Science.gov

Sample records for integrated systems biology

  1. Integrating systems biology models and biomedical ontologies

    PubMed Central

    2011-01-01

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

  2. Systems biology and integrative physiological modelling.

    PubMed

    Hester, Robert L; Iliescu, Radu; Summers, Richard; Coleman, Thomas G

    2011-03-01

    Over the last 10 years, 'Systems Biology' has focused on the integration of biology and medicine with information technology and computation. The current challenge is to use the discoveries of the last 20 years, such as genomics and proteomics, to develop targeted therapeutical strategies. These strategies are the result of understanding the aetiologies of complex diseases. Scientists predict the data will make personalized medicine rapidly available. However, the data need to be considered as a highly complex system comprising multiple inputs and feedback mechanisms. Translational medicine requires the functional and conceptual linkage of genetics to proteins, proteins to cells, cells to organs, organs to systems and systems to the organism. To help understand the complex integration of these systems, a mathematical model of the entire human body, which accurately links the functioning of all organs and systems together, could provide a framework for the development and testing of new hypotheses that will be important in clinical outcomes. There are several efforts to develop a 'Human Physiome', with the strengths and weaknesses of each being presented here. The development of a 'Human Model', with verification, documentation and validation of the underlying and integrative responses, is essential to provide a usable environment. Future development of a 'Human Model' requires integrative physiologists working in collaboration with other scientists, who have expertise in all areas of human biology, to develop the most accurate and usable human model.

  3. 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

  4. Current advances in systems and integrative biology.

    PubMed

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

    2014-08-01

    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.

  5. 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.

  6. 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

  7. A data integration methodology for systems biology

    PubMed Central

    Hwang, Daehee; Rust, Alistair G.; Ramsey, Stephen; Smith, Jennifer J.; Leslie, Deena M.; Weston, Andrea D.; de Atauri, Pedro; Aitchison, John D.; Hood, Leroy; Siegel, Andrew F.; Bolouri, Hamid

    2005-01-01

    Different experimental technologies measure different aspects of a system and to differing depth and breadth. High-throughput assays have inherently high false-positive and false-negative rates. Moreover, each technology includes systematic biases of a different nature. These differences make network reconstruction from multiple data sets difficult and error-prone. Additionally, because of the rapid rate of progress in biotechnology, there is usually no curated exemplar data set from which one might estimate data integration parameters. To address these concerns, we have developed data integration methods that can handle multiple data sets differing in statistical power, type, size, and network coverage without requiring a curated training data set. Our methodology is general in purpose and may be applied to integrate data from any existing and future technologies. Here we outline our methods and then demonstrate their performance by applying them to simulated data sets. The results show that these methods select true-positive data elements much more accurately than classical approaches. In an accompanying companion paper, we demonstrate the applicability of our approach to biological data. We have integrated our methodology into a free open source software package named pointillist. PMID:16301537

  8. A data integration methodology for systems biology.

    PubMed

    Hwang, Daehee; Rust, Alistair G; Ramsey, Stephen; Smith, Jennifer J; Leslie, Deena M; Weston, Andrea D; de Atauri, Pedro; Aitchison, John D; Hood, Leroy; Siegel, Andrew F; Bolouri, Hamid

    2005-11-29

    Different experimental technologies measure different aspects of a system and to differing depth and breadth. High-throughput assays have inherently high false-positive and false-negative rates. Moreover, each technology includes systematic biases of a different nature. These differences make network reconstruction from multiple data sets difficult and error-prone. Additionally, because of the rapid rate of progress in biotechnology, there is usually no curated exemplar data set from which one might estimate data integration parameters. To address these concerns, we have developed data integration methods that can handle multiple data sets differing in statistical power, type, size, and network coverage without requiring a curated training data set. Our methodology is general in purpose and may be applied to integrate data from any existing and future technologies. Here we outline our methods and then demonstrate their performance by applying them to simulated data sets. The results show that these methods select true-positive data elements much more accurately than classical approaches. In an accompanying companion paper, we demonstrate the applicability of our approach to biological data. We have integrated our methodology into a free open source software package named POINTILLIST.

  9. 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.

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

    PubMed

    Smolke, Christina D; Silver, Pamela A

    2011-03-18

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

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

    PubMed Central

    Smolke, Christina D.; Silver, Pamela A.

    2011-01-01

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

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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.

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

    PubMed Central

    Fukushima, Atsushi; Kanaya, Shigehiko; Nishida, Kozo

    2014-01-01

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

  19. 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.

  20. 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

  1. 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

  2. DIPSBC--data integration platform for systems biology collaborations.

    PubMed

    Dreher, Felix; Kreitler, Thomas; Hardt, Christopher; Kamburov, Atanas; Yildirimman, Reha; Schellander, Karl; Lehrach, Hans; Lange, Bodo M H; Herwig, Ralf

    2012-05-08

    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. 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. 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.

  3. 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. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Lean Big Data Integration in Systems Biology and Systems Pharmacology

    PubMed Central

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

    2014-01-01

    Datasets 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 effort can be achieved through the conversion of data from the various resources into single-node-type networks, gene-set libraries, or multi-partite 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. PMID:25109570

  6. A Scalable and Integrative System for Pathway Bioinformatics and Systems Biology

    PubMed Central

    Compani, Behnam; Su, Trent; Chang, Ivan; Cheng, Jianlin; Shah, Kandarp H.; Whisenant, Thomas; Dou, Yimeng; Bergmann, Adriel; Cheong, Raymond; Wold, Barbara; Bardwell, Lee; Levchenko, Andre; Baldi, Pierre; Mjolsness, Eric

    2011-01-01

    Motivation Progress in systems biology depends on developing scalable informatics tools to predictively model, visualize, and flexibly store information about complex biological systems. Scalability of these tools, as well as their ability to integrate within larger frameworks of evolving tools, is critical to address the multi-scale and size complexity of biological systems. Results Using current software technology, such as self-generation of database and object code from UML schemas, facilitates rapid updating of a scalable expert assistance system for modeling biological pathways. Distribution of key components along with connectivity to external data sources and analysis tools is achieved via a web service interface. PMID:20865537

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  9. 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.

  10. Integrated dynamic fluidic lens system for in vivo biological imaging.

    PubMed

    Justis, N B; Zhang, D-Y; Lo, Y H

    2004-01-01

    We have developed an integrated dynamic lens system for in vivo optical imaging. Bioinspired dynamic microfluidic lenses allow for real-time dynamic manipulation of the lens focal length via microfluidic injection into a PDMS membrane-capped chamber. A piezoelectrically actuated micropump is integrated with with the lens to provide highspeed, accurate lens tunability. The 5mm dynamic lens has demonstrated focal length tunability from 8.5mm to 23mm, numerical aperture values from 0.39 to 0.77, and resolution of 40 linepairs/mm. The micropump operates at 5 kHz and achieved a flow rate of approximately 2.4 mL/min. This system can be applied to optical probe techniques to improve diagnosis with real-time depth resolution and variable numerical aperture.

  11. 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.

  12. [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.

  13. 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...

  14. 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...

  15. 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.

  16. '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.

  17. 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

  18. IntegromeDB: an integrated system and biological search engine.

    PubMed

    Baitaluk, Michael; Kozhenkov, Sergey; Dubinina, Yulia; Ponomarenko, Julia

    2012-01-19

    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. 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. 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.

  19. 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.

  20. PathCase-SB: integrating data sources and providing tools for systems biology research

    PubMed Central

    2012-01-01

    Background Integration of metabolic pathways resources and metabolic network models, and deploying new tools on the integrated platform can help perform more effective and more efficient systems biology research on understanding the regulation of metabolic networks. Therefore, the tasks of (a) integrating under a single database environment regulatory metabolic networks and existing models, and (b) building tools to help with modeling and analysis are desirable and intellectually challenging computational tasks. Results PathCase Systems Biology (PathCase-SB) is built and released. This paper describes PathCase-SB user interfaces developed to date. The current PathCase-SB system provides a database-enabled framework and web-based computational tools towards facilitating the development of kinetic models for biological systems. PathCase-SB aims to integrate systems biology models data and metabolic network data of selected biological data sources on the web (currently, BioModels Database and KEGG, respectively), and to provide more powerful and/or new capabilities via the new web-based integrative framework. Conclusions Each of the current four PathCase-SB interfaces, namely, Browser, Visualization, Querying, and Simulation interfaces, have expanded and new capabilities as compared with the original data sources. PathCase-SB is already available on the web and being used by researchers across the globe. PMID:22697505

  1. Integrative Physiology 2.0’: integration of systems biology into physiology and its application to cardiovascular homeostasis

    PubMed Central

    Kuster, Diederik W D; Merkus, Daphne; van der Velden, Jolanda; Verhoeven, Adrie J M; Duncker, Dirk J

    2011-01-01

    Since the completion of the Human Genome Project and the advent of the large scaled unbiased ‘-omics’ techniques, the field of systems biology has emerged. Systems biology aims to move away from the traditional reductionist molecular approach, which focused on understanding the role of single genes or proteins, towards a more holistic approach by studying networks and interactions between individual components of networks. From a conceptual standpoint, systems biology elicits a ‘back to the future’ experience for any integrative physiologist. However, many of the new techniques and modalities employed by systems biologists yield tremendous potential for integrative physiologists to expand their tool arsenal to (quantitatively) study complex biological processes, such as cardiac remodelling and heart failure, in a truly holistic fashion. We therefore advocate that systems biology should not become/stay a separate discipline with ‘-omics’ as its playing field, but should be integrated into physiology to create ‘Integrative Physiology 2.0’. PMID:21224228

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. Network approaches to systems biology analysis of complex disease: integrative methods for multi-omics data.

    PubMed

    Yan, Jingwen; Risacher, Shannon L; Shen, Li; Saykin, Andrew J

    2017-06-30

    In the past decade, significant progress has been made in complex disease research across multiple omics layers from genome, transcriptome and proteome to metabolome. There is an increasing awareness of the importance of biological interconnections, and much success has been achieved using systems biology approaches. However, because of the typical focus on one single omics layer at a time, existing systems biology findings explain only a modest portion of complex disease. Recent advances in multi-omics data collection and sharing present us new opportunities for studying complex diseases in a more comprehensive fashion, and yet simultaneously create new challenges considering the unprecedented data dimensionality and diversity. Here, our goal is to review extant and emerging network approaches that can be applied across multiple biological layers to facilitate a more comprehensive and integrative multilayered omics analysis of complex diseases. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. 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.

  10. Systems Chemical Biology

    PubMed Central

    Oprea, Tudor I.; Tropsha, Alexander; Faulon, Jean-Loup; Rintoul, Mark D.

    2009-01-01

    The increasing availability of data related to genes, proteins and their modulation by small molecules, paralleled by the emergence of simulation tools in systems biology, has provided a vast amount of biological information. However, there is a critical need to develop cheminformatics tools that can integrate chemical knowledge with these biological databases, with the goal of creating systems chemical biology. PMID:17637771

  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. Integration of chemical and biological treatments for textile industry wastewater: a possible zero-discharge system.

    PubMed

    Lee, H H; Chen, G; Yue, P L

    2001-01-01

    Theoretical and experimental studies have established that integrated treatment systems (mostly chemical and biological) for various industrial wastewaters can achieve better quality of treatment and can be cost-effective. In the present study, the objective is to minimize the use of process water in the textile industry by an economical recycle and reuse scheme. The textile wastewater was first characterized in terms of COD, BOD5, salinity and color. In order to recycle such wastewater, the contaminants should be mineralized and/or removed according to the reusable textile water quality standards. Typical results show that this is achievable. An economic analysis has been conducted on the proposed integrated system. The economic analysis shows that the integrated system is economically more attractive than any of the single treatment technologies for achieving the same target of treatment. The information presented in this paper provides a feasible option for the reduction of effluent discharges in the textile industry.

  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. Integrative Radiation Biology

    SciTech Connect

    Barcellos-Hoff, Mary Helen

    2015-02-27

    We plan to study tissue-level mechanisms important to human breast radiation carcinogenesis. We propose that the cell biology of irradiated tissues reveals a coordinated multicellular damage response program in which individual cell contributions are primarily directed towards suppression of carcinogenesis and reestablishment of homeostasis. We identified transforming growth factor β1 (TGFβ) as a pivotal signal. Notably, we have discovered that TGFβ suppresses genomic instability by controlling the intrinsic DNA damage response and centrosome integrity. However, TGFβ also mediates disruption of microenvironment interactions, which drive epithelial to mesenchymal transition in irradiated human mammary epithelial cells. This apparent paradox of positive and negative controls by TGFβ is the topic of the present proposal. First, we postulate that these phenotypes manifest differentially following fractionated or chronic exposures; second, that the interactions of multiple cell types in tissues modify the responses evident in this single cell type culture models. The goals are to: 1) study the effect of low dose rate and fractionated radiation exposure in combination with TGFβ on the irradiated phenotype and genomic instability of non-malignant human epithelial cells; and 2) determine whether stromal-epithelial interactions suppress the irradiated phenotype in cell culture and the humanized mammary mouse model. These data will be used to 3) develop a systems biology model that integrates radiation effects across multiple levels of tissue organization and time. Modeling multicellular radiation responses coordinated via extracellular signaling could have a significant impact on the extrapolation of human health risks from high dose to low dose/rate radiation exposure.

  17. 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.

  18. CHOmine: an integrated data warehouse for CHO systems biology and modeling.

    PubMed

    Gerstl, Matthias P; Hanscho, Michael; Ruckerbauer, David E; Zanghellini, Jürgen; Borth, Nicole

    2017-01-01

    The last decade has seen a surge in published genome-scale information for Chinese hamster ovary (CHO) cells, which are the main production vehicles for therapeutic proteins. While a single access point is available at www.CHOgenome.org, the primary data is distributed over several databases at different institutions. Currently research is frequently hampered by a plethora of gene names and IDs that vary between published draft genomes and databases making systems biology analyses cumbersome and elaborate. Here we present CHOmine, an integrative data warehouse connecting data from various databases and links to other ones. Furthermore, we introduce CHOmodel, a web based resource that provides access to recently published CHO cell line specific metabolic reconstructions. Both resources allow to query CHO relevant data, find interconnections between different types of data and thus provides a simple, standardized entry point to the world of CHO systems biology. http://www.chogenome.org.

  19. Integration of 'omics' data in aging research: from biomarkers to systems biology.

    PubMed

    Zierer, Jonas; Menni, Cristina; Kastenmüller, Gabi; Spector, Tim D

    2015-12-01

    Age is the strongest risk factor for many diseases including neurodegenerative disorders, coronary heart disease, type 2 diabetes and cancer. Due to increasing life expectancy and low birth rates, the incidence of age-related diseases is increasing in industrialized countries. Therefore, understanding the relationship between diseases and aging and facilitating healthy aging are major goals in medical research. In the last decades, the dimension of biological data has drastically increased with high-throughput technologies now measuring thousands of (epi) genetic, expression and metabolic variables. The most common and so far successful approach to the analysis of these data is the so-called reductionist approach. It consists of separately testing each variable for association with the phenotype of interest such as age or age-related disease. However, a large portion of the observed phenotypic variance remains unexplained and a comprehensive understanding of most complex phenotypes is lacking. Systems biology aims to integrate data from different experiments to gain an understanding of the system as a whole rather than focusing on individual factors. It thus allows deeper insights into the mechanisms of complex traits, which are caused by the joint influence of several, interacting changes in the biological system. In this review, we look at the current progress of applying omics technologies to identify biomarkers of aging. We then survey existing systems biology approaches that allow for an integration of different types of data and highlight the need for further developments in this area to improve epidemiologic investigations. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  20. 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.

  1. 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.

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

    USDA-ARS?s Scientific Manuscript database

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

  3. 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%.

  4. 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…

  5. 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…

  6. [Gravitational biology of integrative organisms and ecological system--the road map of space activities].

    PubMed

    Yamashita, M

    2001-10-01

    History of the International Space Station, ISS, and planning of its scientific use are described in this essay. Fundamental gravitational biology and its facility on the ISS have been identified to have the highest priority to conduct scientific experiments with variable G environment in orbit. The road map of space activities is clearly directing the efforts toward manned Mars exploration. The Centrifuge is a core element of the facilities dedicated to this endeavor. Several research subjects are discussed with the results obtained from the past space experiments. Direct effects of gravity on the biological system at the level of integrative organisms are major subjects of study that will be conducted on the large scaled centrifuge.

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

    PubMed

    Mayhew, T M

    2015-04-01

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

  8. Metabolomics and its integration with systems biology: PSI 2014 conference panel discussion report.

    PubMed

    More, Tushar; RoyChoudhury, Sourav; Gollapalli, Kishore; Patel, Sandip K; Gowda, Harsha; Chaudhury, Koel; Rapole, Srikanth

    2015-09-08

    Metabolomics, being a relatively new field, is facing multiple challenges related to data acquisition and interpretation, reproducibility across analytical platforms, integration with other omics approaches and translation into theragnostic biomarkers. There is an immediate need to overcome these challenges in order to make metabolomics more useful and reliable in terms of improving our current understanding of disease biology and help in developing predictive biomarkers. Researchers interested in metabolomics gathered for a panel discussion on 'Metabolomics and its integration with systems biology' during the 6th Annual Meeting of Proteomics Society-India and International Conference on "Proteomics from Discovery to Function" held at the Indian Institute of Technology, Bombay from December 7-9, 2014. The panel discussed various challenges related to metabolomics and also proposed several effective solutions for optimum implementation of metabolomics in clinical practice. The key areas of panel discussion were improvement in metabolite databases with comprehensive spectral libraries, need for extensive bioinformatics tools for integrative approaches and serious considerations for clinical validation of the biomarkers for the successful implementation of metabolomics in clinics. Information drafted in this report is significant for researchers working in metabolomics field to overcome the challenges and successful implementation of metabolomics in clinical practice. This article is part of a special issue titled: Proteomics in India. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. Integration of systems biology with organs-on-chips to humanize therapeutic development

    NASA Astrophysics Data System (ADS)

    Edington, Collin D.; Cirit, Murat; Chen, Wen Li Kelly; Clark, Amanda M.; Wells, Alan; Trumper, David L.; Griffith, Linda G.

    2017-02-01

    "Mice are not little people" - a refrain becoming louder as the gaps between animal models and human disease become more apparent. At the same time, three emerging approaches are headed toward integration: powerful systems biology analysis of cell-cell and intracellular signaling networks in patient-derived samples; 3D tissue engineered models of human organ systems, often made from stem cells; and micro-fluidic and meso-fluidic devices that enable living systems to be sustained, perturbed and analyzed for weeks in culture. Integration of these rapidly moving fields has the potential to revolutionize development of therapeutics for complex, chronic diseases, including those that have weak genetic bases and substantial contributions from gene-environment interactions. Technical challenges in modeling complex diseases with "organs on chips" approaches include the need for relatively large tissue masses and organ-organ cross talk to capture systemic effects, such that current microfluidic formats often fail to capture the required scale and complexity for interconnected systems. These constraints drive development of new strategies for designing in vitro models, including perfusing organ models, as well as "mesofluidic" pumping and circulation in platforms connecting several organ systems, to achieve the appropriate physiological relevance.

  15. 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.

  16. 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

  17. 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."

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

    USDA-ARS?s Scientific Manuscript database

    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...

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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.

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

    PubMed

    Lee, Sang Yup; Park, Jin Hwan

    2010-01-01

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

  5. 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.

  6. 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.

  7. Pathway Tools version 13.0: integrated software for pathway/genome informatics and systems biology.

    PubMed

    Karp, Peter D; Paley, Suzanne M; Krummenacker, Markus; Latendresse, Mario; Dale, Joseph M; Lee, Thomas J; Kaipa, Pallavi; Gilham, Fred; Spaulding, Aaron; Popescu, Liviu; Altman, Tomer; Paulsen, Ian; Keseler, Ingrid M; Caspi, Ron

    2010-01-01

    Pathway Tools is a production-quality software environment for creating a type of model-organism database called a Pathway/Genome Database (PGDB). A PGDB such as EcoCyc integrates the evolving understanding of the genes, proteins, metabolic network and regulatory network of an organism. This article provides an overview of Pathway Tools capabilities. The software performs multiple computational inferences including prediction of metabolic pathways, prediction of metabolic pathway hole fillers and prediction of operons. It enables interactive editing of PGDBs by DB curators. It supports web publishing of PGDBs, and provides a large number of query and visualization tools. The software also supports comparative analyses of PGDBs, and provides several systems biology analyses of PGDBs including reachability analysis of metabolic networks, and interactive tracing of metabolites through a metabolic network. More than 800 PGDBs have been created using Pathway Tools by scientists around the world, many of which are curated DBs for important model organisms. Those PGDBs can be exchanged using a peer-to-peer DB sharing system called the PGDB Registry.

  8. Pathway Tools version 13.0: integrated software for pathway/genome informatics and systems biology

    PubMed Central

    Paley, Suzanne M.; Krummenacker, Markus; Latendresse, Mario; Dale, Joseph M.; Lee, Thomas J.; Kaipa, Pallavi; Gilham, Fred; Spaulding, Aaron; Popescu, Liviu; Altman, Tomer; Paulsen, Ian; Keseler, Ingrid M.; Caspi, Ron

    2010-01-01

    Pathway Tools is a production-quality software environment for creating a type of model-organism database called a Pathway/Genome Database (PGDB). A PGDB such as EcoCyc integrates the evolving understanding of the genes, proteins, metabolic network and regulatory network of an organism. This article provides an overview of Pathway Tools capabilities. The software performs multiple computational inferences including prediction of metabolic pathways, prediction of metabolic pathway hole fillers and prediction of operons. It enables interactive editing of PGDBs by DB curators. It supports web publishing of PGDBs, and provides a large number of query and visualization tools. The software also supports comparative analyses of PGDBs, and provides several systems biology analyses of PGDBs including reachability analysis of metabolic networks, and interactive tracing of metabolites through a metabolic network. More than 800 PGDBs have been created using Pathway Tools by scientists around the world, many of which are curated DBs for important model organisms. Those PGDBs can be exchanged using a peer-to-peer DB sharing system called the PGDB Registry. PMID:19955237

  9. 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.

  10. 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

  11. Recent Achievements in Characterizing the Histone Code and Approaches to Integrating Epigenomics and Systems Biology.

    PubMed

    Janssen, K A; Sidoli, S; Garcia, B A

    2017-01-01

    Functional epigenetic regulation occurs by dynamic modification of chromatin, including genetic material (i.e., DNA methylation), histone proteins, and other nuclear proteins. Due to the highly complex nature of the histone code, mass spectrometry (MS) has become the leading technique in identification of single and combinatorial histone modifications. MS has now overcome antibody-based strategies due to its automation, high resolution, and accurate quantitation. Moreover, multiple approaches to analysis have been developed for global quantitation of posttranslational modifications (PTMs), including large-scale characterization of modification coexistence (middle-down and top-down proteomics), which is not currently possible with any other biochemical strategy. Recently, our group and others have simplified and increased the effectiveness of analyzing histone PTMs by improving multiple MS methods and data analysis tools. This review provides an overview of the major achievements in the analysis of histone PTMs using MS with a focus on the most recent improvements. We speculate that the workflow for histone analysis at its state of the art is highly reliable in terms of identification and quantitation accuracy, and it has the potential to become a routine method for systems biology thanks to the possibility of integrating histone MS results with genomics and proteomics datasets. © 2017 Elsevier Inc. All rights reserved.

  12. Human cancer classification: a systems biology- based model integrating morphology, cancer stem cells, proteomics, and genomics.

    PubMed

    Idikio, Halliday A

    2011-02-22

    Human cancer classification is currently based on the idea of cell of origin, light and electron microscopic attributes of the cancer. What is not yet integrated into cancer classification are the functional attributes of these cancer cells. Recent innovative techniques in biology have provided a wealth of information on the genomic, transcriptomic and proteomic changes in cancer cells. The emergence of the concept of cancer stem cells needs to be included in a classification model to capture the known attributes of cancer stem cells and their potential contribution to treatment response, and metastases. The integrated model of cancer classification presented here incorporates all morphology, cancer stem cell contributions, genetic, and functional attributes of cancer. Integrated cancer classification models could eliminate the unclassifiable cancers as used in current classifications. Future cancer treatment may be advanced by using an integrated model of cancer classification.

  13. HPD: an online integrated human pathway database enabling systems biology studies.

    PubMed

    Chowbina, Sudhir R; Wu, Xiaogang; Zhang, Fan; Li, Peter M; Pandey, Ragini; Kasamsetty, Harini N; Chen, Jake Y

    2009-10-08

    Pathway-oriented experimental and computational studies have led to a significant accumulation of biological knowledge concerning three major types of biological pathway events: molecular signaling events, gene regulation events, and metabolic reaction events. A pathway consists of a series of molecular pathway events that link molecular entities such as proteins, genes, and metabolites. There are approximately 300 biological pathway resources as of April 2009 according to the Pathguide database; however, these pathway databases generally have poor coverage or poor quality, and are difficult to integrate, due to syntactic-level and semantic-level data incompatibilities. We developed the Human Pathway Database (HPD) by integrating heterogeneous human pathway data that are either curated at the NCI Pathway Interaction Database (PID), Reactome, BioCarta, KEGG or indexed from the Protein Lounge Web sites. Integration of pathway data at syntactic, semantic, and schematic levels was based on a unified pathway data model and data warehousing-based integration techniques. HPD provides a comprehensive online view that connects human proteins, genes, RNA transcripts, enzymes, signaling events, metabolic reaction events, and gene regulatory events. At the time of this writing HPD includes 999 human pathways and more than 59,341 human molecular entities. The HPD software provides both a user-friendly Web interface for online use and a robust relational database backend for advanced pathway querying. This pathway tool enables users to 1) search for human pathways from different resources by simply entering genes/proteins involved in pathways or words appearing in pathway names, 2) analyze pathway-protein association, 3) study pathway-pathway similarity, and 4) build integrated pathway networks. We demonstrated the usage and characteristics of the new HPD through three breast cancer case studies. HPD http://bio.informatics.iupui.edu/HPD is a new resource for searching, managing

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

    PubMed

    Zamir, Eli

    2016-09-02

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

  15. 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

  16. A neural systems-based neurobiology and neuropsychiatry course: integrating biology, psychodynamics, and psychology in the psychiatric curriculum.

    PubMed

    Lacy, Timothy; Hughes, John D

    2006-01-01

    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. The authors detail the underlying assumptions and outline of a neural systems-based neuroscience course they teach at the National Capital Consortium Psychiatry Residency Program. They review course assessment reports and classroom observations. Self-report measures and teacher observations are encouraging. By the end of the course, residents are able to discuss both neurobiological and psychodynamic/psychological concepts of distributed biological neural networks. They verbalize an understanding that psychology is biology, that any distinction is artificial, and that both are valuable. A neuroscience curriculum founded on the underlying principles of behavioral neurobiology and neuropsychiatry is inherently anti-reductionistic and facilitates the acquisition of detailed information as well as critical thinking and cross-disciplinary correlations with psychological theories and psychotherapy.

  17. 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

  18. 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.

  19. 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.

  20. ELECANS--an integrated model development environment for multiscale cancer systems biology.

    PubMed

    Chaudhary, Safee Ullah; Shin, Sung-Young; Lee, Daewon; Song, Je-Hoon; Cho, Kwang-Hyun

    2013-04-01

    Computational multiscale models help cancer biologists to study the spatiotemporal dynamics of complex biological systems and to reveal the underlying mechanism of emergent properties. To facilitate the construction of such models, we have developed a next generation modelling platform for cancer systems biology, termed 'ELECANS' (electronic cancer system). It is equipped with a graphical user interface-based development environment for multiscale modelling along with a software development kit such that hierarchically complex biological systems can be conveniently modelled and simulated by using the graphical user interface/software development kit combination. Associated software accessories can also help users to perform post-processing of the simulation data for visualization and further analysis. In summary, ELECANS is a new modelling platform for cancer systems biology and provides a convenient and flexible modelling and simulation environment that is particularly useful for those without an intensive programming background. ELECANS, its associated software accessories, demo examples, documentation and issues database are freely available at http://sbie.kaist.ac.kr/sub_0204.php. Supplementary data are available at Bioinformatics online.

  1. 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."

  2. 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.

  3. 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.

  4. 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].

  5. 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

  6. A Computational Systems Biology Software Platform for Multiscale Modeling and Simulation: Integrating Whole-Body Physiology, Disease Biology, and Molecular Reaction Networks

    PubMed Central

    Eissing, Thomas; Kuepfer, Lars; Becker, Corina; Block, Michael; Coboeken, Katrin; Gaub, Thomas; Goerlitz, Linus; Jaeger, Juergen; Loosen, Roland; Ludewig, Bernd; Meyer, Michaela; Niederalt, Christoph; Sevestre, Michael; Siegmund, Hans-Ulrich; Solodenko, Juri; Thelen, Kirstin; Telle, Ulrich; Weiss, Wolfgang; Wendl, Thomas; Willmann, Stefan; Lippert, Joerg

    2011-01-01

    Today, in silico studies and trial simulations already complement experimental approaches in pharmaceutical R&D and have become indispensable tools for decision making and communication with regulatory agencies. While biology is multiscale by nature, project work, and software tools usually focus on isolated aspects of drug action, such as pharmacokinetics at the organism scale or pharmacodynamic interaction on the molecular level. We present a modeling and simulation software platform consisting of PK-Sim® and MoBi® capable of building and simulating models that integrate across biological scales. A prototypical multiscale model for the progression of a pancreatic tumor and its response to pharmacotherapy is constructed and virtual patients are treated with a prodrug activated by hepatic metabolization. Tumor growth is driven by signal transduction leading to cell cycle transition and proliferation. Free tumor concentrations of the active metabolite inhibit Raf kinase in the signaling cascade and thereby cell cycle progression. In a virtual clinical study, the individual therapeutic outcome of the chemotherapeutic intervention is simulated for a large population with heterogeneous genomic background. Thereby, the platform allows efficient model building and integration of biological knowledge and prior data from all biological scales. Experimental in vitro model systems can be linked with observations in animal experiments and clinical trials. The interplay between patients, diseases, and drugs and topics with high clinical relevance such as the role of pharmacogenomics, drug–drug, or drug–metabolite interactions can be addressed using this mechanistic, insight driven multiscale modeling approach. PMID:21483730

  7. Computational representation of biological systems

    SciTech Connect

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

    2009-04-20

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

  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. 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

  10. 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.

  11. 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.

  12. 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.

  13. Systems biology in animal sciences.

    PubMed

    Woelders, H; Te Pas, M F W; Bannink, A; Veerkamp, R F; Smits, M A

    2011-05-01

    Systems biology is a rapidly expanding field of research and is applied in a number of biological disciplines. In animal sciences, omics approaches are increasingly used, yielding vast amounts of data, but systems biology approaches to extract understanding from these data of biological processes and animal traits are not yet frequently used. This paper aims to explain what systems biology is and which areas of animal sciences could benefit from systems biology approaches. Systems biology aims to understand whole biological systems working as a unit, rather than investigating their individual components. Therefore, systems biology can be considered a holistic approach, as opposed to reductionism. The recently developed 'omics' technologies enable biological sciences to characterize the molecular components of life with ever increasing speed, yielding vast amounts of data. However, biological functions do not follow from the simple addition of the properties of system components, but rather arise from the dynamic interactions of these components. Systems biology combines statistics, bioinformatics and mathematical modeling to integrate and analyze large amounts of data in order to extract a better understanding of the biology from these huge data sets and to predict the behavior of biological systems. A 'system' approach and mathematical modeling in biological sciences are not new in itself, as they were used in biochemistry, physiology and genetics long before the name systems biology was coined. However, the present combination of mass biological data and of computational and modeling tools is unprecedented and truly represents a major paradigm shift in biology. Significant advances have been made using systems biology approaches, especially in the field of bacterial and eukaryotic cells and in human medicine. Similarly, progress is being made with 'system approaches' in animal sciences, providing exciting opportunities to predict and modulate animal traits.

  14. 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

  15. 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

  16. Complete atomistic model of a bacterial cytoplasm for integrating physics, biochemistry, and systems biology.

    PubMed

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

    2015-05-01

    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. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Advances in de novo strain design using integrated systems and synthetic biology tools.

    PubMed

    Ng, Chiam Yu; Khodayari, Ali; Chowdhury, Anupam; Maranas, Costas D

    2015-10-01

    Recent efforts in expanding the range of biofuel and biorenewable molecules using microbial production hosts have focused on the introduction of non-native pathways in model organisms and the bio-prospecting of non-model organisms with desirable features. Current challenges lie in the assembly and coordinated expression of the (non-)native pathways and the elimination of competing pathways and undesirable regulation. Several systems and synthetic biology approaches providing contrasting top-down and bottom-up strategies, respectively, have been developed. In this review, we discuss recent advances in both in silico and experimental approaches for metabolic pathway design and engineering, with a critical assessment of their merits and remaining challenges. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. 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.

  19. Integration of multiscale dendritic spine structure and function data into systems biology models.

    PubMed

    Mancuso, James J; Cheng, Jie; Yin, Zheng; Gilliam, Jared C; Xia, Xiaofeng; Li, Xuping; Wong, Stephen T C

    2014-01-01

    Comprising 10(11) neurons with 10(14) synaptic connections the human brain is the ultimate systems biology puzzle. An increasing body of evidence highlights the observation that changes in brain function, both normal and pathological, consistently correlate with dynamic changes in neuronal anatomy. Anatomical changes occur on a full range of scales from the trafficking of individual proteins, to alterations in synaptic morphology both individually and on a systems level, to reductions in long distance connectivity and brain volume. The major sites of contact for synapsing neurons are dendritic spines, which provide an excellent metric for the number and strength of signaling connections between elements of functional neuronal circuits. A comprehensive model of anatomical changes and their functional consequences would be a holy grail for the field of systems neuroscience but its realization appears far on the horizon. Various imaging technologies have advanced to allow for multi-scale visualization of brain plasticity and pathology, but computational analysis of the big data sets involved forms the bottleneck toward the creation of multiscale models of brain structure and function. While a full accounting of techniques and progress toward a comprehensive model of brain anatomy and function is beyond the scope of this or any other single paper, this review serves to highlight the opportunities for analysis of neuronal spine anatomy and function provided by new imaging technologies and the high-throughput application of older technologies while surveying the strengths and weaknesses of currently available computational analytical tools and room for future improvement.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. Complementary methodologies to investigate human gut microbiota in host health, working towards integrative systems biology.

    PubMed

    Méndez-García, Celia; Barbas, Coral; Ferrer, Manuel; Rojo, David

    2017-09-05

    In 1680, Antonie van Leewenhoek noted compositional differences in his oral and fecal microbiota, pioneering the study of the diversity of the human microbiome. From Leewenhoek to modern successful attempts of changing the gut microbiota landscape to cure disease, there has been an exponential increase in the recognition of our resident microbes as part of ourselves. Thus, the human host and microbiome have evolved in parallel to configure a balanced system in which microbes survive in homeostasis with our innate and acquired immune system, unless disease occurs. A growing number of studies have demonstrated a correlation between the presence/absence of microbial taxa, and some of their functional molecules (i.e. genes, proteins, and metabolites), with health and disease states. Nevertheless, misleading experimental design on human subjects, and the cost and lack of standardized animal models pose challenges to answering the question of whether changes in the microbiome composition are cause or consequence of a certain biological state. In this review, we evaluate the state of the art of methodologies that enable the study of the gut microbiome, encouraging a change in broadly used analytic strategies by choosing effector molecules (proteins, metabolites) in combination with coding nucleic acids. We further explore microbial and effector microbial products imbalances that relate to disease and health. Copyright © 2017 American Society for Microbiology.

  5. 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.

  6. 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.

  7. Agent-based re-engineering of ErbB signaling: a modeling pipeline for integrative systems biology.

    PubMed

    Das, Arya A; Ajayakumar Darsana, T; Jacob, Elizabeth

    2017-03-01

    Experiments in systems biology are generally supported by a computational model which quantitatively estimates the parameters of the system by finding the best fit to the experiment. Mathematical models have proved to be successful in reverse engineering the system. The data generated is interpreted to understand the dynamics of the underlying phenomena. The question we have sought to answer is that - is it possible to use an agent-based approach to re-engineer a biological process, making use of the available knowledge from experimental and modelling efforts? Can the bottom-up approach benefit from the top-down exercise so as to create an integrated modelling formalism for systems biology? We propose a modelling pipeline that learns from the data given by reverse engineering, and uses it for re-engineering the system, to carry out in-silico experiments. A mathematical model that quantitatively predicts co-expression of EGFR-HER2 receptors in activation and trafficking has been taken for this study. The pipeline architecture takes cues from the population model that gives the rates of biochemical reactions, to formulate knowledge-based rules for the particle model. Agent-based simulations using these rules, support the existing facts on EGFR-HER2 dynamics. We conclude that, re-engineering models, built using the results of reverse engineering, opens up the possibility of harnessing the power pack of data which now lies scattered in literature. Virtual experiments could then become more realistic when empowered with the findings of empirical cell biology and modelling studies. Implemented on the Agent Modelling Framework developed in-house. C ++ code templates available in Supplementary material . liz.csir@gmail.com. Supplementary data are available at Bioinformatics online.

  8. InterMine: a flexible data warehouse system for the integration and analysis of heterogeneous biological data.

    PubMed

    Smith, Richard N; Aleksic, Jelena; Butano, Daniela; Carr, Adrian; Contrino, Sergio; Hu, Fengyuan; Lyne, Mike; Lyne, Rachel; Kalderimis, Alex; Rutherford, Kim; Stepan, Radek; Sullivan, Julie; Wakeling, Matthew; Watkins, Xavier; Micklem, Gos

    2012-12-01

    InterMine is an open-source data warehouse system that facilitates the building of databases with complex data integration requirements and a need for a fast customizable query facility. Using InterMine, large biological databases can be created from a range of heterogeneous data sources, and the extensible data model allows for easy integration of new data types. The analysis tools include a flexible query builder, genomic region search and a library of 'widgets' performing various statistical analyses. The results can be exported in many commonly used formats. InterMine is a fully extensible framework where developers can add new tools and functionality. Additionally, there is a comprehensive set of web services, for which client libraries are provided in five commonly used programming languages. Freely available from http://www.intermine.org under the LGPL license. g.micklem@gen.cam.ac.uk Supplementary data are available at Bioinformatics online.

  9. 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…

  10. Palm oil mill effluent treatment using a two-stage microbial fuel cells system integrated with immobilized biological aerated filters.

    PubMed

    Cheng, Jia; Zhu, Xiuping; Ni, Jinren; Borthwick, Alistair

    2010-04-01

    An integrated system of two-stage microbial fuel cells (MFCs) and immobilized biological aerated filters (I-BAFs) was used to treat palm oil mill effluent (POME) at laboratory scale. By replacing the conventional two-stage up-flow anaerobic sludge blanket (UASB) with a newly proposed upflow membrane-less microbial fuel cell (UML-MFC) in the integrated system, significant improvements on NH(3)-N removal were observed and direct electricity generation implemented in both MFC1 and MFC2. Moreover, the coupled iron-carbon micro-electrolysis in the cathode of MFC2 further enhanced treatment efficiency of organic compounds. The I-BAFs played a major role in further removal of NH(3)-N and COD. For influent COD and NH(3)-N of 10,000 and 125 mg/L, respectively, the final effluents COD and NH(3)-N were below 350 and 8 mg/L, with removal rates higher than 96.5% and 93.6%. The GC-MS analysis indicated that most of the contaminants were satisfactorily biodegraded by the integrated system. Copyright 2009 Elsevier Ltd. All rights reserved.

  11. 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...

  12. 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...

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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. Published by Elsevier Ltd.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

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

    PubMed

    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

    2015-07-20

    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

  5. An integrative system biology approach to unravel potential drug candidates for multiple age related disorders.

    PubMed

    Srivastava, Isha; Khurana, Pooja; Yadav, Mohini; Hasija, Yasha

    2017-08-11

    Aging, though an inevitable part of life, is becoming a worldwide social and economic problem. Healthy aging is usually marked by low probability of age related disorders. Good therapeutic approaches are still in need to cure age related disorders. Occurrence of more than one ARD in an individual, expresses the need of discovery of such target proteins, which can affect multiple ARDs. Advanced scientific and medical research technologies throughout last three decades have arrived to the point where lots of key molecular determinants affect human disorders can be examined thoroughly. In this study, we designed and executed an approach to prioritize drugs that may target multiple age related disorders. Our methodology, focused on the analysis of biological pathways and protein protein interaction networks that may contribute to the pharmacology of age related disorders, included various steps such as retrieval and analysis of data, protein-protein interaction network analysis, and statistical and comparative analysis of topological coefficients, pathway, and functional enrichment analysis, and identification of drug-target proteins. We assume that the identified molecular determinants may be prioritized for further screening as novel drug targets to cure multiple ARDs. Based on the analysis, an online tool named as 'ARDnet' has been developed to construct and demonstrate ARD interactions at the level of PPI, ARDs and ARDs protein interaction, ARDs pathway interaction and drug-target interaction. The tool is freely made available at http://genomeinformatics.dtu.ac.in/ARDNet/Index.html. Copyright © 2017. Published by Elsevier B.V.

  6. 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

  7. 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.

  8. 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...

  9. 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...

  10. Integration and visualization of systems biology data in context of the genome

    PubMed Central

    2010-01-01

    Background High-density tiling arrays and new sequencing technologies are generating rapidly increasing volumes of transcriptome and protein-DNA interaction data. Visualization and exploration of this data is critical to understanding the regulatory logic encoded in the genome by which the cell dynamically affects its physiology and interacts with its environment. Results The Gaggle Genome Browser is a cross-platform desktop program for interactively visualizing high-throughput data in the context of the genome. Important features include dynamic panning and zooming, keyword search and open interoperability through the Gaggle framework. Users may bookmark locations on the genome with descriptive annotations and share these bookmarks with other users. The program handles large sets of user-generated data using an in-process database and leverages the facilities of SQL and the R environment for importing and manipulating data. A key aspect of the Gaggle Genome Browser is interoperability. By connecting to the Gaggle framework, the genome browser joins a suite of interconnected bioinformatics tools for analysis and visualization with connectivity to major public repositories of sequences, interactions and pathways. To this flexible environment for exploring and combining data, the Gaggle Genome Browser adds the ability to visualize diverse types of data in relation to its coordinates on the genome. Conclusions Genomic coordinates function as a common key by which disparate biological data types can be related to one another. In the Gaggle Genome Browser, heterogeneous data are joined by their location on the genome to create information-rich visualizations yielding insight into genome organization, transcription and its regulation and, ultimately, a better understanding of the mechanisms that enable the cell to dynamically respond to its environment. PMID:20642854

  11. 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

  12. Systems Approaches to Cancer Biology.

    PubMed

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

    2016-12-01

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

  13. Bioprocess scale-up/down as integrative enabling technology: from fluid mechanics to systems biology and beyond.

    PubMed

    Delvigne, Frank; Takors, Ralf; Mudde, Rob; van Gulik, Walter; Noorman, Henk

    2017-09-01

    Efficient optimization of microbial processes is a critical issue for achieving a number of sustainable development goals, considering the impact of microbial biotechnology in agrofood, environment, biopharmaceutical and chemical industries. Many of these applications require scale-up after proof of concept. However, the behaviour of microbial systems remains unpredictable (at least partially) when shifting from laboratory-scale to industrial conditions. The need for robust microbial systems is thus highly needed in this context, as well as a better understanding of the interactions between fluid mechanics and cell physiology. For that purpose, a full scale-up/down computational framework is already available. This framework links computational fluid dynamics (CFD), metabolic flux analysis and agent-based modelling (ABM) for a better understanding of the cell lifelines in a heterogeneous environment. Ultimately, this framework can be used for the design of scale-down simulators and/or metabolically engineered cells able to cope with environmental fluctuations typically found in large-scale bioreactors. However, this framework still needs some refinements, such as a better integration of gas-liquid flows in CFD, and taking into account intrinsic biological noise in ABM. © 2017 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  14. 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.

  15. Systems Biology of Metabolism.

    PubMed

    Nielsen, Jens

    2017-06-20

    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.

  16. Multiple program/multiple data molecular dynamics method with multiple time step integrator for large biological systems.

    PubMed

    Jung, Jaewoon; Sugita, Yuji

    2017-06-15

    Parallelization of molecular dynamics (MD) simulation is essential for investigating conformational dynamics of large biological systems, such as ribosomes, viruses, and multiple proteins in cellular environments. To improve efficiency in the parallel computation, we have to reduce the amount of data transfer between processors by introducing domain decomposition schemes. Also, it is important to optimize the computational balance between real-space non-bonded interactions and reciprocal-space interactions for long-range electrostatic interactions. Here, we introduce a novel parallelization scheme for large-scale MD simulations on massively parallel supercomputers consisting of only CPUs. We make use of a multiple program/multiple data (MPMD) approach for separating the real-space and reciprocal-space computations on different processors. We also utilize the r-RESPA multiple time step integrator on the framework of the MPMD approach in an efficient way: when the reciprocal-space computations are skipped in r-RESPA, processors assigned for them are utilized for half of the real-space computations. The new scheme allows us to use twice as many as processors that are available in the conventional single program approach. The best performances of all-atom MD simulations for 1 million (STMV), 8.5 million (8_STMV), and 28.8 million (27_STMV) atom systems on K computer are 65, 36, and 24 ns/day, respectively. The MPMD scheme can accelerate 23.4, 10.2, and 9.2 ns/day from the maximum performance of single-program approach for STMV, 8_STMV, and 27_STMV systems, respectively, which correspond to 57%, 39%, and 60% speed up. This suggests significant speedups by increasing the number of processors without losing parallel computational efficiency. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Engineering scalable biological systems

    PubMed Central

    2010-01-01

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

  18. 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.

  19. 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

  20. 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.

  1. Systems biology and addiction.

    PubMed

    Tretter, F; Gebicke-Haerter, P J; Albus, M; an der Heiden, U; Schwegler, H

    2009-05-01

    The onset of addiction is marked with drug induced positive experiences that keep being repeated. During that time, adaptation occurs and addiction is stabilized. Interruption of those processes induces polysymptomatic withdrawal syndromes. Abstinence is accompanied by risks of relapse. These features of addiction suggest adaptive brain dynamics with common pathways in complex neuronal networks. Addiction research has used animal models, where some of those phenomena could be reproduced, to find correlates of addictive behavior. The major thrust of those approaches has been on the involvement of genes and proteins. Recently, an enormous amount of data has been obtained by high throughput technologies in these fields. Therefore, (Computational) "Systems Biology" had to be implemented as a new approach in molecular biology and biochemistry. Conceptually, Systems Biology can be understood as a field of theoretical biology that tries to identify patterns in complex data sets and that reconstructs the cell and cellular networks as complex dynamic, self-organizing systems. This approach is embedded in systems science as an interdisciplinary effort to understand complex dynamical systems and belongs to the field of theoretical neuroscience (Computational Neuroscience). Systems biology, in a similar way as computational neuroscience is based on applied mathematics, computer-based computation and experimental simulation. In terms of addiction research, building up "computational molecular systems biology of the (addicted) neuron" could provide a better molecular biological understanding of addiction on the cellular and network level. Some key issues are addressed in this article.

  2. Integrating chemical and biological criteria.

    PubMed

    Pacheco, Manoel Augusto Whitaker; McIntyre, Dennis Owen; Linton, Tyler Keith

    2005-11-01

    We present a system to derive benchmarks for protection of aquatic organisms that, as chemical criteria, promotes regulation of contaminants and, as biological criteria, focuses on an endpoint that adequately represents species abundance. The proposed method utilizes quantile regression to quantify the decline in maximum number of organisms with increasing contaminant concentrations. This limiting function then is applied to project the contaminant concentration associated with a threshold number of organisms. The threshold value is defined according to the study's objective and level of desired protection. Here, we defined it as 0.8 x 90th quantile of the number of organisms in samples from reference sites. We use the proposed system to derive taxon-specific, field-based effect concentrations (FECs) for copper and zinc in Ohio, USA, rivers and streams. Comparisons of results with respective chronic values suggest that only the draft criteria for copper are adequately protective. Projected zinc FECs were far lower than respective estimates of chronic values. The FECs likely are less sensitive to impacts of confounding factors because high numbers of organism in samples are observed when negative effects of other stressors are absent or minimal. We discuss other advantages, limitations, and potential applications of the proposed system.

  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. WISB: Warwick Integrative Synthetic Biology Centre.

    PubMed

    McCarthy, John

    2016-06-15

    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. © 2016 The Author(s).

  6. 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.

  7. 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

  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

    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.

  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 and immune aging.

    PubMed

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

    2014-11-01

    Many alterations of innate and adaptive immunity are common in the aging population, which reflect a deterioration of the immune system, and have lead to the terms "immune aging" or "immunosenescence". Systems Biology aims to the comprehensive knowledge of the structure, dynamics, control and design that define a given biological system. Systems Biology benefits from the continuous advances in the omics sciences, based on high-throughput and high-content technologies, as well as on bioinformatic tools for data mining and integration. The Systems Biology approach is becoming gradually used to propose and to test comprehensive models of aging, both at the level of the immune system and the whole organism. In this way, immune aging may be described by a dynamic view of the states and interactions of every individual cell and molecule of the immune system and their role in the context of aging and longevity. This mini-review presents a panoramics of the current strategies, tools and challenges for applying Systems Biology to immune aging. Copyright © 2014 Elsevier B.V. All rights reserved.

  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. Data integration in biological research: an overview.

    PubMed

    Lapatas, Vasileios; Stefanidakis, Michalis; Jimenez, Rafael C; Via, Allegra; Schneider, Maria Victoria

    2015-12-01

    Data sharing, integration and annotation are essential to ensure the reproducibility of the analysis and interpretation of the experimental findings. Often these activities are perceived as a role that bioinformaticians and computer scientists have to take with no or little input from the experimental biologist. On the contrary, biological researchers, being the producers and often the end users of such data, have a big role in enabling biological data integration. The quality and usefulness of data integration depend on the existence and adoption of standards, shared formats, and mechanisms that are suitable for biological researchers to submit and annotate the data, so it can be easily searchable, conveniently linked and consequently used for further biological analysis and discovery. Here, we provide background on what is data integration from a computational science point of view, how it has been applied to biological research, which key aspects contributed to its success and future directions.

  13. 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.

  14. 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

  15. 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).

  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. Systems cell biology

    PubMed Central

    Mast, Fred D.; Ratushny, Alexander V.

    2014-01-01

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

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

    USDA-ARS?s Scientific Manuscript database

    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...

  20. Conservation Physiology and Conservation Pathogens: White-Nose Syndrome and Integrative Biology for Host-Pathogen Systems.

    PubMed

    Willis, Craig K R

    2015-10-01

    Conservation physiology aims to apply an understanding of physiological mechanisms to management of imperiled species, populations, or ecosystems. One challenge for physiologists hoping to apply their expertise to conservation is connecting the mechanisms we study, often in the laboratory, with the vital rates of populations in the wild. There is growing appreciation that infectious pathogens can threaten populations and species, and represent an important issue for conservation. Conservation physiology has much to offer in terms of addressing the threat posed to some host species by infectious pathogens. At the same time, the well-developed theoretical framework of disease ecology could provide a model to help advance the application of physiology to a range of other conservation issues. Here, I use white-nose syndrome (WNS) in hibernating North American bats as an example of a conservation problem for which integrative physiological research has been a critical part of research and management. The response to WNS highlights the importance of a well-developed theoretical framework for the application of conservation physiology to a particular threat. I review what is known about physiological mechanisms associated with mortality from WNS and emphasize the value of combining a strong theoretical background with integrative physiological studies in order to connect physiological mechanisms with population processes and thereby maximize the potential benefits of conservation physiology. © The Author 2015. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. Integrating Rehabilitation Engineering Technology With Biologics

    PubMed Central

    Collinger, Jennifer L.; Dicianno, Brad E.; Weber, Douglas J.; Cui, Xinyan Tracy; Wang, Wei; Brienza, David M.; Boninger, Michael L.

    2017-01-01

    Rehabilitation engineers apply engineering principles to improve function or to solve challenges faced by persons with disabilities. It is critical to integrate the knowledge of biologics into the process of rehabilitation engineering to advance the field and maximize potential benefits to patients. Some applications in particular demonstrate the value of a symbiotic relationship between biologics and rehabilitation engineering. In this review we illustrate how researchers working with neural interfaces and integrated prosthetics, assistive technology, and biologics data collection are currently integrating these 2 fields. We also discuss the potential for further integration of biologics and rehabilitation engineering to deliver the best technologies and treatments to patients. Engineers and clinicians must work together to develop technologies that meet clinical needs and are accessible to the intended patient population. PMID:21703573

  6. Integrating chemical and biological control

    Treesearch

    Scott Salom; Albert Mayfield; Tom McAvoy

    2011-01-01

    Research and management efforts to establish an effective biological control program against HWA has received significant support by the U.S. Forest Service over the past 17 years. Other federal and state agencies, universities, and private entities have also contributed to this overall research and management effort. Although a number of HWA-specific predator species...

  7. Raise Test Scores: Integrate Biology and Calculus.

    ERIC Educational Resources Information Center

    Lukens, Jeffrey D.; Feinstein, Sheryl

    This paper presents the results of research that compared the academic achievement of high school students enrolled in an integrated Advanced Placement Biology/Advanced Placement Calculus course with students enrolled in traditional Advanced Placement Biology and Advanced Placement Calculus courses. Study subjects included high school students…

  8. 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.

  9. 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.

  10. 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

  11. The chernobyl tissue bank - a repository for biomaterial and data used in integrative and systems biology modeling the human response to radiation.

    PubMed

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

    2012-05-09

    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.

  12. 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

  13. The emergence of Semantic Systems Biology.

    PubMed

    Antezana, Erick; Mironov, Vladimir; Kuiper, Martin

    2013-03-25

    Over the past decade the biological sciences have been widely embracing Systems Biology and its various data integration approaches to discover new knowledge. Molecular Systems Biology aims to develop hypotheses based on integrated, or modelled data. These hypotheses can be subsequently used to design new experiments for testing, leading to an improved understanding of the biology; a more accurate model of the biological system and therefore an improved ability to develop hypotheses. During the same period the biosciences have also eagerly taken up the emerging Semantic Web as evidenced by the dedicated exploitation of Semantic Web technologies for data integration and sharing in the Life Sciences. We describe how these two approaches merged in Semantic Systems Biology: a data integration and analysis approach complementary to model-based Systems Biology. Semantic Systems Biology augments the integration and sharing of knowledge, and opens new avenues for computational support in quality checking and automated reasoning, and to develop new, testable hypotheses. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Systems cell biology.

    PubMed

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

    2014-09-15

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

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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…

  20. 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…

  1. 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.

  2. 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.

  3. Systems biology of kidney diseases

    PubMed Central

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

    2011-01-01

    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. PMID:21881558

  4. The role of the sociotype in managing chronic disease: integrating bio-psycho-sociology with systems biology.

    PubMed

    Berry, Elliot M

    2011-10-01

    Attempts have been made to replace the bio-medical approach with that of systems biology, which considers dynamic human behavior (internal factors) for chronic (rather than acute) disease management. They have not yet incorporated the Bio-psycho-social (BPS) model of Engel which adds patients' background and cultural beliefs (external factors) contributing to their susceptibility to, and coping strategies for, non-communicable diseases (NCDs) the increasing domain of global Public Health. The problem is how to include the social determinants of disease in a comprehensive model of care, especially in the management of chronic disease. The concept of "sociotype" is proposed as a framework for understanding the interactions between the social, cultural and environmental inputs that influence the growth, development and life-long behavior of a person, including relationships, lifestyle and coping strategies. Pre-/peri-natal influences on development and subsequent susceptibility to chronic disease are examples of interactions between the sociotype, genotype and phenotype. Disorders of the sociotype, encompassing social determinants (e.g. poverty, education, networking), of disease are major contributors to the increase in NCDs, as well as for mental illness and absenteeism. Thus, people are the product of a threefold cord--genotype, phenotype and sociotype. WHAT NEXT?: Holistic management of patients through the BPS model have to be aligned with the relevant elements of systems biology--context, space, time and robustness--that pertain to the sociotype. Medical curricula should balance basic sciences with disciplines such as psychology, sociology, anthropology and public health that attempt to explain human behavior and the social determinants of disease. This requires methodologies combining qualitative and quantitative research to study simultaneous interactions (and their possible mechanisms) between systems biology and the BPS model. The neologism "sociotype

  5. Systems biology, emergence and antireductionism.

    PubMed

    Kesić, Srdjan

    2016-09-01

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

  6. Plant systems biology: insights, advances and challenges.

    PubMed

    Sheth, Bhavisha P; Thaker, Vrinda S

    2014-07-01

    Plants dwelling at the base of biological food chain are of fundamental significance in providing solutions to some of the most daunting ecological and environmental problems faced by our planet. The reductionist views of molecular biology provide only a partial understanding to the phenotypic knowledge of plants. Systems biology offers a comprehensive view of plant systems, by employing a holistic approach integrating the molecular data at various hierarchical levels. In this review, we discuss the basics of systems biology including the various 'omics' approaches and their integration, the modeling aspects and the tools needed for the plant systems research. A particular emphasis is given to the recent analytical advances, updated published examples of plant systems biology studies and the future trends.

  7. 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

  8. Systems biology and inflammation.

    PubMed

    Vodovotz, Yoram; An, Gary

    2010-01-01

    Inflammation is a complex, multiscale biological response to threats - both internal and external - to the body, which is also required for proper healing of injured tissue. In turn, damaged or dysfunctional tissue stimulates further inflammation. Despite continued advances in characterizing the cellular and molecular processes involved in the interactions between inflammation and tissue damage, there exists a significant gap between the knowledge of mechanistic pathophysiology and the development of effective therapies for various inflammatory conditions. We have suggested the concept of translational systems biology, defined as a focused application of computational modeling and engineering principles to pathophysiology primarily in order to revise clinical practice. This chapter reviews the existing, translational applications of computational simulations and related approaches as applied to inflammation.

  9. 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.

  10. Promise and peril in nanomedicine: the challenges and needs for integrated systems biology approaches to define health risk.

    PubMed

    Halappanavar, Sabina; Vogel, Ulla; Wallin, Hakan; Yauk, Carole L

    2017-03-15

    In the 1966s visionary film 'Fantastic Voyage' a submarine crew was shrunk to 100 nm in size and injected into the body of an injured scientist to repair his damaged brain. The movie (written by Harry Kleiner; directed by Richard Fleischer; novel by Isaac Asimov) drew attention to the potential power of engineered nanoscale structures and devices to construct, monitor, control, treat, and repair individual cells. Even more interesting was the fact that the film elegantly noted that the structure had to be miniaturized to a size that is not detected by the body's immune surveillance system, and highlighted the many physiological barriers that are encountered on the submarine's long journey to the target. Although the concept of miniaturizing humans remains an element of science fiction, targeted drug delivery through nanobots to treat diseases such as cancer is now a reality. The ability of nanobots to evade immune surveillance is one of the most attractive features of nanoscale materials that are exploited in the field of medicine for molecular diagnostics, targeted drug delivery, and therapy of diseases. This article will provide a concise opinion on the state-of-the-art, the challenges, and the use of systems biology-another equally revolutionary field of science-to assess the unique health hazards of nanomaterial exposures. For further resources related to this article, please visit the WIREs website. © 2017 Her Majesty the Queen in Right of Canada. WIREs Nanomedicine and Nanobiotechnology published by Wiley Periodicals, Inc.

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. Zebrafish as a model for systems biology.

    PubMed

    Mushtaq, Mian Yahya; Verpoorte, Robert; Kim, Hye Kyong

    2013-01-01

    Zebrafish offer a unique vertebrate model for research areas such as drug development, disease modeling and other biological exploration. There is significant conservation of genetics and other cellular networks among zebrafish and other vertebrate models, including humans. Here we discuss the recent work and efforts made in different fields of biology to explore the potential of zebrafish. Along with this, we also reviewed the concept of systems biology. A biological system is made up of a large number of components that interact in a huge variety of combinations. To understand completely the behavior of a system, it is important to know its components and interactions, and this can be achieved through a systems biology approach. At the end of the paper we present a concept of integrating zebrafish into the systems biology approach.

  16. Integrating Introductory Biology and General Chemistry Laboratories.

    ERIC Educational Resources Information Center

    Godrick, Elizabeth; Hartman, Standish

    2000-01-01

    Introduces a science laboratory integrating biology and chemistry courses that includes four modules: (1) the fundamental process of reactions; (2) a semester-long project on the chemical assay of ascorbic acid; (3) human metabolism of Vitamin C; and (4) an open-ended project on the manipulation of macromolecules. (YDS)

  17. [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.

  18. 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.

  19. 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.

  20. Systems biology approaches for toxicology.

    PubMed

    Slikker, William; Paule, Merle G; Wright, Linnzi K M; Patterson, Tucker A; Wang, Cheng

    2007-01-01

    Systems biology/toxicology involves the iterative and integrative study of perturbations by chemicals and other stressors of gene and protein expression that are linked firmly to toxicological outcome. In this review, the value of systems biology to enhance the understanding of complex biological processes such as neurodegeneration in the developing brain is explored. Exposure of the developing mammal to NMDA (N-methyl-D-aspartate) receptor antagonists perturbs the endogenous NMDA receptor system and results in enhanced neuronal cell death. It is proposed that continuous blockade of NMDA receptors in the developing brain by NMDA antagonists such as ketamine (a dissociative anesthetic) causes a compensatory up-regulation of NMDA receptors, which makes the neurons bearing these receptors subsequently more vulnerable (e.g. after ketamine washout), to the excitotoxic effects of endogenous glutamate: the up-regulation of NMDA receptors allows for the accumulation of toxic levels of intracellular Ca(2+) under normal physiological conditions. Systems biology, as applied to toxicology, provides a framework in which information can be arranged in the form of a biological model. In our ketamine model, for example, blockade of NMDA receptor up-regulation by the co-administration of antisense oligonucleotides that specifically target NMDA receptor NR1 subunit mRNA, dramatically diminishes ketamine-induced cell death. Preliminary gene expression data support the role of apoptosis as a mode of action of ketamine-induced neurotoxicity. In addition, ketamine-induced cell death is also prevented by the inhibition of NF-kappaB translocation into the nucleus. This process is known to respond to changes in the redox state of the cytoplasm and has been shown to respond to NMDA-induced cellular stress. Although comprehensive gene expression/proteomic studies and mathematical modeling remain to be carried out, biological models have been established in an iterative manner to allow for

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. Bioinformatics resource manager v2.3: an integrated software environment for systems biology with microRNA and cross-species analysis tools

    PubMed Central

    2012-01-01

    Background MicroRNAs (miRNAs) are noncoding RNAs that direct post-transcriptional regulation of protein coding genes. Recent studies have shown miRNAs are important for controlling many biological processes, including nervous system development, and are highly conserved across species. Given their importance, computational tools are necessary for analysis, interpretation and integration of high-throughput (HTP) miRNA data in an increasing number of model species. The Bioinformatics Resource Manager (BRM) v2.3 is a software environment for data management, mining, integration and functional annotation of HTP biological data. In this study, we report recent updates to BRM for miRNA data analysis and cross-species comparisons across datasets. Results BRM v2.3 has the capability to query predicted miRNA targets from multiple databases, retrieve potential regulatory miRNAs for known genes, integrate experimentally derived miRNA and mRNA datasets, perform ortholog mapping across species, and retrieve annotation and cross-reference identifiers for an expanded number of species. Here we use BRM to show that developmental exposure of zebrafish to 30 uM nicotine from 6–48 hours post fertilization (hpf) results in behavioral hyperactivity in larval zebrafish and alteration of putative miRNA gene targets in whole embryos at developmental stages that encompass early neurogenesis. We show typical workflows for using BRM to integrate experimental zebrafish miRNA and mRNA microarray datasets with example retrievals for zebrafish, including pathway annotation and mapping to human ortholog. Functional analysis of differentially regulated (p<0.05) gene targets in BRM indicates that nicotine exposure disrupts genes involved in neurogenesis, possibly through misregulation of nicotine-sensitive miRNAs. Conclusions BRM provides the ability to mine complex data for identification of candidate miRNAs or pathways that drive phenotypic outcome and, therefore, is a useful hypothesis

  8. An integrative approach for biological data mining and visualisation.

    PubMed

    Gopalacharyulu, Peddinti V; Lindfors, Erno; Miettinen, Jarkko; Bounsaythip, Catherine K; Oresic, Matej

    2008-01-01

    The emergence of systems biology necessitates development of platforms to organise and interpret plentitude of biological data. We present a system to integrate data across multiple bioinformatics databases and enable mining across various conceptual levels of biological information. The results are represented as complex networks. Context dependent mining of these networks is achieved by use of distances. Our approach is demonstrated with three applications: full metabolic network retrieval with network topology study, exploration of properties and relationships of a set of selected proteins, and combined visualisation and exploration of gene expression data with related pathways and ontologies.

  9. 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.…

  10. 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.…

  11. 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.

  12. 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.

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

    SciTech Connect

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

    2012-01-01

    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 to 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. Integrating molecular biology into the veterinary curriculum.

    PubMed

    Ryan, Marion T; Sweeney, Torres

    2007-01-01

    The modern discipline of molecular biology is gaining increasing relevance in the field of veterinary medicine. This trend must be reflected in the curriculum if veterinarians are to capitalize on opportunities arising from this field and direct its development toward their own goals as a profession. This review outlines current applications of molecular-based technologies that are relevant to the veterinary profession. In addition, the current techniques and technologies employed within the field of molecular biology are discussed. Difficulties associated with teaching a subject such as molecular biology within a veterinary curriculum can be alleviated by effectively integrating molecular topics throughout the curriculum, pitching the subject at an appropriate depth, and employing varied teaching methods throughout.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. Material and energy balances of an integrated biological hydrogen production and purification system and their implications for its potential to reduce greenhouse gas emissions.

    PubMed

    Fukushima, Yasuhiro; Huang, Yu-Jung; Chen, Jhen-Wei; Lin, Hung-Chun; Whang, Liang-Ming; Chu, Hsin; Lo, Young-Chong; Chang, Jo-Shu

    2011-09-01

    The materials and energy in an integrated biological hydrogen production and purification system involving hydrolysis, dark fermentation, photo fermentation, CO2 fixation and anaerobic digestion are balanced by integrating the results from multiple experiments, simulations and the literature. The findings are two fold. First, using 1000 kg rice straw as a substrate, 19.8 kg H2 and 138.0 kg CH4 are obtained. The net energy balance (NEB) and net energy ratio (NER) are -738.4 kWh and 77.8%, respectively, both of which imply an unfavorable energy production system. Opportunities to improve the performance particularly lie in the photo fermentation process. Second, greenhouse gas emissions are evaluated for various options. The results were comparable with the emission inventory of electricity generated from fossil fuels. NEB and NER under a zero-carbon-emission constraint were discussed in detail to clarify completely the implications of the energy and material balances on greenhouse gas emissions. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Mammalian Synthetic Biology: Engineering Biological Systems.

    PubMed

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

    2017-06-21

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

  6. 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

  7. 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.

    PubMed

    Fostel, Jennifer; Choi, Danielle; Zwickl, Craig; Morrison, Norman; Rashid, Asif; Hasan, Atif; Bao, Wenjun; Richard, Ann; Tong, Weida; Bushel, Pierre R; Brown, Roger; Bruno, Maribel; Cunningham, Michael L; Dix, David; Eastin, William; Frade, Carlos; Garcia, Alex; Heinloth, Alexandra; Irwin, Rick; Madenspacher, Jennifer; Merrick, B Alex; Papoian, Thomas; Paules, Richard; Rocca-Serra, Philippe; Sansone, Assunta-Susanna; Stevens, James; Tomer, Kenneth; Yang, Chihae; Waters, Michael

    2005-12-01

    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 during a period of time for the purpose of obtaining data, and the Study Design Description captures the methods, timing, and organization of the Study. The CEBS Data Dictionary (CEBS-DD) has been designed to define and organize terms in an attempt to standardize nomenclature needed to describe a toxicogenomics Study in a structured yet intuitive format and provide a flexible means to describe a Study as conceptualized by the investigator. The CEBS-DD will organize and annotate information from a variety of sources, thereby facilitating the capture and display of toxicogenomics data in biological context in CEBS, i.e., associating molecular events detected in highly-parallel data with the toxicology/pathology phenotype as observed in the individual Study Subjects and linked to the experimental treatments. The CEBS-DD has been developed with a focus on acute toxicity studies, but with a design that will permit it to be extended to other areas of toxicology and biology with the addition of domain-specific terms. To illustrate the utility of the CEBS-DD, we present an example of integrating data from two proteomics and transcriptomics studies of the response to acute acetaminophen toxicity (A. N. Heinloth et al., 2004, Toxicol. Sci. 80, 193-202).

  8. 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.

  9. Human Systems Integration Requirements

    DTIC Science & Technology

    2009-09-01

    HUMAN SYSTEMS INTEGRATION OFFICE HUMAN SYSTEMS INTEGRATION REQUIREMENTS POCKET GUIDE SEPTEMBER 2009 Report Documentation Page Form ApprovedOMB No...collection of information if it does not display a currently valid OMB control number. 1. REPORT DATE SEP 2009 2. REPORT TYPE Pocket Guide 3. DATES...COVERED 00-09-2009 to 00-12-2011 4. TITLE AND SUBTITLE Human Systems Integration Requirements Pocket Guide 5a. CONTRACT NUMBER 5b. GRANT NUMBER

  10. 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.

  11. 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.

  12. Systems biology of coagulation.

    PubMed

    Diamond, S L

    2013-06-01

    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, modeling 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 mobilization or inside-out signaling, 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. © 2013 International Society on Thrombosis and Haemostasis.

  13. An engineering design approach to systems biology.

    PubMed

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

    2017-07-17

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

  14. 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.

  15. Systems biology of myasthenia gravis, integration of aberrant lncRNA and mRNA expression changes.

    PubMed

    Luo, ZhaoHui; Li, Ye; Liu, XiaoFang; Luo, MengChuan; Xu, LiQun; Luo, YueBei; Xiao, Bo; Yang, Huan

    2015-03-18

    A novel class of transcripts, long non-coding RNAs (lncRNAs), has recently emerged as a key player in several biological processes, and important roles for these molecules have been reported in a number of complex human diseases, such as autoimmune diseases, neurological disorders, and various cancers. However, the aberrant lncRNAs implicated in myasthenia gravis (MG) remain unknown. The aim of the present study was to explore the abnormal expression of lncRNAs in peripheral blood mononuclear cells (PBMCs) and examine mRNA regulatory relationship networks among MG patients with or without thymoma. Microarray assays were performed, and the outstanding differences between lncRNAs or mRNA expression were verified through RT-PCR. The lncRNAs functions were annotated for the target genes using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway. The potential regulatory relationships between the lncRNAs and target genes were analyzed using the 'cis' and 'trans' model. Outstanding lncRNAs were organized to generate a TF-lncRNA-gene network using Cytoscape software. The lncRNA and mRNA expression profile analysis revealed subsets of differentially expressed genes in MG patients with or without thymoma. A total of 12 outstanding dysregulated expression lncRNAs, such as lncRNA oebiotech_11933, were verified through real-time PCR. Several GO terms including the cellular response to interferon-γ, platelet degranulation, chemokine receptor binding and cytokine interactions were very important in MG pathogenesis. The chromosome locations of some lncRNAs and associated co-expression genes were demonstrated using 'cis' analysis. The results of the 'trans' analysis revealed that some TFs (i.e., CTCF, TAF1and MYC) regulate lncRNA and gene expression. The outstanding lncRNAs in each group were implicated in the regulation of the TF-lncRNA-target gene network. The results of the present study provide a perspective on lncRNA expression in MG

  16. 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.

  17. 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

  18. Enhanced Biological Phosphorus Removal at low Sludge Retention Time in view of its integration in A-stage systems.

    PubMed

    Chan, Carlos; Guisasola, Albert; Baeza, Juan Antonio

    2017-07-01

    The two-stage A/B WWTP configuration is being studied as a possible wastewater treatment with low energy consumption or even with a net energy generation. The first phase, A-stage, is designed to remove organic matter at very short Sludge Retention Time (SRT), while the B-stage is based on autotrophic nitrogen removal. However, P-removal in the A/B process usually only relies on precipitation. This work studies the potential inclusion of Enhanced Biological Phosphorus Removal (EBPR) in the A-stage phase. For this aim, the long-term operation of three different Sequencing Batch Reactors (SBR) enriched in Accumulibacter at low SRT was thoroughly monitored for more than three months each one. This work shows that EBPR can be sustained with a minimal SRT of 3.6 d at 25 °C. Lower values, SRT = 3 d, led to the PAO washout because of a reduction in P-release and P-uptake, an increase of the VSS/TSS ratio and a decrease of the P/C ratio. The Yobs could be related to the SRT with the parameters Y = 0.39 ± 0.05 gCODX·g(-1)CODS and kD = 0.06 ± 0.04 d(-1) which leads to a 24% increase of biomass yield when SRT was reduced from 10 to 4 d. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. 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.

  20. 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.

  1. 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…

  2. Top-down systems biology integration of conditional prebiotic modulated transgenomic interactions in a humanized microbiome mouse model

    PubMed Central

    Martin, Francois-Pierre J; Wang, Yulan; Sprenger, Norbert; Yap, Ivan K S; Rezzi, Serge; Ramadan, Ziad; Peré-Trepat, Emma; Rochat, Florence; Cherbut, Christine; van Bladeren, Peter; Fay, Laurent B; Kochhar, Sunil; Lindon, John C; Holmes, Elaine; Nicholson, Jeremy K

    2008-01-01

    Gut microbiome–host metabolic interactions affect human health and can be modified by probiotic and prebiotic supplementation. Here, we have assessed the effects of consumption of a combination of probiotics (Lactobacillus paracasei or L. rhamnosus) and two galactosyl-oligosaccharide prebiotics on the symbiotic microbiome–mammalian supersystem using integrative metabolic profiling and modeling of multiple compartments in germ-free mice inoculated with a model of human baby microbiota. We have shown specific impacts of two prebiotics on the microbial populations of HBM mice when co-administered with two probiotics. We observed an increase in the populations of Bifidobacterium longum and B. breve, and a reduction in Clostridium perfringens, which were more marked when combining prebiotics with L. rhamnosus. In turn, these microbial effects were associated with modulation of a range of host metabolic pathways observed via changes in lipid profiles, gluconeogenesis, and amino-acid and methylamine metabolism associated to fermentation of carbohydrates by different bacterial strains. These results provide evidence for the potential use of prebiotics for beneficially modifying the gut microbial balance as well as host energy and lipid homeostasis. PMID:18628745

  3. Systems biology of innate immunity

    PubMed Central

    Zak, Daniel E.; Aderem, Alan

    2009-01-01

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

  4. 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

  5. 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

  6. 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.

  7. Developing an integrating biological dosimeter for spaceflight

    NASA Astrophysics Data System (ADS)

    Zhao, Yang; Jones, Martin; Baillie, David; Rose, Ann

    2007-09-01

    Exposure to harmful radiation is one of the major threats to human beings in outer-space; however, the biological consequences of long term exposure are not well understood. It would be useful to have a means of measuring the effect of space radiation on a living organism during space flights. We conducted a pilot project as part of the International Caenorhabditis elegans Experiment First Flight (ICE-First) project on the International Space Station (ISS). Using a mutational capture system, the eT1 balancer, along with other mutation detection systems, we analyzed the mutational effects of the 11 day mission. Upon recovery, classical genetic approaches and comparative genomic hybridization (CGH) microarrays were used to isolate and characterize mutant strains. Although in this short period of time, as expected no increase in mutational background was observed, we were able to demonstrate the potential of this system for longer-term measurement of biological damage. A sixmonth exposure experiment using the same system is currently in progress on the ISS. The relative simplicity and robustness of this model system demonstrate its potential for use as a biological dosimeter.

  8. 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.

  9. [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.

  10. Systems biology: leading the revolution in ecotoxicology.

    PubMed

    Garcia-Reyero, Natàlia; Perkins, Edward J

    2011-02-01

    The rapid development of new technologies such as transcriptomics, proteomics, and metabolomics (Omics) are changing the way ecotoxicology is practiced. The data deluge has begun with genomes of over 65 different aquatic species that are currently being sequenced, and many times that number with at least some level of transcriptome sequencing. Integrating these top-down methodologies is an essential task in the field of systems biology. Systems biology is a biology-based interdisciplinary field that focuses on complex interactions in biological systems, with the intent to model and discover emergent properties of the system. Recent studies demonstrate that Omics technologies provide valuable insight into ecotoxicity, both in laboratory exposures with model organisms and with animals exposed in the field. However, these approaches require a context of the whole animal and population to be relevant. Powerful approaches using reverse engineering to determine interacting networks of genes, proteins, or biochemical reactions are uncovering unique responses to toxicants. Modeling efforts in aquatic animals are evolving to interrelate the interacting networks of a system and the flow of information linking these elements. Just as is happening in medicine, systems biology approaches that allow the integration of many different scales of interaction and information are already driving a revolution in understanding the impacts of pollutants on aquatic systems. © 2010 SETAC.

  11. 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.

  12. Metabolic systems biology: a brief primer.

    PubMed

    Edwards, Lindsay M

    2017-05-01

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

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. A Philosophical Perspective on Evolutionary Systems Biology

    PubMed Central

    Soyer, Orkun S.; Siegal, Mark L.

    2015-01-01

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

  18. 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.

  19. 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

  20. 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.

  1. Human Systems Integration Introduction

    NASA Image and Video Library

    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...

  2. 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

  3. 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.

  4. Text mining for systems biology.

    PubMed

    Fluck, Juliane; Hofmann-Apitius, Martin

    2014-02-01

    Scientific communication in biomedicine is, by and large, still text based. Text mining technologies for the automated extraction of useful biomedical information from unstructured text that can be directly used for systems biology modelling have been substantially improved over the past few years. In this review, we underline the importance of named entity recognition and relationship extraction as fundamental approaches that are relevant to systems biology. Furthermore, we emphasize the role of publicly organized scientific benchmarking challenges that reflect the current status of text-mining technology and are important in moving the entire field forward. Given further interdisciplinary development of systems biology-orientated ontologies and training corpora, we expect a steadily increasing impact of text-mining technology on systems biology in the future. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. 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.

  6. 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.

  7. 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.…

  8. 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.…

  9. 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.

  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. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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 Central

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

    2016-01-01

    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. PMID:26793622

  17. Kinetic Modeling of Biological Systems

    SciTech Connect

    Resat, Haluk; Petzold, Linda; Pettigrew, Michel F.

    2009-04-21

    The dynamics of how its constituent components interact define the spatio-temporal response of a natural 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.

  18. 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.

  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. Integrated Flexible Welding System.

    DTIC Science & Technology

    1985-11-09

    systems are employed at the top of the 7 INTEGRATED FLEXIBLE WELDING SYSTEM ARCHMiECTURE II * II COMUN CAD DEMUI=TNS WELD IAIN CMMUNICATTHNSCO UTION A TA...planning and online functional processes is successful in this case because much is known for certain about the environment and task. Thus, it is

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. Model selection in systems and synthetic biology.

    PubMed

    Kirk, Paul; Thorne, Thomas; Stumpf, Michael P H

    2013-08-01

    Developing mechanistic models has become an integral aspect of systems biology, as has the need to differentiate between alternative models. Parameterizing mathematical models has been widely perceived as a formidable challenge, which has spurred the development of statistical and optimisation routines for parameter inference. But now focus is increasingly shifting to problems that require us to choose from among a set of different models to determine which one offers the best description of a given biological system. We will here provide an overview of recent developments in the area of model selection. We will focus on approaches that are both practical as well as build on solid statistical principles and outline the conceptual foundations and the scope for application of such methods in systems biology. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. 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.

  7. 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...

  8. 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...

  9. 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…

  10. 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…

  11. Using Pseudomonas spp. for Integrated Biological Control.

    PubMed

    Stockwell, Virginia O; Stack, James P

    2007-02-01

    ABSTRACT Pseudomonas spp. have been studied for decades as model organisms for biological control of plant disease. Currently, there are three commercial formulations of pseudomonads registered with the U.S. Environmental Protection Agency for plant disease suppression, Bio-Save 10 LP, Bio-Save 11 LP, and BlightBan A506. Bio-Save 10 LP and Bio-Save 11 LP, products of Jet Harvest Solutions, Longwood, FL, contain Pseudomonas syringae strains ESC-10 and ESC-11, respectively. These products are applied in packinghouses to prevent postharvest fungal diseases during storage of citrus, pome, stone fruits, and potatoes. BlightBan A506, produced by NuFarm Americas, Burr Ridge, IL, contains P. fluorescens strain A506. BlightBan A506 is applied primarily to pear and apple trees during bloom to suppress the bacterial disease fire blight. Combining BlightBan A506 with the antibiotic streptomycin improves control of fire blight, even in areas with streptomycin-resistant populations of the pathogen. BlightBan A506 also may reduce fruit russet and mild frost injury. These biocontrol products consisting of Pseudomonas spp. provide moderate to excellent efficacy against multiple production constraints, are relatively easy to apply, and they can be integrated with conventional products for disease control. These characteristics will contribute to the adoption of these products by growers and packinghouses.

  12. 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.

  13. An integrated global chemomics and system biology approach to analyze the mechanisms of the traditional Chinese medicinal preparation Eriobotrya japonica - Fritillaria usuriensis dropping pills for pulmonary diseases.

    PubMed

    Tao, Jin; Hou, Yuanyuan; Ma, Xiaoyao; Liu, Dan; Tong, Yongling; Zhou, Hong; Gao, Jie; Bai, Gang

    2016-01-08

    Traditional Chinese medicine (TCM) herbal formulae provide valuable therapeutic strategies. However, the active ingredients and mechanisms of action remain unclear for most of these formulae. Therefore, the identification of complex mechanisms is a major challenge in TCM research. This study used a network pharmacology approach to clarify the anti-inflammatory and cough suppressing mechanisms of the Chinese medicinal preparation Eriobotrya japonica - Fritillaria usuriensis dropping pills (ChuanbeiPipa dropping pills, CBPP). The chemical constituents of CBPP were identified by high-quality ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS), and anti-inflammatory ingredients were selected and analyzed using the PharmMapper and Kyoto Encyclopedia of Genes and Genomes (KEGG) bioinformatics websites to predict the target proteins and related pathways, respectively. Then, an RNA-sequencing (RNA-Seq) analysis was carried out to investigate the different expression of genes in the lung tissue of rats with chronic bronchitis. Six main constituents affected 19 predicted pathways, including ursolic acid and oleanolic acid from Eriobotrya japonica (Thunb.) Lindl. (Eri), peiminine from Fritillaria usuriensis Maxim. (Fri), platycodigenin and polygalacic acid from Platycodon grandiflorum (Jacq.) A. DC. (Pla) and guanosine from Pinellia ternata (Thunb.) Makino. (Pin). Expression of 34 genes was significantly decreased after CBPP treatment, affecting four therapeutic functions: immunoregulation, anti-inflammation, collagen formation and muscle contraction. The active components acted on the mitogen activated protein kinase (MAPK) pathway, transforming growth factor (TGF)-beta pathway, focal adhesion, tight junctions and the action cytoskeleton to exert anti-inflammatory effects, resolve phlegm, and relieve cough. This novel approach of global chemomics-integrated systems biology represents an effective and accurate strategy for

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. A Systemic Process Approach to the Analysis of Biological Phenomena.

    ERIC Educational Resources Information Center

    Barak, Judith; Gorodetsky, Malka

    This study suggests the use of a systemic process approach to the analysis of students' understanding of biological systems. A unified model was employed to enable the capture of the dynamic nature of biological processes and phenomena. The study is based on the integration of two conceptual frameworks, one related to systems and the other to the…

  19. 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

  20. The Systems Biology Graphical Notation.

    PubMed

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

    2009-08-01

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

  1. 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,...

  2. 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,...

  3. 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.

  4. Integrated Modeling Systems

    DTIC Science & Technology

    1989-01-01

    Management , UCLA. Federgruen, A. and Zipkin , P. (1984), ’A Combined Vehicle Routing and Inventory Allocation Problem’, Operations Research 32(5), 1019-1037...Completion Based Inventory Systems: Optimal Policies for Repair Kits and Spare Machines," Management Science, 31:6 (June 1985). WMSI Working Paper 318. 210...Reprint No. 238 Computer Science in Economics and Management 2 (1989), pp. 3-15 AD-A215 219 INTEGRATED MODELING SYSTEMS by Arthur M. Geoffrion DTIC0

  5. 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.

  6. 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.

  7. 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.

  8. 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.

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

    PubMed Central

    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

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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. © 2011 American Chemical Society

  15. Delivering the Benefits of Chemical-Biological Integration in ...

    EPA Pesticide Factsheets

    Slide Presentation at the German Cheminformatics Conference on Delivering the Benefits of Chemical-Biological Integration in Computational Toxicology at the EPA. Presentation at the German Cheminformatics Conference on Delivering the Benefits of Chemical-Biological Integration in Computational Toxicology at the EPA.

  16. 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.

  17. 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.

  18. 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…

  19. 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…

  20. 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…

  1. 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.

  2. Radiation interactions with biological systems.

    PubMed

    Islam, Muhammad Torequl

    2017-05-01

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

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. The road from systems biology to systems medicine.

    PubMed

    Wolkenhauer, Olaf; Auffray, Charles; Jaster, Robert; Steinhoff, Gustav; Dammann, Olaf

    2013-04-01

    As research institutions prepare roadmaps for "systems medicine," we ask how this differs from applications of systems biology approaches in medicine and what we (should) have learned from about one decade of funding in systems biology. After surveying the area, we conclude that systems medicine is the logical next step and necessary extension of systems biology, and we focus on clinically relevant applications. We specifically discuss three related notions. First, more interdisciplinary collaborations are needed to face the challenges of integrating basic research and clinical practice: integration, analysis, and interpretation of clinical and nonclinical data for diagnosis, prognosis, and therapy require advanced statistical, computational, and mathematical tools. Second, strategies are required to (i) develop and maintain computational platforms for the integration of clinical and nonclinical data, (ii) further develop technologies for quantitative and time-resolved tracking of changes in gene expression, cell signaling, and metabolism in relation to environmental and lifestyle influences, and (iii) develop methodologies for mathematical and statistical analyses of integrated data sets and multilevel models. Third, interdisciplinary collaborations represent a major challenge and are difficult to implement. For an efficient and successful initiation of interdisciplinary systems medicine programs, we argue that epistemological, ontological, and sociological aspects require attention.

  8. Systems Biology to Support Nanomaterial Grouping.

    PubMed

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

    2017-01-01

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

  9. 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.

  10. 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.

  11. 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.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  13. 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…

  14. Biologically inspired dynamic material systems.

    PubMed

    Studart, André R

    2015-03-09

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

  15. 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

  16. Dupuytren's: a systems biology disease

    PubMed Central

    2011-01-01

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

  17. Gravitational effects on biological systems.

    PubMed

    Boncinelli, P; Vanni, P

    1998-10-01

    The possible effects of the earth's gravitational field on biological systems have been studied from a quantitative point of view, focusing the attention to a very simple system, a solution containing proteins, which biochemists might use in experiments. Gravity has been compared with other forces which are known to influence protein activity, including thermic agitation, weak electrostatic interactions, Van der Waals forces and viscous dissipation. Comparisons have been described in terms of the energy of the interaction per mole, referring to some physically simple cases and substances of biological interest. From this study it is evident that the earth's gravitational energy should be taken into account when considering the chemical behaviour of solutions containing substances that have high molecular weight, such as a typical protein, since its value is comparable to other weak interactions. Moreover, since solutions represent the basis of much more complex biological processes taking place inside cells, the influence of gravity should extend also to cellular biochemical behaviour, especially in presence of altered gravity, both in microgravity (such as on satellites orbiting around the earth), and in macrogravity (such as in a centrifugating biological system).

  18. 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)

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. CARGO: a web portal to integrate customized biological information

    PubMed Central

    Cases, Ildefonso; Pisano, David G.; Andres, Eduardo; Carro, Angel; Fernández, José M.; Gómez-López, Gonzalo; Rodriguez, Jose M.; Vera, Jaime F.; Valencia, Alfonso; Rojas, Ana M.

    2007-01-01

    There is a huge quantity of information generated in Life Sciences, and it is dispersed in many databases and repositories. Despite the broad availability of the information, there is a great demand for methods that are able to look for, gather and display distributed data in a standardized and friendly way. CARGO (Cancer And Related Genes Online) is a configurable biological web portal designed as a tool to facilitate, integrate and visualize results from Internet resources, independently of their native format or access method. Through the use of small agents, called widgets, supported by a Rich Internet Application (RIA) paradigm based on AJAX, CARGO provides pieces of minimal, relevant and descriptive biological information. The tool is designed to be used by experimental biologists with no training in bioinformatics. In the current state, the system presents a list of human cancer genes. Available at http://cargo.bioinfo.cnio.es PMID:17483515

  4. CARGO: a web portal to integrate customized biological information.

    PubMed

    Cases, Ildefonso; Pisano, David G; Andres, Eduardo; Carro, Angel; Fernández, José M; Gómez-López, Gonzalo; Rodriguez, Jose M; Vera, Jaime F; Valencia, Alfonso; Rojas, Ana M

    2007-07-01

    There is a huge quantity of information generated in Life Sciences, and it is dispersed in many databases and repositories. Despite the broad availability of the information, there is a great demand for methods that are able to look for, gather and display distributed data in a standardized and friendly way. CARGO (Cancer And Related Genes Online) is a configurable biological web portal designed as a tool to facilitate, integrate and visualize results from Internet resources, independently of their native format or access method. Through the use of small agents, called widgets, supported by a Rich Internet Application (RIA) paradigm based on AJAX, CARGO provides pieces of minimal, relevant and descriptive biological information. The tool is designed to be used by experimental biologists with no training in bioinformatics. In the current state, the system presents a list of human cancer genes. Available at http://cargo.bioinfo.cnio.es.

  5. Computational systems biology for aging research.

    PubMed

    Mc Auley, Mark T; Mooney, Kathleen M

    2015-01-01

    Computational modelling is a key component of systems biology and integrates with the other techniques discussed thus far in this book by utilizing a myriad of data that are being generated to quantitatively represent and simulate biological systems. This chapter will describe what computational modelling involves; the rationale for using it, and the appropriateness of modelling for investigating the aging process. How a model is assembled and the different theoretical frameworks that can be used to build a model are also discussed. In addition, the chapter will describe several models which demonstrate the effectiveness of each computational approach for investigating the constituents of a healthy aging trajectory. Specifically, a number of models will be showcased which focus on the complex age-related disorders associated with unhealthy aging. To conclude, we discuss the future applications of computational systems modelling to aging research. 2015 S. Karger AG, Basel.

  6. 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.

  7. From functional genomics to systems biology: concepts and practices.

    PubMed

    Auffray, Charles; Imbeaud, Sandrine; Roux-Rouquié, Magali; Hood, Leroy

    2003-01-01

    Systems biology is the iterative and integrative study of biological systems as systems in response to perturbations. It is founded on hypotheses formalized in models built from the results of global functional genomics analyses of the complexity of the genome, transcriptome, proteome, metabolome, etc. Its implementation by cross-disciplinary teams in a standardized mode under quality assurance should allow accessing the small variations of the large number of elements determining functioning of biological systems. Galactose utilization in yeast, and sea urchin development are two examples of emerging systems biology.

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

    PubMed Central

    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. PMID:24591504

  9. 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.

  10. 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.

  11. 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.

  12. 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...

  13. 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...

  14. 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.

  15. 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.

  16. 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.

  17. Integrated microfluidic systems.

    PubMed

    Kaneda, Shohei; Fujii, Teruo

    2010-01-01

    Using unique physical phenomena at the microscale, such as laminar flow, mixing by diffusion, relative increase of the efficiency of heat exchange, surface tension and friction due to the increase of surface-to-volume ratio by downscaling, research in the field of microfluidic devices, aims at miniaturization of (bio)chemical apparatus for high-throughput analyses. Microchannel networks as core components of microfluidic devices are fabricated on various materials, such as silicon, glass, polymers, metals, etc., using microfabrication techniques adopted from the semiconductor industry and microelectromechanical systems (MEMS) technology, enabling integration of the components capable of performing various operations in microchannel networks. This chapter describes examples of diverse integrated microfluidic devices that incorporate functional components such as heaters for reaction temperature control, micropumps for liquid transportation, air vent structures for pneumatic manipulation of small volume droplets, optical fibers with aspherical lens structures for fluorescence detection, and electrochemical sensors for monitoring of glucose consumption during cell culture. The focus of this review is these integrated components and systems that realize useful functionalities for biochemical analyses.

  18. Integrated Microfluidic Systems

    NASA Astrophysics Data System (ADS)

    Kaneda, Shohei; Fujii, Teruo

    Using unique physical phenomena at the microscale, such as laminar flow, mixing by diffusion, relative increase of the efficiency of heat exchange, surface tension and friction due to the increase of surface-to-volume ratio by downscaling, research in the field of microfluidic devices, aims at miniaturization of (bio)chemical apparatus for high-throughput analyses. Microchannel networks as core components of microfluidic devices are fabricated on various materials, such as silicon, glass, polymers, metals, etc., using microfabrication techniques adopted from the semiconductor industry and microelectromechanical systems (MEMS) technology, enabling integration of the components capable of performing various operations in microchannel networks. This chapter describes examples of diverse integrated microfluidic devices that incorporate functional components such as heaters for reaction temperature control, micropumps for liquid transportation, air vent structures for pneumatic manipulation of small volume droplets, optical fibers with aspherical lens structures for fluorescence detection, and electrochemical sensors for monitoring of glucose consumption during cell culture. The focus of this review is these integrated components and systems that realize useful functionalities for biochemical analyses.

  19. Systems biology of diuretic resistance

    PubMed Central

    Knepper, Mark A.

    2015-01-01

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

  20. 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

  1. 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

  2. Biological Potential in Serpentinizing Systems

    NASA Technical Reports Server (NTRS)

    Hoehler, Tori M.

    2016-01-01

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

  3. Integrated cellular systems

    NASA Astrophysics Data System (ADS)

    Harper, Jason C.

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

  4. 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.

  5. 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.

  6. From growth physiology to systems biology.

    PubMed

    Schaechter, Moselio

    2006-09-01

    As it focuses on the integrated behavior of the entire cell, systems biology is a powerful extension of growth physiology. Here, I briefly trace some of the origins of modern-day bacterial growth physiology and its relevance to systems biology. I describe how growth physiology emerged from the foggy picture of the growth curve as a self-contained entity. For this insight, we can thank Henrici, Hershey, Monod, Maaløe, and others. As a result of their work, growth rate is understood to be the unitary manifestation of the response to nutritional conditions and to the control condition for studies on the effect of environmental stresses. For this response to be usefully reproducible, cultures must be in the steady state known as balanced growth. I point out that present-day experimenters are not always aware of this imperative and thus do not always use conditions that ensure the balanced growth of their control cultures.

  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. 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.

  9. Biological fixed-film systems

    SciTech Connect

    Chen, J.M.; Lim, B.S.; Al-Ghusain, I.A.; Hao, O.J.; Lin, C.F.; Davis, A.P.; Kim, M.H.; Huang, J.

    1993-06-01

    This paper includes reports on several biological fixed film systems in wastewater and hazardous waste treatment. Biological treatment of a refinery wastewater was studied in a rotating biological contactor (RBC) unit coupled with polyurethane foam (PUF) as a porous biomass support attached on both sides of the biodisks. The RBC-PUF bioreactor exhibited better performance than conventional RBCs for the removal of chemical oxygen demand (COD), NH{sub 3}-N, phenol, hydrocarbons, and suspended solids because of higher concentrations of active biomass. Successful performance of an anaerobic-aerobic treatment process using a combination of RCBs with activated sludge was achieved for treating a dye wastewater. Two high-rate trickling filters, cross-flow (CF) and vertical flow, were examined over a two year period for biological treatment of seafood processing wastewater. Results suggested superior performance of CF plastic media with substrate removal following a pseudo half-order kinetic reaction. Submerged structured packings in biofilm reactors were tested and characterized for a wide range of applications. Their efficiency was discussed in terms of contaminant removals and SS retention.

  10. [Systemic integration of dominating motivation].

    PubMed

    Zilov, V G

    1994-01-01

    The paper analyzes the investigations into the central architectonics of biological motivations, which have been performed by the P.K. Anokhin scientific school. Each biological motivation is postulated to be a result of specific integration of heterochemical mechanisms of biological motivations. The chemical plasticity of biological motivations is evidenced by the findings of the duplication of different neurotransmitters in cortical-subcortical interrelations, as well as the potentialities of the chemical rearrangement ("chemical compensation") of neurotransmitter mechanisms of biological motivations in case of bilateral failure of hypothalamic motivational centers of the hypothalamus. Some cerebral oligopeptides are found to be able to temporarily and selectively modify the pattern of motivational behavioral responses evoked by electric stimulation of various hypothalamic formations. It is concluded that the biological motivations are a result of the integrative performance of the whole brain wherein hypothalamic pacemakers play the leading but not final role.

  11. 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.

  12. Study of a multitrophical integrated aquatic system for the teaching-learning of the subjects physics, chemistry and biology in the bachelor

    NASA Astrophysics Data System (ADS)

    Ramirez, Eva; Espinosa, Cecilia

    2017-04-01

    In Mexico exist due to the lack of water in the City, which is where the College of Sciences and Humanities Orient (at UNAM) is located. This is because a point of view from the Chemical, Physics and Biology subjects is important to find learning strategies that motivate students to seek solutions to problems such as these. As Science Mentors, students were asked to propose water treatment from the homes they live in. From these investigations the students concluded that it was necessary to study in depth the wetlands like Multi-trophic Aquatic System that allow the treatment of gray water, so that a prototype of Micro-scale Multitrophic Aquatic System was set up in the laboratory, where the pH was measured , The concentration of oxygen, phosphates, from a Chemical perspective. As for the subject of Biology, we worked on the search for mycorrhizal fungi associated with the growth of plants for the purification of water. In physics we worked the sedimentation system. Artificial wetlands are man-made zones in which, in a controlled manner, mechanisms for the removal of contaminants present in wastewater, occurring in natural wetlands through physical, biological and chemical processes, are constructed mechanically and Is waterproofed to prevent losses of water to the subsoil, the use of substrates different from the original land for rooting the plants and their selection that will colonize the wetland benefit the recovery of water. The present project aims to structure an Artificial Wetland to carry out didactic strategies, activities with students, as well as work on research projects in the sciences of Chemistry, Physics and Biology. Through the application of chemical, biological and physical concepts and processes, so that students of the different semesters of the College of Sciences and Humanities Plantel Oriente, appropriate the relevant knowledge in the area of experimental sciences, developing thinking skills and achieve Significant learning, which are

  13. 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

  14. 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.

  15. 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…

  16. 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…

  17. 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.

  18. Integrating Biological Activity and Exposure in the US EPA's ...

    EPA Pesticide Factsheets

    presentation at the IUTOX meeting in Mexico on Oct. 3, 2016. on Integrating Biological Activity and Exposure in the US EPA's Toxcast Program. presentation at the IUTOX meeting in Mexico on Oct. 3, 2016.

  19. 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.

  20. 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.

  1. 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.

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

    PubMed

    Fletcher, Liz; Rosser, Susan; Elfick, Alistair

    2016-06-15

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

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

    PubMed Central

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

    2013-01-01

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

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. History matters: ecometrics and integrative climate change biology

    PubMed Central

    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

    2011-01-01

    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. PMID:21227966

  10. 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…

  11. 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…

  12. 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 ...

  13. 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 ...

  14. Integrating child health information systems.

    PubMed

    Hinman, Alan R; Eichwald, John; Linzer, Deborah; Saarlas, Kristin N

    2005-11-01

    The Health Resources and Services Administration and All Kids Count (a national technical assistance center fostering development of integrated child health information systems) have been working together to foster development of integrated child health information systems. Activities have included: identification of key elements for successful integration of systems; development of principles and core functions for the systems; a survey of state and local integration efforts; and a conference to develop a common vision for child health information systems to meet medical care and public health needs. We provide 1 state (Utah) as an example that is well on the way to development of integrated child health information systems.

  15. Integrating Child Health Information Systems

    PubMed Central

    Hinman, Alan R.; Eichwald, John; Linzer, Deborah; Saarlas, Kristin N.

    2005-01-01

    The Health Resources and Services Administration and All Kids Count (a national technical assistance center fostering development of integrated child health information systems) have been working together to foster development of integrated child health information systems. Activities have included: identification of key elements for successful integration of systems; development of principles and core functions for the systems; a survey of state and local integration efforts; and a conference to develop a common vision for child health information systems to meet medical care and public health needs. We provide 1 state (Utah) as an example that is well on the way to development of integrated child health information systems. PMID:16195524

  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. 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

  18. 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.

  19. Rationale and Design of Family-Based Approach in a Minority Community Integrating Systems-Biology for Promotion of Health (FAMILIA).

    PubMed

    Bansilal, Sameer; Vedanthan, Rajesh; Kovacic, Jason C; Soto, Ana Victoria; Latina, Jacqueline; Björkegren, Johan L M; Jaslow, Risa; Santana, Maribel; Sartori, Samantha; Giannarelli, Chiara; Mani, Venkatesh; Hajjar, Roger; Schadt, Eric; Kasarskis, Andrew; Fayad, Zahi A; Fuster, Valentin

    2017-05-01

    The 2020 American Heart Association Impact Goal aims to improve cardiovascular health of all Americans by 20% while reducing deaths from cardiovascular disease and stroke by 20%. A large step toward this goal would be to better understand and take advantage of the significant intersection between behavior and biology across the entire life-span. In the proposed FAMILIA studies, we aim to directly address this major knowledge and clinical health gap by implementing an integrated family-centric health promotion intervention and focusing on the intersection of environment and behavior, while understanding the genetic and biologic basis of cardiovascular disease. We plan to recruit 600 preschool children and their 600 parents or caregivers from 12-15 Head Start schools in Harlem, NY, and perform a 2:1 (2 intervention/1 control) cluster randomization of the schools. The preschool children will receive our intensive 37-hour educational program as the intervention for 4 months. For the adults, those in the "intervention" group will be randomly assigned to 1 of 2 intervention programs: an "individual-focused" or "peer-to-peer based." The primary outcome in children will be a composite score of knowledge (K), attitudes (A), habits (H), related to body mass index Z score (B), exercise (E), and alimentation (A) (KAH-BEA), using questionnaires and anthropometric measurements. For adults, the primary outcome will be a composite score for behaviors/outcomes related to blood pressure, exercise, weight, alimentation (diet) and tobacco (smoking; Fuster-BEWAT score). Saliva will be collected from the children for SNP genotyping, and blood will be collected from adults for RNA sequencing to identify network models and predictors of primary prevention outcomes. The FAMILIA studies seek to demonstrate that targeting a younger age group (3-5 years) and using a family-based approach may be a critical strategy in promoting cardiovascular health across the life-span. Copyright © 2017

  20. 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.

  1. 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

  2. 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…

  3. 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…

  4. 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.

  5. Integrated heat pump system

    SciTech Connect

    Reedy, W.R.

    1988-03-01

    An integrated heat pump and hot water system is described that includes: a heat pump having an indoor heat exchanger and an outdoor heat exchanger that are selectively connected to the suction line and the discharge line respectively of a compressor by a flow reversing means, and to each other by a liquid line having an expansion device mounted therein, whereby heating and cooling is provided to an indoor comfort zone by cycling the flow reversing means, a refrigerant to water heat exchanger having a hot water flow circuit in heat transfer relation with a first refrigerant condensing circuit and a second refrigerant evaporating circuit, a connection mounted in the liquid between the indoor heat exchanger and the expansion device, control means for regulating the flow of refrigerant through the refrigerant to water heat exchanger to selectively transfer heat into and out of the hot water flow circuit.

  6. 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.

  7. 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.

  8. Integrating biological invasions, climate change and phenotypic plasticity

    PubMed Central

    Tollrian, Ralph; Jeschke, Jonathan M

    2011-01-01

    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. PMID:21980551

  9. 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.

  10. 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

  11. Integrating cell biology and proteomic approaches in plants.

    PubMed

    Takáč, Tomáš; Šamajová, Olga; Šamaj, Jozef

    2017-04-22

    Significant improvements of protein extraction, separation, mass spectrometry and bioinformatics nurtured advancements of proteomics during the past years. The usefulness of proteomics in the investigation of biological problems can be enhanced by integration with other experimental methods from cell biology, genetics, biochemistry, pharmacology, molecular biology and other omics approaches including transcriptomics and metabolomics. This review aims to summarize current trends integrating cell biology and proteomics in plant science. Cell biology approaches are most frequently used in proteomic studies investigating subcellular and developmental proteomes, however, they were also employed in proteomic studies exploring abiotic and biotic stress responses, vesicular transport, cytoskeleton and protein posttranslational modifications. They are used either for detailed cellular or ultrastructural characterization of the object subjected to proteomic study, validation of proteomic results or to expand proteomic data. In this respect, a broad spectrum of methods is employed to support proteomic studies including ultrastructural electron microscopy studies, histochemical staining, immunochemical localization, in vivo imaging of fluorescently tagged proteins and visualization of protein-protein interactions. Thus, cell biological observations on fixed or living cell compartments, cells, tissues and organs are feasible, and in some cases fundamental for the validation and complementation of proteomic data. Validation of proteomic data by independent experimental methods requires development of new complementary approaches. Benefits of cell biology methods and techniques are not sufficiently highlighted in current proteomic studies. This encouraged us to review most popular cell biology methods used in proteomic studies and to evaluate their relevance and potential for proteomic data validation and enrichment of purely proteomic analyses. We also provide examples of

  12. 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

  13. Systems biology of the structural proteome.

    PubMed

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

    2016-03-11

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

  14. 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.

  15. Biological treatment and ozone oxidation: Integration or coupling?

    PubMed

    Di Iaconi, Claudio

    2012-02-01

    Wastewaters generated by many economically relevant industrial activities contain recalcitrant organic compounds which pass unaltered through biological stage of the treatment plant making it difficult to meet the discharge limits currently in force. Therefore, an additional treatment is usually required to remove these compounds. In this study, the application of ozonation together with biological treatment was investigated. In particular, the effectiveness of biological degradation followed by or integrated with ozonation for treating the effluents produced by three environmentally relevant activities (i.e., leather and textile processing and municipal waste landfilling) are compared in the present paper. The results show that biological treatment followed by ozonation does not guarantee depurative levels sufficient for discharge for landfill leachates and tannery wastewater. On the contrary, thanks to the synergy between biological degradation and ozonation, integrated treatment significantly improves the process performance for all the investigated wastewaters, thus allowing the discharge limits to be met. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. Integrated Compliance Information System (ICIS)

    EPA Pesticide Factsheets

    The purpose of ICIS is to meet evolving Enforcement and Compliance business needs for EPA and State users by integrating information into a single integrated data system that supports both management and programmatic requirements of the Enforcement and Compliance programs.

  2. Integrating computational biology and forward genetics in Drosophila.

    PubMed

    Aerts, Stein; Vilain, Sven; Hu, Shu; Tranchevent, Leon-Charles; Barriot, Roland; Yan, Jiekun; Moreau, Yves; Hassan, Bassem A; Quan, Xiao-Jiang

    2009-01-01

    Genetic screens are powerful methods for the discovery of gene-phenotype associations. However, a systems biology approach to genetics must leverage the massive amount of "omics" data to enhance the power and speed of functional gene discovery in vivo. Thus far, few computational methods for gene function prediction have been rigorously tested for their performance on a genome-wide scale in vivo. In this work, we demonstrate that integrating genome-wide computational gene prioritization with large-scale genetic screening is a powerful tool for functional gene discovery. To discover genes involved in neural development in Drosophila, we extend our strategy for the prioritization of human candidate disease genes to functional prioritization in Drosophila. We then integrate this prioritization strategy with a large-scale genetic screen for interactors of the proneural transcription factor Atonal using genomic deficiencies and mutant and RNAi collections. Using the prioritized genes validated in our genetic screen, we describe a novel genetic interaction network for Atonal. Lastly, we prioritize the whole Drosophila genome and identify candidate gene associations for ten receptor-signaling pathways. This novel database of prioritized pathway candidates, as well as a web application for functional prioritization in Drosophila, called Endeavour-HighFly, and the Atonal network, are publicly available resources. A systems genetics approach that combines the power of computational predictions with in vivo genetic screens strongly enhances the process of gene function and gene-gene association discovery.

  3. 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...

  4. 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...

  5. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. OceanCubes: An Affordable Cabled Observatory System for Integrated Long-Term, High Frequency Biological, Chemical, and Physical Measurements for Understanding Coastal Ecosystems

    NASA Astrophysics Data System (ADS)

    Gallager, S. M.

    2016-02-01

    Understanding how coastal ocean processes are forcing and/or responding to ecosystem change is a central premise in current oceanographic research and monitoring. A distributed, high capacity observing capability is necessary to address biological processes requiring high frequency observations on short ( turbulence, internal waves), moderate (typhoons), and decadal time scales (e.g., NAO, El Nino-SO, PDO). The current belief that ocean observing systems need to be expensive, large, difficult to deploy and limited in capacity was tested by developing OceanCubes, an end-to-end cabled observational system with real-time telemetry, state-of-the-art sensor packages, high level of expandability, and diver maintained to reduce operating costs. A modular approach allows for a scalable system that can grow over time to accommodate budgets. The control volume design allows for measurement of material flux and energy from the water column to the benthos at a rate of s-1. The sensor package is connected by electro-optical cable to shore providing the capability for internet-based teleoperation by scientists world-wide. The central node provides underwater mateable connections for > 22 serial and Ethernet-based sensors (CTD, four ADCPs, chlorophyll and CDOM fluorescence, O2, nitrate, pCO2, pH, a bio-optical package, a Continuous Plankton Imaging and Classification Sensor (CPICS) for mesoplankton, a pan and tilt webcam, and two stereo cameras to observe and track fish communities. ADCPs and temperature strings mark the corners of the 162,000 m3 control volume. Disparate data streams are remotely archived, correlated, and analyzed while plankton and fish are identified using state-of-the-art machine vision and learning techniques. Two OceanCubes have been installed in Japan (Okinawa and Oshima Island, Tokyo) and have survived several typhoon seasons. Two additional systems are planned for either side of the Panamanian Isthmus. Results of these systems will be discussed.

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. Enterprise Information System Integration Technology

    NASA Astrophysics Data System (ADS)

    Tanaka, Tetsuo; Yumoto, Masaki; Itsuki, Rei

    In the current rapidly changing business environment, companies need to be efficient and agile to survive and thrive. That is why flexible systems integration is urgent and crucial concern for any enterprise. For the meanwhile, systems integration technology is getting more complicated, and middleware types are beginning blur for decades. We sort system integration into four different types, “Delayed Federation", “Real-time Federation", “Delayed Integration", and “Real-time Integration". We also outline appropriate technology and architecture for each type.

  13. 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.

  14. 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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Insights from Systems Biology in Physiological Studies: Learning from Context.

    PubMed

    Imenez Silva, Pedro Henrique; Melo, Diogo; de Mendonça, Pedro Omori Ribeiro

    2017-06-26

    Systems biology presents an integrated view of biological systems, focusing on the relations between elements, whether functional or evolutionary, and providing a rich framework for the comprehension of life. At the same time, many low-throughput experimental studies are performed without influence from this integrated view, whilst high-throughput experiments use low-throughput results in their validation and interpretation. We propose an inversion in this logic, and ask which benefits could be obtained from a holistic view coming from high-throughput studies-and systems biology in particular-in interpreting and designing low-throughput experiments. By exploring some key examples from the renal and adrenal physiology, we try to show that network and modularity theory, along with observed patterns of association between elements in a biological system, can have profound effects on our ability to draw meaningful conclusions from experiments. © 2017 The Author(s). Published by S. Karger AG, Basel.

  16. 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.

  17. 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.

  18. Integrative and comparative reproductive biology: From alligators to xenobiotics.

    PubMed

    McCoy, Krista A; Roark, Alison M; Boggs, Ashley S P; Bowden, John A; Cruze, Lori; Edwards, Thea M; Hamlin, Heather J; Cantu, Theresa M; McCoy, Jessica A; McNabb, Nicole A; Wenzel, Abby G; Williams, Cameron E; Kohno, Satomi

    2016-11-01

    Dr. Louis J. Guillette Jr. thought of himself as a reproductive biologist. However, his interest in reproductive biology transcended organ systems, life history stages, species, and environmental contexts. His integrative and collaborative nature led to diverse and fascinating research projects conducted all over the world. He doesn't leave us with a single legacy. Instead, he entrusts us with several. The purpose of this review is to highlight those legacies, in both breadth and diversity, and to illustrate Dr. Guillette's grand contributions to the field of reproductive biology. He has challenged the field to reconsider how we think about our data, championed development of novel and innovative techniques to measure endocrine function, helped define the field of endocrine disruption, and lead projects to characterize new endocrine disrupting chemicals. He significantly influenced our understanding of evolution, and took bold and important steps to translate all that he has learned into advances in human reproductive health. We hope that after reading this manuscript our audience will appreciate and continue Dr. Guillette's practice of open-minded and passionate collaboration to understand the basic mechanisms driving reproductive physiology and to ultimately apply those findings to protect and improve wildlife and human health. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. 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. © 2011 Blackwell Publishing Ltd/CNRS.

  20. 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...

  1. 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...

  2. 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

  3. 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

  4. The Simbios National Center: Systems Biology in Motion.

    PubMed

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

    2008-08-01

    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.

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. [Combinatorial optimization of synthetic biological systems].

    PubMed

    Gu, Qun; Li, Yifan; Chen, Tao

    2013-08-01

    A major challenge in synthetic biology is to engineer complex biological systems with novel functions. Due to the inherent complexity of biological systems, it is often difficult to rationally design every component in a synthetic gene network to achive an optimal performance. Combinatorial engineering is an important solution to this problem and can greatly facilitate the construction of novel biological functions. Here, we review methods and techniques developed in recent years for combinatorial optimization of synthetic biological systems, including methods for fine-tuning pathway components, strategies for systematically optimization of metabolic pathways, and techniques for introducing multiplex genome wide perturbations.

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

    PubMed Central

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

    2011-01-01

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

  15. 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.

  16. 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.

  17. Determination of Death: A Scientific Perspective on Biological Integration

    PubMed Central

    Condic, Maureen L.

    2016-01-01

    Human life is operationally defined by the onset and cessation of organismal function. At postnatal stages of life, organismal integration critically and uniquely requires a functioning brain. In this article, a distinction is drawn between integrated and coordinated biologic activities. While communication between cells can provide a coordinated biologic response to specific signals, it does not support the integrated function that is characteristic of a living human being. Determining the loss of integrated function can be complicated by medical interventions (i.e., “life support”) that uncouple elements of the natural biologic hierarchy underlying our intuitive understanding of death. Such medical interventions can allow living human beings who are no longer able to function in an integrated manner to be maintained in a living state. In contrast, medical intervention can also allow the cells and tissues of an individual who has died to be maintained in a living state. To distinguish between a living human being and living human cells, two criteria are proposed: either the persistence of any form of brain function or the persistence of autonomous integration of vital functions. Either of these criteria is sufficient to determine a human being is alive. PMID:27075193

  18. Problems with integrating legacy systems.

    PubMed Central

    van Mulligen, E. M.; Cornet, R.; Timmers, T.

    1995-01-01

    The economic and organizational impact of imposing state-of-the-art technology to the large number of proprietary legacy systems operational in most hospitals requires integrated clinical professional workstations to provide flexible encapsulation mechanisms for these systems rather than reengineering these systems to this new technology. In this paper the implications of different input/output and translation models of legacy systems for their integration into a clinical workstation is described. Examples of legacy systems that have been integrated in the HERMES clinical workstation are presented as examples of the range of difficulties one might encounter. The features that an integrated workstation should offer for integrating a broad range of legacy systems are also addressed in this paper. PMID:8563389

  19. 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%).

  20. Biologic agents in systemic vasculitis

    PubMed Central

    Henderson, Charles F; Seo, Philip

    2012-01-01

    The treatment of systemic necrotizing vasculitis has made great strides in both efficacy and outcomes. Standard therapies, however, are associated with numerous side effects, and not all patients will respond to conventional immunosuppression. These realities have prompted the search for safer and more efficacious treatments, most notably among biologic agents. For example, the role of TNF-α in the pathophysiology of several vasculitides has led to the investigation of targeted inhibitors of this cytokine, albeit with mixed results. There have been some disappointing results in the area of giant cell arteritis and Wegener’s granulomatosis (granulomatosis with polygiitis), but anti-TNF therapy has shown promise in the treatment of Takayasu’s arteritis, although additional trials to demonstrate its efficacy are required. Anti-B-cell therapy seems to be the most promising advance in the management of these diseases. Complete and partial responses have been seen in both primary and secondary mixed cryoglobulinemic vasculitis. Recent trials have demonstrated that rituximab is effective for the treatment of Wegener’s granulomatosis and microscopic polyangiitis. These trials have, however, raised concerns regarding the long-term safety of these agents. The future holds promise for additional targeted therapies with improved patient response and fewer side effects. PMID:23785387

  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. Spatial Aspects in Biological System Simulations

    SciTech Connect

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

    2011-01-30

    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 spatio-temporal 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.

  3. 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

  4. 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.

  5. 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.

  6. Introducing systems biology for nursing science.

    PubMed

    Founds, Sandra A

    2009-07-01

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

  7. Genetic Robots: An Integrated Art and Biology Curriculum.

    ERIC Educational Resources Information Center

    Schramm, Susan L.

    2000-01-01

    Describes the design and implementation of an integrated art and science curriculum "Genetic Robotics: A Three-Dimensional Scientific Inquiry" for high school art and biology students at Madeira Junior/Senior High School in Cincinnati, Ohio. States that the project aimed at recognizing individual differences while enabling students to become…

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

    USDA-ARS?s Scientific Manuscript database

    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...

  9. 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