A pedagogical walkthrough of computational modeling and simulation of Wnt signaling pathway using static causal models in MATLAB

OpenAIRE

Sinha, Shriprakash

2016-01-01

Simulation study in systems biology involving computational experiments dealing with Wnt signaling pathways abound in literature but often lack a pedagogical perspective that might ease the understanding of beginner students and researchers in transition, who intend to work on the modeling of the pathway. This paucity might happen due to restrictive business policies which enforce an unwanted embargo on the sharing of important scientific knowledge. A tutorial introduction to computational mo...

Dehydrogenation of aromatic molecules under a scanning tunneling microscope: pathways and inelastic spectroscopy simulations.

Science.gov (United States)

Lesnard, Hervé; Bocquet, Marie-Laure; Lorente, Nicolas

2007-04-11

We have performed a theoretical study on the dehydrogenation of benzene and pyridine molecules on Cu(100) induced by a scanning tunneling microscope (STM). Density functional theory calculations have been used to characterize benzene, pyridine, and different dehydrogenation products. The adiabatic pathways for single and double dehydrogenation have been evaluated with the nudge elastic band method. After identification of the transition states, the analysis of the electronic structure along the reaction pathway yields interesting information on the electronic process that leads to H-scission. The adiabatic barriers show that the formation of double dehydrogenated fragments is difficult and probably beyond reach under the actual experimental conditions. However, nonadiabatic processes cannot be ruled out. Hence, in order to identify the final dehydrogenation products, the inelastic spectra are simulated and compared with the experimental ones. We can then assign phenyl (C6H5) and alpha-pyridil (alpha-C5H4N) as the STM-induced dehydrogenation products of benzene and pyridine, respectively. Our simulations permit us to understand why phenyl, pyridine, and alpha-pyridil present tunneling-active C-H stretch modes in opposition to benzene.

Photodegradation of malachite green under simulated and natural irradiation: kinetics, products, and pathways.

Science.gov (United States)

Yong, Li; Zhanqi, Gao; Yuefei, Ji; Xiaobin, Hu; Cheng, Sun; Shaogui, Yang; Lianhong, Wang; Qingeng, Wang; Die, Fang

2015-03-21

In this work photodegradation rates and pathways of malachite green were studied under simulated and solar irradiation with the goal of assessing the potential of photolysis as a removal mechanism in real aquatic environment. Factors influencing the photodegradation process were investigated, including pH, humic acid, Fe(2+), Ca(2+), HCO3(-), and NO3(-), of which favorable conditions were optimized by the orthogonal array design under simulated sunlight irradiation in the presence of dissolved oxygen. The degradation processes of malachite green conformed to pseudo first-order kinetics and their degradation rate constants were between 0.0062 and 0.4012 h(-1). Under solar irradiation, the decolorization efficiency of most tests can reach almost 100%, and relatively thorough mineralization could be observed. Forty degradation products were detected by liquid chromatography-mass spectrometry, and thirteen small molecular products were identified by gas chromatography-mass spectrometry. Based on the analyses of the degradation products and calculation of the frontier electron density, the pathways were proposed: decomposition of conjugated structure, N-demethylation reactions, hydroxyl addition reactions, the removal of benzene ring, and the ring-opening reaction. This study has provided a reference, both for photodegradation of malachite green and future safety applications and predictions of decontamination of related triphenylmethane dyes under real conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

Modeling of coupled differential equations for cellular chemical signaling pathways: Implications for assay protocols utilized in cellular engineering.

Science.gov (United States)

O'Clock, George D

2016-08-01

Cellular engineering involves modification and control of cell properties, and requires an understanding of fundamentals and mechanisms of action for cellular derived product development. One of the keys to success in cellular engineering involves the quality and validity of results obtained from cell chemical signaling pathway assays. The accuracy of the assay data cannot be verified or assured if the effect of positive feedback, nonlinearities, and interrelationships between cell chemical signaling pathway elements are not understood, modeled, and simulated. Nonlinearities and positive feedback in the cell chemical signaling pathway can produce significant aberrations in assay data collection. Simulating the pathway can reveal potential instability problems that will affect assay results. A simulation, using an electrical analog for the coupled differential equations representing each segment of the pathway, provides an excellent tool for assay validation purposes. With this approach, voltages represent pathway enzyme concentrations and operational amplifier feedback resistance and input resistance values determine pathway gain and rate constants. The understanding provided by pathway modeling and simulation is strategically important in order to establish experimental controls for assay protocol structure, time frames specified between assays, and assay concentration variation limits; to ensure accuracy and reproducibility of results.

Simulation and estimation of gene number in a biological pathway using almost complete saturation mutagenesis screening of haploid mouse cells.

Science.gov (United States)

Tokunaga, Masahiro; Kokubu, Chikara; Maeda, Yusuke; Sese, Jun; Horie, Kyoji; Sugimoto, Nakaba; Kinoshita, Taroh; Yusa, Kosuke; Takeda, Junji

2014-11-24

Genome-wide saturation mutagenesis and subsequent phenotype-driven screening has been central to a comprehensive understanding of complex biological processes in classical model organisms such as flies, nematodes, and plants. The degree of "saturation" (i.e., the fraction of possible target genes identified) has been shown to be a critical parameter in determining all relevant genes involved in a biological function, without prior knowledge of their products. In mammalian model systems, however, the relatively large scale and labor intensity of experiments have hampered the achievement of actual saturation mutagenesis, especially for recessive traits that require biallelic mutations to manifest detectable phenotypes. By exploiting the recently established haploid mouse embryonic stem cells (ESCs), we present an implementation of almost complete saturation mutagenesis in a mammalian system. The haploid ESCs were mutagenized with the chemical mutagen N-ethyl-N-nitrosourea (ENU) and processed for the screening of mutants defective in various steps of the glycosylphosphatidylinositol-anchor biosynthetic pathway. The resulting 114 independent mutant clones were characterized by a functional complementation assay, and were shown to be defective in any of 20 genes among all 22 known genes essential for this well-characterized pathway. Ten mutants were further validated by whole-exome sequencing. The predominant generation of single-nucleotide substitutions by ENU resulted in a gene mutation rate proportional to the length of the coding sequence, which facilitated the experimental design of saturation mutagenesis screening with the aid of computational simulation. Our study enables mammalian saturation mutagenesis to become a realistic proposition. Computational simulation, combined with a pilot mutagenesis experiment, could serve as a tool for the estimation of the number of genes essential for biological processes such as drug target pathways when a positive selection of

Electron-cloud simulation results for the SPS and recent results for the LHC

International Nuclear Information System (INIS)

Furman, M.A.; Pivi, M.T.F.

2002-01-01

We present an update of computer simulation results for some features of the electron cloud at the Large Hadron Collider (LHC) and recent simulation results for the Super Proton Synchrotron (SPS). We focus on the sensitivity of the power deposition on the LHC beam screen to the emitted electron spectrum, which we study by means of a refined secondary electron (SE) emission model recently included in our simulation code

Comparison Of Simulation Results When Using Two Different Methods For Mold Creation In Moldflow Simulation

Directory of Open Access Journals (Sweden)

Kaushikbhai C. Parmar

2017-04-01

Full Text Available Simulation gives different results when using different methods for the same simulation. Autodesk Moldflow Simulation software provide two different facilities for creating mold for the simulation of injection molding process. Mold can be created inside the Moldflow or it can be imported as CAD file. The aim of this paper is to study the difference in the simulation results like mold temperature part temperature deflection in different direction time for the simulation and coolant temperature for this two different methods.

Oxygen diffusion pathways in a cofactor-independent dioxygenase

Science.gov (United States)

Di Russo, Natali V.; Condurso, Heather L.; Li, Kunhua; Bruner, Steven D.; Roitberg, Adrian E.

2015-01-01

Molecular oxygen plays an important role in a wide variety of enzymatic reactions. Through recent research efforts combining computational and experimental methods a new view of O2 diffusion is emerging, where specific channels guide O2 to the active site. The focus of this work is DpgC, a cofactor-independent oxygenase. Molecular dynamics simulations, together with mutagenesis experiments and xenon-binding data, reveal that O2 reaches the active site of this enzyme using three main pathways and four different access points. These pathways connect a series of dynamic hydrophobic pockets, concentrating O2 at a specific face of the enzyme substrate. Extensive molecular dynamics simulations provide information about which pathways are more frequently used. This data is consistent with the results of kinetic measurements on mutants and is difficult to obtain using computational cavity-location methods. Taken together, our results reveal that although DpgC is rare in its ability of activating O2 in the absence of cofactors or metals, the way O2 reaches the active site is similar to that reported for other O2-using proteins: multiple access channels are available, and the architecture of the pathway network can provide regio- and stereoselectivity. Our results point to the existence of common themes in O2 access that are conserved among very different types of proteins. PMID:26508997

Toward a quantitative understanding of the Wnt/ β -catenin pathway through simulation and experiment

KAUST Repository

Lloyd-Lewis, Bethan

2013-03-29

Wnt signaling regulates cell survival, proliferation, and differentiation throughout development and is aberrantly regulated in cancer. The pathway is activated when Wnt ligands bind to specific receptors on the cell surface, resulting in the stabilization and nuclear accumulation of the transcriptional co-activator β-catenin. Mathematical and computational models have been used to study the spatial and temporal regulation of the Wnt/β-catenin pathway and to investigate the functional impact of mutations in key components. Such models range in complexity, from time-dependent, ordinary differential equations that describe the biochemical interactions between key pathway components within a single cell, to complex, multiscale models that incorporate the role of the Wnt/β-catenin pathway target genes in tissue homeostasis and carcinogenesis. This review aims to summarize recent progress in mathematical modeling of the Wnt pathway and to highlight new biological results that could form the basis for future theoretical investigations designed to increase the utility of theoretical models of Wnt signaling in the biomedical arena. © 2013 Wiley Periodicals, Inc.

Pathway Distiller - multisource biological pathway consolidation.

Science.gov (United States)

Doderer, Mark S; Anguiano, Zachry; Suresh, Uthra; Dashnamoorthy, Ravi; Bishop, Alexander J R; Chen, Yidong

2012-01-01

One method to understand and evaluate an experiment that produces a large set of genes, such as a gene expression microarray analysis, is to identify overrepresentation or enrichment for biological pathways. Because pathways are able to functionally describe the set of genes, much effort has been made to collect curated biological pathways into publicly accessible databases. When combining disparate databases, highly related or redundant pathways exist, making their consolidation into pathway concepts essential. This will facilitate unbiased, comprehensive yet streamlined analysis of experiments that result in large gene sets. After gene set enrichment finds representative pathways for large gene sets, pathways are consolidated into representative pathway concepts. Three complementary, but different methods of pathway consolidation are explored. Enrichment Consolidation combines the set of the pathways enriched for the signature gene list through iterative combining of enriched pathways with other pathways with similar signature gene sets; Weighted Consolidation utilizes a Protein-Protein Interaction network based gene-weighting approach that finds clusters of both enriched and non-enriched pathways limited to the experiments' resultant gene list; and finally the de novo Consolidation method uses several measurements of pathway similarity, that finds static pathway clusters independent of any given experiment. We demonstrate that the three consolidation methods provide unified yet different functional insights of a resultant gene set derived from a genome-wide profiling experiment. Results from the methods are presented, demonstrating their applications in biological studies and comparing with a pathway web-based framework that also combines several pathway databases. Additionally a web-based consolidation framework that encompasses all three methods discussed in this paper, Pathway Distiller (http://cbbiweb.uthscsa.edu/PathwayDistiller), is established to allow

MUSICA MetOp/IASI {H2O,δD} pair retrieval simulations for validating tropospheric moisture pathways in atmospheric models

Science.gov (United States)

Schneider, Matthias; Borger, Christian; Wiegele, Andreas; Hase, Frank; García, Omaira E.; Sepúlveda, Eliezer; Werner, Martin

2017-02-01

The project MUSICA (MUlti-platform remote Sensing of Isotopologues for investigating the Cycle of Atmospheric water) has shown that the sensor IASI aboard the satellite MetOp can measure the free tropospheric {H2O,δD} pair distribution twice per day on a quasi-global scale. Such data are very promising for investigating tropospheric moisture pathways, however, the complex data characteristics compromise their usage in the context of model evaluation studies. Here we present a tool that allows for simulating MUSICA MetOp/IASI {H2O,δD} pair remote sensing data for a given model atmosphere, thereby creating model data that have the remote sensing data characteristics assimilated. This model data can then be compared to the MUSICA data. The retrieval simulation method is based on the physical principles of radiative transfer and we show that the uncertainty of the simulations is within the uncertainty of the MUSICA MetOp/IASI products, i.e. the retrieval simulations are reliable enough. We demonstrate the working principle of the simulator by applying it to ECHAM5-wiso model data. The few case studies clearly reveal the large potential of the MUSICA MetOp/IASI {H2O,δD} data pairs for evaluating modelled moisture pathways. The tool is made freely available in form of MATLAB and Python routines and can be easily connected to any atmospheric water vapour isotopologue model.

Pathways for School Finance in California. Technical Appendix

Science.gov (United States)

Rose, Heather; Sonstelie, Jon; Weston, Margaret

2010-01-01

This is a technical appendix for the report, "Pathways for School Finance in California" (ED515651). "Pathways for School Finance in California" simulates alternatives to California's current school finance system. This appendix provides more information about the revenues used in those simulations. The first section describes…

Discrete event simulations for glycolysis pathway and energy balance

NARCIS (Netherlands)

Zwieten, van D.A.J.; Rooda, J.E.; Armbruster, H.D.; Nagy, J.D.

2010-01-01

In this report, the biological network of the glycolysis pathway has been modeled using discrete event models (DEMs). The most important feature of this pathway is that energy is released. To create a stable steady-state system an energy molecule equilibrating enzyme and metabolic reactions have

Simulation Results of Double Forward Converter

Directory of Open Access Journals (Sweden)

P. Vijaya KUMAR

2009-12-01

Full Text Available This work aims to find a better forward converter for DC to DC conversion.Simulation of double forward converter in SMPS system is discussed in this paper. Aforward converter with RCD snubber to synchronous rectifier and/or to current doubleris also discussed. The evolution of the forward converter is first reviewed in a tutorialfashion. Performance parameters are discussed including operating principle, voltageconversion ratio, efficiency, device stress, small-signal dynamics, noise and EMI. Itscircuit operation and its performance characteristics of the forward converter with RCDsnubber and double forward converter are described and the simulation results arepresented.

Computational fluid dynamics simulations and validations of results

CSIR Research Space (South Africa)

Sitek, MA

2013-09-01

Full Text Available Wind flow influence on a high-rise building is analyzed. The research covers full-scale tests, wind-tunnel experiments and numerical simulations. In the present paper computational model used in simulations is described and the results, which were...

Presenting simulation results in a nested loop plot.

Science.gov (United States)

Rücker, Gerta; Schwarzer, Guido

2014-12-12

Statisticians investigate new methods in simulations to evaluate their properties for future real data applications. Results are often presented in a number of figures, e.g., Trellis plots. We had conducted a simulation study on six statistical methods for estimating the treatment effect in binary outcome meta-analyses, where selection bias (e.g., publication bias) was suspected because of apparent funnel plot asymmetry. We varied five simulation parameters: true treatment effect, extent of selection, event proportion in control group, heterogeneity parameter, and number of studies in meta-analysis. In combination, this yielded a total number of 768 scenarios. To present all results using Trellis plots, 12 figures were needed. Choosing bias as criterion of interest, we present a 'nested loop plot', a diagram type that aims to have all simulation results in one plot. The idea was to bring all scenarios into a lexicographical order and arrange them consecutively on the horizontal axis of a plot, whereas the treatment effect estimate is presented on the vertical axis. The plot illustrates how parameters simultaneously influenced the estimate. It can be combined with a Trellis plot in a so-called hybrid plot. Nested loop plots may also be applied to other criteria such as the variance of estimation. The nested loop plot, similar to a time series graph, summarizes all information about the results of a simulation study with respect to a chosen criterion in one picture and provides a suitable alternative or an addition to Trellis plots.

Milestone M4900: Simulant Mixing Analytical Results

Energy Technology Data Exchange (ETDEWEB)

Kaplan, D.I.

2001-07-26

This report addresses Milestone M4900, ''Simulant Mixing Sample Analysis Results,'' and contains the data generated during the ''Mixing of Process Heels, Process Solutions, and Recycle Streams: Small-Scale Simulant'' task. The Task Technical and Quality Assurance Plan for this task is BNF-003-98-0079A. A report with a narrative description and discussion of the data will be issued separately.

Force and Stress along Simulated Dissociation Pathways of Cucurbituril-Guest Systems.

Science.gov (United States)

Velez-Vega, Camilo; Gilson, Michael K

2012-03-13

The field of host-guest chemistry provides computationally tractable yet informative model systems for biomolecular recognition. We applied molecular dynamics simulations to study the forces and mechanical stresses associated with forced dissociation of aqueous cucurbituril-guest complexes with high binding affinities. First, the unbinding transitions were modeled with constant velocity pulling (steered dynamics) and a soft spring constant, to model atomic force microscopy (AFM) experiments. The computed length-force profiles yield rupture forces in good agreement with available measurements. We also used steered dynamics with high spring constants to generate paths characterized by a tight control over the specified pulling distance; these paths were then equilibrated via umbrella sampling simulations and used to compute time-averaged mechanical stresses along the dissociation pathways. The stress calculations proved to be informative regarding the key interactions determining the length-force profiles and rupture forces. In particular, the unbinding transition of one complex is found to be a stepwise process, which is initially dominated by electrostatic interactions between the guest's ammoniums and the host's carbonyl groups, and subsequently limited by the extraction of the guest's bulky bicyclooctane moiety; the latter step requires some bond stretching at the cucurbituril's extraction portal. Conversely, the dissociation of a second complex with a more slender guest is mainly driven by successive electrostatic interactions between the different guest's ammoniums and the host's carbonyl groups. The calculations also provide information on the origins of thermodynamic irreversibilities in these forced dissociation processes.

Comparative study on gene set and pathway topology-based enrichment methods.

Science.gov (United States)

Bayerlová, Michaela; Jung, Klaus; Kramer, Frank; Klemm, Florian; Bleckmann, Annalen; Beißbarth, Tim

2015-10-22

Enrichment analysis is a popular approach to identify pathways or sets of genes which are significantly enriched in the context of differentially expressed genes. The traditional gene set enrichment approach considers a pathway as a simple gene list disregarding any knowledge of gene or protein interactions. In contrast, the new group of so called pathway topology-based methods integrates the topological structure of a pathway into the analysis. We comparatively investigated gene set and pathway topology-based enrichment approaches, considering three gene set and four topological methods. These methods were compared in two extensive simulation studies and on a benchmark of 36 real datasets, providing the same pathway input data for all methods. In the benchmark data analysis both types of methods showed a comparable ability to detect enriched pathways. The first simulation study was conducted with KEGG pathways, which showed considerable gene overlaps between each other. In this study with original KEGG pathways, none of the topology-based methods outperformed the gene set approach. Therefore, a second simulation study was performed on non-overlapping pathways created by unique gene IDs. Here, methods accounting for pathway topology reached higher accuracy than the gene set methods, however their sensitivity was lower. We conducted one of the first comprehensive comparative works on evaluating gene set against pathway topology-based enrichment methods. The topological methods showed better performance in the simulation scenarios with non-overlapping pathways, however, they were not conclusively better in the other scenarios. This suggests that simple gene set approach might be sufficient to detect an enriched pathway under realistic circumstances. Nevertheless, more extensive studies and further benchmark data are needed to systematically evaluate these methods and to assess what gain and cost pathway topology information introduces into enrichment analysis. Both

Using relational databases to collect and store discrete-event simulation results

DEFF Research Database (Denmark)

Poderys, Justas; Soler, José

2016-01-01

, export the results to a data carrier file and then process the results stored in a file using the data processing software. In this work, we propose to save the simulation results directly from a simulation tool to a computer database. We implemented a link between the discrete-even simulation tool...... and the database and performed performance evaluation of 3 different open-source database systems. We show, that with a right choice of a database system, simulation results can be collected and exported up to 2.67 times faster, and use 1.78 times less disk space when compared to using simulation software built...

Titan's organic chemistry: Results of simulation experiments

Science.gov (United States)

Sagan, Carl; Thompson, W. Reid; Khare, Bishun N.

1992-01-01

Recent low pressure continuous low plasma discharge simulations of the auroral electron driven organic chemistry in Titan's mesosphere are reviewed. These simulations yielded results in good accord with Voyager observations of gas phase organic species. Optical constants of the brownish solid tholins produced in similar experiments are in good accord with Voyager observations of the Titan haze. Titan tholins are rich in prebiotic organic constituents; the Huygens entry probe may shed light on some of the processes that led to the origin of life on Earth.

Normal mode-guided transition pathway generation in proteins.

Directory of Open Access Journals (Sweden)

Byung Ho Lee

Full Text Available The biological function of proteins is closely related to its structural motion. For instance, structurally misfolded proteins do not function properly. Although we are able to experimentally obtain structural information on proteins, it is still challenging to capture their dynamics, such as transition processes. Therefore, we need a simulation method to predict the transition pathways of a protein in order to understand and study large functional deformations. Here, we present a new simulation method called normal mode-guided elastic network interpolation (NGENI that performs normal modes analysis iteratively to predict transition pathways of proteins. To be more specific, NGENI obtains displacement vectors that determine intermediate structures by interpolating the distance between two end-point conformations, similar to a morphing method called elastic network interpolation. However, the displacement vector is regarded as a linear combination of the normal mode vectors of each intermediate structure, in order to enhance the physical sense of the proposed pathways. As a result, we can generate more reasonable transition pathways geometrically and thermodynamically. By using not only all normal modes, but also in part using only the lowest normal modes, NGENI can still generate reasonable pathways for large deformations in proteins. This study shows that global protein transitions are dominated by collective motion, which means that a few lowest normal modes play an important role in this process. NGENI has considerable merit in terms of computational cost because it is possible to generate transition pathways by partial degrees of freedom, while conventional methods are not capable of this.

Pathways to Performance: An Examination of Entry Pathway and First-Year University Results

Science.gov (United States)

Diamond, Mark R.; O'Brien-Malone, Angela

2018-01-01

Although diversity at universities has increased dramatically over the past 150 years, many groups are still under-represented relative to their proportion in the general population. Initiatives to improve diversity have included the increased use of entry pathways other than direct admission from secondary school. As admissions via these…

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.

Metabolic pathways for the whole community.

Science.gov (United States)

Hanson, Niels W; Konwar, Kishori M; Hawley, Alyse K; Altman, Tomer; Karp, Peter D; Hallam, Steven J

2014-07-22

A convergence of high-throughput sequencing and computational power is transforming biology into information science. Despite these technological advances, converting bits and bytes of sequence information into meaningful insights remains a challenging enterprise. Biological systems operate on multiple hierarchical levels from genomes to biomes. Holistic understanding of biological systems requires agile software tools that permit comparative analyses across multiple information levels (DNA, RNA, protein, and metabolites) to identify emergent properties, diagnose system states, or predict responses to environmental change. Here we adopt the MetaPathways annotation and analysis pipeline and Pathway Tools to construct environmental pathway/genome databases (ePGDBs) that describe microbial community metabolism using MetaCyc, a highly curated database of metabolic pathways and components covering all domains of life. We evaluate Pathway Tools' performance on three datasets with different complexity and coding potential, including simulated metagenomes, a symbiotic system, and the Hawaii Ocean Time-series. We define accuracy and sensitivity relationships between read length, coverage and pathway recovery and evaluate the impact of taxonomic pruning on ePGDB construction and interpretation. Resulting ePGDBs provide interactive metabolic maps, predict emergent metabolic pathways associated with biosynthesis and energy production and differentiate between genomic potential and phenotypic expression across defined environmental gradients. This multi-tiered analysis provides the user community with specific operating guidelines, performance metrics and prediction hazards for more reliable ePGDB construction and interpretation. Moreover, it demonstrates the power of Pathway Tools in predicting metabolic interactions in natural and engineered ecosystems.

Probing the folded state and mechanical unfolding pathways of T4 lysozyme using all-atom and coarse-grained molecular simulation

Energy Technology Data Exchange (ETDEWEB)

Zheng, Wenjun, E-mail: wjzheng@buffalo.edu; Glenn, Paul [Department of Physics, University at Buffalo, Buffalo, New York 14260 (United States)

2015-01-21

The Bacteriophage T4 Lysozyme (T4L) is a prototype modular protein comprised of an N-terminal and a C-domain domain, which was extensively studied to understand the folding/unfolding mechanism of modular proteins. To offer detailed structural and dynamic insights to the folded-state stability and the mechanical unfolding behaviors of T4L, we have performed extensive equilibrium and steered molecular dynamics simulations of both the wild-type (WT) and a circular permutation (CP) variant of T4L using all-atom and coarse-grained force fields. Our all-atom and coarse-grained simulations of the folded state have consistently found greater stability of the C-domain than the N-domain in isolation, which is in agreement with past thermostatic studies of T4L. While the all-atom simulation cannot fully explain the mechanical unfolding behaviors of the WT and the CP variant observed in an optical tweezers study, the coarse-grained simulations based on the Go model or a modified elastic network model (mENM) are in qualitative agreement with the experimental finding of greater unfolding cooperativity in the WT than the CP variant. Interestingly, the two coarse-grained models predict different structural mechanisms for the observed change in cooperativity between the WT and the CP variant—while the Go model predicts minor modification of the unfolding pathways by circular permutation (i.e., preserving the general order that the N-domain unfolds before the C-domain), the mENM predicts a dramatic change in unfolding pathways (e.g., different order of N/C-domain unfolding in the WT and the CP variant). Based on our simulations, we have analyzed the limitations of and the key differences between these models and offered testable predictions for future experiments to resolve the structural mechanism for cooperative folding/unfolding of T4L.

Medical Simulation Practices 2010 Survey Results

Science.gov (United States)

McCrindle, Jeffrey J.

2011-01-01

Medical Simulation Centers are an essential component of our learning infrastructure to prepare doctors and nurses for their careers. Unlike the military and aerospace simulation industry, very little has been published regarding the best practices currently in use within medical simulation centers. This survey attempts to provide insight into the current simulation practices at medical schools, hospitals, university nursing programs and community college nursing programs. Students within the MBA program at Saint Joseph's University conducted a survey of medical simulation practices during the summer 2010 semester. A total of 115 institutions responded to the survey. The survey resus discuss overall effectiveness of current simulation centers as well as the tools and techniques used to conduct the simulation activity

Magnocellular pathway for rotation invariant Neocognitron.

Science.gov (United States)

Ting, C H

1993-03-01

In the mammalian visual system, magnocellular pathway and parvocellular pathway cooperatively process visual information in parallel. The magnocellular pathway is more global and less particular about the details while the parvocellular pathway recognizes objects based on the local features. In many aspects, Neocognitron may be regarded as the artificial analogue of the parvocellular pathway. It is interesting then to model the magnocellular pathway. In order to achieve "rotation invariance" for Neocognitron, we propose a neural network model after the magnocellular pathway and expand its roles to include surmising the orientation of the input pattern prior to recognition. With the incorporation of the magnocellular pathway, a basic shift in the original paradigm has taken place. A pattern is now said to be recognized when and only when one of the winners of the magnocellular pathway is validified by the parvocellular pathway. We have implemented the magnocellular pathway coupled with Neocognitron parallel on transputers; our simulation programme is now able to recognize numerals in arbitrary orientation.

Electron-cloud simulation results for the PSR and SNS

International Nuclear Information System (INIS)

Pivi, M.; Furman, M.A.

2002-01-01

We present recent simulation results for the main features of the electron cloud in the storage ring of the Spallation Neutron Source (SNS) at Oak Ridge, and updated results for the Proton Storage Ring (PSR) at Los Alamos. In particular, a complete refined model for the secondary emission process including the so called true secondary, rediffused and backscattered electrons has been included in the simulation code

Comparison the Results of Numerical Simulation And Experimental Results for Amirkabir Plasma Focus Facility

Science.gov (United States)

Goudarzi, Shervin; Amrollahi, R.; Niknam Sharak, M.

2014-06-01

In this paper the results of the numerical simulation for Amirkabir Mather-type Plasma Focus Facility (16 kV, 36μF and 115 nH) in several experiments with Argon as working gas at different working conditions (different discharge voltages and gas pressures) have been presented and compared with the experimental results. Two different models have been used for simulation: five-phase model of Lee and lumped parameter model of Gonzalez. It is seen that the results (optimum pressures and current signals) of the Lee model at different working conditions show better agreement than lumped parameter model with experimental values.

Comparison the results of numerical simulation and experimental results for Amirkabir plasma focus facility

International Nuclear Information System (INIS)

Goudarzi, Shervin; Amrollahi, R; Sharak, M Niknam

2014-01-01

In this paper the results of the numerical simulation for Amirkabir Mather-type Plasma Focus Facility (16 kV, 36μF and 115 nH) in several experiments with Argon as working gas at different working conditions (different discharge voltages and gas pressures) have been presented and compared with the experimental results. Two different models have been used for simulation: five-phase model of Lee and lumped parameter model of Gonzalez. It is seen that the results (optimum pressures and current signals) of the Lee model at different working conditions show better agreement than lumped parameter model with experimental values.

Reconstructing the ideal results of a perturbed analog quantum simulator

Science.gov (United States)

Schwenk, Iris; Reiner, Jan-Michael; Zanker, Sebastian; Tian, Lin; Leppäkangas, Juha; Marthaler, Michael

2018-04-01

Well-controlled quantum systems can potentially be used as quantum simulators. However, a quantum simulator is inevitably perturbed by coupling to additional degrees of freedom. This constitutes a major roadblock to useful quantum simulations. So far there are only limited means to understand the effect of perturbation on the results of quantum simulation. Here we present a method which, in certain circumstances, allows for the reconstruction of the ideal result from measurements on a perturbed quantum simulator. We consider extracting the value of the correlator 〈Ôi(t ) Ôj(0 ) 〉 from the simulated system, where Ôi are the operators which couple the system to its environment. The ideal correlator can be straightforwardly reconstructed by using statistical knowledge of the environment, if any n -time correlator of operators Ôi of the ideal system can be written as products of two-time correlators. We give an approach to verify the validity of this assumption experimentally by additional measurements on the perturbed quantum simulator. The proposed method can allow for reliable quantum simulations with systems subjected to environmental noise without adding an overhead to the quantum system.

Pathways-driven sparse regression identifies pathways and genes associated with high-density lipoprotein cholesterol in two Asian cohorts.

Directory of Open Access Journals (Sweden)

Matt Silver

2013-11-01

Full Text Available Standard approaches to data analysis in genome-wide association studies (GWAS ignore any potential functional relationships between gene variants. In contrast gene pathways analysis uses prior information on functional structure within the genome to identify pathways associated with a trait of interest. In a second step, important single nucleotide polymorphisms (SNPs or genes may be identified within associated pathways. The pathways approach is motivated by the fact that genes do not act alone, but instead have effects that are likely to be mediated through their interaction in gene pathways. Where this is the case, pathways approaches may reveal aspects of a trait's genetic architecture that would otherwise be missed when considering SNPs in isolation. Most pathways methods begin by testing SNPs one at a time, and so fail to capitalise on the potential advantages inherent in a multi-SNP, joint modelling approach. Here, we describe a dual-level, sparse regression model for the simultaneous identification of pathways and genes associated with a quantitative trait. Our method takes account of various factors specific to the joint modelling of pathways with genome-wide data, including widespread correlation between genetic predictors, and the fact that variants may overlap multiple pathways. We use a resampling strategy that exploits finite sample variability to provide robust rankings for pathways and genes. We test our method through simulation, and use it to perform pathways-driven gene selection in a search for pathways and genes associated with variation in serum high-density lipoprotein cholesterol levels in two separate GWAS cohorts of Asian adults. By comparing results from both cohorts we identify a number of candidate pathways including those associated with cardiomyopathy, and T cell receptor and PPAR signalling. Highlighted genes include those associated with the L-type calcium channel, adenylate cyclase, integrin, laminin, MAPK

Pathways-Driven Sparse Regression Identifies Pathways and Genes Associated with High-Density Lipoprotein Cholesterol in Two Asian Cohorts

Science.gov (United States)

Silver, Matt; Chen, Peng; Li, Ruoying; Cheng, Ching-Yu; Wong, Tien-Yin; Tai, E-Shyong; Teo, Yik-Ying; Montana, Giovanni

2013-01-01

Standard approaches to data analysis in genome-wide association studies (GWAS) ignore any potential functional relationships between gene variants. In contrast gene pathways analysis uses prior information on functional structure within the genome to identify pathways associated with a trait of interest. In a second step, important single nucleotide polymorphisms (SNPs) or genes may be identified within associated pathways. The pathways approach is motivated by the fact that genes do not act alone, but instead have effects that are likely to be mediated through their interaction in gene pathways. Where this is the case, pathways approaches may reveal aspects of a trait's genetic architecture that would otherwise be missed when considering SNPs in isolation. Most pathways methods begin by testing SNPs one at a time, and so fail to capitalise on the potential advantages inherent in a multi-SNP, joint modelling approach. Here, we describe a dual-level, sparse regression model for the simultaneous identification of pathways and genes associated with a quantitative trait. Our method takes account of various factors specific to the joint modelling of pathways with genome-wide data, including widespread correlation between genetic predictors, and the fact that variants may overlap multiple pathways. We use a resampling strategy that exploits finite sample variability to provide robust rankings for pathways and genes. We test our method through simulation, and use it to perform pathways-driven gene selection in a search for pathways and genes associated with variation in serum high-density lipoprotein cholesterol levels in two separate GWAS cohorts of Asian adults. By comparing results from both cohorts we identify a number of candidate pathways including those associated with cardiomyopathy, and T cell receptor and PPAR signalling. Highlighted genes include those associated with the L-type calcium channel, adenylate cyclase, integrin, laminin, MAPK signalling and immune

3D Simulation of External Flooding Events for the RISMC Pathway

International Nuclear Information System (INIS)

Prescott, Steven; Mandelli, Diego; Sampath, Ramprasad; Smith, Curtis; Lin, Linyu

2015-01-01

Incorporating 3D simulations as part of the Risk-Informed Safety Margins Characterization (RISMIC) Toolkit allows analysts to obtain a more complete picture of complex system behavior for events including external plant hazards. External events such as flooding have become more important recently – however these can be analyzed with existing and validated simulated physics toolkits. In this report, we describe these approaches specific to flooding-based analysis using an approach called Smoothed Particle Hydrodynamics. The theory, validation, and example applications of the 3D flooding simulation are described. Integrating these 3D simulation methods into computational risk analysis provides a spatial/visual aspect to the design, improves the realism of results, and can prove visual understanding to validate the analysis of flooding.

3D Simulation of External Flooding Events for the RISMC Pathway

Energy Technology Data Exchange (ETDEWEB)

Prescott, Steven [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mandelli, Diego [Idaho National Lab. (INL), Idaho Falls, ID (United States); Sampath, Ramprasad [Idaho National Lab. (INL), Idaho Falls, ID (United States); Smith, Curtis [Idaho National Lab. (INL), Idaho Falls, ID (United States); Lin, Linyu [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2015-09-01

Incorporating 3D simulations as part of the Risk-Informed Safety Margins Characterization (RISMIC) Toolkit allows analysts to obtain a more complete picture of complex system behavior for events including external plant hazards. External events such as flooding have become more important recently – however these can be analyzed with existing and validated simulated physics toolkits. In this report, we describe these approaches specific to flooding-based analysis using an approach called Smoothed Particle Hydrodynamics. The theory, validation, and example applications of the 3D flooding simulation are described. Integrating these 3D simulation methods into computational risk analysis provides a spatial/visual aspect to the design, improves the realism of results, and can prove visual understanding to validate the analysis of flooding.

Improved Differential Evolution Algorithm for Parameter Estimation to Improve the Production of Biochemical Pathway

Directory of Open Access Journals (Sweden)

Chuii Khim Chong

2012-06-01

Full Text Available This paper introduces an improved Differential Evolution algorithm (IDE which aims at improving its performance in estimating the relevant parameters for metabolic pathway data to simulate glycolysis pathway for yeast. Metabolic pathway data are expected to be of significant help in the development of efficient tools in kinetic modeling and parameter estimation platforms. Many computation algorithms face obstacles due to the noisy data and difficulty of the system in estimating myriad of parameters, and require longer computational time to estimate the relevant parameters. The proposed algorithm (IDE in this paper is a hybrid of a Differential Evolution algorithm (DE and a Kalman Filter (KF. The outcome of IDE is proven to be superior than Genetic Algorithm (GA and DE. The results of IDE from experiments show estimated optimal kinetic parameters values, shorter computation time and increased accuracy for simulated results compared with other estimation algorithms

Oxygen entry through multiple pathways in T-state human hemoglobin.

Science.gov (United States)

Takayanagi, Masayoshi; Kurisaki, Ikuo; Nagaoka, Masataka

2013-05-23

The heme oxygen (O2) binding site of human hemoglobin (HbA) is buried in the interior of the protein, and there is a debate over the O2 entry pathways from solvent to the binding site. As a first step to understand HbA O2 binding process at the atomic level, we detected all significant multiple O2 entry pathways from solvent to the binding site in the α and β subunits of the T-state tetramer HbA by utilizing ensemble molecular dynamics (MD) simulation. By executing 128 independent 8 ns MD trajectories in O2-rich aqueous solvent, we simulated the O2 entry processes and obtained 141 and 425 O2 entry events in the α and β subunits of HbA, respectively. We developed the intrinsic pathway identification by clustering method to achieve a persuasive visualization of the multiple entry pathways including both the shapes and relative importance of each pathway. The rate constants of O2 entry estimated from the MD simulations correspond to the experimentally observed values, suggesting that O2 ligands enter the binding site through multiple pathways. The obtained multiple pathway map can be utilized for future detailed analysis of HbA O2 binding process.

Pathway-Based Kernel Boosting for the Analysis of Genome-Wide Association Studies

Science.gov (United States)

Manitz, Juliane; Burger, Patricia; Amos, Christopher I.; Chang-Claude, Jenny; Wichmann, Heinz-Erich; Kneib, Thomas; Bickeböller, Heike

2017-01-01

The analysis of genome-wide association studies (GWAS) benefits from the investigation of biologically meaningful gene sets, such as gene-interaction networks (pathways). We propose an extension to a successful kernel-based pathway analysis approach by integrating kernel functions into a powerful algorithmic framework for variable selection, to enable investigation of multiple pathways simultaneously. We employ genetic similarity kernels from the logistic kernel machine test (LKMT) as base-learners in a boosting algorithm. A model to explain case-control status is created iteratively by selecting pathways that improve its prediction ability. We evaluated our method in simulation studies adopting 50 pathways for different sample sizes and genetic effect strengths. Additionally, we included an exemplary application of kernel boosting to a rheumatoid arthritis and a lung cancer dataset. Simulations indicate that kernel boosting outperforms the LKMT in certain genetic scenarios. Applications to GWAS data on rheumatoid arthritis and lung cancer resulted in sparse models which were based on pathways interpretable in a clinical sense. Kernel boosting is highly flexible in terms of considered variables and overcomes the problem of multiple testing. Additionally, it enables the prediction of clinical outcomes. Thus, kernel boosting constitutes a new, powerful tool in the analysis of GWAS data and towards the understanding of biological processes involved in disease susceptibility. PMID:28785300

Pathway-Based Kernel Boosting for the Analysis of Genome-Wide Association Studies.

Science.gov (United States)

Friedrichs, Stefanie; Manitz, Juliane; Burger, Patricia; Amos, Christopher I; Risch, Angela; Chang-Claude, Jenny; Wichmann, Heinz-Erich; Kneib, Thomas; Bickeböller, Heike; Hofner, Benjamin

2017-01-01

The analysis of genome-wide association studies (GWAS) benefits from the investigation of biologically meaningful gene sets, such as gene-interaction networks (pathways). We propose an extension to a successful kernel-based pathway analysis approach by integrating kernel functions into a powerful algorithmic framework for variable selection, to enable investigation of multiple pathways simultaneously. We employ genetic similarity kernels from the logistic kernel machine test (LKMT) as base-learners in a boosting algorithm. A model to explain case-control status is created iteratively by selecting pathways that improve its prediction ability. We evaluated our method in simulation studies adopting 50 pathways for different sample sizes and genetic effect strengths. Additionally, we included an exemplary application of kernel boosting to a rheumatoid arthritis and a lung cancer dataset. Simulations indicate that kernel boosting outperforms the LKMT in certain genetic scenarios. Applications to GWAS data on rheumatoid arthritis and lung cancer resulted in sparse models which were based on pathways interpretable in a clinical sense. Kernel boosting is highly flexible in terms of considered variables and overcomes the problem of multiple testing. Additionally, it enables the prediction of clinical outcomes. Thus, kernel boosting constitutes a new, powerful tool in the analysis of GWAS data and towards the understanding of biological processes involved in disease susceptibility.

Intermittent hypoxia simulating obstructive sleep apnea causes pulmonary inflammation and activates the Nrf2/HO-1 pathway.

Science.gov (United States)

Wang, Yeying; Chai, Yanling; He, Xiaojie; Ai, Li; Sun, Xia; Huang, Yiling; Li, Yongxia

2017-10-01

Obstructive sleep apnea (OSA) is a disorder with high morbidity in adults. OSA damages multiple organs and tissues, including the cardiovascular and cerebrovascular systems, the metabolism system, the lungs, liver and heart. OSA-induced damage is earliest and greatest to the pulmonary tissue. The present study established a rat OSA model of differing severity by inducing intermittent hypoxia with different concentrations of O 2 and it was determined that OSA caused a severe oxidative stress response and pulmonary inflammation in a dose-dependent manner. OSA increased serum levels of C-reactive protein and 8-isoprostane and elevated the expression of malondialdehyde, tumor necrosis factor α, interleukin (IL)-1β and IL-6 in the pulmonary tissue. Furthermore, the expression of two important antioxidants, superoxide dismutase and glutathione, was downregulated following intermittent hypoxia. By contrast, levels of cylooxygenase 2 and inducible nitric oxide synthase, which are crucial in the antioxidative response, increased. In addition, OSA activates the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase (OH)-1 antioxidative signaling pathway. Finally, all increases and decreases in levels of inflammatory and antioxidative substances were dependent on oxygen concentrations. Therefore, the present study demonstrated that OSA, simulated by intermittent hypoxia, caused an oxidative stress response and pulmonary inflammation, and activated the canonical antioxidative Nrf2/HO-1 signaling pathway in a dose-dependent manner. These results may facilitate the development of clinical therapies to treat pulmonary diseases caused by OSA.

Simulating Water-Use Efficiency of Piceacrassi folia Forest under Representative Concentration Pathway Scenarios in the Qilian Mountains of Northwest China

Directory of Open Access Journals (Sweden)

Shouzhang Peng

2016-07-01

Full Text Available The current study used the Biome-Bio Geochemical Cycle (Biome-BGC model to simulate water-use efficiency (WUE of Piceacrassi folia (P. crassifolia forest under four representative concentration pathway (RCP scenarios, and investigated the responses of forest WUE to different combinations of climatic changes and CO2 concentrations in the Qilian Mountains of Northwest China. The model was validated by comparing simulated forest net primary productivity and transpiration under current climatic condition with independent field-measured data. Subsequently, the model was used to predict P. crassi folia forest WUE response to different climatic and CO2 change scenarios. Results showed that (1 increases in temperature, precipitation and atmospheric CO2 concentrations led to associated increases in WUE (ranging from 54% to 66% above the reference climate; (2 effect of CO2 concentration (increased WUE from 36% to 42.3% was more significant than that of climate change (increased WUE from 2.4% to 15%; and (3 forest WUE response to future global change was more intense at high elevations than at low ones, with CO2 concentration being the main factor that controlled forest WUE variation. These results provide valuable insight to help understand how these forest types might respond to future changes in climate and atmospheric CO2 concentration.

DoSSiER: Database of Scientific Simulation and Experimental Results

CERN Document Server

Wenzel, Hans; Genser, Krzysztof; Elvira, Daniel; Pokorski, Witold; Carminati, Federico; Konstantinov, Dmitri; Ribon, Alberto; Folger, Gunter; Dotti, Andrea

2017-01-01

The Geant4, GeantV and GENIE collaborations regularly perform validation and regression tests for simulation results. DoSSiER (Database of Scientific Simulation and Experimental Results) is being developed as a central repository to store the simulation results as well as the experimental data used for validation. DoSSiER can be easily accessed via a web application. In addition, a web service allows for programmatic access to the repository to extract records in json or xml exchange formats. In this article, we describe the functionality and the current status of various components of DoSSiER as well as the technology choices we made.

Stochasticity in the yeast mating pathway

International Nuclear Information System (INIS)

Hong-Li, Wang; Zheng-Ping, Fu; Xin-Hang, Xu; Qi, Ouyang

2009-01-01

We report stochastic simulations of the yeast mating signal transduction pathway. The effects of intrinsic and external noise, the influence of cell-to-cell difference in the pathway capacity, and noise propagation in the pathway have been examined. The stochastic temporal behaviour of the pathway is found to be robust to the influence of inherent fluctuations, and intrinsic noise propagates in the pathway in a uniform pattern when the yeasts are treated with pheromones of different stimulus strengths and of varied fluctuations. In agreement with recent experimental findings, extrinsic noise is found to play a more prominent role than intrinsic noise in the variability of proteins. The occurrence frequency for the reactions in the pathway are also examined and a more compact network is obtained by dropping most of the reactions of least occurrence

Well-to-wheels analysis of hydrogen based fuel-cell vehicle pathways in Shanghai

International Nuclear Information System (INIS)

Huang Zhijia; Zhang Xu

2006-01-01

Due to high energy efficiency and zero emissions, some believe fuel cell vehicles (FCVs) could revolutionize the automobile industry by replacing internal combustion engine technology, and first boom in China. However, hydrogen infrastructure is one of the major barriers. Because different H 2 pathways have very different energy and emissions effects, the well-to-wheels (WTW) analyses are necessary for adequately evaluating fuel/vehicle systems. The pathways used to supply H 2 for FCVs must be carefully examined by their WTW energy use, greenhouse gases (GHGs) emissions, total criteria pollutions emissions, and urban criteria pollutions emissions. Ten hydrogen pathways in Shanghai have been simulated. The results include well-to-wheels energy use, GHGs emissions, total criteria pollutions and urban criteria pollutions. A fuel-cycle model developed at Argonne National Laboratory-called the Greenhouse gases, Regulated Emissions, and Energy use in Transportation (GREET) model-was used to evaluate well-to-wheels energy and emissions impacts of hydrogen pathways in this study. Because the initial GREET model had no coal and naphtha-based hydrogen pathways, four hydrogen pathway computer programs were added to GREET in the research. To analyze uncertain impacts, commercial software, Crystal Ball(TM) was used to conduct Monte Carlo simulations. Hence, instead of point estimates, the results of this study were probability distributions. Through the research of H 2 pathways in Shanghai, the following conclusions were achieved:(1)All the pathways have significant reductions in WTW petroleum use, except two H 2 pathways from naphtha, which achieve about 20% reductions in WTW petroleum. (2)All the pathways have significant reductions in WTW urban criteria pollutions emissions, except two H 2 pathways from coal, which result in significant increases in WTW urban SO X emissions. (3)The NG-based H 2 pathways have the best WTW energy efficiencies, and the electrolysis H 2 pathways

Exploring the Unfolding Pathway of Maltose Binding Proteins: An Integrated Computational Approach

KAUST Repository

Guardiani, Carlo; Marino, Daniele Di; Tramontano, Anna; Chinappi, Mauro; Cecconi, Fabio

2014-01-01

© 2014 American Chemical Society. Recent single-molecule force spectroscopy experiments on the Maltose Binding Proteins (MBPs) identified four stable structural units, termed unfoldons, that resist mechanical stress and determine the intermediates of the unfolding pathway. In this work, we analyze the topological origin and the dynamical role of the unfoldons using an integrated approach which combines a graph-theoretical analysis of the interaction network of the MBP native-state with steered molecular dynamics simulations. The topological analysis of the native state, while revealing the structural nature of the unfoldons, provides a framework to interpret the MBP mechanical unfolding pathway. Indeed, the experimental pathway can be effectively predicted by means of molecular dynamics simulations with a simple topology-based and low-resolution model of the MBP. The results obtained from the coarse-grained approach are confirmed and further refined by all-atom molecular dynamics.

Exploring the Unfolding Pathway of Maltose Binding Proteins: An Integrated Computational Approach

KAUST Repository

Guardiani, Carlo

2014-09-09

© 2014 American Chemical Society. Recent single-molecule force spectroscopy experiments on the Maltose Binding Proteins (MBPs) identified four stable structural units, termed unfoldons, that resist mechanical stress and determine the intermediates of the unfolding pathway. In this work, we analyze the topological origin and the dynamical role of the unfoldons using an integrated approach which combines a graph-theoretical analysis of the interaction network of the MBP native-state with steered molecular dynamics simulations. The topological analysis of the native state, while revealing the structural nature of the unfoldons, provides a framework to interpret the MBP mechanical unfolding pathway. Indeed, the experimental pathway can be effectively predicted by means of molecular dynamics simulations with a simple topology-based and low-resolution model of the MBP. The results obtained from the coarse-grained approach are confirmed and further refined by all-atom molecular dynamics.

Simulating an Infection Growth Model in Certain Healthy Metabolic Pathways of Homo sapiens for Highlighting Their Role in Type I Diabetes mellitus Using Fire-Spread Strategy, Feedbacks and Sensitivities

Science.gov (United States)

Tagore, Somnath; De, Rajat K.

2013-01-01

Disease Systems Biology is an area of life sciences, which is not very well understood to date. Analyzing infections and their spread in healthy metabolite networks can be one of the focussed areas in this regard. We have proposed a theory based on the classical forest fire model for analyzing the path of infection spread in healthy metabolic pathways. The theory suggests that when fire erupts in a forest, it spreads, and the surrounding trees also catch fire. Similarly, when we consider a metabolic network, the infection caused in the metabolites of the network spreads like a fire. We have constructed a simulation model which is used to study the infection caused in the metabolic networks from the start of infection, to spread and ultimately combating it. For implementation, we have used two approaches, first, based on quantitative strategies using ordinary differential equations and second, using graph-theory based properties. Furthermore, we are using certain probabilistic scores to complete this task and for interpreting the harm caused in the network, given by a ‘critical value’ to check whether the infection can be cured or not. We have tested our simulation model on metabolic pathways involved in Type I Diabetes mellitus in Homo sapiens. For validating our results biologically, we have used sensitivity analysis, both local and global, as well as for identifying the role of feedbacks in spreading infection in metabolic pathways. Moreover, information in literature has also been used to validate the results. The metabolic network datasets have been collected from the Kyoto Encyclopedia of Genes and Genomes (KEGG). PMID:24039701

Simulating an infection growth model in certain healthy metabolic pathways of Homo sapiens for highlighting their role in Type I Diabetes mellitus using fire-spread strategy, feedbacks and sensitivities.

Directory of Open Access Journals (Sweden)

Somnath Tagore

Full Text Available Disease Systems Biology is an area of life sciences, which is not very well understood to date. Analyzing infections and their spread in healthy metabolite networks can be one of the focussed areas in this regard. We have proposed a theory based on the classical forest fire model for analyzing the path of infection spread in healthy metabolic pathways. The theory suggests that when fire erupts in a forest, it spreads, and the surrounding trees also catch fire. Similarly, when we consider a metabolic network, the infection caused in the metabolites of the network spreads like a fire. We have constructed a simulation model which is used to study the infection caused in the metabolic networks from the start of infection, to spread and ultimately combating it. For implementation, we have used two approaches, first, based on quantitative strategies using ordinary differential equations and second, using graph-theory based properties. Furthermore, we are using certain probabilistic scores to complete this task and for interpreting the harm caused in the network, given by a 'critical value' to check whether the infection can be cured or not. We have tested our simulation model on metabolic pathways involved in Type I Diabetes mellitus in Homo sapiens. For validating our results biologically, we have used sensitivity analysis, both local and global, as well as for identifying the role of feedbacks in spreading infection in metabolic pathways. Moreover, information in literature has also been used to validate the results. The metabolic network datasets have been collected from the Kyoto Encyclopedia of Genes and Genomes (KEGG.

Free energy landscape and molecular pathways of gas hydrate nucleation

Energy Technology Data Exchange (ETDEWEB)

Bi, Yuanfei; Porras, Anna; Li, Tianshu, E-mail: tsli@gwu.edu [Department of Civil and Environmental Engineering, George Washington University, Washington DC 20052 (United States)

2016-12-07

Despite the significance of gas hydrates in diverse areas, a quantitative knowledge of hydrate formation at a molecular level is missing. The impediment to acquiring this understanding is primarily attributed to the stochastic nature and ultra-fine scales of nucleation events, posing a great challenge for both experiment and simulation to explore hydrate nucleation. Here we employ advanced molecular simulation methods, including forward flux sampling (FFS), p{sub B} histogram analysis, and backward flux sampling, to overcome the limit of direct molecular simulation for exploring both the free energy landscape and molecular pathways of hydrate nucleation. First we test the half-cage order parameter (H-COP) which we developed for driving FFS, through conducting the p{sub B} histogram analysis. Our results indeed show that H-COP describes well the reaction coordinates of hydrate nucleation. Through the verified order parameter, we then directly compute the free energy landscape for hydrate nucleation by combining both forward and backward flux sampling. The calculated stationary distribution density, which is obtained independently of nucleation theory, is found to fit well against the classical nucleation theory (CNT). Subsequent analysis of the obtained large ensemble of hydrate nucleation trajectories show that although on average, hydrate formation is facilitated by a two-step like mechanism involving a gradual transition from an amorphous to a crystalline structure, there also exist nucleation pathways where hydrate crystallizes directly, without going through the amorphous stage. The CNT-like free energy profile and the structural diversity suggest the existence of multiple active transition pathways for hydrate nucleation, and possibly also imply the near degeneracy in their free energy profiles among different pathways. Our results thus bring a new perspective to the long standing question of how hydrates crystallize.

Free energy landscape and molecular pathways of gas hydrate nucleation

International Nuclear Information System (INIS)

Bi, Yuanfei; Porras, Anna; Li, Tianshu

2016-01-01

Despite the significance of gas hydrates in diverse areas, a quantitative knowledge of hydrate formation at a molecular level is missing. The impediment to acquiring this understanding is primarily attributed to the stochastic nature and ultra-fine scales of nucleation events, posing a great challenge for both experiment and simulation to explore hydrate nucleation. Here we employ advanced molecular simulation methods, including forward flux sampling (FFS), p B histogram analysis, and backward flux sampling, to overcome the limit of direct molecular simulation for exploring both the free energy landscape and molecular pathways of hydrate nucleation. First we test the half-cage order parameter (H-COP) which we developed for driving FFS, through conducting the p B histogram analysis. Our results indeed show that H-COP describes well the reaction coordinates of hydrate nucleation. Through the verified order parameter, we then directly compute the free energy landscape for hydrate nucleation by combining both forward and backward flux sampling. The calculated stationary distribution density, which is obtained independently of nucleation theory, is found to fit well against the classical nucleation theory (CNT). Subsequent analysis of the obtained large ensemble of hydrate nucleation trajectories show that although on average, hydrate formation is facilitated by a two-step like mechanism involving a gradual transition from an amorphous to a crystalline structure, there also exist nucleation pathways where hydrate crystallizes directly, without going through the amorphous stage. The CNT-like free energy profile and the structural diversity suggest the existence of multiple active transition pathways for hydrate nucleation, and possibly also imply the near degeneracy in their free energy profiles among different pathways. Our results thus bring a new perspective to the long standing question of how hydrates crystallize.

Free energy landscape and molecular pathways of gas hydrate nucleation.

Science.gov (United States)

Bi, Yuanfei; Porras, Anna; Li, Tianshu

2016-12-07

Despite the significance of gas hydrates in diverse areas, a quantitative knowledge of hydrate formation at a molecular level is missing. The impediment to acquiring this understanding is primarily attributed to the stochastic nature and ultra-fine scales of nucleation events, posing a great challenge for both experiment and simulation to explore hydrate nucleation. Here we employ advanced molecular simulation methods, including forward flux sampling (FFS), p B histogram analysis, and backward flux sampling, to overcome the limit of direct molecular simulation for exploring both the free energy landscape and molecular pathways of hydrate nucleation. First we test the half-cage order parameter (H-COP) which we developed for driving FFS, through conducting the p B histogram analysis. Our results indeed show that H-COP describes well the reaction coordinates of hydrate nucleation. Through the verified order parameter, we then directly compute the free energy landscape for hydrate nucleation by combining both forward and backward flux sampling. The calculated stationary distribution density, which is obtained independently of nucleation theory, is found to fit well against the classical nucleation theory (CNT). Subsequent analysis of the obtained large ensemble of hydrate nucleation trajectories show that although on average, hydrate formation is facilitated by a two-step like mechanism involving a gradual transition from an amorphous to a crystalline structure, there also exist nucleation pathways where hydrate crystallizes directly, without going through the amorphous stage. The CNT-like free energy profile and the structural diversity suggest the existence of multiple active transition pathways for hydrate nucleation, and possibly also imply the near degeneracy in their free energy profiles among different pathways. Our results thus bring a new perspective to the long standing question of how hydrates crystallize.

Pathways and mechanisms for product release in the engineered haloalkane dehalogenases explored using classical and random acceleration molecular dynamics simulations.

Science.gov (United States)

Klvana, Martin; Pavlova, Martina; Koudelakova, Tana; Chaloupkova, Radka; Dvorak, Pavel; Prokop, Zbynek; Stsiapanava, Alena; Kuty, Michal; Kuta-Smatanova, Ivana; Dohnalek, Jan; Kulhanek, Petr; Wade, Rebecca C; Damborsky, Jiri

2009-10-09

Eight mutants of the DhaA haloalkane dehalogenase carrying mutations at the residues lining two tunnels, previously observed by protein X-ray crystallography, were constructed and biochemically characterized. The mutants showed distinct catalytic efficiencies with the halogenated substrate 1,2,3-trichloropropane. Release pathways for the two dehalogenation products, 2,3-dichloropropane-1-ol and the chloride ion, and exchange pathways for water molecules, were studied using classical and random acceleration molecular dynamics simulations. Five different pathways, denoted p1, p2a, p2b, p2c, and p3, were identified. The individual pathways showed differing selectivity for the products: the chloride ion releases solely through p1, whereas the alcohol releases through all five pathways. Water molecules play a crucial role for release of both products by breakage of their hydrogen-bonding interactions with the active-site residues and shielding the charged chloride ion during its passage through a hydrophobic tunnel. Exchange of the chloride ions, the alcohol product, and the waters between the buried active site and the bulk solvent can be realized by three different mechanisms: (i) passage through a permanent tunnel, (ii) passage through a transient tunnel, and (iii) migration through a protein matrix. We demonstrate that the accessibility of the pathways and the mechanisms of ligand exchange were modified by mutations. Insertion of bulky aromatic residues in the tunnel corresponding to pathway p1 leads to reduced accessibility to the ligands and a change in mechanism of opening from permanent to transient. We propose that engineering the accessibility of tunnels and the mechanisms of ligand exchange is a powerful strategy for modification of the functional properties of enzymes with buried active sites.

Analysis of Chlorogenic Acid Oxidation Pathway in Simulated ...

African Journals Online (AJOL)

Keywords: Honeysuckle, Chlorogenic acid, Enzymatic browning, Mimic system, Oxidation pathway, ... enzymatic oxidation of CA is the major cause of ..... to the concentration of catechol, o-quinone and current at PPO-modified microcylinder biosensor for diffusion- kinetic model. J Electroanal Chem 2011; 660: 200-208.

Human cerebral venous outflow pathway depends on posture and central venous pressure

DEFF Research Database (Denmark)

Gisolf, J; van Lieshout, J J; van Heusden, K

2004-01-01

Internal jugular veins are the major cerebral venous outflow pathway in supine humans. In upright humans the positioning of these veins above heart level causes them to collapse. An alternative cerebral outflow pathway is the vertebral venous plexus. We set out to determine the effect of posture...... and during a Valsalva manoeuvre in both body positions, correlate highly with model simulation of the jugular cross-sectional area (R(2) = 0.97). The results suggest that the cerebral venous flow distribution depends on posture and CVP: in supine humans the internal jugular veins are the primary pathway...

Toward a quantitative understanding of the Wnt/ β -catenin pathway through simulation and experiment

KAUST Repository

Lloyd-Lewis, Bethan; Fletcher, Alexander G.; Dale, Trevor C.; Byrne, Helen M.

2013-01-01

Wnt signaling regulates cell survival, proliferation, and differentiation throughout development and is aberrantly regulated in cancer. The pathway is activated when Wnt ligands bind to specific receptors on the cell surface, resulting

A physiological production model for cacao : results of model simulations

NARCIS (Netherlands)

Zuidema, P.A.; Leffelaar, P.A.

2002-01-01

CASE2 is a physiological model for cocoa (Theobroma cacao L.) growth and yield. This report introduces the CAcao Simulation Engine for water-limited production in a non-technical way and presents simulation results obtained with the model.

Origin and pathways of Winter Intermediate Water in the Northwestern Mediterranean Sea using observations and numerical simulation

Science.gov (United States)

Juza, Mélanie; Renault, Lionel; Ruiz, Simon; Tintoré, Joaquin

2013-12-01

The study of water masses worldwide (their formation, spreading, mixing, and impact on general circulation) is essential for a better understanding of the ocean circulation and variability. In this paper, the formation and main pathways of Winter Intermediate Water (WIW) in the Northwestern Mediterranean Sea (NWMED) are investigated during the winter-spring 2011 using observations and numerical simulation. The main results show that the WIW, formed along the continental shelves of the Gulf of Lion and Balearic Sea, circulates southward following five preferential pathways depending on the WIW formation site location and the oceanic conditions. WIW joins the northeastern part of the Balearic Sea, or flows along the continental shelves until joining the Balearic Current (maximum of 0.33 Sv in early-April) or further south until the Ibiza Channel entrance. Two additional trajectories, contributing to water mass exchanges with the southern part of the Western Mediterranean Sea, bring the WIW through the Ibiza and Mallorca Channels (maxima of 0.26 Sv in late-March and 0.1 Sv in early-April, respectively). The circulation of WIW over the NWMED at 50-200 m depth, its mixing and spreading over the Western Mediterranean Sea (reaching the south of the Balearic Islands, the Algero-Provencal basin, the Ligurian and the Alboran Seas) suggest that the WIW may have an impact on the ocean circulation by eddy blocking effect, exchange of water masses between north and south subbasins of Western Mediterranean Sea through the Ibiza Channel or modification of the ocean stratification.

Modularized TGFbeta-Smad Signaling Pathway

Science.gov (United States)

Li, Yongfeng; Wang, M.; Carra, C.; Cucinotta, F. A.

2011-01-01

The Transforming Growth Factor beta (TGFbeta) signaling pathway is a prominent regulatory signaling pathway controlling various important cellular processes. It can be induced by several factors, including ionizing radiation. It is regulated by Smads in a negative feedback loop through promoting increases in the regulatory Smads in the cell nucleus, and subsequent expression of inhibitory Smad, Smad7 to form a ubiquitin ligase with Smurf targeting active TGF receptors for degradation. In this work, we proposed a mathematical model to study the radiation-induced Smad-regulated TGF signaling pathway. By modularization, we are able to analyze each module (subsystem) and recover the nonlinear dynamics of the entire network system. Meanwhile the excitability, a common feature observed in the biological systems, along the TGF signaling pathway is discussed by mathematical analysis and numerical simulation.

The path from ITER to a power plant - initial results from the ARIES ''Pathways'' program

International Nuclear Information System (INIS)

Najmabadi, F.

2007-01-01

The US national power plant studies program, ARIES, has initiated a 3-year integrated study, called the ''Pathways Program'' to investigate what the fusion program needs to do, in addition to successful operation of the ITER, in order to transform fusion into a commercial reality. The US power industry and regulatory agencies view the demonstration power plant, DEMO, as a device which is build and operated by industry, possibly with government participation, to demonstrate the commercial readiness of fusion power. As such, the ''Pathways'' programs will investigate what is needed, in addition to successful operation of ITER, to convince industry to move forward with a fusion DEMO. While many reports exists that provide a strategic view of the needs for fusion development; in the ITER era, a much more detailed view is needed to provide the necessary information for program planning. By comparing the anticipated results from ITER and existing facilities with the requirements for a power plant in the first phase of the Pathways study, we will develop a comprehensive list of remaining R and D items for developing fusion, will identify metrics for distributing resources among R and D issues, and will identify which of those items can/should be done in existing or simulation facilities. In the second phase of the study, we will develop potential embodiments for the fusion test facility (ies) and explore their cost/performance parametrically. An important by-product of this study is the identification of key R and D issues that can be performed and resolved in existing facilities to make the fusion facility cheaper and/or a higher performance device. This paper summarizes the results from the first phase of our study. We have adopted a ''holistic'' or integrated approach with the focus on the needs of the customer. In such an approach, the remaining R and D should generate all of the information needed by industry to move forward with the DEMO, i.e., data needed to

Tension-induced vesicle fusion: pathways and pore dynamics

DEFF Research Database (Denmark)

Shillcock, Julian C.

2008-01-01

and eventually opens a pore to complete the fusion process. In pathway II, at higher tension, a stalk is formed during the fusion process that is then transformed by transmembrane pore formation into a fusion pore. Whereas the latter pathway II resembles stalk pathways as observed in other simulation studies......, fusion pathway I, which does not involve any stalk formation, has not been described previously to the best of our knowledge. A statistical analysis of the various processes shows that fusion is the dominant pathway for releasing the tension of the vesicles. The functional dependence of the observed...

Pathways Regulating Spheroid Formation of Human Follicular Thyroid Cancer Cells under Simulated Microgravity Conditions: A Genetic Approach

Directory of Open Access Journals (Sweden)

Stefan Riwaldt

2016-04-01

Full Text Available Microgravity induces three-dimensional (3D growth in numerous cell types. Despite substantial efforts to clarify the underlying mechanisms for spheroid formation, the precise molecular pathways are still not known. The principal aim of this paper is to compare static 1g-control cells with spheroid forming (MCS and spheroid non-forming (AD thyroid cancer cells cultured in the same flask under simulated microgravity conditions. We investigated the morphology and gene expression patterns in human follicular thyroid cancer cells (UCLA RO82-W-1 cell line after a 24 h-exposure on the Random Positioning Machine (RPM and focused on 3D growth signaling processes. After 24 h, spheroid formation was observed in RPM-cultures together with alterations in the F-actin cytoskeleton. qPCR indicated more changes in gene expression in MCS than in AD cells. Of the 24 genes analyzed VEGFA, VEGFD, MSN, and MMP3 were upregulated in MCS compared to 1g-controls, whereas ACTB, ACTA2, KRT8, TUBB, EZR, RDX, PRKCA, CAV1, MMP9, PAI1, CTGF, MCP1 were downregulated. A pathway analysis revealed that the upregulated genes code for proteins, which promote 3D growth (angiogenesis and prevent excessive accumulation of extracellular proteins, while genes coding for structural proteins are downregulated. Pathways regulating the strength/rigidity of cytoskeletal proteins, the amount of extracellular proteins, and 3D growth may be involved in MCS formation.

The Titan Haze Simulation Experiment: Latest Laboratory Results and Dedicated Plasma Chemistry Model

Science.gov (United States)

Sciamma-O'Brien, Ella; Raymond, Alexander; Mazur, Eric; Salama, Farid

2018-06-01

Here, we present the latest results on the gas and solid phase analyses in the Titan Haze Simulation (THS) experiment. The THS experiment, developed at NASA Ames’ COSmIC facility is a unique experimental platform that allows us to simulate Titan’s complex atmospheric chemistry at Titan-like temperature (200 K) by cooling down N2-CH4-based mixtures in a supersonic expansion before inducing the chemistry by plasma.Gas phase: The residence time of the jet-accelerated gas in the active plasma region is less than 4 µs, which results in a truncated chemistry enabling us to control how far in the chain of reactions the chemistry is processing. By adding heavier molecules in the initial gas mixture, it is then possible to study the first and intermediate steps of Titan’s atmospheric chemistry as well as specific chemical pathways, as demonstrated by mass spectrometry and comparison to Cassini CAPS data [1]. A new model was recently developed to simulate the plasma chemistry in the THS. Calculated mass spectra produced by this model are in good agreement with the experimental THS mass spectra, confirming that the short residence time in the plasma cavity limits the growth of larger species [2].Solid phase: Scanning electron microscopy and infrared spectroscopy have been used to investigate the effect of the initial gas mixture on the morphology of the THS Titan aerosol analogs as well as on the level and nature of the nitrogen incorporation into these aerosols. A comparison to Cassini VIMS observational data has shown that the THS aerosols produced in simpler mixtures, i.e., that contain more nitrogen and where the N-incorporation is in isocyanide-type molecules instead of nitriles, are more representative of Titan’s aerosols [3]. In addition, a new optical constant facility has been developed at NASA Ames that allows us to determine the complex refractive indices of THS Titan aerosol analogs from NIR to FIR (0.76-222 cm-1). The facility and preliminary results

A "Bony" Proposition: Pathways Mediating Responses to Simulated Weightlessness and Radiation

Science.gov (United States)

Tahimic, Candice; Globus, Ruth

2016-01-01

There is evidence that weightlessness and radiation, two elements of the spaceflight environment, can lead to detrimental changes in human musculoskeletal tissue, including bone loss and muscle atrophy. This bone loss is thought to be brought about by the increased activity of bone-resorbing osteoclasts and functional changes in bone-forming osteoblasts, cells that give rise to mature osteocytes. My current area of research focuses on understanding the mechanistic basis for the responses of bone to the spaceflight environment using earth-based animal and cellular models. The overarching goal is to identify molecular targets to prevent bone loss in space exploration and earth-based scenarios of radiotherapy, accidental radiation exposure and reduced mobility. In this talk, I will highlight two signaling pathways that potentially play a role in the response of bone to spaceflight-like conditions. Firstly, I will discuss the role of insulin-like growth factor 1 (IGF1) signaling as it pertains to the recovery of bone from simulated weightlessness (rodent hindlimb unloading model). Secondly, I will share recent findings from our study that aims to understand the emerging role of autophagy in maintaining the balance between bone formation and resorption (bone homeostasis) as well as normal skeletal structure.

Modularized Smad-regulated TGFβ signaling pathway.

Science.gov (United States)

Li, Yongfeng; Wang, Minli; Carra, Claudio; Cucinotta, Francis A

2012-12-01

The transforming Growth Factor β (TGFβ) signaling pathway is a prominent regulatory signaling pathway controlling various important cellular processes. TGFβ signaling can be induced by several factors including ionizing radiation. The pathway is regulated in a negative feedback loop through promoting the nuclear import of the regulatory Smads and a subsequent expression of inhibitory Smad7, that forms ubiquitin ligase with Smurf2, targeting active TGFβ receptors for degradation. In this work, we proposed a mathematical model to study the Smad-regulated TGFβ signaling pathway. By modularization, we are able to analyze mathematically each component subsystem and recover the nonlinear dynamics of the entire network system. Meanwhile the excitability, a common feature observed in the biological systems, in the TGFβ signaling pathway is discussed and supported as well by numerical simulation, indicating the robustness of the model. Published by Elsevier Inc.

PSFC: a Pathway Signal Flow Calculator App for Cytoscape [version 2; referees: 2 approved

Directory of Open Access Journals (Sweden)

Lilit Nersisyan

2017-04-01

Full Text Available Cell signaling pathways are sequences of biochemical reactions that propagate an input signal, such as a hormone binding to a cell-surface receptor, into the cell to trigger a reactive process. Assessment of pathway activities is crucial for determining which pathways play roles in disease versus normal conditions. To date various pathway flow/perturbation assessment tools are available, however they are constrained to specific algorithms and specific data types. There are no accepted standards for evaluation of pathway activities or simulation of flow propagation events in pathways, and the results of different software are difficult to compare. Here we present Pathway Signal Flow Calculator (PSFC, a Cytoscape app for calculation of a pathway signal flow based on the pathway topology and node input data. The app provides a rich framework for customization of different signal flow algorithms to allow users to apply various approaches within a single computational framework.

Comparison between the performance of some KEK-klystrons and simulation results

Energy Technology Data Exchange (ETDEWEB)

Fukuda, Shigeki [National Lab. for High Energy Physics, Tsukuba, Ibaraki (Japan)

1997-04-01

Recent developments of various klystron simulation codes have enabled us to realistically design klystrons. This paper presents various simulation results using the FCI code and the performances of tubes manufactured based on this code. Upgrading a 30-MW S-band klystron and developing a 50-MW S-band klystron for the KEKB projects are successful examples based on FCI-code predictions. Mass-productions of these tubes have already started. On the other hand, a discrepancy has been found between the FCI simulation results and the performance of real tubes. In some cases, the simulation results lead to high-efficiency results, while manufactured tubes show the usual value, or a lower value, of the efficiency. One possible cause may come from a data mismatch between the electron-gun simulation and the input data set of the FCI code for the gun region. This kind of discrepancy has been observed in 30-MW S-band pulsed tubes, sub-booster pulsed tubes and L-band high-duty pulsed klystrons. Sometimes, JPNDSK (one-dimensional disk-model code) gives similar results. Some examples using the FCI code are given in this article. An Arsenal-MSU code could be applied to the 50-MW klystron under collaboration with Moscow State University; a good agreement has been found between the prediction of the code and performance. (author)

Pathway-based analyses.

Science.gov (United States)

Kent, Jack W

2016-02-03

New technologies for acquisition of genomic data, while offering unprecedented opportunities for genetic discovery, also impose severe burdens of interpretation and penalties for multiple testing. The Pathway-based Analyses Group of the Genetic Analysis Workshop 19 (GAW19) sought reduction of multiple-testing burden through various approaches to aggregation of highdimensional data in pathways informed by prior biological knowledge. Experimental methods testedincluded the use of "synthetic pathways" (random sets of genes) to estimate power and false-positive error rate of methods applied to simulated data; data reduction via independent components analysis, single-nucleotide polymorphism (SNP)-SNP interaction, and use of gene sets to estimate genetic similarity; and general assessment of the efficacy of prior biological knowledge to reduce the dimensionality of complex genomic data. The work of this group explored several promising approaches to managing high-dimensional data, with the caveat that these methods are necessarily constrained by the quality of external bioinformatic annotation.

First results from simulations of supersymmetric lattices

Science.gov (United States)

Catterall, Simon

2009-01-01

We conduct the first numerical simulations of lattice theories with exact supersymmetry arising from the orbifold constructions of \\cite{Cohen:2003xe,Cohen:2003qw,Kaplan:2005ta}. We consider the Script Q = 4 theory in D = 0,2 dimensions and the Script Q = 16 theory in D = 0,2,4 dimensions. We show that the U(N) theories do not possess vacua which are stable non-perturbatively, but that this problem can be circumvented after truncation to SU(N). We measure the distribution of scalar field eigenvalues, the spectrum of the fermion operator and the phase of the Pfaffian arising after integration over the fermions. We monitor supersymmetry breaking effects by measuring a simple Ward identity. Our results indicate that simulations of Script N = 4 super Yang-Mills may be achievable in the near future.

Task-dependent activation of distinct fast and slow(er) motor pathways during motor imagery.

Science.gov (United States)

Keller, Martin; Taube, Wolfgang; Lauber, Benedikt

2018-02-22

Motor imagery and actual movements share overlapping activation of brain areas but little is known about task-specific activation of distinct motor pathways during mental simulation of movements. For real contractions, it was demonstrated that the slow(er) motor pathways are activated differently in ballistic compared to tonic contractions but it is unknown if this also holds true for imagined contractions. The aim of the present study was to assess the activity of fast and slow(er) motor pathways during mentally simulated movements of ballistic and tonic contractions. H-reflexes were conditioned with transcranial magnetic stimulation at different interstimulus intervals to assess the excitability of fast and slow(er) motor pathways during a) the execution of tonic and ballistic contractions, b) motor imagery of these contraction types, and c) at rest. In contrast to the fast motor pathways, the slow(er) pathways displayed a task-specific activation: for imagined ballistic as well as real ballistic contractions, the activation was reduced compared to rest whereas enhanced activation was found for imagined tonic and real tonic contractions. This study provides evidence that the excitability of fast and slow(er) motor pathways during motor imagery resembles the activation pattern observed during real contractions. The findings indicate that motor imagery results in task- and pathway-specific subliminal activation of distinct subsets of neurons in the primary motor cortex. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Src kinase conformational activation: thermodynamics, pathways, and mechanisms.

Directory of Open Access Journals (Sweden)

Sichun Yang

2008-03-01

Full Text Available Tyrosine kinases of the Src-family are large allosteric enzymes that play a key role in cellular signaling. Conversion of the kinase from an inactive to an active state is accompanied by substantial structural changes. Here, we construct a coarse-grained model of the catalytic domain incorporating experimental structures for the two stable states, and simulate the dynamics of conformational transitions in kinase activation. We explore the transition energy landscapes by constructing a structural network among clusters of conformations from the simulations. From the structural network, two major ensembles of pathways for the activation are identified. In the first transition pathway, we find a coordinated switching mechanism of interactions among the alphaC helix, the activation-loop, and the beta strands in the N-lobe of the catalytic domain. In a second pathway, the conformational change is coupled to a partial unfolding of the N-lobe region of the catalytic domain. We also characterize the switching mechanism for the alphaC helix and the activation-loop in detail. Finally, we test the performance of a Markov model and its ability to account for the structural kinetics in the context of Src conformational changes. Taken together, these results provide a broad framework for understanding the main features of the conformational transition taking place upon Src activation.

PI3K pathway activation results in low efficacy of both trastuzumab and lapatinib

International Nuclear Information System (INIS)

Wang, Leiping; Hu, Xichun; Zhang, Qunling; Zhang, Jian; Sun, Si; Guo, Haiyi; Jia, Zhen; Wang, Biyun; Shao, Zhimin; Wang, Zhonghua

2011-01-01

Human epidermal growth factor receptor 2 (HER2) is the most crucial ErbB receptor tyrosine kinase (RTK) family member in HER2-positive (refered to HER2-overexpressing) breast cancer which are dependent on or 'addictive' to the Phosphatidylinositol-3-kinase (PI3K) pathway. HER2-related target drugs trastuzumab and lapatinib have been the foundation of treatment of HER2--positive breast cancer. This study was designed to explore the relationship between PI3K pathway activation and the sensitivity to lapatinib in HER2--positive metastatic breast cancer patients pretreated with anthracyclins, taxanes and trastuzumab. Sixty-seven HER2-positive metastatic breast cancer patients were recruited into a global lapatinib Expanded Access Program and 57 patients have primary tumor specimens available for determination of PI3K pathway status. PTEN status was determined by immunohistochemical staining and PIK3CA mutations were detected via PCR sequencing. All patients were treated with lapatinib 1250 mg/day continuously and capecitabine 1000 mg/m 2 twice daily on a 2-week-on and 1-week-off schedule until disease progression, death, withdrawal of informed consent, or intolerable toxicity. PIK3CA mutations and PTEN loss were detected in 12.3% (7/57) and 31.6% (18/57) of the patients, respectively. Twenty-two patients with PI3K pathway activation (defined as PIK3CA mutation and/or PTEN expression loss) had a lower clinical benefit rate (36.4% versus 68.6%, P = 0.017) and a lower overall response rate (9.1% versus 31.4%, P = 0.05), when compared with the 35 patients with no activation. A retrospective analysis of first trastuzumab-containing regimen treatment data showed that PI3K pathway activation correlated with a shorter median progression-free survival (4.5 versus 9.0 months, P = 0.013). PIK3CA mutations occur more frequently in elder patients for HER2-positive breast cancer. PIK3CA mutations and PTEN loss are not mutually exclusive. PI3K pathway activation resulting

Fusing Simulation Results From Multifidelity Aero-servo-elastic Simulators - Application To Extreme Loads On Wind Turbine

DEFF Research Database (Denmark)

Abdallah, Imad; Sudret, Bruno; Lataniotis, Christos

2015-01-01

Fusing predictions from multiple simulators in the early stages of the conceptual design of a wind turbine results in reduction in model uncertainty and risk mitigation. Aero-servo-elastic is a term that refers to the coupling of wind inflow, aerodynamics, structural dynamics and controls. Fusing...... the response data from multiple aero-servo-elastic simulators could provide better predictive ability than using any single simulator. The co-Kriging approach to fuse information from multifidelity aero-servo-elastic simulators is presented. We illustrate the co-Kriging approach to fuse the extreme flapwise...... bending moment at the blade root of a large wind turbine as a function of wind speed, turbulence and shear exponent in the presence of model uncertainty and non-stationary noise in the output. The extreme responses are obtained by two widely accepted numerical aero-servo-elastic simulators, FAST...

First-principles determination of the K-conductivity pathways in KAlO2

KAUST Repository

Peskov, Maxim; Schwingenschlö gl, Udo

2015-01-01

Investigation of novel fast ion-conducting materials requires an accurate description of the ionic diffusion. The tiling method proposed by Blatov and coworkers, based on geometric characteristics, is a viable alternative to molecular dynamics simulations, allowing us to build models of the pathway system in crystal structures; however, the reliability is limited. Using first-principles simulations, we calculate the potential barriers of the ionic migration between voids in the structure of KAlO2 with local framework distortions and compare the results with those of the tiling method. We estimate the potential barriers for complex ion-conducting channels including several hopping distances. The effect of Coulomb interaction between charge carriers located in adjacent pathways on the potential barriers is discussed, and the effects of the framework flexibility are analyzed. Quantitative results on the potential barriers of ionic diffusion in a crystal structure and its dependence on the shape of the channels are important for assessing the potential of a specific compound. © 2015 American Chemical Society.

First-principles determination of the K-conductivity pathways in KAlO2

KAUST Repository

Peskov, Maxim

2015-04-30

Investigation of novel fast ion-conducting materials requires an accurate description of the ionic diffusion. The tiling method proposed by Blatov and coworkers, based on geometric characteristics, is a viable alternative to molecular dynamics simulations, allowing us to build models of the pathway system in crystal structures; however, the reliability is limited. Using first-principles simulations, we calculate the potential barriers of the ionic migration between voids in the structure of KAlO2 with local framework distortions and compare the results with those of the tiling method. We estimate the potential barriers for complex ion-conducting channels including several hopping distances. The effect of Coulomb interaction between charge carriers located in adjacent pathways on the potential barriers is discussed, and the effects of the framework flexibility are analyzed. Quantitative results on the potential barriers of ionic diffusion in a crystal structure and its dependence on the shape of the channels are important for assessing the potential of a specific compound. © 2015 American Chemical Society.

ANOVA parameters influence in LCF experimental data and simulation results

Directory of Open Access Journals (Sweden)

Vercelli A.

2010-06-01

Full Text Available The virtual design of components undergoing thermo mechanical fatigue (TMF and plastic strains is usually run in many phases. The numerical finite element method gives a useful instrument which becomes increasingly effective as the geometrical and numerical modelling gets more accurate. The constitutive model definition plays an important role in the effectiveness of the numerical simulation [1, 2] as, for example, shown in Figure 1. In this picture it is shown how a good cyclic plasticity constitutive model can simulate a cyclic load experiment. The component life estimation is the subsequent phase and it needs complex damage and life estimation models [3-5] which take into account of several parameters and phenomena contributing to damage and life duration. The calibration of these constitutive and damage models requires an accurate testing activity. In the present paper the main topic of the research activity is to investigate whether the parameters, which result to be influent in the experimental activity, influence the numerical simulations, thus defining the effectiveness of the models in taking into account of all the phenomena actually influencing the life of the component. To obtain this aim a procedure to tune the parameters needed to estimate the life of mechanical components undergoing TMF and plastic strains is presented for commercial steel. This procedure aims to be easy and to allow calibrating both material constitutive model (for the numerical structural simulation and the damage and life model (for life assessment. The procedure has been applied to specimens. The experimental activity has been developed on three sets of tests run at several temperatures: static tests, high cycle fatigue (HCF tests, low cycle fatigue (LCF tests. The numerical structural FEM simulations have been run on a commercial non linear solver, ABAQUS®6.8. The simulations replied the experimental tests. The stress, strain, thermal results from the thermo

The effect of giant lateral collapses on magma pathways and the location of volcanism.

Science.gov (United States)

Maccaferri, Francesco; Richter, Nicole; Walter, Thomas R

2017-10-23

Flank instability and lateral collapse are recurrent processes during the structural evolution of volcanic edifices, and they affect and are affected by magmatic activity. It is known that dyke intrusions have the potential to destabilise the flanks of a volcano, and that lateral collapses may change the style of volcanism and the arrangement of shallow dykes. However, the effect of a large lateral collapse on the location of a new eruptive centre remains unclear. Here, we use a numerical approach to simulate the pathways of magmatic intrusions underneath the volcanic edifice, after the stress redistribution resulting from a large lateral collapse. Our simulations are quantitatively validated against the observations at Fogo volcano, Cabo Verde. The results reveal that a lateral collapse can trigger a significant deflection of deep magma pathways in the crust, favouring the formation of a new eruptive centre within the collapse embayment. Our results have implications for the long-term evolution of intraplate volcanic ocean islands.

Scientific results and lessons learned from an integrated crewed Mars exploration simulation at the Rio Tinto Mars analogue site

Science.gov (United States)

Orgel, Csilla; Kereszturi, Ákos; Váczi, Tamás; Groemer, Gernot; Sattler, Birgit

2014-02-01

Between 15 and 25 April 2011 in the framework of the PolAres programme of the Austrian Space Forum, a five-day field test of the Aouda.X spacesuit simulator was conducted at the Rio Tinto Mars-analogue site in southern Spain. The field crew was supported by a full-scale Mission Control Center (MCC) in Innsbruck, Austria. The field telemetry data were relayed to the MCC, enabling a Remote Science Support (RSS) team to study field data in near-real-time and adjust the flight planning in a flexible manner. We report on the experiences in the field of robotics, geophysics (Ground Penetrating Radar) and geology as well as life sciences in a simulated spaceflight operational environment. Extravehicular Activity (EVA) maps had been prepared using Google Earth and aerial images. The Rio Tinto mining area offers an excellent location for Mars analogue simulations. It is recognised as a terrestrial Mars analogue site because of the presence of jarosite and related sulphates, which have been identified by the NASA Mars Exploration Rover "Opportunity" in the El Capitan region of Meridiani Planum on Mars. The acidic, high ferric-sulphate content water of Rio Tinto is also considered as a possible analogue in astrobiology regarding the analysis of ferric sulphate related biochemical pathways and produced biomarkers. During our Mars simulation, 18 different types of soil and rock samples were collected by the spacesuit tester. The Raman results confirm the presence of minerals expected, such as jarosite, different Fe oxides and oxi-hydroxides, pyrite and complex Mg and Ca sulphates. Eight science experiments were conducted in the field. In this contribution first we list the important findings during the management and realisation of tests, and also a first summary of the scientific results. Based on these experiences suggestions for future analogue work are also summarised. We finish with recommendations for future field missions, including the preparation of the experiments

Bonding pathways of high-pressure chemical transformations

International Nuclear Information System (INIS)

Hu Anguang; Zhang Fan

2013-01-01

A three-stage bonding pathway towards high-pressure chemical transformations from molecular precursors or intermediate states has been identified by first-principles simulations. With the evolution of principal stress tensor components in the response of chemical bonding to compressive loading, the three stages can be defined as the van der Waals bonding destruction, a bond breaking and forming reaction, and equilibrium of new bonds. The three-stage bonding pathway leads to the establishment of a fundamental principle of chemical bonding under compression. It reveals that during high-pressure chemical transformation, electrons moving away from functional groups follow anti-addition, collision-free paths to form new bonds in counteracting the local stress confinement. In applying this principle, a large number of molecular precursors were identified for high-pressure chemical transformations, resulting in new materials. (fast track communication)

A method for data handling numerical results in parallel OpenFOAM simulations

International Nuclear Information System (INIS)

nd Vasile Pârvan Ave., 300223, TM Timişoara, Romania, alin.anton@cs.upt.ro (Romania))" data-affiliation=" (Faculty of Automatic Control and Computing, Politehnica University of Timişoara, 2nd Vasile Pârvan Ave., 300223, TM Timişoara, Romania, alin.anton@cs.upt.ro (Romania))" >Anton, Alin; th Mihai Viteazu Ave., 300221, TM Timişoara (Romania))" data-affiliation=" (Center for Advanced Research in Engineering Science, Romanian Academy – Timişoara Branch, 24th Mihai Viteazu Ave., 300221, TM Timişoara (Romania))" >Muntean, Sebastian

2015-01-01

Parallel computational fluid dynamics simulations produce vast amount of numerical result data. This paper introduces a method for reducing the size of the data by replaying the interprocessor traffic. The results are recovered only in certain regions of interest configured by the user. A known test case is used for several mesh partitioning scenarios using the OpenFOAM toolkit ® [1]. The space savings obtained with classic algorithms remain constant for more than 60 Gb of floating point data. Our method is most efficient on large simulation meshes and is much better suited for compressing large scale simulation results than the regular algorithms

A method for data handling numerical results in parallel OpenFOAM simulations

Energy Technology Data Exchange (ETDEWEB)

Anton, Alin [Faculty of Automatic Control and Computing, Politehnica University of Timişoara, 2" n" d Vasile Pârvan Ave., 300223, TM Timişoara, Romania, alin.anton@cs.upt.ro (Romania); Muntean, Sebastian [Center for Advanced Research in Engineering Science, Romanian Academy – Timişoara Branch, 24" t" h Mihai Viteazu Ave., 300221, TM Timişoara (Romania)

2015-12-31

Parallel computational fluid dynamics simulations produce vast amount of numerical result data. This paper introduces a method for reducing the size of the data by replaying the interprocessor traffic. The results are recovered only in certain regions of interest configured by the user. A known test case is used for several mesh partitioning scenarios using the OpenFOAM toolkit{sup ®}[1]. The space savings obtained with classic algorithms remain constant for more than 60 Gb of floating point data. Our method is most efficient on large simulation meshes and is much better suited for compressing large scale simulation results than the regular algorithms.

Modeling the effects of a Staphylococcal Enterotoxin B (SEB on the apoptosis pathway

Directory of Open Access Journals (Sweden)

Hammamieh Rasha

2006-05-01

Full Text Available Abstract Background The lack of detailed understanding of the mechanism of action of many biowarfare agents poses an immediate challenge to biodefense efforts. Many potential bioweapons have been shown to affect the cellular pathways controlling apoptosis 1234. For example, pathogen-produced exotoxins such as Staphylococcal Enterotoxin B (SEB and Anthrax Lethal Factor (LF have been shown to disrupt the Fas-mediated apoptotic pathway 24. To evaluate how these agents affect these pathways it is first necessary to understand the dynamics of a normally functioning apoptosis network. This can then serve as a baseline against which a pathogen perturbed system can be compared. Such comparisons can expose both the proteins most susceptible to alteration by the agent as well as the most critical reaction rates to better instill control on a biological network. Results We explore this through the modeling and simulation of the Fas-mediated apoptotic pathway under normal and SEB influenced conditions. We stimulated human Jurkat cells with an anti-Fas antibody in the presence and absence of SEB and determined the relative levels of seven proteins involved in the core pathway at five time points following exposure. These levels were used to impute relative rate constants and build a quantitative model consisting of a series of ordinary differential equations (ODEs that simulate the network under both normal and pathogen-influenced conditions. Experimental results show that cells exposed to SEB exhibit an increase in the rate of executioner caspase expression (and subsequently apoptosis of 1 hour 43 minutes (± 14 minutes, as compared to cells undergoing normal cell death. Conclusion Our model accurately reflects these results and reveals intervention points that can be altered to restore SEB-influenced system dynamics back to levels within the range of normal conditions.

Quantum optimal control pathways of ozone isomerization dynamics subject to competing dissociation: A two-state one-dimensional model

International Nuclear Information System (INIS)

Kurosaki, Yuzuru; Ho, Tak-San; Rabitz, Herschel

2014-01-01

We construct a two-state one-dimensional reaction-path model for ozone open → cyclic isomerization dynamics. The model is based on the intrinsic reaction coordinate connecting the cyclic and open isomers with the O 2 + O asymptote on the ground-state 1 A ′ potential energy surface obtained with the high-level ab initio method. Using this two-state model time-dependent wave packet optimal control simulations are carried out. Two possible pathways are identified along with their respective band-limited optimal control fields; for pathway 1 the wave packet initially associated with the open isomer is first pumped into a shallow well on the excited electronic state potential curve and then driven back to the ground electronic state to form the cyclic isomer, whereas for pathway 2 the corresponding wave packet is excited directly to the primary well of the excited state potential curve. The simulations reveal that the optimal field for pathway 1 produces a final yield of nearly 100% with substantially smaller intensity than that obtained in a previous study [Y. Kurosaki, M. Artamonov, T.-S. Ho, and H. Rabitz, J. Chem. Phys. 131, 044306 (2009)] using a single-state one-dimensional model. Pathway 2, due to its strong coupling to the dissociation channel, is less effective than pathway 1. The simulations also show that nonlinear field effects due to molecular polarizability and hyperpolarizability are small for pathway 1 but could become significant for pathway 2 because much higher field intensity is involved in the latter. The results suggest that a practical control may be feasible with the aid of a few lowly excited electronic states for ozone isomerization

Electron-cloud updated simulation results for the PSR, and recent results for the SNS

International Nuclear Information System (INIS)

Pivi, M.; Furman, M.A.

2002-01-01

Recent simulation results for the main features of the electron cloud in the storage ring of the Spallation Neutron Source (SNS) at Oak Ridge, and updated results for the Proton Storage Ring (PSR) at Los Alamos are presented in this paper. A refined model for the secondary emission process including the so called true secondary, rediffused and backscattered electrons has recently been included in the electron-cloud code

Experiment vs simulation RT WFNDEC 2014 benchmark: CIVA results

International Nuclear Information System (INIS)

Tisseur, D.; Costin, M.; Rattoni, B.; Vienne, C.; Vabre, A.; Cattiaux, G.; Sollier, T.

2015-01-01

The French Atomic Energy Commission and Alternative Energies (CEA) has developed for years the CIVA software dedicated to simulation of NDE techniques such as Radiographic Testing (RT). RT modelling is achieved in CIVA using combination of a determinist approach based on ray tracing for transmission beam simulation and a Monte Carlo model for the scattered beam computation. Furthermore, CIVA includes various detectors models, in particular common x-ray films and a photostimulable phosphor plates. This communication presents the results obtained with the configurations proposed in the World Federation of NDEC 2014 RT modelling benchmark with the RT models implemented in the CIVA software

Experiment vs simulation RT WFNDEC 2014 benchmark: CIVA results

Energy Technology Data Exchange (ETDEWEB)

Tisseur, D., E-mail: david.tisseur@cea.fr; Costin, M., E-mail: david.tisseur@cea.fr; Rattoni, B., E-mail: david.tisseur@cea.fr; Vienne, C., E-mail: david.tisseur@cea.fr; Vabre, A., E-mail: david.tisseur@cea.fr; Cattiaux, G., E-mail: david.tisseur@cea.fr [CEA LIST, CEA Saclay 91191 Gif sur Yvette Cedex (France); Sollier, T. [Institut de Radioprotection et de Sûreté Nucléaire, B.P.17 92262 Fontenay-Aux-Roses (France)

2015-03-31

The French Atomic Energy Commission and Alternative Energies (CEA) has developed for years the CIVA software dedicated to simulation of NDE techniques such as Radiographic Testing (RT). RT modelling is achieved in CIVA using combination of a determinist approach based on ray tracing for transmission beam simulation and a Monte Carlo model for the scattered beam computation. Furthermore, CIVA includes various detectors models, in particular common x-ray films and a photostimulable phosphor plates. This communication presents the results obtained with the configurations proposed in the World Federation of NDEC 2014 RT modelling benchmark with the RT models implemented in the CIVA software.

CAVER 3.0: a tool for the analysis of transport pathways in dynamic protein structures.

Science.gov (United States)

Chovancova, Eva; Pavelka, Antonin; Benes, Petr; Strnad, Ondrej; Brezovsky, Jan; Kozlikova, Barbora; Gora, Artur; Sustr, Vilem; Klvana, Martin; Medek, Petr; Biedermannova, Lada; Sochor, Jiri; Damborsky, Jiri

2012-01-01

Tunnels and channels facilitate the transport of small molecules, ions and water solvent in a large variety of proteins. Characteristics of individual transport pathways, including their geometry, physico-chemical properties and dynamics are instrumental for understanding of structure-function relationships of these proteins, for the design of new inhibitors and construction of improved biocatalysts. CAVER is a software tool widely used for the identification and characterization of transport pathways in static macromolecular structures. Herein we present a new version of CAVER enabling automatic analysis of tunnels and channels in large ensembles of protein conformations. CAVER 3.0 implements new algorithms for the calculation and clustering of pathways. A trajectory from a molecular dynamics simulation serves as the typical input, while detailed characteristics and summary statistics of the time evolution of individual pathways are provided in the outputs. To illustrate the capabilities of CAVER 3.0, the tool was applied for the analysis of molecular dynamics simulation of the microbial enzyme haloalkane dehalogenase DhaA. CAVER 3.0 safely identified and reliably estimated the importance of all previously published DhaA tunnels, including the tunnels closed in DhaA crystal structures. Obtained results clearly demonstrate that analysis of molecular dynamics simulation is essential for the estimation of pathway characteristics and elucidation of the structural basis of the tunnel gating. CAVER 3.0 paves the way for the study of important biochemical phenomena in the area of molecular transport, molecular recognition and enzymatic catalysis. The software is freely available as a multiplatform command-line application at http://www.caver.cz.

CAVER 3.0: a tool for the analysis of transport pathways in dynamic protein structures.

Directory of Open Access Journals (Sweden)

Eva Chovancova

Full Text Available Tunnels and channels facilitate the transport of small molecules, ions and water solvent in a large variety of proteins. Characteristics of individual transport pathways, including their geometry, physico-chemical properties and dynamics are instrumental for understanding of structure-function relationships of these proteins, for the design of new inhibitors and construction of improved biocatalysts. CAVER is a software tool widely used for the identification and characterization of transport pathways in static macromolecular structures. Herein we present a new version of CAVER enabling automatic analysis of tunnels and channels in large ensembles of protein conformations. CAVER 3.0 implements new algorithms for the calculation and clustering of pathways. A trajectory from a molecular dynamics simulation serves as the typical input, while detailed characteristics and summary statistics of the time evolution of individual pathways are provided in the outputs. To illustrate the capabilities of CAVER 3.0, the tool was applied for the analysis of molecular dynamics simulation of the microbial enzyme haloalkane dehalogenase DhaA. CAVER 3.0 safely identified and reliably estimated the importance of all previously published DhaA tunnels, including the tunnels closed in DhaA crystal structures. Obtained results clearly demonstrate that analysis of molecular dynamics simulation is essential for the estimation of pathway characteristics and elucidation of the structural basis of the tunnel gating. CAVER 3.0 paves the way for the study of important biochemical phenomena in the area of molecular transport, molecular recognition and enzymatic catalysis. The software is freely available as a multiplatform command-line application at http://www.caver.cz.

CAVER 3.0: A Tool for the Analysis of Transport Pathways in Dynamic Protein Structures

Science.gov (United States)

Strnad, Ondrej; Brezovsky, Jan; Kozlikova, Barbora; Gora, Artur; Sustr, Vilem; Klvana, Martin; Medek, Petr; Biedermannova, Lada; Sochor, Jiri; Damborsky, Jiri

2012-01-01

Tunnels and channels facilitate the transport of small molecules, ions and water solvent in a large variety of proteins. Characteristics of individual transport pathways, including their geometry, physico-chemical properties and dynamics are instrumental for understanding of structure-function relationships of these proteins, for the design of new inhibitors and construction of improved biocatalysts. CAVER is a software tool widely used for the identification and characterization of transport pathways in static macromolecular structures. Herein we present a new version of CAVER enabling automatic analysis of tunnels and channels in large ensembles of protein conformations. CAVER 3.0 implements new algorithms for the calculation and clustering of pathways. A trajectory from a molecular dynamics simulation serves as the typical input, while detailed characteristics and summary statistics of the time evolution of individual pathways are provided in the outputs. To illustrate the capabilities of CAVER 3.0, the tool was applied for the analysis of molecular dynamics simulation of the microbial enzyme haloalkane dehalogenase DhaA. CAVER 3.0 safely identified and reliably estimated the importance of all previously published DhaA tunnels, including the tunnels closed in DhaA crystal structures. Obtained results clearly demonstrate that analysis of molecular dynamics simulation is essential for the estimation of pathway characteristics and elucidation of the structural basis of the tunnel gating. CAVER 3.0 paves the way for the study of important biochemical phenomena in the area of molecular transport, molecular recognition and enzymatic catalysis. The software is freely available as a multiplatform command-line application at http://www.caver.cz. PMID:23093919

Molecular dynamics simulations suggest ligand's binding to nicotinamidase/pyrazinamidase.

Science.gov (United States)

Zhang, Ji-Long; Zheng, Qing-Chuan; Li, Zheng-Qiang; Zhang, Hong-Xing

2012-01-01

The research on the binding process of ligand to pyrazinamidase (PncA) is crucial for elucidating the inherent relationship between resistance of Mycobacterium tuberculosis and PncA's activity. In the present study, molecular dynamics (MD) simulation methods were performed to investigate the unbinding process of nicotinamide (NAM) from two PncA enzymes, which is the reverse of the corresponding binding process. The calculated potential of mean force (PMF) based on the steered molecular dynamics (SMD) simulations sheds light on an optimal binding/unbinding pathway of the ligand. The comparative analyses between two PncAs clearly exhibit the consistency of the binding/unbinding pathway in the two enzymes, implying the universality of the pathway in all kinds of PncAs. Several important residues dominating the pathway were also determined by the calculation of interaction energies. The structural change of the proteins induced by NAM's unbinding or binding shows the great extent interior motion in some homologous region adjacent to the active sites of the two PncAs. The structure comparison substantiates that this region should be very important for the ligand's binding in all PncAs. Additionally, MD simulations also show that the coordination position of the ligand is displaced by one water molecule in the unliganded enzymes. These results could provide the more penetrating understanding of drug resistance of M. tuberculosis and be helpful for the development of new antituberculosis drugs.

Survival associated pathway identification with group Lp penalized global AUC maximization

Directory of Open Access Journals (Sweden)

Liu Zhenqiu

2010-08-01

Full Text Available Abstract It has been demonstrated that genes in a cell do not act independently. They interact with one another to complete certain biological processes or to implement certain molecular functions. How to incorporate biological pathways or functional groups into the model and identify survival associated gene pathways is still a challenging problem. In this paper, we propose a novel iterative gradient based method for survival analysis with group Lp penalized global AUC summary maximization. Unlike LASSO, Lp (p 1. We first extend Lp for individual gene identification to group Lp penalty for pathway selection, and then develop a novel iterative gradient algorithm for penalized global AUC summary maximization (IGGAUCS. This method incorporates the genetic pathways into global AUC summary maximization and identifies survival associated pathways instead of individual genes. The tuning parameters are determined using 10-fold cross validation with training data only. The prediction performance is evaluated using test data. We apply the proposed method to survival outcome analysis with gene expression profile and identify multiple pathways simultaneously. Experimental results with simulation and gene expression data demonstrate that the proposed procedures can be used for identifying important biological pathways that are related to survival phenotype and for building a parsimonious model for predicting the survival times.

Comparisons of the simulation results using different codes for ADS spallation target

International Nuclear Information System (INIS)

Yu Hongwei; Fan Sheng; Shen Qingbiao; Zhao Zhixiang; Wan Junsheng

2002-01-01

The calculations to the standard thick target were made by using different codes. The simulation of the thick Pb target with length of 60 cm, diameter of 20 cm bombarded with 800, 1000, 1500 and 2000 MeV energetic proton beam was carried out. The yields and the spectra of emitted neutron were studied. The spallation target was simulated by SNSP, SHIELD, DCM/CEM (Dubna Cascade Model /Cascade Evaporation Mode) and LAHET codes. The Simulation Results were compared with experiments. The comparisons show good agreement between the experiments and the SNSP simulated leakage neutron yield. The SHIELD simulated leakage neutron spectra are in good agreement with the LAHET and the DCM/CEM simulated leakage neutron spectra

Competition between meiotic and apomictic pathways during ovule and seed development results in clonality.

Science.gov (United States)

Hojsgaard, Diego H; Martínez, Eric J; Quarin, Camilo L

2013-01-01

Meiotic and apomictic reproductive pathways develop simultaneously in facultative aposporous species, and compete to form a seed as a final goal. This developmental competition was evaluated in tetraploid genotypes of Paspalum malacophyllum in order to understand the low level of sexuality in facultative apomictic populations. Cyto-embryology on ovules, flow cytometry on seeds and progeny tests by DNA fingerprinting were used to measure the relative incidence of each meiotic or apomictic pathway along four different stages of the plant's life cycle, namely the beginning and end of gametogenesis, seed formation and adult offspring. A high variation in the frequencies of sexual and apomictic pathways occurred at the first two stages. A trend of radical decline in realized sexuality was then observed. Sexual and apomictic seeds were produced, but the efficiency of the sexual pathway dropped drastically, and exclusively clonal offspring remained. Both reproductive pathways are unstable at the beginning of development, and only the apomictic one remains functional. Key factors reducing sexuality are the faster growth and parthenogenetic development in the aposporous pathway, and an (epi)genetically negative background related to the extensive gene de-regulation pattern responsible for apomixis. The effects of inbreeding depression during post-fertilization development may further decrease the frequency of effective sexuality. No claim to original US government works. New Phytologist © 2012 New Phytologist Trust.

Synergy between methylerythritol phosphate pathway and mevalonate pathway for isoprene production in Escherichia coli.

Science.gov (United States)

Yang, Chen; Gao, Xiang; Jiang, Yu; Sun, Bingbing; Gao, Fang; Yang, Sheng

2016-09-01

Isoprene, a key building block of synthetic rubber, is currently produced entirely from petrochemical sources. In this work, we engineered both the methylerythritol phosphate (MEP) pathway and the mevalonate (MVA) pathway for isoprene production in E. coli. The synergy between the MEP pathway and the MVA pathway was demonstrated by the production experiment, in which overexpression of both pathways improved the isoprene yield about 20-fold and 3-fold, respectively, compared to overexpression of the MEP pathway or the MVA pathway alone. The (13)C metabolic flux analysis revealed that simultaneous utilization of the two pathways resulted in a 4.8-fold increase in the MEP pathway flux and a 1.5-fold increase in the MVA pathway flux. The synergy of the dual pathway was further verified by quantifying intracellular flux responses of the MEP pathway and the MVA pathway to fosmidomycin treatment and mevalonate supplementation. Our results strongly suggest that coupling of the complementary reducing equivalent demand and ATP requirement plays an important role in the synergy of the dual pathway. Fed-batch cultivation of the engineered strain overexpressing the dual pathway resulted in production of 24.0g/L isoprene with a yield of 0.267g/g of glucose. The synergy of the MEP pathway and the MVA pathway also successfully increased the lycopene productivity in E. coli, which demonstrates that it can be used to improve the production of a broad range of terpenoids in microorganisms. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Copper-transporting P-type ATPases use a unique ion-release pathway

DEFF Research Database (Denmark)

Andersson, Magnus; Mattle, Daniel; Sitsel, Oleg

2014-01-01

Heavy metals in cells are typically regulated by PIB-type ATPases. The first structure of the class, a Cu(+)-ATPase from Legionella pneumophila (LpCopA), outlined a copper transport pathway across the membrane, which was inferred to be occluded. Here we show by molecular dynamics simulations...... that extracellular water solvated the transmembrane (TM) domain, results indicative of a Cu(+)-release pathway. Furthermore, a new LpCopA crystal structure determined at 2.8-Å resolution, trapped in the preceding E2P state, delineated the same passage, and site-directed-mutagenesis activity assays support...... a functional role for the conduit. The structural similarities between the TM domains of the two conformations suggest that Cu(+)-ATPases couple dephosphorylation and ion extrusion differently than do the well-characterized PII-type ATPases. The ion pathway explains why certain Menkes' and Wilson's disease...

Comparison of multiple-criteria decision-making methods - results of simulation study

Directory of Open Access Journals (Sweden)

Michał Adamczak

2016-12-01

Full Text Available Background: Today, both researchers and practitioners have many methods for supporting the decision-making process. Due to the conditions in which supply chains function, the most interesting are multi-criteria methods. The use of sophisticated methods for supporting decisions requires the parameterization and execution of calculations that are often complex. So is it efficient to use sophisticated methods? Methods: The authors of the publication compared two popular multi-criteria decision-making methods: the  Weighted Sum Model (WSM and the Analytic Hierarchy Process (AHP. A simulation study reflects these two decision-making methods. Input data for this study was a set of criteria weights and the value of each in terms of each criterion. Results: The iGrafx Process for Six Sigma simulation software recreated how both multiple-criteria decision-making methods (WSM and AHP function. The result of the simulation was a numerical value defining the preference of each of the alternatives according to the WSM and AHP methods. The alternative producing a result of higher numerical value  was considered preferred, according to the selected method. In the analysis of the results, the relationship between the values of the parameters and the difference in the results presented by both methods was investigated. Statistical methods, including hypothesis testing, were used for this purpose. Conclusions: The simulation study findings prove that the results obtained with the use of two multiple-criteria decision-making methods are very similar. Differences occurred more frequently in lower-value parameters from the "value of each alternative" group and higher-value parameters from the "weight of criteria" group.

Integrated visualization of simulation results and experimental devices in virtual-reality space

International Nuclear Information System (INIS)

Ohtani, Hiroaki; Ishiguro, Seiji; Shohji, Mamoru; Kageyama, Akira; Tamura, Yuichi

2011-01-01

We succeeded in integrating the visualization of both simulation results and experimental device data in virtual-reality (VR) space using CAVE system. Simulation results are shown using Virtual LHD software, which can show magnetic field line, particle trajectory, and isosurface of plasma pressure of the Large Helical Device (LHD) based on data from the magnetohydrodynamics equilibrium simulation. A three-dimensional mouse, or wand, determines the initial position and pitch angle of a drift particle or the starting point of a magnetic field line, interactively in the VR space. The trajectory of a particle and the stream-line of magnetic field are calculated using the Runge-Kutta-Huta integration method on the basis of the results obtained after pointing the initial condition. The LHD vessel is objectively visualized based on CAD-data. By using these results and data, the simulated LHD plasma can be interactively drawn in the objective description of the LHD experimental vessel. Through this integrated visualization, it is possible to grasp the three-dimensional relationship of the positions between the device and plasma in the VR space, opening a new path in contribution to future research. (author)

Benchmarking pathway interaction network for colorectal cancer to identify dysregulated pathways

Directory of Open Access Journals (Sweden)

Q. Wang

Full Text Available Different pathways act synergistically to participate in many biological processes. Thus, the purpose of our study was to extract dysregulated pathways to investigate the pathogenesis of colorectal cancer (CRC based on the functional dependency among pathways. Protein-protein interaction (PPI information and pathway data were retrieved from STRING and Reactome databases, respectively. After genes were aligned to the pathways, each pathway activity was calculated using the principal component analysis (PCA method, and the seed pathway was discovered. Subsequently, we constructed the pathway interaction network (PIN, where each node represented a biological pathway based on gene expression profile, PPI data, as well as pathways. Dysregulated pathways were then selected from the PIN according to classification performance and seed pathway. A PIN including 11,960 interactions was constructed to identify dysregulated pathways. Interestingly, the interaction of mRNA splicing and mRNA splicing-major pathway had the highest score of 719.8167. Maximum change of the activity score between CRC and normal samples appeared in the pathway of DNA replication, which was selected as the seed pathway. Starting with this seed pathway, a pathway set containing 30 dysregulated pathways was obtained with an area under the curve score of 0.8598. The pathway of mRNA splicing, mRNA splicing-major pathway, and RNA polymerase I had the maximum genes of 107. Moreover, we found that these 30 pathways had crosstalks with each other. The results suggest that these dysregulated pathways might be used as biomarkers to diagnose CRC.

A techno-economic analysis of EU renewable electricity policy pathways in 2030

International Nuclear Information System (INIS)

Río, Pablo del; Resch, Gustav; Ortner, Andre; Liebmann, Lukas; Busch, Sebastian; Panzer, Christian

2017-01-01

The aim of this paper is to assess several pathways of a harmonised European policy framework for supporting renewable electricity (RES-E) in a 2030 horizon according to different criteria. The pathways combine two main dimensions: degrees of harmonisation and instruments and design elements. A quantitative model-based analysis with the Green-X model is provided. The results of the simulations show that there are small differences between the evaluated cases regarding effectiveness. All the policy pathways score similarly with respect to RES-E deployment, i.e., with different degrees of harmonisation and whether using a feed-in tariff, a feed-in premium, a quota system with banding or a quota without banding scheme. In contrast, the policy costs clearly differ across the pathways, but the differences can mostly be attributed to the instruments rather than to the degrees of harmonisation. This is also the case with other criteria (static and dynamic efficiency and the socioeconomic and environmental benefits in terms of CO2 emissions and fossil fuels avoided). Both the degree of harmonisation and the choice of instrument influence the distribution of support costs across countries. Finally, our findings suggest that keeping strengthened national support leads to similar results to other policy pathways. - Highlights: • Pathways of a harmonised European policy framework for renewable electricity in 2030. • Two main dimensions: degrees of harmonisation and instruments. • A quantitative model-based analysis based on the Green-X model. • Small differences between the pathways regarding the effectiveness criterion. • Important differences between pathways regarding other assessment criteria.

A simplified method for power-law modelling of metabolic pathways from time-course data and steady-state flux profiles

Directory of Open Access Journals (Sweden)

Sugimoto Masahiro

2006-07-01

Full Text Available Abstract Background In order to improve understanding of metabolic systems there have been attempts to construct S-system models from time courses. Conventionally, non-linear curve-fitting algorithms have been used for modelling, because of the non-linear properties of parameter estimation from time series. However, the huge iterative calculations required have hindered the development of large-scale metabolic pathway models. To solve this problem we propose a novel method involving power-law modelling of metabolic pathways from the Jacobian of the targeted system and the steady-state flux profiles by linearization of S-systems. Results The results of two case studies modelling a straight and a branched pathway, respectively, showed that our method reduced the number of unknown parameters needing to be estimated. The time-courses simulated by conventional kinetic models and those described by our method behaved similarly under a wide range of perturbations of metabolite concentrations. Conclusion The proposed method reduces calculation complexity and facilitates the construction of large-scale S-system models of metabolic pathways, realizing a practical application of reverse engineering of dynamic simulation models from the Jacobian of the targeted system and steady-state flux profiles.

Molecular dynamics simulations suggest ligand's binding to nicotinamidase/pyrazinamidase.

Directory of Open Access Journals (Sweden)

Ji-Long Zhang

Full Text Available The research on the binding process of ligand to pyrazinamidase (PncA is crucial for elucidating the inherent relationship between resistance of Mycobacterium tuberculosis and PncA's activity. In the present study, molecular dynamics (MD simulation methods were performed to investigate the unbinding process of nicotinamide (NAM from two PncA enzymes, which is the reverse of the corresponding binding process. The calculated potential of mean force (PMF based on the steered molecular dynamics (SMD simulations sheds light on an optimal binding/unbinding pathway of the ligand. The comparative analyses between two PncAs clearly exhibit the consistency of the binding/unbinding pathway in the two enzymes, implying the universality of the pathway in all kinds of PncAs. Several important residues dominating the pathway were also determined by the calculation of interaction energies. The structural change of the proteins induced by NAM's unbinding or binding shows the great extent interior motion in some homologous region adjacent to the active sites of the two PncAs. The structure comparison substantiates that this region should be very important for the ligand's binding in all PncAs. Additionally, MD simulations also show that the coordination position of the ligand is displaced by one water molecule in the unliganded enzymes. These results could provide the more penetrating understanding of drug resistance of M. tuberculosis and be helpful for the development of new antituberculosis drugs.

Simulation Results: Optimization of Contact Ratio for Interdigitated Back-Contact Solar Cells

Directory of Open Access Journals (Sweden)

Vinay Budhraja

2017-01-01

Full Text Available In the fabrication of interdigitated back contact (IBC solar cells, it is very important to choose the right size of contact to achieve the maximum efficiency. Line contacts and point contacts are the two possibilities, which are being chosen for IBC structure. It is expected that the point contacts would give better results because of the reduced recombination rate. In this work, we are simulating the effect of contact size on the performance of IBC solar cells. Simulations were done in three dimension using Quokka, which numerically solves the charge carrier transport. Our simulation results show that around 10% of contact ratio is able to achieve optimum cell efficiency.

Simulation results of the electron-proton telescope for Solar Orbiter

Energy Technology Data Exchange (ETDEWEB)

Boden, Sebastian; Steinhagen, Jan; Kulkarni, Shrinivasrao; Grunau, Jan; Paspirgilis, Rolf; Martin, Cesar; Boettcher, Stephan; Seimetz, Lars; Schuster, Bjoern; Kulemzin, Alexander; Wimmer-Schweingruber, Robert F. [Christian-Albrechts-Universitaet Kiel (Germany)

2013-07-01

The Electron Proton Telescope (EPT) is one of five instruments in the Energetic Particle Detector suite for Solar Orbiter. It investigates low energy electrons and protons of solar events. EPT covers an energy range from 20400 keV for electrons and 20 keV-7 MeV for protons and distinguishes electrons from protons using a magnet/foil technique with silicon detectors. There will be two EPT units, each with double-barreled telescopes, one looking sunwards/antisunwards and the other north/south. EPT is designed using the GEometry ANd Tracking (GEANT) simulation toolkit developed by CERN for Monte Carlo calculations. Here we present the details of our simulations and the simulation results with respect to energy coverage and the geometrical factor of the EPT instrument. We also look at the far-field of the EPT magnets, which is important for electromagnetic cleanliness considerations.

Pathway enrichment analysis approach based on topological structure and updated annotation of pathway.

Science.gov (United States)

Yang, Qian; Wang, Shuyuan; Dai, Enyu; Zhou, Shunheng; Liu, Dianming; Liu, Haizhou; Meng, Qianqian; Jiang, Bin; Jiang, Wei

2017-08-16

Pathway enrichment analysis has been widely used to identify cancer risk pathways, and contributes to elucidating the mechanism of tumorigenesis. However, most of the existing approaches use the outdated pathway information and neglect the complex gene interactions in pathway. Here, we first reviewed the existing widely used pathway enrichment analysis approaches briefly, and then, we proposed a novel topology-based pathway enrichment analysis (TPEA) method, which integrated topological properties and global upstream/downstream positions of genes in pathways. We compared TPEA with four widely used pathway enrichment analysis tools, including database for annotation, visualization and integrated discovery (DAVID), gene set enrichment analysis (GSEA), centrality-based pathway enrichment (CePa) and signaling pathway impact analysis (SPIA), through analyzing six gene expression profiles of three tumor types (colorectal cancer, thyroid cancer and endometrial cancer). As a result, we identified several well-known cancer risk pathways that could not be obtained by the existing tools, and the results of TPEA were more stable than that of the other tools in analyzing different data sets of the same cancer. Ultimately, we developed an R package to implement TPEA, which could online update KEGG pathway information and is available at the Comprehensive R Archive Network (CRAN): https://cran.r-project.org/web/packages/TPEA/. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Coniferous tree plantations in forest conditions-economic analysis of dedicated and semi-dedicated pathways to increase wood production

International Nuclear Information System (INIS)

Rakotoarison, Hanitra; Richter, Claudine; Cailly, Priscilla; Deleuze, Christine; Berthelot, Alain

2015-01-01

To meet growing demand for wood, particularly softwoods, the authors study a number of new silvicultural pathways for planting 3 species: Douglas fir, spruce and maritime pine. The goal of these pathways is to achieve specialised production of either industrial and workable timber, or a mixture of industrial and workable timber with medium-diameter workable timber. Pathways of this type have already been standardised for hardwoods, generally on fertile farmland. In a less fertile forest context, softwoods have a significant potential for woody production but specialized pathways and their profitability have yet to be studied. This article describes the innovative work being done to construct and simulate profitable production, new potential pathways, where plantation density, rotation time, the level of fertility are made to vary using the data from the FCBA test network in conjunction with the FCBA growth models (Oasis for spruce and Douglas fir, Sylveco for maritime pine). Economic data is derived from auction sales statistics and the ONF management and forestry work costs for the period 2012-2015. The Economics module developed by FCBA and ONF on the Capsis platform in the framework of the ICI project (Futurol) was used for the economic simulations. The analyses show that compared to conventional pathways, these pathways generally increase productivity but are nonetheless less profitable than current economic assumptions, although results vary according to species, fertility and the particular pathway. The sensitivity study shows that variations in the price of wood could alter the performance ratings as between conventional and specialised pathways. (authors)

A novel dysregulated pathway-identification analysis based on global influence of within-pathway effects and crosstalk between pathways

Science.gov (United States)

Han, Junwei; Li, Chunquan; Yang, Haixiu; Xu, Yanjun; Zhang, Chunlong; Ma, Jiquan; Shi, Xinrui; Liu, Wei; Shang, Desi; Yao, Qianlan; Zhang, Yunpeng; Su, Fei; Feng, Li; Li, Xia

2015-01-01

Identifying dysregulated pathways from high-throughput experimental data in order to infer underlying biological insights is an important task. Current pathway-identification methods focus on single pathways in isolation; however, consideration of crosstalk between pathways could improve our understanding of alterations in biological states. We propose a novel method of pathway analysis based on global influence (PAGI) to identify dysregulated pathways, by considering both within-pathway effects and crosstalk between pathways. We constructed a global gene–gene network based on the relationships among genes extracted from a pathway database. We then evaluated the extent of differential expression for each gene, and mapped them to the global network. The random walk with restart algorithm was used to calculate the extent of genes affected by global influence. Finally, we used cumulative distribution functions to determine the significance values of the dysregulated pathways. We applied the PAGI method to five cancer microarray datasets, and compared our results with gene set enrichment analysis and five other methods. Based on these analyses, we demonstrated that PAGI can effectively identify dysregulated pathways associated with cancer, with strong reproducibility and robustness. We implemented PAGI using the freely available R-based and Web-based tools (http://bioinfo.hrbmu.edu.cn/PAGI). PMID:25551156

Protein kinase A (PKA) phosphorylation of Na+/K+-ATPase opens intracellular C-terminal water pathway leading to third Na+-binding site in molecular dynamics simulations

DEFF Research Database (Denmark)

Poulsen, Hanne; Nissen, Poul; Mouritsen, Ole G.

2012-01-01

-atom Molecular Dynamics (MD) simulations to investigate the structural consequences of phosphorylating the Na+/K+- ATPase (NKA) residue S936, which is the best characterized phosphorylation site in NKA, targeted in vivo by Protein Kinase A (PKA) (1-3). The MD simulations suggest that S936 phosphorylation opens......Phosphorylation is one of the major mechanisms for posttranscriptional modification of proteins. The addition of a compact, negatively charged moiety to a protein can significantly change its function and localization by affecting its structure and interaction network. We have used all...... a C-terminal hydrated pathway leading to D926, a transmembrane residue proposed to form part of the third sodium ion-binding site (4). Simulations of a S936E mutant form, for which only subtle effects are observed when expressed in Xenopus oocytes and studied with electrophysiology, does not mimic...

Investigating multiple dysregulated pathways in rheumatoid arthritis based on pathway interaction network.

Science.gov (United States)

Song, Xian-Dong; Song, Xian-Xu; Liu, Gui-Bo; Ren, Chun-Hui; Sun, Yuan-Bo; Liu, Ke-Xin; Liu, Bo; Liang, Shuang; Zhu, Zhu

2018-03-01

The traditional methods of identifying biomarkers in rheumatoid arthritis (RA) have focussed on the differentially expressed pathways or individual pathways, which however, neglect the interactions between pathways. To better understand the pathogenesis of RA, we aimed to identify dysregulated pathway sets using a pathway interaction network (PIN), which considered interactions among pathways. Firstly, RA-related gene expression profile data, protein-protein interactions (PPI) data and pathway data were taken up from the corresponding databases. Secondly, principal component analysis method was used to calculate the pathway activity of each of the pathway, and then a seed pathway was identified using data gleaned from the pathway activity. A PIN was then constructed based on the gene expression profile, pathway data, and PPI information. Finally, the dysregulated pathways were extracted from the PIN based on the seed pathway using the method of support vector machines and an area under the curve (AUC) index. The PIN comprised of a total of 854 pathways and 1064 pathway interactions. The greatest change in the activity score between RA and control samples was observed in the pathway of epigenetic regulation of gene expression, which was extracted and regarded as the seed pathway. Starting with this seed pathway, one maximum pathway set containing 10 dysregulated pathways was extracted from the PIN, having an AUC of 0.8249, and the result indicated that this pathway set could distinguish RA from the controls. These 10 dysregulated pathways might be potential biomarkers for RA diagnosis and treatment in the future.

Validation of a virtual reality-based simulator for shoulder arthroscopy.

Science.gov (United States)

Rahm, Stefan; Germann, Marco; Hingsammer, Andreas; Wieser, Karl; Gerber, Christian

2016-05-01

This study was to determine face and construct validity of a new virtual reality-based shoulder arthroscopy simulator which uses passive haptic feedback. Fifty-one participants including 25 novices (100 shoulder arthroscopies) completed two tests: for assessment of face validity, a questionnaire was filled out concerning quality of simulated reality and training potential using a 7-point Likert scale (range 1-7). Construct validity was tested by comparing simulator metrics (operation time in seconds, camera and grasper pathway in centimetre and grasper openings) between novices and experts test results. Overall simulated reality was rated high with a median value of 5.5 (range 2.8-7) points. Training capacity scored a median value of 5.8 (range 3-7) points. Experts were significantly faster in the diagnostic test with a median of 91 (range 37-208) s than novices with 1177 (range 81-383) s (p < 0.0001) and in the therapeutic test 102 (range 58-283) s versus 229 (range 114-399) s (p < 0.0001). Similar results were seen in the other metric values except in the camera pathway in the therapeutic test. The tested simulator achieved high scores in terms of realism and training capability. It reliably discriminated between novices and experts. Further improvements of the simulator, especially in the field of therapeutic arthroscopy, might improve its value as training and assessment tool for shoulder arthroscopy skills. II.

A comparison among observations and earthquake simulator results for the allcal2 California fault model

Science.gov (United States)

Tullis, Terry. E.; Richards-Dinger, Keith B.; Barall, Michael; Dieterich, James H.; Field, Edward H.; Heien, Eric M.; Kellogg, Louise; Pollitz, Fred F.; Rundle, John B.; Sachs, Michael K.; Turcotte, Donald L.; Ward, Steven N.; Yikilmaz, M. Burak

2012-01-01

In order to understand earthquake hazards we would ideally have a statistical description of earthquakes for tens of thousands of years. Unfortunately the ∼100‐year instrumental, several 100‐year historical, and few 1000‐year paleoseismological records are woefully inadequate to provide a statistically significant record. Physics‐based earthquake simulators can generate arbitrarily long histories of earthquakes; thus they can provide a statistically meaningful history of simulated earthquakes. The question is, how realistic are these simulated histories? This purpose of this paper is to begin to answer that question. We compare the results between different simulators and with information that is known from the limited instrumental, historic, and paleoseismological data.As expected, the results from all the simulators show that the observational record is too short to properly represent the system behavior; therefore, although tests of the simulators against the limited observations are necessary, they are not a sufficient test of the simulators’ realism. The simulators appear to pass this necessary test. In addition, the physics‐based simulators show similar behavior even though there are large differences in the methodology. This suggests that they represent realistic behavior. Different assumptions concerning the constitutive properties of the faults do result in enhanced capabilities of some simulators. However, it appears that the similar behavior of the different simulators may result from the fault‐system geometry, slip rates, and assumed strength drops, along with the shared physics of stress transfer.This paper describes the results of running four earthquake simulators that are described elsewhere in this issue of Seismological Research Letters. The simulators ALLCAL (Ward, 2012), VIRTCAL (Sachs et al., 2012), RSQSim (Richards‐Dinger and Dieterich, 2012), and ViscoSim (Pollitz, 2012) were run on our most recent all‐California fault

Which downstream signal transduction pathway(s) of H-ras are necessary for the cellular response(s) to ionizing radiation? (Results of an astro research fellowship year)

International Nuclear Information System (INIS)

Rudoltz, Marc S.; Muschel, Ruth J.; McKenna, W. Gillies

1996-01-01

the cells were washed with fresh media. Selection was begun at 48 hours. Independent clones were identified, expanded, and characterized. Results and Conclusion: As expected, morphologic transformation was obtained only in the MR4 cells transfected with V12Ras. However, MR4 cells transfected with T35S, E37G, or T35S+E37G did not show evidence of morphologic transformation. The effect of the C40 mutation on transformation will also be evaluated. In addition, cells will be evaluated in order to determine the downstream signal transduction pathways of H-ras responsible for regulation of growth rate, suppression of radiation-induced apoptosis, cell cycle kinetics, and radiation resistance

Improving the trust in results of numerical simulations and scientific data analytics

Energy Technology Data Exchange (ETDEWEB)

Cappello, Franck [Argonne National Lab. (ANL), Argonne, IL (United States); Constantinescu, Emil [Argonne National Lab. (ANL), Argonne, IL (United States); Hovland, Paul [Argonne National Lab. (ANL), Argonne, IL (United States); Peterka, Tom [Argonne National Lab. (ANL), Argonne, IL (United States); Phillips, Carolyn [Argonne National Lab. (ANL), Argonne, IL (United States); Snir, Marc [Argonne National Lab. (ANL), Argonne, IL (United States); Wild, Stefan [Argonne National Lab. (ANL), Argonne, IL (United States)

2015-04-30

This white paper investigates several key aspects of the trust that a user can give to the results of numerical simulations and scientific data analytics. In this document, the notion of trust is related to the integrity of numerical simulations and data analytics applications. This white paper complements the DOE ASCR report on Cybersecurity for Scientific Computing Integrity by (1) exploring the sources of trust loss; (2) reviewing the definitions of trust in several areas; (3) providing numerous cases of result alteration, some of them leading to catastrophic failures; (4) examining the current notion of trust in numerical simulation and scientific data analytics; (5) providing a gap analysis; and (6) suggesting two important research directions and their respective research topics. To simplify the presentation without loss of generality, we consider that trust in results can be lost (or the results’ integrity impaired) because of any form of corruption happening during the execution of the numerical simulation or the data analytics application. In general, the sources of such corruption are threefold: errors, bugs, and attacks. Current applications are already using techniques to deal with different types of corruption. However, not all potential corruptions are covered by these techniques. We firmly believe that the current level of trust that a user has in the results is at least partially founded on ignorance of this issue or the hope that no undetected corruptions will occur during the execution. This white paper explores the notion of trust and suggests recommendations for developing a more scientifically grounded notion of trust in numerical simulation and scientific data analytics. We first formulate the problem and show that it goes beyond previous questions regarding the quality of results such as V&V, uncertainly quantification, and data assimilation. We then explore the complexity of this difficult problem, and we sketch complementary general

Genome-scale consequences of cofactor balancing in engineered pentose utilization pathways in Saccharomyces cerevisiae.

Directory of Open Access Journals (Sweden)

Amit Ghosh

Full Text Available Biofuels derived from lignocellulosic biomass offer promising alternative renewable energy sources for transportation fuels. Significant effort has been made to engineer Saccharomyces cerevisiae to efficiently ferment pentose sugars such as D-xylose and L-arabinose into biofuels such as ethanol through heterologous expression of the fungal D-xylose and L-arabinose pathways. However, one of the major bottlenecks in these fungal pathways is that the cofactors are not balanced, which contributes to inefficient utilization of pentose sugars. We utilized a genome-scale model of S. cerevisiae to predict the maximal achievable growth rate for cofactor balanced and imbalanced D-xylose and L-arabinose utilization pathways. Dynamic flux balance analysis (DFBA was used to simulate batch fermentation of glucose, D-xylose, and L-arabinose. The dynamic models and experimental results are in good agreement for the wild type and for the engineered D-xylose utilization pathway. Cofactor balancing the engineered D-xylose and L-arabinose utilization pathways simulated an increase in ethanol batch production of 24.7% while simultaneously reducing the predicted substrate utilization time by 70%. Furthermore, the effects of cofactor balancing the engineered pentose utilization pathways were evaluated throughout the genome-scale metabolic network. This work not only provides new insights to the global network effects of cofactor balancing but also provides useful guidelines for engineering a recombinant yeast strain with cofactor balanced engineered pathways that efficiently co-utilizes pentose and hexose sugars for biofuels production. Experimental switching of cofactor usage in enzymes has been demonstrated, but is a time-consuming effort. Therefore, systems biology models that can predict the likely outcome of such strain engineering efforts are highly useful for motivating which efforts are likely to be worth the significant time investment.

Reconstruction and flux analysis of coupling between metabolic pathways of astrocytes and neurons: application to cerebral hypoxia

Directory of Open Access Journals (Sweden)

Akιn Ata

2007-12-01

Full Text Available Abstract Background It is a daunting task to identify all the metabolic pathways of brain energy metabolism and develop a dynamic simulation environment that will cover a time scale ranging from seconds to hours. To simplify this task and make it more practicable, we undertook stoichiometric modeling of brain energy metabolism with the major aim of including the main interacting pathways in and between astrocytes and neurons. Model The constructed model includes central metabolism (glycolysis, pentose phosphate pathway, TCA cycle, lipid metabolism, reactive oxygen species (ROS detoxification, amino acid metabolism (synthesis and catabolism, the well-known glutamate-glutamine cycle, other coupling reactions between astrocytes and neurons, and neurotransmitter metabolism. This is, to our knowledge, the most comprehensive attempt at stoichiometric modeling of brain metabolism to date in terms of its coverage of a wide range of metabolic pathways. We then attempted to model the basal physiological behaviour and hypoxic behaviour of the brain cells where astrocytes and neurons are tightly coupled. Results The reconstructed stoichiometric reaction model included 217 reactions (184 internal, 33 exchange and 216 metabolites (183 internal, 33 external distributed in and between astrocytes and neurons. Flux balance analysis (FBA techniques were applied to the reconstructed model to elucidate the underlying cellular principles of neuron-astrocyte coupling. Simulation of resting conditions under the constraints of maximization of glutamate/glutamine/GABA cycle fluxes between the two cell types with subsequent minimization of Euclidean norm of fluxes resulted in a flux distribution in accordance with literature-based findings. As a further validation of our model, the effect of oxygen deprivation (hypoxia on fluxes was simulated using an FBA-derivative approach, known as minimization of metabolic adjustment (MOMA. The results show the power of the

Kinetics of Huperzine A Dissociation from Acetylcholinesterase via Multiple Unbinding Pathways.

Science.gov (United States)

Rydzewski, Jakub; Jakubowski, Rafal; Nowak, Wieslaw; Grubmüller, Helmut

2018-05-01

The dissociation of huperzine A (hupA) from Torpedo californica acetylcholinesterase (TcAChE) was investigated by 4-microsecond unbiased and biased all-atom molecular dynamics (MD) simulations in explicit solvent. We performed our study using memetic sampling (MS) for the determination of reaction pathways (RPs), metadynamics to calculate free energy, and maximum-likelihood estimation (MLE) to recover kinetic rates from unbiased MD simulations. Our simulations suggest that the dissociation of hupA occurs mainly via two RPs: a front-door along the axis of the active-site gorge (pwf) and through a new transient side-door (pws), i.e., formed by the Omega-loop (residues 67--94 of TcAChE). Analysis of the inhibitor unbinding along the RPs suggests that pws is opened transiently after hupA and the Omega-loop reach a low free-energy transition state characterized by the orientation of the pyridone group of the inhibitor directed toward the Omega-loop plane. Unlike pws, pwf does not require large structural changes of TcAChE to be accessible. The estimated free energies and rates agree well with available experimental data. The dissociation rates along the unbinding pathways are similar, suggesting that the dissociation of hupA along pws is likely to be relevant. This indicates that perturbations to hupA-TcAChE interactions could potentially induce pathway hopping. In summary, out results characterize the slow-onset inhibition of TcAChE by hupA, which may provide the structural and energetic basis for the rational design of the next-generation slow-onset inhibitors with optimized pharmacokinetic properties for the treatment of Alzheimer's disease.

Molecular Dynamics Simulations Suggest Ligand’s Binding to Nicotinamidase/Pyrazinamidase

Science.gov (United States)

Zhang, Ji-Long; Zheng, Qing-Chuan; Li, Zheng-Qiang; Zhang, Hong-Xing

2012-01-01

The research on the binding process of ligand to pyrazinamidase (PncA) is crucial for elucidating the inherent relationship between resistance of Mycobacterium tuberculosis and PncA’s activity. In the present study, molecular dynamics (MD) simulation methods were performed to investigate the unbinding process of nicotinamide (NAM) from two PncA enzymes, which is the reverse of the corresponding binding process. The calculated potential of mean force (PMF) based on the steered molecular dynamics (SMD) simulations sheds light on an optimal binding/unbinding pathway of the ligand. The comparative analyses between two PncAs clearly exhibit the consistency of the binding/unbinding pathway in the two enzymes, implying the universality of the pathway in all kinds of PncAs. Several important residues dominating the pathway were also determined by the calculation of interaction energies. The structural change of the proteins induced by NAM’s unbinding or binding shows the great extent interior motion in some homologous region adjacent to the active sites of the two PncAs. The structure comparison substantiates that this region should be very important for the ligand’s binding in all PncAs. Additionally, MD simulations also show that the coordination position of the ligand is displaced by one water molecule in the unliganded enzymes. These results could provide the more penetrating understanding of drug resistance of M. tuberculosis and be helpful for the development of new antituberculosis drugs. PMID:22761821

Solubility of indium-tin oxide in simulated lung and gastric fluids: Pathways for human intake.

Science.gov (United States)

Andersen, Jens Christian Østergård; Cropp, Alastair; Paradise, Diane Caroline

2017-02-01

From being a metal with very limited natural distribution, indium (In) has recently become disseminated throughout the human society. Little is known of how In compounds behave in the natural environment, but recent medical studies link exposure to In compounds to elevated risk of respiratory disorders. Animal tests suggest that exposure may lead to more widespread damage in the body, notably the liver, kidneys and spleen. In this paper, we investigate the solubility of the most widely used In compound, indium-tin oxide (ITO) in simulated lung and gastric fluids in order to better understand the potential pathways for metals to be introduced into the bloodstream. Our results show significant potential for release of In and tin (Sn) in the deep parts of the lungs (artificial lysosomal fluid) and digestive tract, while the solubility in the upper parts of the lungs (the respiratory tract or tracheobronchial tree) is very low. Our study confirms that ITO is likely to remain as solid particles in the upper parts of the lungs, but that particles are likely to slowly dissolve in the deep lungs. Considering the prolonged residence time of inhaled particles in the deep lung, this environment is likely to provide the major route for uptake of In and Sn from inhaled ITO nano- and microparticles. Although dissolution through digestion may also lead to some uptake, the much shorter residence time is likely to lead to much lower risk of uptake. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Binding mechanism and dynamic conformational change of C subunit of PKA with different pathways.

Science.gov (United States)

Chu, Wen-Ting; Chu, Xiakun; Wang, Jin

2017-09-19

The catalytic subunit of PKA (PKAc) exhibits three major conformational states (open, intermediate, and closed) during the biocatalysis process. Both ATP and substrate/inhibitor can effectively induce the conformational changes of PKAc from open to closed states. Aiming to explore the mechanism of this allosteric regulation, we developed a coarse-grained model and analyzed the dynamics of conformational changes of PKAc during binding by performing molecular dynamics simulations for apo PKAc, binary PKAc (PKAc with ATP, PKAc with PKI), and ternary PKAc (PKAc with ATP and PKI). Our results suggest a mixed binding mechanism of induced fit and conformational selection, with the induced fit dominant. The ligands can drive the movements of Gly-rich loop as well as some regions distal to the active site in PKAc and stabilize them at complex state. In addition, there are two parallel pathways (pathway with PKAc-ATP as an intermediate and pathway PKAc-PKI as an intermediate) during the transition from open to closed states. By molecular dynamics simulations and rate constant analyses, we find that the pathway through PKAc-ATP intermediate is the main binding route from open to closed state because of the fact that the bound PKI will hamper ATP from successful binding and significantly increase the barrier for the second binding subprocess. These findings will provide fundamental insights of the mechanisms of PKAc conformational change upon binding.

Influence of Various Irradiance Models and Their Combination on Simulation Results of Photovoltaic Systems

Directory of Open Access Journals (Sweden)

Martin Hofmann

2017-09-01

Full Text Available We analyze the output of various state-of-the-art irradiance models for photovoltaic systems. The models include two sun position algorithms, three types of input data time series, nine diffuse fraction models and five transposition models (for tilted surfaces, resulting in 270 different model chains for the photovoltaic (PV system simulation. These model chains are applied to 30 locations worldwide and three different module tracking types, totaling in 24,300 simulations. We show that the simulated PV yearly energy output varies between −5% and +8% for fixed mounted PV modules and between −26% and +14% for modules with two-axis tracking. Model quality varies strongly between locations; sun position algorithms have negligible influence on the simulation results; diffuse fraction models add a lot of variability; and transposition models feature the strongest influence on the simulation results. To highlight the importance of irradiance with high temporal resolution, we present an analysis of the influence of input temporal resolution and simulation models on the inverter clipping losses at varying PV system sizing factors for Lindenberg, Germany. Irradiance in one-minute resolution is essential for accurately calculating inverter clipping losses.

CR2-mediated activation of the complement alternative pathway results in formation of membrane attack complexes on human B lymphocytes

DEFF Research Database (Denmark)

Nielsen, C H; Marquart, H V; Prodinger, W M

2001-01-01

the alternative pathway. Blockade of the CR2 ligand-binding site with the monoclonal antibody FE8 resulted in 56 +/- 13% and 71 +/- 9% inhibition of the C3-fragment and MAC deposition, respectively, whereas the monoclonal antibody HB135, directed against an irrelevant CR2 epitope, had no effect. Blockade......Normal human B lymphocytes activate the alternative pathway of complement via complement receptor type 2 (CR2, CD21), that binds hydrolysed C3 (iC3) and thereby promotes the formation of a membrane-bound C3 convertase. We have investigated whether this might lead to the generation of a C5...... processes on CR2, indicate that MAC formation is a consequence of alternative pathway activation....

First results from the IllustrisTNG simulations: the galaxy colour bimodality

Science.gov (United States)

Nelson, Dylan; Pillepich, Annalisa; Springel, Volker; Weinberger, Rainer; Hernquist, Lars; Pakmor, Rüdiger; Genel, Shy; Torrey, Paul; Vogelsberger, Mark; Kauffmann, Guinevere; Marinacci, Federico; Naiman, Jill

2018-03-01

We introduce the first two simulations of the IllustrisTNG project, a next generation of cosmological magnetohydrodynamical simulations, focusing on the optical colours of galaxies. We explore TNG100, a rerun of the original Illustris box, and TNG300, which includes 2 × 25003 resolution elements in a volume 20 times larger. Here, we present first results on the galaxy colour bimodality at low redshift. Accounting for the attenuation of stellar light by dust, we compare the simulated (g - r) colours of 109 1011 M⊙ which redden at z z = 0 mass post-reddening; at the same time, ˜18 per cent of such massive galaxies acquire half or more of their final stellar mass while on the red sequence.

Extended post processing for simulation results of FEM synthesized UHF-RFID transponder antennas

Directory of Open Access Journals (Sweden)

R. Herschmann

2007-06-01

Full Text Available The computer aided design process of sophisticated UHF-RFID transponder antennas requires the application of reliable simulation software. This paper describes a Matlab implemented extension of the post processor capabilities of the commercially available three dimensional field simulation programme Ansoft HFSS to compute an accurate solution of the antenna's surface current distribution. The accuracy of the simulated surface currents, which are physically related to the impedance at the feeding point of the antenna, depends on the convergence of the electromagnetic fields inside the simulation volume. The introduced method estimates the overall quality of the simulation results by combining the surface currents with the electromagnetic fields extracted from the field solution of Ansoft HFSS.

Modeling results for a linear simulator of a divertor

International Nuclear Information System (INIS)

Hooper, E.B.; Brown, M.D.; Byers, J.A.; Casper, T.A.; Cohen, B.I.; Cohen, R.H.; Jackson, M.C.; Kaiser, T.B.; Molvik, A.W.; Nevins, W.M.; Nilson, D.G.; Pearlstein, L.D.; Rognlien, T.D.

1993-01-01

A divertor simulator, IDEAL, has been proposed by S. Cohen to study the difficult power-handling requirements of the tokamak program in general and the ITER program in particular. Projections of the power density in the ITER divertor reach ∼ 1 Gw/m 2 along the magnetic fieldlines and > 10 MW/m 2 on a surface inclined at a shallow angle to the fieldlines. These power densities are substantially greater than can be handled reliably on the surface, so new techniques are required to reduce the power density to a reasonable level. Although the divertor physics must be demonstrated in tokamaks, a linear device could contribute to the development because of its flexibility, the easy access to the plasma and to tested components, and long pulse operation (essentially cw). However, a decision to build a simulator requires not just the recognition of its programmatic value, but also confidence that it can meet the required parameters at an affordable cost. Accordingly, as reported here, it was decided to examine the physics of the proposed device, including kinetic effects resulting from the intense heating required to reach the plasma parameters, and to conduct an independent cost estimate. The detailed role of the simulator in a divertor program is not explored in this report

Verification of results of core physics on-line simulation by NGFM code

International Nuclear Information System (INIS)

Zhao Yu; Cao Xinrong; Zhao Qiang

2008-01-01

Nodal Green's Function Method program NGFM/TNGFM has been trans- planted to windows system. The 2-D and 3-D benchmarks have been checked by this program. And the program has been used to check the results of QINSHAN-II reactor simulation. It is proved that the NGFM/TNGFM program is applicable for reactor core physics on-line simulation system. (authors)

Systems Biology Genetic Approach Identifies Serotonin Pathway as a Possible Target for Obstructive Sleep Apnea: Results from a Literature Search Review

Directory of Open Access Journals (Sweden)

Ram Jagannathan

2017-01-01

Full Text Available Rationale. Overall validity of existing genetic biomarkers in the diagnosis of obstructive sleep apnea (OSA remains unclear. The objective of this systematic genetic study is to identify “novel” biomarkers for OSA using systems biology approach. Methods. Candidate genes for OSA were extracted from PubMed, MEDLINE, and Embase search engines and DisGeNET database. The gene ontology (GO analyses and candidate genes prioritization were performed using Enrichr tool. Genes pertaining to the top 10 pathways were extracted and used for Ingenuity Pathway Analysis. Results. In total, we have identified 153 genes. The top 10 pathways associated with OSA include (i serotonin receptor interaction, (ii pathways in cancer, (iii AGE-RAGE signaling in diabetes, (iv infectious diseases, (v serotonergic synapse, (vi inflammatory bowel disease, (vii HIF-1 signaling pathway, (viii PI3-AKT signaling pathway, (ix regulation lipolysis in adipocytes, and (x rheumatoid arthritis. After removing the overlapping genes, we have identified 23 candidate genes, out of which >30% of the genes were related to the genes involved in the serotonin pathway. Among these 4 serotonin receptors SLC6A4, HTR2C, HTR2A, and HTR1B were strongly associated with OSA. Conclusions. This preliminary report identifies several potential candidate genes associated with OSA and also describes the possible regulatory mechanisms.

Some GCM simulation results on present and possible future climate in northern Europe

Energy Technology Data Exchange (ETDEWEB)

Raeisaenen, J [Helsinki Univ. (Finland). Dept. of Meteorology

1996-12-31

The Intergovernmental Panel on Climate Change initiated in 1993 a project entitled `Evaluation of Regional Climate Simulations`. The two basic aims of this project were to assess the skill of current general circulation models (GCMs) in simulating present climate at a regional level and to intercompare the regional response of various GCMs to increased greenhouse gas concentrations. The public data base established for the comparison included simulation results from several modelling centres, but most of the data were available in the form of time-averaged seasonal means only, and important quantities like precipitation were totally lacking in many cases. This presentation summarizes the intercomparison results for surface air temperature and sea level pressure in northern Europe. The quality of the control simulations and the response of the models to increased CO{sub 2} are addressed in both winter (December-February) and summer (June-August)

Some GCM simulation results on present and possible future climate in northern Europe

Energy Technology Data Exchange (ETDEWEB)

Raeisaenen, J. [Helsinki Univ. (Finland). Dept. of Meteorology

1995-12-31

The Intergovernmental Panel on Climate Change initiated in 1993 a project entitled `Evaluation of Regional Climate Simulations`. The two basic aims of this project were to assess the skill of current general circulation models (GCMs) in simulating present climate at a regional level and to intercompare the regional response of various GCMs to increased greenhouse gas concentrations. The public data base established for the comparison included simulation results from several modelling centres, but most of the data were available in the form of time-averaged seasonal means only, and important quantities like precipitation were totally lacking in many cases. This presentation summarizes the intercomparison results for surface air temperature and sea level pressure in northern Europe. The quality of the control simulations and the response of the models to increased CO{sub 2} are addressed in both winter (December-February) and summer (June-August)

Evacuation Simulation in Kalayaan Residence Hall, up Diliman Using Gama Simulation Software

Science.gov (United States)

Claridades, A. R. C.; Villanueva, J. K. S.; Macatulad, E. G.

2016-09-01

Agent-Based Modeling (ABM) has recently been adopted in some studies for the modelling of events as a dynamic system given a set of events and parameters. In principle, ABM employs individual agents with assigned attributes and behaviors and simulates their behavior around their environment and interaction with other agents. This can be a useful tool in both micro and macroscale-applications. In this study, a model initially created and applied to an academic building was implemented in a dormitory. In particular, this research integrates three-dimensional Geographic Information System (GIS) with GAMA as the multi-agent based evacuation simulation and is implemented in Kalayaan Residence Hall. A three-dimensional GIS model is created based on the floor plans and demographic data of the dorm, including respective pathways as networks, rooms, floors, exits and appropriate attributes. This model is then re-implemented in GAMA. Different states of the agents and their effect on their evacuation time were then observed. GAMA simulation with varying path width was also implemented. It has been found out that compared to their original states, panic, eating and studying will hasten evacuation, and on the other hand, sleeping and being on the bathrooms will be impedances. It is also concluded that evacuation time will be halved when path widths are doubled, however it is recommended for further studies for pathways to be modeled as spaces instead of lines. A more scientific basis for predicting agent behavior in these states is also recommended for more realistic results.

Identification of altered pathways in breast cancer based on individualized pathway aberrance score.

Science.gov (United States)

Shi, Sheng-Hong; Zhang, Wei; Jiang, Jing; Sun, Long

2017-08-01

The objective of the present study was to identify altered pathways in breast cancer based on the individualized pathway aberrance score (iPAS) method combined with the normal reference (nRef). There were 4 steps to identify altered pathways using the iPAS method: Data preprocessing conducted by the robust multi-array average (RMA) algorithm; gene-level statistics based on average Z ; pathway-level statistics according to iPAS; and a significance test dependent on 1 sample Wilcoxon test. The altered pathways were validated by calculating the changed percentage of each pathway in tumor samples and comparing them with pathways from differentially expressed genes (DEGs). A total of 688 altered pathways with Ppathways were involved in the total 688 altered pathways, which may validate the present results. In addition, there were 324 DEGs and 155 common genes between DEGs and pathway genes. DEGs and common genes were enriched in the same 9 significant terms, which also were members of altered pathways. The iPAS method was suitable for identifying altered pathways in breast cancer. Altered pathways (such as KIF and PLK mediated events) were important for understanding breast cancer mechanisms and for the future application of customized therapeutic decisions.

Non Linear Programming (NLP) formulation for quantitative modeling of protein signal transduction pathways.

Science.gov (United States)

Mitsos, Alexander; Melas, Ioannis N; Morris, Melody K; Saez-Rodriguez, Julio; Lauffenburger, Douglas A; Alexopoulos, Leonidas G

2012-01-01

Modeling of signal transduction pathways plays a major role in understanding cells' function and predicting cellular response. Mathematical formalisms based on a logic formalism are relatively simple but can describe how signals propagate from one protein to the next and have led to the construction of models that simulate the cells response to environmental or other perturbations. Constrained fuzzy logic was recently introduced to train models to cell specific data to result in quantitative pathway models of the specific cellular behavior. There are two major issues in this pathway optimization: i) excessive CPU time requirements and ii) loosely constrained optimization problem due to lack of data with respect to large signaling pathways. Herein, we address both issues: the former by reformulating the pathway optimization as a regular nonlinear optimization problem; and the latter by enhanced algorithms to pre/post-process the signaling network to remove parts that cannot be identified given the experimental conditions. As a case study, we tackle the construction of cell type specific pathways in normal and transformed hepatocytes using medium and large-scale functional phosphoproteomic datasets. The proposed Non Linear Programming (NLP) formulation allows for fast optimization of signaling topologies by combining the versatile nature of logic modeling with state of the art optimization algorithms.

Non Linear Programming (NLP formulation for quantitative modeling of protein signal transduction pathways.

Directory of Open Access Journals (Sweden)

Alexander Mitsos

Full Text Available Modeling of signal transduction pathways plays a major role in understanding cells' function and predicting cellular response. Mathematical formalisms based on a logic formalism are relatively simple but can describe how signals propagate from one protein to the next and have led to the construction of models that simulate the cells response to environmental or other perturbations. Constrained fuzzy logic was recently introduced to train models to cell specific data to result in quantitative pathway models of the specific cellular behavior. There are two major issues in this pathway optimization: i excessive CPU time requirements and ii loosely constrained optimization problem due to lack of data with respect to large signaling pathways. Herein, we address both issues: the former by reformulating the pathway optimization as a regular nonlinear optimization problem; and the latter by enhanced algorithms to pre/post-process the signaling network to remove parts that cannot be identified given the experimental conditions. As a case study, we tackle the construction of cell type specific pathways in normal and transformed hepatocytes using medium and large-scale functional phosphoproteomic datasets. The proposed Non Linear Programming (NLP formulation allows for fast optimization of signaling topologies by combining the versatile nature of logic modeling with state of the art optimization algorithms.

A mechanistic understanding of allosteric immune escape pathways in the HIV-1 envelope glycoprotein.

Directory of Open Access Journals (Sweden)

Anurag Sethi

Full Text Available The HIV-1 envelope (Env spike, which consists of a compact, heterodimeric trimer of the glycoproteins gp120 and gp41, is the target of neutralizing antibodies. However, the high mutation rate of HIV-1 and plasticity of Env facilitates viral evasion from neutralizing antibodies through various mechanisms. Mutations that are distant from the antibody binding site can lead to escape, probably by changing the conformation or dynamics of Env; however, these changes are difficult to identify and define mechanistically. Here we describe a network analysis-based approach to identify potential allosteric immune evasion mechanisms using three known HIV-1 Env gp120 protein structures from two different clades, B and C. First, correlation and principal component analyses of molecular dynamics (MD simulations identified a high degree of long-distance coupled motions that exist between functionally distant regions within the intrinsic dynamics of the gp120 core, supporting the presence of long-distance communication in the protein. Then, by integrating MD simulations with network theory, we identified the optimal and suboptimal communication pathways and modules within the gp120 core. The results unveil both strain-dependent and -independent characteristics of the communication pathways in gp120. We show that within the context of three structurally homologous gp120 cores, the optimal pathway for communication is sequence sensitive, i.e. a suboptimal pathway in one strain becomes the optimal pathway in another strain. Yet the identification of conserved elements within these communication pathways, termed inter-modular hotspots, could present a new opportunity for immunogen design, as this could be an additional mechanism that HIV-1 uses to shield vulnerable antibody targets in Env that induce neutralizing antibody breadth.

Transcriptomics, NF-κB Pathway, and Their Potential Spaceflight-Related Health Consequences.

Science.gov (United States)

Zhang, Ye; Moreno-Villanueva, Maria; Krieger, Stephanie; Ramesh, Govindarajan T; Neelam, Srujana; Wu, Honglu

2017-05-31

In space, living organisms are exposed to multiple stress factors including microgravity and space radiation. For humans, these harmful environmental factors have been known to cause negative health impacts such as bone loss and immune dysfunction. Understanding the mechanisms by which spaceflight impacts human health at the molecular level is critical not only for accurately assessing the risks associated with spaceflight, but also for developing effective countermeasures. Over the years, a number of studies have been conducted under real or simulated space conditions. RNA and protein levels in cellular and animal models have been targeted in order to identify pathways affected by spaceflight. Of the many pathways responsive to the space environment, the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) network appears to commonly be affected across many different cell types under the true or simulated spaceflight conditions. NF-κB is of particular interest, as it is associated with many of the spaceflight-related health consequences. This review intends to summarize the transcriptomics studies that identified NF-κB as a responsive pathway to ground-based simulated microgravity or the true spaceflight condition. These studies were carried out using either human cell or animal models. In addition, the review summarizes the studies that focused specifically on NF-κB pathway in specific cell types or organ tissues as related to the known spaceflight-related health risks including immune dysfunction, bone loss, muscle atrophy, central nerve system (CNS) dysfunction, and risks associated with space radiation. Whether the NF-κB pathway is activated or inhibited in space is dependent on the cell type, but the potential health impact appeared to be always negative. It is argued that more studies on NF-κB should be conducted to fully understand this particular pathway for the benefit of crew health in space.

Transcriptomics, NF-κB Pathway, and Their Potential Spaceflight-Related Health Consequences

Directory of Open Access Journals (Sweden)

Ye Zhang

2017-05-01

Full Text Available In space, living organisms are exposed to multiple stress factors including microgravity and space radiation. For humans, these harmful environmental factors have been known to cause negative health impacts such as bone loss and immune dysfunction. Understanding the mechanisms by which spaceflight impacts human health at the molecular level is critical not only for accurately assessing the risks associated with spaceflight, but also for developing effective countermeasures. Over the years, a number of studies have been conducted under real or simulated space conditions. RNA and protein levels in cellular and animal models have been targeted in order to identify pathways affected by spaceflight. Of the many pathways responsive to the space environment, the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB network appears to commonly be affected across many different cell types under the true or simulated spaceflight conditions. NF-κB is of particular interest, as it is associated with many of the spaceflight-related health consequences. This review intends to summarize the transcriptomics studies that identified NF-κB as a responsive pathway to ground-based simulated microgravity or the true spaceflight condition. These studies were carried out using either human cell or animal models. In addition, the review summarizes the studies that focused specifically on NF-κB pathway in specific cell types or organ tissues as related to the known spaceflight-related health risks including immune dysfunction, bone loss, muscle atrophy, central nerve system (CNS dysfunction, and risks associated with space radiation. Whether the NF-κB pathway is activated or inhibited in space is dependent on the cell type, but the potential health impact appeared to be always negative. It is argued that more studies on NF-κB should be conducted to fully understand this particular pathway for the benefit of crew health in space.

An Electrostatic Funnel in the GABA-Binding Pathway.

Directory of Open Access Journals (Sweden)

Timothy S Carpenter

2016-04-01

Full Text Available The γ-aminobutyric acid type A receptor (GABAA-R is a major inhibitory neuroreceptor that is activated by the binding of GABA. The structure of the GABAA-R is well characterized, and many of the binding site residues have been identified. However, most of these residues are obscured behind the C-loop that acts as a cover to the binding site. Thus, the mechanism by which the GABA molecule recognizes the binding site, and the pathway it takes to enter the binding site are both unclear. Through the completion and detailed analysis of 100 short, unbiased, independent molecular dynamics simulations, we have investigated this phenomenon of GABA entering the binding site. In each system, GABA was placed quasi-randomly near the binding site of a GABAA-R homology model, and atomistic simulations were carried out to observe the behavior of the GABA molecules. GABA fully entered the binding site in 19 of the 100 simulations. The pathway taken by these molecules was consistent and non-random; the GABA molecules approach the binding site from below, before passing up behind the C-loop and into the binding site. This binding pathway is driven by long-range electrostatic interactions, whereby the electrostatic field acts as a 'funnel' that sweeps the GABA molecules towards the binding site, at which point more specific atomic interactions take over. These findings define a nuanced mechanism whereby the GABAA-R uses the general zwitterionic features of the GABA molecule to identify a potential ligand some 2 nm away from the binding site.

[Numerical simulation of the effect of virtual stent release pose on the expansion results].

Science.gov (United States)

Li, Jing; Peng, Kun; Cui, Xinyang; Fu, Wenyu; Qiao, Aike

2018-04-01

The current finite element analysis of vascular stent expansion does not take into account the effect of the stent release pose on the expansion results. In this study, stent and vessel model were established by Pro/E. Five kinds of finite element assembly models were constructed by ABAQUS, including 0 degree without eccentricity model, 3 degree without eccentricity model, 5 degree without eccentricity model, 0 degree axial eccentricity model and 0 degree radial eccentricity model. These models were divided into two groups of experiments for numerical simulation with respect to angle and eccentricity. The mechanical parameters such as foreshortening rate, radial recoil rate and dog boning rate were calculated. The influence of angle and eccentricity on the numerical simulation was obtained by comparative analysis. Calculation results showed that the residual stenosis rates were 38.3%, 38.4%, 38.4%, 35.7% and 38.2% respectively for the 5 models. The results indicate that the pose has less effect on the numerical simulation results so that it can be neglected when the accuracy of the result is not highly required, and the basic model as 0 degree without eccentricity model is feasible for numerical simulation.

[3D Virtual Reality Laparoscopic Simulation in Surgical Education - Results of a Pilot Study].

Science.gov (United States)

Kneist, W; Huber, T; Paschold, M; Lang, H

2016-06-01

The use of three-dimensional imaging in laparoscopy is a growing issue and has led to 3D systems in laparoscopic simulation. Studies on box trainers have shown differing results concerning the benefit of 3D imaging. There are currently no studies analysing 3D imaging in virtual reality laparoscopy (VRL). Five surgical fellows, 10 surgical residents and 29 undergraduate medical students performed abstract and procedural tasks on a VRL simulator using conventional 2D and 3D imaging in a randomised order. No significant differences between the two imaging systems were shown for students or medical professionals. Participants who preferred three-dimensional imaging showed significantly better results in 2D as wells as in 3D imaging. First results on three-dimensional imaging on box trainers showed different results. Some studies resulted in an advantage of 3D imaging for laparoscopic novices. This study did not confirm the superiority of 3D imaging over conventional 2D imaging in a VRL simulator. In the present study on 3D imaging on a VRL simulator there was no significant advantage for 3D imaging compared to conventional 2D imaging. Georg Thieme Verlag KG Stuttgart · New York.

Planck 2015 results: XII. Full focal plane simulations

DEFF Research Database (Denmark)

Ade, P. A R; Aghanim, N.; Arnaud, M.

2016-01-01

We present the 8th full focal plane simulation set (FFP8), deployed in support of the Planck 2015 results. FFP8 consists of 10 fiducial mission realizations reduced to 18 144 maps, together with the most massive suite of Monte Carlo realizations of instrument noise and CMB ever generated, compris...

STEP-TRAMM - A modeling interface for simulating localized rainfall induced shallow landslides and debris flow runout pathways

Science.gov (United States)

Or, D.; von Ruette, J.; Lehmann, P.

2017-12-01

Landslides and subsequent debris-flows initiated by rainfall represent a common natural hazard in mountainous regions. We integrated a landslide hydro-mechanical triggering model with a simple model for debris flow runout pathways and developed a graphical user interface (GUI) to represent these natural hazards at catchment scale at any location. The STEP-TRAMM GUI provides process-based estimates of the initiation locations and sizes of landslides patterns based on digital elevation models (SRTM) linked with high resolution global soil maps (SoilGrids 250 m resolution) and satellite based information on rainfall statistics for the selected region. In the preprocessing phase the STEP-TRAMM model estimates soil depth distribution to supplement other soil information for delineating key hydrological and mechanical properties relevant to representing local soil failure. We will illustrate this publicly available GUI and modeling platform to simulate effects of deforestation on landslide hazards in several regions and compare model outcome with satellite based information.

Relative importance of food and water pathways in the bio-accumulation of zinc

International Nuclear Information System (INIS)

Renfro, W.C.; Fowler, S.W.; Heyraud, M.; LaRosa, J.

1974-01-01

The relative importance of the food versus water pathway as a source of radionuclides to aquatic organisms is studied through laboratory experiments allowing groups of animals to accumulate 65 Zn from the two pathways simultaneously in the same simulated ecosystem. Mean whole body concentration factors of 65 Zn and stable zinc in shrimp, crab, fish and mussels are recorded. In shrimp and fish accumulation of 65 Zn through the food pathway is reported more than the water pathway though fluctuations in food quality and feeding rates could alter zinc absorption kinetics

From single Debye-Hückel chains to polyelectrolyte solutions: Simulation results

Science.gov (United States)

Kremer, Kurt

1996-03-01

This lecture will present results from simulations of single weakly charged flexible chains, where the electrostatic part of the interaction is modeled by a Debye-Hückel potential,( with U. Micka, IFF, Forschungszentrum Jülich, 52425 Jülich, Germany) as well as simulations of polyelectrolyte solutions, where the counterions are explicitly taken into account( with M. J. Stevens, Sandia Nat. Lab., Albuquerque, NM 87185-1111) ( M. J. Stevens, K. Kremer, JCP 103), 1669 (1995). The first set of the simulations is meant to clear a recent contoversy on the dependency of the persistence length LP on the screening length Γ. While the analytic theories give Lp ~ Γ^x with either x=1 or x=2, the simulations find for all experimentally accessible chain lengths a varying exponent, which is significantly smaller than 1. This causes serious doubts on the applicability of this model for weakly charged polyelectrolytes in general. The second part deals with strongly charged flexible polyelectrolytes in salt free solution. These simulations are performed for multichain systems. The full Coulomb interactions of the monomers and counterions are treated explicitly. Experimental measurements of the osmotic pressure and the structure factor are reproduced and extended. The simulations reveal a new picture of the chain structure based on calculations of the structure factor, persistence length, end-to-end distance, etc. Even at very low density, the chains show significant bending. Furthermore, the chains contract significantly before they start to overlap. We also show that counterion condensation dramatically alters the chain structure, even for a good solvent backbone.

A simplified method for power-law modelling of metabolic pathways from time-course data and steady-state flux profiles.

Science.gov (United States)

Kitayama, Tomoya; Kinoshita, Ayako; Sugimoto, Masahiro; Nakayama, Yoichi; Tomita, Masaru

2006-07-17

In order to improve understanding of metabolic systems there have been attempts to construct S-system models from time courses. Conventionally, non-linear curve-fitting algorithms have been used for modelling, because of the non-linear properties of parameter estimation from time series. However, the huge iterative calculations required have hindered the development of large-scale metabolic pathway models. To solve this problem we propose a novel method involving power-law modelling of metabolic pathways from the Jacobian of the targeted system and the steady-state flux profiles by linearization of S-systems. The results of two case studies modelling a straight and a branched pathway, respectively, showed that our method reduced the number of unknown parameters needing to be estimated. The time-courses simulated by conventional kinetic models and those described by our method behaved similarly under a wide range of perturbations of metabolite concentrations. The proposed method reduces calculation complexity and facilitates the construction of large-scale S-system models of metabolic pathways, realizing a practical application of reverse engineering of dynamic simulation models from the Jacobian of the targeted system and steady-state flux profiles.

Growth Kinetics of the Homogeneously Nucleated Water Droplets: Simulation Results

International Nuclear Information System (INIS)

Mokshin, Anatolii V; Galimzyanov, Bulat N

2012-01-01

The growth of homogeneously nucleated droplets in water vapor at the fixed temperatures T = 273, 283, 293, 303, 313, 323, 333, 343, 353, 363 and 373 K (the pressure p = 1 atm.) is investigated on the basis of the coarse-grained molecular dynamics simulation data with the mW-model. The treatment of simulation results is performed by means of the statistical method within the mean-first-passage-time approach, where the reaction coordinate is associated with the largest droplet size. It is found that the water droplet growth is characterized by the next features: (i) the rescaled growth law is unified at all the considered temperatures and (ii) the droplet growth evolves with acceleration and follows the power law.

Separation of electron ion ring components (computational simulation and experimental results)

International Nuclear Information System (INIS)

Aleksandrov, V.S.; Dolbilov, G.V.; Kazarinov, N.Yu.; Mironov, V.I.; Novikov, V.G.; Perel'shtejn, Eh.A.; Sarantsev, V.P.; Shevtsov, V.F.

1978-01-01

The problems of the available polarization value of electron-ion rings in the regime of acceleration and separation of its components at the final stage of acceleration are studied. The results of computational simulation by use of the macroparticle method and experiments on the ring acceleration and separation are given. The comparison of calculation results with experiment is presented

Functional Relevance of Different Basal Ganglia Pathways Investigated in a Spiking Model with Reward Dependent Plasticity

Directory of Open Access Journals (Sweden)

Pierre Berthet

2016-07-01

Full Text Available The brain enables animals to behaviourally adapt in order to survive in a complex and dynamic environment, but how reward-oriented behaviours are achieved and computed by its underlying neural circuitry is an open question. To address this concern, we have developed a spiking model of the basal ganglia (BG that learns to dis-inhibit the action leading to a reward despite ongoing changes in the reward schedule. The architecture of the network features the two pathways commonly described in BG, the direct (denoted D1 and the indirect (denoted D2 pathway, as well as a loop involving striatum and the dopaminergic system. The activity of these dopaminergic neurons conveys the reward prediction error (RPE, which determines the magnitude of synaptic plasticity within the different pathways. All plastic connections implement a versatile four-factor learning rule derived from Bayesian inference that depends upon pre- and postsynaptic activity, receptor type and dopamine level. Synaptic weight updates occur in the D1 or D2 pathways depending on the sign of the RPE, and an efference copy informs upstream nuclei about the action selected. We demonstrate successful performance of the system in a multiple-choice learning task with a transiently changing reward schedule. We simulate lesioning of the various pathways and show that a condition without the D2 pathway fares worse than one without D1. Additionally, we simulate the degeneration observed in Parkinson’s disease (PD by decreasing the number of dopaminergic neurons during learning. The results suggest that the D1 pathway impairment in PD might have been overlooked. Furthermore, an analysis of the alterations in the synaptic weights shows that using the absolute reward value instead of the RPE leads to a larger change in D1.

Novel personalized pathway-based metabolomics models reveal key metabolic pathways for breast cancer diagnosis

DEFF Research Database (Denmark)

Huang, Sijia; Chong, Nicole; Lewis, Nathan

2016-01-01

diagnosis. We applied this method to predict breast cancer occurrence, in combination with correlation feature selection (CFS) and classification methods. Results: The resulting all-stage and early-stage diagnosis models are highly accurate in two sets of testing blood samples, with average AUCs (Area Under.......993. Moreover, important metabolic pathways, such as taurine and hypotaurine metabolism and the alanine, aspartate, and glutamate pathway, are revealed as critical biological pathways for early diagnosis of breast cancer. Conclusions: We have successfully developed a new type of pathway-based model to study...... metabolomics data for disease diagnosis. Applying this method to blood-based breast cancer metabolomics data, we have discovered crucial metabolic pathway signatures for breast cancer diagnosis, especially early diagnosis. Further, this modeling approach may be generalized to other omics data types for disease...

Position-specific isotope modeling of organic micropollutants transformation through different reaction pathways

International Nuclear Information System (INIS)

Jin, Biao; Rolle, Massimo

2016-01-01

The degradation of organic micropollutants occurs via different reaction pathways. Compound specific isotope analysis is a valuable tool to identify such degradation pathways in different environmental systems. We propose a mechanism-based modeling approach that provides a quantitative framework to simultaneously evaluate concentration as well as bulk and position-specific multi-element isotope evolution during the transformation of organic micropollutants. The model explicitly simulates position-specific isotopologues for those atoms that experience isotope effects and, thereby, provides a mechanistic description of isotope fractionation occurring at different molecular positions. To demonstrate specific features of the modeling approach, we simulated the degradation of three selected organic micropollutants: dichlorobenzamide (BAM), isoproturon (IPU) and diclofenac (DCF). The model accurately reproduces the multi-element isotope data observed in previous experimental studies. Furthermore, it precisely captures the dual element isotope trends characteristic of different reaction pathways as well as their range of variation consistent with observed bulk isotope fractionation. It was also possible to directly validate the model capability to predict the evolution of position-specific isotope ratios with available experimental data. Therefore, the approach is useful both for a mechanism-based evaluation of experimental results and as a tool to explore transformation pathways in scenarios for which position-specific isotope data are not yet available. - Highlights: • Mechanism-based, position-specific isotope modeling of micropollutants degradation. • Simultaneous description of concentration and primary and secondary isotope effects. • Key features of the model are demonstrated with three illustrative examples. • Model as a tool to explore reaction mechanisms and to design experiments. - We propose a modeling approach incorporating mechanistic information and

Marvel-ous Dwarfs: Results from Four Heroically Large Simulated Volumes of Dwarf Galaxies

Science.gov (United States)

Munshi, Ferah; Brooks, Alyson; Weisz, Daniel; Bellovary, Jillian; Christensen, Charlotte

2018-01-01

We present results from high resolution, fully cosmological simulations of cosmic sheets that contain many dwarf galaxies. Together, they create the largest collection of simulated dwarf galaxies to date, with z=0 stellar masses comparable to the LMC or smaller. In total, we have simulated almost 100 luminous dwarf galaxies, forming a sample of simulated dwarfs which span a wide range of physical (stellar and halo mass) and evolutionary properties (merger history). We show how they can be calibrated against a wealth of observations of nearby galaxies including star formation histories, HI masses and kinematics, as well as stellar metallicities. We present preliminary results answering the following key questions: What is the slope of the stellar mass function at extremely low masses? Do halos with HI and no stars exist? What is the scatter in the stellar to halo mass relationship as a function of dwarf mass? What drives the scatter? With this large suite, we are beginning to statistically characterize dwarf galaxies and identify the types and numbers of outliers to expect.

Ozone database in support of CMIP5 simulations: results and corresponding radiative forcing

Directory of Open Access Journals (Sweden)

I. Cionni

2011-11-01

Full Text Available A continuous tropospheric and stratospheric vertically resolved ozone time series, from 1850 to 2099, has been generated to be used as forcing in global climate models that do not include interactive chemistry. A multiple linear regression analysis of SAGE I+II satellite observations and polar ozonesonde measurements is used for the stratospheric zonal mean dataset during the well-observed period from 1979 to 2009. In addition to terms describing the mean annual cycle, the regression includes terms representing equivalent effective stratospheric chlorine (EESC and the 11-yr solar cycle variability. The EESC regression fit coefficients, together with pre-1979 EESC values, are used to extrapolate the stratospheric ozone time series backward to 1850. While a similar procedure could be used to extrapolate into the future, coupled chemistry climate model (CCM simulations indicate that future stratospheric ozone abundances are likely to be significantly affected by climate change, and capturing such effects through a regression model approach is not feasible. Therefore, the stratospheric ozone dataset is extended into the future (merged in 2009 with multi-model mean projections from 13 CCMs that performed a simulation until 2099 under the SRES (Special Report on Emission Scenarios A1B greenhouse gas scenario and the A1 adjusted halogen scenario in the second round of the Chemistry-Climate Model Validation (CCMVal-2 Activity. The stratospheric zonal mean ozone time series is merged with a three-dimensional tropospheric data set extracted from simulations of the past by two CCMs (CAM3.5 and GISS-PUCCINI and of the future by one CCM (CAM3.5. The future tropospheric ozone time series continues the historical CAM3.5 simulation until 2099 following the four different Representative Concentration Pathways (RCPs. Generally good agreement is found between the historical segment of the ozone database and satellite observations, although it should be noted that

Monte Carlo simulation of a TRIGA source driven core configuration: Preliminary results

International Nuclear Information System (INIS)

Burgio, N.; Ciavola, C.; Santagata, A.

2002-01-01

The different core configurations with a k eff ranging from 0.93 to 0.98, and their response when driven by a pulsed neutron source were simulated with MCNP4C3 (Los Alamos - Monte Carlo N Particles). Simulation results could be considered both as preliminary check for nuclear data and a conceptual design for 'source jerk' experiments on the frame of TRIGA Accelerator Driven Experiment (TRADE) on the reactor facility of Casaccia research center. (author)

Hydrogen-Bonded Networks Along and Bifurcation of the E-Pathway in Quinol: Fumarate Reductase

Energy Technology Data Exchange (ETDEWEB)

Herzog, Elena; Gu, Wei; Juhnke, Hanno D.; Haas, Alexander H.; Mantele, Werner; Simon, Jorg; Helms, Volkhard H.; Lancaster , C. Roy D.

2012-09-19

The E-pathway of transmembrane proton transfer has been demonstrated previously to be essential for catalysis by the diheme-containing quinol:fumarate reductase (QFR) of Wolinella succinogenes. Two constituents of this pathway, Glu- C180 and heme bD ring C (bD-C-) propionate, have been validated experimentally. Here, we identify further constituents of the E-pathway by analysis of molecular dynamics simulations. The redox state of heme groups has a crucial effect on the connectivity patterns of mobile internal water molecules that can transiently support proton transfer from the bD-C-propionate to Glu-C180. The short H-bonding paths formed in the reduced states can lead to high proton conduction rates and thus provide a plausible explanation for the required opening of the E-pathway in reduced QFR. We found evidence that the bD-C-propionate group is the previously postulated branching point connecting proton transfer to the E-pathway from the quinol-oxidation site via interactions with the heme bD ligand His-C44. An essential functional role of His-C44 is supported experimentally by site-directed mutagenesis resulting in its replacement with Glu. Although the H44E variant enzyme retains both heme groups, it is unable to catalyze quinol oxidation. All results obtained are relevant to the QFR enzymes from the human pathogens Campylobacter jejuni and Helicobacter pylori.

BWR Full Integral Simulation Test (FIST). Phase I test results

International Nuclear Information System (INIS)

Hwang, W.S.; Alamgir, M.; Sutherland, W.A.

1984-09-01

A new full height BWR system simulator has been built under the Full-Integral-Simulation-Test (FIST) program to investigate the system responses to various transients. The test program consists of two test phases. This report provides a summary, discussions, highlights and conclusions of the FIST Phase I tests. Eight matrix tests were conducted in the FIST Phase I. These tests have investigated the large break, small break and steamline break LOCA's, as well as natural circulation and power transients. Results and governing phenomena of each test have been evaluated and discussed in detail in this report. One of the FIST program objectives is to assess the TRAC code by comparisons with test data. Two pretest predictions made with TRACB02 are presented and compared with test data in this report

Activation of the PI3K/AKT pathway by microRNA-22 results in CLL B-cell proliferation.

Science.gov (United States)

Palacios, F; Abreu, C; Prieto, D; Morande, P; Ruiz, S; Fernández-Calero, T; Naya, H; Libisch, G; Robello, C; Landoni, A I; Gabus, R; Dighiero, G; Oppezzo, P

2015-01-01

Chronic lymphocytic leukemia (CLL) is characterized by accumulation of clonal B cells arrested in G0/G1 stages that coexist, in different proportions, with proliferative B cells. Understanding the crosstalk between the proliferative subsets and their milieu could provide clues on CLL biology. We previously identified one of these subpopulations in the peripheral blood from unmutated patients that appears to be a hallmark of a progressive disease. Aiming to characterize the molecular mechanism underlying this proliferative behavior, we performed gene expression analysis comparing the global mRNA and microRNA expression of this leukemic subpopulation, and compared it with their quiescent counterparts. Our results suggest that proliferation of this fraction depend on microRNA-22 overexpression that induces phosphatase and tensin homolog downregulation and phosphoinositide 3-kinase (PI3K)/AKT pathway activation. Transfection experiments demonstrated that miR-22 overexpression in CLL B cells switches on PI3K/AKT, leading to downregulation of p27(-Kip1) and overexpression of Survivin and Ki-67 proteins. We also demonstrated that this pathway could be triggered by microenvironment signals like CD40 ligand/interleukin-4 and, more importantly, that this regulatory loop is also present in lymph nodes from progressive unmutated patients. Altogether, these results underline the key role of PI3K/AKT pathway in the generation of the CLL proliferative pool and provide additional rationale for the usage of PI3K inhibitors.

An efficient method of exploring simulation models by assimilating literature and biological observational data.

Science.gov (United States)

Hasegawa, Takanori; Nagasaki, Masao; Yamaguchi, Rui; Imoto, Seiya; Miyano, Satoru

2014-07-01

Recently, several biological simulation models of, e.g., gene regulatory networks and metabolic pathways, have been constructed based on existing knowledge of biomolecular reactions, e.g., DNA-protein and protein-protein interactions. However, since these do not always contain all necessary molecules and reactions, their simulation results can be inconsistent with observational data. Therefore, improvements in such simulation models are urgently required. A previously reported method created multiple candidate simulation models by partially modifying existing models. However, this approach was computationally costly and could not handle a large number of candidates that are required to find models whose simulation results are highly consistent with the data. In order to overcome the problem, we focused on the fact that the qualitative dynamics of simulation models are highly similar if they share a certain amount of regulatory structures. This indicates that better fitting candidates tend to share the basic regulatory structure of the best fitting candidate, which can best predict the data among candidates. Thus, instead of evaluating all candidates, we propose an efficient explorative method that can selectively and sequentially evaluate candidates based on the similarity of their regulatory structures. Furthermore, in estimating the parameter values of a candidate, e.g., synthesis and degradation rates of mRNA, for the data, those of the previously evaluated candidates can be utilized. The method is applied here to the pharmacogenomic pathways for corticosteroids in rats, using time-series microarray expression data. In the performance test, we succeeded in obtaining more than 80% of consistent solutions within 15% of the computational time as compared to the comprehensive evaluation. Then, we applied this approach to 142 literature-recorded simulation models of corticosteroid-induced genes, and consequently selected 134 newly constructed better models. The

Real-Time ECG Simulation for Hybrid Mock Circulatory Loops.

Science.gov (United States)

Korn, Leonie; Rüschen, Daniel; Zander, Niklas; Leonhardt, Steffen; Walter, Marian

2018-02-01

Classically, mock circulatory loops only simulate mechanical properties of the circulation. To connect the hydraulic world with electrophysiology, we present a real-time electrical activity model of the heart and show how to integrate this model into a real-time mock loop simulation. The model incorporates a predefined conduction pathway and a simplified volume conductor to solve the bidomain equations and the forward problem of electrocardiography, resulting in a physiological simulation of the electrocardiogram (ECG) at arbitrary electrode positions. A complete physiological simulation of the heart's excitation would be too CPU intensive. Thus, in our model, complexity was reduced to allow real-time simulation of ECG-triggered medical systems in vitro; this decreases time and cost in the development process. Conversely, the presented model can still be adapted to various pathologies by locally changing the properties of the heart's conduction pathway. To simulate the ECG, the heart is divided into suitable areas, which are innervated by the hierarchically structured conduction system. To distinguish different cardiac regions, a segmentation of the heart was performed. In these regions, Prim's algorithm was applied to identify the directed minimal spanning trees for conduction orientation. Each node of the tree was assigned to a cardiac action potential generated by its hybrid automaton to represent the heart's conduction system by the spatial distribution of action potentials. To generate the ECG output, the bidomain equations were implemented and a simple model of the volume conductor of the body was used to solve the forward problem of electrocardiography. As a result, the model simulates potentials at arbitrary electrode positions in real-time. To verify the developed real-time ECG model, measurements were made within a hybrid mock circulatory loop, including a simple ECG-triggered ventricular assist device control. The model's potential value is to simulate

Results of Aging Tests of Vendor-Produced Blended Feed Simulant

International Nuclear Information System (INIS)

Russell, Renee L.; Buchmiller, William C.; Cantrell, Kirk J.; Peterson, Reid A.; Rinehart, Donald E.

2009-01-01

The Hanford Tank Waste Treatment and Immobilization Plant (WTP) is procuring through Pacific Northwest National Laboratory (PNNL) a minimum of five 3,500 gallon batches of waste simulant for Phase 1 testing in the Pretreatment Engineering Platform (PEP). To make sure that the quality of the simulant is acceptable, the production method was scaled up starting from laboratory-prepared simulant through 15-gallon vendor prepared simulant and 250-gallon vendor prepared simulant before embarking on the production of the 3500-gallon simulant batch by the vendor. The 3500-gallon PEP simulant batches were packaged in 250-gallon high molecular weight polyethylene totes at NOAH Technologies. The simulant was stored in an environmentally controlled environment at NOAH Technologies within their warehouse before blending or shipping. For the 15-gallon, 250-gallon, and 3500-gallon batch 0, the simulant was shipped in ambient temperature trucks with shipment requiring nominally 3 days. The 3500-gallon batch 1 traveled in a 70-75 F temperature controlled truck. Typically the simulant was uploaded in a PEP receiving tank within 24-hours of receipt. The first uploading required longer with it stored outside. Physical and chemical characterization of the 250-gallon batch was necessary to determine the effect of aging on the simulant in transit from the vendor and in storage before its use in the PEP. Therefore, aging tests were conducted on the 250-gallon batch of the vendor-produced PEP blended feed simulant to identify and determine any changes to the physical characteristics of the simulant when in storage. The supernate was also chemically characterized. Four aging scenarios for the vendor-produced blended simulant were studied: (1) stored outside in a 250-gallon tote, (2) stored inside in a gallon plastic bottle, (3) stored inside in a well mixed 5-L tank, and (4) subject to extended temperature cycling under summer temperature conditions in a gallon plastic bottle. The following

SKPDB: a structural database of shikimate pathway enzymes

Directory of Open Access Journals (Sweden)

de Azevedo Walter F

2010-01-01

Full Text Available Abstract Background The functional and structural characterisation of enzymes that belong to microbial metabolic pathways is very important for structure-based drug design. The main interest in studying shikimate pathway enzymes involves the fact that they are essential for bacteria but do not occur in humans, making them selective targets for design of drugs that do not directly impact humans. Description The ShiKimate Pathway DataBase (SKPDB is a relational database applied to the study of shikimate pathway enzymes in microorganisms and plants. The current database is updated regularly with the addition of new data; there are currently 8902 enzymes of the shikimate pathway from different sources. The database contains extensive information on each enzyme, including detailed descriptions about sequence, references, and structural and functional studies. All files (primary sequence, atomic coordinates and quality scores are available for downloading. The modeled structures can be viewed using the Jmol program. Conclusions The SKPDB provides a large number of structural models to be used in docking simulations, virtual screening initiatives and drug design. It is freely accessible at http://lsbzix.rc.unesp.br/skpdb/.

Simulation Loop between CAD systems, Geant4 and GeoModel: Implementation and Results

CERN Document Server

Sharmazanashvili, Alexander; The ATLAS collaboration

2015-01-01

Data_vs_MonteCarlo discrepancy is one of the most important field of investigation for ATLAS simulation studies. There are several reasons of above mentioned discrepancies but primary interest is falling on geometry studies and investigation of how geometry descriptions of detector in simulation adequately representing “as-built” descriptions. Shapes consistency and detalization is not important while adequateness of volumes and weights of detector components are essential for tracking. There are 2 main reasons of faults of geometry descriptions in simulation: 1/ Inconsistency to “as-built” geometry descriptions; 2/Internal inaccuracies of transactions added by simulation packages itself. Georgian Engineering team developed hub on the base of CATIA platform and several tools enabling to read in CATIA different descriptions used by simulation packages, like XML/Persint->CATIA; IV/VP1->CATIA; GeoModel->CATIA; Geant4->CATIA. As a result it becomes possible to compare different descriptions with each othe...

Mathematical modeling of the Phoenix Rising pathway.

Directory of Open Access Journals (Sweden)

Chad Liu

2014-02-01

Full Text Available Apoptosis is a tightly controlled process in mammalian cells. It is important for embryogenesis, tissue homoeostasis, and cancer treatment. Apoptosis not only induces cell death, but also leads to the release of signals that promote rapid proliferation of surrounding cells through the Phoenix Rising (PR pathway. To quantitatively understand the kinetics of interactions of different molecules in this pathway, we developed a mathematical model to simulate the effects of various changes in the PR pathway on the secretion of prostaglandin E2 (PGE2, a key factor for promoting cell proliferation. These changes include activation of caspase 3 (C3, caspase 7 (C7, and nuclear factor κB (NFκB. In addition, we simulated the effects of cyclooxygenase-2 (COX2 inhibition and C3 knockout on the level of secreted PGE2. The model predictions on PGE2 in MEF and 4T1 cells at 48 hours after 10-Gray radiation were quantitatively consistent with the experimental data in the literature. Compared to C7, the model predicted that C3 activation was more critical for PGE2 production. The model also predicted that PGE2 production could be significantly reduced when COX2 expression was blocked via either NFκB inactivation or treatment of cells with exogenous COX2 inhibitors, which led to a decrease in the rate of conversion from arachidonic acid to prostaglandin H2 in the PR pathway. In conclusion, the mathematical model developed in this study yielded new insights into the process of tissue regrowth stimulated by signals from apoptotic cells. In future studies, the model can be used for experimental data analysis and assisting development of novel strategies/drugs for improving cancer treatment or normal tissue regeneration.

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....

Economic modelling of diagnostic and treatment pathways in National Institute for Health and Care Excellence clinical guidelines: the Modelling Algorithm Pathways in Guidelines (MAPGuide) project.

Science.gov (United States)

Lord, J; Willis, S; Eatock, J; Tappenden, P; Trapero-Bertran, M; Miners, A; Crossan, C; Westby, M; Anagnostou, A; Taylor, S; Mavranezouli, I; Wonderling, D; Alderson, P; Ruiz, F

2013-12-01

National Institute for Health and Care Excellence (NICE) clinical guidelines (CGs) make recommendations across large, complex care pathways for broad groups of patients. They rely on cost-effectiveness evidence from the literature and from new analyses for selected high-priority topics. An alternative approach would be to build a model of the full care pathway and to use this as a platform to evaluate the cost-effectiveness of multiple topics across the guideline recommendations. In this project we aimed to test the feasibility of building full guideline models for NICE guidelines and to assess if, and how, such models can be used as a basis for cost-effectiveness analysis (CEA). A 'best evidence' approach was used to inform the model parameters. Data were drawn from the guideline documentation, advice from clinical experts and rapid literature reviews on selected topics. Where possible we relied on good-quality, recent UK systematic reviews and meta-analyses. Two published NICE guidelines were used as case studies: prostate cancer and atrial fibrillation (AF). Discrete event simulation (DES) was used to model the recommended care pathways and to estimate consequent costs and outcomes. For each guideline, researchers not involved in model development collated a shortlist of topics suggested for updating. The modelling teams then attempted to evaluate options related to these topics. Cost-effectiveness results were compared with opinions about the importance of the topics elicited in a survey of stakeholders. The modelling teams developed simulations of the guideline pathways and disease processes. Development took longer and required more analytical time than anticipated. Estimates of cost-effectiveness were produced for six of the nine prostate cancer topics considered, and for five of eight AF topics. The other topics were not evaluated owing to lack of data or time constraints. The modelled results suggested 'economic priorities' for an update that differed from

Study on driver model for hybrid truck based on driving simulator experimental results

Directory of Open Access Journals (Sweden)

Dam Hoang Phuc

2018-04-01

Full Text Available In this paper, a proposed car-following driver model taking into account some features of both the compensatory and anticipatory model representing the human pedal operation has been verified by driving simulator experiments with several real drivers. The comparison between computer simulations performed by determined model parameters with the experimental results confirm the correctness of this mathematical driver model and identified model parameters. Then the driver model is joined to a hybrid vehicle dynamics model and the moderate car following maneuver simulations with various driver parameters are conducted to investigate influences of driver parameters on vehicle dynamics response and fuel economy. Finally, major driver parameters involved in the longitudinal control of drivers are clarified. Keywords: Driver model, Driver-vehicle closed-loop system, Car Following, Driving simulator/hybrid electric vehicle (B1

PathwayAccess: CellDesigner plugins for pathway databases.

Science.gov (United States)

Van Hemert, John L; Dickerson, Julie A

2010-09-15

CellDesigner provides a user-friendly interface for graphical biochemical pathway description. Many pathway databases are not directly exportable to CellDesigner models. PathwayAccess is an extensible suite of CellDesigner plugins, which connect CellDesigner directly to pathway databases using respective Java application programming interfaces. The process is streamlined for creating new PathwayAccess plugins for specific pathway databases. Three PathwayAccess plugins, MetNetAccess, BioCycAccess and ReactomeAccess, directly connect CellDesigner to the pathway databases MetNetDB, BioCyc and Reactome. PathwayAccess plugins enable CellDesigner users to expose pathway data to analytical CellDesigner functions, curate their pathway databases and visually integrate pathway data from different databases using standard Systems Biology Markup Language and Systems Biology Graphical Notation. Implemented in Java, PathwayAccess plugins run with CellDesigner version 4.0.1 and were tested on Ubuntu Linux, Windows XP and 7, and MacOSX. Source code, binaries, documentation and video walkthroughs are freely available at http://vrac.iastate.edu/~jlv.

SPACE CHARGE SIMULATION METHODS INCORPORATED IN SOME MULTI - PARTICLE TRACKING CODES AND THEIR RESULTS COMPARISON

International Nuclear Information System (INIS)

BEEBE - WANG, J.; LUCCIO, A.U.; D IMPERIO, N.; MACHIDA, S.

2002-01-01

Space charge in high intensity beams is an important issue in accelerator physics. Due to the complicity of the problems, the most effective way of investigating its effect is by computer simulations. In the resent years, many space charge simulation methods have been developed and incorporated in various 2D or 3D multi-particle-tracking codes. It has becoming necessary to benchmark these methods against each other, and against experimental results. As a part of global effort, we present our initial comparison of the space charge methods incorporated in simulation codes ORBIT++, ORBIT and SIMPSONS. In this paper, the methods included in these codes are overviewed. The simulation results are presented and compared. Finally, from this study, the advantages and disadvantages of each method are discussed

SPACE CHARGE SIMULATION METHODS INCORPORATED IN SOME MULTI - PARTICLE TRACKING CODES AND THEIR RESULTS COMPARISON.

Energy Technology Data Exchange (ETDEWEB)

BEEBE - WANG,J.; LUCCIO,A.U.; D IMPERIO,N.; MACHIDA,S.

2002-06-03

Space charge in high intensity beams is an important issue in accelerator physics. Due to the complicity of the problems, the most effective way of investigating its effect is by computer simulations. In the resent years, many space charge simulation methods have been developed and incorporated in various 2D or 3D multi-particle-tracking codes. It has becoming necessary to benchmark these methods against each other, and against experimental results. As a part of global effort, we present our initial comparison of the space charge methods incorporated in simulation codes ORBIT++, ORBIT and SIMPSONS. In this paper, the methods included in these codes are overviewed. The simulation results are presented and compared. Finally, from this study, the advantages and disadvantages of each method are discussed.

Comparisons of numerical simulations with ASTRID code against experimental results in rod bundle geometry for boiling flows

International Nuclear Information System (INIS)

Larrauri, D.; Briere, E.

1997-12-01

After different validation simulations of flows through cylindrical and annular channels, a subcooled boiling flow through a rod bundle has been simulated with ASTRID Steam-Water of software. The experiment simulated is called Poseidon. It is a vertical rectangular channel with three heating rods inside. The thermohydraulic conditions of the simulated flow were close to the DNB conditions. The simulation results were analysed and compared against the available measurements of liquid and wall temperatures. ASTRID Steam-Water produced satisfactory results. The wall and the liquid temperatures were well predicted in the different parts of the flow. The void fraction reached 40 % in the vicinity of the heating rods. The distribution of the different calculated variables showed that a three-dimensional simulation gives essential information for the analysis of the physical phenomena involved in this kind of flow. The good results obtained in Poseidon geometry will encourage future rod bundle flow simulations and analyses with ASTRID Steam-Water code. (author)

Environmental-pathways analysis for evaluation of a low-level waste disposal site

International Nuclear Information System (INIS)

Lee, D.W.; Ketelle, R.H.; Pin, F.G.; Hill, G.S.

1983-01-01

The suitability of a site for the shallow land burial of low-level waste is evaluated by an environmental-pathways analysis. The environmental-pathways analysis considers the probable paths for the transport of contamination to man and models the long-term transport of contamination to determine the resulting dose-to-man. The model of the long-term transport of contamination is developed for a proposed site using data obtained from a comprehensive laboratory and field investigation. The proposed site is located at the US Department of Energy Portsmouth Reservation, Piketon, Ohio and is planned to accept low-level radioactive waste generated by the enrichment of uranium. Laboratory studies were performed to characterize the waste and determine the wastes' leaching and retardation characteristics with site soils and groundwater. Comprehensive drilling, sampling and laboratory investigations were performed to provide the necessary information for interpreting the site's geology and hydrology. Field tests were performed to further quantify the site's hydrology. The pathway of greatest concern is the migration of contaminated groundwater and subsequent consumption by man. This pathway was modeled using a numerical simulation of the long-term transport of contamination. Conservative scenarios were developed for leachate generation and migration through the geohydrologic system. The dose-to-man determined from the pathways analysis formed the basis for evaluating site acceptability and providing recommendations for site design and development

Environmental pathways analysis for evaluation of a low-level waste disposal site

International Nuclear Information System (INIS)

Lee, D.W.; Ketelle, R.H.; Pin, F.G.; Hill, G.S.

1984-01-01

The suitability of a site for the shallow land burial of low-level waste is evaluated by an environmental pathways analysis. The environmental pathways analysis considers the probable paths for the transport of contamination to man and models the long-term transport of contamination to determine the resulting dose to man. The model of the long-term transport of contamination is developed for a proposed site using data obtained from a comprehensive laboratory and field investigation. The proposed site is located at the US Department of Energy Portsmouth Reservation, Piketon, Ohio, and is planned to accept low-level radioactive waste generated by the enrichment of uranium. Laboratory studies were performed to characterize the waste and determine the wastes' leaching and retardation characteristics with site soils and groundwater. Comprehensive drilling, sampling and laboratory investigations were performed to provide the necessary information for interpreting the site's geology and hydrology. Field tests were performed to further quantify the site's hydrology. The pathway of greatest concern is the migration of contaminated groundwater and subsequent consumption by man. This pathway was modelled using a numerical simulation of the long-term transport of contamination. Conservative scenarios were developed for leachate generation and migration through the geohydrologic system. The dose to man determined from the pathways analysis formed the basis for evaluating site acceptability and providing recommendations for site design and development. (author)

Bayesian network model for identification of pathways by integrating protein interaction with genetic interaction data.

Science.gov (United States)

Fu, Changhe; Deng, Su; Jin, Guangxu; Wang, Xinxin; Yu, Zu-Guo

2017-09-21

Molecular interaction data at proteomic and genetic levels provide physical and functional insights into a molecular biosystem and are helpful for the construction of pathway structures complementarily. Despite advances in inferring biological pathways using genetic interaction data, there still exists weakness in developed models, such as, activity pathway networks (APN), when integrating the data from proteomic and genetic levels. It is necessary to develop new methods to infer pathway structure by both of interaction data. We utilized probabilistic graphical model to develop a new method that integrates genetic interaction and protein interaction data and infers exquisitely detailed pathway structure. We modeled the pathway network as Bayesian network and applied this model to infer pathways for the coherent subsets of the global genetic interaction profiles, and the available data set of endoplasmic reticulum genes. The protein interaction data were derived from the BioGRID database. Our method can accurately reconstruct known cellular pathway structures, including SWR complex, ER-Associated Degradation (ERAD) pathway, N-Glycan biosynthesis pathway, Elongator complex, Retromer complex, and Urmylation pathway. By comparing N-Glycan biosynthesis pathway and Urmylation pathway identified from our approach with that from APN, we found that our method is able to overcome its weakness (certain edges are inexplicable). According to underlying protein interaction network, we defined a simple scoring function that only adopts genetic interaction information to avoid the balance difficulty in the APN. Using the effective stochastic simulation algorithm, the performance of our proposed method is significantly high. We developed a new method based on Bayesian network to infer detailed pathway structures from interaction data at proteomic and genetic levels. The results indicate that the developed method performs better in predicting signaling pathways than previously

First experimental results and simulation for gas optimisation of the MART-LIME detector

International Nuclear Information System (INIS)

Bazzano, A.; Brunetti, M.T.; Cocchi, M.; Hall, C.J.; Lewis, R.A.; Natalucci, L.; Ortuno-Prados, F.; Ubertini, P.

1996-01-01

A large area high pressure multi-wire proportional counter (MWPC), with both spatial and spectroscopic capabilities, is being jointly developed by the Istituto di Astrofisica Spaziale (IAS), CNR, Frascati, Italy and the Daresbury Laboratory (DL), Warrington, UK as part of the MART-LIME telescope. Recent test results (October-December 1995) carried out at the DL facilities are presented. A brief study, by means of a simulation program, on the possible gas mixtures to be employed in the MART-LIME detector is also reported. The results of the simulation are compared with the experimental data obtained from the tests. (orig.)

Some results of simulation on radiation effects in crystals

International Nuclear Information System (INIS)

Baier, T.; AN SSSR, Novosibirsk

1993-05-01

Simulations concerning radiation in oriented silicon and tungsten crystals of different thicknesses are developed. Conditions are those of experiments done at Kharkov (Ukraine) and Tomsk (Russia) with electron beams in the 1 GeV range. Systematic comparisons between experimental and simulated spectra associated to real spectrum, radiation energy and angular distribution of the photons are developed. The ability of the simulation program to describe crystal effects in the considered energy range is analysed. (author) 11 refs.; 8 figs

Virtual simulation. First clinical results in patients with prostate cancer

International Nuclear Information System (INIS)

Buchali, A.; Dinges, S.; Koswig, S.; Rosenthal, P.; Salk, S.; Harder, C.; Schlenger, L.; Budach, V.

1998-01-01

Investigation of options of virtual simulation in patients with localized prostate cancer. Twenty-four patients suffering from prostate cancer were virtual simulated. The clinical target volume was contoured and the planning target volume was defined after CT scan. The isocenter of the planning target volume was determined and marked at patient's skin. The precision of patients marking was controlled with conventional simulation after physical radiation treatment planning. Mean differences of the patient's mark revealed between the 2 simulations in all room axes around 1 mm. The organs at risk were visualized in the digital reconstructed radiographs. The precise patient's mark of the isocentre by virtual simulation allows to skip the conventional simulation. The visualisation of organs at risk leeds to an unnecessarity of an application of contrast medium and to a further relieve of the patient. The personal requirement is not higher in virtual simulation than in conventional CT based radiation treatment planning. (orig./MG) [de

Simulation Results of Closed Loop Controlled Interline Power Flow Controller System

Directory of Open Access Journals (Sweden)

P. USHA RANI

2016-01-01

Full Text Available The Interline Power Flow Controller (IPFC is the latest generation of Flexible AC Transmission Systems (FACTS devices which can be used to control power flows of multiple transmission lines. A dispatch strategy is proposed for an IPFC operating at rated capacity, in which the power circulation between the two series converters is used as the parameter to optimize the voltage profile and power transfer. Voltage stability curves for test system are shown to illustrate the effectiveness of this proposed strategy. In this paper, a circuit model for IPFC is developed and simulation of interline power flow controller is done using the proposed circuit model. Simulation is done using MATLAB simulink and the results are presented.

Penalized differential pathway analysis of integrative oncogenomics studies.

Science.gov (United States)

van Wieringen, Wessel N; van de Wiel, Mark A

2014-04-01

Through integration of genomic data from multiple sources, we may obtain a more accurate and complete picture of the molecular mechanisms underlying tumorigenesis. We discuss the integration of DNA copy number and mRNA gene expression data from an observational integrative genomics study involving cancer patients. The two molecular levels involved are linked through the central dogma of molecular biology. DNA copy number aberrations abound in the cancer cell. Here we investigate how these aberrations affect gene expression levels within a pathway using observational integrative genomics data of cancer patients. In particular, we aim to identify differential edges between regulatory networks of two groups involving these molecular levels. Motivated by the rate equations, the regulatory mechanism between DNA copy number aberrations and gene expression levels within a pathway is modeled by a simultaneous-equations model, for the one- and two-group case. The latter facilitates the identification of differential interactions between the two groups. Model parameters are estimated by penalized least squares using the lasso (L1) penalty to obtain a sparse pathway topology. Simulations show that the inclusion of DNA copy number data benefits the discovery of gene-gene interactions. In addition, the simulations reveal that cis-effects tend to be over-estimated in a univariate (single gene) analysis. In the application to real data from integrative oncogenomic studies we show that inclusion of prior information on the regulatory network architecture benefits the reproducibility of all edges. Furthermore, analyses of the TP53 and TGFb signaling pathways between ER+ and ER- samples from an integrative genomics breast cancer study identify reproducible differential regulatory patterns that corroborate with existing literature.

SISMA: A SOFTWARE FOR DYNAMIC SIMULATION OF METABOLIC PATHWAYS IN BIOCHEMICAL EDUCATION

Directory of Open Access Journals (Sweden)

J.A. Macedo

2008-05-01

Full Text Available The main purpose of metabolic pathway charts is  clarifying the flow of reactants and products  devised by enzyme  catalytic  reactions . Learning the wealth of information in metabolic pathways , however, is both challenging and overwhelming for students, mainly due to the static nature of printed charts.  In this sense the goal of this work was to develop a software environment for  metabolic chart studies, enhancing both student learning and retention. The system named SISMA (Sistema de Simulações Metabólicas was developed using  the  Unified Modeling Language (UML and Rational Unified Process (RUP tools for specifying, visualizing, constructing, and documenting  the  software system.  SISMA  was modelled with  JAVA programming  language, due to its versatility, efficiency, platform portability, and security. Use Case diagrams were constructing to describe the available functionality of  the software  and  the set of scenarios describing the interactions with the end user, with constraints defined by B usiness  Rules.  In brief, SISMA  can  dynamically  illustrate standard and physiopathological  flow of reactants, create and modifiy compounds, pathways,  and co-factors, and report kinectic data,  among others.  In this way SISMA  can be used as a complementary tool on both conventional full-time as distance learning courses in biochemistry and biotechnology.

Driving simulator test results Deliverable no D6.3. Final draft

NARCIS (Netherlands)

Weiland, J.; Mattes, S.; Kuhn, F.; Gelau, Ch.; Schindhelm, R.; Hoedemaeker, D.D.M.

2003-01-01

Deliverable 6.3 reports the procedure and results from a driving simulator study. This study was carried out to test the efficiency of the principles of the in-vehicle information manager, which was developed within the Comunicar project. Thirty-six subjects were tested in a fixed-base driving

A quality assurance program of simulators in radiotherapy. Pt. 2. Extent and results of long-term quality assurance tests on a therapy simulator

International Nuclear Information System (INIS)

Mueller-Sievers, K.; Kober, B.

1997-01-01

Background: Since 1990 we follow a quality assurance program with periodical tests of functional performance values of a 16-year-old simulator. Material and Method: For this purpose we adopted and modified German standards for quality assurance on linear accelerators and international standards elaborated for simulators (International Electrotechnical Commission). The tests are subdivided into daily visual checks (light field indication, optical distance indicator, isocentre-indicating devices, indication of gantry and collimator angles) and monthly and annually tests of relevant simulator parameters. Some important examples demonstrate the small variation of parameters over 6 years: Position of the light field centre when rotating the collimator, diameter of the isocentre circle when rotating the gantry, accuracy of the isocentre indication device, and coincidence of light field and simulated radiation field. Results: As an important result we can state, that by these rigid periodic tests it was possible to detect and compensate deteriorations of simulators quality rapidly. Conclusions: Technical improvements and specific calling-in of maintenance personnel whenever felt appropriate provided performance characteristics of our old simulator which are required by international recommendations as a basis for modern radiotherapy. (orig.) [de

Quench simulation results for a 12-T twin-aperture dipole magnet

Science.gov (United States)

Cheng, Da; Salmi, Tiina; Xu, Qingjin; Peng, Quanling; Wang, Chengtao; Wang, Yingzhe; Kong, Ershuai; Zhang, Kai

2018-06-01

A 12-T twin-aperture subscale dipole magnet is being developed for SPPC pre-study at the Institute of High Energy Physics (IHEP). The magnet is comprised of 6 double-pancake coils which include 2 Nb3Sn coils and 4 NbTi coils. As the stored energy of the magnet is 0.452 MJ and the operation margin is only about 20% at 4.2 K, a quick and effective quench protection system is necessary during the test of this high field magnet. For the design of the quench protection system, attention was not only paid to the hotspot temperature and terminal voltage, but also the temperature gradient during the quench process due to the poor mechanical characteristics of the Nb3Sn cables. With the adiabatic analysis, numerical simulation and the finite element simulation, an optimized protection method is adopted, which contains a dump resistor and quench heaters. In this paper, the results of adiabatic analysis and quench simulation, such as current decay, hot-spot temperature and terminal voltage are presented in details.

Numerical simulations of hydrothermal circulation resulting from basalt intrusions in a buried spreading center

Science.gov (United States)

Fisher, A.T.; Narasimhan, T.N.

1991-01-01

A two-dimensional, one by two-kilometer section through the seafloor was simulated with a numerical model to investigate coupled fluid and heat flow resulting from basalt intrusions in a buried spreading center. Boundary and initial conditions and physical properties of both sediments and basalt were constrained by field surveys and drilling in the Guaymas Basin, central Gulf of California. Parametric variations in these studies included sediment and basalt permeability, anisotropy in sediment permeability, and the size of heat sources. Faults were introduced through new intrusions both before and after cooling.Background heat input caused fluid convection at velocities ≤ 3 cm a−1 through shallow sediments. Eighty to ninety percent of the heat introduced at the base of the simulations exited through the upper, horizontal surface, even when the vertical boundaries were made permeable to fluid flow. The simulated injection of a 25–50 m thick basalt intrusion at a depth of 250 m resulted in about 10 yr of pore-fluid expulsion through the sea-floor in all cases, leaving the sediments above the intrusions strongly underpressured. A longer period of fluid recharge followed, sometimes accompanied by reductions in total seafloor heat output of 10% in comparison to pre-intrusion values. Additional discharge-recharge events were dispersed chaotically through the duration of the cooling period. These cycles in heat and fluid flow resulted from the response of the simulated system to a thermodynamic shock, the sudden emplacement of a large heat source, and not from mechanical displacement of sediments and pore fluids, which was not simulated.Water/rock mass ratios calculated from numerical simulations are in good agreement with geochemical estimates from materials recovered from the Guaymas Basin, assuming a bulk basalt permeability value of at least 10−17 m2/(10−2 mD). The addition of faults through intrusions and sediments in these simulations did not facilitate

Recent simulation results of the magnetic induction tomography forward problem

Directory of Open Access Journals (Sweden)

Stawicki Krzysztof

2016-06-01

Full Text Available In this paper we present the results of simulations of the Magnetic Induction Tomography (MIT forward problem. Two complementary calculation techniques have been implemented and coupled, namely: the finite element method (applied in commercial software Comsol Multiphysics and the second, algebraic manipulations on basic relationships of electromagnetism in Matlab. The developed combination saves a lot of time and makes a better use of the available computer resources.

Interleukins and their signaling pathways in the Reactome biological pathway database.

Science.gov (United States)

Jupe, Steve; Ray, Keith; Roca, Corina Duenas; Varusai, Thawfeek; Shamovsky, Veronica; Stein, Lincoln; D'Eustachio, Peter; Hermjakob, Henning

2018-04-01

There is a wealth of biological pathway information available in the scientific literature, but it is spread across many thousands of publications. Alongside publications that contain definitive experimental discoveries are many others that have been dismissed as spurious, found to be irreproducible, or are contradicted by later results and consequently now considered controversial. Many descriptions and images of pathways are incomplete stylized representations that assume the reader is an expert and familiar with the established details of the process, which are consequently not fully explained. Pathway representations in publications frequently do not represent a complete, detailed, and unambiguous description of the molecules involved; their precise posttranslational state; or a full account of the molecular events they undergo while participating in a process. Although this might be sufficient to be interpreted by an expert reader, the lack of detail makes such pathways less useful and difficult to understand for anyone unfamiliar with the area and of limited use as the basis for computational models. Reactome was established as a freely accessible knowledge base of human biological pathways. It is manually populated with interconnected molecular events that fully detail the molecular participants linked to published experimental data and background material by using a formal and open data structure that facilitates computational reuse. These data are accessible on a Web site in the form of pathway diagrams that have descriptive summaries and annotations and as downloadable data sets in several formats that can be reused with other computational tools. The entire database and all supporting software can be downloaded and reused under a Creative Commons license. Pathways are authored by expert biologists who work with Reactome curators and editorial staff to represent the consensus in the field. Pathways are represented as interactive diagrams that include as

High-Alpha Research Vehicle Lateral-Directional Control Law Description, Analyses, and Simulation Results

Science.gov (United States)

Davidson, John B.; Murphy, Patrick C.; Lallman, Frederick J.; Hoffler, Keith D.; Bacon, Barton J.

1998-01-01

This report contains a description of a lateral-directional control law designed for the NASA High-Alpha Research Vehicle (HARV). The HARV is a F/A-18 aircraft modified to include a research flight computer, spin chute, and thrust-vectoring in the pitch and yaw axes. Two separate design tools, CRAFT and Pseudo Controls, were integrated to synthesize the lateral-directional control law. This report contains a description of the lateral-directional control law, analyses, and nonlinear simulation (batch and piloted) results. Linear analysis results include closed-loop eigenvalues, stability margins, robustness to changes in various plant parameters, and servo-elastic frequency responses. Step time responses from nonlinear batch simulation are presented and compared to design guidelines. Piloted simulation task scenarios, task guidelines, and pilot subjective ratings for the various maneuvers are discussed. Linear analysis shows that the control law meets the stability margin guidelines and is robust to stability and control parameter changes. Nonlinear batch simulation analysis shows the control law exhibits good performance and meets most of the design guidelines over the entire range of angle-of-attack. This control law (designated NASA-1A) was flight tested during the Summer of 1994 at NASA Dryden Flight Research Center.

Vibrational energy flow in the villin headpiece subdomain: Master equation simulations

Energy Technology Data Exchange (ETDEWEB)

Leitner, David M., E-mail: dml@unr.edu, E-mail: stock@physik.uni-freiburg.de [Department of Chemistry and Chemical Physics Program, University of Nevada, Reno, Nevada 89557 (United States); Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, Freiburg (Germany); Buchenberg, Sebastian; Brettel, Paul [Biomolecular Dynamics, Institute of Physics, University of Freiburg, Freiburg (Germany); Stock, Gerhard, E-mail: dml@unr.edu, E-mail: stock@physik.uni-freiburg.de [Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, Freiburg (Germany); Biomolecular Dynamics, Institute of Physics, University of Freiburg, Freiburg (Germany)

2015-02-21

We examine vibrational energy flow in dehydrated and hydrated villin headpiece subdomain HP36 by master equation simulations. Transition rates used in the simulations are obtained from communication maps calculated for HP36. In addition to energy flow along the main chain, we identify pathways for energy transport in HP36 via hydrogen bonding between residues quite far in sequence space. The results of the master equation simulations compare well with all-atom non-equilibrium simulations to about 1 ps following initial excitation of the protein, and quite well at long times, though for some residues we observe deviations between the master equation and all-atom simulations at intermediate times from about 1–10 ps. Those deviations are less noticeable for hydrated than dehydrated HP36 due to energy flow into the water.

Vibrational energy flow in the villin headpiece subdomain: Master equation simulations

International Nuclear Information System (INIS)

Leitner, David M.; Buchenberg, Sebastian; Brettel, Paul; Stock, Gerhard

2015-01-01

We examine vibrational energy flow in dehydrated and hydrated villin headpiece subdomain HP36 by master equation simulations. Transition rates used in the simulations are obtained from communication maps calculated for HP36. In addition to energy flow along the main chain, we identify pathways for energy transport in HP36 via hydrogen bonding between residues quite far in sequence space. The results of the master equation simulations compare well with all-atom non-equilibrium simulations to about 1 ps following initial excitation of the protein, and quite well at long times, though for some residues we observe deviations between the master equation and all-atom simulations at intermediate times from about 1–10 ps. Those deviations are less noticeable for hydrated than dehydrated HP36 due to energy flow into the water

Magnetic Compression Experiment at General Fusion with Simulation Results

Science.gov (United States)

Dunlea, Carl; Khalzov, Ivan; Hirose, Akira; Xiao, Chijin; Fusion Team, General

2017-10-01

The magnetic compression experiment at GF was a repetitive non-destructive test to study plasma physics applicable to Magnetic Target Fusion compression. A spheromak compact torus (CT) is formed with a co-axial gun into a containment region with an hour-glass shaped inner flux conserver, and an insulating outer wall. External coil currents keep the CT off the outer wall (levitation) and then rapidly compress it inwards. The optimal external coil configuration greatly improved both the levitated CT lifetime and the rate of shots with good compressional flux conservation. As confirmed by spectrometer data, the improved levitation field profile reduced plasma impurity levels by suppressing the interaction between plasma and the insulating outer wall during the formation process. We developed an energy and toroidal flux conserving finite element axisymmetric MHD code to study CT formation and compression. The Braginskii MHD equations with anisotropic heat conduction were implemented. To simulate plasma / insulating wall interaction, we couple the vacuum field solution in the insulating region to the full MHD solution in the remainder of the domain. We see good agreement between simulation and experiment results. Partly funded by NSERC and MITACS Accelerate.

Test results of the new NSSS thermal-hydraulics program of the KNPEC-2 simulator

International Nuclear Information System (INIS)

Jeong, J. Z.; Kim, K. D.; Lee, M. S.; Hong, J. H.; Lee, Y. K.; Seo, J. S.; Kweon, K. J.; Lee, S. W.

2001-01-01

As a part of the KNPEC-2 Simulator Upgrade Project, KEPRI and KAERI have developed a new NSSS thermal-hydraulics program, which is based on the best-estimate system code, RETRAN. The RETRAN code was originally developed for realistic simulation of thermal-hydraulic transient in power plant systems. The capability of 'real-time simulation' and robustness' should be first developed before being implemented in full-scope simulators. For this purpose, we have modified the RETRAN code by (i) eliminating the correlations' discontinuities between flow regime maps, (ii) simplifying physical correlations, (iii) correcting errors in the original program, and (iv) others. This paper briefly presents the test results fo the new NSSS thermal-hydraulics program

Posterior Inferotemporal Cortex Cells Use Multiple Input Pathways for Shape Encoding.

Science.gov (United States)

Ponce, Carlos R; Lomber, Stephen G; Livingstone, Margaret S

2017-05-10

In the macaque monkey brain, posterior inferior temporal (PIT) cortex cells contribute to visual object recognition. They receive concurrent inputs from visual areas V4, V3, and V2. We asked how these different anatomical pathways shape PIT response properties by deactivating them while monitoring PIT activity in two male macaques. We found that cooling of V4 or V2|3 did not lead to consistent changes in population excitatory drive; however, population pattern analyses showed that V4-based pathways were more important than V2|3-based pathways. We did not find any image features that predicted decoding accuracy differences between both interventions. Using the HMAX hierarchical model of visual recognition, we found that different groups of simulated "PIT" units with different input histories (lacking "V2|3" or "V4" input) allowed for comparable levels of object-decoding performance and that removing a large fraction of "PIT" activity resulted in similar drops in performance as in the cooling experiments. We conclude that distinct input pathways to PIT relay similar types of shape information, with V1-dependent V4 cells providing more quantitatively useful information for overall encoding than cells in V2 projecting directly to PIT. SIGNIFICANCE STATEMENT Convolutional neural networks are the best models of the visual system, but most emphasize input transformations across a serial hierarchy akin to the primary "ventral stream" (V1 → V2 → V4 → IT). However, the ventral stream also comprises parallel "bypass" pathways: V1 also connects to V4, and V2 to IT. To explore the advantages of mixing long and short pathways in the macaque brain, we used cortical cooling to silence inputs to posterior IT and compared the findings with an HMAX model with parallel pathways. Copyright © 2017 the authors 0270-6474/17/375019-16$15.00/0.

Probabilistic pathway construction.

Science.gov (United States)

Yousofshahi, Mona; Lee, Kyongbum; Hassoun, Soha

2011-07-01

Expression of novel synthesis pathways in host organisms amenable to genetic manipulations has emerged as an attractive metabolic engineering strategy to overproduce natural products, biofuels, biopolymers and other commercially useful metabolites. We present a pathway construction algorithm for identifying viable synthesis pathways compatible with balanced cell growth. Rather than exhaustive exploration, we investigate probabilistic selection of reactions to construct the pathways. Three different selection schemes are investigated for the selection of reactions: high metabolite connectivity, low connectivity and uniformly random. For all case studies, which involved a diverse set of target metabolites, the uniformly random selection scheme resulted in the highest average maximum yield. When compared to an exhaustive search enumerating all possible reaction routes, our probabilistic algorithm returned nearly identical distributions of yields, while requiring far less computing time (minutes vs. years). The pathways identified by our algorithm have previously been confirmed in the literature as viable, high-yield synthesis routes. Prospectively, our algorithm could facilitate the design of novel, non-native synthesis routes by efficiently exploring the diversity of biochemical transformations in nature. Copyright © 2011 Elsevier Inc. All rights reserved.

Uncertainty versus variability in Monte Carlo simulations of human exposure through food pathways

International Nuclear Information System (INIS)

McKone, T.E.

1994-01-01

An important issue in both the risk characterization and subsequent risk management of contaminated soil is how precisely we can characterize the distribution among individuals of potential doses associated with chemical contaminants in soil and whether this level of precision favors the use of population distributions of exposure over the use of single scenario representations. For lipophilic contaminants, such as dioxins, furans, polychlorinated biphenyls, pesticides, and for metals such as lead and mercury, exposures through food have been demonstrated to be dominant contributors to total dose within non-occupationally exposed populations. However, overall uncertainties in estimating potential doses through food chains are much larger than uncertainties associated with other exposure pathways. A general model is described here for estimating the ratio of potential dose to contaminant concentration in soil for homegrown foods contaminated by lipophilic, nonionic organic chemicals. This model includes parameters describing homegrown food consumption rates, exposure duration, biotransfer factors, and partition factors. For the parameters needed in this model, the mean and variance are often the only moments of the parameter distribution available. Parameters are divided into three categories, uncertain parameters, variable parameters, and mixed uncertain/variable parameters. Using soils contaminated by hexachlorbenzene (HCB) and benzo(a)pyrene (BaP) as cases studies, a stepwise Monte Carlo analysis is used to develop a histogram that apportions variance in the outcome (ratio of potential dose by food pathways to soil concentration) to variance in each of the three input categories. The results represent potential doses in households consuming homegrown foods

Sensing coral reef connectivity pathways from space

KAUST Repository

Raitsos, Dionysios E.; Brewin, Robert J. W.; Zhan, Peng; Dreano, Denis; Pradhan, Yaswant; Nanninga, Gerrit B.; Hoteit, Ibrahim

2017-01-01

Coral reefs rely on inter-habitat connectivity to maintain gene flow, biodiversity and ecosystem resilience. Coral reef communities of the Red Sea exhibit remarkable genetic homogeneity across most of the Arabian Peninsula coastline, with a genetic break towards the southern part of the basin. While previous studies have attributed these patterns to environmental heterogeneity, we hypothesize that they may also emerge as a result of dynamic circulation flow; yet, such linkages remain undemonstrated. Here, we integrate satellite-derived biophysical observations, particle dispersion model simulations, genetic population data and ship-borne in situ profiles to assess reef connectivity in the Red Sea. We simulated long-term (>20 yrs.) connectivity patterns driven by remotely-sensed sea surface height and evaluated results against estimates of genetic distance among populations of anemonefish, Amphiprion bicinctus, along the eastern Red Sea coastline. Predicted connectivity was remarkably consistent with genetic population data, demonstrating that circulation features (eddies, surface currents) formulate physical pathways for gene flow. The southern basin has lower physical connectivity than elsewhere, agreeing with known genetic structure of coral reef organisms. The central Red Sea provides key source regions, meriting conservation priority. Our analysis demonstrates a cost-effective tool to estimate biophysical connectivity remotely, supporting coastal management in data-limited regions.

Sensing coral reef connectivity pathways from space

KAUST Repository

Raitsos, Dionysios E.

2017-08-18

Coral reefs rely on inter-habitat connectivity to maintain gene flow, biodiversity and ecosystem resilience. Coral reef communities of the Red Sea exhibit remarkable genetic homogeneity across most of the Arabian Peninsula coastline, with a genetic break towards the southern part of the basin. While previous studies have attributed these patterns to environmental heterogeneity, we hypothesize that they may also emerge as a result of dynamic circulation flow; yet, such linkages remain undemonstrated. Here, we integrate satellite-derived biophysical observations, particle dispersion model simulations, genetic population data and ship-borne in situ profiles to assess reef connectivity in the Red Sea. We simulated long-term (>20 yrs.) connectivity patterns driven by remotely-sensed sea surface height and evaluated results against estimates of genetic distance among populations of anemonefish, Amphiprion bicinctus, along the eastern Red Sea coastline. Predicted connectivity was remarkably consistent with genetic population data, demonstrating that circulation features (eddies, surface currents) formulate physical pathways for gene flow. The southern basin has lower physical connectivity than elsewhere, agreeing with known genetic structure of coral reef organisms. The central Red Sea provides key source regions, meriting conservation priority. Our analysis demonstrates a cost-effective tool to estimate biophysical connectivity remotely, supporting coastal management in data-limited regions.

Design and CFD Simulation of the Drift Eliminators in Comparison with PIV Results

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Stodůlka Jiří

2015-01-01

Full Text Available Drift eliminators are the essential part of all modern cooling towers preventing significant losses of liquid water escaping to the enviroment. These eliminators need to be effective in terms of water capture but on the other hand causing only minimal pressure loss as well. A new type of such eliminator was designed and numerically simulated using CFD tools. Results of the simulation are compared with PIV visulisation on the prototype model.

Aquatic pathways model to predict the fate of phenolic compounds

Energy Technology Data Exchange (ETDEWEB)

Aaberg, R.L.; Peloquin, R.A.; Strenge, D.L.; Mellinger, P.J.

1983-04-01

Organic materials released from energy-related activities could affect human health and the environment. To better assess possible impacts, we developed a model to predict the fate of spills or discharges of pollutants into flowing or static bodies of fresh water. A computer code, Aquatic Pathways Model (APM), was written to implement the model. The computer programs use compartmental analysis to simulate aquatic ecosystems. The APM estimates the concentrations of chemicals in fish tissue, water and sediment, and is therefore useful for assessing exposure to humans through aquatic pathways. The APM will consider any aquatic pathway for which the user has transport data. Additionally, APM will estimate transport rates from physical and chemical properties of chemicals between several key compartments. The major pathways considered are biodegradation, fish and sediment uptake, photolysis, and evaporation. The model has been implemented with parameters for distribution of phenols, an important class of compounds found in the water-soluble fractions of coal liquids. Current modeling efforts show that, in comparison with many pesticides and polyaromatic hydrocarbons (PAH), the lighter phenolics (the cresols) are not persistent in the environment. The properties of heavier molecular weight phenolics (indanols, naphthols) are not well enough understood at this time to make similar judgements. For the twelve phenolics studied, biodegradation appears to be the major pathway for elimination from aquatic environments. A pond system simulation (using APM) of a spill of solvent refined coal (SRC-II) materials indicates that phenol, cresols, and other single cyclic phenolics are degraded to 16 to 25 percent of their original concentrations within 30 hours. Adsorption of these compounds into sediments and accumulation by fish was minor.

Constraint-based modeling and kinetic analysis of the Smad dependent TGF-beta signaling pathway.

Directory of Open Access Journals (Sweden)

Zhike Zi

Full Text Available BACKGROUND: Investigation of dynamics and regulation of the TGF-beta signaling pathway is central to the understanding of complex cellular processes such as growth, apoptosis, and differentiation. In this study, we aim at using systems biology approach to provide dynamic analysis on this pathway. METHODOLOGY/PRINCIPAL FINDINGS: We proposed a constraint-based modeling method to build a comprehensive mathematical model for the Smad dependent TGF-beta signaling pathway by fitting the experimental data and incorporating the qualitative constraints from the experimental analysis. The performance of the model generated by constraint-based modeling method is significantly improved compared to the model obtained by only fitting the quantitative data. The model agrees well with the experimental analysis of TGF-beta pathway, such as the time course of nuclear phosphorylated Smad, the subcellular location of Smad and signal response of Smad phosphorylation to different doses of TGF-beta. CONCLUSIONS/SIGNIFICANCE: The simulation results indicate that the signal response to TGF-beta is regulated by the balance between clathrin dependent endocytosis and non-clathrin mediated endocytosis. This model is useful to be built upon as new precise experimental data are emerging. The constraint-based modeling method can also be applied to quantitative modeling of other signaling pathways.

Reaction pathways of the dissociation of methylal: A DFT study

Energy Technology Data Exchange (ETDEWEB)

Frey, H -M; Beaud, P; Gerber, T; Mischler, B; Radi, P P; Tzannis, A -P [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

1999-08-01

Schemata for modelling combustion processes do not yet include reaction rates for oxygenated fuels like methylal (DMM) which is considered as an additive or replacement for diesel due to its low sooting propensity. Density functional theory (DFT) studies of the possible reaction pathways for different dissociation steps of methylal are presented. Cleavage of a hydrogen bond to the methoxy group or the central carbon atom were simulated at the BLYP/6-311++G{sup **} level of theory. The results are compared to the experiment when dissociating and/or ionising DMM with femtosecond pulses. (author) 1 fig., 1 tab., 1 ref.

Find_tfSBP: find thermodynamics-feasible and smallest balanced pathways with high yield from large-scale metabolic networks.

Science.gov (United States)

Xu, Zixiang; Sun, Jibin; Wu, Qiaqing; Zhu, Dunming

2017-12-11

Biologically meaningful metabolic pathways are important references in the design of industrial bacterium. At present, constraint-based method is the only way to model and simulate a genome-scale metabolic network under steady-state criteria. Due to the inadequate assumption of the relationship in gene-enzyme-reaction as one-to-one unique association, computational difficulty or ignoring the yield from substrate to product, previous pathway finding approaches can't be effectively applied to find out the high yield pathways that are mass balanced in stoichiometry. In addition, the shortest pathways may not be the pathways with high yield. At the same time, a pathway, which exists in stoichiometry, may not be feasible in thermodynamics. By using mixed integer programming strategy, we put forward an algorithm to identify all the smallest balanced pathways which convert the source compound to the target compound in large-scale metabolic networks. The resulting pathways by our method can finely satisfy the stoichiometric constraints and non-decomposability condition. Especially, the functions of high yield and thermodynamics feasibility have been considered in our approach. This tool is tailored to direct the metabolic engineering practice to enlarge the metabolic potentials of industrial strains by integrating the extensive metabolic network information built from systems biology dataset.

Metabolic signature of sun exposed skin suggests catabolic pathway overweighs anabolic pathway.

Directory of Open Access Journals (Sweden)

Manpreet Randhawa

Full Text Available Skin chronically exposed to sun results in phenotypic changes referred as photoaging. This aspect of aging has been studied extensively through genomic and proteomic tools. Metabolites, the end product are generated as a result of biochemical reactions are often studied as a culmination of complex interplay of gene and protein expression. In this study, we focused exclusively on the metabolome to study effects from sun-exposed and sun-protected skin sites from 25 human subjects. We generated a highly accurate metabolomic signature for the skin that is exposed to sun. Biochemical pathway analysis from this data set showed that sun-exposed skin resides under high oxidative stress and the chains of reactions to produce these metabolites are inclined toward catabolism rather than anabolism. These catabolic activities persuade the skin cells to generate metabolites through the salvage pathway instead of de novo synthesis pathways. Metabolomic profile suggests catabolic pathways and reactive oxygen species operate in a feed forward fashion to alter the biology of sun exposed skin.

KEGGtranslator: visualizing and converting the KEGG PATHWAY database to various formats.

Science.gov (United States)

Wrzodek, Clemens; Dräger, Andreas; Zell, Andreas

2011-08-15

The KEGG PATHWAY database provides a widely used service for metabolic and nonmetabolic pathways. It contains manually drawn pathway maps with information about the genes, reactions and relations contained therein. To store these pathways, KEGG uses KGML, a proprietary XML-format. Parsers and translators are needed to process the pathway maps for usage in other applications and algorithms. We have developed KEGGtranslator, an easy-to-use stand-alone application that can visualize and convert KGML formatted XML-files into multiple output formats. Unlike other translators, KEGGtranslator supports a plethora of output formats, is able to augment the information in translated documents (e.g. MIRIAM annotations) beyond the scope of the KGML document, and amends missing components to fragmentary reactions within the pathway to allow simulations on those. KEGGtranslator is freely available as a Java(™) Web Start application and for download at http://www.cogsys.cs.uni-tuebingen.de/software/KEGGtranslator/. KGML files can be downloaded from within the application. clemens.wrzodek@uni-tuebingen.de Supplementary data are available at Bioinformatics online.

Chemical pathways for the formation of ammonia in Hanford wastes

Energy Technology Data Exchange (ETDEWEB)

Stock, L.M.; Pederson, L.R.

1997-09-01

This report reviews chemical reactions leading to the formation of ammonia in Hanford wastes. The general features of the chemistry of the organic compounds in the Hanford wastes are briefly outlined. The radiolytic and thermal free radical reactions that are responsible for the initiation and propagation of the oxidative degradation reactions of the nitrogen-containing complexants, trisodium HEDTA and tetrasodium EDTA, are outlined. In addition, the roles played by three different ionic reaction pathways for the oxidation of the same compounds and their degradation products are described as a prelude to the discussion of the formation of ammonia. The reaction pathways postulated for its formation are based on tank observations, laboratory studies with simulated and actual wastes, and the review of the scientific literature. Ammonia derives from the reduction of nitrite ion (most important), from the conversion of organic nitrogen in the complexants and their degradation products, and from radiolytic reactions of nitrous oxide and nitrogen (least important). Reduction of nitrite ions is believed to be the most important source of ammonia. Whether by radiolytic or thermal routes, nitrite reduction reactions proceed through nitrogen dioxide, nitric oxide, the nitrosyl anion, and the hyponitrite anion. Nitrite ion is also converted into hydroxylamine, another important intermediate on the pathway to form ammonia. These reaction pathways additionally result in the formation of nitrous oxide and molecular nitrogen, whereas hydrogen formation is produced in a separate reaction sequence.

Chemical pathways for the formation of ammonia in Hanford wastes

International Nuclear Information System (INIS)

Stock, L.M.; Pederson, L.R.

1997-09-01

This report reviews chemical reactions leading to the formation of ammonia in Hanford wastes. The general features of the chemistry of the organic compounds in the Hanford wastes are briefly outlined. The radiolytic and thermal free radical reactions that are responsible for the initiation and propagation of the oxidative degradation reactions of the nitrogen-containing complexants, trisodium HEDTA and tetrasodium EDTA, are outlined. In addition, the roles played by three different ionic reaction pathways for the oxidation of the same compounds and their degradation products are described as a prelude to the discussion of the formation of ammonia. The reaction pathways postulated for its formation are based on tank observations, laboratory studies with simulated and actual wastes, and the review of the scientific literature. Ammonia derives from the reduction of nitrite ion (most important), from the conversion of organic nitrogen in the complexants and their degradation products, and from radiolytic reactions of nitrous oxide and nitrogen (least important). Reduction of nitrite ions is believed to be the most important source of ammonia. Whether by radiolytic or thermal routes, nitrite reduction reactions proceed through nitrogen dioxide, nitric oxide, the nitrosyl anion, and the hyponitrite anion. Nitrite ion is also converted into hydroxylamine, another important intermediate on the pathway to form ammonia. These reaction pathways additionally result in the formation of nitrous oxide and molecular nitrogen, whereas hydrogen formation is produced in a separate reaction sequence

Photolytic debromination pathway of polybrominated diphenyl ethers in hexane by sunlight

International Nuclear Information System (INIS)

Wei, Hua; Zou, Yonghong; Li, An; Christensen, Erik R.; Rockne, Karl J.

2013-01-01

The objective of this work is to identify the photolytic debromination pathways of polybrominated diphenyl ethers (PBDEs). Thirteen PBDEs (BDEs 209, 208, 207, 206, 196, 183, 154, 153, 100, 99, 85, 47 and 28) in hexane were individually exposed to sunlight for up to 64 h. A total of 180 PBDEs were screened and 74 BDE debromination products were detected. The disappearance rate constant increased exponentially with increasing number of bromines. While no evident difference in debromination preference among ortho, meta and para bromines was found for heavier congeners, the vulnerability rank order was meta ≥ ortho > para for the lighter congeners (≤8 Br). The total molar mass of PBDEs continuously decreased during sunlight exposure, indicating PBDEs were transformed to non-PBDE compounds. A stochastic least squares debromination pathway model was developed to simulate the reactions and determine the yields to extend the results beyond the experimental observations. -- Highlights: ► 74 PBDEs are identified as the products of debromination via photolysis. ► Debromination is more likely at meta than para positions for PBDEs with ≤8 bromines. ► The stochastic least squares model results agree with and expand the experimental observations. ► Mass imbalance indicates a significant loss of PBDE mass during sunlight exposure. -- The PBDE debromination products and pathways identified in this work will assist in future studies on their environmental fate

Microphysical Parameterizations for NWP: It's All About the Sizes and Production Pathways of Hydrometeors

Science.gov (United States)

Michelson, Sara A.; Bao, Jian-Wen; Grell, Evelyn D.

2017-04-01

Bulk microphysical parameterization schemes are popularly used in numerical weather prediction (NWP) models to simulate clouds and precpitation. These schemes are based on assumed number distribution functions for individual hydrometeor species, which are integratable over size distributions of diameters from zero to infinity. Typically, hydrometeor mass and number mixing ratios are predicted in these schemes. Some schemes also predict a third parameter of hydrometeor distribution characteristics. In this study, four commonly-used microphysics schemes of various complexity that are available in the Weather Research and Forecasting Model (WRF) are investigated and compared using numerical model simulations of an idealized 2-D squall line and microphysics budget analysis. Diagnoses of the parameterized pathways for hydrometeor production reveal that the differences related to the assumptions of hydrometeor size distributions between the schemes lead to the differences in the simulations due to the net effect of various microphysical processes on the interaction between latent heating/evaporative cooling and flow dynamics as the squall line develops. Results from this study also highlight the possibility that the advantage of double-moment formulations can be overshadowed by the uncertainties in the spectral definition of individual hydrometeor categories and spectrum-dependent microphysical processes. It is concluded that the major differences between the schemes investigated here are in the assumed hydrometeor size distributions and pathways for their production.

SiO2-Ta2O5 sputtering yields: simulated and experimental results

International Nuclear Information System (INIS)

Vireton, E.; Ganau, P.; Mackowski, J.M.; Michel, C.; Pinard, L.; Remillieux, A.

1994-09-01

To improve mirrors coating, we have modeled sputtering of binary oxide targets using TRIM code. First, we have proposed a method to calculate TRIM input parameters using on the one hand thermodynamic cycle and on the other hand Malherbe's results. Secondly, an iterative processing has provided for oxide steady targets caused by ionic bombardment. Thirdly, we have exposed a model to get experimental sputtering yields. Fourthly, for (Ar - SiO 2 ) pair, we have determined that steady target is a silica one. A good agreement between simulated and experimental yields versus ion incident angle has been found. For (Ar - Ta 2 O 5 ) pair, we have to introduce preferential sputtering concept to explain discrepancy between simulation and experiment. In this case, steady target is tantalum monoxide. For (Ar - Ta(+O 2 ) pair, tantalum sputtered by argon ions in reactive oxygen atmosphere, we have to take into account new concept of oxidation stimulated by ion beam. We have supposed that tantalum target becomes a Ta 2 O 5 one in reactive oxygen atmosphere. Then, following mechanism is similar to previous pair. We have obtained steady target of tantalum monoxide too. Comparison between simulated and experimental sputtering yields versus ion incident angle has given very good agreement. By simulation, we have found that tantalum monoxide target has at least 15 angstrom thickness. Those results are compatible with Malherbe's and Taglauer's ones. (authors)

In vivo relevance for photoprotection by the vitamin D rapid response pathway.

Science.gov (United States)

Dixon, K M; Deo, S S; Norman, A W; Bishop, J E; Halliday, G M; Reeve, V E; Mason, R S

2007-03-01

Vitamin D is produced by exposure of 7-dehydrocholesterol in the skin to UV irradiation (UVR) and further converted in the skin to the biologically active metabolite, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) and other compounds. UVR also results in DNA damage producing cyclobutane pyrimidine dimers (CPD). We previously reported that 1,25(OH)(2)D(3) at picomolar concentrations, protects human skin cells from UVR-induced apoptosis, and decreases CPD in surviving cells. 1,25(OH)(2)D(3) has been shown to generate biological responses via two pathways-the classical steroid receptor/genomic pathway or a rapid, non-genomic pathway mediated by a putative membrane receptor. Whether the rapid response pathway is physiologically relevant is unclear. A cis-locked, rapid-acting agonist 1,25(OH)(2)lumisterol(3) (JN), entirely mimicked the actions of 1,25(OH)(2)D(3) to reduce fibroblast and keratinocyte loss and CPD damage after UVR. The effects of 1,25(OH)(2)D(3) were abolished by a rapid-acting antagonist, but not by a genomic antagonist. Skh:hr1 mice exposed to three times the minimal erythemal dose of solar-simulated UVR and treated topically with 1,25(OH)(2)D(3) or JN immediately after UVR showed reduction in UVR-induced UVR-induced sunburn cells (pphotoprotective effects via the rapid pathway and raise the possibility that other D compounds produced in skin may contribute to the photoprotective effects.

Direct photolysis rates and transformation pathways of the lampricides TFM and niclosamide in simulated sunlight

Science.gov (United States)

McConville, Megan B.; Hubert, Terrance D.; Remucal, Christina K.

2016-01-01

The lampricides 3-trifluoromethyl-4-nitrophenol (TFM) and 2′,5-dichloro-4′-nitrosalicylanilide (niclosamide) are directly added to many tributaries of the Great Lakes that harbor the invasive parasitic sea lamprey. Despite their long history of use, the fate of lampricides is not well understood. This study evaluates the rate and pathway of direct photodegradation of both lampricides under simulated sunlight. The estimated half-lives of TFM range from 16.6 ± 0.2 h (pH 9) to 32.9 ± 1.0 h (pH 6), while the half-lives of niclosamide range from 8.88 ± 0.52 days (pH 6) to 382 ± 83 days (pH 9) assuming continuous irradiation over a water depth of 55 cm. Both compounds degrade to form a series of aromatic intermediates, simple organic acids, ring cleavage products, and inorganic ions. Experimental data were used to construct a kinetic model which demonstrates that the aromatic products of TFM undergo rapid photolysis and emphasizes that niclosamide degradation is the rate-limiting step to dehalogenation and mineralization of the lampricide. This study demonstrates that TFM photodegradation is likely to occur on the time scale of lampricide applications (2–5 days), while niclosamide, the less selective lampricide, will undergo minimal direct photodegradation during its passage to the Great Lakes.

Direct Photolysis Rates and Transformation Pathways of the Lampricides TFM and Niclosamide in Simulated Sunlight.

Science.gov (United States)

McConville, Megan B; Hubert, Terrance D; Remucal, Christina K

2016-09-20

The lampricides 3-trifluoromethyl-4-nitrophenol (TFM) and 2',5-dichloro-4'-nitrosalicylanilide (niclosamide) are directly added to many tributaries of the Great Lakes that harbor the invasive parasitic sea lamprey. Despite their long history of use, the fate of lampricides is not well understood. This study evaluates the rate and pathway of direct photodegradation of both lampricides under simulated sunlight. The estimated half-lives of TFM range from 16.6 ± 0.2 h (pH 9) to 32.9 ± 1.0 h (pH 6), while the half-lives of niclosamide range from 8.88 ± 0.52 days (pH 6) to 382 ± 83 days (pH 9) assuming continuous irradiation over a water depth of 55 cm. Both compounds degrade to form a series of aromatic intermediates, simple organic acids, ring cleavage products, and inorganic ions. Experimental data were used to construct a kinetic model which demonstrates that the aromatic products of TFM undergo rapid photolysis and emphasizes that niclosamide degradation is the rate-limiting step to dehalogenation and mineralization of the lampricide. This study demonstrates that TFM photodegradation is likely to occur on the time scale of lampricide applications (2-5 days), while niclosamide, the less selective lampricide, will undergo minimal direct photodegradation during its passage to the Great Lakes.

A comparison of simulation results from two terrestrial carbon cycle models using three climate data sets

International Nuclear Information System (INIS)

Ito, Akihiko; Sasai, Takahiro

2006-01-01

This study addressed how different climate data sets influence simulations of the global terrestrial carbon cycle. For the period 1982-2001, we compared the results of simulations based on three climate data sets (NCEP/NCAR, NCEP/DOE AMIP-II and ERA40) employed in meteorological, ecological and biogeochemical studies and two different models (BEAMS and Sim-CYCLE). The models differed in their parameterizations of photosynthetic and phenological processes but used the same surface climate (e.g. shortwave radiation, temperature and precipitation), vegetation, soil and topography data. The three data sets give different climatic conditions, especially for shortwave radiation, in terms of long-term means, linear trends and interannual variability. Consequently, the simulation results for global net primary productivity varied by 16%-43% only from differences in the climate data sets, especially in these regions where the shortwave radiation data differed markedly: differences in the climate data set can strongly influence simulation results. The differences among the climate data set and between the two models resulted in slightly different spatial distribution and interannual variability in the net ecosystem carbon budget. To minimize uncertainty, we should pay attention to the specific climate data used. We recommend developing an accurate standard climate data set for simulation studies

Numerical simulation of binary collisions using a modified surface tension model with particle method

International Nuclear Information System (INIS)

Sun Zhongguo; Xi Guang; Chen Xi

2009-01-01

The binary collision of liquid droplets is of both practical importance and fundamental value in computational fluid mechanics. We present a modified surface tension model within the moving particle semi-implicit (MPS) method, and carry out two-dimensional simulations to investigate the mechanisms of coalescence and separation of the droplets during binary collision. The modified surface tension model improves accuracy and convergence. A mechanism map is established for various possible deformation pathways encountered during binary collision, as the impact speed is varied; a new pathway is reported when the collision speed is critical. In addition, eccentric collisions are simulated and the effect of the rotation of coalesced particle is explored. The results qualitatively agree with experiments and the numerical protocol may find applications in studying free surface flows and interface deformation

Cooperation as a Service in VANET: Implementation and Simulation Results

Directory of Open Access Journals (Sweden)

Hajar Mousannif

2012-01-01

Full Text Available The past decade has witnessed the emergence of Vehicular Ad-hoc Networks (VANET, specializing from the well-known Mobile Ad Hoc Networks (MANET to Vehicle-to-Vehicle (V2V and Vehicle-to-Infrastructure (V2I wireless communications. While the original motivation for Vehicular Networks was to promote traffic safety, recently it has become increasingly obvious that Vehicular Networks open new vistas for Internet access, providing weather or road condition, parking availability, distributed gaming, and advertisement. In previous papers [27,28], we introduced Cooperation as a Service (CaaS; a new service-oriented solution which enables improved and new services for the road users and an optimized use of the road network through vehicle's cooperation and vehicle-to-vehicle communications. The current paper is an extension of the first ones; it describes an improved version of CaaS and provides its full implementation details and simulation results. CaaS structures the network into clusters, and uses Content Based Routing (CBR for intra-cluster communications and DTN (Delay–and disruption-Tolerant Network routing for inter-cluster communications. To show the feasibility of our approach, we implemented and tested CaaS using Opnet modeler software package. Simulation results prove the correctness of our protocol and indicate that CaaS achieves higher performance as compared to an Epidemic approach.

Multi-pathway model of nuclide transport in fractured media and its application

International Nuclear Information System (INIS)

Li Xun; Yang Zeping; Li Jinxuan

2010-01-01

In order to know the law of nuclide transport in fracture system, the basic differential equations of nuclide transport in fracture and matrix were obtained based on the dual media theory, and the general analytic solutions of nuclide transport in single fractured media with exponential attenuation source in fracture were deduced by Laplace transform, and one-dimensional multi-pathway model of nuclide transport was proposed based on dual media theory and stochastic distribution of fracture parameters. The transport of Th-229, Cs-135 and Se-79 were simulated with this model, the relative concentration of these nuclides in fracture system were predicted. Further more, it was deduced that aperture and velocity can distinctly influence transport of nuclide by comparing with the results which were simulated by single fracture model. (authors)

Modeling reaction histories to study chemical pathways in condensed phase detonation

International Nuclear Information System (INIS)

Scott Stewart, D.; Hernández, Alberto; Lee, Kibaek

2016-01-01

The estimation of pressure and temperature histories, which are required to understand chemical pathways in condensed phase explosives during detonation, is discussed. We argue that estimates made from continuum models, calibrated by macroscopic experiments, are essential to inform modern, atomistic-based reactive chemistry simulations at detonation pressures and temperatures. We present easy to implement methods for general equation of state and arbitrarily complex chemical reaction schemes that can be used to compute reactive flow histories for the constant volume, the energy process, and the expansion process on the Rayleigh line of a steady Chapman-Jouguet detonation. A brief review of state-of-the-art of two-component reactive flow models is given that highlights the Ignition and Growth model of Lee and Tarver [Phys. Fluids 23, 2362 (1980)] and the Wide-Ranging Equation of State model of Wescott, Stewart, and Davis [J. Appl. Phys. 98, 053514 (2005)]. We discuss evidence from experiments and reactive molecular dynamic simulations that motivate models that have several components, instead of the two that have traditionally been used to describe the results of macroscopic detonation experiments. We present simplified examples of a formulation for a hypothetical explosive that uses simple (ideal) equation of state forms and detailed comparisons. Then, we estimate pathways computed from two-component models of real explosive materials that have been calibrated with macroscopic experiments.

Simulation and Analysis of Microwave Transmission through an Electron Cloud, a Comparison of Results

International Nuclear Information System (INIS)

Sonnad, Kiran; Sonnad, Kiran; Furman, Miguel; Veitzer, Seth; Stoltz, Peter; Cary, John

2007-01-01

Simulation studies for transmission of microwaves through electron clouds show good agreement with analytic results. The electron cloud produces a shift in phase of the microwave. Experimental observation of this phenomena would lead to a useful diagnostic tool for accessing the local density of electron clouds in an accelerator. These experiments are being carried out at the CERN SPS and the PEP-II LER at SLAC and is proposed to be done at the Fermilab main injector. In this study, a brief analysis of the phase shift is provided and the results are compared with that obtained from simulations

Evaluation Of Groundwater Pathways And Travel Times From The Nevada Test Site To The Potential Yucca Mountain Repository

International Nuclear Information System (INIS)

K.F. Pohlman; J. Zhu; M. Ye; J. Chapman; C. Russell; D.S. Shafer

2006-01-01

Yucca Mountain (YM), Nevada, has been recommended as a deep geological repository for the disposal of spent fuel and high-level radioactive waste. If YM is licensed as a repository by the Nuclear Regulatory Commission, it will be important to identify the potential for radionuclides to migrate from underground nuclear testing areas located on the Nevada Test Site (NTS) to the hydraulically downgradient repository area to ensure that monitoring does not incorrectly attribute repository failure to radionuclides originating from other sources. In this study, we use the Death Valley Regional Flow System (DVRFS) model developed by the U.S. Geological Survey to investigate potential groundwater migration pathways and associated travel times from the NTS to the proposed YM repository area. Using results from the calibrated DVRFS model and the particle tracking post-processing package MODPATH, we modeled three-dimensional groundwater advective pathways in the NTS and YM region. Our study focuses on evaluating the potential for groundwater pathways between the NTS and YM withdrawal area and whether travel times for advective flow along these pathways coincide with the prospective monitoring timeframe at the proposed repository. We include uncertainty in effective porosity, as this is a critical variable in the determination of time for radionuclides to travel from the NTS region to the YM withdrawal area. Uncertainty in porosity is quantified through evaluation of existing site data and expert judgment and is incorporated in the model through Monte Carlo simulation. Since porosity information is limited for this region, the uncertainty is quite large and this is reflected in the results as a large range in simulated groundwater travel times

Creating and parameterizing patient-specific deep brain stimulation pathway-activation models using the hyperdirect pathway as an example.

Science.gov (United States)

Gunalan, Kabilar; Chaturvedi, Ashutosh; Howell, Bryan; Duchin, Yuval; Lempka, Scott F; Patriat, Remi; Sapiro, Guillermo; Harel, Noam; McIntyre, Cameron C

2017-01-01

Deep brain stimulation (DBS) is an established clinical therapy and computational models have played an important role in advancing the technology. Patient-specific DBS models are now common tools in both academic and industrial research, as well as clinical software systems. However, the exact methodology for creating patient-specific DBS models can vary substantially and important technical details are often missing from published reports. Provide a detailed description of the assembly workflow and parameterization of a patient-specific DBS pathway-activation model (PAM) and predict the response of the hyperdirect pathway to clinical stimulation. Integration of multiple software tools (e.g. COMSOL, MATLAB, FSL, NEURON, Python) enables the creation and visualization of a DBS PAM. An example DBS PAM was developed using 7T magnetic resonance imaging data from a single unilaterally implanted patient with Parkinson's disease (PD). This detailed description implements our best computational practices and most elaborate parameterization steps, as defined from over a decade of technical evolution. Pathway recruitment curves and strength-duration relationships highlight the non-linear response of axons to changes in the DBS parameter settings. Parameterization of patient-specific DBS models can be highly detailed and constrained, thereby providing confidence in the simulation predictions, but at the expense of time demanding technical implementation steps. DBS PAMs represent new tools for investigating possible correlations between brain pathway activation patterns and clinical symptom modulation.

Creating and parameterizing patient-specific deep brain stimulation pathway-activation models using the hyperdirect pathway as an example.

Directory of Open Access Journals (Sweden)

Kabilar Gunalan

Full Text Available Deep brain stimulation (DBS is an established clinical therapy and computational models have played an important role in advancing the technology. Patient-specific DBS models are now common tools in both academic and industrial research, as well as clinical software systems. However, the exact methodology for creating patient-specific DBS models can vary substantially and important technical details are often missing from published reports.Provide a detailed description of the assembly workflow and parameterization of a patient-specific DBS pathway-activation model (PAM and predict the response of the hyperdirect pathway to clinical stimulation.Integration of multiple software tools (e.g. COMSOL, MATLAB, FSL, NEURON, Python enables the creation and visualization of a DBS PAM. An example DBS PAM was developed using 7T magnetic resonance imaging data from a single unilaterally implanted patient with Parkinson's disease (PD. This detailed description implements our best computational practices and most elaborate parameterization steps, as defined from over a decade of technical evolution.Pathway recruitment curves and strength-duration relationships highlight the non-linear response of axons to changes in the DBS parameter settings.Parameterization of patient-specific DBS models can be highly detailed and constrained, thereby providing confidence in the simulation predictions, but at the expense of time demanding technical implementation steps. DBS PAMs represent new tools for investigating possible correlations between brain pathway activation patterns and clinical symptom modulation.

BioNessie - a grid enabled biochemical networks simulation environment

OpenAIRE

Liu, X.; Jiang, J.; Ajayi, O.; Gu, X.; Gilbert, D.; Sinnott, R.O.

2008-01-01

The simulation of biochemical networks provides insight and understanding about the underlying biochemical processes and pathways used by cells and organisms. BioNessie is a biochemical network simulator which has been developed at the University of Glasgow. This paper describes the simulator and focuses in particular on how it has been extended to benefit from a wide variety of high performance compute resources across the UK through Grid technologies to support larger scale simulations.

Certification Criteria for Linked Learning Pathways

Science.gov (United States)

ConnectEd: The California Center for College and Career, 2010

2010-01-01

Pathways offer a promising strategy for transforming high schools and improving student outcomes. However, to achieve these desired results, pathways must be of high quality. To guide sites in planning and implementing such pathways, a design team of experts developed the criteria outlined in this document. Sites can choose to go through a…

Mercury's plasma belt: hybrid simulations results compared to in-situ measurements

Science.gov (United States)

Hercik, D.; Travnicek, P. M.; Schriver, D.; Hellinger, P.

2012-12-01

The presence of plasma belt and trapped particles region in the Mercury's inner magnetosphere has been questionable due to small dimensions of the magnetosphere of Mercury compared to Earth, where these regions are formed. Numerical simulations of the solar wind interaction with Mercury's magnetic field suggested that such a structure could be found also in the vicinity of Mercury. These results has been recently confirmed also by MESSENGER observations. Here we present more detailed analysis of the plasma belt structure and quasi-trapped particle population characteristics and behaviour under different orientations of the interplanetary magnetic field.The plasma belt region is constantly supplied with solar wind protons via magnetospheric flanks and tail current sheet region. Protons inside the plasma belt region are quasi-trapped in the magnetic field of Mercury and perform westward drift along the planet. This region is well separated by a magnetic shell and has higher average temperatures and lower bulk proton current densities than surrounding area. On the day side the population exhibits loss cone distribution function matching the theoretical loss cone angle. Simulations results are also compared to in-situ measurements acquired by MESSENGER MAG and FIPS instruments.

Free energy calculations along entropic pathways. III. Nucleation of capillary bridges and bubbles

Science.gov (United States)

Desgranges, Caroline; Delhommelle, Jerome

2017-05-01

Using molecular simulation, we analyze the capillary condensation and evaporation processes for argon confined in a cylindrical nanopore. For this purpose, we define the entropy of the adsorbed fluid as a reaction coordinate and determine the free energy associated with both processes along entropic pathways. For capillary condensation, we identify a complex free energy profile resulting from the multi-stage nature of this phenomenon. We find capillary condensation to proceed through the nucleation of a liquid bridge across the nanopore, followed by its expansion throughout the pore to give rise to the stable phase of high density. In the case of capillary evaporation, the free energy profile along the entropy pathway also exhibits different regimes, corresponding to the initial destabilization of the layered structure of the fluid followed by the formation, and subsequent expansion, of a bubble across the nanopore.

Environmental pathways of radioactivity to man

International Nuclear Information System (INIS)

Johns, T.F.

1983-01-01

An attempt has been made to discuss environmental pathways and their significance in a way which will be understood by non-specialists. The role of these pathways in the general structure of radiological protection is explained and the more important pathways to man from releases into the air and the aquatic environment are discussed generally. The various mechanisms which lead to the dispersion or reconstruction of radioactive materials are discussed and their importance stressed. The more important pathways for particular groups of radionuclides from the nuclear power industry are dealt with in detail and information resulting from many theoretical and practical studies of the situations at particular locations summarized. There is detailed discussion about the doses to local population groups and about worldwide doses as a result of the release of certain long-lived radioactive species. The corresponding pathways and resulting doses from natural radiation are detailed to illustrate that the doses from the nuclear power industry are small in comparison, and brief consideration is given to animal and plant doses from the industry. (U.K.)

Unexpected Reaction Pathway for butyrylcholinesterase-catalyzed inactivation of “hunger hormone” ghrelin

Science.gov (United States)

Yao, Jianzhuang; Yuan, Yaxia; Zheng, Fang; Zhan, Chang-Guo

2016-02-01

Extensive computational modeling and simulations have been carried out, in the present study, to uncover the fundamental reaction pathway for butyrylcholinesterase (BChE)-catalyzed hydrolysis of ghrelin, demonstrating that the acylation process of BChE-catalyzed hydrolysis of ghrelin follows an unprecedented single-step reaction pathway and the single-step acylation process is rate-determining. The free energy barrier (18.8 kcal/mol) calculated for the rate-determining step is reasonably close to the experimentally-derived free energy barrier (~19.4 kcal/mol), suggesting that the obtained mechanistic insights are reasonable. The single-step reaction pathway for the acylation is remarkably different from the well-known two-step acylation reaction pathway for numerous ester hydrolysis reactions catalyzed by a serine esterase. This is the first time demonstrating that a single-step reaction pathway is possible for an ester hydrolysis reaction catalyzed by a serine esterase and, therefore, one no longer can simply assume that the acylation process must follow the well-known two-step reaction pathway.

Finding Solvable Units of Variables in Nonlinear ODEs of ECM Degradation Pathway Network

Directory of Open Access Journals (Sweden)

Shuji Kawasaki

2017-01-01

Full Text Available We consider ordinary differential equation (ODE model for a pathway network that arises in extracellular matrix (ECM degradation. For solving the ODEs, we propose applying the mass conservation law (MCL, together with a stoichiometry called doubling rule, to them. Then it leads to extracting new units of variables in the ODEs that can be solved explicitly, at least in principle. The simulation results for the ODE solutions show that the numerical solutions are indeed in good accord with theoretical solutions and satisfy the MALs.

Finding Solvable Units of Variables in Nonlinear ODEs of ECM Degradation Pathway Network.

Science.gov (United States)

Kawasaki, Shuji; Minerva, Dhisa; Itano, Keiko; Suzuki, Takashi

2017-01-01

We consider ordinary differential equation (ODE) model for a pathway network that arises in extracellular matrix (ECM) degradation. For solving the ODEs, we propose applying the mass conservation law (MCL), together with a stoichiometry called doubling rule , to them. Then it leads to extracting new units of variables in the ODEs that can be solved explicitly, at least in principle. The simulation results for the ODE solutions show that the numerical solutions are indeed in good accord with theoretical solutions and satisfy the MALs.

Solar collectors and heat pump: Market review and preliminary simulation results

International Nuclear Information System (INIS)

Tepe, Rainer; Roennelid, Mats

2002-01-01

Heating systems that combine solar collectors and a heat pump available on the market in Sweden have been studied. A majority of the systems found combine the solar collectors with a ground source heat pump. The technology for combining the collectors and the heat pump does however vary considerably. In the most simple systems, the collectors heat the return water from the heat pump, i.e. the collectors are used for raising the temperature in the boreholes for the heat pump. In the advanced systems, the solar heat is used for tap water, space heating and for raising the temperature of the heat pump's evaporator. There exist only very few comparative evaluations of the contributions from solar collectors in heat pump systems, and there is a need for finding the potential for this technique. In the present study, results are reported from preliminary simulations of solar collectors and ground source heat pumps installed in one-family houses. Simulations are made for two heating loads: 8,650 and 16,500 kWh/year resp., and a hot water load of 3,000 kWh/year. The study shows that: the temperature of the borehole decreases when solar collectors are not used (about 1.2 deg C in three years): 8 m 2 glazed solar collectors used for hot water production can reduce the electricity consumption with up to 13%, with best results in the house with low heating load: 50 m 2 unglazed solar collectors coupled to the evaporator or the borehole can give reductions of up to 14%, largest reduction in the house with high heating load, where the heat extraction from the borehole is large: the unglazed collectors have the highest economic potential, and can be cost effective for houses with high heating load: the simulations do not include a thorough system optimization, better results can be expected from continued optimization work

Monte Carlo simulations of microchannel plate detectors I: steady-state voltage bias results

Energy Technology Data Exchange (ETDEWEB)

Ming Wu, Craig Kruschwitz, Dane Morgan, Jiaming Morgan

2008-07-01

X-ray detectors based on straight-channel microchannel plates (MCPs) are a powerful diagnostic tool for two-dimensional, time-resolved imaging and timeresolved x-ray spectroscopy in the fields of laser-driven inertial confinement fusion and fast z-pinch experiments. Understanding the behavior of microchannel plates as used in such detectors is critical to understanding the data obtained. The subject of this paper is a Monte Carlo computer code we have developed to simulate the electron cascade in a microchannel plate under a static applied voltage. Also included in the simulation is elastic reflection of low-energy electrons from the channel wall, which is important at lower voltages. When model results were compared to measured microchannel plate sensitivities, good agreement was found. Spatial resolution simulations of MCP-based detectors were also presented and found to agree with experimental measurements.

FINAL SIMULATION RESULTS FOR DEMONSTRATION CASE 1 AND 2

Energy Technology Data Exchange (ETDEWEB)

David Sloan; Woodrow Fiveland

2003-10-15

The goal of this DOE Vision-21 project work scope was to develop an integrated suite of software tools that could be used to simulate and visualize advanced plant concepts. Existing process simulation software did not meet the DOE's objective of ''virtual simulation'' which was needed to evaluate complex cycles. The overall intent of the DOE was to improve predictive tools for cycle analysis, and to improve the component models that are used in turn to simulate equipment in the cycle. Advanced component models are available; however, a generic coupling capability that would link the advanced component models to the cycle simulation software remained to be developed. In the current project, the coupling of the cycle analysis and cycle component simulation software was based on an existing suite of programs. The challenge was to develop a general-purpose software and communications link between the cycle analysis software Aspen Plus{reg_sign} (marketed by Aspen Technology, Inc.), and specialized component modeling packages, as exemplified by industrial proprietary codes (utilized by ALSTOM Power Inc.) and the FLUENT{reg_sign} computational fluid dynamics (CFD) code (provided by Fluent Inc). A software interface and controller, based on an open CAPE-OPEN standard, has been developed and extensively tested. Various test runs and demonstration cases have been utilized to confirm the viability and reliability of the software. ALSTOM Power was tasked with the responsibility to select and run two demonstration cases to test the software--(1) a conventional steam cycle (designated as Demonstration Case 1), and (2) a combined cycle test case (designated as Demonstration Case 2). Demonstration Case 1 is a 30 MWe coal-fired power plant for municipal electricity generation, while Demonstration Case 2 is a 270 MWe, natural gas-fired, combined cycle power plant. Sufficient data was available from the operation of both power plants to complete the cycle

Comparing the results of lattice and off-lattice simulations for the melt of nonconcatenated rings

International Nuclear Information System (INIS)

Halverson, Jonathan D; Kremer, Kurt; Grosberg, Alexander Y

2013-01-01

To study the conformational properties of unknotted and nonconcatenated ring polymers in the melt, we present a detailed qualitative and quantitative comparison of simulation data obtained by molecular dynamics simulation using an off-lattice bead-spring model and by Monte Carlo simulation using a lattice model. We observe excellent, and sometimes even unexpectedly good, agreement between the off-lattice and lattice results for many quantities measured including the gyration radii of the ring polymers, gyration radii of their subchains, contact probabilities, surface characteristics, number of contacts between subchains, and the static structure factors of the rings and their subchains. These results are, in part, put in contrast to Moore curves, and the open, linear polymer counterparts. While our analysis is extensive, our understanding of the ring melt conformations is still rather preliminary. (paper)

Utilisation of simulation in industrial design and resulting business opportunities (SISU) - MASIT18

Energy Technology Data Exchange (ETDEWEB)

Olin, M.; Leppaevuori, J.; Manninen, J. (VTT Technical Research Centre of Finland, Espoo (Finland)); Valli, A.; Hasari, H.; Koistinen, A.; Leppaenen, S. (Helsinki Polytechnic Stadia, City of Helsinki, Helsinki (Finland)); Lahti, S. (EVTEK University of Applied Sciences, Vantaa (Finland))

2008-07-01

In the SISU project, over 10 case studies are carried out in many different fields and applications. Results and experience of developing simulation applications have started to accumulate. One of the most important results this far is that there are many common features, both good and bad, between our test cases. Simulation is a fast, reliable, and often low risk method of studying different systems and processes. On the other hand, many applications need very expensive licences, plenty of parametric data and highly specialised knowledge in order to produce really valuable results. Industrial partners are acting like real customers in the case studies. We hope that this methodology will help us to answer our main question: how do we create a value chain from model development via model application for end users? The best thing to happen will be if partners learn to apply simulation productively. Other scientists and companies will follow, and new value chains will mushroom. In the case study of Mamec and EVTEK - Mixing model - the aim is to develop a fluid mechanical model for a mixing chamber. This study is similar to the preceding case of Watrec. In this study, the main problems have been in material properties area, because of non-Newtonian fluids and multiphase flows. Material property parameters of the non-Newtonian power law have been defined and flow field simulations have started. In the case study of Fortum and EVTEK - MDR - Measurement data reconciliation - the aim is to apply MDR in a power plant environment and study the possibility of developing a commercial additional tool for power plant simulation through the well-proven MDR technique based on linear filtering theory. The MDR method has been applied, for example, to energy and chemical processes. MDR is closely connected with system maintenance, simulation pre-processing and process diagnostics. Experimental work has proceeded from simple unit processes to large and complicated process systems. One

Monju operator training report. Training results and upgrade of the operation training simulator in 2002 YF

International Nuclear Information System (INIS)

Koyagoshi, Naoki; Sasaki, Kazuichi; Sawada, Makoto; Kawanishi, Tomotake; Yoshida, Kazuo

2003-09-01

The prototype fast breeder reactor, Monju, has been performing deliberately the operator training which is composed of the regulated training required by the government and the self-training. The training used a full scope type simulator (MARS: Monju Advanced Reactor Simulator) plays an important role among of the above mentioned trainings and greatly contributes to the Monju operator training for Monju restarting. This report covers the activities of Monju operator training in 2002 FY, i.e. the training results and the remodeling working of the MARS in progress since 1999. (1) Eight simulator training courses were carried out 46 times and 180 trainees participated. Additionally, both the regulated training and self-training were held total 10 times by attended 34 trainees, as besides simulator training. (2) Above training data was reduced compare with the last year's data (69 times (338 trainees)) due to the indispensable training courses in Monju operator training were changed by reorganized operator's number and decreasing of training times owing to remodeling working of the simulator was conducted. (3) By means of upgrading of the MARS completed in 2002 FY, its logic arithmetic time was became speedier and its instructing function was improved remarkably, thus, the simulator training was became to be more effective. Moreover, it's planning to do both remodeling in the next year as the final working: remodeling of reactor core model with the aim of improvement simulating accuracy and corresponding to the sodium leakage measures. Regarding on the Monju training results and simulator's remodeling so far finished, please referring JNC report number of JNC TN 4410 2002-001 Translation of Monju Simulator Training owing Monju Accident and Upgrade of MARS''. (author)

Pathway cross-talk network analysis identifies critical pathways in neonatal sepsis.

Science.gov (United States)

Meng, Yu-Xiu; Liu, Quan-Hong; Chen, Deng-Hong; Meng, Ying

2017-06-01

Despite advances in neonatal care, sepsis remains a major cause of morbidity and mortality in neonates worldwide. Pathway cross-talk analysis might contribute to the inference of the driving forces in bacterial sepsis and facilitate a better understanding of underlying pathogenesis of neonatal sepsis. This study aimed to explore the critical pathways associated with the progression of neonatal sepsis by the pathway cross-talk analysis. By integrating neonatal transcriptome data with known pathway data and protein-protein interaction data, we systematically uncovered the disease pathway cross-talks and constructed a disease pathway cross-talk network for neonatal sepsis. Then, attract method was employed to explore the dysregulated pathways associated with neonatal sepsis. To determine the critical pathways in neonatal sepsis, rank product (RP) algorithm, centrality analysis and impact factor (IF) were introduced sequentially, which synthetically considered the differential expression of genes and pathways, pathways cross-talks and pathway parameters in the network. The dysregulated pathways with the highest IF values as well as RPpathways in neonatal sepsis. By integrating three kinds of data, only 6919 common genes were included to perform the pathway cross-talk analysis. By statistic analysis, a total of 1249 significant pathway cross-talks were selected to construct the pathway cross-talk network. Moreover, 47 dys-regulated pathways were identified via attract method, 20 pathways were identified under RPpathways with the highest IF were also screened from the pathway cross-talk network. Among them, we selected 8 common pathways, i.e. critical pathways. In this study, we systematically tracked 8 critical pathways involved in neonatal sepsis by integrating attract method and pathway cross-talk network. These pathways might be responsible for the host response in infection, and of great value for advancing diagnosis and therapy of neonatal sepsis. Copyright © 2017

Preliminary Analysis and Simulation Results of Microwave Transmission Through an Electron Cloud

International Nuclear Information System (INIS)

Sonnad, Kiran; Sonnad, Kiran; Furman, Miguel; Veitzer, Seth; Stoltz, Peter; Cary, John

2007-01-01

The electromagnetic particle-in-cell (PIC) code VORPAL is being used to simulate the interaction of microwave radiation through an electron cloud. The results so far show good agreement with theory for simple cases. The study has been motivated by previous experimental work on this problem at the CERN SPS [1], experiments at the PEP-II Low Energy Ring (LER) at SLAC [4], and proposed experiments at the Fermilab Main Injector (MI). With experimental observation of quantities such as amplitude, phase and spectrum of the output microwave radiation and with support from simulations for different cloud densities and applied magnetic fields, this technique can prove to be a useful probe for assessing the presence as well as the density of electron clouds

Uncertainty and sensitivity analysis of food pathway results with the MACCS Reactor Accident Consequence Model

International Nuclear Information System (INIS)

Helton, J.C.; Johnson, J.D.; Rollstin, J.A.; Shiver, A.W.; Sprung, J.L.

1995-01-01

Uncertainty and sensitivity analysis techniques based on Latin hypercube sampling, partial correlation analysis and stepwise regression analysis are used in an investigation with the MACCS model of the food pathways associated with a severe accident at a nuclear power station. The primary purpose of this study is to provide guidance on the variables to be considered in future review work to reduce the uncertainty in the important variables used in the calculation of reactor accident consequences. The effects of 87 imprecisely-known input variables on the following reactor accident consequences are studied: crop growing season dose, crop long-term dose, milk growing season dose, total food pathways dose, total ingestion pathways dose, total long-term pathways dose, area dependent cost, crop disposal cost, milk disposal cost, condemnation area, crop disposal area and milk disposal area. When the predicted variables are considered collectively, the following input variables were found to be the dominant contributors to uncertainty: fraction of cesium deposition on grain fields that is retained on plant surfaces and transferred directly to grain, maximum allowable ground concentrations of Cs-137 and Sr-90 for production of crops, ground concentrations of Cs-134, Cs-137 and I-131 at which the disposal of milk will be initiated due to accidents that occur during the growing season, ground concentrations of Cs-134, I-131 and Sr-90 at which the disposal of crops will be initiated due to accidents that occur during the growing season, rate of depletion of Cs-137 and Sr-90 from the root zone, transfer of Sr-90 from soil to legumes, transfer of Cs-137 from soil to pasture, transfer of cesium from animal feed to meat, and the transfer of cesium, iodine and strontium from animal feed to milk

Uncertainty and sensitivity analysis of food pathway results with the MACCS reactor accident consequence model

International Nuclear Information System (INIS)

Helton, J.C.; Johnson, J.D.; Rollstin, J.A.; Shiver, A.W.; Sprung, J.L.

1995-01-01

Uncertainty and sensitivity analysis techniques based on Latin hypercube sampling, partial correlation analysis and stepwise regression analysis are used in an investigation with the MACCS model of the food pathways associated with a severe accident at a nuclear power station. The primary purpose of this study is to provide guidance on the variables to be considered in future review work to reduce the uncertainty in the important variables used in the calculation of reactor accident consequences. The effects of 87 imprecisely-known input variables on the following reactor accident consequences are studied: crop growing-season dose, crop long-term dose, milk growing-season dose, total food pathways dose, total ingestion pathways dose, total long-term pathways dose, area dependent cost, crop disposal cost, milk disposal cost, condemnation area, crop disposal area and milk disposal area. When the predicted variables are considered collectively, the following input variables were found to be the dominant contributors to uncertainty: fraction of cesium deposition on grain fields that is retained on plant surfaces and transferred directly to grain, maximum allowable ground concentrations of Cs-137 and Sr-90 for production of crops, ground concentrations of Cs-134, Cs-137 and I-131 at which the disposal of milk will be initiated due to accidents that occur during the growing season, ground concentrations of Cs-134, I-131 and Sr-90 at which the disposal of crops will be initiated due to accidents that occur during the growing season, rate of depletion of Cs-137 and Sr-90 from the root zone, transfer of Sr-90 from soil to legumes, transfer of Cs-137 from soil to pasture, transfer of cesium from animal feed to meat, and the transfer of cesium, iodine and strontium from animal feed to milk

Validation of thermohydraulic codes by comparison of experimental results with computer simulations

International Nuclear Information System (INIS)

Madeira, A.A.; Galetti, M.R.S.; Pontedeiro, A.C.

1989-01-01

The results obtained by simulation of three cases from CANON depressurization experience, using the TRAC-PF1 computer code, version 7.6, implanted in the VAX-11/750 computer of Brazilian CNEN, are presented. The CANON experience was chosen as first standard problem in thermo-hydraulic to be discussed at ENFIR for comparing results from different computer codes with results obtained experimentally. The ability of TRAC-PF1 code to prevent the depressurization phase of a loss of primary collant accident in pressurized water reactors is evaluated. (M.C.K.) [pt

Some results on ethnic conflicts based on evolutionary game simulation

Science.gov (United States)

Qin, Jun; Yi, Yunfei; Wu, Hongrun; Liu, Yuhang; Tong, Xiaonian; Zheng, Bojin

2014-07-01

The force of the ethnic separatism, essentially originating from the negative effect of ethnic identity, is damaging the stability and harmony of multiethnic countries. In order to eliminate the foundation of the ethnic separatism and set up a harmonious ethnic relationship, some scholars have proposed a viewpoint: ethnic harmony could be promoted by popularizing civic identity. However, this viewpoint is discussed only from a philosophical prospective and still lacks support of scientific evidences. Because ethnic group and ethnic identity are products of evolution and ethnic identity is the parochialism strategy under the perspective of game theory, this paper proposes an evolutionary game simulation model to study the relationship between civic identity and ethnic conflict based on evolutionary game theory. The simulation results indicate that: (1) the ratio of individuals with civic identity has a negative association with the frequency of ethnic conflicts; (2) ethnic conflict will not die out by killing all ethnic members once for all, and it also cannot be reduced by a forcible pressure, i.e., increasing the ratio of individuals with civic identity; (3) the average frequencies of conflicts can stay in a low level by promoting civic identity periodically and persistently.

Forecasting civil conflict along the shared socioeconomic pathways

International Nuclear Information System (INIS)

Hegre, Håvard; Buhaug, Halvard; Norwegian University of Science and Technology, Trondheim; Calvin, Katherine V.

2016-01-01

Climate change and armed civil conflict are both linked to socioeconomic development, although conditions that facilitate peace may not necessarily facilitate mitigation and adaptation to climate change. While economic growth lowers the risk of conflict, it is generally associated with increased greenhouse gas emissions and costs of climate mitigation policies. Here, this study investigates the links between growth, climate change, and conflict by simulating future civil conflict using new scenario data for five alternative socioeconomic pathways with different mitigation and adaptation assumptions, known as the shared socioeconomic pathways (SSPs). We develop a statistical model of the historical effect of key socioeconomic variables on country-specific conflict incidence, 1960–2013. We then forecast the annual incidence of conflict, 2014–2100, along the five SSPs. We find that SSPs with high investments in broad societal development are associated with the largest reduction in conflict risk. This is most pronounced for the least developed countries—poverty alleviation and human capital investments in poor countries are much more effective instruments to attain global peace and stability than further improvements to wealthier economies. Moreover, the SSP that describes a sustainability pathway, which poses the lowest climate change challenges, is as conducive to global peace as the conventional development pathway.

Defining the Simulation Technician Role: Results of a Survey-Based Study.

Science.gov (United States)

Bailey, Rachel; Taylor, Regina G; FitzGerald, Michael R; Kerrey, Benjamin T; LeMaster, Thomas; Geis, Gary L

2015-10-01

In health care simulation, simulation technicians perform multiple tasks to support various educational offerings. Technician responsibilities and the tasks that accompany them seem to vary between centers. The objectives were to identify the range and frequency of tasks that technicians perform and to determine if there is a correspondence between what technicians do and what they feel their responsibilities should be. We hypothesized that there is a core set of responsibilities and tasks for the technician position regardless of background, experience, and type of simulation center. We conducted a prospective, survey-based study of individuals currently functioning in a simulation technician role in a simulation center. This survey was designed internally and piloted within 3 academic simulation centers. Potential respondents were identified through a national mailing list, and the survey was distributed electronically during a 3-week period. A survey request was sent to 280 potential participants, 136 (49%) responded, and 73 met inclusion criteria. Five core tasks were identified as follows: equipment setup and breakdown, programming scenarios into software, operation of software during simulation, audiovisual support for courses, and on-site simulator maintenance. Independent of background before they were hired, technicians felt unprepared for their role once taking the position. Formal training was identified as a need; however, the majority of technicians felt experience over time was the main contributor toward developing knowledge and skills within their role. This study represents a first step in defining the technician role within simulation-based education and supports the need for the development of a formal job description to allow recruitment, development, and certification.

Degenerative Pathways of Lumbar Motion Segments

DEFF Research Database (Denmark)

Jensen, Rikke K.; Kjaer, Per; Jensen, Tue S.

2016-01-01

pathways of degeneration based on scientific knowledge of disco-vertebral degeneration, and (iii) compare these clusters and degenerative pathways between samples. METHODS: We performed a secondary cross-sectional analysis on two dissimilar MRI samples collected in a hospital department: (1) data from...... pathways of degeneration. RESULTS: Six clusters of MRI findings were identified in each of the two samples. The content of the clusters in the two samples displayed some differences but had the same overall pattern of MRI findings. Although the hypothetical degenerative pathways identified in the two...... samples were not identical, the overall pattern of increasing degeneration within the pathways was the same. CONCLUSIONS: It was expected that different clusters could emerge from different samples, however, when organised into hypothetical pathways of degeneration, the overall pattern of increasing...

Direct Numerical Simulations of NOx formation in spatially developing turbulent premixed Bunsen flames with mixture inhomogeneity

KAUST Repository

Luca, Stefano

2017-01-05

Direct Numerical Simulation of three-dimensional spatially developing turbulent methane/air flames are performed. Four flames are simulated; they differ for the level of premixing of the fuel inlet: one has a fully premixed inlet, the other three have a partially premixed inlet that mimic a common injection strategy in stationary gas turbines. The jet consist of a methane/air mixture with global equivalence ratio ɸ = 0.7 and temperature of 800 K. The simulations are performed at 4 atm. The inlet velocity field and the fuel/air fields were extracted from a fully developed turbulent channel simulation. Chemistry is treated with a new skeletal chemical mechanism consisting of 33 species developed specifically for the DNS. The data are analyzed to study possible influences of partial premixing on the flame structure and the combustion efficiency. The results show that increasing the level of partial premixing, the fluctuations of heat release rate increase, due to the richer and leaner pockets of mixture in the flame, while the conditional mean decreases. Increasing the level of partial premixing, the peak of NO and the range of NO values for a given temperature increase. An analysis of NO production is performed categorizing the different initiation steps in the Ndecomposition through four pathways: thermal, prompt, NNH and NO. Different behaviour with respect to laminar flames is found for the NNH pathway suggesting that turbulence influences this pathway of formation of NO.

Migration pathways in soils

International Nuclear Information System (INIS)

Gronow, J.R.

1986-01-01

This study looked at diffusive migration through three types of deformation; the projectile pathways, hydraulic fractures of the sediments and faults, and was divided into three experimental areas: autoradiography, the determination of diffusion coefficients and electron microscopy of model projectile pathways in clay. For the autoradiography, unstressed samples were exposed to two separate isotopes, Pm-147 (a possible model for Am behaviour) and the poorly sorbed iodide-125. The results indicated that there was no enhanced migration through deformed kaolin samples nor through fractured Great Meteor East (GME) sediment, although some was evident through the projectile pathways in GME and possibly through the GME sheared samples. The scanning electron microscopy of projectile pathways in clay showed that emplacement of a projectile appeared to have no effect on the orientation of particles at distances greater than two projectile radii from the centre of a projectile pathway. It showed that the particles were not simply aligned with the direction of motion of the projectile but that, the closer to the surface of a particular pathway, the closer the particles lay to their original orientation. This finding was of interest from two points of view: i) the ease of migration of a pollutant along the pathway, and ii) possible mechanisms of hole closure. It was concluded that, provided that there is no advective migration, the transport of radionuclides through sediments containing these defects would not be significantly more rapid than in undeformed sediments. (author)

Saltstone Matrix Characterization And Stadium Simulation Results

International Nuclear Information System (INIS)

Langton, C.

2009-01-01

SIMCO Technologies, Inc. was contracted to evaluate the durability of the saltstone matrix material and to measure saltstone transport properties. This information will be used to: (1) Parameterize the STADIUM(reg s ign) service life code, (2) Predict the leach rate (degradation rate) for the saltstone matrix over 10,000 years using the STADIUM(reg s ign) concrete service life code, and (3) Validate the modeled results by conducting leaching (water immersion) tests. Saltstone durability for this evaluation is limited to changes in the matrix itself and does not include changes in the chemical speciation of the contaminants in the saltstone. This report summarized results obtained to date which include: characterization data for saltstone cured up to 365 days and characterization of saltstone cured for 137 days and immersed in water for 31 days. Chemicals for preparing simulated non-radioactive salt solution were obtained from chemical suppliers. The saltstone slurry was mixed according to directions provided by SRNL. However SIMCO Technologies Inc. personnel made a mistake in the premix proportions. The formulation SIMCO personnel used to prepare saltstone premix was not the reference mix proportions: 45 wt% slag, 45 wt% fly ash, and 10 wt% cement. SIMCO Technologies Inc. personnel used the following proportions: 21 wt% slag, 65 wt% fly ash, and 14 wt% cement. The mistake was acknowledged and new mixes have been prepared and are curing. The results presented in this report are assumed to be conservative since the excessive fly ash was used in the SIMCO saltstone. The SIMCO mixes are low in slag which is very reactive in the caustic salt solution. The impact is that the results presented in this report are expected to be conservative since the samples prepared were deficient in slag and contained excess fly ash. The hydraulic reactivity of slag is about four times that of fly ash so the amount of hydrated binder formed per unit volume in the SIMCO saltstone samples

Human cerebral venous outflow pathway depends on posture and central venous pressure

Science.gov (United States)

Gisolf, J; van Lieshout, J J; van Heusden, K; Pott, F; Stok, W J; Karemaker, J M

2004-01-01

Internal jugular veins are the major cerebral venous outflow pathway in supine humans. In upright humans the positioning of these veins above heart level causes them to collapse. An alternative cerebral outflow pathway is the vertebral venous plexus. We set out to determine the effect of posture and central venous pressure (CVP) on the distribution of cerebral outflow over the internal jugular veins and the vertebral plexus, using a mathematical model. Input to the model was a data set of beat-to-beat cerebral blood flow velocity and CVP measurements in 10 healthy subjects, during baseline rest and a Valsalva manoeuvre in the supine and standing position. The model, consisting of 2 jugular veins, each a chain of 10 units containing nonlinear resistances and capacitors, and a vertebral plexus containing a resistance, showed blood flow mainly through the internal jugular veins in the supine position, but mainly through the vertebral plexus in the upright position. A Valsalva manoeuvre while standing completely re-opened the jugular veins. Results of ultrasound imaging of the right internal jugular vein cross-sectional area at the level of the laryngeal prominence in six healthy subjects, before and during a Valsalva manoeuvre in both body positions, correlate highly with model simulation of the jugular cross-sectional area (R2 = 0.97). The results suggest that the cerebral venous flow distribution depends on posture and CVP: in supine humans the internal jugular veins are the primary pathway. The internal jugular veins are collapsed in the standing position and blood is shunted to an alternative venous pathway, but a marked increase in CVP while standing completely re-opens the jugular veins. PMID:15284348

Quantitative evaluation for training results of nuclear plant operator on BWR simulator

International Nuclear Information System (INIS)

Sato, Takao; Sato, Tatsuaki; Onishi, Hiroshi; Miyakita, Kohji; Mizuno, Toshiyuki

1985-01-01

Recently, the reliability of neclear power plants has largely risen, and the abnormal phenomena in the actual plants are rarely encountered. Therefore, the training using simulators becomes more and more important. In BWR Operator Training Center Corp., the training of the operators of BWR power plants has been continued for about ten years using a simulator having the nearly same function as the actual plants. The recent high capacity ratio of nuclear power plants has been mostly supported by excellent operators trained in this way. Taking the opportunity of the start of operation of No.2 simulator, effort has been exerted to quantitatively grasp the effect of training and to heighten the quality of training. The outline of seven training courses is shown. The technical ability required for operators, the items of quantifying the effect of training, that is, operational errors and the time required for operation, the method of quantifying, the method of collecting the data and the results of the application to the actual training are described. It was found that this method is suitable to quantify the effect of training. (Kako, I.)

Designing a Care Pathway Model – A Case Study of the Outpatient Total Hip Arthroplasty Care Pathway

Directory of Open Access Journals (Sweden)

Robin I. Oosterholt

2017-03-01

Full Text Available Introduction: Although the clinical attributes of total hip arthroplasty (THA care pathways have been thoroughly researched, a detailed understanding of the equally important organisational attributes is still lacking. The aim of this article is to contribute with a model of the outpatient THA care pathway that depicts how the care team should be organised to enable patient discharge on the day of surgery. Theory: The outpatient THA care pathway enables patients to be discharged on the day of surgery, short- ening the length of stay and intensifying the provision and organisation of care. We utilise visual care modelling to construct a visual design of the organisation of the care pathway. Methods: An embedded case study was conducted of the outpatient THA care pathway at a teaching hospital in the Netherlands. The data were collected using a visual care modelling toolkit in 16 semi- structured interviews. Problems and inefficiencies in the care pathway were identified and addressed in the iterative design process. Results: The results are two visual models of the most critical phases of the outpatient THA care pathway: diagnosis & preparation (1 and mobilisation & discharge (4. The results show the care team composition, critical value exchanges, and sequence that enable patient discharge on the day of surgery. Conclusion: The design addressed existing problems and is an optimisation of the case hospital’s pathway. The network of actors consists of the patient (1, radiologist (1, anaesthetist (1, nurse specialist (1, pharmacist (1, orthopaedic surgeon (1,4, physiotherapist (1,4, nurse (4, doctor (4 and patient applica- tion (1,4. The critical value exchanges include patient preparation (mental and practical, patient education, aligned care team, efficient sequence of value exchanges, early patient mobilisation, flexible availability of the physiotherapist, functional discharge criteria, joint decision making and availability of the care team.

An early colonisation pathway into northwest Australia 70-60,000 years ago

Science.gov (United States)

Norman, Kasih; Inglis, Josha; Clarkson, Chris; Faith, J. Tyler; Shulmeister, James; Harris, Daniel

2018-01-01

Colonisation of Sahul 70-60 thousand years ago (kya) represents the first great maritime migration undertaken by anatomically modern humans in one of the final phases of the Out of Africa dispersal. Visual connectivity network analyses, agent-based simulations and ocean current modelling reveal that modern humans could follow numerous northern and southern migration pathways into Sahul. Our results support a southern route out of Africa through South Asia with entry into ISEA through the Banda Arc, culminating in an early colonisation of Sahul on the northwest shelf. Our results show multiple colonisation events through other entry points were also probable, and raise interesting possibilities for complex regional migration and population histories.

Simulated Microgravity Modulates Differentiation Processes of Embryonic Stem Cells

Directory of Open Access Journals (Sweden)

Vaibhav Shinde

2016-04-01

Full Text Available Background/Aims: Embryonic developmental studies under microgravity conditions in space are very limited. To study the effects of altered gravity on the embryonic development processes we established an in vitro methodology allowing differentiation of mouse embryonic stem cells (mESCs under simulated microgravity within a fast-rotating clinostat (clinorotation and capture of microarray-based gene signatures. Methods: The differentiating mESCs were cultured in a 2D pipette clinostat. The microarray and bioinformatics tools were used to capture genes that are deregulated by simulated microgravity and their impact on developmental biological processes. Results: The data analysis demonstrated that differentiation of mESCs in pipettes for 3 days resultet to early germ layer differentiation and then to the different somatic cell types after further 7 days of differentiation in the Petri dishes. Clinorotation influences differentiation as well as non-differentiation related biological processes like cytoskeleton related 19 genes were modulated. Notably, simulated microgravity deregulated genes Cyr61, Thbs1, Parva, Dhrs3, Jun, Tpm1, Fzd2 and Dll1 are involved in heart morphogenesis as an acute response on day 3. If the stem cells were further cultivated under normal gravity conditions (1 g after clinorotation, the expression of cardiomyocytes specific genes such as Tnnt2, Rbp4, Tnni1, Csrp3, Nppb and Mybpc3 on day 10 was inhibited. This correlated well with a decreasing beating activity of the 10-days old embryoid bodies (EBs. Finally, we captured Gadd45g, Jun, Thbs1, Cyr61and Dll1 genes whose expressions were modulated by simulated microgravity and by real microgravity in various reported studies. Simulated microgravity also deregulated genes belonging to the MAP kinase and focal dhesion signal transduction pathways. Conclusion: One of the most prominent biological processes affected by simulated microgravity was the process of cardiomyogenesis. The

Simulated cosmic microwave background maps at 0.5 deg resolution: Basic results

Science.gov (United States)

Hinshaw, G.; Bennett, C. L.; Kogut, A.

1995-01-01

We have simulated full-sky maps of the cosmic microwave background (CMB) anisotropy expected from cold dark matter (CDM) models at 0.5 deg and 1.0 deg angular resolution. Statistical properties of the maps are presented as a function of sky coverage, angular resolution, and instrument noise, and the implications of these results for observability of the Doppler peak are discussed. The rms fluctuations in a map are not a particularly robust probe of the existence of a Doppler peak; however, a full correlation analysis can provide reasonable sensitivity. We find that sensitivity to the Doppler peak depends primarily on the fraction of sky covered, and only secondarily on the angular resolution and noise level. Color plates of the simulated maps are presented to illustrate the anisotropies.

Mechanistic pathways of recognition of a solvent-inaccessible cavity of protein by a ligand

Science.gov (United States)

Mondal, Jagannath; Pandit, Subhendu; Dandekar, Bhupendra; Vallurupalli, Pramodh

One of the puzzling questions in the realm of protein-ligand recognition is how a solvent-inaccessible hydrophobic cavity of a protein gets recognized by a ligand. We address the topic by simulating, for the first time, the complete binding process of benzene from aqueous media to the well-known buried cavity of L99A T4 Lysozyme at an atomistic resolution. Our multiple unbiased microsecond-long trajectories, which were completely blind to the location of target binding site, are able to unequivocally identify the kinetic pathways along which benzene molecule meanders across the solvent and protein and ultimately spontaneously recognizes the deeply buried cavity of L99A T4 Lysozyme at an accurate precision. Our simulation, combined with analysis based on markov state model and free energy calculation, reveals that there are more than one distinct ligand binding pathways. Intriguingly, each of the identified pathways involves the transient opening of a channel of the protein prior to ligand binding. The work will also decipher rich mechanistic details on unbinding kinetics of the ligand as obtained from enhanced sampling techniques.

Chiropractic Integrated Care Pathway for Low Back Pain in Veterans: Results of a Delphi Consensus Process.

Science.gov (United States)

Lisi, Anthony J; Salsbury, Stacie A; Hawk, Cheryl; Vining, Robert D; Wallace, Robert B; Branson, Richard; Long, Cynthia R; Burgo-Black, A Lucille; Goertz, Christine M

2018-02-01

The purpose of this study was to develop an integrated care pathway for doctors of chiropractic, primary care providers, and mental health professionals who manage veterans with low back pain, with or without mental health comorbidity, within Department of Veterans Affairs health care facilities. The research method used was a consensus process. A multidisciplinary investigative team reviewed clinical guidelines and Veterans Affairs pain and mental health initiatives to develop seed statements and care algorithms to guide chiropractic management and collaborative care of veterans with low back pain. A 5-member advisory committee approved initial recommendations. Veterans Affairs-based panelists (n = 58) evaluated the pathway via e-mail using a modified RAND/UCLA methodology. Consensus was defined as agreement by 80% of panelists. The modified Delphi process was conducted in July to December 2016. Most (93%) seed statements achieved consensus during the first round, with all statements reaching consensus after 2 rounds. The final care pathway addressed the topics of informed consent, clinical evaluation including history and examination, screening for red flags, documentation, diagnostic imaging, patient-reported outcomes, adverse event reporting, chiropractic treatment frequency and duration standards, tailored approaches to chiropractic care in veteran populations, and clinical presentation of common mental health conditions. Care algorithms outlined chiropractic case management and interprofessional collaboration and referrals between doctors of chiropractic and primary care and mental health providers. This study offers an integrative care pathway that includes chiropractic care for veterans with low back pain. Copyright © 2018. Published by Elsevier Inc.

A Novel Simulation Technician Laboratory Design: Results of a Survey-Based Study.

Science.gov (United States)

Ahmed, Rami; Hughes, Patrick G; Friedl, Ed; Ortiz Figueroa, Fabiana; Cepeda Brito, Jose R; Frey, Jennifer; Birmingham, Lauren E; Atkinson, Steven Scott

2016-03-16

OBJECTIVE : The purpose of this study was to elicit feedback from simulation technicians prior to developing the first simulation technician-specific simulation laboratory in Akron, OH. Simulation technicians serve a vital role in simulation centers within hospitals/health centers around the world. The first simulation technician degree program in the US has been approved in Akron, OH. To satisfy the requirements of this program and to meet the needs of this special audience of learners, a customized simulation lab is essential. A web-based survey was circulated to simulation technicians prior to completion of the lab for the new program. The survey consisted of questions aimed at identifying structural and functional design elements of a novel simulation center for the training of simulation technicians. Quantitative methods were utilized to analyze data. Over 90% of technicians (n=65) think that a lab designed explicitly for the training of technicians is novel and beneficial. Approximately 75% of respondents think that the space provided appropriate audiovisual (AV) infrastructure and space to evaluate the ability of technicians to be independent. The respondents think that the lab needed more storage space, visualization space for a large number of students, and more space in the technical/repair area. CONCLUSIONS : A space designed for the training of simulation technicians was considered to be beneficial. This laboratory requires distinct space for technical repair, adequate bench space for the maintenance and repair of simulators, an appropriate AV infrastructure, and space to evaluate the ability of technicians to be independent.

Exposures from aquatic pathways

International Nuclear Information System (INIS)

Berkovski, V.; Voitsekhovitch, O.; Nasvit, O.; Zhelezniak, M.; Sansone, U.

1996-01-01

Methods for estimation aquatic pathways contribution to the total population exposure are discussed. Aquatic pathways are the major factor for radionuclides spreading from the Chernobyl Exclusion zone. An annual outflow of 90 Sr and 137 Cs comprised 10-20 TBq and 2-4 TBq respectively and the population exposed by this effluence constitutes almost 30 million people. The dynamic of doses from 90 Sr and ' C s, which Dnieper water have to delivered, is calculated. The special software has been developed to simulate the process of dose formation in the of diverse Dnieper regions. Regional peculiarities of municipal tap, fishing and irrigation are considered. Seventy-year prediction of dose structure and function of dose forming is performed. The exposure is estimated for 12 regions of the Dnieper basin and the Crimea. The maximal individual annual committed effective doses due to the use of water by ordinary members of the population in Kiev region from 90 Sr and 137 Cs in 1986 are 1.7*10 -5 Sv and 2.7*10 -5 Sv respectively. A commercial fisherman on Kiev reservoir in 1986 received 4.7*10 -4 Sv and 5*10 -3 Sv from 90 Sr and 137 Cs, respectively. The contributions to the collective cumulative (over 70 years) committed effective dose (CCCED 70 ) of irrigation, municipal tap water and fish consumption for members of the population respectively are 18%, 43%, 39% in Kiev region, 8%, 25%, 67% in Poltava region, and 50%, 50%, 0% (consumption of Dnieper fish is absent) in the Crimea. The predicted contribution of the Strontium-90 to CCCED 70 resulting from the use of water is 80%. The CCCED 70 to the population of the Dnieper regions (32.5 million people) is 3000 person-Sv due to the use the Dnieper water

YAP and the Hippo pathway in pediatric cancer.

Science.gov (United States)

Ahmed, Atif A; Mohamed, Abdalla D; Gener, Melissa; Li, Weijie; Taboada, Eugenio

2017-01-01

The Hippo pathway is an important signaling pathway that controls cell proliferation and apoptosis. It is evolutionarily conserved in mammals and is stimulated by cell-cell contact, inhibiting cell proliferation in response to increased cell density. During early embryonic development, the Hippo signaling pathway regulates organ development and size, and its functions result in the coordinated balance between proliferation, apoptosis, and differentiation. Its principal effectors, YAP and TAZ, regulate signaling by the embryonic stem cells and determine cell fate and histogenesis. Dysfunction of this pathway contributes to cancer development in adults and children. Emerging studies have shed light on the upregulation of Hippo pathway members in several pediatric cancers and may offer prognostic information on rhabdomyosarcoma, osteosarcoma, Wilms tumor, neuroblastoma, medulloblastoma, and other brain gliomas. We review the results of such published studies and highlight the potential clinical application of this pathway in pediatric oncologic and pathologic studies. These studies support targeting this pathway as a novel treatment strategy.

2D and 3D core-collapse supernovae simulation results obtained with the CHIMERA code

Energy Technology Data Exchange (ETDEWEB)

Bruenn, S W; Marronetti, P; Dirk, C J [Physics Department, Florida Atlantic University, 777 W. Glades Road, Boca Raton, FL 33431-0991 (United States); Mezzacappa, A; Hix, W R [Physics Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6354 (United States); Blondin, J M [Department of Physics, North Carolina State University, Raleigh, NC 27695-8202 (United States); Messer, O E B [Center for Computational Sciences, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6354 (United States); Yoshida, S, E-mail: bruenn@fau.ed [Max-Planck-Institut fur Gravitationsphysik, Albert Einstein Institut, Golm (Germany)

2009-07-01

Much progress in realistic modeling of core-collapse supernovae has occurred recently through the availability of multi-teraflop machines and the increasing sophistication of supernova codes. These improvements are enabling simulations with enough realism that the explosion mechanism, long a mystery, may soon be delineated. We briefly describe the CHIMERA code, a supernova code we have developed to simulate core-collapse supernovae in 1, 2, and 3 spatial dimensions. We then describe the results of an ongoing suite of 2D simulations initiated from a 12, 15, 20, and 25 M{sub o-dot} progenitor. These have all exhibited explosions and are currently in the expanding phase with the shock at between 5,000 and 20,000 km. We also briefly describe an ongoing simulation in 3 spatial dimensions initiated from the 15 M{sub o-dot} progenitor.

How do rigid-lid assumption affect LES simulation results at high Reynolds flows?

Science.gov (United States)

Khosronejad, Ali; Farhadzadeh, Ali; SBU Collaboration

2017-11-01

This research is motivated by the work of Kara et al., JHE, 2015. They employed LES to model flow around a model of abutment at a Re number of 27,000. They showed that first-order turbulence characteristics obtained by rigid-lid (RL) assumption compares fairly well with those of level-set (LS) method. Concerning the second-order statistics, however, their simulation results showed a significant dependence on the method used to describe the free surface. This finding can have important implications for open channel flow modeling. The Reynolds number for typical open channel flows, however, could be much larger than that of Kara et al.'s test case. Herein, we replicate the reported study by augmenting the geometric and hydraulic scales to reach a Re number of one order of magnitude larger ( 200,000). The Virtual Flow Simulator (VFS-Geophysics) model in its LES mode is used to simulate the test case using both RL and LS methods. The computational results are validated using measured flow and free-surface data from our laboratory experiments. Our goal is to investigate the effects of RL assumption on both first-order and second order statistics at high Reynolds numbers that occur in natural waterways. Acknowledgment: Computational resources are provided by the Center of Excellence in Wireless & Information Technology (CEWIT) of Stony Brook University.

Results from Tight and Loose Coupled Multiphysics in Nuclear Fuels Performance Simulations using BISON

Energy Technology Data Exchange (ETDEWEB)

S. R. Novascone; B. W. Spencer; D. Andrs; R. L. Williamson; J. D. Hales; D. M. Perez

2013-05-01

The behavior of nuclear fuel in the reactor environment is affected by multiple physics, most notably heat conduction and solid mechanics, which can have a strong influence on each other. To provide credible solutions, a fuel performance simulation code must have the ability to obtain solutions for each of the physics, including coupling between them. Solution strategies for solving systems of coupled equations can be categorized as loosely-coupled, where the individual physics are solved separately, keeping the solutions for the other physics fixed at each iteration, or tightly coupled, where the nonlinear solver simultaneously drives down the residual for each physics, taking into account the coupling between the physics in each nonlinear iteration. In this paper, we compare the performance of loosely and tightly coupled solution algorithms for thermomechanical problems involving coupled thermal and mechanical contact, which is a primary source of interdependence between thermal and mechanical solutions in fuel performance models. The results indicate that loosely-coupled simulations require significantly more nonlinear iterations, and may lead to convergence trouble when the thermal conductivity of the gap is too small. We also apply the tightly coupled solution strategy to a nuclear fuel simulation of an experiment in a test reactor. Studying the results from these simulations indicates that perhaps convergence for either approach may be problem dependent, i.e., there may be problems for which a loose coupled approach converges, where tightly coupled won’t converge and vice versa.

Results from tight and loose coupled multiphysics in nuclear fuels performance simulations using BISON

International Nuclear Information System (INIS)

Novascone, S. R.; Spencer, B. W.; Andrs, D.; Williamson, R. L.; Hales, J. D.; Perez, D. M.

2013-01-01

The behavior of nuclear fuel in the reactor environment is affected by multiple physics, most notably heat conduction and solid mechanics, which can have a strong influence on each other. To provide credible solutions, a fuel performance simulation code must have the ability to obtain solutions for each of the physics, including coupling between them. Solution strategies for solving systems of coupled equations can be categorized as loosely-coupled, where the individual physics are solved separately, keeping the solutions for the other physics fixed at each iteration, or tightly coupled, where the nonlinear solver simultaneously drives down the residual for each physics, taking into account the coupling between the physics in each nonlinear iteration. In this paper, we compare the performance of loosely and tightly coupled solution algorithms for thermomechanical problems involving coupled thermal and mechanical contact, which is a primary source of interdependence between thermal and mechanical solutions in fuel performance models. The results indicate that loosely-coupled simulations require significantly more nonlinear iterations, and may lead to convergence trouble when the thermal conductivity of the gap is too small. We also apply the tightly coupled solution strategy to a nuclear fuel simulation of an experiment in a test reactor. Studying the results from these simulations indicates that perhaps convergence for either approach may be problem dependent, i.e., there may be problems for which a loose coupled approach converges, where tightly coupled won't converge and vice versa. (authors)

Parallel of semi-empirical results simulated by MCNP of X-ray spectra with a semiconductor

International Nuclear Information System (INIS)

Santos, L.R.; Vivolo, V.; Potiens, M.P.A.; Navarro, M.V.T.; Santos, W.S.

2016-01-01

The aim of this study was to use the MCNPX radiation transport code to simulate X-ray spectra generated by a constant voltage system in a CdTe semiconductor detector. As part of the validation process, we obtained a series of experimental spectra. Comparatively, in all cases there is a good correlation between the two spectra. There were no statistically significant differences between the experimental results with the simulated. (author)

Atomistic Simulation of Initiation in Hexanitrostilbene

Science.gov (United States)

Shan, Tzu-Ray; Wixom, Ryan; Yarrington, Cole; Thompson, Aidan

2015-06-01

We report on the effect of cylindrical voids on hot spot formation, growth and chemical reaction initiation in hexanitrostilbene (HNS) crystals subjected to shock. Large-scale, reactive molecular dynamics simulations are performed using the reactive force field (ReaxFF) as implemented in the LAMMPS software. The ReaxFF force field description for HNS has been validated previously by comparing the isothermal equation of state to available diamond anvil cell (DAC) measurements and density function theory (DFT) calculations and by comparing the primary dissociation pathway to ab initio calculations. Micron-scale molecular dynamics simulations of a supported shockwave propagating through the HNS crystal along the [010] orientation are performed with an impact velocity (or particle velocity) of 1.25 km/s, resulting in shockwave propagation at 4.0 km/s in the bulk material and a bulk shock pressure of ~ 11GPa. The effect of cylindrical void sizes varying from 0.02 to 0.1 μm on hot spot formation and growth rate has been studied. Interaction between multiple voids in the HNS crystal and its effect on hot spot formation will also be addressed. Results from the micron-scale atomistic simulations are compared with hydrodynamics simulations. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. DOE National Nuclear Security Administration under Contract DE-AC04-94AL85000.

Analysis of l-glutamic acid fermentation by using a dynamic metabolic simulation model of Escherichia coli

OpenAIRE

Nishio, Yousuke; Ogishima, Soichi; Ichikawa, Masao; Yamada, Yohei; Usuda, Yoshihiro; Masuda, Tadashi; Tanaka, Hiroshi

2013-01-01

Background Understanding the process of amino acid fermentation as a comprehensive system is a challenging task. Previously, we developed a literature-based dynamic simulation model, which included transcriptional regulation, transcription, translation, and enzymatic reactions related to glycolysis, the pentose phosphate pathway, the tricarboxylic acid (TCA) cycle, and the anaplerotic pathway of Escherichia coli. During simulation, cell growth was defined such as to reproduce the experimental...

The development of a comprehensive multidisciplinary care pathway for patients with a hip fracture: design and results of a clinical trial.

Science.gov (United States)

Flikweert, Elvira R; Izaks, Gerbrand J; Knobben, Bas A S; Stevens, Martin; Wendt, Klaus

2014-05-30

Hip fractures frequently occur in older persons and severely decrease life expectancy and independence. Several care pathways have been developed to lower the risk of negative outcomes but most pathways are limited to only one aspect of care. The aim of this study was therefore to develop a comprehensive care pathway for older persons with a hip fracture and to conduct a preliminary analysis of its effect. A comprehensive multidisciplinary care pathway for patients aged 60 years or older with a hip fracture was developed by a multidisciplinary team. The new care pathway was evaluated in a clinical trial with historical controls. The data of the intervention group were collected prospectively. The intervention group included all patients with a hip fracture who were admitted to University Medical Center Groningen between 1 July 2009 and 1 July 2011. The data of the control group were collected retrospectively. The control group comprised all patients with a hip fracture who were admitted between 1 January 2006 and 1 January 2008. The groups were compared with the independent sample t-test, the Mann-Whitney U-test or the Chi-squared test (Phi test). The effect of the intervention on fasting time and length of stay was adjusted by linear regression analysis for differences between the intervention and control group. The intervention group included 256 persons (women, 68%; mean age (SD), 78 (9) years) and the control group 145 persons (women, 72%; mean age (SD), 80 (10) years). Median preoperative fasting time and median length of hospital stay were significantly lower in the intervention group: 9 vs. 17 hours (p < 0.001), and 7 vs. 11 days (p < 0.001), respectively. A similar result was found after adjustment for age, gender, living condition and American Society of Anesthesiologists (ASA) classification. In-hospital mortality was also lower in the intervention group: 2% vs. 6% (p < 0.05). There were no statistically significant differences in other

Some Experimental and Simulation Results on the Dynamic Behaviour of Spur and Helical Geared Transmissions with Journal Bearings

Directory of Open Access Journals (Sweden)

R. Fargère

2012-01-01

Full Text Available Some interactions between the dynamic and tribological behaviour of geared transmissions are examined, and a number of experimental and simulation results are compared. A model is introduced which incorporates most of the possible interactions between gears, shafts and hydrodynamic journal bearings. It combines (i a specific element for wide-faced gears that includes the normal contact conditions between actual mating teeth, that is, with tooth shape deviations and mounting errors, (ii shaft finite elements, and (iii the external forces generated by journal bearings determined by directly solving Reynolds' equation. The simulation results are compared with the measurement obtained on a high-precision test rig with single-stage spur and helical gears supported by hydrodynamic journal bearings. The experimental and simulation results compare well thus validating the simulation strategy both at the global and local scales.

Development of CANDU prototype fuel handling simulator - concept and some simulation results with physical network modeling approach

Energy Technology Data Exchange (ETDEWEB)

Xu, X.P. [Candu Energy Inc, Mississauga, Ontario (Canada)

2012-07-01

This paper reviewed the need for a fuel handling(FH) simulator in training operators and maintenance personnel, in FH design enhancement based on operating experience (OPEX), and the potential application of Virtual Reality (VR) based simulation technology. Modeling and simulation of the fuelling machine (FM) magazine drive plant (one of the CANDU FH sub-systems) was described. The work established the feasibility of modeling and simulating a physical FH drive system using the physical network approach and computer software tools. The concept and approach can be applied similarly to create the other FH subsystem plant models, which are expected to be integrated with control modules to develop a master FH control model and further to create a virtual FH system. (author)

Development of CANDU prototype fuel handling simulator - concept and some simulation results with physical network modeling approach

International Nuclear Information System (INIS)

Xu, X.P.

2012-01-01

This paper reviewed the need for a fuel handling(FH) simulator in training operators and maintenance personnel, in FH design enhancement based on operating experience (OPEX), and the potential application of Virtual Reality (VR) based simulation technology. Modeling and simulation of the fuelling machine (FM) magazine drive plant (one of the CANDU FH sub-systems) was described. The work established the feasibility of modeling and simulating a physical FH drive system using the physical network approach and computer software tools. The concept and approach can be applied similarly to create the other FH subsystem plant models, which are expected to be integrated with control modules to develop a master FH control model and further to create a virtual FH system. (author)

Pathways to space: A mission to foster the next generation of scientists and engineers

Science.gov (United States)

Dougherty, Kerrie; Oliver, Carol; Fergusson, Jennifer

2014-06-01

The first education project funded under the Australian Government's Australian Space Research Program (ASRP), Pathways to Space was a unique project combining education, science communication research and research in astrobiology and robotics. It drew upon the challenges of space exploration to inspire students to consider study and careers in science and engineering. A multi-faceted program, Pathways to Space provided hands-on opportunities for high school and university students to participate in realistic simulations of a robotic Mars exploration mission for astrobiology. Its development was a collaboration between the Australian Centre for Astrobiology (University of New South Wales), the Australian Centre for Field Robotics (University of Sydney), the Powerhouse Museum and industry partner, Cisco. Focused on students in Years 9-10 (15-16 years of age), this program provided them with the opportunity to engage directly with space engineers and astrobiologists, while carrying out a simulated Mars mission using the digital learning facilities available at the Powerhouse Museum. As a part of their program, the students operated robotic mini-rovers in the Powerhouse Museum's “Mars Yard”, a highly accurate simulation of the Martian surface, where university students also carry out the development and testing of experimental Mars roving vehicles. This aspect of the program has brought real science and engineering research into the public space of the museum. As they undertook the education program, the students participated in a research study aimed at understanding the effectiveness of the project in achieving its key objective - encouraging students to consider space related courses and careers. This paper outlines the development and operation of the Pathways to Space project over its 3-year funding period, during which it met and exceeded all the requirements of its ASRP grant. It will look at the goals of the project, the rationale behind the education and

Phonocatalysis. An ab initio simulation experiment

Directory of Open Access Journals (Sweden)

Kwangnam Kim

2016-06-01

Full Text Available Using simulations, we postulate and show that heterocatalysis on large-bandgap semiconductors can be controlled by substrate phonons, i.e., phonocatalysis. With ab initio calculations, including molecular dynamic simulations, the chemisorbed dissociation of XeF6 on h-BN surface leads to formation of XeF4 and two surface F/h-BN bonds. The reaction pathway and energies are evaluated, and the sorption and reaction emitted/absorbed phonons are identified through spectral analysis of the surface atomic motion. Due to large bandgap, the atomic vibration (phonon energy transfer channels dominate and among them is the match between the F/h-BN covalent bond stretching and the optical phonons. We show that the chemisorbed dissociation (the pathway activation ascent requires absorption of large-energy optical phonons. Then using progressively heavier isotopes of B and N atoms, we show that limiting these high-energy optical phonons inhibits the chemisorbed dissociation, i.e., controllable phonocatalysis.

Simulating Pacific Northwest Forest Response to Climate Change: How We Made Model Results Useful for Vulnerability Assessments

Science.gov (United States)

Kim, J. B.; Kerns, B. K.; Halofsky, J.

2014-12-01

GCM-based climate projections and downscaled climate data proliferate, and there are many climate-aware vegetation models in use by researchers. Yet application of fine-scale DGVM based simulation output in national forest vulnerability assessments is not common, because there are technical, administrative and social barriers for their use by managers and policy makers. As part of a science-management climate change adaptation partnership, we performed simulations of vegetation response to climate change for four national forests in the Blue Mountains of Oregon using the MC2 dynamic global vegetation model (DGVM) for use in vulnerability assessments. Our simulation results under business-as-usual scenarios suggest a starkly different future forest conditions for three out of the four national forests in the study area, making their adoption by forest managers a potential challenge. However, using DGVM output to structure discussion of potential vegetation changes provides a suitable framework to discuss the dynamic nature of vegetation change compared to using more commonly available model output (e.g. species distribution models). From the onset, we planned and coordinated our work with national forest managers to maximize the utility and the consideration of the simulation results in planning. Key lessons from this collaboration were: (1) structured and strategic selection of a small number climate change scenarios that capture the range of variability in future conditions simplified results; (2) collecting and integrating data from managers for use in simulations increased support and interest in applying output; (3) a structured, regionally focused, and hierarchical calibration of the DGVM produced well-validated results; (4) simple approaches to quantifying uncertainty in simulation results facilitated communication; and (5) interpretation of model results in a holistic context in relation to multiple lines of evidence produced balanced guidance. This latest

RF feedback simulation results for PEP-II

International Nuclear Information System (INIS)

Tighe, R.; Corredoura, P.

1995-06-01

A model of the RF feedback system for PEP-II has been developed to provide time-domain simulation and frequency-domain analysis of the complete system. The model includes the longitudinal beam dynamics, cavity fundamental resonance, feedback loops, and the nonlinear klystron operating near saturation. Transients from an ion clearing gap and a reference phase modulation from the longitudinal feedback system are also studied. Growth rates are predicted and overall system stability examined

Designing a Care Pathway Model - A Case Study of the Outpatient Total Hip Arthroplasty Care Pathway.

Science.gov (United States)

Oosterholt, Robin I; Simonse, Lianne Wl; Boess, Stella U; Vehmeijer, Stephan Bw

2017-03-09

Although the clinical attributes of total hip arthroplasty (THA) care pathways have been thoroughly researched, a detailed understanding of the equally important organisational attributes is still lacking. The aim of this article is to contribute with a model of the outpatient THA care pathway that depicts how the care team should be organised to enable patient discharge on the day of surgery. The outpatient THA care pathway enables patients to be discharged on the day of surgery, shortening the length of stay and intensifying the provision and organisation of care. We utilise visual care modelling to construct a visual design of the organisation of the care pathway. An embedded case study was conducted of the outpatient THA care pathway at a teaching hospital in the Netherlands. The data were collected using a visual care modelling toolkit in 16 semi-structured interviews. Problems and inefficiencies in the care pathway were identified and addressed in the iterative design process. The results are two visual models of the most critical phases of the outpatient THA care pathway: diagnosis & preparation (1) and mobilisation & discharge (4). The results show the care team composition, critical value exchanges, and sequence that enable patient discharge on the day of surgery. The design addressed existing problems and is an optimisation of the case hospital's pathway. The network of actors consists of the patient (1), radiologist (1), anaesthetist (1), nurse specialist (1), pharmacist (1), orthopaedic surgeon (1,4), physiotherapist (1,4), nurse (4), doctor (4) and patient application (1,4). The critical value exchanges include patient preparation (mental and practical), patient education, aligned care team, efficient sequence of value exchanges, early patient mobilisation, flexible availability of the physiotherapist, functional discharge criteria, joint decision making and availability of the care team.

Molecular Pathways

Science.gov (United States)

Lok, Benjamin H.; Powell, Simon N.

2012-01-01

The Rad52 protein was largely ignored in humans and other mammals when the mouse knockout revealed a largely “no-effect” phenotype. However, using synthetic lethal approaches to investigate context dependent function, new studies have shown that Rad52 plays a key survival role in cells lacking the function of the BRCA1-BRCA2 pathway of homologous recombination. Biochemical studies also showed significant differences between yeast and human Rad52, in which yeast Rad52 can promote strand invasion of RPA-coated single-stranded DNA in the presence of Rad51, but human Rad52 cannot. This results in the paradox of how is human Rad52 providing Rad51 function: presumably there is something missing in the biochemical assays that exists in-vivo, but the nature of this missing factor is currently unknown. Recent studies have suggested that Rad52 provides back-up Rad51 function for all members of the BRCA1-BRCA2 pathway, suggesting that Rad52 may be a target for therapy in BRCA pathway deficient cancers. Screening for ways to inhibit Rad52 would potentially provide a complementary strategy for targeting BRCA-deficient cancers in addition to PARP inhibitors. PMID:23071261

Assessment of exposure pathways connected with construction and operation of concrete bridge reinforced with very low level radioactive steel

International Nuclear Information System (INIS)

Panik, M.; Necas, V.

2012-01-01

Large amount of low level radioactive material arises during decommissioning of nuclear power plants. Material mostly comprises metal scrap and concrete ruble. Paper deals with recycling and reuse of metal scrap and its utilization as part of reinforcement of concrete bridges under the conditional release concept. Radiation exposure originating in very low level reinforcement steel consists of several exposure pathways. Short-term radiation impact is represented mostly by external exposure pathway and it is relevant to the construction workers and users of the bridge. Long-term radiation impacts on inhabitants living near finished bridge and it is divided into inhalation and ingestion of radionuclides-internal exposure pathways. Radiation impact caused by utilization of very low level radioactive waste was calculated using simulation software VISIPLAN 3D ALARA and GOLDSIM. Results of calculations provide fair summary of possibilities of utilization of conditionally released steel as reinforcement of concrete bridges. (Authors)

Creation and Implementation of an Outpatient Pathway for Atrial Fibrillation in the Emergency Department Setting: Results of an Expert Panel.

Science.gov (United States)

Baugh, Christopher W; Clark, Carol L; Wilson, Jason W; Stiell, Ian G; Kocheril, Abraham G; Luck, Krista K; Myers, Troy D; Pollack, Charles V; Roumpf, Steven K; Tomassoni, Gery F; Williams, James M; Patel, Brian B; Wu, Fred; Pines, Jesse M

2018-03-10

Atrial fibrillation and flutter (AF) is a common condition among emergency department (ED) patients in the United States. Traditionally, ED care for primary complaints related to AF focus on rate control, and patients are often admitted to an inpatient setting for further care. Inpatient care may include further telemetry monitoring and diagnostic testing, rhythm control, a search for identification of AF etiology, and stroke prophylaxis. However, many patients are eligible for safe and effective outpatient management pathways. They are widely used in Canada and other countries but less widely adopted in the United States. In this project, we convened an expert panel to create a practical framework for the process of creating, implementing, and maintaining an outpatient AF pathway for emergency physicians to assess and treat AF patients, safely reduce hospitalization rates, ensure appropriate stroke prophylaxis, and effectively transition patients to longitudinal outpatient treatment settings from the ED and/or observation unit. To support local pathway creation, the panel also reached agreement on a protocol development plan, a sample pathway, consensus recommendations for pathway components, sample pathway metrics, and a structured literature review framework using a modified Delphi technique by a technical expert panel of emergency medicine, cardiology, and other stakeholder groups. © 2018 by the Society for Academic Emergency Medicine.

Stable water isotope simulation by current land-surface schemes:Results of IPILPS phase 1

Energy Technology Data Exchange (ETDEWEB)

Henderson-Sellers, A.; Fischer, M.; Aleinov, I.; McGuffie, K.; Riley, W.J.; Schmidt, G.A.; Sturm, K.; Yoshimura, K.; Irannejad, P.

2005-10-31

Phase 1 of isotopes in the Project for Intercomparison of Land-surface Parameterization Schemes (iPILPS) compares the simulation of two stable water isotopologues ({sup 1}H{sub 2} {sup 18}O and {sup 1}H{sup 2}H{sup 16}O) at the land-atmosphere interface. The simulations are off-line, with forcing from an isotopically enabled regional model for three locations selected to offer contrasting climates and ecotypes: an evergreen tropical forest, a sclerophyll eucalypt forest and a mixed deciduous wood. Here we report on the experimental framework, the quality control undertaken on the simulation results and the method of intercomparisons employed. The small number of available isotopically-enabled land-surface schemes (ILSSs) limits the drawing of strong conclusions but, despite this, there is shown to be benefit in undertaking this type of isotopic intercomparison. Although validation of isotopic simulations at the land surface must await more, and much more complete, observational campaigns, we find that the empirically-based Craig-Gordon parameterization (of isotopic fractionation during evaporation) gives adequately realistic isotopic simulations when incorporated in a wide range of land-surface codes. By introducing two new tools for understanding isotopic variability from the land surface, the Isotope Transfer Function and the iPILPS plot, we show that different hydrological parameterizations cause very different isotopic responses. We show that ILSS-simulated isotopic equilibrium is independent of the total water and energy budget (with respect to both equilibration time and state), but interestingly the partitioning of available energy and water is a function of the models' complexity.

Modelling and performance analysis of clinical pathways using the stochastic process algebra PEPA.

Science.gov (United States)

Yang, Xian; Han, Rui; Guo, Yike; Bradley, Jeremy; Cox, Benita; Dickinson, Robert; Kitney, Richard

2012-01-01

Hospitals nowadays have to serve numerous patients with limited medical staff and equipment while maintaining healthcare quality. Clinical pathway informatics is regarded as an efficient way to solve a series of hospital challenges. To date, conventional research lacks a mathematical model to describe clinical pathways. Existing vague descriptions cannot fully capture the complexities accurately in clinical pathways and hinders the effective management and further optimization of clinical pathways. Given this motivation, this paper presents a clinical pathway management platform, the Imperial Clinical Pathway Analyzer (ICPA). By extending the stochastic model performance evaluation process algebra (PEPA), ICPA introduces a clinical-pathway-specific model: clinical pathway PEPA (CPP). ICPA can simulate stochastic behaviours of a clinical pathway by extracting information from public clinical databases and other related documents using CPP. Thus, the performance of this clinical pathway, including its throughput, resource utilisation and passage time can be quantitatively analysed. A typical clinical pathway on stroke extracted from a UK hospital is used to illustrate the effectiveness of ICPA. Three application scenarios are tested using ICPA: 1) redundant resources are identified and removed, thus the number of patients being served is maintained with less cost; 2) the patient passage time is estimated, providing the likelihood that patients can leave hospital within a specific period; 3) the maximum number of input patients are found, helping hospitals to decide whether they can serve more patients with the existing resource allocation. ICPA is an effective platform for clinical pathway management: 1) ICPA can describe a variety of components (state, activity, resource and constraints) in a clinical pathway, thus facilitating the proper understanding of complexities involved in it; 2) ICPA supports the performance analysis of clinical pathway, thereby assisting

Exact and Approximate Stochastic Simulation of Intracellular Calcium Dynamics

Directory of Open Access Journals (Sweden)

Nicolas Wieder

2011-01-01

pathways. The purpose of the present paper is to provide an overview of the aforementioned simulation approaches and their mutual relationships in the spectrum ranging from stochastic to deterministic algorithms.

Simulation and Non-Simulation Based Human Reliability Analysis Approaches

Energy Technology Data Exchange (ETDEWEB)

Boring, Ronald Laurids [Idaho National Lab. (INL), Idaho Falls, ID (United States); Shirley, Rachel Elizabeth [Idaho National Lab. (INL), Idaho Falls, ID (United States); Joe, Jeffrey Clark [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mandelli, Diego [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2014-12-01

Part of the U.S. Department of Energy’s Light Water Reactor Sustainability (LWRS) Program, the Risk-Informed Safety Margin Characterization (RISMC) Pathway develops approaches to estimating and managing safety margins. RISMC simulations pair deterministic plant physics models with probabilistic risk models. As human interactions are an essential element of plant risk, it is necessary to integrate human actions into the RISMC risk model. In this report, we review simulation-based and non-simulation-based human reliability assessment (HRA) methods. Chapter 2 surveys non-simulation-based HRA methods. Conventional HRA methods target static Probabilistic Risk Assessments for Level 1 events. These methods would require significant modification for use in dynamic simulation of Level 2 and Level 3 events. Chapter 3 is a review of human performance models. A variety of methods and models simulate dynamic human performance; however, most of these human performance models were developed outside the risk domain and have not been used for HRA. The exception is the ADS-IDAC model, which can be thought of as a virtual operator program. This model is resource-intensive but provides a detailed model of every operator action in a given scenario, along with models of numerous factors that can influence operator performance. Finally, Chapter 4 reviews the treatment of timing of operator actions in HRA methods. This chapter is an example of one of the critical gaps between existing HRA methods and the needs of dynamic HRA. This report summarizes the foundational information needed to develop a feasible approach to modeling human interactions in the RISMC simulations.

A regional climate model for northern Europe: model description and results from the downscaling of two GCM control simulations

Science.gov (United States)

Rummukainen, M.; Räisänen, J.; Bringfelt, B.; Ullerstig, A.; Omstedt, A.; Willén, U.; Hansson, U.; Jones, C.

This work presents a regional climate model, the Rossby Centre regional Atmospheric model (RCA1), recently developed from the High Resolution Limited Area Model (HIRLAM). The changes in the HIRLAM parametrizations, necessary for climate-length integrations, are described. A regional Baltic Sea ocean model and a modeling system for the Nordic inland lake systems have been coupled with RCA1. The coupled system has been used to downscale 10-year time slices from two different general circulation model (GCM) simulations to provide high-resolution regional interpretation of large-scale modeling. A selection of the results from the control runs, i.e. the present-day climate simulations, are presented: large-scale free atmospheric fields, the surface temperature and precipitation results and results for the on-line simulated regional ocean and lake surface climates. The regional model modifies the surface climate description compared to the GCM simulations, but it is also substantially affected by the biases in the GCM simulations. The regional model also improves the representation of the regional ocean and the inland lakes, compared to the GCM results.

A regional climate model for northern Europe: model description and results from the downscaling of two GCM control simulations

Energy Technology Data Exchange (ETDEWEB)

Rummukainen, M.; Raeisaenen, J.; Bringfelt, B.; Ullerstig, A.; Omstedt, A.; Willen, U.; Hansson, U.; Jones, C. [Rossby Centre, Swedish Meteorological and Hydrological Inst., Norrkoeping (Sweden)

2001-03-01

This work presents a regional climate model, the Rossby Centre regional Atmospheric model (RCA1), recently developed from the High Resolution Limited Area Model (HIRLAM). The changes in the HIRLAM parametrizations, necessary for climate-length integrations, are described. A regional Baltic Sea ocean model and a modeling system for the Nordic inland lake systems have been coupled with RCA1. The coupled system has been used to downscale 10-year time slices from two different general circulation model (GCM) simulations to provide high-resolution regional interpretation of large-scale modeling. A selection of the results from the control runs, i.e. the present-day climate simulations, are presented: large-scale free atmospheric fields, the surface temperature and precipitation results and results for the on-line simulated regional ocean and lake surface climates. The regional model modifies the surface climate description compared to the GCM simulations, but it is also substantially affected by the biases in the GCM simulations. The regional model also improves the representation of the regional ocean and the inland lakes, compared to the GCM results. (orig.)

Chemical compatibility screening results of plastic packaging to mixed waste simulants

International Nuclear Information System (INIS)

Nigrey, P.J.; Dickens, T.G.

1995-01-01

We have developed a chemical compatibility program for evaluating transportation packaging components for transporting mixed waste forms. We have performed the first phase of this experimental program to determine the effects of simulant mixed wastes on packaging materials. This effort involved the screening of 10 plastic materials in four liquid mixed waste simulants. The testing protocol involved exposing the respective materials to ∼3 kGy of gamma radiation followed by 14 day exposures to the waste simulants of 60 C. The seal materials or rubbers were tested using VTR (vapor transport rate) measurements while the liner materials were tested using specific gravity as a metric. For these tests, a screening criteria of ∼1 g/m 2 /hr for VTR and a specific gravity change of 10% was used. It was concluded that while all seal materials passed exposure to the aqueous simulant mixed waste, EPDM and SBR had the lowest VTRs. In the chlorinated hydrocarbon simulant mixed waste, only VITON passed the screening tests. In both the simulant scintillation fluid mixed waste and the ketone mixture simulant mixed waste, none of the seal materials met the screening criteria. It is anticipated that those materials with the lowest VTRs will be evaluated in the comprehensive phase of the program. For specific gravity testing of liner materials the data showed that while all materials with the exception of polypropylene passed the screening criteria, Kel-F, HDPE, and XLPE were found to offer the greatest resistance to the combination of radiation and chemicals

Robust de novo pathway enrichment with KeyPathwayMiner 5 [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Nicolas Alcaraz

2016-06-01

Full Text Available Identifying functional modules or novel active pathways, recently termed de novo pathway enrichment, is a computational systems biology challenge that has gained much attention during the last decade. Given a large biological interaction network, KeyPathwayMiner extracts connected subnetworks that are enriched for differentially active entities from a series of molecular profiles encoded as binary indicator matrices. Since interaction networks constantly evolve, an important question is how robust the extracted results are when the network is modified. We enable users to study this effect through several network perturbation techniques and over a range of perturbation degrees. In addition, users may now provide a gold-standard set to determine how enriched extracted pathways are with relevant genes compared to randomized versions of the original network.

Recent electron-cloud simulation results for the main damping rings of the NLC and TESLA linear colliders

International Nuclear Information System (INIS)

Pivi, M.; Raubenheimer, T.O.; Furman, M.A.

2003-01-01

In the beam pipe of the Main Damping Ring (MDR) of the Next Linear Collider (NLC), ionization of residual gases and secondary emission give rise to an electron-cloud which stabilizes to equilibrium after few bunch trains. In this paper, we present recent computer simulation results for the main features of the electron cloud at the NLC and preliminary simulation results for the TESLA main damping rings, obtained with the code POSINST that has been developed at LBNL, and lately in collaboration with SLAC, over the past 7 years. Possible remedies to mitigate the effect are also discussed. We have recently included the possibility to simulate different magnetic field configurations in our code including solenoid, quadrupole, sextupole and wiggler

A Compact Synchronous Cellular Model of Nonlinear Calcium Dynamics: Simulation and FPGA Synthesis Results.

Science.gov (United States)

Soleimani, Hamid; Drakakis, Emmanuel M

2017-06-01

Recent studies have demonstrated that calcium is a widespread intracellular ion that controls a wide range of temporal dynamics in the mammalian body. The simulation and validation of such studies using experimental data would benefit from a fast large scale simulation and modelling tool. This paper presents a compact and fully reconfigurable cellular calcium model capable of mimicking Hopf bifurcation phenomenon and various nonlinear responses of the biological calcium dynamics. The proposed cellular model is synthesized on a digital platform for a single unit and a network model. Hardware synthesis, physical implementation on FPGA, and theoretical analysis confirm that the proposed cellular model can mimic the biological calcium behaviors with considerably low hardware overhead. The approach has the potential to speed up large-scale simulations of slow intracellular dynamics by sharing more cellular units in real-time. To this end, various networks constructed by pipelining 10 k to 40 k cellular calcium units are compared with an equivalent simulation run on a standard PC workstation. Results show that the cellular hardware model is, on average, 83 times faster than the CPU version.

Simple Kinematic Pathway Approach (KPA) to Catchment-scale Travel Time and Water Age Distributions

Science.gov (United States)

Soltani, S. S.; Cvetkovic, V.; Destouni, G.

2017-12-01

The distribution of catchment-scale water travel times is strongly influenced by morphological dispersion and is partitioned between hillslope and larger, regional scales. We explore whether hillslope travel times are predictable using a simple semi-analytical "kinematic pathway approach" (KPA) that accounts for dispersion on two levels of morphological and macro-dispersion. The study gives new insights to shallow (hillslope) and deep (regional) groundwater travel times by comparing numerical simulations of travel time distributions, referred to as "dynamic model", with corresponding KPA computations for three different real catchment case studies in Sweden. KPA uses basic structural and hydrological data to compute transient water travel time (forward mode) and age (backward mode) distributions at the catchment outlet. Longitudinal and morphological dispersion components are reflected in KPA computations by assuming an effective Peclet number and topographically driven pathway length distributions, respectively. Numerical simulations of advective travel times are obtained by means of particle tracking using the fully-integrated flow model MIKE SHE. The comparison of computed cumulative distribution functions of travel times shows significant influence of morphological dispersion and groundwater recharge rate on the compatibility of the "kinematic pathway" and "dynamic" models. Zones of high recharge rate in "dynamic" models are associated with topographically driven groundwater flow paths to adjacent discharge zones, e.g. rivers and lakes, through relatively shallow pathway compartments. These zones exhibit more compatible behavior between "dynamic" and "kinematic pathway" models than the zones of low recharge rate. Interestingly, the travel time distributions of hillslope compartments remain almost unchanged with increasing recharge rates in the "dynamic" models. This robust "dynamic" model behavior suggests that flow path lengths and travel times in shallow

Multistage reaction pathways in detonating high explosives

International Nuclear Information System (INIS)

Li, Ying; Kalia, Rajiv K.; Nakano, Aiichiro; Nomura, Ken-ichi; Vashishta, Priya

2014-01-01

Atomistic mechanisms underlying the reaction time and intermediate reaction products of detonating high explosives far from equilibrium have been elusive. This is because detonation is one of the hardest multiscale physics problems, in which diverse length and time scales play important roles. Here, large spatiotemporal-scale reactive molecular dynamics simulations validated by quantum molecular dynamics simulations reveal a two-stage reaction mechanism during the detonation of cyclotrimethylenetrinitramine crystal. Rapid production of N 2 and H 2 O within ∼10 ps is followed by delayed production of CO molecules beyond ns. We found that further decomposition towards the final products is inhibited by the formation of large metastable carbon- and oxygen-rich clusters with fractal geometry. In addition, we found distinct unimolecular and intermolecular reaction pathways, respectively, for the rapid N 2 and H 2 O productions

Multistage reaction pathways in detonating high explosives

Energy Technology Data Exchange (ETDEWEB)

Li, Ying [Collaboratory for Advanced Computing and Simulations, Department of Physics and Astronomy, Department of Computer Science, and Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California 90089-0242 (United States); Argonne Leadership Computing Facility, Argonne National Laboratory, Argonne, Illinois 60439 (United States); Kalia, Rajiv K.; Nakano, Aiichiro; Nomura, Ken-ichi; Vashishta, Priya [Collaboratory for Advanced Computing and Simulations, Department of Physics and Astronomy, Department of Computer Science, and Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California 90089-0242 (United States)

2014-11-17

Atomistic mechanisms underlying the reaction time and intermediate reaction products of detonating high explosives far from equilibrium have been elusive. This is because detonation is one of the hardest multiscale physics problems, in which diverse length and time scales play important roles. Here, large spatiotemporal-scale reactive molecular dynamics simulations validated by quantum molecular dynamics simulations reveal a two-stage reaction mechanism during the detonation of cyclotrimethylenetrinitramine crystal. Rapid production of N{sub 2} and H{sub 2}O within ∼10 ps is followed by delayed production of CO molecules beyond ns. We found that further decomposition towards the final products is inhibited by the formation of large metastable carbon- and oxygen-rich clusters with fractal geometry. In addition, we found distinct unimolecular and intermolecular reaction pathways, respectively, for the rapid N{sub 2} and H{sub 2}O productions.

A gene expression signature of RAS pathway dependence predicts response to PI3K and RAS pathway inhibitors and expands the population of RAS pathway activated tumors

Directory of Open Access Journals (Sweden)

Paweletz Cloud

2010-06-01

Full Text Available Abstract Background Hyperactivation of the Ras signaling pathway is a driver of many cancers, and RAS pathway activation can predict response to targeted therapies. Therefore, optimal methods for measuring Ras pathway activation are critical. The main focus of our work was to develop a gene expression signature that is predictive of RAS pathway dependence. Methods We used the coherent expression of RAS pathway-related genes across multiple datasets to derive a RAS pathway gene expression signature and generate RAS pathway activation scores in pre-clinical cancer models and human tumors. We then related this signature to KRAS mutation status and drug response data in pre-clinical and clinical datasets. Results The RAS signature score is predictive of KRAS mutation status in lung tumors and cell lines with high (> 90% sensitivity but relatively low (50% specificity due to samples that have apparent RAS pathway activation in the absence of a KRAS mutation. In lung and breast cancer cell line panels, the RAS pathway signature score correlates with pMEK and pERK expression, and predicts resistance to AKT inhibition and sensitivity to MEK inhibition within both KRAS mutant and KRAS wild-type groups. The RAS pathway signature is upregulated in breast cancer cell lines that have acquired resistance to AKT inhibition, and is downregulated by inhibition of MEK. In lung cancer cell lines knockdown of KRAS using siRNA demonstrates that the RAS pathway signature is a better measure of dependence on RAS compared to KRAS mutation status. In human tumors, the RAS pathway signature is elevated in ER negative breast tumors and lung adenocarcinomas, and predicts resistance to cetuximab in metastatic colorectal cancer. Conclusions These data demonstrate that the RAS pathway signature is superior to KRAS mutation status for the prediction of dependence on RAS signaling, can predict response to PI3K and RAS pathway inhibitors, and is likely to have the most clinical

Distributions and climate effects of atmospheric aerosols from the preindustrial era to 2100 along Representative Concentration Pathways (RCPs simulated using the global aerosol model SPRINTARS

Directory of Open Access Journals (Sweden)

T. Takemura

2012-12-01

Full Text Available Global distributions and associated climate effects of atmospheric aerosols were simulated using a global aerosol climate model, SPRINTARS, from 1850 to the present day and projected forward to 2100. Aerosol emission inventories used by the Coupled Model Intercomparison Project Phase 5 (CMIP5 were applied to this study. Scenarios based on the Representative Concentration Pathways (RCPs were used for the future projection. Aerosol loading in the atmosphere has already peaked and is now reducing in Europe and North America. However, in Asia where rapid economic growth is ongoing, aerosol loading is estimated to reach a maximum in the first half of this century. Atmospheric aerosols originating from the burning of biomass have maintained high loadings throughout the 21st century in Africa, according to the RCPs. Evolution of the adjusted forcing by direct and indirect aerosol effects over time generally correspond to the aerosol loading. The probable future pathways of global mean forcing differ based on the aerosol direct effect for different RCPs. Because aerosol forcing will be close to the preindustrial level by the end of the 21st century for all RCPs despite the continuous increases in greenhouse gases, global warming will be accelerated with reduced aerosol negative forcing.

'BioNessie(G) - a grid enabled biochemical networks simulation environment

OpenAIRE

Liu, X; Jiang, J; Ajayi, O; Gu, X; Gilbert, D; Sinnott, R

2008-01-01

The simulation of biochemical networks provides insight and understanding about the underlying biochemical processes and pathways used by cells and organisms. BioNessie is a biochemical network simulator which has been developed at the University of Glasgow. This paper describes the simulator and focuses in particular on how it has been extended to benefit from a wide variety of high performance compute resources across the UK through Grid technologies to support larger scal...

Simulations of ITER disruption and VDE scenarios with TSC and comparison with DINA results

International Nuclear Information System (INIS)

Bandyopadhyay, I.

2008-01-01

Vertical Displacement Events (VDEs) and plasma current disruptions pose one of the major concerns for the lifetime of in-vessel components in ITER, as well as for machine robustness, as large electromagnetic and thermal loads will induced at such events. Hence, accurate modelling of such events is crucial for estimating disruption induced forces. In the past, ITER disruption modelling has been carried out for ITER using the DINA code. However, since predictive simulations of such events depend on a large number of model assumptions, there exists chances of large error bars on the model predictions. As such it is imperative to validate the code results with other models. Towards this objective, we have carried out the VDE and Disruption simulations using the TSC code and the results are compared with the earlier DINA predictions. A detailed electromagnetic model of the ITER vessel, blankets and the first wall components has been created in TSC. In both VDE and disruption cases, the initial plasma is taken as ITER reference scenario 2 end of burn (EOB) specifications with I p = 15 MA, B t = 5 .3 T, e > 8.8 keV, e > = 1.1 x 10 20 m -3 . The plasma current disruption is initiated by dropping the plasma β in 1 msec, so that after the β crash e > = 6 eV, following which the plasma position control is switched off, resulting in a plasma current quench in about 65 msec. On the other hand, in the VDE case, the plasma control is switched off which results in either upward or downward VDE depending on the initial position of the plasma current centroid. In this case the plasma current remains close to 15 MA for a much longer time, about 700 msec in the simulations till the edge safety factor (q) becomes less than 1.5, following which the β is crashed resulting in plasma current quench. Significant differences exist in the DINA and TSC models, for example, even though the plasma current quench rate predicted by the models matches well in till the halo currents start flowing

Estimating stepwise debromination pathways of polybrominated diphenyl ethers with an analogue Markov Chain Monte Carlo algorithm.

Science.gov (United States)

Zou, Yonghong; Christensen, Erik R; Zheng, Wei; Wei, Hua; Li, An

2014-11-01

A stochastic process was developed to simulate the stepwise debromination pathways for polybrominated diphenyl ethers (PBDEs). The stochastic process uses an analogue Markov Chain Monte Carlo (AMCMC) algorithm to generate PBDE debromination profiles. The acceptance or rejection of the randomly drawn stepwise debromination reactions was determined by a maximum likelihood function. The experimental observations at certain time points were used as target profiles; therefore, the stochastic processes are capable of presenting the effects of reaction conditions on the selection of debromination pathways. The application of the model is illustrated by adopting the experimental results of decabromodiphenyl ether (BDE209) in hexane exposed to sunlight. Inferences that were not obvious from experimental data were suggested by model simulations. For example, BDE206 has much higher accumulation at the first 30 min of sunlight exposure. By contrast, model simulation suggests that, BDE206 and BDE207 had comparable yields from BDE209. The reason for the higher BDE206 level is that BDE207 has the highest depletion in producing octa products. Compared to a previous version of the stochastic model based on stochastic reaction sequences (SRS), the AMCMC approach was determined to be more efficient and robust. Due to the feature of only requiring experimental observations as input, the AMCMC model is expected to be applicable to a wide range of PBDE debromination processes, e.g. microbial, photolytic, or joint effects in natural environments. Copyright © 2014 Elsevier Ltd. All rights reserved.

Stochastic Modeling of the Clathrin-dependent and -independent Endocytic Pathways

Science.gov (United States)

Deng, Hua; Dutta, Prashanta; Liu, Jin

2017-11-01

Endocytosis is one of the important processes that bioparticles use to enter the cells. During endocytosis the membrane-bound vesicles are formed by the invagination of plasma membrane as a result of interactions among many proteins and cytoskeletons. The clathrin-mediated endocytosis is one of the most significant form of endocytosis, where the dynamic assembly of clathrin-coated pits play a critical role. While herpes simplex virus-1 has recently shown to infect cell by a novel phagocytosis-like endocytic pathway where actin polymerization may facilitate the viral entry. In this work, we propose a stochastic model for both clathrin-dependent and -independent endocytic pathways based on Monte Carlo simulations. The important roles of clathrin coating and actin cytoskeleton as well as the impact of other biological parameters are studied. Our preliminary results indicate that there exist an intermediate particle size and ligand density that maximize the internalization efficiency. Below a critical size or surface ligand density, it is difficult for the entry of a single particle, which means clustering may needed for more efficient internalization. We also find that lower membrane bending rigidity may help promote the bioparticle entry. Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R01GM122081.

DMPD: Regulatory pathways in inflammation. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 17967718 Regulatory pathways in inflammation. Mantovani A, Garlanda C, Locati M, Ro....html) (.csml) Show Regulatory pathways in inflammation. PubmedID 17967718 Title Regulatory pathways in infl

Estimating pathway-specific contributions to biodegradation in aquifers based on dual isotope analysis: Theoretical analysis and reactive transport simulations

NARCIS (Netherlands)

Centler, F.; Heße, F.; Thullner, M.

2013-01-01

At field sites with varying redox conditions, different redox-specific microbial degradation pathways contribute to total contaminant degradation. The identification of pathway-specific contributions to total contaminant removal is of high practical relevance, yet difficult to achieve with current

CR2-mediated activation of the complement alternative pathway results in formation of membrane attack complexes on human B lymphocytes

DEFF Research Database (Denmark)

Nielsen, C H; Marquart, H V; Prodinger, W M

2001-01-01

of the CR1 binding site with the monoclonal antibody 3D9 also resulted in a minor reduction in MAC deposition, while FE8 and 3D9, in combination, markedly reduced deposition of both C3 fragments (91 +/- 5%) and C9 (95 +/- 3%). The kinetics of C3-fragment and MAC deposition, as well as the dependence of both......Normal human B lymphocytes activate the alternative pathway of complement via complement receptor type 2 (CR2, CD21), that binds hydrolysed C3 (iC3) and thereby promotes the formation of a membrane-bound C3 convertase. We have investigated whether this might lead to the generation of a C5...... convertase and consequent formation of membrane attack complexes (MAC). Deposition of C3 fragments and MAC was assessed on human peripheral B lymphocytes in the presence of 30% autologous serum containing 4.4 mM MgCl2/20 mM EGTA, which abrogates the classical pathway of complement without affecting...

D-Serine exposure resulted in gene expression changes indicative of activation of fibrogenic pathways and down-regulation of energy metabolism and oxidative stress response

International Nuclear Information System (INIS)

Soto, Armando; DelRaso, Nicholas J.; Schlager, John J.; Chan, Victor T.

2008-01-01

Renal toxicity can commonly occur after exposure to xenobiotics, pharmaceutical agents or environmental pollutants. Changes in the gene expression in kidney parenchymal cells that precede and/or accompany renal injury may be hallmark critical events in the onset of pathologic changes of renal functions. Over the last several years, transcriptomic analysis has evolved to enable simultaneous analysis of the expression profiles of tens of thousands of genes in response to various endogenous and exogenous stimuli. In this study, we investigated gene expression changes in the kidney after acute exposure to a nephrotoxin, D-serine, which targets the proximal tubule of the kidney. Male F-344 rats injected intraperitoneally with a single dose of D-serine (5, 20, 50, 200 or 500 mg/kg), and gene expression profiles in the kidney were determined using the Affymetrix RAE230A gene arrays at 96 h post-dosing. D-Serine treatment resulted in the up- and down-regulation of 1158 and 749 genes, respectively, over the entire dose range based on the intersection of the results of t-test, p < 0.01 over two consecutive doses, and ANOVA with Bonferonni correction for multiple testing. Interestingly, both the up-and down-regulated genes show a unified dose response pattern as revealed in the self-organized map clustering analysis using the expression profiles of the 1907 differentially expressed genes as input data. There appears to be minimal changes in the expression level of these genes in the dose range of 5-50 mg/kg, while the most prominent changes were observed at the highest doses tested, i.e. 200 and 500 mg/kg. Pathway analysis of the differentially expressed genes showed perturbation of a large number of biological processes/pathways after D-serine exposure. Among the up-regulated pathways are actin cytoskeleton biogenesis and organization, apoptosis, cell cycle regulation, chromatin assembly, excision repair of damaged DNA, DNA replication and packaging, protein biosynthesis

GEM System: automatic prototyping of cell-wide metabolic pathway models from genomes

Directory of Open Access Journals (Sweden)

Nakayama Yoichi

2006-03-01

Full Text Available Abstract Background Successful realization of a "systems biology" approach to analyzing cells is a grand challenge for our understanding of life. However, current modeling approaches to cell simulation are labor-intensive, manual affairs, and therefore constitute a major bottleneck in the evolution of computational cell biology. Results We developed the Genome-based Modeling (GEM System for the purpose of automatically prototyping simulation models of cell-wide metabolic pathways from genome sequences and other public biological information. Models generated by the GEM System include an entire Escherichia coli metabolism model comprising 968 reactions of 1195 metabolites, achieving 100% coverage when compared with the KEGG database, 92.38% with the EcoCyc database, and 95.06% with iJR904 genome-scale model. Conclusion The GEM System prototypes qualitative models to reduce the labor-intensive tasks required for systems biology research. Models of over 90 bacterial genomes are available at our web site.

Caution: Precision Error in Blade Alignment Results in Faulty Unsteady CFD Simulation

Science.gov (United States)

Lewis, Bryan; Cimbala, John; Wouden, Alex

2012-11-01

Turbomachinery components experience unsteady loads at several frequencies. The rotor frequency corresponds to the time for one rotor blade to rotate between two stator vanes, and is normally dominant for rotor torque oscillations. The guide vane frequency corresponds to the time for two rotor blades to pass by one guide vane. The machine frequency corresponds to the machine RPM. Oscillations at the machine frequency are always present due to minor blade misalignments and imperfections resulting from manufacturing defects. However, machine frequency oscillations should not be present in CFD simulations if the mesh is free of both blade misalignment and surface imperfections. The flow through a Francis hydroturbine was modeled with unsteady Reynolds-Averaged Navier-Stokes (URANS) CFD simulations and a dynamic rotating grid. Spectral analysis of the unsteady torque on the rotor blades revealed a large component at the machine frequency. Close examination showed that one blade was displaced by 0 .0001° due to round-off errors during mesh generation. A second mesh without blade misalignment was then created. Subsequently, large machine frequency oscillations were not observed for this mesh. These results highlight the effect of minor geometry imperfections on CFD solutions. This research was supported by a grant from the DoE and a National Defense Science and Engineering Graduate Fellowship.

Synthetic Metabolic Pathways

DEFF Research Database (Denmark)

topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Synthetic Metabolic Pathways: Methods and Protocols aims to ensure successful results in the further study...

Predicting protein folding pathways at the mesoscopic level based on native interactions between secondary structure elements

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Sze Sing-Hoi

2008-07-01

Full Text Available Abstract Background Since experimental determination of protein folding pathways remains difficult, computational techniques are often used to simulate protein folding. Most current techniques to predict protein folding pathways are computationally intensive and are suitable only for small proteins. Results By assuming that the native structure of a protein is known and representing each intermediate conformation as a collection of fully folded structures in which each of them contains a set of interacting secondary structure elements, we show that it is possible to significantly reduce the conformation space while still being able to predict the most energetically favorable folding pathway of large proteins with hundreds of residues at the mesoscopic level, including the pig muscle phosphoglycerate kinase with 416 residues. The model is detailed enough to distinguish between different folding pathways of structurally very similar proteins, including the streptococcal protein G and the peptostreptococcal protein L. The model is also able to recognize the differences between the folding pathways of protein G and its two structurally similar variants NuG1 and NuG2, which are even harder to distinguish. We show that this strategy can produce accurate predictions on many other proteins with experimentally determined intermediate folding states. Conclusion Our technique is efficient enough to predict folding pathways for both large and small proteins at the mesoscopic level. Such a strategy is often the only feasible choice for large proteins. A software program implementing this strategy (SSFold is available at http://faculty.cs.tamu.edu/shsze/ssfold.

Neural Networks Simulation of the Transport of Contaminants in Groundwater

Directory of Open Access Journals (Sweden)

Enrico Zio

2009-12-01

Full Text Available The performance assessment of an engineered solution for the disposal of radioactive wastes is based on mathematical models of the disposal system response to predefined accidental scenarios, within a probabilistic approach to account for the involved uncertainties. As the most significant potential pathway for the return of radionuclides to the biosphere is groundwater flow, intensive computational efforts are devoted to simulating the behaviour of the groundwater system surrounding the waste deposit, for different values of its hydrogeological parameters and for different evolution scenarios. In this paper, multilayered neural networks are trained to simulate the transport of contaminants in monodimensional and bidimensional aquifers. The results obtained in two case studies indicate that the approximation errors are within the uncertainties which characterize the input data.

Simulated physiological stretch increases expression of extracellular matrix proteins in human bladder smooth muscle cells via integrin α4/αv-FAK-ERK1/2 signaling pathway.

Science.gov (United States)

Chen, Shulian; Peng, Chuandu; Wei, Xin; Luo, Deyi; Lin, Yifei; Yang, Tongxin; Jin, Xi; Gong, Lina; Li, Hong; Wang, Kunjie

2017-08-01

To investigate the effect of simulated physiological stretch on the expression of extracellular matrix (ECM) proteins and the role of integrin α4/αv, focal adhesion kinase (FAK), extracellular regulated protein kinases 1/2 (ERK1/2) in the stretch-induced ECM protein expression of human bladder smooth muscle cells (HBSMCs). HBSMCs were seeded onto silicone membrane and subjected to simulated physiological stretch at the range of 5, 10, and 15% elongation. Expression of primary ECM proteins in HBSMCs was analyzed by real-time polymerase chain reaction and Western blot. Specificity of the FAK and ERK1/2 was determined by Western blot with FAK inhibitor and ERK1/2 inhibitor (PD98059). Specificity of integrin α4 and integrin αv was determined with small interfering ribonucleic acid (siRNA) transfection. The expression of collagen I (Col1), collagen III (Col3), and fibronectin (Fn) was increased significantly under the simulated physiological stretch of 10 and 15%. Integrin α4 and αv, FAK, ERK1/2 were activated by 10% simulated physiological stretch compared with the static condition. Pretreatment of ERK1/2 inhibitor, FAK inhibitor, integrin α4 siRNA, or integrin αv siRNA reduced the stretch-induced expression of ECM proteins. And FAK inhibitor decreased the stretch-induced ERK1/2 activity and ECM protein expression. Integrin α4 siRNA or integrin αv siRNA inhibited the stretch-induced activity of FAK. Simulated physiological stretch increases the expression of ECM proteins in HBSMCs, and integrin α4/αv-FAK-ERK1/2 signaling pathway partly modulates the mechano-transducing process.

Low-cost autonomous orbit control about Mars: Initial simulation results

Science.gov (United States)

Dawson, S. D.; Early, L. W.; Potterveld, C. W.; Königsmann, H. J.

1999-11-01

Interest in studying the possibility of extraterrestrial life has led to the re-emergence of the Red Planet as a major target of planetary exploration. Currently proposed missions in the post-2000 period are routinely calling for rendezvous with ascent craft, long-term orbiting of, and sample-return from Mars. Such missions would benefit greatly from autonomous orbit control as a means to reduce operations costs and enable contact with Mars ground stations out of view of the Earth. This paper present results from initial simulations of autonomously controlled orbits around Mars, and points out possible uses of the technology and areas of routine Mars operations where such cost-conscious and robust autonomy could prove most effective. These simulations have validated the approach and control philosophies used in the development of this autonomous orbit controller. Future work will refine the controller, accounting for systematic and random errors in the navigation of the spacecraft from the sensor suite, and will produce prototype flight code for inclusion on future missions. A modified version of Microcosm's commercially available High Precision Orbit Propagator (HPOP) was used in the preparation of these results due to its high accuracy and speed of operation. Control laws were developed to allow an autonomously controlled spacecraft to continuously control to a pre-defined orbit about Mars with near-optimal propellant usage. The control laws were implemented as an adjunct to HPOP. The GSFC-produced 50 × 50 field model of the Martian gravitational potential was used in all simulations. The Martian atmospheric drag was modeled using an exponentially decaying atmosphere based on data from the Mars-GRAM NASA Ames model. It is hoped that the simple atmosphere model that was implemented can be significantly improved in the future so as to approach the fidelity of the Mars-GRAM model in its predictions of atmospheric density at orbital altitudes. Such additional work

Comparison of simulation and experimental results for a model aqueous tert-butanol solution

Science.gov (United States)

Overduin, S. D.; Patey, G. N.

2017-07-01

Molecular dynamics simulations are used to investigate the behavior of aqueous tert-butanol (TBA) solutions for a range of temperatures, using the CHARMM generalized force field (CGenFF) to model TBA and the TIP4P/2005 or TIP4P-Ew water model. Simulation results for the density, isothermal compressibility, constant pressure heat capacity, and self-diffusion coefficients are in good accord with experimental measurements. Agreement with the experiment is particularly good at low TBA concentration, where experiments have revealed anomalies in a number of thermodynamic properties. Importantly, the CGenFF model does not exhibit liquid-liquid demixing at temperatures between 290 and 320 K (for systems of 32 000 molecules), in contrast with the situation for several other common TBA models [R. Gupta and G. N. Patey, J. Chem. Phys. 137, 034509 (2012)]. However, whereas real water and TBA are miscible at all temperatures where the liquid is stable, we observe some evidence of demixing at 340 K and above. To evaluate the structural properties at low concentrations, we compare with both neutron scattering and recent spectroscopic measurements. This reveals that while the CGenFF model is a definite improvement over other models that have been considered, the TBA molecules still exhibit a tendency to associate at low concentrations that is somewhat stronger than that indicated by experiments. Finally, we discuss the range and decay times of the long-range correlations, providing an indication of the system size and simulation times that are necessary in order to obtain reliable results for certain properties.

Experimental and computer simulation results of the spot welding process using SORPAS software

International Nuclear Information System (INIS)

Al-Jader, M A; Cullen, J D; Athi, N; Al-Shamma'a, A I

2009-01-01

The highly competitive nature of the automotive industry drives demand for improvements and increased precision engineering in resistance spot welding. Currently there are about 4300 weld points on the average steel vehicle. Current industrial monitoring systems check the quality of the nugget after processing 15 cars, once every two weeks. The nuggets are examined off line using a destructive process, which takes approximately 10 days to complete causing a long delay in the production process. This paper presents a simulation of the spot welding growth curves, along with a comparison to growth curves performed on an industrial spot welding machine. The correlation of experimental results shows that SORPAS simulations can be used as an off line measurement to reduce factory energy usage. The first section in your paper

Hydration status regulates sodium flux and inflammatory pathways through epithelial sodium channel (ENaC) in the skin.

Science.gov (United States)

Xu, Wei; Hong, Seok Jong; Zeitchek, Michael; Cooper, Garry; Jia, Shengxian; Xie, Ping; Qureshi, Hannan A; Zhong, Aimei; Porterfield, Marshall D; Galiano, Robert D; Surmeier, D James; Mustoe, Thomas A

2015-03-01

Although it is known that the inflammatory response that results from disruption of epithelial barrier function after injury results in excessive scarring, the upstream signals remain unknown. It has also been observed that epithelial disruption results in reduced hydration status and that the use of occlusive dressings that prevent water loss from wounds decreases scar formation. We hypothesized that hydration status changes sodium homeostasis and induces sodium flux in keratinocytes, which result in activation of pathways responsible for keratinocyte-fibroblast signaling and ultimately lead to activation of fibroblasts. Here, we demonstrate that perturbations in epithelial barrier function lead to increased sodium flux in keratinocytes. We identified that sodium flux in keratinocytes is mediated by epithelial sodium channels (ENaCs) and causes increased secretion of proinflammatory cytokines, which activate fibroblast via the cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2) pathway. Similar changes in signal transduction and sodium flux occur by increased sodium concentration, which simulates reduced hydration, in the media in epithelial cultures or human ex vivo skin cultures. Blockade of ENaC, prostaglandin synthesis, or PGE2 receptors all reduce markers of fibroblast activation and collagen synthesis. In addition, employing a validated in vivo excessive scar model in the rabbit ear, we demonstrate that utilization of either an ENaC blocker or a COX-2 inhibitor results in a marked reduction in scarring. Other experiments demonstrate that the activation of COX-2 in response to increased sodium flux is mediated through the PIK3/Akt pathway. Our results indicate that ENaC responds to small changes in sodium concentration with inflammatory mediators and suggest that the ENaC pathway is a potential target for a strategy to prevent fibrosis.

Comparing Results of SPH/N-body Impact Simulations Using Both Solid and Rubble-pile Target Asteroids

Science.gov (United States)

Durda, Daniel D.; Bottke, W. F.; Enke, B. L.; Nesvorný, D.; Asphaug, E.; Richardson, D. C.

2006-09-01

We have been investigating the properties of satellites and the morphology of size-frequency distributions (SFDs) resulting from a suite of 160 SPH/N-body simulations of impacts into 100-km diameter parent asteroids (Durda et al. 2004, Icarus 170, 243-257; Durda et al. 2006, Icarus, in press). These simulations have produced many valuable insights into the outcomes of cratering and disruptive impacts but were limited to monolithic basalt targets. As a natural consequence of collisional evolution, however, many asteroids have undergone a series of battering impacts that likely have left their interiors substantially fractured, if not completely rubblized. In light of this, we have re-mapped the matrix of simulations using rubble-pile target objects. We constructed the rubble-pile targets by filling the interior of the 100-km diameter spherical shell (the target envelope) with randomly sized solid spheres in mutual contact. We then assigned full damage (which reduces tensile and shear stresses to zero) to SPH particles in the contacts between the components; the remaining volume is void space. The internal spherical components have a power-law distribution of sizes simulating fragments of a pre-shattered parent object. First-look analysis of the rubble-pile results indicate some general similarities to the simulations with the monolithic targets (e.g., similar trends in the number of small, gravitationally bound satellite systems as a function of impact conditions) and some significant differences (e.g., size of largest remnants and smaller debris affecting size frequency distributions of resulting families). We will report details of a more thorough analysis and the implications for collisional models of the main asteroid belt. This work is supported by the National Science Foundation, grant number AST0407045.

Simulation of the oxidation pathway on Si(100) using high-resolution EELS

Energy Technology Data Exchange (ETDEWEB)

Hogan, Conor [Consiglio Nazionale delle Ricerche, Istituto di Struttura della Materia (CNR-ISM), Rome (Italy); Dipartimento di Fisica, Universita di Roma ' ' Tor Vergata' ' , Roma (Italy); European Theoretical Spectroscopy Facility (ETSF), Roma (Italy); Caramella, Lucia; Onida, Giovanni [Dipartimento di Fisica, Universita degli Studi di Milano (Italy); European Theoretical Spectroscopy Facility (ETSF), Milano (Italy)

2012-06-15

We compute high-resolution electron energy loss spectra (HREELS) of possible structural motifs that form during the dynamic oxidation process on Si(100), including the important metastable precursor silanone and an adjacent-dimer bridge (ADB) structure that may seed oxide formation. Spectroscopic fingerprints of single site, silanone, and ''seed'' structures are identified and related to changes in the surface bandstructure of the clean surface. Incorporation of oxygen into the silicon lattice through adsorption and dissociation of water is also examined. Results are compared to available HREELS spectra and surface optical data, which are closely related. Our simulations confirm that HREELS offers complementary evidence to surface optical spectroscopy, and show that its high sensitivity allows it to distinguish between energetically and structurally similar oxidation models. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Results from pion calibration runs for the H1 liquid argon calorimeter and comparisons with simulations

International Nuclear Information System (INIS)

Andrieu, B.; Ban, J.; Barrelet, E.; Bergstein, H.; Bernardi, G.; Besancon, M.; Binder, E.; Blume, H.; Borras, K.; Boudry, V.; Brasse, F.; Braunschweig, W.; Brisson, V.; Campbell, A.J.; Carli, T.; Colombo, M.; Coutures, C.; Cozzika, G.; David, M.; Delcourt, B.; DelBuono, L.; Devel, M.; Dingus, P.; Drescher, A.; Duboc, J.; Duenger, O.; Ebbinghaus, R.; Egli, S.; Ellis, N.N.; Feltesse, J.; Feng, Y.; Ferrarotto, F.; Flauger, W.; Flieser, M.; Gamerdinger, K.; Gayler, J.; Godfrey, L.; Goerlich, L.; Goldberg, M.; Graessler, R.; Greenshaw, T.; Greif, H.; Haguenauer, M.; Hajduk, L.; Hamon, O.; Hartz, P.; Haustein, V.; Haydar, R.; Hildesheim, W.; Huot, N.; Jabiol, M.A.; Jacholkowska, A.; Jaffre, M.; Jung, H.; Just, F.; Kiesling, C.; Kirchhoff, T.; Kole, F.; Korbel, V.; Korn, M.; Krasny, W.; Kubenka, J.P.; Kuester, H.; Kurzhoefer, J.; Kuznik, B.; Lander, R.; Laporte, J.F.; Lenhardt, U.; Loch, P.; Lueers, D.; Marks, J.; Martyniak, J.; Merz, T.; Naroska, B.; Nau, A.; Nguyen, H.K.; Niebergall, F.; Oberlack, H.; Obrock, U.; Ould-Saada, F.; Pascaud, C.; Pyo, H.B.; Rauschnabel, K.; Ribarics, P.; Rietz, M.; Royon, C.; Rusinov, V.; Sahlmann, N.; Sanchez, E.; Schacht, P.; Schleper, P.; Schlippe, W. von; Schmidt, C.; Schmidt, D.; Shekelyan, V.; Shooshtari, H.; Sirois, Y.; Staroba, P.; Steenbock, M.; Steiner, H.; Stella, B.; Straumann, U.; Turnau, J.; Tutas, J.; Urban, L.; Vallee, C.; Vecko, M.; Verrecchia, P.; Villet, G.; Vogel, E.; Wagener, A.; Wegener, D.; Wegner, A.; Wellisch, H.P.; Yiou, T.P.; Zacek, J.; Zeitnitz, Ch.; Zomer, F.

1993-01-01

We present results on calibration runs performed with pions at CERN SPS for different modules of the H1 liquid argon calorimeter which consists of an electromagnetic section with lead absorbers and a hadronic section with steel absorbers. The data cover an energy range from 3.7 to 205 GeV. Detailed comparisons of the data and simulation with GHEISHA 8 in the framework of GEANT 3.14 are presented. The measured pion induced shower profiles are well described by the simulation. The total signal of pions on an energy scale determined from electron measurements is reproduced to better than 3% in various module configurations. After application of weighting functions, determined from Monte Carlo data and needed to achieve compensation, the reconstructed measured energies agree with simulation to about 3%. The energies of hadronic showers are reconstructed with a resolution of about 50%/√E + 2%. This result is achieved by inclusion of signals from an iron streamer tube tail catcher behind the liquid argon stacks. (orig.)

Do consumers prefer foods with nutrition and health claims? Results of a purchase simulation

DEFF Research Database (Denmark)

Aschemann-Witzel, Jessica; Hamm, U.

2010-01-01

This contribution reports findings of a close-to-realistic purchase simulation for foods labelled with nutrition and health claims. The results show that products with a claim are clearly preferred, but that the determining factors of choice differ between the food categories. Choice was positively...

AUTOMATIC INTERPRETATION OF HIGH RESOLUTION SAR IMAGES: FIRST RESULTS OF SAR IMAGE SIMULATION FOR SINGLE BUILDINGS

Directory of Open Access Journals (Sweden)

J. Tao

2012-09-01

Full Text Available Due to the all-weather data acquisition capabilities, high resolution space borne Synthetic Aperture Radar (SAR plays an important role in remote sensing applications like change detection. However, because of the complex geometric mapping of buildings in urban areas, SAR images are often hard to interpret. SAR simulation techniques ease the visual interpretation of SAR images, while fully automatic interpretation is still a challenge. This paper presents a method for supporting the interpretation of high resolution SAR images with simulated radar images using a LiDAR digital surface model (DSM. Line features are extracted from the simulated and real SAR images and used for matching. A single building model is generated from the DSM and used for building recognition in the SAR image. An application for the concept is presented for the city centre of Munich where the comparison of the simulation to the TerraSAR-X data shows a good similarity. Based on the result of simulation and matching, special features (e.g. like double bounce lines, shadow areas etc. can be automatically indicated in SAR image.

An Automated Pipeline for Engineering Many-Enzyme Pathways: Computational Sequence Design, Pathway Expression-Flux Mapping, and Scalable Pathway Optimization.

Science.gov (United States)

Halper, Sean M; Cetnar, Daniel P; Salis, Howard M

2018-01-01

Engineering many-enzyme metabolic pathways suffers from the design curse of dimensionality. There are an astronomical number of synonymous DNA sequence choices, though relatively few will express an evolutionary robust, maximally productive pathway without metabolic bottlenecks. To solve this challenge, we have developed an integrated, automated computational-experimental pipeline that identifies a pathway's optimal DNA sequence without high-throughput screening or many cycles of design-build-test. The first step applies our Operon Calculator algorithm to design a host-specific evolutionary robust bacterial operon sequence with maximally tunable enzyme expression levels. The second step applies our RBS Library Calculator algorithm to systematically vary enzyme expression levels with the smallest-sized library. After characterizing a small number of constructed pathway variants, measurements are supplied to our Pathway Map Calculator algorithm, which then parameterizes a kinetic metabolic model that ultimately predicts the pathway's optimal enzyme expression levels and DNA sequences. Altogether, our algorithms provide the ability to efficiently map the pathway's sequence-expression-activity space and predict DNA sequences with desired metabolic fluxes. Here, we provide a step-by-step guide to applying the Pathway Optimization Pipeline on a desired multi-enzyme pathway in a bacterial host.

Pathways of topological rank analysis (PoTRA): a novel method to detect pathways involved in hepatocellular carcinoma.

Science.gov (United States)

Li, Chaoxing; Liu, Li; Dinu, Valentin

2018-01-01

Complex diseases such as cancer are usually the result of a combination of environmental factors and one or several biological pathways consisting of sets of genes. Each biological pathway exerts its function by delivering signaling through the gene network. Theoretically, a pathway is supposed to have a robust topological structure under normal physiological conditions. However, the pathway's topological structure could be altered under some pathological condition. It is well known that a normal biological network includes a small number of well-connected hub nodes and a large number of nodes that are non-hubs. In addition, it is reported that the loss of connectivity is a common topological trait of cancer networks, which is an assumption of our method. Hence, from normal to cancer, the process of the network losing connectivity might be the process of disrupting the structure of the network, namely, the number of hub genes might be altered in cancer compared to that in normal or the distribution of topological ranks of genes might be altered. Based on this, we propose a new PageRank-based method called Pathways of Topological Rank Analysis (PoTRA) to detect pathways involved in cancer. We use PageRank to measure the relative topological ranks of genes in each biological pathway, then select hub genes for each pathway, and use Fisher's exact test to test if the number of hub genes in each pathway is altered from normal to cancer. Alternatively, if the distribution of topological ranks of gene in a pathway is altered between normal and cancer, this pathway might also be involved in cancer. Hence, we use the Kolmogorov-Smirnov test to detect pathways that have an altered distribution of topological ranks of genes between two phenotypes. We apply PoTRA to study hepatocellular carcinoma (HCC) and several subtypes of HCC. Very interestingly, we discover that all significant pathways in HCC are cancer-associated generally, while several significant pathways in subtypes

Pathway Interaction Network Analysis Identifies Dysregulated Pathways in Human Monocytes Infected by Listeria monocytogenes

Directory of Open Access Journals (Sweden)

Wufeng Fan

2017-01-01

Full Text Available In our study, we aimed to extract dysregulated pathways in human monocytes infected by Listeria monocytogenes (LM based on pathway interaction network (PIN which presented the functional dependency between pathways. After genes were aligned to the pathways, principal component analysis (PCA was used to calculate the pathway activity for each pathway, followed by detecting seed pathway. A PIN was constructed based on gene expression profile, protein-protein interactions (PPIs, and cellular pathways. Identifying dysregulated pathways from the PIN was performed relying on seed pathway and classification accuracy. To evaluate whether the PIN method was feasible or not, we compared the introduced method with standard network centrality measures. The pathway of RNA polymerase II pretranscription events was selected as the seed pathway. Taking this seed pathway as start, one pathway set (9 dysregulated pathways with AUC score of 1.00 was identified. Among the 5 hub pathways obtained using standard network centrality measures, 4 pathways were the common ones between the two methods. RNA polymerase II transcription and DNA replication owned a higher number of pathway genes and DEGs. These dysregulated pathways work together to influence the progression of LM infection, and they will be available as biomarkers to diagnose LM infection.

Virtual simulation in clinical practice at the Saint-Andre hospital

International Nuclear Information System (INIS)

Trouette, R.; Causse, N.; Maire, J.P.; Dahan, O.; Recaldini, L.; Demeaux, H.; Baumont, G.; Caudry, M.; Houlard, J.P.

1997-01-01

The purpose of this article is a prospective evaluation of a virtual simulation technique. In our department, virtual simulation has become a routine technique of treatment planning for deep-seated tumors. This technique remains time consuming for radiation oncologists: about 2 hours. but it stimulates reflexion on anatomy, tumor extension pathways, target volumes, and is becoming an excellent pedagogical tool. (author)

Thermal-Hydraulic Results for the Boiling Water Reactor Dry Cask Simulator.

Energy Technology Data Exchange (ETDEWEB)

Durbin, Samuel [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Lindgren, Eric R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2017-09-01

The thermal performance of commercial nuclear spent fuel dry storage casks is evaluated through detailed numerical analysis. These modeling efforts are completed by the vendor to demonstrate performance and regulatory compliance. The calculations are then independently verified by the Nuclear Regulatory Commission (NRC). Carefully measured data sets generated from testing of full sized casks or smaller cask analogs are widely recognized as vital for validating these models. Recent advances in dry storage cask designs have significantly increased the maximum thermal load allowed in a cask in part by increasing the efficiency of internal conduction pathways and by increasing the internal convection through greater canister helium pressure. These same canistered cask systems rely on ventilation between the canister and the overpack to convect heat away from the canister to the environment for both aboveground and belowground configurations. While several testing programs have been previously conducted, these earlier validation attempts did not capture the effects of elevated helium pressures or accurately portray the external convection of aboveground and belowground canistered dry cask systems. The purpose of this investigation was to produce validation-quality data that can be used to test the validity of the modeling presently used to determine cladding temperatures in modern vertical dry casks. These cladding temperatures are critical to evaluate cladding integrity throughout the storage cycle. To produce these data sets under well-controlled boundary conditions, the dry cask simulator (DCS) was built to study the thermal-hydraulic response of fuel under a variety of heat loads, internal vessel pressures, and external configurations. An existing electrically heated but otherwise prototypic BWR Incoloy-clad test assembly was deployed inside of a representative storage basket and cylindrical pressure vessel that represents a vertical canister system. The symmetric

Molecular Simulation Results on Charged Carbon Nanotube Forest-Based Supercapacitors.

Science.gov (United States)

Muralidharan, Ajay; Pratt, Lawrence R; Hoffman, Gary G; Chaudhari, Mangesh I; Rempe, Susan B

2018-05-03

Electrochemical double-layer capacitances of charged carbon nanotube (CNT) forests with tetraethyl ammonium tetrafluoro borate electrolyte in propylene carbonate are studied on the basis of molecular dynamics simulation. Direct molecular simulation of the filling of pore spaces of the forest is feasible even with realistic, small CNT spacings. The numerical solution of the Poisson equation based on the extracted average charge densities then yields a regular experimental dependence on the width of the pore spaces, in contrast to the anomalous pattern observed in experiments on other carbon materials and also in simulations on planar slot-like pores. The capacitances obtained have realistic magnitudes but are insensitive to electric potential differences between the electrodes in this model. This agrees with previous calculations on CNT forest supercapacitors, but not with experiments which have suggested electrochemical doping for these systems. Those phenomena remain for further theory/modeling work. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rainout assessment: the ACRA system and summaries of simulation results

International Nuclear Information System (INIS)

Watson, C.W.; Barr, S.; Allenson, R.E.

1977-09-01

A generalized, three-dimensional, integrated computer code system was developed to estimate collateral-damage threats from precipitation-scavenging (rainout) of airborne debris-clouds from defensive tactical nuclear engagements. This code system, called ACRA for Atmospheric-Contaminant Rainout Assessment, is based on Monte Carlo statistical simulation methods that allow realistic, unbiased simulations of probabilistic storm, wind, and precipitation fields that determine actual magnitudes and probabilities of rainout threats. Detailed models (or data bases) are included for synoptic-scale storm and wind fields; debris transport and dispersal (with the roles of complex flow fields, time-dependent diffusion, and multidimensional shear effects accounted for automatically); microscopic debris-precipitation interactions and scavenging probabilities; air-to-ground debris transport; local demographic features, for assessing actual threats to populations; and nonlinear effects accumulations from multishot scenarios. We simulated several hundred representative shots for West European scenarios and climates to study single-shot and multishot sensitivities of rainout effects to variations in pertinent physical variables

Magnetoencephalographic accuracy profiles for the detection of auditory pathway sources.

Science.gov (United States)

Bauer, Martin; Trahms, Lutz; Sander, Tilmann

2015-04-01

The detection limits for cortical and brain stem sources associated with the auditory pathway are examined in order to analyse brain responses at the limits of the audible frequency range. The results obtained from this study are also relevant to other issues of auditory brain research. A complementary approach consisting of recordings of magnetoencephalographic (MEG) data and simulations of magnetic field distributions is presented in this work. A biomagnetic phantom consisting of a spherical volume filled with a saline solution and four current dipoles is built. The magnetic fields outside of the phantom generated by the current dipoles are then measured for a range of applied electric dipole moments with a planar multichannel SQUID magnetometer device and a helmet MEG gradiometer device. The inclusion of a magnetometer system is expected to be more sensitive to brain stem sources compared with a gradiometer system. The same electrical and geometrical configuration is simulated in a forward calculation. From both the measured and the simulated data, the dipole positions are estimated using an inverse calculation. Results are obtained for the reconstruction accuracy as a function of applied electric dipole moment and depth of the current dipole. We found that both systems can localize cortical and subcortical sources at physiological dipole strength even for brain stem sources. Further, we found that a planar magnetometer system is more suitable if the position of the brain source can be restricted in a limited region of the brain. If this is not the case, a helmet-shaped sensor system offers more accurate source estimation.

A new approach to model-based simulation of disordered polymer blend solar cells

Energy Technology Data Exchange (ETDEWEB)

Stenzel, Ole; Thiedmann, Ralf; Schmidt, Volker [Institute of Stochastics, Ulm University, Ulm, 89069 (Germany); Koster, L.J.A. [Molecular Electronics, Zernike Institute for Advanced Materials, University of Groningen, Groningen, 9747 AG (Netherlands); Oosterhout, Stefan D.; Janssen, Rene A.J. [Chemical Engineering and Chemistry, Molecular Materials and Nanosystems, Eindhoven University of Technology, Eindhoven, 5600 MB (Netherlands)

2012-03-21

The 3D nanomorphology of blends of two different (organic and inorganic) solid phases as used in bulk heterojunction solar cells is described by a spatial stochastic model. The model is fitted to 3D image data describing the photoactive layer of poly(3-hexylthiophene)-ZnO (P3HT-ZnO) solar cells fabricated with varying spin-coating velocities. A scenario analysis is performed where 3D morphologies are simulated for different spin-coating velocities to elucidate the correlation between processing conditions, morphology, and efficiency of hybrid P3HT-ZnO solar cells. The simulated morphologies are analyzed quantitatively in terms of structural and physical characteristics. It is found that there is a tendency for the morphology to coarsen with increasing spin-coating velocity, creating larger domains of P3HT and ZnO. The impact of the spin-coating velocity on the connectivity of the morphology and the existence of percolation pathways for charge carriers in the resulting films appears insignificant, but the quality of percolation pathways, considering the charge carrier mobility, strongly varies with the spin-coating velocity, especially in the ZnO phase. Also, the exciton quenching efficiency decreases significantly for films deposited at large spin-coating velocities. The stochastic simulation model investigated is compared to a simulated annealing model and is found to provide a better fit to the experimental data. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Final report on the Pathway Analysis Task

International Nuclear Information System (INIS)

Whicker, F.W.; Kirchner, T.B.

1993-04-01

The Pathway Analysis Task constituted one of several multi-laboratory efforts to estimate radiation doses to people, considering all important pathways of exposure, from the testing of nuclear devices at the Nevada Test Site (NTS). The primary goal of the Pathway Analysis Task was to predict radionuclide ingestion by residents of Utah, Nevada, and portions of seven other adjoining western states following radioactive fallout deposition from individual events at the NTS. This report provides comprehensive documentation of the activities and accomplishments of Colorado State University's Pathway Analysis Task during the entire period of support (1979--91). The history of the project will be summarized, indicating the principal dates and milestones, personnel involved, subcontractors, and budget information. Accomplishments, both primary and auxiliary, will be summarized with general results rather than technical details being emphasized. This will also serve as a guide to the reports and open literature publications produced, where the methodological details and specific results are documented. Selected examples of results on internal dose estimates are provided in this report because the data have not been published elsewhere

Final report on the Pathway Analysis Task

Energy Technology Data Exchange (ETDEWEB)

Whicker, F.W.; Kirchner, T.B. [Colorado State Univ., Fort Collins, CO (United States)

1993-04-01

The Pathway Analysis Task constituted one of several multi-laboratory efforts to estimate radiation doses to people, considering all important pathways of exposure, from the testing of nuclear devices at the Nevada Test Site (NTS). The primary goal of the Pathway Analysis Task was to predict radionuclide ingestion by residents of Utah, Nevada, and portions of seven other adjoining western states following radioactive fallout deposition from individual events at the NTS. This report provides comprehensive documentation of the activities and accomplishments of Colorado State University`s Pathway Analysis Task during the entire period of support (1979--91). The history of the project will be summarized, indicating the principal dates and milestones, personnel involved, subcontractors, and budget information. Accomplishments, both primary and auxiliary, will be summarized with general results rather than technical details being emphasized. This will also serve as a guide to the reports and open literature publications produced, where the methodological details and specific results are documented. Selected examples of results on internal dose estimates are provided in this report because the data have not been published elsewhere.

A limited assessment of the ASEP human reliability analysis procedure using simulator examination results

International Nuclear Information System (INIS)

Gore, B.R.; Dukelow, J.S. Jr.; Mitts, T.M.; Nicholson, W.L.

1995-10-01

This report presents a limited assessment of the conservatism of the Accident Sequence Evaluation Program (ASEP) human reliability analysis (HRA) procedure described in NUREG/CR-4772. In particular, the, ASEP post-accident, post-diagnosis, nominal HRA procedure is assessed within the context of an individual's performance of critical tasks on the simulator portion of requalification examinations administered to nuclear power plant operators. An assessment of the degree to which operator perforn:Lance during simulator examinations is an accurate reflection of operator performance during actual accident conditions was outside the scope of work for this project; therefore, no direct inference can be made from this report about such performance. The data for this study are derived from simulator examination reports from the NRC requalification examination cycle. A total of 4071 critical tasks were identified, of which 45 had been failed. The ASEP procedure was used to estimate human error probability (HEP) values for critical tasks, and the HEP results were compared with the failure rates observed in the examinations. The ASEP procedure was applied by PNL operator license examiners who supplemented the limited information in the examination reports with expert judgment based upon their extensive simulator examination experience. ASEP analyses were performed for a sample of 162 critical tasks selected randomly from the 4071, and the results were used to characterize the entire population. ASEP analyses were also performed for all of the 45 failed critical tasks. Two tests were performed to assess the bias of the ASEP HEPs compared with the data from the requalification examinations. The first compared the average of the ASEP HEP values with the fraction of the population actually failed and it found a statistically significant factor of two bias on the average

PathNet: a tool for pathway analysis using topological information

Directory of Open Access Journals (Sweden)

Dutta Bhaskar

2012-09-01

Full Text Available Abstract Background Identification of canonical pathways through enrichment of differentially expressed genes in a given pathway is a widely used method for interpreting gene lists generated from high-throughput experimental studies. However, most algorithms treat pathways as sets of genes, disregarding any inter- and intra-pathway connectivity information, and do not provide insights beyond identifying lists of pathways. Results We developed an algorithm (PathNet that utilizes the connectivity information in canonical pathway descriptions to help identify study-relevant pathways and characterize non-obvious dependencies and connections among pathways using gene expression data. PathNet considers both the differential expression of genes and their pathway neighbors to strengthen the evidence that a pathway is implicated in the biological conditions characterizing the experiment. As an adjunct to this analysis, PathNet uses the connectivity of the differentially expressed genes among all pathways to score pathway contextual associations and statistically identify biological relations among pathways. In this study, we used PathNet to identify biologically relevant results in two Alzheimer’s disease microarray datasets, and compared its performance with existing methods. Importantly, PathNet identified de-regulation of the ubiquitin-mediated proteolysis pathway as an important component in Alzheimer’s disease progression, despite the absence of this pathway in the standard enrichment analyses. Conclusions PathNet is a novel method for identifying enrichment and association between canonical pathways in the context of gene expression data. It takes into account topological information present in pathways to reveal biological information. PathNet is available as an R workspace image from http://www.bhsai.org/downloads/pathnet/.

N-of-1-pathways MixEnrich: advancing precision medicine via single-subject analysis in discovering dynamic changes of transcriptomes.

Science.gov (United States)

Li, Qike; Schissler, A Grant; Gardeux, Vincent; Achour, Ikbel; Kenost, Colleen; Berghout, Joanne; Li, Haiquan; Zhang, Hao Helen; Lussier, Yves A

2017-05-24

Transcriptome analytic tools are commonly used across patient cohorts to develop drugs and predict clinical outcomes. However, as precision medicine pursues more accurate and individualized treatment decisions, these methods are not designed to address single-patient transcriptome analyses. We previously developed and validated the N-of-1-pathways framework using two methods, Wilcoxon and Mahalanobis Distance (MD), for personal transcriptome analysis derived from a pair of samples of a single patient. Although, both methods uncover concordantly dysregulated pathways, they are not designed to detect dysregulated pathways with up- and down-regulated genes (bidirectional dysregulation) that are ubiquitous in biological systems. We developed N-of-1-pathways MixEnrich, a mixture model followed by a gene set enrichment test, to uncover bidirectional and concordantly dysregulated pathways one patient at a time. We assess its accuracy in a comprehensive simulation study and in a RNA-Seq data analysis of head and neck squamous cell carcinomas (HNSCCs). In presence of bidirectionally dysregulated genes in the pathway or in presence of high background noise, MixEnrich substantially outperforms previous single-subject transcriptome analysis methods, both in the simulation study and the HNSCCs data analysis (ROC Curves; higher true positive rates; lower false positive rates). Bidirectional and concordant dysregulated pathways uncovered by MixEnrich in each patient largely overlapped with the quasi-gold standard compared to other single-subject and cohort-based transcriptome analyses. The greater performance of MixEnrich presents an advantage over previous methods to meet the promise of providing accurate personal transcriptome analysis to support precision medicine at point of care.

Targeting Apoptosis Signaling Pathways for Anticancer Therapy

Energy Technology Data Exchange (ETDEWEB)

Fulda, Simone, E-mail: simone.fulda@kgu.de [Institute for Experimental Cancer Research in Pediatrics, Goethe-University, Frankfurt (Germany)

2011-08-29

Treatment approaches for cancer, for example chemotherapy, radiotherapy, or immunotherapy, primarily act by inducing cell death in cancer cells. Consequently, the inability to trigger cell death pathways or alternatively, evasion of cancer cells to the induction of cell death pathways can result in resistance of cancers to current treatment protocols. Therefore, in order to overcome treatment resistance a better understanding of the underlying mechanisms that regulate cell death and survival pathways in cancers and in response to cancer therapy is necessary to develop molecular-targeted therapies. This strategy should lead to more effective and individualized treatment strategies that selectively target deregulated signaling pathways in a tumor type- and patient-specific manner.

Targeting Apoptosis Signaling Pathways for Anticancer Therapy

International Nuclear Information System (INIS)

Fulda, Simone

2011-01-01

Treatment approaches for cancer, for example chemotherapy, radiotherapy, or immunotherapy, primarily act by inducing cell death in cancer cells. Consequently, the inability to trigger cell death pathways or alternatively, evasion of cancer cells to the induction of cell death pathways can result in resistance of cancers to current treatment protocols. Therefore, in order to overcome treatment resistance a better understanding of the underlying mechanisms that regulate cell death and survival pathways in cancers and in response to cancer therapy is necessary to develop molecular-targeted therapies. This strategy should lead to more effective and individualized treatment strategies that selectively target deregulated signaling pathways in a tumor type- and patient-specific manner.

Dynamic Modelling Reveals 'Hotspots' on the Pathway to Enzyme-Substrate Complex Formation.

Directory of Open Access Journals (Sweden)

Shane E Gordon

2016-03-01

Full Text Available Dihydrodipicolinate synthase (DHDPS catalyzes the first committed step in the diaminopimelate pathway of bacteria, yielding amino acids required for cell wall and protein biosyntheses. The essentiality of the enzyme to bacteria, coupled with its absence in humans, validates DHDPS as an antibacterial drug target. Conventional drug design efforts have thus far been unsuccessful in identifying potent DHDPS inhibitors. Here, we make use of contemporary molecular dynamics simulation and Markov state models to explore the interactions between DHDPS from the human pathogen Staphylococcus aureus and its cognate substrate, pyruvate. Our simulations recover the crystallographic DHDPS-pyruvate complex without a priori knowledge of the final bound structure. The highly conserved residue Arg140 was found to have a pivotal role in coordinating the entry of pyruvate into the active site from bulk solvent, consistent with previous kinetic reports, indicating an indirect role for the residue in DHDPS catalysis. A metastable binding intermediate characterized by multiple points of intermolecular interaction between pyruvate and key DHDPS residue Arg140 was found to be a highly conserved feature of the binding trajectory when comparing alternative binding pathways. By means of umbrella sampling we show that these binding intermediates are thermodynamically metastable, consistent with both the available experimental data and the substrate binding model presented in this study. Our results provide insight into an important enzyme-substrate interaction in atomistic detail that offers the potential to be exploited for the discovery of more effective DHDPS inhibitors and, in a broader sense, dynamic protein-drug interactions.

Modeling of the Dorsal Gradient across Species Reveals Interaction between Embryo Morphology and Toll Signaling Pathway during Evolution

Science.gov (United States)

Koslen, Hannah R.; Chiel, Hillel J.; Mizutani, Claudia Mieko

2014-01-01

Morphogenetic gradients are essential to allocate cell fates in embryos of varying sizes within and across closely related species. We previously showed that the maternal NF-κB/Dorsal (Dl) gradient has acquired different shapes in Drosophila species, which result in unequally scaled germ layers along the dorso-ventral axis and the repositioning of the neuroectodermal borders. Here we combined experimentation and mathematical modeling to investigate which factors might have contributed to the fast evolutionary changes of this gradient. To this end, we modified a previously developed model that employs differential equations of the main biochemical interactions of the Toll (Tl) signaling pathway, which regulates Dl nuclear transport. The original model simulations fit well the D. melanogaster wild type, but not mutant conditions. To broaden the applicability of this model and probe evolutionary changes in gradient distributions, we adjusted a set of 19 independent parameters to reproduce three quantified experimental conditions (i.e. Dl levels lowered, nuclear size and density increased or decreased). We next searched for the most relevant parameters that reproduce the species-specific Dl gradients. We show that adjusting parameters relative to morphological traits (i.e. embryo diameter, nuclear size and density) alone is not sufficient to reproduce the species Dl gradients. Since components of the Tl pathway simulated by the model are fast-evolving, we next asked which parameters related to Tl would most effectively reproduce these gradients and identified a particular subset. A sensitivity analysis reveals the existence of nonlinear interactions between the two fast-evolving traits tested above, namely the embryonic morphological changes and Tl pathway components. Our modeling further suggests that distinct Dl gradient shapes observed in closely related melanogaster sub-group lineages may be caused by similar sequence modifications in Tl pathway components, which

WikiPathways: a multifaceted pathway database bridging metabolomics to other omics research.

Science.gov (United States)

Slenter, Denise N; Kutmon, Martina; Hanspers, Kristina; Riutta, Anders; Windsor, Jacob; Nunes, Nuno; Mélius, Jonathan; Cirillo, Elisa; Coort, Susan L; Digles, Daniela; Ehrhart, Friederike; Giesbertz, Pieter; Kalafati, Marianthi; Martens, Marvin; Miller, Ryan; Nishida, Kozo; Rieswijk, Linda; Waagmeester, Andra; Eijssen, Lars M T; Evelo, Chris T; Pico, Alexander R; Willighagen, Egon L

2018-01-04

WikiPathways (wikipathways.org) captures the collective knowledge represented in biological pathways. By providing a database in a curated, machine readable way, omics data analysis and visualization is enabled. WikiPathways and other pathway databases are used to analyze experimental data by research groups in many fields. Due to the open and collaborative nature of the WikiPathways platform, our content keeps growing and is getting more accurate, making WikiPathways a reliable and rich pathway database. Previously, however, the focus was primarily on genes and proteins, leaving many metabolites with only limited annotation. Recent curation efforts focused on improving the annotation of metabolism and metabolic pathways by associating unmapped metabolites with database identifiers and providing more detailed interaction knowledge. Here, we report the outcomes of the continued growth and curation efforts, such as a doubling of the number of annotated metabolite nodes in WikiPathways. Furthermore, we introduce an OpenAPI documentation of our web services and the FAIR (Findable, Accessible, Interoperable and Reusable) annotation of resources to increase the interoperability of the knowledge encoded in these pathways and experimental omics data. New search options, monthly downloads, more links to metabolite databases, and new portals make pathway knowledge more effortlessly accessible to individual researchers and research communities. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

A Novel Method to Identify Differential Pathways in Hippocampus Alzheimer's Disease.

Science.gov (United States)

Liu, Chun-Han; Liu, Lian

2017-05-08

BACKGROUND Alzheimer's disease (AD) is the most common type of dementia. The objective of this paper is to propose a novel method to identify differential pathways in hippocampus AD. MATERIAL AND METHODS We proposed a combined method by merging existed methods. Firstly, pathways were identified by four known methods (DAVID, the neaGUI package, the pathway-based co-expressed method, and the pathway network approach), and differential pathways were evaluated through setting weight thresholds. Subsequently, we combined all pathways by a rank-based algorithm and called the method the combined method. Finally, common differential pathways across two or more of five methods were selected. RESULTS Pathways obtained from different methods were also different. The combined method obtained 1639 pathways and 596 differential pathways, which included all pathways gained from the four existing methods; hence, the novel method solved the problem of inconsistent results. Besides, a total of 13 common pathways were identified, such as metabolism, immune system, and cell cycle. CONCLUSIONS We have proposed a novel method by combining four existing methods based on a rank product algorithm, and identified 13 significant differential pathways based on it. These differential pathways might provide insight into treatment and diagnosis of hippocampus AD.

The Cardiopulmonary Effects of Ambient Air Pollution and Mechanistic Pathways: A Comparative Hierarchical Pathway Analysis

Science.gov (United States)

Thomas, Duncan C.; Zhang, Junfeng; Kipen, Howard M.; Rich, David Q.; Zhu, Tong; Huang, Wei; Hu, Min; Wang, Guangfa; Wang, Yuedan; Zhu, Ping; Lu, Shou-En; Ohman-Strickland, Pamela; Diehl, Scott R.; Eckel, Sandrah P.

2014-01-01

Previous studies have investigated the associations between exposure to ambient air pollution and biomarkers of physiological pathways, yet little has been done on the comparison across biomarkers of different pathways to establish the temporal pattern of biological response. In the current study, we aim to compare the relative temporal patterns in responses of candidate pathways to different pollutants. Four biomarkers of pulmonary inflammation and oxidative stress, five biomarkers of systemic inflammation and oxidative stress, ten parameters of autonomic function, and three biomarkers of hemostasis were repeatedly measured in 125 young adults, along with daily concentrations of ambient CO, PM2.5, NO2, SO2, EC, OC, and sulfate, before, during, and after the Beijing Olympics. We used a two-stage modeling approach, including Stage I models to estimate the association between each biomarker and pollutant over each of 7 lags, and Stage II mixed-effect models to describe temporal patterns in the associations when grouping the biomarkers into the four physiological pathways. Our results show that candidate pathway groupings of biomarkers explained a significant amount of variation in the associations for each pollutant, and the temporal patterns of the biomarker-pollutant-lag associations varied across candidate pathways (p<0.0001) and were not linear (from lag 0 to lag 3: p = 0.0629, from lag 3 to lag 6: p = 0.0005). These findings suggest that, among this healthy young adult population, the pulmonary inflammation and oxidative stress pathway is the first to respond to ambient air pollution exposure (within 24 hours) and the hemostasis pathway responds gradually over a 2–3 day period. The initial pulmonary response may contribute to the more gradual systemic changes that likely ultimately involve the cardiovascular system. PMID:25502951

The cardiopulmonary effects of ambient air pollution and mechanistic pathways: a comparative hierarchical pathway analysis.

Directory of Open Access Journals (Sweden)

Ananya Roy

Full Text Available Previous studies have investigated the associations between exposure to ambient air pollution and biomarkers of physiological pathways, yet little has been done on the comparison across biomarkers of different pathways to establish the temporal pattern of biological response. In the current study, we aim to compare the relative temporal patterns in responses of candidate pathways to different pollutants. Four biomarkers of pulmonary inflammation and oxidative stress, five biomarkers of systemic inflammation and oxidative stress, ten parameters of autonomic function, and three biomarkers of hemostasis were repeatedly measured in 125 young adults, along with daily concentrations of ambient CO, PM2.5, NO2, SO2, EC, OC, and sulfate, before, during, and after the Beijing Olympics. We used a two-stage modeling approach, including Stage I models to estimate the association between each biomarker and pollutant over each of 7 lags, and Stage II mixed-effect models to describe temporal patterns in the associations when grouping the biomarkers into the four physiological pathways. Our results show that candidate pathway groupings of biomarkers explained a significant amount of variation in the associations for each pollutant, and the temporal patterns of the biomarker-pollutant-lag associations varied across candidate pathways (p<0.0001 and were not linear (from lag 0 to lag 3: p = 0.0629, from lag 3 to lag 6: p = 0.0005. These findings suggest that, among this healthy young adult population, the pulmonary inflammation and oxidative stress pathway is the first to respond to ambient air pollution exposure (within 24 hours and the hemostasis pathway responds gradually over a 2-3 day period. The initial pulmonary response may contribute to the more gradual systemic changes that likely ultimately involve the cardiovascular system.

Pan-cancer analysis of TCGA data reveals notable signaling pathways

International Nuclear Information System (INIS)

Neapolitan, Richard; Horvath, Curt M.; Jiang, Xia

2015-01-01

A signal transduction pathway (STP) is a network of intercellular information flow initiated when extracellular signaling molecules bind to cell-surface receptors. Many aberrant STPs have been associated with various cancers. To develop optimal treatments for cancer patients, it is important to discover which STPs are implicated in a cancer or cancer-subtype. The Cancer Genome Atlas (TCGA) makes available gene expression level data on cases and controls in ten different types of cancer including breast cancer, colon adenocarcinoma, glioblastoma, kidney renal papillary cell carcinoma, low grade glioma, lung adenocarcinoma, lung squamous cell carcinoma, ovarian carcinoma, rectum adenocarcinoma, and uterine corpus endometriod carcinoma. Signaling Pathway Impact Analysis (SPIA) is a software package that analyzes gene expression data to identify whether a pathway is relevant in a given condition. We present the results of a study that uses SPIA to investigate all 157 signaling pathways in the KEGG PATHWAY database. We analyzed each of the ten cancer types mentioned above separately, and we perform a pan-cancer analysis by grouping the data for all the cancer types. In each analysis several pathways were found to be markedly more significant than all the other pathways. We call them notable. Research has already established a connection between many of these pathways and the corresponding cancer type. However, some of our discovered pathways appear to be new findings. Altogether there were 37 notable findings in the separate analyses, 26 of them occurred in 7 pathways. These 7 pathways included the 4 notable pathways discovered in the pan-cancer analysis. So, our results suggest that these 7 pathways account for much of the mechanisms of cancer. Furthermore, by looking at the overlap among pathways, we identified possible regions on the pathways where the aberrant activity is occurring. We obtained 37 notable findings concerning 18 pathways. Some of them appear to be

Neurophysiology and itch pathways.

Science.gov (United States)

Schmelz, Martin

2015-01-01

As we all can easily differentiate the sensations of itch and pain, the most straightforward neurophysiologic concept would consist of two specific pathways that independently encode itch and pain. Indeed, a neuronal pathway for histamine-induced itch in the peripheral and central nervous system has been described in animals and humans, and recently several non-histaminergic pathways for itch have been discovered in rodents that support a dichotomous concept differentiated into a pain and an itch pathway, with both pathways being composed of different "flavors." Numerous markers and mediators have been found that are linked to itch processing pathways. Thus, the delineation of neuronal pathways for itch from pain pathways seemingly proves that all sensory aspects of itch are based on an itch-specific neuronal pathway. However, such a concept is incomplete as itch can also be induced by the activation of the pain pathway in particular when the stimulus is applied in a highly localized spatial pattern. These opposite views reflect the old dispute between specificity and pattern theories of itch. Rather than only being of theoretic interest, this conceptual problem has key implication for the strategy to treat chronic itch as key therapeutic targets would be either itch-specific pathways or unspecific nociceptive pathways.

Verification of simulation model with COBRA-IIIP code by confrontment of experimental results

International Nuclear Information System (INIS)

Silva Galetti, M.R. da; Pontedeiro, A.C.; Oliveira Barroso, A.C. de

1985-01-01

It is presented an evaluation of the COBRA IIIP/MIT code (of thermal hydraulic analysis by subchannels), comparing their results with experimental data obtained in stationary and transient regimes. It was done a study to calculate the spatial and temporal critical heat flux. It is presented a sensitivity study of simulation model related to the turbulent mixture and the number of axial intervals. (M.C.K.) [pt

Specificity in mediated pathways by anxiety symptoms linking adolescent stress profiles to depressive symptoms: Results of a moderated mediation approach.

Science.gov (United States)

Anyan, Frederick; Bizumic, Boris; Hjemdal, Odin

2018-03-01

We investigated the specificity in mediated pathways that separately link specific stress dimensions through anxiety to depressive symptoms and the protective utility of resilience. Thus, this study goes beyond lumping together potential mediating and moderating processes that can explain the relations between stress and (symptoms of) psychopathology and the buffering effect of resilience. Ghanaian adolescents between 13 and 17 years (female = 285; male = 244) completed the Adolescent Stress Questionnaire (ASQ), Spielberger State Anxiety Inventory (STAI), Short Mood Feeling Questionnaire (SMFQ) and the Resilience Scale for Adolescents (READ). Independent samples t-test, multivariate analysis of covariance with follow-up tests and moderated mediation analyses were performed. Evidences were found for specificity in the associations between dimensions of adolescent stressors and depressive symptoms independent of transient anxiety. Transient anxiety partly accounted for the indirect effects of eight stress dimensions on depressive symptoms. Except stress of school attendance and school/leisure conflict, resilience moderated the indirect effects of specific stress dimensions on depressive symptoms. Results suggested differences in how Ghanaian adolescents view the various stress dimensions, and mediated pathways associated with anxiety and depressive symptoms. Use of cross-sectional data does not show causal process and temporal changes over time. Findings support and clarify the specificity in the interrelations and mediated pathways among dimensions of adolescent stress, transient anxiety, and depressive symptoms. Conditional process analyses shows that resilience does not only buffer direct, but also indirect psychological adversities. Interventions for good mental health may focus on low resilience subgroups in specific stress dimensions while minimizing transient anxiety. Copyright © 2017 Elsevier B.V. All rights reserved.

Flow pathways in the Slapton Wood catchment using temperature as a tracer

Science.gov (United States)

Birkinshaw, Stephen J.; Webb, Bruce

2010-03-01

SummaryThis study investigates the potential of temperature as a tracer to provide insights into flow pathways. The approach couples fieldwork and modelling experiments for the Eastergrounds Hollow within the Slapton Wood catchment, South Devon, UK. Measurements in the Eastergrounds Hollow were carried out for soil temperature, spring temperature, and the stream temperature and use was made of an existing 1989-1991 data set for the entire Slapton Wood catchment. The predominant flow in this hollow is a result of subsurface stormflow, and previous work has suggested that the water flows vertically down through the soil and then subsurface stormflow occurs at the soil/bedrock interface where the water is deflected laterally. The depth of the subsurface stormflow was previously thought to be around 2.2 m. However, analysis of the new spring, stream and soil temperature data suggests a deeper pathway for the subsurface stormflow. Modelling of water flow and heat transport was carried out using SHETRAN and this was calibrated to reproduce the water flow in the entire Slapton Wood catchment and soil temperatures in the Eastergrounds Hollow. The model was tested for the entire Eastergrounds Hollow with two different soil depths. A depth of 2.2 m, based on previous knowledge, was unable to reproduce the Eastergrounds spring temperature. A depth of 3.7 m produced an excellent comparison between measured and simulated stream and spring temperatures in the Eastergrounds Hollow. This work suggests that the depth of the flow pathways that produce the subsurface stormflow are deeper than previously thought. It also provides a demonstration on the use of temperature as a tracer to understand flow pathways.

Energy Landscape and Pathways for Transitions between Watson-Crick and Hoogsteen Base Pairing in DNA.

Science.gov (United States)

Chakraborty, Debayan; Wales, David J

2018-01-04

The recent discovery that Hoogsteen (HG) base pairs are widespread in DNA across diverse sequences and positional contexts could have important implications for understanding DNA replication and DNA-protein recognition. While evidence is emerging that the Hoogsteen conformation could be a thermodynamically accessible conformation of the DNA duplex and provide a means to expand its functionality, relatively little is known about the molecular mechanism underlying the Watson-Crick (WC) to HG transition. In this Perspective, we describe pathways and kinetics for this transition at an atomic level of detail, using the energy landscape perspective. We show that competition between the duplex conformations results in a double funnel landscape, which explains some recent experimental observations. The interconversion pathways feature a number of intermediates, with a variable number of WC and HG base pairs. The relatively slow kinetics, with possible deviations from two-state behavior, suggest that this conformational switch is likely to be a challenging target for both simulation and experiment.

Transfer of radionuclides to man through environmental pathways

International Nuclear Information System (INIS)

Mitchell, N.T.

1974-01-01

The most widely accepted method in current use for the evaluation of environmental impact from releases of radioactivity that may cause human radiation exposure used an environmental pathway model. The more important aspects of the model involve the use of critical pathway techniques to set controls on the releases of radioactive material to the environment and to assess the human radiation exposure arising as a consequence. The basic concepts of the environmental pathway model and its application are discussed. The model depends on achieving an understanding of radionuclide behavior in the environment, from the moment of release up to the time when contamination results in radiation exposure to the public. Exposure may be as a result of contaminated material entering the body-as air, water or a foodstuff; alternatively, it may be due to radiation whose source is external to the body. For each of these types of exposure pathway the sequence of events can be divided up into a number of compartments, between which transfer takes place. Transfer along the pathway is a dynamic process and can be described mathematically in terms of transfer functions between interacting compartments. Alternatively, for the situation of a regular discharge resulting in a steady-state condition the relationship between compartments can be expressed as a 'concentration factor'. The derivation of both of these terms is described and some aspects of their use are discussed. The paper then goes on to discuss the types of environmental pathway that are encountered as a result of release of radionuclides to the atmospheric and aquatic environments. Disposal to the ground is regarded as a special case of release to the aquatic environment. Some ot the literature on the subject is reviewed in discussingthe better known pathways showing what, to date, have been the most important mechanisms of transfer of radionuclides to man. (author)

Simulated building energy demand biases resulting from the use of representative weather stations

Energy Technology Data Exchange (ETDEWEB)

Burleyson, Casey D.; Voisin, Nathalie; Taylor, Z. Todd; Xie, Yulong; Kraucunas, Ian

2018-01-01

Numerical building models are typically forced with weather data from a limited number of “representative cities” or weather stations representing different climate regions. The use of representative weather stations reduces computational costs, but often fails to capture spatial heterogeneity in weather that may be important for simulations aimed at understanding how building stocks respond to a changing climate. We quantify the potential reduction in bias from using an increasing number of weather stations over the western U.S. The approach is based on deriving temperature and load time series using incrementally more weather stations, ranging from 8 to roughly 150, to capture weather across different seasons. Using 8 stations, one from each climate zone, across the western U.S. results in an average absolute summertime temperature bias of 7.2°F with respect to a spatially-resolved gridded dataset. The mean absolute bias drops to 2.8°F using all available weather stations. Temperature biases of this magnitude could translate to absolute summertime mean simulated load biases as high as 13.8%, a significant error for capacity expansion planners who may use these types of simulations. Increasing the size of the domain over which biases are calculated reduces their magnitude as positive and negative biases may cancel out. Using 8 representative weather stations can lead to a 20-40% overestimation of peak building loads during both summer and winter. Using weather stations close to population centers reduces both mean and peak load biases. This approach could be used by others designing aggregate building simulations to understand the sensitivity to their choice of weather stations used to drive the models.

Free energy landscape and transition pathways from Watson–Crick to Hoogsteen base pairing in free duplex DNA

Science.gov (United States)

Yang, Changwon; Kim, Eunae; Pak, Youngshang

2015-01-01

Houghton (HG) base pairing plays a central role in the DNA binding of proteins and small ligands. Probing detailed transition mechanism from Watson–Crick (WC) to HG base pair (bp) formation in duplex DNAs is of fundamental importance in terms of revealing intrinsic functions of double helical DNAs beyond their sequence determined functions. We investigated a free energy landscape of a free B-DNA with an adenosine–thymine (A–T) rich sequence to probe its conformational transition pathways from WC to HG base pairing. The free energy landscape was computed with a state-of-art two-dimensional umbrella molecular dynamics simulation at the all-atom level. The present simulation showed that in an isolated duplex DNA, the spontaneous transition from WC to HG bp takes place via multiple pathways. Notably, base flipping into the major and minor grooves was found to play an important role in forming these multiple transition pathways. This finding suggests that naked B-DNA under normal conditions has an inherent ability to form HG bps via spontaneous base opening events. PMID:26250116

Pathway Analysis in Attention Deficit Hyperactivity Disorder: An Ensemble Approach

Science.gov (United States)

Mooney, Michael A.; McWeeney, Shannon K.; Faraone, Stephen V.; Hinney, Anke; Hebebrand, Johannes; Nigg, Joel T.; Wilmot, Beth

2016-01-01

Despite a wealth of evidence for the role of genetics in attention deficit hyperactivity disorder (ADHD), specific and definitive genetic mechanisms have not been identified. Pathway analyses, a subset of gene-set analyses, extend the knowledge gained from genome-wide association studies (GWAS) by providing functional context for genetic associations. However, there are numerous methods for association testing of gene sets and no real consensus regarding the best approach. The present study applied six pathway analysis methods to identify pathways associated with ADHD in two GWAS datasets from the Psychiatric Genomics Consortium. Methods that utilize genotypes to model pathway-level effects identified more replicable pathway associations than methods using summary statistics. In addition, pathways implicated by more than one method were significantly more likely to replicate. A number of brain-relevant pathways, such as RhoA signaling, glycosaminoglycan biosynthesis, fibroblast growth factor receptor activity, and pathways containing potassium channel genes, were nominally significant by multiple methods in both datasets. These results support previous hypotheses about the role of regulation of neurotransmitter release, neurite outgrowth and axon guidance in contributing to the ADHD phenotype and suggest the value of cross-method convergence in evaluating pathway analysis results. PMID:27004716

Relative solvation free energies calculated using an ab initio QM/MM-based free energy perturbation method: dependence of results on simulation length.

Science.gov (United States)

Reddy, M Rami; Erion, Mark D

2009-12-01

Molecular dynamics (MD) simulations in conjunction with thermodynamic perturbation approach was used to calculate relative solvation free energies of five pairs of small molecules, namely; (1) methanol to ethane, (2) acetone to acetamide, (3) phenol to benzene, (4) 1,1,1 trichloroethane to ethane, and (5) phenylalanine to isoleucine. Two studies were performed to evaluate the dependence of the convergence of these calculations on MD simulation length and starting configuration. In the first study, each transformation started from the same well-equilibrated configuration and the simulation length was varied from 230 to 2,540 ps. The results indicated that for transformations involving small structural changes, a simulation length of 860 ps is sufficient to obtain satisfactory convergence. In contrast, transformations involving relatively large structural changes, such as phenylalanine to isoleucine, require a significantly longer simulation length (>2,540 ps) to obtain satisfactory convergence. In the second study, the transformation was completed starting from three different configurations and using in each case 860 ps of MD simulation. The results from this study suggest that performing one long simulation may be better than averaging results from three different simulations using a shorter simulation length and three different starting configurations.

Reprogramming One-Carbon Metabolic Pathways To Decouple l-Serine Catabolism from Cell Growth in Corynebacterium glutamicum.

Science.gov (United States)

Zhang, Yun; Shang, Xiuling; Lai, Shujuan; Zhang, Yu; Hu, Qitiao; Chai, Xin; Wang, Bo; Liu, Shuwen; Wen, Tingyi

2018-02-16

l-Serine, the principal one-carbon source for DNA biosynthesis, is difficult for microorganisms to accumulate due to the coupling of l-serine catabolism and microbial growth. Here, we reprogrammed the one-carbon unit metabolic pathways in Corynebacterium glutamicum to decouple l-serine catabolism from cell growth. In silico model-based simulation showed a negative influence on glyA-encoding serine hydroxymethyltransferase flux with l-serine productivity. Attenuation of glyA transcription resulted in increased l-serine accumulation, and a decrease in purine pools, poor growth and longer cell shapes. The gcvTHP-encoded glycine cleavage (Gcv) system from Escherichia coli was introduced into C. glutamicum, allowing glycine-derived 13 CH 2 to be assimilated into intracellular purine synthesis, which resulted in an increased amount of one-carbon units. Gcv introduction not only restored cell viability and morphology but also increased l-serine accumulation. Moreover, comparative proteomic analysis indicated that abundance changes of the enzymes involved in one-carbon unit cycles might be responsible for maintaining one-carbon unit homeostasis. Reprogramming of the one-carbon metabolic pathways allowed cells to reach a comparable growth rate to accumulate 13.21 g/L l-serine by fed-batch fermentation in minimal medium. This novel strategy provides new insights into the regulation of cellular properties and essential metabolite accumulation by introducing an extrinsic pathway.

Nonlinear excitation of electron cyclotron waves by a monochromatic strong microwave: computer simulation analysis of the MINIX results

Energy Technology Data Exchange (ETDEWEB)

Matsumoto, H.; Kimura, T.

1986-01-01

Triggered by the experimental results of the MINIX, a computer simulation study was initiated on the nonlinear excitation of electrostatic electron cyclotron waves by a monochromatic electromagnetic wave such as the transmitted microwave in the MINIX. The model used assumes that both of the excited waves and exciting (pumping) electromagnetic wave as well as the idler electromagnetic wave propagate in the direction perpendicular to the external magnetic field. The simulation code used for this study was the one-and-two-half dimensional electromagnetic particle code named KEMPO. The simulation result shows the high power electromagnetic wave produces both the backscattered electromagnetic wave and electrostatic electron cyclotron waves as a result of nonlinear parametric instability. Detailed nonlinear microphysics related to the wave excitation is discussed in terms of the nonlinear wave-wave couplings and associated ponderomotive force produced by the high power electromagnetic waves. 2 references, 4 figures.

The Holinger apartment house in Oberdorf, Switzerland - Measurement results and simulations; Mehrfamilienhaus Holinger, Oberdorf BL. Messungen und Simulationen

Energy Technology Data Exchange (ETDEWEB)

Blatter, M. [Max Blatter, Bremgarten, former in Muenchenstein (Switzerland); Bruehwiler, D. [Daniel Bruehwiler, Energietechnik und Informatik, Faellanden (Switzerland)

2000-12-15

This comprehensive final report for the Swiss Federal Office of Energy (SFOE) as part of the research program on solar architecture discusses the results of measurements and simulations made on a four-family home. The heating system of the building which uses a window and roof air collector system combined with wood-fired ovens is described. The most important findings are presented and discussed. Schematics of the heat-collection systems are presented and discussed and the heat-recovery system is described. The measurement system is described and the results obtained are analysed, as are the monthly and annual energy balances of the building. The results of a computer simulation are presented and discussed and compared with the actual measurements made. System optimisation was simulated. The possibility of using the system in summer to pre-heat domestic hot water is looked at. The conclusions drawn from the project are discussed.

Nonlinear excitation of electron cyclotron waves by a monochromatic strong microwave: computer simulation analysis of the MINIX results

International Nuclear Information System (INIS)

Matsumoto, H.; Kimura, T.

1986-01-01

Triggered by the experimental results of the MINIX, a computer simulation study was initiated on the nonlinear excitation of electrostatic electron cyclotron waves by a monochromatic electromagnetic wave such as the transmitted microwave in the MINIX. The model used assumes that both of the excited waves and exciting (pumping) electromagnetic wave as well as the idler electromagnetic wave propagate in the direction perpendicular to the external magnetic field. The simulation code used for this study was the one-and-two-half dimensional electromagnetic particle code named KEMPO. The simulation result shows the high power electromagnetic wave produces both the backscattered electromagnetic wave and electrostatic electron cyclotron waves as a result of nonlinear parametric instability. Detailed nonlinear microphysics related to the wave excitation is discussed in terms of the nonlinear wave-wave couplings and associated ponderomotive force produced by the high power electromagnetic waves. 2 references, 4 figures

Sub-millimeter planar imaging with positron emitters: EGS4 code simulation and experimental results

International Nuclear Information System (INIS)

Bollini, D.; Del Guerra, A.; Di Domenico, G.

1996-01-01

Experimental data for Planar Imaging with positron emitters (pulse height, efficiency and spatial resolution) obtained with two matrices of 25 crystals (2 x 2 x 30 mm 3 each) of YAP:Ce coupled with a Position Sensitive PhotoMultiplier (Hamamatsu R2486-06) have been reproduced with high accuracy using the EGS4 code. Extensive simulation provides a detailed description of the performance of this type of detector as a function of the matrix granularity, the geometry of the detector and detection threshold. We present the Monte Carlo simulation and the preliminary experimental results of a prototype planar imaging system made of two matrices, each one consisting of 400 (2 x 2 x 30 mm 3 ) crystals of YAP-Ce

Predicting pathway cross-talks in ankylosing spondylitis through investigating the interactions among pathways.

Science.gov (United States)

Gu, Xiang; Liu, Cong-Jian; Wei, Jian-Jie

2017-11-13

Given that the pathogenesis of ankylosing spondylitis (AS) remains unclear, the aim of this study was to detect the potentially functional pathway cross-talk in AS to further reveal the pathogenesis of this disease. Using microarray profile of AS and biological pathways as study objects, Monte Carlo cross-validation method was used to identify the significant pathway cross-talks. In the process of Monte Carlo cross-validation, all steps were iterated 50 times. For each run, detection of differentially expressed genes (DEGs) between two groups was conducted. The extraction of the potential disrupted pathways enriched by DEGs was then implemented. Subsequently, we established a discriminating score (DS) for each pathway pair according to the distribution of gene expression levels. After that, we utilized random forest (RF) classification model to screen out the top 10 paired pathways with the highest area under the curve (AUCs), which was computed using 10-fold cross-validation approach. After 50 bootstrap, the best pairs of pathways were identified. According to their AUC values, the pair of pathways, antigen presentation pathway and fMLP signaling in neutrophils, achieved the best AUC value of 1.000, which indicated that this pathway cross-talk could distinguish AS patients from normal subjects. Moreover, the paired pathways of SAPK/JNK signaling and mitochondrial dysfunction were involved in 5 bootstraps. Two paired pathways (antigen presentation pathway and fMLP signaling in neutrophil, as well as SAPK/JNK signaling and mitochondrial dysfunction) can accurately distinguish AS and control samples. These paired pathways may be helpful to identify patients with AS for early intervention.

Conservation of Planar Polarity Pathway Function Across the Animal Kingdom.

Science.gov (United States)

Hale, Rosalind; Strutt, David

2015-01-01

Planar polarity is a well-studied phenomenon resulting in the directional coordination of cells in the plane of a tissue. In invertebrates and vertebrates, planar polarity is established and maintained by the largely independent core and Fat/Dachsous/Four-jointed (Ft-Ds-Fj) pathways. Loss of function of these pathways can result in a wide range of developmental or cellular defects, including failure of gastrulation and problems with placement and function of cilia. This review discusses the conservation of these pathways across the animal kingdom. The lack of vital core pathway components in basal metazoans suggests that the core planar polarity pathway evolved shortly after, but not necessarily alongside, the emergence of multicellularity.

Geoelectrical monitoring of simulated subsurface leakage to support high-hazard nuclear decommissioning at the Sellafield Site, UK

Energy Technology Data Exchange (ETDEWEB)

Kuras, Oliver, E-mail: oku@bgs.ac.uk [British Geological Survey, Keyworth, Nottingham NG12 5GG (United Kingdom); Wilkinson, Paul B.; Meldrum, Philip I.; Oxby, Lucy S. [British Geological Survey, Keyworth, Nottingham NG12 5GG (United Kingdom); Uhlemann, Sebastian [British Geological Survey, Keyworth, Nottingham NG12 5GG (United Kingdom); ETH-Swiss Federal Institute of Technology, Institute of Geophysics, Sonneggstr. 5, 8092 Zurich (Switzerland); Chambers, Jonathan E. [British Geological Survey, Keyworth, Nottingham NG12 5GG (United Kingdom); Binley, Andrew [Lancaster Environment Centre, Lancaster University, Lancaster LA1 4YQ (United Kingdom); Graham, James [National Nuclear Laboratory, Central Laboratory, Sellafield, Seascale, Cumbria CA20 1PG (United Kingdom); Smith, Nicholas T. [National Nuclear Laboratory, Central Laboratory, Sellafield, Seascale, Cumbria CA20 1PG (United Kingdom); School of Earth, Atmospheric and Environmental Sciences, Williamson Building, University of Manchester, Oxford Road, Manchester M13 9PL (United Kingdom); Atherton, Nick [Sellafield Ltd, Albion Square, Swingpump Lane, Whitehaven CA28 7NE (United Kingdom)

2016-10-01

A full-scale field experiment applying 4D (3D time-lapse) cross-borehole Electrical Resistivity Tomography (ERT) to the monitoring of simulated subsurface leakage was undertaken at a legacy nuclear waste silo at the Sellafield Site, UK. The experiment constituted the first application of geoelectrical monitoring in support of decommissioning work at a UK nuclear licensed site. Images of resistivity changes occurring since a baseline date prior to the simulated leaks revealed likely preferential pathways of silo liquor simulant flow in the vadose zone and upper groundwater system. Geophysical evidence was found to be compatible with historic contamination detected in permeable facies in sediment cores retrieved from the ERT boreholes. Results indicate that laterally discontinuous till units forming localized hydraulic barriers substantially affect flow patterns and contaminant transport in the shallow subsurface at Sellafield. We conclude that only geophysical imaging of the kind presented here has the potential to provide the detailed spatial and temporal information at the (sub-)meter scale needed to reduce the uncertainty in models of subsurface processes at nuclear sites. - Graphical abstract: 3D fractional resistivity change (resistivity change Δρ divided by baseline resistivity ρ{sub 0}) image showing results of Stage 1 silo liquor simulant injection. The black line delineates the preferential flow path; green cylinders show regions of historic contamination found in sediment cores from ERT boreholes. - Highlights: • 4D geoelectrical monitoring at Sellafield detected and tracked simulated silo leaks. • ERT revealed likely pathways of silo liquor simulant flow in the subsurface. • The method can reduce uncertainty in subsurface process models at nuclear sites. • Has been applied in this form at a UK nuclear licensed site for the first time • Study demonstrates value of 4D geophysics for nuclear decommissioning.

Polarimetric Emission of Rain Events: Simulation and Experimental Results at X-Band

Directory of Open Access Journals (Sweden)

Nuria Duffo

2009-06-01

Full Text Available Accurate models are used today for infrared and microwave satellite radiance simulations of the first two Stokes elements in the physical retrieval, data assimilation etc. of surface and atmospheric parameters. Although in the past a number of theoretical and experimental works have studied the polarimetric emission of some natural surfaces, specially the sea surface roughened by the wind (Windsat mission, very limited studies have been conducted on the polarimetric emission of rain cells or other natural surfaces. In this work, the polarimetric emission (four Stokes elements of a rain cell is computed using the polarimetric radiative transfer equation assuming that raindrops are described by Pruppacher-Pitter shapes and that their size distribution follows the Laws-Parsons law. The Boundary Element Method (BEM is used to compute the exact bistatic scattering coefficients for each raindrop shape and different canting angles. Numerical results are compared to the Rayleigh or Mie scattering coefficients, and to Oguchi’s ones, showing that above 1-2 mm raindrop size the exact formulation is required to model properly the scattering. Simulation results using BEM are then compared to the experimental data gathered with a X-band polarimetric radiometer. It is found that the depolarization of the radiation caused by the scattering of non-spherical raindrops induces a non-zero third Stokes parameter, and the differential phase of the scattering coefficients induces a non-zero fourth Stokes parameter.

RESULTS OF COPPER CATALYZED PEROXIDE OXIDATION (CCPO) OF TANK 48H SIMULANTS

Energy Technology Data Exchange (ETDEWEB)

Peters, T.; Pareizs, J.; Newell, J.; Fondeur, F.; Nash, C.; White, T.; Fink, S.

2012-08-14

Savannah River National Laboratory (SRNL) performed a series of laboratory-scale experiments that examined copper-catalyzed hydrogen peroxide (H{sub 2}O{sub 2}) aided destruction of organic components, most notably tetraphenylborate (TPB), in Tank 48H simulant slurries. The experiments were designed with an expectation of conducting the process within existing vessels of Building 241-96H with minimal modifications to the existing equipment. Results of the experiments indicate that TPB destruction levels exceeding 99.9% are achievable, dependent on the reaction conditions. The following observations were made with respect to the major processing variables investigated. A lower reaction pH provides faster reaction rates (pH 7 > pH 9 > pH 11); however, pH 9 reactions provide the least quantity of organic residual compounds within the limits of species analyzed. Higher temperatures lead to faster reaction rates and smaller quantities of organic residual compounds. Higher concentrations of the copper catalyst provide faster reaction rates, but the highest copper concentration (500 mg/L) also resulted in the second highest quantity of organic residual compounds. Faster rates of H{sub 2}O{sub 2} addition lead to faster reaction rates and lower quantities of organic residual compounds. Testing with simulated slurries continues. Current testing is examining lower copper concentrations, refined peroxide addition rates, and alternate acidification methods. A revision of this report will provide updated findings with emphasis on defining recommended conditions for similar tests with actual waste samples.

Evaluation of stratospheric temperature simulation results by the global GRAPES model

Science.gov (United States)

Liu, Ningwei; Wang, Yangfeng; Ma, Xiaogang; Zhang, Yunhai

2017-12-01

Global final analysis (FNL) products and the general circulation spectral model (ECHAM) were used to evaluate the simulation of stratospheric temperature by the global assimilation and prediction system (GRAPES). Through a series of comparisons, it was shown that the temperature variations at 50 hPa simulated by GRAPES were significantly elevated in the southern hemisphere, whereas simulations by ECHAM and FNL varied little over time. The regional warming predicted by GRAPES seemed to be too distinct and uncontrolled to be reasonable. The temperature difference between GRAPES and FNL (GRAPES minus FNL) was small at the start time on the global scale. Over time, the positive values became larger in more locations, especially in parts of the southern hemisphere, where the warming predicted by GRAPES was dominant, with a maximal value larger than 24 K. To determine the reasons for the stratospheric warming, we considered the model initial conditions and ozone data to be possible factors; however, a comparison and sensitivity test indicated that the errors produced by GRAPES were not significantly related to either factor. Further research focusing on the impact of factors such as vapor, heating rate, and the temperature tendency on GRAPES simulations will be conducted.

Solar Potential Analysis and Integration of the Time-Dependent Simulation Results for Semantic 3d City Models Using Dynamizers

Science.gov (United States)

Chaturvedi, K.; Willenborg, B.; Sindram, M.; Kolbe, T. H.

2017-10-01

Semantic 3D city models play an important role in solving complex real-world problems and are being adopted by many cities around the world. A wide range of application and simulation scenarios directly benefit from the adoption of international standards such as CityGML. However, most of the simulations involve properties, whose values vary with respect to time, and the current generation semantic 3D city models do not support time-dependent properties explicitly. In this paper, the details of solar potential simulations are provided operating on the CityGML standard, assessing and estimating solar energy production for the roofs and facades of the 3D building objects in different ways. Furthermore, the paper demonstrates how the time-dependent simulation results are better-represented inline within 3D city models utilizing the so-called Dynamizer concept. This concept not only allows representing the simulation results in standardized ways, but also delivers a method to enhance static city models by such dynamic property values making the city models truly dynamic. The dynamizer concept has been implemented as an Application Domain Extension of the CityGML standard within the OGC Future City Pilot Phase 1. The results are given in this paper.

Dynamic colloidal assembly pathways via low dimensional models

Energy Technology Data Exchange (ETDEWEB)

Yang, Yuguang; Bevan, Michael A., E-mail: mabevan@jhu.edu [Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218 (United States); Thyagarajan, Raghuram; Ford, David M. [Chemical Engineering, University of Massachusetts, Amherst, Massachusetts 01003 (United States)

2016-05-28

Here we construct a low-dimensional Smoluchowski model for electric field mediated colloidal crystallization using Brownian dynamic simulations, which were previously matched to experiments. Diffusion mapping is used to infer dimensionality and confirm the use of two order parameters, one for degree of condensation and one for global crystallinity. Free energy and diffusivity landscapes are obtained as the coefficients of a low-dimensional Smoluchowski equation to capture the thermodynamics and kinetics of microstructure evolution. The resulting low-dimensional model quantitatively captures the dynamics of different assembly pathways between fluid, polycrystal, and single crystals states, in agreement with the full N-dimensional data as characterized by first passage time distributions. Numerical solution of the low-dimensional Smoluchowski equation reveals statistical properties of the dynamic evolution of states vs. applied field amplitude and system size. The low-dimensional Smoluchowski equation and associated landscapes calculated here can serve as models for predictive control of electric field mediated assembly of colloidal ensembles into two-dimensional crystalline objects.

Pathways of topological rank analysis (PoTRA: a novel method to detect pathways involved in hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

Chaoxing Li

2018-04-01

Full Text Available Complex diseases such as cancer are usually the result of a combination of environmental factors and one or several biological pathways consisting of sets of genes. Each biological pathway exerts its function by delivering signaling through the gene network. Theoretically, a pathway is supposed to have a robust topological structure under normal physiological conditions. However, the pathway’s topological structure could be altered under some pathological condition. It is well known that a normal biological network includes a small number of well-connected hub nodes and a large number of nodes that are non-hubs. In addition, it is reported that the loss of connectivity is a common topological trait of cancer networks, which is an assumption of our method. Hence, from normal to cancer, the process of the network losing connectivity might be the process of disrupting the structure of the network, namely, the number of hub genes might be altered in cancer compared to that in normal or the distribution of topological ranks of genes might be altered. Based on this, we propose a new PageRank-based method called Pathways of Topological Rank Analysis (PoTRA to detect pathways involved in cancer. We use PageRank to measure the relative topological ranks of genes in each biological pathway, then select hub genes for each pathway, and use Fisher’s exact test to test if the number of hub genes in each pathway is altered from normal to cancer. Alternatively, if the distribution of topological ranks of gene in a pathway is altered between normal and cancer, this pathway might also be involved in cancer. Hence, we use the Kolmogorov–Smirnov test to detect pathways that have an altered distribution of topological ranks of genes between two phenotypes. We apply PoTRA to study hepatocellular carcinoma (HCC and several subtypes of HCC. Very interestingly, we discover that all significant pathways in HCC are cancer-associated generally, while several

Quantitative trait loci and metabolic pathways

Science.gov (United States)

McMullen, M. D.; Byrne, P. F.; Snook, M. E.; Wiseman, B. R.; Lee, E. A.; Widstrom, N. W.; Coe, E. H.

1998-01-01

The interpretation of quantitative trait locus (QTL) studies is limited by the lack of information on metabolic pathways leading to most economic traits. Inferences about the roles of the underlying genes with a pathway or the nature of their interaction with other loci are generally not possible. An exception is resistance to the corn earworm Helicoverpa zea (Boddie) in maize (Zea mays L.) because of maysin, a C-glycosyl flavone synthesized in silks via a branch of the well characterized flavonoid pathway. Our results using flavone synthesis as a model QTL system indicate: (i) the importance of regulatory loci as QTLs, (ii) the importance of interconnecting biochemical pathways on product levels, (iii) evidence for “channeling” of intermediates, allowing independent synthesis of related compounds, (iv) the utility of QTL analysis in clarifying the role of specific genes in a biochemical pathway, and (v) identification of a previously unknown locus on chromosome 9S affecting flavone level. A greater understanding of the genetic basis of maysin synthesis and associated corn earworm resistance should lead to improved breeding strategies. More broadly, the insights gained in relating a defined genetic and biochemical pathway affecting a quantitative trait should enhance interpretation of the biological basis of variation for other quantitative traits. PMID:9482823

Entry, Descent and Landing Systems Analysis: Exploration Class Simulation Overview and Results

Science.gov (United States)

DwyerCianciolo, Alicia M.; Davis, Jody L.; Shidner, Jeremy D.; Powell, Richard W.

2010-01-01

NASA senior management commissioned the Entry, Descent and Landing Systems Analysis (EDL-SA) Study in 2008 to identify and roadmap the Entry, Descent and Landing (EDL) technology investments that the agency needed to make in order to successfully land large payloads at Mars for both robotic and exploration or human-scale missions. The year one exploration class mission activity considered technologies capable of delivering a 40-mt payload. This paper provides an overview of the exploration class mission study, including technologies considered, models developed and initial simulation results from the EDL-SA year one effort.

Simulation of single-phase rod bundle flow. Comparison between CFD-code ESTET, PWR core code THYC and experimental results

International Nuclear Information System (INIS)

Mur, J.; Larrauri, D.

1998-07-01

Computer simulation of flow in configurations close to pressurized water reactor (PWR) geometry is of great interest for Electricite de France (EDF). Although simulation of the flow through a whole PWR core with an all purpose CFD-code is not yet achievable, such a tool cna be quite useful to perform numerical experiments in order to try and improve the modeling introduced in computer codes devoted to reactor core thermal-hydraulic analysis. Further to simulation in small bare rod bundle configurations, the present study is focused on the simulation, with CFD-code ESTET and PWR core code THYC, of the flow in the experimental configuration VATICAN-1. ESTET simulation results are compared on the one hand to local velocity and concentration measurements, on the other hand with subchannel averaged values calculated by THYC. As far as the comparison with measurements is concerned, ESTET results are quite satisfactory relatively to available experimental data and their uncertainties. The effect of spacer grids and the prediction of the evolution of an unbalanced velocity profile seem to be correctly treated. As far as the comparison with THYC subchannel averaged values is concerned, the difficulty of a direct comparison between subchannel averaged and local values is pointed out. ESTET calculated local values are close to experimental local values. ESTET subchannel averaged values are also close to THYC calculation results. Thus, THYC results are satisfactory whereas their direct comparison to local measurements could show some disagreement. (author)

A novel method to identify hub pathways of rheumatoid arthritis based on differential pathway networks.

Science.gov (United States)

Wei, Shi-Tong; Sun, Yong-Hua; Zong, Shi-Hua

2017-09-01

The aim of the current study was to identify hub pathways of rheumatoid arthritis (RA) using a novel method based on differential pathway network (DPN) analysis. The present study proposed a DPN where protein‑protein interaction (PPI) network was integrated with pathway‑pathway interactions. Pathway data was obtained from background PPI network and the Reactome pathway database. Subsequently, pathway interactions were extracted from the pathway data by building randomized gene‑gene interactions and a weight value was assigned to each pathway interaction using Spearman correlation coefficient (SCC) to identify differential pathway interactions. Differential pathway interactions were visualized using Cytoscape to construct a DPN. Topological analysis was conducted to identify hub pathways that possessed the top 5% degree distribution of DPN. Modules of DPN were mined according to ClusterONE. A total of 855 pathways were selected to build pathway interactions. By filtrating pathway interactions of weight values >0.7, a DPN with 312 nodes and 791 edges was obtained. Topological degree analysis revealed 15 hub pathways, such as heparan sulfate/heparin‑glycosaminoglycan (HS‑GAG) degradation, HS‑GAG metabolism and keratan sulfate degradation for RA based on DPN. Furthermore, hub pathways were also important in modules, which validated the significance of hub pathways. In conclusion, the proposed method is a computationally efficient way to identify hub pathways of RA, which identified 15 hub pathways that may be potential biomarkers and provide insight to future investigation and treatment of RA.

Exploring pathway interactions in insulin resistant mouse liver

NARCIS (Netherlands)

Kelder, T.; Eijssen, L.; Kleemann, R.; Erk, M. van; Kooistra, T.; Evelo, C.

2011-01-01

Background: Complex phenotypes such as insulin resistance involve different biological pathways that may interact and influence each other. Interpretation of related experimental data would be facilitated by identifying relevant pathway interactions in the context of the dataset.Results: We

The effect of nitrate, bicarbonate and natural organic matter on the degradation of sunscreen agent p-aminobenzoic acid by simulated solar irradiation

Energy Technology Data Exchange (ETDEWEB)

Mao, Liang, E-mail: lmao@nju.edu.cn [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093 (China); Meng, Cui; Zeng, Chao; Ji, Yuefei [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093 (China); Yang, Xi, E-mail: yangxi@nju.edu.cn [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093 (China); State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen 361005 (China); Gao, Shixiang [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093 (China)

2011-11-15

Our experiments revealed that a model sunscreen agent, p-aminobenzoic acid (PABA), can be effectively transformed through reactions that are mediated by simulated solar irradiation. We systematically explored the effects of nitrate ions, bicarbonate and different types of natural organic matter (NOM) on the degradation of PABA by simulated solar irradiation. Experimental data suggest that these components ubiquitous in nature water have different influence on the rates of the photoinduced removal of PABA. Products were extracted and analyzed using LC/MS and a total of four products probably resulting from {center_dot}OH and {center_dot}NO{sub 2} radicals attack were identified and the possible reaction pathways were proposed. The findings in this study provide useful information for understanding the environmental transformation of sunscreen agent in aquatic system. - Highlights: {yields} In this study, we found that p-aminobenzoic acid (PABA) can be removed by simulated solar irradiation from water. {yields} Influence of environmental components on the photodegradation of PABA was further studied. {yields} We verified using LC/MS that PABA was transformed into four compounds. {yields} We proposed the possible reaction pathways probably resulting from {center_dot}OH and {center_dot}NO{sub 2} radicals attack to PABA.

The effect of nitrate, bicarbonate and natural organic matter on the degradation of sunscreen agent p-aminobenzoic acid by simulated solar irradiation

International Nuclear Information System (INIS)

Mao, Liang; Meng, Cui; Zeng, Chao; Ji, Yuefei; Yang, Xi; Gao, Shixiang

2011-01-01

Our experiments revealed that a model sunscreen agent, p-aminobenzoic acid (PABA), can be effectively transformed through reactions that are mediated by simulated solar irradiation. We systematically explored the effects of nitrate ions, bicarbonate and different types of natural organic matter (NOM) on the degradation of PABA by simulated solar irradiation. Experimental data suggest that these components ubiquitous in nature water have different influence on the rates of the photoinduced removal of PABA. Products were extracted and analyzed using LC/MS and a total of four products probably resulting from ·OH and ·NO 2 radicals attack were identified and the possible reaction pathways were proposed. The findings in this study provide useful information for understanding the environmental transformation of sunscreen agent in aquatic system. - Highlights: → In this study, we found that p-aminobenzoic acid (PABA) can be removed by simulated solar irradiation from water. → Influence of environmental components on the photodegradation of PABA was further studied. → We verified using LC/MS that PABA was transformed into four compounds. → We proposed the possible reaction pathways probably resulting from ·OH and ·NO 2 radicals attack to PABA.

Improving CTE Student Retention and Transfer at Rend Lake College with Degree Audit and Reengagment Strategies. Pathways to Results: Implementation Partnerships Strategy Brief

Science.gov (United States)

Rockey, Marci

2016-01-01

Rend Lake College (RLC) has participated in several Pathways to Results (PTR) projects over the last five years. The PTR model has been an essential tool to drive evidence-based changes throughout the College. In 2015, RLC used the PTR Model to evaluate institutional processes related to the Perkins Career and Technical Education (CTE) Student…

Spectrally constrained NIR tomography for breast imaging: simulations and clinical results

Science.gov (United States)

Srinivasan, Subhadra; Pogue, Brian W.; Jiang, Shudong; Dehghani, Hamid; Paulsen, Keith D.

2005-04-01

A multi-spectral direct chromophore and scattering reconstruction for frequency domain NIR tomography has been implemented using constraints of the known molar spectra of the chromophores and a Mie theory approximation for scattering. This was tested in a tumor-simulating phantom containing an inclusion with higher hemoglobin, lower oxygenation and contrast in scatter. The recovered images were quantitatively accurate and showed substantial improvement over existing methods; and in addition, showed robust results tested for up to 5% noise in amplitude and phase measurements. When applied to a clinical subject with fibrocystic disease, the tumor was visible in hemoglobin and water, but no decrease in oxygenation was observed, making oxygen saturation, a potential diagnostic indicator.

Role of care pathways in interprofessional teamwork.

Science.gov (United States)

Scaria, Minimol Kulakkottu

2016-08-24

Cohesive interprofessional teamwork is essential to successful healthcare services. Interprofessional teamwork is the means by which different healthcare professionals - with diverse knowledge, skills and talents - collaborate to achieve a common goal. Several interventions are available to improve teamwork in the healthcare setting. This article explores the role of care pathways in improving interprofessional teamwork. Care pathways enhance teamwork by promoting coordination, collaboration, communication and decision making to achieve optimal healthcare outcomes. They result in improved staff knowledge, communication, documentation and interprofessional relations. Care pathways also contribute to patient-centred care and increase patient satisfaction.

DMPD: Parallel pathways of virus recognition. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 16713969 Parallel pathways of virus recognition. Tenoever BR, Maniatis T. Immunity.... 2006 May;24(5):510-2. (.png) (.svg) (.html) (.csml) Show Parallel pathways of virus recognition. PubmedID 1...6713969 Title Parallel pathways of virus recognition. Authors Tenoever BR, Maniatis T. Publication Immunity.

Determining Pathways to Improvements in Fatigue in Rheumatoid Arthritis: Results From the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis.

Science.gov (United States)

Druce, Katie L; Jones, Gareth T; Macfarlane, Gary J; Basu, Neil

2015-09-01

There is debate as to the role of inflammatory disease activity in the etiology of rheumatoid arthritis (RA)-related fatigue. We undertook this study to determine the relationship of fatigue to disease activity by examining pathways associated with change in fatigue in subjects starting anti-tumor necrosis factor (anti-TNF) therapy for the first time. Participants who had been recruited to the British Society for Rheumatology Biologics Register for RA provided information on fatigue (Short Form 36 [SF-36] vitality scale) and other health status variables at the start of anti-TNF therapy and 6 months later. The Disease Activity Score in 28 joints (DAS28) and inflammation (erythrocyte sedimentation rate [ESR]/C-reactive protein [CRP] level) were also reported. A path analysis model comprising changes in fatigue, pain, disease activity, disability, and mental health, along with effects of sex and a history of depression, was used to examine those with high levels of fatigue at baseline (score of ≤12.5 units on the SF-36 vitality scale). The DAS28 was substituted for ESR/CRP to delineate the specific role of inflammation. With a total of 2,652 participants, we identified a well-fitting model (χ2  = 0.18, P = 0.98) accounting for 40% of the variance in fatigue change. There was no direct pathway from change in inflammation to change in fatigue; instead, significant pathways to change in fatigue were observed from changes in disease activity, pain, mental health, and disability, along with effects of sex and a history of depression. A total of 82% of the effect of change in disease activity was indirect, of which ∼50% was mediated through a change in pain. Improvements in fatigue do not appear to be driven by inflammatory disease activity; instead, they appear to result indirectly from improvements in pain. Additional significant pathways through disability and mental health suggest potentially modifiable factors that could be targeted to improve clinically

A systems biology approach for pathway level analysis

OpenAIRE

Draghici, Sorin; Khatri, Purvesh; Tarca, Adi Laurentiu; Amin, Kashyap; Done, Arina; Voichita, Calin; Georgescu, Constantin; Romero, Roberto

2007-01-01

A common challenge in the analysis of genomics data is trying to understand the underlying phenomenon in the context of all complex interactions taking place on various signaling pathways. A statistical approach using various models is universally used to identify the most relevant pathways in a given experiment. Here, we show that the existing pathway analysis methods fail to take into consideration important biological aspects and may provide incorrect results in certain situations. By usin...

Machine learning methods for metabolic pathway prediction

Directory of Open Access Journals (Sweden)

Karp Peter D

2010-01-01

Full Text Available Abstract Background A key challenge in systems biology is the reconstruction of an organism's metabolic network from its genome sequence. One strategy for addressing this problem is to predict which metabolic pathways, from a reference database of known pathways, are present in the organism, based on the annotated genome of the organism. Results To quantitatively validate methods for pathway prediction, we developed a large "gold standard" dataset of 5,610 pathway instances known to be present or absent in curated metabolic pathway databases for six organisms. We defined a collection of 123 pathway features, whose information content we evaluated with respect to the gold standard. Feature data were used as input to an extensive collection of machine learning (ML methods, including naïve Bayes, decision trees, and logistic regression, together with feature selection and ensemble methods. We compared the ML methods to the previous PathoLogic algorithm for pathway prediction using the gold standard dataset. We found that ML-based prediction methods can match the performance of the PathoLogic algorithm. PathoLogic achieved an accuracy of 91% and an F-measure of 0.786. The ML-based prediction methods achieved accuracy as high as 91.2% and F-measure as high as 0.787. The ML-based methods output a probability for each predicted pathway, whereas PathoLogic does not, which provides more information to the user and facilitates filtering of predicted pathways. Conclusions ML methods for pathway prediction perform as well as existing methods, and have qualitative advantages in terms of extensibility, tunability, and explainability. More advanced prediction methods and/or more sophisticated input features may improve the performance of ML methods. However, pathway prediction performance appears to be limited largely by the ability to correctly match enzymes to the reactions they catalyze based on genome annotations.

Machine learning methods for metabolic pathway prediction

Science.gov (United States)

2010-01-01

Background A key challenge in systems biology is the reconstruction of an organism's metabolic network from its genome sequence. One strategy for addressing this problem is to predict which metabolic pathways, from a reference database of known pathways, are present in the organism, based on the annotated genome of the organism. Results To quantitatively validate methods for pathway prediction, we developed a large "gold standard" dataset of 5,610 pathway instances known to be present or absent in curated metabolic pathway databases for six organisms. We defined a collection of 123 pathway features, whose information content we evaluated with respect to the gold standard. Feature data were used as input to an extensive collection of machine learning (ML) methods, including naïve Bayes, decision trees, and logistic regression, together with feature selection and ensemble methods. We compared the ML methods to the previous PathoLogic algorithm for pathway prediction using the gold standard dataset. We found that ML-based prediction methods can match the performance of the PathoLogic algorithm. PathoLogic achieved an accuracy of 91% and an F-measure of 0.786. The ML-based prediction methods achieved accuracy as high as 91.2% and F-measure as high as 0.787. The ML-based methods output a probability for each predicted pathway, whereas PathoLogic does not, which provides more information to the user and facilitates filtering of predicted pathways. Conclusions ML methods for pathway prediction perform as well as existing methods, and have qualitative advantages in terms of extensibility, tunability, and explainability. More advanced prediction methods and/or more sophisticated input features may improve the performance of ML methods. However, pathway prediction performance appears to be limited largely by the ability to correctly match enzymes to the reactions they catalyze based on genome annotations. PMID:20064214

Metabolism of cysteine by cyteinesulfinate-independent pathway(s) in rat hepatocytes

International Nuclear Information System (INIS)

Stipanuk, M.H.; De La Rosa, J.; Drake, M.R.

1986-01-01

The metabolism of cysteine (CYS) and that of cysteinesulfinate (CSA) were studied in freshly isolated hepatocytes from fed rats. In incubations of rat hepatocytes with either 1 or 25 mM CSA, over 90% of the 14 CO 2 formed from [1- 14 C]CSA could be accounted for by production of hypotaurine plus taurine. In similar incubations with 1 or 25 mM CYS, only 4% of 14 CO 2 evolution from [1- 14 C]CYS could be accounted for by production of hypotaurine plus taurine. Addition of unlabeled CSA inhibited recovery of label from [1- 14 C]CYS as 14 CO 2 by 33%. Metabolism of CYS and of CSA were affected differently by addition of α-ketoglutarate, a cosubstrate for transamination, or of propargylglycine, an inhibitor of cystathionase activity. These data suggest that a substantial proportion of CYS is catabolized by CSA-independent pathways in the rat hepatocyte. Although addition of α-ketoglutarate to incubations of hepatocytes with CSA resulted in a marked increase in CSA catabolism via the transamination pathway, addition of keto acids to incubation systems had little or no effect on production of any metabolite from CYS. Thus, CYS transamination does not appear to be a major pathway of CYS metabolism in the hepatocyte. Inhibition of cystathionase with propargylglycine reduced both 14 CO 2 production from [1- 14 C]CYS and ammonia plus urea nitrogen production from CYS by about 50%; CSA catabolism was not affected. Thus, cleavage of cyst(e)ine by cystathionase may be an important physiological pathway for CYS catabolism in the liver

Characterization results and Markov chain Monte Carlo algorithms including exact simulation for some spatial point processes

DEFF Research Database (Denmark)

Häggström, Olle; Lieshout, Marie-Colette van; Møller, Jesper

1999-01-01

The area-interaction process and the continuum random-cluster model are characterized in terms of certain functional forms of their respective conditional intensities. In certain cases, these two point process models can be derived from a bivariate point process model which in many respects...... is simpler to analyse and simulate. Using this correspondence we devise a two-component Gibbs sampler, which can be used for fast and exact simulation by extending the recent ideas of Propp and Wilson. We further introduce a Swendsen-Wang type algorithm. The relevance of the results within spatial statistics...

DMPD: Signaling pathways activated by microorganisms. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 17303405 Signaling pathways activated by microorganisms. Takeuchi O, Akira S. Curr ...Opin Cell Biol. 2007 Apr;19(2):185-91. Epub 2007 Feb 15. (.png) (.svg) (.html) (.csml) Show Signaling pathways activated by microorg...anisms. PubmedID 17303405 Title Signaling pathways activated by microorganisms. Auth

Advanced Instrumentation, Information, and Control Systems Technologies Pathway: FY 2016 External Review

Energy Technology Data Exchange (ETDEWEB)

Thomas, Kenneth David [Idaho National Lab. (INL), Idaho Falls, ID (United States); Hallbert, Bruce Perry [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2016-11-01

This report describes an External Review conducted by the LWRS Program Advanced Instrumentation, Information, and Control (II&C) Systems Technologies Pathway to solicit feedback on the topics and results of the ongoing II&C research program. This review was held in conjunction with the Nuclear Energy Institute (NEI) Digital I&C Working Group meeting that was held at Idaho National Laboratory (INL) on August 9-10, 2016. Given the opportunity to visit INL and see the pathway research projects, NEI agreed that the Working Group would serve as the External Review panel for the purpose of obtaining expert input on the value and timing of the research projects. This consisted of demonstrations in the Human Systems Simulation Laboratory followed by presentations on the II&C research program in general as well as the five technology development areas. Following the meeting, the presentations were sent to each of the attendees so they could review them in more detail and refer to them in completing the feedback form. Follow-up activities were conducted with the attendees following the meeting to obtain the completed feedback forms. A total of 13 forms were returned. The feedback forms were reviewed by the pathway to compile the data and comments received, which are documented in the report. In all, the feedback provided by the External Review participants is taken to be a strong endorsement of the types of projects being conducted by the pathway, the value they hold for the nuclear plants, and the general timing of need. The feedback aligns well with the priorities, levels of efforts allocated for the research projects, and project schedules. The feedback also represents realistic observations on the practicality of some aspects of implementing these technologies. In some cases, the participants provided thoughtful challenges to certain assumptions in the formulation of the technologies or in deployment plans. These deserve further review and revision of plans if warranted

Advanced Instrumentation, Information, and Control Systems Technologies Pathway: FY 2016 External Review

International Nuclear Information System (INIS)

Thomas, Kenneth David; Hallbert, Bruce Perry

2016-01-01

This report describes an External Review conducted by the LWRS Program Advanced Instrumentation, Information, and Control (II&C) Systems Technologies Pathway to solicit feedback on the topics and results of the ongoing II&C research program. This review was held in conjunction with the Nuclear Energy Institute (NEI) Digital I&C Working Group meeting that was held at Idaho National Laboratory (INL) on August 9-10, 2016. Given the opportunity to visit INL and see the pathway research projects, NEI agreed that the Working Group would serve as the External Review panel for the purpose of obtaining expert input on the value and timing of the research projects. This consisted of demonstrations in the Human Systems Simulation Laboratory followed by presentations on the II&C research program in general as well as the five technology development areas. Following the meeting, the presentations were sent to each of the attendees so they could review them in more detail and refer to them in completing the feedback form. Follow-up activities were conducted with the attendees following the meeting to obtain the completed feedback forms. A total of 13 forms were returned. The feedback forms were reviewed by the pathway to compile the data and comments received, which are documented in the report. In all, the feedback provided by the External Review participants is taken to be a strong endorsement of the types of projects being conducted by the pathway, the value they hold for the nuclear plants, and the general timing of need. The feedback aligns well with the priorities, levels of efforts allocated for the research projects, and project schedules. The feedback also represents realistic observations on the practicality of some aspects of implementing these technologies. In some cases, the participants provided thoughtful challenges to certain assumptions in the formulation of the technologies or in deployment plans. These deserve further review and revision of plans if warranted

Pathways to a low-carbon economy for the UK with the macro-econometric E3MG model

International Nuclear Information System (INIS)

Dagoumas, A.S.; Barker, T.S.

2010-01-01

This paper examines different carbon pathways for achieving deep CO 2 reduction targets for the UK using a macro-econometric hybrid model E3MG, which stands for Energy-Economy-Environment Model at the Global level. The E3MG, with the UK as one of its regions, combines a top-down approach for modeling the global economy and for estimating the aggregate and disaggregate energy demand and a bottom-up approach (Energy Technology subModel, ETM) for simulating the power sector, which then provides feedback to the energy demand equations and the whole economy. The ETM submodel uses a probabilistic approach and historical data for estimating the penetration levels of the different technologies, considering their economic, technical and environmental characteristics. Three pathway scenarios (CFH, CLC and CAM) simulate the CO 2 reduction by 40%, 60% and 80% by 2050 compared to 1990 levels respectively and are compared with a reference scenario (REF), with no reduction target. The targets are modeled as the UK contribution to an international mitigation effort, such as achieving the G8 reduction targets, which is a more realistic political framework for the UK to move towards deep reductions rather than moving alone. This paper aims to provide modeling evidence that deep reduction targets can be met through different carbon pathways while also assessing the macroeconomic effects of the pathways on GDP and investment.

Analysis of l-glutamic acid fermentation by using a dynamic metabolic simulation model of Escherichia coli

Science.gov (United States)

2013-01-01

Background Understanding the process of amino acid fermentation as a comprehensive system is a challenging task. Previously, we developed a literature-based dynamic simulation model, which included transcriptional regulation, transcription, translation, and enzymatic reactions related to glycolysis, the pentose phosphate pathway, the tricarboxylic acid (TCA) cycle, and the anaplerotic pathway of Escherichia coli. During simulation, cell growth was defined such as to reproduce the experimental cell growth profile of fed-batch cultivation in jar fermenters. However, to confirm the biological appropriateness of our model, sensitivity analysis and experimental validation were required. Results We constructed an l-glutamic acid fermentation simulation model by removing sucAB, a gene encoding α-ketoglutarate dehydrogenase. We then performed systematic sensitivity analysis for l-glutamic acid production; the results of this process corresponded with previous experimental data regarding l-glutamic acid fermentation. Furthermore, it allowed us to predicted the possibility that accumulation of 3-phosphoglycerate in the cell would regulate the carbon flux into the TCA cycle and lead to an increase in the yield of l-glutamic acid via fermentation. We validated this hypothesis through a fermentation experiment involving a model l-glutamic acid-production strain, E. coli MG1655 ΔsucA in which the phosphoglycerate kinase gene had been amplified to cause accumulation of 3-phosphoglycerate. The observed increase in l-glutamic acid production verified the biologically meaningful predictive power of our dynamic metabolic simulation model. Conclusions In this study, dynamic simulation using a literature-based model was shown to be useful for elucidating the precise mechanisms involved in fermentation processes inside the cell. Further exhaustive sensitivity analysis will facilitate identification of novel factors involved in the metabolic regulation of amino acid fermentation. PMID

Making assessments while taking repeated risks: a pattern of multiple response pathways.

Science.gov (United States)

Pleskac, Timothy J; Wershbale, Avishai

2014-02-01

Beyond simply a decision process, repeated risky decisions also require a number of cognitive processes including learning, search and exploration, and attention. In this article, we examine how multiple response pathways develop over repeated risky decisions. Using the Balloon Analogue Risk Task (BART) as a case study, we show that 2 different response pathways emerge over the course of the task. The assessment pathway is a slower, more controlled pathway where participants deliberate over taking a risk. The 2nd pathway is a faster, more automatic process where no deliberation occurs. Results imply the slower assessment pathway is taken as choice conflict increases and that the faster automatic response is a learned response. Based on these results, we modify an existing formal cognitive model of decision making during the BART to account for these dual response pathways. The slower more deliberative response process is modeled with a sequential sampling process where evidence is accumulated to a threshold, while the other response is given automatically. We show that adolescents with conduct disorder and substance use disorder symptoms not only evaluate risks differently during the BART but also differ in the rate at which they develop the more automatic response. More broadly, our results suggest cognitive models of judgment decision making need to transition from treating observed decisions as the result of a single response pathway to the result of multiple response pathways that change and develop over time.

Simulation of Water Gas Shift Zeolite Membrane Reactor

Science.gov (United States)

Makertiharta, I. G. B. N.; Rizki, Z.; Zunita, Megawati; Dharmawijaya, P. T.

2017-07-01

The search of alternative energy sources keeps growing from time to time. Various alternatives have been introduced to reduce the use of fossil fuel, including hydrogen. Many pathways can be used to produce hydrogen. Among all of those, the Water Gas Shift (WGS) reaction is the most common pathway to produce high purity hydrogen. The WGS technique faces a downstream processing challenge due to the removal hydrogen from the product stream itself since it contains a mixture of hydrogen, carbon dioxide and also the excess reactants. An integrated process using zeolite membrane reactor has been introduced to improve the performance of the process by selectively separate the hydrogen whilst boosting the conversion. Furthermore, the zeolite membrane reactor can be further improved via optimizing the process condition. This paper discusses the simulation of Zeolite Membrane Water Gas Shift Reactor (ZMWGSR) with variation of process condition to achieve an optimum performance. The simulation can be simulated into two consecutive mechanisms, the reaction prior to the permeation of gases through the zeolite membrane. This paper is focused on the optimization of the process parameters (e.g. temperature, initial concentration) and also membrane properties (e.g. pore size) to achieve an optimum product specification (concentration, purity).

Pathways Intern Report

Science.gov (United States)

Huggett, Daniel James

2017-01-01

The National Aeronautics and Space Administration (NASA) provides a formal training program for prospective employees titled, Pathways Intern Employment. The Pathways program targets graduate and undergraduate students who strive to become an active contributor to NASA's goal of space exploration. The report herein provides an account of Daniel Huggett's Pathways experience for the Spring and Summer 2017 semesters.

Pathway analysis: State of the art

Directory of Open Access Journals (Sweden)

Miguel Angel eGarcía-Campos

2015-12-01

Full Text Available Pathway analysis is a set of widely used tools for research in life sciences intended to give meaning to high-throughput biological data. The methodology of these tools settles in the gathering and usage of knowledge that comprise biomolecular functioning, coupled with statistical testing and other algorithms. Despite their wide employment, pathway analysis foundations and overall background may not be fully understood, leading to misinterpretation of analysis results. This review attempts to comprise the fundamental knowledge to take into consideration when using pathway analysis as a hypothesis generation tool. We discuss the key elements that are part of these methodologies, their capabilities and current deficiencies. We also present an overview of current and all-time popular methods, highlighting different classes across them. In doing so, we show the exploding diversity of methods that pathway analysis encompasses, point out commonly overlooked caveats, and direct attention to a potential new class of methods that attempt to zoom the analysis scope to the sample scale.

Analysis of emittance compensation and simulation results to photo-cathode RF gun

CERN Document Server

LiuShengGuang

2002-01-01

The emittance compensation technology will be used on the photo-cathode RF gun for Shanghai SDUV-FEL. The space charge force and its effect on electron beam transverse emittance in RF gun is studied, the principle of emittance compensation in phase-space is discussed. The authors have designed a compensation solenoid and calculated its magnetic field distribution. Its performance has been studied by the code PARMELA. A simulation result indicates that the normalized transverse RMS emittance for electron beam of 1.5 nC is 1.612 pi mm centre dot mrad, electron energy E = 5.71 MeV

Molecular evolution of the lysine biosynthetic pathways.

Science.gov (United States)

Velasco, A M; Leguina, J I; Lazcano, A

2002-10-01

Among the different biosynthetic pathways found in extant organisms, lysine biosynthesis is peculiar because it has two different anabolic routes. One is the diaminopimelic acid pathway (DAP), and the other over the a-aminoadipic acid route (AAA). A variant of the AAA route that includes some enzymes involved in arginine and leucine biosyntheses has been recently reported in Thermus thermophilus (Nishida et al. 1999). Here we describe the results of a detailed genomic analysis of each of the sequences involved in the two lysine anabolic routes, as well as of genes from other routes related to them. No evidence was found of an evolutionary relationship between the DAP and AAA enzymes. Our results suggest that the DAP pathway is related to arginine metabolism, since the lysC, asd, dapC, dapE, and lysA genes from lysine biosynthesis are related to the argB, argC, argD, argE, and speAC genes, respectively, whose products catalyze different steps in arginine metabolism. This work supports previous reports on the relationship between AAA gene products and some enzymes involved in leucine biosynthesis and the tricarboxylic acid cycle (Irvin and Bhattacharjee 1998; Miyazaki et al. 2001). Here we discuss the significance of the recent finding that several genes involved in the arginine (Arg) and leucine (Leu) biosynthesis participate in a new alternative route of the AAA pathway (Miyazaki et al. 2001). Our results demonstrate a clear relationship between the DAP and Arg routes, and between the AAA and Leu pathways.

Impact of Assimilation on Heavy Rainfall Simulations Using WRF Model: Sensitivity of Assimilation Results to Background Error Statistics

Science.gov (United States)

Rakesh, V.; Kantharao, B.

2017-03-01

Data assimilation is considered as one of the effective tools for improving forecast skill of mesoscale models. However, for optimum utilization and effective assimilation of observations, many factors need to be taken into account while designing data assimilation methodology. One of the critical components that determines the amount and propagation observation information into the analysis, is model background error statistics (BES). The objective of this study is to quantify how BES in data assimilation impacts on simulation of heavy rainfall events over a southern state in India, Karnataka. Simulations of 40 heavy rainfall events were carried out using Weather Research and Forecasting Model with and without data assimilation. The assimilation experiments were conducted using global and regional BES while the experiment with no assimilation was used as the baseline for assessing the impact of data assimilation. The simulated rainfall is verified against high-resolution rain-gage observations over Karnataka. Statistical evaluation using several accuracy and skill measures shows that data assimilation has improved the heavy rainfall simulation. Our results showed that the experiment using regional BES outperformed the one which used global BES. Critical thermo-dynamic variables conducive for heavy rainfall like convective available potential energy simulated using regional BES is more realistic compared to global BES. It is pointed out that these results have important practical implications in design of forecast platforms while decision-making during extreme weather events

Precipitation and total power consumption in the ionosphere: Global MHD simulation results compared with Polar and SNOE observations

Directory of Open Access Journals (Sweden)

M. Palmroth

2006-05-01

Full Text Available We compare the ionospheric electron precipitation morphology and power from a global MHD simulation (GUMICS-4 with direct measurements of auroral energy flux during a pair of substorms on 28-29 March 1998. The electron precipitation power is computed directly from global images of auroral light observed by the Polar satellite ultraviolet imager (UVI. Independent of the Polar UVI measurements, the electron precipitation energy is determined from SNOE satellite observations on the thermospheric nitric oxide (NO density. We find that the GUMICS-4 simulation reproduces the spatial variation of the global aurora rather reliably in the sense that the onset of the substorm is shown in GUMICS-4 simulation as enhanced precipitation in the right location at the right time. The total integrated precipitation power in the GUMICS-4 simulation is in quantitative agreement with the observations during quiet times, i.e., before the two substorm intensifications. We find that during active times the GUMICS-4 integrated precipitation is a factor of 5 lower than the observations indicate. However, we also find factor of 2-3 differences in the precipitation power among the three different UVI processing methods tested here. The findings of this paper are used to complete an earlier objective, in which the total ionospheric power deposition in the simulation is forecasted from a mathematical expression, which is a function of solar wind density, velocity and magnetic field. We find that during this event, the correlation coefficient between the outcome of the forecasting expression and the simulation results is 0.83. During the event, the simulation result on the total ionospheric power deposition agrees with observations (correlation coefficient 0.8 and the AE index (0.85.

Interactions among oscillatory pathways in NF-kappa B signaling

Directory of Open Access Journals (Sweden)

White Michael RH

2011-02-01

Full Text Available Abstract Background Sustained stimulation with tumour necrosis factor alpha (TNF-alpha induces substantial oscillations—observed at both the single cell and population levels—in the nuclear factor kappa B (NF-kappa B system. Although the mechanism has not yet been elucidated fully, a core system has been identified consisting of a negative feedback loop involving NF-kappa B (RelA:p50 hetero-dimer and its inhibitor I-kappa B-alpha. Many authors have suggested that this core oscillator should couple to other oscillatory pathways. Results First we analyse single-cell data from experiments in which the NF-kappa B system is forced by short trains of strong pulses of TNF-alpha. Power spectra of the ratio of nuclear-to-cytoplasmic concentration of NF-kappa B suggest that the cells' responses are entrained by the pulsing frequency. Using a recent model of the NF-kappa B system due to Caroline Horton, we carried out extensive numerical simulations to analyze the response frequencies induced by trains of pulses of TNF-alpha stimulation having a wide range of frequencies and amplitudes. These studies suggest that for sufficiently weak stimulation, various nonlinear resonances should be observable. To explore further the possibility of probing alternative feedback mechanisms, we also coupled the model to sinusoidal signals with a wide range of strengths and frequencies. Our results show that, at least in simulation, frequencies other than those of the forcing and the main NF-kappa B oscillator can be excited via sub- and superharmonic resonance, producing quasiperiodic and even chaotic dynamics. Conclusions Our numerical results suggest that the entrainment phenomena observed in pulse-stimulated experiments is a consequence of the high intensity of the stimulation. Computational studies based on current models suggest that resonant interactions between periodic pulsatile forcing and the system's natural frequencies may become evident for sufficiently

Impacts of Four SO2 Oxidation Pathways on Wintertime Sulfate Concentrations

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Sarwar, G.; Fahey, K.; Zhang, Y.; Kang, D.; Mathur, R.; Xing, J.; Wei, C.; Cheng, Y.

2017-12-01

Air quality models tend to under-estimate winter-time sulfate concentrations compared to observed data. Such under-estimations are particularly acute in China where very high concentrations of sulfate have been measured. Sulfate is produced by oxidation of sulfur dioxide (SO2) in gas-phase by hydroxyl radical and in aqueous-phase by hydrogen peroxide, ozone, etc. and most air quality models employ such typical reactions. Several additional SO2 oxidation pathways have recently been proposed. Heterogeneous reaction on dust has been suggested to be an important sink for SO2. Oxidation of SO2 on fine particles in presence of nitrogen dioxide (NO2) and ammonia (NH3) at high relative humidity has been implicated for sulfate formation in Chinese haze and London fog. Reactive nitrogen chemistry in aerosol water has also been suggested to produce winter-time sulfate in China. Specifically, high aerosol water can trap SO2 which can be subsequently oxidized by NO2 to form sulfate. Aqueous-phase (in-cloud) oxidation of SO2 by NO2 can also produce sulfate. Here, we use the hemispheric Community Multiscale Air Quality (CMAQ) modeling system to examine the potential impacts of these SO2 oxidation pathways on sulfate formation. We use anthropogenic emissions from the Emissions Database for Global Atmospheric Research and biogenic emissions from Global Emissions InitiAtive. We performed simulations without and with these SO2 oxidation pathways for October-December of 2014 using meteorological fields obtained from the Weather Research and Forecasting model. The standard CMAQ model contains one gas-phase chemical reaction and five aqueous-phase chemical reactions for SO2 oxidation. We implement four additional SO2 oxidation pathways into the CMAQ model. Our preliminary results suggest that the dust chemistry enhances mean sulfate over parts of China and Middle-East, the in-cloud SO2 oxidation by NO2 enhances sulfate over parts of western Europe, oxidation of SO2 by NO2 and NH3 on

Aquatic pathway 2

International Nuclear Information System (INIS)

1977-01-01

This third part of the investigation discusses the preliminary results of sub-investigations concerning problems of the release of radioactive substances into the environment via the water pathway. On the basis of papers on the emission into the draining ditch and the exchange processes there, investigations of a possible incorporation via different exposure pathways are reported. Special regard is paid to drinking water supply aquatic foodstuffs, the river sediment, the utilisation of the agricultural surfaces and the draining ditch including its pre-pollution. The dynamics of contamination processes is reported on with regard to the problem of accidents. The colloquium will give an outline of the progress made so far and admit participants' suggestions for further work on the sub-investigations. The following colloquia will report further findings, in particular effects on aquatic ecosystems. (orig.) [de

Predicting metabolic pathways by sub-network extraction.

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Faust, Karoline; van Helden, Jacques

2012-01-01

Various methods result in groups of functionally related genes obtained from genomes (operons, regulons, syntheny groups, and phylogenetic profiles), transcriptomes (co-expression groups) and proteomes (modules of interacting proteins). When such groups contain two or more enzyme-coding genes, graph analysis methods can be applied to extract a metabolic pathway that interconnects them. We describe here the way to use the Pathway extraction tool available on the NeAT Web server ( http://rsat.ulb.ac.be/neat/ ) to piece together the metabolic pathway from a group of associated, enzyme-coding genes. The tool identifies the reactions that can be catalyzed by the products of the query genes (seed reactions), and applies sub-graph extraction algorithms to extract from a metabolic network a sub-network that connects the seed reactions. This sub-network represents the predicted metabolic pathway. We describe here the pathway prediction process in a step-by-step way, give hints about the main parametric choices, and illustrate how this tool can be used to extract metabolic pathways from bacterial genomes, on the basis of two study cases: the isoleucine-valine operon in Escherichia coli and a predicted operon in Cupriavidus (Ralstonia) metallidurans.

Examination of tetrahydrobiopterin pathway genes in autism.

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Schnetz-Boutaud, N C; Anderson, B M; Brown, K D; Wright, H H; Abramson, R K; Cuccaro, M L; Gilbert, J R; Pericak-Vance, M A; Haines, J L

2009-11-01

Autism is a complex disorder with a high degree of heritability and significant phenotypic and genotypic heterogeneity. Although candidate gene studies and genome-wide screens have failed to identify major causal loci associated with autism, numerous studies have proposed association with several variations in genes in the dopaminergic and serotonergic pathways. Because tetrahydrobiopterin (BH4) is the essential cofactor in the synthesis of these two neurotransmitters, we genotyped 25 SNPs in nine genes of the BH4 pathway in a total of 403 families. Significant nominal association was detected in the gene for 6-pyruvoyl-tetrahydropterin synthase, PTS (chromosome 11), with P = 0.009; this result was not restricted to an affected male-only subset. Multilocus interaction was detected in the BH4 pathway alone, but not across the serotonin, dopamine and BH4 pathways.

Targeting the GPI biosynthetic pathway.

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Yadav, Usha; Khan, Mohd Ashraf

2018-02-27

The GPI (Glycosylphosphatidylinositol) biosynthetic pathway is a multistep conserved pathway in eukaryotes that culminates in the generation of GPI glycolipid which in turn anchors many proteins (GPI-APs) to the cell surface. In spite of the overall conservation of the pathway, there still exist subtle differences in the GPI pathway of mammals and other eukaryotes which holds a great promise so far as the development of drugs/inhibitors against specific targets in the GPI pathway of pathogens is concerned. Many of the GPI structures and their anchored proteins in pathogenic protozoans and fungi act as pathogenicity factors. Notable examples include GPI-anchored variant surface glycoprotein (VSG) in Trypanosoma brucei, GPI-anchored merozoite surface protein 1 (MSP1) and MSP2 in Plasmodium falciparum, protein-free GPI related molecules like lipophosphoglycans (LPGs) and glycoinositolphospholipids (GIPLs) in Leishmania spp., GPI-anchored Gal/GalNAc lectin and proteophosphoglycans in Entamoeba histolytica or the GPI-anchored mannoproteins in pathogenic fungi like Candida albicans. Research in this active area has already yielded encouraging results in Trypanosoma brucei by the development of parasite-specific inhibitors of GlcNCONH 2 -β-PI, GlcNCONH 2 -(2-O-octyl)-PI and salicylic hydroxamic acid (SHAM) targeting trypanosomal GlcNAc-PI de-N-acetylase as well as the development of antifungal inhibitors like BIQ/E1210/gepinacin/G365/G884 and YW3548/M743/M720 targeting the GPI specific fungal inositol acyltransferase (Gwt1) and the phosphoethanolamine transferase-I (Mcd4), respectively. These confirm the fact that the GPI pathway continues to be the focus of researchers, given its implications for the betterment of human life.

Free energy landscape and transition pathways from Watson-Crick to Hoogsteen base pairing in free duplex DNA.

Science.gov (United States)

Yang, Changwon; Kim, Eunae; Pak, Youngshang

2015-09-18

Houghton (HG) base pairing plays a central role in the DNA binding of proteins and small ligands. Probing detailed transition mechanism from Watson-Crick (WC) to HG base pair (bp) formation in duplex DNAs is of fundamental importance in terms of revealing intrinsic functions of double helical DNAs beyond their sequence determined functions. We investigated a free energy landscape of a free B-DNA with an adenosine-thymine (A-T) rich sequence to probe its conformational transition pathways from WC to HG base pairing. The free energy landscape was computed with a state-of-art two-dimensional umbrella molecular dynamics simulation at the all-atom level. The present simulation showed that in an isolated duplex DNA, the spontaneous transition from WC to HG bp takes place via multiple pathways. Notably, base flipping into the major and minor grooves was found to play an important role in forming these multiple transition pathways. This finding suggests that naked B-DNA under normal conditions has an inherent ability to form HG bps via spontaneous base opening events. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Optimal structural inference of signaling pathways from unordered and overlapping gene sets.

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Acharya, Lipi R; Judeh, Thair; Wang, Guangdi; Zhu, Dongxiao

2012-02-15

A plethora of bioinformatics analysis has led to the discovery of numerous gene sets, which can be interpreted as discrete measurements emitted from latent signaling pathways. Their potential to infer signaling pathway structures, however, has not been sufficiently exploited. Existing methods accommodating discrete data do not explicitly consider signal cascading mechanisms that characterize a signaling pathway. Novel computational methods are thus needed to fully utilize gene sets and broaden the scope from focusing only on pairwise interactions to the more general cascading events in the inference of signaling pathway structures. We propose a gene set based simulated annealing (SA) algorithm for the reconstruction of signaling pathway structures. A signaling pathway structure is a directed graph containing up to a few hundred nodes and many overlapping signal cascades, where each cascade represents a chain of molecular interactions from the cell surface to the nucleus. Gene sets in our context refer to discrete sets of genes participating in signal cascades, the basic building blocks of a signaling pathway, with no prior information about gene orderings in the cascades. From a compendium of gene sets related to a pathway, SA aims to search for signal cascades that characterize the optimal signaling pathway structure. In the search process, the extent of overlap among signal cascades is used to measure the optimality of a structure. Throughout, we treat gene sets as random samples from a first-order Markov chain model. We evaluated the performance of SA in three case studies. In the first study conducted on 83 KEGG pathways, SA demonstrated a significantly better performance than Bayesian network methods. Since both SA and Bayesian network methods accommodate discrete data, use a 'search and score' network learning strategy and output a directed network, they can be compared in terms of performance and computational time. In the second study, we compared SA and

3D electromagnetic simulation of spatial autoresonance acceleration of electron beams