Regulatory activities; Actividades regulatorias

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-07-01

This publication, compiled in 8 chapters, presents the regulatory system developed by the Nuclear Regulatory Authority (NRA) of the Argentine Republic. The following activities and developed topics in this document describe: the evolution of the nuclear regulatory activity in Argentina; the Argentine regulatory system; the nuclear regulatory laws and standards; the inspection and safeguards of nuclear facilities; the emergency systems; the environmental systems; the environmental monitoring; the analysis laboratories on physical and biological dosimetry, prenatal irradiation, internal irradiation, radiation measurements, detection techniques on nuclear testing, medical program on radiation protection; the institutional relations with national and international organization; the training courses and meeting; the technical information.

Systems Biology Approach to the Dissection of the Complexity of Regulatory Networks in the S. scrofa Cardiocirculatory System

Directory of Open Access Journals (Sweden)

Paolo Martini

2013-11-01

Full Text Available Genome-wide experiments are routinely used to increase the understanding of the biological processes involved in the development and maintenance of a variety of pathologies. Although the technical feasibility of this type of experiment has improved in recent years, data analysis remains challenging. In this context, gene set analysis has emerged as a fundamental tool for the interpretation of the results. Here, we review strategies used in the gene set approach, and using datasets for the pig cardiocirculatory system as a case study, we demonstrate how the use of a combination of these strategies can enhance the interpretation of results. Gene set analyses are able to distinguish vessels from the heart and arteries from veins in a manner that is consistent with the different cellular composition of smooth muscle cells. By integrating microRNA elements in the regulatory circuits identified, we find that vessel specificity is maintained through specific miRNAs, such as miR-133a and miR-143, which show anti-correlated expression with their mRNA targets.

A systems biology approach identified different regulatory networks targeted by KSHV miR-K12-11 in B cells and endothelial cells.

Science.gov (United States)

Yang, Yajie; Boss, Isaac W; McIntyre, Lauren M; Renne, Rolf

2014-08-08

Kaposi's sarcoma associated herpes virus (KSHV) is associated with tumors of endothelial and lymphoid origin. During latent infection, KSHV expresses miR-K12-11, an ortholog of the human tumor gene hsa-miR-155. Both gene products are microRNAs (miRNAs), which are important post-transcriptional regulators that contribute to tissue specific gene expression. Advances in target identification technologies and molecular interaction databases have allowed a systems biology approach to unravel the gene regulatory networks (GRNs) triggered by miR-K12-11 in endothelial and lymphoid cells. Understanding the tissue specific function of miR-K12-11 will help to elucidate underlying mechanisms of KSHV pathogenesis. Ectopic expression of miR-K12-11 differentially affected gene expression in BJAB cells of lymphoid origin and TIVE cells of endothelial origin. Direct miRNA targeting accounted for a small fraction of the observed transcriptome changes: only 29 genes were identified as putative direct targets of miR-K12-11 in both cell types. However, a number of commonly affected biological pathways, such as carbohydrate metabolism and interferon response related signaling, were revealed by gene ontology analysis. Integration of transcriptome profiling, bioinformatic algorithms, and databases of protein-protein interactome from the ENCODE project identified different nodes of GRNs utilized by miR-K12-11 in a tissue-specific fashion. These effector genes, including cancer associated transcription factors and signaling proteins, amplified the regulatory potential of a single miRNA, from a small set of putative direct targets to a larger set of genes. This is the first comparative analysis of miRNA-K12-11's effects in endothelial and B cells, from tissues infected with KSHV in vivo. MiR-K12-11 was able to broadly modulate gene expression in both cell types. Using a systems biology approach, we inferred that miR-K12-11 establishes its GRN by both repressing master TFs and influencing

Systems Biology of Industrial Microorganisms

Science.gov (United States)

Papini, Marta; Salazar, Margarita; Nielsen, Jens

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

A canonical correlation analysis-based dynamic bayesian network prior to infer gene regulatory networks from multiple types of biological data.

Science.gov (United States)

Baur, Brittany; Bozdag, Serdar

2015-04-01

One of the challenging and important computational problems in systems biology is to infer gene regulatory networks (GRNs) of biological systems. Several methods that exploit gene expression data have been developed to tackle this problem. In this study, we propose the use of copy number and DNA methylation data to infer GRNs. We developed an algorithm that scores regulatory interactions between genes based on canonical correlation analysis. In this algorithm, copy number or DNA methylation variables are treated as potential regulator variables, and expression variables are treated as potential target variables. We first validated that the canonical correlation analysis method is able to infer true interactions in high accuracy. We showed that the use of DNA methylation or copy number datasets leads to improved inference over steady-state expression. Our results also showed that epigenetic and structural information could be used to infer directionality of regulatory interactions. Additional improvements in GRN inference can be gleaned from incorporating the result in an informative prior in a dynamic Bayesian algorithm. This is the first study that incorporates copy number and DNA methylation into an informative prior in dynamic Bayesian framework. By closely examining top-scoring interactions with different sources of epigenetic or structural information, we also identified potential novel regulatory interactions.

Strengthening the regulatory system through the implementation and use of a quality management system

Directory of Open Access Journals (Sweden)

Reinhold Eisner

2017-04-01

Full Text Available ABSTRACT Quality management systems (QMS, based on ISO 9001 requirements, are applicable to government service organizations such as Health Canada’s Biologics and Genetic Therapies Directorate (BGTD. This communication presents the process that the BGTD followed since the early 2000s to implement a quality management system and describes how the regulatory system was improved as a result of this project. BGTD undertook the implementation of a quality management system based on ISO 9001 and containing aspects of ISO 17025 with the goal of strengthening the regulatory system through improvements in the people, processes, and services of the organization. We discuss the strategy used by BGTD to implement the QMS and the benefits that were realized from the various stages of implementation. The eight quality principals upon which the QMS standards of the ISO 9000 series are based were used by senior management as a framework to guide QMS implementation.

Systems Biology for Organotypic Cell Cultures

Energy Technology Data Exchange (ETDEWEB)

Grego, Sonia [RTI International, Research Triangle Park, NC (United States); Dougherty, Edward R. [Texas A & M Univ., College Station, TX (United States); Alexander, Francis J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Auerbach, Scott S. [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Berridge, Brian R. [GlaxoSmithKline, Research Triangle Park, NC (United States); Bittner, Michael L. [Translational Genomics Research Inst., Phoenix, AZ (United States); Casey, Warren [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Cooley, Philip C. [RTI International, Research Triangle Park, NC (United States); Dash, Ajit [HemoShear Therapeutics, Charlottesville, VA (United States); Ferguson, Stephen S. [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Fennell, Timothy R. [RTI International, Research Triangle Park, NC (United States); Hawkins, Brian T. [RTI International, Research Triangle Park, NC (United States); Hickey, Anthony J. [RTI International, Research Triangle Park, NC (United States); Kleensang, Andre [Johns Hopkins Univ., Baltimore, MD (United States). Center for Alternatives to Animal Testing; Liebman, Michael N. [IPQ Analytics, Kennett Square, PA (United States); Martin, Florian [Phillip Morris International, Neuchatel (Switzerland); Maull, Elizabeth A. [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Paragas, Jason [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Qiao, Guilin [Defense Threat Reduction Agency, Ft. Belvoir, VA (United States); Ramaiahgari, Sreenivasa [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Sumner, Susan J. [RTI International, Research Triangle Park, NC (United States); Yoon, Miyoung [The Hamner Inst. for Health Sciences, Research Triangle Park, NC (United States); ScitoVation, Research Triangle Park, NC (United States)

2016-08-04

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

Comparing genomes to computer operating systems in terms of the topology and evolution of their regulatory control networks.

Science.gov (United States)

Yan, Koon-Kiu; Fang, Gang; Bhardwaj, Nitin; Alexander, Roger P; Gerstein, Mark

2010-05-18

The genome has often been called the operating system (OS) for a living organism. A computer OS is described by a regulatory control network termed the call graph, which is analogous to the transcriptional regulatory network in a cell. To apply our firsthand knowledge of the architecture of software systems to understand cellular design principles, we present a comparison between the transcriptional regulatory network of a well-studied bacterium (Escherichia coli) and the call graph of a canonical OS (Linux) in terms of topology and evolution. We show that both networks have a fundamentally hierarchical layout, but there is a key difference: The transcriptional regulatory network possesses a few global regulators at the top and many targets at the bottom; conversely, the call graph has many regulators controlling a small set of generic functions. This top-heavy organization leads to highly overlapping functional modules in the call graph, in contrast to the relatively independent modules in the regulatory network. We further develop a way to measure evolutionary rates comparably between the two networks and explain this difference in terms of network evolution. The process of biological evolution via random mutation and subsequent selection tightly constrains the evolution of regulatory network hubs. The call graph, however, exhibits rapid evolution of its highly connected generic components, made possible by designers' continual fine-tuning. These findings stem from the design principles of the two systems: robustness for biological systems and cost effectiveness (reuse) for software systems.

Construction of an integrated gene regulatory network link to stress-related immune system in cattle.

Science.gov (United States)

Behdani, Elham; Bakhtiarizadeh, Mohammad Reza

2017-10-01

The immune system is an important biological system that is negatively impacted by stress. This study constructed an integrated regulatory network to enhance our understanding of the regulatory gene network used in the stress-related immune system. Module inference was used to construct modules of co-expressed genes with bovine leukocyte RNA-Seq data. Transcription factors (TFs) were then assigned to these modules using Lemon-Tree algorithms. In addition, the TFs assigned to each module were confirmed using the promoter analysis and protein-protein interactions data. Therefore, our integrated method identified three TFs which include one TF that is previously known to be involved in immune response (MYBL2) and two TFs (E2F8 and FOXS1) that had not been recognized previously and were identified for the first time in this study as novel regulatory candidates in immune response. This study provides valuable insights on the regulatory programs of genes involved in the stress-related immune system.

Evolving a lingua franca and associated software infrastructure for computational systems biology: the Systems Biology Markup Language (SBML) project.

Science.gov (United States)

Hucka, M; Finney, A; Bornstein, B J; Keating, S M; Shapiro, B E; Matthews, J; Kovitz, B L; Schilstra, M J; Funahashi, A; Doyle, J C; Kitano, H

2004-06-01

Biologists are increasingly recognising that computational modelling is crucial for making sense of the vast quantities of complex experimental data that are now being collected. The systems biology field needs agreed-upon information standards if models are to be shared, evaluated and developed cooperatively. Over the last four years, our team has been developing the Systems Biology Markup Language (SBML) in collaboration with an international community of modellers and software developers. SBML has become a de facto standard format for representing formal, quantitative and qualitative models at the level of biochemical reactions and regulatory networks. In this article, we summarise the current and upcoming versions of SBML and our efforts at developing software infrastructure for supporting and broadening its use. We also provide a brief overview of the many SBML-compatible software tools available today.

Management systems for regulatory authorities

International Nuclear Information System (INIS)

Mpandanyama, Rujeko Lynette

2015-02-01

For a regulatory body to fulfil its statutory obligations, there is need to develop and implement a regulatory management system that has the necessary arrangements for achieving and maintaining high quality performance in regulating the safety of nuclear and radiation facilities under its authority. Hence, the regulatory management system needs to fully integrate the human resources, processes and physical resources of the organization. This study sought to provide an understanding of the concept, principles, policies and fundamentals of management systems as they relate to regulatory systems in the field of radiation protection and to make appropriate recommendations to ensure that an effective management system exists for the control of ionizing radiation and radiation sources and addresses all relevant stakeholders in Zimbabwe. A comparative analysis was done on the current management status and the ideal management system, which led to the identification of the gaps existing. The main key that was found to be of significance was lack of linkages between processes and management tools within the institution. (au)

Spatiotemporal network motif reveals the biological traits of developmental gene regulatory networks in Drosophila melanogaster

Directory of Open Access Journals (Sweden)

Kim Man-Sun

2012-05-01

Full Text Available Abstract Background Network motifs provided a “conceptual tool” for understanding the functional principles of biological networks, but such motifs have primarily been used to consider static network structures. Static networks, however, cannot be used to reveal time- and region-specific traits of biological systems. To overcome this limitation, we proposed the concept of a “spatiotemporal network motif,” a spatiotemporal sequence of network motifs of sub-networks which are active only at specific time points and body parts. Results On the basis of this concept, we analyzed the developmental gene regulatory network of the Drosophila melanogaster embryo. We identified spatiotemporal network motifs and investigated their distribution pattern in time and space. As a result, we found how key developmental processes are temporally and spatially regulated by the gene network. In particular, we found that nested feedback loops appeared frequently throughout the entire developmental process. From mathematical simulations, we found that mutual inhibition in the nested feedback loops contributes to the formation of spatial expression patterns. Conclusions Taken together, the proposed concept and the simulations can be used to unravel the design principle of developmental gene regulatory networks.

Newton, Laplace, and The Epistemology of Systems Biology

Science.gov (United States)

Bittner, Michael L.; Dougherty, Edward R.

2012-01-01

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

An Integrated Biological Control System At Hanford

International Nuclear Information System (INIS)

Johnson, A.R.; Caudill, J.G.; Giddings, R.F.; Rodriguez, J.M.; Roos, R.C.; Wilde, J.W.

2010-01-01

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

AN INTEGRATED BIOLOGICAL CONTROL SYSTEM AT HANFORD

Energy Technology Data Exchange (ETDEWEB)

JOHNSON AR; CAUDILL JG; GIDDINGS RF; RODRIGUEZ JM; ROOS RC; WILDE JW

2010-02-11

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

Programming Morphogenesis through Systems and Synthetic Biology.

Science.gov (United States)

Velazquez, Jeremy J; Su, Emily; Cahan, Patrick; Ebrahimkhani, Mo R

2018-04-01

Mammalian tissue development is an intricate, spatiotemporal process of self-organization that emerges from gene regulatory networks of differentiating stem cells. A major goal in stem cell biology is to gain a sufficient understanding of gene regulatory networks and cell-cell interactions to enable the reliable and robust engineering of morphogenesis. Here, we review advances in synthetic biology, single cell genomics, and multiscale modeling, which, when synthesized, provide a framework to achieve the ambitious goal of programming morphogenesis in complex tissues and organoids. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sociotechnical systems as a framework for regulatory system design and evaluation: Using Work Domain Analysis to examine a new regulatory system.

Science.gov (United States)

Carden, Tony; Goode, Natassia; Read, Gemma J M; Salmon, Paul M

2017-03-15

Like most work systems, the domain of adventure activities has seen a series of serious incidents and subsequent calls to improve regulation. Safety regulation systems aim to promote safety and reduce accidents. However, there is scant evidence they have led to improved safety outcomes. In fact there is some evidence that the poor integration of regulatory system components has led to adverse safety outcomes in some contexts. Despite this, there is an absence of methods for evaluating regulatory and compliance systems. This article argues that sociotechnical systems theory and methods provide a suitable framework for evaluating regulatory systems. This is demonstrated through an analysis of a recently introduced set of adventure activity regulations. Work Domain Analysis (WDA) was used to describe the regulatory system in terms of its functional purposes, values and priority measures, purpose-related functions, object-related processes and cognitive objects. This allowed judgement to be made on the nature of the new regulatory system and on the constraints that may impact its efficacy following implementation. Importantly, the analysis suggests that the new system's functional purpose of ensuring safe activities is not fully supported in terms of the functions and objects available to fulfil them. Potential improvements to the design of the system are discussed along with the implications for regulatory system design and evaluation across the safety critical domains generally. Copyright © 2017 Elsevier Ltd. All rights reserved.

Understanding genetic variation - the value of systems biology.

Science.gov (United States)

Hütt, Marc-Thorsten

2014-04-01

Pharmacology is currently transformed by the vast amounts of genome-associated information available for system-level interpretation. Here I review the potential of systems biology to facilitate this interpretation, thus paving the way for the emerging field of systems pharmacology. In particular, I will show how gene regulatory and metabolic networks can serve as a framework for interpreting high throughput data and as an interface to detailed dynamical models. In addition to the established connectivity analyses of effective networks, I suggest here to also analyze higher order architectural properties of effective networks. © 2013 The British Pharmacological Society.

Using synthetic biology to distinguish and overcome regulatory and functional barriers related to nitrogen fixation.

Directory of Open Access Journals (Sweden)

Xia Wang

Full Text Available Biological nitrogen fixation is a complex process requiring multiple genes working in concert. To date, the Klebsiella pneumoniae nif gene cluster, divided into seven operons, is one of the most studied systems. Its nitrogen fixation capacity is subject to complex cascade regulation and physiological limitations. In this report, the entire K. pneumoniae nif gene cluster was reassembled as operon-based BioBrick parts in Escherichia coli. It provided ~100% activity of native K. pneumoniae system. Based on the expression levels of these BioBrick parts, a T7 RNA polymerase-LacI expression system was used to replace the σ(54-dependent promoters located upstream of nif operons. Expression patterns of nif operons were critical for the maximum activity of the recombinant system. By mimicking these expression levels with variable-strength T7-dependent promoters, ~42% of the nitrogenase activity of the σ(54-dependent nif system was achieved in E. coli. When the newly constructed T7-dependent nif system was challenged with different genetic and physiological conditions, it bypassed the original complex regulatory circuits, with minor physiological limitations. Therefore, we have successfully replaced the nif regulatory elements with a simple expression system that may provide the first step for further research of introducing nif genes into eukaryotic organelles, which has considerable potentials in agro-biotechnology.

Logical knowledge representation of regulatory relations in biomedical pathways

DEFF Research Database (Denmark)

Zambach, Sine; Hansen, Jens Ulrik

2010-01-01

Knowledge on regulatory relations, in for example regulatory pathways in biology, is used widely in experiment design by biomedical researchers and in systems biology. The knowledge has typically either been represented through simple graphs or through very expressive differential equation...... simulations of smaller parts of a pathway. In this work we suggest a knowledge representation of the most basic relations in regulatory processes regulates, positively regulates and negatively regulates in logics based on a semantic analysis. We discuss the usage of these relations in biology and in articial...... intelligence for hypothesis development in drug discovery....

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

International Nuclear Information System (INIS)

Wang, Rui-Sheng; Albert, Réka; Saadatpour, Assieh

2012-01-01

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

7th Annual Systems Biology Symposium: Systems Biology and Engineering

Energy Technology Data Exchange (ETDEWEB)

Galitski, Timothy P.

2008-04-01

Systems biology recognizes the complex multi-scale organization of biological systems, from molecules to ecosystems. The International Symposium on Systems Biology has been hosted by the Institute for Systems Biology in Seattle, Washington, since 2002. The annual two-day event gathers the most influential researchers transforming biology into an integrative discipline investingating complex systems. Engineering and application of new technology is a central element of systems biology. Genome-scale, or very small-scale, biological questions drive the enigneering of new technologies, which enable new modes of experimentation and computational analysis, leading to new biological insights and questions. Concepts and analytical methods in engineering are now finding direct applications in biology. Therefore, the 2008 Symposium, funded in partnership with the Department of Energy, featured global leaders in "Systems Biology and Engineering."

A Checklist for Successful Quantitative Live Cell Imaging in Systems Biology

Science.gov (United States)

Sung, Myong-Hee

2013-01-01

Mathematical modeling of signaling and gene regulatory networks has provided unique insights about systems behaviors for many cell biological problems of medical importance. Quantitative single cell monitoring has a crucial role in advancing systems modeling of molecular networks. However, due to the multidisciplinary techniques that are necessary for adaptation of such systems biology approaches, dissemination to a wide research community has been relatively slow. In this essay, I focus on some technical aspects that are often under-appreciated, yet critical in harnessing live cell imaging methods to achieve single-cell-level understanding and quantitative modeling of molecular networks. The importance of these technical considerations will be elaborated with examples of successes and shortcomings. Future efforts will benefit by avoiding some pitfalls and by utilizing the lessons collectively learned from recent applications of imaging in systems biology. PMID:24709701

Polynomial algebra of discrete models in systems biology.

Science.gov (United States)

Veliz-Cuba, Alan; Jarrah, Abdul Salam; Laubenbacher, Reinhard

2010-07-01

An increasing number of discrete mathematical models are being published in Systems Biology, ranging from Boolean network models to logical models and Petri nets. They are used to model a variety of biochemical networks, such as metabolic networks, gene regulatory networks and signal transduction networks. There is increasing evidence that such models can capture key dynamic features of biological networks and can be used successfully for hypothesis generation. This article provides a unified framework that can aid the mathematical analysis of Boolean network models, logical models and Petri nets. They can be represented as polynomial dynamical systems, which allows the use of a variety of mathematical tools from computer algebra for their analysis. Algorithms are presented for the translation into polynomial dynamical systems. Examples are given of how polynomial algebra can be used for the model analysis. alanavc@vt.edu Supplementary data are available at Bioinformatics online.

Low doses of ionizing radiation: Biological effects and regulatory control. Contributed papers

International Nuclear Information System (INIS)

1997-11-01

The International Atomic Energy Agency and the World Health Organization, in cooperation with the United Nations Scientific Committee on the Effects of Atomic Radiation, organized an international conference on Low Doses of Ionizing Radiation: Biological Effects and Regulatory Control, held in seville, Spain, from 17 to 21 November 1997. This technical document contains concise papers submitted to the conference

Prokaryotic regulatory systems biology: Common principles governing the functional architectures of Bacillus subtilis and Escherichia coli unveiled by the natural decomposition approach.

Science.gov (United States)

Freyre-González, Julio A; Treviño-Quintanilla, Luis G; Valtierra-Gutiérrez, Ilse A; Gutiérrez-Ríos, Rosa María; Alonso-Pavón, José A

2012-10-31

Escherichia coli and Bacillus subtilis are two of the best-studied prokaryotic model organisms. Previous analyses of their transcriptional regulatory networks have shown that they exhibit high plasticity during evolution and suggested that both converge to scale-free-like structures. Nevertheless, beyond this suggestion, no analyses have been carried out to identify the common systems-level components and principles governing these organisms. Here we show that these two phylogenetically distant organisms follow a set of common novel biologically consistent systems principles revealed by the mathematically and biologically founded natural decomposition approach. The discovered common functional architecture is a diamond-shaped, matryoshka-like, three-layer (coordination, processing, and integration) hierarchy exhibiting feedback, which is shaped by four systems-level components: global transcription factors (global TFs), locally autonomous modules, basal machinery and intermodular genes. The first mathematical criterion to identify global TFs, the κ-value, was reassessed on B. subtilis and confirmed its high predictive power by identifying all the previously reported, plus three potential, master regulators and eight sigma factors. The functionally conserved cores of modules, basal cell machinery, and a set of non-orthologous common physiological global responses were identified via both orthologous genes and non-orthologous conserved functions. This study reveals novel common systems principles maintained between two phylogenetically distant organisms and provides a comparison of their lifestyle adaptations. Our results shed new light on the systems-level principles and the fundamental functions required by bacteria to sustain life. Copyright © 2012 Elsevier B.V. All rights reserved.

Systems Biology Graphical Notation: Process Description language Level 1 Version 1.3.

Science.gov (United States)

Moodie, Stuart; Le Novère, Nicolas; Demir, Emek; Mi, Huaiyu; Villéger, Alice

2015-09-04

The Systems Biological Graphical Notation (SBGN) is an international community effort for standardized graphical representations of biological pathways and networks. The goal of SBGN is to provide unambiguous pathway and network maps for readers with different scientific backgrounds as well as to support efficient and accurate exchange of biological knowledge between different research communities, industry, and other players in systems biology. Three SBGN languages, Process Description (PD), Entity Relationship (ER) and Activity Flow (AF), allow for the representation of different aspects of biological and biochemical systems at different levels of detail. The SBGN Process Description language represents biological entities and processes between these entities within a network. SBGN PD focuses on the mechanistic description and temporal dependencies of biological interactions and transformations. The nodes (elements) are split into entity nodes describing, e.g., metabolites, proteins, genes and complexes, and process nodes describing, e.g., reactions and associations. The edges (connections) provide descriptions of relationships (or influences) between the nodes, such as consumption, production, stimulation and inhibition. Among all three languages of SBGN, PD is the closest to metabolic and regulatory pathways in biological literature and textbooks, but its well-defined semantics offer a superior precision in expressing biological knowledge.

Regulatory and biosafety issues in relation to transgenic animals in food and agriculture, feeds containing genetically modified organisms (GMO) and veterinary biologics

International Nuclear Information System (INIS)

Kochhar, H.P.S.; Gifford, G.A.; Kahn, S.

2005-01-01

Development of an effective regulatory system for genetically engineered animals and their products has been the subject of increasing discussion among researchers, industry and policy developers, as well as the public. Since transgenesis and cloning are relatively new scientific techniques, transgenic animals are new organisms for which there is limited information. The issues associated with the regulation and biosafety of transgenic animals pertain to environmental impact, human food safety, animal health and welfare, trade and ethics. To regulate this new and powerful technology predicated on limited background information is a challenge not only for the regulators, but also for the developers of such animals, who strive to prove that the animals are safe and merit bio-equivalency to their conventional counterparts. In principle, an effective regulatory sieve should permit safe products while forming a formidable barrier for those assessed of posing an unacceptable risk. Adoption of transgenic technology for use in agriculture will depend upon various factors that range from perceived benefits for humans and animals, to safe propagation, animal welfare considerations and integrity of species, as well as effects on bio-diversity. A regulatory framework designed to address the concerns connected with the environmental release of transgenic animals needs to also take into account the ability of genetically modified animals to survive and compete with conventional populations. Regulatory initiatives for biotechnology-derived animals and their products should ensure high standards for human and animal health; a sound scientific basis for evaluation; transparency and public involvement; and maintenance of genetic diversity. Feeds obtained by use of biotechnology have to be evaluated for animal and human safety by using parameters that define their molecular characterization, nutritional qualities and toxicological aspects, while veterinary biologics derived from

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

Science.gov (United States)

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

2012-01-01

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

Regulatory inhibition of biological tissue mineralization by calcium phosphate through post-nucleation shielding by fetuin-A

Energy Technology Data Exchange (ETDEWEB)

Chang, Joshua C., E-mail: joshchang@ucla.edu [Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA and Mathematical Biosciences Institute, The Ohio State University, Columbus, Ohio 43210 (United States); Miura, Robert M., E-mail: miura@njit.edu [Department of Mathematical Sciences, New Jersey Institute of Technology, Newark, New Jersey 07102 (United States)

2016-04-21

In vertebrates, insufficient availability of calcium and inorganic phosphate ions in extracellular fluids leads to loss of bone density and neuronal hyper-excitability. To counteract this problem, calcium ions are usually present at high concentrations throughout bodily fluids—at concentrations exceeding the saturation point. This condition leads to the opposite situation where unwanted mineral sedimentation may occur. Remarkably, ectopic or out-of-place sedimentation into soft tissues is rare, in spite of the thermodynamic driving factors. This fortunate fact is due to the presence of auto-regulatory proteins that are found in abundance in bodily fluids. Yet, many important inflammatory disorders such as atherosclerosis and osteoarthritis are associated with this undesired calcification. Hence, it is important to gain an understanding of the regulatory process and the conditions under which it can go awry. In this manuscript, we extend mean-field continuum classical nucleation theory of the growth of clusters to encompass surface shielding. We use this formulation to study the regulation of sedimentation of calcium phosphate salts in biological tissues through the mechanism of post-nuclear shielding of nascent mineral particles by binding proteins. We develop a mathematical description of this phenomenon using a countable system of hyperbolic partial differential equations. A critical concentration of regulatory protein is identified as a function of the physical parameters that describe the system.

Low doses of ionizing radiation: Biological effects and regulatory control. Contributed papers

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-11-01

The International Atomic Energy Agency and the World Health Organization, in cooperation with the United Nations Scientific Committee on the Effects of Atomic Radiation, organized an international conference on Low Doses of Ionizing Radiation: Biological Effects and Regulatory Control, held in seville, Spain, from 17 to 21 November 1997. This technical document contains concise papers submitted to the conference. Refs, figs, tabs.

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

Science.gov (United States)

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

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

Directory of Open Access Journals (Sweden)

Bor-Sen Chen

2013-10-01

Full Text Available 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.

Risk undermined in the bilateral pharmaceutical regulatory system in Taiwan.

Science.gov (United States)

Wang, Hui-Po; Wang, Chun-Li

2018-04-01

The concept of Pharmacovigilance Planning and Risk Minimization Planning (PVP/RMP), initiated by the International Conference on Harmonization (ICH), addressed an important conceptual change from monitoring the safety of individual medicine to proactively conducting risk prevention for the minimization of medication error. However, the implementation of PVP/RMP is a challenge in societies like Taiwan where irrational medication and co-medication is prevalent. It is even more difficult in Taiwan where two regulatory bodies are governing pharmaceutical affairs, namely Taiwan Food and Drug Administration (TFDA) in charge of Western Medicine (WM) and the Department of Chinese Medicine and Pharmacy (DCMP) in charge of Traditional Chinese Medicine (TCM). There are thus dual-tract drug approval panels, two GMP controls and two independent adverse drug event reporting systems. This rendered irrational co-medication of WM and TCM undetectable and the standard tools for monitoring pharmacovigilance inapplicable. The bilateral regulatory system is conceptually unscientific in accordance with PVP/RMP and unethical from humanity point of view. The first part of this review delivers (1) social aspects of polypharmacy in Taiwan; (2) regulatory aspects of pharmaceutical administration; (3) risks undermined in the bilateral regulatory system and (4) pharmacoepidemiology in relation to the risk of polypharmacy. As evidence-based medicine (EBM) forms the fundamental risk-benefit assessment on medication, the second part of this review delivers (1) the scientific aspects of the beauty and the odds of biological system that governs host-xenobiotics interaction; (2) conceptual evolution from product management (pharmacovigilance) to risk management (PVP/RMP); (3) non-biased due process is essential for risk-benefit assessment on medicinal products and (4) the opinion of the authors on system building for safe medication. Copyright © 2018. Published by Elsevier B.V.

Mammalian synthetic biology for studying the cell.

Science.gov (United States)

Mathur, Melina; Xiang, Joy S; Smolke, Christina D

2017-01-02

Synthetic biology is advancing the design of genetic devices that enable the study of cellular and molecular biology in mammalian cells. These genetic devices use diverse regulatory mechanisms to both examine cellular processes and achieve precise and dynamic control of cellular phenotype. Synthetic biology tools provide novel functionality to complement the examination of natural cell systems, including engineered molecules with specific activities and model systems that mimic complex regulatory processes. Continued development of quantitative standards and computational tools will expand capacities to probe cellular mechanisms with genetic devices to achieve a more comprehensive understanding of the cell. In this study, we review synthetic biology tools that are being applied to effectively investigate diverse cellular processes, regulatory networks, and multicellular interactions. We also discuss current challenges and future developments in the field that may transform the types of investigation possible in cell biology. © 2017 Mathur et al.

Applying differential dynamic logic to reconfigurable biological networks.

Science.gov (United States)

Figueiredo, Daniel; Martins, Manuel A; Chaves, Madalena

2017-09-01

Qualitative and quantitative modeling frameworks are widely used for analysis of biological regulatory networks, the former giving a preliminary overview of the system's global dynamics and the latter providing more detailed solutions. Another approach is to model biological regulatory networks as hybrid systems, i.e., systems which can display both continuous and discrete dynamic behaviors. Actually, the development of synthetic biology has shown that this is a suitable way to think about biological systems, which can often be constructed as networks with discrete controllers, and present hybrid behaviors. In this paper we discuss this approach as a special case of the reconfigurability paradigm, well studied in Computer Science (CS). In CS there are well developed computational tools to reason about hybrid systems. We argue that it is worth applying such tools in a biological context. One interesting tool is differential dynamic logic (dL), which has recently been developed by Platzer and applied to many case-studies. In this paper we discuss some simple examples of biological regulatory networks to illustrate how dL can be used as an alternative, or also as a complement to methods already used. Copyright © 2017 Elsevier Inc. All rights reserved.

Transcriptional regulatory programs underlying barley germination and regulatory functions of Gibberellin and abscisic acid

Science.gov (United States)

2011-01-01

germination. Those genes and metabolic pathways are likely to be important parts of transcriptional regulatory networks underlying GA and ABA regulation of seed germination and seedling growth. Conclusions The studies developed a model depicting transcriptional regulatory programs underlying barley germination and GA and ABA regulation of germination at gene, pathway and systems levels, and established a standard transcriptome reference for further integration with various -omics and biological data to illustrate biological networks underlying seed germination. The studies also generated a great amount of systems biological evidence for previously proposed hypotheses, and developed a number of new hypotheses on transcriptional regulation of seed germination for further experimental validation. PMID:21668981

Transcriptional regulatory programs underlying barley germination and regulatory functions of Gibberellin and abscisic acid

Directory of Open Access Journals (Sweden)

Lin Li

2011-06-01

-regulated by both GA and seed germination. Those genes and metabolic pathways are likely to be important parts of transcriptional regulatory networks underlying GA and ABA regulation of seed germination and seedling growth. Conclusions The studies developed a model depicting transcriptional regulatory programs underlying barley germination and GA and ABA regulation of germination at gene, pathway and systems levels, and established a standard transcriptome reference for further integration with various -omics and biological data to illustrate biological networks underlying seed germination. The studies also generated a great amount of systems biological evidence for previously proposed hypotheses, and developed a number of new hypotheses on transcriptional regulation of seed germination for further experimental validation.

Using systems and structure biology tools to dissect cellular phenotypes.

Science.gov (United States)

Floratos, Aris; Honig, Barry; Pe'er, Dana; Califano, Andrea

2012-01-01

The Center for the Multiscale Analysis of Genetic Networks (MAGNet, http://magnet.c2b2.columbia.edu) was established in 2005, with the mission of providing the biomedical research community with Structural and Systems Biology algorithms and software tools for the dissection of molecular interactions and for the interaction-based elucidation of cellular phenotypes. Over the last 7 years, MAGNet investigators have developed many novel analysis methodologies, which have led to important biological discoveries, including understanding the role of the DNA shape in protein-DNA binding specificity and the discovery of genes causally related to the presentation of malignant phenotypes, including lymphoma, glioma, and melanoma. Software tools implementing these methodologies have been broadly adopted by the research community and are made freely available through geWorkbench, the Center's integrated analysis platform. Additionally, MAGNet has been instrumental in organizing and developing key conferences and meetings focused on the emerging field of systems biology and regulatory genomics, with special focus on cancer-related research.

Emotion: The Self-regulatory Sense.

Science.gov (United States)

Peil, Katherine T

2014-03-01

While emotion is a central component of human health and well-being, traditional approaches to understanding its biological function have been wanting. A dynamic systems model, however, broadly redefines and recasts emotion as a primary sensory system-perhaps the first sensory system to have emerged, serving the ancient autopoietic function of "self-regulation." Drawing upon molecular biology and revelations from the field of epigenetics, the model suggests that human emotional perceptions provide an ongoing stream of "self-relevant" sensory information concerning optimally adaptive states between the organism and its immediate environment, along with coupled behavioral corrections that honor a universal self-regulatory logic, one still encoded within cellular signaling and immune functions. Exemplified by the fundamental molecular circuitry of sensorimotor control in the E coli bacterium, the model suggests that the hedonic (affective) categories emerge directly from positive and negative feedback processes, their good/bad binary appraisals relating to dual self-regulatory behavioral regimes-evolutionary purposes, through which organisms actively participate in natural selection, and through which humans can interpret optimal or deficit states of balanced being and becoming. The self-regulatory sensory paradigm transcends anthropomorphism, unites divergent theoretical perspectives and isolated bodies of literature, while challenging time-honored assumptions. While suppressive regulatory strategies abound, it suggests that emotions are better understood as regulating us, providing a service crucial to all semantic language, learning systems, evaluative decision-making, and fundamental to optimal physical, mental, and social health.

Regulatory system reform of occupational health and safety in China.

Science.gov (United States)

Wu, Fenghong; Chi, Yan

2015-01-01

With the explosive economic growth and social development, China's regulatory system of occupational health and safety now faces more and more challenges. This article reviews the history of regulatory system of occupational health and safety in China, as well as the current reform of this regulatory system in the country. Comprehensive, a range of laws, regulations and standards that promulgated by Chinese government, duties and responsibilities of the regulatory departments are described. Problems of current regulatory system, the ongoing adjustments and changes for modifying and improving regulatory system are discussed. The aim of reform and the incentives to drive forward more health and safety conditions in workplaces are also outlined.

Regulatory control of physical protection systems

International Nuclear Information System (INIS)

Rajdeep; Mayya, Y.S.

2017-01-01

The safety of facilities in BARC is under the regulatory oversight of BSC. The security architecture for these facilities incorporates multiple layers of Physical Protection Systems. The demands of safety may sometimes conflict with the needs of security. Realizing the need to identify these interfaces and extend the regulatory coverage to Physical Protection Systems, a Standing Committee named Physical Protection System Review Committee (PPSRC) has been constituted as a 2"n"d tier entity of BSC. PPSRC includes experts from various domains concerned with nuclear security, viz. physical protection systems, cyber security, radiation safety, security operations, technical services and security administration

Regulatory system reform of occupational health and safety in China

Science.gov (United States)

WU, Fenghong; CHI, Yan

2015-01-01

With the explosive economic growth and social development, China’s regulatory system of occupational health and safety now faces more and more challenges. This article reviews the history of regulatory system of occupational health and safety in China, as well as the current reform of this regulatory system in the country. Comprehensive, a range of laws, regulations and standards that promulgated by Chinese government, duties and responsibilities of the regulatory departments are described. Problems of current regulatory system, the ongoing adjustments and changes for modifying and improving regulatory system are discussed. The aim of reform and the incentives to drive forward more health and safety conditions in workplaces are also outlined. PMID:25843565

Complex biological and bio-inspired systems

Energy Technology Data Exchange (ETDEWEB)

Ecke, Robert E [Los Alamos National Laboratory

2009-01-01

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

Regulatory issues associated with the Multi-Purpose (MPC) system

International Nuclear Information System (INIS)

Roberts, J.P.; Desell, L.J.; Birch, M.L.; Morgan, R.G.

1994-01-01

The US Department of Energy Office of Civilian Radioactive Waste Management is developing a Multi-Purpose Canister system to promote compatibility between the waste program elements of storage, transportation, and disposal. The development of a Multi-Purpose Canister system requires meeting various regulatory requirements. These regulatory requirements are set forth in environmental and Nuclear Regulatory Commission (NRC) regulations. This paper discusses the more significant regulatory issues that must be addressed in the development of a Multi-Purpose Canister system by the Department of Energy

Feedback dynamics and cell function: Why systems biology is called Systems Biology.

Science.gov (United States)

Wolkenhauer, Olaf; Mesarovic, Mihajlo

2005-05-01

A new paradigm, like Systems Biology, should challenge the way research has been conducted previously. This Opinion article aims to present Systems Biology, not as the application of engineering principles to biology but as a merger of systems- and control theory with molecular- and cell biology. In our view, the central dogma of Systems Biology is that it is system dynamics that gives rise to the functioning and function of cells. The concepts of feedback regulation and control of pathways and the coordination of cell function are emphasized as an important area of Systems Biology research. The hurdles and risks for this area are discussed from the perspective of dynamic pathway modelling. Most of all, the aim of this article is to promote mathematical modelling and simulation as a part of molecular- and cell biology. Systems Biology is a success if it is widely accepted that there is nothing more practical than a good theory.

Identification and Characterization of 5′ Untranslated Regions (5′UTRs in Zymomonas mobilis as Regulatory Biological Parts

Directory of Open Access Journals (Sweden)

Seung Hee Cho

2017-12-01

Full Text Available Regulatory RNA regions within a transcript, particularly in the 5′ untranslated region (5′UTR, have been shown in a variety of organisms to control the expression levels of these mRNAs in response to various metabolites or environmental conditions. Considering the unique tolerance of Zymomonas mobilis to ethanol and the growing interest in engineering microbial strains with enhanced tolerance to industrial inhibitors, we searched natural cis-regulatory regions in this microorganism using transcriptomic data and bioinformatics analysis. Potential regulatory 5′UTRs were identified and filtered based on length, gene function, relative gene counts, and conservation in other organisms. An in vivo fluorescence-based screening system was developed to confirm the responsiveness of 36 5′UTR candidates to ethanol, acetate, and xylose stresses. UTR_ZMO0347 (5′UTR of gene ZMO0347 encoding the RNA binding protein Hfq was found to down-regulate downstream gene expression under ethanol stress. Genomic deletion of UTR_ZMO0347 led to a general decrease of hfq expression at the transcript level and increased sensitivity for observed changes in Hfq expression at the protein level. The role of UTR_ZMO0347 and other 5′UTRs gives us insight into the regulatory network of Z. mobilis in response to stress and unlocks new strategies for engineering robust industrial strains as well as for harvesting novel responsive regulatory biological parts for controllable gene expression platforms in this organism.

Assessing the effectiveness of nuclear regulatory system in India

International Nuclear Information System (INIS)

Gandhia, Sonal; Choi, Kwang Sik

2012-01-01

The Fukushima accident brought up the issue of regulatory effectiveness in the fore. One of the causes of the accident has been attributed to the problems in effectiveness of the Japanese regulatory system. Regulatory reform is underway in Japan and in other countries many efforts have also been made to improve the effectiveness and independence of the regulatory bodies. It is important that the regulatory bodies make self-assessment of their weaknesses and strengths, to achieve the ultimate regulatory goal of assuring acceptable level of nuclear safety. In this paper an assessment has been done for the effectiveness of Indian nuclear regulatory system as implemented by the Atomic Energy Regulatory board (AERB). A number of good practices of AERB have been found and some areas have been identified where improvements are necessary

Emotion: The Self-regulatory Sense

Science.gov (United States)

2014-01-01

While emotion is a central component of human health and well-being, traditional approaches to understanding its biological function have been wanting. A dynamic systems model, however, broadly redefines and recasts emotion as a primary sensory system—perhaps the first sensory system to have emerged, serving the ancient autopoietic function of “self-regulation.” Drawing upon molecular biology and revelations from the field of epigenetics, the model suggests that human emotional perceptions provide an ongoing stream of “self-relevant” sensory information concerning optimally adaptive states between the organism and its immediate environment, along with coupled behavioral corrections that honor a universal self-regulatory logic, one still encoded within cellular signaling and immune functions. Exemplified by the fundamental molecular circuitry of sensorimotor control in the E coli bacterium, the model suggests that the hedonic (affective) categories emerge directly from positive and negative feedback processes, their good/bad binary appraisals relating to dual self-regulatory behavioral regimes—evolutionary purposes, through which organisms actively participate in natural selection, and through which humans can interpret optimal or deficit states of balanced being and becoming. The self-regulatory sensory paradigm transcends anthropomorphism, unites divergent theoretical perspectives and isolated bodies of literature, while challenging time-honored assumptions. While suppressive regulatory strategies abound, it suggests that emotions are better understood as regulating us, providing a service crucial to all semantic language, learning systems, evaluative decision-making, and fundamental to optimal physical, mental, and social health. PMID:24808986

Information system fur the management of a regulatory programme

International Nuclear Information System (INIS)

Ortiz, P.; Mrabit, K.; Miaw, S.

1998-01-01

A Regulatory Programme to monitor safety of activities involving radiation sources, implies the existence of a Regulatory Authority empowered by legislation to issue radiation protection regulations and to monitor compliance with those regulations. The core element of the programme is a system of notification and authorization (registration and licensing), inspection and enforcement. The efficiency of this system is largely dependent on the availability of reliable information on the inventory of radiation sources and installations, the administrative status of the facilities (authorization), prompt processing of inspection reports and follow up of regulatory actions, including monitoring deadlines. Essential data relevant to safety, such as personal dosimetry for occupationally exposed individuals, inspection findings and incident reports would provide, in addition, an insight on the overall safety of the country. A simple but comprehensive Regulatory Authority Information System (RAIS) linked to the authorization and inspection process will largely facilitate regulatory decisions and actions. A readily available and reliable information from the various regulatory activities will facilitate planning, optimization of resources, monitoring safety related data, disseminating safety information, making decisions and follow up regulatory actions including monitoring dead lines. The implementation of the system in more than 50 countries will contribute to experience exchange and harmonization of regulatory activities. (author)

Mapping biological systems to network systems

CERN Document Server

Rathore, Heena

2016-01-01

The book presents the challenges inherent in the paradigm shift of network systems from static to highly dynamic distributed systems – it proposes solutions that the symbiotic nature of biological systems can provide into altering networking systems to adapt to these changes. The author discuss how biological systems – which have the inherent capabilities of evolving, self-organizing, self-repairing and flourishing with time – are inspiring researchers to take opportunities from the biology domain and map them with the problems faced in network domain. The book revolves around the central idea of bio-inspired systems -- it begins by exploring why biology and computer network research are such a natural match. This is followed by presenting a broad overview of biologically inspired research in network systems -- it is classified by the biological field that inspired each topic and by the area of networking in which that topic lies. Each case elucidates how biological concepts have been most successfully ...

Regulatory authority information system RAIS

International Nuclear Information System (INIS)

Ortiz, P.; Mrabit, K.; Miaw, S.

2000-01-01

In this lecture the principles of the regulatory authority information system (RAIS) are presented. RAIS is a tool currently being developed by the IAEA for the Regulatory Authorities. It is a part of a set of supporting actions designed to assist member states in achieving the objectives of the Model project on radiation and waste safety infrastructure. RAIS is a tool that provides the management of the Regulatory Authority with the key information needed for the planning and implementation of activities and to ensure confidence that resources are optimally used. The RAIS contains five modules: Inventory of installations and radiation sources; Authorization process; Inspection and follow-up actions; Information on personal dosimetry; Assessment of effectiveness by means of performance indicators

On the Interplay between Entropy and Robustness of Gene Regulatory Networks

Directory of Open Access Journals (Sweden)

Bor-Sen Chen

2010-05-01

Full Text Available The interplay between entropy and robustness of gene network is a core mechanism of systems biology. The entropy is a measure of randomness or disorder of a physical system due to random parameter fluctuation and environmental noises in gene regulatory networks. The robustness of a gene regulatory network, which can be measured as the ability to tolerate the random parameter fluctuation and to attenuate the effect of environmental noise, will be discussed from the robust H∞ stabilization and filtering perspective. In this review, we will also discuss their balancing roles in evolution and potential applications in systems and synthetic biology.

Steady-State-Preserving Simulation of Genetic Regulatory Systems

Directory of Open Access Journals (Sweden)

Ruqiang Zhang

2017-01-01

Full Text Available A novel family of exponential Runge-Kutta (expRK methods are designed incorporating the stable steady-state structure of genetic regulatory systems. A natural and convenient approach to constructing new expRK methods on the base of traditional RK methods is provided. In the numerical integration of the one-gene, two-gene, and p53-mdm2 regulatory systems, the new expRK methods are shown to be more accurate than their prototype RK methods. Moreover, for nonstiff genetic regulatory systems, the expRK methods are more efficient than some traditional exponential RK integrators in the scientific literature.

Life as physics and chemistry: A system view of biology.

Science.gov (United States)

Baverstock, Keith

2013-04-01

Cellular life can be viewed as one of many physical natural systems that extract free energy from their environments in the most efficient way, according to fundamental physical laws, and grow until limited by inherent physical constraints. Thus, it can be inferred that it is the efficiency of this process that natural selection acts upon. The consequent emphasis on metabolism, rather than replication, points to a metabolism-first origin of life with the adoption of DNA template replication as a second stage development. This order of events implies a cellular regulatory system that pre-dates the involvement of DNA and might, therefore, be based on the information acquired as peptides fold into proteins, rather than on genetic regulatory networks. Such an epigenetic cell regulatory model, the independent attractor model, has already been proposed to explain the phenomenon of radiation induced genomic instability. Here it is extended to provide an epigenetic basis for the morphological and functional diversity that evolution has yielded, based on natural selection of the most efficient free energy transduction. Empirical evidence which challenges the current genetic basis of cell and molecular biology and which supports the above proposal is discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Computational Systems Chemical Biology

OpenAIRE

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

2011-01-01

There is a critical need for improving the level of chemistry awareness in systems biology. The data and information related to modulation of genes and proteins by small molecules continue to accumulate at the same time as simulation tools in systems biology and whole body physiologically-based pharmacokinetics (PBPK) continue to evolve. We called this emerging area at the interface between chemical biology and systems biology systems chemical biology, SCB (Oprea et al., 2007).

Regulatory systems-based licensing guidance documentation

International Nuclear Information System (INIS)

Delligatti, M.S.

1991-01-01

The US Nuclear Regulatory Commission (NRC) has developed a series of licensing guidance documents based on the regulatory requirements in Part 60 of Title 10 of the Code of Federal Regulations (10 CFR Part 60). This regulatory systems-based approach to licensing guidance documentation relies on the definition of the high-level waste repository in 10 CFR Part 60. A document which is important for the frame-work it gives to other programmatic licensing guidance is the Draft Regulatory Guide open-quotes Format and Content for the License Application for the High-Level Waste Repositoryclose quotes (FCRG). The FCRG describes a format and content acceptable to NRC for a high-level waste repository license application pursuant to the requirements of 10 CFR Part 60. Other licensing guidance documents will be compatible with the FCRG

Sieve-based relation extraction of gene regulatory networks from biological literature.

Science.gov (United States)

Žitnik, Slavko; Žitnik, Marinka; Zupan, Blaž; Bajec, Marko

2015-01-01

Relation extraction is an essential procedure in literature mining. It focuses on extracting semantic relations between parts of text, called mentions. Biomedical literature includes an enormous amount of textual descriptions of biological entities, their interactions and results of related experiments. To extract them in an explicit, computer readable format, these relations were at first extracted manually from databases. Manual curation was later replaced with automatic or semi-automatic tools with natural language processing capabilities. The current challenge is the development of information extraction procedures that can directly infer more complex relational structures, such as gene regulatory networks. We develop a computational approach for extraction of gene regulatory networks from textual data. Our method is designed as a sieve-based system and uses linear-chain conditional random fields and rules for relation extraction. With this method we successfully extracted the sporulation gene regulation network in the bacterium Bacillus subtilis for the information extraction challenge at the BioNLP 2013 conference. To enable extraction of distant relations using first-order models, we transform the data into skip-mention sequences. We infer multiple models, each of which is able to extract different relationship types. Following the shared task, we conducted additional analysis using different system settings that resulted in reducing the reconstruction error of bacterial sporulation network from 0.73 to 0.68, measured as the slot error rate between the predicted and the reference network. We observe that all relation extraction sieves contribute to the predictive performance of the proposed approach. Also, features constructed by considering mention words and their prefixes and suffixes are the most important features for higher accuracy of extraction. Analysis of distances between different mention types in the text shows that our choice of transforming

Modeling drug- and chemical- induced hepatotoxicity with systems biology approaches

Directory of Open Access Journals (Sweden)

Sudin eBhattacharya

2012-12-01

Full Text Available We provide an overview of computational systems biology approaches as applied to the study of chemical- and drug-induced toxicity. The concept of ‘toxicity pathways’ is described in the context of the 2007 US National Academies of Science report, Toxicity testing in the 21st Century: A Vision and A Strategy. Pathway mapping and modeling based on network biology concepts are a key component of the vision laid out in this report for a more biologically-based analysis of dose-response behavior and the safety of chemicals and drugs. We focus on toxicity of the liver (hepatotoxicity – a complex phenotypic response with contributions from a number of different cell types and biological processes. We describe three case studies of complementary multi-scale computational modeling approaches to understand perturbation of toxicity pathways in the human liver as a result of exposure to environmental contaminants and specific drugs. One approach involves development of a spatial, multicellular virtual tissue model of the liver lobule that combines molecular circuits in individual hepatocytes with cell-cell interactions and blood-mediated transport of toxicants through hepatic sinusoids, to enable quantitative, mechanistic prediction of hepatic dose-response for activation of the AhR toxicity pathway. Simultaneously, methods are being developing to extract quantitative maps of intracellular signaling and transcriptional regulatory networks perturbed by environmental contaminants, using a combination of gene expression and genome-wide protein-DNA interaction data. A predictive physiological model (DILIsymTM to understand drug-induced liver injury (DILI, the most common adverse event leading to termination of clinical development programs and regulatory actions on drugs, is also described. The model initially focuses on reactive metabolite-induced DILI in response to administration of acetaminophen, and spans multiple biological scales.

From systems biology to systems biomedicine.

Science.gov (United States)

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

2012-08-01

Systems Biology is about combining theory, technology, and targeted experiments in a way that drives not only data accumulation but knowledge as well. The challenge in Systems Biomedicine is to furthermore translate mechanistic insights in biological systems to clinical application, with the central aim of improving patients' quality of life. The challenge is to find theoretically well-chosen models for the contextually correct and intelligible representation of multi-scale biological systems. In this review, we discuss the current state of Systems Biology, highlight the emergence of Systems Biomedicine, and highlight some of the topics and views that we think are important for the efficient application of Systems Theory in Biomedicine. Copyright © 2011 Elsevier Ltd. All rights reserved.

Systems Biology and Health Systems Complexity in;

NARCIS (Netherlands)

Donald Combs, C.; Barham, S.R.; Sloot, P.M.A.

2016-01-01

Systems biology addresses interactions in biological systems at different scales of biological organization, from the molecular to the cellular, organ, organism, societal, and ecosystem levels. This chapter expands on the concept of systems biology, explores its implications for individual patients

Synthetic biological networks

International Nuclear Information System (INIS)

Archer, Eric; Süel, Gürol M

2013-01-01

Despite their obvious relationship and overlap, the field of physics is blessed with many insightful laws, while such laws are sadly absent in biology. Here we aim to discuss how the rise of a more recent field known as synthetic biology may allow us to more directly test hypotheses regarding the possible design principles of natural biological networks and systems. In particular, this review focuses on synthetic gene regulatory networks engineered to perform specific functions or exhibit particular dynamic behaviors. Advances in synthetic biology may set the stage to uncover the relationship of potential biological principles to those developed in physics. (review article)

Systems Biology-an interdisciplinary approach.

Science.gov (United States)

Friboulet, Alain; Thomas, Daniel

2005-06-15

System-level approaches in biology are not new but foundations of "Systems Biology" are achieved only now at the beginning of the 21st century [Kitano, H., 2001. Foundations of Systems Biology. MIT Press, Cambridge, MA]. The renewed interest for a system-level approach is linked to the progress in collecting experimental data and to the limits of the "reductionist" approach. System-level understanding of native biological and pathological systems is needed to provide potential therapeutic targets. Examples of interdisciplinary approach in Systems Biology are described in U.S., Japan and Europe. Robustness in biology, metabolic engineering and idiotypic networks are discussed in the framework of Systems Biology.

VANESA - A Software Application for the Visualization and Analysis of Networks in Systems Biology Applications

Directory of Open Access Journals (Sweden)

Brinkrolf Christoph

2014-06-01

Full Text Available VANESA is a modeling software for the automatic reconstruction and analysis of biological networks based on life-science database information. Using VANESA, scientists are able to model any kind of biological processes and systems as biological networks. It is now possible for scientists to automatically reconstruct important molecular systems with information from the databases KEGG, MINT, IntAct, HPRD, and BRENDA. Additionally, experimental results can be expanded with database information to better analyze the investigated elements and processes in an overall context. Users also have the possibility to use graph theoretical approaches in VANESA to identify regulatory structures and significant actors within the modeled systems. These structures can then be further investigated in the Petri net environment of VANESA. It is platform-independent, free-of-charge, and available at http://vanesa.sf.net.

Stability Analysis of Nonlinear Time–Delayed Systems with Application to Biological Models

Directory of Open Access Journals (Sweden)

Kruthika H.A.

2017-03-01

Full Text Available In this paper, we analyse the local stability of a gene-regulatory network and immunotherapy for cancer modelled as nonlinear time-delay systems. A numerically generated kernel, using the sum-of-squares decomposition of multivariate polynomials, is used in the construction of an appropriate Lyapunov–Krasovskii functional for stability analysis of the networks around an equilibrium point. This analysis translates to verifying equivalent LMI conditions. A delay-independent asymptotic stability of a second-order model of a gene regulatory network, taking into consideration multiple commensurate delays, is established. In the case of cancer immunotherapy, a predator–prey type model is adopted to describe the dynamics with cancer cells and immune cells contributing to the predator–prey population, respectively. A delay-dependent asymptotic stability of the cancer-free equilibrium point is proved. Apart from the system and control point of view, in the case of gene-regulatory networks such stability analysis of dynamics aids mimicking gene networks synthetically using integrated circuits like neurochips learnt from biological neural networks, and in the case of cancer immunotherapy it helps determine the long-term outcome of therapy and thus aids oncologists in deciding upon the right approach.

Epidemiologic studies of occupational pesticide exposure and cancer: regulatory risk assessments and biologic plausibility.

Science.gov (United States)

Acquavella, John; Doe, John; Tomenson, John; Chester, Graham; Cowell, John; Bloemen, Louis

2003-01-01

Epidemiologic studies frequently show associations between self-reported use of specific pesticides and human cancers. These findings have engendered debate largely on methodologic grounds. However, biologic plausibility is a more fundamental issue that has received only superficial attention. The purpose of this commentary is to review briefly the toxicology and exposure data that are developed as part of the pesticide regulatory process and to discuss the applicability of this data to epidemiologic research. The authors also provide a generic example of how worker pesticide exposures might be estimated and compared to relevant toxicologic dose levels. This example provides guidance for better characterization of exposure and for consideration of biologic plausibility in epidemiologic studies of pesticides.

BiologicalNetworks 2.0 - an integrative view of genome biology data

Directory of Open Access Journals (Sweden)

Ponomarenko Julia

2010-12-01

Full Text Available Abstract 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.

Approaches to Quality Risk Management When Using Single-Use Systems in the Manufacture of Biologics.

Science.gov (United States)

Ishii-Watabe, Akiko; Hirose, Akihiko; Katori, Noriko; Hashii, Norikata; Arai, Susumu; Awatsu, Hirotoshi; Eiza, Akira; Hara, Yoshiaki; Hattori, Hideshi; Inoue, Tomomi; Isono, Tetsuya; Iwakura, Masahiro; Kajihara, Daisuke; Kasahara, Nobuo; Matsuda, Hiroyuki; Murakami, Sei; Nakagawa, Taishiro; Okumura, Takehiro; Omasa, Takeshi; Takuma, Shinya; Terashima, Iyo; Tsukahara, Masayoshi; Tsutsui, Maiko; Yano, Takahiro; Kawasaki, Nana

2015-10-01

Biologics manufacturing technology has made great progress in the last decade. One of the most promising new technologies is the single-use system, which has improved the efficiency of biologics manufacturing processes. To ensure safety of biologics when employing such single-use systems in the manufacturing process, various issues need to be considered including possible extractables/leachables and particles arising from the components used in single-use systems. Japanese pharmaceutical manufacturers, together with single-use suppliers, members of the academia and regulatory authorities have discussed the risks of using single-use systems and established control strategies for the quality assurance of biologics. In this study, we describe approaches for quality risk management when employing single-use systems in the manufacturing of biologics. We consider the potential impact of impurities related to single-use components on drug safety and the potential impact of the single-use system on other critical quality attributes as well as the stable supply of biologics. We also suggest a risk-mitigating strategy combining multiple control methods which includes the selection of appropriate single-use components, their inspections upon receipt and before releasing for use and qualification of single-use systems. Communication between suppliers of single-use systems and the users, as well as change controls in the facilities both of suppliers and users, are also important in risk-mitigating strategies. Implementing these control strategies can mitigate the risks attributed to the use of single-use systems. This study will be useful in promoting the development of biologics as well as in ensuring their safety, quality and stable supply.

Organizing principles as tools for bridging the gap between system theory and biological experimentation.

Science.gov (United States)

Mekios, Constantinos

2016-04-01

Twentieth-century theoretical efforts towards the articulation of general system properties came short of having the significant impact on biological practice that their proponents envisioned. Although the latter did arrive at preliminary mathematical formulations of such properties, they had little success in showing how these could be productively incorporated into the research agenda of biologists. Consequently, the gap that kept system-theoretic principles cut-off from biological experimentation persisted. More recently, however, simple theoretical tools have proved readily applicable within the context of systems biology. In particular, examples reviewed in this paper suggest that rigorous mathematical expressions of design principles, imported primarily from engineering, could produce experimentally confirmable predictions of the regulatory properties of small biological networks. But this is not enough for contemporary systems biologists who adopt the holistic aspirations of early systemologists, seeking high-level organizing principles that could provide insights into problems of biological complexity at the whole-system level. While the presented evidence is not conclusive about whether this strategy could lead to the realization of the lofty goal of a comprehensive explanatory integration, it suggests that the ongoing quest for organizing principles is pragmatically advantageous for systems biologists. The formalisms postulated in the course of this process can serve as bridges between system-theoretic concepts and the results of molecular experimentation: they constitute theoretical tools for generalizing molecular data, thus producing increasingly accurate explanations of system-wide phenomena.

Biological conversion system

Science.gov (United States)

Scott, C.D.

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

A Non-Homogeneous Dynamic Bayesian Network with Sequentially Coupled Interaction Parameters for Applications in Systems and Synthetic Biology

NARCIS (Netherlands)

Grzegorczyk, Marco; Husmeier, Dirk

2012-01-01

An important and challenging problem in systems biology is the inference of gene regulatory networks from short non-stationary time series of transcriptional profiles. A popular approach that has been widely applied to this end is based on dynamic Bayesian networks (DBNs), although traditional

Development trend of radiation biology research-systems radiation biology

International Nuclear Information System (INIS)

Min Rui

2010-01-01

Radiation biology research has past 80 years. We have known much more about fundamentals, processes and results of biology effects induced by radiation and various factors that influence biology effects wide and deep, however many old and new scientific problems occurring in the field of radiation biology research remain to be illustrated. To explore and figure these scientific problems need systemic concept, methods and multi dimension view on the base of considerations of complexity of biology system, diversity of biology response, temporal and spatial process of biological effects during occurrence, and complex feed back network of biological regulations. (authors)

Constitutive, Institutive and Up-Regulation of Carotenogenesis Regulatory Mechanism via In Vitro Culture Model System and Elicitors

International Nuclear Information System (INIS)

Rashidi Othman; Fatimah Azzahra Mohd Zaifuddin; Norazian Mohd Hassan

2015-01-01

Phyto hormone abscisic acid (ABA) plays a regulatory role in many physiological processes in plants and is regulated and controlled by specific key factors or genes. Different environmental stress conditions such as water, drought, cold, light, and temperature result in increased amounts of ABA. The action of ABA involves modification of gene expression and analysis of in vitro callus model system cultures revealed several potential of constitutive, institutive and up-regulation acting regulatory mechanisms. Therefore, this study was aimed at establishing in vitro cultures as potential research tools to study the regulatory mechanisms of the carotenoid biosynthesis in selected plant species through a controlled environment. The presence and absence of zeaxanthin and neoxanthin in callus cultures and intact plants could be explained by changes in gene expression in response to stress. Abiotic stress can alter gene expression and trigger cellular metabolism in plants. This study suggested that the key factors which involved in regulatory mechanisms of individual carotenoid biosynthesis in a particular biology system of plants can be either be silenced or activated. Therefore, based on the results in this study environmental stress is made possible for enhancement or enrichment of certain carotenoid of interest in food crops without altering the genes. (author)

An integer optimization algorithm for robust identification of non-linear gene regulatory networks

Directory of Open Access Journals (Sweden)

Chemmangattuvalappil Nishanth

2012-09-01

Full Text Available Abstract Background Reverse engineering gene networks and identifying regulatory interactions are integral to understanding cellular decision making processes. Advancement in high throughput experimental techniques has initiated innovative data driven analysis of gene regulatory networks. However, inherent noise associated with biological systems requires numerous experimental replicates for reliable conclusions. Furthermore, evidence of robust algorithms directly exploiting basic biological traits are few. Such algorithms are expected to be efficient in their performance and robust in their prediction. Results We have developed a network identification algorithm to accurately infer both the topology and strength of regulatory interactions from time series gene expression data in the presence of significant experimental noise and non-linear behavior. In this novel formulism, we have addressed data variability in biological systems by integrating network identification with the bootstrap resampling technique, hence predicting robust interactions from limited experimental replicates subjected to noise. Furthermore, we have incorporated non-linearity in gene dynamics using the S-system formulation. The basic network identification formulation exploits the trait of sparsity of biological interactions. Towards that, the identification algorithm is formulated as an integer-programming problem by introducing binary variables for each network component. The objective function is targeted to minimize the network connections subjected to the constraint of maximal agreement between the experimental and predicted gene dynamics. The developed algorithm is validated using both in silico and experimental data-sets. These studies show that the algorithm can accurately predict the topology and connection strength of the in silico networks, as quantified by high precision and recall, and small discrepancy between the actual and predicted kinetic parameters

Biology-inspired Microphysiological System Approaches to Solve the Prediction Dilemma of Substance Testing

Science.gov (United States)

Marx, Uwe; Andersson, Tommy B.; Bahinski, Anthony; Beilmann, Mario; Beken, Sonja; Cassee, Flemming R.; Cirit, Murat; Daneshian, Mardas; Fitzpatrick, Susan; Frey, Olivier; Gaertner, Claudia; Giese, Christoph; Griffith, Linda; Hartung, Thomas; Heringa, Minne B.; Hoeng, Julia; de Jong, Wim H.; Kojima, Hajime; Kuehnl, Jochen; Luch, Andreas; Maschmeyer, Ilka; Sakharov, Dmitry; Sips, Adrienne J. A. M.; Steger-Hartmann, Thomas; Tagle, Danilo A.; Tonevitsky, Alexander; Tralau, Tewes; Tsyb, Sergej; van de Stolpe, Anja; Vandebriel, Rob; Vulto, Paul; Wang, Jufeng; Wiest, Joachim; Rodenburg, Marleen; Roth, Adrian

2017-01-01

Summary The recent advent of microphysiological systems – microfluidic biomimetic devices that aspire to emulate the biology of human tissues, organs and circulation in vitro – is envisaged to enable a global paradigm shift in drug development. An extraordinary US governmental initiative and various dedicated research programs in Europe and Asia have led recently to the first cutting-edge achievements of human single-organ and multi-organ engineering based on microphysiological systems. The expectation is that test systems established on this basis would model various disease stages, and predict toxicity, immunogenicity, ADME profiles and treatment efficacy prior to clinical testing. Consequently, this technology could significantly affect the way drug substances are developed in the future. Furthermore, microphysiological system-based assays may revolutionize our current global programs of prioritization of hazard characterization for any new substances to be used, for example, in agriculture, food, ecosystems or cosmetics, thus, replacing laboratory animal models used currently. Thirty-five experts from academia, industry and regulatory bodies present here the results of an intensive workshop (held in June 2015, Berlin, Germany). They review the status quo of microphysiological systems available today against industry needs, and assess the broad variety of approaches with fit-for-purpose potential in the drug development cycle. Feasible technical solutions to reach the next levels of human biology in vitro are proposed. Furthermore, key organ-on-a-chip case studies, as well as various national and international programs are highlighted. Finally, a roadmap into the future is outlined, to allow for more predictive and regulatory-accepted substance testing on a global scale. PMID:27180100

National Strategy for Modernizing the Regulatory System for Biotechnology Products

Science.gov (United States)

This National Strategy for Modernizing the Regulatory System for Biotechnology Products sets forth a vision for ensuring that the federal regulatory system is prepared to efficiently assess the risks, if any, of the future products of biotechnology.

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

Science.gov (United States)

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.

Review of regulatory requirements for digital I and C systems

Energy Technology Data Exchange (ETDEWEB)

Kwon, Kee Choon; Lee, Cheol Kwon; Lee, Jang Soo [and others

2001-11-01

This work analyzed and summarized systematically various regulatory requirements that are necessary to develop digital nuclear instrumentation and control (I and C) systems, especially safety systems. The requirements are categorized into system, hardware, software, and quality assurance aspects. This report provides the explanations of terms and abbreviations to help readers understand. Furthermore, appendices of this report summarize the code and standards corresponding to each principal regulatory requirement. The hierarchical structure of regulatory requirements has Nuclear Energy Laws, Enforcement Regulations of Nuclear Energy Laws, and Notifications of Ministry of Science and Technology as utmost level requirements [In case of the US, 10 CFR 50 Appendix A, 10 CFR 50 Appendix B, 10 CFR 50.55a(h), 10 CFR 50.49, etc.]. The requirements include the Draft Regulatory Guidelines for Digital I and C Systems [In case of the US, Standard Review Plan (NUREG-0800), Regulatory Guide, Branch Technical Position (BTP)], KEPIC as standards [In case of the US, IEEE Standards, IEC Standards, ISA, Military Standard, etc.], and various reports issued by Korea Institute of Nuclear Safety [In case of the US, NUREG reports, EPRI reports, etc.]. This report can be referred for the development of safety grade control equipment, plant protection system, and engineered safety feature actuation system.

Review of regulatory requirements for digital I and C systems

International Nuclear Information System (INIS)

Kwon, Kee Choon; Lee, Cheol Kwon; Lee, Jang Soo

2001-11-01

This work analyzed and summarized systematically various regulatory requirements that are necessary to develop digital nuclear instrumentation and control (I and C) systems, especially safety systems. The requirements are categorized into system, hardware, software, and quality assurance aspects. This report provides the explanations of terms and abbreviations to help readers understand. Furthermore, appendices of this report summarize the code and standards corresponding to each principal regulatory requirement. The hierarchical structure of regulatory requirements has Nuclear Energy Laws, Enforcement Regulations of Nuclear Energy Laws, and Notifications of Ministry of Science and Technology as utmost level requirements [In case of the US, 10 CFR 50 Appendix A, 10 CFR 50 Appendix B, 10 CFR 50.55a(h), 10 CFR 50.49, etc.]. The requirements include the Draft Regulatory Guidelines for Digital I and C Systems [In case of the US, Standard Review Plan (NUREG-0800), Regulatory Guide, Branch Technical Position (BTP)], KEPIC as standards [In case of the US, IEEE Standards, IEC Standards, ISA, Military Standard, etc.], and various reports issued by Korea Institute of Nuclear Safety [In case of the US, NUREG reports, EPRI reports, etc.]. This report can be referred for the development of safety grade control equipment, plant protection system, and engineered safety feature actuation system

Fostering synergy between cell biology and systems biology.

Science.gov (United States)

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. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

What is a comprehensive system of regulatory governance?

International Nuclear Information System (INIS)

Real diaz, F. J.

2011-01-01

The progressive evolution and diversification of regulations concerning industrial safety has made their management increasingly complex, requiring more resources of organizations. Therefore, it is advisable that this management be made more efficient through systematization, specialization and the use of computing technologies. This is supported by the implementation of integrated regulatory management systems. This article explain the concept of integrated regulatory management systems, their structure and their advantages. It also includes a model for implementing them in an organization. (Author)

Modeling stochasticity and robustness in gene regulatory networks.

Science.gov (United States)

Garg, Abhishek; Mohanram, Kartik; Di Cara, Alessandro; De Micheli, Giovanni; Xenarios, Ioannis

2009-06-15

Understanding gene regulation in biological processes and modeling the robustness of underlying regulatory networks is an important problem that is currently being addressed by computational systems biologists. Lately, there has been a renewed interest in Boolean modeling techniques for gene regulatory networks (GRNs). However, due to their deterministic nature, it is often difficult to identify whether these modeling approaches are robust to the addition of stochastic noise that is widespread in gene regulatory processes. Stochasticity in Boolean models of GRNs has been addressed relatively sparingly in the past, mainly by flipping the expression of genes between different expression levels with a predefined probability. This stochasticity in nodes (SIN) model leads to over representation of noise in GRNs and hence non-correspondence with biological observations. In this article, we introduce the stochasticity in functions (SIF) model for simulating stochasticity in Boolean models of GRNs. By providing biological motivation behind the use of the SIF model and applying it to the T-helper and T-cell activation networks, we show that the SIF model provides more biologically robust results than the existing SIN model of stochasticity in GRNs. Algorithms are made available under our Boolean modeling toolbox, GenYsis. The software binaries can be downloaded from http://si2.epfl.ch/ approximately garg/genysis.html.

Regulation of mutagenesis by exogenous biological factors in the eukaryotic cell systems

Directory of Open Access Journals (Sweden)

Lukash L. L.

2013-07-01

Full Text Available The representations of the mutations and the nature of spontaneous mutation process and mutagenesis induced by exogenous oncoviruses, DNAs and proteins-mitogens are analysed. Exogenous biological factors induce DNA damages in regulatory-informational way, acting on the cellular systems for maintenance of genetical stability. Molecular mechanisms are the same as at spontaneous mutagenesis but they are realized with the participation of alien genetical material. Among biological mutagens, the oncoviruses and mobile genetic elements (MGEs are distinguished as the strongest destabilizing factors which direct tumor transformation of somatic mammalian cells. Genetical reprogramming or changing the programs of gene expression at the differentiation of stem and progenitor cells under growth factors and citokines is probably followed by mutations and recombinations as well.

Global Banking System Regulatory Environment

Directory of Open Access Journals (Sweden)

Oleh Mozhovyi

2017-03-01

Full Text Available The international and domestic experience shows that the main factors of financial destabilization during the financial crises are in the banking sector. The article reveals that the vulnerability of the financial system is connected with functions, deposit and credit transactions, risks distribution and ensuring liquidity; banks act as a major factor in stabilisation measures in the current context of globalization processes, since the economic stability of banking activities relates directly to all the entities and only stable banking system can withstand the crisis phenomena. Therefore, as a result of the analysis, it is proved that not only reduction of risks of banks is needed, but also introduction of the effective supervision system over implementation of the requirements and standards to prevent these risks. According to modern international approaches, banks use the so-called prudential supervision, which is based on the risk management assessment policy on the part of the Bank’s management, and regulatory bodies contribute to implementation of such policy. The authors have concluded that not only modern specificity of banks, but also the impact of supervision systems and regulation of modern trends in development of the banking should be analysed. Application of the general regulatory principles and banking risks methodology is required. The task of supervision is distribution of reliable risk management practices in the banking system, taking into account national peculiarities of development.

Food safety regulatory systems in Europe and China：A study of how co-regulation can improve regulatory effectiveness

Institute of Scientific and Technical Information of China (English)

Kevin Chen; WANG Xin-xin; SONG Hai-ying

2015-01-01

Food safety has received a great deal of attention in both developed and developing countries in recent years. In China, the numerous food scandals and scares that have struck over the past decade have spurred signiifcant food safety regulatory reform, which has been increasingly oriented towards the public-private partnership model adopted by the Europe Union’s (EU) food safety regulatory system. This paper analyzes the development of both the EU’s and China’s food safety regu-latory systems, identiifes the current chalenges for China and additionaly considers the role of public-private partnership. The success of co-regulation in the food regulatory system would bring signiifcant beneifts and opportunities for China. Finaly, this paper recommends additional measures like training and grants to improve the private’s sector effectiveness in co-regulating China’s food safety issues.

Proteome-wide Structural Analysis of PTM Hotspots Reveals Regulatory Elements Predicted to Impact Biological Function and Disease.

Science.gov (United States)

Torres, Matthew P; Dewhurst, Henry; Sundararaman, Niveda

2016-11-01

Post-translational modifications (PTMs) regulate protein behavior through modulation of protein-protein interactions, enzymatic activity, and protein stability essential in the translation of genotype to phenotype in eukaryotes. Currently, less than 4% of all eukaryotic PTMs are reported to have biological function - a statistic that continues to decrease with an increasing rate of PTM detection. Previously, we developed SAPH-ire (Structural Analysis of PTM Hotspots) - a method for the prioritization of PTM function potential that has been used effectively to reveal novel PTM regulatory elements in discrete protein families (Dewhurst et al., 2015). Here, we apply SAPH-ire to the set of eukaryotic protein families containing experimental PTM and 3D structure data - capturing 1,325 protein families with 50,839 unique PTM sites organized into 31,747 modified alignment positions (MAPs), of which 2010 (∼6%) possess known biological function. Here, we show that using an artificial neural network model (SAPH-ire NN) trained to identify MAP hotspots with biological function results in prediction outcomes that far surpass the use of single hotspot features, including nearest neighbor PTM clustering methods. We find the greatest enhancement in prediction for positions with PTM counts of five or less, which represent 98% of all MAPs in the eukaryotic proteome and 90% of all MAPs found to have biological function. Analysis of the top 1092 MAP hotspots revealed 267 of truly unknown function (containing 5443 distinct PTMs). Of these, 165 hotspots could be mapped to human KEGG pathways for normal and/or disease physiology. Many high-ranking hotspots were also found to be disease-associated pathogenic sites of amino acid substitution despite the lack of observable PTM in the human protein family member. Taken together, these experiments demonstrate that the functional relevance of a PTM can be predicted very effectively by neural network models, revealing a large but testable

An electronic regulatory document management system for a clinical trial network.

Science.gov (United States)

Zhao, Wenle; Durkalski, Valerie; Pauls, Keith; Dillon, Catherine; Kim, Jaemyung; Kolk, Deneil; Silbergleit, Robert; Stevenson, Valerie; Palesch, Yuko

2010-01-01

A computerized regulatory document management system has been developed as a module in a comprehensive Clinical Trial Management System (CTMS) designed for an NIH-funded clinical trial network in order to more efficiently manage and track regulatory compliance. Within the network, several institutions and investigators are involved in multiple trials, and each trial has regulatory document requirements. Some of these documents are trial specific while others apply across multiple trials. The latter causes a possible redundancy in document collection and management. To address these and other related challenges, a central regulatory document management system was designed. This manuscript shares the design of the system as well as examples of it use in current studies. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Regulatory issues of digital instrumentation and control system in Lungmen project

International Nuclear Information System (INIS)

Chuang, C.F.; Chou, H.P.

2004-01-01

The Lungmen Nuclear Power Station (LNPS) is currently under construction in Taiwan, which consists of 2 advanced boiling water reactor (ABWR) units. The instrumentation and control (IC) systems of the LNPS are based on the state-of-the-art modernized fully integrated digital design. These IC systems possess many advantages and distinguished features comparing to traditional analog IC systems, they enjoy set-point stability, self-diagnostic and automatic testing ability, fault tolerance and avoidance, low power requirements, data handling and storage capability, as well as enhanced human-machine interfaces. This paper presents regulatory overviews, regulatory requirements, current major regulatory issues, as well as the areas of regulatory concerns and the lessons learned on the digital IC systems in the Lungmen Project

RNA SURVEILLANCE– AN EMERGING ROLE FOR RNA REGULATORY NETWORKS IN AGING

OpenAIRE

Montano, Monty; Long, Kimberly

2010-01-01

In this review, we describe recent advances in the field of RNA regulatory biology and relate these advances to aging science. We introduce a new term, RNA surveillance, an RNA regulatory process that is conserved in metazoans, and describe how RNA surveillance represents molecular cross-talk between two emerging RNA regulatory systems – RNA interference and RNA editing. We discuss how RNA surveillance mechanisms influence mRNA and microRNA expression and activity during lifespan. Additionall...

Review of Biological Network Data and Its Applications

Directory of Open Access Journals (Sweden)

Donghyeon Yu

2013-12-01

Full Text Available Studying biological networks, such as protein-protein interactions, is key to understanding complex biological activities. Various types of large-scale biological datasets have been collected and analyzed with high-throughput technologies, including DNA microarray, next-generation sequencing, and the two-hybrid screening system, for this purpose. In this review, we focus on network-based approaches that help in understanding biological systems and identifying biological functions. Accordingly, this paper covers two major topics in network biology: reconstruction of gene regulatory networks and network-based applications, including protein function prediction, disease gene prioritization, and network-based genome-wide association study.

Systems biology of adipose tissue metabolism: regulation of growth, signaling and inflammation.

Science.gov (United States)

Manteiga, Sara; Choi, Kyungoh; Jayaraman, Arul; Lee, Kyongbum

2013-01-01

Adipose tissue (AT) depots actively regulate whole body energy homeostasis by orchestrating complex communications with other physiological systems as well as within the tissue. Adipocytes readily respond to hormonal and nutritional inputs to store excess nutrients as intracellular lipids or mobilize the stored fat for utilization. Co-ordinated regulation of metabolic pathways balancing uptake, esterification, and hydrolysis of lipids is accomplished through positive and negative feedback interactions of regulatory hubs comprising several pleiotropic protein kinases and nuclear receptors. Metabolic regulation in adipocytes encompasses biogenesis and remodeling of uniquely large lipid droplets (LDs). The regulatory hubs also function as energy and nutrient sensors, and integrate metabolic regulation with intercellular signaling. Over-nutrition causes hypertrophic expansion of adipocytes, which, through incompletely understood mechanisms, initiates a cascade of metabolic and signaling events leading to tissue remodeling and immune cell recruitment. Macrophage activation and polarization toward a pro-inflammatory phenotype drives a self-reinforcing cycle of pro-inflammatory signals in the AT, establishing an inflammatory state. Sustained inflammation accelerates lipolysis and elevates free fatty acids in circulation, which robustly correlates with development of obesity-related diseases. The adipose regulatory network coupling metabolism, growth, and signaling of multiple cell types is exceedingly complex. While components of the regulatory network have been individually studied in exquisite detail, systems approaches have rarely been utilized to comprehensively assess the relative engagements of the components. Thus, need and opportunity exist to develop quantitative models of metabolic and signaling networks to achieve a more complete understanding of AT biology in both health and disease. Copyright © 2013 Wiley Periodicals, Inc.

Systemic Risk and Optimal Regulatory Architecture

NARCIS (Netherlands)

Espinosa-Vega, M.A.; Kahn, C.; Matta, R.; Sole, J.

2011-01-01

Until the recent financial crisis, the safety and soundness of financial institutions was assessed from the perspective of the individual institution. The financial crisis highlighted the need to take systemic externalities seriously when rethinking prudential oversight and the regulatory

Micro-separation toward systems biology.

Science.gov (United States)

Liu, Bi-Feng; Xu, Bo; Zhang, Guisen; Du, Wei; Luo, Qingming

2006-02-17

Current biology is experiencing transformation in logic or philosophy that forces us to reevaluate the concept of cell, tissue or entire organism as a collection of individual components. Systems biology that aims at understanding biological system at the systems level is an emerging research area, which involves interdisciplinary collaborations of life sciences, computational and mathematical sciences, systems engineering, and analytical technology, etc. For analytical chemistry, developing innovative methods to meet the requirement of systems biology represents new challenges as also opportunities and responsibility. In this review, systems biology-oriented micro-separation technologies are introduced for comprehensive profiling of genome, proteome and metabolome, characterization of biomolecules interaction and single cell analysis such as capillary electrophoresis, ultra-thin layer gel electrophoresis, micro-column liquid chromatography, and their multidimensional combinations, parallel integrations, microfabricated formats, and nano technology involvement. Future challenges and directions are also suggested.

Nutritional Systems Biology

DEFF Research Database (Denmark)

Jensen, Kasper

and network biology has the potential to increase our understanding of how small molecules affect metabolic pathways and homeostasis, how this perturbation changes at the disease state, and to what extent individual genotypes contribute to this. A fruitful strategy in approaching and exploring the field...... biology research. The paper also shows as a proof-of-concept that a systems biology approach to diet is meaningful and demonstrates some basic principles on how to work with diet systematic. The second chapter of this thesis we developed the resource NutriChem v1.0. A foodchemical database linking...... sites of diet on the disease pathway. We propose a framework for interrogating the critical targets in colon cancer process and identifying plant-based dietary interventions as important modifiers using a systems chemical biology approach. The fifth chapter of the thesis is on discovering of novel anti...

Hydrogen mitigation systems - a Canadian regulatory perspective

International Nuclear Information System (INIS)

Khosla, J.K.; Rizk, M.

1997-01-01

This is a discussion paper to examine the regulatory requirements that may be necessary for the design, operation and maintenance of the hydrogen mitigation systems. These systems (if deemed necessary to maintain the containment function), may be considered to be a part of the containment systems. Therefore, these requirements are derived mostly from the AECB Regulatory Document R-7, which specifies the requirements for containment systems for CANDU nuclear power plants. Some additional requirements, which are specific to these systems have also been included. These requirements relate to a systematic examination of the hazards of hydrogen, the design basis for the mitigation systems, their functional and design requirements, analytical support to justify their selection, and operating and testing requirements. The requirements for severe accident have not yet been developed. It is, however, anticipated that the design of the hydrogen mitigation system would be such that future requirement can be accommodated. These requirements are intended for application to the new reactors in Canada. For the existing reactors, their application will be subjected to practicability. (author)

Informing biological design by integration of systems and synthetic biology.

Science.gov (United States)

Smolke, Christina D; Silver, Pamela A

2011-03-18

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

78 FR 38053 - Regulatory Systems Strengthening

Science.gov (United States)

2013-06-25

... current state of medical product regulation globally, including challenges, risks, and emerging trends... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0010... product regulation; generation and analysis of evidence of regulatory systems performance; and provision...

Proteome-wide Structural Analysis of PTM Hotspots Reveals Regulatory Elements Predicted to Impact Biological Function and Disease*

Science.gov (United States)

Dewhurst, Henry; Sundararaman, Niveda

2016-01-01

Post-translational modifications (PTMs) regulate protein behavior through modulation of protein-protein interactions, enzymatic activity, and protein stability essential in the translation of genotype to phenotype in eukaryotes. Currently, less than 4% of all eukaryotic PTMs are reported to have biological function - a statistic that continues to decrease with an increasing rate of PTM detection. Previously, we developed SAPH-ire (Structural Analysis of PTM Hotspots) - a method for the prioritization of PTM function potential that has been used effectively to reveal novel PTM regulatory elements in discrete protein families (Dewhurst et al., 2015). Here, we apply SAPH-ire to the set of eukaryotic protein families containing experimental PTM and 3D structure data - capturing 1,325 protein families with 50,839 unique PTM sites organized into 31,747 modified alignment positions (MAPs), of which 2010 (∼6%) possess known biological function. Here, we show that using an artificial neural network model (SAPH-ire NN) trained to identify MAP hotspots with biological function results in prediction outcomes that far surpass the use of single hotspot features, including nearest neighbor PTM clustering methods. We find the greatest enhancement in prediction for positions with PTM counts of five or less, which represent 98% of all MAPs in the eukaryotic proteome and 90% of all MAPs found to have biological function. Analysis of the top 1092 MAP hotspots revealed 267 of truly unknown function (containing 5443 distinct PTMs). Of these, 165 hotspots could be mapped to human KEGG pathways for normal and/or disease physiology. Many high-ranking hotspots were also found to be disease-associated pathogenic sites of amino acid substitution despite the lack of observable PTM in the human protein family member. Taken together, these experiments demonstrate that the functional relevance of a PTM can be predicted very effectively by neural network models, revealing a large but testable

A systems biology approach to transcription factor binding site prediction.

Directory of Open Access Journals (Sweden)

Xiang Zhou

2010-03-01

Full Text Available The elucidation of mammalian transcriptional regulatory networks holds great promise for both basic and translational research and remains one the greatest challenges to systems biology. Recent reverse engineering methods deduce regulatory interactions from large-scale mRNA expression profiles and cross-species conserved regulatory regions in DNA. Technical challenges faced by these methods include distinguishing between direct and indirect interactions, associating transcription regulators with predicted transcription factor binding sites (TFBSs, identifying non-linearly conserved binding sites across species, and providing realistic accuracy estimates.We address these challenges by closely integrating proven methods for regulatory network reverse engineering from mRNA expression data, linearly and non-linearly conserved regulatory region discovery, and TFBS evaluation and discovery. Using an extensive test set of high-likelihood interactions, which we collected in order to provide realistic prediction-accuracy estimates, we show that a careful integration of these methods leads to significant improvements in prediction accuracy. To verify our methods, we biochemically validated TFBS predictions made for both transcription factors (TFs and co-factors; we validated binding site predictions made using a known E2F1 DNA-binding motif on E2F1 predicted promoter targets, known E2F1 and JUND motifs on JUND predicted promoter targets, and a de novo discovered motif for BCL6 on BCL6 predicted promoter targets. Finally, to demonstrate accuracy of prediction using an external dataset, we showed that sites matching predicted motifs for ZNF263 are significantly enriched in recent ZNF263 ChIP-seq data.Using an integrative framework, we were able to address technical challenges faced by state of the art network reverse engineering methods, leading to significant improvement in direct-interaction detection and TFBS-discovery accuracy. We estimated the accuracy

Excited states in biological systems

International Nuclear Information System (INIS)

Cilento, G.; Zinner, K.; Bechara, E.J.H.; Duran, N.; Baptista, R.C. de; Shimizu, Y.; Augusto, O.; Faljoni-Alario, A.; Vidigal, C.C.C.; Oliveira, O.M.M.F.; Haun, M.

1979-01-01

Some aspects of bioluminescence related to bioenergetics are discussed: 1. chemical generation of excited species, by means of two general processes: electron transference and cyclic - and linear peroxide cleavage; 2. biological systems capable of generating excited states and 3. biological functions of these states, specially the non-emissive ones (tripletes). The production and the role of non-emissive excited states in biological systems are analysed, the main purpose of the study being the search for non-emissive states. Experiences carried out in biological systems are described; results and conclusions are given. (M.A.) [pt

USNRC regulatory guidance for engineered safety feature air cleaning systems

International Nuclear Information System (INIS)

Bellamy, R.R.

1991-01-01

The need for clear, technically appropriate, and easily implementable guidance for the design, testing, and maintenance of nuclear air cleaning systems has long been recognized. Numerous industry consensus standards have been issued and revised over the last 30 years. Guidance has also been published by the US Nuclear Regulatory Commission in the form of regulations, regulatory guides, standard review plans, NUREG documents, and information notices. This paper will summarize the latest revisions to these documents and emphasize Regulatory Guide 1.52, Design, Testing, and Maintenance Criteria for Post-Accident Engineered-Safety-Feature Atmosphere Cleanup System Air Filtration and Adsorption Units of Light-Water-Cooled Nuclear Power Plants, which was last revised in 1978. The USNRC has undertaken a project to revise this regulatory guide, and the status of that revision is highlighted

Regulatory networks, legal federalism, and multi-level regulatory systems

OpenAIRE

Kerber, Wolfgang; Wendel, Julia

2016-01-01

Transnational regulatory networks play important roles in multi-level regulatory regimes, as e.g, the European Union. In this paper we analyze the role of regulatory networks from the perspective of the economic theory of legal federalism. Often sophisticated intermediate institutional solutions between pure centralisation and pure decentralisation can help to solve complex tradeoff problems between the benefits and problems of centralised and decentralised solutions. Drawing upon the insight...

Modernizing the Regulatory System for Biotechnology Products

Science.gov (United States)

This Web page describes the continuing effort to modernize the federal regulatory system for biotechnology products as well as clarify various roles of EPA, FDA and USDA in evaluating new biotechnology products.

Telemetry System of Biological Parameters

Directory of Open Access Journals (Sweden)

Jan Spisak

2005-01-01

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

Towards a predictive theory for genetic regulatory networks

Science.gov (United States)

Tkacik, Gasper

When cells respond to changes in the environment by regulating the expression levels of their genes, we often draw parallels between these biological processes and engineered information processing systems. One can go beyond this qualitative analogy, however, by analyzing information transmission in biochemical ``hardware'' using Shannon's information theory. Here, gene regulation is viewed as a transmission channel operating under restrictive constraints set by the resource costs and intracellular noise. We present a series of results demonstrating that a theory of information transmission in genetic regulatory circuits feasibly yields non-trivial, testable predictions. These predictions concern strategies by which individual gene regulatory elements, e.g., promoters or enhancers, read out their signals; as well as strategies by which small networks of genes, independently or in spatially coupled settings, respond to their inputs. These predictions can be quantitatively compared to the known regulatory networks and their function, and can elucidate how reproducible biological processes, such as embryonic development, can be orchestrated by networks built out of noisy components. Preliminary successes in the gap gene network of the fruit fly Drosophila indicate that a full ab initio theoretical prediction of a regulatory network is possible, a feat that has not yet been achieved for any real regulatory network. We end by describing open challenges on the path towards such a prediction.

Development Perspective of Regulatory Audit Code System for SFR Nuclear Safety Evaluation

Energy Technology Data Exchange (ETDEWEB)

Bae, Moo Hoon; Lee, Gil Soo; Shin, An Dong; Suh, Nam Duk [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

2012-05-15

A sodium-cooled fast reactor (SFR) in Korea is based on the KALIMER-600 concept developed by KAERI. Based on 'Long-term R and D Plan for Future Reactor Systems' which was approved by the Korea Atomic Energy Commission in 2008, the KAERI designer is scheduled to apply the design certification of the prototype SFR in 2017. In order to establish regulatory infrastructure for the licensing of a prototype SFR, KINS has develop the regulatory requirements for the demonstration SFR since 2010, and are scheduled to develop the regulatory audit code systems in regard to core, fuel, and system, etc. since 2012. In this study, the domestic code systems used for core design and safety evaluation of PWRs and the nuclear physics and code system for SFRs were briefly reviewed, and the development perspective of regulatory audit code system for SFR nuclear safety evaluation were derived

Logical analysis of biological systems

DEFF Research Database (Denmark)

Mardare, Radu Iulian

2005-01-01

R. Mardare, Logical analysis of biological systems. Fundamenta Informaticae, N 64:271-285, 2005.......R. Mardare, Logical analysis of biological systems. Fundamenta Informaticae, N 64:271-285, 2005....

Attraction Basins as Gauges of Robustness against Boundary Conditions in Biological Complex Systems

Science.gov (United States)

Demongeot, Jacques; Goles, Eric; Morvan, Michel; Noual, Mathilde; Sené, Sylvain

2010-01-01

One fundamental concept in the context of biological systems on which researches have flourished in the past decade is that of the apparent robustness of these systems, i.e., their ability to resist to perturbations or constraints induced by external or boundary elements such as electromagnetic fields acting on neural networks, micro-RNAs acting on genetic networks and even hormone flows acting both on neural and genetic networks. Recent studies have shown the importance of addressing the question of the environmental robustness of biological networks such as neural and genetic networks. In some cases, external regulatory elements can be given a relevant formal representation by assimilating them to or modeling them by boundary conditions. This article presents a generic mathematical approach to understand the influence of boundary elements on the dynamics of regulation networks, considering their attraction basins as gauges of their robustness. The application of this method on a real genetic regulation network will point out a mathematical explanation of a biological phenomenon which has only been observed experimentally until now, namely the necessity of the presence of gibberellin for the flower of the plant Arabidopsis thaliana to develop normally. PMID:20700525

Attraction basins as gauges of robustness against boundary conditions in biological complex systems.

Directory of Open Access Journals (Sweden)

Jacques Demongeot

Full Text Available One fundamental concept in the context of biological systems on which researches have flourished in the past decade is that of the apparent robustness of these systems, i.e., their ability to resist to perturbations or constraints induced by external or boundary elements such as electromagnetic fields acting on neural networks, micro-RNAs acting on genetic networks and even hormone flows acting both on neural and genetic networks. Recent studies have shown the importance of addressing the question of the environmental robustness of biological networks such as neural and genetic networks. In some cases, external regulatory elements can be given a relevant formal representation by assimilating them to or modeling them by boundary conditions. This article presents a generic mathematical approach to understand the influence of boundary elements on the dynamics of regulation networks, considering their attraction basins as gauges of their robustness. The application of this method on a real genetic regulation network will point out a mathematical explanation of a biological phenomenon which has only been observed experimentally until now, namely the necessity of the presence of gibberellin for the flower of the plant Arabidopsis thaliana to develop normally.

The global regulatory system Csr senses glucose through the phosphoenolpyruvate: carbohydrate phosphotransferase system.

Science.gov (United States)

Pérez-Morales, Deyanira; Bustamante, Víctor H

2016-02-01

A novel connection between two regulatory systems controlling crucial biological processes in bacteria, the carbon storage regulator (Csr) system and the glucose-specific phosphotransferase system (PTS), is reported by Leng et al. in this issue. This involves the interaction of unphosphorylated EIIA(Glc), a component of the glucose-specific PTS, with the CsrD protein, which accelerates the decay of the CsrB and CsrC small RNAs via RNase E in Escherichia coli. As unphosphorylated EIIA(G) (lc) is generated in the presence of glucose, the PTS thus acts as a sensor of glucose for the Csr system. Interestingly, another pathway can operate for communication between the Csr system and the glucose-specific PTS. The absence of glucose generates phosphorylated EIIA(Glc) , which activates the enzyme adenylate cyclase to produce cyclic adenosine monophosphate (cAMP) that, in turn, binds to the regulator cAMP receptor protein (CRP). Leng et al. show that the complex cAMP-CRP modestly reduces CsrB decay independently of CsrD. On the other hand, a previous study indicates that the complex cAMP-CRP positively regulates the transcription of CsrB and CsrC in Salmonella enterica. Therefore, EIIA(G) (lc) could work as a molecular switch that regulates the activity of the Csr system, in response to its phosphorylation state determined by the presence or absence of glucose, in order to control gene expression. © 2015 John Wiley & Sons Ltd.

Institute for Genomics and Systems Biology

Science.gov (United States)

Institute for Genomics and Systems Biology Discover. Predict. Improve. Advancing Human and , 2015 See all Research Papers Featured Video Introduction to Systems Biology Video: Introduction to Systems Biology News Jack Gilbert Heading UChicago Startup that Aims to Predict Behavior of Trillions of

Biophysics and systems biology.

Science.gov (United States)

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.

Development of an air-operated actuator performance monitoring system for regulatory usage

International Nuclear Information System (INIS)

Sung, K. Y.; Kwon, S. J.

2004-01-01

The performance monitoring system of air-operated actuators for regulatory usage has been being developed. Essential elements and operating parameters affecting the actuator performance have been investigated to provide basic information for system development. The monitoring system including an air-operated actuator testing facility and analysis softwares for monitoring and evaluation are also introduced in this paper. As a result of simulated tests, it was known that the system could be a useful tool for the effective monitoring of actuator performance change and fault conditions. This system would be applied to regulatory inspection for utility's data validation and to the training of regulatory staff in future after some modification and expansion

Inverse problems in systems biology

International Nuclear Information System (INIS)

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

2009-01-01

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

Systems biology in critical-care nursing.

Science.gov (United States)

Schallom, Lynn; Thimmesch, Amanda R; Pierce, Janet D

2011-01-01

Systems biology applies advances in technology and new fields of study including genomics, transcriptomics, proteomics, and metabolomics to the development of new treatments and approaches of care for the critically ill and injured patient. An understanding of systems biology enhances a nurse's ability to implement evidence-based practice and to educate patients and families on novel testing and therapies. Systems biology is an integrated and holistic view of humans in relationship with the environment. Biomarkers are used to measure the presence and severity of disease and are rapidly expanding in systems biology endeavors. A systems biology approach using predictive, preventive, and participatory involvement is being utilized in a plethora of conditions of critical illness and injury including sepsis, cancer, pulmonary disease, and traumatic injuries.

Compartmental study of biological systems

International Nuclear Information System (INIS)

Moretti, J.L.

1975-01-01

The compartmental analysis of biological system is dealt with on several chapters devoted successively to: terminology; a mathematical and symbolic account of a system at equilibrium; different compartment systems; analysis of the experimental results. For this it is pointed out that the application of compartmental systems to biological phenomena is not always without danger. Sometimes the compartmental system established in a reference subject fails to conform in the patient. The compartments can divide into two or join together, completely changing the aspect of the system so that parameters calculated with the old model become entirely false. The conclusion is that the setting up of a compartmental system to represent a biological phenomenon is a tricky undertaking and the results must be constantly criticized and questioned [fr

Regulatory control analysis and design for sewer systems

DEFF Research Database (Denmark)

Mollerup, Ane Loft; Mikkelsen, Peter Steen; Thornberg, Dines

2015-01-01

A systematic methodology for regulatory control analysis and design is adapted for sewer system operation and evaluated. The main challenge with adapting the methodology is the handling of the stochastic and transient nature of the rainfall disturbances, inherent to sewer system operation...

Philosophy of Systems and Synthetic Biology

DEFF Research Database (Denmark)

Green, Sara

2017-01-01

This entry aims to clarify how systems and synthetic biology contribute to and extend discussions within philosophy of science. Unlike fields such as developmental biology or molecular biology, systems and synthetic biology are not easily demarcated by a focus on a specific subject area or level...... of organization. Rather, they are characterized by the development and application of mathematical, computational, and synthetic modeling strategies in response to complex problems and challenges within the life sciences. Proponents of systems and synthetic biology often stress the necessity of a perspective...... that goes beyond the scope of molecular biology and genetic engineering, respectively. With the emphasis on systems and interaction networks, the approaches explicitly engage in one of the oldest philosophical discussions on the relationship between parts and wholes, or between reductionism and holism...

Human factors in annunciation systems - Recommendations for a Canadian regulatory framework

Energy Technology Data Exchange (ETDEWEB)

Beattie, J D; Rochford, S; Vicente, K J [Humansystems Inc., ON (Canada)

1997-09-01

Under a contract with the Atomic Energy Control Board (AECB) of Canada, brief reviews were conducted of the annunciation systems in Canadian nuclear power plant control rooms; of regulatory practices in other countries and relevant international guidelines; and of the human factors literature related to annunciation systems. Based on these reviews, a framework is proposed for regulatory criteria which could be applied to new annunciation system designs. (author). 29 refs.

Human factors in annunciation systems - Recommendations for a Canadian regulatory framework

International Nuclear Information System (INIS)

Beattie, J.D.; Rochford, S.; Vicente, K.J.

1997-01-01

Under a contract with the Atomic Energy Control Board (AECB) of Canada, brief reviews were conducted of the annunciation systems in Canadian nuclear power plant control rooms; of regulatory practices in other countries and relevant international guidelines; and of the human factors literature related to annunciation systems. Based on these reviews, a framework is proposed for regulatory criteria which could be applied to new annunciation system designs. (author). 29 refs

Carcinogenesis: alterations in reciprocal interactions of normal functional structure of biologic systems.

Science.gov (United States)

Davydyan, Garri

2015-12-01

The evolution of biologic systems (BS) includes functional mechanisms that in some conditions may lead to the development of cancer. Using mathematical group theory and matrix analysis, previously, it was shown that normally functioning BS are steady functional structures regulated by three basis regulatory components: reciprocal links (RL), negative feedback (NFB) and positive feedback (PFB). Together, they form an integrative unit maintaining system's autonomy and functional stability. It is proposed that phylogenetic development of different species is implemented by the splitting of "rudimentary" characters into two relatively independent functional parts that become encoded in chromosomes. The functional correlate of splitting mechanisms is RL. Inversion of phylogenetic mechanisms during ontogenetic development leads cell differentiation until cells reach mature states. Deterioration of reciprocal structure in the genome during ontogenesis gives rise of pathological conditions characterized by unsteadiness of the system. Uncontrollable cell proliferation and invasive cell growth are the leading features of the functional outcomes of malfunctioning systems. The regulatory element responsible for these changes is RL. In matrix language, pathological regulation is represented by matrices having positive values of diagonal elements ( TrA  > 0) and also positive values of matrix determinant ( detA  > 0). Regulatory structures of that kind can be obtained if the negative entry of the matrix corresponding to RL is replaced with the positive one. To describe not only normal but also pathological states of BS, a unit matrix should be added to the basis matrices representing RL, NFB and PFB. A mathematical structure corresponding to the set of these four basis functional patterns (matrices) is a split quaternion (coquaternion). The structure and specific role of basis elements comprising four-dimensional linear space of split quaternions help to understand what

Antibody-drug conjugates for cancer therapy: The technological and regulatory challenges of developing drug-biologic hybrids.

Science.gov (United States)

Hamilton, Gregory S

2015-09-01

Antibody-drug conjugates (ADCs) are a new class of therapeutic agents that combine the targeting ability of monoclonal antibodies (mAbs) with small molecule drugs. The combination of a mAb targeting a cancer-specific antigen with a cytotoxin has tremendous promise as a new type of targeted cancer therapy. Two ADCs have been approved and many more are in clinical development, suggesting that this new class of drugs is coming to the forefront. Because of their unique nature as biologic-small drug hybrids, ADCs are challenging to develop, from both the scientific and regulatory perspectives. This review discusses both these aspects in current practice, and surveys the current state of the art of ADC drug development. Copyright © 2015 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Global Acceptance of Biosimilars: Importance of Regulatory Consistency, Education, and Trust.

Science.gov (United States)

Cazap, Eduardo; Jacobs, Ira; McBride, Ali; Popovian, Robert; Sikora, Karol

2018-05-16

Globally, biosimilars are expected to have a key role in improving patient access to biological therapies and addressing concerns regarding the escalating cost of health care. Indeed, in Europe, increased use of biologics and reduced drug prices have been observed after the introduction of biosimilars. Recently, several monoclonal antibody biosimilars of anticancer therapies have been approved, and numerous others are in various stages of clinical development. Biosimilars are authorized via a regulatory pathway separate from that used for generic drugs; they are also regulated separately from novel biologics. Biosimilar approval pathways in many major regulatory regions worldwide are, to a broad degree, scientifically aligned. However, owing to regional differences in health care priorities, policies, and resources, some important regulatory inconsistencies are evident. Acceptance of biosimilars by health care systems, health care professionals, and patients will be a key factor in the uptake of these therapies, and such regulatory variations could contribute to confusion and diminished confidence regarding the quality, efficacy, and reliability of these agents. Furthermore, the need for manufacturers to account for regulatory inconsistencies introduces inefficiencies and delays into biosimilar development programs. These issues should be addressed if biosimilars are to attain their maximal global potential. This review summarizes the evolution of the global biosimilar landscape and provides examples of inconsistencies between regulatory requirements in different regions. In addition, we review ongoing efforts to improve regulatory alignment and highlight the importance of education as a crucial factor in generating trust in, and acceptance of, biosimilars on a worldwide scale. Biosimilars of monoclonal antibody anticancer therapies are beginning to emerge, and more are likely to become available for clinical use in the near future. The extent to which biosimilars

Systems Biology

Indian Academy of Sciences (India)

IAS Admin

study and understand the function of biological systems, particu- larly, the response of such .... understand the organisation and behaviour of prokaryotic sys- tems. ... relationship of the structure of a target molecule to its ability to bind a certain ...

Integrating systems biology models and biomedical ontologies.

Science.gov (United States)

Hoehndorf, Robert; Dumontier, Michel; Gennari, John H; Wimalaratne, Sarala; de Bono, Bernard; Cook, Daniel L; Gkoutos, Georgios V

2011-08-11

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

Calculating life? Duelling discourses in interdisciplinary systems biology.

Science.gov (United States)

Calvert, Jane; Fujimura, Joan H

2011-06-01

A high profile context in which physics and biology meet today is in the new field of systems biology. Systems biology is a fascinating subject for sociological investigation because the demands of interdisciplinary collaboration have brought epistemological issues and debates front and centre in discussions amongst systems biologists in conference settings, in publications, and in laboratory coffee rooms. One could argue that systems biologists are conducting their own philosophy of science. This paper explores the epistemic aspirations of the field by drawing on interviews with scientists working in systems biology, attendance at systems biology conferences and workshops, and visits to systems biology laboratories. It examines the discourses of systems biologists, looking at how they position their work in relation to previous types of biological inquiry, particularly molecular biology. For example, they raise the issue of reductionism to distinguish systems biology from molecular biology. This comparison with molecular biology leads to discussions about the goals and aspirations of systems biology, including epistemic commitments to quantification, rigor and predictability. Some systems biologists aspire to make biology more similar to physics and engineering by making living systems calculable, modelable and ultimately predictable-a research programme that is perhaps taken to its most extreme form in systems biology's sister discipline: synthetic biology. Other systems biologists, however, do not think that the standards of the physical sciences are the standards by which we should measure the achievements of systems biology, and doubt whether such standards will ever be applicable to 'dirty, unruly living systems'. This paper explores these epistemic tensions and reflects on their sociological dimensions and their consequences for future work in the life sciences. Copyright © 2010 Elsevier Ltd. All rights reserved.

Heuristic Strategies in Systems Biology

Directory of Open Access Journals (Sweden)

Fridolin Gross

2016-06-01

Full Text Available Systems biology is sometimes presented as providing a superior approach to the problem of biological complexity. Its use of ‘unbiased’ methods and formal quantitative tools might lead to the impression that the human factor is effectively eliminated. However, a closer look reveals that this impression is misguided. Systems biologists cannot simply assemble molecular information and compute biological behavior. Instead, systems biology’s main contribution is to accelerate the discovery of mechanisms by applying models as heuristic tools. These models rely on a variety of idealizing and simplifying assumptions in order to be efficient for this purpose. The strategies of systems biologists are similar to those of experimentalists in that they attempt to reduce the complexity of the discovery process. Analyzing and comparing these strategies, or ‘heuristics’, reveals the importance of the human factor in computational approaches and helps to situate systems biology within the epistemic landscape of the life sciences.

Structure, Biology, and Therapeutic Application of Toxin-Antitoxin Systems in Pathogenic Bacteria.

Science.gov (United States)

Lee, Ki-Young; Lee, Bong-Jin

2016-10-22

Bacterial toxin-antitoxin (TA) systems have received increasing attention for their diverse identities, structures, and functional implications in cell cycle arrest and survival against environmental stresses such as nutrient deficiency, antibiotic treatments, and immune system attacks. In this review, we describe the biological functions and the auto-regulatory mechanisms of six different types of TA systems, among which the type II TA system has been most extensively studied. The functions of type II toxins include mRNA/tRNA cleavage, gyrase/ribosome poison, and protein phosphorylation, which can be neutralized by their cognate antitoxins. We mainly explore the similar but divergent structures of type II TA proteins from 12 important pathogenic bacteria, including various aspects of protein-protein interactions. Accumulating knowledge about the structure-function correlation of TA systems from pathogenic bacteria has facilitated a novel strategy to develop antibiotic drugs that target specific pathogens. These molecules could increase the intrinsic activity of the toxin by artificially interfering with the intermolecular network of the TA systems.

In silico analysis of cis-acting regulatory elements in 5' regulatory regions of sucrose transporter gene families in rice (Oryza sativa Japonica) and Arabidopsis thaliana.

Science.gov (United States)

Ibraheem, Omodele; Botha, Christiaan E J; Bradley, Graeme

2010-12-01

The regulation of gene expression involves a multifarious regulatory system. Each gene contains a unique combination of cis-acting regulatory sequence elements in the 5' regulatory region that determines its temporal and spatial expression. Cis-acting regulatory elements are essential transcriptional gene regulatory units; they control many biological processes and stress responses. Thus a full understanding of the transcriptional gene regulation system will depend on successful functional analyses of cis-acting elements. Cis-acting regulatory elements present within the 5' regulatory region of the sucrose transporter gene families in rice (Oryza sativa Japonica cultivar-group) and Arabidopsis thaliana, were identified using a bioinformatics approach. The possible cis-acting regulatory elements were predicted by scanning 1.5kbp of 5' regulatory regions of the sucrose transporter genes translational start sites, using Plant CARE, PLACE and Genomatix Matinspector professional databases. Several cis-acting regulatory elements that are associated with plant development, plant hormonal regulation and stress response were identified, and were present in varying frequencies within the 1.5kbp of 5' regulatory region, among which are; A-box, RY, CAT, Pyrimidine-box, Sucrose-box, ABRE, ARF, ERE, GARE, Me-JA, ARE, DRE, GA-motif, GATA, GT-1, MYC, MYB, W-box, and I-box. This result reveals the probable cis-acting regulatory elements that possibly are involved in the expression and regulation of sucrose transporter gene families in rice and Arabidopsis thaliana during cellular development or environmental stress conditions. Copyright © 2010 Elsevier Ltd. All rights reserved.

Improving the Timed Automata Approach to Biological Pathway Dynamics

NARCIS (Netherlands)

Langerak, R.; Pol, Jaco van de; Post, Janine N.; Schivo, Stefano; Aceto, Luca; Bacci, Giorgio; Bacci, Giovanni; Ingólfsdóttir, Anna; Legay, Axel; Mardare, Radu

2017-01-01

Biological systems such as regulatory or gene networks can be seen as a particular type of distributed systems, and for this reason they can be modeled within the Timed Automata paradigm, which was developed in the computer science context. However, tools designed to model distributed systems often

Low doses of ionizing radiation: Biological effects and regulatory control. Invited papers and discussions. Proceedings of an international conference

International Nuclear Information System (INIS)

1998-01-01

The levels and biological effects resulting from exposure to ionizing radiation are continuously reviewed by the United Nations Committee on the Effects of Atomic Radiation (UNSCEAR). Since its creation in 1928, the International Commission on Radiological Protection (ICRP) has issued recommendations on protection against ionizing radiation. The UNSCEAR estimates and the ICRP recommendations have served as the basis for national and international safety standards on radiation safety, including those developed by the International Atomic Energy Agency (IAEA) and the World Health Organization (WHO). Concerning health effects of low doses of ionizing radiation, the international standards are based on the plausible assumption that, above the unavoidable background radiation dose, the probability of effects increases linearly with dose, i.e. on a 'linear, no threshold' (LNT) assumption. However, in recent years the biological estimates of health effects of low doses of ionizing radiation and the regulatory approach to the control of low level radiation exposure have been much debated. To foster information exchange on the relevant issues, an International Conference on Low Doses of Ionizing Radiation: Biological Effects and Regulatory Control, jointly sponsored by the IAEA and WHO in co-operation with UNSCEAR, was held from 17-21 November 1997 at Seville, Spain. These Proceedings contain the invited special reports, keynote papers, summaries of discussions, session summaries and addresses presented at the opening and closing of the Conference

Understanding Biological Regulation Through Synthetic Biology.

Science.gov (United States)

Bashor, Caleb J; Collins, James J

2018-03-16

Engineering synthetic gene regulatory circuits proceeds through iterative cycles of design, building, and testing. Initial circuit designs must rely on often-incomplete models of regulation established by fields of reductive inquiry-biochemistry and molecular and systems biology. As differences in designed and experimentally observed circuit behavior are inevitably encountered, investigated, and resolved, each turn of the engineering cycle can force a resynthesis in understanding of natural network function. Here, we outline research that uses the process of gene circuit engineering to advance biological discovery. Synthetic gene circuit engineering research has not only refined our understanding of cellular regulation but furnished biologists with a toolkit that can be directed at natural systems to exact precision manipulation of network structure. As we discuss, using circuit engineering to predictively reorganize, rewire, and reconstruct cellular regulation serves as the ultimate means of testing and understanding how cellular phenotype emerges from systems-level network function. Expected final online publication date for the Annual Review of Biophysics Volume 47 is May 20, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Mammalian Synthetic Biology: Engineering Biological Systems.

Science.gov (United States)

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

2017-06-21

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

Applicability of Computational Systems Biology in Toxicology

DEFF Research Database (Denmark)

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

2014-01-01

be used to establish hypotheses on links between the chemical and human diseases. Such information can also be applied for designing more intelligent animal/cell experiments that can test the established hypotheses. Here, we describe how and why to apply an integrative systems biology method......Systems biology as a research field has emerged within the last few decades. Systems biology, often defined as the antithesis of the reductionist approach, integrates information about individual components of a biological system. In integrative systems biology, large data sets from various sources...... and databases are used to model and predict effects of chemicals on, for instance, human health. In toxicology, computational systems biology enables identification of important pathways and molecules from large data sets; tasks that can be extremely laborious when performed by a classical literature search...

Contribution of a fuzzy expert system to regulatory impact analysis

Directory of Open Access Journals (Sweden)

Marco Antônio da Cunha

2015-09-01

Full Text Available Regulatory Impact Analysis (RIA has been consolidating in Brazilian regulatory agencies throughout the last decades. The RIA methodology aims to examine the regulatory process, measure the costs and benefits generated, as well as other effects of social, political or economic nature caused by a new or an existing regulation. By analysing each regulatory option, the expert or regulator faces a myriad of variables, usually of qualitative nature, that are difficult to measure and with a high degree of uncertainty. This research complements the existing literature, given the scarcity of decision support models in RIA that – regardless of the problem treated – incorporate the tacit knowledge of the regulation expert. This paper proposes an exploratory approach using a Fuzzy Expert System, which therefore helps to enrich the decision process in the final stage of comparison of the regulatory options.

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

Science.gov (United States)

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

2010-03-01

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

Editorial overview : Systems biology for biotechnology

NARCIS (Netherlands)

Heinemann, Matthias; Pilpel, Yitzhak

About 15 years ago, systems biology was introduced as a novel approach to biological research. On the one side, its introduction was a result of the recognition that through solely the reductionist approach, we would ulti- mately not be able to understand how biological systems function as a whole.

Development of regulatory guidance for risk-informing digital system reviews

International Nuclear Information System (INIS)

Arndt, S. A.

2006-01-01

In 1995, the U.S. Nuclear Regulatory Commission (NRC) issued the Probabilistic Risk Assessment (PRA) Policy Statement, which encourages the increased use of PRA and associated analyses in all regulatory matters to the extent supported by the state-of-the-art in PRA and the data. This policy applies, in part, to the review of digital systems, which offer the potential to improve plant safety and reliability through such features as increased hardware reliability and stability and improved failure detection capability. However, there are presently no universally accepted methods for modeling digital systems in current-generation PRAs. Further, there are ongoing debates among the PRA technical community regarding the level of detail that any digital system reliability model must have to adequately model the complex system interactions that can contribute to digital system failure modes. Moreover, for PRA modeling of digital reactor protection and control systems, direct interactions between system components and indirect interactions through controlled/supervised plant processes may necessitate the use of dynamic PRA methodologies. This situation has led the NRC to consider developing performance based rather than prescriptive regulatory guidance in this area. This paper will discuss the development of this guidance and some preliminary concepts. (authors)

Quantum Effects in Biological Systems

CERN Document Server

2016-01-01

Since the last decade the study of quantum mechanical phenomena in biological systems has become a vibrant field of research. Initially sparked by evidence of quantum effects in energy transport that is instrumental for photosynthesis, quantum biology asks the question of how methods and models from quantum theory can help us to understand fundamental mechanisms in living organisms. This approach entails a paradigm change challenging the related disciplines: The successful framework of quantum theory is taken out of its low-temperature, microscopic regimes and applied to hot and dense macroscopic environments, thereby extending the toolbox of biology and biochemistry at the same time. The Quantum Effects in Biological Systems conference is a platform for researchers from biology, chemistry and physics to present and discuss the latest developments in the field of quantum biology. After meetings in Lisbon (2009), Harvard (2010), Ulm (2011), Berkeley (2012), Vienna (2013), Singapore (2014) and Florence (2015),...

International Conference on Effective Nuclear Regulatory Systems: Sustaining Improvements Globally. Book of Abstracts

International Nuclear Information System (INIS)

2016-01-01

The objective of this conference is to review and assess ways of further improving the effectiveness of regulatory systems for nuclear facilities and activities for both nuclear safety and nuclear security. The action items in the summary presented by the President of the conference held in 2013 in Ottawa, the lessons of the Fukushima Daiichi accident, the discussions at other international conferences and at international experts’ meetings conducted within the framework of the IAEA Action Plan on Nuclear Safety, as well as the CNS and the principles outlined in the Vienna Declaration on Nuclear Safety, will continue to have a significant impact on regulatory systems. All the aforementioned need to be taken into account to sustain improvements to regulatory systems. The expected outcomes of the conference are: - Enhanced safety and security of nuclear installations worldwide; - Challenges in regulating radiation sources and radioactive waste addressed; - Enhanced international cooperation for sustaining regulatory effectiveness; - Strengthened and sustained regulatory competence for nuclear safety and security; and - Strategies and actions for the future identified, as well as issues for consideration by governments, regulatory bodies and international organizations.

Static Analysis for Systems Biology

DEFF Research Database (Denmark)

Nielson, Flemming; Nielson, Hanne Riis; Rosa, D. Schuch da

2004-01-01

This paper shows how static analysis techniques can help understanding biological systems. Based on a simple example we illustrate the outcome of performing three different analyses extracting information of increasing precision. We conclude by reporting on the potential impact and exploitation o...... of these techniques in systems biology....

Omics/systems biology and cancer cachexia.

Science.gov (United States)

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

2016-06-01

Cancer cachexia is a complex syndrome generated by interaction between the host and tumour cells with a background of treatment effects and toxicity. The complexity of the physiological pathways likely involved in cancer cachexia necessitates a holistic view of the relevant biology. Emergent properties are characteristic of complex systems with the result that the end result is more than the sum of its parts. Recognition of the importance of emergent properties in biology led to the concept of systems biology wherein a holistic approach is taken to the biology at hand. Systems biology approaches will therefore play an important role in work to uncover key mechanisms with therapeutic potential in cancer cachexia. The 'omics' technologies provide a global view of biological systems. Genomics, transcriptomics, proteomics, lipidomics and metabolomics approaches all have application in the study of cancer cachexia to generate systems level models of the behaviour of this syndrome. The current work reviews recent applications of these technologies to muscle atrophy in general and cancer cachexia in particular with a view to progress towards integration of these approaches to better understand the pathology and potential treatment pathways in cancer cachexia. Copyright © 2016. Published by Elsevier Ltd.

Analyzing the Biology on the System Level

OpenAIRE

Tong, Wei

2016-01-01

Although various genome projects have provided us enormous static sequence information, understanding of the sophisticated biology continues to require integrating the computational modeling, system analysis, technology development for experiments, and quantitative experiments all together to analyze the biology architecture on various levels, which is just the origin of systems biology subject. This review discusses the object, its characteristics, and research attentions in systems biology,...

RNA-ID, a Powerful Tool for Identifying and Characterizing Regulatory Sequences.

Science.gov (United States)

Brule, C E; Dean, K M; Grayhack, E J

2016-01-01

The identification and analysis of sequences that regulate gene expression is critical because regulated gene expression underlies biology. RNA-ID is an efficient and sensitive method to discover and investigate regulatory sequences in the yeast Saccharomyces cerevisiae, using fluorescence-based assays to detect green fluorescent protein (GFP) relative to a red fluorescent protein (RFP) control in individual cells. Putative regulatory sequences can be inserted either in-frame or upstream of a superfolder GFP fusion protein whose expression, like that of RFP, is driven by the bidirectional GAL1,10 promoter. In this chapter, we describe the methodology to identify and study cis-regulatory sequences in the RNA-ID system, explaining features and variations of the RNA-ID reporter, as well as some applications of this system. We describe in detail the methods to analyze a single regulatory sequence, from construction of a single GFP variant to assay of variants by flow cytometry, as well as modifications required to screen libraries of different strains simultaneously. We also describe subsequent analyses of regulatory sequences. © 2016 Elsevier Inc. All rights reserved.

Adapting to Biology: Maintaining Container-Closure System Compatibility with the Therapeutic Biologic Revolution.

Science.gov (United States)

Degrazio, Dominick

Many pharmaceutical companies are transitioning their research and development drug product pipeline from traditional small-molecule injectables to the dimension of evolving therapeutic biologics. Important concerns associated with this changeover are becoming forefront, as challenges develop of varying complexity uncommon with the synthesis and production of traditional drugs. Therefore, alternative measures must be established that aim to preserve the efficacy and functionality of a biologic that might not be implemented for small molecules. Conserving protein stability is relative to perpetuating a net equilibrium of both intrinsic and extrinsic factors. Key to sustaining this balance is the ability of container-closure systems to maintain their compatibility with the ever-changing dynamics of therapeutic biologics. Failure to recognize and adjust the material properties of packaging components to support compatibility with therapeutic biologics can compromise patient safety, drug productivity, and biological stability. This review will examine the differences between small-molecule drugs and therapeutic biologics, lay a basic foundation for understanding the stability of therapeutic biologics, and demonstrate potential sources of container-closure systems' incompatibilities with therapeutic biologics at a mechanistic level. Many pharmaceutical companies are transitioning their research and development drug product pipeline from traditional small-molecule injectables to recombinantly derived therapeutic biologics. Concerns associated with this transformation are becoming prominent, as therapeutic biologics are uncharacteristic to small-molecule drugs. Maintaining the stability of a therapeutic biologic is a combination of balancing intrinsic factors and external elements within the biologic's microenvironment. An important aspect of this balance is relegated to the overall compatibility of primary, parenteral container-closure systems with therapeutic biologics

Nuclear whistleblower protection system in U.S. and its implication to Japanese regulatory system

International Nuclear Information System (INIS)

Tanabe, Tomoyuki; Suzuki, Tatsujiro

2003-01-01

The nuclear whistleblower protection system in U.S.A consists of two programs: 1) allegation program and 2) whistleblower protection system. The former is explained by basic act, definition of allegation, anonymous allegation, direct allegation to NRC (Nuclear Regulatory Commission), number of allegation from 1997 to 2001, procedure and period of investigation and notice of allegation to licensees. The latter is explained by basis act, outline of the system, enforcement by NRC and DOL (Department of Labor), number of discrimination compliant and anxiety of licensees. The system is good conditions in U.S.A depend on 1) prevent of illegal act and increase, 2) preparation of procedure and its transparency and 3) enforcement system. However, a hostile act to licensees is found in the whistleblower protection system. There are many problems in Japanese regulatory system. The improvement points of Japanese system are proposed. (S.Y.)

Deliberations on nuclear safety regulatory system in a changing industrial environment

International Nuclear Information System (INIS)

Kim, H.J.

2001-01-01

Nuclear safety concern, which may accompany such external environmental factors as privatization and restructuring of the electric power industry, is emerging as an international issue. In order to cope with the concern about nuclear safety, it is important to feedback valuable experiences of advanced countries that restructured their electric power industries earlier and further to reflect the current safety issues, which are raised internationally, fully into the nuclear safety regulatory system. This paper is to review the safety issues that might take place in the process of increasing competition in the nuclear power industry, and further to present a basic direction and effective measures for ensuring nuclear safety in response thereto from the viewpoint of safety regulation. It includes a political direction for a regulatory body's efforts to rationalize and enforce efficiently its regulation. It proposes to ensure that regulatory specialty and regulatory cost are stably secured. Also, this paper proposes maintaining a sound nuclear safety regulatory system to monitor thoroughly the safety management activities of the industry, which might be neglected as a result of focusing on reduction of the cost for producing electric power. (author)

Large-scale modeling of condition-specific gene regulatory networks by information integration and inference.

Science.gov (United States)

Ellwanger, Daniel Christian; Leonhardt, Jörn Florian; Mewes, Hans-Werner

2014-12-01

Understanding how regulatory networks globally coordinate the response of a cell to changing conditions, such as perturbations by shifting environments, is an elementary challenge in systems biology which has yet to be met. Genome-wide gene expression measurements are high dimensional as these are reflecting the condition-specific interplay of thousands of cellular components. The integration of prior biological knowledge into the modeling process of systems-wide gene regulation enables the large-scale interpretation of gene expression signals in the context of known regulatory relations. We developed COGERE (http://mips.helmholtz-muenchen.de/cogere), a method for the inference of condition-specific gene regulatory networks in human and mouse. We integrated existing knowledge of regulatory interactions from multiple sources to a comprehensive model of prior information. COGERE infers condition-specific regulation by evaluating the mutual dependency between regulator (transcription factor or miRNA) and target gene expression using prior information. This dependency is scored by the non-parametric, nonlinear correlation coefficient η(2) (eta squared) that is derived by a two-way analysis of variance. We show that COGERE significantly outperforms alternative methods in predicting condition-specific gene regulatory networks on simulated data sets. Furthermore, by inferring the cancer-specific gene regulatory network from the NCI-60 expression study, we demonstrate the utility of COGERE to promote hypothesis-driven clinical research. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Analysis of a Plant Transcriptional Regulatory Network Using Transient Expression Systems.

Science.gov (United States)

Díaz-Triviño, Sara; Long, Yuchen; Scheres, Ben; Blilou, Ikram

2017-01-01

In plant biology, transient expression systems have become valuable approaches used routinely to rapidly study protein expression, subcellular localization, protein-protein interactions, and transcriptional activity prior to in vivo studies. When studying transcriptional regulation, luciferase reporter assays offer a sensitive readout for assaying promoter behavior in response to different regulators or environmental contexts and to confirm and assess the functional relevance of predicted binding sites in target promoters. This chapter aims to provide detailed methods for using luciferase reporter system as a rapid, efficient, and versatile assay to analyze transcriptional regulation of target genes by transcriptional regulators. We describe a series of optimized transient expression systems consisting of Arabidopsis thaliana protoplasts, infiltrated Nicotiana benthamiana leaves, and human HeLa cells to study the transcriptional regulations of two well-characterized transcriptional regulators SCARECROW (SCR) and SHORT-ROOT (SHR) on one of their targets, CYCLIN D6 (CYCD6).Here, we illustrate similarities and differences in outcomes when using different systems. The plant-based systems revealed that the SCR-SHR complex enhances CYCD6 transcription, while analysis in HeLa cells showed that the complex is not sufficient to strongly induce CYCD6 transcription, suggesting that additional, plant-specific regulators are required for full activation. These results highlight the importance of the system and suggest that including heterologous systems, such as HeLa cells, can provide a more comprehensive analysis of a complex gene regulatory network.

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

Science.gov (United States)

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

2016-06-17

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

Quantitative inference of dynamic regulatory pathways via microarray data

Directory of Open Access Journals (Sweden)

Chen Bor-Sen

2005-03-01

Full Text Available Abstract Background The cellular signaling pathway (network is one of the main topics of organismic investigations. The intracellular interactions between genes in a signaling pathway are considered as the foundation of functional genomics. Thus, what genes and how much they influence each other through transcriptional binding or physical interactions are essential problems. Under the synchronous measures of gene expression via a microarray chip, an amount of dynamic information is embedded and remains to be discovered. Using a systematically dynamic modeling approach, we explore the causal relationship among genes in cellular signaling pathways from the system biology approach. Results In this study, a second-order dynamic model is developed to describe the regulatory mechanism of a target gene from the upstream causality point of view. From the expression profile and dynamic model of a target gene, we can estimate its upstream regulatory function. According to this upstream regulatory function, we would deduce the upstream regulatory genes with their regulatory abilities and activation delays, and then link up a regulatory pathway. Iteratively, these regulatory genes are considered as target genes to trace back their upstream regulatory genes. Then we could construct the regulatory pathway (or network to the genome wide. In short, we can infer the genetic regulatory pathways from gene-expression profiles quantitatively, which can confirm some doubted paths or seek some unknown paths in a regulatory pathway (network. Finally, the proposed approach is validated by randomly reshuffling the time order of microarray data. Conclusion We focus our algorithm on the inference of regulatory abilities of the identified causal genes, and how much delay before they regulate the downstream genes. With this information, a regulatory pathway would be built up using microarray data. In the present study, two signaling pathways, i.e. circadian regulatory

Regulatory System of Radiation Protection in Taiwan

International Nuclear Information System (INIS)

Tang, F. T.; Huang, C. C.

2004-01-01

After the radioactive contaminated buildings incident occurred in Taiwan in 1993, the competent authority for radiation protection the Atomic Energy Council (AEC) started to review the structured problem of radiation protection regulatory system. Through several years' investigation and study, the AEC has improved two important tools in radiation protection regulatory system, i.e., control regulations and actual practice, and made them more rigorous and efficient. This paper will make a brief introduction of the efforts that Taiwan has made in this respect. Taiwan's radiation protection control was based on the Atomic Energy Law promulgated in 1968, but the control idea and authorization scope were not sufficient to appropriately respond to the highly developed economy and democracy in Taiwan. After several years' legislative process, the Ionizing Radiation Protection Law (IRP Law) was promulgated and entered into force on February 1, 2003. This IRP Law specifically emphasizes categorized risk management of radiation sources, establishment of personnel licenses and training system, enhancement of public safety control, and implementation of quality assurance program for medical exposure. The Legislative Yuan (Congress) fully authorized the competent authority to establish various technological control regulations according to control necessity without prior review by the Legislative Yuan in advance. As to the penalties of the violations of the IRP Law, the AEC adopts high-rated administrative fines and applies the Criminal Law to those who seriously contaminate the environment. In actual practice, the AEC has constructed a Radiation Protection Control Information System compatible with the IRP Law that fully combines the functions of computers and Internet. The information of facility operators who own radiation sources, radiation protection specialists, and operating personnel are entered into this system, starting from the submission of application of the

Inference of cancer-specific gene regulatory networks using soft computing rules.

Science.gov (United States)

Wang, Xiaosheng; Gotoh, Osamu

2010-03-24

Perturbations of gene regulatory networks are essentially responsible for oncogenesis. Therefore, inferring the gene regulatory networks is a key step to overcoming cancer. In this work, we propose a method for inferring directed gene regulatory networks based on soft computing rules, which can identify important cause-effect regulatory relations of gene expression. First, we identify important genes associated with a specific cancer (colon cancer) using a supervised learning approach. Next, we reconstruct the gene regulatory networks by inferring the regulatory relations among the identified genes, and their regulated relations by other genes within the genome. We obtain two meaningful findings. One is that upregulated genes are regulated by more genes than downregulated ones, while downregulated genes regulate more genes than upregulated ones. The other one is that tumor suppressors suppress tumor activators and activate other tumor suppressors strongly, while tumor activators activate other tumor activators and suppress tumor suppressors weakly, indicating the robustness of biological systems. These findings provide valuable insights into the pathogenesis of cancer.

Signal-regulated systems and networks

CSIR Research Space (South Africa)

Van Zyl, TL

2010-07-01

Full Text Available The article presents the use of signal regulatory networks (SRNs), a biologically inspired model based on gene regulatory networks. SRNs are a way of understanding a class of self-organizing IT systems, signal-regulated systems (SRSs). This article...

Establishing a regulatory value chain model: An innovative approach to strengthening medicines regulatory systems in resource-constrained settings.

Science.gov (United States)

Chahal, Harinder Singh; Kashfipour, Farrah; Susko, Matt; Feachem, Neelam Sekhri; Boyle, Colin

2016-05-01

Medicines Regulatory Authorities (MRAs) are an essential part of national health systems and are charged with protecting and promoting public health through regulation of medicines. However, MRAs in resource-constrained settings often struggle to provide effective oversight of market entry and use of health commodities. This paper proposes a regulatory value chain model (RVCM) that policymakers and regulators can use as a conceptual framework to guide investments aimed at strengthening regulatory systems. The RVCM incorporates nine core functions of MRAs into five modules: (i) clear guidelines and requirements; (ii) control of clinical trials; (iii) market authorization of medical products; (iv) pre-market quality control; and (v) post-market activities. Application of the RVCM allows national stakeholders to identify and prioritize investments according to where they can add the most value to the regulatory process. Depending on the economy, capacity, and needs of a country, some functions can be elevated to a regional or supranational level, while others can be maintained at the national level. In contrast to a "one size fits all" approach to regulation in which each country manages the full regulatory process at the national level, the RVCM encourages leveraging the expertise and capabilities of other MRAs where shared processes strengthen regulation. This value chain approach provides a framework for policymakers to maximize investment impact while striving to reach the goal of safe, affordable, and rapidly accessible medicines for all.

Challenges posed to the European pharmaceutical regulatory system by highly personalized medicines.

Science.gov (United States)

Johnston, John D; Feldschreiber, Peter

2014-03-01

The European pharmaceutical regulatory system has not yet been challenged by issues related to highly personalized medicines such as those to be found with active substances that affect RNA biochemistry. We review the current status of RNA-based pharmacology and present three possible case histories. The implications for the European pharmaceutical regulatory system are discussed. © 2013 The British Pharmacological Society.

Ten questions about systems biology

DEFF Research Database (Denmark)

Joyner, Michael J; Pedersen, Bente K

2011-01-01

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......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...

Ten questions about systems biology

DEFF Research Database (Denmark)

Joyner, Michael J; Pedersen, Bente K

2011-01-01

In this paper we raise 'ten questions' broadly related to 'omics', the term systems biology, and why the new biology has failed to deliver major therapeutic advances for many common diseases, especially diabetes and cardiovascular disease. We argue that a fundamentally narrow and reductionist...... to understand how whole animals adapt to the real world. We argue that a lack of fluency in these concepts is a major stumbling block for what has been narrowly defined as 'systems biology' by some of its leading advocates. We also point out that it is a failure of regulation at multiple levels that causes many...

Nuclear knowledge management system in the regulatory activity

International Nuclear Information System (INIS)

Nosovskij, A.V.; Klevtsov, A.L.; Kravchenko, N.A.

2010-01-01

Important issues on collection, storage and spread of knowledge among organisation dealing with the use of nuclear technologies, role of close cooperation between enterprises and organizations in developing knowledge management, general requirements for creating a nuclear knowledge management system are considered. Recommendations and the main mechanisms are identified to create the knowledge management system in technical support organizations of the regulatory authority.

Genomes, Phylogeny, and Evolutionary Systems Biology

Energy Technology Data Exchange (ETDEWEB)

Medina, Monica

2005-03-25

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

Aspergilli: Systems biology and industrial applications

DEFF Research Database (Denmark)

Knuf, Christoph; Nielsen, Jens

2012-01-01

possible to implement systems biology tools to advance metabolic engineering. These tools include genome-wide transcription analysis and genome-scale metabolic models. Herein, we review achievements in the field and highlight the impact of Aspergillus systems biology on industrial biotechnology....

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

Science.gov (United States)

Young, Eric; Alper, Hal

2010-01-01

The general central dogma frames the emergent properties of life, which make biology both necessary and difficult to engineer. In a process engineering paradigm, each biological process stream and process unit is heavily influenced by regulatory interactions and interactions with the surrounding environment. Synthetic biology is developing the tools and methods that will increase control over these interactions, eventually resulting in an integrative synthetic biology that will allow ground-up cellular optimization. In this review, we attempt to contextualize the areas of synthetic biology into three tiers: (1) the process units and associated streams of the central dogma, (2) the intrinsic regulatory mechanisms, and (3) the extrinsic physical and chemical environment. Efforts at each of these three tiers attempt to control cellular systems and take advantage of emerging tools and approaches. Ultimately, it will be possible to integrate these approaches and realize the vision of integrative synthetic biology when cells are completely rewired for biotechnological goals. This review will highlight progress towards this goal as well as areas requiring further research. PMID:20150964

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

Directory of Open Access Journals (Sweden)

Eric Young

2010-01-01

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

Synthetic biology: tools to design, build, and optimize cellular processes.

Science.gov (United States)

Young, Eric; Alper, Hal

2010-01-01

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

Model checking biological systems described using ambient calculus

DEFF Research Database (Denmark)

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

2005-01-01

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

Systems Biology, Systems Medicine, Systems Pharmacology: The What and The Why.

Science.gov (United States)

Stéphanou, Angélique; Fanchon, Eric; Innominato, Pasquale F; Ballesta, Annabelle

2018-05-09

Systems biology is today such a widespread discipline that it becomes difficult to propose a clear definition of what it really is. For some, it remains restricted to the genomic field. For many, it designates the integrated approach or the corpus of computational methods employed to handle the vast amount of biological or medical data and investigate the complexity of the living. Although defining systems biology might be difficult, on the other hand its purpose is clear: systems biology, with its emerging subfields systems medicine and systems pharmacology, clearly aims at making sense of complex observations/experimental and clinical datasets to improve our understanding of diseases and their treatments without putting aside the context in which they appear and develop. In this short review, we aim to specifically focus on these new subfields with the new theoretical tools and approaches that were developed in the context of cancer. Systems pharmacology and medicine now give hope for major improvements in cancer therapy, making personalized medicine closer to reality. As we will see, the current challenge is to be able to improve the clinical practice according to the paradigm shift of systems sciences.

Complexity, Analysis and Control of Singular Biological Systems

CERN Document Server

Zhang, Qingling; Zhang, Xue

2012-01-01

Complexity, Analysis and Control of Singular Biological Systems follows the control of real-world biological systems at both ecological and phyisological levels concentrating on the application of now-extensively-investigated singular system theory. Much effort has recently been dedicated to the modelling and analysis of developing bioeconomic systems and the text establishes singular examples of these, showing how proper control can help to maintain sustainable economic development of biological resources. The book begins from the essentials of singular systems theory and bifurcations before tackling  the use of various forms of control in singular biological systems using examples including predator-prey relationships and viral vaccination and quarantine control. Researchers and graduate students studying the control of complex biological systems are shown how a variety of methods can be brought to bear and practitioners working with the economics of biological systems and their control will also find the ...

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

Science.gov (United States)

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

2017-09-01

Several studies in Bioinformatics, Computational Biology and Systems Biology rely on the definition of physico-chemical or mathematical models of biological systems at different scales and levels of complexity, ranging from the interaction of atoms in single molecules up to genome-wide interaction networks. Traditional computational methods and software tools developed in these research fields share a common trait: they can be computationally demanding on Central Processing Units (CPUs), therefore limiting their applicability in many circumstances. To overcome this issue, general-purpose Graphics Processing Units (GPUs) are gaining an increasing attention by the scientific community, as they can considerably reduce the running time required by standard CPU-based software, and allow more intensive investigations of biological systems. In this review, we present a collection of GPU tools recently developed to perform computational analyses in life science disciplines, emphasizing the advantages and the drawbacks in the use of these parallel architectures. The complete list of GPU-powered tools here reviewed is available at http://bit.ly/gputools. © The Author 2016. Published by Oxford University Press.

Development of digital library system on regulatory documents for nuclear power plants

International Nuclear Information System (INIS)

Lee, K. H.; Kim, K. J.; Yoon, Y. H.; Kim, M. W.; Lee, J. I.

2001-01-01

The main objective of this study is to establish nuclear regulatory document retrieval system based on internet. With the advancement of internet and information processing technology, information management patterns are going through a new paradigm. Getting along the current of the time, it is general tendency to transfer paper-type documents into electronic-type documents through document scanning and indexing. This system consists of nuclear regulatory documents, nuclear safety documents, digital library, and information system with index and full text

Biological Systems Thinking for Control Engineering Design

Directory of Open Access Journals (Sweden)

D. J. Murray-Smith

2004-01-01

Full Text Available Artificial neural networks and genetic algorithms are often quoted in discussions about the contribution of biological systems thinking to engineering design. This paper reviews work on the neuromuscular system, a field in which biological systems thinking could make specific contributions to the development and design of automatic control systems for mechatronics and robotics applications. The paper suggests some specific areas in which a better understanding of this biological control system could be expected to contribute to control engineering design methods in the future. Particular emphasis is given to the nonlinear nature of elements within the neuromuscular system and to processes of neural signal processing, sensing and system adaptivity. Aspects of the biological system that are of particular significance for engineering control systems include sensor fusion, sensor redundancy and parallelism, together with advanced forms of signal processing for adaptive and learning control. 

Network Analyses in Systems Biology: New Strategies for Dealing with Biological Complexity

DEFF Research Database (Denmark)

Green, Sara; Serban, Maria; Scholl, Raphael

2018-01-01

of biological networks using tools from graph theory to the application of dynamical systems theory to understand the behavior of complex biological systems. We show how network approaches support and extend traditional mechanistic strategies but also offer novel strategies for dealing with biological...... strategies? When and how can network and mechanistic approaches interact in productive ways? In this paper we address these questions by focusing on how biological networks are represented and analyzed in a diverse class of case studies. Our examples span from the investigation of organizational properties...

Identifying niche-mediated regulatory factors of stem cell phenotypic state: a systems biology approach.

Science.gov (United States)

Ravichandran, Srikanth; Del Sol, Antonio

2017-02-01

Understanding how the cellular niche controls the stem cell phenotype is often hampered due to the complexity of variegated niche composition, its dynamics, and nonlinear stem cell-niche interactions. Here, we propose a systems biology view that considers stem cell-niche interactions as a many-body problem amenable to simplification by the concept of mean field approximation. This enables approximation of the niche effect on stem cells as a constant field that induces sustained activation/inhibition of specific stem cell signaling pathways in all stem cells within heterogeneous populations exhibiting the same phenotype (niche determinants). This view offers a new basis for the development of single cell-based computational approaches for identifying niche determinants, which has potential applications in regenerative medicine and tissue engineering. © 2017 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Systems biology definition of the core proteome of metabolism and expression is consistent with high-throughput data.

Science.gov (United States)

Yang, Laurence; Tan, Justin; O'Brien, Edward J; Monk, Jonathan M; Kim, Donghyuk; Li, Howard J; Charusanti, Pep; Ebrahim, Ali; Lloyd, Colton J; Yurkovich, James T; Du, Bin; Dräger, Andreas; Thomas, Alex; Sun, Yuekai; Saunders, Michael A; Palsson, Bernhard O

2015-08-25

Finding the minimal set of gene functions needed to sustain life is of both fundamental and practical importance. Minimal gene lists have been proposed by using comparative genomics-based core proteome definitions. A definition of a core proteome that is supported by empirical data, is understood at the systems-level, and provides a basis for computing essential cell functions is lacking. Here, we use a systems biology-based genome-scale model of metabolism and expression to define a functional core proteome consisting of 356 gene products, accounting for 44% of the Escherichia coli proteome by mass based on proteomics data. This systems biology core proteome includes 212 genes not found in previous comparative genomics-based core proteome definitions, accounts for 65% of known essential genes in E. coli, and has 78% gene function overlap with minimal genomes (Buchnera aphidicola and Mycoplasma genitalium). Based on transcriptomics data across environmental and genetic backgrounds, the systems biology core proteome is significantly enriched in nondifferentially expressed genes and depleted in differentially expressed genes. Compared with the noncore, core gene expression levels are also similar across genetic backgrounds (two times higher Spearman rank correlation) and exhibit significantly more complex transcriptional and posttranscriptional regulatory features (40% more transcription start sites per gene, 22% longer 5'UTR). Thus, genome-scale systems biology approaches rigorously identify a functional core proteome needed to support growth. This framework, validated by using high-throughput datasets, facilitates a mechanistic understanding of systems-level core proteome function through in silico models; it de facto defines a paleome.

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

Science.gov (United States)

Hodgkinson, Matt J; Webb, Penelope A

2007-09-04

BMC Systems Biology is the first open access journal spanning the growing field of systems biology from molecules up to ecosystems. The journal has launched as more and more institutes are founded that are similarly dedicated to this new approach. BMC Systems Biology builds on the ongoing success of the BMC series, providing a venue for all sound research in the systems-level analysis of biology.

Hierarchical structure of biological systems: a bioengineering approach.

Science.gov (United States)

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.

SBR-Blood: systems biology repository for hematopoietic cells.

Science.gov (United States)

Lichtenberg, Jens; Heuston, Elisabeth F; Mishra, Tejaswini; Keller, Cheryl A; Hardison, Ross C; Bodine, David M

2016-01-04

Extensive research into hematopoiesis (the development of blood cells) over several decades has generated large sets of expression and epigenetic profiles in multiple human and mouse blood cell types. However, there is no single location to analyze how gene regulatory processes lead to different mature blood cells. We have developed a new database framework called hematopoietic Systems Biology Repository (SBR-Blood), available online at http://sbrblood.nhgri.nih.gov, which allows user-initiated analyses for cell type correlations or gene-specific behavior during differentiation using publicly available datasets for array- and sequencing-based platforms from mouse hematopoietic cells. SBR-Blood organizes information by both cell identity and by hematopoietic lineage. The validity and usability of SBR-Blood has been established through the reproduction of workflows relevant to expression data, DNA methylation, histone modifications and transcription factor occupancy profiles. Published by Oxford University Press on behalf of Nucleic Acids Research 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

An engineering design approach to systems biology.

Science.gov (United States)

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

2017-07-17

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

The Feasibility of Systems Thinking in Biology Education

Science.gov (United States)

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

2011-01-01

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

Regulatory monitoring systems of fortified salt and wheat flour in selected ASEAN countries.

Science.gov (United States)

van den Wijngaart, Annoek; Bégin, France; Codling, Karen; Randall, Philip; Johnson, Quentin W

2013-06-01

Considerable efforts have been made over the past decade to address vitamin and mineral deficiencies. An increasing number of countries in the Association of Southeast Asian Nations (ASEAN) are adopting mandatory food fortification as one of the primary strategies to overcome these deficiencies. Experience shows that fortified foods can reach large parts of the population, including the poor, if the fortification is done on a mandatory rather than a voluntary basis and if the food vehicle is widely consumed. To review the importance of regulatory monitoring as an essential component of food fortification efforts in selected ASEAN countries, with special focus on the available information on regulatory monitoring systems for iodized salt and fortified wheat flour. The role of regulatory monitoring in strengthening food fortification programs was discussed during a joint regional meeting of the World Health Organization, UNICEF, the Flour Fortification Initiative, the Global Alliance for Improved Nutrition, the Micronutrient Initiative, and the World Bank on regulatory monitoring of salt and wheat flour fortification programs in Asia, which took place in Manila, Philippines, on 27-29 September 2011. This paper reviews the regulatory monitoring systems of selected ASEAN countries that participated in this meeting. Problems and challenges in regulatory monitoring systems for iodized salt and fortified wheat flour in selected ASEAN countries are identified, and a description of the role of regulatory monitoring in strengthening food fortification initiatives, particularly of salt and flour, and highlights of areas for improvement are presented. Regulatory monitoring consists of monitoring activities conducted at the production level, at customs warehouses, and at retail stores by concerned regulatory authorities, and at the production level by producers themselves, as part of quality control and assurance efforts. Unless there are appropriate enforcement and quality

Formal modeling and analysis of ER-α associated Biological Regulatory Network in breast cancer

Directory of Open Access Journals (Sweden)

Samra Khalid

2016-10-01

Full Text Available Background Breast cancer (BC is one of the leading cause of death among females worldwide. The increasing incidence of BC is due to various genetic and environmental changes which lead to the disruption of cellular signaling network(s. It is a complex disease in which several interlinking signaling cascades play a crucial role in establishing a complex regulatory network. The logical modeling approach of René Thomas has been applied to analyze the behavior of estrogen receptor-alpha (ER-α associated Biological Regulatory Network (BRN for a small part of complex events that leads to BC metastasis. Methods A discrete model was constructed using the kinetic logic formalism and its set of logical parameters were obtained using the model checking technique implemented in the SMBioNet software which is consistent with biological observations. The discrete model was further enriched with continuous dynamics by converting it into an equivalent Petri Net (PN to analyze the logical parameters of the involved entities. Results In-silico based discrete and continuous modeling of ER-α associated signaling network involved in BC provides information about behaviors and gene-gene interaction in detail. The dynamics of discrete model revealed, imperative behaviors represented as cyclic paths and trajectories leading to pathogenic states such as metastasis. Results suggest that the increased expressions of receptors ER-α, IGF-1R and EGFR slow down the activity of tumor suppressor genes (TSGs such as BRCA1, p53 and Mdm2 which can lead to metastasis. Therefore, IGF-1R and EGFR are considered as important inhibitory targets to control the metastasis in BC. Conclusion The in-silico approaches allow us to increase our understanding of the functional properties of living organisms. It opens new avenues of investigations of multiple inhibitory targets (ER-α, IGF-1R and EGFR for wet lab experiments as well as provided valuable insights in the treatment of cancers

Mutational robustness of gene regulatory networks.

Directory of Open Access Journals (Sweden)

Aalt D J van Dijk

Full Text Available Mutational robustness of gene regulatory networks refers to their ability to generate constant biological output upon mutations that change network structure. Such networks contain regulatory interactions (transcription factor-target gene interactions but often also protein-protein interactions between transcription factors. Using computational modeling, we study factors that influence robustness and we infer several network properties governing it. These include the type of mutation, i.e. whether a regulatory interaction or a protein-protein interaction is mutated, and in the case of mutation of a regulatory interaction, the sign of the interaction (activating vs. repressive. In addition, we analyze the effect of combinations of mutations and we compare networks containing monomeric with those containing dimeric transcription factors. Our results are consistent with available data on biological networks, for example based on evolutionary conservation of network features. As a novel and remarkable property, we predict that networks are more robust against mutations in monomer than in dimer transcription factors, a prediction for which analysis of conservation of DNA binding residues in monomeric vs. dimeric transcription factors provides indirect evidence.

Answering biological questions: Querying a systems biology database for nutrigenomics

NARCIS (Netherlands)

Evelo, C.T.; Bochove, K. van; Saito, J.T.

2011-01-01

The requirement of systems biology for connecting different levels of biological research leads directly to a need for integrating vast amounts of diverse information in general and of omics data in particular. The nutritional phenotype database addresses this challenge for nutrigenomics. A

System engineering in the Nuclear Regulatory Commission licensing process: Program architecture process and structure

International Nuclear Information System (INIS)

Romine, D.T.

1989-01-01

In October 1987, the U.S. Nuclear Regulatory Commission (NRC) established the Center for Nuclear Waste Regulatory Analyses at Southwest Research Institute in San Antonio, Texas. The overall mission of the center is to provide a sustained level of high-quality research and technical assistance in support of NRC regulatory responsibilities under the Nuclear Waste Policy Act (NWPA). A key part of that mission is to assist the NRC in the development of the program architecture - the systems approach to regulatory analysis for the NRC high-level waste repository licensing process - and the development and implementation of the computer-based Program Architecture Support System (PASS). This paper describes the concept of program architecture, summarizes the process and basic structure of the PASS relational data base, and describes the applications of the system

Regulatory issues resolved through design certification on the System 80+trademark standard plant design

International Nuclear Information System (INIS)

Ritterbusch, S.E.; Brinkman, C.B.

1996-01-01

The US Nuclear Regulatory Commission (NRC) has completed its review of the System 80+trademark Standard Plant Design, approving advanced design features and closing severe accident licensing issues. Final Design Approval was granted in July 1994. The NRC review was extensive, requiring written responses to over 4,950 questions and formal printing of over 50,000 Safety Analysis Report pages. New safety issues never before addressed in a regulatory atmosphere had to be resolved with detailed analysis and evaluation of design features. the System 80+ review demonstrated that regulatory issues can be firmly resolved only through presentation of a detailed design and completion of a comprehensive regulatory review

Integrated systems approach identifies risk regulatory pathways and key regulators in coronary artery disease.

Science.gov (United States)

Zhang, Yan; Liu, Dianming; Wang, Lihong; Wang, Shuyuan; Yu, Xuexin; Dai, Enyu; Liu, Xinyi; Luo, Shanshun; Jiang, Wei

2015-12-01

Coronary artery disease (CAD) is the most common type of heart disease. However, the molecular mechanisms of CAD remain elusive. Regulatory pathways are known to play crucial roles in many pathogenic processes. Thus, inferring risk regulatory pathways is an important step toward elucidating the mechanisms underlying CAD. With advances in high-throughput data, we developed an integrated systems approach to identify CAD risk regulatory pathways and key regulators. Firstly, a CAD-related core subnetwork was identified from a curated transcription factor (TF) and microRNA (miRNA) regulatory network based on a random walk algorithm. Secondly, candidate risk regulatory pathways were extracted from the subnetwork by applying a breadth-first search (BFS) algorithm. Then, risk regulatory pathways were prioritized based on multiple CAD-associated data sources. Finally, we also proposed a new measure to prioritize upstream regulators. We inferred that phosphatase and tensin homolog (PTEN) may be a key regulator in the dysregulation of risk regulatory pathways. This study takes a closer step than the identification of disease subnetworks or modules. From the risk regulatory pathways, we could understand the flow of regulatory information in the initiation and progression of the disease. Our approach helps to uncover its potential etiology. We developed an integrated systems approach to identify risk regulatory pathways. We proposed a new measure to prioritize the key regulators in CAD. PTEN may be a key regulator in dysregulation of the risk regulatory pathways.

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

Science.gov (United States)

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

XcisClique: analysis of regulatory bicliques

Directory of Open Access Journals (Sweden)

Grene Ruth

2006-04-01

Full Text Available Abstract Background Modeling of cis-elements or regulatory motifs in promoter (upstream regions of genes is a challenging computational problem. In this work, set of regulatory motifs simultaneously present in the promoters of a set of genes is modeled as a biclique in a suitably defined bipartite graph. A biologically meaningful co-occurrence of multiple cis-elements in a gene promoter is assessed by the combined analysis of genomic and gene expression data. Greater statistical significance is associated with a set of genes that shares a common set of regulatory motifs, while simultaneously exhibiting highly correlated gene expression under given experimental conditions. Methods XcisClique, the system developed in this work, is a comprehensive infrastructure that associates annotated genome and gene expression data, models known cis-elements as regular expressions, identifies maximal bicliques in a bipartite gene-motif graph; and ranks bicliques based on their computed statistical significance. Significance is a function of the probability of occurrence of those motifs in a biclique (a hypergeometric distribution, and on the new sum of absolute values statistic (SAV that uses Spearman correlations of gene expression vectors. SAV is a statistic well-suited for this purpose as described in the discussion. Results XcisClique identifies new motif and gene combinations that might indicate as yet unidentified involvement of sets of genes in biological functions and processes. It currently supports Arabidopsis thaliana and can be adapted to other organisms, assuming the existence of annotated genomic sequences, suitable gene expression data, and identified regulatory motifs. A subset of Xcis Clique functionalities, including the motif visualization component MotifSee, source code, and supplementary material are available at https://bioinformatics.cs.vt.edu/xcisclique/.

Regulatory Anatomy

DEFF Research Database (Denmark)

Hoeyer, Klaus

2015-01-01

This article proposes the term “safety logics” to understand attempts within the European Union (EU) to harmonize member state legislation to ensure a safe and stable supply of human biological material for transplants and transfusions. With safety logics, I refer to assemblages of discourses, le...... they arise. In short, I expose the regulatory anatomy of the policy landscape....

Network biology: Describing biological systems by complex networks. Comment on "Network science of biological systems at different scales: A review" by M. Gosak et al.

Science.gov (United States)

Jalili, Mahdi

2018-03-01

I enjoyed reading Gosak et al. review on analysing biological systems from network science perspective [1]. Network science, first started within Physics community, is now a mature multidisciplinary field of science with many applications ranging from Ecology to biology, medicine, social sciences, engineering and computer science. Gosak et al. discussed how biological systems can be modelled and described by complex network theory which is an important application of network science. Although there has been considerable progress in network biology over the past two decades, this is just the beginning and network science has a great deal to offer to biology and medical sciences.

GeneLab: A Systems Biology Platform for Spaceflight Omics Data

Science.gov (United States)

Reinsch, Sigrid S.; Lai, San-Huei; Chen, Rick; Thompson, Terri; Berrios, Daniel; Fogle, Homer; Marcu, Oana; Timucin, Linda; Chakravarty, Kaushik; Coughlan, Joseph

2015-01-01

deep curation of metadata for integrative analysis, allowing researchers to uncover cellular networks as observed in systems biology platforms. Consequently, the scientific community will have access to a more complete picture of functional and regulatory networks responsive to the spaceflight environment.. Analysis of GeneLab data will contribute fundamental knowledge of how the space environment affects biological systems, and enable emerging terrestrial benefits resulting from mitigation strategies to prevent effects observed during exposure to space. As a result, open access to the data will foster new hypothesis-driven research for future spaceflight studies spanning basic science to translational science.

Preparation of safety regulatory requirements for new technology like digital system

Energy Technology Data Exchange (ETDEWEB)

NONE

2013-08-15

The current regulatory requirements on digital instrumentation and control system have been reviewed by JNES, considering international trend discussed in DICWG of MDEP. MDEP DICWG held in OECD/NEA gives the opportunity to identify the convergence of applicable standards. The working group's activities include: identifying and prioritising the member countries' challenges, practices, and needs regarding standards and regulatory guidance on digital instrumentation and control; identifying areas of importance and needs for convergence of existing standards and guidance or development of new standards; sharing of information; and identifying common positions among the member countries for areas of particular importance and need. The DICWG drafted common positions on specific issues which are based on the existing standards, national regulatory guidance, best practices, and group inputs using an agreed process and framework. The following four general common positions have been discussed in this fiscal year. The Treatment of Common Cause Failure Resulting from Software within Digital Safety Systems, The Treatment of Hardware Description Language(HDL) Programmed Devices for Use in Nuclear Safety System, Factory Acceptance Test and Site Acceptance Test, The Use of Automatic Tests to Perform Surveilance for Digital Systems. (author)

On the role of sparseness in the evolution of modularity in gene regulatory networks.

Science.gov (United States)

Espinosa-Soto, Carlos

2018-05-01

Modularity is a widespread property in biological systems. It implies that interactions occur mainly within groups of system elements. A modular arrangement facilitates adjustment of one module without perturbing the rest of the system. Therefore, modularity of developmental mechanisms is a major factor for evolvability, the potential to produce beneficial variation from random genetic change. Understanding how modularity evolves in gene regulatory networks, that create the distinct gene activity patterns that characterize different parts of an organism, is key to developmental and evolutionary biology. One hypothesis for the evolution of modules suggests that interactions between some sets of genes become maladaptive when selection favours additional gene activity patterns. The removal of such interactions by selection would result in the formation of modules. A second hypothesis suggests that modularity evolves in response to sparseness, the scarcity of interactions within a system. Here I simulate the evolution of gene regulatory networks and analyse diverse experimentally sustained networks to study the relationship between sparseness and modularity. My results suggest that sparseness alone is neither sufficient nor necessary to explain modularity in gene regulatory networks. However, sparseness amplifies the effects of forms of selection that, like selection for additional gene activity patterns, already produce an increase in modularity. That evolution of new gene activity patterns is frequent across evolution also supports that it is a major factor in the evolution of modularity. That sparseness is widespread across gene regulatory networks indicates that it may have facilitated the evolution of modules in a wide variety of cases.

Inference of Cancer-specific Gene Regulatory Networks Using Soft Computing Rules

Directory of Open Access Journals (Sweden)

Xiaosheng Wang

2010-03-01

Full Text Available Perturbations of gene regulatory networks are essentially responsible for oncogenesis. Therefore, inferring the gene regulatory networks is a key step to overcoming cancer. In this work, we propose a method for inferring directed gene regulatory networks based on soft computing rules, which can identify important cause-effect regulatory relations of gene expression. First, we identify important genes associated with a specific cancer (colon cancer using a supervised learning approach. Next, we reconstruct the gene regulatory networks by inferring the regulatory relations among the identified genes, and their regulated relations by other genes within the genome. We obtain two meaningful findings. One is that upregulated genes are regulated by more genes than downregulated ones, while downregulated genes regulate more genes than upregulated ones. The other one is that tumor suppressors suppress tumor activators and activate other tumor suppressors strongly, while tumor activators activate other tumor activators and suppress tumor suppressors weakly, indicating the robustness of biological systems. These findings provide valuable insights into the pathogenesis of cancer.

Preparation of safety regulatory requirements for new technology like digital system

International Nuclear Information System (INIS)

2012-01-01

The current regulatory requirements on digital instrumentation and control system have been reviewed by JNES, considering international trend discussed in DICWG of MDEP. MDEP DICWG held in OECD/NEA gives the opportunity to identify the convergence of applicable standards. The working group's activities include: identifying and prioritising the member countries' challenges, practices, and needs regarding standards and regulatory guidance on digital instrumentation and control; identifying areas of importance and needs for convergence of existing standards and guidance or development of new standards; sharing of information; and identifying common positions among the member countries for areas of particular importance and need. The DICWG drafted common positions on specific issues which are based on the existing standards, national regulatory guidance, best practices, and group inputs using an agreed process and framework. The following two general common positions are discussed and to be issued in this fiscal year. Verification and Validation throughout the life cycle of safety systems using digital computers. The Impact of Cyber Security Features on Digital I and C Safety Systems. (author)

International Nuclear Safety Experts Conclude IAEA Peer Review of Korea's Regulatory System

International Nuclear Information System (INIS)

2011-01-01

Full text: An international team of senior nuclear safety experts concluded today a two-week mission to review the regulatory framework for nuclear safety in the Republic of Korea. The team identified good practices and gave advice on areas for future improvements. The IAEA has conveyed the team's main conclusions to the Government of Korea, while the final report will be submitted by the end of summer 2011. At the request of the Korean Government, the IAEA assembled a team of 16 senior regulatory experts from 14 nations to conduct the Integrated Regulatory Review Service (IRRS) mission involving the Korean Ministry for Education, Science and Technology (MEST) and the Korean Institute for Nuclear Safety (KINS). The mission is a peer-review based on the IAEA Safety Standards. ''This was the first IRRS mission organized after Japan's Fukushima Daiichi nuclear accident and it included a review of the regulatory implications of that event,' explains Denis Flory, IAEA Deputy Director General and Head of the Department of Nuclear Safety and Security. William Borchardt, Executive Director of Operations from the US Nuclear Regulatory Commission and Team Leader of this mission commended the Korean authorities for their openness and commitment to sharing their experience with the world's nuclear safety community. ''IRRS missions such as the one that was just concluded here in the Republic of Korea are crucial to the enhancement of nuclear safety worldwide,'' he said. The IRRS team reviewed Korea's current regulatory framework while acknowledging the fact that the country's Government has already decided to establish, as of October 2011, a new independent regulatory body to be called Nuclear Safety Commission (NSC). As a consequence, KINS role will be as a regulatory expert organization reporting to the NSC, while MEST's role will be restricted to promoting the utilization of nuclear energy. The IRRS team identified particular strengths in the Korean regulatory system

Integrative radiation systems biology

International Nuclear Information System (INIS)

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

International nuclear safety experts conclude IAEA peer review of China's regulatory system

International Nuclear Information System (INIS)

2010-01-01

Full text: An international team of senior experts on nuclear safety regulation today completed a two-week International Atomic Energy Agency (IAEA) review of the governmental and regulatory framework for nuclear safety in the People's Republic of China. The team identified good practices within the system and gave advice on areas for future improvements. The IAEA has conveyed the team's main conclusions to the Government of the People's Republic of China. The final report will be submitted to China by Autumn 2010. At the request of Chinese authorities, the IAEA assembled a team of 22 experts to conduct an Integrated Regulatory Review Service (IRRS) mission. This mission is a peer review based on the IAEA Safety Standards . It is not an inspection, nor an audit. The experts came from 15 different countries: Australia, Canada, the Czech Republic, Finland, France, Hungary, Japan, Pakistan, the Republic of Korea, Slovenia, South Africa, Sweden, the United Kingdom, Ukraine and the United States. Mike Weightman, the United Kingdom's Head of Nuclear Directorate, HSE and HM Chief Inspector of Nuclear Installations said: ''I was honoured and pleased to lead such a team of senior regulatory experts from around the world, and I was impressed by their commitment, experience and hard work to provide their best advice possible. We had very constructive interactions with the Chinese authority to maximize the beneficial impact of the mission.'' The scope of the mission included the regulation of nuclear and radiation safety of the facilities and activities regulated by the Ministry of Environmental Protection (MEP) National Nuclear Safety Administration (NNSA). The mission was conducted from 18 to 30 July, mainly in Beijing. To observe Chinese regulatory activities, the IRRS team visited several nuclear facilities, including a nuclear power plant, a manufacturer of safety components for nuclear power plants, a research reactor, a fuel cycle facility, a waste management facility

A Systems Biology Analysis Unfolds the Molecular Pathways and Networks of Two Proteobacteria in Spaceflight and Simulated Microgravity Conditions.

Science.gov (United States)

Roy, Raktim; Shilpa, P Phani; Bagh, Sangram

2016-09-01

Bacteria are important organisms for space missions due to their increased pathogenesis in microgravity that poses risks to the health of astronauts and for projected synthetic biology applications at the space station. We understand little about the effect, at the molecular systems level, of microgravity on bacteria, despite their significant incidence. In this study, we proposed a systems biology pipeline and performed an analysis on published gene expression data sets from multiple seminal studies on Pseudomonas aeruginosa and Salmonella enterica serovar Typhimurium under spaceflight and simulated microgravity conditions. By applying gene set enrichment analysis on the global gene expression data, we directly identified a large number of new, statistically significant cellular and metabolic pathways involved in response to microgravity. Alteration of metabolic pathways in microgravity has rarely been reported before, whereas in this analysis metabolic pathways are prevalent. Several of those pathways were found to be common across studies and species, indicating a common cellular response in microgravity. We clustered genes based on their expression patterns using consensus non-negative matrix factorization. The genes from different mathematically stable clusters showed protein-protein association networks with distinct biological functions, suggesting the plausible functional or regulatory network motifs in response to microgravity. The newly identified pathways and networks showed connection with increased survival of pathogens within macrophages, virulence, and antibiotic resistance in microgravity. Our work establishes a systems biology pipeline and provides an integrated insight into the effect of microgravity at the molecular systems level. Systems biology-Microgravity-Pathways and networks-Bacteria. Astrobiology 16, 677-689.

17 CFR 249.821 - Form PILOT, information required of self-regulatory organizations operating pilot trading systems...

Science.gov (United States)

2010-04-01

... required of self-regulatory organizations operating pilot trading systems pursuant to § 240.19b-5 of this... Associations § 249.821 Form PILOT, information required of self-regulatory organizations operating pilot trading systems pursuant to § 240.19b-5 of this chapter. This form shall be used by all self-regulatory...

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

DEFF Research Database (Denmark)

Fletcher, Eugene; Krivoruchko, Anastasia; Nielsen, Jens

2016-01-01

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

Metabolomics: Definitions and Significance in Systems Biology.

Science.gov (United States)

Klassen, Aline; Faccio, Andréa Tedesco; Canuto, Gisele André Baptista; da Cruz, Pedro Luis Rocha; Ribeiro, Henrique Caracho; Tavares, Marina Franco Maggi; Sussulini, Alessandra

2017-01-01

Nowadays, there is a growing interest in deeply understanding biological mechanisms not only at the molecular level (biological components) but also the effects of an ongoing biological process in the organism as a whole (biological functionality), as established by the concept of systems biology. Within this context, metabolomics is one of the most powerful bioanalytical strategies that allow obtaining a picture of the metabolites of an organism in the course of a biological process, being considered as a phenotyping tool. Briefly, metabolomics approach consists in identifying and determining the set of metabolites (or specific metabolites) in biological samples (tissues, cells, fluids, or organisms) under normal conditions in comparison with altered states promoted by disease, drug treatment, dietary intervention, or environmental modulation. The aim of this chapter is to review the fundamentals and definitions used in the metabolomics field, as well as to emphasize its importance in systems biology and clinical studies.

Using hexamers to predict cis-regulatory motifs in Drosophila

Directory of Open Access Journals (Sweden)

Kibler Dennis

2005-10-01

Full Text Available Abstract Background Cis-regulatory modules (CRMs are short stretches of DNA that help regulate gene expression in higher eukaryotes. They have been found up to 1 megabase away from the genes they regulate and can be located upstream, downstream, and even within their target genes. Due to the difficulty of finding CRMs using biological and computational techniques, even well-studied regulatory systems may contain CRMs that have not yet been discovered. Results We present a simple, efficient method (HexDiff based only on hexamer frequencies of known CRMs and non-CRM sequence to predict novel CRMs in regulatory systems. On a data set of 16 gap and pair-rule genes containing 52 known CRMs, predictions made by HexDiff had a higher correlation with the known CRMs than several existing CRM prediction algorithms: Ahab, Cluster Buster, MSCAN, MCAST, and LWF. After combining the results of the different algorithms, 10 putative CRMs were identified and are strong candidates for future study. The hexamers used by HexDiff to distinguish between CRMs and non-CRM sequence were also analyzed and were shown to be enriched in regulatory elements. Conclusion HexDiff provides an efficient and effective means for finding new CRMs based on known CRMs, rather than known binding sites.

Information processing in the transcriptional regulatory network of yeast: Functional robustness

Directory of Open Access Journals (Sweden)

Dehmer Matthias

2009-03-01

Full Text Available Abstract Background Gene networks are considered to represent various aspects of molecular biological systems meaningfully because they naturally provide a systems perspective of molecular interactions. In this respect, the functional understanding of the transcriptional regulatory network is considered as key to elucidate the functional organization of an organism. Results In this paper we study the functional robustness of the transcriptional regulatory network of S. cerevisiae. We model the information processing in the network as a first order Markov chain and study the influence of single gene perturbations on the global, asymptotic communication among genes. Modification in the communication is measured by an information theoretic measure allowing to predict genes that are 'fragile' with respect to single gene knockouts. Our results demonstrate that the predicted set of fragile genes contains a statistically significant enrichment of so called essential genes that are experimentally found to be necessary to ensure vital yeast. Further, a structural analysis of the transcriptional regulatory network reveals that there are significant differences between fragile genes, hub genes and genes with a high betweenness centrality value. Conclusion Our study does not only demonstrate that a combination of graph theoretical, information theoretical and statistical methods leads to meaningful biological results but also that such methods allow to study information processing in gene networks instead of just their structural properties.

Prediction of regulatory elements

DEFF Research Database (Denmark)

Sandelin, Albin

2008-01-01

Finding the regulatory mechanisms responsible for gene expression remains one of the most important challenges for biomedical research. A major focus in cellular biology is to find functional transcription factor binding sites (TFBS) responsible for the regulation of a downstream gene. As wet......-lab methods are time consuming and expensive, it is not realistic to identify TFBS for all uncharacterized genes in the genome by purely experimental means. Computational methods aimed at predicting potential regulatory regions can increase the efficiency of wet-lab experiments significantly. Here, methods...

Modeling of nonlinear biological phenomena modeled by S-systems.

Science.gov (United States)

Mansouri, Majdi M; Nounou, Hazem N; Nounou, Mohamed N; Datta, Aniruddha A

2014-03-01

A central challenge in computational modeling of biological systems is the determination of the model parameters. In such cases, estimating these variables or parameters from other easily obtained measurements can be extremely useful. For example, time-series dynamic genomic data can be used to develop models representing dynamic genetic regulatory networks, which can be used to design intervention strategies to cure major diseases and to better understand the behavior of biological systems. Unfortunately, biological measurements are usually highly infected by errors that hide the important characteristics in the data. Therefore, these noisy measurements need to be filtered to enhance their usefulness in practice. This paper addresses the problem of state and parameter estimation of biological phenomena modeled by S-systems using Bayesian approaches, where the nonlinear observed system is assumed to progress according to a probabilistic state space model. The performances of various conventional and state-of-the-art state estimation techniques are compared. These techniques include the extended Kalman filter (EKF), unscented Kalman filter (UKF), particle filter (PF), and the developed variational Bayesian filter (VBF). Specifically, two comparative studies are performed. In the first comparative study, the state variables (the enzyme CadA, the model cadBA, the cadaverine Cadav and the lysine Lys for a model of the Cad System in Escherichia coli (CSEC)) are estimated from noisy measurements of these variables, and the various estimation techniques are compared by computing the estimation root mean square error (RMSE) with respect to the noise-free data. In the second comparative study, the state variables as well as the model parameters are simultaneously estimated. In this case, in addition to comparing the performances of the various state estimation techniques, the effect of the number of estimated model parameters on the accuracy and convergence of these

Effect of regulatory architecture on broad versus narrow sense heritability.

Directory of Open Access Journals (Sweden)

Yunpeng Wang

Full Text Available Additive genetic variance (VA and total genetic variance (VG are core concepts in biomedical, evolutionary and production-biology genetics. What determines the large variation in reported VA /VG ratios from line-cross experiments is not well understood. Here we report how the VA /VG ratio, and thus the ratio between narrow and broad sense heritability (h(2 /H(2 , varies as a function of the regulatory architecture underlying genotype-to-phenotype (GP maps. We studied five dynamic models (of the cAMP pathway, the glycolysis, the circadian rhythms, the cell cycle, and heart cell dynamics. We assumed genetic variation to be reflected in model parameters and extracted phenotypes summarizing the system dynamics. Even when imposing purely linear genotype to parameter maps and no environmental variation, we observed quite low VA /VG ratios. In particular, systems with positive feedback and cyclic dynamics gave more non-monotone genotype-phenotype maps and much lower VA /VG ratios than those without. The results show that some regulatory architectures consistently maintain a transparent genotype-to-phenotype relationship, whereas other architectures generate more subtle patterns. Our approach can be used to elucidate these relationships across a whole range of biological systems in a systematic fashion.

An evaluation model for the definition of regulatory requirements on spent fuel pool cooling systems

International Nuclear Information System (INIS)

Izquierdo, J.M.

1979-01-01

A calculation model is presented for establishing regulatory requirements in the SFPCS System. The major design factors, regulatory and design limits and key parameters are discussed. A regulatory position for internal use is proposed. Finally, associated problems and experience are presented. (author)

What's the Regulatory Value of a Target Product Profile?

Science.gov (United States)

Breder, Christopher D; Du, Wenny; Tyndall, Adria

2017-07-01

Target product profiles (TPPs) are used as a regulatory tool for dialog on clinical development or manufacturing plans. Drugs and biologics approved by the FDA that mention TPPs are associated with more efficient regulatory review times, perhaps as a result of increased planning or because the TPP promotes well-organized regulatory dialog. Published by Elsevier Ltd.

Modeling Dynamic Regulatory Processes in Stroke

Science.gov (United States)

McDermott, Jason E.; Jarman, Kenneth; Taylor, Ronald; Lancaster, Mary; Shankaran, Harish; Vartanian, Keri B.; Stevens, Susan L.; Stenzel-Poore, Mary P.; Sanfilippo, Antonio

2012-01-01

The ability to examine the behavior of biological systems in silico has the potential to greatly accelerate the pace of discovery in diseases, such as stroke, where in vivo analysis is time intensive and costly. In this paper we describe an approach for in silico examination of responses of the blood transcriptome to neuroprotective agents and subsequent stroke through the development of dynamic models of the regulatory processes observed in the experimental gene expression data. First, we identified functional gene clusters from these data. Next, we derived ordinary differential equations (ODEs) from the data relating these functional clusters to each other in terms of their regulatory influence on one another. Dynamic models were developed by coupling these ODEs into a model that simulates the expression of regulated functional clusters. By changing the magnitude of gene expression in the initial input state it was possible to assess the behavior of the networks through time under varying conditions since the dynamic model only requires an initial starting state, and does not require measurement of regulatory influences at each time point in order to make accurate predictions. We discuss the implications of our models on neuroprotection in stroke, explore the limitations of the approach, and report that an optimized dynamic model can provide accurate predictions of overall system behavior under several different neuroprotective paradigms. PMID:23071432

Evolution of regulatory networks towards adaptability and stability in a changing environment

Science.gov (United States)

Lee, Deok-Sun

2014-11-01

Diverse biological networks exhibit universal features distinguished from those of random networks, calling much attention to their origins and implications. Here we propose a minimal evolution model of Boolean regulatory networks, which evolve by selectively rewiring links towards enhancing adaptability to a changing environment and stability against dynamical perturbations. We find that sparse and heterogeneous connectivity patterns emerge, which show qualitative agreement with real transcriptional regulatory networks and metabolic networks. The characteristic scaling behavior of stability reflects the balance between robustness and flexibility. The scaling of fluctuation in the perturbation spread shows a dynamic crossover, which is analyzed by investigating separately the stochasticity of internal dynamics and the network structure differences depending on the evolution pathways. Our study delineates how the ambivalent pressure of evolution shapes biological networks, which can be helpful for studying general complex systems interacting with environments.

Sensitivity analysis approaches applied to systems biology models.

Science.gov (United States)

Zi, Z

2011-11-01

With the rising application of systems biology, sensitivity analysis methods have been widely applied to study the biological systems, including metabolic networks, signalling pathways and genetic circuits. Sensitivity analysis can provide valuable insights about how robust the biological responses are with respect to the changes of biological parameters and which model inputs are the key factors that affect the model outputs. In addition, sensitivity analysis is valuable for guiding experimental analysis, model reduction and parameter estimation. Local and global sensitivity analysis approaches are the two types of sensitivity analysis that are commonly applied in systems biology. Local sensitivity analysis is a classic method that studies the impact of small perturbations on the model outputs. On the other hand, global sensitivity analysis approaches have been applied to understand how the model outputs are affected by large variations of the model input parameters. In this review, the author introduces the basic concepts of sensitivity analysis approaches applied to systems biology models. Moreover, the author discusses the advantages and disadvantages of different sensitivity analysis methods, how to choose a proper sensitivity analysis approach, the available sensitivity analysis tools for systems biology models and the caveats in the interpretation of sensitivity analysis results.

International nuclear safety experts complete IAEA peer review of German regulatory system

International Nuclear Information System (INIS)

2008-01-01

Full text: An international expert team has today completed a two-week IAEA review of Germany's nuclear regulatory system. The team identified good practices within the system and gave advice on some areas for further improvement. The IAEA has conveyed the initial findings to German authorities but the final report will be submitted within two months. At the request of the Government of the Federal Republic of Germany, the International Atomic Energy Agency (IAEA) assembled a team of 14 experts to conduct an Integrated Regulatory Review Service (IRRS) mission. This is a peer review based on IAEA Standards. It is not an inspection, nor an audit. The scope of the mission was limited to the safety regulation of nuclear power plants. Experts from Canada, the Czech Republic, Finland, France, Japan, the Netherlands, Republic of Korea, Spain, Switzerland, the UK, the US and from the IAEA took part in the mission, which was conducted from 7 to 19 September in Bonn, Stuttgart and Berlin. The main basis for the review was a well-prepared self-assessment made by the Federal Ministry of Environment, Nature Conservation and Nuclear Safety (BMU) and the Ministry of Environment of the federal state of Baden-Wuerttemberg (UM BW). 'The team members were impressed by the extensive preparation and dedication of the staff both at BMU and UM BW to excellence in nuclear safety,' said Mike Weightman, IRRS Team Leader and Chief Inspector of the UK nuclear regulatory body, the Nuclear Directorate of the Health and Safety Executive. 'We hope the IRRS mission will facilitate further improvements in the safety regulation of nuclear power in Germany and throughout the world.' 'Germany's invitation to undergo such a detailed review is a clear demonstration of its openness and commitment to continuously improve nuclear safety regulation,' said Philippe Jamet, Director of the IAEA's Nuclear Installation Safety Division. Among the particular strengths of BMU and UM BW associated with their

Impact of Thermodynamic Principles in Systems Biology

NARCIS (Netherlands)

Heijnen, J.J.

2010-01-01

It is shown that properties of biological systems which are relevant for systems biology motivated mathematical modelling are strongly shaped by general thermodynamic principles such as osmotic limit, Gibbs energy dissipation, near equilibria and thermodynamic driving force. Each of these aspects

Systems Biology of Metabolism: Annual Review of Biochemistry

DEFF Research Database (Denmark)

Nielsen, Jens

2017-01-01

Metabolism is highly complex and involves thousands of different connected reactions; it is therefore necessary to use mathematical models for holistic studies. The use of mathematical models in biology is referred to as systems biology. In this review, the principles of systems biology are descr...

A genomic approach to identify regulatory nodes in the transcriptional network of systemic acquired resistance in plants.

Directory of Open Access Journals (Sweden)

Dong Wang

2006-11-01

Full Text Available Many biological processes are controlled by intricate networks of transcriptional regulators. With the development of microarray technology, transcriptional changes can be examined at the whole-genome level. However, such analysis often lacks information on the hierarchical relationship between components of a given system. Systemic acquired resistance (SAR is an inducible plant defense response involving a cascade of transcriptional events induced by salicylic acid through the transcription cofactor NPR1. To identify additional regulatory nodes in the SAR network, we performed microarray analysis on Arabidopsis plants expressing the NPR1-GR (glucocorticoid receptor fusion protein. Since nuclear translocation of NPR1-GR requires dexamethasone, we were able to control NPR1-dependent transcription and identify direct transcriptional targets of NPR1. We show that NPR1 directly upregulates the expression of eight WRKY transcription factor genes. This large family of 74 transcription factors has been implicated in various defense responses, but no specific WRKY factor has been placed in the SAR network. Identification of NPR1-regulated WRKY factors allowed us to perform in-depth genetic analysis on a small number of WRKY factors and test well-defined phenotypes of single and double mutants associated with NPR1. Among these WRKY factors we found both positive and negative regulators of SAR. This genomics-directed approach unambiguously positioned five WRKY factors in the complex transcriptional regulatory network of SAR. Our work not only discovered new transcription regulatory components in the signaling network of SAR but also demonstrated that functional studies of large gene families have to take into consideration sequence similarity as well as the expression patterns of the candidates.

Synthetic biology and occupational risk.

Science.gov (United States)

Howard, John; Murashov, Vladimir; Schulte, Paul

2017-03-01

Synthetic biology is an emerging interdisciplinary field of biotechnology that involves applying the principles of engineering and chemical design to biological systems. Biosafety professionals have done an excellent job in addressing research laboratory safety as synthetic biology and gene editing have emerged from the larger field of biotechnology. Despite these efforts, risks posed by synthetic biology are of increasing concern as research procedures scale up to industrial processes in the larger bioeconomy. A greater number and variety of workers will be exposed to commercial synthetic biology risks in the future, including risks to a variety of workers from the use of lentiviral vectors as gene transfer devices. There is a need to review and enhance current protection measures in the field of synthetic biology, whether in experimental laboratories where new advances are being researched, in health care settings where treatments using viral vectors as gene delivery systems are increasingly being used, or in the industrial bioeconomy. Enhanced worker protection measures should include increased injury and illness surveillance of the synthetic biology workforce; proactive risk assessment and management of synthetic biology products; research on the relative effectiveness of extrinsic and intrinsic biocontainment methods; specific safety guidance for synthetic biology industrial processes; determination of appropriate medical mitigation measures for lentiviral vector exposure incidents; and greater awareness and involvement in synthetic biology safety by the general occupational safety and health community as well as by government occupational safety and health research and regulatory agencies.

A developmental systems perspective on epistasis: computational exploration of mutational interactions in model developmental regulatory networks.

Directory of Open Access Journals (Sweden)

Jayson Gutiérrez

2009-09-01

Full Text Available The way in which the information contained in genotypes is translated into complex phenotypic traits (i.e. embryonic expression patterns depends on its decoding by a multilayered hierarchy of biomolecular systems (regulatory networks. Each layer of this hierarchy displays its own regulatory schemes (i.e. operational rules such as +/- feedback and associated control parameters, resulting in characteristic variational constraints. This process can be conceptualized as a mapping issue, and in the context of highly-dimensional genotype-phenotype mappings (GPMs epistatic events have been shown to be ubiquitous, manifested in non-linear correspondences between changes in the genotype and their phenotypic effects. In this study I concentrate on epistatic phenomena pervading levels of biological organization above the genetic material, more specifically the realm of molecular networks. At this level, systems approaches to studying GPMs are specially suitable to shed light on the mechanistic basis of epistatic phenomena. To this aim, I constructed and analyzed ensembles of highly-modular (fully interconnected networks with distinctive topologies, each displaying dynamic behaviors that were categorized as either arbitrary or functional according to early patterning processes in the Drosophila embryo. Spatio-temporal expression trajectories in virtual syncytial embryos were simulated via reaction-diffusion models. My in silico mutational experiments show that: 1 the average fitness decay tendency to successively accumulated mutations in ensembles of functional networks indicates the prevalence of positive epistasis, whereas in ensembles of arbitrary networks negative epistasis is the dominant tendency; and 2 the evaluation of epistatic coefficients of diverse interaction orders indicates that, both positive and negative epistasis are more prevalent in functional networks than in arbitrary ones. Overall, I conclude that the phenotypic and fitness effects of

Circuitry linking the Csr and stringent response global regulatory systems.

Science.gov (United States)

Edwards, Adrianne N; Patterson-Fortin, Laura M; Vakulskas, Christopher A; Mercante, Jeffrey W; Potrykus, Katarzyna; Vinella, Daniel; Camacho, Martha I; Fields, Joshua A; Thompson, Stuart A; Georgellis, Dimitris; Cashel, Michael; Babitzke, Paul; Romeo, Tony

2011-06-01

CsrA protein regulates important cellular processes by binding to target mRNAs and altering their translation and/or stability. In Escherichia coli, CsrA binds to sRNAs, CsrB and CsrC, which sequester CsrA and antagonize its activity. Here, mRNAs for relA, spoT and dksA of the stringent response system were found among 721 different transcripts that copurified with CsrA. Many of the transcripts that copurified with CsrA were previously determined to respond to ppGpp and/or DksA. We examined multiple regulatory interactions between the Csr and stringent response systems. Most importantly, DksA and ppGpp robustly activated csrB/C transcription (10-fold), while they modestly activated csrA expression. We propose that CsrA-mediated regulation is relieved during the stringent response. Gel shift assays confirmed high affinity binding of CsrA to relA mRNA leader and weaker interactions with dksA and spoT. Reporter fusions, qRT-PCR and immunoblotting showed that CsrA repressed relA expression, and (p)ppGpp accumulation during stringent response was enhanced in a csrA mutant. CsrA had modest to negligible effects on dksA and spoT expression. Transcription of dksA was negatively autoregulated via a feedback loop that tended to mask CsrA effects. We propose that the Csr system fine-tunes the stringent response and discuss biological implications of the composite circuitry. © Published 2011. This article is a US Government work and is in the public domain in the USA.

Safety Justification of Software Systems. Software Based Safety Systems. Regulatory Inspection Handbook

International Nuclear Information System (INIS)

Dahll, Gustav; Liwang, Bo; Wainwright, Norman

2006-01-01

The introduction of new software based technology in the safety systems in nuclear power plants also makes it necessary to develop new strategies for regulatory review and assessment of these new systems that is more focused on reviewing the processes at the different phases in design phases during the system life cycle. It is a general requirement that the licensee shall perform different kinds of reviews. From a regulatory point of view it is more cost effective to assess that the design activities at the suppliers and the review activities within the development project are performed with good quality. But the change from more technical reviews over to the development process oriented approach also cause problems. When reviewing development and quality aspects there are no 'hard facts' that can be judged against some specified criteria, the issues are more 'soft' and are more to build up structure of arguments and evidences that the requirements are met. The regulatory review strategy must therefore change to follow the development process over the whole life cycle from concept phase until installation and operation. Even if we know what factors that is of interest we need some guidance on how to interpret and judge the information.For that purpose SKl started research activities in this area at the end of the 1990s. In the first phase, in co-operation with Gustav Dahll at the Halden project, a life cycle model was selected. For the different phases a qualitative influence net was constructed of the type that is used in Bayesian Believe Network together with a discussion on different issues involved. In the second phase of the research work, in co-operation with Norman Wainwright, a former NII inspector, information from a selection of the most important sources as guidelines, IAEA and EC reports etc, was mapped into the influence net structure (the total list on used sources are in the report). The result is presented in the form of questions (Q) and a

Safety Justification of Software Systems. Software Based Safety Systems. Regulatory Inspection Handbook

Energy Technology Data Exchange (ETDEWEB)

Dahll, Gustav (OECD Halden Project, Halden (NO)); Liwaang, Bo (Swedish Nuclear Power Inspectorate, Stockholm (Sweden)); Wainwright, Norman (Wainwright Safety Advice (GB))

2006-07-01

The introduction of new software based technology in the safety systems in nuclear power plants also makes it necessary to develop new strategies for regulatory review and assessment of these new systems that is more focused on reviewing the processes at the different phases in design phases during the system life cycle. It is a general requirement that the licensee shall perform different kinds of reviews. From a regulatory point of view it is more cost effective to assess that the design activities at the suppliers and the review activities within the development project are performed with good quality. But the change from more technical reviews over to the development process oriented approach also cause problems. When reviewing development and quality aspects there are no 'hard facts' that can be judged against some specified criteria, the issues are more 'soft' and are more to build up structure of arguments and evidences that the requirements are met. The regulatory review strategy must therefore change to follow the development process over the whole life cycle from concept phase until installation and operation. Even if we know what factors that is of interest we need some guidance on how to interpret and judge the information.For that purpose SKl started research activities in this area at the end of the 1990s. In the first phase, in co-operation with Gustav Dahll at the Halden project, a life cycle model was selected. For the different phases a qualitative influence net was constructed of the type that is used in Bayesian Believe Network together with a discussion on different issues involved. In the second phase of the research work, in co-operation with Norman Wainwright, a former NII inspector, information from a selection of the most important sources as guidelines, IAEA and EC reports etc, was mapped into the influence net structure (the total list on used sources are in the report). The result is presented in the form of

Toxicity of silver nanoparticles in biological systems: Does the complexity of biological systems matter?

Science.gov (United States)

Vazquez-Muñoz, Roberto; Borrego, Belen; Juárez-Moreno, Karla; García-García, Maritza; Mota Morales, Josué D; Bogdanchikova, Nina; Huerta-Saquero, Alejandro

2017-07-05

Currently, nanomaterials are more frequently in our daily life, specifically in biomedicine, electronics, food, textiles and catalysis just to name a few. Although nanomaterials provide many benefits, recently their toxicity profiles have begun to be explored. In this work, the toxic effects of silver nanoparticles (35nm-average diameter and Polyvinyl-Pyrrolidone-coated) on biological systems of different levels of complexity was assessed in a comprehensive and comparatively way, through a variety of viability and toxicological assays. The studied organisms included viruses, bacteria, microalgae, fungi, animal and human cells (including cancer cell lines). It was found that biological systems of different taxonomical groups are inhibited at concentrations of silver nanoparticles within the same order of magnitude. Thus, the toxicity of nanomaterials on biological/living systems, constrained by their complexity, e.g. taxonomic groups, resulted contrary to the expected. The fact that cells and virus are inhibited with a concentration of silver nanoparticles within the same order of magnitude could be explained considering that silver nanoparticles affects very primitive cellular mechanisms by interacting with fundamental structures for cells and virus alike. Copyright © 2017 Elsevier B.V. All rights reserved.

The Systems Biology Research Tool: evolvable open-source software

Directory of Open Access Journals (Sweden)

Wright Jeremiah

2008-06-01

Full Text Available Abstract Background Research in the field of systems biology requires software for a variety of purposes. Software must be used to store, retrieve, analyze, and sometimes even to collect the data obtained from system-level (often high-throughput experiments. Software must also be used to implement mathematical models and algorithms required for simulation and theoretical predictions on the system-level. Results We introduce a free, easy-to-use, open-source, integrated software platform called the Systems Biology Research Tool (SBRT to facilitate the computational aspects of systems biology. The SBRT currently performs 35 methods for analyzing stoichiometric networks and 16 methods from fields such as graph theory, geometry, algebra, and combinatorics. New computational techniques can be added to the SBRT via process plug-ins, providing a high degree of evolvability and a unifying framework for software development in systems biology. Conclusion The Systems Biology Research Tool represents a technological advance for systems biology. This software can be used to make sophisticated computational techniques accessible to everyone (including those with no programming ability, to facilitate cooperation among researchers, and to expedite progress in the field of systems biology.

A computational systems biology software platform for multiscale modeling and simulation: Integrating whole-body physiology, disease biology, and molecular reaction networks

Directory of Open Access Journals (Sweden)

Thomas eEissing

2011-02-01

Full Text Available 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 multi-scale 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.

Plant Systems Biology at the Single-Cell Level.

Science.gov (United States)

Libault, Marc; Pingault, Lise; Zogli, Prince; Schiefelbein, John

2017-11-01

Our understanding of plant biology is increasingly being built upon studies using 'omics and system biology approaches performed at the level of the entire plant, organ, or tissue. Although these approaches open new avenues to better understand plant biology, they suffer from the cellular complexity of the analyzed sample. Recent methodological advances now allow plant scientists to overcome this limitation and enable biological analyses of single-cells or single-cell-types. Coupled with the development of bioinformatics and functional genomics resources, these studies provide opportunities for high-resolution systems analyses of plant phenomena. In this review, we describe the recent advances, current challenges, and future directions in exploring the biology of single-cells and single-cell-types to enhance our understanding of plant biology as a system. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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

2015-03-01

This paper proposes a critical analysis of the existing literature on mathematical tools developed toward systems biology approaches and, out of this overview, develops a new approach whose main features can be briefly summarized as follows: derivation of mathematical structures suitable to capture the complexity of biological, hence living, systems, modeling, by appropriate mathematical tools, Darwinian type dynamics, namely mutations followed by selection and evolution. Moreover, multiscale methods to move from genes to cells, and from cells to tissue are analyzed in view of a new systems biology approach. Copyright © 2014 Elsevier B.V. All rights reserved.

Computational Modeling of Biological Systems From Molecules to Pathways

CERN Document Server

2012-01-01

Computational modeling is emerging as a powerful new approach for studying and manipulating biological systems. Many diverse methods have been developed to model, visualize, and rationally alter these systems at various length scales, from atomic resolution to the level of cellular pathways. Processes taking place at larger time and length scales, such as molecular evolution, have also greatly benefited from new breeds of computational approaches. Computational Modeling of Biological Systems: From Molecules to Pathways provides an overview of established computational methods for the modeling of biologically and medically relevant systems. It is suitable for researchers and professionals working in the fields of biophysics, computational biology, systems biology, and molecular medicine.

US Competitiveness in Synthetic Biology.

Science.gov (United States)

Gronvall, Gigi Kwik

2015-01-01

Synthetic biology is an emerging technical field that aims to make biology easier to engineer; the field has applications in strategically important sectors for the US economy. While the United States currently leads in synthetic biology R&D, other nations are heavily investing in order to boost their economies, which will inevitably diminish the US leadership position. This outcome is not entirely negative--additional investments will expand markets--but it is critical that the US government take steps to remain competitive: There are applications from which the US population and economy may benefit; there are specific applications with importance for national defense; and US technical leadership will ensure that US experts have a leading role in synthetic biology governance, regulation, and oversight. Measures to increase competitiveness in S&T generally are broadly applicable for synthetic biology and should be pursued. However, the US government will also need to take action on fundamental issues that will affect the field's development, such as countering anti-GMO (genetically modified organism) sentiments and anti-GMO legislation. The United States should maintain its regulatory approach so that it is the product that is regulated, not the method used to create a product. At the same time, the United States needs to ensure that the regulatory framework is updated so that synthetic biology products do not fall into regulatory gaps. Finally, the United States needs to pay close attention to how synthetic biology applications may be governed internationally, such as through the Nagoya Protocol of the Convention on Biological Diversity, so that beneficial applications may be realized.

Systems Biology — the Broader Perspective

Directory of Open Access Journals (Sweden)

Jonathan Bard

2013-06-01

Full Text Available Systems biology has two general aims: a narrow one, which is to discover how complex networks of proteins work, and a broader one, which is to integrate the molecular and network data with the generation and function of organism phenotypes. Doing all this involves complex methodologies, but underpinning the subject are more general conceptual problems about upwards and downwards causality, complexity and information storage, and their solutions provide the constraints within which these methodologies can be used. This essay considers these general aspects and the particular role of protein networks; their functional outputs are often the processes driving phenotypic change and physiological function—networks are, in a sense, the units of systems biology much as proteins are for molecular biology. It goes on to argue that the natural language for systems-biological descriptions of biological phenomena is the mathematical graph (a set of connected facts of the general form [process] (e.g., [activates] . Such graphs not only integrate events at different levels but emphasize the distributed nature of control as well as displaying a great deal of data. The implications and successes of these ideas for physiology, pharmacology, development and evolution are briefly considered. The paper concludes with some challenges for the future.

Facilitating a More Efficient Commercial Review Process for Pediatric Drugs and Biologics

Directory of Open Access Journals (Sweden)

Ryan D. Rykhus

2017-12-01

Full Text Available Over the past two decades, the biopharmaceutical industry has seen unprecedented expansion and innovation in concert with significant technological advancements. While the industry has experienced marked growth, the regulatory system in the United States still operates at a capacity much lower than the influx of new drug and biologic candidates. As a result, it has become standard for months or even years of waiting for commercial approval by the U.S. Food and Drug Administration. These regulatory delays have generated a system that stifles growth and innovation due to the exorbitant costs associated with awaiting approval from the nation’s sole regulatory agency. The recent re-emergence of diseases that impact pediatric demographics represents one particularly acute reason for developing a regulatory system that facilitates a more efficient commercial review process. Herein, we present a range of initiatives that could represent early steps toward alleviating the delays in approving life-saving therapeutics.

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

Science.gov (United States)

Fletcher, Eugene; Krivoruchko, Anastasia; Nielsen, Jens

2016-06-01

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

Optoelectronic system and apparatus for connection to biological systems

Science.gov (United States)

Okandan, Murat; Nielson, Gregory N.

2018-03-06

The present invention relates to a biological probe structure, as well as apparatuses, systems, and methods employing this structure. In particular embodiments, the structure includes a hermetically sealed unit configured to receive and transmit one or more optical signals. Furthermore, the structure can be implanted subcutaneously and interrogated externally. In this manner, a minimally invasive method can be employed to detect, treat, and/or assess the biological target. Additional methods and systems are also provided.

Genotet: An Interactive Web-based Visual Exploration Framework to Support Validation of Gene Regulatory Networks.

Science.gov (United States)

Yu, Bowen; Doraiswamy, Harish; Chen, Xi; Miraldi, Emily; Arrieta-Ortiz, Mario Luis; Hafemeister, Christoph; Madar, Aviv; Bonneau, Richard; Silva, Cláudio T

2014-12-01

Elucidation of transcriptional regulatory networks (TRNs) is a fundamental goal in biology, and one of the most important components of TRNs are transcription factors (TFs), proteins that specifically bind to gene promoter and enhancer regions to alter target gene expression patterns. Advances in genomic technologies as well as advances in computational biology have led to multiple large regulatory network models (directed networks) each with a large corpus of supporting data and gene-annotation. There are multiple possible biological motivations for exploring large regulatory network models, including: validating TF-target gene relationships, figuring out co-regulation patterns, and exploring the coordination of cell processes in response to changes in cell state or environment. Here we focus on queries aimed at validating regulatory network models, and on coordinating visualization of primary data and directed weighted gene regulatory networks. The large size of both the network models and the primary data can make such coordinated queries cumbersome with existing tools and, in particular, inhibits the sharing of results between collaborators. In this work, we develop and demonstrate a web-based framework for coordinating visualization and exploration of expression data (RNA-seq, microarray), network models and gene-binding data (ChIP-seq). Using specialized data structures and multiple coordinated views, we design an efficient querying model to support interactive analysis of the data. Finally, we show the effectiveness of our framework through case studies for the mouse immune system (a dataset focused on a subset of key cellular functions) and a model bacteria (a small genome with high data-completeness).

Regulatory RNA design through evolutionary computation and strand displacement.

Science.gov (United States)

Rostain, William; Landrain, Thomas E; Rodrigo, Guillermo; Jaramillo, Alfonso

2015-01-01

The discovery and study of a vast number of regulatory RNAs in all kingdoms of life over the past decades has allowed the design of new synthetic RNAs that can regulate gene expression in vivo. Riboregulators, in particular, have been used to activate or repress gene expression. However, to accelerate and scale up the design process, synthetic biologists require computer-assisted design tools, without which riboregulator engineering will remain a case-by-case design process requiring expert attention. Recently, the design of RNA circuits by evolutionary computation and adapting strand displacement techniques from nanotechnology has proven to be suited to the automated generation of DNA sequences implementing regulatory RNA systems in bacteria. Herein, we present our method to carry out such evolutionary design and how to use it to create various types of riboregulators, allowing the systematic de novo design of genetic control systems in synthetic biology.

A review of imaging techniques for systems biology

Directory of Open Access Journals (Sweden)

Po Ming J

2008-08-01

Full Text Available Abstract This paper presents a review of imaging techniques and of their utility in system biology. During the last decade systems biology has matured into a distinct field and imaging has been increasingly used to enable the interplay of experimental and theoretical biology. In this review, we describe and compare the roles of microscopy, ultrasound, CT (Computed Tomography, MRI (Magnetic Resonance Imaging, PET (Positron Emission Tomography, and molecular probes such as quantum dots and nanoshells in systems biology. As a unified application area among these different imaging techniques, examples in cancer targeting are highlighted.

Radiation and the regulatory landscape of neo2-Darwinism

International Nuclear Information System (INIS)

Rollo, C. David

2006-01-01

Several recently revealed features of eukaryotic genomes were not predicted by earlier evolutionary paradigms, including the relatively small number of genes, the very large amounts of non-functional code and its quarantine in heterochromatin, the remarkable conservation of many functionally important genes across relatively enormous phylogenetic distances, and the prevalence of extra-genomic information associated with chromatin structure and histone proteins. All of these emphasize a paramount role for regulatory evolution, which is further reinforced by recent perspectives highlighting even higher-order regulation governing epigenetics and development (EVO-DEVO). Modern neo 2 -Darwinism, with its emphasis on regulatory mechanisms and regulatory evolution provides new vision for understanding radiation biology, particularly because free radicals and redox states are central to many regulatory mechanisms and free radicals generated by radiation mimic and amplify endogenous signalling. This paper explores some of these aspects and their implications for low-dose radiation biology

Radiation and the regulatory landscape of neo2-Darwinism.

Science.gov (United States)

Rollo, C David

2006-05-11

Several recently revealed features of eukaryotic genomes were not predicted by earlier evolutionary paradigms, including the relatively small number of genes, the very large amounts of non-functional code and its quarantine in heterochromatin, the remarkable conservation of many functionally important genes across relatively enormous phylogenetic distances, and the prevalence of extra-genomic information associated with chromatin structure and histone proteins. All of these emphasize a paramount role for regulatory evolution, which is further reinforced by recent perspectives highlighting even higher-order regulation governing epigenetics and development (EVO-DEVO). Modern neo2-Darwinism, with its emphasis on regulatory mechanisms and regulatory evolution provides new vision for understanding radiation biology, particularly because free radicals and redox states are central to many regulatory mechanisms and free radicals generated by radiation mimic and amplify endogenous signalling. This paper explores some of these aspects and their implications for low-dose radiation biology.

Plant synthetic biology for molecular engineering of signalling and development.

Science.gov (United States)

Nemhauser, Jennifer L; Torii, Keiko U

2016-03-02

Molecular genetic studies of model plants in the past few decades have identified many key genes and pathways controlling development, metabolism and environmental responses. Recent technological and informatics advances have led to unprecedented volumes of data that may uncover underlying principles of plants as biological systems. The newly emerged discipline of synthetic biology and related molecular engineering approaches is built on this strong foundation. Today, plant regulatory pathways can be reconstituted in heterologous organisms to identify and manipulate parameters influencing signalling outputs. Moreover, regulatory circuits that include receptors, ligands, signal transduction components, epigenetic machinery and molecular motors can be engineered and introduced into plants to create novel traits in a predictive manner. Here, we provide a brief history of plant synthetic biology and significant recent examples of this approach, focusing on how knowledge generated by the reference plant Arabidopsis thaliana has contributed to the rapid rise of this new discipline, and discuss potential future directions.

The regulatory function of self-esteem: testing the epistemic and acceptance signaling systems.

Science.gov (United States)

Stinson, Danu Anthony; Logel, Christine; Holmes, John G; Wood, Joanne V; Forest, Amanda L; Gaucher, Danielle; Fitzsimons, Grainné M; Kath, Jennifer

2010-12-01

The authors draw on sociometer theory (e.g., Leary, 2004) and self-verification theory (e.g., Swann, 1997) to propose an expanded model of the regulatory function of self-esteem. The model suggests that people not only possess an acceptance signaling system that indicates whether relational value is high or low but also possess an epistemic signaling system that indicates whether social feedback is consistent or inconsistent with chronic perceived relational value (i.e., global self-esteem). One correlational study and 5 experiments, with diverse operationalizations of social feedback, demonstrated that the epistemic signaling system responds to self-esteem consistent or inconsistent relational-value feedback with increases or deceases in epistemic certainty. Moreover, Studies 3-6 demonstrated that the acceptance and epistemic signaling systems respond uniquely to social feedback. Finally, Studies 5 and 6 provide evidence that the epistemic signaling system is part of a broader self-regulatory system: Self-esteem inconsistent feedback caused cognitive efforts to decrease the discrepancy between self-views and feedback and caused depleted self-regulatory capacity on a subsequent self-control task. PsycINFO Database Record (c) 2010 APA, all rights reserved.

Inferring the conservative causal core of gene regulatory networks

Directory of Open Access Journals (Sweden)

Emmert-Streib Frank

2010-09-01

Full Text Available Abstract Background Inferring gene regulatory networks from large-scale expression data is an important problem that received much attention in recent years. These networks have the potential to gain insights into causal molecular interactions of biological processes. Hence, from a methodological point of view, reliable estimation methods based on observational data are needed to approach this problem practically. Results In this paper, we introduce a novel gene regulatory network inference (GRNI algorithm, called C3NET. We compare C3NET with four well known methods, ARACNE, CLR, MRNET and RN, conducting in-depth numerical ensemble simulations and demonstrate also for biological expression data from E. coli that C3NET performs consistently better than the best known GRNI methods in the literature. In addition, it has also a low computational complexity. Since C3NET is based on estimates of mutual information values in conjunction with a maximization step, our numerical investigations demonstrate that our inference algorithm exploits causal structural information in the data efficiently. Conclusions For systems biology to succeed in the long run, it is of crucial importance to establish methods that extract large-scale gene networks from high-throughput data that reflect the underlying causal interactions among genes or gene products. Our method can contribute to this endeavor by demonstrating that an inference algorithm with a neat design permits not only a more intuitive and possibly biological interpretation of its working mechanism but can also result in superior results.

Inferring the conservative causal core of gene regulatory networks.

Science.gov (United States)

Altay, Gökmen; Emmert-Streib, Frank

2010-09-28

Inferring gene regulatory networks from large-scale expression data is an important problem that received much attention in recent years. These networks have the potential to gain insights into causal molecular interactions of biological processes. Hence, from a methodological point of view, reliable estimation methods based on observational data are needed to approach this problem practically. In this paper, we introduce a novel gene regulatory network inference (GRNI) algorithm, called C3NET. We compare C3NET with four well known methods, ARACNE, CLR, MRNET and RN, conducting in-depth numerical ensemble simulations and demonstrate also for biological expression data from E. coli that C3NET performs consistently better than the best known GRNI methods in the literature. In addition, it has also a low computational complexity. Since C3NET is based on estimates of mutual information values in conjunction with a maximization step, our numerical investigations demonstrate that our inference algorithm exploits causal structural information in the data efficiently. For systems biology to succeed in the long run, it is of crucial importance to establish methods that extract large-scale gene networks from high-throughput data that reflect the underlying causal interactions among genes or gene products. Our method can contribute to this endeavor by demonstrating that an inference algorithm with a neat design permits not only a more intuitive and possibly biological interpretation of its working mechanism but can also result in superior results.

Asymmetric positive feedback loops reliably control biological responses.

Science.gov (United States)

Ratushny, Alexander V; Saleem, Ramsey A; Sitko, Katherine; Ramsey, Stephen A; Aitchison, John D

2012-04-24

Positive feedback is a common mechanism enabling biological systems to respond to stimuli in a switch-like manner. Such systems are often characterized by the requisite formation of a heterodimer where only one of the pair is subject to feedback. This ASymmetric Self-UpREgulation (ASSURE) motif is central to many biological systems, including cholesterol homeostasis (LXRα/RXRα), adipocyte differentiation (PPARγ/RXRα), development and differentiation (RAR/RXR), myogenesis (MyoD/E12) and cellular antiviral defense (IRF3/IRF7). To understand why this motif is so prevalent, we examined its properties in an evolutionarily conserved transcriptional regulatory network in yeast (Oaf1p/Pip2p). We demonstrate that the asymmetry in positive feedback confers a competitive advantage and allows the system to robustly increase its responsiveness while precisely tuning the response to a consistent level in the presence of varying stimuli. This study reveals evolutionary advantages for the ASSURE motif, and mechanisms for control, that are relevant to pharmacologic intervention and synthetic biology applications.

Improvement of the regulatory system by implementation new safety demands

International Nuclear Information System (INIS)

Iglesias, R.; Alfonso, C.

1996-01-01

The work describes in broad terms, the analysis that is being performed aiming at the adoption of a regulatory system that could meet the current safety demands, but which, at the same time, could be a general system that might allow different safety assessments to be done by making use of more specific technical standards of the technology supplier

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

OpenAIRE

Webb Penelope A; Hodgkinson Matt J

2007-01-01

Abstract BMC Systems Biology is the first open access journal spanning the growing field of systems biology from molecules up to ecosystems. The journal has launched as more and more institutes are founded that are similarly dedicated to this new approach. BMC Systems Biology builds on the ongoing success of the BMC series, providing a venue for all sound research in the systems-level analysis of biology.

Systems biology of neutrophil differentiation and immune response

DEFF Research Database (Denmark)

Theilgaard-Mönch, Kim; Porse, Bo T; Borregaard, Niels

2005-01-01

Systems biology has emerged as a new scientific field, which aims at investigating biological processes at the genomic and proteomic levels. Recent studies have unravelled aspects of neutrophil differentiation and immune responses at the systems level using high-throughput technologies. These stu......Systems biology has emerged as a new scientific field, which aims at investigating biological processes at the genomic and proteomic levels. Recent studies have unravelled aspects of neutrophil differentiation and immune responses at the systems level using high-throughput technologies....... These studies have identified a plethora of novel effector proteins stored in the granules of neutrophils. In addition, these studies provide evidence that neutrophil differentiation and immune response are governed by a highly coordinated transcriptional programme that regulates cellular fate and function...

Biological Potential in Serpentinizing Systems

Science.gov (United States)

Hoehler, Tori M.

2016-01-01

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

Transportation of radioactive materials: the legislative and regulatory information system

International Nuclear Information System (INIS)

Fore, C.S.

1982-03-01

The US Department of Energy is carrying out a national program to assure the safe shipment of radioactive materials. As part of this overall effort, the Hazardous Materials Information Center of Oak Ridge National Laboratory has developed the comprehensive Legislative and Regulatory Information System, which contains information on federal-, state-, and local-level legislative and regulatory actions pertaining primarily to the shipment of radioactive materials. Specific subject areas chosen to highlight particular transportation restrictions include: (1) identification of state agency responsible for regulating transportation, (2) type of escorts required, (3) areas requiring prior notification, (4) areas requiring permits or licenses, and (5) areas totally banning transportation of all radioactive materials. Other legislative information being categorized and of immediate relevance to the transportation issues is covered under the areas of disposal, storage, and management of radioactive materials; establishment of additional regulations; emergency response regulations; moratoriums on power plant construction and siting; radiation safety and control studies; and remedial action studies. The collected information is abstracted, indexed, and input into one of the two data bases developed under this information system - Current Legislation Data Base and Historical Legislation Data Base. An appendix is included which provides a summary of the state and local laws affecting the transportation of radioactive materials throughout the United States. The Legislative and Regulatory Information System is supported by the Transportation Technology Center located at Sandia National Laboratories, Albuquerque, New Mexico

Transportation of radioactive materials: the legislative and regulatory information system

Energy Technology Data Exchange (ETDEWEB)

Fore, C.S.

1982-03-01

The US Department of Energy is carrying out a national program to assure the safe shipment of radioactive materials. As part of this overall effort, the Hazardous Materials Information Center of Oak Ridge National Laboratory has developed the comprehensive Legislative and Regulatory Information System, which contains information on federal-, state-, and local-level legislative and regulatory actions pertaining primarily to the shipment of radioactive materials. Specific subject areas chosen to highlight particular transportation restrictions include: (1) identification of state agency responsible for regulating transportation, (2) type of escorts required, (3) areas requiring prior notification, (4) areas requiring permits or licenses, and (5) areas totally banning transportation of all radioactive materials. Other legislative information being categorized and of immediate relevance to the transportation issues is covered under the areas of disposal, storage, and management of radioactive materials; establishment of additional regulations; emergency response regulations; moratoriums on power plant construction and siting; radiation safety and control studies; and remedial action studies. The collected information is abstracted, indexed, and input into one of the two data bases developed under this information system - Current Legislation Data Base and Historical Legislation Data Base. An appendix is included which provides a summary of the state and local laws affecting the transportation of radioactive materials throughout the United States. The Legislative and Regulatory Information System is supported by the Transportation Technology Center located at Sandia National Laboratories, Albuquerque, New Mexico.

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

Science.gov (United States)

Gomez-Ramirez, Jaime; Sanz, Ricardo

2013-09-01

One of the most important scientific challenges today is the quantitative and predictive understanding of biological function. Classical mathematical and computational approaches have been enormously successful in modeling inert matter, but they may be inadequate to address inherent features of biological systems. We address the conceptual and methodological obstacles that lie in the inverse problem in biological systems modeling. We introduce a full Bayesian approach (FBA), a theoretical framework to study biological function, in which probability distributions are conditional on biophysical information that physically resides in the biological system that is studied by the scientist. Copyright © 2013 Elsevier Ltd. All rights reserved.

Systems biology approach to bioremediation

Energy Technology Data Exchange (ETDEWEB)

Chakraborty, Romy; Wu, Cindy H.; Hazen, Terry C.

2012-06-01

Bioremediation has historically been approached as a ‘black box’ in terms of our fundamental understanding. Thus it succeeds and fails, seldom without a complete understanding of why. Systems biology is an integrated research approach to study complex biological systems, by investigating interactions and networks at the molecular, cellular, community, and ecosystem level. The knowledge of these interactions within individual components is fundamental to understanding the dynamics of the ecosystem under investigation. Finally, understanding and modeling functional microbial community structure and stress responses in environments at all levels have tremendous implications for our fundamental understanding of hydrobiogeochemical processes and the potential for making bioremediation breakthroughs and illuminating the ‘black box’.

BetaWB - A language for modular representation of biological systems

DEFF Research Database (Denmark)

Ihekwaba, Adoha; Larcher, Roberto; Mardare, Radu Iulian

2007-01-01

A. Ihekwaba, R. Larcher, R. Mardare, C. Priami. BetaWB - A language for modular representation of biological systems. In Proc. of International Conference on Systems Biology (ICSB), 2007......A. Ihekwaba, R. Larcher, R. Mardare, C. Priami. BetaWB - A language for modular representation of biological systems. In Proc. of International Conference on Systems Biology (ICSB), 2007...

Systems biology elucidates common pathogenic mechanisms between nonalcoholic and alcoholic-fatty liver disease.

Directory of Open Access Journals (Sweden)

Silvia Sookoian

Full Text Available The abnormal accumulation of fat in the liver is often related either to metabolic risk factors associated with metabolic syndrome in the absence of alcohol consumption (nonalcoholic fatty liver disease, NAFLD or to chronic alcohol consumption (alcoholic fatty liver disease, AFLD. Clinical and histological studies suggest that NAFLD and AFLD share pathogenic mechanisms. Nevertheless, current data are still inconclusive as to whether the underlying biological process and disease pathways of NAFLD and AFLD are alike. Our primary aim was to integrate omics and physiological data to answer the question of whether NAFLD and AFLD share molecular processes that lead to disease development. We also explored the extent to which insulin resistance (IR is a distinctive feature of NAFLD. To answer these questions, we used systems biology approaches, such as gene enrichment analysis, protein-protein interaction networks, and gene prioritization, based on multi-level data extracted by computational data mining. We observed that the leading disease pathways associated with NAFLD did not significantly differ from those of AFLD. However, systems biology revealed the importance of each molecular process behind each of the two diseases, and dissected distinctive molecular NAFLD and AFLD-signatures. Comparative co-analysis of NAFLD and AFLD clarified the participation of NAFLD, but not AFLD, in cardiovascular disease, and showed that insulin signaling is impaired in fatty liver regardless of the noxa, but the putative regulatory mechanisms associated with NAFLD seem to encompass a complex network of genes and proteins, plausible of epigenetic modifications. Gene prioritization showed a cancer-related functional map that suggests that the fatty transformation of the liver tissue is regardless of the cause, an emerging mechanism of ubiquitous oncogenic activation. In conclusion, similar underlying disease mechanisms lead to NAFLD and AFLD, but specific ones depict a

Strengthening Regulatory Competence in a Changing Nuclear Regulatory Environment

International Nuclear Information System (INIS)

Illizastigui, P.F.

2016-01-01

The paper addresses the approach followed by the Cuban National Center for Nuclear Safety for the management of current and new competences of its regulatory staff with the aim of allowing those staff to effectively fulfill their core regulatory functions. The approach is realized through an Integrated System for Competence Building, which is based on the IAEA recommendations, shown to be effective in ensuring the necessary competence in the relevant areas. In the author’s opinion, competence of the regulatory staff in the area of human and organizational factors is of paramount importance and needs to be further strengthened in order to be able to assess safety performance at the facilities and detect early signs of deteriorating safety performance. The former is defined by the author as the core regulatory function “Analysis” which covers the entire spectrum of assessment tasks carried out by the regulatory staff to: a) detect declining safety performance, b) diagnose latent weaknesses (root causes) and c) make effective safety culture interventions. The author suggests that competence associated with the fulfillment of the analysis function is distinctly identified and dealt with separately in the current system of managing regulatory competence. (author)

Predicting gene regulatory networks of soybean nodulation from RNA-Seq transcriptome data.

Science.gov (United States)

Zhu, Mingzhu; Dahmen, Jeremy L; Stacey, Gary; Cheng, Jianlin

2013-09-22

High-throughput RNA sequencing (RNA-Seq) is a revolutionary technique to study the transcriptome of a cell under various conditions at a systems level. Despite the wide application of RNA-Seq techniques to generate experimental data in the last few years, few computational methods are available to analyze this huge amount of transcription data. The computational methods for constructing gene regulatory networks from RNA-Seq expression data of hundreds or even thousands of genes are particularly lacking and urgently needed. We developed an automated bioinformatics method to predict gene regulatory networks from the quantitative expression values of differentially expressed genes based on RNA-Seq transcriptome data of a cell in different stages and conditions, integrating transcriptional, genomic and gene function data. We applied the method to the RNA-Seq transcriptome data generated for soybean root hair cells in three different development stages of nodulation after rhizobium infection. The method predicted a soybean nodulation-related gene regulatory network consisting of 10 regulatory modules common for all three stages, and 24, 49 and 70 modules separately for the first, second and third stage, each containing both a group of co-expressed genes and several transcription factors collaboratively controlling their expression under different conditions. 8 of 10 common regulatory modules were validated by at least two kinds of validations, such as independent DNA binding motif analysis, gene function enrichment test, and previous experimental data in the literature. We developed a computational method to reliably reconstruct gene regulatory networks from RNA-Seq transcriptome data. The method can generate valuable hypotheses for interpreting biological data and designing biological experiments such as ChIP-Seq, RNA interference, and yeast two hybrid experiments.

Computational challenges in modeling gene regulatory events.

Science.gov (United States)

Pataskar, Abhijeet; Tiwari, Vijay K

2016-10-19

Cellular transcriptional programs driven by genetic and epigenetic mechanisms could be better understood by integrating "omics" data and subsequently modeling the gene-regulatory events. Toward this end, computational biology should keep pace with evolving experimental procedures and data availability. This article gives an exemplified account of the current computational challenges in molecular biology.

Predictive regulatory models in Drosophila melanogaster by integrative inference of transcriptional networks

Science.gov (United States)

Marbach, Daniel; Roy, Sushmita; Ay, Ferhat; Meyer, Patrick E.; Candeias, Rogerio; Kahveci, Tamer; Bristow, Christopher A.; Kellis, Manolis

2012-01-01

Gaining insights on gene regulation from large-scale functional data sets is a grand challenge in systems biology. In this article, we develop and apply methods for transcriptional regulatory network inference from diverse functional genomics data sets and demonstrate their value for gene function and gene expression prediction. We formulate the network inference problem in a machine-learning framework and use both supervised and unsupervised methods to predict regulatory edges by integrating transcription factor (TF) binding, evolutionarily conserved sequence motifs, gene expression, and chromatin modification data sets as input features. Applying these methods to Drosophila melanogaster, we predict ∼300,000 regulatory edges in a network of ∼600 TFs and 12,000 target genes. We validate our predictions using known regulatory interactions, gene functional annotations, tissue-specific expression, protein–protein interactions, and three-dimensional maps of chromosome conformation. We use the inferred network to identify putative functions for hundreds of previously uncharacterized genes, including many in nervous system development, which are independently confirmed based on their tissue-specific expression patterns. Last, we use the regulatory network to predict target gene expression levels as a function of TF expression, and find significantly higher predictive power for integrative networks than for motif or ChIP-based networks. Our work reveals the complementarity between physical evidence of regulatory interactions (TF binding, motif conservation) and functional evidence (coordinated expression or chromatin patterns) and demonstrates the power of data integration for network inference and studies of gene regulation at the systems level. PMID:22456606

Predictive regulatory models in Drosophila melanogaster by integrative inference of transcriptional networks.

Science.gov (United States)

Marbach, Daniel; Roy, Sushmita; Ay, Ferhat; Meyer, Patrick E; Candeias, Rogerio; Kahveci, Tamer; Bristow, Christopher A; Kellis, Manolis

2012-07-01

Gaining insights on gene regulation from large-scale functional data sets is a grand challenge in systems biology. In this article, we develop and apply methods for transcriptional regulatory network inference from diverse functional genomics data sets and demonstrate their value for gene function and gene expression prediction. We formulate the network inference problem in a machine-learning framework and use both supervised and unsupervised methods to predict regulatory edges by integrating transcription factor (TF) binding, evolutionarily conserved sequence motifs, gene expression, and chromatin modification data sets as input features. Applying these methods to Drosophila melanogaster, we predict ∼300,000 regulatory edges in a network of ∼600 TFs and 12,000 target genes. We validate our predictions using known regulatory interactions, gene functional annotations, tissue-specific expression, protein-protein interactions, and three-dimensional maps of chromosome conformation. We use the inferred network to identify putative functions for hundreds of previously uncharacterized genes, including many in nervous system development, which are independently confirmed based on their tissue-specific expression patterns. Last, we use the regulatory network to predict target gene expression levels as a function of TF expression, and find significantly higher predictive power for integrative networks than for motif or ChIP-based networks. Our work reveals the complementarity between physical evidence of regulatory interactions (TF binding, motif conservation) and functional evidence (coordinated expression or chromatin patterns) and demonstrates the power of data integration for network inference and studies of gene regulation at the systems level.

Yeast systems biology to unravel the network of life

DEFF Research Database (Denmark)

Mustacchi, Roberta; Hohmann, S; Nielsen, Jens

2006-01-01

Systems biology focuses on obtaining a quantitative description of complete biological systems, even complete cellular function. In this way, it will be possible to perform computer-guided design of novel drugs, advanced therapies for treatment of complex diseases, and to perform in silico design....... Furthermore, it serves as an industrial workhorse for production of a wide range of chemicals and pharmaceuticals. Systems biology involves the combination of novel experimental techniques from different disciplines as well as functional genomics, bioinformatics and mathematical modelling, and hence no single...... laboratory has access to all the necessary competences. For this reason the Yeast Systems Biology Network (YSBN) has been established. YSBN will coordinate research efforts, in yeast systems biology and, through the recently obtained EU funding for a Coordination Action, it will be possible to set...

3S - Systematic, systemic, and systems biology and toxicology.

Science.gov (United States)

Smirnova, Lena; Kleinstreuer, Nicole; Corvi, Raffaella; Levchenko, Andre; Fitzpatrick, Suzanne C; Hartung, Thomas

2018-01-01

A biological system is more than the sum of its parts - it accomplishes many functions via synergy. Deconstructing the system down to the molecular mechanism level necessitates the complement of reconstructing functions on all levels, i.e., in our conceptualization of biology and its perturbations, our experimental models and computer modelling. Toxicology contains the somewhat arbitrary subclass "systemic toxicities"; however, there is no relevant toxic insult or general disease that is not systemic. At least inflammation and repair are involved that require coordinated signaling mechanisms across the organism. However, the more body components involved, the greater the challenge to reca-pitulate such toxicities using non-animal models. Here, the shortcomings of current systemic testing and the development of alternative approaches are summarized. We argue that we need a systematic approach to integrating existing knowledge as exemplified by systematic reviews and other evidence-based approaches. Such knowledge can guide us in modelling these systems using bioengineering and virtual computer models, i.e., via systems biology or systems toxicology approaches. Experimental multi-organ-on-chip and microphysiological systems (MPS) provide a more physiological view of the organism, facilitating more comprehensive coverage of systemic toxicities, i.e., the perturbation on organism level, without using substitute organisms (animals). The next challenge is to establish disease models, i.e., micropathophysiological systems (MPPS), to expand their utility to encompass biomedicine. Combining computational and experimental systems approaches and the chal-lenges of validating them are discussed. The suggested 3S approach promises to leverage 21st century technology and systematic thinking to achieve a paradigm change in studying systemic effects.

Sequence-based model of gap gene regulatory network.

Science.gov (United States)

Kozlov, Konstantin; Gursky, Vitaly; Kulakovskiy, Ivan; Samsonova, Maria

2014-01-01

The detailed analysis of transcriptional regulation is crucially important for understanding biological processes. The gap gene network in Drosophila attracts large interest among researches studying mechanisms of transcriptional regulation. It implements the most upstream regulatory layer of the segmentation gene network. The knowledge of molecular mechanisms involved in gap gene regulation is far less complete than that of genetics of the system. Mathematical modeling goes beyond insights gained by genetics and molecular approaches. It allows us to reconstruct wild-type gene expression patterns in silico, infer underlying regulatory mechanism and prove its sufficiency. We developed a new model that provides a dynamical description of gap gene regulatory systems, using detailed DNA-based information, as well as spatial transcription factor concentration data at varying time points. We showed that this model correctly reproduces gap gene expression patterns in wild type embryos and is able to predict gap expression patterns in Kr mutants and four reporter constructs. We used four-fold cross validation test and fitting to random dataset to validate the model and proof its sufficiency in data description. The identifiability analysis showed that most model parameters are well identifiable. We reconstructed the gap gene network topology and studied the impact of individual transcription factor binding sites on the model output. We measured this impact by calculating the site regulatory weight as a normalized difference between the residual sum of squares error for the set of all annotated sites and for the set with the site of interest excluded. The reconstructed topology of the gap gene network is in agreement with previous modeling results and data from literature. We showed that 1) the regulatory weights of transcription factor binding sites show very weak correlation with their PWM score; 2) sites with low regulatory weight are important for the model output; 3

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

Science.gov (United States)

Pornputtapong, Natapol; Wanichthanarak, Kwanjeera; Nilsson, Avlant; Nookaew, Intawat; Nielsen, Jens

2014-01-01

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. 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. 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.

Strategies for structuring interdisciplinary education in Systems Biology

DEFF Research Database (Denmark)

Cvijovic, Marija; Höfer, Thomas; Aćimović, Jure

2016-01-01

function by employing experimental data, mathematical models and computational simulations. As Systems Biology is inherently multidisciplinary, education within this field meets numerous hurdles including departmental barriers, availability of all required expertise locally, appropriate teaching material...... and example curricula. As university education at the Bachelor’s level is traditionally built upon disciplinary degrees, we believe that the most effective way to implement education in Systems Biology would be at the Master’s level, as it offers a more flexible framework. Our team of experts and active...... performers of Systems Biology education suggest here (i) a definition of the skills that students should acquire within a Master’s programme in Systems Biology, (ii) a possible basic educational curriculum with flexibility to adjust to different application areas and local research strengths, (iii...

Automated Identification of Core Regulatory Genes in Human Gene Regulatory Networks.

Directory of Open Access Journals (Sweden)

Vipin Narang

Full Text Available Human gene regulatory networks (GRN can be difficult to interpret due to a tangle of edges interconnecting thousands of genes. We constructed a general human GRN from extensive transcription factor and microRNA target data obtained from public databases. In a subnetwork of this GRN that is active during estrogen stimulation of MCF-7 breast cancer cells, we benchmarked automated algorithms for identifying core regulatory genes (transcription factors and microRNAs. Among these algorithms, we identified K-core decomposition, pagerank and betweenness centrality algorithms as the most effective for discovering core regulatory genes in the network evaluated based on previously known roles of these genes in MCF-7 biology as well as in their ability to explain the up or down expression status of up to 70% of the remaining genes. Finally, we validated the use of K-core algorithm for organizing the GRN in an easier to interpret layered hierarchy where more influential regulatory genes percolate towards the inner layers. The integrated human gene and miRNA network and software used in this study are provided as supplementary materials (S1 Data accompanying this manuscript.

Recurrent neural network based hybrid model for reconstructing gene regulatory network.

Science.gov (United States)

Raza, Khalid; Alam, Mansaf

2016-10-01

One of the exciting problems in systems biology research is to decipher how genome controls the development of complex biological system. The gene regulatory networks (GRNs) help in the identification of regulatory interactions between genes and offer fruitful information related to functional role of individual gene in a cellular system. Discovering GRNs lead to a wide range of applications, including identification of disease related pathways providing novel tentative drug targets, helps to predict disease response, and also assists in diagnosing various diseases including cancer. Reconstruction of GRNs from available biological data is still an open problem. This paper proposes a recurrent neural network (RNN) based model of GRN, hybridized with generalized extended Kalman filter for weight update in backpropagation through time training algorithm. The RNN is a complex neural network that gives a better settlement between biological closeness and mathematical flexibility to model GRN; and is also able to capture complex, non-linear and dynamic relationships among variables. Gene expression data are inherently noisy and Kalman filter performs well for estimation problem even in noisy data. Hence, we applied non-linear version of Kalman filter, known as generalized extended Kalman filter, for weight update during RNN training. The developed model has been tested on four benchmark networks such as DNA SOS repair network, IRMA network, and two synthetic networks from DREAM Challenge. We performed a comparison of our results with other state-of-the-art techniques which shows superiority of our proposed model. Further, 5% Gaussian noise has been induced in the dataset and result of the proposed model shows negligible effect of noise on results, demonstrating the noise tolerance capability of the model. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Reconstruction and Analysis of Gene Regulatory Networks.

Science.gov (United States)

Zheng, Guangyong; Huang, Tao

2018-01-01

In post-genomic era, an important task is to explore the function of individual biological molecules (i.e., gene, noncoding RNA, protein, metabolite) and their organization in living cells. For this end, gene regulatory networks (GRNs) are constructed to show relationship between biological molecules, in which the vertices of network denote biological molecules and the edges of network present connection between nodes (Strogatz, Nature 410:268-276, 2001; Bray, Science 301:1864-1865, 2003). Biologists can understand not only the function of biological molecules but also the organization of components of living cells through interpreting the GRNs, since a gene regulatory network is a comprehensively physiological map of living cells and reflects influence of genetic and epigenetic factors (Strogatz, Nature 410:268-276, 2001; Bray, Science 301:1864-1865, 2003). In this paper, we will review the inference methods of GRN reconstruction and analysis approaches of network structure. As a powerful tool for studying complex diseases and biological processes, the applications of the network method in pathway analysis and disease gene identification will be introduced.

Sharing regulatory data as tools for strengthening health systems in the Region of the Americas

Directory of Open Access Journals (Sweden)

Varley Dias Sousa

Full Text Available ABSTRACT Regulatory transparency is an imperative characteristic of a reliable National Regulatory Authority. In the region of the Americas, the process of building an open government is still fragile and fragmented across various Health Regulatory Agencies (HRAs and Regional Reference Authorities (RRAs. This study assessed the transparency status of RRAs, focusing on various medicine life-cycle documents (the Medicine Dossier, Clinical Trial Report, and Inspection Report as tools for strengthening health systems. Based on a narrative (nonsystematic review of RRA regulatory transparency, transparency status was classified as one of two types: public disclosure of information (intra-agency data and data- and work-sharing (inter-agency data. The risks/benefits of public disclosure of medicine-related information were assessed, taking into account 1 the involvement and roles of multiple stakeholders (health care professionals, regulators, industry, community, and academics and 2 the protection of commercial and personal confidential data. Inter-agency data- and work-sharing was evaluated in the context of harmonization and cooperation projects that focus on regulatory convergence. Technical and practical steps for establishing an openness directive for the pharmaceutical regulatory environment are proposed to improve and strengthen health systems in the Americas. Addressing these challenges requires leadership from entities such as the Pan American Health Organization to steer and support collaborative regional alliances that advance the development and establishment of a trustworthy regulatory environment and a sustainable public health system in the Americas, using international successful initiatives as reference and taking into account the domestic characteristics and experiences of each individual country.

Sharing regulatory data as tools for strengthening health systems in the Region of the Americas.

Science.gov (United States)

Sousa, Varley Dias; Ramalho, Pedro I; Silveira, Dâmaris

2016-05-01

Regulatory transparency is an imperative characteristic of a reliable National Regulatory Authority. In the region of the Americas, the process of building an open government is still fragile and fragmented across various Health Regulatory Agencies (HRAs) and Regional Reference Authorities (RRAs). This study assessed the transparency status of RRAs, focusing on various medicine life-cycle documents (the Medicine Dossier, Clinical Trial Report, and Inspection Report) as tools for strengthening health systems. Based on a narrative (nonsystematic) review of RRA regulatory transparency, transparency status was classified as one of two types: public disclosure of information (intra-agency data) and data- and work-sharing (inter-agency data). The risks/benefits of public disclosure of medicine-related information were assessed, taking into account 1) the involvement and roles of multiple stakeholders (health care professionals, regulators, industry, community, and academics) and 2) the protection of commercial and personal confidential data. Inter-agency data- and work-sharing was evaluated in the context of harmonization and cooperation projects that focus on regulatory convergence. Technical and practical steps for establishing an openness directive for the pharmaceutical regulatory environment are proposed to improve and strengthen health systems in the Americas. Addressing these challenges requires leadership from entities such as the Pan American Health Organization to steer and support collaborative regional alliances that advance the development and establishment of a trustworthy regulatory environment and a sustainable public health system in the Americas, using international successful initiatives as reference and taking into account the domestic characteristics and experiences of each individual country.

Systems biology and genome-wide approaches to unveil the molecular players involved in the pre-germinative metabolism: implications on seed technology traits.

Science.gov (United States)

Macovei, Anca; Pagano, Andrea; Leonetti, Paola; Carbonera, Daniela; Balestrazzi, Alma; Araújo, Susana S

2017-05-01

The pre-germinative metabolism is among the most fascinating aspects of seed biology. The early seed germination phase, or pre-germination, is characterized by rapid water uptake (imbibition), which directs a series of dynamic biochemical events. Among those are enzyme activation, DNA damage and repair, and use of reserve storage compounds, such as lipids, carbohydrates and proteins. Industrial seedling production and intensive agricultural production systems require seed stocks with high rate of synchronized germination and low dormancy. Consequently, seed dormancy, a quantitative trait related to the activation of the pre-germinative metabolism, is probably the most studied seed trait in model species and crops. Single omics, systems biology, QTLs and GWAS mapping approaches have unveiled a list of molecules and regulatory mechanisms acting at transcriptional, post-transcriptional and post-translational levels. Most of the identified candidate genes encode for regulatory proteins targeting ROS, phytohormone and primary metabolisms, corroborating the data obtained from simple molecular biology approaches. Emerging evidences show that epigenetic regulation plays a crucial role in the regulation of these mentioned processes, constituting a still unexploited strategy to modulate seed traits. The present review will provide an up-date of the current knowledge on seed pre-germinative metabolism, gathering the most relevant results from physiological, genetics, and omics studies conducted in model and crop plants. The effects exerted by the biotic and abiotic stresses and priming are also addressed. The possible implications derived from the modulation of pre-germinative metabolism will be discussed from the point of view of seed quality and technology.

Redefining plant systems biology: from cell to ecosystem

NARCIS (Netherlands)

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

2011-01-01

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

Multiple regulatory systems coordinate DNA replication with cell growth in Bacillus subtilis.

Science.gov (United States)

Murray, Heath; Koh, Alan

2014-10-01

In many bacteria the rate of DNA replication is linked with cellular physiology to ensure that genome duplication is coordinated with growth. Nutrient-mediated growth rate control of DNA replication initiation has been appreciated for decades, however the mechanism(s) that connects these cell cycle activities has eluded understanding. In order to help address this fundamental question we have investigated regulation of DNA replication in the model organism Bacillus subtilis. Contrary to the prevailing view we find that changes in DnaA protein level are not sufficient to account for nutrient-mediated growth rate control of DNA replication initiation, although this regulation does require both DnaA and the endogenous replication origin. We go on to report connections between DNA replication and several essential cellular activities required for rapid bacterial growth, including respiration, central carbon metabolism, fatty acid synthesis, phospholipid synthesis, and protein synthesis. Unexpectedly, the results indicate that multiple regulatory systems are involved in coordinating DNA replication with cell physiology, with some of the regulatory systems targeting oriC while others act in a oriC-independent manner. We propose that distinct regulatory systems are utilized to control DNA replication in response to diverse physiological and chemical changes.

Multi-level and hybrid modelling approaches for systems biology.

Science.gov (United States)

Bardini, R; Politano, G; Benso, A; Di Carlo, S

2017-01-01

During the last decades, high-throughput techniques allowed for the extraction of a huge amount of data from biological systems, unveiling more of their underling complexity. Biological systems encompass a wide range of space and time scales, functioning according to flexible hierarchies of mechanisms making an intertwined and dynamic interplay of regulations. This becomes particularly evident in processes such as ontogenesis, where regulative assets change according to process context and timing, making structural phenotype and architectural complexities emerge from a single cell, through local interactions. The information collected from biological systems are naturally organized according to the functional levels composing the system itself. In systems biology, biological information often comes from overlapping but different scientific domains, each one having its own way of representing phenomena under study. That is, the different parts of the system to be modelled may be described with different formalisms. For a model to have improved accuracy and capability for making a good knowledge base, it is good to comprise different system levels, suitably handling the relative formalisms. Models which are both multi-level and hybrid satisfy both these requirements, making a very useful tool in computational systems biology. This paper reviews some of the main contributions in this field.

Half dozen of one, six billion of the other: What can small- and large-scale molecular systems biology learn from one another?

Science.gov (United States)

Mellis, Ian A; Raj, Arjun

2015-10-01

Small-scale molecular systems biology, by which we mean the understanding of a how a few parts work together to control a particular biological process, is predicated on the assumption that cellular regulation is arranged in a circuit-like structure. Results from the omics revolution have upset this vision to varying degrees by revealing a high degree of interconnectivity, making it difficult to develop a simple, circuit-like understanding of regulatory processes. We here outline the limitations of the small-scale systems biology approach with examples from research into genetic algorithms, genetics, transcriptional network analysis, and genomics. We also discuss the difficulties associated with deriving true understanding from the analysis of large data sets and propose that the development of new, intelligent, computational tools may point to a way forward. Throughout, we intentionally oversimplify and talk about things in which we have little expertise, and it is likely that many of our arguments are wrong on one level or another. We do believe, however, that developing a true understanding via molecular systems biology will require a fundamental rethinking of our approach, and our goal is to provoke thought along these lines. © 2015 Mellis and Raj; Published by Cold Spring Harbor Laboratory Press.

Robustness: confronting lessons from physics and biology.

Science.gov (United States)

Lesne, Annick

2008-11-01

The term robustness is encountered in very different scientific fields, from engineering and control theory to dynamical systems to biology. The main question addressed herein is whether the notion of robustness and its correlates (stability, resilience, self-organisation) developed in physics are relevant to biology, or whether specific extensions and novel frameworks are required to account for the robustness properties of living systems. To clarify this issue, the different meanings covered by this unique term are discussed; it is argued that they crucially depend on the kind of perturbations that a robust system should by definition withstand. Possible mechanisms underlying robust behaviours are examined, either encountered in all natural systems (symmetries, conservation laws, dynamic stability) or specific to biological systems (feedbacks and regulatory networks). Special attention is devoted to the (sometimes counterintuitive) interrelations between robustness and noise. A distinction between dynamic selection and natural selection in the establishment of a robust behaviour is underlined. It is finally argued that nested notions of robustness, relevant to different time scales and different levels of organisation, allow one to reconcile the seemingly contradictory requirements for robustness and adaptability in living systems.

In silico discovery of transcription regulatory elements in Plasmodium falciparum

Directory of Open Access Journals (Sweden)

Le Roch Karine G

2008-02-01

Full Text Available Abstract Background With the sequence of the Plasmodium falciparum genome and several global mRNA and protein life cycle expression profiling projects now completed, elucidating the underlying networks of transcriptional control important for the progression of the parasite life cycle is highly pertinent to the development of new anti-malarials. To date, relatively little is known regarding the specific mechanisms the parasite employs to regulate gene expression at the mRNA level, with studies of the P. falciparum genome sequence having revealed few cis-regulatory elements and associated transcription factors. Although it is possible the parasite may evoke mechanisms of transcriptional control drastically different from those used by other eukaryotic organisms, the extreme AT-rich nature of P. falciparum intergenic regions (~90% AT presents significant challenges to in silico cis-regulatory element discovery. Results We have developed an algorithm called Gene Enrichment Motif Searching (GEMS that uses a hypergeometric-based scoring function and a position-weight matrix optimization routine to identify with high-confidence regulatory elements in the nucleotide-biased and repeat sequence-rich P. falciparum genome. When applied to promoter regions of genes contained within 21 co-expression gene clusters generated from P. falciparum life cycle microarray data using the semi-supervised clustering algorithm Ontology-based Pattern Identification, GEMS identified 34 putative cis-regulatory elements associated with a variety of parasite processes including sexual development, cell invasion, antigenic variation and protein biosynthesis. Among these candidates were novel motifs, as well as many of the elements for which biological experimental evidence already exists in the Plasmodium literature. To provide evidence for the biological relevance of a cell invasion-related element predicted by GEMS, reporter gene and electrophoretic mobility shift assays

Electromagnetic fields in biological systems

National Research Council Canada - National Science Library

Lin, James C

2012-01-01

"Focusing on exposure, induced fields, and absorbed energy, this volume covers the interaction of electromagnetic fields and waves with biological systems, spanning static fields to terahertz waves...

Tunable promoters in synthetic and systems biology

DEFF Research Database (Denmark)

Dehli, Tore; Solem, Christian; Jensen, Peter Ruhdal

2012-01-01

in synthetic biology. A number of tools exist to manipulate the steps in between gene sequence and functional protein in living cells, but out of these the most straight-forward approach is to alter the gene expression level by manipulating the promoter sequence. Some of the promoter tuning tools available......Synthetic and systems biologists need standardized, modular and orthogonal tools yielding predictable functions in vivo. In systems biology such tools are needed to quantitatively analyze the behavior of biological systems while the efficient engineering of artificial gene networks is central...... for accomplishing such altered gene expression levels are discussed here along with examples of their use, and ideas for new tools are described. The road ahead looks very promising for synthetic and systems biologists as tools to achieve just about anything in terms of tuning and timing multiple gene expression...

A system-level model for the microbial regulatory genome.

Science.gov (United States)

Brooks, Aaron N; Reiss, David J; Allard, Antoine; Wu, Wei-Ju; Salvanha, Diego M; Plaisier, Christopher L; Chandrasekaran, Sriram; Pan, Min; Kaur, Amardeep; Baliga, Nitin S

2014-07-15

Microbes can tailor transcriptional responses to diverse environmental challenges despite having streamlined genomes and a limited number of regulators. Here, we present data-driven models that capture the dynamic interplay of the environment and genome-encoded regulatory programs of two types of prokaryotes: Escherichia coli (a bacterium) and Halobacterium salinarum (an archaeon). The models reveal how the genome-wide distributions of cis-acting gene regulatory elements and the conditional influences of transcription factors at each of those elements encode programs for eliciting a wide array of environment-specific responses. We demonstrate how these programs partition transcriptional regulation of genes within regulons and operons to re-organize gene-gene functional associations in each environment. The models capture fitness-relevant co-regulation by different transcriptional control mechanisms acting across the entire genome, to define a generalized, system-level organizing principle for prokaryotic gene regulatory networks that goes well beyond existing paradigms of gene regulation. An online resource (http://egrin2.systemsbiology.net) has been developed to facilitate multiscale exploration of conditional gene regulation in the two prokaryotes. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

Mining biological networks from full-text articles.

Science.gov (United States)

Czarnecki, Jan; Shepherd, Adrian J

2014-01-01

The study of biological networks is playing an increasingly important role in the life sciences. Many different kinds of biological system can be modelled as networks; perhaps the most important examples are protein-protein interaction (PPI) networks, metabolic pathways, gene regulatory networks, and signalling networks. Although much useful information is easily accessible in publicly databases, a lot of extra relevant data lies scattered in numerous published papers. Hence there is a pressing need for automated text-mining methods capable of extracting such information from full-text articles. Here we present practical guidelines for constructing a text-mining pipeline from existing code and software components capable of extracting PPI networks from full-text articles. This approach can be adapted to tackle other types of biological network.

Systems biology solutions for biochemical production challenges

DEFF Research Database (Denmark)

Hansen, Anne Sofie Lærke; Lennen, Rebecca M; Sonnenschein, Nikolaus

2017-01-01

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

PeTTSy: a computational tool for perturbation analysis of complex systems biology models.

Science.gov (United States)

Domijan, Mirela; Brown, Paul E; Shulgin, Boris V; Rand, David A

2016-03-10

Over the last decade sensitivity analysis techniques have been shown to be very useful to analyse complex and high dimensional Systems Biology models. However, many of the currently available toolboxes have either used parameter sampling, been focused on a restricted set of model observables of interest, studied optimisation of a objective function, or have not dealt with multiple simultaneous model parameter changes where the changes can be permanent or temporary. Here we introduce our new, freely downloadable toolbox, PeTTSy (Perturbation Theory Toolbox for Systems). PeTTSy is a package for MATLAB which implements a wide array of techniques for the perturbation theory and sensitivity analysis of large and complex ordinary differential equation (ODE) based models. PeTTSy is a comprehensive modelling framework that introduces a number of new approaches and that fully addresses analysis of oscillatory systems. It examines sensitivity analysis of the models to perturbations of parameters, where the perturbation timing, strength, length and overall shape can be controlled by the user. This can be done in a system-global setting, namely, the user can determine how many parameters to perturb, by how much and for how long. PeTTSy also offers the user the ability to explore the effect of the parameter perturbations on many different types of outputs: period, phase (timing of peak) and model solutions. PeTTSy can be employed on a wide range of mathematical models including free-running and forced oscillators and signalling systems. To enable experimental optimisation using the Fisher Information Matrix it efficiently allows one to combine multiple variants of a model (i.e. a model with multiple experimental conditions) in order to determine the value of new experiments. It is especially useful in the analysis of large and complex models involving many variables and parameters. PeTTSy is a comprehensive tool for analysing large and complex models of regulatory and

Synthetic Biology: Engineering Living Systems from Biophysical Principles.

Science.gov (United States)

Bartley, Bryan A; Kim, Kyung; Medley, J Kyle; Sauro, Herbert M

2017-03-28

Synthetic biology was founded as a biophysical discipline that sought explanations for the origins of life from chemical and physical first principles. Modern synthetic biology has been reinvented as an engineering discipline to design new organisms as well as to better understand fundamental biological mechanisms. However, success is still largely limited to the laboratory and transformative applications of synthetic biology are still in their infancy. Here, we review six principles of living systems and how they compare and contrast with engineered systems. We cite specific examples from the synthetic biology literature that illustrate these principles and speculate on their implications for further study. To fully realize the promise of synthetic biology, we must be aware of life's unique properties. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Radiation and the regulatory landscape of neo{sup 2}-Darwinism

Energy Technology Data Exchange (ETDEWEB)

Rollo, C. David [Department of Biology, Life Sciences Building, 1280 Main St. West, Hamilton, Ont., Canada L8S 4K1 (Canada)]. E-mail: rollocd@mcmaster.ca

2006-05-11

Several recently revealed features of eukaryotic genomes were not predicted by earlier evolutionary paradigms, including the relatively small number of genes, the very large amounts of non-functional code and its quarantine in heterochromatin, the remarkable conservation of many functionally important genes across relatively enormous phylogenetic distances, and the prevalence of extra-genomic information associated with chromatin structure and histone proteins. All of these emphasize a paramount role for regulatory evolution, which is further reinforced by recent perspectives highlighting even higher-order regulation governing epigenetics and development (EVO-DEVO). Modern neo{sup 2}-Darwinism, with its emphasis on regulatory mechanisms and regulatory evolution provides new vision for understanding radiation biology, particularly because free radicals and redox states are central to many regulatory mechanisms and free radicals generated by radiation mimic and amplify endogenous signalling. This paper explores some of these aspects and their implications for low-dose radiation biology.

Manufacturing of biodrugs: need for harmonization in regulatory standards.

Science.gov (United States)

Sahoo, Niharika; Choudhury, Koel; Manchikanti, Padmavati

2009-01-01

Biodrugs (biologics) are much more complex than chemically synthesized drugs because of their structural heterogeneity and interactions within a given biologic system. The manufacturing process in the biodrug industry varies with each type of molecule and is far more elaborate and stringent due to the use of living organisms and complex substrates. Product purity and altered structural characteristics leading to potential immunogenicity have often been of concern when establishing quality and safety in the use of biodrugs. Regulatory compliance in manufacturing and commercialization of biodrugs involves quality control, quality assurance, and batch documentation. Many factors such as host cell development, cell bank establishment, cell culture, protein production, purification, analysis, formulation, storage, and handling are critical for ensuring the purity, activity, and safety of the finished product. Good Manufacturing Practice (GMP) for biodrugs has been developed in certain regions such as the EU, US, and Japan. Due to differences in manufacturing methods and systems, product-specific GMP guidelines are evolving. In general, there are variations in GMP guidelines between countries, which lead to difficulty for the manufacturers in conforming to different standards, thus entailing delays in the commercialization of biodrugs. There is a need to develop a unified regulatory guideline for biodrug manufacturing across various countries, which would be helpful in the marketing of products and trade. This review deals with the comparative framework and analysis of GMP regulation of biodrugs.

Preparation of safety regulatory requirements for new technology like digital system

International Nuclear Information System (INIS)

Ito, Juichiro; Takita, Masami

2011-01-01

The current regulatory requirements on digital instrumentation and control system have been reviewed by JNES, considering international trend discussed in DICWG (Digital Instrumentation and Control Working Group) of MDEP (Multinational Design Evaluation Program). MDEP DICWG held in OECD/NEA (Organisation for Economic Co-operation and Development/Nuclear Energy Agency) gives the opportunity to identify the convergence of applicable standards. The working group's activities include: identifying and prioritising the member countries' challenges, practices, and needs regarding standards and regulatory guidance regarding digital instrumentation and control; identifying areas of importance and needs for convergence of existing standards and guidance or development of new standards; sharing of information; and identifying common positions among the member countries for areas of particular importance and need. The DICWG drafted common positions on specific issues which are based on the existing standards, national regulatory guidance, best practices, and group inputs using an agreed upon process and framework. Five general common positions are under discussion in this fiscal year. Simplicity in Design, Software Common Cause Failures, Software Tools, Data communication, Verification and Validation throughout the life cycle of safety systems using digital computers. In addition, the technical evaluation of standards of the Japan Electric Association about digital system for safety was made to support NISA (Nuclear and Industrial Safety Agency). (author)

The aims of systems biology: between molecules and organisms.

Science.gov (United States)

Noble, D

2011-05-01

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

Systems Biology Approaches to Discerning Striated Muscle Pathologies

OpenAIRE

Mukund, Kavitha

2016-01-01

The human muscular system represents nearly 75% of the body mass and encompasses two major muscle forms- striated and smooth. Striated muscle, composed broadly of myofibers, accompanying membrane systems, cytoskeletal networks together with the metabolic and regulatory machinery, have revealed complexities in composition, structure and function. A disruption to any component within this complex system of interactions lead to disorders of the muscle, typically characterized by muscle fiber los...

A non-homogeneous dynamic Bayesian network with sequentially coupled interaction parameters for applications in systems and synthetic biology.

Science.gov (United States)

Grzegorczyk, Marco; Husmeier, Dirk

2012-07-12

An important and challenging problem in systems biology is the inference of gene regulatory networks from short non-stationary time series of transcriptional profiles. A popular approach that has been widely applied to this end is based on dynamic Bayesian networks (DBNs), although traditional homogeneous DBNs fail to model the non-stationarity and time-varying nature of the gene regulatory processes. Various authors have therefore recently proposed combining DBNs with multiple changepoint processes to obtain time varying dynamic Bayesian networks (TV-DBNs). However, TV-DBNs are not without problems. Gene expression time series are typically short, which leaves the model over-flexible, leading to over-fitting or inflated inference uncertainty. In the present paper, we introduce a Bayesian regularization scheme that addresses this difficulty. Our approach is based on the rationale that changes in gene regulatory processes appear gradually during an organism's life cycle or in response to a changing environment, and we have integrated this notion in the prior distribution of the TV-DBN parameters. We have extensively tested our regularized TV-DBN model on synthetic data, in which we have simulated short non-homogeneous time series produced from a system subject to gradual change. We have then applied our method to real-world gene expression time series, measured during the life cycle of Drosophila melanogaster, under artificially generated constant light condition in Arabidopsis thaliana, and from a synthetically designed strain of Saccharomyces cerevisiae exposed to a changing environment.

Reconstructing the regulatory circuit of cell fate determination in yeast mating response.

Science.gov (United States)

Shao, Bin; Yuan, Haiyu; Zhang, Rongfei; Wang, Xuan; Zhang, Shuwen; Ouyang, Qi; Hao, Nan; Luo, Chunxiong

2017-07-01

Massive technological advances enabled high-throughput measurements of proteomic changes in biological processes. However, retrieving biological insights from large-scale protein dynamics data remains a challenging task. Here we used the mating differentiation in yeast Saccharomyces cerevisiae as a model and developed integrated experimental and computational approaches to analyze the proteomic dynamics during the process of cell fate determination. When exposed to a high dose of mating pheromone, the yeast cell undergoes growth arrest and forms a shmoo-like morphology; however, at intermediate doses, chemotropic elongated growth is initialized. To understand the gene regulatory networks that control this differentiation switch, we employed a high-throughput microfluidic imaging system that allows real-time and simultaneous measurements of cell growth and protein expression. Using kinetic modeling of protein dynamics, we classified the stimulus-dependent changes in protein abundance into two sources: global changes due to physiological alterations and gene-specific changes. A quantitative framework was proposed to decouple gene-specific regulatory modes from the growth-dependent global modulation of protein abundance. Based on the temporal patterns of gene-specific regulation, we established the network architectures underlying distinct cell fates using a reverse engineering method and uncovered the dose-dependent rewiring of gene regulatory network during mating differentiation. Furthermore, our results suggested a potential crosstalk between the pheromone response pathway and the target of rapamycin (TOR)-regulated ribosomal biogenesis pathway, which might underlie a cell differentiation switch in yeast mating response. In summary, our modeling approach addresses the distinct impacts of the global and gene-specific regulation on the control of protein dynamics and provides new insights into the mechanisms of cell fate determination. We anticipate that our

Systems Biology: Impressions from a Newcomer Graduate Student in 2016

Science.gov (United States)

Simpson, Melanie Rae

2016-01-01

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

Conserved Transcriptional Regulatory Programs Underlying Rice and Barley Germination

Science.gov (United States)

Lin, Li; Tian, Shulan; Kaeppler, Shawn; Liu, Zongrang; An, Yong-Qiang (Charles)

2014-01-01

Germination is a biological process important to plant development and agricultural production. Barley and rice diverged 50 million years ago, but share a similar germination process. To gain insight into the conservation of their underlying gene regulatory programs, we compared transcriptomes of barley and rice at start, middle and end points of germination, and revealed that germination regulated barley and rice genes (BRs) diverged significantly in expression patterns and/or protein sequences. However, BRs with higher protein sequence similarity tended to have more conserved expression patterns. We identified and characterized 316 sets of conserved barley and rice genes (cBRs) with high similarity in both protein sequences and expression patterns, and provided a comprehensive depiction of the transcriptional regulatory program conserved in barley and rice germination at gene, pathway and systems levels. The cBRs encoded proteins involved in a variety of biological pathways and had a wide range of expression patterns. The cBRs encoding key regulatory components in signaling pathways often had diverse expression patterns. Early germination up-regulation of cell wall metabolic pathway and peroxidases, and late germination up-regulation of chromatin structure and remodeling pathways were conserved in both barley and rice. Protein sequence and expression pattern of a gene change quickly if it is not subjected to a functional constraint. Preserving germination-regulated expression patterns and protein sequences of those cBRs for 50 million years strongly suggests that the cBRs are functionally significant and equivalent in germination, and contribute to the ancient characteristics of germination preserved in barley and rice. The functional significance and equivalence of the cBR genes predicted here can serve as a foundation to further characterize their biological functions and facilitate bridging rice and barley germination research with greater confidence. PMID

Regulatory Concerns on the In-Containment Water Storage System of the Korean Next Generation Reactor

International Nuclear Information System (INIS)

Ahn, Hyung-Joon; Lee, Jae-Hun; Bang, Young-Seok; Kim, Hho-Jung

2002-01-01

The in-containment water storage system (IWSS) is a newly adopted system in the design of the Korean Next Generation Reactor (KNGR). It consists of the in-containment refueling water storage tank, holdup volume tank, and cavity flooding system (CFS). The IWSS has the function of steam condensation and heat sink for the steam release from the pressurizer and provides cooling water to the safety injection system and containment spray system in an accident condition and to the CFS in a severe accident condition. With the progress of the KNGR design, the Korea Institute of Nuclear Safety has been developing Safety and Regulatory Requirements and Guidances for safety review of the KNGR. In this paper, regarding the IWSS of the KNGR, the major contents of the General Safety Criteria, Specific Safety Requirements, Safety Regulatory Guides, and Safety Review Procedures were introduced, and the safety review items that have to be reviewed in-depth from the regulatory viewpoint were also identified

Mathematical methods in systems biology.

Science.gov (United States)

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

2016-12-01

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

Nanoscale technology in biological systems

CERN Document Server

Greco, Ralph S; Smith, R Lane

2004-01-01

Reviewing recent accomplishments in the field of nanobiology Nanoscale Technology in Biological Systems introduces the application of nanoscale matrices to human biology. It focuses on the applications of nanotechnology fabrication to biomedical devices and discusses new physical methods for cell isolation and manipulation and intracellular communication at the molecular level. It also explores the application of nanobiology to cardiovascular diseases, oncology, transplantation, and a range of related disciplines. This book build a strong background in nanotechnology and nanobiology ideal for

The development of regulatory expectations for computer-based safety systems for the UK nuclear programme

Energy Technology Data Exchange (ETDEWEB)

Hughes, P. J. [HM Nuclear Installations Inspectorate Marine Engineering Submarines Defence Nuclear Safety Regulator Serco Assurance Redgrave Court, Merton Road, Bootle L20 7HS (United Kingdom); Westwood, R.N; Mark, R. T. [FLEET HQ, Leach Building, Whale Island, Portsmouth, PO2 8BY (United Kingdom); Tapping, K. [Serco Assurance,Thomson House, Risley, Warrington, WA3 6GA (United Kingdom)

2006-07-01

The Nuclear Installations Inspectorate (NII) of the UK's Health and Safety Executive (HSE) has completed a review of their Safety Assessment Principles (SAPs) for Nuclear Installations recently. During the period of the SAPs review in 2004-2005 the designers of future UK naval reactor plant were optioneering the control and protection systems that might be implemented. Because there was insufficient regulatory guidance available in the naval sector to support this activity the Defence Nuclear Safety Regulator (DNSR) invited the NII to collaborate with the production of a guidance document that provides clarity of regulatory expectations for the production of safety cases for computer based safety systems. A key part of producing regulatory expectations was identifying the relevant extant standards and sector guidance that reflect good practice. The three principal sources of such good practice were: IAEA Safety Guide NS-G-1.1 (Software for Computer Based Systems Important to Safety in Nuclear Power Plants), European Commission consensus document (Common Position of European Nuclear Regulators for the Licensing of Safety Critical Software for Nuclear Reactors) and IEC nuclear sector standards such as IEC60880. A common understanding has been achieved between the NII and DNSR and regulatory guidance developed which will be used by both NII and DNSR in the assessment of computer-based safety systems and in the further development of more detailed joint technical assessment guidance for both regulatory organisations. (authors)

Modeling of biological intelligence for SCM system optimization.

Science.gov (United States)

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

2012-01-01

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

Modeling of Biological Intelligence for SCM System Optimization

Directory of Open Access Journals (Sweden)

Shengyong Chen

2012-01-01

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

Modeling of Biological Intelligence for SCM System Optimization

Science.gov (United States)

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

2012-01-01

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

Systems biology at work

NARCIS (Netherlands)

Martins Dos Santos, V.A.P.; Damborsky, J.

2010-01-01

In his editorial overview for the 2008 Special Issue on this topic, the late Jaroslav Stark pointedly noted that systems biology is no longer a niche pursuit, but a recognized discipline in its own right “noisily” coming of age [1]. Whilst general underlying principles and basic techniques are now

News from the Biological Stain Commission no. 12

DEFF Research Database (Denmark)

Lyon, H O

2012-01-01

In this 12(th) issue of News from the Biological Stain Commission (BSC) under the heading of Regulatory affairs, the Biological Stain Commission's International Affairs Committee presents information from the meetings of ISO/TC 212/WG 1 Quality and competence in the medical laboratory and ISO....../TC 212/WG 3 In vitro diagnostic products both held on 2 - 3 June 2010, plus information on the second plenary meeting of ISO/TC 212 Clinical laboratory testing and in vitro diagnostic test systems held on 4 June 2010. All meetings took place in Seoul, Republic of Korea. Finally, information is provided...

Digest: Ant workers might use ancient regulatory pathways to divide labor

Czech Academy of Sciences Publication Activity Database

Ernst, Ulrich R.

2017-01-01

Roč. 71, č. 1 (2017), s. 193-194 ISSN 0014-3820 Institutional support: RVO:61388963 Keywords : regulatory pathways * social insect * ants Subject RIV: EH - Ecology, Behaviour OBOR OECD: Biology (theoretical, mathematical, thermal, cryobiology, biological rhythm), Evolutionary biology Impact factor: 4.201, year: 2016

Advances in Structural Biology and the Application to Biological Filament Systems.

Science.gov (United States)

Popp, David; Koh, Fujiet; Scipion, Clement P M; Ghoshdastider, Umesh; Narita, Akihiro; Holmes, Kenneth C; Robinson, Robert C

2018-04-01

Structural biology has experienced several transformative technological advances in recent years. These include: development of extremely bright X-ray sources (microfocus synchrotron beamlines and free electron lasers) and the use of electrons to extend protein crystallography to ever decreasing crystal sizes; and an increase in the resolution attainable by cryo-electron microscopy. Here we discuss the use of these techniques in general terms and highlight their application for biological filament systems, an area that is severely underrepresented in atomic resolution structures. We assemble a model of a capped tropomyosin-actin minifilament to demonstrate the utility of combining structures determined by different techniques. Finally, we survey the methods that attempt to transform high resolution structural biology into more physiological environments, such as the cell. Together these techniques promise a compelling decade for structural biology and, more importantly, they will provide exciting discoveries in understanding the designs and purposes of biological machines. © 2018 The Authors. BioEssays Published by WILEY Periodicals, Inc.

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

Science.gov (United States)

Medina, Miguel Ángel

2013-03-01

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

Nuclear Experts Complete IAEA Follow-up Review of German Regulatory System

International Nuclear Information System (INIS)

2011-01-01

Full text: Nuclear safety experts concluded a seven-day mission to review the German Regulatory System, conducted from 4-10 September in Bonn, Stuttgart and Berlin. At the request of the Government of the Federal Republic of Germany, the International Atomic Energy Agency assembled a peer-review team of six high-level regulatory experts from six nations (Finland, France, the Netherlands, Switzerland, the UK, the US and three IAEA senior staff members) to conduct a follow-up assessment of an Integrated Regulatory Review Service (IRRS) mission conducted in 2008. This follow-up IRRS mission examined the progress in acting upon the recommendations and suggestions made during the 2008 IRRS mission and reviewed the areas of significant regulatory changes since that review at both the Federal Ministry of Environment, Nature Conservation and Nuclear Safety (BMU) and the Ministry of Environment of the federal state of Baden-Wurttemberg (UM BW). The first mission reviewed Germany's regulatory framework against IAEA Safety Standards and fostered the exchange of information and experience on safety regulation. This is a peer review based on IAEA Standards. It is not an inspection, nor an audit. The scope of the mission was limited to the safety regulation of nuclear power plants. IRRS team leader, Mr. McCree, of the US Nuclear Safety Commission (USNRC), said, ''This was an important IRRS mission, particularly given the recent Fukushima Daiichi Nuclear Power Plant accident and the related insights which underscore the importance of having an independent, credible nuclear safety regulator.'' ''The IRRS team identified several strengths of the German nuclear safety regulators, including the prompt and coordinated incident response activities of BMU and UM BW to the Fukushima accident. Some suggestions were also made to further strengthen nuclear safety regulations concerning the future work of BMU,'' he said. The review team found that important progress has been made toward

Multiple regulatory systems coordinate DNA replication with cell growth in Bacillus subtilis.

Directory of Open Access Journals (Sweden)

Heath Murray

2014-10-01

Full Text Available In many bacteria the rate of DNA replication is linked with cellular physiology to ensure that genome duplication is coordinated with growth. Nutrient-mediated growth rate control of DNA replication initiation has been appreciated for decades, however the mechanism(s that connects these cell cycle activities has eluded understanding. In order to help address this fundamental question we have investigated regulation of DNA replication in the model organism Bacillus subtilis. Contrary to the prevailing view we find that changes in DnaA protein level are not sufficient to account for nutrient-mediated growth rate control of DNA replication initiation, although this regulation does require both DnaA and the endogenous replication origin. We go on to report connections between DNA replication and several essential cellular activities required for rapid bacterial growth, including respiration, central carbon metabolism, fatty acid synthesis, phospholipid synthesis, and protein synthesis. Unexpectedly, the results indicate that multiple regulatory systems are involved in coordinating DNA replication with cell physiology, with some of the regulatory systems targeting oriC while others act in a oriC-independent manner. We propose that distinct regulatory systems are utilized to control DNA replication in response to diverse physiological and chemical changes.

Multiple Regulatory Systems Coordinate DNA Replication with Cell Growth in Bacillus subtilis

Science.gov (United States)

Murray, Heath; Koh, Alan

2014-01-01

In many bacteria the rate of DNA replication is linked with cellular physiology to ensure that genome duplication is coordinated with growth. Nutrient-mediated growth rate control of DNA replication initiation has been appreciated for decades, however the mechanism(s) that connects these cell cycle activities has eluded understanding. In order to help address this fundamental question we have investigated regulation of DNA replication in the model organism Bacillus subtilis. Contrary to the prevailing view we find that changes in DnaA protein level are not sufficient to account for nutrient-mediated growth rate control of DNA replication initiation, although this regulation does require both DnaA and the endogenous replication origin. We go on to report connections between DNA replication and several essential cellular activities required for rapid bacterial growth, including respiration, central carbon metabolism, fatty acid synthesis, phospholipid synthesis, and protein synthesis. Unexpectedly, the results indicate that multiple regulatory systems are involved in coordinating DNA replication with cell physiology, with some of the regulatory systems targeting oriC while others act in a oriC-independent manner. We propose that distinct regulatory systems are utilized to control DNA replication in response to diverse physiological and chemical changes. PMID:25340815

Plant Systems Biology (editorial)

Science.gov (United States)

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

Regulatory variation: an emerging vantage point for cancer biology.

Science.gov (United States)

Li, Luolan; Lorzadeh, Alireza; Hirst, Martin

2014-01-01

Transcriptional regulation involves complex and interdependent interactions of noncoding and coding regions of the genome with proteins that interact and modify them. Genetic variation/mutation in coding and noncoding regions of the genome can drive aberrant transcription and disease. In spite of accounting for nearly 98% of the genome comparatively little is known about the contribution of noncoding DNA elements to disease. Genome-wide association studies of complex human diseases including cancer have revealed enrichment for variants in the noncoding genome. A striking finding of recent cancer genome re-sequencing efforts has been the previously underappreciated frequency of mutations in epigenetic modifiers across a wide range of cancer types. Taken together these results point to the importance of dysregulation in transcriptional regulatory control in genesis of cancer. Powered by recent technological advancements in functional genomic profiling, exploration of normal and transformed regulatory networks will provide novel insight into the initiation and progression of cancer and open new windows to future prognostic and diagnostic tools. © 2013 Wiley Periodicals, Inc.

The nomenclature of MHC class I gene regulatory regions - the case of two different downstream regulatory elements

Czech Academy of Sciences Publication Activity Database

Hatina, J.; Jansa, Petr; Forejt, Jiří

2001-01-01

Roč. 37, 12-13 (2001), s. 799-800 ISSN 0161-5890 Institutional research plan: CEZ:AV0Z5052915 Keywords : MHC I gene regulatory elements Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.973, year: 2001

Multilayer network modeling of integrated biological systems. Comment on "Network science of biological systems at different scales: A review" by Gosak et al.

Science.gov (United States)

De Domenico, Manlio

2018-03-01

Biological systems, from a cell to the human brain, are inherently complex. A powerful representation of such systems, described by an intricate web of relationships across multiple scales, is provided by complex networks. Recently, several studies are highlighting how simple networks - obtained by aggregating or neglecting temporal or categorical description of biological data - are not able to account for the richness of information characterizing biological systems. More complex models, namely multilayer networks, are needed to account for interdependencies, often varying across time, of biological interacting units within a cell, a tissue or parts of an organism.

Recent Status of Indonesian Nuclear Regulatory System Development in Responding the Results of IRRS Mission

International Nuclear Information System (INIS)

Pramono, Y.

2016-01-01

BAPETEN as Nuclear Energy Regulatory Agency of Indonesia faces challenges in performing its tasks for assuring the safety, security, and safeguards in nuclear energy utilization through the regulatory system. Based on the recent IRRS mission to Indonesia, hosted by BAPETEN, several recommendations and suggestions shall require special attention to provide strategic action plans in following them up. Some of the recommendations include the necessity of the Government to develop and document a national policy and strategy for safety, to provide BAPETEN with human and financial resources to ensure adequate discharge of its statutory regulatory obligations, to ensure that prime responsibility of safety is assigned to the person or organization responsible for a facility or an activity through the legal framework, to ensure appropriate coordination and liaison between BAPETEN and other relevant authorities in the areas of medical application of radiation and transport of radioactive material. The suggestions cover, among others, the need of having a graded approach policy in implementing all regulatory functions, clarifying the responsibility of the individual reporting on the performance of the management system to senior management, establishing procedures for assessing the safety and appropriateness of the working environment and enhancing the implementation of self-assessments by including safety culture aspects. As part of the action plans, BAPETEN is currently drafting the national policy and strategy on nuclear and radiation safety. Furthermore, BAPETEN is revising the existing act on nuclear energy in order to assign the prime responsibility of safety to be borne by the licensees, to ensure the adequacy of its human and financial resources, and to provide clearer distinction of responsibilities between BAPETEN and other relevant authorities in the areas of medical application of radiation and transport of radioactive material. To counter the issue on

The renin-angiotensin-aldosterone system and calcium-regulatory hormones.

Science.gov (United States)

Vaidya, A; Brown, J M; Williams, J S

2015-09-01

There is increasing evidence of a clinically relevant interplay between the renin-angiotensin-aldosterone system and calcium-regulatory systems. Classically, the former is considered a key regulator of sodium and volume homeostasis, while the latter is most often associated with skeletal health. However, emerging evidence suggests an overlap in regulatory control. Hyperaldosteronism and hyperparathyroidism represent pathophysiologic conditions that may contribute to or perpetuate each other; aldosterone regulates parathyroid hormone and associates with adverse skeletal complications, and parathyroid hormone regulates aldosterone and associates with adverse cardiovascular complications. As dysregulation in both systems is linked to poor cardiovascular and skeletal health, it is increasingly important to fully characterize how they interact to more precisely understand their impact on human health and potential therapies to modulate these interactions. This review describes the known clinical interactions between these two systems including observational and interventional studies. Specifically, we review studies describing the inhibition of renin activity by calcium and vitamin D, and a potentially bidirectional and stimulatory relationship between aldosterone and parathyroid hormone. Deciphering these relationships might clarify variability in outcomes research, inform the design of future intervention studies and provide insight into the results of prior and ongoing intervention studies. However, before these opportunities can be addressed, more effort must be placed on shifting observational data to the proof of concept phase. This will require reallocation of resources to conduct interventional studies and secure the necessary talent.

Systems biology solutions for biochemical production challenges.

Science.gov (United States)

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

2017-06-01

There is an urgent need to significantly accelerate the development of microbial cell factories to produce fuels and chemicals from renewable feedstocks in order to facilitate the transition to a biobased society. Methods commonly used within the field of systems biology including omics characterization, genome-scale metabolic modeling, and adaptive laboratory evolution can be readily deployed in metabolic engineering projects. However, high performance strains usually carry tens of genetic modifications and need to operate in challenging environmental conditions. This additional complexity compared to basic science research requires pushing systems biology strategies to their limits and often spurs innovative developments that benefit fields outside metabolic engineering. Here we survey recent advanced applications of systems biology methods in engineering microbial production strains for biofuels and -chemicals. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

GPSR: A Resource for Genomics Proteomics and Systems Biology

Indian Academy of Sciences (India)

GPSR: A Resource for Genomics Proteomics and Systems Biology · Simple Calculation Programs for Biology Immunological Methods · Simple Calculation Programs for Biology Methods in Molecular Biology · Simple Calculation Programs for Biology Other Methods · PowerPoint Presentation · Slide 6 · Slide 7 · Prediction of ...

Advancing metabolic engineering through systems biology of industrial microorganisms

DEFF Research Database (Denmark)

Dai, Zongjie; Nielsen, Jens

2015-01-01

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

Analysis of deterministic cyclic gene regulatory network models with delays

CERN Document Server

Ahsen, Mehmet Eren; Niculescu, Silviu-Iulian

2015-01-01

This brief examines a deterministic, ODE-based model for gene regulatory networks (GRN) that incorporates nonlinearities and time-delayed feedback. An introductory chapter provides some insights into molecular biology and GRNs. The mathematical tools necessary for studying the GRN model are then reviewed, in particular Hill functions and Schwarzian derivatives. One chapter is devoted to the analysis of GRNs under negative feedback with time delays and a special case of a homogenous GRN is considered. Asymptotic stability analysis of GRNs under positive feedback is then considered in a separate chapter, in which conditions leading to bi-stability are derived. Graduate and advanced undergraduate students and researchers in control engineering, applied mathematics, systems biology and synthetic biology will find this brief to be a clear and concise introduction to the modeling and analysis of GRNs.

Efficient Reverse-Engineering of a Developmental Gene Regulatory Network

Science.gov (United States)

Cicin-Sain, Damjan; Ashyraliyev, Maksat; Jaeger, Johannes

2012-01-01

Understanding the complex regulatory networks underlying development and evolution of multi-cellular organisms is a major problem in biology. Computational models can be used as tools to extract the regulatory structure and dynamics of such networks from gene expression data. This approach is called reverse engineering. It has been successfully applied to many gene networks in various biological systems. However, to reconstitute the structure and non-linear dynamics of a developmental gene network in its spatial context remains a considerable challenge. Here, we address this challenge using a case study: the gap gene network involved in segment determination during early development of Drosophila melanogaster. A major problem for reverse-engineering pattern-forming networks is the significant amount of time and effort required to acquire and quantify spatial gene expression data. We have developed a simplified data processing pipeline that considerably increases the throughput of the method, but results in data of reduced accuracy compared to those previously used for gap gene network inference. We demonstrate that we can infer the correct network structure using our reduced data set, and investigate minimal data requirements for successful reverse engineering. Our results show that timing and position of expression domain boundaries are the crucial features for determining regulatory network structure from data, while it is less important to precisely measure expression levels. Based on this, we define minimal data requirements for gap gene network inference. Our results demonstrate the feasibility of reverse-engineering with much reduced experimental effort. This enables more widespread use of the method in different developmental contexts and organisms. Such systematic application of data-driven models to real-world networks has enormous potential. Only the quantitative investigation of a large number of developmental gene regulatory networks will allow us to

Dietary antioxidant synergy in chemical and biological systems.

Science.gov (United States)

Wang, Sunan; Zhu, Fan

2017-07-24

Antioxidant (AOX) synergies have been much reported in chemical ("test-tube" based assays focusing on pure chemicals), biological (tissue culture, animal and clinical models), and food systems during the past decade. Tentative synergies differ from each other due to the composition of AOX and the quantification methods. Regeneration mechanism responsible for synergy in chemical systems has been discussed. Solvent effects could contribute to the artifacts of synergy observed in the chemical models. Synergy in chemical models may hardly be relevant to biological systems that have been much less studied. Apparent discrepancies exist in understanding the molecular mechanisms in both chemical and biological systems. This review discusses diverse variables associated with AOX synergy and molecular scenarios for explanation. Future research to better utilize the synergy is suggested.

It's the System, Stupid: How Systems Biology Is Transforming.

Science.gov (United States)

2010-01-01

So far, little is known about systems biology and its potential for changing how we diagnose and treat disease. That will change soon, say the systems experts, who advise payers to begin learning now about how it could make healthcare efficient.

Seasonal allergic rhinitis and systems biology-oriented biomarker discovery

NARCIS (Netherlands)

Baars, E.W.; Nierop, A.F.M.; Savelkoul, H.F.J.

2015-01-01

There is an increasing interest in science and medicine in the systems approach. Instead of the reductionist approach that focuses on the physical and chemical properties of the individual components, systems biology aims to describe, understand, and explain from the complex biological systems

Interactive analysis of systems biology molecular expression data

Directory of Open Access Journals (Sweden)

Prabhakar Sunil

2008-02-01

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

Tracing organizing principles: Learning from the history of systems biology

DEFF Research Database (Denmark)

Green, Sara; Wolkenhauer, Olaf

2014-01-01

on this historical background in order to increase the understanding of the motivation behind the search for general principles and to clarify different epistemic aims within systems biology. We pinpoint key aspects of earlier approaches that also underlie the current practice. These are i) the focus on relational......With the emergence of systems biology, the identification of organizing principles is being highlighted as a key research aim. Researchers attempt to “reverse engineer” the functional organization of biological systems using methodologies from mathematics, engineering and computer science while...... taking advantage of data produced by new experimental techniques. While systems biology is a relatively new approach, the quest for general principles of biological organization dates back to systems theoretic approaches in early and mid-twentieth century. The aim of this paper is to draw...

FDA Regulation of Follow-On Biologics

Science.gov (United States)

2009-02-24

opening a pathway for the approval of follow-on biologics. A biologic is a preparation, such as a drug or a vaccine , that is made from living...2006 Drug Trend Report, April 2006, p. 38. C Biologic vs. Follow-on Biologic A biologic is a preparation, such as a drug or a vaccine , that is...doc9496/s1695.pdf. 19 Thijs J. Giezen, Aukje K. Mantel-Teeuwisse, and Sabine M. J. M. Straus, et al., “Safety-related regulatory actions for biologicals

An online model composition tool for system biology models.

Science.gov (United States)

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

2013-09-05

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

A primer on thermodynamic-based models for deciphering transcriptional regulatory logic.

Science.gov (United States)

Dresch, Jacqueline M; Richards, Megan; Ay, Ahmet

2013-09-01

A rigorous analysis of transcriptional regulation at the DNA level is crucial to the understanding of many biological systems. Mathematical modeling has offered researchers a new approach to understanding this central process. In particular, thermodynamic-based modeling represents the most biophysically informed approach aimed at connecting DNA level regulatory sequences to the expression of specific genes. The goal of this review is to give biologists a thorough description of the steps involved in building, analyzing, and implementing a thermodynamic-based model of transcriptional regulation. The data requirements for this modeling approach are described, the derivation for a specific regulatory region is shown, and the challenges and future directions for the quantitative modeling of gene regulation are discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

From trial to triumph: How Canada’s past financial crises helped shape a superior regulatory system

Directory of Open Access Journals (Sweden)

Lawrie Savage

2015-09-01

Full Text Available As anyone paying attention during the 2008–2009 financial crisis is aware, the Canadian financial system weathered the storm uniquely well. Exactly why Canada’s system remained so comparatively stable, while so many other foreign systems broke down, is a question that remains largely unsettled. One explanation may be that the regulatory system that emerged from a very specific history of prior crises had both prepared Canada well for such a crisis, and responded effectively as the crisis unfolded. But the very regulatory system that provided stability in recent years may also be at risk of becoming warped by its own success, with regulators so emboldened by the acclaim for their recent achievements that they overreach to ensure their track record remains unblemished in the future. The stunning collapse of a pair of western Canadian banks, a number of major Canadian trust companies and several insurance companies, as well as some other precarious near misses in the 1980s and 1990s, were a shock to the financial regulatory system, highlighting deficiencies that would be addressed with new regulations and, most notably, the creation of the Office of the Superintendent of Financial Institutions (OSFI. Canada’s centralized regulatory approach, through the OSFI and just four other major regulatory bodies, has proved both more elegant and effective than, for instance, the more complicated, more convoluted and more decentralized American financial-oversight system. But some regulated companies, insurers in particular, have long maintained that the concentration of power in Canada’s large banks has resulted in a one-size-fits-all regulatory approach that does not offer a relatively lighter burden for smaller institutions, potentially stifling growth. In other words, an over-emphasis on stability may be hampering market efficiency. Nor is there any economic evidence to shed light on whether those and other costs of regulating stability are

From Trial to Triumph: How Canada’s Past Financial Crises Helped Shape a Superior Regulatory System

Directory of Open Access Journals (Sweden)

Lawrie Savage

2014-05-01

Full Text Available As anyone paying attention during the 2008–2009 financial crisis is aware, the Canadian financial system weathered the storm uniquely well. Exactly why Canada’s system remained so comparatively stable, while so many other foreign systems broke down, is a question that remains largely unsettled. One explanation may be that the regulatory system that emerged from a very specific history of prior crises had both prepared Canada well for such a crisis, and responded effectively as the crisis unfolded. But the very regulatory system that provided stability in recent years may also be at risk of becoming warped by its own success, with regulators so emboldened by the acclaim for their recent achievements that they overreach to ensure their track record remains unblemished in the future. The stunning collapse of a pair of western Canadian banks, a number of major Canadian trust companies and several insurance companies, as well as some other precarious near misses in the 1980s and 1990s, were a shock to the financial regulatory system, highlighting deficiencies that would be addressed with new regulations and, most notably, the creation of the Office of the Superintendent of Financial Institutions (OSFI. Canada’s centralized regulatory approach, through the OSFI and just four other major regulatory bodies, has proved both more elegant and effective than, for instance, the more complicated, more convoluted and more decentralized American financial-oversight system. But some regulated companies, insurers in particular, have long maintained that the concentration of power in Canada’s large banks has resulted in a one-size-fits-all regulatory approach that does not offer a relatively lighter burden for smaller institutions, potentially stifling growth. In other words, an over-emphasis on stability may be hampering market efficiency. Nor is there any economic evidence to shed light on whether those and other costs of regulating stability are

Legitimacy challenges of intermediary gatekeeping in the Chinese internet regulatory system

NARCIS (Netherlands)

Wei, Lulu

2018-01-01

Legitimacy Challenges of Intermediary Gatekeeping in the Chinese Internet Regulatory System In the Chinese legal and political framework, in order for the government to maintain control over information posted on social media platforms, commercial internet intermediaries are assigned the role of

SEEK: a systems biology data and model management platform.

Science.gov (United States)

Wolstencroft, Katherine; Owen, Stuart; Krebs, Olga; Nguyen, Quyen; Stanford, Natalie J; Golebiewski, Martin; Weidemann, Andreas; Bittkowski, Meik; An, Lihua; Shockley, David; Snoep, Jacky L; Mueller, Wolfgang; Goble, Carole

2015-07-11

Systems biology research typically involves the integration and analysis of heterogeneous data types in order to model and predict biological processes. Researchers therefore require tools and resources to facilitate the sharing and integration of data, and for linking of data to systems biology models. There are a large number of public repositories for storing biological data of a particular type, for example transcriptomics or proteomics, and there are several model repositories. However, this silo-type storage of data and models is not conducive to systems biology investigations. Interdependencies between multiple omics datasets and between datasets and models are essential. Researchers require an environment that will allow the management and sharing of heterogeneous data and models in the context of the experiments which created them. The SEEK is a suite of tools to support the management, sharing and exploration of data and models in systems biology. The SEEK platform provides an access-controlled, web-based environment for scientists to share and exchange data and models for day-to-day collaboration and for public dissemination. A plug-in architecture allows the linking of experiments, their protocols, data, models and results in a configurable system that is available 'off the shelf'. Tools to run model simulations, plot experimental data and assist with data annotation and standardisation combine to produce a collection of resources that support analysis as well as sharing. Underlying semantic web resources additionally extract and serve SEEK metadata in RDF (Resource Description Format). SEEK RDF enables rich semantic queries, both within SEEK and between related resources in the web of Linked Open Data. The SEEK platform has been adopted by many systems biology consortia across Europe. It is a data management environment that has a low barrier of uptake and provides rich resources for collaboration. This paper provides an update on the functions and

Advancing metabolic engineering through systems biology of industrial microorganisms.

Science.gov (United States)

Dai, Zongjie; Nielsen, Jens

2015-12-01

Development of sustainable processes to produce bio-based compounds is necessary due to the severe environmental problems caused by the use of fossil resources. Metabolic engineering can facilitate the development of highly efficient cell factories to produce these compounds from renewable resources. The objective of systems biology is to gain a comprehensive and quantitative understanding of living cells and can hereby enhance our ability to characterize and predict cellular behavior. Systems biology of industrial microorganisms is therefore valuable for metabolic engineering. Here we review the application of systems biology tools for the identification of metabolic engineering targets which may lead to reduced development time for efficient cell factories. Finally, we present some perspectives of systems biology for advancing metabolic engineering further. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Regulatory Evaluation of Vaccines for Human Use.

Science.gov (United States)

Baylor, Norman W

2016-01-01

A vaccine is an immunogen, the administration of which is intended to stimulate the immune system to result in the prevention, amelioration, or therapy of any disease or infection (US Food and Drug Administration. Guidance for Industry: content and format of chemistry, manufacturing, and controls information and establishment description information for a vaccine or related product). A vaccine may be a live attenuated preparation of microorganisms, inactivated (killed) whole organisms, living irradiated cells, crude fractions, or purified immunogens, including those derived from recombinant DNA in a host cell, conjugates formed by covalent linkage of components, synthetic antigens, polynucleotides (such as the plasmid DNA vaccines), living vectored cells expressing specific heterologous immunogens, or cells pulsed with immunogen. Vaccines are highly complex products that differ from small molecule drugs because of the biological nature of the source materials such as those derived from microorganisms as well as the various cell substrates from which some are derived. Regardless of the technology used, because of their complexities, vaccines must undergo extensive characterization and testing. Special expertise and procedures are needed for their manufacture, control, and regulation. The Food and Drug Administration (FDA) is the National Regulatory Authority (NRA) in the United States responsible for assuring quality, safety, and effectiveness of all human medical products, including vaccines for human use.The Center for Biologics Evaluation and Research (CBER) within the US FDA is responsible for overseeing the regulation of therapeutic and preventative vaccines against infectious diseases. Authority for the regulation of vaccines resides in Section 351 of the Public Health Service Act and specific sections of the Federal Food, Drug, and Cosmetic Act (FD&C). Vaccines are regulated as biologics and licensed based on the demonstration of safety and effectiveness. The

The use of information systems to transform utilities and regulatory commissions: The application of geographic information systems

Energy Technology Data Exchange (ETDEWEB)

Wirick, D.W.; Montgomery, G.E.; Wagman, D.C.; Spiers, J.

1995-09-01

One technology that can assist utilities remain financially viable in competitive markets and help utilities and regulators to better serve the public is information technology. Because geography is an important part of an electric, natural gas, telecommunications, or water utility, computer-based Geographic Information Systems (GIS) and related Automated Mapping/Facilities Management systems are emerging as core technologies for managing an ever-expanding variety of formerly manual or paper-based tasks. This report focuses on GIS as an example of the types of information systems that can be used by utilities and regulatory commissions. Chapter 2 provides general information about information systems and effects of information on organizations; Chapter 3 explores the conversion of an organization to an information-based one; Chapters 4 and 5 set out GIS as an example of the use of information technologies to transform the operations of utilities and commissions; Chapter 6 describes the use of GIS and other information systems for organizational reengineering efforts; and Chapter 7 examines the regulatory treatment of information systems.

Genome Scale Modeling in Systems Biology: Algorithms and Resources

Science.gov (United States)

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

Regulatory T-Cell-Associated Cytokines in Systemic Lupus Erythematosus

Directory of Open Access Journals (Sweden)

Akiko Okamoto

2011-01-01

Full Text Available Systemic lupus erythematosus (SLE is an autoimmune disease characterized by autoantibody production, complement activation, and immune complex deposition, resulting in tissue and organ damage. An understanding of the mechanisms responsible for homeostatic control of inflammation, which involve both innate and adoptive immune responses, will enable the development of novel therapies for SLE. Regulatory T cells (Treg play critical roles in the induction of peripheral tolerance to self- and foreign antigens. Naturally occurring CD4+CD25+ Treg, which characteristically express the transcription factor forkhead box protein P3 (Foxp3, have been intensively studied because their deficiency abrogates self-tolerance and causes autoimmune disease. Moreover, regulatory cytokines such as interleukin-10 (IL-10 also play a central role in controlling inflammatory processes. This paper focuses on Tregs and Treg-associated cytokines which might regulate the pathogenesis of SLE and, hence, have clinical applications.

Experimental Systems-Biology Approaches for Clostridia-Based Bioenergy Production

Energy Technology Data Exchange (ETDEWEB)

Papoutsakis, Elefterios [Univ. of Delaware, Newark, DE (United States)

2015-04-30

This is the final project report for project "Experimental Systems-Biology Approaches for Clostridia-Based Bioenergy Production" for the funding period of 9/1/12 to 2/28/2015 (three years with a 6-month no-cost extension) OVERVIEW AND PROJECT GOALS The bottleneck of achieving higher rates and titers of toxic metabolites (such as solvents and carboxylic acids that can used as biofuels or biofuel precursors) can be overcome by engineering the stress response system. Thus, understanding and modeling the response of cells to toxic metabolites is a problem of great fundamental and practical significance. In this project, our goal is to dissect at the molecular systems level and build models (conceptual and quantitative) for the stress response of C. acetobutylicum (Cac) to its two toxic metabolites: butanol (BuOH) and butyrate (BA). Transcriptional (RNAseq and microarray based), proteomic and fluxomic data and their analysis are key requirements for this goal. Transcriptional data from mid-exponential cultures of Cac under 4 different levels of BuOH and BA stress was obtained using both microarrays (Papoutsakis group) and deep sequencing (RNAseq; Meyers and Papoutsakis groups). These two sets of data do not only serve to validate each other, but are also used for identification of stress-induced changes in transcript levels, small regulatory RNAs, & in transcriptional start sites. Quantitative proteomic data (Lee group), collected using the iTRAQ technology, are essential for understanding of protein levels and turnover under stress and the various protein-protein interactions that orchestrate the stress response. Metabolic flux changes (Antoniewicz group) of core pathways, which provide important information on the re-allocation of energy and carbon resources under metabolite stress, were examined using 13C-labelled chemicals. Omics data are integrated at different levels and scales. At the metabolic-pathway level, omics data are integrated into a 2nd generation genome

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

Energy Technology Data Exchange (ETDEWEB)

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

2009-03-01

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

Managing Regulatory Body Competence

International Nuclear Information System (INIS)

2013-01-01

In 2001, the IAEA published TECDOC 1254, which examined the way in which the recognized functions of a regulatory body for nuclear facilities results in competence needs. Using the systematic approach to training (SAT), TECDOC 1254 provided a framework for regulatory bodies for managing training and developing and their maintaining their competence. It has been successfully used by many regulators. The IAEA has also introduced a methodology and an assessment tool - Guidelines for Systematic Assessment of Regulatory Competence Needs (SARCoN) - which provides practical guidance on analysing the training and development needs of a regulatory body and, through a gap analysis, guidance on establishing competence needs and how to meet them. In 2009, the IAEA established a steering committee (supported by a bureau) with the mission to advise the IAEA on how it could best assist Member States to develop suitable competence management systems for their regulatory bodies. The committee recommended the development of a safety report on managing staff competence as an integral part of a regulatory body's management system. This Safety Report was developed in response to this request. It supersedes TECDOC 1254, broadens its application to regulatory bodies for all facilities and activities, and builds upon the experience gained through the application of TECDOC 1254 and SARCoN and the feedback received from Member States. This Safety Report applies to the management of adequate competence as needs change, and as such is equally applicable to the needs of States 'embarking' on a nuclear power programme. It also deals with the special case of building up the competence of regulatory bodies as part of the overall process of establishing an 'embarking' State's regulatory system

Functions of MicroRNAs in Cardiovascular Biology and Disease

Science.gov (United States)

Hata, Akiko

2015-01-01

In 1993, lin-4 was discovered as a critical modulator of temporal development in Caenorhabditis elegans and, most notably, as the first in the class of small, single-stranded noncoding RNAs now defined as microRNAs (miRNAs). Another eight years elapsed before miRNA expression was detected in mammalian cells. Since then, explosive advancements in the field of miRNA biology have elucidated the basic mechanism of miRNA biogenesis, regulation, and gene-regulatory function. The discovery of this new class of small RNAs has augmented the complexity of gene-regulatory programs as well as the understanding of developmental and pathological processes in the cardiovascular system. Indeed, the contributions of miRNAs in cardiovascular development and function have been widely explored, revealing the extensive role of these small regulatory RNAs in cardiovascular physiology. PMID:23157557

Harnessing diversity towards the reconstructing of large scale gene regulatory networks.

Directory of Open Access Journals (Sweden)

Takeshi Hase

Full Text Available Elucidating gene regulatory network (GRN from large scale experimental data remains a central challenge in systems biology. Recently, numerous techniques, particularly consensus driven approaches combining different algorithms, have become a potentially promising strategy to infer accurate GRNs. Here, we develop a novel consensus inference algorithm, TopkNet that can integrate multiple algorithms to infer GRNs. Comprehensive performance benchmarking on a cloud computing framework demonstrated that (i a simple strategy to combine many algorithms does not always lead to performance improvement compared to the cost of consensus and (ii TopkNet integrating only high-performance algorithms provide significant performance improvement compared to the best individual algorithms and community prediction. These results suggest that a priori determination of high-performance algorithms is a key to reconstruct an unknown regulatory network. Similarity among gene-expression datasets can be useful to determine potential optimal algorithms for reconstruction of unknown regulatory networks, i.e., if expression-data associated with known regulatory network is similar to that with unknown regulatory network, optimal algorithms determined for the known regulatory network can be repurposed to infer the unknown regulatory network. Based on this observation, we developed a quantitative measure of similarity among gene-expression datasets and demonstrated that, if similarity between the two expression datasets is high, TopkNet integrating algorithms that are optimal for known dataset perform well on the unknown dataset. The consensus framework, TopkNet, together with the similarity measure proposed in this study provides a powerful strategy towards harnessing the wisdom of the crowds in reconstruction of unknown regulatory networks.

Exploring Synthetic and Systems Biology at the University of Edinburgh.

Science.gov (United States)

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. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

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

Science.gov (United States)

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

2015-08-21

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

Noninvasive biological sensor system for detection of drunk driving.

Science.gov (United States)

Murata, Kohji; Fujita, Etsunori; Kojima, Shigeyuki; Maeda, Shinitirou; Ogura, Yumi; Kamei, Tsutomu; Tsuji, Toshio; Kaneko, Shigehiko; Yoshizumi, Masao; Suzuki, Nobutaka

2011-01-01

Systems capable of monitoring the biological condition of a driver and issuing warnings during instances of drowsiness have recently been studied. Moreover, many researchers have reported that biological signals, such as brain waves, pulsation waves, and heart rate, are different between people who have and have not consumed alcohol. Currently, we are developing a noninvasive system to detect individuals driving under the influence of alcohol by measuring biological signals. We used the frequency time series analysis to attempt to distinguish between normal and intoxicated states of a person as the basis of the sensing system.

International Nuclear and Radiation Safety Experts Conclude IAEA Peer Review of Slovenia's Regulatory System

International Nuclear Information System (INIS)

2011-01-01

Full text: An international team of senior nuclear safety experts today concluded a 10-day mission to review the regulatory framework for nuclear and radiation safety in Slovenia. The team identified good practices and gave advice on areas for future improvements. The IAEA has conveyed the team's main conclusions to the Government of Slovenia and a final report will be submitted by the end of 2011. At the request of the Slovenian Government, the IAEA assembled a team of 10 senior regulatory experts from nine nations to conduct the Integrated Regulatory Review Service (IRRS) mission involving the Slovenian Nuclear Safety Administration (SNSA). The mission is a peer review based on the IAEA Safety Standards. Andrej Stritar, Director of Slovenian Nuclear Safety Administration, stressed ''how important it is for a small country like Slovenia to tightly follow international standards in the area of nuclear safety.'' He also expressed his gratitude to the IAEA, and the countries from which team members came, for their support and for their intensive work during the last ten days. Mission Team Leader Colin Patchett, Deputy Chief Inspector from the UK's Office for Nuclear Regulation commended ''the Slovenian authorities for their commitment to nuclear and radiation safety regulation and for sharing their experience.'' The IRRS team reviewed Slovenia's current regulatory framework and all SNSA-regulated facilities and activities, as well as the regulatory implications of the TEPCO Fukushima Daiichi accident. The IRRS team identified particular strengths in the Slovenian regulatory system, including: Through its legal framework, the Slovenian government has appointed SNSA to regulate its nuclear safety program and SNSA has in place an effective process for carrying out this responsibility; and Slovenia's response to the accident at the TEPCO Fukushima Daiichi power plant has been prompt and effective. Communications with the public, development of actions for improvement

Risk management of biologicals: a regulatory and clinical perspective

NARCIS (Netherlands)

Giezen, T.J.|info:eu-repo/dai/nl/304823112

2011-01-01

Biologicals are a relatively new class of drugs and are important treatment options for a variety of chronic and/or serious conditions. Biologicals have different characteristics as compared to the traditional chemically synthesised drugs, which may result in different risk profiles and the need for

Unsolved problems in applying U.S. regulatory guides to control system equipment

International Nuclear Information System (INIS)

Stade, R.E.

1978-01-01

Two current problems encountered when designing control systems to the United States Regulatory Guide requirements are discussed. They are: 1) Level of surge voltages that should be specified when procuring solid state control and instrumentation systems and equipment. 2) The approach to be used qualifying equipment that must meet the aging requirements. (author)

Modular and coordinated expression of immune system regulatory and signaling components in the developing and adult nervous system.

Science.gov (United States)

Monzón-Sandoval, Jimena; Castillo-Morales, Atahualpa; Crampton, Sean; McKelvey, Laura; Nolan, Aoife; O'Keeffe, Gerard; Gutierrez, Humberto

2015-01-01

During development, the nervous system (NS) is assembled and sculpted through a concerted series of neurodevelopmental events orchestrated by a complex genetic programme. While neural-specific gene expression plays a critical part in this process, in recent years, a number of immune-related signaling and regulatory components have also been shown to play key physiological roles in the developing and adult NS. While the involvement of individual immune-related signaling components in neural functions may reflect their ubiquitous character, it may also reflect a much wider, as yet undescribed, genetic network of immune-related molecules acting as an intrinsic component of the neural-specific regulatory machinery that ultimately shapes the NS. In order to gain insights into the scale and wider functional organization of immune-related genetic networks in the NS, we examined the large scale pattern of expression of these genes in the brain. Our results show a highly significant correlated expression and transcriptional clustering among immune-related genes in the developing and adult brain, and this correlation was the highest in the brain when compared to muscle, liver, kidney and endothelial cells. We experimentally tested the regulatory clustering of immune system (IS) genes by using microarray expression profiling in cultures of dissociated neurons stimulated with the pro-inflammatory cytokine TNF-alpha, and found a highly significant enrichment of immune system-related genes among the resulting differentially expressed genes. Our findings strongly suggest a coherent recruitment of entire immune-related genetic regulatory modules by the neural-specific genetic programme that shapes the NS.

Bioseguridad in Mexico: Pursuing Security between Local and Global Biologies.

Science.gov (United States)

Wanderer, Emily Mannix

2017-09-01

In the aftermath of the 2009 outbreak of H1N1 influenza, scientists in Mexico sought to develop bioseguridad, that is, to protect biological life in Mexico by safely conducting research on infectious disease. Drawing on ethnographic research in laboratories and with scientists in Mexico, I look at how scientists make claims about local differences in regulations, infrastructure, bodies, and culture. The scientists working with infectious microbes sought to establish how different microbial ecologies, human immune systems, and political and regulatory systems made the risks of research different in Mexico from other countries. In developing bioseguridad, the idea of globalized biology that animates many public health projects was undermined as scientists attended to the elements of place that affected human health and safety. Scientists argued for the importance of local biologies, generating tension with global public health projects and regulations premised on the universality of biology. © 2016 by the American Anthropological Association.

Physical limits of feedback noise-suppression in biological networks

International Nuclear Information System (INIS)

Zhang, Jiajun; Yuan, Zhanjiang; Zhou, Tianshou

2009-01-01

Feedback is a ubiquitous control mechanism of biological networks, and has also been identified in a variety of regulatory systems and organisms. It has been shown that, for a given gain and with negligible intrinsic noise, negative feedback impairs noise buffering whereas positive feedback enhances noise buffering. We further investigate the influence of negative and positive feedback on noise in output signals by considering both intrinsic and extrinsic noise as well as operator noise. We find that, while maintaining the system sensitivity, either there exists a minimum of the output noise intensity corresponding to a biologically feasible feedback strength, or the output noise intensity is a monotonic function of feedback strength bounded by both biological and dynamical constraints. In both cases, feedback noise-suppression is physically limited. In other words, noise suppressed by negative or positive feedback cannot be reduced without limitation even in the case of slow transcription

Set membership experimental design for biological systems

Directory of Open Access Journals (Sweden)

Marvel Skylar W

2012-03-01

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

Selected legal and regulatory concerns affecting domestic energy transportation systems

International Nuclear Information System (INIS)

Schuller, C.R.

1979-07-01

This report provides assessments of eight legal and regulatory concerns that may affect energy material transportation in the US during the rest of the century: state authority to regulate nuclear materials transport, divestiture of petroleum pipelines from major integrated oil companies, problems affecting the natural gas transportation system, capabilities of energy transportation systems during emergencies, Federal coal pipeline legislation, ability of Federal agencies to anticipate railroad difficulties, abandonment of uneconomic railroad lines, and impact of the Panama Canal treaty upon US energy transportation

Biocellion: accelerating computer simulation of multicellular biological system models.

Science.gov (United States)

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

2014-11-01

Biological system behaviors are often the outcome of complex interactions among a large number of cells and their biotic and abiotic environment. Computational biologists attempt to understand, predict and manipulate biological system behavior through mathematical modeling and computer simulation. Discrete agent-based modeling (in combination with high-resolution grids to model the extracellular environment) is a popular approach for building biological system models. However, the computational complexity of this approach forces computational biologists to resort to coarser resolution approaches to simulate large biological systems. High-performance parallel computers have the potential to address the computing challenge, but writing efficient software for parallel computers is difficult and time-consuming. We have developed Biocellion, a high-performance software framework, to solve this computing challenge using parallel computers. To support a wide range of multicellular biological system models, Biocellion asks users to provide their model specifics by filling the function body of pre-defined model routines. Using Biocellion, modelers without parallel computing expertise can efficiently exploit parallel computers with less effort than writing sequential programs from scratch. We simulate cell sorting, microbial patterning and a bacterial system in soil aggregate as case studies. Biocellion runs on x86 compatible systems with the 64 bit Linux operating system and is freely available for academic use. Visit http://biocellion.com for additional information. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

SEEK: a systems biology data and model management platform.

NARCIS (Netherlands)

Wolstencroft, K.J.; Owen, S.; Krebs, O.; Nguyen, Q.; Stanford, N.J.; Golebiewski, M.; Weidemann, A.; Bittkowski, M.; An, L.; Shockley, D.; Snoep, J.L.; Mueller, W.; Goble, C.

2015-01-01

Background: Systems biology research typically involves the integration and analysis of heterogeneous data types in order to model and predict biological processes. Researchers therefore require tools and resources to facilitate the sharing and integration of data, and for linking of data to systems

Safety culture as a matter of regulatory control and regulatory effectiveness

International Nuclear Information System (INIS)

Camargo, C.T.M.; Furieri, E.B.; Arrieta, L.A.I.; Almeida, C.U.C.

2002-01-01

More than 15 years have passed since the term 'safety culture' was introduced by the International Nuclear Safety Advisory Group (INSAG), and although the concept now is widely accepted, practical applications and characteristics have been disseminated mainly for nuclear power plant operating organizations. There is still a lack of international guidance on the use of safety culture as a regulatory matter and on the application of the concept within regulatory organizations. This work explores the meaning of safety culture in two different fields: as an element of safety management systems it shall be a matter of regulatory control; as a complementary tool for quality management it should be used to enhance regulatory effectiveness. Brazilian recent experience on regulating nuclear power reactors provide some examples on how the concept of safety culture may influence regulatory strategies and regulatory management. (author)

MicroRNAs as regulatory elements in psoriasis

Directory of Open Access Journals (Sweden)

Liu Yuan

2016-01-01

Full Text Available Psoriasis is a chronic, autoimmune, and complex genetic disorder that affects 23% of the European population. The symptoms of Psoriatic skin are inflammation, raised and scaly lesions. microRNA, which is short, nonprotein-coding, regulatory RNAs, plays critical roles in psoriasis. microRNA participates in nearly all biological processes, such as cell differentiation, development and metabolism. Recent researches reveal that multitudinous novel microRNAs have been identified in skin. Some of these substantial novel microRNAs play as a class of posttranscriptional gene regulator in skin disease, such as psoriasis. In order to insight into microRNAs biological functions and verify microRNAs biomarker, we review diverse references about characterization, profiling and subtype of microRNAs. Here we will share our opinions about how and which microRNAs are as regulatory in psoriasis.

Tunable promoters in systems biology

DEFF Research Database (Denmark)

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

2005-01-01

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

Design Automation in Synthetic Biology.

Science.gov (United States)

Appleton, Evan; Madsen, Curtis; Roehner, Nicholas; Densmore, Douglas

2017-04-03

Design automation refers to a category of software tools for designing systems that work together in a workflow for designing, building, testing, and analyzing systems with a target behavior. In synthetic biology, these tools are called bio-design automation (BDA) tools. In this review, we discuss the BDA tools areas-specify, design, build, test, and learn-and introduce the existing software tools designed to solve problems in these areas. We then detail the functionality of some of these tools and show how they can be used together to create the desired behavior of two types of modern synthetic genetic regulatory networks. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Regulatory challenges and approaches to characterize nanomedicines and their follow-on similars.

Science.gov (United States)

Mühlebach, Stefan; Borchard, Gerrit; Yildiz, Selcan

2015-03-01

Nanomedicines are highly complex products and are the result of difficult to control manufacturing processes. Nonbiological complex drugs and their biological counterparts can comprise nanoparticles and therefore show nanomedicine characteristics. They consist of not fully known nonhomomolecular structures, and can therefore not be characterized by physicochemical means only. Also, intended copies of nanomedicines (follow-on similars) may have clinically meaningful differences, creating the regulatory challenge of how to grant a high degree of assurance for patients' benefit and safety. As an example, the current regulatory approach for marketing authorization of intended copies of nonbiological complex drugs appears inappropriate; also, a valid strategy incorporating the complexity of such systems is undefined. To demonstrate sufficient similarity and comparability, a stepwise quality, nonclinical and clinical approach is necessary to obtain market authorization for follow-on products as therapeutic alternatives, substitution and/or interchangeable products. To fill the regulatory gap, harmonized and science-based standards are needed.

The role of mechanics in biological and bio-inspired systems.

Science.gov (United States)

Egan, Paul; Sinko, Robert; LeDuc, Philip R; Keten, Sinan

2015-07-06

Natural systems frequently exploit intricate multiscale and multiphasic structures to achieve functionalities beyond those of man-made systems. Although understanding the chemical make-up of these systems is essential, the passive and active mechanics within biological systems are crucial when considering the many natural systems that achieve advanced properties, such as high strength-to-weight ratios and stimuli-responsive adaptability. Discovering how and why biological systems attain these desirable mechanical functionalities often reveals principles that inform new synthetic designs based on biological systems. Such approaches have traditionally found success in medical applications, and are now informing breakthroughs in diverse frontiers of science and engineering.

Heavy-ion microbeam system at JAEA-Takasaki for microbeam biology

International Nuclear Information System (INIS)

Funayama, Tomoo; Wada, Seiichi; Yokota, Yuichiro

2008-01-01

Research concerning cellular responses to low dose irradiation, radiation-induced bystander effects, and the biological track structure of charged particles has recently received particular attention in the field of radiation biology. Target irradiation employing a microbeam represents a useful means of advancing this research by obviating some of the disadvantages associated with the conventional irradiation strategies. The heavy-ion microbeam system at Japan Atomic Energy Agency (JAEA)-Takasaki, which was planned in 1987 and started in the early 1990's, can provide target irradiation of heavy charged particles to biological material at atmospheric pressure using a minimum beam size 5 μm in diameter. A variety of biological material has been irradiated using this microbeam system including cultured mammalian and higher plant cells, isolated fibers of mouse skeletal muscle, silkworm (Bombyx mori) embryos and larvae, Arabidopsis thaliana roots, and the nematode Caenorhabditis elegans. The system can be applied to the investigation of mechanisms within biological organisms not only in the context of radiation biology, but also in the fields of general biology such as physiology, developmental biology and neurobiology, and should help to establish and contribute to the field of 'microbeam biology'. (author)

Reconstruction of gene regulatory modules from RNA silencing of IFN-α modulators: experimental set-up and inference method.

Science.gov (United States)

Grassi, Angela; Di Camillo, Barbara; Ciccarese, Francesco; Agnusdei, Valentina; Zanovello, Paola; Amadori, Alberto; Finesso, Lorenzo; Indraccolo, Stefano; Toffolo, Gianna Maria

2016-03-12

Inference of gene regulation from expression data may help to unravel regulatory mechanisms involved in complex diseases or in the action of specific drugs. A challenging task for many researchers working in the field of systems biology is to build up an experiment with a limited budget and produce a dataset suitable to reconstruct putative regulatory modules worth of biological validation. Here, we focus on small-scale gene expression screens and we introduce a novel experimental set-up and a customized method of analysis to make inference on regulatory modules starting from genetic perturbation data, e.g. knockdown and overexpression data. To illustrate the utility of our strategy, it was applied to produce and analyze a dataset of quantitative real-time RT-PCR data, in which interferon-α (IFN-α) transcriptional response in endothelial cells is investigated by RNA silencing of two candidate IFN-α modulators, STAT1 and IFIH1. A putative regulatory module was reconstructed by our method, revealing an intriguing feed-forward loop, in which STAT1 regulates IFIH1 and they both negatively regulate IFNAR1. STAT1 regulation on IFNAR1 was object of experimental validation at the protein level. Detailed description of the experimental set-up and of the analysis procedure is reported, with the intent to be of inspiration for other scientists who want to realize similar experiments to reconstruct gene regulatory modules starting from perturbations of possible regulators. Application of our approach to the study of IFN-α transcriptional response modulators in endothelial cells has led to many interesting novel findings and new biological hypotheses worth of validation.

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

Science.gov (United States)

Ippolito, Corey; Plice, Laura; Pisanich, Greg

2003-01-01

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

Deciphering the genetic regulatory code using an inverse error control coding framework.

Energy Technology Data Exchange (ETDEWEB)

Rintoul, Mark Daniel; May, Elebeoba Eni; Brown, William Michael; Johnston, Anna Marie; Watson, Jean-Paul

2005-03-01

We have found that developing a computational framework for reconstructing error control codes for engineered data and ultimately for deciphering genetic regulatory coding sequences is a challenging and uncharted area that will require advances in computational technology for exact solutions. Although exact solutions are desired, computational approaches that yield plausible solutions would be considered sufficient as a proof of concept to the feasibility of reverse engineering error control codes and the possibility of developing a quantitative model for understanding and engineering genetic regulation. Such evidence would help move the idea of reconstructing error control codes for engineered and biological systems from the high risk high payoff realm into the highly probable high payoff domain. Additionally this work will impact biological sensor development and the ability to model and ultimately develop defense mechanisms against bioagents that can be engineered to cause catastrophic damage. Understanding how biological organisms are able to communicate their genetic message efficiently in the presence of noise can improve our current communication protocols, a continuing research interest. Towards this end, project goals include: (1) Develop parameter estimation methods for n for block codes and for n, k, and m for convolutional codes. Use methods to determine error control (EC) code parameters for gene regulatory sequence. (2) Develop an evolutionary computing computational framework for near-optimal solutions to the algebraic code reconstruction problem. Method will be tested on engineered and biological sequences.

Collaborative Systems Biology Projects for the Military Medical Community.

Science.gov (United States)

Zalatoris, Jeffrey J; Scheerer, Julia B; Lebeda, Frank J

2017-09-01

This pilot study was conducted to examine, for the first time, the ongoing systems biology research and development projects within the laboratories and centers of the U.S. Army Medical Research and Materiel Command (USAMRMC). The analysis has provided an understanding of the breadth of systems biology activities, resources, and collaborations across all USAMRMC subordinate laboratories. The Systems Biology Collaboration Center at USAMRMC issued a survey regarding systems biology research projects to the eight U.S.-based USAMRMC laboratories and centers in August 2016. This survey included a data call worksheet to gather self-identified project and programmatic information. The general topics focused on the investigators and their projects, on the project's research areas, on omics and other large data types being collected and stored, on the analytical or computational tools being used, and on identifying intramural (i.e., USAMRMC) and extramural collaborations. Among seven of the eight laboratories, 62 unique systems biology studies were funded and active during the final quarter of fiscal year 2016. Of 29 preselected medical Research Task Areas, 20 were associated with these studies, some of which were applicable to two or more Research Task Areas. Overall, studies were categorized among six general types of objectives: biological mechanisms of disease, risk of/susceptibility to injury or disease, innate mechanisms of healing, diagnostic and prognostic biomarkers, and host/patient responses to vaccines, and therapeutic strategies including host responses to therapies. We identified eight types of omics studies and four types of study subjects. Studies were categorized on a scale of increasing complexity from single study subject/single omics technology studies (23/62) to studies integrating results across two study subject types and two or more omics technologies (13/62). Investigators at seven USAMRMC laboratories had collaborations with systems biology experts

Systems Biology Graphical Notation: Entity Relationship language Level 1 Version 2

Directory of Open Access Journals (Sweden)

Sorokin Anatoly

2015-06-01

Full Text Available The Systems Biological Graphical Notation (SBGN is an international community effort for standardized graphical representations of biological pathways and networks. The goal of SBGN is to provide unambiguous pathway and network maps for readers with different scientific backgrounds as well as to support efficient and accurate exchange of biological knowledge between different research communities, industry, and other players in systems biology. Three SBGN languages, Process Description (PD, Entity Relationship (ER and Activity Flow (AF, allow for the representation of different aspects of biological and biochemical systems at different levels of detail.

Impact of systems biology on metabolic engineering of Saccharomyces cerevisiae

DEFF Research Database (Denmark)

Nielsen, Jens; Jewett, Michael Christopher

2008-01-01

in the industrial application of this yeast. Developments in genomics and high-throughput systems biology tools are enhancing one's ability to rapidly characterize cellular behaviour, which is valuable in the field of metabolic engineering where strain characterization is often the bottleneck in strain development...... programmes. Here, the impact of systems biology on metabolic engineering is reviewed and perspectives on the role of systems biology in the design of cell factories are given....

EURASIP journal on bioinformatics & systems biology

National Research Council Canada - National Science Library

2006-01-01

"The overall aim of "EURASIP Journal on Bioinformatics and Systems Biology" is to publish research results related to signal processing and bioinformatics theories and techniques relevant to a wide...

Agent-Based Modeling in Molecular Systems Biology.

Science.gov (United States)

Soheilypour, Mohammad; Mofrad, Mohammad R K

2018-06-08

Molecular systems orchestrating the biology of the cell typically involve a complex web of interactions among various components and span a vast range of spatial and temporal scales. Computational methods have advanced our understanding of the behavior of molecular systems by enabling us to test assumptions and hypotheses, explore the effect of different parameters on the outcome, and eventually guide experiments. While several different mathematical and computational methods are developed to study molecular systems at different spatiotemporal scales, there is still a need for methods that bridge the gap between spatially-detailed and computationally-efficient approaches. In this review, we summarize the capabilities of agent-based modeling (ABM) as an emerging molecular systems biology technique that provides researchers with a new tool in exploring the dynamics of molecular systems/pathways in health and disease. © 2018 WILEY Periodicals, Inc.

Marine biological data and information management system

Digital Repository Service at National Institute of Oceanography (India)

Sarupria, J.S.

Indian National Oceanographic Data Centre (INODC) is engaged in developing a marine biological data and information management system (BIODIMS). This system will contain the information on zooplankton in the water column, zoobenthic biomass...

Predictive modelling of complex agronomic and biological systems.

Science.gov (United States)

Keurentjes, Joost J B; Molenaar, Jaap; Zwaan, Bas J

2013-09-01

Biological systems are tremendously complex in their functioning and regulation. Studying the multifaceted behaviour and describing the performance of such complexity has challenged the scientific community for years. The reduction of real-world intricacy into simple descriptive models has therefore convinced many researchers of the usefulness of introducing mathematics into biological sciences. Predictive modelling takes such an approach another step further in that it takes advantage of existing knowledge to project the performance of a system in alternating scenarios. The ever growing amounts of available data generated by assessing biological systems at increasingly higher detail provide unique opportunities for future modelling and experiment design. Here we aim to provide an overview of the progress made in modelling over time and the currently prevalent approaches for iterative modelling cycles in modern biology. We will further argue for the importance of versatility in modelling approaches, including parameter estimation, model reduction and network reconstruction. Finally, we will discuss the difficulties in overcoming the mathematical interpretation of in vivo complexity and address some of the future challenges lying ahead. © 2013 John Wiley & Sons Ltd.

Modular arrangement of regulatory RNA elements.

Science.gov (United States)

Roßmanith, Johanna; Narberhaus, Franz

2017-03-04

Due to their simple architecture and control mechanism, regulatory RNA modules are attractive building blocks in synthetic biology. This is especially true for riboswitches, which are natural ligand-binding regulators of gene expression. The discovery of various tandem riboswitches inspired the design of combined RNA modules with activities not yet found in nature. Riboswitches were placed in tandem or in combination with a ribozyme or temperature-responsive RNA thermometer resulting in new functionalities. Here, we compare natural examples of tandem riboswitches with recently designed artificial RNA regulators suggesting substantial modularity of regulatory RNA elements. Challenges associated with modular RNA design are discussed.

Applications of biological tools or biomarkers in aquatic biota: A case study of the Tamar estuary, South West England.

Science.gov (United States)