Science.gov

Sample records for integrated systems biology

  1. Integrative radiation systems biology.

    PubMed

    Unger, Kristian

    2014-01-01

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

  2. Current advances in systems and integrative biology

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Chen, Bor-Sen; Wu, Chia-Chou

    2013-01-01

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

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

    PubMed

    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

  5. 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.

  6. Integrative Systems Biology for Data Driven Knowledge Discovery

    PubMed Central

    Greene, Casey S.; Troyanskaya, Olga G.

    2015-01-01

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

  7. A data integration methodology for systems biology: Experimental verification

    PubMed Central

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

    2005-01-01

    The integration of data from multiple global assays is essential to understanding dynamic spatiotemporal interactions within cells. In a companion paper, we reported a data integration methodology, designated Pointillist, that can handle multiple data types from technologies with different noise characteristics. Here we demonstrate its application to the integration of 18 data sets relating to galactose utilization in yeast. These data include global changes in mRNA and protein abundance, genome-wide protein–DNA interaction data, database information, and computational predictions of protein–DNA and protein–protein interactions. We divided the integration task to determine three network components: key system elements (genes and proteins), protein–protein interactions, and protein–DNA interactions. Results indicate that the reconstructed network efficiently focuses on and recapitulates the known biology of galactose utilization. It also provided new insights, some of which were verified experimentally. The methodology described here, addresses a critical need across all domains of molecular and cell biology, to effectively integrate large and disparate data sets. PMID:16301536

  8. 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

  9. 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…

  10. 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.

  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. 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...

  13. 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

  14. Network integration and graph analysis in mammalian molecular systems biology

    PubMed Central

    Ma'ayan, A.

    2009-01-01

    Abstraction of intracellular biomolecular interactions into networks is useful for data integration and graph analysis. Network analysis tools facilitate predictions of novel functions for proteins, prediction of functional interactions and identification of intracellular modules. These efforts are linked with drug and phenotype data to accelerate drug-target and biomarker discovery. This review highlights the currently available varieties of mammalian biomolecular networks, and surveys methods and tools to construct, compare, integrate, visualise and analyse such networks. PMID:19045817

  15. 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

  16. 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.

  17. 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

  18. Perceptual issues in the recovery and visualisation of integrated systems biology data

    NASA Astrophysics Data System (ADS)

    Pridmore, Tony

    2011-03-01

    The systems approach to biological research emphasises understanding of complete biological systems, rather than a reductionist focus on tightly defined component parts. Systems biology is naturally interdisciplinary; research groups active in this area typically contain experimental and theoretical biologists, mathematicians, statisticians, computer scientists and engineers. A wide range of tools are used to generate a variety of data types which must be integrated, presented to and analysed by researchers from any and all of the contributing disciplines. The goal here is to create predictive models of the system of interest; the models produced must also be analysed, and in the context of the data from which they were generated. Effective, integrated data and model visualisation methods are crucial if scientificallyappropriate judgments are to be made. The Nottingham Centre for Plant Integrative Biology (CPIB) takes a systems approach to the study of the root of the model plant Arabidopsis Thaliana. A rich mixture of data types, many extracted via automatic analysis of individual and time-ordered sequences of standard CCD and confocal laser microscope images, is used to create models of different aspects of the growth of the Arabidopsis root. This talk briefly reviews the data sets and flow of information within CPIB, and discuss issues raised by the need to interpret images of the Arabidopsis root and integrate and present the resulting data and models to an interdisciplinary audience.

  19. 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

  20. 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. PMID:20419428

  1. Tav4SB: integrating tools for analysis of kinetic models of biological systems

    PubMed Central

    2012-01-01

    Background Progress in the modeling of biological systems strongly relies on the availability of specialized computer-aided tools. To that end, the Taverna Workbench eases integration of software tools for life science research and provides a common workflow-based framework for computational experiments in Biology. Results The Taverna services for Systems Biology (Tav4SB) project provides a set of new Web service operations, which extend the functionality of the Taverna Workbench in a domain of systems biology. Tav4SB operations allow you to perform numerical simulations or model checking of, respectively, deterministic or stochastic semantics of biological models. On top of this functionality, Tav4SB enables the construction of high-level experiments. As an illustration of possibilities offered by our project we apply the multi-parameter sensitivity analysis. To visualize the results of model analysis a flexible plotting operation is provided as well. Tav4SB operations are executed in a simple grid environment, integrating heterogeneous software such as Mathematica, PRISM and SBML ODE Solver. The user guide, contact information, full documentation of available Web service operations, workflows and other additional resources can be found at the Tav4SB project’s Web page: http://bioputer.mimuw.edu.pl/tav4sb/. Conclusions The Tav4SB Web service provides a set of integrated tools in the domain for which Web-based applications are still not as widely available as for other areas of computational biology. Moreover, we extend the dedicated hardware base for computationally expensive task of simulating cellular models. Finally, we promote the standardization of models and experiments as well as accessibility and usability of remote services. PMID:22480273

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

    PubMed Central

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

    2010-01-01

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

  3. NETTAB 2014: From high-throughput structural bioinformatics to integrative systems biology.

    PubMed

    Romano, Paolo; Cordero, Francesca

    2016-01-01

    The fourteenth NETTAB workshop, NETTAB 2014, was devoted to a range of disciplines going from structural bioinformatics, to proteomics and to integrative systems biology. The topics of the workshop were centred around bioinformatics methods, tools, applications, and perspectives for models, standards and management of high-throughput biological data, structural bioinformatics, functional proteomics, mass spectrometry, drug discovery, and systems biology.43 scientific contributions were presented at NETTAB 2014, including keynote, special guest and tutorial talks, oral communications, and posters. Full papers from some of the best contributions presented at the workshop were later submitted to a special Call for this Supplement.Here, we provide an overview of the workshop and introduce manuscripts that have been accepted for publication in this Supplement. PMID:26960985

  4. Systems biology of cancer: moving toward the integrative study of the metabolic alterations in cancer cells

    PubMed Central

    Hernández Patiño, Claudia E.; Jaime-Muñoz, Gustavo; Resendis-Antonio, Osbaldo

    2013-01-01

    One of the main objectives in systems biology is to understand the biological mechanisms that give rise to the phenotype of a microorganism by using high-throughput technologies (HTs) and genome-scale mathematical modeling. The computational modeling of genome-scale metabolic reconstructions is one systemic and quantitative strategy for characterizing the metabolic phenotype associated with human diseases and potentially for designing drugs with optimal clinical effects. The purpose of this short review is to describe how computational modeling, including the specific case of constraint-based modeling, can be used to explore, characterize, and predict the metabolic capacities that distinguish the metabolic phenotype of cancer cell lines. As we show herein, this computational framework is far from a pure theoretical description, and to ensure proper biological interpretation, it is necessary to integrate high-throughput data and generate predictions for later experimental assessment. Hence, genome-scale modeling serves as a platform for the following: (1) the integration of data from HTs, (2) the assessment of how metabolic activity is related to phenotype in cancer cell lines, and (3) the design of new experiments to evaluate the outcomes of the in silico analysis. By combining the functions described above, we show that computational modeling is a useful methodology to construct an integrative, systemic, and quantitative scheme for understanding the metabolic profiles of cancer cell lines, a first step to determine the metabolic mechanism by which cancer cells maintain and support their malignant phenotype in human tissues. PMID:23316163

  5. Systems Biology

    SciTech Connect

    Wiley, H S.

    2006-06-01

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

  6. 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.

  7. 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

  8. 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. PMID:26749523

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  10. 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…

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

    PubMed

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

    2015-01-01

    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 × 10(6) 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%. PMID:26638983

  12. 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%.

  13. 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

  14. 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.

  15. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  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." PMID:25462871

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

    SciTech Connect

    Banfield, Jillian; Thomas, Brian

    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.

  19. 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.

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

    PubMed

    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

  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

    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. PMID:15980575

  3. 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

  4. An integrated systems biology approach identifies positive cofactor 4 as a factor that increases reprogramming efficiency

    PubMed Central

    Jo, Junghyun; Hwang, Sohyun; Kim, Hyung Joon; Hong, Soomin; Lee, Jeoung Eun; Lee, Sung-Geum; Baek, Ahmi; Han, Heonjong; Lee, Jin Il; Lee, Insuk; Lee, Dong Ryul

    2016-01-01

    Spermatogonial stem cells (SSCs) can spontaneously dedifferentiate into embryonic stem cell (ESC)-like cells, which are designated as multipotent SSCs (mSSCs), without ectopic expression of reprogramming factors. Interestingly, SSCs express key pluripotency genes such as Oct4, Sox2, Klf4 and Myc. Therefore, molecular dissection of mSSC reprogramming may provide clues about novel endogenous reprogramming or pluripotency regulatory factors. Our comparative transcriptome analysis of mSSCs and induced pluripotent stem cells (iPSCs) suggests that they have similar pluripotency states but are reprogrammed via different transcriptional pathways. We identified 53 genes as putative pluripotency regulatory factors using an integrated systems biology approach. We demonstrated a selected candidate, Positive cofactor 4 (Pc4), can enhance the efficiency of somatic cell reprogramming by promoting and maintaining transcriptional activity of the key reprograming factors. These results suggest that Pc4 has an important role in inducing spontaneous somatic cell reprogramming via up-regulation of key pluripotency genes. PMID:26740582

  5. 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

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

    PubMed Central

    2009-01-01

    Background 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. Results 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. Conclusion HPD http://bio.informatics.iupui.edu/HPD is a new

  7. 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.

  8. 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.

  9. Building a BRIDGE for the integration of heterogeneous data from functional genomics into a platform for systems biology.

    PubMed

    Goesmann, Alexander; Linke, Burkhard; Rupp, Oliver; Krause, Lutz; Bartels, Daniela; Dondrup, Michael; McHardy, Alice C; Wilke, Andreas; Pühler, Alfred; Meyer, Folker

    2003-12-19

    The flood of data acquired from the increasing number of publicly available genomes has led to new demands for bioinformatics software. With the growing amount of information resulting from high throughput experiments new questions arise that often focus on the comparison of genes, genomes, and their expression profiles. Inferring new knowledge by combining different kinds of "post-genomics" data obviously necessitates the development of new approaches that allow the integration of variable data sources into a flexible framework. In this paper, we describe our concept for the integration of heterogeneous data into a platform for systems biology. We have implemented a Bioinformatics Resource for the Integration of heterogeneous Data from Genomic Explorations (BRIDGE) and illustrate the usability of our approach as a platform for systems biology for two sample applications. PMID:14651858

  10. 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

  11. 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."

  12. 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 Central

    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. PMID:24748913

  13. Evaluating the informatics for integrating biology and the bedside system for clinical research

    PubMed Central

    2009-01-01

    Background Selecting patient cohorts is a critical, iterative, and often time-consuming aspect of studies involving human subjects; informatics tools for helping streamline the process have been identified as important infrastructure components for enabling clinical and translational research. We describe the evaluation of a free and open source cohort selection tool from the Informatics for Integrating Biology and the Bedside (i2b2) group: the i2b2 hive. Methods Our evaluation included the usability and functionality of the i2b2 hive using several real world examples of research data requests received electronically at the University of Utah Health Sciences Center between 2006 - 2008. The hive server component and the visual query tool application were evaluated for their suitability as a cohort selection tool on the basis of the types of data elements requested, as well as the effort required to fulfill each research data request using the i2b2 hive alone. Results We found the i2b2 hive to be suitable for obtaining estimates of cohort sizes and generating research cohorts based on simple inclusion/exclusion criteria, which consisted of about 44% of the clinical research data requests sampled at our institution. Data requests that relied on post-coordinated clinical concepts, aggregate values of clinical findings, or temporal conditions in their inclusion/exclusion criteria could not be fulfilled using the i2b2 hive alone, and required one or more intermediate data steps in the form of pre- or post-processing, modifications to the hive metadata, etc. Conclusion The i2b2 hive was found to be a useful cohort-selection tool for fulfilling common types of requests for research data, and especially in the estimation of initial cohort sizes. For another institution that might want to use the i2b2 hive for clinical research, we recommend that the institution would need to have structured, coded clinical data and metadata available that can be transformed to fit the

  14. 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

  15. 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.

  16. 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

  17. 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. PMID:22492191

  18. Studies of Complex Biological Systems with Applications to Molecular Medicine: The Need to Integrate Transcriptomic and Proteomic Approaches

    PubMed Central

    Silvestri, Elena; Lombardi, Assunta; de Lange, Pieter; Glinni, Daniela; Senese, Rosalba; Cioffi, Federica; Lanni, Antonia; Goglia, Fernando; Moreno, Maria

    2011-01-01

    Omics approaches to the study of complex biological systems with potential applications to molecular medicine are attracting great interest in clinical as well as in basic biological research. Genomics, transcriptomics and proteomics are characterized by the lack of an a priori definition of scope, and this gives sufficient leeway for investigators (a) to discern all at once a globally altered pattern of gene/protein expression and (b) to examine the complex interactions that regulate entire biological processes. Two popular platforms in “omics” are DNA microarrays, which measure messenger RNA transcript levels, and proteomic analyses, which identify and quantify proteins. Because of their intrinsic strengths and weaknesses, no single approach can fully unravel the complexities of fundamental biological events. However, an appropriate combination of different tools could lead to integrative analyses that would furnish new insights not accessible through one-dimensional datasets. In this review, we will outline some of the challenges associated with integrative analyses relating to the changes in metabolic pathways that occur in complex pathophysiological conditions (viz. ageing and altered thyroid state) in relevant metabolically active tissues. In addition, we discuss several new applications of proteomic analysis to the investigation of mitochondrial activity. PMID:20981256

  19. Calciomics: integrative studies of Ca2+-binding proteins and their interactomes in biological systems

    PubMed Central

    Zhou, Yubin; Xue, Shenghui; Yang, Jenny J.

    2013-01-01

    Calcium ion (Ca2+), the fifth most common chemical element in the earth’s crust, represents the most abundant mineral in the human body. By binding to a myriad of proteins distributed in different cellular organelles, Ca2+ impacts nearly every aspect of cellular life. In prokaryotes, Ca2+ plays an important role in bacterial movement, chemotaxis, survival reactions and sporulation. In eukaryotes, Ca2+ has been chosen through evolution to function as a universal and versatile intracellular signal. Viruses, as obligate intracellular parasites, also develop smart strategies to manipulate the host Ca2+ signaling machinery to benefit their own life cycles. This review focuses on recent advances in applying both bioinformatic and experimental approaches to predict and validate Ca2+-binding proteins and their interactomes in biological systems on genome-wide scale (termed “calciomics”). Calmodulin is used as an example of Ca2+-binding protein (CaBP) to demonstrate the role of CaBPs on the regulation of biological functions. This review is anticipated to rekindle interest in investigating Ca2+-binding proteins and Ca2+-modulated functions at the systems level in the post-genomic era. PMID:23235533

  20. An integrated systems biology approach to the study of preterm birth using "-omic" technology - a guideline for research

    PubMed Central

    2011-01-01

    Preterm birth is the leading cause of neonatal mortality and perinatal morbidity. The etiology of preterm is multi-factorial and still unclear. As evidence increases for a genetic contribution to PTB, so does the need to explore genomics, transcriptomics, proteomics and metabolomics in its study. This review suggests research guidelines for the conduct of high throughput systems biology investigations into preterm birth with the expectation that this will facilitate the sharing of samples and data internationally through consortia, generating the power needed to study preterm birth using integrated "-omics" technologies. The issues to be addressed include: (1) integrated "-omics" approaches, (2) phenotyping, (3) sample collection, (4) data management-integrative databases, (5) international consortia and (6) translational feasibility. This manuscript is the product of discussions initiated by the "-Omics" Working Group at the Preterm Birth International Collaborative Meeting held at the World Health Organization, Geneva, Switzerland in April 2009. PMID:21992798

  1. 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.

  2. 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.

  3. 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

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

    PubMed Central

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

    2014-01-01

    Comprising 1011 neurons with 1014 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. PMID:25429262

  5. Systems biology at the Institute for Systems Biology.

    PubMed

    Hood, Leroy; Rowen, Lee; Galas, David J; Aitchison, John D

    2008-07-01

    Systems biology represents an experimental approach to biology that attempts to study biological systems in a holistic rather than an atomistic manner. Ideally this involves gathering dynamic and global data sets as well as phenotypic data from different levels of the biological information hierarchy, integrating them and modeling them graphically and/or mathematically to generate mechanistic explanations for the emergent systems properties. This requires that the biological frontiers drive the development of new measurement and visualization technologies and the pioneering of new computational and mathematical tools-all of which requires a cross-disciplinary environment composed of biologists, chemists, computer scientists, engineers, mathematicians, physicists, and physicians speaking common discipline languages. The Institute for Systems Biology has aspired to pioneer and seamlessly integrate each of these concepts. PMID:18579616

  6. 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. PMID:26130662

  7. 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

  8. The Legume Information System (LIS): an integrated information resource for comparative legume biology.

    PubMed

    Gonzales, Michael D; Archuleta, Eric; Farmer, Andrew; Gajendran, Kamal; Grant, David; Shoemaker, Randy; Beavis, William D; Waugh, Mark E

    2005-01-01

    The Legume Information System (LIS) (http://www.comparative-legumes.org), developed by the National Center for Genome Resources in cooperation with the USDA Agricultural Research Service (ARS), is a comparative legume resource that integrates genetic and molecular data from multiple legume species enabling cross-species genomic and transcript comparisons. The LIS virtual plant interface allows simplified and intuitive navigation of transcript data from Medicago truncatula, Lotus japonicus, Glycine max and Arabidopsis thaliana. Transcript libraries are represented as images of plant organs in different developmental stages, which are selected to query the analyzed and annotated data. Complex queries can be accomplished by adding modifiers, keywords and sequence names. The LIS also contains annotated genomic data featuring transcript alignments to validate gene predictions as well as motif and similarity analyses. The genomic browser supports comparative analysis via novel dynamic functional annotation comparisons. CMap, developed as part of the GMOD project (http://www.gmod.org/cmap/index.shtml), has been incorporated to support comparative analyses of community linkage and physical map data. LIS is being expanded to incorporate gene expression and biochemical pathways which will be seamlessly integrated forming a knowledge discovery framework. PMID:15608283

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

    PubMed

    Kahl, Michael D; Villeneuve, Daniel L; Stevens, Kyle; Schroeder, Anthony; Makynen, Elizabeth A; LaLone, Carlie A; Jensen, Kathleen M; Hughes, Meagan; Holmen, Bruce A; Eid, Evan; Durhan, Elizabeth J; Cavallin, Jenna E; Berninger, Jason; Ankley, Gerald T

    2014-07-01

    Assessment of potential risks of complex contaminant mixtures in the environment requires integrated chemical and biological approaches. In support of the US Great Lakes Restoration Initiative, the US Environmental Protection Agency lab in Duluth, MN, is developing these types of methods for assessing possible risks of aquatic contaminants in near-shore Great Lakes (USA) sites. One component involves an exposure system for caged fathead minnow (Pimephales promelas) adults suitable for the wide range of habitat and deployment situations encountered in and around the Great Lakes. To complement the fish exposure system, the authors developed an automated device for collection of composite water samples that could be simultaneously deployed with the cages and reflect a temporally integrated exposure of the animals. The present study describes methodological details of the design, construction, and deployment of a flexible yet comparatively inexpensive (<600 USD) caged-fish/autosampler system. The utility and performance of the system were demonstrated with data collected from deployments at several Great Lakes sites. For example, over 3 field seasons, only 2 of 130 deployed cages were lost, and approximately 99% of successfully deployed adult fish were recovered after exposures of 4 d or longer. A number of molecular, biochemical, and apical endpoints were successfully measured in recovered animals, changes in which reflected known characteristics of the study sites (e.g., upregulation of hepatic genes involved in xenobiotic metabolism in fish held in the vicinity of wastewater treatment plants). The automated composite samplers proved robust with regard to successful water collection (>95% of deployed units in the latest field season), and low within- and among-unit variations were found relative to programmed collection volumes. Overall, the test system has excellent potential for integrated chemical-biological monitoring of contaminants in a variety of field

  10. 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…

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

    PubMed Central

    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

    2012-01-01

    Summary: 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. Availability: Freely available from http://www.intermine.org under the LGPL license. Contact: g.micklem@gen.cam.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online. PMID:23023984

  12. Biophysics and systems biology.

    PubMed

    Noble, Denis

    2010-03-13

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

  13. Biophysics and systems biology

    PubMed Central

    Noble, Denis

    2010-01-01

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

  14. 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...

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

    PubMed

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

    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(III)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. PMID:17310734

  16. 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

  17. 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.

  18. Enabling Systems Biology Approaches Through Microfabricated Systems

    PubMed Central

    Zhan, Mei; Chingozha, Loice; Lu, Hang

    2014-01-01

    With the experimental tools and knowledge that have accrued from a long history of reductionist biology, we can now start to put the pieces together and begin to understand how biological systems function as an integrated whole. Here, we describe how microfabricated tools have demonstrated promise in addressing experimental challenges in throughput, resolution and sensitivity to support systems-based approaches to biological understanding. PMID:23984862

  19. NERISK: AN EXPERT SYSTEM TO ENHANCE THE INTEGRATION OF PESTICIDES WITH ARTHROPOD BIOLOGICAL CONTROL

    EPA Science Inventory

    An expert system termed NERISK was developed to evaluate the effects of pesticides on arthropod predators and parasitoids in a variety of agroecosystems. ased on a shell system (RECOG) with minor coding modifications, the system was designed to let even a novice user access the v...

  20. 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...

  1. 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

  2. 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

    2015-01-01

    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

  3. ProPortal: a resource for integrated systems biology of Prochlorococcus and its phage.

    PubMed

    Kelly, Libusha; Huang, Katherine H; Ding, Huiming; Chisholm, Sallie W

    2012-01-01

    ProPortal (http://proportal.mit.edu/) is a database containing genomic, metagenomic, transcriptomic and field data for the marine cyanobacterium Prochlorococcus. Our goal is to provide a source of cross-referenced data across multiple scales of biological organization--from the genome to the ecosystem--embracing the full diversity of ecotypic variation within this microbial taxon, its sister group, Synechococcus and phage that infect them. The site currently contains the genomes of 13 Prochlorococcus strains, 11 Synechococcus strains and 28 cyanophage strains that infect one or both groups. Cyanobacterial and cyanophage genes are clustered into orthologous groups that can be accessed by keyword search or through a genome browser. Users can also identify orthologous gene clusters shared by cyanobacterial and cyanophage genomes. Gene expression data for Prochlorococcus ecotypes MED4 and MIT9313 allow users to identify genes that are up or downregulated in response to environmental stressors. In addition, the transcriptome in synchronized cells grown on a 24-h light-dark cycle reveals the choreography of gene expression in cells in a 'natural' state. Metagenomic sequences from the Global Ocean Survey from Prochlorococcus, Synechococcus and phage genomes are archived so users can examine the differences between populations from diverse habitats. Finally, an example of cyanobacterial population data from the field is included. PMID:22102570

  4. Uncovering the molecular machinery of the human spindle--an integration of wet and dry systems biology.

    PubMed

    Rojas, Ana M; Santamaria, Anna; Malik, Rainer; Jensen, Thomas Skøt; Körner, Roman; Morilla, Ian; de Juan, David; Krallinger, Martin; Hansen, Daniel Aaen; Hoffmann, Robert; Lees, Jonathan; Reid, Adam; Yeats, Corin; Wehner, Anja; Elowe, Sabine; Clegg, Andrew B; Brunak, Søren; Nigg, Erich A; Orengo, Christine; Valencia, Alfonso; Ranea, Juan A G

    2012-01-01

    The mitotic spindle is an essential molecular machine involved in cell division, whose composition has been studied extensively by detailed cellular biology, high-throughput proteomics, and RNA interference experiments. However, because of its dynamic organization and complex regulation it is difficult to obtain a complete description of its molecular composition. We have implemented an integrated computational approach to characterize novel human spindle components and have analysed in detail the individual candidates predicted to be spindle proteins, as well as the network of predicted relations connecting known and putative spindle proteins. The subsequent experimental validation of a number of predicted novel proteins confirmed not only their association with the spindle apparatus but also their role in mitosis. We found that 75% of our tested proteins are localizing to the spindle apparatus compared to a success rate of 35% when expert knowledge alone was used. We compare our results to the previously published MitoCheck study and see that our approach does validate some findings by this consortium. Further, we predict so-called "hidden spindle hub", proteins whose network of interactions is still poorly characterised by experimental means and which are thought to influence the functionality of the mitotic spindle on a large scale. Our analyses suggest that we are still far from knowing the complete repertoire of functionally important components of the human spindle network. Combining integrated bio-computational approaches and single gene experimental follow-ups could be key to exploring the still hidden regions of the human spindle system. PMID:22427808

  5. 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

  6. Development of an Integrated Microfluidic Perfusion Cell Culture System for Real-Time Microscopic Observation of Biological Cells

    PubMed Central

    Lin, Lung; Wang, Shih-Siou; Wu, Min-Hsien; Oh-Yang, Chih-Chin

    2011-01-01

    This study reports an integrated microfluidic perfusion cell culture system consisting of a microfluidic cell culture chip, and an indium tin oxide (ITO) glass-based microheater chip for micro-scale perfusion cell culture, and its real-time microscopic observation. The system features in maintaining both uniform, and stable chemical or thermal environments, and providing a backflow-free medium pumping, and a precise thermal control functions. In this work, the performance of the medium pumping scheme, and the ITO glass microheater were experimentally evaluated. Results show that the medium delivery mechanism was able to provide pumping rates ranging from 15.4 to 120.0 μL·min−1. In addition, numerical simulation and experimental evaluation were conducted to verify that the ITO glass microheater was capable of providing a spatially uniform thermal environment, and precise temperature control with a mild variation of ±0.3 °C. Furthermore, a perfusion cell culture was successfully demonstrated, showing the cultured cells were kept at high cell viability of 95 ± 2%. In the process, the cultured chondrocytes can be clearly visualized microscopically. As a whole, the proposed cell culture system has paved an alternative route to carry out real-time microscopic observation of biological cells in a simple, user-friendly, and low cost manner. PMID:22164082

  7. Complete and integrated pyrene degradation pathway in Mycobacterium vanbaalenii PYR-1 based on systems biology.

    PubMed

    Kim, Seong-Jae; Kweon, Ohgew; Jones, Richard C; Freeman, James P; Edmondson, Ricky D; Cerniglia, Carl E

    2007-01-01

    Mycobacterium vanbaalenii PYR-1 was the first bacterium isolated by virtue of its ability to metabolize the high-molecular-weight polycyclic aromatic hydrocarbon (PAH) pyrene. We used metabolic, genomic, and proteomic approaches in this investigation to construct a complete and integrated pyrene degradation pathway for M. vanbaalenii PYR-1. Genome sequence analyses identified genes involved in the pyrene degradation pathway that we have proposed for this bacterium. To identify proteins involved in the degradation, we conducted a proteome analysis of cells exposed to pyrene using one-dimensional gel electrophoresis in combination with liquid chromatography-tandem mass spectrometry. Database searching performed with the M. vanbaalenii PYR-1 genome resulted in identification of 1,028 proteins with a protein false discovery rate of <1%. Based on both genomic and proteomic data, we identified 27 enzymes necessary for constructing a complete pathway for pyrene degradation. Our analyses indicate that this bacterium degrades pyrene to central intermediates through o-phthalate and the beta-ketoadipate pathway. Proteomic analysis also revealed that 18 enzymes in the pathway were upregulated more than twofold, as indicated by peptide counting when the organism was grown with pyrene; three copies of the terminal subunits of ring-hydroxylating oxygenase (NidAB2, MvanDraft_0817/0818, and PhtAaAb), dihydrodiol dehydrogenase (MvanDraft_0815), and ring cleavage dioxygenase (MvanDraft_3242) were detected only in pyrene-grown cells. The results presented here provide a comprehensive picture of pyrene metabolism in M. vanbaalenii PYR-1 and a useful framework for understanding cellular processes involved in PAH degradation. PMID:17085566

  8. An Integrated Biology and Chemistry Curriculum.

    ERIC Educational Resources Information Center

    Squire, Clayton R.

    This document describes a two-year integrated biology and chemistry curriculum for ninth and tenth grade students. The first chapter outlines the rationale for integrating biology and chemistry and presents the topic sequence for the integrated curriculum. Chapter 2 discusses the developmental, cognitive, and philosophical issues that form the…

  9. Imaging methodologies for systems biology.

    PubMed

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

    2014-01-01

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

  10. Uncovering the Molecular Machinery of the Human Spindle—An Integration of Wet and Dry Systems Biology

    PubMed Central

    Körner, Roman; Morilla, Ian; de Juan, David; Krallinger, Martin; Hansen, Daniel Aaen; Hoffmann, Robert; Lees, Jonathan; Reid, Adam; Yeats, Corin; Wehner, Anja; Elowe, Sabine; Clegg, Andrew B.; Brunak, Søren; Nigg, Erich A.; Orengo, Christine; Valencia, Alfonso; Ranea, Juan A. G.

    2012-01-01

    The mitotic spindle is an essential molecular machine involved in cell division, whose composition has been studied extensively by detailed cellular biology, high-throughput proteomics, and RNA interference experiments. However, because of its dynamic organization and complex regulation it is difficult to obtain a complete description of its molecular composition. We have implemented an integrated computational approach to characterize novel human spindle components and have analysed in detail the individual candidates predicted to be spindle proteins, as well as the network of predicted relations connecting known and putative spindle proteins. The subsequent experimental validation of a number of predicted novel proteins confirmed not only their association with the spindle apparatus but also their role in mitosis. We found that 75% of our tested proteins are localizing to the spindle apparatus compared to a success rate of 35% when expert knowledge alone was used. We compare our results to the previously published MitoCheck study and see that our approach does validate some findings by this consortium. Further, we predict so-called “hidden spindle hub”, proteins whose network of interactions is still poorly characterised by experimental means and which are thought to influence the functionality of the mitotic spindle on a large scale. Our analyses suggest that we are still far from knowing the complete repertoire of functionally important components of the human spindle network. Combining integrated bio-computational approaches and single gene experimental follow-ups could be key to exploring the still hidden regions of the human spindle system. PMID:22427808

  11. 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

  12. Biological and chemical interaction of oxygen on the reduction of Fe(III)EDTA in a chemical absorption-biological reduction integrated NOx removal system.

    PubMed

    Zhang, Shi-Han; Shi, Yao; Li, Wei

    2012-03-01

    A promising chemical absorption-biological reduction integrated process has been proposed. A major problem of the process is oxidation of the active absorbent, ferrous ethylenediaminetetraacetate (Fe(II)EDTA), to the ferric species, leading to a significant decrease in NO removal efficiency. Thus the biological reduction of Fe(III)EDTA is vitally important for the continuous NO removal. Oxygen, an oxidizing agent and biological inhibitor, is typically present in the flue gas. It can significantly retard the application of the integrated process. This study investigated the influence mechanism of oxygen on the regeneration of Fe(II)EDTA in order to provide insight on how to eliminate or decrease the oxygen influence. The experimental results revealed that the dissolved oxygen and Fe(III)EDTA simultaneously served as electron acceptor for the microorganism. The Fe(III)EDTA reduction activity were directly inhibited by the dissolved oxygen. When the bioreactor was supplied with 3% and 8% oxygen in the gas phase, the concentration of initial dissolved oxygen in the liquid phase was 0.28 and 0.68 mg l(-1). Correspondingly, the instinct Fe(III)EDTA reduction activity of the microorganism determined under anoxic condition in a rotation shaker decreased from 1.09 to 0.84 and 0.49 mM h(-1). The oxidation of Fe(II)EDTA with dissolved oxygen prevented more dissolved oxygen access to the microorganism and eased the inhibition of dissolved oxygen on the microorganisms. PMID:21931973

  13. 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

  14. 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. PMID:27284024

  15. 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. PMID:24303294

  16. 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’.

  17. 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

  18. 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. PMID:26336651

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

    PubMed

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

    2015-01-01

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

  20. 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

  1. 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. PMID:25012162

  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. 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…

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  5. 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.

  6. 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.

  7. Plant Systems Biology (editorial)

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  8. 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

  9. 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

  10. Application of Hierarchical Dissociated Neural Network in Closed-Loop Hybrid System Integrating Biological and Mechanical Intelligence

    PubMed Central

    Zhang, Bin; Wang, Yuechao; Li, Hongyi

    2015-01-01

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

  11. 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.

  12. 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

  13. 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…

  14. Systems biology, emergence and antireductionism.

    PubMed

    Kesić, Srdjan

    2016-09-01

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

  15. Biological life-support systems

    NASA Technical Reports Server (NTRS)

    Shepelev, Y. Y.

    1975-01-01

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

  16. 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. PMID:26523481

  17. A kinetic analysis and experimental validation of an integrated system of anaerobic filter and biological aerated filter.

    PubMed

    Lim, Seung Joo; Fox, Peter

    2011-11-01

    An anaerobic/aerobic filter (AF/BAF) system was developed treating dairy wastewater. The influent was blended with recirculated effluent to allow for pre-denitrification in the AF followed by nitrification in the BAF. The recirculation ratio ranged 100-300%. The average chemical oxygen demand (COD) removal efficiency was 79.8-86.8% in the AF and the average total nitrogen removal efficiency was 50.5-80.8% in the AF/BAF system. Steady-state mass balances on the AF were used to analyze removal kinetics in the AF. The kinetic model values for effluent COD in the AF were overestimated as compared with experimental data. The integrated suspended and attached biomass growth rates in the AF were estimated. The specific growth rate of the integrated biomass at each recirculation ratios was 0.6213, 0.6647, and 1.20831/day, respectively. The increase in specific growth rate corresponded to increases in biomass sloughing as the recirculation ratio increased. PMID:21958523

  18. System biology of gene regulation.

    PubMed

    Baitaluk, Michael

    2009-01-01

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

  19. 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

  20. 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. PMID:26013981

  1. 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

  2. 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)

  3. 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. PMID:19891008

  4. 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...

  5. 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...

  6. 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...

  7. 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. PMID:20506061

  8. 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.…

  9. 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.

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

    PubMed Central

    2010-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  13. Report from the First Snake Genomics and Integrative Biology Meeting

    PubMed Central

    Castoe, Todd A.; Braun, Edward L.; Bronikowski, Anne M.; Cox, Christian L.; Rabosky, Alison R. Davis; Jason de Koning, A.P.; Dobry, Jason; Fujita, Matthew K.; Giorgianni, Matt W; Hargreaves, Adam; Henkel, Christiaan V.; Mackessy, Stephen P.; O’Meally, Denis; Rokyta, Darin R.; Secor, Stephen M.; Streicher, Jeffrey W.; Wray, Kenneth P.; Yokoyama, Ken D.; Pollock, David D.

    2012-01-01

    This report summarizes the proceedings of the 1st Snake Genomics and Integrative Biology Meeting held in Vail, CO USA, 5-8 October 2011. The meeting had over twenty registered participants, and was conducted as a single session of presentations. Goals of the meeting included coordination of genomic data collection and fostering collaborative interactions among researchers using snakes as model systems. PMID:23451292

  14. Systems biology: a biologist's viewpoint.

    PubMed

    Bose, Biplab

    2013-12-01

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

  15. Ten questions about systems biology

    PubMed Central

    Joyner, Michael J; Pedersen, Bente K

    2011-01-01

    In this paper we raise ‘ten questions’ broadly related to ‘omics’, the term systems biology, and why the new biology has failed to deliver major therapeutic advances for many common diseases, especially diabetes and cardiovascular disease. We argue that a fundamentally narrow and reductionist perspective about the contribution of genes and genetic variants to disease is a key reason ‘omics’ has failed to deliver the anticipated breakthroughs. We then point out the critical utility of key concepts from physiology like homeostasis, regulated systems and redundancy as major intellectual tools to understand how whole animals adapt to the real world. We argue that a lack of fluency in these concepts is a major stumbling block for what has been narrowly defined as ‘systems biology’ by some of its leading advocates. We also point out that it is a failure of regulation at multiple levels that causes many common diseases. Finally, we attempt to integrate our critique of reductionism into a broader social framework about so-called translational research in specific and the root causes of common diseases in general. Throughout we offer ideas and suggestions that might be incorporated into the current biomedical environment to advance the understanding of disease through the perspective of physiology in conjunction with epidemiology as opposed to bottom-up reductionism alone. PMID:21224238

  16. A Systems Biology-Based Investigation into the Pharmacological Mechanisms of Wu Tou Tang Acting on Rheumatoid Arthritis by Integrating Network Analysis

    PubMed Central

    Zhang, Yanqiong; Lin, Na

    2013-01-01

    Aim. To investigate pharmacological mechanisms of Wu Tou Tang acting on rheumatoid arthritis (RA) by integrating network analysis at a system level. Methods and Results. Drug similarity search tool in Therapeutic Targets Database was used to screen 153 drugs with similar structures to compositive compounds of each ingredient in Wu Tou Tang and to identify 56 known targets of these similar drugs as predicted molecules which Wu Tou Tang affects. The recall, precision, accuracy, and F1-score, which were calculated to evaluate the performance of this method, were, respectively, 0.98, 0.61, 59.67%, and 0.76. Then, the predicted effector molecules of Wu Tou Tang were significantly enriched in neuroactive ligand-receptor interaction and calcium signaling pathway. Next, the importance of these predicted effector molecules was evaluated by analyzing their network topological features, such as degree, betweenness, and k-coreness. We further elucidated the biological significance of nine major candidate effector molecules of Wu Tou Tang for RA therapy and validated their associations with compositive compounds in Wu Tou Tang by the molecular docking simulation. Conclusion. Our data suggest the potential pharmacological mechanisms of Wu Tou Tang acting on RA by combining the strategies of systems biology and network pharmacology. PMID:23690848

  17. Biological Resource Centers and Systems Biology

    PubMed Central

    Wang, Yufeng

    2009-01-01

    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. PMID:20157346

  18. 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.

  19. 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.

  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. PMID:26307096

  1. 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

  2. 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

  3. Systems biology in vaccine design

    PubMed Central

    Six, Adrien; Bellier, Bertrand; Thomas‐Vaslin, Véronique; Klatzmann, David

    2012-01-01

    Summary Vaccines are the most effective tools to prevent infectious diseases and to minimize their impact on humans or animals. Despite the successful development of vaccines that are able to elicit potent and protective immune responses, the majority of vaccines have been so far developed empirically and mechanistic events leading to protective immune responses are often poorly understood. This hampers the development of new prophylactic as well as therapeutic vaccines for infectious diseases and cancer. Biological correlates of immune‐mediated protection are currently based on standard readout such as antibody titres and ELISPOT assays. The development of successful vaccines for difficult settings, such as infectious agents leading to chronic infection (HIV, HCV. . .) or cancer, calls for novel ‘readout systems’ or ‘correlates’ of immune‐mediated protection that would reliably predict immune responses to novel vaccines in vivo. Systems biology offers a new approach to vaccine design that is based upon understanding the molecular network mobilized by vaccination. Systems vaccinology approaches investigate more global correlates of successful vaccination, beyond the specific immune response to the antigens administered, providing new methods for measuring early vaccine efficacy and ultimately generating hypotheses for understanding the mechanisms that underlie successful immunogenicity. Using functional genomics, specific molecular signatures of individual vaccine can be identified and used as predictors of vaccination efficiency. The immune response to vaccination involves the coordinated induction of master transcription factors that leads to the development of a broad, polyfunctional and persistent immune response integrating all effector cells of the immune systems. PMID:22189033

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. SYSTEMS BIOLOGY MODEL DEVELOPMENT AND APPLICATION

    EPA Science Inventory

    System biology models holistically describe, in a quantitative fashion, the relationships between different levels of a biologic system. Relationships between individual components of a system are delineated. System biology models describe how the components of the system inter...

  10. 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. PMID:26793622

  11. Pervasive robustness in biological systems.

    PubMed

    Félix, Marie-Anne; Barkoulas, Michalis

    2015-08-01

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

  12. 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.

  13. 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.

  14. 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…

  15. Machine Learning in Systems Biology

    PubMed Central

    d'Alché-Buc, Florence; Wehenkel, Louis

    2008-01-01

    This supplement contains extended versions of a selected subset of papers presented at the workshop MLSB 2007, Machine Learning in Systems Biology, Evry, France, from September 24 to 25, 2007. PMID:19091048

  16. Machine learning in systems biology.

    PubMed

    d'Alché-Buc, Florence; Wehenkel, Louis

    2008-01-01

    This supplement contains extended versions of a selected subset of papers presented at the workshop MLSB 2007, Machine Learning in Systems Biology, Evry, France, from September 24 to 25, 2007. PMID:19091048

  17. Mass Spec Studio for Integrative Structural Biology

    PubMed Central

    Rey, Martial; Sarpe, Vladimir; Burns, Kyle; Buse, Joshua; Baker, Charles A.H.; van Dijk, Marc; Wordeman, Linda; Bonvin, Alexandre M.J.J.; Schriemer, David C.

    2015-01-01

    SUMMARY The integration of biophysical data from multiple sources is critical for developing accurate structural models of large multiprotein systems and their regulators. Mass spectrometry (MS) can be used to measure the insertion location for a wide range of topographically sensitive chemical probes, and such insertion data provide a rich, but disparate set of modeling restraints. We have developed a software platform that integrates the analysis of label-based MS data with protein modeling activities (Mass Spec Studio). Analysis packages can mine any labeling data from any mass spectrometer in a proteomics-grade manner, and link labeling methods with data-directed protein interaction modeling using HADDOCK. Support is provided for hydrogen/ deuterium exchange (HX) and covalent labeling chemistries, including novel acquisition strategies such as targeted HX-tandem MS (MS2) and data-independent HX-MS2. The latter permits the modeling of highly complex systems, which we demonstrate by the analysis of microtubule interactions. PMID:25242457

  18. 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

  19. 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.…

  20. 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.

  1. Omics/systems biology and cancer cachexia.

    PubMed

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

    2016-06-01

    Cancer cachexia is a complex syndrome generated by interaction between the host and tumour cells with a background of treatment effects and toxicity. The complexity of the physiological pathways likely involved in cancer cachexia necessitates a holistic view of the relevant biology. Emergent properties are characteristic of complex systems with the result that the end result is more than the sum of its parts. Recognition of the importance of emergent properties in biology led to the concept of systems biology wherein a holistic approach is taken to the biology at hand. Systems biology approaches will therefore play an important role in work to uncover key mechanisms with therapeutic potential in cancer cachexia. The 'omics' technologies provide a global view of biological systems. Genomics, transcriptomics, proteomics, lipidomics and metabolomics approaches all have application in the study of cancer cachexia to generate systems level models of the behaviour of this syndrome. The current work reviews recent applications of these technologies to muscle atrophy in general and cancer cachexia in particular with a view to progress towards integration of these approaches to better understand the pathology and potential treatment pathways in cancer cachexia. PMID:26783720

  2. Proteomics technology in systems biology.

    PubMed

    Smith, Jeffrey C; Figeys, Daniel

    2006-08-01

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

  3. 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.

  4. 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. PMID:21227966

  5. Kinetic Modeling of Biological Systems

    PubMed Central

    Petzold, Linda; Pettigrew, Michel F.

    2010-01-01

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

  6. 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

  7. 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

  8. 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. PMID:18944382

  9. 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

    2015-01-01

    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

  10. 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

  11. Human Systems Integration Introduction

    NASA Video Gallery

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

  12. 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…

  13. 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. PMID:26357233

  14. A Decade of Systems Biology

    PubMed Central

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

    2012-01-01

    Systems biology provides a framework for assembling models of biological systems from systematic measurements. Since the field was first introduced a decade ago, considerable progress has been made in technologies for global cell measurement and in computational analyses of these data to map and model cell function. It has also greatly expanded into the translational sciences, with approaches pioneered in yeast now being applied to elucidate human development and disease. Here, we review the state of the field with a focus on four emerging applications of systems biology that are likely to be of particular importance during the decade to follow: (a) pathway-based biomarkers, (b) global genetic interaction maps, (c) systems approaches to identify disease genes, and (d) stem cell systems biology. We also cover recent advances in software tools that allow biologists to explore system-wide models and to formulate new hypotheses. The applications and methods covered in this review provide a set of prime exemplars useful to cell and developmental biologists wishing to apply systems approaches to areas of interest. PMID:20604711

  15. 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. PMID:26152902

  16. Workshop Introduction: Systems Biology and Biological Models

    EPA Science Inventory

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

  17. Integrated Avionics System (IAS)

    NASA Technical Reports Server (NTRS)

    Hunter, D. J.

    2001-01-01

    As spacecraft designs converge toward miniaturization and with the volumetric and mass constraints placed on avionics, programs will continue to advance the 'state of the art' in spacecraft systems development with new challenges to reduce power, mass, and volume. Although new technologies have improved packaging densities, a total system packaging architecture is required that not only reduces spacecraft volume and mass budgets, but increase integration efficiencies, provide modularity and scalability to accommodate multiple missions. With these challenges in mind, a novel packaging approach incorporates solutions that provide broader environmental applications, more flexible system interconnectivity, scalability, and simplified assembly test and integration schemes. This paper will describe the fundamental elements of the Integrated Avionics System (IAS), Horizontally Mounted Cube (HMC) hardware design, system and environmental test results. Additional information is contained in the original extended abstract.

  18. Modular integrated video system

    SciTech Connect

    Gaertner, K.J.; Heaysman, B.; Holt, R.; Sonnier, C.

    1986-01-01

    The Modular Integrated Video System (MIVS) is intended to provide a simple, highly reliable closed circuit television (CCTV) system capable of replacing the IAEA Twin Minolta Film Camera Systems in those safeguards facilities where mains power is readily available, and situations where it is desired to have the CCTV camera separated from the CCTV recording console. This paper describes the MIVS and the Program Plan which is presently being followed for the development, testing, and implementation of the system.

  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: 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. PMID:11589586

  2. Teaching the Fundamentals of Biological Data Integration Using Classroom Games

    PubMed Central

    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. PMID:23300402

  3. 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.

  4. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  6. 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…

  7. 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.

  8. 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.

  9. 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

  10. Optical systems integrated modeling

    NASA Technical Reports Server (NTRS)

    Shannon, Robert R.; Laskin, Robert A.; Brewer, SI; Burrows, Chris; Epps, Harlan; Illingworth, Garth; Korsch, Dietrich; Levine, B. Martin; Mahajan, Vini; Rimmer, Chuck

    1992-01-01

    An integrated modeling capability that provides the tools by which entire optical systems and instruments can be simulated and optimized is a key technology development, applicable to all mission classes, especially astrophysics. Many of the future missions require optical systems that are physically much larger than anything flown before and yet must retain the characteristic sub-micron diffraction limited wavefront accuracy of their smaller precursors. It is no longer feasible to follow the path of 'cut and test' development; the sheer scale of these systems precludes many of the older techniques that rely upon ground evaluation of full size engineering units. The ability to accurately model (by computer) and optimize the entire flight system's integrated structural, thermal, and dynamic characteristics is essential. Two distinct integrated modeling capabilities are required. These are an initial design capability and a detailed design and optimization system. The content of an initial design package is shown. It would be a modular, workstation based code which allows preliminary integrated system analysis and trade studies to be carried out quickly by a single engineer or a small design team. A simple concept for a detailed design and optimization system is shown. This is a linkage of interface architecture that allows efficient interchange of information between existing large specialized optical, control, thermal, and structural design codes. The computing environment would be a network of large mainframe machines and its users would be project level design teams. More advanced concepts for detailed design systems would support interaction between modules and automated optimization of the entire system. Technology assessment and development plans for integrated package for initial design, interface development for detailed optimization, validation, and modeling research are presented.

  11. 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. PMID:24591504

  12. Toward efficient riparian restoration: integrating economic, physical, and biological models.

    PubMed

    Watanabe, Michio; Adams, Richard M; Wu, Junjie; Bolte, John P; Cox, Matt M; Johnson, Sherri L; Liss, William J; Boggess, William G; Ebersole, Joseph L

    2005-04-01

    This paper integrates economic, biological, and physical models to explore the efficient combination and spatial allocation of conservation efforts to protect water quality and increase salmonid populations in the Grande Ronde basin, Oregon. We focus on the effects of shade on water temperatures and the subsequent impacts on endangered juvenile salmonid populations. The integrated modeling system consists of a physical model that links riparian conditions and hydrological characteristics to water temperature; a biological model that links water temperature and riparian conditions to salmonid abundance, and an economic model that incorporates both physical and biological models to estimate minimum cost allocations of conservation efforts. Our findings indicate that conservation alternatives such as passive and active riparian restoration, the width of riparian restoration zones, and the types of vegetation used in restoration activities should be selected based on the spatial distribution of riparian characteristics in the basin. The relative effectiveness of passive and active restoration plays an important role in determining the efficient allocations of conservation efforts. The time frame considered in the restoration efforts and the magnitude of desired temperature reductions also affect the efficient combinations of restoration activities. If the objective of conservation efforts is to maximize fish populations, then fishery benefits should be directly targeted. Targeting other criterion such as water temperatures would result in different allocations of conservation efforts, and therefore are not generally efficient. PMID:15763152

  13. 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.

  14. 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.

  15. Biologically inspired dynamic material systems.

    PubMed

    Studart, André R

    2015-03-01

    Numerous examples of material systems that dynamically interact with and adapt to the surrounding environment are found in nature, from hair-based mechanoreceptors in animals to self-shaping seed dispersal units in plants to remodeling bone in vertebrates. Inspired by such fascinating biological structures, a wide range of synthetic material systems have been created to replicate the design concepts of dynamic natural architectures. Examples of biological structures and their man-made counterparts are herein revisited to illustrate how dynamic and adaptive responses emerge from the intimate microscale combination of building blocks with intrinsic nanoscale properties. By using top-down photolithographic methods and bottom-up assembly approaches, biologically inspired dynamic material systems have been created 1) to sense liquid flow with hair-inspired microelectromechanical systems, 2) to autonomously change shape by utilizing plantlike heterogeneous architectures, 3) to homeostatically influence the surrounding environment through self-regulating adaptive surfaces, and 4) to spatially concentrate chemical species by using synthetic microcompartments. The ever-increasing complexity and remarkable functionalities of such synthetic systems offer an encouraging perspective to the rich set of dynamic and adaptive properties that can potentially be implemented in future man-made material systems. PMID:25583299

  16. Meeting report: Signal transduction meets systems biology

    PubMed Central

    2012-01-01

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

  17. 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

  18. 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). PMID:11541902

  19. 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. PMID:25790483

  20. 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...

  1. Power systems integration

    SciTech Connect

    Brantley, L.W.

    1982-06-01

    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.

  2. 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

  3. 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.

  4. 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…

  5. 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.

  6. 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.

  7. Integrating and Interfacing Library Systems.

    ERIC Educational Resources Information Center

    Boss, Richard W.

    1985-01-01

    This overview of local library online systems that integrate several functions covers functional integration, benefits of integrated systems, turnkey systems, minicomputer and microcomputer-based systems, interfacing automated systems, types of interfaces, linking homogenous and heterogeneous systems, role of vendors, library applications, linking…

  8. Pegasys: software for executing and integrating analyses of biological sequences

    PubMed Central

    Shah, Sohrab P; He, David YM; Sawkins, Jessica N; Druce, Jeffrey C; Quon, Gerald; Lett, Drew; Zheng, Grace XY; Xu, Tao; Ouellette, BF Francis

    2004-01-01

    Background We present Pegasys – a flexible, modular and customizable software system that facilitates the execution and data integration from heterogeneous biological sequence analysis tools. Results The Pegasys system includes numerous tools for pair-wise and multiple sequence alignment, ab initio gene prediction, RNA gene detection, masking repetitive sequences in genomic DNA as well as filters for database formatting and processing raw output from various analysis tools. We introduce a novel data structure for creating workflows of sequence analyses and a unified data model to store its results. The software allows users to dynamically create analysis workflows at run-time by manipulating a graphical user interface. All non-serial dependent analyses are executed in parallel on a compute cluster for efficiency of data generation. The uniform data model and backend relational database management system of Pegasys allow for results of heterogeneous programs included in the workflow to be integrated and exported into General Feature Format for further analyses in GFF-dependent tools, or GAME XML for import into the Apollo genome editor. The modularity of the design allows for new tools to be added to the system with little programmer overhead. The database application programming interface allows programmatic access to the data stored in the backend through SQL queries. Conclusions The Pegasys system enables biologists and bioinformaticians to create and manage sequence analysis workflows. The software is released under the Open Source GNU General Public License. All source code and documentation is available for download at . PMID:15096276

  9. 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…

  10. ECOLOGICAL IMPACT OF INTEGRATED CHEMICAL AND BIOLOGICAL AQUATIC WEED CONTROL

    EPA Science Inventory

    This final report presents results of a four-year study of the ecological impacts of chemical, biological, and integrated methods of aquatic weed control. Biological and water quality changes occurred as abundance of macrophytic vegetation was altered by natural factors or manage...

  11. 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. PMID:27284029

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

    PubMed

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

    2016-01-01

    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. PMID:27036106

  13. 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

  14. 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.

  15. Slimplectic Integrators: Variational Integrators for Nonconservative systems

    NASA Astrophysics Data System (ADS)

    Tsang, David

    2016-01-01

    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. In this Letter, we develop 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 the principle of stationary nonconservative action developed in Galley et al. 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.

  16. 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

  17. 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

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

    EPA Science Inventory

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

  19. Integrated traffic system

    SciTech Connect

    Creighton, H. ); Allen, R.; Stewart, S.; Hayto, S. )

    1990-11-01

    The traffic congestion on our roads today is becoming a critical problem. There is increased fuel consumption as cars wait along poorly timed arterials. Safety is threatened as poor traffic flow leads to collisions. This paper reports that Transport Canada and the Ministry of Transportation Ontario has developed an integrated traffic system (ITS). The system is designed to enable the optimization of traffic flow on existing roadways. The ITS system contains a data-base management system for traffic data (including accidents, roadway volumes, and signal timing details) and links this data base to the traffic analysis programs. This will ease the data management situation within the municipalities and standardize the traffic operations and reduce duplication of computerization development efforts.

  20. 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…

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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. PMID:22206914

  7. 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.

  8. 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

  9. BIOLOGICAL DIVERSITY AND BIOLOGICAL INTEGRITY: CURRENT CONCERNS FOR LAKES AND STREAMS

    EPA Science Inventory

    In discussing various concepts of biological diversity and biological integrity, we trace development of the terms from a focus on species to a consideration of ecosystems. e urge the public to extend its concern with species extinction and tropical rain forests to include temper...

  10. 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...

  11. 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. PMID:25724695

  12. 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

  13. 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.

  14. 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.

  15. Seasonal Variations in Biological Characteristics of the South Australian Shelf Waters - Results from the Southern Australian Integrated Marine Observing System (SAIMOS)

    NASA Astrophysics Data System (ADS)

    Leterme, S. C.; James, C.; Luick, J.; Middleton, J.; van Dongen Vogels, V.; Paterson, J.; Seuront, L.

    2009-04-01

    The Southern Australia Integrated Marine Observing System, or SAIMOS, is one of five nodes operating as part of the Australia-wide Integrated Marine Observing System (IMOS). This is a collaborative program designed to observe Australia's oceans, both coastal and blue-water. Since February 2008, and the occurrence of a record upwelling event on the South Australian continental shelf, the abundance and composition of viral, bacterial and pico- and nanoplankton communities have been investigating during 8 cross-shelf surveys and related to the physical and chemical properties of the water column. In summer, the space-time dynamic of viral, bacterial and pico- and nanoplankton communities is generally driven by the plume of upwelled, cool and nutrient rich water that flows across the continental shelf, and is locally heavily influenced by the level of vertical stability of the water column. In winter, the qualitative and quantitative nature of the plankton community is related to the local physical properties of the water column, which include the presence of a dense plume of bottom waters outflowing from the Spencer Gulf, the vertical stability of the water column and the presence of a deep chlorophyll maximum (DCM).

  16. 6th Annual Systems Biology Symposium: Systems Biology and the Environment

    SciTech Connect

    Galitski, Timothy, P.

    2007-04-01

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

  17. 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.

  18. 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. PMID:24169619

  19. Principles of Systems Biology, No. 8.

    PubMed

    2016-08-01

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

  20. 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.

  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. 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

  3. 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.

  4. 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.

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

    PubMed

    Witzany, Guenther

    2016-01-01

    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

  6. 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

  7. iCTNet2: integrating heterogeneous biological interactions to understand complex traits

    PubMed Central

    Wang, Lili; Himmelstein, Daniel S.; Santaniello, Adam; Parvin, Mousavi; Baranzini, Sergio E.

    2015-01-01

    iCTNet (integrated Complex Traits Networks) version 2 is a Cytoscape app and database that allows researchers to build heterogeneous networks by integrating a variety of biological interactions, thus offering a systems-level view of human complex traits. iCTNet2 is built from a variety of large-scale biological datasets, collected from public repositories to facilitate the building, visualization and analysis of heterogeneous biological networks in a comprehensive fashion via the Cytoscape platform. iCTNet2 is freely available at the Cytoscape app store. PMID:26834985

  8. 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

  9. 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

  10. Symmetry and quaternionic integrable systems

    NASA Astrophysics Data System (ADS)

    Gaeta, G.; Rodríguez, M. A.

    2015-01-01

    Given a hyperkahler manifold M, the hyperkahler structure defines a triple of symplectic structures on M; with these, a triple of Hamiltonians defines a so-called hyperHamiltonian dynamical system on M. These systems are integrable when can be mapped to a system of quaternionic oscillators. We discuss the symmetry of integrable hyperHamiltonian systems, i.e. quaternionic oscillators, and conversely how these symmetries characterize, at least in the Euclidean case, integrable hyperHamiltonian systems.

  11. Complex biological and bio-inspired systems

    SciTech Connect

    Ecke, Robert E

    2009-01-01

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

  12. Arcjet system integration development

    NASA Technical Reports Server (NTRS)

    Zafran, Sidney

    1994-01-01

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

  13. 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.

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

    PubMed

    Condic, Maureen L

    2016-06-01

    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

  15. Inference on biological mechanisms using an integrated phenotype prediction model.

    PubMed

    Enomoto, Yumi; Ushijima, Masaru; Miyata, Satoshi; Matsuura, Masaaki; Ohtaki, Megu

    2008-03-01

    We propose a methodology for constructing an integrated phenotype prediction model that accounts for multiple pathways regulating a targeted phenotype. The method uses multiple prediction models, each expressing a particular pattern of gene-to-gene interrelationship, such as epistasis. We also propose a methodology using Gene Ontology annotations to infer a biological mechanism from the integrated phenotype prediction model. To construct the integrated models, we employed multiple logistic regression models using a two-step learning approach to examine a number of patterns of gene-to-gene interrelationships. We first selected individual prediction models with acceptable goodness of fit, and then combined the models. The resulting integrated model predicts phenotype as a logical sum of predicted results from the individual models. We used published microarray data on neuroblastoma from Ohira et al (2005) for illustration, constructing an integrated model to predict prognosis and infer the biological mechanisms controlling prognosis. Although the resulting integrated model comprised a small number of genes compared to a previously reported analysis of these data, the model demonstrated excellent performance, with an error rate of 0.12 in a validation analysis. Gene Ontology analysis suggested that prognosis of patients with neuroblastoma may be influenced by biological processes such as cell growth, G-protein signaling, phosphoinositide-mediated signaling, alcohol metabolism, glycolysis, neurophysiological processes, and catecholamine catabolism. PMID:18578362

  16. Integrated Management Tracking System

    Energy Science and Technology Software Center (ESTSC)

    2000-03-30

    The Integrated Management Tracking System (IMTS) is a "Web Enabled" Client/Server Business application that provides for the Identification and Resolution of commitments, situations, events and problems. The IMTS engine is written with Microsoft Active Server Pages (ASP) for IIS4. The system provides for reporting, entering, editing, closing and administration over a Intranet, Extranet or Internet. This Application facilitates: Electronic assignment, acceptance and tracking to completion. Email notifications of assigned action. Establishment of Due Dates. Electronicmore » search and retrieval based on keywords in combination with user specified database parameters (Document Type, Date Ranges, etc.). Coded for Trending and Reporting. User selected reports. Various levels of access for reports and administration. The "Server" side of this application consists of a Microsoft Access database running on a NT Server with Internet Information Server (IIS). As the "Client" side of the application runs on any Web browser, this solution is a cost effective, user friendly application that lends itself to organizations not physically colocated in one location providing information immediately available to everyone at once.« less

  17. Integrated Management Tracking System

    SciTech Connect

    Garrett, Terrance

    2000-03-30

    The Integrated Management Tracking System (IMTS) is a "Web Enabled" Client/Server Business application that provides for the Identification and Resolution of commitments, situations, events and problems. The IMTS engine is written with Microsoft Active Server Pages (ASP) for IIS4. The system provides for reporting, entering, editing, closing and administration over a Intranet, Extranet or Internet. This Application facilitates: Electronic assignment, acceptance and tracking to completion. Email notifications of assigned action. Establishment of Due Dates. Electronic search and retrieval based on keywords in combination with user specified database parameters (Document Type, Date Ranges, etc.). Coded for Trending and Reporting. User selected reports. Various levels of access for reports and administration. The "Server" side of this application consists of a Microsoft Access database running on a NT Server with Internet Information Server (IIS). As the "Client" side of the application runs on any Web browser, this solution is a cost effective, user friendly application that lends itself to organizations not physically colocated in one location providing information immediately available to everyone at once.

  18. Integrated clinical information system.

    PubMed

    Brousseau, G

    1995-01-01

    SIDOCI (Système Informatisé de DOnnées Cliniques Intégrées) is a Canadian joint venture introducing newly-operating paradigms into hospitals. The main goal of SIDOCI is to maintain the quality of care in todayUs tightening economy. SIDOCI is a fully integrated paperless patient-care system which automates and links all information about a patient. Data is available on-line and instantaneously to doctors, nurses, and support staff in the format that best suits their specific requirements. SIDOCI provides a factual and chronological summary of the patient's progress by drawing together clinical information provided by all professionals working with the patient, regardless of their discipline, level of experience, or physical location. It also allows for direct entry of the patient's information at the bedside. Laboratory results, progress notes, patient history and graphs are available instantaneously on screen, eliminating the need for physical file transfers. The system, incorporating a sophisticated clinical information database, an intuitive graphical user interface, and customized screens for each medical discipline, guides the user through standard procedures. Unlike most information systems created for the health care industry, SIDOCI is longitudinal, covering all aspects of the health care process through its link to various vertical systems already in place. A multidisciplinary team has created a clinical dictionary that provides the user with most of the information she would normally use: symptoms, signs, diagnoses, allergies, medications, interventions, etc. This information is structured and displayed in such a manner that health care professionals can document the clinical situation at the touch of a finger. The data is then encoded into the patient's file. Once encoded, the structured data is accessible for research, statistics, education, and quality assurance. This dictionary complies with national and international nomenclatures. It also

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

    EPA Science Inventory

    This paper integrates economic, biological, and physical models to explore the efficient combination and spatial allocation of conservation efforts to protect water quality and increase salmonid populations in the Grande Ronde basin, Oregon. We focus on the effects of shade on wa...

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

    ERIC Educational Resources Information Center

    Bisbee, Gregory D.; Kaiser, Cheryl A.

    1997-01-01

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

  1. Integrating Biological Measures into the Study of Bullying

    ERIC Educational Resources Information Center

    Hazler, Richard J.; Carney, JoLynn V.; Granger, Douglas A.

    2006-01-01

    The emergence of minimally intrusive techniques for collecting biological data creates a case for the inclusion of these data into bullying research models. This integration would produce a more comprehensive understanding of the problems and better direct intervention and prevention techniques, which are currently based primarily on self-report,…

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  3. 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.

  4. Introducing systems biology for nursing science.

    PubMed

    Founds, Sandra A

    2009-07-01

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

  5. 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.

  6. 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.

  7. Systems biology approaches in aging research.

    PubMed

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

    2015-01-01

    Aging is a systemic process which progressively manifests itself at multiple levels of structural and functional organization from molecular reactions and cell-cell interactions in tissues to the physiology of an entire organ. There is ever increasing data on biomedical relevant network interactions for the aging process at different scales of time and space. To connect the aging process at different structural, temporal and spatial scales, extensive systems biological approaches need to be deployed. Systems biological approaches can not only systematically handle the large-scale datasets (like high-throughput data) and the complexity of interactions (feedback loops, cross talk), but also can delve into nonlinear behaviors exhibited by several biological processes which are beyond intuitive reasoning. Several public-funded agencies have identified the synergistic role of systems biology in aging research. Using one of the notable public-funded programs (GERONTOSYS), we discuss how systems biological approaches are helping the scientists to find new frontiers in aging research. We elaborate on some systems biological approaches deployed in one of the projects of the consortium (ROSage). The systems biology field in aging research is at its infancy. It is open to adapt existing systems biological methodologies from other research fields and devise new aging-specific systems biological methodologies. PMID:25341520

  8. Teaching Systems Biology: An Active-learning Approach

    PubMed Central

    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 opportunities and obstacles: The benefit of exposing students to this cutting-edge scientific methodology is manifest, yet how does one convey the breadth and advantage of systems biology while still engaging the student? Here, I describe an active-learning approach to the presentation of systems biology. In graduate classes at the University of Michigan, Ann Arbor, I divided students into small groups and asked each group to interpret a sample data set (e.g., microarray data, two-hybrid data, homology-search results) describing a hypothetical signaling pathway. Mimicking realistic experimental results, each data set revealed a portion of this pathway; however, students were only able to reconstruct the full pathway by integrating all data sets, thereby exemplifying the utility in a systems biology approach. Student response to this cooperative exercise was extremely positive. In total, this approach provides an effective introduction to systems biology appropriate for students at both the undergraduate and graduate levels. PMID:16341259

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

    PubMed Central

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

    2014-01-01

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

  10. 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%). PMID:27085988

  11. Method of measurement in biological systems

    DOEpatents

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

    1993-05-11

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

  12. 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. Systems biology and mechanics of growth.

    PubMed

    Eskandari, Mona; Kuhl, Ellen

    2015-01-01

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

  14. An integrative computational systems biology approach identifies differentially regulated dynamic transcriptome signatures which drive the initiation of human T helper cell differentiation

    PubMed Central

    2012-01-01

    Background A proper balance between different T helper (Th) cell subsets is necessary for normal functioning of the adaptive immune system. Revealing key genes and pathways driving the differentiation to distinct Th cell lineages provides important insight into underlying molecular mechanisms and new opportunities for modulating the immune response. Previous computational methods to quantify and visualize kinetic differential expression data of three or more lineages to identify reciprocally regulated genes have relied on clustering approaches and regression methods which have time as a factor, but have lacked methods which explicitly model temporal behavior. Results We studied transcriptional dynamics of human umbilical cord blood T helper cells cultured in absence and presence of cytokines promoting Th1 or Th2 differentiation. To identify genes that exhibit distinct lineage commitment dynamics and are specific for initiating differentiation to different Th cell subsets, we developed a novel computational methodology (LIGAP) allowing integrative analysis and visualization of multiple lineages over whole time-course profiles. Applying LIGAP to time-course data from multiple Th cell lineages, we identified and experimentally validated several differentially regulated Th cell subset specific genes as well as reciprocally regulated genes. Combining differentially regulated transcriptional profiles with transcription factor binding site and pathway information, we identified previously known and new putative transcriptional mechanisms involved in Th cell subset differentiation. All differentially regulated genes among the lineages together with an implementation of LIGAP are provided as an open-source resource. Conclusions The LIGAP method is widely applicable to quantify differential time-course dynamics of many types of datasets and generalizes to any number of conditions. It summarizes all the time-course measurements together with the associated uncertainty for

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

    PubMed

    Salvucci, Emiliano

    2012-01-01

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

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

    PubMed Central

    Salvucci, Emiliano

    2012-01-01

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

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

    PubMed

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

    2016-01-01

    Interpreting molecular profiles in a biological context requires specialized analysis strategies. Initially, lists of relevant genes were screened to identify enriched concepts associated with pathways or specific molecular processes. However, the shortcoming of interpreting gene lists by using predefined sets of genes has resulted in the development of novel methods that heavily rely on network-based concepts. These algorithms have the advantage that they allow a more holistic view of the signaling properties of the condition under study as well as that they are suitable for integrating different data types like gene expression, gene mutation, and even histological parameters. PMID:27311441

  18. Systems biology of circadian-immune interactions

    PubMed Central

    Mavroudis, P.D.; Scheff, J.D.; Calvano, S.E.; Androulakis, I.P.

    2013-01-01

    There is increasing evidence that immune system is regulated by circadian rhythms. A wide range of immune parameters, such as the number of red blood cells and peripheral blood mononuclear cells as well as the level of critical immune mediators such as cytokines, undergo daily fluctuations. Current experimental data indicates that circadian information reaches immune tissues mainly through diurnal patterns of autonomic and endocrine rhythms. In addition, immune factors such as cytokines can also influence the phase of the circadian clock, providing bidirectional flow of circadian information between the neuroendocrine and immune system. This network of neuroendocrine-immune interactions consists of complexly integrated molecular feedback and feedforward loops that function in synchrony in order to optimize immune response. Chronic stress can disrupt this intrinsic orchestration, as several endocrine signals of chronically stressed patients present blunted rhythmic characteristics. Reprogramming of biological rhythms has recently gained much attention as a potent method to leverage homeostatic circadian controls to ultimately improve clinical outcomes. Elucidation of the intrinsic properties of such complex systems and optimization of intervention strategies requires not only an accurate identification of the signaling pathways that mediate host’s response, but also a systems-level description and evaluation. PMID:23006670

  19. Systems biology of circadian-immune interactions.

    PubMed

    Mavroudis, P D; Scheff, J D; Calvano, S E; Androulakis, I P

    2013-01-01

    There is increasing evidence that the immune system is regulated by circadian rhythms. A wide range of immune parameters, such as the number of red blood cells and peripheral blood mononuclear cells as well as the level of critical immune mediators, such as cytokines, undergo daily fluctuations. Current experimental data indicate that circadian information reaches immune tissues mainly through diurnal patterns of autonomic and endocrine rhythms. In addition, immune factors such as cytokines can also influence the phase of the circadian clock, providing bidirectional flow of circadian information between the neuroendocrine and immune systems. This network of neuroendocrine-immune interactions consists of complexly integrated molecular feedback and feedforward loops that function in synchrony in order to optimize immune response. Chronic stress can disrupt this intrinsic orchestration, as several endocrine signals of chronically stressed patients present blunted rhythmic characteristics. Reprogramming of biological rhythms has recently gained much attention as a potent method to leverage homeostatic circadian controls to ultimately improve clinical outcomes. Elucidation of the intrinsic properties of such complex systems and optimization of intervention strategies require not only an accurate identification of the signaling pathways that mediate host responses, but also a system-level description and evaluation. PMID:23006670

  20. 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.

  1. 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

    2014-06-10

    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.

  2. 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.

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

    PubMed

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

    2016-01-01

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

  4. Generating new blood flow: integrating developmental biology and tissue engineering.

    PubMed

    Krenning, Guido; Moonen, Jan-Renier A J; van Luyn, Marja J A; Harmsen, Martin C

    2008-11-01

    Vascular tissue engineering aims to restore blood flow by seeding artificial tubular scaffolds with endothelial and smooth muscle cells, thus creating bioartificial blood vessels. Herein, the progenitors of smooth muscle and endothelial cells hold great promise because they efficiently differentiate and harbor longevity. In this review, we describe a novel tissue engineering approach that uses current insights from developmental biology, that is, progenitor cell plasticity, and the latest advances in biomaterial design. We focus specifically on developmental processes that regulate progenitor cell (trans)differentiation and offer a platform for the integration of these molecular clues into biomaterial design. We propose a novel engineering paradigm for the creation of a small-diameter blood vessel wherein progenitor cell differentiation and tissue organization are instructed by the biomaterial solely. With this review, we emphasize the power of integrating developmental biology and material science for vascular tissue engineering. PMID:19345319

  5. Genomes, Phylogeny, and Evolutionary Systems Biology

    SciTech Connect

    Medina, Monica

    2005-03-25

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

  6. Integrated Learning Management Systems

    ERIC Educational Resources Information Center

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

    2004-01-01

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

  7. The emergence of modularity in biological systems

    NASA Astrophysics Data System (ADS)

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

    2011-06-01

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

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

    PubMed Central

    2011-01-01

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

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

    PubMed

    Carbonell, Pablo; Currin, Andrew; Jervis, Adrian J; Rattray, Nicholas J W; Swainston, Neil; Yan, Cunyu; Takano, Eriko; Breitling, Rainer

    2016-08-27

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

  10. Biological control in greenhouse systems.

    PubMed

    Paulitz, T C; Bélanger, R R

    2001-01-01

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

  11. Developmental systems biology flourishing on new technologies.

    PubMed

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

    2008-10-01

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

  12. The Evolving Contribution of Mass Spectrometry to Integrative Structural Biology

    NASA Astrophysics Data System (ADS)

    Faini, Marco; Stengel, Florian; Aebersold, Ruedi

    2016-06-01

    Protein complexes are key catalysts and regulators for the majority of cellular processes. Unveiling their assembly and structure is essential to understanding their function and mechanism of action. Although conventional structural techniques such as X-ray crystallography and NMR have solved the structure of important protein complexes, they cannot consistently deal with dynamic and heterogeneous assemblies, limiting their applications to small scale experiments. A novel methodological paradigm, integrative structural biology, aims at overcoming such limitations by combining complementary data sources into a comprehensive structural model. Recent applications have shown that a range of mass spectrometry (MS) techniques are able to generate interaction and spatial restraints (cross-linking MS) information on native complexes or to study the stoichiometry and connectivity of entire assemblies (native MS) rapidly, reliably, and from small amounts of substrate. Although these techniques by themselves do not solve structures, they do provide invaluable structural information and are thus ideally suited to contribute to integrative modeling efforts. The group of Brian Chait has made seminal contributions in the use of mass spectrometric techniques to study protein complexes. In this perspective, we honor the contributions of the Chait group and discuss concepts and milestones of integrative structural biology. We also review recent examples of integration of structural MS techniques with an emphasis on cross-linking MS. We then speculate on future MS applications that would unravel the dynamic nature of protein complexes upon diverse cellular states.

  13. The Evolving Contribution of Mass Spectrometry to Integrative Structural Biology

    NASA Astrophysics Data System (ADS)

    Faini, Marco; Stengel, Florian; Aebersold, Ruedi

    2016-04-01

    Protein complexes are key catalysts and regulators for the majority of cellular processes. Unveiling their assembly and structure is essential to understanding their function and mechanism of action. Although conventional structural techniques such as X-ray crystallography and NMR have solved the structure of important protein complexes, they cannot consistently deal with dynamic and heterogeneous assemblies, limiting their applications to small scale experiments. A novel methodological paradigm, integrative structural biology, aims at overcoming such limitations by combining complementary data sources into a comprehensive structural model. Recent applications have shown that a range of mass spectrometry (MS) techniques are able to generate interaction and spatial restraints (cross-linking MS) information on native complexes or to study the stoichiometry and connectivity of entire assemblies (native MS) rapidly, reliably, and from small amounts of substrate. Although these techniques by themselves do not solve structures, they do provide invaluable structural information and are thus ideally suited to contribute to integrative modeling efforts. The group of Brian Chait has made seminal contributions in the use of mass spectrometric techniques to study protein complexes. In this perspective, we honor the contributions of the Chait group and discuss concepts and milestones of integrative structural biology. We also review recent examples of integration of structural MS techniques with an emphasis on cross-linking MS. We then speculate on future MS applications that would unravel the dynamic nature of protein complexes upon diverse cellular states.

  14. The Evolving Contribution of Mass Spectrometry to Integrative Structural Biology.

    PubMed

    Faini, Marco; Stengel, Florian; Aebersold, Ruedi

    2016-06-01

    Protein complexes are key catalysts and regulators for the majority of cellular processes. Unveiling their assembly and structure is essential to understanding their function and mechanism of action. Although conventional structural techniques such as X-ray crystallography and NMR have solved the structure of important protein complexes, they cannot consistently deal with dynamic and heterogeneous assemblies, limiting their applications to small scale experiments. A novel methodological paradigm, integrative structural biology, aims at overcoming such limitations by combining complementary data sources into a comprehensive structural model. Recent applications have shown that a range of mass spectrometry (MS) techniques are able to generate interaction and spatial restraints (cross-linking MS) information on native complexes or to study the stoichiometry and connectivity of entire assemblies (native MS) rapidly, reliably, and from small amounts of substrate. Although these techniques by themselves do not solve structures, they do provide invaluable structural information and are thus ideally suited to contribute to integrative modeling efforts. The group of Brian Chait has made seminal contributions in the use of mass spectrometric techniques to study protein complexes. In this perspective, we honor the contributions of the Chait group and discuss concepts and milestones of integrative structural biology. We also review recent examples of integration of structural MS techniques with an emphasis on cross-linking MS. We then speculate on future MS applications that would unravel the dynamic nature of protein complexes upon diverse cellular states. Graphical Abstract ᅟ. PMID:27056566

  15. Systems Biology and Ecology of Streamlined Bacterioplankton

    NASA Astrophysics Data System (ADS)

    Giovannoni, S. J.

    2014-12-01

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

  16. Systems Biology Analysis of Heterocellular Signaling.

    PubMed

    Tape, Christopher J

    2016-08-01

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

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

    ERIC Educational Resources Information Center

    Tribe, Michael; Pritchard, Alan J.

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

  18. Which coordinate system for modelling path integration?

    PubMed

    Vickerstaff, Robert J; Cheung, Allen

    2010-03-21

    Path integration is a navigation strategy widely observed in nature where an animal maintains a running estimate, called the home vector, of its location during an excursion. Evidence suggests it is both ancient and ubiquitous in nature, and has been studied for over a century. In that time, canonical and neural network models have flourished, based on a wide range of assumptions, justifications and supporting data. Despite the importance of the phenomenon, consensus and unifying principles appear lacking. A fundamental issue is the neural representation of space needed for biological path integration. This paper presents a scheme to classify path integration systems on the basis of the way the home vector records and updates the spatial relationship between the animal and its home location. Four extended classes of coordinate systems are used to unify and review both canonical and neural network models of path integration, from the arthropod and mammalian literature. This scheme demonstrates analytical equivalence between models which may otherwise appear unrelated, and distinguishes between models which may superficially appear similar. A thorough analysis is carried out of the equational forms of important facets of path integration including updating, steering, searching and systematic errors, using each of the four coordinate systems. The type of available directional cue, namely allothetic or idiothetic, is also considered. It is shown that on balance, the class of home vectors which includes the geocentric Cartesian coordinate system, appears to be the most robust for biological systems. A key conclusion is that deducing computational structure from behavioural data alone will be difficult or impossible, at least in the absence of an analysis of random errors. Consequently it is likely that further theoretical insights into path integration will require an in-depth study of the effect of noise on the four classes of home vectors. PMID:19962387

  19. Potential Role of Atomic Force Microscopy in Systems Biology

    PubMed Central

    Ramachandran, Srinivasan; Arce, Fernando Teran; Lal, Ratnesh

    2011-01-01

    Systems biology is a quantitative approach for understanding a biological system at its global level through systematic perturbation and integrated analysis of all its components. Simultaneous acquisition of information datasets pertaining to the system components (e.g., genome, proteome) is essential to implement this approach. There are limitations to such an approach in measuring gene expression levels and accounting for all proteins in the system. The success of genomic studies is critically dependent on PCR for its amplification, but PCR is very uneven in amplifying the samples, ineffective in scarce samples and unreliable in low copy number transcripts. On the other hand, lack of amplifying techniques for proteins critically limits their identification to only a small fraction of high concentration proteins. Atomic force microscopy (AFM), AFM cantilever sensors and AFM force spectroscopy in particular, could address these issues directly. In this article, we reviewed and assessed their potential role in systems biology. PMID:21766465

  20. Potential role of atomic force microscopy in systems biology.

    PubMed

    Ramachandran, Srinivasan; Teran Arce, Fernando; Lal, Ratnesh

    2011-01-01

    Systems biology is a quantitative approach for understanding a biological system at its global level through systematic perturbation and integrated analysis of all its components. Simultaneous acquisition of information data sets pertaining to the system components (e.g., genome, proteome) is essential to implement this approach. There are limitations to such an approach in measuring gene expression levels and accounting for all proteins in the system. The success of genomic studies is critically dependent on polymerase chain reaction (PCR) for its amplification, but PCR is very uneven in amplifying the samples, ineffective in scarce samples and unreliable in low copy number transcripts. On the other hand, lack of amplifying techniques for proteins critically limits their identification to only a small fraction of high concentration proteins. Atomic force microscopy (AFM), AFM cantilever sensors, and AFM force spectroscopy in particular, could address these issues directly. In this article, we reviewed and assessed their potential role in systems biology. PMID:21766465

  1. Programmable temperature control system for biological materials

    NASA Technical Reports Server (NTRS)

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

    1982-01-01

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

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

    PubMed Central

    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 biology. With the assistance of an HHMI-funded mini-grant, led by Karl Joplin of East Tennessee State University, and support in institutional HHMI grants at Emory and University of Delaware, these institutions held a series of summer institutes and workshops to document progress toward and address the challenges of implementing a more quantitative approach to undergraduate biology education. This report summarizes the results of the four summer institutes (2007–2010). The group developed four draft white papers, a wiki site, and a listserv. One major outcome of these meetings is this issue of CBE—Life Sciences Education, which resulted from proposals at our 2008 meeting and a January 2009 planning session. Many of the papers in this issue emerged from or were influenced by these meetings. PMID:20810946

  3. Integrated Workforce Modeling System

    NASA Technical Reports Server (NTRS)

    Moynihan, Gary P.

    2000-01-01

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

  4. Integrated multiplexed capillary electrophoresis system

    SciTech Connect

    Yeung, Edward S.; Tan, Hongdong

    2002-05-14

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

  5. Dovetailing biology and chemistry: integrating the Gene Ontology with the ChEBI chemical ontology

    PubMed Central

    2013-01-01

    Background The Gene Ontology (GO) facilitates the description of the action of gene products in a biological context. Many GO terms refer to chemical entities that participate in biological processes. To facilitate accurate and consistent systems-wide biological representation, it is necessary to integrate the chemical view of these entities with the biological view of GO functions and processes. We describe a collaborative effort between the GO and the Chemical Entities of Biological Interest (ChEBI) ontology developers to ensure that the representation of chemicals in the GO is both internally consistent and in alignment with the chemical expertise captured in ChEBI. Results We have examined and integrated the ChEBI structural hierarchy into the GO resource through computationally-assisted manual curation of both GO and ChEBI. Our work has resulted in the creation of computable definitions of GO terms that contain fully defined semantic relationships to corresponding chemical terms in ChEBI. Conclusions The set of logical definitions using both the GO and ChEBI has already been used to automate aspects of GO development and has the potential to allow the integration of data across the domains of biology and chemistry. These logical definitions are available as an extended version of the ontology from http://purl.obolibrary.org/obo/go/extensions/go-plus.owl. PMID:23895341

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

    PubMed Central

    Bunyavanich, Supinda; Schadt, Eric E.

    2014-01-01

    Systems biology is an approach to understanding living systems that focuses on modeling diverse types of high-dimensional interactions to develop a more comprehensive understanding of complex phenotypes manifested by the system. High throughput molecular, cellular, and physiologic profiling of populations is coupled with bioinformatic and computational techniques to identify new functional roles for genes, regulatory elements, and metabolites in the context of the molecular networks that define biological processes associated with system physiology. Given the complexity and heterogeneity of asthma and allergic diseases, a systems biology approach is attractive, as it has the potential to model the myriad connections and interdependencies between genetic predisposition, environmental perturbations, regulatory intermediaries, and molecular sequelae that ultimately lead to diverse disease phenotypes and treatment responses across individuals. The increasing availability of high-throughput technologies has enabled system-wide profiling of the genome, transcriptome, epigenome, microbiome, and metabolome, providing fodder for systems biology approaches to examine asthma and allergy at a more holistic level. In this article, we review the technologies and approaches for system-wide profiling as well as their more recent applications to asthma and allergy. We discuss approaches for integrating multiscale data through network analyses and provide perspective on how individually-captured health profiles will contribute to more accurate systems biology views of asthma and allergy. PMID:25468194

  7. Functional Translational Readthrough: A Systems Biology Perspective.

    PubMed

    Schueren, Fabian; Thoms, Sven

    2016-08-01

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

  8. Functional Translational Readthrough: A Systems Biology Perspective

    PubMed Central

    Schueren, Fabian

    2016-01-01

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

  9. Bioferroelectricity and optical properties of biological systems

    NASA Astrophysics Data System (ADS)

    Bystrov, Vladimir; Bystrova, Natalia

    2003-08-01

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

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

    PubMed Central

    Fong, Stephen S.

    2014-01-01

    Metabolic engineering modifies cellular function to address various biochemical applications. Underlying metabolic engineering efforts are a host of tools and knowledge that are integrated to enable successful outcomes. Concurrent development of computational and experimental tools has enabled different approaches to metabolic engineering. One approach is to leverage knowledge and computational tools to prospectively predict designs to achieve the desired outcome. An alternative approach is to utilize combinatorial experimental tools to empirically explore the range of cellular function and to screen for desired traits. This mini-review focuses on computational systems biology and synthetic biology tools that can be used in combination for prospective in silico strain design. PMID:25379141

  11. Digital system bus integrity

    NASA Technical Reports Server (NTRS)

    Eldredge, Donald; Hitt, Ellis F.

    1987-01-01

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

  12. Voice integrated systems

    NASA Technical Reports Server (NTRS)

    Curran, P. Mike

    1977-01-01

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

  13. Integrated Communication Systems.

    ERIC Educational Resources Information Center

    Simpson, Ward

    2003-01-01

    Describes the Internet-based information system that has provided effective communications and reporting for the upgrade to K-12 schools in Scottsdale, Arizona. The Website and software applications created valuable communications in the construction process and improved reporting on progress. (SLD)

  14. Intelligent Integrated System Health Management

    NASA Technical Reports Server (NTRS)

    Figueroa, Fernando

    2012-01-01

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

  15. Human System Integration: Regulatory Analysis

    NASA Technical Reports Server (NTRS)

    2005-01-01

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

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

    PubMed

    Mazzocchi, Fulvio

    2012-01-01

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

  17. Introduction to Network Analysis in Systems Biology

    PubMed Central

    Ma’ayan, Avi

    2011-01-01

    This Teaching Resource provides lecture notes, slides, and a problem set for a set of three lectures from a course entitled “Systems Biology: Biomedical Modeling.” The materials are from three separate lectures introducing applications of graph theory and network analysis in systems biology. The first lecture describes different types of intracellular networks, methods for constructing biological networks, and different types of graphs used to represent regulatory intracellular networks. The second lecture surveys milestones and key concepts in network analysis by introducing topological measures, random networks, growing network models, and topological observations from molecular biological systems abstracted to networks. The third lecture discusses methods for analyzing lists of genes and experimental data in the context of prior knowledge networks to make predictions. PMID:21917719

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

  19. Systems biology of natural SIV infections

    PubMed Central

    Bosinger, Steven E.; Jacquelin, Béatrice; Benecke, Arndt; Silvestri, Guido; Müller-Trutwin, Michaela

    2012-01-01

    Purpose of review A key factor driving AIDS-associated immunopathogenesis is chronic immune activation. SIV infection of African natural host species leads to high viremia, but low immune activation and absence of disease. Considerable progress in our understanding of pathological immune activation have come from comparative studies of SIV infection in pathogenic Asian macaque species and natural hosts. The focus of this review is to highlight recent work on the natural host model using high throughput genomics. Recent findings Several groups have independently conducted microarray gene expression profiling comparing in vivo SIV infection in natural and non-natural hosts. A consistent finding between these studies is that both pathogenic SIV infection of macaques and nonpathogenic infections of natural hosts have strong induction of interferon-stimulated genes (ISGs) early on, but a key difference was that natural hosts downmodulated the interferon response rapidly after acute infection. The development of new genome-based resources for further study of the natural host model is discussed. Summary Initial efforts using high throughput biology to study SIV infection of natural hosts have effectively identified the ability of natural hosts to resolve interferon responses and immune activation. Further application of ‘omic’-based technologies coupled with integrative systems-based analysis should continue to yield progress. PMID:22134342

  20. Integrated agricultural energy system

    NASA Astrophysics Data System (ADS)

    Taylor, R. M.

    1985-08-01

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

  1. Nonequilibrium Thermodynamics in Biological Systems

    NASA Astrophysics Data System (ADS)

    Aoki, I.

    2005-12-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2005-04-01

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

  3. Integrated Building Management System (IBMS)

    SciTech Connect

    Anita Lewis

    2012-07-01

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

  4. Method of measurement in biological systems

    DOEpatents

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

    1994-12-27

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

  5. Method of measurement in biological systems

    DOEpatents

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

    1994-01-01

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

  6. Method of measurement in biological systems

    DOEpatents

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

    1993-05-11

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

  7. Integrated high power VCSEL systems

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  8. Symplectic integrators for spin systems.

    PubMed

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

    2014-06-01

    We present a symplectic integrator, based on the implicit midpoint method, for classical spin systems where each spin is a unit vector in R{3}. Unlike splitting methods, it is defined for all Hamiltonians and is O(3)-equivariant, i.e., coordinate-independent. It is a rare example of a generating function for symplectic maps of a noncanonical phase space. It yields a new integrable discretization of the spinning top. PMID:25019718

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

    PubMed Central

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

    2014-01-01

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

  10. A Systems Biology Approach to Iron Metabolism

    PubMed Central

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

    2015-01-01

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

  11. Aquaporin Biology and Nervous System

    PubMed Central

    Barbara, Buffoli

    2010-01-01

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

  12. Networks’ Characteristics Matter for Systems Biology

    PubMed Central

    Rider, Andrew K.; Milenković, Tijana; Siwo, Geoffrey H.; Pinapati, Richard S.; Emrich, Scott J.; Ferdig, Michael T.; Chawla, Nitesh V.

    2015-01-01

    A fundamental goal of systems biology is to create models that describe relationships between biological components. Networks are an increasingly popular approach to this problem. However, a scientist interested in modeling biological (e.g., gene expression) data as a network is quickly confounded by the fundamental problem: how to construct the network? It is fairly easy to construct a network, but is it the network for the problem being considered? This is an important problem with three fundamental issues: How to weight edges in the network in order to capture actual biological interactions? What is the effect of the type of biological experiment used to collect the data from which the network is constructed? How to prune the weighted edges (or what cut-off to apply)? Differences in the construction of networks could lead to different biological interpretations. Indeed, we find that there are statistically significant dissimilarities in the functional content and topology between gene co-expression networks constructed using different edge weighting methods, data types, and edge cut-offs. We show that different types of known interactions, such as those found through Affinity Capture-Luminescence or Synthetic Lethality experiments, appear in significantly varying amounts in networks constructed in different ways. Hence, we demonstrate that different biological questions may be answered by the different networks. Consequently, we posit that the approach taken to build a network can be matched to biological questions to get targeted answers. More study is required to understand the implications of different network inference approaches and to draw reliable conclusions from networks used in the field of systems biology. PMID:26500772

  13. Numerical simulations and modeling for stochastic biological systems with jumps

    NASA Astrophysics Data System (ADS)

    Zou, Xiaoling; Wang, Ke

    2014-05-01

    This paper gives a numerical method to simulate sample paths for stochastic differential equations (SDEs) driven by Poisson random measures. It provides us a new approach to simulate systems with jumps from a different angle. The driving Poisson random measures are assumed to be generated by stationary Poisson point processes instead of Lévy processes. Methods provided in this paper can be used to simulate SDEs with Lévy noise approximately. The simulation is divided into two parts: the part of jumping integration is based on definition without approximation while the continuous part is based on some classical approaches. Biological explanations for stochastic integrations with jumps are motivated by several numerical simulations. How to model biological systems with jumps is showed in this paper. Moreover, method of choosing integrands and stationary Poisson point processes in jumping integrations for biological models are obtained. In addition, results are illustrated through some examples and numerical simulations. For some examples, earthquake is chose as a jumping source which causes jumps on the size of biological population.

  14. The Systems Librarian: Re-Integrating the "Integrated" Library System

    ERIC Educational Resources Information Center

    Breeding, Marshall

    2005-01-01

    This article discusses the current environment of the ILS (Integrated Library System) plus add-ons tailored for electronic content and its future. It suggests that while the ILS may be mature, the supplemental products are not and the linkages among them are even less so. On the technical front, the recent interest in Web services gives reason to…

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

    PubMed

    Maunder, R

    1996-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  17. Interactive analysis of systems biology molecular expression data

    PubMed Central

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

    2008-01-01

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

  18. Intelligent systems technology infrastructure for integrated systems

    NASA Technical Reports Server (NTRS)

    Lum, Henry, Jr.

    1991-01-01

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

  19. Gendering Genetics: Biological Contingencies in the Protective Effects of Social Integration for Men and Women.

    PubMed

    Perry, Brea L

    2016-05-01

    Evidence that social and biological processes are intertwined in producing health and human behavior is rapidly accumulating. Using a feminist approach, this research explores how gender moderates the interaction between biological processes and men's and women's behavioral and emotional responses to similar social environments. Using data from the Collaborative Study on the Genetics of Alcoholism, the influence of gender, social integration, and genetic risk on nicotine and alcohol dependence is examined. Three-way interaction models reveal gender-specific moderation of interactions between genetic risk score and social integration. Namely, being currently married and reporting positive social psychological integration are predictive of reduced risk of nicotine dependence among men with genetic susceptibility to strong nicotine cravings in the presence of social cues like stress. In contrast, the protective effects of marital status and social integration are substantially attenuated and absent, respectively, among women with high-risk genotypes. This pattern reflects the dualism (i.e., simultaneous costs and benefits) inherent in social integration for women, which may disproportionately affect those with a genetic sensitivity to stress. These findings contest the notion of genotype as static biological hardwiring that is independent from social and cultural systems of gender difference. PMID:27416652

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

    PubMed

    Voit, E O; Kemp, M L

    2011-01-01

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

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

    PubMed Central

    2014-01-01

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

  2. Microbiological evaluation of the mobile biological isolator system

    NASA Technical Reports Server (NTRS)

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

    1979-01-01

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

  3. Systems Biology Approach to Developing “Systems Therapeutics”

    PubMed Central

    2014-01-01

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

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

    PubMed

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

    2012-01-01

    Electronic Integrated Disease Surveillance System (EIDSS) has been used to strengthen and support monitoring and prevention of dangerous diseases within One Health concept by integrating veterinary and human surveillance, passive and active approaches, case-based records including disease-specific clinical data based on standardised case definitions and aggregated data, laboratory data including sample tracking linked to each case and event with test results and epidemiological investigations. Information was collected and shared in secure way by different means: through the distributed nodes which are continuously synchronised amongst each other, through the web service, through the handheld devices. Electronic Integrated Disease Surveillance System provided near real time information flow that has been then disseminated to the appropriate organisations in a timely manner. It has been used for comprehensive analysis and visualisation capabilities including real time mapping of case events as these unfold enhancing decision making. Electronic Integrated Disease Surveillance System facilitated countries to comply with the IHR 2005 requirements through a data transfer module reporting diseases electronically to the World Health Organisation (WHO) data center as well as establish authorised data exchange with other electronic system using Open Architecture approach. Pathogen Asset Control System (PACS) has been used for accounting, management and control of biological agent stocks. Information on samples and strains of any kind throughout their entire lifecycle has been tracked in a comprehensive and flexible solution PACS.Both systems have been used in a combination and individually. Electronic Integrated Disease Surveillance System and PACS are currently deployed in the Republics of Kazakhstan, Georgia and Azerbaijan as a part of the Cooperative Biological Engagement Program (CBEP) sponsored by the US Defense Threat Reduction Agency (DTRA). PMID:23327375

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

    NASA Astrophysics Data System (ADS)

    Tsiganov, A. V.

    2016-03-01

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

  6. A framework for integrating thermal biology into fragmentation research.

    PubMed

    Tuff, K T; Tuff, T; Davies, K F

    2016-04-01

    Habitat fragmentation changes thermal conditions in remnant patches, and thermal conditions strongly influence organism morphology, distribution, and activity patterns. However, few studies explore temperature as a mechanism driving ecological responses to fragmentation. Here we offer a conceptual framework that integrates thermal biology into fragmentation research to better understand individual, species, community, and ecosystem-level responses to fragmentation. Specifically, the framework addresses how fragmentation changes temperature and how the effects of those temperature changes spread through the ecosystem, from organism response via thermal sensitivity, to changes in species distribution and activity patterns, to shifts in community structure following species' responses, and ultimately to changes in ecosystem functions. We place a strong emphasis on future research directions by outlining "Critical gaps" for each step of the framework. Empirical efforts to apply and test this framework promise new understanding of fragmentation's ecological consequences and new strategies for conservation in an increasingly fragmented and warmer world. PMID:26892491

  7. Semantic Annotation for Biological Information Retrieval System

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

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

    2010-09-30

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

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

    PubMed

    Prathipati, Philip; Mizuguchi, Kenji

    2016-01-01

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

  10. Integrative Biology Identifies Shared Transcriptional Networks in CKD

    PubMed Central

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

    2014-01-01

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

  11. Lunar materials processing system integration

    NASA Technical Reports Server (NTRS)

    Sherwood, Brent

    1992-01-01

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

  12. Lunar materials processing system integration

    NASA Astrophysics Data System (ADS)

    Sherwood, Brent

    1992-02-01

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

  13. Designing the Cloud-based DOE Systems Biology Knowledgebase

    SciTech Connect

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

    2011-09-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-06-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2008-03-01

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

  17. Integrated Systems Health Management for Intelligent Systems

    NASA Technical Reports Server (NTRS)

    Figueroa, Fernando; Melcher, Kevin

    2011-01-01

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

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

    PubMed Central

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

    2015-01-01

    Biological wastewater treatment plants harbour diverse and complex microbial communities which prominently serve as models for microbial ecology and mixed culture biotechnological processes. Integrated omic analyses (combined metagenomics, metatranscriptomics, metaproteomics and metabolomics) are currently gaining momentum towards providing enhanced understanding of community structure, function and dynamics in situ as well as offering the potential to discover novel biological functionalities within the framework of Eco-Systems Biology. The integration of information from genome to metabolome allows the establishment of associations between genetic potential and final phenotype, a feature not realizable by only considering single ‘omes’. Therefore, in our opinion, integrated omics will become the future standard for large-scale characterization of microbial consortia including those underpinning biological wastewater treatment processes. Systematically obtained time and space-resolved omic datasets will allow deconvolution of structure–function relationships by identifying key members and functions. Such knowledge will form the foundation for discovering novel genes on a much larger scale compared with previous efforts. In general, these insights will allow us to optimize microbial biotechnological processes either through better control of mixed culture processes or by use of more efficient enzymes in bioengineering applications. PMID:25678254

  19. Integrated anaerobic/aerobic biological treatment for intensive swine production.

    PubMed

    Bortone, Giuseppe

    2009-11-01

    Manure processing could help farmers to effectively manage nitrogen (N) surplus load. Many pig farms have to treat wastewater. Piggery wastewater treatment is a complex challenge, due to the high COD and N concentrations and low C/N ratio. Anaerobic digestion (AD) could be a convenient pre-treatment, particularly from the energetic view point and farm income, but this causes further reduction of C/N ratio and makes denitrification difficult. N removal can only be obtained integrating anaerobic/aerobic treatment by taking into account the best use of electron donors. Experiences gained in Italy during development of integrated biological treatment approaches for swine manure, from bench to full scale, are reported in this paper. Solid/liquid separation as pre-treatment of raw manure is an efficient strategy to facilitate liquid fraction treatment without significantly lowering C/N ratio. In Italy, two full scale SBRs showed excellent efficiency and reliability. Current renewable energy policy and incentives makes economically attractive the application of AD to the separated solid fraction using high solid anaerobic digester (HSAD) technology. Economic evaluation showed that energy production can reduce costs up to 60%, making sustainable the overall treatment. PMID:19135363

  20. Studies on Semantic Systems Chemical Biology

    ERIC Educational Resources Information Center

    Chen, Bin

    2012-01-01

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

  1. Modular microfluidic system for biological sample preparation

    SciTech Connect

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

    2015-09-29

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

  2. Promoting Systems Thinking through Biology Lessons

    ERIC Educational Resources Information Center

    Riess, Werner; Mischo, Christoph

    2010-01-01

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

  3. Radiological/biological/aerosol removal system

    DOEpatents

    Haslam, Jeffery J

    2015-03-17

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

  4. Glucose Disappearance in Biological Treatment Systems

    PubMed Central

    Jeris, John S.; Cardenas, Raul R.

    1966-01-01

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

  5. Microbial Stress Tolerance for Biofuels: Systems Biology

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed

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

    2016-02-01

    The overall aim of physiological research is to understand how living systems function in an integrative manner. Consequently, the discipline of physiology has since its infancy attempted to link multiple levels of biological organization. Increasingly this has involved mathematical and computational approaches, typically to model a small number of components spanning several levels of biological organization. With the advent of "omics" technologies, which can characterize the molecular state of a cell or tissue (intended as the level of expression and/or activity of its molecular components), the number of molecular components we can quantify has increased exponentially. Paradoxically, the unprecedented amount of experimental data has made it more difficult to derive conceptual models underlying essential mechanisms regulating mammalian physiology. We present an overview of state-of-the-art methods currently used to identifying biological networks underlying genomewide responses. These are based on a data-driven approach that relies on advanced computational methods designed to "learn" biology from observational data. In this review, we illustrate an application of these computational methodologies using a case study integrating an in vivo model representing the transcriptional state of hypoxic skeletal muscle with a clinical study representing muscle wasting in chronic obstructive pulmonary disease patients. The broader application of these approaches to modeling multiple levels of biological data in the context of modern physiology is discussed. PMID:26542523

  7. Integrated Aeropropulsion Control System Design

    NASA Technical Reports Server (NTRS)

    Lin, C. -F.; Hurley, Francis X.; Huang, Jie; Hadaegh, F. Y.

    1996-01-01

    %T Integrated Aeropropulsion Control System Design%A C-F. Lin%A Francis X. Hurley%A Jie Huang%A F. Y. Hadaegh%J International Conference on Control and Information(psi)995%C Hong Kong%D June 1995%K aeropropulsion, control, system%U http://jpltrs.jpl.nasa.gov/1995/95-0658.pdfAn integrated intelligent control approach is proposed to design a high performance control system for aeropropulsion systems based on advanced sensor processing, nonlinear control and neural fuzzy control integration. Our approach features the following innovations:??e complexity and uncertainty issues are addressed via the distributed parallel processing, learning, and online reoptimization properties of neural networks.??e nonlinear dynamics and the severe coupling can be naturally incorporated into the design framework.??e knowledge base and decision making logic furnished by fuzzy systems leads to a human intelligence enhanced control scheme.In addition, fault tolerance, health monitoring and reconfigurable control strategies will be accommodated by this approach to ensure stability, graceful degradation and reoptimization in the case of failures, malfunctions and damage.!.

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

    PubMed Central

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

    2012-01-01

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

  9. In Vitro Electrochemistry of Biological Systems

    NASA Astrophysics Data System (ADS)

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

    2008-07-01

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

  10. Systems biology driven software design for the research enterprise

    PubMed Central

    Boyle, John; Cavnor, Christopher; Killcoyne, Sarah; Shmulevich, Ilya

    2008-01-01

    Background In systems biology, and many other areas of research, there is a need for the interoperability of tools and data sources that were not originally designed to be integrated. Due to the interdisciplinary nature of systems biology, and its association with high throughput experimental platforms, there is an additional need to continually integrate new technologies. As scientists work in isolated groups, integration with other groups is rarely a consideration when building the required software tools. Results We illustrate an approach, through the discussion of a purpose built software architecture, which allows disparate groups to reuse tools and access data sources in a common manner. The architecture allows for: the rapid development of distributed applications; interoperability, so it can be used by a wide variety of developers and computational biologists; development using standard tools, so that it is easy to maintain and does not require a large development effort; extensibility, so that new technologies and data types can be incorporated; and non intrusive development, insofar as researchers need not to adhere to a pre-existing object model. Conclusion By using a relatively simple integration strategy, based upon a common identity system and dynamically discovered interoperable services, a light-weight software architecture can become the focal point through which scientists can both get access to and analyse the plethora of experimentally derived data. PMID:18578887

  11. Systems Biology, Bioinformatics, and Biomarkers in Neuropsychiatry

    PubMed Central

    Alawieh, Ali; Zaraket, Fadi A.; Li, Jian-Liang; Mondello, Stefania; Nokkari, Amaly; Razafsha, Mahdi; Fadlallah, Bilal; Boustany, Rose-Mary; Kobeissy, Firas H.

    2012-01-01

    Although neuropsychiatric (NP) disorders are among the top causes of disability worldwide with enormous financial costs, they can still be viewed as part of the most complex disorders that are of unknown etiology and incomprehensible pathophysiology. The complexity of NP disorders arises from their etiologic heterogeneity and the concurrent influence of environmental and genetic factors. In addition, the absence of rigid boundaries between the normal and diseased state, the remarkable overlap of symptoms among conditions, the high inter-individual and inter-population variations, and the absence of discriminative molecular and/or imaging biomarkers for these diseases makes difficult an accurate diagnosis. Along with the complexity of NP disorders, the practice of psychiatry suffers from a “top-down” method that relied on symptom checklists. Although checklist diagnoses cost less in terms of time and money, they are less accurate than a comprehensive assessment. Thus, reliable and objective diagnostic tools such as biomarkers are needed that can detect and discriminate among NP disorders. The real promise in understanding the pathophysiology of NP disorders lies in bringing back psychiatry to its biological basis in a systemic approach which is needed given the NP disorders’ complexity to understand their normal functioning and response to perturbation. This approach is implemented in the systems biology discipline that enables the discovery of disease-specific NP biomarkers for diagnosis and therapeutics. Systems biology involves the use of sophisticated computer software “omics”-based discovery tools and advanced performance computational techniques in order to understand the behavior of biological systems and identify diagnostic and prognostic biomarkers specific for NP disorders together with new targets of therapeutics. In this review, we try to shed light on the need of systems biology, bioinformatics, and biomarkers in neuropsychiatry, and

  12. Engineering biological systems with synthetic RNA molecules

    PubMed Central

    Liang, Joe C.; Bloom, Ryan J.; Smolke, Christina D.

    2011-01-01

    RNA molecules play diverse functional roles in natural biological systems. There has been growing interest in designing synthetic RNA counterparts for programming biological function. The design of synthetic RNA molecules that exhibit diverse activities, including sensing, regulatory, information processing, and scaffolding activities, has highlighted the advantages of RNA as a programmable design substrate. Recent advances in implementing these engineered RNA molecules as key control elements in synthetic genetic networks are highlighting the functional relevance of this class of synthetic elements in programming cellular behaviors. PMID:21925380

  13. Fiber optic control system integration

    NASA Technical Reports Server (NTRS)

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

    1987-01-01

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

  14. Modeling autism: a systems biology approach

    PubMed Central

    2012-01-01

    Autism is the fastest growing developmental disorder in the world today. The prevalence of autism in the US has risen from 1 in 2500 in 1970 to 1 in 88 children today. People with autism present with repetitive movements and with social and communication impairments. These impairments can range from mild to profound. The estimated total lifetime societal cost of caring for one individual with autism is $3.2 million US dollars. With the rapid growth in this disorder and the great expense of caring for those with autism, it is imperative for both individuals and society that techniques be developed to model and understand autism. There is increasing evidence that those individuals diagnosed with autism present with highly diverse set of abnormalities affecting multiple systems of the body. To this date, little to no work has been done using a whole body systems biology approach to model the characteristics of this disorder. Identification and modelling of these systems might lead to new and improved treatment protocols, better diagnosis and treatment of the affected systems, which might lead to improved quality of life by themselves, and, in addition, might also help the core symptoms of autism due to the potential interconnections between the brain and nervous system with all these other systems being modeled. This paper first reviews research which shows that autism impacts many systems in the body, including the metabolic, mitochondrial, immunological, gastrointestinal and the neurological. These systems interact in complex and highly interdependent ways. Many of these disturbances have effects in most of the systems of the body. In particular, clinical evidence exists for increased oxidative stress, inflammation, and immune and mitochondrial dysfunction which can affect almost every cell in the body. Three promising research areas are discussed, hierarchical, subgroup analysis and modeling over time. This paper reviews some of the systems disturbed in autism and

  15. Information Integration from Semantically Heterogeneous Biological Data Sources.

    PubMed

    Caragea, Doina; Bao, Jie; Pathak, Jyotishman; Silvescu, Adrian; Andorf, Carson; Dobbs, Drena; Honavar, Vasant

    2005-08-26

    We present the first prototype of INDUS (Intelligent Data Understanding System), a federated, query-centric system for information integration and knowledge acquisition from distributed, semantically heterogeneous data sources that can be viewed (conceptually) as tables. INDUS employs ontologies and inter-ontology mappings, to enable a user to view a collection of such data sources (regardless of location, internal structure and query interfaces) as though they were a collection of tables structured according to an ontology supplied by the user. This allows INDUS to answer user queries against distributed, semantically heterogeneous data sources without the need for a centralized data warehouse or a common global ontology. PMID:20802821

  16. Light manipulation principles in biological photonic systems

    NASA Astrophysics Data System (ADS)

    Starkey, Tim; Vukusic, Pete

    2013-10-01

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

  17. Techniques for optimization of queries on integrated biological resources.

    PubMed

    Lacroix, Zoé; Raschid, Louiqa; Eckman, Barbara A

    2004-06-01

    Today, scientific data are inevitably digitized, stored in a wide variety of formats, and are accessible over the Internet. Scientific discovery increasingly involves accessing multiple heterogeneous data sources, integrating the results of complex queries, and applying further analysis and visualization applications in order to collect datasets of interest. Building a scientific integration platform to support these critical tasks requires accessing and manipulating data extracted from flat files or databases, documents retrieved from the Web, as well as data that are locally materialized in warehouses or generated by software. The lack of efficiency of existing approaches can significantly affect the process with lengthy delays while accessing critical resources or with the failure of the system to report any results. Some queries take so much time to be answered that their results are returned via email, making their integration with other results a tedious task. This paper presents several issues that need to be addressed to provide seamless and efficient integration of biomolecular data. Identified challenges include: capturing and representing various domain specific computational capabilities supported by a source including sequence or text search engines and traditional query processing; developing a methodology to acquire and represent semantic knowledge and metadata about source contents, overlap in source contents, and access costs; developing cost and semantics based decision support tools to select sources and capabilities, and to generate efficient query evaluation plans. PMID:15297988

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

    PubMed Central

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

    2013-01-01

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

  19. Complexity and Stability in Biological Systems

    NASA Astrophysics Data System (ADS)

    Demongeot, Jacques; Demetrius, Lloyd A.

    2015-06-01

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

  20. Advanced integrated life support system update

    NASA Technical Reports Server (NTRS)

    Whitley, Phillip E.

    1994-01-01

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

  1. Firefighters Integrated Response Equipment System

    NASA Technical Reports Server (NTRS)

    Kaplan, H.; Abeles, F.

    1978-01-01

    The Firefighters Integrated Response Equipment System (Project FIRES) is a joint National Fire Prevention and Control Administration (NFPCA)/National Aeronautics and Space Administration (NASA) program for the development of an 'ultimate' firefighter's protective ensemble. The overall aim of Project FIRES is to improve firefighter protection against hazards, such as heat, flame, smoke, toxic fumes, moisture, impact penetration, and electricity and, at the same time, improve firefighter performance by increasing maneuverability, lowering weight, and improving human engineering design of his protective ensemble.

  2. Controlled biological and biomimetic systems for landmine detection.

    PubMed

    Habib, Maki K

    2007-08-30

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-10-01

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

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

    PubMed Central

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

    2008-01-01

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

  6. Integrated nonthermal treatment system study

    SciTech Connect

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

    1997-01-01

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

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

    PubMed Central

    Rahnavard, Gholamali; Waldron, Levi; McIver, Lauren; Shafquat, Afrah; Franzosa, Eric A.; Miropolsky, Larissa; Sweeney, Christopher

    2015-01-01

    Modern biological research requires rapid, complex, and reproducible integration of multiple experimental results generated both internally and externally (e.g., from public repositories). Although large systematic meta-analyses are among the most effective approaches both for clinical biomarker discovery and for computational inference of biomolecular mechanisms, identifying, acquiring, and integrating relevant experimental results from multiple sources for a given study can be time-consuming and error-prone. To enable efficient and reproducible integration of diverse experimental results, we developed a novel approach for standardized acquisition and analysis of high-throughput and heterogeneous biological data. This allowed, first, novel biomolecular network reconstruction in human prostate cancer, which correctly recovered and extended the NFκB signaling pathway. Next, we investigated host-microbiome interactions. In less than an hour of analysis time, the system retrieved data and integrated six germ-free murine intestinal gene expression datasets to identify the genes most influenced by the gut microbiota, which comprised a set of immune-response and carbohydrate metabolism processes. Finally, we constructed integrated functional interaction networks to compare connectivity of peptide secretion pathways in the model organisms Escherichia coli, Bacillus subtilis, and Pseudomonas aeruginosa. PMID:26157642

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

    PubMed

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

    2016-06-17

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

  9. An integrated biological approach for treatment of cyanidation wastewater.

    PubMed

    Mekuto, Lukhanyo; Ntwampe, S K O; Akcil, Ata

    2016-11-15

    The cyanidation process has been, and still remains, a profitable and highly efficient process for the recovery of precious metals from ores. However, this process has contributed to environmental deterioration and potable water reserve contamination due to the discharge of poorly treated, or untreated, cyanide containing wastewater. The process produces numerous cyanide complexes in addition to the gold cyanocomplex. Additionally, the discharge constituents also include hydrogen cyanide (HCN) - metallic complexes with iron, nickel, copper, zinc, cobalt and other metals; thiocyanate (SCN); and cyanate (CNO). The fate of these complexes in the environment dictates the degree to which these species pose a threat to living organisms. This paper reviews the impact that the cyanidation process has on the environment, the ecotoxicology of the cyanidation wastewater and the treatment methods that are currently utilised to treat cyanidation wastewater. Furthermore, this review proposes an integrated biological approach for the treatment of the cyanidation process wastewater using microbial consortia that is insensitive and able to degrade cyanide species, in all stages of the proposed process. PMID:27424119

  10. TOPICAL REVIEW: Carbon nanomaterials in biological systems

    NASA Astrophysics Data System (ADS)

    Ke, Pu Chun; Qiao, Rui

    2007-09-01

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

  11. Origin of homochirality in biological systems

    NASA Astrophysics Data System (ADS)

    Toxvaerd, S.

    2005-01-01

    Models for segregation of racemic mixtures of chiral amphiphiles and lipophiles in aqueous solutions show that the amphiphiles with active isomerization kinetics can perform a spontaneous symmetry break during the segregation and self-assemble to homochiral matter. Based on physico-chemical facts, it is argued that D-glyceraldehyde, which was synthesized from the volatiles at the hydrothermal reactors at the origin of life, could be the origin of homochirality in biological systems.

  12. Autonomous power system: Integrated scheduling

    NASA Technical Reports Server (NTRS)

    Ringer, Mark J.

    1992-01-01

    The Autonomous Power System (APS) project at NASA Lewis Research Center is designed to demonstrate the abilities of integrated intelligent diagnosis, control and scheduling techniques to space power distribution hardware. The project consists of three elements: the Autonomous Power Expert System (APEX) for fault diagnosis, isolation, and recovery (FDIR), the Autonomous Intelligent Power Scheduler (AIPS) to determine system configuration, and power hardware (Brassboard) to simulate a space-based power system. Faults can be introduced into the Brassboard and in turn, be diagnosed and corrected by APEX and AIPS. The Autonomous Intelligent Power Scheduler controls the execution of loads attached to the Brassboard. Each load must be executed in a manner that efficiently utilizes available power and satisfies all load, resource, and temporal constraints. In the case of a fault situation on the Brassboard, AIPS dynamically modifies the existing schedule in order to resume efficient operation conditions. A database is kept of the power demand, temporal modifiers, priority of each load, and the power level of each source. AIPS uses a set of heuristic rules to assign start times and resources to each load based on load and resource constraints. A simple improvement engine based upon these heuristics is also available to improve the schedule efficiency. This paper describes the operation of the Autonomous Intelligent Power Scheduler as a single entity, as well as its integration with APEX and the Brassboard. Future plans are discussed for the growth of the Autonomous Intelligent Power Scheduler.

  13. Information Security and Integrity Systems

    NASA Technical Reports Server (NTRS)

    1990-01-01

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

  14. The Emergence of Modularity in Biological Systems

    PubMed Central

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

    2015-01-01

    In this review, we discuss modularity and hierarchy in biological systems. We review examples from protein structure, genetics, and biological networks of modular partitioning of the geometry of biological space. We review theories to explain modular organization of biology, with a focus on explaining how biology may spontaneously organize to a structured form. That is, we seek to explain how biology nucleated from among the many possibilities in chemistry. The emergence of modular organization of biological structure will be described as a symmetry-breaking phase transition, with modularity as the order parameter. Experimental support for this description will be reviewed. Examples will be presented from pathogen structure, metabolic networks, gene networks, and protein-protein interaction networks. Additional examples will be presented from ecological food networks, developmental pathways, physiology, and social networks. There once were two watchmakers, named Hora and Tempus, who manufactured very fine watches. Both of them were highly regarded, and the phones in their workshops rang frequently — new customers were constantly calling them. However, Hora prospered, while Tempus became poorer and poorer and finally lost his shop. What was the reason? The watches the men made consisted of about 1,000 parts each. Tempus had so constructed his that if he had one partly assembled and had to put it down — to answer the phone say— it immediately fell to pieces and had to be reassembled from the elements. The better the customers liked his watches, the more they phoned him, the more difficult it became for him to find enough uninterrupted time to finish a watch. The watches that Hora made were no less complex than those of Tempus. But he had designed them so that he could put together subassemblies of about ten elements each. Ten of these subassemblies, again, could be put together into a larger subassembly; and a system of ten of the latter sub

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

    SciTech Connect

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

    2013-01-01

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

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

    DOEpatents

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

    2000-08-01

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

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

    PubMed Central

    2011-01-01

    The natural environment for plants is composed of a complex set of abiotic stresses and biotic stresses. Plant responses to these stresses are equally complex. Systems biology approaches facilitate a multi-targeted approach by allowing one to identify regulatory hubs in complex networks. Systems biology takes the molecular parts (transcripts, proteins and metabolites) of an organism and attempts to fit them into functional networks or models designed to describe and predict the dynamic activities of that organism in different environments. In this review, research progress in plant responses to abiotic stresses is summarized from the physiological level to the molecular level. New insights obtained from the integration of omics datasets are highlighted. Gaps in our knowledge are identified, providing additional focus areas for crop improvement research in the future. PMID:22094046

  18. Integrated Energy System Dispatch Optimization

    SciTech Connect

    Firestone, Ryan; Stadler, Michael; Marnay, Chris

    2006-06-16

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

  19. Integrity in flight control systems

    NASA Technical Reports Server (NTRS)

    Kurzhals, P. R.; Deloach, R.

    1977-01-01

    In connection with advances in technology, mainly in the electronic area, aircraft flight control applications have evolved from simple pilot-relief autopilots to flight-critical and redundant fly-by-wire and active control systems. For flight-critical implementations which required accommodation of inflight failures, additional levels of redundancy were incorporated to provide fail-safe and fail-operative performance. The current status of flight control systems reliability is examined and high-reliability approaches are discussed. Attention is given to the design of ring laser gyros and magnetohydrodynamic rate sensors, redundancy configurations for component failure protection, improvements of hydraulic actuators made on the component level, integrated actuators, problems of software reliability, lightning considerations, and failure detection methods for component and system failures.

  20. Integrated risk information system (IRIS)

    SciTech Connect

    Tuxen, L.

    1990-12-31

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

  1. Systems Biology of the Vervet Monkey

    PubMed Central

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

    2013-01-01

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

  2. Integrated Systems Health Management for Intelligent Systems

    NASA Technical Reports Server (NTRS)

    Figueroa, Fernando; Melcher, Kevin

    2011-01-01

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

  3. Integrated multisensor perimeter detection systems

    NASA Astrophysics Data System (ADS)

    Kent, P. J.; Fretwell, P.; Barrett, D. J.; Faulkner, D. A.

    2007-10-01

    The report describes the results of a multi-year programme of research aimed at the development of an integrated multi-sensor perimeter detection system capable of being deployed at an operational site. The research was driven by end user requirements in protective security, particularly in threat detection and assessment, where effective capability was either not available or prohibitively expensive. Novel video analytics have been designed to provide robust detection of pedestrians in clutter while new radar detection and tracking algorithms provide wide area day/night surveillance. A modular integrated architecture based on commercially available components has been developed. A graphical user interface allows intuitive interaction and visualisation with the sensors. The fusion of video, radar and other sensor data provides the basis of a threat detection capability for real life conditions. The system was designed to be modular and extendable in order to accommodate future and legacy surveillance sensors. The current sensor mix includes stereoscopic video cameras, mmWave ground movement radar, CCTV and a commercially available perimeter detection cable. The paper outlines the development of the system and describes the lessons learnt after deployment in a pilot trial.

  4. Physical methods for investigating structural colours in biological systems

    PubMed Central

    Vukusic, P.; Stavenga, D.G.

    2009-01-01

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

  5. Engineering biological systems toward a sustainable bioeconomy.

    PubMed

    Lopes, Mateus Schreiner Garcez

    2015-06-01

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

  6. Advantages and Pitfalls of Mass Spectrometry Based Metabolome Profiling in Systems Biology

    PubMed Central

    Aretz, Ina; Meierhofer, David

    2016-01-01

    Mass spectrometry-based metabolome profiling became the method of choice in systems biology approaches and aims to enhance biological understanding of complex biological systems. Genomics, transcriptomics, and proteomics are well established technologies and are commonly used by many scientists. In comparison, metabolomics is an emerging field and has not reached such high-throughput, routine and coverage than other omics technologies. Nevertheless, substantial improvements were achieved during the last years. Integrated data derived from multi-omics approaches will provide a deeper understanding of entire biological systems. Metabolome profiling is mainly hampered by its diversity, variation of metabolite concentration by several orders of magnitude and biological data interpretation. Thus, multiple approaches are required to cover most of the metabolites. No software tool is capable of comprehensively translating all the data into a biologically meaningful context yet. In this review, we discuss the advantages of metabolome profiling and main obstacles limiting progress in systems biology. PMID:27128910

  7. Systems Biology of HBOC-Induced Vasoconstriction

    PubMed Central

    Hai, Chi-Ming

    2011-01-01

    Vasoconstriction is a major adverse effect of HBOCs. The use of a single drug for attenuating HBOC-induced vasoconstriction has been tried with limited success. Since HBOC causes disruptions at multiple levels of organization in the vascular system, a systems approach is helpful to explore avenues to counteract the effects of HBOC at multiple levels by targeting multiple sites in the system. A multi-target approach is especially appropriate for HBOC-induced vasoconstriction, because HBOC disrupts the cascade of amplification by NO-cGMP signaling and protein phosphorylation, ultimately resulting in vasoconstriction. Targeting multiple steps in the cascade may alter the overall gain of amplification, thereby limiting the propagation of disruptive effects through the cascade. As a result, targeting multiple sites may accomplish a relatively high overall efficacy at submaximal drug doses. Identifying targets and doses for developing a multi-target combination HBOC regimen for oxygen therapeutics requires a detailed understanding of the systems biology and phenotypic heterogeneity of the vascular system at multiple layers of organization, which can be accomplished by successive iterations between experimental studies and mathematical modeling at multiple levels of vascular systems and organ systems. Towards this goal, this article addresses the following topics: a) NO-scavenging by HBOC, b) HBOC autoxidation-induced reactive oxygen species generation and endothelial barrier dysfunction, c) NO- cGMP signaling in vascular smooth muscle cells, d) NO and cGMP-dependent regulation of contractile filaments in vascular smooth muscle cells, e) phenotypic heterogeneity of vascular systems, f) systems biology as an approach to developing a multi-target HBOC regimen. PMID:21726185

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

    ERIC Educational Resources Information Center

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

    2007-01-01

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

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

    USGS Publications Warehouse

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

    2003-01-01

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

  10. Recognition of metal cations by biological systems.

    PubMed

    Truter, M R

    1975-11-01

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

  11. Toward an integrated software platform for systems pharmacology

    PubMed Central

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

    2013-01-01

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

  12. The systems biology simulation core algorithm

    PubMed Central

    2013-01-01

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

  13. A Free Energy Principle for Biological Systems

    PubMed Central

    Karl, Friston

    2012-01-01

    This paper describes a free energy principle that tries to explain the ability of biological systems to resist a natural tendency to disorder. It appeals to circular causality of the sort found in synergetic formulations of self-organization (e.g., the slaving principle) and models of coupled dynamical systems, using nonlinear Fokker Planck equations. Here, circular causality is induced by separating the states of a random dynamical system into external and internal states, where external states are subject to random fluctuations and internal states are not. This reduces the problem to finding some (deterministic) dynamics of the internal states that ensure the system visits a limited number of external states; in other words, the measure of its (random) attracting set, or the Shannon entropy of the external states is small. We motivate a solution using a principle of least action based on variational free energy (from statistical physics) and establish the conditions under which it is formally equivalent to the information bottleneck method. This approach has proved useful in understanding the functional architecture of the brain. The generality of variational free energy minimisation and corresponding information theoretic formulations may speak to interesting applications beyond the neurosciences; e.g., in molecular or evolutionary biology. PMID:23204829

  14. Apollo cryogenic integrated systems program

    NASA Technical Reports Server (NTRS)

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

    1971-01-01

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

  15. Integrated control system and method

    SciTech Connect

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

    2013-10-29

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

  16. The Feasibility of Systems Thinking in Biology Education

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  17. The semantic metadatabase (SEMEDA): ontology based integration of federated molecular biological data sources.

    PubMed

    Köhler, Jacob; Schulze-Kremer, Steffen

    2002-01-01

    A system for "intelligent" semantic integration and querying of federated databases is being implemented by using three main components: A component which enables SQL access to integrated databases by database federation (MARGBench), an ontology based semantic metadatabase (SEMEDA) and an ontology based query interface (SEMEDA-query). In this publication we explain and demonstrate the principles, architecture and the use of SEMEDA. Since SEMEDA is implemented as 3 tiered web application database providers can enter all relevant semantic and technical information about their databases by themselves via a web browser. SEMEDA' s collaborative ontology editing feature is not restricted to database integration, and might also be useful for ongoing ontology developments, such as the "Gene Ontology" [2]. SEMEDA can be found at http://www-bm.cs.uni-magdeburg.de/semeda/. We explain how this ontologically structured information can be used for semantic database integration. In addition, requirements to ontologies for molecular biological database integration are discussed and relevant existing ontologies are evaluated. We further discuss how ontologies and structured knowledge sources can be used in SEMEDA and whether they can be merged supplemented or updated to meet the requirements for semantic database integration. PMID:12542408

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

    PubMed

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

    2016-01-01

    Small molecules are indispensable to modern medical therapy. However, their use may lead to unintended, negative medical outcomes commonly referred to as adverse drug reactions (ADRs). These effects vary widely in mechanism, severity, and populations affected, making ADR prediction and identification important public health concerns. Current methods rely on clinical trials and postmarket surveillance programs to find novel ADRs; however, clinical trials are limited by small sample size, whereas postmarket surveillance methods may be biased and inherently leave patients at risk until sufficient clinical evidence has been gathered. Systems pharmacology, an emerging interdisciplinary field combining network and chemical biology, provides important tools to uncover and understand ADRs and may mitigate the drawbacks of traditional methods. In particular, network analysis allows researchers to integrate heterogeneous data sources and quantify the interactions between biological and chemical entities. Recent work in this area has combined chemical, biological, and large-scale observational health data to predict ADRs in both individual patients and global populations. In this review, we explore the rapid expansion of systems pharmacology in the study of ADRs. We enumerate the existing methods and strategies and illustrate progress in the field with a model framework that incorporates crucial data elements, such as diet and comorbidities, known to modulate ADR risk. Using this framework, we highlight avenues of research that may currently be underexplored, representing opportunities for future work. PMID:26559926

  19. Laminated plastic microfluidic components for biological and chemical systems

    SciTech Connect

    Martin, P.M.; Matson, D.W.; Bennett, W.D.; Lin, Y.; Hammerstrom, D.J.

    1999-07-01

    Laminated plastic microfluidic components are being developed for biological testing systems and chemical sensors. Applications include a DNA thermal cycler, DNA analytical systems, electrophoretic flow systems, dialysis systems, and metal sensors for ground water. This article describes fabrication processes developed for these plastic microfluidic components, and the fabrication of a chromium metal sensor and a microdialysis device. Most of the components have a stacked architecture. Using this architecture, the fluid flows, or is pumped through, as many as nine laminated functional levels. Functions include pumping, mixing, reaction, detection, reservoirs, separations, and electronics. Polyimide, poly(methylmethacrylate) (PMMA), and polycarbonate materials with thicknesses between 25 and 125 {mu}m are used to construct the components. This makes the components low cost, inert to many biological fluids and chemicals, and disposable. The components are fabricated by excimer laser micromachining the microchannel patterns and microstructures in the various laminates. In some cases, micropumps are integrated into these components to move the fluids. Vias and interconnects are also cut by the laser and integrated with micropumps. The laminates are sealed and bonded by adhesive and thermal processes and are leak tight. The parts withstand pressures as high as 790 kPa. Typical channel widths are 50 to 100 {mu}m, with aspect ratios near 5. {copyright} {ital 1999 American Vacuum Society.}

  20. Integrated roof wind energy system

    NASA Astrophysics Data System (ADS)

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

    2012-10-01

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

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

    PubMed Central

    2011-01-01

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

  2. Systems pharmacology: bridging systems biology and pharmacokinetics-pharmacodynamics (PKPD) in drug discovery and development.

    PubMed

    van der Graaf, Piet H; Benson, Neil

    2011-07-01

    Mechanistic PKPD models are now advocated not only by academic and industrial researchers, but also by regulators. A recent development in this area is based on the growing realisation that innovation could be dramatically catalysed by creating synergy at the interface between Systems Biology and PKPD, two disciplines which until now have largely existed in 'parallel universes' with a limited track record of impactful collaboration. This has led to the emergence of systems pharmacology. Broadly speaking, this is the quantitative analysis of the dynamic interactions between drug(s) and a biological system to understand the behaviour of the system as a whole, as opposed to the behaviour of its individual constituents; thus, it has become the interface between PKPD and systems biology. It applies the concepts of Systems Engineering, Systems Biology, and PKPD to the study of complex biological systems through iteration between computational and/or mathematical modelling and experimentation. Application of systems pharmacology can now impact across all stages of drug research and development, ranging from very early discovery programs to large-scale Phase 3/4 patient studies, and has the potential to become an integral component of a new 'enhanced quantitative drug discovery and development' (EQD3) R&D paradigm. PMID:21560018

  3. Integrated Raman and angular scattering of single biological cells

    NASA Astrophysics Data System (ADS)

    Smith, Zachary J.

    2009-12-01

    Raman, or inelastic, scattering and angle-resolved elastic scattering are two optical processes that have found wide use in the study of biological systems. Raman scattering quantitatively reports on the chemical composition of a sample by probing molecular vibrations, while elastic scattering reports on the morphology of a sample by detecting structure-induced coherent interference between incident and scattered light. We present the construction of a multimodal microscope platform capable of gathering both elastically and inelastically scattered light from a 38 mum2 region in both epi- and trans-illumination geometries. Simultaneous monitoring of elastic and inelastic scattering from a microscopic region allows noninvasive characterization of a living sample without the need for exogenous dyes or labels. A sample is illuminated either from above or below with a focused 785 nm TEM00 mode laser beam, with elastic and inelastic scattering collected by two separate measurement arms. The measurements may be made either simultaneously, if identical illumination geometries are used, or sequentially, if the two modalities utilize opposing illumination paths. In the inelastic arm, Stokes-shifted light is dispersed by a spectrograph onto a CCD array. In the elastic scattering collection arm, a relay system images the microscope's back aperture onto a CCD detector array to yield an angle-resolved elastic scattering pattern. Post-processing of the inelastic scattering to remove fluorescence signals yields high quality Raman spectra that report on the sample's chemical makeup. Comparison of the elastically scattered pupil images to generalized Lorenz-Mie theory yields estimated size distributions of scatterers within the sample. In this thesis we will present validations of the IRAM instrument through measurements performed on single beads of a few microns in size, as well as on ensembles of sub-micron particles of known size distributions. The benefits and drawbacks of the

  4. Integrated microfluidic systems for DNA analysis.

    PubMed

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

    2011-01-01

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

  5. Systems Biology - A Pivotal Research Methodology for Understanding the Mechanisms of Traditional Medicine

    PubMed Central

    Lee, Soojin

    2015-01-01

    Objectives: Systems biology is a novel subject in the field of life science that aims at a systems’ level understanding of biological systems. Because of the significant progress in high-throughput technologies and molecular biology, systems biology occupies an important place in research during the post-genome era. Methods: The characteristics of systems biology and its applicability to traditional medicine research have been discussed from three points of view: data and databases, network analysis and inference, and modeling and systems prediction. Results: The existing databases are mostly associated with medicinal herbs and their activities, but new databases reflecting clinical situations and platforms to extract, visualize and analyze data easily need to be constructed. Network pharmacology is a key element of systems biology, so addressing the multi-component, multi-target aspect of pharmacology is important. Studies of network pharmacology highlight the drug target network and network target. Mathematical modeling and simulation are just in their infancy, but mathematical modeling of dynamic biological processes is a central aspect of systems biology. Computational simulations allow structured systems and their functional properties to be understood and the effects of herbal medicines in clinical situations to be predicted. Conclusion: Systems biology based on a holistic approach is a pivotal research methodology for understanding the mechanisms of traditional medicine. If systems biology is to be incorporated into traditional medicine, computational technologies and holistic insights need to be integrated. PMID:26388998

  6. Biological Diversity in the Patent System

    PubMed Central

    Oldham, Paul; Hall, Stephen; Forero, Oscar

    2013-01-01

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

  7. The melanocortin system in leukocyte biology.

    PubMed

    Catania, Anna

    2007-02-01

    The melanocortin system is composed of the melanocortin peptides, adrenocorticotropic hormone and alpha-, beta-, and gamma-melanocyte-stimulating hormone, the melanocortin receptors (MCRs), and the endogenous antagonists agouti- and agouti-related protein. Melanocortin peptides exert multiple effects upon the host, including anti-inflammatory and immunomodulatory effects. Leukocytes are a source of melanocortins and a major target for these peptides. Because of reduced translocation of the nuclear factor NF-kappaB to the nucleus, MCR activation by their ligands causes a collective reduction of the most important molecules involved in the inflammatory process. This review examines how melanocortin peptides and their receptors participate in leukocyte biology. PMID:17041004

  8. Integrated Farm System Model: Reference Manual, Version 2.1

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Integrated Farm System Model simulates the major biological and physical processes of a crop, beef, or dairy farm. Crop production, feed use, and the return of manure nutrients back to the land are simulated over each of 25 years of weather. Growth and development of alfalfa, grass, corn, soybea...

  9. An Integrated Biology-Chemistry Freshman Laboratory Project in Biotechnology.

    ERIC Educational Resources Information Center

    Schendel, Marilyn Shimizu

    1999-01-01

    Describes a freshman biology laboratory project that uses the polymerase chain reaction to introduce students to the interrelationship between biology and chemistry. Students must develop their own experimental protocol, perform calculations introduced in freshman classes, and evaluate group dynamics. (Author/WRM)

  10. On the Edge of Mathematics and Biology Integration: Improving Quantitative Skills in Undergraduate Biology Education

    ERIC Educational Resources Information Center

    Feser, Jason; Vasaly, Helen; Herrera, Jose

    2013-01-01

    In this paper, the authors describe how two institutions are helping their undergraduate biology students build quantitative competencies. Incorporation of quantitative skills and reasoning in biology are framed through a discussion of two cases that both concern introductory biology courses, but differ in the complexity of the mathematics and the…

  11. Intelligent systems technology infrastructure for integrated systems

    NASA Technical Reports Server (NTRS)

    Lum, Henry

    1991-01-01

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

  12. WRATS Integrated Data Acquisition System

    NASA Technical Reports Server (NTRS)

    Piatak, David J.

    2008-01-01

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

  13. Systems Integration Challenges for a National Space Launch System

    NASA Technical Reports Server (NTRS)

    May, Todd A.

    2011-01-01

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

  14. Adaptation of sensor morphology: an integrative view of perception from biologically inspired robotics perspective.

    PubMed

    Iida, Fumiya; Nurzaman, Surya G

    2016-08-01

    Sensor morphology, the morphology of a sensing mechanism which plays a role of shaping the desired response from physical stimuli from surroundings to generate signals usable as sensory information, is one of the key common aspects of sensing processes. This paper presents a structured review of researches on bioinspired sensor morphology implemented in robotic systems, and discusses the fundamental design principles. Based on literature review, we propose two key arguments: first, owing to its synthetic nature, biologically inspired robotics approach is a unique and powerful methodology to understand the role of sensor morphology and how it can evolve and adapt to its task and environment. Second, a consideration of an integrative view of perception by looking into multidisciplinary and overarching mechanisms of sensor morphology adaptation across biology and engineering enables us to extract relevant design principles that are important to extend our understanding of the unfinished concepts in sensing and perception. PMID:27499843

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

    PubMed

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

    2016-01-01

    It is due to the advances in high-throughput omics data generation that RNA species have re-entered the focus of biomedical research. International collaborate efforts, like the ENCODE and GENCODE projects, have spawned thousands of previously unknown functional non-coding RNAs (ncRNAs) with various but primarily regulatory roles. Many of these are linked to the emergence and progression of human diseases. In particular, interdisciplinary studies integrating bioinformatics, systems biology, and biotechnological approaches have successfully characterized the role of ncRNAs in different human cancers. These efforts led to the identification of a new tool-kit for cancer diagnosis, monitoring, and treatment, which is now starting to enter and impact on clinical practice. This chapter is to elaborate on the state of the art in RNA systems biology, including a review and perspective on clinical applications toward an integrative RNA systems medicine approach. The focus is on the role of ncRNAs in cancer. PMID:26677189

  16. Microbial diversity of biological filters in recirculating aquaculture systems.

    PubMed

    Schreier, Harold J; Mirzoyan, Natella; Saito, Keiko

    2010-06-01

    Development of environmentally sustainable farming of marine and freshwater species using recirculating aquaculture systems (RASs) requires a complete understanding of the biological component involved in wastewater treatment. This component integrates biofilters composed of microbial communities whose structure, dynamics, and activities are responsible for system success. Engineering highly efficient, environmentally sound, disease-free, and economically viable systems necessitates a thorough knowledge of microbial processes involved in all facets of RAS biofilters and has only recently been the focus of comprehensive studies. These studies have included the application of molecular tools to characterize community diversity and have identified key processes useful for improving system performance. In this paper we summarize the current understanding of the microbial diversity and physiology of RAS biofilters and discuss directions for future studies. PMID:20371171

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

    PubMed

    Hood, Leroy

    2013-04-01

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

  18. A Practical Guide for Exploring Opportunities of Repurposing Drugs for CNS Diseases in Systems Biology.

    PubMed

    Mei, Hongkang; Feng, Gang; Zhu, Jason; Lin, Simon; Qiu, Yang; Wang, Yue; Xia, Tian

    2016-01-01

    Systems biology has shown its potential in facilitating pathway-focused therapy development for central nervous system (CNS) diseases. An integrated network can be utilized to explore the multiple disease mechanisms and to discover repositioning opportunities. This review covers current therapeutic gaps for CNS diseases and the role of systems biology in pharmaceutical industry. We conclude with a Multiple Level Network Modeling (MLNM) example to illustrate the great potential of systems biology for CNS diseases. The system focuses on the benefit and practical applications in pathway centric therapy and drug repositioning. PMID:26235090

  19. Integrated delivery systems. Evolving oligopolies.

    PubMed

    Malone, T A

    1998-01-01

    The proliferation of Integrated Delivery Systems (IDSs) in regional health care markets has resulted in the movement of these markets from a monopolistic competitive model of behavior to an oligopoly. An oligopoly is synonymous with competition among the few, as a small number of firms supply a dominant share of an industry's total output. The basic characteristics of a market with competition among the few are: (1) A mutual interdependence among the actions and behaviors of competing firms; (2) competition tends to rely on the differentiation of products; (3) significant barriers to entering the market exist; (4) the demand curve for services may be kinked; and (5) firms can benefit from economies of scale. An understanding of these characteristics is essential to the survival of IDSs as regional managed care markets mature. PMID:10180497

  20. Integrated solar energy system optimization

    NASA Astrophysics Data System (ADS)

    Young, S. K.

    1982-11-01

    The computer program SYSOPT, intended as a tool for optimizing the subsystem sizing, performance, and economics of integrated wind and solar energy systems, is presented. The modular structure of the methodology additionally allows simulations when the solar subsystems are combined with conventional technologies, e.g., a utility grid. Hourly energy/mass flow balances are computed for interconnection points, yielding optimized sizing and time-dependent operation of various subsystems. The program requires meteorological data, such as insolation, diurnal and seasonal variations, and wind speed at the hub height of a wind turbine, all of which can be taken from simulations like the TRNSYS program. Examples are provided for optimization of a solar-powered (wind turbine and parabolic trough-Rankine generator) desalinization plant, and a design analysis for a solar powered greenhouse.

  1. Environmental Control of Root System Biology.

    PubMed

    Rellán-Álvarez, Rubén; Lobet, Guillaume; Dinneny, José R

    2016-04-29

    The plant root system traverses one of the most complex environments on earth. Understanding how roots support plant life on land requires knowing how soil properties affect the availability of nutrients and water and how roots manipulate the soil environment to optimize acquisition of these resources. Imaging of roots in soil allows the integrated analysis and modeling of environmental interactions occurring at micro- to macroscales. Advances in phenotyping of root systems is driving innovation in cross-platform-compatible methods for data analysis. Root systems acclimate to the environment through architectural changes that act at the root-type level as well as through tissue-specific changes that affect the metabolic needs of the root and the efficiency of nutrient uptake. A molecular understanding of the signaling mechanisms that guide local and systemic signaling is providing insight into the regulatory logic of environmental responses and has identified points where crosstalk between pathways occurs. PMID:26905656

  2. Bringing together an ocean of information: An extensible data integration framework for biological oceanography

    NASA Astrophysics Data System (ADS)

    Stocks, Karen I.; Condit, Chris; Qian, Xufei; Brewin, Paul E.; Gupta, Amarnath

    2009-09-01

    As increasing volumes and varieties of data are becoming available online, the challenges of accessing and using heterogeneous data resources are growing. We have developed a mediator-based data integration system called Cartel for biological oceanography data. A mediation approach is appropriate in cases where a single central warehouse is not desirable, such as when the needed data sources change frequently through time, or when there are advantages for holding heterogeneous data in their native formats. Through Cartel, data sources of a variety of types can be registered to the system, and users can query against simplified virtual schemas, without needing to know the underlying schema and computational capabilities of each data source. The system can operate on a variety of relational and geospatial data formats, and can perform joins between formats. We tested the performance of the Cartel mediator in two biological oceanography application areas, and found that the system was able to support the variety of data types needed in a typical ecology study, but that the response times were unacceptably slow when very large databases (i.e. Ocean Biogeographic Information System and the World Ocean Atlas) were used. Indexing and caching are currently being added to the system to improve response times. The mediator is an open-source product, and was developed to be a generic, extensible component available to projects developing oceanography data systems.

  3. Harnessing the Power of Integrated Mitochondrial Biology and Physiology: A Special Report on the NHLBI Mitochondria in Heart Diseases Initiative.

    PubMed

    Ping, Peipei; Gustafsson, Åsa B; Bers, Don M; Blatter, Lothar A; Cai, Hua; Jahangir, Arshad; Kelly, Daniel; Muoio, Deborah; O'Rourke, Brian; Rabinovitch, Peter; Trayanova, Natalia; Van Eyk, Jennifer; Weiss, James N; Wong, Renee; Schwartz Longacre, Lisa

    2015-07-17

    Mitochondrial biology is the sum of diverse phenomena from molecular profiles to physiological functions. A mechanistic understanding of mitochondria in disease development, and hence the future prospect of clinical translations, relies on a systems-level integration of expertise from multiple fields of investigation. Upon the successful conclusion of a recent National Institutes of Health, National Heart, Lung, and Blood Institute initiative on integrative mitochondrial biology in cardiovascular diseases, we reflect on the accomplishments made possible by this unique interdisciplinary collaboration effort and exciting new fronts on the study of these remarkable organelles. PMID:26185209

  4. Advanced integrated solvent extraction systems

    SciTech Connect

    Horwitz, E.P.; Dietz, M.L.; Leonard, R.A.

    1997-10-01

    Advanced integrated solvent extraction systems are a series of novel solvent extraction (SX) processes that will remove and recover all of the major radioisotopes from acidic-dissolved sludge or other acidic high-level wastes. The major focus of this effort during the last 2 years has been the development of a combined cesium-strontium extraction/recovery process, the Combined CSEX-SREX Process. The Combined CSEX-SREX Process relies on a mixture of a strontium-selective macrocyclic polyether and a novel cesium-selective extractant based on dibenzo 18-crown-6. The process offers several potential advantages over possible alternatives in a chemical processing scheme for high-level waste treatment. First, if the process is applied as the first step in chemical pretreatment, the radiation level for all subsequent processing steps (e.g., transuranic extraction/recovery, or TRUEX) will be significantly reduced. Thus, less costly shielding would be required. The second advantage of the Combined CSEX-SREX Process is that the recovered Cs-Sr fraction is non-transuranic, and therefore will decay to low-level waste after only a few hundred years. Finally, combining individual processes into a single process will reduce the amount of equipment required to pretreat the waste and therefore reduce the size and cost of the waste processing facility. In an ongoing collaboration with Lockheed Martin Idaho Technology Company (LMITCO), the authors have successfully tested various segments of the Advanced Integrated Solvent Extraction Systems. Eichrom Industries, Inc. (Darien, IL) synthesizes and markets the Sr extractant and can supply the Cs extractant on a limited basis. Plans are under way to perform a test of the Combined CSEX-SREX Process with real waste at LMITCO in the near future.

  5. A Systems Biology View of Cancer

    PubMed Central

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

    2009-01-01

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

  6. NASA UAS Integration into the NAS Project: Human Systems Integration

    NASA Technical Reports Server (NTRS)

    Shively, Jay

    2016-01-01

    This presentation provides an overview of the work the Human Systems Integration (HSI) sub-project has done on detect and avoid (DAA) displays while working on the UAS (Unmanned Aircraft System) Integration into the NAS project. The most recent simulation on DAA interoperability with Traffic Collision Avoidance System (TCAS) is discussed in the most detail. The relationship of the work to the larger UAS community and next steps are also detailed.

  7. Sensorimotor Integration by Corticospinal System

    PubMed Central

    Moreno-López, Yunuen; Olivares-Moreno, Rafael; Cordero-Erausquin, Matilde; Rojas-Piloni, Gerardo

    2016-01-01

    The corticospinal (CS) tract is a complex system which targets several areas of the spinal cord. In particular, the CS descending projection plays a major role in motor command, which results from direct and indirect control of spinal cord pre-motor interneurons as well as motoneurons. But in addition, this system is also involved in a selective and complex modulation of sensory feedback. Despite recent evidence confirms that CS projections drive distinct segmental neural circuits that are part of the sensory and pre-motor pathways, little is known about the spinal networks engaged by the corticospinal tract (CST), the organization of CS projections, the intracortical microcircuitry, and the synaptic interactions in the sensorimotor cortex (SMC) that may encode different cortical outputs to the spinal cord. Here is stressed the importance of integrated approaches for the study of sensorimotor function of CS system, in order to understand the functional compartmentalization and hierarchical organization of layer 5 output neurons, who are key elements for motor control and hence, of behavior. PMID:27013985

  8. Macroscopic Quantum-Type Potentials in Theoretical Systems Biology

    PubMed Central

    Nottale, Laurent

    2014-01-01

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

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

    PubMed

    Nottale, Laurent

    2013-01-01

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

  10. Preventing Integrator Windup In A Control System

    NASA Technical Reports Server (NTRS)

    Kaminer, Isaac

    1992-01-01

    Design concept for control system addresses how to prevent control inputs to plant from exceeding electrical limits imposed by mechanical limits of control actuators in plant, and prevent windup in integrators in control system. Concept consists of two parts. First, to rearrange terms of control equation to move integrators into output path of control system. Second, involves limiting inputs to integrators when one control input of plant reaches its limit. Concept applicable to control systems typical of aircraft autopilot systems.

  11. Are Biological Systems Poised at Criticality?

    NASA Astrophysics Data System (ADS)

    Mora, Thierry; Bialek, William

    2011-07-01

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

  12. Biological Systems for Hydrogen Photoproduction (Presentation)

    SciTech Connect

    Ghirardi, M. L.

    2012-05-01

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

  13. "Slimplectic" Integrators: Variational Integrators for General Nonconservative Systems

    NASA Astrophysics Data System (ADS)

    Tsang, David; Galley, Chad R.; Stein, Leo C.; Turner, Alec

    2015-08-01

    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. In this Letter, we develop 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 the principle of stationary nonconservative action developed in Galley et al. 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.

  14. iTools: A Framework for Classification, Categorization and Integration of Computational Biology Resources

    PubMed Central

    Dinov, Ivo D.; Rubin, Daniel; Lorensen, William; Dugan, Jonathan; Ma, Jeff; Murphy, Shawn; Kirschner, Beth; Bug, William; Sherman, Michael; Floratos, Aris; Kennedy, David; Jagadish, H. V.; Schmidt, Jeanette; Athey, Brian; Califano, Andrea; Musen, Mark; Altman, Russ; Kikinis, Ron; Kohane, Isaac; Delp, Scott; Parker, D. Stott; Toga, Arthur W.

    2008-01-01

    The advancement of the computational biology field hinges on progress in three fundamental directions – the development of new computational algorithms, the availability of informatics resource management infrastructures and the capability of tools to interoperate and synergize. There is an explosion in algorithms and tools for computational biology, which makes it difficult for biologists to find, compare and integrate such resources. We describe a new infrastructure, iTools, for managing the query, traversal and comparison of diverse computational biology resources. Specifically, iTools stores information about three types of resources–data, software tools and web-services. The iTools design, implementation and resource meta - data content reflect the broad research, computational, applied and scientific expertise available at the seven National Centers for Biomedical Computing. iTools provides a system for classification, categorization and integration of different computational biology resources across space-and-time scales, biomedical problems, computational infrastructures and mathematical foundations. A large number of resources are already iTools-accessible to the community and this infrastructure is rapidly growing. iTools includes human and machine interfaces to its resource meta-data repository. Investigators or computer programs may utilize these interfaces to search, compare, expand, revise and mine meta-data descriptions of existent computational biology resources. We propose two ways to browse and display the iTools dynamic collection of resources. The first one is based on an ontology of computational biology resources, and the second one is derived from hyperbolic projections of manifolds or complex structures onto planar discs. iTools is an open source project both in terms of the source code development as well as its meta-data content. iTools employs a decentralized, portable, scalable and lightweight framework for long-term resource

  15. Using quantum mechanical approaches to study biological systems.

    PubMed

    Merz, Kenneth M

    2014-09-16

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

  16. Noise effects in two different biological systems

    NASA Astrophysics Data System (ADS)

    Spagnolo, B.; Spezia, S.; Curcio, L.; Pizzolato, N.; Fiasconaro, A.; Valenti, D.; Lo Bue, P.; Peri, E.; Colazza, S.

    2009-05-01

    We investigate the role of the colored noise in two biological systems: (i) adults of Nezara viridula (L.) (Heteroptera: Pentatomidae), and (ii) polymer translocation. In the first system we analyze, by directionality tests, the response of N. viridula individuals to subthreshold signals plus noise in their mating behaviour. The percentage of insects that react to the subthreshold signal shows a nonmonotonic behaviour, characterized by the presence of a maximum, as a function of the noise intensity. This is the signature of the non-dynamical stochastic resonance phenomenon. By using a “soft” threshold model we find that the maximum of the input-output cross correlation occurs in the same range of noise intensity values for which the behavioural activation of the insects has a maximum. Moreover this maximum value is lowered and shifted towards higher noise intensities, compared to the case of white noise. In the second biological system the noise driven translocation of short polymers in crowded solutions is analyzed. An improved version of the Rouse model for a flexible polymer is adopted to mimic the molecular dynamics by taking into account both the interactions between adjacent monomers and the effects of a Lennard-Jones potential between all beads. The polymer dynamics is simulated in a two-dimensional domain by numerically solving the Langevin equations of motion in the presence of thermal fluctuations and a colored noise source. At low temperatures or for strong colored noise intensities the translocation process of the polymer chain is delayed. At low noise intensity, as the polymer length increases, we find a nonmonotonic behaviour for the mean first translocation time of the polymer centre of inertia. We show how colored noise influences the motion of short polymers, by inducing two different regimes of translocation in the dynamics of molecule transport.

  17. The primary glomerulonephritides: a systems biology approach

    PubMed Central

    Jiang, Song; Chuang, Peter Y.; Liu, Zhi-Hong; He, John C.

    2014-01-01

    Our understanding of the pathogenesis of most primary glomerular diseases, including IgA nephropathy, membranous nephropathy and focal segmental glomerulosclerosis, is limited. Advances in molecular technology now permit genome-wide, high-throughput characterization of genes and gene products from biological samples. Comprehensive examinations of the genome, transcriptome, proteome and metabolome (collectively known as omics analyses), have been applied to the study of IgA nephropathy, membranous nephropathy and focal segmental glomerulosclerosis in both animal models and human patients. However, most omics studies of primary glomerular diseases, with the exception of large genomic studies, have been limited by inadequate sample sizes and the lack of kidney-specific data sets derived from kidney biopsy samples. Collaborative efforts to develop a standardized approach for prospective recruitment of patients, scheduled monitoring of clinical outcomes, and protocols for sampling of kidney tissues will be instrumental in uncovering the mechanisms that drive these diseases. Integration of molecular data sets with the results of clinical and histopathological studies will ultimately enable these diseases to be characterized in a comprehensive and systematic manner, and is expected to improve the diagnosis and treatment of these diseases. PMID:23856995

  18. Liquid crystal assemblies in biologically inspired systems

    PubMed Central

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

    2013-01-01

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

  19. Dielectrophoretic Force Imaging of Biological Systems

    NASA Astrophysics Data System (ADS)

    Simpson, Garth J.

    2004-03-01

    A new scanning probe microscopic technique is demonstrated, exploiting AC electrokinetic forces for real-time functional imaging of biological interfaces with nanometer-scale spatial resolution. Dielectrophoresis (DEP) describes the mobility of particles in radio-frequency AC electric fields and is related to the frequency-dependent polarizability. Similar to the forces in optical trapping, DEP interactions are greatest for large field gradients, such as those adjacent to highly curved electrodes. Moderate AC potentials (5 Vpp) are more than sufficient to induce surface forces strong enough for reliable feedback during imaging. Simply changing the AC frequency can change the nature of the DEP force from repulsive to attractive. By scanning the AC frequency, dielectrophoretic spectroscopy using light with a wavelength of ˜ 1/2 km can be performed with spatial resolution of a few nanometers (about 11 to 12 orders of magnitude below the diffraction-limit), representing a new level of achievement in near-field microscopy. Among other things, the facile applicability of DEP imaging in aqueous media is ideally suited for ultrahigh resolution microscopy of biological systems, including supported lipid bilayer membranes, immobilized organelles, and living cells.

  20. Metabolic syndrome: from epidemiology to systems biology

    PubMed Central

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

    2010-01-01

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

  1. Microarray-integrated optoelectrofluidic immunoassay system.

    PubMed

    Han, Dongsik; Park, Je-Kyun

    2016-05-01

    A microarray-based analytical platform has been utilized as a powerful tool in biological assay fields. However, an analyte depletion problem due to the slow mass transport based on molecular diffusion causes low reaction efficiency, resulting in a limitation for practical applications. This paper presents a novel method to improve the efficiency of microarray-based immunoassay via an optically induced electrokinetic phenomenon by integrating an optoelectrofluidic device with a conventional glass slide-based microarray format. A sample droplet was loaded between the microarray slide and the optoelectrofluidic device on which a photoconductive layer was deposited. Under the application of an AC voltage, optically induced AC electroosmotic flows caused by a microarray-patterned light actively enhanced the mass transport of target molecules at the multiple assay spots of the microarray simultaneously, which reduced tedious reaction time from more than 30 min to 10 min. Based on this enhancing effect, a heterogeneous immunoassay with a tiny volume of sample (5 μl) was successfully performed in the microarray-integrated optoelectrofluidic system using immunoglobulin G (IgG) and anti-IgG, resulting in improved efficiency compared to the static environment. Furthermore, the application of multiplex assays was also demonstrated by multiple protein detection. PMID:27190571

  2. Developing Metrics in Systems Integration (ISS Program COTS Integration Model)

    NASA Technical Reports Server (NTRS)

    Lueders, Kathryn

    2007-01-01

    This viewgraph presentation reviews some of the complications in developing metrics for systems integration. Specifically it reviews a case study of how two programs within NASA try to develop and measure performance while meeting the encompassing organizational goals.

  3. Assuring structural integrity in Army systems

    NASA Technical Reports Server (NTRS)

    1985-01-01

    The object of this study was to recommend possible improvements in the manner in which structural integrity of Army systems is assured. The elements of a structural integrity program are described, and relevant practices used in various industries and government organizations are reviewed. Some case histories of Army weapon systems are examined. The mandatory imposition of a structural integrity program patterned after the Air Force Aircraft Structural Integrity Program is recommended and the benefits of such an action are identified.

  4. Power Systems Integration Laboratory (Fact Sheet)

    SciTech Connect

    Not Available

    2011-10-01

    This fact sheet describes the purpose, lab specifications, applications scenarios, and information on how to partner with NREL's Power Systems Integration Laboratory at the Energy Systems Integration Facility. At NREL's Power Systems Integration Laboratory in the Energy Systems Integration Facility (ESIF), research focuses on developing and testing large-scale distributed energy systems for grid-connected, stand-alone, and microgrid applications. The laboratory can accommodate large power system components such as inverters for photovoltaic (PV) and wind systems, diesel and natural gas generators, battery packs, microgrid interconnection switchgear, and vehicles. Closely coupled with the research electrical distribution bus at the ESIF, the Power Systems Integration Laboratory will offer power testing capability of megawatt-scale DC and AC power systems, as well as advanced hardware-in-the-loop and model-in-the-loop simulation capabilities. Thermal heating and cooling loops and fuel also allow testing of combined heating/cooling and power systems (CHP).

  5. Introducing Systems Biology to Bioscience Students through Mathematical Modelling. A Practical Module

    ERIC Educational Resources Information Center

    Torres, Nestor V.

    2013-01-01

    Systems Biology, one of the current approaches to the understanding of living things, aims to understand the behaviour of living systems through the creation of mathematical models that integrate the available knowledge of the system's component parts and the relations among them. Accordingly, model building should play a central part in any…

  6. Making Biology Learning Relevant to Students: Integrating People, History, and Context into College Biology Teaching

    ERIC Educational Resources Information Center

    Chamany, Katayoun; Allen, Deborah; Tanner, Kimberly

    2008-01-01

    Teaching students to make connections between what they learn in the classroom and what they see in everyday life is imperative. As biology instructors, they may choose to teach biology devoid of social context, believing that students can make these connections on their own. However, students model their instructors' behaviors, and follow their…

  7. Systems biology of human benzene exposure

    PubMed Central

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

    2010-01-01

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

  8. Integrative Medicine System Based on Music.

    PubMed

    Balasubramanian, Sai Venkatesh; Balasubramanian, Gomathi; Ramanathan, Ganapathy

    2016-04-01

    Today, the world's ever-changing lifestyles demand a reliable, comprehensive system of integrative medicine with minimal side effects. One of the most prominent candidates for such a system is music, an enjoyable health care approach, and in response to the need for that system, the present article formulates one that is music based. Specifically, the authors have explored the physician-patient interaction, developing a model of that interaction within the context of music therapy. That model is based on ancient Ayurvedic principles and on research from modern physics and biology, such as that on quantum consciousness, chaos theory, the statistical theory of communication, information theory, and neurodynamics. The authors formulated 6 dimensions for that model: (1) physiological-Tridoshas, (2) emotional-Trigunas, (3) sociological-temperament, (4) psychological-brain waves, (5) spiritual-Chakras, and (6) informational-landscape. The connections between music and those dimensions are explored in the current article. The model opens the doors for a reliable, enjoyable, holistic health care, using music, with minimal side effects. PMID:27089526

  9. Health systems, communicable diseases and integration.

    PubMed

    Shigayeva, Altynay; Atun, Rifat; McKee, Martin; Coker, Richard

    2010-11-01

    The HIV/AIDS, tuberculosis and malaria pandemics pose substantial challenges globally and to health systems in the countries they affect. This demands an institutional approach that can integrate disease control programmes within health and social care systems. Whilst integration is intuitively appealing, evidence of its benefits remains uncertain and evaluation is beset by lack of a common understanding of what it involves. The aim of this paper is to better define integration in health systems relevant to communicable disease control. We conducted a critical review of published literature on concepts, definitions, and analytical and methodological approaches to integration as applied to health system responses to communicable disease. We found that integration is understood and pursued in many ways in different health systems. We identified a variety of typologies that relate to three fundamental questions associated with integration: (1) why is integration a goal (that is, what are the driving forces for integration); (2) what structures and/or functions at different levels of health system are affected by integration (or the lack of); and (3) how does integration influence interactions between health system components or stakeholders. The frameworks identified were evaluated in terms of these questions, as well as the extent to which they took account of health system characteristics, the wider contextual environment in which health systems sit, and the roles of key stakeholders. We did not find any one framework that explicitly addressed all of these three questions and therefore propose an analytical framework to help address these questions, building upon existing frameworks and extending our conceptualization of the 'how' of integration to identify a continuum of interactions that extends from no interactions, to partial integration that includes linkage and coordination, and ultimately to integration. We hope that our framework may provide a basis for

  10. Integrated analysis environment for high impact systems

    SciTech Connect

    Martinez, M.; Davis, J.; Scott, J.; Sztipanovits, J.; Karsai, G.

    1998-02-01

    Modeling and analysis of high consequence, high assurance systems requires special modeling considerations. System safety and reliability information must be captured in the models. Previously, high consequence systems were modeled using separate, disjoint models for safety, reliability, and security. The MultiGraph Architecture facilitates the implementation of a model integrated system for modeling and analysis of high assurance systems. Model integrated computing allows an integrated modeling technique to be applied to high consequence systems. Among the tools used for analyzing safety and reliability are a behavioral simulator and an automatic fault tree generation and analysis tool. Symbolic model checking techniques are used to efficiently investigate the system models. A method for converting finite state machine models to ordered binary decision diagrams allows the application of symbolic model checking routines to the integrated system models. This integrated approach to modeling and analysis of high consequence systems ensures consistency between the models and the different analysis tools.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-04-01

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

  13. Integrated System for Autonomous Science

    NASA Technical Reports Server (NTRS)

    Chien, Steve; Sherwood, Robert; Tran, Daniel; Cichy, Benjamin; Davies, Ashley; Castano, Rebecca; Rabideau, Gregg; Frye, Stuart; Trout, Bruce; Shulman, Seth; Doggett, Thomas; Ip, Felipe; Greeley, Ron; Baker, Victor; Dohn, James; Boyer, Darrell

    2006-01-01

    The New Millennium Program Space Technology 6 Project Autonomous Sciencecraft software implements an integrated system for autonomous planning and execution of scientific, engineering, and spacecraft-coordination actions. A prior version of this software was reported in "The TechSat 21 Autonomous Sciencecraft Experiment" (NPO-30784), NASA Tech Briefs, Vol. 28, No. 3 (March 2004), page 33. This software is now in continuous use aboard the Earth Orbiter 1 (EO-1) spacecraft mission and is being adapted for use in the Mars Odyssey and Mars Exploration Rovers missions. This software enables EO-1 to detect and respond to such events of scientific interest as volcanic activity, flooding, and freezing and thawing of water. It uses classification algorithms to analyze imagery onboard to detect changes, including events of scientific interest. Detection of such events triggers acquisition of follow-up imagery. The mission-planning component of the software develops a response plan that accounts for visibility of targets and operational constraints. The plan is then executed under control by a task-execution component of the software that is capable of responding to anomalies.

  14. Circadian systems biology: When time matters

    PubMed Central

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

    2015-01-01

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

  15. Biomarkers of Nanoparticles Impact on Biological Systems

    NASA Astrophysics Data System (ADS)

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

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

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

    PubMed

    Whitacre, James Michael

    2012-01-01

    Robustness has been studied through the analysis of data sets, simulations, and a variety of experimental techniques that each have their own limitations but together confirm the ubiquity of biological robustness. Recent trends suggest that different types of perturbation (e.g., mutational, environmental) are commonly stabilized by similar mechanisms, and system sensitivities often display a long-tailed distribution with relatively few perturbations representing the majority of sensitivities. Conceptual paradigms from network theory, control theory, complexity science, and natural selection have been used to understand robustness, however each paradigm has a limited scope of applicability and there has been little discussion of the conditions that determine this scope or the relationships between paradigms. Systems properties such as modularity, bow-tie architectures, degeneracy, and other topological features are often positively associated with robust traits, however common underlying mechanisms are rarely mentioned. For instance, many system properties support robustness through functional redundancy or through response diversity with responses regulated by competitive exclusion and cooperative facilitation. Moreover, few studies compare and contrast alternative strategies for achieving robustness such as homeostasis, adaptive plasticity, environment shaping, and environment tracking. These strategies share similarities in their utilization of adaptive and self-organization processes that are not well appreciated yet might be suggestive of reusable building blocks for generating robust behavior. PMID:22593762

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

    PubMed Central

    Whitacre, James Michael

    2012-01-01

    Robustness has been studied through the analysis of data sets, simulations, and a variety of experimental techniques that each have their own limitations but together confirm the ubiquity of biological robustness. Recent trends suggest that different types of perturbation (e.g., mutational, environmental) are commonly stabilized by similar mechanisms, and system sensitivities often display a long-tailed distribution with relatively few perturbations representing the majority of sensitivities. Conceptual paradigms from network theory, control theory, complexity science, and natural selection have been used to understand robustness, however each paradigm has a limited scope of applicability and there has been little discussion of the conditions that determine this scope or the relationships between paradigms. Systems properties such as modularity, bow-tie architectures, degeneracy, and other topological features are often positively associated with robust traits, however common underlying mechanisms are rarely mentioned. For instance, many system properties support robustness through functional redundancy or through response diversity with responses regulated by competitive exclusion and cooperative facilitation. Moreover, few studies compare and contrast alternative strategies for achieving robustness such as homeostasis, adaptive plasticity, environment shaping, and environment tracking. These strategies share similarities in their utilization of adaptive and self-organization processes that are not well appreciated yet might be suggestive of reusable building blocks for generating robust behavior. PMID:22593762

  18. Expert systems guide biological phosphorus removal

    SciTech Connect

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

    1991-10-01

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

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

    PubMed Central

    Materi, Wayne; Wishart, David S.

    2007-01-01

    In recent years it has become clear that carcinogenesis is a complex process, both at the molecular and cellular levels. Understanding the origins, growth and spread of cancer, therefore requires an integrated or system-wide approach. Computational systems biology is an emerging sub-discipline in systems biology that utilizes the wealth of data from genomic, proteomic and metabolomic studies to build computer simulations of intra and intercellular processes. Several useful descriptive and predictive models of the origin, growth and spread of cancers have been developed in an effort to better understand the disease and potential therapeutic approaches. In this review we describe and assess the practical and theoretical underpinnings of commonly-used modeling approaches, including ordinary and partial differential equations, petri nets, cellular automata, agent based models and hybrid systems. A number of computer-based formalisms have been implemented to improve the accessibility of the various approaches to researchers whose primary interest lies outside of model development. We discuss several of these and describe how they have led to novel insights into tumor genesis, growth, apoptosis, vascularization and therapy. PMID:19936081

  20. DEMONSTRATION OF AN INTEGRATED, PASSIVE BIOLOGICAL TREATMENT PROCESS FOR AMD

    EPA Science Inventory

    An innovative, cost-effective, biological treatment process has been designed by MSE Technology Applications, Inc. to treat acid mine drainage (AMD). A pilot-scale demonstration is being conducted under the Mine Waste Technology Program using water flowing from an abandoned mine ...

  1. Integrating biological control into pecan weevil management: a sustainable approach

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The pecan weevil, Curculio caryae, is a key pest of pecans. This article summarizes research and makes recommendations based on a project that was funded in part by the USDA-Sustainable Agriculture Research and Education program and that was aimed at developing biological methods of C. caryae contr...

  2. Building Better Biology Undergraduates through Information Literacy Integration

    ERIC Educational Resources Information Center

    Winterman, Brian

    2009-01-01

    Biology undergraduates at Indiana University have often been expected to find information for course exercises or written reports, but the skills necessary to do so are not taught consistently in the curriculum. Other efforts described in the literature have been successful in teaching information literacy skills, but not always in a way that is…

  3. Evaluating Biology Achievement Scores in an ICT Integrated PBL Environment

    ERIC Educational Resources Information Center

    Osman, Kamisah; Kaur, Simranjeet Judge

    2014-01-01

    Students' achievement in Biology is often looked up as a benchmark to evaluate the mode of teaching and learning in higher education. Problem-based learning (PBL) is an approach that focuses on students' solving a problem through collaborative groups. There were eighty samples involved in this study. The samples were divided into three…

  4. DNA barcodes for assessment of the biological integrity of aquatic ecosystems

    EPA Science Inventory

    Water quality regulations and aquatic ecosystem monitoring increasingly rely on direct assessments of biological integrity. Because these aquatic “bioassessments” evaluate the incidence and abundance of sensitive aquatic species, they are able to measure cumulative ecosystem eff...

  5. Support Systems for Treatment Integrity

    ERIC Educational Resources Information Center

    Goense, Pauline Brigitta; Boendermaker, Leonieke; van Yperen, Tom

    2016-01-01

    Objective: This systematic review evaluates the content of effective support provided to practitioners of evidence-based interventions in order to establish and maintain treatment integrity. Method: Four articles covering six outcome studies are included in this review, these studies (1) adequately operationalized treatment integrity procedures…

  6. INTEGRATED HYDROGEN STORAGE SYSTEM MODEL

    SciTech Connect

    Hardy, B

    2007-11-16

    Hydrogen storage is recognized as a key technical hurdle that must be overcome for the realization of hydrogen powered vehicles. Metal hydrides and their doped variants have shown great promise as a storage material and significant advances have been made with this technology. In any practical storage system the rate of H2 uptake will be governed by all processes that affect the rate of mass transport through the bed and into the particles. These coupled processes include heat and mass transfer as well as chemical kinetics and equilibrium. However, with few exceptions, studies of metal hydrides have focused primarily on fundamental properties associated with hydrogen storage capacity and kinetics. A full understanding of the complex interplay of physical processes that occur during the charging and discharging of a practical storage system requires models that integrate the salient phenomena. For example, in the case of sodium alanate, the size of NaAlH4 crystals is on the order of 300nm and the size of polycrystalline particles may be approximately 10 times larger ({approx}3,000nm). For the bed volume to be as small as possible, it is necessary to densely pack the hydride particles. Even so, in packed beds composed of NaAlH{sub 4} particles alone, it has been observed that the void fraction is still approximately 50-60%. Because of the large void fraction and particle to particle thermal contact resistance, the thermal conductivity of the hydride is very low, on the order of 0.2 W/m-{sup o}C, Gross, Majzoub, Thomas and Sandrock [2002]. The chemical reaction for hydrogen loading is exothermic. Based on the data in Gross [2003], on the order of 10{sup 8}J of heat of is released for the uptake of 5 kg of H{sub 2}2 and complete conversion of NaH to NaAlH{sub 4}. Since the hydride reaction transitions from hydrogen loading to discharge at elevated temperatures, it is essential to control the temperature of the bed. However, the low thermal conductivity of the hydride

  7. Biological soil crusts as an integral component of desert environments

    USGS Publications Warehouse

    Belnap, Jayne; Weber, Bettina

    2013-01-01

    The biology and ecology of biological soil crusts, a soil surface community of mosses, lichens, cyanobacteria, green algae, fungi, and bacteria, have only recently been a topic of research. Most efforts began in the western U.S. (Cameron, Harper, Rushforth, and St. Clair), Australia (Rogers), and Israel (Friedmann, Evenari, and Lange) in the late 1960s and 1970s (e.g., Friedmann et al. 1967; Evenari 1985reviewed in Harper and Marble 1988). However, these groups worked independently of each other and, in fact, were often not aware of each other’s work. In addition, biological soil crust communities were seen as more a novelty than a critical component of dryland ecosystems. Since then, researchers have investigated many different aspects of these communities and have shown that although small to microscopic, biological soil crusts are critical in many ecological processes of deserts. They often cover most of desert soil surfaces and substantially mediate inputs and outputs from desert soils (Belnap et al. 2003). They can be a large source of biodiversity for deserts, as they can contain more species than the surrounding vascular plant community (Rosentreter 1986). These communities are important in reducing soil erosion and increasing soil fertility through the capture of dust and the fixation of atmospheric nitrogen and carbon into forms available to other life forms (Elbert et al. 2012). Because of their many effects on soil characteristics, such as external and internal morphological characteristics, aggregate stability, soil moisture, and permeability, they also affect seed germination and establishment and local hydrological cycles. Covering up to 70% of the surface area in many arid and semi-arid regions around the world (Belnap and Lange 2003), biological soil crusts are a key component within desert environments.

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

    PubMed Central

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

    2009-01-01

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

  9. The Structural Biology of CRISPR-Cas Systems

    PubMed Central

    Jiang, Fuguo; Doudna, Jennifer A.

    2015-01-01

    Prokaryotic CRISPR-Cas genomic loci encode RNA-mediated adaptive immune systems that bear some functional similarities with eukaryotic RNA interference. Acquired and heritable immunity against bacteriophage and plasmids begins with integration of ~30 base pair foreign DNA sequences into the host genome. CRISPR-derived transcripts assemble with CRISPR-associated (Cas) proteins to target complementary nucleic acids for degradation. Here we review recent advances in the structural biology of these targeting complexes, with a focus on structural studies of the multisubunit Type I CRISPR RNA-guided surveillance and the Cas9 DNA endonuclease found in Type II CRISPR-Cas systems. These complexes have distinct structures that are each capable of site-specific double-stranded DNA binding and local helix unwinding. PMID:25723899

  10. Systems Biology of Recombinant Protein Production in Bacillus megaterium

    NASA Astrophysics Data System (ADS)

    Biedendieck, Rebekka; Bunk, Boyke; Fürch, Tobias; Franco-Lara, Ezequiel; Jahn, Martina; Jahn, Dieter

    Over the last two decades the Gram-positive bacterium Bacillus megaterium was systematically developed to a useful alternative protein production host. Multiple vector systems for high yield intra- and extracellular protein production were constructed. Strong inducible promoters were combined with DNA sequences for optimised ribosome binding sites, various leader peptides for protein export and N- as well as C-terminal affinity tags for affinity chromatographic purification of the desired protein. High cell density cultivation and recombinant protein production were successfully tested. For further system biology based control and optimisation of the production process the genomes of two B. megaterium strains were completely elucidated, DNA arrays designed, proteome, fluxome and metabolome analyses performed and all data integrated using the bioinformatics platform MEGABAC. Now, solid theoretical and experimental bases for primary modeling attempts of the production process are available.

  11. Campus Eco Tours: An Integrative & Interactive Field Project for Undergraduate Biology Students

    ERIC Educational Resources Information Center

    Boes, Katie E.

    2013-01-01

    Outdoor areas within or near college campuses offer an opportunity for biology students to observe the natural world and apply concepts from class. Here, I describe an engaging and integrative project where undergraduate non-major biology students work in teams to develop and present professional "eco tours." This project takes place over multiple…

  12. Systems Biology in the Context of Big Data and Networks

    PubMed Central

    Altaf-Ul-Amin, Md.; Afendi, Farit Mochamad; Kiboi, Samuel Kuria; Kanaya, Shigehiko

    2014-01-01

    Science is going through two rapidly changing phenomena: one is the increasing capabilities of the computers and software tools from terabytes to petabytes and beyond, and the other is the advancement in high-throughput molecular biology producing piles of data related to genomes, transcriptomes, proteomes, metabolomes, interactomes, and so on. Biology has become a data intensive science and as a consequence biology and computer science have become complementary to each other bridged by other branches of science such as statistics, mathematics, physics, and chemistry. The combination of versatile knowledge has caused the advent of big-data biology, network biology, and other new branches of biology. Network biology for instance facilitates the system-level understanding of the cell or cellular components and subprocesses. It is often also referred to as systems biology. The purpose of this field is to understand organisms or cells as a whole at various levels of functions and mechanisms. Systems biology is now facing the challenges of analyzing big molecular biological data and huge biological networks. This review gives an overview of the progress in big-data biology, and data handling and also introduces some applications of networks and multivariate analysis in systems biology. PMID:24982882

  13. Modeling Integrated Farm Systems: A Tool for Developing more Economically and Environmentally Sustainable Farming Systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A number of models have been developed to represent farm systems, but only a few actually integrate all or most of the major biological, physical, and economic processes of a farm. Farm system models are used for decision support, education, and research purposes. Because of differences in the type ...

  14. Systems biology of recombinant protein production using Bacillus megaterium.

    PubMed

    Biedendieck, Rebekka; Borgmeier, Claudia; Bunk, Boyke; Stammen, Simon; Scherling, Christian; Meinhardt, Friedhelm; Wittmann, Christoph; Jahn, Dieter

    2011-01-01

    The Gram-negative bacterium Escherichia coli is the most widely used production host for recombinant proteins in both academia and industry. The Gram-positive bacterium Bacillus megaterium represents an increasingly used alternative for high yield intra- and extracellular protein synthesis. During the past two decades, multiple tools including gene expression plasmids and production strains have been developed. Introduction of free replicating and integrative plasmids into B. megaterium is possible via protoplasts transformation or transconjugation. Using His(6)- and StrepII affinity tags, the intra- or extracellular produced proteins can easily be purified in one-step procedures. Different gene expression systems based on the xylose controlled promoter P(xylA) and various phage RNA polymerase (T7, SP6, K1E) driven systems enable B. megaterium to produce up to 1.25g of recombinant protein per liter. Biomass concentrations of up to 80g/l can be achieved by high cell density cultivations in bioreactors. Gene knockouts and gene replacements in B. megaterium are possible via an optimized gene disruption system. For a safe application in industry, sporulation and protease-deficient as well as UV-sensitive mutants are available. With the help of the recently published B. megaterium genome sequence, it is possible to characterize bottle necks in the protein production process via systems biology approaches based on transcriptome, proteome, metabolome, and fluxome data. The bioinformatical platform (Megabac, http://www.megabac.tu-bs.de) integrates obtained theoretical and experimental data. PMID:21943898

  15. Fractal analysis in a Systems Biology approach to cancer

    PubMed Central

    Bizzarri, M.; Giuliani, A.; Cucina, A.; Anselmi, F. D; Soto, A. M.; Sonnenschein, C.

    2011-01-01

    Cancer is a highly complex disease due to the disruption of tissue architecture. Thus, tissues, and not individual cells, are the proper level of observation for the study of carcinogenesis. This paradigm shift from a reductionist approach to a systems biology approach is long overdue. Indeed, cell phenotypes are emergent modes arising through collective non-linear interactions among different cellular and microenvironmental components, generally described by “phase space diagrams”, where stable states (attractors) are embedded into a landscape model. Within this framework, cell states and cell transitions are generally conceived as mainly specified by gene-regulatory networks. However, the system s dynamics is not reducible to the integrated functioning of the genome-proteome network alone; the epithelia-stroma interacting system must be taken into consideration in order to give a more comprehensive picture. Given that cell shape represents the spatial geometric configuration acquired as a result of the integrated set of cellular and environmental cues, we posit that fractal-shape parameters represent “omics descriptors of the epithelium-stroma system. Within this framework, function appears to follow form, and not the other way around. PMID:21514387

  16. Interactive exploration of integrated biological datasets using context-sensitive workflows

    PubMed Central

    Horn, Fabian; Rittweger, Martin; Taubert, Jan; Lysenko, Artem; Rawlings, Christopher; Guthke, Reinhard

    2013-01-01

    Network inference utilizes experimental high-throughput data for the reconstruction of molecular interaction networks where new relationships between the network entities can be predicted. Despite the increasing amount of experimental data, the parameters of each modeling technique cannot be optimized based on the experimental data alone, but needs to be qualitatively assessed if the components of the resulting network describe the experimental setting. Candidate list prioritization and validation builds upon data integration and data visualization. The application of tools supporting this procedure is limited to the exploration of smaller information networks because the display and interpretation of large amounts of information is challenging regarding the computational effort and the users' experience. The Ondex software framework was extended with customizable context-sensitive menus which allow additional integration and data analysis options for a selected set of candidates during interactive data exploration. We provide new functionalities for on-the-fly data integration using InterProScan, PubMed Central literature search, and sequence-based homology search. We applied the Ondex system to the integration of publicly available data for Aspergillus nidulans and analyzed transcriptome data. We demonstrate the advantages of our approach by proposing new hypotheses for the functional annotation of specific genes of differentially expressed fungal gene clusters. Our extension of the Ondex framework makes it possible to overcome the separation between data integration and interactive analysis. More specifically, computationally demanding calculations can be performed on selected sub-networks without losing any information from the whole network. Furthermore, our extensions allow for direct access to online biological databases which helps to keep the integrated information up-to-date. PMID:24600467

  17. Membrane curvature in cell biology: An integration of molecular mechanisms.

    PubMed

    Jarsch, Iris K; Daste, Frederic; Gallop, Jennifer L

    2016-08-15

    Curving biological membranes establishes the complex architecture of the cell and mediates membrane traffic to control flux through subcellular compartments. Common molecular mechanisms for bending membranes are evident in different cell biological contexts across eukaryotic phyla. These mechanisms can be intrinsic to the membrane bilayer (either the lipid or protein components) or can be brought about by extrinsic factors, including the cytoskeleton. Here, we review examples of membrane curvature generation in animals, fungi, and plants. We showcase the molecular mechanisms involved and how they collaborate and go on to highlight contexts of curvature that are exciting areas of future research. Lessons from how membranes are bent in yeast and mammals give hints as to the molecular mechanisms we expect to see used by plants and protists. PMID:27528656

  18. “Turn-on” fluorescence probe integrated polymer nanoparticles for sensing biological thiol molecules

    PubMed Central

    Ang, Chung Yen; Tan, Si Yu; Lu, Yunpeng; Bai, Linyi; Li, Menghuan; Li, Peizhou; Zhang, Quan; Selvan, Subramanian Tamil; Zhao, Yanli

    2014-01-01

    A “turn-on” thiol-responsive fluorescence probe was synthesized and integrated into polymeric nanoparticles for sensing intracellular thiols. There is a photo-induced electron transfer process in the off state of the probe, and this process is terminated upon the reaction with thiol compounds. Configuration interaction singles (CIS) calculation was performed to confirm the mechanism of this process. A series of sensing studies were carried out, showing that the probe-integrated nanoparticles were highly selective towards biological thiol compounds over non-thiolated amino acids. Kinetic studies were also performed to investigate the relative reaction rate between the probe and the thiolated amino acids. Subsequently, the Gibbs free energy of the reactions was explored by means of the electrochemical method. Finally, the detection system was employed for sensing intracellular thiols in cancer cells, and the sensing selectivity could be further enhanced with the use of a cancer cell-targeting ligand in the nanoparticles. This development paves a path for the sensing and detection of biological thiols, serving as a potential diagnostic tool in the future. PMID:25394758

  19. Integrating ethical analysis "into the DNA" of synthetic biology.

    PubMed

    Heavey, Patrick

    2015-02-01

    Current ethical analysis tends to evaluate synthetic biology at an overview level. Synthetic biology, however, is an umbrella term that covers a variety of areas of research. These areas contain, in turn, a hierarchy of different research fields. This abstraction hierarchy-the term is borrowed from engineering-permits synthetic biologists to specialise to a very high degree. Though synthetic biology per se may create profound ethical challenges, much of the day-to-day research does not. Yet seemingly innocuous research could lead to ethically problematic results. For example, Dolly the sheep resulted from a long series of research steps, none of which presented any ethical problems. The atomic bomb was developed as a result of Einstein's uncontentions theoretical research that proved the equivalence of matter and energy. Therefore it would seem wise for ethicists to evaluate synbio research across its subfields and through its abstraction hierarchies, comparing and inter-relating the various areas of research. In addition, it would be useful if journals that publish synbio papers require an ethical statement from authors, as standard practice, so as to encourage scientists to constantly engage with ethical issues in their work. Also, this would allow an ethical snapshot of the state of the research at any given time to exist, allowing for accurate evaluation by scientists and ethicists, regulators and policymakers. PMID:25185871

  20. Integrated graphene/nanoparticle hybrids for biological and electronic applications.

    PubMed

    Nguyen, Kim Truc; Zhao, Yanli

    2014-06-21

    The development of novel graphene/nanoparticle hybrid materials is currently the subject of tremendous research interest. The intrinsic exceptional assets of both graphene (including graphene oxide and reduced graphene oxide) and nanoparticles render their hybrid materials synergic properties that can be useful in various applications. In this feature review, we highlight recent developments in graphene/nanoparticle hybrids and their promising potential in electronic and biological applications. First, the latest advances in synthetic methods for the preparation of the graphene/nanoparticle hybrids are introduced, with the emphasis on approaches to (1) decorate nanoparticles onto two-dimensional graphene and (2) wrap nanoparticles with graphene sheets. The pros and cons of large-scale synthesis are also discussed. Then, the state-of-the-art of graphene/nanoparticle hybrids in electronic and biological applications is reviewed. For electronic applications, we focus on the advantages of using these hybrids in transparent conducting films, as well as energy harvesting and storage. Biological applications, electrochemical biosensing, bioimaging, and drug delivery using the hybrids are showcased. Finally, the future research prospects and challenges in this rapidly developing area are discussed. PMID:24752364