of mechanisms and principles that underlie cell function.

  17. A Philosophical Perspective on Evolutionary Systems Biology.

    PubMed

    O'Malley, Maureen A; Soyer, Orkun S; Siegal, Mark L

    2015-03-01

    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.

  18. 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

  19. Integrated library systems.

    PubMed Central

    Goldstein, C M

    1983-01-01

    The development of integrated library systems is discussed. The four major discussion points are (1) initial efforts; (2) network resources; (3) minicomputer-based systems; and (4) beyond library automation. Four existing systems are cited as examples of current systems. PMID:6354321

  20. Data Integration and Mining for Synthetic Biology Design.

    PubMed

    Mısırlı, Göksel; Hallinan, Jennifer; Pocock, Matthew; Lord, Phillip; McLaughlin, James Alastair; Sauro, Herbert; Wipat, Anil

    2016-10-21

    One aim of synthetic biologists is to create novel and predictable biological systems from simpler modular parts. This approach is currently hampered by a lack of well-defined and characterized parts and devices. However, there is a wealth of existing biological information, which can be used to identify and characterize biological parts, and their design constraints in the literature and numerous biological databases. However, this information is spread among these databases in many different formats. New computational approaches are required to make this information available in an integrated format that is more amenable to data mining. A tried and tested approach to this problem is to map disparate data sources into a single data set, with common syntax and semantics, to produce a data warehouse or knowledge base. Ontologies have been used extensively in the life sciences, providing this common syntax and semantics as a model for a given biological domain, in a fashion that is amenable to computational analysis and reasoning. Here, we present an ontology for applications in synthetic biology design, SyBiOnt, which facilitates the modeling of information about biological parts and their relationships. SyBiOnt was used to create the SyBiOntKB knowledge base, incorporating and building upon existing life sciences ontologies and standards. The reasoning capabilities of ontologies were then applied to automate the mining of biological parts from this knowledge base. We propose that this approach will be useful to speed up synthetic biology design and ultimately help facilitate the automation of the biological engineering life cycle.

  1. Integrated Systems Biology Analysis of Transcriptomes Reveals Candidate Genes for Acidity Control in Developing Fruits of Sweet Orange (Citrus sinensis L. Osbeck)

    PubMed Central

    Huang, Dingquan; Zhao, Yihong; Cao, Minghao; Qiao, Liang; Zheng, Zhi-Liang

    2016-01-01

    Organic acids, such as citrate and malate, are important contributors for the sensory traits of fleshy fruits. Although their biosynthesis has been illustrated, regulatory mechanisms of acid accumulation remain to be dissected. To provide transcriptional architecture and identify candidate genes for citrate accumulation in fruits, we have selected for transcriptome analysis four varieties of sweet orange (Citrus sinensis L. Osbeck) with varying fruit acidity, Succari (acidless), Bingtang (low acid), and Newhall and Xinhui (normal acid). Fruits of these varieties at 45 days post anthesis (DPA), which corresponds to Stage I (cell division), had similar acidity, but they displayed differential acid accumulation at 142 DPA (Stage II, cell expansion). Transcriptomes of fruits at 45 and 142 DPA were profiled using RNA sequencing and analyzed with three different algorithms (Pearson correlation, gene coexpression network and surrogate variable analysis). Our network analysis shows that the acid-correlated genes belong to three distinct network modules. Several of these candidate fruit acidity genes encode regulatory proteins involved in transport (such as AHA10), degradation (such as APD2) and transcription (such as AIL6) and act as hubs in the citrate accumulation gene networks. Taken together, our integrated systems biology analysis has provided new insights into the fruit citrate accumulation gene network and led to the identification of candidate genes likely associated with the fruit acidity control. PMID:27092171

  2. Integrated Systems Biology Analysis of Transcriptomes Reveals Candidate Genes for Acidity Control in Developing Fruits of Sweet Orange (Citrus sinensis L. Osbeck).

    PubMed

    Huang, Dingquan; Zhao, Yihong; Cao, Minghao; Qiao, Liang; Zheng, Zhi-Liang

    2016-01-01

    Organic acids, such as citrate and malate, are important contributors for the sensory traits of fleshy fruits. Although their biosynthesis has been illustrated, regulatory mechanisms of acid accumulation remain to be dissected. To provide transcriptional architecture and identify candidate genes for citrate accumulation in fruits, we have selected for transcriptome analysis four varieties of sweet orange (Citrus sinensis L. Osbeck) with varying fruit acidity, Succari (acidless), Bingtang (low acid), and Newhall and Xinhui (normal acid). Fruits of these varieties at 45 days post anthesis (DPA), which corresponds to Stage I (cell division), had similar acidity, but they displayed differential acid accumulation at 142 DPA (Stage II, cell expansion). Transcriptomes of fruits at 45 and 142 DPA were profiled using RNA sequencing and analyzed with three different algorithms (Pearson correlation, gene coexpression network and surrogate variable analysis). Our network analysis shows that the acid-correlated genes belong to three distinct network modules. Several of these candidate fruit acidity genes encode regulatory proteins involved in transport (such as AHA10), degradation (such as APD2) and transcription (such as AIL6) and act as hubs in the citrate accumulation gene networks. Taken together, our integrated systems biology analysis has provided new insights into the fruit citrate accumulation gene network and led to the identification of candidate genes likely associated with the fruit acidity control.

  3. Magellan: a web based system for the integrated analysis of heterogeneous biological data and annotations; application to DNA copy number and expression data in ovarian cancer.

    PubMed

    Kingsley, Chris B; Kuo, Wen-Lin; Polikoff, Daniel; Berchuck, Andy; Gray, Joe W; Jain, Ajay N

    2007-02-05

    Recent advances in high throughput biological methods allow researchers to generate enormous amounts of data from a single experiment. In order to extract meaningful conclusions from this tidal wave of data, it will be necessary to develop analytical methods of sufficient power and utility. It is particularly important that biologists themselves be able to perform many of these analyses, such that their background knowledge of the experimental system under study can be used to interpret results and direct further inquiries. We have developed a web-based system, Magellan, which allows the upload, storage, and analysis of multivariate data and textual or numerical annotations. Data and annotations are treated as abstract entities, to maximize the different types of information the system can store and analyze. Annotations can be used in analyses/visualizations, as a means of subsetting data to reduce dimensionality, or as a means of projecting variables from one data type or data set to another. Analytical methods are deployed within Magellan such that new functionalities can be added in a straightforward fashion. Using Magellan, we performed an integrated analysis of genome-wide comparative genomic hybridization (CGH), mRNA expression, and clinical data from ovarian tumors. Analyses included the use of permutation-based methods to identify genes whose mRNA expression levels correlated with patient survival, a nearest neighbor classifier to predict patient survival from CGH data, and curated annotations such as genomic position and derived annotations such as statistical computations to explore the quantitative relationship between CGH and mRNA expression data.

  4. Systems Integration Fact Sheet

    SciTech Connect

    2016-06-01

    This fact sheet is an overview of the Systems Integration subprogram at the U.S. Department of Energy SunShot Initiative. The Systems Integration subprogram enables the widespread deployment of safe, reliable, and cost-effective solar energy technologies by addressing the associated technical and non-technical challenges. These include timely and cost-effective interconnection procedures, optimal system planning, accurate prediction of solar resources, monitoring and control of solar power, maintaining grid reliability and stability, and many more. To address the challenges associated with interconnecting and integrating hundreds of gigawatts of solar power onto the electricity grid, the Systems Integration program funds research, development, and demonstration projects in four broad, interrelated focus areas: grid performance and reliability, dispatchability, power electronics, and communications.

  5. Human Systems Integration Introduction

    NASA Video Gallery

    This lecture provides an overview of Human Systems Integration (HSI), its implementation cost and return on investment, HSI domains, how HSI fits into the NASA organization structure, HSI roles and...

  6. Semiconductor Devices Inspired By and Integrated With Biology

    SciTech Connect

    Rogers, John

    2012-04-25

    Biology is curved, soft and elastic; silicon wafers are not. Semiconductor technologies that can bridge this gap in form and mechanics will create new opportunities in devices that adopt biologically inspired designs or require intimate integration with the human body. This talk describes the development of ideas for electronics that offer the performance of state-of-the-art, wafer- based systems but with the mechanical properties of a rubber band. We explain the underlying materials science and mechanics of these approaches, and illustrate their use in (1) bio- integrated, ‘tissue-like’ electronics with unique capabilities for mapping cardiac and neural electrophysiology, and (2) bio-inspired, ‘eyeball’ cameras with exceptional imaging properties enabled by curvilinear, Petzval designs.

  7. History matters: ecometrics and integrative climate change biology.

    PubMed

    Polly, P David; Eronen, Jussi T; Fred, Marianne; Dietl, Gregory P; Mosbrugger, Volker; Scheidegger, Christoph; Frank, David C; Damuth, John; Stenseth, Nils C; Fortelius, Mikael

    2011-04-22

    Climate change research is increasingly focusing on the dynamics among species, ecosystems and climates. Better data about the historical behaviours of these dynamics are urgently needed. Such data are already available from ecology, archaeology, palaeontology and geology, but their integration into climate change research is hampered by differences in their temporal and geographical scales. One productive way to unite data across scales is the study of functional morphological traits, which can form a common denominator for studying interactions between species and climate across taxa, across ecosystems, across space and through time-an approach we call 'ecometrics'. The sampling methods that have become established in palaeontology to standardize over different scales can be synthesized with tools from community ecology and climate change biology to improve our understanding of the dynamics among species, ecosystems, climates and earth systems over time. Developing these approaches into an integrative climate change biology will help enrich our understanding of the changes our modern world is undergoing.

  8. 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.

  9. 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.…

  10. 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.

  11. Integration of culture and biology in human development.

    PubMed

    Mistry, Jayanthi

    2013-01-01

    The challenge of integrating biology and culture is addressed in this chapter by emphasizing human development as involving mutually constitutive, embodied, and epigenetic processes. Heuristically rich constructs extrapolated from cultural psychology and developmental science, such as embodiment, action, and activity, are presented as promising approaches to the integration of cultural and biology in human development. These theoretical notions are applied to frame the nascent field of cultural neuroscience as representing this integration of culture and biology. Current empirical research in cultural neuroscience is then synthesized to illustrate emerging trends in this body of literature that examine the integration of biology and culture.

  12. 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

  13. Biological condition gradient: Applying a framework for determining the biological integrity of coral reefs

    EPA Science Inventory

    The goals of the U.S. Clean Water Act (CWA) are to restore and maintain the chemical, physical and biological integrity of water resources. Although clean water is a goal, another is to safeguard biological communities by defining levels of biological integrity to protect aquatic...

  14. A Systems Biology-Based Investigation into the Pharmacological Mechanisms of Sheng-ma-bie-jia-tang Acting on Systemic Lupus Erythematosus by Multi-Level Data Integration

    PubMed Central

    Huang, Lin; Lv, Qi; Liu, Fenfen; Shi, Tieliu; Wen, Chengping

    2015-01-01

    Sheng-ma-bie-jia-tang (SMBJT) is a Traditional Chinese Medicine (TCM) formula that is widely used for the treatment of Systemic Lupus Erythematosus (SLE) in China. However, molecular mechanism behind this formula remains unknown. Here, we systematically analyzed targets of the ingredients in SMBJT to evaluate its potential molecular mechanism. First, we collected 1,267 targets from our previously published database, the Traditional Chinese Medicine Integrated Database (TCMID). Next, we conducted gene ontology and pathway enrichment analyses for these targets and determined that they were enriched in metabolism (amino acids, fatty acids, etc.) and signaling pathways (chemokines, Toll-like receptors, adipocytokines, etc.). 96 targets, which are known SLE disease proteins, were identified as essential targets and the rest 1,171 targets were defined as common targets of this formula. The essential targets directly interacted with SLE disease proteins. Besides, some common targets also had essential connections to both key targets and SLE disease proteins in enriched signaling pathway, e.g. toll-like receptor signaling pathway. We also found distinct function of essential and common targets in immune system processes. This multi-level approach to deciphering the underlying mechanism of SMBJT treatment of SLE details a new perspective that will further our understanding of TCM formulas. PMID:26560501

  15. A Systems Biology-Based Investigation into the Pharmacological Mechanisms of Sheng-ma-bie-jia-tang Acting on Systemic Lupus Erythematosus by Multi-Level Data Integration.

    PubMed

    Huang, Lin; Lv, Qi; Liu, Fenfen; Shi, Tieliu; Wen, Chengping

    2015-11-12

    Sheng-ma-bie-jia-tang (SMBJT) is a Traditional Chinese Medicine (TCM) formula that is widely used for the treatment of Systemic Lupus Erythematosus (SLE) in China. However, molecular mechanism behind this formula remains unknown. Here, we systematically analyzed targets of the ingredients in SMBJT to evaluate its potential molecular mechanism. First, we collected 1,267 targets from our previously published database, the Traditional Chinese Medicine Integrated Database (TCMID). Next, we conducted gene ontology and pathway enrichment analyses for these targets and determined that they were enriched in metabolism (amino acids, fatty acids, etc.) and signaling pathways (chemokines, Toll-like receptors, adipocytokines, etc.). 96 targets, which are known SLE disease proteins, were identified as essential targets and the rest 1,171 targets were defined as common targets of this formula. The essential targets directly interacted with SLE disease proteins. Besides, some common targets also had essential connections to both key targets and SLE disease proteins in enriched signaling pathway, e.g. toll-like receptor signaling pathway. We also found distinct function of essential and common targets in immune system processes. This multi-level approach to deciphering the underlying mechanism of SMBJT treatment of SLE details a new perspective that will further our understanding of TCM formulas.

  16. 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

  17. Integrated biogas systems

    NASA Astrophysics Data System (ADS)

    Amaratunga, M.

    1980-01-01

    Integrated biogas systems as alternatives to fossil fuels in Sri Lanka are considered from standpoints of population growth, land availability, and employment opportunities. Agricultural practices would be improved by use of chemical fertilizers, and health/nutrition problems be alleviated by using biogas systems. Fuel for cooking and rural industries will become more easily available; water weeds, such as water hyacinth and salvinia which pose a threat to waterways and rice paddy lands could be used for the production of biogas and fertilizers. A concept of an integrated biogas system comprising photosynthesis and anaerobic degradation processes to produce food and energy is presented.

  18. Improving Integration Effectiveness of ID Mapping Based Biological Record Linkage.

    PubMed

    Jamil, Hasan M

    2015-01-01

    Traditionally, biological objects such as genes, proteins, and pathways are represented by a convenient identifier, or ID, which is then used to cross reference, link and describe objects in biological databases. Relationships among the objects are often established using non-trivial and computationally complex ID mapping systems or converters, and are stored in authoritative databases such as UniGene, GeneCards, PIR and BioMart. Despite best efforts, such mappings are largely incomplete and riddled with false negatives. Consequently, data integration using record linkage that relies on these mappings produces poor quality of data, inadvertently leading to erroneous conclusions. In this paper, we discuss this largely ignored dimension of data integration, examine how the ubiquitous use of identifiers in biological databases is a significant barrier to knowledge fusion using distributed computational pipelines, and propose two algorithms for ad hoc and restriction free ID mapping of arbitrary types using online resources. We also propose two declarative statements for ID conversion and data integration based on ID mapping on-the-fly.

  19. The "Integrated Library System."

    ERIC Educational Resources Information Center

    Dowlin, Kenneth E.

    1985-01-01

    Reviews internal and external dimensions of library environment that must be taken into account by library managers when choosing an integrated library system. The selection, acquisition, and implementation stages of Maggie III--a computerized library system sensitive to the internal and external organizational environment--are described. (MBR)

  20. Aviation Data Integration System

    NASA Technical Reports Server (NTRS)

    Kulkarni, Deepak; Wang, Yao; Windrem, May; Patel, Hemil; Keller, Richard

    2003-01-01

    During the analysis of flight data and safety reports done in ASAP and FOQA programs, airline personnel are not able to access relevant aviation data for a variety of reasons. We have developed the Aviation Data Integration System (ADIS), a software system that provides integrated heterogeneous data to support safety analysis. Types of data available in ADIS include weather, D-ATIS, RVR, radar data, and Jeppesen charts, and flight data. We developed three versions of ADIS to support airlines. The first version has been developed to support ASAP teams. A second version supports FOQA teams, and it integrates aviation data with flight data while keeping identification information inaccessible. Finally, we developed a prototype that demonstrates the integration of aviation data into flight data analysis programs. The initial feedback from airlines is that ADIS is very useful in FOQA and ASAP analysis.

  1. On Quantum Integrable Systems

    SciTech Connect

    Danilov, Viatcheslav; Nagaitsev, Sergei; /Fermilab

    2011-11-01

    Many quantum integrable systems are obtained using an accelerator physics technique known as Ermakov (or normalized variables) transformation. This technique was used to create classical nonlinear integrable lattices for accelerators and nonlinear integrable plasma traps. Now, all classical results are carried over to a nonrelativistic quantum case. In this paper we have described an extension of the Ermakov-like transformation to the Schroedinger and Pauli equations. It is shown that these newly found transformations create a vast variety of time dependent quantum equations that can be solved in analytic functions, or, at least, can be reduced to time-independent ones.

  2. 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…

  3. Integrated work management system.

    SciTech Connect

    Williams, Edward J., Jr.; Henry, Karen Lynne

    2010-06-01

    Sandia National Laboratories develops technologies to: (1) sustain, modernize, and protect our nuclear arsenal (2) Prevent the spread of weapons of mass destruction; (3) Provide new capabilities to our armed forces; (4) Protect our national infrastructure; (5) Ensure the stability of our nation's energy and water supplies; and (6) Defend our nation against terrorist threats. We identified the need for a single overarching Integrated Workplace Management System (IWMS) that would enable us to focus on customer missions and improve FMOC processes. Our team selected highly configurable commercial-off-the-shelf (COTS) software with out-of-the-box workflow processes that integrate strategic planning, project management, facility assessments, and space management, and can interface with existing systems, such as Oracle, PeopleSoft, Maximo, Bentley, and FileNet. We selected the Integrated Workplace Management System (IWMS) from Tririga, Inc. Facility Management System (FMS) Benefits are: (1) Create a single reliable source for facility data; (2) Improve transparency with oversight organizations; (3) Streamline FMOC business processes with a single, integrated facility-management tool; (4) Give customers simple tools and real-time information; (5) Reduce indirect costs; (6) Replace approximately 30 FMOC systems and 60 homegrown tools (such as Microsoft Access databases); and (7) Integrate with FIMS.

  4. Investigation of ifosfamide and chloroacetaldehyde renal toxicity through integration of in vitro liver-kidney microfluidic data and pharmacokinetic-system biology models.

    PubMed

    Leclerc, Eric; Hamon, Jeremy; Bois, Frederic Yves

    2016-02-01

    We have integrated in vitro and in silico data to describe the toxicity of chloroacetaldehyde (CAA) on renal cells via its production from the metabolism of ifosfamide (IFO) by hepatic cells. A pharmacokinetic (PK) model described the production of CAA by the hepatocytes and its transport to the renal cells. A system biology model was coupled to the PK model to describe the production of reactive oxygen species (ROS) induced by CAA in the renal cells. In response to the ROS production, the metabolism of glutathione (GSH) and its depletion were modeled by the action of an NFE2L2 gene-dependent pathway. The model parameters were estimated in a Bayesian context via Markov Chain Monte Carlo (MCMC) simulations based on microfluidic experiments and literature in vitro data. Hepatic IFO and CAA in vitro intrinsic clearances were estimated to be 1.85 x 10(-9) μL s(-1) cell(-1) and 0.185 x 10(-9) μL s(-1) cell(-1) ,respectively (corresponding to an in vivo intrinsic IFO clearance estimate of 1.23 l h(-1) , to be compared to IFO published values ranging from 3 to 10 l h(-1) ). After model calibration, simulations made at therapeutic doses of IFO showed CAA renal intracellular concentrations ranging from 11 to 131 μM. Intracellular CAA concentrations above 70 μM induced intense ROS production and GSH depletion. Those responses were time and dose dependent, showing transient and non-linear kinetics. Those results are in agreement with literature data reporting that intracellular CAA toxic concentrations range from 35 to 320 μM, after therapeutic ifosfamide dosing. The results were also consistent with in vitro CAA renal cytotoxicity data.

  5. Systems Biology: The Next Frontier for Bioinformatics

    PubMed Central

    Likić, Vladimir A.; McConville, Malcolm J.; Lithgow, Trevor; Bacic, Antony

    2010-01-01

    Biochemical systems biology augments more traditional disciplines, such as genomics, biochemistry and molecular biology, by championing (i) mathematical and computational modeling; (ii) the application of traditional engineering practices in the analysis of biochemical systems; and in the past decade increasingly (iii) the use of near-comprehensive data sets derived from ‘omics platform technologies, in particular “downstream” technologies relative to genome sequencing, including transcriptomics, proteomics and metabolomics. The future progress in understanding biological principles will increasingly depend on the development of temporal and spatial analytical techniques that will provide high-resolution data for systems analyses. To date, particularly successful were strategies involving (a) quantitative measurements of cellular components at the mRNA, protein and metabolite levels, as well as in vivo metabolic reaction rates, (b) development of mathematical models that integrate biochemical knowledge with the information generated by high-throughput experiments, and (c) applications to microbial organisms. The inevitable role bioinformatics plays in modern systems biology puts mathematical and computational sciences as an equal partner to analytical and experimental biology. Furthermore, mathematical and computational models are expected to become increasingly prevalent representations of our knowledge about specific biochemical systems. PMID:21331364

  6. Bayesian integration of position and orientation cues in perception of biological and non-biological forms.

    PubMed

    Thurman, Steven M; Lu, Hongjing

    2014-01-01

    Visual form analysis is fundamental to shape perception and likely plays a central role in perception of more complex dynamic shapes, such as moving objects or biological motion. Two primary form-based cues serve to represent the overall shape of an object: the spatial position and the orientation of locations along the boundary of the object. However, it is unclear how the visual system integrates these two sources of information in dynamic form analysis, and in particular how the brain resolves ambiguities due to sensory uncertainty and/or cue conflict. In the current study, we created animations of sparsely-sampled dynamic objects (human walkers or rotating squares) comprised of oriented Gabor patches in which orientation could either coincide or conflict with information provided by position cues. When the cues were incongruent, we found a characteristic trade-off between position and orientation information whereby position cues increasingly dominated perception as the relative uncertainty of orientation increased and vice versa. Furthermore, we found no evidence for differences in the visual processing of biological and non-biological objects, casting doubt on the claim that biological motion may be specialized in the human brain, at least in specific terms of form analysis. To explain these behavioral results quantitatively, we adopt a probabilistic template-matching model that uses Bayesian inference within local modules to estimate object shape separately from either spatial position or orientation signals. The outputs of the two modules are integrated with weights that reflect individual estimates of subjective cue reliability, and integrated over time to produce a decision about the perceived dynamics of the input data. Results of this model provided a close fit to the behavioral data, suggesting a mechanism in the human visual system that approximates rational Bayesian inference to integrate position and orientation signals in dynamic form analysis.

  7. Multifunctional integration: from biological to bio-inspired materials.

    PubMed

    Liu, Kesong; Jiang, Lei

    2011-09-27

    Nature is a school for human beings. Learning from nature has long been a source of bioinspiration for scientists and engineers. Multiscale structures are characteristic for biological materials, exhibiting inherent multifunctional integration. Optimized biological solutions provide inspiration for scientists and engineers to design and to fabricate multiscale structured materials for multifunctional integration.

  8. Integrated system design report

    SciTech Connect

    Not Available

    1989-07-01

    The primary objective of the integrated system test phase is to demonstrate the commercial potential of a coal fueled diesel engine in its actual operating environment. The integrated system in this project is defined as a coal fueled diesel locomotive. This locomotive, shown on drawing 41D715542, is described in the separate Concept Design Report. The test locomotive will be converted from an existing oil fueled diesel locomotive in three stages, until it nearly emulates the concept locomotive. Design drawings of locomotive components (diesel engine, locomotive, flatcar, etc.) are included.

  9. Integrated transducer systems

    NASA Astrophysics Data System (ADS)

    Syrzycki, Marek; Parameswaran, M.; Chapman, Glenn H.

    1995-06-01

    In the paper we discuss possible solutions to problems pertaining the implementation of integrated transducer systems, based on examples of WSI image transducers, magnetic field sensors and tactile sensors arrays, as well as arrays of chemical sensors. We also present the issues common to large area transducer arrays, such as building-in redundancy into WSI transducer arrays, and frequency domain circuits for the future communication pathway in integrated transducer systems. Advantages of standard CMOS technology, enhanced with various post-fabrication processes such as silicon micromachining and laser linking, are also stressed.

  10. Teaching the fundamentals of biological data integration using classroom games.

    PubMed

    Schneider, Maria Victoria; Jimenez, Rafael C

    2012-01-01

    This article aims to introduce the nature of data integration to life scientists. Generally, the subject of data integration is not discussed outside the field of computational science and is not covered in any detail, or even neglected, when teaching/training trainees. End users (hereby defined as wet-lab trainees, clinicians, lab researchers) will mostly interact with bioinformatics resources and tools through web interfaces that mask the user from the data integration processes. However, the lack of formal training or acquaintance with even simple database concepts and terminology often results in a real obstacle to the full comprehension of the resources and tools the end users wish to access. Understanding how data integration works is fundamental to empowering trainees to see the limitations as well as the possibilities when exploring, retrieving, and analysing biological data from databases. Here we introduce a game-based learning activity for training/teaching the topic of data integration that trainers/educators can adopt and adapt for their classroom. In particular we provide an example using DAS (Distributed Annotation Systems) as a method for data integration.

  11. SysBioCube: A Data Warehouse and Integrative Data Analysis Platform Facilitating Systems Biology Studies of Disorders of Military Relevance

    DTIC Science & Technology

    2013-12-18

    Robert Stephens 1 1 Advanced Biomedical Computing Center, Frederick National Laboratory for Cancer Research/SAIC-Frederick Inc., Frederick, MD 2...data types (Figure 2) such as mouse behavioral studies, neurohistology, histopathology, transcriptomics, epigenomics, metabolomics and physiological...epigenome and metabolome profiling have become important as they provide better understanding of the biological systems4-6. An effective way to interpret

  12. Integrating Mathematics into the Introductory Biology Laboratory Course

    ERIC Educational Resources Information Center

    White, James D.; Carpenter, Jenna P.

    2008-01-01

    Louisiana Tech University has an integrated science curriculum for its mathematics, chemistry, physics, computer science, biology-research track and secondary mathematics and science education majors. The curriculum focuses on the calculus sequence and introductory labs in biology, physics, and chemistry. In the introductory biology laboratory…

  13. Integrated Modular Teaching of Human Biology for Primary Care Practitioners

    ERIC Educational Resources Information Center

    Glasgow, Michael S.

    1977-01-01

    Describes the use of integrated modular teaching of the human biology component of the Health Associate Program at Johns Hopkins University, where the goal is to develop an understanding of the sciences as applied to primary care. Discussion covers the module sequence, the human biology faculty, goals of the human biology faculty, laboratory…

  14. 2K09 and thereafter : the coming era of integrative bioinformatics, systems biology and intelligent computing for functional genomics and personalized medicine research.

    PubMed

    Yang, Jack Y; Niemierko, Andrzej; Bajcsy, Ruzena; Xu, Dong; Athey, Brian D; Zhang, Aidong; Ersoy, Okan K; Li, Guo-Zheng; Borodovsky, Mark; Zhang, Joe C; Arabnia, Hamid R; Deng, Youping; Dunker, A Keith; Liu, Yunlong; Ghafoor, Arif

    2010-12-01

    Significant interest exists in establishing synergistic research in bioinformatics, systems biology and intelligent computing. Supported by the United States National Science Foundation (NSF), International Society of Intelligent Biological Medicine (http://www.ISIBM.org), International Journal of Computational Biology and Drug Design (IJCBDD) and International Journal of Functional Informatics and Personalized Medicine, the ISIBM International Joint Conferences on Bioinformatics, Systems Biology and Intelligent Computing (ISIBM IJCBS 2009) attracted more than 300 papers and 400 researchers and medical doctors world-wide. It was the only inter/multidisciplinary conference aimed to promote synergistic research and education in bioinformatics, systems biology and intelligent computing. The conference committee was very grateful for the valuable advice and suggestions from honorary chairs, steering committee members and scientific leaders including Dr. Michael S. Waterman (USC, Member of United States National Academy of Sciences), Dr. Chih-Ming Ho (UCLA, Member of United States National Academy of Engineering and Academician of Academia Sinica), Dr. Wing H. Wong (Stanford, Member of United States National Academy of Sciences), Dr. Ruzena Bajcsy (UC Berkeley, Member of United States National Academy of Engineering and Member of United States Institute of Medicine of the National Academies), Dr. Mary Qu Yang (United States National Institutes of Health and Oak Ridge, DOE), Dr. Andrzej Niemierko (Harvard), Dr. A. Keith Dunker (Indiana), Dr. Brian D. Athey (Michigan), Dr. Weida Tong (FDA, United States Department of Health and Human Services), Dr. Cathy H. Wu (Georgetown), Dr. Dong Xu (Missouri), Drs. Arif Ghafoor and Okan K Ersoy (Purdue), Dr. Mark Borodovsky (Georgia Tech, President of ISIBM), Dr. Hamid R. Arabnia (UGA, Vice-President of ISIBM), and other scientific leaders. The committee presented the 2009 ISIBM Outstanding Achievement Awards to Dr. Joydeep Ghosh (UT

  15. 2K09 and thereafter : the coming era of integrative bioinformatics, systems biology and intelligent computing for functional genomics and personalized medicine research

    PubMed Central

    2010-01-01

    Significant interest exists in establishing synergistic research in bioinformatics, systems biology and intelligent computing. Supported by the United States National Science Foundation (NSF), International Society of Intelligent Biological Medicine (http://www.ISIBM.org), International Journal of Computational Biology and Drug Design (IJCBDD) and International Journal of Functional Informatics and Personalized Medicine, the ISIBM International Joint Conferences on Bioinformatics, Systems Biology and Intelligent Computing (ISIBM IJCBS 2009) attracted more than 300 papers and 400 researchers and medical doctors world-wide. It was the only inter/multidisciplinary conference aimed to promote synergistic research and education in bioinformatics, systems biology and intelligent computing. The conference committee was very grateful for the valuable advice and suggestions from honorary chairs, steering committee members and scientific leaders including Dr. Michael S. Waterman (USC, Member of United States National Academy of Sciences), Dr. Chih-Ming Ho (UCLA, Member of United States National Academy of Engineering and Academician of Academia Sinica), Dr. Wing H. Wong (Stanford, Member of United States National Academy of Sciences), Dr. Ruzena Bajcsy (UC Berkeley, Member of United States National Academy of Engineering and Member of United States Institute of Medicine of the National Academies), Dr. Mary Qu Yang (United States National Institutes of Health and Oak Ridge, DOE), Dr. Andrzej Niemierko (Harvard), Dr. A. Keith Dunker (Indiana), Dr. Brian D. Athey (Michigan), Dr. Weida Tong (FDA, United States Department of Health and Human Services), Dr. Cathy H. Wu (Georgetown), Dr. Dong Xu (Missouri), Drs. Arif Ghafoor and Okan K Ersoy (Purdue), Dr. Mark Borodovsky (Georgia Tech, President of ISIBM), Dr. Hamid R. Arabnia (UGA, Vice-President of ISIBM), and other scientific leaders. The committee presented the 2009 ISIBM Outstanding Achievement Awards to Dr. Joydeep Ghosh (UT

  16. 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,...

  17. 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.

  18. Biological engineering and systems biology--new opportunities for engineers in the pharmaceutical industry.

    PubMed

    Lauffenburger, Douglas A

    2004-01-01

    The consecutive life science revolutions of molecular biology and genomic biology have led to the promise for improving human health by molecular-level interventions--but the accompanying challenge of doing so in a rational, predictive manner. Addressing this challenge, and meeting this promise, requires understanding of complex biological processes with molecular detail but in integrative fashion; the emerging field aimed at this endeavor is now commonly termed 'systems biology'. In many ways, this field is an ideal application area for the biological engineering discipline, and offers tremendous opportunities for biology-based engineers. This talk will present a view of key aspects of this vision.

  19. Theoretical aspects of Systems Biology.

    PubMed

    Bizzarri, Mariano; Palombo, Alessandro; Cucina, Alessandra

    2013-05-01

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

  20. Systems biology for organotypic cell cultures.

    PubMed

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

    2016-11-14

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

  1. Systems Biology for Organotypic Cell Cultures

    SciTech Connect

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

    2016-08-04

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

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

    PubMed

    Wolkenhauer, O

    2001-09-01

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

  3. Power Systems integration

    NASA Technical Reports Server (NTRS)

    Brantley, L. W.

    1982-01-01

    Power systems integration in large flexible space structures is discussed with emphasis upon body control. A solar array is discussed as a typical example of spacecraft configuration problems. Information on how electric batteries dominate life-cycle costs is presented in chart form. Information is given on liquid metal droplet generators and collectors, hot spot analysis, power dissipation in solar arrays, solar array protection optimization, and electromagnetic compatibility for a power system platform.

  4. Integrating Functional, Developmental and Evolutionary Biology into Biology Curricula

    ERIC Educational Resources Information Center

    Haave, Neil

    2012-01-01

    A complete understanding of life involves how organisms are able to function in their environment and how they arise. Understanding how organisms arise involves both their evolution and development. Thus to completely comprehend living things, biology must study their function, development and evolution. Previous proposals for standardized…

  5. Flower biology and biologically-based integrated fire blight management

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fire blight infection is generally initiated in flowers, and thus, research has been directed to the biology and microbial ecology of flowers as related to this disease. In addition to investigations involving apple and pear flowers, Manchurian crab apple (Malus manchurica), closely related to appl...

  6. Integrated chemical-biological treatment of benzo[a]pyrene

    SciTech Connect

    Zeng, Yu; Hong, P.K.A.; Wavrek, D.A.

    2000-03-01

    Benzo[a]pyrene of natural and anthropogenic sources is one of the toxic, mutagenic, polycyclic aromatic hydrocarbons (PAHs) listed as priority pollutants. This study focuses on an integrated treatment of benzo[a]pyrene involving sequential chemical oxidation and biological degradation. The objectives are to (1) provide mechanistic details in the ozone-mediated degradation of benzo[a]pyrene in the aqueous phase, (2) test the biodegradability of resultant intermediates, and (3) test the feasibility for the coupled chemical-biological treatment of the five-ring PAH. Batch and packed column reactors were used to examine the degradation pathways of benzo[a]pyrene subject to ozonation in the aqueous phase. After different ozonation times, samples containing reaction intermediates and byproducts from both reactors were collected, identified for organic contents, and further biologically inoculated to determine their biodegradability. The O{sub 3}-pretreated samples were incubated for 5, 10, 15, and 20 days; afterward biochemical oxygen demand (BOD), chemical oxygen demand (COD), and E. coli toxicity tests were conducted along with qualitative and quantitative determinations of benzo[a]pyrene, intermediates, and reaction products by GC/FID and GC/MS methods. Prevalent intermediates identified at different stages included ring-opened aldehydes, phthalic derivatives, and aliphatics. The degradation of benzo[a]pyrene is primarily initiated via O{sub 3}-mediated ring-opening, followed by O{sub 3} and hydroxyl radical fragmentation, and ultimately brought to complete mineralization primarily via hydroxyl radicals. Intermediates formed during chemical oxidation were biodegradable with a measured first-order rate constant (k{sub 0}) of 0.18 day{sup {minus}1}. The integrated chemical-biological system seems feasible for treating recalcitrant compounds, while pretreatment by chemical oxidation appears useful in promoting soluble intermediates from otherwise highly insoluble

  7. Integrating Value Clarification with High School Biology

    ERIC Educational Resources Information Center

    Barman, Charles R.

    1975-01-01

    Reports on research to see if value clarification would affect student attitudes toward science and biology and improve achievement in a BSCS Yellow Version biology course. Results indicated higher achievement by the group exposed to value clarification but no significant difference in attitudes between this group and the control group. (BR)

  8. Using Multiple Ontologies to Integrate Complex Biological Data

    PubMed Central

    Petri, Victoria; Pasko, Dean; Bromberg, Susan; Wu, Wenhua; Chen, Jiali; Nenasheva, Nataliya; Kwitek, Anne; Twigger, Simon; Jacob, Howard

    2005-01-01

    The strength of the rat as a model organism lies in its utility in pharmacology, biochemistry and physiology research. Data resulting from such studies is difficult to represent in databases and the creation of user-friendly data mining tools has proved difficult. The Rat Genome Database has developed a comprehensive ontology-based data structure and annotation system to integrate physiological data along with environmental and experimental factors, as well as genetic and genomic information. RGD uses multiple ontologies to integrate complex biological information from the molecular level to the whole organism, and to develop data mining and presentation tools. This approach allows RGD to indicate not only the phenotypes seen in a strain but also the specific values under each diet and atmospheric condition, as well as gender differences. Harnessing the power of ontologies in this way allows the user to gather and filter data in a customized fashion, so that a researcher can retrieve all phenotype readings for which a high hypoxia is a factor. Utilizing the same data structure for expression data, pathways and biological processes, RGD will provide a comprehensive research platform which allows users to investigate the conditions under which biological processes are altered and to elucidate the mechanisms of disease. PMID:18629202

  9. Experimental Data from the Proteomics Research Center for Integrative Biology

    DOE Data Explorer

    Smith, Richard D.

    The possible roles and importance of proteomics are rapidly growing across essentially all areas of biological research. The precise and comprehensive measurement of levels of expressed proteins and their modified forms can provide new insights into the molecular nature of cell-signaling pathways and networks, the cell cycle, cellular differentiation, and other processes relevant to understanding human health and the progression of various disease states. The ability to characterize protein complexes complements this capability, allowing hypotheses to be tested and the biological system operation to be defined. The Proteomics Research Center for Integrative Biology is a national user facility established and funded by the National Institute of General Medical Sciences component of the National Institutes of Health. This Center has been established to serve the biomedical research community by developing and integrating new proteomic technologies for collaborative and service studies, disseminating the new technologies, and training scientists in their use. The Center is housed in DOE’s William R. Wiley Environmental Molecular Sciences Laboratory (EMSL) at the Pacific Northwest National Laboratory.

  10. Systems biology of industrial microorganisms.

    PubMed

    Papini, Marta; Salazar, Margarita; Nielsen, Jens

    2010-01-01

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

  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. Stochastic simulation in systems biology

    PubMed Central

    Székely, Tamás; Burrage, Kevin

    2014-01-01

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

  13. Stochastic simulation in systems biology.

    PubMed

    Székely, Tamás; Burrage, Kevin

    2014-11-01

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

  14. Integrating quantitative thinking into an introductory biology course improves students' mathematical reasoning in biological contexts.

    PubMed

    Hester, Susan; Buxner, Sanlyn; Elfring, Lisa; Nagy, Lisa

    2014-01-01

    Recent calls for improving undergraduate biology education have emphasized the importance of students learning to apply quantitative skills to biological problems. Motivated by students' apparent inability to transfer their existing quantitative skills to biological contexts, we designed and taught an introductory molecular and cell biology course in which we integrated application of prerequisite mathematical skills with biology content and reasoning throughout all aspects of the course. In this paper, we describe the principles of our course design and present illustrative examples of course materials integrating mathematics and biology. We also designed an outcome assessment made up of items testing students' understanding of biology concepts and their ability to apply mathematical skills in biological contexts and administered it as a pre/postcourse test to students in the experimental section and other sections of the same course. Precourse results confirmed students' inability to spontaneously transfer their prerequisite mathematics skills to biological problems. Pre/postcourse outcome assessment comparisons showed that, compared with students in other sections, students in the experimental section made greater gains on integrated math/biology items. They also made comparable gains on biology items, indicating that integrating quantitative skills into an introductory biology course does not have a deleterious effect on students' biology learning.

  15. EUCLIS--an information system for circadian systems biology.

    PubMed

    Batista, R T B; Ramirez, D B; Santos, R D; del Rosario, M C I; Mendoza, E R

    2007-09-01

    A major barrier to progress in systems biology is the absence of suitable infrastructure for data and software integration, which would enable working biologists to use and manipulate the techniques directly. We describe the incremental development of key components of such an infrastructure for a research community focused on a specific (but important) biological system. EUCLOCK combines the expertise of 34 chronobiology laboratories from 29 institutions in 11 European countries in a 5-year effort to understand how circadian clocks are synchronised to their specific cyclic environment (entrainment). We envision that the EUCLOCK Information System (EUCLIS) will subsequently evolve to support the worldwide chronobiology community. The architecture of EUCLIS integrates a database for circadian systems biology, containing modules for experimental data (Clock Experiments) and models (Clock Models) with a digital library (Clock KnowledgeBase) for the research community. The digital library paradigm is superior to the simple 'access' or 'mining' as well as the 'data warehouse' approaches currently used in other systems as it provides a flexible framework for community information needs and the potential to use emerging reference models and standards, which will enable easier integration with other systems in the future. The main Clock KnowledgeBase components for EUCLIS V1.0, Clock Genes and Clock Library, are described in detail. An important aspect this work will need to address in the future is the integration of the database and digital library management functions.

  16. Integrating interactive computational modeling in biology curricula.

    PubMed

    Helikar, Tomáš; Cutucache, Christine E; Dahlquist, Lauren M; Herek, Tyler A; Larson, Joshua J; Rogers, Jim A

    2015-03-01

    While the use of computer tools to simulate complex processes such as computer circuits is normal practice in fields like engineering, the majority of life sciences/biological sciences courses continue to rely on the traditional textbook and memorization approach. To address this issue, we explored the use of the Cell Collective platform as a novel, interactive, and evolving pedagogical tool to foster student engagement, creativity, and higher-level thinking. Cell Collective is a Web-based platform used to create and simulate dynamical models of various biological processes. Students can create models of cells, diseases, or pathways themselves or explore existing models. This technology was implemented in both undergraduate and graduate courses as a pilot study to determine the feasibility of such software at the university level. First, a new (In Silico Biology) class was developed to enable students to learn biology by "building and breaking it" via computer models and their simulations. This class and technology also provide a non-intimidating way to incorporate mathematical and computational concepts into a class with students who have a limited mathematical background. Second, we used the technology to mediate the use of simulations and modeling modules as a learning tool for traditional biological concepts, such as T cell differentiation or cell cycle regulation, in existing biology courses. Results of this pilot application suggest that there is promise in the use of computational modeling and software tools such as Cell Collective to provide new teaching methods in biology and contribute to the implementation of the "Vision and Change" call to action in undergraduate biology education by providing a hands-on approach to biology.

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

    PubMed

    Louridas, George E; Lourida, Katerina G

    2017-02-21

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

  18. Conceptual Foundations of Systems Biology Explaining Complex Cardiac Diseases

    PubMed Central

    Louridas, George E.; Lourida, Katerina G.

    2017-01-01

    Systems biology is an important concept that connects molecular biology and genomics with computing science, mathematics and engineering. An endeavor is made in this paper to associate basic conceptual ideas of systems biology with clinical medicine. Complex cardiac diseases are clinical phenotypes generated by integration of genetic, molecular and environmental factors. Basic concepts of systems biology like network construction, modular thinking, biological constraints (downward biological direction) and emergence (upward biological direction) could be applied to clinical medicine. Especially, in the field of cardiology, these concepts can be used to explain complex clinical cardiac phenotypes like chronic heart failure and coronary artery disease. Cardiac diseases are biological complex entities which like other biological phenomena can be explained by a systems biology approach. The above powerful biological tools of systems biology can explain robustness growth and stability during disease process from modulation to phenotype. The purpose of the present review paper is to implement systems biology strategy and incorporate some conceptual issues raised by this approach into the clinical field of complex cardiac diseases. Cardiac disease process and progression can be addressed by the holistic realistic approach of systems biology in order to define in better terms earlier diagnosis and more effective therapy. PMID:28230815

  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. Mathematical methods in systems biology.

    PubMed

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

    2016-12-01

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

  1. Integration of ecological-biological thresholds in conservation decision making.

    PubMed

    Mavrommati, Georgia; Bithas, Kostas; Borsuk, Mark E; Howarth, Richard B

    2016-12-01

    In the Anthropocene, coupled human and natural systems dominate and only a few natural systems remain relatively unaffected by human influence. On the one hand, conservation criteria based on areas of minimal human impact are not relevant to much of the biosphere. On the other hand, conservation criteria based on economic factors are problematic with respect to their ability to arrive at operational indicators of well-being that can be applied in practice over multiple generations. Coupled human and natural systems are subject to economic development which, under current management structures, tends to affect natural systems and cross planetary boundaries. Hence, designing and applying conservation criteria applicable in real-world systems where human and natural systems need to interact and sustainably coexist is essential. By recognizing the criticality of satisfying basic needs as well as the great uncertainty over the needs and preferences of future generations, we sought to incorporate conservation criteria based on minimal human impact into economic evaluation. These criteria require the conservation of environmental conditions such that the opportunity for intergenerational welfare optimization is maintained. Toward this end, we propose the integration of ecological-biological thresholds into decision making and use as an example the planetary-boundaries approach. Both conservation scientists and economists must be involved in defining operational ecological-biological thresholds that can be incorporated into economic thinking and reflect the objectives of conservation, sustainability, and intergenerational welfare optimization.

  2. Integrated oxygen recovery system

    NASA Technical Reports Server (NTRS)

    Lee, M. Gene; Davenport, Ronald J.

    1993-01-01

    Life Systems has conceptualized an innovative Integrated Oxygen Recovery System (IORS) applicable to advanced mission air revitalization. The IORS provides the capability to electrochemically generate metabolic oxygen (O2) and recover O2 from the space habitat atmosphere via a carbon dioxide (CO2) reduction process within a single assembly. To achieve this capability, the IORS utilizes a Solid Metal Cathode (SMC) water electrolysis unit that simultaneously serves as the Sabatier CO2 reduction reactor. The IORS enables two major life support systems currently baselined in closed loop air revitalization systems to be combined into one smaller, less complex system. This concept reduces fluidic and electrical interface requirements and eliminates a hydrogen (H2) interface. Life Systems is performing an evaluation of the IORS process directed at demonstrating performance and quantifying key physical characteristics including power, weight, and volume. Technical progress achieved during the first two months of the program is summarized.

  3. Integrated oxygen recovery system

    NASA Technical Reports Server (NTRS)

    Lee, M. Gene; Davenport, Ronald J.

    1993-01-01

    Life Systems has conceptualized an innovative Integrated Oxygen Recovery System (IORS) applicable to advanced mission air revitalization. The IORS provides the capability to electrochemically generate metabolic oxygen (O2) and recover O2 from the space habitat atmosphere via a carbon dioxide (CO2) reduction process within a single assembly. To achieve this capability, the IORS utilizes a Solid Metal Cathode (SMC) water electrolysis unit that simultaneously serves as the Sabatier CO2 reduction reactor. The IORS enables two major life support systems currently baselined in closed loop air revitalization systems to be combined into one smaller, less complex system. This concept reduces fluidic and electrical interface requirements and eliminates a hydrogen (H2) interface. Life Systems is performing an evaluation of the IORS process directed at demonstrating performance and quantifying key physical characteristics including power, weight, and volume. The results of the checkout, shakedown, and initial parametric tests are summarized.

  4. CHEMICAL EFFECTS IN BIOLOGICAL SYSTEMS – DATA DICTIONARY (CEBS-DD): A COMPENDIUM OF TERMS FOR THE CAPTURE AND INTEGRATION OF BIOLOGICAL STUDY DESIGN DESCRIPTION, CONVENTIONAL PHENOTYPES AND ‘OMICS’ DATA

    EPA Science Inventory

    A critical component in the design of the Chemical Effects in Biological Systems (CEBS) Knowledgebase is a strategy to capture toxicogenomics study protocols and the toxicity endpoint data (clinical pathology and histopathology). A Study is generally an experiment carried out du...

  5. Integrated multisensor navigation systems

    NASA Technical Reports Server (NTRS)

    Vangraas, Frank

    1988-01-01

    The multisensor navigation systems research evolved from the availability of several stand alone navigation systems and the growing concern for aircraft navigation reliability and safety. The intent is to develop a multisensor navigation system during the next decade that will be capable of providing reliable aircraft position data. These data will then be transmitted directly, or by satellite, to surveillance centers to aid the process of air traffic flow control. In order to satisfy the requirements for such a system, the following issues need to be examined: performance, coverage, reliability, availability, and integrity. The presence of a multisensor navigation system in all aircraft will improve safety for the aviation community and allow for more economical operation.

  6. Slimplectic Integrators: Variational Integrators for Nonconservative systems

    NASA Astrophysics Data System (ADS)

    Tsang, David

    2016-05-01

    Symplectic integrators are widely used for long-term integration of conservative astrophysical problems due to their ability to preserve the constants of motion; however, they cannot in general be applied in the presence of nonconservative interactions. Here we present the “slimplectic” integrator, a new type of numerical integrator that shares many of the benefits of traditional symplectic integrators yet is applicable to general nonconservative systems. We utilize a fixed-time-step variational integrator formalism applied to a newly developed principle of stationary nonconservative action (Galley, 2013, Galley et al 2014). As a result, the generalized momenta and energy (Noether current) evolutions are well-tracked. We discuss several example systems, including damped harmonic oscillators, Poynting-Robertson drag, and gravitational radiation reaction, by utilizing our new publicly available code to demonstrate the slimplectic integrator algorithm. Slimplectic integrators are well-suited for integrations of systems where nonconservative effects play an important role in the long-term dynamical evolution. As such they are particularly appropriate for cosmological or celestial N-body dynamics problems where nonconservative interactions, e.g., gas interactions or dissipative tides, can play an important role.

  7. Integration of biological networks and pathways with genetic association studies.

    PubMed

    Sun, Yan V

    2012-10-01

    Millions of genetic variants have been assessed for their effects on the trait of interest in genome-wide association studies (GWAS). The complex traits are affected by a set of inter-related genes. However, the typical GWAS only examine the association of a single genetic variant at a time. The individual effects of a complex trait are usually small, and the simple sum of these individual effects may not reflect the holistic effect of the genetic system. High-throughput methods enable genomic studies to produce a large amount of data to expand the knowledge base of the biological systems. Biological networks and pathways are built to represent the functional or physical connectivity among genes. Integrated with GWAS data, the network- and pathway-based methods complement the approach of single genetic variant analysis, and may improve the power to identify trait-associated genes. Taking advantage of the biological knowledge, these approaches are valuable to interpret the functional role of the genetic variants, and to further understand the molecular mechanism influencing the traits. The network- and pathway-based methods have demonstrated their utilities, and will be increasingly important to address a number of challenges facing the mainstream GWAS.

  8. 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.

  9. Systems biology for enhanced plant nitrogen nutrition.

    PubMed

    Gutiérrez, Rodrigo A

    2012-06-29

    Nitrogen (N)-based fertilizers increase agricultural productivity but have detrimental effects on the environment and human health. Research is generating improved understanding of the signaling components plants use to sense N and regulate metabolism, physiology, and growth and development. However, we still need to integrate these regulatory factors into signal transduction pathways and connect them to downstream response pathways. Systems biology approaches facilitate identification of new components and N-regulatory networks linked to other plant processes. A holistic view of plant N nutrition should open avenues to translate this knowledge into effective strategies to improve N-use efficiency and enhance crop production systems for more sustainable agricultural practices.

  10. 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.

  11. Inspiring Integration in College Students Reading Multiple Biology Texts

    ERIC Educational Resources Information Center

    Firetto, Carla

    2013-01-01

    Introductory biology courses typically present topics on related biological systems across separate chapters and lectures. A complete foundational understanding requires that students understand how these biological systems are related. Unfortunately, spontaneous generation of these connections is rare for novice learners. These experiments focus…

  12. BIOLOGICAL INTEGRITY IN MID-ATLANTIC COASTAL PLAINS HEADWATER STREAMS

    EPA Science Inventory

    The objective of this study was to assess the applicability of landscape metrics, in conjunction with stream water quality to estimate the biological integrity of headwater streams in the Mid-Atlantic Coastal Plains using multivariate techniques.

  13. 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

  14. Decentralized Multisensory Information Integration in Neural Systems

    PubMed Central

    Zhang, Wen-hao; Chen, Aihua

    2016-01-01

    How multiple sensory cues are integrated in neural circuitry remains a challenge. The common hypothesis is that information integration might be accomplished in a dedicated multisensory integration area receiving feedforward inputs from the modalities. However, recent experimental evidence suggests that it is not a single multisensory brain area, but rather many multisensory brain areas that are simultaneously involved in the integration of information. Why many mutually connected areas should be needed for information integration is puzzling. Here, we investigated theoretically how information integration could be achieved in a distributed fashion within a network of interconnected multisensory areas. Using biologically realistic neural network models, we developed a decentralized information integration system that comprises multiple interconnected integration areas. Studying an example of combining visual and vestibular cues to infer heading direction, we show that such a decentralized system is in good agreement with anatomical evidence and experimental observations. In particular, we show that this decentralized system can integrate information optimally. The decentralized system predicts that optimally integrated information should emerge locally from the dynamics of the communication between brain areas and sheds new light on the interpretation of the connectivity between multisensory brain areas. SIGNIFICANCE STATEMENT To extract information reliably from ambiguous environments, the brain integrates multiple sensory cues, which provide different aspects of information about the same entity of interest. Here, we propose a decentralized architecture for multisensory integration. In such a system, no processor is in the center of the network topology and information integration is achieved in a distributed manner through reciprocally connected local processors. Through studying the inference of heading direction with visual and vestibular cues, we show that

  15. Network dynamics and systems biology

    NASA Astrophysics Data System (ADS)

    Norrell, Johannes A.

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

  16. A systems biology starter kit for arenaviruses.

    PubMed

    Droniou-Bonzom, Magali E; Cannon, Paula M

    2012-12-01

    Systems biology approaches in virology aim to integrate viral and host biological networks, and thus model the infection process. The growing availability of high-throughput “-omics” techniques and datasets, as well as the ever-increasing sophistication of in silico modeling tools, has resulted in a corresponding rise in the complexity of the analyses that can be performed. The present study seeks to review and organize published evidence regarding virus-host interactions for the arenaviruses, from alterations in the host proteome during infection, to reported protein-protein interactions. In this way, we hope to provide an overview of the interplay between arenaviruses and the host cell, and lay the foundations for complementing current arenavirus research with a systems-level approach.

  17. 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.

  18. Integrated Chemistry and Biology for First-Year College Students

    ERIC Educational Resources Information Center

    Abdella, Beth R. J.; Walczak, Mary M.; Kandl, Kim A.; Schwinefus, Jeffrey J.

    2011-01-01

    A three-course sequence for first-year students that integrates beginning concepts in biology and chemistry has been designed. The first two courses that emphasize chemistry and its capacity to inform biological applications are described here. The content of the first course moves from small to large particles with an emphasis on membrane…

  19. Using biological networks to integrate, visualize and analyze genomics data.

    PubMed

    Charitou, Theodosia; Bryan, Kenneth; Lynn, David J

    2016-03-31

    Network biology is a rapidly developing area of biomedical research and reflects the current view that complex phenotypes, such as disease susceptibility, are not the result of single gene mutations that act in isolation but are rather due to the perturbation of a gene's network context. Understanding the topology of these molecular interaction networks and identifying the molecules that play central roles in their structure and regulation is a key to understanding complex systems. The falling cost of next-generation sequencing is now enabling researchers to routinely catalogue the molecular components of these networks at a genome-wide scale and over a large number of different conditions. In this review, we describe how to use publicly available bioinformatics tools to integrate genome-wide 'omics' data into a network of experimentally-supported molecular interactions. In addition, we describe how to visualize and analyze these networks to identify topological features of likely functional relevance, including network hubs, bottlenecks and modules. We show that network biology provides a powerful conceptual approach to integrate and find patterns in genome-wide genomic data but we also discuss the limitations and caveats of these methods, of which researchers adopting these methods must remain aware.

  20. Video integrated measurement system.

    PubMed

    Spector, B; Eilbert, L; Finando, S; Fukuda, F

    1982-06-01

    A Video Integrated Measurement (VIM) System is described which incorporates the use of various noninvasive diagnostic procedures (moire contourography, electromyography, posturometry, infrared thermography, etc.), used individually or in combination, for the evaluation of neuromusculoskeletal and other disorders and their management with biofeedback and other therapeutic procedures. The system provides for measuring individual diagnostic and therapeutic modes, or multiple modes by split screen superimposition, of real time (actual) images of the patient and idealized (ideal-normal) models on a video monitor, along with analog and digital data, graphics, color, and other transduced symbolic information. It is concluded that this system provides an innovative and efficient method by which the therapist and patient can interact in biofeedback training/learning processes and holds considerable promise for more effective measurement and treatment of a wide variety of physical and behavioral disorders.

  1. 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.

  2. The Integral System

    PubMed Central

    2011-01-01

    The Integral System is a total care management system based on the Integral Theory which states ‘prolapse and symptoms of urinary stress, urge, abnormal bowel & bladder emptying, and some forms of pelvic pain, mainly arise, for different reasons, from laxity in the vagina or its supporting ligaments, a result of altered connective tissue’. Normal function The organs are suspended by ligaments against which muscles contract to open or close the their outlet tubes, urethra and anus. These ligaments fall naturally into a three-zone zone classification, anterior, middle, and posterior. Dysfunction Damaged ligaments weaken the force of muscle contraction, causing prolapse and abnormal bladder and bowel symptoms Diagnosis A pictorial diagnostic algorithm relates specific symptoms to damaged ligaments in each zone. Treatment In mild cases, new pelvic floor muscle exercises based on a squatting principle strengthen the natural closure muscles and their ligamentous insertions, thereby improving the symptoms predicted by the Theory. With more severe cases, polypropylene tapes applied through “keyhole” incision using special instruments reinforce the damaged ligaments, restoring structure and function. Problems that can be potentially addressed by application of the Integral System Urinary stress incontinenceUrinary urge incontinenceAbnormal bladder emptyingFacal incontinence and “obstructed evacuation” (“constipation”)Pelvic pain, and some types of vulvodynia and interstitial cystitisOrgan prolapse Conclusions Organ prolapse and symptoms are related, and both are mainly caused by laxity in the four main suspensory ligaments and perineal body. Restoration of ligament/fascial length and tension is required to restore anatomy and function. PMID:24578877

  3. Decavanadate effects in biological systems.

    PubMed

    Aureliano, Manuel; Gândara, Ricardo M C

    2005-05-01

    Vanadium biological studies often disregarded the formation of decameric vanadate species known to interact, in vitro, with high-affinity with many proteins such as myosin and sarcoplasmic reticulum calcium pump and also to inhibit these biochemical systems involved in energy transduction. Moreover, very few in vivo animal studies involving vanadium consider the contribution of decavanadate to vanadium biological effects. Recently, it has been shown that an acute exposure to decavanadate but not to other vanadate oligomers induced oxidative stress and a different fate in vanadium intracellular accumulation. Several markers of oxidative stress analyzed on hepatic and cardiac tissue were monitored after in vivo effect of an acute exposure (12, 24 h and 7 days), to a sub-lethal concentration (5 mM; 1 mg/kg) of two vanadium solutions ("metavanadate" and "decavanadate"). It was observed that "decavanadate" promote different effects than other vanadate oligomers in catalase activity, glutathione content, lipid peroxidation, mitochondrial superoxide anion production and vanadium accumulation, whereas both solutions seem to equally depress reactive oxygen species (ROS) production as well as total intracellular reducing power. Vanadium is accumulated in mitochondria in particular when "decavanadate" is administered. These recent findings, that are now summarized, point out the decameric vanadate species contributions to in vivo and in vitro effects induced by vanadium in biological systems.

  4. 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.

  5. Integrated power system

    SciTech Connect

    Waddington, C.

    1987-10-13

    An integrated power system is described for transmitting power from a gas turbine engine, including a gas producer and a free turbine engine, to the driving elements of a vehicle comprising: a pair of independent output shafts; a pair of combining planetary gear systems, each being drivingly coupled to an associated one of the output shafts; a variable speed transmission drivingly coupled to the free power turbine; drive means operatively connecting the transmission and each of the combining planetary gear systems; steering means operatively coupled to each of the combining planetary gear systems for selectively driving at least one of the combining planetary gear systems; the steering means including a variable displacement hydraulic motor in driving engagement with the planetary gear systems and an hydraulic pump in driving engagement with the transmission for supplying fluid under pressure to the hydraulic motor to thereby effect steering of the vehicle; a fuel control for controlling the power output of the gas turbine engine; and an adjustable relief valve operatively interposed between the hydraulic motor and the hydraulic pump, the valve being responsive to the fuel control to establish a maximum fluid pressure imparted by the hydraulic pump to the hydraulic motor.

  6. 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 ...

  7. 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

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

    PubMed

    Matsuoka, Yukiko; Ghosh, Samik; Kitano, Hiroaki

    2009-08-06

    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.

  9. Toward Integration: From Quantitative Biology to Mathbio-Biomath?

    ERIC Educational Resources Information Center

    Marsteller, Pat; de Pillis, Lisette; Findley, Ann; Joplin, Karl; Pelesko, John; Nelson, Karen; Thompson, Katerina; Usher, David; Watkins, Joseph

    2010-01-01

    In response to the call of "BIO2010" for integrating quantitative skills into undergraduate biology education, 30 Howard Hughes Medical Institute (HHMI) Program Directors at the 2006 HHMI Program Directors Meeting established a consortium to investigate, implement, develop, and disseminate best practices resulting from the integration of math and…

  10. An Automated Biological Dosimetry System

    NASA Astrophysics Data System (ADS)

    Lorch, T.; Bille, J.; Frieben, M.; Stephan, G.

    1986-04-01

    The scoring of structural chromosome aberrations in peripheral human blood lymphocytes can be used in biological dosimetry to estimate the radiation dose which an individual has received. Especially the dicentric chromosome is a rather specific indicator for an exposure to ionizing radiation. For statistical reasons, in the low dose range a great number of cells must be analysed, which is a very tedious task. The resulting high cost of a biological dose estimation limits the application of this method to cases of suspected irradiation for which physical dosimetry is not possible or not sufficient. Therefore an automated system has been designed to do the major part of the routine work. It uses a standard light microscope with motorized scanning stage, a Plumbicon TV-camera, a real-time hardware preprocessor, a binary and a grey level image buffer system. All computations are performed by a very powerful multi-microprocessor-system (POLYP) based on a MIMD-architecture. The task of the automated system can be split in finding the metaphases (see Figure 1) at low microscope magnification and scoring dicentrics at high magnification. The metaphase finding part has been completed and is now in routine use giving good results. The dicentric scoring part is still under development.

  11. Systems Biology of the Microvasculature

    PubMed Central

    Clegg, Lindsay E.; Mac Gabhann, Feilim

    2015-01-01

    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. PMID:25839068

  12. Integrated renewable energy systems

    SciTech Connect

    Ramakumar, R.

    1995-02-01

    Utilization of several manifestations of solar energy in tandem by means of integrated renewable energy systems (IRES) to supply a variety of energy and other needs has the potential to energize (in contrast to electrification) remote rural areas in a cost-effective manner. Such actions can dramatically improve the quality of life for hundreds of millions of people living in remote villages in the continents of Asia, Africa, and Latin America. The environmentally benign nature of renewable resource utilization and the potability of exploiting locally available resources with the consequent growth of job opportunities are some of the many benefits that can accrue by the deployment of IRES. Even small amounts of energy can be very beneficial in remote rural areas of developing countries with no grid connection as compared to the massive urban sprawls in both developed and developing countries. A concerted global effort in this direction can build the much-needed market potential for renewables now, resulting in future cost reductions. Summaries of the three panel session presentations are assembled here for the readers of the IEEE Power Engineering Review: Designing an Integrated Renewable Energy System, by K. Ashenayi, The University of Tulsa, Tulsa, Oklahoma; Africa-1000: Water in Thousands of Villages, by C. Kashkari Founder, Africa-1000, The University of Akron, Akron, Ohio; Renewables in Mexico, by J. Gutierrez-Vera, Energia Del Siglo 21, Mexico D.F.

  13. Integral habitat transport system

    NASA Technical Reports Server (NTRS)

    Elliott, Bill; Frazer, Scott; Higgs, Joey; Huff, Jason; Milam, Tigree

    1994-01-01

    In the 1993 Fall quarter, the ME 4182 design class was sponsored to study various scenarios that needed to be studied for Martian travel. The class was sponsored by NASA and there were several different design projects. The design that group three chose was an integral transport system for a Martian habitat. An integral transport system means the design had to be one that was attached to the habitat. There were several criteria that the design had to meet. Group three performed an in depth study of the Martian environment and looked at several different design ideas. The concept group three developed involved the use of kinematic linkages and the use of Martian gravity to move the habitat. The various design concepts, the criteria matrices and all other aspects that helped group three develop their design can be found in their 1993 ME 4182 design report. Now it is Winter quarter 1994 and group three is faced with another problem. The problem is building a working prototype of their Fall design. The limitations this quarter were the parts. The group had to make the prototype work with existing manufactured parts or make the parts themselves in a machine shop. The prototype was scaled down roughly about twelve times smaller than the original design. The following report describes the actions taken by group three to build a working model.

  14. Integrating biological invasions, climate change and phenotypic plasticity.

    PubMed

    Engel, Katharina; Tollrian, Ralph; Jeschke, Jonathan M

    2011-05-01

    Invasive species frequently change the ecosystems where they are introduced, e.g., by affecting species interactions and population densities of native species. We outline the connectedness of biological invasions, climate change and the phenomenon of phenotypic plasticity. Integrating these hot topics is important for understanding the biology of many species, their information transfer and general interactions with other organisms. One example where this is particularly true is the zooplankton species Daphnia lumholtzi, which has successfully invaded North America. The combination of a high thermal tolerance and a phenotypically plastic defense in D. lumholtzi might be responsible for its invasion success. Its morphological defense consists of rigid spines and is formed after sensory detecting the presence of native fish predators. The integration of biological invasions, climate change and phenotypic plasticity is an important goal for integrative biology.

  15. Biologics in Dermatology: An Integrated Review

    PubMed Central

    Sehgal, Virendra N; Pandhi, Deepika; Khurana, Ananta

    2014-01-01

    The advent of biologics in dermatologic treatment armentarium has added refreshing dimensions, for it is a major breakthrough. Several agents are now available for use. It is therefore imperative to succinctly comprehend their pharmacokinetics for their apt use. A concerted endeavor has been made to delve on this subject. The major groups of biologics have been covered and include: Drugs acting against TNF-α, Alefacept, Ustekinumab, Rituximab, IVIG and Omalizumab. The relevant pharmacokinetic characteristics have been detailed. Their respective label (approved) and off-label (unapproved) indications have been defined, highlighting their dosage protocol, availability and mode of administration. The evidence level of each indication has also been discussed to apprise the clinician of their current and prospective uses. Individual anti-TNF drugs are not identical in their actions and often one is superior to the other in a particular disease. Hence, the section on anti-TNF agents mentions the literature on each drug separately, and not as a group. The limitations for their use have also been clearly brought out. PMID:25284845

  16. Choosing the Right Systems Integration

    NASA Astrophysics Data System (ADS)

    Péči, Matúš; Važan, Pavel

    2014-12-01

    The paper examines systems integration and its main levels at higher levels of control. At present, the systems integration is one of the main aspects participating in the consolidation processes and financial flows of a company. Systems Integration is a complicated emotionconsuming process and it is often a problem to choose the right approach and level of integration. The research focused on four levels of integration, while each of them is characterized by specific conditions. At each level, there is a summary of recommendations and practical experience. The paper also discusses systems integration between the information and MES levels. The main part includes user-level integration where we describe an example of such integration. Finally, we list recommendations and also possible predictions of the systems integration as one of the important factors in the future.

  17. 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

  18. 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.

  19. 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.

  20. Defining the biological integrity of coral reefs using a biological condition gradient framework

    EPA Science Inventory

    Under authority of the Clean Water Act (CWA), the US EPA is committed to protecting the biological integrity of tropical ecosystems, including mangroves, seagrasses and coral reefs that lie within the 3-mile limit of the territorial seas. The biological condition gradient (BCG) w...

  1. Advanced treatment of biologically pretreated coal gasification wastewater by a novel integration of heterogeneous Fenton oxidation and biological process.

    PubMed

    Xu, Peng; Han, Hongjun; Zhuang, Haifeng; Hou, Baolin; Jia, Shengyong; Xu, Chunyan; Wang, Dexin

    2015-04-01

    Laboratorial scale experiments were conducted in order to investigate a novel system integrating heterogeneous Fenton oxidation (HFO) with anoxic moving bed biofilm reactor (ANMBBR) and biological aerated filter (BAF) process on advanced treatment of biologically pretreated coal gasification wastewater (CGW). The results indicated that HFO with the prepared catalyst (FeOx/SBAC, sewage sludge based activated carbon (SBAC) which loaded Fe oxides) played a key role in eliminating COD and COLOR as well as in improving the biodegradability of raw wastewater. The surface reaction and hydroxyl radicals (OH) oxidation were the mechanisms for FeOx/SBAC catalytic reaction. Compared with ANMBBR-BAF process, the integrated system was more effective in abating COD, BOD5, total phenols (TPs), total nitrogen (TN) and COLOR and could shorten the retention time. Therefore, the integrated system was a promising technology for engineering applications.

  2. Integrated fluorescence analysis system

    DOEpatents

    Buican, Tudor N.; Yoshida, Thomas M.

    1992-01-01

    An integrated fluorescence analysis system enables a component part of a sample to be virtually sorted within a sample volume after a spectrum of the component part has been identified from a fluorescence spectrum of the entire sample in a flow cytometer. Birefringent optics enables the entire spectrum to be resolved into a set of numbers representing the intensity of spectral components of the spectrum. One or more spectral components are selected to program a scanning laser microscope, preferably a confocal microscope, whereby the spectrum from individual pixels or voxels in the sample can be compared. Individual pixels or voxels containing the selected spectral components are identified and an image may be formed to show the morphology of the sample with respect to only those components having the selected spectral components. There is no need for any physical sorting of the sample components to obtain the morphological information.

  3. Physical Constraints on Biological Integral Control Design for Homeostasis and Sensory Adaptation

    PubMed Central

    Ang, Jordan; McMillen, David R.

    2013-01-01

    Synthetic biology includes an effort to use design-based approaches to create novel controllers, biological systems aimed at regulating the output of other biological processes. The design of such controllers can be guided by results from control theory, including the strategy of integral feedback control, which is central to regulation, sensory adaptation, and long-term robustness. Realization of integral control in a synthetic network is an attractive prospect, but the nature of biochemical networks can make the implementation of even basic control structures challenging. Here we present a study of the general challenges and important constraints that will arise in efforts to engineer biological integral feedback controllers or to analyze existing natural systems. Constraints arise from the need to identify target output values that the combined process-plus-controller system can reach, and to ensure that the controller implements a good approximation of integral feedback control. These constraints depend on mild assumptions about the shape of input-output relationships in the biological components, and thus will apply to a variety of biochemical systems. We summarize our results as a set of variable constraints intended to provide guidance for the design or analysis of a working biological integral feedback controller. PMID:23442873

  4. Physical constraints on biological integral control design for homeostasis and sensory adaptation.

    PubMed

    Ang, Jordan; McMillen, David R

    2013-01-22

    Synthetic biology includes an effort to use design-based approaches to create novel controllers, biological systems aimed at regulating the output of other biological processes. The design of such controllers can be guided by results from control theory, including the strategy of integral feedback control, which is central to regulation, sensory adaptation, and long-term robustness. Realization of integral control in a synthetic network is an attractive prospect, but the nature of biochemical networks can make the implementation of even basic control structures challenging. Here we present a study of the general challenges and important constraints that will arise in efforts to engineer biological integral feedback controllers or to analyze existing natural systems. Constraints arise from the need to identify target output values that the combined process-plus-controller system can reach, and to ensure that the controller implements a good approximation of integral feedback control. These constraints depend on mild assumptions about the shape of input-output relationships in the biological components, and thus will apply to a variety of biochemical systems. We summarize our results as a set of variable constraints intended to provide guidance for the design or analysis of a working biological integral feedback controller.

  5. Controlled annotations for systems biology.

    PubMed

    Juty, Nick; Laibe, Camille; Le Novère, Nicolas

    2013-01-01

    The aim of this chapter is to provide sufficient information to enable a reader, new to the subject of Systems Biology, to create and use effectively controlled annotations, using resolvable Identifiers.org Uniform Resource Identifiers (URIs). The text details the underlying requirements that have led to the development of such an identification scheme and infrastructure, the principles that underpin its syntax and the benefits derived through its use. It also places into context the relationship with other standardization efforts, how it differs from other pre-existing identification schemes, recent improvements to the system, as well as those that are planned in the future. Throughout, the reader is provided with explicit examples of use and directed to supplementary information where necessary.

  6. Integrating utility communication systems

    SciTech Connect

    Batra, S.K. ); Colley, R.; Iveson, R.H.; Malcolm, W.P. )

    1992-01-01

    Today, utilities are facing increasing pressures of deregulation, competition, changing business conditions and varying customer requirements. Existing computers and communications systems were installed with limited capabilities to communicate with other systems. The result, say many utilities, is an electronic Tower of Babel among computers that are unable to readily talk to one another or, if they can, haven't much say because of vastly different database structures. This paper reports that estimates of the industry's operating costs for telecommunications range from $2 billion to more likely $5 billion a year, with some individual company budgets growing as much as 25% a year. A typical medium-size utility will spend $35 million in annual telecommunication expenses. EPRI has been tasked by it member utilities to develop guidelines and specification that would support the development of integrated nonproprietary, interoperable utility communications systems. Substantial cost savings and improved performance are the key reasons for communications for new products and services result when a utility can share information, across all operations, in an effective and timely manner.

  7. Advanced Integrated Traction System

    SciTech Connect

    Greg Smith; Charles Gough

    2011-08-31

    The United States Department of Energy elaborates the compelling need for a commercialized competitively priced electric traction drive system to proliferate the acceptance of HEVs, PHEVs, and FCVs in the market. The desired end result is a technically and commercially verified integrated ETS (Electric Traction System) product design that can be manufactured and distributed through a broad network of competitive suppliers to all auto manufacturers. The objectives of this FCVT program are to develop advanced technologies for an integrated ETS capable of 55kW peak power for 18 seconds and 30kW of continuous power. Additionally, to accommodate a variety of automotive platforms the ETS design should be scalable to 120kW peak power for 18 seconds and 65kW of continuous power. The ETS (exclusive of the DC/DC Converter) is to cost no more than $660 (55kW at $12/kW) to produce in quantities of 100,000 units per year, should have a total weight less than 46kg, and have a volume less than 16 liters. The cost target for the optional Bi-Directional DC/DC Converter is $375. The goal is to achieve these targets with the use of engine coolant at a nominal temperature of 105C. The system efficiency should exceed 90% at 20% of rated torque over 10% to 100% of maximum speed. The nominal operating system voltage is to be 325V, with consideration for higher voltages. This project investigated a wide range of technologies, including ETS topologies, components, and interconnects. Each technology and its validity for automotive use were verified and then these technologies were integrated into a high temperature ETS design that would support a wide variety of applications (fuel cell, hybrids, electrics, and plug-ins). This ETS met all the DOE 2010 objectives of cost, weight, volume and efficiency, and the specific power and power density 2015 objectives. Additionally a bi-directional converter was developed that provides charging and electric power take-off which is the first step

  8. Leveraging systems biology approaches in clinical pharmacology

    PubMed Central

    Melas, Ioannis N; Kretsos, Kosmas; Alexopoulos, Leonidas G

    2013-01-01

    Computational modeling has been adopted in all aspects of drug research and development, from the early phases of target identification and drug discovery to the late-stage clinical trials. The different questions addressed during each stage of drug R&D has led to the emergence of different modeling methodologies. In the research phase, systems biology couples experimental data with elaborate computational modeling techniques to capture lifecycle and effector cellular functions (e.g. metabolism, signaling, transcription regulation, protein synthesis and interaction) and integrates them in quantitative models. These models are subsequently used in various ways, i.e. to identify new targets, generate testable hypotheses, gain insights on the drug's mode of action (MOA), translate preclinical findings, and assess the potential of clinical drug efficacy and toxicity. In the development phase, pharmacokinetic/pharmacodynamic (PK/PD) modeling is the established way to determine safe and efficacious doses for testing at increasingly larger, and more pertinent to the target indication, cohorts of subjects. First, the relationship between drug input and its concentration in plasma is established. Second, the relationship between this concentration and desired or undesired PD responses is ascertained. Recognizing that the interface of systems biology with PK/PD will facilitate drug development, systems pharmacology came into existence, combining methods from PK/PD modeling and systems engineering explicitly to account for the implicated mechanisms of the target system in the study of drug–target interactions. Herein, a number of popular system biology methodologies are discussed, which could be leveraged within a systems pharmacology framework to address major issues in drug development. PMID:23983165

  9. Integrated Modeling Systems

    DTIC Science & Technology

    1989-01-01

    Summer 1979). WMSI Working Paper No. 291A. 173 Dyer , J. and R. Sarin. "Measurable Multiattribute Value Functions," Operations Research. 27:4 (July...J. McCall. "Expected Utility Maximizing Job Search," Chapter 7 of Studies in the Economics of Search, 1979, North-Holland. WMSI Working Paper No. 274...model integration, solver integration, and integration of various utilities . Model integration is further divided into four subtypes based on a four-level

  10. Integration in biology: Philosophical perspectives on the dynamics of interdisciplinarity.

    PubMed

    Brigandt, Ingo

    2013-12-01

    This introduction to the special section on integration in biology provides an overview of the different contributions. In addition to motivating the philosophical significance of analyzing integration and interdisciplinary research, I lay out common themes and novel insights found among the special section contributions, and indicate how they exhibit current trends in the philosophical study of integration. One upshot of the contributed papers is that there are different aspects to and kinds of integration, so that rather than attempting to offer a universal construal of what integrations is, philosophers have to analyze in concrete cases in what respects particular aspects of scientific theorizing and/or practice are 'integrative' and how this instance of integration works and was achieved.

  11. Arcjet system integration development

    NASA Astrophysics Data System (ADS)

    Zafran, Sidney

    1994-03-01

    Compatibility between an arcjet propulsion system and a communications satellite was verified by testing a Government-furnished, 1.4 kW hydrazine arcjet system with the FLTSATCOM qualification model satellite in a 9.1-meter (30-foot) diameter thermal-vacuum test chamber. Background pressure was maintained at 10(exp -5) torr during arcjet operation by cryopumping the thruster exhaust with an array of 5 K liquid helium cooled panels. Power for the arcjet system was obtained from the FLTSATCOM battery simulator. Spacecraft telemetry was monitored during each thruster firing period. No changes in telemetry data attributable to arcjet operation were detected in any of the tests. Electromagnetic compatibility data obtained included radiated emission measurements, conducted emission measurements, and cable coupling measurements. Significant noise was observed at lower frequencies. Above 500 MHz, radiated emissions were generally within limits, indicating that communication links at S-band and higher frequencies will not be affected. Other test data taken with a diagnostic array of calorimeters, radiometers, witness plates, and a residual gas analyzer evidenced compatible operation, and added to the data base for arcjet system integration. Two test series were conducted. The first series only included the arcjet and diagnostic array operating at approximately 0.1 torr background pressure. The second series added the qualification model spacecraft, a solar panel, and the helium cryopanels. Tests were conducted at 0.1 torr and 10(exp-5) torr. The arcjet thruster was canted 20 degrees relative to the solar panel axis, typical of the configuration used for stationkeeping thrusters on geosynchronous communications satellites.

  12. Arcjet system integration development

    NASA Technical Reports Server (NTRS)

    Zafran, Sidney

    1994-01-01

    Compatibility between an arcjet propulsion system and a communications satellite was verified by testing a Government-furnished, 1.4 kW hydrazine arcjet system with the FLTSATCOM qualification model satellite in a 9.1-meter (30-foot) diameter thermal-vacuum test chamber. Background pressure was maintained at 10(exp -5) torr during arcjet operation by cryopumping the thruster exhaust with an array of 5 K liquid helium cooled panels. Power for the arcjet system was obtained from the FLTSATCOM battery simulator. Spacecraft telemetry was monitored during each thruster firing period. No changes in telemetry data attributable to arcjet operation were detected in any of the tests. Electromagnetic compatibility data obtained included radiated emission measurements, conducted emission measurements, and cable coupling measurements. Significant noise was observed at lower frequencies. Above 500 MHz, radiated emissions were generally within limits, indicating that communication links at S-band and higher frequencies will not be affected. Other test data taken with a diagnostic array of calorimeters, radiometers, witness plates, and a residual gas analyzer evidenced compatible operation, and added to the data base for arcjet system integration. Two test series were conducted. The first series only included the arcjet and diagnostic array operating at approximately 0.1 torr background pressure. The second series added the qualification model spacecraft, a solar panel, and the helium cryopanels. Tests were conducted at 0.1 torr and 10(exp-5) torr. The arcjet thruster was canted 20 degrees relative to the solar panel axis, typical of the configuration used for stationkeeping thrusters on geosynchronous communications satellites.

  13. Toward an integration of evolutionary biology and ecosystem science.

    PubMed

    Matthews, Blake; Narwani, Anita; Hausch, Stephen; Nonaka, Etsuko; Peter, Hannes; Yamamichi, Masato; Sullam, Karen E; Bird, Kali C; Thomas, Mridul K; Hanley, Torrance C; Turner, Caroline B

    2011-07-01

    At present, the disciplines of evolutionary biology and ecosystem science are weakly integrated. As a result, we have a poor understanding of how the ecological and evolutionary processes that create, maintain, and change biological diversity affect the flux of energy and materials in global biogeochemical cycles. The goal of this article was to review several research fields at the interfaces between ecosystem science, community ecology and evolutionary biology, and suggest new ways to integrate evolutionary biology and ecosystem science. In particular, we focus on how phenotypic evolution by natural selection can influence ecosystem functions by affecting processes at the environmental, population and community scale of ecosystem organization. We develop an eco-evolutionary model to illustrate linkages between evolutionary change (e.g. phenotypic evolution of producer), ecological interactions (e.g. consumer grazing) and ecosystem processes (e.g. nutrient cycling). We conclude by proposing experiments to test the ecosystem consequences of evolutionary changes.

  14. What is Energy Systems Integration?

    ScienceCinema

    Kroposki, Ben; Lundstrom, Blake; Hannegan, Bryan; Symko-Davies, Martha

    2016-10-19

    To achieve the most efficient, flexible, and reliable energy system, NREL’s Energy Systems Integration researchers work with manufacturers, utilities, and other research organizations to find solutions to big energy challenges. This video describes the concept of energy systems integration, an approach that explores ways for energy systems to work more efficiently on their own and with each other.

  15. What is Energy Systems Integration?

    SciTech Connect

    Kroposki, Ben; Lundstrom, Blake; Hannegan, Bryan; Symko-Davies, Martha

    2016-10-14

    To achieve the most efficient, flexible, and reliable energy system, NREL’s Energy Systems Integration researchers work with manufacturers, utilities, and other research organizations to find solutions to big energy challenges. This video describes the concept of energy systems integration, an approach that explores ways for energy systems to work more efficiently on their own and with each other.

  16. 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.

  17. 6th Institute for Systems Biology International Symposium: Systems Biology and the Environment

    SciTech Connect

    Galitski, Timothy P.

    2007-04-23

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

  18. 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.

  19. Application of Moving Bed Biofilm Reactor (MBBR) and Integrated Fixed Activated Sludge (IFAS) for Biological River Water Purification System: A Short Review

    NASA Astrophysics Data System (ADS)

    Lariyah, M. S.; Mohiyaden, H. A.; Hayder, G.; Hayder, G.; Hussein, A.; Basri, H.; Sabri, A. F.; Noh, MN

    2016-03-01

    This review paper present the MBBR and IFAS technology for urban river water purification including both conventional methods and new emerging technologies. The aim of this paper is to present the MBBR and IFAS technology as an alternative and successful method for treating different kinds of effluents under different condition. There are still current treatment technologies being researched and the outcomes maybe available in a while. The review also includes many relevant researches carried out at the laboratory and pilot scales. This review covers the important processes on MBBR and IFAS basic treatment process, affecting of carrier type and influent types. However, the research concluded so far are compiled herein and reported for the first time to acquire a better perspective and insight on the subject with a view of meeting the news approach. The research concluded so far are compiled herein and reported for the first time to acquire a better perspective and insight on the subject with a view of meeting the news approach. To this end, the most feasible technology could be the combination of advanced biological process (bioreactor systems) including MBBR and IFAS system.

  20. 77 FR 2521 - Integrated System Power Rates

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-18

    ... Southwestern Power Administration Integrated System Power Rates AGENCY: Southwestern Power Administration, DOE... System pursuant to the Integrated System Rate Schedules which supersede the existing rate schedules... Integrated System pursuant to the following Integrated System Rate Schedules: Rate Schedule P-11,...

  1. The biocommunication method: On the road to an integrative biology

    PubMed Central

    Witzany, Guenther

    2016-01-01

    ABSTRACT Although molecular biology, genetics, and related special disciplines represent a large amount of empirical data, a practical method for the evaluation and overview of current knowledge is far from being realized. The main concepts and narratives in these fields have remained nearly the same for decades and the more recent empirical data concerning the role of noncoding RNAs and persistent viruses and their defectives do not fit into this scenario. A more innovative approach such as applied biocommunication theory could translate empirical data into a coherent perspective on the functions within and between biological organisms and arguably lead to a sustainable integrative biology. PMID:27195071

  2. Forgetfulness during aging: an integrated biology.

    PubMed

    Gold, Paul E; Korol, Donna L

    2014-07-01

    Age-related impairments in memory are often attributed to failures, at either systems or molecular levels, of memory storage processes. A major characteristic of changes in memory with increasing age is the advent of forgetfulness in old vs. young animals. This review examines the contribution of a dysfunction of the mechanisms responsible for modulating the maintenance of memory in aged rats. A memory-modulating system that includes epinephrine, acting through release of glucose from liver glycogen stores, potently enhances memory in young rats. In old rats, epinephrine loses its ability to release glucose and loses its efficacy in enhancing memory. Brain measures of extracellular levels of glucose in the hippocampus during memory testing show decreases in glucose in both young and old rats, but the decreases are markedly greater in extent and duration in old rats. Importantly, the old rats do not have the ability to increase blood glucose levels in response to arousal-related epinephrine release, which is retained and even increased in aged rats. Glucose appears to be able to reverse fully the increased rate of forgetting seen in old rats. This set of findings suggests that physiological mechanisms outside of the brain, i.e. changes in neuroendocrine functions, may contribute substantially to the onset of rapid forgetting in aged animals.

  3. 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

  4. 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.

  5. 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

  6. 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...

  7. Integrated system checkout report

    SciTech Connect

    Not Available

    1991-08-14

    The planning and preparation phase of the Integrated Systems Checkout Program (ISCP) was conducted from October 1989 to July 1991. A copy of the ISCP, DOE-WIPP 90--002, is included in this report as an appendix. The final phase of the Checkout was conducted from July 10, 1991, to July 23, 1991. This phase exercised all the procedures and equipment required to receive, emplace, and retrieve contact handled transuranium (CH TRU) waste filled dry bins. In addition, abnormal events were introduced to simulate various equipment failures, loose surface radioactive contamination events, and personnel injury. This report provides a detailed summary of each days activities during this period. Qualification of personnel to safely conduct the tasks identified in the procedures and the abnormal events were verified by observers familiar with the Bin-Scale CH TRU Waste Test requirements. These observers were members of the staffs of Westinghouse WID Engineering, QA, Training, Health Physics, Safety, and SNL. Observers representing a number of DOE departments, the state of new Mexico, and the Defense Nuclear Facilities Safety Board observed those Checkout activities conducted during the period from July 17, 1991, to July 23, 1991. Observer comments described in this report are those obtained from the staff member observers. 1 figs., 1 tab.

  8. Immunogenomics and systems biology of vaccines

    PubMed Central

    Buonaguro, Luigi; Pulendran, Bali

    2011-01-01

    Summary Vaccines represent a potent tool to prevent or contain infectious diseases with high morbidity or mortality. However, despite their widespread use, we still have a limited understanding of the mechanisms underlying the effective elicitation of protective immune responses by vaccines. Recent research suggests that this represents the cooperative action of the innate and adaptive immune systems. Immunity is made of a multifaceted set of integrated responses involving a dynamic interaction of thousands of molecules, whose list is constantly updated to fill the several empty spaces of this puzzle. The recent development of new technologies and computational tools permits the comprehensive and quantitative analysis of the interactions between all of the components of immunity over time. Here, we review the role of the innate immunity in the host response to vaccine antigens and the potential of systems biology in providing relevant and novel insights in the mechanisms of action of vaccines to improve their design and effectiveness. PMID:21198673

  9. A systems biology approach to learning autophagy.

    PubMed

    Klionsky, Daniel J; Kumar, Anuj

    2006-01-01

    With its relevance to our understanding of eukaryotic cell function in the normal and disease state, autophagy is an important topic in modern cell biology; yet, few textbooks discuss autophagy beyond a two- or three-sentence summary. Here, we report an undergraduate/graduate class lesson for the in-depth presentation of autophagy using an active learning approach. By our method, students will work in small groups to solve problems and interpret an actual data set describing genes involved in autophagy. The problem-solving exercises and data set analysis will instill within the students a much greater understanding of the autophagy pathway than can be achieved by simple rote memorization of lecture materials; furthermore, the students will gain a general appreciation of the process by which data are interpreted and eventually formed into an understanding of a given pathway. As the data sets used in these class lessons are largely genomic and complementary in content, students will also understand first-hand the advantage of an integrative or systems biology study: No single data set can be used to define the pathway in full-the information from multiple complementary studies must be integrated in order to recapitulate our present understanding of the pathways mediating autophagy. In total, our teaching methodology offers an effective presentation of autophagy as well as a general template for the discussion of nearly any signaling pathway within the eukaryotic kingdom.

  10. Integrative Genomics and Computational Systems Medicine

    SciTech Connect

    McDermott, Jason E.; Huang, Yufei; Zhang, Bing; Xu, Hua; Zhao, Zhongming

    2014-01-01

    The exponential growth in generation of large amounts of genomic data from biological samples has driven the emerging field of systems medicine. This field is promising because it improves our understanding of disease processes at the systems level. However, the field is still in its young stage. There exists a great need for novel computational methods and approaches to effectively utilize and integrate various omics data.

  11. 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

  12. Anion selectivity in biological systems.

    PubMed

    Wright, E M; Diamond, J M

    1977-01-01

    As background for appreciating the still-unsolved problems of monovalent anion selectivity, we summarize the facts and intepretations that seem reasonably well established. In section II we saw that specific effects of monovalent anions on biological and physical systems define qualitative patterns, in that only certain sequences of anion effects are observed. For example, the 4 halides can be permitted on paper as 4! = 24 sequences, yet only 5 of these sequences have been observed in nature as potency sequences. In addition, there are quantitative regularities in anion potency that permit the construction of so-called empirical selectivity isotherms (Figs. 4 and 13). That is, a given potency sequence is found to be associated with only a certain modest range of selectivity ratios. The sequences and isotherms apply to effects with a nonequilibrium component (e.g., permeability and conductance sequences) as well as to purely equilibrium effects. Since students of cation selectivity have had difficulty accepting this conclusion, we discuss the reasons why it is not as paradoxical as it at first seems. In sections III and IV we develop four theoretical models to account for the observed anion potency sequences as sequences of equilibrium binding energies. Two of these models involve calculation of electrostatic binding energies between anions and monopolar or dipolar cationic sites, assuming anions as well as sites to be rigid and nonpolarizable. The other two models use thermochemically measured binding energies between anions and thealkali cations or occasionally alkaline-earth cations, which in fact approximate rigid, nonpolarizable spheres. All four models consider the anion selectivity pattern of a given cationic site to be determined by anion differences in the balance between hydration energies and ion-site binding energies. Site differences in anion selectivity pattern are attributed to site differences in radius, charge, coordination number, or dipole length

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

    PubMed

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

    2011-01-01

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

  14. Robert Rosen in the age of systems biology.

    PubMed

    Thomas, S Randall

    2007-10-01

    The widespread use of the term Systems Biology (SB) signals a welcome recognition that organisms must be understood as integrated systems. Although just what this is taken to mean varies from one group to another, it generally implies a focus on biological functions and processes rather than on biological parts and a reliance on mathematical modeling to arrive at an understanding of these biological processes based on biological observations or measurements. SB, thus, falls directly in the line of reflection carried out by Robert Rosen throughout his work. In the present article, we briefly introduce the various currents of SB and then point out several ways Rosen's work can be used to avoid certain pitfalls associated with the use of dynamical systems models for the study of complex systems, as well as to inspire a productive path forward based on loosely organized cooperation among dispersed laboratories.

  15. Integrated management of Scotch broom (Cytisus scoparius) using biological control

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Integrated weed management (IWM) strategies are being advocated and employed to control invasive plants species. In this study, we compared the impact of three management strategies [biological control alone (BC), BC with fire (BC + F), and BC with mowing (BC + M)] to determine if combining fire or...

  16. Milkweed Seed Dispersal: A Means for Integrating Biology and Physics.

    ERIC Educational Resources Information Center

    Bisbee, Gregory D.; Kaiser, Cheryl A.

    1997-01-01

    Describes an activity that integrates biology and physics concepts by experimenting with the seed dispersal of common milkweed or similar wind-dispersed seeds. Student teams collect seeds and measure several parameters, review principles of trajectory motion, perform experiments, and graph data. Students examine the ideas of…

  17. Noncommutative integrable systems and quasideterminants

    SciTech Connect

    Hamanaka, Masashi

    2010-03-08

    We discuss extension of soliton theories and integrable systems into noncommutative spaces. In the framework of noncommutative integrable hierarchy, we give infinite conserved quantities and exact soliton solutions for many noncommutative integrable equations, which are represented in terms of Strachan's products and quasi-determinants, respectively. We also present a relation to an noncommutative anti-self-dual Yang-Mills equation, and make comments on how 'integrability' should be considered in noncommutative spaces.

  18. Novel integrated mechanical biological chemical treatment (MBCT) systems for the production of levulinic acid from fraction of municipal solid waste: A comprehensive techno-economic analysis.

    PubMed

    Sadhukhan, Jhuma; Ng, Kok Siew; Martinez-Hernandez, Elias

    2016-09-01

    This paper, for the first time, reports integrated conceptual MBCT/biorefinery systems for unlocking the value of organics in municipal solid waste (MSW) through the production of levulinic acid (LA by 5wt%) that increases the economic margin by 110-150%. After mechanical separation recovering recyclables, metals (iron, aluminium, copper) and refuse derived fuel (RDF), lignocelluloses from remaining MSW are extracted by supercritical-water for chemical valorisation, comprising hydrolysis in 2wt% dilute H2SO4 catalyst producing LA, furfural, formic acid (FA), via C5/C6 sugar extraction, in plug flow (210-230°C, 25bar, 12s) and continuous stirred tank (195-215°C, 14bar, 20min) reactors; char separation and LA extraction/purification by methyl isobutyl ketone solvent; acid/solvent and by-product recovery. The by-product and pulping effluents are anaerobically digested into biogas and fertiliser. Produced biogas (6.4MWh/t), RDF (5.4MWh/t), char (4.5MWh/t) are combusted, heat recovered into steam generation in boiler (efficiency: 80%); on-site heat/steam demand is met; balance of steam is expanded into electricity in steam turbines (efficiency: 35%).

  19. 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

  20. 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.

  1. Central Fan Integrated Ventilation Systems

    SciTech Connect

    2009-05-12

    This information sheet describes one example of a ventilation system design, a central fan integrated supply (CFIS) system, a mechanical ventilation and pollutant source control to ensure that there is reasonable indoor air quality inside the house.

  2. 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

  3. Energy Systems Integration Facility Overview

    ScienceCinema

    Arvizu, Dan; Chistensen, Dana; Hannegan, Bryan; Garret, Bobi; Kroposki, Ben; Symko-Davies, Martha; Post, David; Hammond, Steve; Kutscher, Chuck; Wipke, Keith

    2016-07-12

    The U.S. Department of Energy's Energy Systems Integration Facility (ESIF) is located at the National Renewable Energy Laboratory is the right tool, at the right time... a first-of-its-kind facility that addresses the challenges of large-scale integration of clean energy technologies into the energy systems that power the nation.

  4. Energy Systems Integration Facility Overview

    SciTech Connect

    Arvizu, Dan; Chistensen, Dana; Hannegan, Bryan; Garret, Bobi; Kroposki, Ben; Symko-Davies, Martha; Post, David; Hammond, Steve; Kutscher, Chuck; Wipke, Keith

    2014-02-28

    The U.S. Department of Energy's Energy Systems Integration Facility (ESIF) is located at the National Renewable Energy Laboratory is the right tool, at the right time... a first-of-its-kind facility that addresses the challenges of large-scale integration of clean energy technologies into the energy systems that power the nation.

  5. CAM - Geometric systems integration

    NASA Astrophysics Data System (ADS)

    Dunlap, G. C.

    The integration of geometric and nongeometric information for efficient use of CAM is examined. Requirements for engineering drawings requested by management are noted to involve large volumes of nongeometric data to define the materials and quantity variables which impinge on the required design, so that the actual design may be the last and smaller step in the CAM process. Geometric classification and coding are noted to offer an alpha/numeric identifier for integrating the engineering design, manufacturing, and quality assurance functions. An example is provided of a turbine gear part coding in terms of polycode and monocode displays, showing a possible covering of more than 10 trillion features. Software is stressed as the key to integration of company-wide data.

  6. Delivering The Benefits of Chemical-Biological Integration in ...

    EPA Pesticide Factsheets

    Abstract: Researchers at the EPA’s National Center for Computational Toxicology integrate advances in biology, chemistry, and computer science to examine the toxicity of chemicals and help prioritize chemicals for further research based on potential human health risks. The intention of this research program is to quickly evaluate thousands of chemicals for potential risk but with much reduced cost relative to historical approaches. This work involves computational and data driven approaches including high-throughput screening, modeling, text-mining and the integration of chemistry, exposure and biological data. We have developed a number of databases and applications that are delivering on the vision of developing a deeper understanding of chemicals and their effects on exposure and biological processes that are supporting a large community of scientists in their research efforts. This presentation will provide an overview of our work to bring together diverse large scale data from the chemical and biological domains, our approaches to integrate and disseminate these data, and the delivery of models supporting computational toxicology. This abstract does not reflect U.S. EPA policy. Presentation at ACS TOXI session on Computational Chemistry and Toxicology in Chemical Discovery and Assessement (QSARs).

  7. Integrated Learning Management Systems

    ERIC Educational Resources Information Center

    Clark, Sharon; Cossarin, Mary; Doxsee, Harry; Schwartz, Linda

    2004-01-01

    Four integrated learning management packages were reviewed: "CentraOne", "IntraLearn", "Lyceum", and "Silicon Chalk". These products provide different combinations of synchronous and asynchronous tools. The current report examines the products in relation to their specific value for distance educators and students.

  8. 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.

  9. Ultrasonic microdevices for integrated on-chip biological sample processing

    NASA Astrophysics Data System (ADS)

    Dougherty, George Michael

    Integrated lab-on-a-chip devices, also known as micro total analysis systems (mu-TAS), are expected to play a leading role in biological research and medicine in the 21st century, and on-chip sample processing is a key function of such devices. A new class of ultrasonic microfluidic sample processing devices is presented, based on a single common fundamental unit---a capacitive micromachined ultrasonic transducer---and fabricated using a single common process. Arrays of the transducers are integrated with fluidic microchannels, allowing devices with different functions to be realized simply by altering the physical arrangement and electrical drive signals of the array elements. The efficient, in-plane manipulation of particle-laden liquids is achieved by the use of phased, co-planar transducers, allowing the generation of in-plane, cavity-mode standing waves in the microchannels, and permitting the efficient manipulation of suspended particles such as cells by acoustic radiation forces. Fabricated prototype devices include several types of ultrasonic particle filters, flow-through particle fractionators, particle collimators for cell alignment, devices for the ultrasonic lysing of cells, ultrasonic pumps and ultrasonic mixers. As part of the development effort, an investigation of the thin film silicon material known as "permeable polysilicon" was performed, resulting in the discovery that the material's liquid-permeability properties are caused by nanoscale pores that form spontaneously within an unusual morphological growth regime. A new, one-step porous polysilicon process is presented that allows the quick and easy fabrication of porous polysilicon films for a wide range of applications. The process is used to fabricate the ultrasonic immersion transducers used in the device arrays, and allows the convenient fabrication of a wide variety of microstructures that would be difficult or impossible to fabricate by other means. In addition, a new simulation code is

  10. [Intratumoral administration of biological preparations--recommendation for integrative medicine].

    PubMed

    Ebina, T

    2001-10-01

    The antitumor effect of biological preparations was examined in a double grafted tumor system. PSK is a hot water extract of cultured mycelia from Coliolus versicolor. Its protein content is about 38% and the main glycoside portion of PSK is beta-D-glucan. Lentinan is purified from fruit bodies of Lentinus edodes and is a beta-1, 3-glucan. Cepharanthin is an extract from the root of Stephania cepharantha HAYATA, consisting of 4 kinds of biscoclaurine alkaloids. TAHEEBO tea is a hot water extract of Tabebuia avellanedae, the active ingredient of which is naphthoquinones. If protein-bound polysaccharides were to be used in Western medicine, these polysaccharides would be purified, but purified beta-glucan loses its beneficial effects. Similarly, when raw Cepharanthin is purified to isolate its active ingredient (an alkaloid cepharanthine), its anti-tumor effect is weakened. Clear IAP induction was observed in serum of mice treated with extracts of Coliolus versicolor and Stephania cepharantha. However, IAP induction was not observed in the serum of mice treated with purified beta-glucan or purified alkaloid. This suggests that macrophages may recognize extracts but not purified substances. In Western medicine, purified substances with known chemical structures are recognized as drugs, but overdoses of these drugs are toxic to the body, thus adverse reactions are always an issue. In Chinese medicine, mixtures containing several crude drugs are recognized as drugs, whose active ingredients are not identified. In integrative medicine, drugs are extracts that contain active ingredients with known structures and functions. We propose a Japanese version of integrative medicine which is neither Western nor Chinese.

  11. Selfishness, warfare, and economics; or integration, cooperation, and biology.

    PubMed

    Salvucci, Emiliano

    2012-01-01

    The acceptance of Darwin's theory of evolution by natural selection is not complete and it has been pointed out its limitation to explain the complex processes that constitute the transformation of species. It is necessary to discuss the explaining power of the dominant paradigm. It is common that new discoveries bring about contradictions that are intended to be overcome by adjusting results to the dominant reductionist paradigm using all sorts of gradations and combinations that are admitted for each case. In addition to the discussion on the validity of natural selection, modern findings represent a challenge to the interpretation of the observations with the Darwinian view of competition and struggle for life as theoretical basis. New holistic interpretations are emerging related to the Net of Life, in which the interconnection of ecosystems constitutes a dynamic and self-regulating biosphere: viruses are recognized as a macroorganism with a huge collection of genes, most unknown that constitute the major planet's gene pool. They play a fundamental role in evolution since their sequences are capable of integrating into the genomes in an "infective" way and become an essential part of multicellular organisms. They have content with "biological sense" i.e., they appear as part of normal life processes and have a serious role as carrier elements of complex genetic information. Antibiotics are cell signals with main effects on general metabolism and transcription on bacterial cells and communities. The hologenome theory considers an organism and all of its associated symbiotic microbes (parasites, mutualists, synergists, amensalists) as a result of symbiopoiesis. Microbes, helmints, that are normally understood as parasites are cohabitants and they have cohabited with their host and drive the evolution and existence of the partners. Each organism is the result of integration of complex systems. The eukaryotic organism is the result of combination of bacterial

  12. Selfishness, warfare, and economics; or integration, cooperation, and biology

    PubMed Central

    Salvucci, Emiliano

    2012-01-01

    The acceptance of Darwin's theory of evolution by natural selection is not complete and it has been pointed out its limitation to explain the complex processes that constitute the transformation of species. It is necessary to discuss the explaining power of the dominant paradigm. It is common that new discoveries bring about contradictions that are intended to be overcome by adjusting results to the dominant reductionist paradigm using all sorts of gradations and combinations that are admitted for each case. In addition to the discussion on the validity of natural selection, modern findings represent a challenge to the interpretation of the observations with the Darwinian view of competition and struggle for life as theoretical basis. New holistic interpretations are emerging related to the Net of Life, in which the interconnection of ecosystems constitutes a dynamic and self-regulating biosphere: viruses are recognized as a macroorganism with a huge collection of genes, most unknown that constitute the major planet's gene pool. They play a fundamental role in evolution since their sequences are capable of integrating into the genomes in an “infective” way and become an essential part of multicellular organisms. They have content with “biological sense” i.e., they appear as part of normal life processes and have a serious role as carrier elements of complex genetic information. Antibiotics are cell signals with main effects on general metabolism and transcription on bacterial cells and communities. The hologenome theory considers an organism and all of its associated symbiotic microbes (parasites, mutualists, synergists, amensalists) as a result of symbiopoiesis. Microbes, helmints, that are normally understood as parasites are cohabitants and they have cohabited with their host and drive the evolution and existence of the partners. Each organism is the result of integration of complex systems. The eukaryotic organism is the result of combination of

  13. 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.

  14. 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.

  15. An integrated physical and biological model for anaerobic lagoons.

    PubMed

    Wu, Binxin; Chen, Zhenbin

    2011-04-01

    A computational fluid dynamics (CFD) model that integrates physical and biological processes for anaerobic lagoons is presented. In the model development, turbulence is represented using a transition k-ω model, heat conduction and solar radiation are included in the thermal model, biological oxygen demand (BOD) reduction is characterized by first-order kinetics, and methane yield rate is expressed as a linear function of temperature. A test of the model applicability is conducted in a covered lagoon digester operated under tropical climate conditions. The commercial CFD software, ANSYS-Fluent, is employed to solve the integrated model. The simulation procedures include solving fluid flow and heat transfer, predicting local resident time based on the converged flow fields, and calculating the BOD reduction and methane production. The simulated results show that monthly methane production varies insignificantly, but the time to achieve a 99% BOD reduction in January is much longer than that in July.

  16. Impact of yeast systems biology on industrial biotechnology.

    PubMed

    Petranovic, Dina; Vemuri, Goutham N

    2009-11-01

    Systems biology is yet an emerging discipline that aims to quantitatively describe and predict the functioning of a biological system. This nascent discipline relies on the recent advances in the analytical technology (such as DNA microarrays, mass spectromety, etc.) to quantify cellular characteristics (such as gene expression, protein and metabolite abundance, etc.) and computational methods to integrate information from these measurements. The model eukaryote, Saccharomyces cerevisiae, has played a pivotal role in the development of many of these analytical and computational methods and consequently is the biological system of choice for testing new hypotheses. The knowledge gained from such studies in S. cerevisiae is proving to be extremely useful in designing metabolism that is targeted to specific industrial applications. As a result, the portfolio of products that are being produced using this yeast is expanding rapidly. We review the recent developments in yeast systems biology and how they relate to industrial biotechnology.

  17. Systems biology and mechanics of growth

    PubMed Central

    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 in 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 sytems biology of living systems in light of biochemical and optical stimuli and classify different types of growth to facilitate the design of growth models for various biological systems within this generic framework. Exploring the systems biology of growth introduces a new venue to control and manipulate embryonic development, disease progression, and clinical intervention. PMID:26352286

  18. Integrating biological redesign: where synthetic biology came from and where it needs to go.

    PubMed

    Way, Jeffrey C; Collins, James J; Keasling, Jay D; Silver, Pamela A

    2014-03-27

    Synthetic biology seeks to extend approaches from engineering and computation to redesign of biology, with goals such as generating new chemicals, improving human health, and addressing environmental issues. Early on, several guiding principles of synthetic biology were articulated, including design according to specification, separation of design from fabrication, use of standardized biological parts and organisms, and abstraction. We review the utility of these principles over the past decade in light of the field's accomplishments in building complex systems based on microbial transcription and metabolism and describe the progress in mammalian cell engineering.

  19. 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.

  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. Bioinformatics for the synthetic biology of natural products: integrating across the Design–Build–Test cycle

    PubMed Central

    Currin, Andrew; Jervis, Adrian J.; Rattray, Nicholas J. W.; Swainston, Neil; Yan, Cunyu; Breitling, Rainer

    2016-01-01

    Covering: 2000 to 2016 Progress in synthetic biology is enabled by powerful bioinformatics tools allowing the integration of the design, build and test stages of the biological engineering cycle. In this review we illustrate how this integration can be achieved, with a particular focus on natural products discovery and production. Bioinformatics tools for the DESIGN and BUILD stages include tools for the selection, synthesis, assembly and optimization of parts (enzymes and regulatory elements), devices (pathways) and systems (chassis). TEST tools include those for screening, identification and quantification of metabolites for rapid prototyping. The main advantages and limitations of these tools as well as their interoperability capabilities are highlighted. PMID:27185383

  2. Advances in Systems Biology, Advances in Experimental Medicine and Biology Volume 547

    SciTech Connect

    Opresko, Lee; Gephart, Julie M.; Mann, Michaela B.

    2002-12-02

    This is the inaugural year for a new series of symposia on systems biology. Particular focus will be on identifying current breakthrough technologies and their application to important model systems. By integrating computational sciences, high-throughput technologies and quantitative biology, we hope to facilitate advancements in this important new area of research.In this first year we are focusing on the four different research areas contained within the new U.S. Department of Energy (DOE) Genomes to Life program. This program is the successor to the Human Genome Project and exceeds it in scope and ambition. Its goal is to understand the basis of life and ?to venture beyond characterizing such individual life components as genes and other DNA sequences toward a more comprehensive, integrated view of biology at a whole-systems level.? These goals will be met by1. identifying the protein machines that carry out critical life functions2. characterizing the gene regulatory networks that control these machines3. exploring the functional repertoire of complex microbial communities in their natural environments to provide a foundation for understanding and using their remarkably diverse capabilities to address DOE missions4. developing the computational capabilities to integrate and understand these data and begin to model complex biological systems.

  3. 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.

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

    PubMed

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

    2016-07-08

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

  5. Integrated multiplexed capillary electrophoresis system

    DOEpatents

    Yeung, Edward S.; Tan, Hongdong

    2002-05-14

    The present invention provides an integrated multiplexed capillary electrophoresis system for the analysis of sample analytes. The system integrates and automates multiple components, such as chromatographic columns and separation capillaries, and further provides a detector for the detection of analytes eluting from the separation capillaries. The system employs multiplexed freeze/thaw valves to manage fluid flow and sample movement. The system is computer controlled and is capable of processing samples through reaction, purification, denaturation, pre-concentration, injection, separation and detection in parallel fashion. Methods employing the system of the invention are also provided.

  6. Integrated Workforce Modeling System

    NASA Technical Reports Server (NTRS)

    Moynihan, Gary P.

    2000-01-01

    There are several computer-based systems, currently in various phases of development at KSC, which encompass some component, aspect, or function of workforce modeling. These systems may offer redundant capabilities and/or incompatible interfaces. A systems approach to workforce modeling is necessary in order to identify and better address user requirements. This research has consisted of two primary tasks. Task 1 provided an assessment of existing and proposed KSC workforce modeling systems for their functionality and applicability to the workforce planning function. Task 2 resulted in the development of a proof-of-concept design for a systems approach to workforce modeling. The model incorporates critical aspects of workforce planning, including hires, attrition, and employee development.

  7. The emergence of modularity in biological systems

    NASA Astrophysics Data System (ADS)

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

    2011-06-01

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

  8. The benefit of multisensory integration with biological motion signals.

    PubMed

    Mendonça, Catarina; Santos, Jorge A; López-Moliner, Joan

    2011-09-01

    Assessing intentions, direction, and velocity of others is necessary for most daily tasks, and such information is often made available by both visual and auditory motion cues. Therefore, it is not surprising our great ability to perceive human motion. Here, we explore the multisensory integration of cues of biological motion walking speed. After testing for audiovisual asynchronies (visual signals led auditory ones by 30 ms in simultaneity temporal windows of 76.4 ms), in the main experiment, visual, auditory, and bimodal stimuli were compared to a standard audiovisual walker in a velocity discrimination task. Results in variance reduction conformed to optimal integration of congruent bimodal stimuli across all subjects. Interestingly, the perceptual judgements were still close to optimal for stimuli at the smallest level of incongruence. Comparison of slopes allows us to estimate an integration window of about 60 ms, which is smaller than that reported in audiovisual speech.

  9. Biological identification systems: genetic markers.

    PubMed

    Cunningham, E P; Meghen, C M

    2001-08-01

    Individual animals differ from each other on a number of biological levels. At the most basic level, the deoxyribonucleic acid (DNA) of each animal is different, and transcription of the DNA code yields variations at the protein level, which in turn give rise to individual diversity at the physical level. In recent years, accessing the primary genetic code of individual animals has become straightforward. The authors briefly review the development of biological identification technologies and then consider in more detail the application of current DNA testing technologies to issues of traceability of live animals and derived products. Although largely focused on cattle and beef traceability, the principles described are relevant to ovine, porcine and equine traceability. The accelerating pace of innovation and development within the field of molecular genetics suggests that the technologies described may soon be superseded. However, the principles of genetic identification will remain unchanged.

  10. 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.

  11. Digital system bus integrity

    NASA Technical Reports Server (NTRS)

    Eldredge, Donald; Hitt, Ellis F.

    1987-01-01

    This report summarizes and describes the results of a study of current or emerging multiplex data buses as applicable to digital flight systems, particularly with regard to civil aircraft. Technology for pre-1995 and post-1995 timeframes has been delineated and critiqued relative to the requirements envisioned for those periods. The primary emphasis has been an assured airworthiness of the more prevalent type buses, with attention to attributes such as fault tolerance, environmental susceptibility, and problems under continuing investigation. Additionally, the capacity to certify systems relying on such buses has been addressed.

  12. Intelligent Integrated System Health Management

    NASA Technical Reports Server (NTRS)

    Figueroa, Fernando

    2012-01-01

    Intelligent Integrated System Health Management (ISHM) is the management of data, information, and knowledge (DIaK) with the purposeful objective of determining the health of a system (Management: storage, distribution, sharing, maintenance, processing, reasoning, and presentation). Presentation discusses: (1) ISHM Capability Development. (1a) ISHM Knowledge Model. (1b) Standards for ISHM Implementation. (1c) ISHM Domain Models (ISHM-DM's). (1d) Intelligent Sensors and Components. (2) ISHM in Systems Design, Engineering, and Integration. (3) Intelligent Control for ISHM-Enabled Systems

  13. Human System Integration: Regulatory Analysis

    NASA Technical Reports Server (NTRS)

    2005-01-01

    This document was intended as an input to the Access 5 Policy Integrated Product team. Using a Human System Integration (HIS) perspective, a regulatory analyses of the FARS (specifically Part 91), the Airman s Information Manual (AIM) and the FAA Controllers Handbook (7110.65) was conducted as part of a front-end approach needed to derive HSI requirements for Unmanned Aircraft Systems (UAS) operations in the National Airspace System above FL430. The review of the above aviation reference materials yielded eighty-four functions determined to be necessary or highly desirable for flight within the Air Traffic Management System. They include categories for Flight, Communications, Navigation, Surveillance, and Hazard Avoidance.

  14. Systems Biology and Ecology of Streamlined Bacterioplankton

    NASA Astrophysics Data System (ADS)

    Giovannoni, S. J.

    2014-12-01

    The salient feature of streamlined cells is their small genome size, but "streamlining" refers more generally to selection that favors minimization of cell size and complexity. The essence of streamlining theory is that selection is most efficient in organisms that have large effective population sizes, and, in nutrient-limited systems, favors cell architecture that minimizes resources required for replication. Regardless of the cause of genome reduction, lost coding potential eventually dictates loss of function, raising the questions, what genome features are expendable, and how do cells become highly successful with a minimal genomic repertoire? One consequence of reductive evolution in streamlined organisms is atypical patterns of prototrophy, for example the recent discovery of a requirement for the thiamin precursor 4-amino-5-hydroxymethyl-2-methylpyrimidine in some plankton taxa. Examples such as this fit within the framework of the Black Queen Hypothesis, which describes genome reduction that results in reliance on community goods and increased community connectivity. Other examples of genome reduction include losses of regulatory functions, or replacement with simpler regulatory systems, and increased metabolic integration. In one such case, in the order Pelagibacterales, the PII system for regulating responses to N limitation has been replaced with a simpler system composed of fewer genes. Both the absence of common regulatory systems and atypical patterns of prototrophy have been linked to difficulty in culturing Pelagibacterales, lending credibility to the idea that streamlining might broadly explain the phenomenon of the uncultured microbial majority. The success of streamlined osmotrophic bacterioplankton suggests that they successfully compete for labile organic matter and capture a large share of this resource, but an alternative theory postulates they are not good resource competitors and instead prosper by avoiding predation. The answers to these

  15. Cardiac lineage selection: integrating biological complexity into computational models.

    PubMed

    Foley, Ann

    2009-01-01

    The emergence of techniques to study developmental processes using systems biology approaches offers exciting possibilities for the developmental biologist. In particular cardiac lineage selection may be particularly amenable to these types of studies since the heart is the first fully functional organ to form in vertebrates. However there are many technical obstacles that need to be overcome for these studies to proceed. Here we present a brief overview of cardiomyocyte lineage deterimination and discuss how different aspects of this process either benefit from or present unique challenges for the development of systems biology approaches.

  16. RIS integrated IMAC system

    NASA Astrophysics Data System (ADS)

    Angelhed, Jan-Erik; Carlsson, Goeran; Gustavsson, Staffan; Karlsson, Anders; Larsson, Lars E. G.; Svensson, Sune; Tylen, Ulf

    1998-07-01

    An Image Management And Communication (IMAC) system adapted to the X-ray department at Sahlgrenska University Hospital has been developed using standard components. Two user demands have been considered primary: Rapid access to (display of) images and an efficient worklist management. To fulfil these demands a connection between the IMAC system and the existing Radiological Information System (RIS) has been implemented. The functional modules are: check of information consistency in data exported from image sources, a (logically) central storage of image data, viewing facility for high speed-, large volume-, clinical work, and an efficient interface to the RIS. Also, an image related database extension has been made to the RIS. The IMAC system has a strictly modular design with a simple structure. The image archive and short term storage are logically the same and acts as a huge disk. Through NFS all image data is available to all the connected workstations. All patient selection for viewing is through worklists, which are created by selection criteria in the RIS, by the use of barcodes, or, in singular cases, by entering the patient ID by hand.

  17. Voice integrated systems

    NASA Technical Reports Server (NTRS)

    Curran, P. Mike

    1977-01-01

    The program at Naval Air Development Center was initiated to determine the desirability of interactive voice systems for use in airborne weapon systems crew stations. A voice recognition and synthesis system (VRAS) was developed and incorporated into a human centrifuge. The speech recognition aspect of VRAS was developed using a voice command system (VCS) developed by Scope Electronics. The speech synthesis capability was supplied by a Votrax, VS-5, speech synthesis unit built by Vocal Interface. The effects of simulated flight on automatic speech recognition were determined by repeated trials in the VRAS-equipped centrifuge. The relationship of vibration, G, O2 mask, mission duration, and cockpit temperature and voice quality was determined. The results showed that: (1) voice quality degrades after 0.5 hours with an O2 mask; (2) voice quality degrades under high vibration; and (3) voice quality degrades under high levels of G. The voice quality studies are summarized. These results were obtained with a baseline of 80 percent recognition accuracy with VCS.

  18. Integrated fuel management system

    SciTech Connect

    Barbeau, D.E.

    1987-09-29

    An aircraft fuel management system to regulate fuel from an airframe reservoir is described. The system comprises: an aircraft turbine engine having a combustor providing propulsion for the aircraft; a fuel pump receiving fuel from the reservoir and supplying fuel to the turbine engine; a motor controlling the pump so as to provide fuel to the turbine engine; means for sensing at least one engine condition; means responsive to the sensing means for controlling fuel flow to the turbine engine, and wherein the pump and the motor are of the constant speed type and further comprising valve means for controlling the fuel flow rate to the turbine engine and wherein the controlling means modulates the position of the valve means.

  19. Standards and ontologies in computational systems biology.

    PubMed

    Sauro, Herbert M; Bergmann, Frank T

    2008-01-01

    With the growing importance of computational models in systems biology there has been much interest in recent years to develop standard model interchange languages that permit biologists to easily exchange models between different software tools. In the present chapter two chief model exchange standards, SBML (Systems Biology Markup Language) 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 modelling languages and visualization tools in systems biology.

  20. Integrated Application Software System.

    DTIC Science & Technology

    1982-12-01

    12 B, WORD PROCESO *3...*.....e..... 14 C, DATSSASE "ANACEMENT SYSTEM*.*.*.*,* 1 0, ELECTPONICS3P49AD-SHECT *......... 20 to FnR"S GVNERATOR o...12, Natural Join NJ In the folloing sectlons each of the five included aplication Packages will be covered as to use of the Conceptual Level and their...terms of a previously defined apliceation ooerationt the crevlous operation will appear In brackets, W". As EDVTORYWORD PROCESSOR As discussed In Chanter

  1. Human Systems Integration Requirements

    DTIC Science & Technology

    2009-09-01

    conditions? (Night, All Weather) 5. Is there special gear required that may impact task performance (Mission Oriented Protective Posture (MOPP...or from personal protective equipment? 21. Does the system meet vibration and shock requirements under all operational conditions? 22. Are there...11. Is the system’s ability to distinguish between friendly and enemy targets compatible with mission oriented protective posture level IV (MOPP

  2. 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.

  3. Soldier Integrated Headwear System: System Design Process

    DTIC Science & Technology

    2006-10-01

    Nationale Canada Abstract The aim of the Soldier Integrated Headwear System –Technology Demonstration Project (SIHS-TDP) is to empirically...determine the most promising headwear integration concept that significantly enhances the survivability and effectiveness of the future Canadian

  4. Neuroscience in the era of functional genomics and systems biology.

    PubMed

    Geschwind, Daniel H; Konopka, Genevieve

    2009-10-15

    Advances in genetics and genomics have fuelled a revolution in discovery-based, or hypothesis-generating, research that provides a powerful complement to the more directly hypothesis-driven molecular, cellular and systems neuroscience. Genetic and functional genomic studies have already yielded important insights into neuronal diversity and function, as well as disease. One of the most exciting and challenging frontiers in neuroscience involves harnessing the power of large-scale genetic, genomic and phenotypic data sets, and the development of tools for data integration and mining. Methods for network analysis and systems biology offer the promise of integrating these multiple levels of data, connecting molecular pathways to nervous system function.

  5. 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…

  6. Integrated agricultural energy system

    NASA Astrophysics Data System (ADS)

    Taylor, R. M.

    1985-08-01

    The purpose of this program is to show New England farmers and other New England energy users how they can use alternative energy sources to reduce their energy cost and dependency on conventional sources. The project demonstrates alternative energy technologies in solar, alcohol and methane. Dissemination is planned through tours to be conducted by the Worcester County Extension Service. Most of these goals were completed as planned. A few things have yet to be completed. The solar panels and solar hot water tanks have to be installed. The fermenter's agitating and cooling system have to be secured inside the fermenter. Once these items are complete tours will begin early in the spring.

  7. Integrated blending control system

    SciTech Connect

    Cogbill, R.B.; Dodd, T.J.; Heilman, P.W.; Heronemus, D.L.; Sears, L.R.; Berryman, L.N.; Baker, R.L.; Guffee, L.E.; Prucha, D.A.; Roberts, D.M.

    1989-07-25

    This patent describes a proppant control system. It comprises: storage bin means for storing particulate material; surge bin means for receiving a flow of the particulate material from the storage bin means; first conveyor means for providing a flow of particulate material to the surge bin means from the storage bin means; second conveyor means for transferring a controllable quantity of the particulate material from the surge bin means; and proppant control means. The control means include: first speed control means for remotely controlling the speed of the first conveyor means; and second speed control means for remotely controlling the speed of the second conveyor means.

  8. Integrative biology approach identifies cytokine targeting strategies for psoriasis.

    PubMed

    Perera, Gayathri K; Ainali, Chrysanthi; Semenova, Ekaterina; Hundhausen, Christian; Barinaga, Guillermo; Kassen, Deepika; Williams, Andrew E; Mirza, Muddassar M; Balazs, Mercedesz; Wang, Xiaoting; Rodriguez, Robert Sanchez; Alendar, Andrej; Barker, Jonathan; Tsoka, Sophia; Ouyang, Wenjun; Nestle, Frank O

    2014-02-12

    Cytokines are critical checkpoints of inflammation. The treatment of human autoimmune disease has been revolutionized by targeting inflammatory cytokines as key drivers of disease pathogenesis. Despite this, there exist numerous pitfalls when translating preclinical data into the clinic. We developed an integrative biology approach combining human disease transcriptome data sets with clinically relevant in vivo models in an attempt to bridge this translational gap. We chose interleukin-22 (IL-22) as a model cytokine because of its potentially important proinflammatory role in epithelial tissues. Injection of IL-22 into normal human skin grafts produced marked inflammatory skin changes resembling human psoriasis. Injection of anti-IL-22 monoclonal antibody in a human xenotransplant model of psoriasis, developed specifically to test potential therapeutic candidates, efficiently blocked skin inflammation. Bioinformatic analysis integrating both the IL-22 and anti-IL-22 cytokine transcriptomes and mapping them onto a psoriasis disease gene coexpression network identified key cytokine-dependent hub genes. Using knockout mice and small-molecule blockade, we show that one of these hub genes, the so far unexplored serine/threonine kinase PIM1, is a critical checkpoint for human skin inflammation and potential future therapeutic target in psoriasis. Using in silico integration of human data sets and biological models, we were able to identify a new target in the treatment of psoriasis.

  9. 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.

  10. 3D Scan Systems Integration

    DTIC Science & Technology

    2007-11-02

    AGENCY USE ONLY (Leave Blank) 2. REPORT DATE 5 Feb 98 4. TITLE AND SUBTITLE 3D Scan Systems Integration REPORT TYPE AND DATES COVERED...2-89) Prescribed by ANSI Std. Z39-1 298-102 [ EDO QUALITY W3PECTEDI DLA-ARN Final Report for US Defense Logistics Agency on DDFG-T2/P3: 3D...SCAN SYSTEMS INTEGRATION Contract Number SPO100-95-D-1014 Contractor Ohio University Delivery Order # 0001 Delivery Order Title 3D Scan Systems

  11. Integrated Building Management System (IBMS)

    SciTech Connect

    Anita Lewis

    2012-07-01

    This project provides a combination of software and services that more easily and cost-effectively help to achieve optimized building performance and energy efficiency. Featuring an open-platform, cloud- hosted application suite and an intuitive user experience, this solution simplifies a traditionally very complex process by collecting data from disparate building systems and creating a single, integrated view of building and system performance. The Fault Detection and Diagnostics algorithms developed within the IBMS have been designed and tested as an integrated component of the control algorithms running the equipment being monitored. The algorithms identify the normal control behaviors of the equipment without interfering with the equipment control sequences. The algorithms also work without interfering with any cooperative control sequences operating between different pieces of equipment or building systems. In this manner the FDD algorithms create an integrated building management system.

  12. 78 FR 39280 - Integrated System Power Rates

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-01

    ... Doc No: 2013-15685] DEPARTMENT OF ENERGY Southwestern Power Administration Integrated System Power... hydroelectric generating facilities. The Administrator of Southwestern has developed proposed Integrated System... revenues received under the Integrated System rates, as are those of Southwestern's transmission...

  13. Integrated high power VCSEL systems

    NASA Astrophysics Data System (ADS)

    Moench, Holger; Conrads, Ralf; Gronenborn, Stephan; Gu, Xi; Miller, Michael; Pekarski, Pavel; Pollmann-Retsch, Jens; Pruijmboom, Armand; Weichmann, Ulrich

    2016-03-01

    High power VCSEL systems are a novel laser source used for thermal treatment in industrial manufacturing. These systems will be applied in many applications, which have not used a laser source before. This is enabled by the unique combination of efficiency, compactness and robustness. High power VCSEL system technology encompasses elements far beyond the VCSEL chip itself: i.e. heat sinks, bonding technology and integrated optics. This paper discusses the optimization of these components and processes specifically for building high-power laser systems with VCSEL arrays. New approaches help to eliminate components and process steps and make the system more robust and easier to manufacture. New cooler concepts with integrated electrical and mechanical interfaces have been investigated and offer advantages for high power system design. The bonding process of chips on sub-mounts and coolers has been studied extensively and for a variety of solder materials. High quality of the interfaces as well as good reliability under normal operation and thermal cycling have been realized. A viable alternative to soldering is silver sintering. The very positive results which have been achieved with a variety of technologies indicate the robustness of the VCSEL chips and their suitability for high power systems. Beam shaping micro-optics can be integrated on the VCSEL chip in a wafer scale process by replication of lenses in a polymer layer. The performance of VCSEL arrays with integrated collimation lenses has been positively evaluated and the integrated chips are fully compatible with all further assembly steps. The integrated high power systems make the application even easier and more robust. New examples in laser material processing and pumping of solid state lasers are presented.

  14. DKIST facility management system integration

    NASA Astrophysics Data System (ADS)

    White, Charles R.; Phelps, LeEllen

    2016-07-01

    The Daniel K. Inouye Solar Telescope (DKIST) Observatory is under construction at Haleakalā, Maui, Hawai'i. When complete, the DKIST will be the largest solar telescope in the world. The Facility Management System (FMS) is a subsystem of the high-level Facility Control System (FCS) and directly controls the Facility Thermal System (FTS). The FMS receives operational mode information from the FCS while making process data available to the FCS and includes hardware and software to integrate and control all aspects of the FTS including the Carousel Cooling System, the Telescope Chamber Environmental Control Systems, and the Temperature Monitoring System. In addition it will integrate the Power Energy Management System and several service systems such as heating, ventilation, and air conditioning (HVAC), the Domestic Water Distribution System, and the Vacuum System. All of these subsystems must operate in coordination to provide the best possible observing conditions and overall building management. Further, the FMS must actively react to varying weather conditions and observational requirements. The physical impact of the facility must not interfere with neighboring installations while operating in a very environmentally and culturally sensitive area. The FMS system will be comprised of five Programmable Automation Controllers (PACs). We present a pre-build overview of the functional plan to integrate all of the FMS subsystems.

  15. Symplectic integrators for spin systems

    NASA Astrophysics Data System (ADS)

    McLachlan, Robert I.; Modin, Klas; Verdier, Olivier

    2014-06-01

    We present a symplectic integrator, based on the implicit midpoint method, for classical spin systems where each spin is a unit vector in R3. Unlike splitting methods, it is defined for all Hamiltonians and is O (3)-equivariant, i.e., coordinate-independent. It is a rare example of a generating function for symplectic maps of a noncanonical phase space. It yields a new integrable discretization of the spinning top.

  16. Durable resistance to the wheat rusts: Integrating systems biology and traditional phenotype-based research methods to guide the deployment of resistance genes

    PubMed Central

    Lowe, Iago; Cantu, Dario; Dubcovsky, Jorge

    2016-01-01

    Genes which confer partial resistance to the rusts in wheat figure prominently in discussions of potential durable resistance strategies. The positional cloning of the first of these genes, Lr34/Yr18 and Yr36, has revealed different protein structures, suggesting that the category of partial resistance genes, as defined by phenotype, likely groups together suites of functionally heterogenous genes. With the number of mapped partial rust resistance genes increasing rapidly as a result of ongoing advances in marker and sequencing technologies, breeding programs needing to select and prioritize genes for deployment confront a fundamental question: which genes or gene combinations are more likely to provide durable protection against these evolving pathogens? We argue that a refined classification of partial rust resistance genes is required to start answering this question, one based not merely on disease phenotype but also on gene cloning, molecular functional characterization, and interactions with other host and pathogen proteins. Combined with accurate and detailed disease phenotyping and standard genetic studies, an integrated wheat-rust interactome promises to provide the basis for a functional classification of partial resistance genes and thus a conceptual framework for their rational deployment. PMID:26900170

  17. A systems biology perspective of wine fermentations.

    PubMed

    Pizarro, Francisco; Vargas, Felipe A; Agosin, Eduardo

    2007-11-01

    The yeast Saccharomyces cerevisiae is an important industrial microorganism. Nowadays, it is being used as a cell factory for the production of pharmaceuticals such as insulin, although this yeast has long been utilized in the bakery to raise dough, and in the production of alcoholic beverages, fermenting the sugars derived from rice, wheat, barley, corn and grape juice. S. cerevisiae has also been extensively used as a model eukaryotic system. In the last decade, genomic techniques have revealed important features of its molecular biology. For example, DNA array technologies are routinely used for determining gene expression levels in cells under different physiological conditions or environmental stimuli. Laboratory strains of S. cerevisiae are different from wine strains. For instance, laboratory yeasts are unable to completely transform all the sugar in the grape must into ethanol under winemaking conditions. In fact, standard culture conditions are usually very different from winemaking conditions, where multiple stresses occur simultaneously and sequentially throughout the fermentation. The response of wine yeasts to these stimuli differs in some aspects from laboratory strains, as suggested by the increasing number of studies in functional genomics being conducted on wine strains. In this paper we review the most recent applications of post-genomic techniques to understand yeast physiology in the wine industry. We also report recent advances in wine yeast strain improvement and propose a reference framework for integration of genomic information, bioinformatic tools and molecular biology techniques for cellular and metabolic engineering. Finally, we discuss the current state and future perspectives for using 'modern' biotechnology in the wine industry.

  18. Improved system integration for integrated gasification combined cycle (IGCC) systems.

    PubMed

    Frey, H Christopher; Zhu, Yunhua

    2006-03-01

    Integrated gasification combined cycle (IGCC) systems are a promising technology for power generation. They include an air separation unit (ASU), a gasification system, and a gas turbine combined cycle power block, and feature competitive efficiency and lower emissions compared to conventional power generation technology. IGCC systems are not yet in widespread commercial use and opportunities remain to improve system feasibility via improved process integration. A process simulation model was developed for IGCC systems with alternative types of ASU and gas turbine integration. The model is applied to evaluate integration schemes involving nitrogen injection, air extraction, and combinations of both, as well as different ASU pressure levels. The optimal nitrogen injection only case in combination with an elevated pressure ASU had the highest efficiency and power output and approximately the lowest emissions per unit output of all cases considered, and thus is a recommended design option. The optimal combination of air extraction coupled with nitrogen injection had slightly worse efficiency, power output, and emissions than the optimal nitrogen injection only case. Air extraction alone typically produced lower efficiency, lower power output, and higher emissions than all other cases. The recommended nitrogen injection only case is estimated to provide annualized cost savings compared to a nonintegrated design. Process simulation modeling is shown to be a useful tool for evaluation and screening of technology options.

  19. 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

  20. 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

  1. Integrated Graduate Program in Physical and Engineering Biology at Yale University

    NASA Astrophysics Data System (ADS)

    Caballero, Diego; Noble, Dorottya; Pollard, Thomas; Mochrie, Simon; O'Hern, Corey; Regan, Lynne

    2014-03-01

    Quantitative, integrated approaches are necessary to solve biology's grand challenges. Yale's Integrated Graduate Program in Physical and Engineering Biology (IGPPEB) prepares students to excel at applying physics and engineering approaches, whilst also ensuring that they are sufficiently biologically sophisticated that they can readily identify and tackle cutting-edge problems. Students enter the program through a ``home'' department but also take a set of IGPPEB core courses with students from other departments. The IGPPEB curriculum is co-taught by faculty from a wide array of departments and motivates students to work together and learn from each other. The curriculum complements those of the home departments and includes primer courses to rapidly bring all students to a level where they ``speak each others language.'' The program is a member of the NSF's Physics of Living Systems: Student Research Network, which connects graduate students from different institutions that are engaged in research at the interface of physics and biology. Convergent research thrusts at Yale include Cellular Shape and Motion; Mechanical Force Generation and Sensing; Biomaterials and Bioinspired Design; Systems and Synthetic Biology; Modeling Biological Processes and Methods Development.

  2. Controlled vocabularies and semantics in systems biology.

    PubMed

    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

    2011-10-25

    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.

  3. First steps in computational systems biology: A practical session in metabolic modeling and simulation.

    PubMed

    Reyes-Palomares, Armando; Sánchez-Jiménez, Francisca; Medina, Miguel Ángel

    2009-05-01

    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 faster numerical simulations of mathematical models. Mathematical modeling plays an essential role in new systems biology approaches. As a complex, integrated system, metabolism is a suitable topic of study for systems biology approaches. However, up until recently, this topic has not been properly covered in biochemistry courses. This communication reports the development and implementation of a practical lesson plan on metabolic modeling and simulation.

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

    PubMed

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

    2013-04-01

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

  5. An integrated, low noise patch-clamp amplifier for biological nanopore applications.

    PubMed

    Wang, Gang; Dunbar, William B

    2010-01-01

    We present an integrated, low noise patch-clamp amplifier for biological nanopore applications. Our amplifier consists of an integrator-differentiator architecture coupled with a novel opamp design in the CMOS 0.35 µm process. The post-layout full-chip simulation shows the input referred noise of the amplifier is 0.49 pA RMS over a 5 kHz bandwidth using a verified electrical model for the biological nanopore system. In our biological nanopore experiments studying protein-DNA interactions, we encounter capacitive transients with a nominal settling time of 5 ms. Our amplifier design reduces the settling time to 0.2 ms, without requiring any compensation circuitry.

  6. Improved integrated sniper location system

    NASA Astrophysics Data System (ADS)

    Figler, Burton D.; Spera, Timothy J.

    1999-01-01

    In July of 1995, Lockheed Martin IR Imaging Systems, of Lexington, Massachusetts began the development of an integrated sniper location system for the Defense Advanced Research Projects Agency and for the Department of the Navy's Naval Command Control & Ocean Surveillance Center, RDTE Division in San Diego, California. The I-SLS integrates acoustic and uncooled infrared sensing technologies to provide an affordable and highly effective sniper detection and location capability. This system, its performance and results from field tests at Camp Pendleton, California, in October 1996 were described in a paper presented at the November 1996 SPIE Photonics East Symposium1 on Enabling Technologies for Law Enforcement and Security. The I-SLS combines an acoustic warning system with an uncooled infrared warning system. The acoustic warning system has been developed by SenTech, Inc., of Lexington, Massachusetts. This acoustic warning system provides sniper detection and coarse location information based upon the muzzle blast of the sniper's weapon and/or upon the shock wave produced by the sniper's bullet, if the bullet is supersonic. The uncooled infrared warning system provides sniper detection and fine location information based upon the weapon's muzzle flash. In addition, the uncooled infrared warning system can provide thermal imagery that can be used to accurately locate and identify the sniper. Combining these two technologies improves detection probability, reduces false alarm rate and increases utility. In the two years since the last report of the integrated sniper location system, improvements have been made and a second field demonstration was planned. In this paper, we describe the integrated sniper location system modifications in preparation for the new field demonstration. In addition, fundamental improvements in the uncooled infrared sensor technology continue to be made. These improvements include higher sensitivity (lower minimum resolvable temperature

  7. Intelligent systems technology infrastructure for integrated systems

    NASA Technical Reports Server (NTRS)

    Lum, Henry, Jr.

    1991-01-01

    Significant advances have occurred during the last decade in intelligent systems technologies (a.k.a. knowledge-based systems, KBS) including research, feasibility demonstrations, and technology implementations in operational environments. Evaluation and simulation data obtained to date in real-time operational environments suggest that cost-effective utilization of intelligent systems technologies can be realized for Automated Rendezvous and Capture applications. The successful implementation of these technologies involve a complex system infrastructure integrating the requirements of transportation, vehicle checkout and health management, and communication systems without compromise to systems reliability and performance. The resources that must be invoked to accomplish these tasks include remote ground operations and control, built-in system fault management and control, and intelligent robotics. To ensure long-term evolution and integration of new validated technologies over the lifetime of the vehicle, system interfaces must also be addressed and integrated into the overall system interface requirements. An approach for defining and evaluating the system infrastructures including the testbed currently being used to support the on-going evaluations for the evolutionary Space Station Freedom Data Management System is presented and discussed. Intelligent system technologies discussed include artificial intelligence (real-time replanning and scheduling), high performance computational elements (parallel processors, photonic processors, and neural networks), real-time fault management and control, and system software development tools for rapid prototyping capabilities.

  8. Biological detection of low radiation doses with integrated photothermal assay

    NASA Astrophysics Data System (ADS)

    Zharov, Vladimir P.; Viegas, Mark; Soderberg, Lee S. F.

    2005-04-01

    The goal of this paper was to evaluate the diagnostic value of integrated photothermal (PT) assay with additional fluorescent and photoacoustic (PA) modules to assess both the "safety limit" of exposure to ionizing γ-radiation and optimal therapeutic doses for cancer treatment. With this assay, the influences of γ irradiation on cancer cells (pancreatic-AR42J and hepatocytes-hepG2) and healthy cells (mouse lymphocytes and erythrocytes) was examined as a function of exposure dose (0.6-5 Gy) and time after irradiation, in vitro and in vivo. Independent verification of data obtained with conventional assays revealed that integrated PT assay allowed us to detect the different stages of radiation impact, including changes in cell metabolism at low dose, or stages related to cell death (apoptosis and necrosis) at high doses with a threshold sensitivity of at least three orders of magnitude better than existing assays. Also, PT assay was capable of quantitatively differentiating the biological action of γ irradiation alone and in combination with drug and nicotine impact. Finally, we demonstrated on an animal model that IPT assay has the potential for use in routine rapid evaluation of biological consequences of low-dose exposure a few days after irradiation.

  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. A Systems Biology-Based Approach to Uncovering the Molecular Mechanisms Underlying the Effects of Dragon's Blood Tablet in Colitis, Involving the Integration of Chemical Analysis, ADME Prediction, and Network Pharmacology

    PubMed Central

    Gao, Xiumei; Zhai, Huaqiang; Lin, Na; Tang, Shihuan; Liang, Rixin; Ma, Yan; Li, Defeng; Zhang, Yi; Zhu, Guangrong; Yang, Hongjun; Huang, Luqi

    2014-01-01

    Traditional Chinese medicine (TCM) is one of the oldest East Asian medical systems. The present study adopted a systems biology-based approach to provide new insights relating to the active constituents and molecular mechanisms underlying the effects of dragon's blood (DB) tablets for the treatment of colitis. This study integrated chemical analysis, prediction of absorption, distribution, metabolism, and excretion (ADME), and network pharmacology. Firstly, a rapid, reliable, and accurate ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry method was employed to identify 48 components of DB tablets. In silico prediction of the passive absorption of these compounds, based on Caco-2 cell permeability, and their P450 metabolism enabled the identification of 22 potentially absorbed components and 8 metabolites. Finally, networks were constructed to analyze interactions between these DB components/metabolites absorbed and their putative targets, and between the putative DB targets and known therapeutic targets for colitis. This study provided a great opportunity to deepen the understanding of the complex pharmacological mechanisms underlying the effects of DB in colitis treatment. PMID:25068885

  11. Towards Improving the Integration of Undergraduate Biology and Mathematics Education

    PubMed Central

    Bergevin, Christopher

    2010-01-01

    Arguments have recently asserted the need for change in undergraduate biology education, particularly with regard to the role of mathematics. The crux of these protests is that rapidly developing technology is expanding the types of measurements and subsequent data available to biologists. Thus future generations of biologists will require a set of quantitative and analytic skills that will allow them to handle these types of data in order to tackle relevant questions of interest. In this spirit, we describe here strategies (or lessons learned) for undergraduate educators with regard to better preparing undergraduate biology majors for the new types of challenges that lay ahead. The topics covered here span a broad range, from classroom approaches to the administrative level (e.g., fostering inter-departmental communication, student advising) and beyond. A key theme here is the need for an attitude shift with regard to mathematics education by both students and faculty alike. Such a shift will facilitate the development and implementation of new teaching strategies with regard to improving integration of mathematics and biology pedagogy. PMID:23653694

  12. Two integrable systems with integrals of motion of degree four

    NASA Astrophysics Data System (ADS)

    Tsiganov, A. V.

    2016-03-01

    We discuss the possibility of using second-order Killing tensors to construct Liouville-integrable Hamiltonian systems that are not Nijenhuis integrable. As an example, we consider two Killing tensors with a nonzero Haantjes torsion that satisfy weaker geometric conditions and also three-dimensional systems corresponding to them that are integrable in Euclidean space and have two quadratic integrals of motion and one fourth-order integral in momenta.

  13. Integrating paleobiology, archeology, and history to inform biological conservation.

    PubMed

    Rick, Torben C; Lockwood, Rowan

    2013-02-01

    The search for novel approaches to establishing ecological baselines (reference conditions) is constrained by the fact that most ecological studies span the past few decades, at most, and investigate ecosystems that have been substantially altered by human activities for decades, centuries, or more. Paleobiology, archeology, and history provide historical ecological context for biological conservation, remediation, and restoration. We argue that linking historical ecology explicitly with conservation can help unify related disciplines of conservation paleobiology, conservation archeobiology, and environmental history. Differences in the spatial and temporal resolution and extent (scale) of prehistoric, historic, and modern ecological data remain obstacles to integrating historical ecology and conservation biology, but the prolonged temporal extents of historical ecological data can help establish more complete baselines for restoration, document a historical range of ecological variability, and assist in determining desired future conditions. We used the eastern oyster (Crassostrea virginica) fishery of the Chesapeake Bay (U.S.A.) to demonstrate the utility of historical ecological data for elucidating oyster conservation and the need for an approach to conservation that transcends disciplinary boundaries. Historical ecological studies from the Chesapeake have documented dramatic declines (as much as 99%) in oyster abundance since the early to mid-1800 s, changes in oyster size in response to different nutrient levels from the sixteenth to nineteenth centuries, and substantial reductions in oyster accretion rates (from 10 mm/year to effectively 0 mm/year) from the Late Holocene to modern times. Better integration of different historical ecological data sets and increased collaboration between paleobiologists, geologists, archeologists, environmental historians, and ecologists to create standardized research designs and methodologies will help unify prehistoric

  14. Integration of photosynthesis, development and stress as an opportunity for plant biology.

    PubMed

    Allahverdiyeva, Yagut; Battchikova, Natalia; Brosché, Mikael; Fujii, Hiroaki; Kangasjärvi, Saijaliisa; Mulo, Paula; Mähönen, Ari Pekka; Nieminen, Kaisa; Overmyer, Kirk; Salojärvi, Jarkko; Wrzaczek, Michael

    2015-11-01

    With the tremendous progress of the past decades, molecular plant science is becoming more unified than ever. We now have the exciting opportunity to further connect subdisciplines and understand plants as whole organisms, as will be required to efficiently utilize them in natural and agricultural systems to meet human needs. The subfields of photosynthesis, plant developmental biology and plant stress are used as examples to discuss how plant science can become better integrated. The challenges, strategies and rich opportunities for the integration of the plant sciences are discussed. In recent years, more and more overlap between various subdisciplines has been inadvertently discovered including tradeoffs that may occur in plants engineered for biotechnological applications. Already important, bioinformatics and computational modelling will become even more central to structuring and understanding the ever growing amounts of data. The process of integrating and overlapping fields in plant biology research is advancing, but plant science will benefit from dedicating more effort and urgency to reach across its boundaries.

  15. Electronic integrated disease surveillance system and pathogen asset control system.

    PubMed

    Wahl, Tom G; Burdakov, Aleksey V; Oukharov, Andrey O; Zhilokov, Azamat K

    2012-06-20

    Electronic Integrated Disease Surveillance System (EIDSS) has been used to strengthen and support monitoring and prevention of dangerous diseases within One Health concept by integrating veterinary and human surveillance, passive and active approaches, case-based records including disease-specific clinical data based on standardised case definitions and aggregated data, laboratory data including sample tracking linked to each case and event with test results and epidemiological investigations. Information was collected and shared in secure way by different means: through the distributed nodes which are continuously synchronised amongst each other, through the web service, through the handheld devices. Electronic Integrated Disease Surveillance System provided near real time information flow that has been then disseminated to the appropriate organisations in a timely manner. It has been used for comprehensive analysis and visualisation capabilities including real time mapping of case events as these unfold enhancing decision making. Electronic Integrated Disease Surveillance System facilitated countries to comply with the IHR 2005 requirements through a data transfer module reporting diseases electronically to the World Health Organisation (WHO) data center as well as establish authorised data exchange with other electronic system using Open Architecture approach. Pathogen Asset Control System (PACS) has been used for accounting, management and control of biological agent stocks. Information on samples and strains of any kind throughout their entire lifecycle has been tracked in a comprehensive and flexible solution PACS.Both systems have been used in a combination and individually. Electronic Integrated Disease Surveillance System and PACS are currently deployed in the Republics of Kazakhstan, Georgia and Azerbaijan as a part of the Cooperative Biological Engagement Program (CBEP) sponsored by the US Defense Threat Reduction Agency (DTRA).

  16. Mining maximal cohesive induced subnetworks and patterns by integrating biological networks with gene profile data.

    PubMed

    Alroobi, Rami; Ahmed, Syed; Salem, Saeed

    2013-09-01

    With the availability of vast amounts of protein-protein, protein-DNA interactions, and genome-wide mRNA expression data for several organisms, identifying biological complexes has emerged as a major task in systems biology. Most of the existing approaches for complex identification have focused on utilizing one source of data. Recent research has shown that systematic integration of gene profile data with interaction data yields significant patterns. In this paper, we introduce the problem of mining maximal cohesive subnetworks that satisfy user-defined constraints defined over the gene profiles of the reported subnetworks. Moreover, we introduce the problem of finding maximal cohesive patterns which are sets of cohesive genes. Experiments on Yeast and Human datasets show the effectiveness of the proposed approach by assessing the overlap of the discovered subnetworks with known biological complexes. Moreover, GO enrichment analysis shows that the discovered subnetworks are biologically significant.

  17. Method of measurement in biological systems

    DOEpatents

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

    1993-05-11

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

  18. Method of measurement in biological systems

    DOEpatents

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

    1994-01-01

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

  19. 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.

  20. Lunar materials processing system integration

    NASA Technical Reports Server (NTRS)

    Sherwood, Brent

    1992-01-01

    The theme of this paper is that governmental resources will not permit the simultaneous development of all viable lunar materials processing (LMP) candidates. Choices will inevitably be made, based on the results of system integration trade studies comparing candidates to each other for high-leverage applications. It is in the best long-term interest of the LMP community to lead the selection process itself, quickly and practically. The paper is in five parts. The first part explains what systems integration means and why the specialized field of LMP needs this activity now. The second part defines the integration context for LMP -- by outlining potential lunar base functions, their interrelationships and constraints. The third part establishes perspective for prioritizing the development of LMP methods, by estimating realistic scope, scale, and timing of lunar operations. The fourth part describes the use of one type of analytical tool for gaining understanding of system interactions: the input/output model. A simple example solved with linear algebra is used to illustrate. The fifth and closing part identifies specific steps needed to refine the current ability to study lunar base system integration. Research specialists have a crucial role to play now in providing the data upon which this refinement process must be based.

  1. Advanced Studies of Integrable Systems.

    DTIC Science & Technology

    1986-12-18

    Fluctuations in Magnetized Plasmas (Phys. Fluids 27, 1169-75 (1984)] (coauthored with S.N. Antani) The nonlinear interactions of whistler waves with density... Dynamica Problems in Soliton Systems, pp 12-22. ed. S. Takeno, Springer-Verlag, NY (1985)]. S 11. Forced Integrable Systems - An Overview, D. J. Kaup...Kaup, P.J. Hansen, S. Roy Choudhury and Gary E. Thomas (accepted for publication in Phys. Fluids ). A singular perturbation method is used to solve this

  2. 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.

  3. Integration and macroevolutionary patterns in the pollination biology of conifers.

    PubMed

    Leslie, Andrew B; Beaulieu, Jeremy M; Crane, Peter R; Knopf, Patrick; Donoghue, Michael J

    2015-06-01

    Integration influences patterns of trait evolution, but the relationship between these patterns and the degree of trait integration is not well understood. To explore this further, we study a specialized pollination mechanism in conifers whose traits are linked through function but not development. This mechanism depends on interactions among three characters: pollen that is buoyant, ovules that face downward at pollination, and the production of a liquid droplet that buoyant grains float through to enter the ovule. We use a well-sampled phylogeny of conifers to test correlated evolution among these characters and specific sequences of character change. Using likelihood models of character evolution, we find that pollen morphology and ovule characters evolve in a concerted manner, where the flotation mechanism breaks down irreversibly following changes in orientation or drop production. The breakdown of this functional constraint, which may be facilitated by the lack of developmental integration among the constituent traits, is associated with increased trait variation and more diverse pollination strategies. Although this functional "release" increases diversity in some ways, the irreversible way in which the flotation mechanism is lost may eventually result in its complete disappearance from seed plant reproductive biology.

  4. Integrated Systems Health Management for Intelligent Systems

    NASA Technical Reports Server (NTRS)

    Figueroa, Fernando; Melcher, Kevin

    2011-01-01

    The implementation of an integrated system health management (ISHM) capability is fundamentally linked to the management of data, information, and knowledge (DIaK) with the purposeful objective of determining the health of a system. It is akin to having a team of experts who are all individually and collectively observing and analyzing a complex system, and communicating effectively with each other in order to arrive at an accurate and reliable assessment of its health. In this paper, concepts, procedures, and approaches are presented as a foundation for implementing an intelligent systems ]relevant ISHM capability. The capability stresses integration of DIaK from all elements of a system. Both ground-based (remote) and on-board ISHM capabilities are compared and contrasted. The information presented is the result of many years of research, development, and maturation of technologies, and of prototype implementations in operational systems.

  5. 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

  6. Anion transporters and biological systems.

    PubMed

    Gale, Philip A; Pérez-Tomás, Ricardo; Quesada, Roberto

    2013-12-17

    In this Account, we discuss the development of new lipid bilayer anion transporters based on the structure of anionophoric natural products (the prodigiosins) and purely synthetic supramolecular systems. We have studied the interaction of these compounds with human cancer cell lines, and, in general, the most active anion transporter compounds possess the greatest anti-cancer properties. Initially, we describe the anion transport properties of synthetic molecules that are based on the structure of the family of natural products known as the prodiginines. Obatoclax, for example, is a prodiginine derivative with an indole ring that is currently in clinical trials for use as an anti-cancer drug. The anion transport properties of the compounds were correlated with their toxicity toward small cell human lung cancer GLC4 cells. We studied related compounds with enamine moieties, tambjamines, that serve as active transporters. These molecules and others in this series could depolarize acidic compartments within GLC4 cells and trigger apoptosis. In a study of the variation of lipophilicity of a series of these compounds, we observed that, as log P increases, the anion transport efficiency reaches a peak and then decreases. In addition, we discuss the anion transport properties of series of synthetic supramolecular anion receptor species. We synthesized trisureas and thioureas based on the tren backbone, and found that the thiourea compounds effectively transport anions. Fluorination of the pendant phenyl groups in this series of compounds greatly enhances the transport properties. Similar to our earlier results, the most active anion transporters reduced the viability of human cancer cell lines by depolarizing acidic compartments in GLC4 cells and triggering apoptosis. In an attempt to produce simpler transporters that obey Lipinski's Rule of Five, we synthesized simpler systems containing a single urea or thiourea group. Once again the thiourea systems, and in particular

  7. 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

  8. The vascular biological stereotype and the achievement problem of the neurohumoral integration during phylogenesis.

    PubMed

    Mârza, V D

    1982-01-01

    There is developed Bertalanffy's theory of systems on the evolution process of biological stereotypes (theory of Mârza, Repciuc, Eskenasy 1962) and the systemic theory nomenclature used in biology is critically discussed. A more complete definition of the reactivity is attempted. Biological stereotypes are analogous to the Pavlovian absolute reflexes and represent specialized and integrated parts of the reactivity, which forms a unity of contraries with the metabolism. There is considered that a biological stereotypes achieves to form a system when the specific organ is differentiated. On this basis is pursued the achievement of the systemic stage of nervous, emunctory (excretory), alimentary, vascular, respiratory subsystems. The nervous subsystem--and implicitly the nervous integration--is the first subsystem to be differentiated in phylogeny. The humoral integration is tardier appeared. The formation of the vascular subsystem represents a qualitative leap which allowed the evolution of all the other subsystems, inclusively of the nervous and endocrine ones, as well as of the homeostasis system. The last chapter present 6 phases of the vascular subsystem evolution starting from the structural plan of circulation in Annelida, and passing through those of Stomochordata, of fishes, of Dipnoi fishes, of Anura and Mammalia. The highly stable characters of the structural plan of the vascular subsystem evolution (the morphofunctional stereotypes of Mârza, Repciuc and Eskenasy 1962) are pointed out. This stability is interpreted in the light of the stabilizing selection. The cardiac pump and the lymphatics are differentiated from venous vessels. The integration of the arterial circulation with the heart starts in Dipnoi fishes and reached the highest form only in mammalians.

  9. 78 FR 62616 - Integrated System Power Rates

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-22

    ... Southwestern Power Administration Integrated System Power Rates AGENCY: Southwestern Power Administration, DOE... Integrated System pursuant to the Integrated System Rate Schedules to supersede the existing rate schedules... into effect on an interim basis, increases the power rates for the Integrated System pursuant to...

  10. Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders

    PubMed Central

    Parikshak, Neelroop N.; Gandal, Michael J.; Geschwind, Daniel H.

    2015-01-01

    Genetic and genomic approaches have implicated hundreds of genetic loci in neurodevelopmental disorders and neurodegeneration, but mechanistic understanding continues to lag behind the pace of gene discovery. Understanding the role of specific genetic variants in the brain involves dissecting a functional hierarchy that encompasses molecular pathways, diverse cell types, neural circuits and, ultimately, cognition and behaviour. With a focus on transcriptomics, this Review discusses how high-throughput molecular, integrative and network approaches inform disease biology by placing human genetics in a molecular systems and neurobiological context. We provide a framework for interpreting network biology studies and leveraging big genomics data sets in neurobiology. PMID:26149713

  11. 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.

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

    PubMed Central

    2014-01-01

    Background Advances in high-throughput technologies have enabled extensive generation of multi-level omics data. These data are crucial for systems biology research, though they are complex, heterogeneous, highly dynamic, incomplete and distributed among public databases. This leads to difficulties in data accessibility and often results in errors when data are merged and integrated from varied resources. Therefore, integration and management of systems biological data remain very challenging. Methods To overcome this, we designed and developed a dedicated database system that can serve and solve the vital issues in data management and hereby facilitate data integration, modeling and analysis in systems biology within a sole database. In addition, a yeast data repository was implemented as an integrated database environment which is operated by the database system. Two applications were implemented to demonstrate extensibility and utilization of the system. Both illustrate how the user can access the database via the web query function and implemented scripts. These scripts are specific for two sample cases: 1) Detecting the pheromone pathway in protein interaction networks; and 2) Finding metabolic reactions regulated by Snf1 kinase. Results and conclusion In this study we present the design of database system which offers an extensible environment to efficiently capture the majority of biological entities and relations encountered in systems biology. Critical functions and control processes were designed and implemented to ensure consistent, efficient, secure and reliable transactions. The two sample cases on the yeast integrated data clearly demonstrate the value of a sole database environment for systems biology research. PMID:25053973

  13. Systems biology solutions for biochemical production challenges.

    PubMed

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

    2017-03-16

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

  14. Fiber optic control system integration

    NASA Technical Reports Server (NTRS)

    Poppel, G. L.; Glasheen, W. M.; Russell, J. C.

    1987-01-01

    A total fiber optic, integrated propulsion/flight control system concept for advanced fighter aircraft is presented. Fiber optic technology pertaining to this system is identified and evaluated for application readiness. A fiber optic sensor vendor survey was completed, and the results are reported. The advantages of centralized/direct architecture are reviewed, and the concept of the protocol branch is explained. Preliminary protocol branch selections are made based on the F-18/F404 application. Concepts for new optical tools are described. Development plans for the optical technology and the described system are included.

  15. Moss systems biology en route: phytohormones in Physcomitrella development.

    PubMed

    Decker, E L; Frank, W; Sarnighausen, E; Reski, R

    2006-05-01

    The moss Physcomitrella patens has become a powerful model system in modern plant biology. Highly standardized cell culture techniques, as well as the necessary tools for computational biology, functional genomics and proteomics have been established. Large EST collections are available and the complete moss genome will be released soon. A simple body plan and the small number of different cell types in Physcomitrella facilitate the study of developmental processes. In the filamentous juvenile moss tissue, developmental decisions rely on the differentiation of single cells. Developmental steps are controlled by distinct phytohormones and integration of environmental signals. Especially the phytohormones auxin, cytokinin, and abscisic acid have distinct effects on early moss development. In this article, we review current knowledge about phytohormone influences on early moss development in an attempt to fully unravel the complex regulatory signal transduction networks underlying the developmental decisions of single plant cells in a holistic systems biology approach.

  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. Antiestrogen Resistance and the Application of Systems Biology

    PubMed Central

    Bouker, Kerrie B.; Wang, Yue; Xuan, Jianhua; Clarke, Robert

    2012-01-01

    Understanding the molecular changes that drive an acquired antiestrogen resistance phenotype is of major clinical relevance. Previous methodologies for addressing this question have taken a single gene/pathway approach and the resulting gains have been limited in terms of their clinical impact. Recent systems biology approaches allow for the integration of data from high throughput “-omics” technologies. We highlight recent advances in the field of antiestrogen resistance with a focus on transcriptomics, proteomics and methylomics. PMID:23539064

  18. Integrative biology identifies shared transcriptional networks in CKD.

    PubMed

    Martini, Sebastian; Nair, Viji; Keller, Benjamin J; Eichinger, Felix; Hawkins, Jennifer J; Randolph, Ann; Böger, Carsten A; Gadegbeku, Crystal A; Fox, Caroline S; Cohen, Clemens D; Kretzler, Matthias

    2014-11-01

    A previous meta-analysis of genome-wide association data by the Cohorts for Heart and Aging Research in Genomic Epidemiology and CKDGen consortia identified 16 loci associated with eGFR. To define how each of these single-nucleotide polymorphisms (SNPs) could affect renal function, we integrated GFR-associated loci with regulatory pathways, producing a molecular map of CKD. In kidney biopsy specimens from 157 European subjects representing nine different CKDs, renal transcript levels for 18 genes in proximity to the SNPs significantly correlated with GFR. These 18 genes were mapped into their biologic context by testing coregulated transcripts for enriched pathways. A network of 97 pathways linked by shared genes was constructed and characterized. Of these pathways, 56 pathways were reported previously to be associated with CKD; 41 pathways without prior association with CKD were ranked on the basis of the number of candidate genes connected to the respective pathways. All pathways aggregated into a network of two main clusters comprising inflammation- and metabolism-related pathways, with the NRF2-mediated oxidative stress response pathway serving as the hub between the two clusters. In all, 78 pathways and 95% of the connections among those pathways were verified in an independent North American biopsy cohort. Disease-specific analyses showed that most pathways are shared between sets of three diseases, with closest interconnection between lupus nephritis, IgA nephritis, and diabetic nephropathy. Taken together, the network integrates candidate genes from genome-wide association studies into their functional context, revealing interactions and defining established and novel biologic mechanisms of renal impairment in renal diseases.

  19. Integrative Biology Identifies Shared Transcriptional Networks in CKD

    PubMed Central

    Martini, Sebastian; Nair, Viji; Keller, Benjamin J.; Eichinger, Felix; Hawkins, Jennifer J.; Randolph, Ann; Böger, Carsten A.; Gadegbeku, Crystal A.; Fox, Caroline S.; Cohen, Clemens D.

    2014-01-01

    A previous meta-analysis of genome-wide association data by the Cohorts for Heart and Aging Research in Genomic Epidemiology and CKDGen consortia identified 16 loci associated with eGFR. To define how each of these single-nucleotide polymorphisms (SNPs) could affect renal function, we integrated GFR-associated loci with regulatory pathways, producing a molecular map of CKD. In kidney biopsy specimens from 157 European subjects representing nine different CKDs, renal transcript levels for 18 genes in proximity to the SNPs significantly correlated with GFR. These 18 genes were mapped into their biologic context by testing coregulated transcripts for enriched pathways. A network of 97 pathways linked by shared genes was constructed and characterized. Of these pathways, 56 pathways were reported previously to be associated with CKD; 41 pathways without prior association with CKD were ranked on the basis of the number of candidate genes connected to the respective pathways. All pathways aggregated into a network of two main clusters comprising inflammation- and metabolism-related pathways, with the NRF2-mediated oxidative stress response pathway serving as the hub between the two clusters. In all, 78 pathways and 95% of the connections among those pathways were verified in an independent North American biopsy cohort. Disease-specific analyses showed that most pathways are shared between sets of three diseases, with closest interconnection between lupus nephritis, IgA nephritis, and diabetic nephropathy. Taken together, the network integrates candidate genes from genome-wide association studies into their functional context, revealing interactions and defining established and novel biologic mechanisms of renal impairment in renal diseases. PMID:24925724

  20. 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

  1. 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

  2. Oryzabase. An integrated biological and genome information database for rice.

    PubMed

    Kurata, Nori; Yamazaki, Yukiko

    2006-01-01

    The aim of Oryzabase is to create a comprehensive view of rice (Oryza sativa) as a model monocot plant by integrating biological data with molecular genomic information (http://www.shigen.nig.ac.jp/rice/oryzabase/top/top.jsp). The database contains information about rice development and anatomy, rice mutants, and genetic resources, especially for wild varieties of rice. The anatomical description of rice development is unique and is the first known representation for rice. Developmental and anatomical descriptions include in situ gene expression data serving as stage and tissue markers. The systematic presentation of a large number of rice mutant and mutant trait genes is indispensable, as is description of research in wild strains, core collections, and their detailed characterization. Several genetic, physical, and expression maps with full genome and cDNA sequences are also combined with biological data in Oryzabase. These datasets, when pooled together, could provide a useful tool for gaining greater knowledge about the life cycle of rice, the relationship between phenotype and gene function, and rice genetic diversity. For exchanging community information, Oryzabase publishes the Rice Genetics Newsletter organized by the Rice Genetics Cooperative and provides a mailing service, rice-e-net/rice-net.

  3. Three-dimensional identification of biological microorganism using integral imaging

    NASA Astrophysics Data System (ADS)

    Javidi, Bahram; Moon, Inkyu; Yeom, Seokwon

    2006-12-01

    In this paper, we address the identification of biological microorganisms using microscopic integral imaging (II). II senses multi-view directional information of 3D objects illuminated by incoherent light. A micro-lenslet array generates a set of elemental images by projecting a 3D scene onto a detector array. In computational reconstruction of II, 3D volumetric scenes are numerically reconstructed by means of a geometrical ray projection method. The identification of the biological samples is performed using the 3D volume of the reconstructed object. In one approach, the multivariate statistical distribution of the reference sample is measured in 3D space and compared with an unknown input sample by means of statistical discriminant functions. The multivariate empirical cumulative density of the 3D volume image is determined for classification. On the other approach, the graph matching technique is applied to 3D volumetric images with Gabor feature extraction. The reference morphology is identified in unknown input samples using 3D grids. Experimental results are presented for the identification of sphacelaria alga and tribonema aequale alga. We present experimental results for both 3D and 2D imaging. To the best of our knowledge, this is the first report on 3D identification of microorganisms using II.

  4. Three-dimensional identification of biological microorganism using integral imaging.

    PubMed

    Javidi, Bahram; Moon, Inkyu; Yeom, Seokwon

    2006-12-11

    In this paper, we address the identification of biological microorganisms using microscopic integral imaging (II). II senses multi-view directional information of 3D objects illuminated by incoherent light. A micro-lenslet array generates a set of elemental images by projecting a 3D scene onto a detector array. In computational reconstruction of II, 3D volumetric scenes are numerically reconstructed by means of a geometrical ray projection method. The identification of the biological samples is performed using the 3D volume of the reconstructed object. In one approach, the multivariate statistical distribution of the reference sample is measured in 3D space and compared with an unknown input sample by means of statistical discriminant functions. The multivariate empirical cumulative density of the 3D volume image is determined for classification. On the other approach, the graph matching technique is applied to 3D volumetric images with Gabor feature extraction. The reference morphology is identified in unknown input samples using 3D grids. Experimental results are presented for the identification of sphacelaria alga and tribonema aequale alga. We present experimental results for both 3D and 2D imaging. To the best of our knowledge, this is the first report on 3D identification of microorganisms using II.

  5. 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.

  6. Competency-Based Reforms of the Undergraduate Biology Curriculum: Integrating the Physical and Biological Sciences

    PubMed Central

    Thompson, Katerina V.; Chmielewski, Jean; Gaines, Michael S.; Hrycyna, Christine A.; LaCourse, William R.

    2013-01-01

    The National Experiment in Undergraduate Science Education project funded by the Howard Hughes Medical Institute is a direct response to the Scientific Foundations for Future Physicians report, which urged a shift in premedical student preparation from a narrow list of specific course work to a more flexible curriculum that helps students develop broad scientific competencies. A consortium of four universities is working to create, pilot, and assess modular, competency-based curricular units that require students to use higher-order cognitive skills and reason across traditional disciplinary boundaries. Purdue University; the University of Maryland, Baltimore County; and the University of Miami are each developing modules and case studies that integrate the biological, chemical, physical, and mathematical sciences. The University of Maryland, College Park, is leading the effort to create an introductory physics for life sciences course that is reformed in both content and pedagogy. This course has prerequisites of biology, chemistry, and calculus, allowing students to apply strategies from the physical sciences to solving authentic biological problems. A comprehensive assessment plan is examining students’ conceptual knowledge of physics, their attitudes toward interdisciplinary approaches, and the development of specific scientific competencies. Teaching modules developed during this initial phase will be tested on multiple partner campuses in preparation for eventual broad dissemination. PMID:23737624

  7. Competency-based reforms of the undergraduate biology curriculum: integrating the physical and biological sciences.

    PubMed

    Thompson, Katerina V; Chmielewski, Jean; Gaines, Michael S; Hrycyna, Christine A; LaCourse, William R

    2013-06-01

    The National Experiment in Undergraduate Science Education project funded by the Howard Hughes Medical Institute is a direct response to the Scientific Foundations for Future Physicians report, which urged a shift in premedical student preparation from a narrow list of specific course work to a more flexible curriculum that helps students develop broad scientific competencies. A consortium of four universities is working to create, pilot, and assess modular, competency-based curricular units that require students to use higher-order cognitive skills and reason across traditional disciplinary boundaries. Purdue University; the University of Maryland, Baltimore County; and the University of Miami are each developing modules and case studies that integrate the biological, chemical, physical, and mathematical sciences. The University of Maryland, College Park, is leading the effort to create an introductory physics for life sciences course that is reformed in both content and pedagogy. This course has prerequisites of biology, chemistry, and calculus, allowing students to apply strategies from the physical sciences to solving authentic biological problems. A comprehensive assessment plan is examining students' conceptual knowledge of physics, their attitudes toward interdisciplinary approaches, and the development of specific scientific competencies. Teaching modules developed during this initial phase will be tested on multiple partner campuses in preparation for eventual broad dissemination.

  8. 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.

  9. Integrated omics for the identification of key functionalities in biological wastewater treatment microbial communities.

    PubMed

    Narayanasamy, Shaman; Muller, Emilie E L; Sheik, Abdul R; Wilmes, Paul

    2015-05-01

    Biological wastewater treatment plants harbour diverse and complex microbial communities which prominently serve as models for microbial ecology and mixed culture biotechnological processes. Integrated omic analyses (combined metagenomics, metatranscriptomics, metaproteomics and metabolomics) are currently gaining momentum towards providing enhanced understanding of community structure, function and dynamics in situ as well as offering the potential to discover novel biological functionalities within the framework of Eco-Systems Biology. The integration of information from genome to metabolome allows the establishment of associations between genetic potential and final phenotype, a feature not realizable by only considering single 'omes'. Therefore, in our opinion, integrated omics will become the future standard for large-scale characterization of microbial consortia including those underpinning biological wastewater treatment processes. Systematically obtained time and space-resolved omic datasets will allow deconvolution of structure-function relationships by identifying key members and functions. Such knowledge will form the foundation for discovering novel genes on a much larger scale compared with previous efforts. In general, these insights will allow us to optimize microbial biotechnological processes either through better control of mixed culture processes or by use of more efficient enzymes in bioengineering applications.

  10. Workshop Report: Systems Biology for Organotypic Cell Cultures

    SciTech Connect

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

    2016-11-14

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

  11. Workshop Report: Systems Biology for Organotypic Cell Cultures

    DOE PAGES

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

    2016-11-14

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

  12. Integrated forage crop refinery system

    SciTech Connect

    Barrier, J.W.; Broder, J.D.; Madewell, C.E.; Mays, D.A.

    1985-04-01

    The proposed program involves the development of an integrated agricultural-chemical refining system for converting forage crops to useful foods, feeds, fuels, and chemicals. TVA has facilities and resources available to support extensive research and development activities. Modification can easily be made in the existing experimental facility being used to develop acid hydrolysis of corn stover, to include production of products other than fuel ethanol from forages. These products include protein, lignin-derived products, chemicals, single-cell protein, methane, aquaculture feed, and distillers solids. Refining forage crops in this manner has potential to increase the value of that crop and produce an economical integrated system. The results of the program will also be directly applicable to other areas and regions of the US. 11 refs., 7 figs., 9 tabs.

  13. 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.

  14. 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

  15. Advanced integrated life support system update

    NASA Technical Reports Server (NTRS)

    Whitley, Phillip E.

    1994-01-01

    The Advanced Integrated Life Support System Program (AILSS) is an advanced development effort to integrate the life support and protection requirements using the U.S. Navy's fighter/attack mission as a starting point. The goal of AILSS is to optimally mate protection from altitude, acceleration, chemical/biological agent, thermal environment (hot, cold, and cold water immersion) stress as well as mission enhancement through improved restraint, night vision, and head-mounted reticules and displays to ensure mission capability. The primary emphasis to date has been to establish garment design requirements and tradeoffs for protection. Here the garment and the human interface are treated as a system. Twelve state-off-the-art concepts from government and industry were evaluated for design versus performance. On the basis of a combination of centrifuge, thermal manikin data, thermal modeling, and mobility studies, some key design parameters have been determined. Future efforts will concentrate on the integration of protection through garment design and the use of a single layer, multiple function concept to streamline the garment system.

  16. Multilevel functional genomics data integration as a tool for understanding physiology: a network biology perspective.

    PubMed

    Davidsen, Peter K; Turan, Nil; Egginton, Stuart; Falciani, Francesco

    2016-02-01

    The overall aim of physiological research is to understand how living systems function in an integrative manner. Consequently, the discipline of physiology has since its infancy attempted to link multiple levels of biological organization. Increasingly this has involved mathematical and computational approaches, typically to model a small number of components spanning several levels of biological organization. With the advent of "omics" technologies, which can characterize the molecular state of a cell or tissue (intended as the level of expression and/or activity of its molecular components), the number of molecular components we can quantify has increased exponentially. Paradoxically, the unprecedented amount of experimental data has made it more difficult to derive conceptual models underlying essential mechanisms regulating mammalian physiology. We present an overview of state-of-the-art methods currently used to identifying biological networks underlying genomewide responses. These are based on a data-driven approach that relies on advanced computational methods designed to "learn" biology from observational data. In this review, we illustrate an application of these computational methodologies using a case study integrating an in vivo model representing the transcriptional state of hypoxic skeletal muscle with a clinical study representing muscle wasting in chronic obstructive pulmonary disease patients. The broader application of these approaches to modeling multiple levels of biological data in the context of modern physiology is discussed.

  17. Integrated nonthermal treatment system study

    SciTech Connect

    Biagi, C.; Bahar, D.; Teheranian, B.; Vetromile, J.; Quapp, W.J.; Bechtold, T.; Brown, B.; Schwinkendorf, W.; Swartz, G.

    1997-01-01

    This report presents the results of a study of nonthermal treatment technologies. The study consisted of a systematic assessment of five nonthermal treatment alternatives. The treatment alternatives consist of widely varying technologies for safely destroying the hazardous organic components, reducing the volume, and preparing for final disposal of the contact-handled mixed low-level waste (MLLW) currently stored in the US Department of Energy complex. The alternatives considered were innovative nonthermal treatments for organic liquids and sludges, process residue, soil and debris. Vacuum desorption or various washing approaches are considered for treatment of soil, residue and debris. Organic destruction methods include mediated electrochemical oxidation, catalytic wet oxidation, and acid digestion. Other methods studied included stabilization technologies and mercury separation of treatment residues. This study is a companion to the integrated thermal treatment study which examined 19 alternatives for thermal treatment of MLLW waste. The quantities and physical and chemical compositions of the input waste are based on the inventory database developed by the US Department of Energy. The Integrated Nonthermal Treatment Systems (INTS) systems were evaluated using the same waste input (2,927 pounds per hour) as the Integrated Thermal Treatment Systems (ITTS). 48 refs., 68 figs., 37 tabs.

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

    PubMed

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

    2014-01-01

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

  19. Systems biology 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

  20. 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…

  1. Support system considerations for STS biological investigations

    NASA Technical Reports Server (NTRS)

    Bowman, G. H.; Sebesta, P. D.

    1978-01-01

    Equipment required for Space Transportation System biological experiments is considered, and environmental factors and operational constraints affecting the performance of experiments are examined. Specimen housing is discussed, problems associated with telemetry procedures are characterized, and attention is directed to the problems of handling hazardous fixatives, radioisotopes, and chemicals.

  2. Glucose Disappearance in Biological Treatment Systems

    PubMed Central

    Jeris, John S.; Cardenas, Raul R.

    1966-01-01

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

  3. 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.

  4. 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…

  5. Systems Biology of Glucocorticoids in Muscle Disease

    DTIC Science & Technology

    2010-10-01

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

  6. Optical systems for integration with microfluidics

    NASA Astrophysics Data System (ADS)

    Godin, Jessica M.

    My thesis research has focused on means of integrating optical systems into microfluidic chips, specifically for the creation of lab-on-a-chip flow cytometers. The benefits of microfluidics are perhaps most often applied to biological assays, which frequently employ optical readout of fluorescence or light scatter. By integrating the optical system onto the microfluidic chip, we can facilitate chip interfacing while ensuring optical alignment to a tiny sample. Integrated optical systems also offer the ability to collect light from a localized area, allowing for the collection of true angular light scatter (which carries much information about cells) and can furthermore significantly improve the signal to noise ratio (SNR) relative to simple fiber or waveguide based approaches to integrated light collection. This work explores both the unique challenges and advantages encountered when creating optical systems integrated with mold-replicated microfluidic devices. The first contribution presented is the demonstration of fluid-filled lenses integrated alongside microfluidic channels using a slab waveguiding structure. The use of fluid represents an important tradeoff between lens power and Fresnel reflections. The creation of a slab waveguiding structure is critically important to control light losses when utilizing lens systems for light collection. The second contribution in this work is the demonstration of a microfluidic chip emplying a number of lenses to perform both localized excitation of the samples as well as light collection from localized areas defined by a specific angular range. Sample coefficients of variation (CVs) ranged from 9-16% for a single bead population, far exceeding previously-published CVs of 25-35%. The last contribution is an atypical approach to optical systems based on the unique advantages offered by microfabricated architectures, namely small sizes and close proximities to the sample. Using only custom-shaped total internal reflection

  7. 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

  8. 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

  9. Degeneracy and complexity in biological systems

    PubMed Central

    Edelman, Gerald M.; Gally, Joseph A.

    2001-01-01

    Degeneracy, the ability of elements that are structurally different to perform the same function or yield the same output, is a well known characteristic of the genetic code and immune systems. Here, we point out that degeneracy is a ubiquitous biological property and argue that it is a feature of complexity at genetic, cellular, system, and population levels. Furthermore, it is both necessary for, and an inevitable outcome of, natural selection. PMID:11698650

  10. Biological Indicator Systems in Floodplains - a Review

    NASA Astrophysics Data System (ADS)

    Dziock, Frank; Henle, Klaus; Foeckler, Francis; Follner, Klaus; Scholz, Mathias

    2006-08-01

    Based on a literature review, the different approaches to biological indicator systems in floodplains are summarised. Four general categories of bioindication are defined and proposed here: 1. Classification indicators, 2.1 Environmental indicators, 2.2 Biodiversity indicators, 3. Valuation indicators. Furthermore, existing approaches in floodplains are classified according to the four categories. Relevant and widely used approaches in floodplains are explained in more detail. The results of the RIVA project are put into the context of these indication approaches. It is concluded that especially functional assessment approaches using biological traits of the species can be seen as very promising and deserve more attention by conservation biologists and floodplain ecologists.

  11. Information Security and Integrity Systems

    NASA Technical Reports Server (NTRS)

    1990-01-01

    Viewgraphs from the Information Security and Integrity Systems seminar held at the University of Houston-Clear Lake on May 15-16, 1990 are presented. A tutorial on computer security is presented. The goals of this tutorial are the following: to review security requirements imposed by government and by common sense; to examine risk analysis methods to help keep sight of forest while in trees; to discuss the current hot topic of viruses (which will stay hot); to examine network security, now and in the next year to 30 years; to give a brief overview of encryption; to review protection methods in operating systems; to review database security problems; to review the Trusted Computer System Evaluation Criteria (Orange Book); to comment on formal verification methods; to consider new approaches (like intrusion detection and biometrics); to review the old, low tech, and still good solutions; and to give pointers to the literature and to where to get help. Other topics covered include security in software applications and development; risk management; trust: formal methods and associated techniques; secure distributed operating system and verification; trusted Ada; a conceptual model for supporting a B3+ dynamic multilevel security and integrity in the Ada runtime environment; and information intelligence sciences.

  12. Integrated Deployment and the Energy Systems Integration Facility: Workshop Proceedings

    SciTech Connect

    Kroposki, B.; Werner, M.; Spikes, A.; Komomua, C.

    2013-01-01

    This report summarizes the workshop entitled: Integrated Deployment and the Energy Systems Integration Facility. In anticipation of the opening of the ESIF, NREL held the workshop August 21-23, 2012 and invited participants from utilities, government, industry, and academia to discuss renewable integration challenges and discover new ways to meet them by taking advantage of the ESIF's capabilities.

  13. Current challenges and approaches for the synergistic use of systems biology data in the scientific community.

    PubMed

    Ahrens, Christian H; Wagner, Ulrich; Rehrauer, Hubert K; Türker, Can; Schlapbach, Ralph

    2007-01-01

    Today's rapid development and broad application of high-throughput analytical technologies are transforming biological research and provide an amount of data and analytical opportunities to understand the fundamentals of biological processes undreamt of in past years. To fully exploit the potential of the large amount of data, scientists must be able to understand and interpret the information in an integrative manner. While the sheer data volume and heterogeneity of technical platforms within each discipline already poses a significant challenge, the heterogeneity of platforms and data formats across disciplines makes the integrative management, analysis, and interpretation of data a significantly more difficult task. This challenge thus lies at the heart of systems biology, which aims at a quantitative understanding of biological systems to the extent that systemic features can be predicted. In this chapter, we discuss several key issues that need to be addressed in order to put an integrated systems biology data analysis and mining within reach.

  14. An integrated cell-free metabolic platform for protein production and synthetic biology

    PubMed Central

    Jewett, Michael C; Calhoun, Kara A; Voloshin, Alexei; Wuu, Jessica J; Swartz, James R

    2008-01-01

    Cell-free systems offer a unique platform for expanding the capabilities of natural biological systems for useful purposes, i.e. synthetic biology. They reduce complexity, remove structural barriers, and do not require the maintenance of cell viability. Cell-free systems, however, have been limited by their inability to co-activate multiple biochemical networks in a single integrated platform. Here, we report the assessment of biochemical reactions in an Escherichia coli cell-free platform designed to activate natural metabolism, the Cytomim system. We reveal that central catabolism, oxidative phosphorylation, and protein synthesis can be co-activated in a single reaction system. Never before have these complex systems been shown to be simultaneously activated without living cells. The Cytomim system therefore promises to provide the metabolic foundation for diverse ab initio cell-free synthetic biology projects. In addition, we describe an improved Cytomim system with enhanced protein synthesis yields (up to 1200 mg/l in 2 h) and lower costs to facilitate production of protein therapeutics and biochemicals that are difficult to make in vivo because of their toxicity, complexity, or unusual cofactor requirements. PMID:18854819

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

    PubMed Central

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

    2013-01-01

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

  16. System integration for laser restructuring

    NASA Astrophysics Data System (ADS)

    Moreno, Wilfrido A.; Saini, Nitin; Acon, Otto

    1995-09-01

    The Center for Microelectronics Research (CMR) at the University of South Florida has pursued the development of new technologies in the area of high density interconnects. The laser restructuring of electronic circuits, fabricated using standard Very Large Scale Integration (VLSI) process techniques, is an excellent alternative for custom programming of electronic circuits that allows for low cost and quick turn around of the restructured parts. A Laser System for restructuring Electronic Systems has been integrated using state of the art hardware components. This Laser System is fully computer controlled using a newly developed Microsoft Windows based software application running on a 486-66 MHz IBM compatible computer. The laser system consists of a high energy 5 watt Argon CW laser, a 2 watt double frequency pulsed Nd:YAG laser, a blocking shutter, electro-optic shutter (EOS), optic delivery system, a high precision x-y translation stage, and a video camera system used to observe the surface under laser processing. All the system components are mounted on granite table installed on four self leveling pneumatic legs for a vibration free process environment. The z-axis mechanisms consists of a stepper motor based translation stage for automatic focus controls. All control software was written using C++ programming language utilizing the power of readily available plug in boards which provide resources such as: counters, timers, image processing and IEEE-488 interfacing for remote laser control. The control environment exhibits a high degree of consistency with widely accepted visually programmed graphical 'point- and-click' interfaces.

  17. 75 FR 1363 - Integrated System Power Rates

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-11

    ... Southwestern Power Administration Integrated System Power Rates AGENCY: Southwestern Power Administration, DOE... System pursuant to the following Integrated System Rate Schedules: Rate Schedule P-09, Wholesale Rates...) Administrator has determined based on the 2009 Integrated System Current Power Repayment Study, that...

  18. A reproducible approach to high-throughput biological data acquisition and integration.

    PubMed

    Börnigen, Daniela; Moon, Yo Sup; Rahnavard, Gholamali; Waldron, Levi; McIver, Lauren; Shafquat, Afrah; Franzosa, Eric A; Miropolsky, Larissa; Sweeney, Christopher; Morgan, Xochitl C; Garrett, Wendy S; Huttenhower, Curtis

    2015-01-01

    Modern biological research requires rapid, complex, and reproducible integration of multiple experimental results generated both internally and externally (e.g., from public repositories). Although large systematic meta-analyses are among the most effective approaches both for clinical biomarker discovery and for computational inference of biomolecular mechanisms, identifying, acquiring, and integrating relevant experimental results from multiple sources for a given study can be time-consuming and error-prone. To enable efficient and reproducible integration of diverse experimental results, we developed a novel approach for standardized acquisition and analysis of high-throughput and heterogeneous biological data. This allowed, first, novel biomolecular network reconstruction in human prostate cancer, which correctly recovered and extended the NFκB signaling pathway. Next, we investigated host-microbiome interactions. In less than an hour of analysis time, the system retrieved data and integrated six germ-free murine intestinal gene expression datasets to identify the genes most influenced by the gut microbiota, which comprised a set of immune-response and carbohydrate metabolism processes. Finally, we constructed integrated functional interaction networks to compare connectivity of peptide secretion pathways in the model organisms Escherichia coli, Bacillus subtilis, and Pseudomonas aeruginosa.

  19. B chromosomes: from cytogenetics to systems biology.

    PubMed

    Valente, Guilherme T; Nakajima, Rafael T; Fantinatti, Bruno E A; Marques, Diego F; Almeida, Rodrigo O; Simões, Rafael P; Martins, Cesar

    2017-02-01

    Though hundreds to thousands of reports have described the distribution of B chromosomes among diverse eukaryote groups, a comprehensive theory of their biological role has not yet clearly emerged. B chromosomes are classically understood as a sea of repetitive DNA sequences that are poor in genes and are maintained by a parasitic-drive mechanism during cell division. Recent developments in high-throughput DNA/RNA analyses have increased the resolution of B chromosome biology beyond those of classical and molecular cytogenetic methods; B chromosomes contain many transcriptionally active sequences, including genes, and can modulate the activity of autosomal genes. Furthermore, the most recent knowledge obtained from omics analyses, which is associated with a systemic view, has demonstrated that B chromosomes can influence cell biology in a complex way, possibly favoring their own maintenance and perpetuation.

  20. Light manipulation principles in biological photonic systems

    NASA Astrophysics Data System (ADS)

    Starkey, Tim; Vukusic, Pete

    2013-10-01

    The science of light and colour manipulation continues to generate interest across a range of disciplines, from mainstream biology, across multiple physics-based fields, to optical engineering. Furthermore, the study of light production and manipulation is of significant value to a variety of industrial processes and commercial products. Among the several key methods by which colour is produced in the biological world, this review sets out to describe, in some detail, the specifics of the method involving photonics in animal and plant systems; namely, the mechanism commonly referred to as structural colour generation. Not only has this theme been a very rapidly growing area of physics-based interest, but also it is increasingly clear that the biological world is filled with highly evolved structural designs by which light and colour strongly influence behaviours and ecological functions.

  1. Primo vascular system as a new morphofunctional integrated system.

    PubMed

    Stefanov, Miroslav; Kim, Jungdae

    2012-10-01

    The purpose of this review is to describe the methodology, instruments, and subject animals used until now for studies of the meridian (Kyungrak) system and the primo vascular system (PVS). The PVS is observed as an anatomical system distributed in cavities, organs, and tissues throughout the body. We analyzed the most important points of the PVS based on the results obtained until the present. Our main effort has been directed to describing the main thesis relating to the morphological structures and their topography, the functional mechanisms of the PVS, and possible roles of the PVS in pathological processes. The substance of the PVS in all its aspects is as a system covering the whole body and regulating and coordinating the biological processes that are the basis for life. In conclusion, we suggest that the finding of the PVS represents the discovery of a new integrated morphological-functional system.

  2. Integrated Energy System Dispatch Optimization

    SciTech Connect

    Firestone, Ryan; Stadler, Michael; Marnay, Chris

    2006-06-16

    On-site cogeneration of heat and electricity, thermal and electrical storage, and curtailing/rescheduling demand options are often cost-effective to commercial and industrial sites. This collection of equipment and responsive consumption can be viewed as an integrated energy system(IES). The IES can best meet the sites cost or environmental objectives when controlled in a coordinated manner. However, continuously determining this optimal IES dispatch is beyond the expectations for operators of smaller systems. A new algorithm is proposed in this paper to approximately solve the real-time dispatch optimization problem for a generic IES containing an on-site cogeneration system subject to random outages, limited curtailment opportunities, an intermittent renewable electricity source, and thermal storage. An example demonstrates how this algorithm can be used in simulation to estimate the value of IES components.

  3. Integrated risk information system (IRIS)

    SciTech Connect

    Tuxen, L.

    1990-12-31

    The Integrated Risk Information System (IRIS) is an electronic information system developed by the US Environmental Protection Agency (EPA) containing information related to health risk assessment. IRIS is the Agency`s primary vehicle for communication of chronic health hazard information that represents Agency consensus following comprehensive review by intra-Agency work groups. The original purpose for developing IRIS was to provide guidance to EPA personnel in making risk management decisions. This original purpose for developing IRIS was to guidance to EPA personnel in making risk management decisions. This role has expanded and evolved with wider access and use of the system. IRIS contains chemical-specific information in summary format for approximately 500 chemicals. IRIS is available to the general public on the National Library of Medicine`s Toxicology Data Network (TOXNET) and on diskettes through the National Technical Information Service (NTIS).

  4. Rhythmic biological systems under microgravity conditions.

    PubMed

    Johnsson, A; Eidesmo, T

    1989-01-01

    Rhythmic phenomena in biology cover a wide frequency spectrum. In Space, the rhythms will encounter microgravity conditions which can, therefore, be a valuable tool for their understanding. A review and discussion of important effects of gravity/absence of gravity on biological systems will be given. Convection will be emphasized as a mechanism which is drastically reduced in Space. Microgravity might also affect the coupling between individual oscillators in a multi-oscillatory system. The environmental interference with rhythms will be discussed with a simple feedback as a starting point. Model simulations will be presented and clinostat and microgravity-conditions will be discussed in a specific case, viz. the gravitropical system of plants which can show sustained oscillations.

  5. Integrated Systems Health Management for Intelligent Systems

    NASA Technical Reports Server (NTRS)

    Figueroa, Fernando; Melcher, Kevin

    2011-01-01

    The implementation of an integrated system health management (ISHM) capability is fundamentally linked to the management of data, information, and knowledge (DIaK) with the purposeful objective of determining the health of a system. Management implies storage, distribution, sharing, maintenance, processing, reasoning, and presentation. ISHM is akin to having a team of experts who are all individually and collectively observing and analyzing a complex system, and communicating effectively with each other in order to arrive at an accurate and reliable assessment of its health. In this chapter, concepts, procedures, and approaches are presented as a foundation for implementing an ISHM capability relevant to intelligent systems. The capability stresses integration of DIaK from all elements of a system, emphasizing an advance toward an on-board, autonomous capability. Both ground-based and on-board ISHM capabilities are addressed. The information presented is the result of many years of research, development, and maturation of technologies, and of prototype implementations in operational systems.

  6. DORIS system and integrity survey

    NASA Astrophysics Data System (ADS)

    Jayles, C.; Chauveau, J. P.; Didelot, F.; Auriol, A.; Tourain, C.

    2016-12-01

    DORIS, as other techniques for space geodesy (SLR, VLBI, GPS) has regularly progressed to meet the ever increasing needs of the scientific community in oceanography, geodesy or geophysics. Over the past 10 years, a particular emphasis has been placed on integrity monitoring of the system, which has contributed to the enhancement of the overall availability and quality of DORIS data products. A high level of monitoring is now provided by a centralized control of the whole system, including the global network of beacons and the onboard instruments, which perform a constant end-to-end survey. At first signs of any unusual behavior, a dedicated team is activated with well-established tools to investigate, to anticipate and to contain the impact of any potential failures. The procedure has increased the availability of DORIS beacons to 90%. The core topic of this article is to demonstrate that DORIS has implemented a high-level integrity control of its data. Embedded in the DORIS receiver, DIODE (DORIS Immediate Orbit Determination) is a Real-Time On-Board Orbit Determination software. Its accuracy has also been dramatically improved when compared to Precise Orbit Ephemeris (P.O.E.), down to 2.7 cm RMS on Jason-2, 3.0 cm on Saral and 3.3 cm on CryoSat-2. Specific quality indices were derived from the DIODE-based Kalman filters and are used to monitor network and system performance. This paper covers the definition of these indices and how the reliability and the reactiveness to incidents or anomalies of the system are improved. From these indices, we have provided detailed diagnostic information about the DORIS system, which is available in real-time, on-board each DORIS satellite. Using these capabilities, we have developed real-time functions that give an immediate diagnosis of the status of key components in the DORIS system. The Near-Real Time navigation system was improved and can distinguish and handle both satellite events and beacon anomalies. The next missions

  7. 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.

  8. Integrated Sensor Systems for UAS

    DTIC Science & Technology

    2008-04-01

    narrow band filtered image (1.635μm to 1.645μm) clearly identifying regions of irrigation fallow and treed lands10. Integrated Sensor Systems for UAS...trees, 2) dry fallow land, 3) irrigated land, and 4) water body10. Radio Frequency (RF) Sensing – The use of radio waves reflected from objects of...project, the Micro - SAR stack containing the RF boards and data acquisition module (PC104 A/D and single board computer with two FlashDisks) was

  9. Integrated self-powered microchip biosensor for endogenous biological cyanide.

    PubMed

    Deng, Liu; Chen, Chaogui; Zhou, Ming; Guo, Shaojun; Wang, Erkang; Dong, Shaojun

    2010-05-15

    In this work we developed a fully integrated biofuel cell on a microchip, which consisted of glucose dehydrogenase supported (carbon nanotubes/thionine/gold nanoparticles)(8) multilayer as the anode, and the (carbon nanotubes/polylysine/laccase)(15) multilayer as the cathode. The as-obtained biofuel cell produced open circuit potential 620 mV and power density 302 microW cm(-2), showing great potential as a small power resource of portable electronics. Most importantly, for the first time we demonstrated the feasibility of developing a self-powered biosensor based on the inhibitive effect on microchip enzyme biofuel cell. With cyanide employed as the model analyte, this method showed a linear range of 3.0 x 10(-7) to 5.0 x 10(-4) M and a detection limit with 1.0 x 10(-7) M under the optimal conditions. The detection limit was lower than the acceptable cyanide concentration in drinking water (1.9 x 10(-6) M) according to the World Health Organization (WHO). This self-powered sensor was successfully used to detect the cyanide concentration in a real sample, cassava, which is the main carbohydrate resource in South America and Africa. This presented biosensor combined with a resistor and a multimeter demonstrated the general applicability as a fast and simple detection method in the determination of endogenous biological cyanide.

  10. KPFM and PFM of Biological Systems

    SciTech Connect

    Rodriguez, Brian; Kalinin, Sergei V

    2011-01-01

    Surface potentials and electrostatic interactions in biological systems are a key element of cellular regulation and interaction. Examples include cardiac and muscular activity, voltage-gated ion channels, protein folding and assembly, and electroactive cells and electrotransduction. The coupling between electrical, mechanical, and chemical signals and responses in cellular systems necessitates the development of tools capable of measuring the distribution of charged species, surface potentials, and mechanical responses to applied electrical stimuli and vice versa, ultimately under physiological conditions. In this chapter, applications of voltage-modulated atomic force microscopy (AFM) methods including Kelvin probe force microscopy (KPFM) and piezoresponse force microscopy (PFM) to biological systems are discussed. KPFM is a force-sensitive non-contact or intermittent-contact mode AFM technique that allows electrostatic interactions and surface potentials to be addressed. Beyond long-range electrostatic interactions, the application of bias can lead to a mechanical response, e.g., due to linear piezoelectric coupling in polar biopolymers or via more complex electrotransduction and redox pathways in other biosystems. The use and development of PFM, based on direct electromechanical detection, to biological systems will also be addressed. The similarities and limitations of measuring surface potentials and electromechanical coupling in solution will be outlined.

  11. Workshop on Biological Integrity of Coral Reefs August 21-22 ...

    EPA Pesticide Factsheets

    This report summarizes an EPA-sponsored workshop on coral reef biological integrity held at the Caribbean Coral Reef Institute in La Parguera, Puerto Rico on August 21-22, 2012. The goals of this workshop were to:• Identify key qualitative and quantitative ecological characteristics (reef attributes) that determine the condition of linear coral reefs inhabiting shallow waters (<12 m) in southwestern Puerto Rico.• Use those reef attributes to recommend categorical condition rankings for establishing a biological condition gradient.• Ascertain through expert consensus those reef attributes that characterize biological integrity (a natural, fully-functioning system of organisms and communities) for coral reefs. • Develop a conceptual, narrative model that describes how biological attributes of coral reefs change along a gradient of increasing anthropogenic stress.The workshop brought together scientists with expertise in coral reef taxonomic groups (e.g., stony corals, fishes, sponges, gorgonians, algae, seagrasses and macroinvertebrates), as well as community structure, organism condition, ecosystem function and ecosystem connectivity. The experts evaluated photos and videos from 12 stations collected during EPA Coral Reef surveys (2010 & 2011) from Puerto Rico on coral reefs exhibiting a wide range of conditions. The experts individually rated each station as to observed condition (“good”, “fair” or “poor”) and documented their rationale for

  12. Dynamical Systems++ for a Theory of Biological System

    NASA Astrophysics Data System (ADS)

    Kaneko, Kunihiko

    2014-12-01

    Biological dynamical systems can autonomously change their rule governing the dynamics. To deal with the change in their rule, possible approaches to extend dynamical-systems theory are discussed: They include chaotic itinerancy in high-dimensional dynamical systems, discreteness-induced switches of states, and interference between slow and fast modes. Applications of these concepts to cell differentiation, adaptation, and memory are briefly reviewed, while biological evolution is discussed as selection of dynamical systems by dynamical systems. Finally, necessity of mathematical framework to deal with self-referential dynamics for the rule formation is stressed.

  13. 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.

  14. 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.

  15. Apollo cryogenic integrated systems program

    NASA Technical Reports Server (NTRS)

    Seto, R. K. M.; Cunningham, J. E.

    1971-01-01

    The integrated systems program is capable of simulating both nominal and anomalous operation of the Apollo cryogenics storage system (CSS). Two versions of the program exist; one for the Apollo 14 configuration and the other for J Type Mission configurations. The program consists of two mathematical models which are dynamically coupled. A model of the CSS components and lines determines the oxygen and hydrogen flowrate from each storage tank given the tank pressures and temperatures, and the electrical power subsystem and environmental control subsystem flow demands. Temperatures and pressures throughout the components and lines are also determined. A model of the CSS tankage determines the pressure and temperatures in the tanks given the flowrate from each tank and the thermal environment. The model accounts for tank stretch and includes simplified oxygen tank heater and stratification routines. The program is currently operational on the Univac 1108 computer.

  16. Integrated control system and method

    DOEpatents

    Wang, Paul Sai Keat; Baldwin, Darryl; Kim, Myoungjin

    2013-10-29

    An integrated control system for use with an engine connected to a generator providing electrical power to a switchgear is disclosed. The engine receives gas produced by a gasifier. The control system includes an electronic controller associated with the gasifier, engine, generator, and switchgear. A gas flow sensor monitors a gas flow from the gasifier to the engine through an engine gas control valve and provides a gas flow signal to the electronic controller. A gas oversupply sensor monitors a gas oversupply from the gasifier and provides an oversupply signal indicative of gas not provided to the engine. A power output sensor monitors a power output of the switchgear and provide a power output signal. The electronic controller changes gas production of the gasifier and the power output rating of the switchgear based on the gas flow signal, the oversupply signal, and the power output signal.

  17. 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.

  18. 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.

  19. The plasminogen activator system: biology and regulation.

    PubMed

    Irigoyen, J P; Muñoz-Cánoves, P; Montero, L; Koziczak, M; Nagamine, Y

    1999-10-01

    The regulation of plasminogen activation involves genes for two plasminogen activators (tissue type and urokinase type), two specific inhibitors (type 1 and type 2), and a membrane-anchored urokinase-type plasminogen-activator-specific receptor. This system plays an important role in various biological processes involving extracellular proteolysis. Recent studies have revealed that the system, through interplay with integrins and the extracellular matrix protein vitronectin, is also involved in the regulation of cell migration and proliferation in a manner independent of proteolytic activity. The genes are expressed in many different cell types and their expression is under the control of diverse extracellular signals. Gene expression reflects the levels of the corresponding mRNA, which should be the net result of synthesis and degradation. Thus, modulation of mRNA stability is an important factor in overall regulation. This review summarizes current understanding of the biology and regulation of genes involved in plasminogen activation at different levels.

  20. Integrated roof wind energy system

    NASA Astrophysics Data System (ADS)

    Suma, A. B.; Ferraro, R. M.; Dano, B.; Moonen, S. P. G.

    2012-10-01

    Wind is an attractive renewable source of energy. Recent innovations in research and design have reduced to a few alternatives with limited impact on residential construction. Cost effective solutions have been found at larger scale, but storage and delivery of energy to the actual location it is used, remain a critical issue. The Integrated Roof Wind Energy System is designed to overcome the current issues of urban and larger scale renewable energy system. The system is built up by an axial array of skewed shaped funnels that make use of the Venturi Effect to accelerate the wind flow. This inventive use of shape and geometry leads to a converging air capturing inlet to create high wind mass flow and velocity toward a vertical-axis wind turbine in the top of the roof for generation of a relatively high amount of energy. The methods used in this overview of studies include an array of tools from analytical modelling, PIV wind tunnel testing, and CFD simulation studies. The results define the main design parameters for an efficient system, and show the potential for the generation of high amounts of renewable energy with a novel and effective system suited for the built environment.

  1. 76 FR 48159 - Integrated System Power Rates

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-08

    ... Southwestern Power Administration Integrated System Power Rates AGENCY: Southwestern Power Administration, DOE... facilities. The Administrator has developed proposed Integrated System rates, which are supported by a rate... 24 projects are repaid via revenues received under the Integrated System rates, as are those...

  2. 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.

  3. Toward an integrated software platform for systems pharmacology

    PubMed Central

    Ghosh, Samik; Matsuoka, Yukiko; Asai, Yoshiyuki; Hsin, Kun-Yi; Kitano, Hiroaki

    2013-01-01

    Understanding complex biological systems requires the extensive support of computational tools. This is particularly true for systems pharmacology, which aims to understand the action of drugs and their interactions in a systems context. Computational models play an important role as they can be viewed as an explicit representation of biological hypotheses to be tested. A series of software and data resources are used for model development, verification and exploration of the possible behaviors of biological systems using the model that may not be possible or not cost effective by experiments. Software platforms play a dominant role in creativity and productivity support and have transformed many industries, techniques that can be applied to biology as well. Establishing an integrated software platform will be the next important step in the field. © 2013 The Authors. Biopharmaceutics & Drug Disposition published by John Wiley & Sons, Ltd. PMID:24150748

  4. Toward an integrated software platform for systems pharmacology.

    PubMed

    Ghosh, Samik; Matsuoka, Yukiko; Asai, Yoshiyuki; Hsin, Kun-Yi; Kitano, Hiroaki

    2013-12-01

    Understanding complex biological systems requires the extensive support of computational tools. This is particularly true for systems pharmacology, which aims to understand the action of drugs and their interactions in a systems context. Computational models play an important role as they can be viewed as an explicit representation of biological hypotheses to be tested. A series of software and data resources are used for model development, verification and exploration of the possible behaviors of biological systems using the model that may not be possible or not cost effective by experiments. Software platforms play a dominant role in creativity and productivity support and have transformed many industries, techniques that can be applied to biology as well. Establishing an integrated software platform will be the next important step in the field.

  5. Integrated microfluidic systems for DNA analysis.

    PubMed

    Njoroge, Samuel K; Chen, Hui-Wen; Witek, Małgorzata A; Soper, Steven A

    2011-01-01

    The potential utility of genome-related research in terms of evolving basic discoveries in biology has generated widespread use of DNA diagnostics and DNA forensics and driven the accelerated development of fully integrated microfluidic systems for genome processing. To produce a microsystem with favorable performance characteristics for genetic-based analyses, several key operational elements must be strategically chosen, including device substrate material, temperature control, fluidic control, and reaction product readout. As a matter of definition, a microdevice is a chip that performs a single processing step, for example microchip electrophoresis. Several microdevices can be integrated to a single wafer, or combined on a control board as separate devices to form a microsystem. A microsystem is defined as a chip composed of at least two microdevices. Among the many documented analytical microdevices, those focused on the ability to perform the polymerase chain reaction (PCR) have been reported extensively due to the importance of this processing step in most genetic-based assays. Other microdevices that have been detailed in the literature include those for solid-phase extractions, microchip electrophoresis, and devices composed of DNA microarrays used for interrogating DNA primary structure. Great progress has also been made in the areas of chip fabrication, bonding and sealing to enclose fluidic networks, evaluation of different chip substrate materials, surface chemistries, and the architecture of reaction conduits for basic processing steps such as mixing. Other important elements that have been developed to realize functional systems include miniaturized readout formats comprising optical or electrochemical transduction and interconnect technologies. These discoveries have led to the development of fully autonomous and functional integrated systems for genome processing that can supply "sample in/answer out" capabilities. In this chapter, we focus on

  6. 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

  7. 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.

  8. System Integration - A Major Step toward Lab on a Chip

    PubMed Central

    2011-01-01

    Microfluidics holds great promise to revolutionize various areas of biological engineering, such as single cell analysis, environmental monitoring, regenerative medicine, and point-of-care diagnostics. Despite the fact that intensive efforts have been devoted into the field in the past decades, microfluidics has not yet been adopted widely. It is increasingly realized that an effective system integration strategy that is low cost and broadly applicable to various biological engineering situations is required to fully realize the potential of microfluidics. In this article, we review several promising system integration approaches for microfluidics and discuss their advantages, limitations, and applications. Future advancements of these microfluidic strategies will lead toward translational lab-on-a-chip systems for a wide spectrum of biological engineering applications. PMID:21612614

  9. 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.

  10. Integrating Quantitative Thinking into an Introductory Biology Course Improves Students' Mathematical Reasoning in Biological Contexts

    ERIC Educational Resources Information Center

    Hester, Susan; Buxner, Sanlyn; Elfring, Lisa; Nagy, Lisa

    2014-01-01

    Recent calls for improving undergraduate biology education have emphasized the importance of students learning to apply quantitative skills to biological problems. Motivated by students' apparent inability to transfer their existing quantitative skills to biological contexts, we designed and taught an introductory molecular and cell biology course…

  11. Intelligent systems technology infrastructure for integrated systems

    NASA Technical Reports Server (NTRS)

    Lum, Henry

    1991-01-01

    A system infrastructure must be properly designed and integrated from the conceptual development phase to accommodate evolutionary intelligent technologies. Several technology development activities were identified that may have application to rendezvous and capture systems. Optical correlators in conjunction with fuzzy logic control might be used for the identification, tracking, and capture of either cooperative or non-cooperative targets without the intensive computational requirements associated with vision processing. A hybrid digital/analog system was developed and tested with a robotic arm. An aircraft refueling application demonstration is planned within two years. Initially this demonstration will be ground based with a follow-on air based demonstration. System dependability measurement and modeling techniques are being developed for fault management applications. This involves usage of incremental solution/evaluation techniques and modularized systems to facilitate reuse and to take advantage of natural partitions in system models. Though not yet commercially available and currently subject to accuracy limitations, technology is being developed to perform optical matrix operations to enhance computational speed. Optical terrain recognition using camera image sequencing processed with optical correlators is being developed to determine position and velocity in support of lander guidance. The system is planned for testing in conjunction with Dryden Flight Research Facility. Advanced architecture technology is defining open architecture design constraints, test bed concepts (processors, multiple hardware/software and multi-dimensional user support, knowledge/tool sharing infrastructure), and software engineering interface issues.

  12. Systems Integration Challenges for a National Space Launch System

    NASA Technical Reports Server (NTRS)

    May, Todd A.

    2011-01-01

    System Integration was refined through the complexity and early failures experienced in rocket flight. System Integration encompasses many different viewpoints of the system development. System Integration must ensure consistency in development and operations activities. Human Space Flight tends toward large, complex systems. Understanding the system fs operational and use context is the guiding principle for System Integration: (1) Sizeable costs can be driven into systems by not fully understanding context (2). Adhering to the system context throughout the system fs life cycle is essential to maintaining efficient System Integration. System Integration exists within the System Architecture. Beautiful systems are simple in use and operation -- Block upgrades facilitate manageable steps in functionality evolution. Effective System Integration requires a stable system concept. Communication is essential to system simplicity

  13. [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.

  14. Systems Biology of the Vervet Monkey

    PubMed Central

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

    2013-01-01

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

  15. Future of Chemical Engineering: Integrating Biology into the Undergraduate ChE Curriculum

    ERIC Educational Resources Information Center

    Mosto, Patricia; Savelski, Mariano; Farrell, Stephanie H.; Hecht, Gregory B.

    2007-01-01

    Integrating biology in the chemical engineering curriculum seems to be the future for chemical engineering programs nation and worldwide. Rowan University's efforts to address this need include a unique chemical engineering curriculum with an intensive biology component integrated throughout from freshman to senior years. Freshman and Sophomore…

  16. An index of biological integrity (IBI) for Pacific Northwest rivers

    USGS Publications Warehouse

    Mebane, C.A.; Maret, T.R.; Hughes, R.M.

    2003-01-01

    The index of biotic integrity (IBI) is a commonly used measure of relative aquatic ecosystem condition; however, its application to coldwater rivers over large geographic areas has been limited. A seven-step process was used to construct and test an IBI applicable to fish assemblages in coldwater rivers throughout the U.S. portion of the Pacific Northwest. First, fish data from the region were compiled from previous studies and candidate metrics were selected. Second, reference conditions were estimated from historical reports and minimally disturbed reference sites in the region. Third, data from the upper Snake River basin were used to test metrics and develop the initial index. Fourth, candidate metrics were evaluated for their redundancy, variability, precision, and ability to reflect a wide range of conditions while distinguishing reference sites from disturbed sites. Fifth, the selected metrics were standardized by being scored continuously from 0 to 1 and then weighted as necessary to produce an IBI ranging from 0 to 100. The resulting index included 10 metrics: number of native coldwater species, number of age-classes of sculpins Cottus spp., percentage of sensitive native individuals, percentage of coldwater individuals, percentage of tolerant individuals, number of alien species, percentage of common carp Cyprinus carpio individuals, number of selected salmonid age-classes, catch per unit effort of coldwater individuals, and percentage of individuals with selected anomalies. Sixth, the IBI responses were tested with additional data sets from throughout the Pacific Northwest. Last, scores from two minimally disturbed reference rivers were evaluated for longitudinal gradients along the river continuum. The IBI responded to environmental disturbances and was spatially and temporally stable at over 150 sites in the Pacific Northwest. The results support its use across a large geographic area to describe the relative biological condition of coolwater and

  17. Energy Systems Integration: Demonstrating Distributed Resource Communications

    SciTech Connect

    2017-01-01

    Overview fact sheet about the Electric Power Research Institute (EPRI) and Schneider Electric Integrated Network Testbed for Energy Grid Research and Technology Experimentation (INTEGRATE) project at the Energy Systems Integration Facility. INTEGRATE is part of the U.S. Department of Energy's Grid Modernization Initiative.

  18. WRATS Integrated Data Acquisition System

    NASA Technical Reports Server (NTRS)

    Piatak, David J.

    2008-01-01

    The Wing and Rotor Aeroelastic Test System (WRATS) data acquisition system (DAS) is a 64-channel data acquisition display and analysis system specifically designed for use with the WRATS 1/5-scale V-22 tiltrotor model of the Bell Osprey. It is the primary data acquisition system for experimental aeroelastic testing of the WRATS model for the purpose of characterizing the aeromechanical and aeroelastic stability of prototype tiltrotor configurations. The WRATS DAS was also used during aeroelastic testing of Bell Helicopter Textron s Quad-Tiltrotor (QTR) design concept, a test which received international attention. The LabVIEW-based design is portable and capable of powering and conditioning over 64 channels of dynamic data at sampling rates up to 1,000 Hz. The system includes a 60-second circular data archive, an integrated model swashplate excitation system, a moving block damping application for calculation of whirl flutter mode subcritical damping, a loads and safety monitor, a pilot-control console display, data analysis capabilities, and instrumentation calibration functions. Three networked computers running custom-designed LabVIEW software acquire data through National Instruments data acquisition hardware. The aeroelastic model (see figure) was tested with the DAS at two facilities at NASA Langley, the Transonic Dynamics Tunnel (TDT) and the Rotorcraft Hover Test Facility (RHTF). Because of the need for seamless transition between testing at these facilities, DAS is portable. The software is capable of harmonic analysis of periodic time history data, Fast Fourier Transform calculations, power spectral density calculations, and on-line calibration of test instrumentation. DAS has a circular buffer archive to ensure critical data is not lost in event of model failure/incident, as well as a sample-and-hold capability for phase-correct time history data.

  19. Advantages and Pitfalls of Mass Spectrometry Based Metabolome Profiling in