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...

Systems biology approach to developing S2RM-based ＂systemstherapeutics＂ and naturally induced pluripotent stem cells

Institute of Scientific and Technical Information of China (English)

2015-01-01

The degree to, and the mechanisms through, whichstem cells are able to build, maintain, and heal the bodyhave only recently begun to be understood. Much of thestem cell＇s power resides in the release of a multitudeof molecules, called stem cell released molecules （SRM）.A fundamentally new type of therapeutic, namely＂systems therapeutic＂, can be realized by reverseengineering the mechanisms of the SRM processes.Recent data demonstrates that the composition of theSRM is different for each type of stem cell, as well asfor different states of each cell type. Although systemsbiology has been successfully used to analyze multiplepathways, the approach is often used to develop a smallmolecule interacting at only one pathway in the system.A new model is emerging in biology where systemsbiology is used to develop a new technology actingat multiple pathways called ＂systems therapeutics＂. Anatural set of healing pathways in the human that usesSRM is instructive and of practical use in developingsystems therapeutics. Endogenous SRM processes inthe human body use a combination of SRM from twoor more stem cell types, designated as S2RM, doing sounder various state dependent conditions for each celltype. Here we describe our approach in using statedependentSRM from two or more stem cell types,S2RM technology, to develop a new class of therapeuticscalled ＂systems therapeutics.＂ Given the ubiquitous andpowerful nature of innate S2RM-based healing in thehuman body, this ＂systems therapeutic＂ approach usingS2RM technology will be important for the developmentof anti-cancer therapeutics, antimicrobials, woundcare products and procedures, and a number of othertherapeutics for many indications.

Introducing spatial information into predictive NF-kappaB modelling--an agent-based approach.

Directory of Open Access Journals (Sweden)

Mark Pogson

2008-06-01

Full Text Available Nature is governed by local interactions among lower-level sub-units, whether at the cell, organ, organism, or colony level. Adaptive system behaviour emerges via these interactions, which integrate the activity of the sub-units. To understand the system level it is necessary to understand the underlying local interactions. Successful models of local interactions at different levels of biological organisation, including epithelial tissue and ant colonies, have demonstrated the benefits of such 'agent-based' modelling. Here we present an agent-based approach to modelling a crucial biological system--the intracellular NF-kappaB signalling pathway. The pathway is vital to immune response regulation, and is fundamental to basic survival in a range of species. Alterations in pathway regulation underlie a variety of diseases, including atherosclerosis and arthritis. Our modelling of individual molecules, receptors and genes provides a more comprehensive outline of regulatory network mechanisms than previously possible with equation-based approaches. The method also permits consideration of structural parameters in pathway regulation; here we predict that inhibition of NF-kappaB is directly affected by actin filaments of the cytoskeleton sequestering excess inhibitors, therefore regulating steady-state and feedback behaviour.

Development of an image-based screening system for inhibitors of the plastidial MEP pathway and of protein geranylgeranylation

Science.gov (United States)

Hartmann, Michael; Gas-Pascual, Elisabet; Hemmerlin, Andrea; Rohmer, Michel; Bach, Thomas J.

2015-01-01

In a preceding study we have recently established an in vivo visualization system for the geranylgeranylation of proteins in a stably transformed tobacco BY-2 cell line, which involves expressing a dexamethasone-inducible GFP fused to the prenylable, carboxy-terminal basic domain of the rice calmodulin CaM61, which naturally bears a CaaL geranylgeranylation motif (GFP-BD-CVIL). By using pathway-specific inhibitors it was there demonstrated that inhibition of the methylerythritol phosphate (MEP) pathway with oxoclomazone and fosmidomycin, as well as inhibition of protein geranylgeranyl transferase type 1 (PGGT-1), shifted the localization of the GFP-BD-CVIL protein from the membrane to the nucleus. In contrast, the inhibition of the mevalonate (MVA) pathway with mevinolin did not affect this localization. Furthermore, in this initial study complementation assays with pathway-specific intermediates confirmed that the precursors for the cytosolic isoprenylation of this fusion protein are predominantly provided by the MEP pathway. In order to optimize this visualization system from a more qualitative assay to a statistically trustable medium or a high-throughput screening system, we established now new conditions that permit culture and analysis in 96-well microtiter plates, followed by fluorescence microscopy. For further refinement, the existing GFP-BD-CVIL cell line was transformed with an estradiol-inducible vector driving the expression of a RFP protein, C-terminally fused to a nuclear localization signal (NLS-RFP). We are thus able to quantify the total number of viable cells versus the number of inhibited cells after various treatments. This approach also includes a semi-automatic counting system, based on the freely available image processing software. As a result, the time of image analysis as well as the risk of user-generated bias is reduced to a minimum. Moreover, there is no cross-induction of gene expression by dexamethasone and estradiol, which is an

A systems genetics approach provides a bridge from discovered genetic variants to biological pathways in rheumatoid arthritis.

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Hirofumi Nakaoka

Full Text Available Genome-wide association studies (GWAS have yielded novel genetic loci underlying common diseases. We propose a systems genetics approach to utilize these discoveries for better understanding of the genetic architecture of rheumatoid arthritis (RA. Current evidence of genetic associations with RA was sought through PubMed and the NHGRI GWAS catalog. The associations of 15 single nucleotide polymorphisms and HLA-DRB1 alleles were confirmed in 1,287 cases and 1,500 controls of Japanese subjects. Among these, HLA-DRB1 alleles and eight SNPs showed significant associations and all but one of the variants had the same direction of effect as identified in the previous studies, indicating that the genetic risk factors underlying RA are shared across populations. By receiver operating characteristic curve analysis, the area under the curve (AUC for the genetic risk score based on the selected variants was 68.4%. For seropositive RA patients only, the AUC improved to 70.9%, indicating good but suboptimal predictive ability. A simulation study shows that more than 200 additional loci with similar effect size as recent GWAS findings or 20 rare variants with intermediate effects are needed to achieve AUC = 80.0%. We performed the random walk with restart (RWR algorithm to prioritize genes for future mapping studies. The performance of the algorithm was confirmed by leave-one-out cross-validation. The RWR algorithm pointed to ZAP70 in the first rank, in which mutation causes RA-like autoimmune arthritis in mice. By applying the hierarchical clustering method to a subnetwork comprising RA-associated genes and top-ranked genes by the RWR, we found three functional modules relevant to RA etiology: "leukocyte activation and differentiation", "pattern-recognition receptor signaling pathway", and "chemokines and their receptors".These results suggest that the systems genetics approach is useful to find directions of future mapping strategies to illuminate

A hybrid agent-based approach for modeling microbiological systems.

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Guo, Zaiyi; Sloot, Peter M A; Tay, Joc Cing

2008-11-21

Models for systems biology commonly adopt Differential Equations or Agent-Based modeling approaches for simulating the processes as a whole. Models based on differential equations presuppose phenomenological intracellular behavioral mechanisms, while models based on Multi-Agent approach often use directly translated, and quantitatively less precise if-then logical rule constructs. We propose an extendible systems model based on a hybrid agent-based approach where biological cells are modeled as individuals (agents) while molecules are represented by quantities. This hybridization in entity representation entails a combined modeling strategy with agent-based behavioral rules and differential equations, thereby balancing the requirements of extendible model granularity with computational tractability. We demonstrate the efficacy of this approach with models of chemotaxis involving an assay of 10(3) cells and 1.2x10(6) molecules. The model produces cell migration patterns that are comparable to laboratory observations.

Integrated Pathway-Based Approach Identifies Association between Genomic Regions at CTCF and CACNB2 and Schizophrenia

NARCIS (Netherlands)

Juraeva, Dilafruz; Haenisch, Britta; Zapatka, Marc; Frank, Josef; Witt, Stephanie H.; Mühleisen, Thomas W.; Treutlein, Jens; Strohmaier, Jana; Meier, Sandra; Degenhardt, Franziska; Giegling, Ina; Ripke, Stephan; Leber, Markus; Lange, Christoph; Schulze, Thomas G.; Mössner, Rainald; Nenadic, Igor; Sauer, Heinrich; Rujescu, Dan; Maier, Wolfgang; Børglum, Anders; Ophoff, Roel; Cichon, Sven; Nöthen, Markus M.; Rietschel, Marcella; Mattheisen, Manuel; Brors, Benedikt; Kahn, René S.; Cahn, Wiepke; Linszen, Don H.; de Haan, Lieuwe; van Os, Jim; Krabbendam, Lydia; Myin-Germeys, Inez; Wiersma, Durk; Bruggeman, Richard; Mors, O.; Børglum, A. D.; Mortensen, P. B.; Pedersen, C. B.; Demontis, D.; Grove, J.; Mattheisen, M.; Hougaard, D. M.

2014-01-01

In the present study, an integrated hierarchical approach was applied to: (1) identify pathways associated with susceptibility to schizophrenia; (2) detect genes that may be potentially affected in these pathways since they contain an associated polymorphism; and (3) annotate the functional

Component-Based Approach in Learning Management System Development

Science.gov (United States)

Zaitseva, Larisa; Bule, Jekaterina; Makarov, Sergey

2013-01-01

The paper describes component-based approach (CBA) for learning management system development. Learning object as components of e-learning courses and their metadata is considered. The architecture of learning management system based on CBA being developed in Riga Technical University, namely its architecture, elements and possibilities are…

Emerging systems biology approaches in nanotoxicology: Towards a mechanism-based understanding of nanomaterial hazard and risk

Energy Technology Data Exchange (ETDEWEB)

Costa, Pedro M.; Fadeel, Bengt, E-mail: Bengt.Fadeel@ki.se

2016-05-15

Engineered nanomaterials are being developed for a variety of technological applications. However, the increasing use of nanomaterials in society has led to concerns about their potential adverse effects on human health and the environment. During the first decade of nanotoxicological research, the realization has emerged that effective risk assessment of the multitudes of new nanomaterials would benefit from a comprehensive understanding of their toxicological mechanisms, which is difficult to achieve with traditional, low-throughput, single end-point oriented approaches. Therefore, systems biology approaches are being progressively applied within the nano(eco)toxicological sciences. This novel paradigm implies that the study of biological systems should be integrative resulting in quantitative and predictive models of nanomaterial behaviour in a biological system. To this end, global ‘omics’ approaches with which to assess changes in genes, proteins, metabolites, etc. are deployed allowing for computational modelling of the biological effects of nanomaterials. Here, we highlight omics and systems biology studies in nanotoxicology, aiming towards the implementation of a systems nanotoxicology and mechanism-based risk assessment of nanomaterials. - Highlights: • Systems nanotoxicology is a multi-disciplinary approach to quantitative modelling. • Transcriptomics, proteomics and metabolomics remain the most common methods. • Global “omics” techniques should be coupled to computational modelling approaches. • The discovery of nano-specific toxicity pathways and biomarkers is a prioritized goal. • Overall, experimental nanosafety research must endeavour reproducibility and relevance.

Emerging systems biology approaches in nanotoxicology: Towards a mechanism-based understanding of nanomaterial hazard and risk

International Nuclear Information System (INIS)

Costa, Pedro M.; Fadeel, Bengt

2016-01-01

Engineered nanomaterials are being developed for a variety of technological applications. However, the increasing use of nanomaterials in society has led to concerns about their potential adverse effects on human health and the environment. During the first decade of nanotoxicological research, the realization has emerged that effective risk assessment of the multitudes of new nanomaterials would benefit from a comprehensive understanding of their toxicological mechanisms, which is difficult to achieve with traditional, low-throughput, single end-point oriented approaches. Therefore, systems biology approaches are being progressively applied within the nano(eco)toxicological sciences. This novel paradigm implies that the study of biological systems should be integrative resulting in quantitative and predictive models of nanomaterial behaviour in a biological system. To this end, global ‘omics’ approaches with which to assess changes in genes, proteins, metabolites, etc. are deployed allowing for computational modelling of the biological effects of nanomaterials. Here, we highlight omics and systems biology studies in nanotoxicology, aiming towards the implementation of a systems nanotoxicology and mechanism-based risk assessment of nanomaterials. - Highlights: • Systems nanotoxicology is a multi-disciplinary approach to quantitative modelling. • Transcriptomics, proteomics and metabolomics remain the most common methods. • Global “omics” techniques should be coupled to computational modelling approaches. • The discovery of nano-specific toxicity pathways and biomarkers is a prioritized goal. • Overall, experimental nanosafety research must endeavour reproducibility and relevance.

Bottom-up and middle-out approaches to electronic patient information systems: a focus on healthcare pathways

Directory of Open Access Journals (Sweden)

Ken Eason

2013-12-01

Full Text Available Background A study is reported that examines the use of electronic health record (EHR systems in two UK local health communities.Objective These systems were developed locally and the aim of the study was to explore how well they were supporting the coordination of care along healthcare pathways that cross the organisational boundaries between the agencies delivering health care.Results The paper presents the findings for two healthcare pathways; the Stroke Pathway and a pathway for the care of the frail elderly in their own homes. All the pathways examined involved multiple agencies and many locally tailored EHR systems are in use to aid the coordination of care. However, the ability to share electronic patient information along the pathways was patchy. The development of systems that enabled effective sharing of information was characterised by sociotechnical system development, i.e. associating the technical development with process changes and organisational changes, with local development teams that drew on all the relevant agencies in the local health community and on evolutionary development, as experience grew of the benefits that EHR systems could deliver.Conclusions The study concludes that whilst there may be a role for a national IT strategy, for example, to set standards for systems procurement that facilitate data interchange, most systems development work needs to be done at a ‘middle-out’ level in the local health community, where joint planning between healthcare agencies can occur, and at the local healthcare pathway level where systems can be matched to specific needs for information sharing.

An Event-Based Approach to Distributed Diagnosis of Continuous Systems

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Daigle, Matthew; Roychoudhurry, Indranil; Biswas, Gautam; Koutsoukos, Xenofon

2010-01-01

Distributed fault diagnosis solutions are becoming necessary due to the complexity of modern engineering systems, and the advent of smart sensors and computing elements. This paper presents a novel event-based approach for distributed diagnosis of abrupt parametric faults in continuous systems, based on a qualitative abstraction of measurement deviations from the nominal behavior. We systematically derive dynamic fault signatures expressed as event-based fault models. We develop a distributed diagnoser design algorithm that uses these models for designing local event-based diagnosers based on global diagnosability analysis. The local diagnosers each generate globally correct diagnosis results locally, without a centralized coordinator, and by communicating a minimal number of measurements between themselves. The proposed approach is applied to a multi-tank system, and results demonstrate a marked improvement in scalability compared to a centralized approach.

A protein prioritization approach tailored for the FA/BRCA pathway.

Directory of Open Access Journals (Sweden)

Anneke Haitjema

Full Text Available Fanconi anemia (FA is a heterogeneous recessive disorder associated with a markedly elevated risk to develop cancer. To date sixteen FA genes have been identified, three of which predispose heterozygous mutation carriers to breast cancer. The FA proteins work together in a genome maintenance pathway, the so-called FA/BRCA pathway which is important during the S phase of the cell cycle. Since not all FA patients can be linked to (one of the sixteen known complementation groups, new FA genes remain to be identified. In addition the complex FA network remains to be further unravelled. One of the FA genes, FANCI, has been identified via a combination of bioinformatic techniques exploiting FA protein properties and genetic linkage. The aim of this study was to develop a prioritization approach for proteins of the entire human proteome that potentially interact with the FA/BRCA pathway or are novel candidate FA genes. To this end, we combined the original bioinformatics approach based on the properties of the first thirteen FA proteins identified with publicly available tools for protein-protein interactions, literature mining (Nermal and a protein function prediction tool (FuncNet. Importantly, the three newest FA proteins FANCO/RAD51C, FANCP/SLX4, and XRCC2 displayed scores in the range of the already known FA proteins. Likewise, a prime candidate FA gene based on next generation sequencing and having a very low score was subsequently disproven by functional studies for the FA phenotype. Furthermore, the approach strongly enriches for GO terms such as DNA repair, response to DNA damage stimulus, and cell cycle-regulated genes. Additionally, overlaying the top 150 with a haploinsufficiency probability score, renders the approach more tailored for identifying breast cancer related genes. This approach may be useful for prioritization of putative novel FA or breast cancer genes from next generation sequencing efforts.

Toxicity testing in the 21 century: defining new risk assessment approaches based on perturbation of intracellular toxicity pathways.

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Sudin Bhattacharya

Full Text Available The approaches to quantitatively assessing the health risks of chemical exposure have not changed appreciably in the past 50 to 80 years, the focus remaining on high-dose studies that measure adverse outcomes in homogeneous animal populations. This expensive, low-throughput approach relies on conservative extrapolations to relate animal studies to much lower-dose human exposures and is of questionable relevance to predicting risks to humans at their typical low exposures. It makes little use of a mechanistic understanding of the mode of action by which chemicals perturb biological processes in human cells and tissues. An alternative vision, proposed by the U.S. National Research Council (NRC report Toxicity Testing in the 21(st Century: A Vision and a Strategy, called for moving away from traditional high-dose animal studies to an approach based on perturbation of cellular responses using well-designed in vitro assays. Central to this vision are (a "toxicity pathways" (the innate cellular pathways that may be perturbed by chemicals and (b the determination of chemical concentration ranges where those perturbations are likely to be excessive, thereby leading to adverse health effects if present for a prolonged duration in an intact organism. In this paper we briefly review the original NRC report and responses to that report over the past 3 years, and discuss how the change in testing might be achieved in the U.S. and in the European Union (EU. EU initiatives in developing alternatives to animal testing of cosmetic ingredients have run very much in parallel with the NRC report. Moving from current practice to the NRC vision would require using prototype toxicity pathways to develop case studies showing the new vision in action. In this vein, we also discuss how the proposed strategy for toxicity testing might be applied to the toxicity pathways associated with DNA damage and repair.

SNP-based pathway enrichment analysis for genome-wide association studies

Directory of Open Access Journals (Sweden)

Potkin Steven G

2011-04-01

Full Text Available Abstract Background Recently we have witnessed a surge of interest in using genome-wide association studies (GWAS to discover the genetic basis of complex diseases. Many genetic variations, mostly in the form of single nucleotide polymorphisms (SNPs, have been identified in a wide spectrum of diseases, including diabetes, cancer, and psychiatric diseases. A common theme arising from these studies is that the genetic variations discovered by GWAS can only explain a small fraction of the genetic risks associated with the complex diseases. New strategies and statistical approaches are needed to address this lack of explanation. One such approach is the pathway analysis, which considers the genetic variations underlying a biological pathway, rather than separately as in the traditional GWAS studies. A critical challenge in the pathway analysis is how to combine evidences of association over multiple SNPs within a gene and multiple genes within a pathway. Most current methods choose the most significant SNP from each gene as a representative, ignoring the joint action of multiple SNPs within a gene. This approach leads to preferential identification of genes with a greater number of SNPs. Results We describe a SNP-based pathway enrichment method for GWAS studies. The method consists of the following two main steps: 1 for a given pathway, using an adaptive truncated product statistic to identify all representative (potentially more than one SNPs of each gene, calculating the average number of representative SNPs for the genes, then re-selecting the representative SNPs of genes in the pathway based on this number; and 2 ranking all selected SNPs by the significance of their statistical association with a trait of interest, and testing if the set of SNPs from a particular pathway is significantly enriched with high ranks using a weighted Kolmogorov-Smirnov test. We applied our method to two large genetically distinct GWAS data sets of schizophrenia, one

A residence-time-based transport approach for the groundwater pathway in performance assessment models

Science.gov (United States)

Robinson, Bruce A.; Chu, Shaoping

2013-03-01

This paper presents the theoretical development and numerical implementation of a new modeling approach for representing the groundwater pathway in risk assessment or performance assessment model of a contaminant transport system. The model developed in the present study, called the Residence Time Distribution (RTD) Mixing Model (RTDMM), allows for an arbitrary distribution of fluid travel times to be represented, to capture the effects on the breakthrough curve of flow processes such as channelized flow and fast pathways and complex three-dimensional dispersion. Mathematical methods for constructing the model for a given RTD are derived directly from the theory of residence time distributions in flowing systems. A simple mixing model is presented, along with the basic equations required to enable an arbitrary RTD to be reproduced using the model. The practical advantages of the RTDMM include easy incorporation into a multi-realization probabilistic simulation; computational burden no more onerous than a one-dimensional model with the same number of grid cells; and straightforward implementation into available flow and transport modeling codes, enabling one to then utilize advanced transport features of that code. For example, in this study we incorporated diffusion into the stagnant fluid in the rock matrix away from the flowing fractures, using a generalized dual porosity model formulation. A suite of example calculations presented herein showed the utility of the RTDMM for the case of a radioactive decay chain, dual porosity transport and sorption.

Pathway-based Analysis of the Hidden Genetic Heterogeneities in Cancers

Directory of Open Access Journals (Sweden)

Xiaolei Zhao

2014-02-01

Full Text Available Many cancers apparently showing similar phenotypes are actually distinct at the molecular level, leading to very different responses to the same treatment. It has been recently demonstrated that pathway-based approaches are robust and reliable for genetic analysis of cancers. Nevertheless, it remains unclear whether such function-based approaches are useful in deciphering molecular heterogeneities in cancers. Therefore, we aimed to test this possibility in the present study. First, we used a NCI60 dataset to validate the ability of pathways to correctly partition samples. Next, we applied the proposed method to identify the hidden subtypes in diffuse large B-cell lymphoma (DLBCL. Finally, the clinical significance of the identified subtypes was verified using survival analysis. For the NCI60 dataset, we achieved highly accurate partitions that best fit the clinical cancer phenotypes. Subsequently, for a DLBCL dataset, we identified three hidden subtypes that showed very different 10-year overall survival rates (90%, 46% and 20% and were highly significantly (P = 0.008 correlated with the clinical survival rate. This study demonstrated that the pathway-based approach is promising for unveiling genetic heterogeneities in complex human diseases.

Simulating Chemical Kinetics Without Differential Equations: A Quantitative Theory Based on Chemical Pathways.

Science.gov (United States)

Bai, Shirong; Skodje, Rex T

2017-08-17

A new approach is presented for simulating the time-evolution of chemically reactive systems. This method provides an alternative to conventional modeling of mass-action kinetics that involves solving differential equations for the species concentrations. The method presented here avoids the need to solve the rate equations by switching to a representation based on chemical pathways. In the Sum Over Histories Representation (or SOHR) method, any time-dependent kinetic observable, such as concentration, is written as a linear combination of probabilities for chemical pathways leading to a desired outcome. In this work, an iterative method is introduced that allows the time-dependent pathway probabilities to be generated from a knowledge of the elementary rate coefficients, thus avoiding the pitfalls involved in solving the differential equations of kinetics. The method is successfully applied to the model Lotka-Volterra system and to a realistic H 2 combustion model.

Experimental Systems-Biology Approaches for Clostridia-Based Bioenergy Production

Energy Technology Data Exchange (ETDEWEB)

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

2015-04-30

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

Analyzing the genes related to Alzheimer's disease via a network and pathway-based approach.

Science.gov (United States)

Hu, Yan-Shi; Xin, Juncai; Hu, Ying; Zhang, Lei; Wang, Ju

2017-04-27

means of network and pathway-based methodology, we explored the pathogenetic mechanism underlying AD at a systems biology level. Results from our work could provide valuable clues for understanding the molecular mechanism underlying AD. In addition, the framework proposed in this study could be used to investigate the pathological molecular network and genes relevant to other complex diseases or phenotypes.

Evolution of branched regulatory genetic pathways: directional selection on pleiotropic loci accelerates developmental system drift.

Science.gov (United States)

Johnson, Norman A; Porter, Adam H

2007-01-01

Developmental systems are regulated by a web of interacting loci. One common and useful approach in studying the evolution of development is to focus on classes of interacting elements within these systems. Here, we use individual-based simulations to study the evolution of traits controlled by branched developmental pathways involving three loci, where one locus regulates two different traits. We examined the system under a variety of selective regimes. In the case where one branch was under stabilizing selection and the other under directional selection, we observed "developmental system drift": the trait under stabilizing selection showed little phenotypic change even though the loci underlying that trait showed considerable evolutionary divergence. This occurs because the pleiotropic locus responds to directional selection and compensatory mutants are then favored in the pathway under stabilizing selection. Though developmental system drift may be caused by other mechanisms, it seems likely that it is accelerated by the same underlying genetic mechanism as that producing the Dobzhansky-Muller incompatibilities that lead to speciation in both linear and branched pathways. We also discuss predictions of our model for developmental system drift and how different selective regimes affect probabilities of speciation in the branched pathway system.

Approaches in anomaly-based network intrusion detection systems

NARCIS (Netherlands)

Bolzoni, D.; Etalle, S.; Di Pietro, R.; Mancini, L.V.

2008-01-01

Anomaly-based network intrusion detection systems (NIDSs) can take into consideration packet headers, the payload, or a combination of both. We argue that payload-based approaches are becoming the most effective methods to detect attacks. Nowadays, attacks aim mainly to exploit vulnerabilities at

Approaches in Anomaly-based Network Intrusion Detection Systems

NARCIS (Netherlands)

Bolzoni, D.; Etalle, Sandro

Anomaly-based network intrusion detection systems (NIDSs) can take into consideration packet headers, the payload, or a combination of both. We argue that payload-based approaches are becoming the most effective methods to detect attacks. Nowadays, attacks aim mainly to exploit vulnerabilities at

Characterizability of metabolic pathway systems from time series data.

Science.gov (United States)

Voit, Eberhard O

2013-12-01

Over the past decade, the biomathematical community has devoted substantial effort to the complicated challenge of estimating parameter values for biological systems models. An even more difficult issue is the characterization of functional forms for the processes that govern these systems. Most parameter estimation approaches tacitly assume that these forms are known or can be assumed with some validity. However, this assumption is not always true. The recently proposed method of Dynamic Flux Estimation (DFE) addresses this problem in a genuinely novel fashion for metabolic pathway systems. Specifically, DFE allows the characterization of fluxes within such systems through an analysis of metabolic time series data. Its main drawback is the fact that DFE can only directly be applied if the pathway system contains as many metabolites as unknown fluxes. This situation is unfortunately rare. To overcome this roadblock, earlier work in this field had proposed strategies for augmenting the set of unknown fluxes with independent kinetic information, which however is not always available. Employing Moore-Penrose pseudo-inverse methods of linear algebra, the present article discusses an approach for characterizing fluxes from metabolic time series data that is applicable even if the pathway system is underdetermined and contains more fluxes than metabolites. Intriguingly, this approach is independent of a specific modeling framework and unaffected by noise in the experimental time series data. The results reveal whether any fluxes may be characterized and, if so, which subset is characterizable. They also help with the identification of fluxes that, if they could be determined independently, would allow the application of DFE. Copyright © 2013 Elsevier Inc. All rights reserved.

Pathway Relevance Ranking for Tumor Samples through Network-Based Data Integration.

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Lieven P C Verbeke

Full Text Available The study of cancer, a highly heterogeneous disease with different causes and clinical outcomes, requires a multi-angle approach and the collection of large multi-omics datasets that, ideally, should be analyzed simultaneously. We present a new pathway relevance ranking method that is able to prioritize pathways according to the information contained in any combination of tumor related omics datasets. Key to the method is the conversion of all available data into a single comprehensive network representation containing not only genes but also individual patient samples. Additionally, all data are linked through a network of previously identified molecular interactions. We demonstrate the performance of the new method by applying it to breast and ovarian cancer datasets from The Cancer Genome Atlas. By integrating gene expression, copy number, mutation and methylation data, the method's potential to identify key pathways involved in breast cancer development shared by different molecular subtypes is illustrated. Interestingly, certain pathways were ranked equally important for different subtypes, even when the underlying (epi-genetic disturbances were diverse. Next to prioritizing universally high-scoring pathways, the pathway ranking method was able to identify subtype-specific pathways. Often the score of a pathway could not be motivated by a single mutation, copy number or methylation alteration, but rather by a combination of genetic and epi-genetic disturbances, stressing the need for a network-based data integration approach. The analysis of ovarian tumors, as a function of survival-based subtypes, demonstrated the method's ability to correctly identify key pathways, irrespective of tumor subtype. A differential analysis of survival-based subtypes revealed several pathways with higher importance for the bad-outcome patient group than for the good-outcome patient group. Many of the pathways exhibiting higher importance for the bad

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

A functional genomics approach using metabolomics and in silico pathway analysis

DEFF Research Database (Denmark)

Förster, Jochen; Gombert, Andreas Karoly; Nielsen, Jens

2002-01-01

analysis techniques and changes in the genotype will in many cases lead to different metabolite profiles. Here, a theoretical framework that may be applied to identify the function of orphan genes is presented. The approach is based on a combination of metabolome analysis combined with in silico pathway...

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

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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.

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.

Linear systems a measurement based approach

CERN Document Server

Bhattacharyya, S P; Mohsenizadeh, D N

2014-01-01

This brief presents recent results obtained on the analysis, synthesis and design of systems described by linear equations. It is well known that linear equations arise in most branches of science and engineering as well as social, biological and economic systems. The novelty of this approach is that no models of the system are assumed to be available, nor are they required. Instead, a few measurements made on the system can be processed strategically to directly extract design values that meet specifications without constructing a model of the system, implicitly or explicitly. These new concepts are illustrated by applying them to linear DC and AC circuits, mechanical, civil and hydraulic systems, signal flow block diagrams and control systems. These applications are preliminary and suggest many open problems. The results presented in this brief are the latest effort in this direction and the authors hope these will lead to attractive alternatives to model-based design of engineering and other systems.

Space nuclear reactor system diagnosis: Knowledge-based approach

International Nuclear Information System (INIS)

Ting, Y.T.D.

1990-01-01

SP-100 space nuclear reactor system development is a joint effort by the Department of Energy, the Department of Defense and the National Aeronautics and Space Administration. The system is designed to operate in isolation for many years, and is possibly subject to little or no remote maintenance. This dissertation proposes a knowledge based diagnostic system which, in principle, can diagnose the faults which can either cause reactor shutdown or lead to another serious problem. This framework in general can be applied to the fully specified system if detailed design information becomes available. The set of faults considered herein is identified based on heuristic knowledge about the system operation. The suitable approach to diagnostic problem solving is proposed after investigating the most prevalent methodologies in Artificial Intelligence as well as the causal analysis of the system. Deep causal knowledge modeling based on digraph, fault-tree or logic flowgraph methodology would present a need for some knowledge representation to handle the time dependent system behavior. A proposed qualitative temporal knowledge modeling methodology, using rules with specified time delay among the process variables, has been proposed and is used to develop the diagnostic sufficient rule set. The rule set has been modified by using a time zone approach to have a robust system design. The sufficient rule set is transformed to a sufficient and necessary one by searching the whole knowledge base. Qualitative data analysis is proposed in analyzing the measured data if in a real time situation. An expert system shell - Intelligence Compiler is used to develop the prototype system. Frames are used for the process variables. Forward chaining rules are used in monitoring and backward chaining rules are used in diagnosis

Development and implementation of a clinical pathway approach to simulation-based training for foregut surgery.

Science.gov (United States)

Miyasaka, Kiyoyuki W; Buchholz, Joseph; LaMarra, Denise; Karakousis, Giorgos C; Aggarwal, Rajesh

2015-01-01

Contemporary demands on resident education call for integration of simulation. We designed and implemented a simulation-based curriculum for Post Graduate Year 1 surgery residents to teach technical and nontechnical skills within a clinical pathway approach for a foregut surgery patient, from outpatient visit through surgery and postoperative follow-up. The 3-day curriculum for groups of 6 residents comprises a combination of standardized patient encounters, didactic sessions, and hands-on training. The curriculum is underpinned by a summative simulation "pathway" repeated on days 1 and 3. The "pathway" is a series of simulated preoperative, intraoperative, and postoperative encounters in following up a single patient through a disease process. The resident sees a standardized patient in the clinic presenting with distal gastric cancer and then enters an operating room to perform a gastrojejunostomy on a porcine tissue model. Finally, the resident engages in a simulated postoperative visit. All encounters are rated by faculty members and the residents themselves, using standardized assessment forms endorsed by the American Board of Surgery. A total of 18 first-year residents underwent this curriculum. Faculty ratings of overall operative performance significantly improved following the 3-day module. Ratings of preoperative and postoperative performance were not significantly changed in 3 days. Resident self-ratings significantly improved for all encounters assessed, as did reported confidence in meeting the defined learning objectives. Conventional surgical simulation training focuses on technical skills in isolation. Our novel "pathway" curriculum targets an important gap in training methodologies by placing both technical and nontechnical skills in their clinical context as part of managing a surgical patient. Results indicate consistent improvements in assessments of performance as well as confidence and support its continued usage to educate surgery residents

Environmental sciences and computations: a modular data based systems approach

International Nuclear Information System (INIS)

Crawford, T.V.; Bailey, C.E.

1975-07-01

A major computer code for environmental calculations is under development at the Savannah River Laboratory. The primary aim is to develop a flexible, efficient capability to calculate, for all significant pathways, the dose to man resulting from releases of radionuclides from the Savannah River Plant and from other existing and potential radioactive sources in the southeastern United States. The environmental sciences programs at SRP are described, with emphasis on the development of the calculational system. It is being developed as a modular data-based system within the framework of the larger JOSHUA Computer System, which provides data management, terminal, and job execution facilities. (U.S.)

System-based strategies for p53 recovery.

Science.gov (United States)

Azam, Muhammad Rizwan; Fazal, Sahar; Ullah, Mukhtar; Bhatti, Aamer I

2018-06-01

The authors have proposed a systems theory-based novel drug design approach for the p53 pathway. The pathway is taken as a dynamic system represented by ordinary differential equations-based mathematical model. Using control engineering practices, the system analysis and subsequent controller design is performed for the re-activation of wild-type p53. p53 revival is discussed for both modes of operation, i.e. the sustained and oscillatory. To define the problem in control system paradigm, modification in the existing mathematical model is performed to incorporate the effect of Nutlin. Attractor point analysis is carried out to select the suitable domain of attraction. A two-loop negative feedback control strategy is devised to drag the system trajectories to the attractor point and to regulate cellular concentration of Nutlin, respectively. An integrated framework is constituted to incorporate the pharmacokinetic effects of Nutlin in the cancerous cells. Bifurcation analysis is also performed on the p53 model to see the conditions for p53 oscillation.

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.

Representative Agricultural Pathways: A Trans-Disciplinary Approach to Agricultural Model Inter-comparison, Improvement, Climate Impact Assessment and Stakeholder Engagement

Science.gov (United States)

Antle, J. M.; Valdivia, R. O.; Claessens, L.; Nelson, G. C.; Rosenzweig, C.; Ruane, A. C.; Vervoort, J.

2013-12-01

The global change research community has recognized that new pathway and scenario concepts are needed to implement impact and vulnerability assessment that is logically consistent across local, regional and global scales. For impact and vulnerability assessment, new socio-economic pathway and scenario concepts are being developed. Representative Agricultural Pathways (RAPs) are designed to extend global pathways to provide the detail needed for global and regional assessment of agricultural systems. In addition, research by the Agricultural Model Inter-comparison and Improvement Project (AgMIP) shows that RAPs provide a powerful way to engage stakeholders in climate-related research throughout the research process and in communication of research results. RAPs are based on the integrated assessment framework developed by AgMIP. This framework shows that both bio-physical and socio-economic drivers are essential components of agricultural pathways and logically precede the definition of adaptation and mitigation scenarios that embody associated capabilities and challenges. This approach is based on a trans-disciplinary process for designing pathways and then translating them into parameter sets for bio-physical and economic models that are components of agricultural integrated assessments of climate impact, adaptation and mitigation. RAPs must be designed to be part of a logically consistent set of drivers and outcomes from global to regional and local. Global RAPs are designed to be consistent with higher-level global socio-economic pathways, but add key agricultural drivers such as agricultural growth trends that are not specified in more general pathways, as illustrated in a recent inter-comparison of global agricultural models. To create pathways at regional or local scales, further detail is needed. At this level, teams of scientists and other experts with knowledge of the agricultural systems and regions work together through a step-wise process. Experiences

Mobile Agent-Based Software Systems Modeling Approaches: A Comparative Study

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Aissam Belghiat

2016-06-01

Full Text Available Mobile agent-based applications are special type of software systems which take the advantages of mobile agents in order to provide a new beneficial paradigm to solve multiple complex problems in several fields and areas such as network management, e-commerce, e-learning, etc. Likewise, we notice lack of real applications based on this paradigm and lack of serious evaluations of their modeling approaches. Hence, this paper provides a comparative study of modeling approaches of mobile agent-based software systems. The objective is to give the reader an overview and a thorough understanding of the work that has been done and where the gaps in the research are.

Radiology information system: a workflow-based approach

International Nuclear Information System (INIS)

Zhang, Jinyan; Lu, Xudong; Nie, Hongchao; Huang, Zhengxing; Aalst, W.M.P. van der

2009-01-01

Introducing workflow management technology in healthcare seems to be prospective in dealing with the problem that the current healthcare Information Systems cannot provide sufficient support for the process management, although several challenges still exist. The purpose of this paper is to study the method of developing workflow-based information system in radiology department as a use case. First, a workflow model of typical radiology process was established. Second, based on the model, the system could be designed and implemented as a group of loosely coupled components. Each component corresponded to one task in the process and could be assembled by the workflow management system. The legacy systems could be taken as special components, which also corresponded to the tasks and were integrated through transferring non-work- flow-aware interfaces to the standard ones. Finally, a workflow dashboard was designed and implemented to provide an integral view of radiology processes. The workflow-based Radiology Information System was deployed in the radiology department of Zhejiang Chinese Medicine Hospital in China. The results showed that it could be adjusted flexibly in response to the needs of changing process, and enhance the process management in the department. It can also provide a more workflow-aware integration method, comparing with other methods such as IHE-based ones. The workflow-based approach is a new method of developing radiology information system with more flexibility, more functionalities of process management and more workflow-aware integration. The work of this paper is an initial endeavor for introducing workflow management technology in healthcare. (orig.)

Requirements and potential development pathways for fission energy supply infrastructures of the 21st century - a systems viewpoint

International Nuclear Information System (INIS)

Wade, D. C.

1999-01-01

Using an energy supply systems approach, we envision attributes and characteristic needs of a future global fission-based energy supply infrastructure, enumerate potential pathways for meeting those needs, and identify the underlying enabling science and technology developments for R and D efforts to meet the needs

Synchronization approach for chaotic time-varying delay system based on Wirtinger inequality

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Zhanshan Zhao

2017-01-01

Full Text Available A novel control approach based on Wirtinger inequality is designed for nonlinear chaos synchronization time delay system. In order to reduce the conservatism for the stability criterion, a Lyapunov–Krasovskii functional with triple-integral term is constructed. The improved Wirtinger inequality is used to reduce the conservative which is caused by Jensen inequality, and a stability criterion is proposed by reciprocally convex method. Furthermore, a state feedback controller is designed to synchronize the master-slave systems based on the proposed criteria through cone complementary linearization approach. Finally, a simulation for Lorenz chaos time delay system is given to prove the validity based on the proposed synchronization control approach.

A systems-level approach for investigating organophosphorus pesticide toxicity.

Science.gov (United States)

Zhu, Jingbo; Wang, Jing; Ding, Yan; Liu, Baoyue; Xiao, Wei

2018-03-01

The full understanding of the single and joint toxicity of a variety of organophosphorus (OP) pesticides is still unavailable, because of the extreme complex mechanism of action. This study established a systems-level approach based on systems toxicology to investigate OP pesticide toxicity by incorporating ADME/T properties, protein prediction, and network and pathway analysis. The results showed that most OP pesticides are highly toxic according to the ADME/T parameters, and can interact with significant receptor proteins to cooperatively lead to various diseases by the established OP pesticide -protein and protein-disease networks. Furthermore, the studies that multiple OP pesticides potentially act on the same receptor proteins and/or the functionally diverse proteins explained that multiple OP pesticides could mutually enhance toxicological synergy or additive on a molecular/systematic level. To the end, the integrated pathways revealed the mechanism of toxicity of the interaction of OP pesticides and elucidated the pathogenesis induced by OP pesticides. This study demonstrates a systems-level approach for investigating OP pesticide toxicity that can be further applied to risk assessments of various toxins, which is of significant interest to food security and environmental protection. Copyright © 2017 Elsevier Inc. All rights reserved.

Precise generation of systems biology models from KEGG pathways.

Science.gov (United States)

Wrzodek, Clemens; Büchel, Finja; Ruff, Manuel; Dräger, Andreas; Zell, Andreas

2013-02-21

The KEGG PATHWAY database provides a plethora of pathways for a diversity of organisms. All pathway components are directly linked to other KEGG databases, such as KEGG COMPOUND or KEGG REACTION. Therefore, the pathways can be extended with an enormous amount of information and provide a foundation for initial structural modeling approaches. As a drawback, KGML-formatted KEGG pathways are primarily designed for visualization purposes and often omit important details for the sake of a clear arrangement of its entries. Thus, a direct conversion into systems biology models would produce incomplete and erroneous models. Here, we present a precise method for processing and converting KEGG pathways into initial metabolic and signaling models encoded in the standardized community pathway formats SBML (Levels 2 and 3) and BioPAX (Levels 2 and 3). This method involves correcting invalid or incomplete KGML content, creating complete and valid stoichiometric reactions, translating relations to signaling models and augmenting the pathway content with various information, such as cross-references to Entrez Gene, OMIM, UniProt ChEBI, and many more.Finally, we compare several existing conversion tools for KEGG pathways and show that the conversion from KEGG to BioPAX does not involve a loss of information, whilst lossless translations to SBML can only be performed using SBML Level 3, including its recently proposed qualitative models and groups extension packages. Building correct BioPAX and SBML signaling models from the KEGG database is a unique characteristic of the proposed method. Further, there is no other approach that is able to appropriately construct metabolic models from KEGG pathways, including correct reactions with stoichiometry. The resulting initial models, which contain valid and comprehensive SBML or BioPAX code and a multitude of cross-references, lay the foundation to facilitate further modeling steps.

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

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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.

Integration of deep geothermal energy and woody biomass conversion pathways in urban systems

International Nuclear Information System (INIS)

Moret, Stefano; Peduzzi, Emanuela; Gerber, Léda; Maréchal, François

2016-01-01

Highlights: • Novel optimization-based methodology to integrate renewable energy systems in cities. • Multiperiod model including storage, heat integration and Life Cycle Assessment. • Case study: systematic assessment of deep geothermal and wood conversion pathways. • Identification of novel wood-geothermal hybrid systems leading to higher efficiencies. • Extensive Supplementary Material to ensure full reproducibility of the work. - Abstract: Urban systems account for about two-thirds of global primary energy consumption and energy-related greenhouse gas emissions, with a projected increasing trend. Deep geothermal energy and woody biomass can be used for the production of heat, electricity and biofuels, thus constituting a renewable alternative to fossil fuels for all end-uses in cities: heating, cooling, electricity and mobility. This paper presents a methodology to assess the potential for integrating deep geothermal energy and woody biomass in an urban energy system. The city is modeled in its entirety as a multiperiod optimization problem with the total annual cost as an objective, assessing as well the environmental impact with a Life Cycle Assessment approach. For geothermal energy, deep aquifers and Enhanced Geothermal Systems are considered for stand-alone production of heat and electricity, and for cogeneration. For biomass, besides direct combustion and cogeneration, conversion to biofuels by a set of alternative processes (pyrolysis, Fischer-Tropsch synthesis and synthetic natural gas production) is studied. With a scenario-based approach, all pathways are first individually evaluated. Secondly, all possible combinations between geothermal and biomass options are systematically compared, taking into account the possibility of hybrid systems. Results show that integrating these two resources generates configurations featuring both lower costs and environmental impacts. In particular, synergies are found in innovative hybrid systems using

Improved regional-scale Brazilian cropping systems' mapping based on a semi-automatic object-based clustering approach

Science.gov (United States)

Bellón, Beatriz; Bégué, Agnès; Lo Seen, Danny; Lebourgeois, Valentine; Evangelista, Balbino Antônio; Simões, Margareth; Demonte Ferraz, Rodrigo Peçanha

2018-06-01

Cropping systems' maps at fine scale over large areas provide key information for further agricultural production and environmental impact assessments, and thus represent a valuable tool for effective land-use planning. There is, therefore, a growing interest in mapping cropping systems in an operational manner over large areas, and remote sensing approaches based on vegetation index time series analysis have proven to be an efficient tool. However, supervised pixel-based approaches are commonly adopted, requiring resource consuming field campaigns to gather training data. In this paper, we present a new object-based unsupervised classification approach tested on an annual MODIS 16-day composite Normalized Difference Vegetation Index time series and a Landsat 8 mosaic of the State of Tocantins, Brazil, for the 2014-2015 growing season. Two variants of the approach are compared: an hyperclustering approach, and a landscape-clustering approach involving a previous stratification of the study area into landscape units on which the clustering is then performed. The main cropping systems of Tocantins, characterized by the crop types and cropping patterns, were efficiently mapped with the landscape-clustering approach. Results show that stratification prior to clustering significantly improves the classification accuracies for underrepresented and sparsely distributed cropping systems. This study illustrates the potential of unsupervised classification for large area cropping systems' mapping and contributes to the development of generic tools for supporting large-scale agricultural monitoring across regions.

A Pathway Based Classification Method for Analyzing Gene Expression for Alzheimer's Disease Diagnosis.

Science.gov (United States)

Voyle, Nicola; Keohane, Aoife; Newhouse, Stephen; Lunnon, Katie; Johnston, Caroline; Soininen, Hilkka; Kloszewska, Iwona; Mecocci, Patrizia; Tsolaki, Magda; Vellas, Bruno; Lovestone, Simon; Hodges, Angela; Kiddle, Steven; Dobson, Richard Jb

2016-01-01

Recent studies indicate that gene expression levels in blood may be able to differentiate subjects with Alzheimer's disease (AD) from normal elderly controls and mild cognitively impaired (MCI) subjects. However, there is limited replicability at the single marker level. A pathway-based interpretation of gene expression may prove more robust. This study aimed to investigate whether a case/control classification model built on pathway level data was more robust than a gene level model and may consequently perform better in test data. The study used two batches of gene expression data from the AddNeuroMed (ANM) and Dementia Case Registry (DCR) cohorts. Our study used Illumina Human HT-12 Expression BeadChips to collect gene expression from blood samples. Random forest modeling with recursive feature elimination was used to predict case/control status. Age and APOE ɛ4 status were used as covariates for all analysis. Gene and pathway level models performed similarly to each other and to a model based on demographic information only. Any potential increase in concordance from the novel pathway level approach used here has not lead to a greater predictive ability in these datasets. However, we have only tested one method for creating pathway level scores. Further, we have been able to benchmark pathways against genes in datasets that had been extensively harmonized. Further work should focus on the use of alternative methods for creating pathway level scores, in particular those that incorporate pathway topology, and the use of an endophenotype based approach.

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

Science.gov (United States)

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

2016-06-16

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

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

Mathematical and Statistical Techniques for Systems Medicine: The Wnt Signaling Pathway as a Case Study

KAUST Repository

MacLean, Adam L.

2015-12-16

The last decade has seen an explosion in models that describe phenomena in systems medicine. Such models are especially useful for studying signaling pathways, such as the Wnt pathway. In this chapter we use the Wnt pathway to showcase current mathematical and statistical techniques that enable modelers to gain insight into (models of) gene regulation and generate testable predictions. We introduce a range of modeling frameworks, but focus on ordinary differential equation (ODE) models since they remain the most widely used approach in systems biology and medicine and continue to offer great potential. We present methods for the analysis of a single model, comprising applications of standard dynamical systems approaches such as nondimensionalization, steady state, asymptotic and sensitivity analysis, and more recent statistical and algebraic approaches to compare models with data. We present parameter estimation and model comparison techniques, focusing on Bayesian analysis and coplanarity via algebraic geometry. Our intention is that this (non-exhaustive) review may serve as a useful starting point for the analysis of models in systems medicine.

Chaos based on Riemannian geometric approach to Abelian-Higgs dynamical system

International Nuclear Information System (INIS)

Kawabe, Tetsuji

2003-01-01

Based on the Riemannian geometric approach, we study chaos of the Abelian-Higgs dynamical system derived from a classical field equation consisting of a spatially homogeneous Abelian gauge field and Higgs field. Using the global indicator of chaos formulated by the sectional curvature of the ambient manifold, we show that this approach brings the same qualitative and quantitative information about order and chaos as has been provided by the Lyapunov exponents in the conventional and phenomenological approach. We confirm that the mechanism of chaos is a parametric instability of the system. By analyzing a close relation between the sectional curvature and the Gaussian curvature, we point out that the Toda-Brumer criterion becomes a sufficient condition to the criterion based on this geometric approach as to the stability condition

Distributed, price-based control approach to market-based operation of future power systems

NARCIS (Netherlands)

Jokic, A.; Bosch, van den P.P.J.; Hermans, R.M.

2009-01-01

In this paper we present, discuss and illustrate on examples the price-based control paradigm as a suitable approach to solve some of the challenging problems facing future, market-based power systems. It is illustrated how global objectives and constraints are optimally translated into time-varying

A systems biology approach to study systemic inflammation.

Science.gov (United States)

Chen, Bor-Sen; Wu, Chia-Chou

2014-01-01

Systemic inflammation needs a precise control on the sequence and magnitude of occurring events. The high throughput data on the host-pathogen interactions gives us an opportunity to have a glimpse on the systemic inflammation. In this article, a dynamic Candida albicans-zebrafish interactive infectious network is built as an example to demonstrate how systems biology approach can be used to study systematic inflammation. In particular, based on microarray data of C. albicans and zebrafish during infection, the hyphal growth, zebrafish, and host-pathogen intercellular PPI networks were combined to form an integrated infectious PPI network that helps us understand the systematic mechanisms underlying the pathogenicity of C. albicans and the immune response of the host. The signaling pathways for morphogenesis and hyphal growth of C. albicans were 2 significant interactions found in the intercellular PPI network. Two cellular networks were also developed corresponding to the different infection stages (adhesion and invasion), and then compared with each other to identify proteins to gain more insight into the pathogenic role of hyphal development in the C. albicans infection process. Important defense-related proteins in zebrafish were predicted using the same approach. This integrated network consisting of intercellular invasion and cellular defense processes during infection can improve medical therapies and facilitate development of new antifungal drugs.

Developing students’ ideas about lens imaging: teaching experiments with an image-based approach

Science.gov (United States)

Grusche, Sascha

2017-07-01

Lens imaging is a classic topic in physics education. To guide students from their holistic viewpoint to the scientists’ analytic viewpoint, an image-based approach to lens imaging has recently been proposed. To study the effect of the image-based approach on undergraduate students’ ideas, teaching experiments are performed and evaluated using qualitative content analysis. Some of the students’ ideas have not been reported before, namely those related to blurry lens images, and those developed by the proposed teaching approach. To describe learning pathways systematically, a conception-versus-time coordinate system is introduced, specifying how teaching actions help students advance toward a scientific understanding.

Allergic asthma biomarkers using systems approaches

Directory of Open Access Journals (Sweden)

Gaurab eSircar

2014-01-01

Full Text Available Asthma is characterized by lung inflammation caused by complex interaction between the immune system and environmental factors such as allergens and inorganic pollutants. Recent research in this field is focused on discovering new biomarkers associated with asthma pathogenesis. This review illustrates updated research associating biomarkers of allergic asthma and their potential use in systems biology of the disease. We focus on biomolecules with altered expression, which may serve as inflammatory, diagnostic and therapeutic biomarkers of asthma discovered in human or experimental asthma model using genomic, proteomic and epigenomic approaches for gene and protein expression profiling. These include high-throughput technologies such as state of the art microarray and proteomics Mass Spectrometry (MS platforms. Emerging concepts of molecular interactions and pathways may provide new insights in searching potential clinical biomarkers. We summarized certain pathways with significant linkage to asthma pathophysiology by analyzing the compiled biomarkers. Systems approaches with this data can identify the regulating networks, which will eventually identify the key biomarkers to be used for diagnostics and drug discovery.

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.

Consensus statement understanding health and malnutrition through a systems approach: the ENOUGH program for early life

NARCIS (Netherlands)

Kaput, J.; Ommen, B. van; Kremer, S.H.A.; Priami, C.; Pontes Monteiro, J.; Morine, M.; Pepping, F.; Diaz, Z.; Fenech, M.; He, Y.; Albers, R.; Drevon, C.A.; Evelo, C.T.; Hancock, R.E.W.; IJsselmuiden, C.; Lumey, L.H.; Minihane, A.M.; Muller, M.; Murgia, C.; Radonjic, M.; Sobral, B.; West, K.P. Jr.

2014-01-01

Nutrition research, like most biomedical disciplines, adopted and often uses experimental approaches based on Beadle and Tatum’s one gene—one polypeptide hypothesis, thereby reducing biological processes to single reactions or pathways. Systems thinking is needed to understand the complexity of

Consensus statement understanding health and malnutrition through a systems approach: the ENOUGH program for early life.

NARCIS (Netherlands)

Kaput, J.; Ommen, van B.; Kremer, B.; Priami, C.; Pontes Monteiro, J.; Morine, M.; Pepping, F.; Diaz, Z.; Fenech, M.; He, Y.; Albers, R.; Drevon, C.A.; Evelo, C.T.; Hancock, R.E.W.; Ijsselmuiden, C.; Lumey, L.H.; Minihane, A.M.; Muller, M.R.; Murgia, C.; Radonjic, M.; Sobral, B.W.S.; West Jr., K.P.

2014-01-01

Nutrition research, like most biomedical disciplines, adopted and often uses experimental approaches based on Beadle and Tatum’s one gene—one polypeptide hypothesis, thereby reducing biological processes to single reactions or pathways. Systems thinking is needed to understand the complexity of

Development and Deployment of Systems-Based Approaches for the Management of Soilborne Plant Pathogens.

Science.gov (United States)

Chellemi, D O; Gamliel, A; Katan, J; Subbarao, K V

2016-03-01

Biological suppression of soilborne diseases with minimal use of outside interventive actions has been difficult to achieve in high input conventional crop production systems due to the inherent risk of pest resurgence. This review examines previous approaches to the management of soilborne disease as precursors to the evolution of a systems-based approach, in which plant disease suppression through natural biological feedback mechanisms in soil is incorporated into the design and operation of cropping systems. Two case studies are provided as examples in which a systems-based approach is being developed and deployed in the production of high value crops: lettuce/strawberry production in the coastal valleys of central California (United States) and sweet basil and other herb crop production in Israel. Considerations for developing and deploying system-based approaches are discussed and operational frameworks and metrics to guide their development are presented with the goal of offering a credible alternative to conventional approaches to soilborne disease management.

Pathway-based identification of biomarkers for targeted therapeutics: personalized oncology with PI3K pathway inhibitors.

Science.gov (United States)

Andersen, Jannik N; Sathyanarayanan, Sriram; Di Bacco, Alessandra; Chi, An; Zhang, Theresa; Chen, Albert H; Dolinski, Brian; Kraus, Manfred; Roberts, Brian; Arthur, William; Klinghoffer, Rich A; Gargano, Diana; Li, Lixia; Feldman, Igor; Lynch, Bethany; Rush, John; Hendrickson, Ronald C; Blume-Jensen, Peter; Paweletz, Cloud P

2010-08-04

Although we have made great progress in understanding the complex genetic alterations that underlie human cancer, it has proven difficult to identify which molecularly targeted therapeutics will benefit which patients. Drug-specific modulation of oncogenic signaling pathways in specific patient subpopulations can predict responsiveness to targeted therapy. Here, we report a pathway-based phosphoprofiling approach to identify and quantify clinically relevant, drug-specific biomarkers for phosphatidylinositol 3-kinase (PI3K) pathway inhibitors that target AKT, phosphoinositide-dependent kinase 1 (PDK1), and PI3K-mammalian target of rapamycin (mTOR). We quantified 375 nonredundant PI3K pathway-relevant phosphopeptides, all containing AKT, PDK1, or mitogen-activated protein kinase substrate recognition motifs. Of these phosphopeptides, 71 were drug-regulated, 11 of them by all three inhibitors. Drug-modulated phosphoproteins were enriched for involvement in cytoskeletal reorganization (filamin, stathmin, dynamin, PAK4, and PTPN14), vesicle transport (LARP1, VPS13D, and SLC20A1), and protein translation (S6RP and PRAS40). We then generated phosphospecific antibodies against selected, drug-regulated phosphorylation sites that would be suitable as biomarker tools for PI3K pathway inhibitors. As proof of concept, we show clinical translation feasibility for an antibody against phospho-PRAS40(Thr246). Evaluation of binding of this antibody in human cancer cell lines, a PTEN (phosphatase and tensin homolog deleted from chromosome 10)-deficient mouse prostate tumor model, and triple-negative breast tumor tissues showed that phospho-PRAS40(Thr246) positively correlates with PI3K pathway activation and predicts AKT inhibitor sensitivity. In contrast to phosphorylation of AKT(Thr308), the phospho-PRAS40(Thr246) epitope is highly stable in tissue samples and thus is ideal for immunohistochemistry. In summary, our study illustrates a rational approach for discovery of drug

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

DEFF Research Database (Denmark)

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 ...

Automated retinofugal visual pathway reconstruction with multi-shell HARDI and FOD-based analysis.

Science.gov (United States)

Kammen, Alexandra; Law, Meng; Tjan, Bosco S; Toga, Arthur W; Shi, Yonggang

2016-01-15

Diffusion MRI tractography provides a non-invasive modality to examine the human retinofugal projection, which consists of the optic nerves, optic chiasm, optic tracts, the lateral geniculate nuclei (LGN) and the optic radiations. However, the pathway has several anatomic features that make it particularly challenging to study with tractography, including its location near blood vessels and bone-air interface at the base of the cerebrum, crossing fibers at the chiasm, somewhat-tortuous course around the temporal horn via Meyer's Loop, and multiple closely neighboring fiber bundles. To date, these unique complexities of the visual pathway have impeded the development of a robust and automated reconstruction method using tractography. To overcome these challenges, we develop a novel, fully automated system to reconstruct the retinofugal visual pathway from high-resolution diffusion imaging data. Using multi-shell, high angular resolution diffusion imaging (HARDI) data, we reconstruct precise fiber orientation distributions (FODs) with high order spherical harmonics (SPHARM) to resolve fiber crossings, which allows the tractography algorithm to successfully navigate the complicated anatomy surrounding the retinofugal pathway. We also develop automated algorithms for the identification of ROIs used for fiber bundle reconstruction. In particular, we develop a novel approach to extract the LGN region of interest (ROI) based on intrinsic shape analysis of a fiber bundle computed from a seed region at the optic chiasm to a target at the primary visual cortex. By combining automatically identified ROIs and FOD-based tractography, we obtain a fully automated system to compute the main components of the retinofugal pathway, including the optic tract and the optic radiation. We apply our method to the multi-shell HARDI data of 215 subjects from the Human Connectome Project (HCP). Through comparisons with post-mortem dissection measurements, we demonstrate the retinotopic

Verification of FPGA-based NPP I and C systems. General approach and techniques

International Nuclear Information System (INIS)

Andrashov, Anton; Kharchenko, Vyacheslav; Sklyar, Volodymir; Reva, Lubov; Siora, Alexander

2011-01-01

This paper presents a general approach and techniques for design and verification of Field Programmable Gates Arrays (FPGA)-based Instrumentation and Control (I and C) systems for Nuclear Power Plants (NPP). Appropriate regulatory documents used for I and C systems design, development, verification and validation (V and V) are discussed considering the latest international standards and guidelines. Typical development and V and V processes of FPGA electronic design for FPGA-based NPP I and C systems are presented. Some safety-related features of implementation process are discussed. Corresponding development artifacts, related to design and implementation activities are outlined. An approach to test-based verification of FPGA electronic design algorithms, used in FPGA-based reactor trip systems is proposed. The results of application of test-based techniques for assessment of FPGA electronic design algorithms for reactor trip system (RTS) produced by Research and Production Corporation (RPC) 'Radiy' are presented. Some principles of invariant-oriented verification for FPGA-based safety-critical systems are outlined. (author)

Using A Model-Based Systems Engineering Approach For Exploration Medical System Development

Science.gov (United States)

Hanson, A.; Mindock, J.; McGuire, K.; Reilly, J.; Cerro, J.; Othon, W.; Rubin, D.; Urbina, M.; Canga, M.

2017-01-01

NASA's Human Research Program's Exploration Medical Capabilities (ExMC) element is defining the medical system needs for exploration class missions. ExMC's Systems Engineering (SE) team will play a critical role in successful design and implementation of the medical system into exploration vehicles. The team's mission is to "Define, develop, validate, and manage the technical system design needed to implement exploration medical capabilities for Mars and test the design in a progression of proving grounds." Development of the medical system is being conducted in parallel with exploration mission architecture and vehicle design development. Successful implementation of the medical system in this environment will require a robust systems engineering approach to enable technical communication across communities to create a common mental model of the emergent engineering and medical systems. Model-Based Systems Engineering (MBSE) improves shared understanding of system needs and constraints between stakeholders and offers a common language for analysis. The ExMC SE team is using MBSE techniques to define operational needs, decompose requirements and architecture, and identify medical capabilities needed to support human exploration. Systems Modeling Language (SysML) is the specific language the SE team is utilizing, within an MBSE approach, to model the medical system functional needs, requirements, and architecture. Modeling methods are being developed through the practice of MBSE within the team, and tools are being selected to support meta-data exchange as integration points to other system models are identified. Use of MBSE is supporting the development of relationships across disciplines and NASA Centers to build trust and enable teamwork, enhance visibility of team goals, foster a culture of unbiased learning and serving, and be responsive to customer needs. The MBSE approach to medical system design offers a paradigm shift toward greater integration between

A Metrics-Based Approach to Intrusion Detection System Evaluation for Distributed Real-Time Systems

Science.gov (United States)

2002-04-01

Based Approach to Intrusion Detection System Evaluation for Distributed Real - Time Systems Authors: G. A. Fink, B. L. Chappell, T. G. Turner, and...Distributed, Security. 1 Introduction Processing and cost requirements are driving future naval combat platforms to use distributed, real - time systems of...distributed, real - time systems . As these systems grow more complex, the timing requirements do not diminish; indeed, they may become more constrained

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.

Intelligent Flowcharting Developmental Approach to Legal Knowledge Based System

Directory of Open Access Journals (Sweden)

Nitin Balaji Bilgi

2011-10-01

Full Text Available The basic aim of this research, described in this paper is to develop a hybrid legal expert system/ knowledge based system, with specific reference to the transfer of property act, within the Indian legal system which is often in demand. In this paper the authors discuss an traditional approach to combining two types of reasoning methodologies, Rule Based Reasoning (RBR and Case Based Reasoning (CBR. In RBR module we have interpreted and implemented rules that occur in legal statutes of the Transfer of property act. In the CBR module we have an implementation to find the related cases. The VisiRule software made available by Logic Programming Associates is used in the development of RBR part this expert system. The authors have used java Net Beans for development of CBR. VisiRule is a decision charting tool, in which the rules are defined by a combination of graphical shapes and pieces of text, and produces rules.

Modular and Stochastic Approaches to Molecular Pathway Models of ATM, TGF beta, and WNT Signaling

Science.gov (United States)

Cucinotta, Francis A.; O'Neill, Peter; Ponomarev, Artem; Carra, Claudio; Whalen, Mary; Pluth, Janice M.

2009-01-01

Deterministic pathway models that describe the biochemical interactions of a group of related proteins, their complexes, activation through kinase, etc. are often the basis for many systems biology models. Low dose radiation effects present a unique set of challenges to these models including the importance of stochastic effects due to the nature of radiation tracks and small number of molecules activated, and the search for infrequent events that contribute to cancer risks. We have been studying models of the ATM, TGF -Smad and WNT signaling pathways with the goal of applying pathway models to the investigation of low dose radiation cancer risks. Modeling challenges include introduction of stochastic models of radiation tracks, their relationships to more than one substrate species that perturb pathways, and the identification of a representative set of enzymes that act on the dominant substrates. Because several pathways are activated concurrently by radiation the development of modular pathway approach is of interest.

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.

Modeling a terminology-based electronic nursing record system: an object-oriented approach.

Science.gov (United States)

Park, Hyeoun-Ae; Cho, InSook; Byeun, NamSoo

2007-10-01

The aim of this study was to present our perspectives on healthcare information analysis at a conceptual level and the lessons learned from our experience with the development of a terminology-based enterprise electronic nursing record system - which was one of components in an EMR system at a tertiary teaching hospital in Korea - using an object-oriented system analysis and design concept. To ensure a systematic approach and effective collaboration, the department of nursing constituted a system modeling team comprising a project manager, systems analysts, user representatives, an object-oriented methodology expert, and healthcare informaticists (including the authors). A rational unified process (RUP) and the Unified Modeling Language were used as a development process and for modeling notation, respectively. From the scenario and RUP approach, user requirements were formulated into use case sets and the sequence of activities in the scenario was depicted in an activity diagram. The structure of the system was presented in a class diagram. This approach allowed us to identify clearly the structural and behavioral states and important factors of a terminology-based ENR system (e.g., business concerns and system design concerns) according to the viewpoints of both domain and technical experts.

The node-weighted Steiner tree approach to identify elements of cancer-related signaling pathways.

Science.gov (United States)

Sun, Yahui; Ma, Chenkai; Halgamuge, Saman

2017-12-28

Cancer constitutes a momentous health burden in our society. Critical information on cancer may be hidden in its signaling pathways. However, even though a large amount of money has been spent on cancer research, some critical information on cancer-related signaling pathways still remains elusive. Hence, new works towards a complete understanding of cancer-related signaling pathways will greatly benefit the prevention, diagnosis, and treatment of cancer. We propose the node-weighted Steiner tree approach to identify important elements of cancer-related signaling pathways at the level of proteins. This new approach has advantages over previous approaches since it is fast in processing large protein-protein interaction networks. We apply this new approach to identify important elements of two well-known cancer-related signaling pathways: PI3K/Akt and MAPK. First, we generate a node-weighted protein-protein interaction network using protein and signaling pathway data. Second, we modify and use two preprocessing techniques and a state-of-the-art Steiner tree algorithm to identify a subnetwork in the generated network. Third, we propose two new metrics to select important elements from this subnetwork. On a commonly used personal computer, this new approach takes less than 2 s to identify the important elements of PI3K/Akt and MAPK signaling pathways in a large node-weighted protein-protein interaction network with 16,843 vertices and 1,736,922 edges. We further analyze and demonstrate the significance of these identified elements to cancer signal transduction by exploring previously reported experimental evidences. Our node-weighted Steiner tree approach is shown to be both fast and effective to identify important elements of cancer-related signaling pathways. Furthermore, it may provide new perspectives into the identification of signaling pathways for other human diseases.

Quantifying nitrous oxide production pathways in wastewater treatment systems using isotope technology - A critical review.

Science.gov (United States)

Duan, Haoran; Ye, Liu; Erler, Dirk; Ni, Bing-Jie; Yuan, Zhiguo

2017-10-01

Nitrous oxide (N 2 O) is an important greenhouse gas and an ozone-depleting substance which can be emitted from wastewater treatment systems (WWTS) causing significant environmental impacts. Understanding the N 2 O production pathways and their contribution to total emissions is the key to effective mitigation. Isotope technology is a promising method that has been applied to WWTS for quantifying the N 2 O production pathways. Within the scope of WWTS, this article reviews the current status of different isotope approaches, including both natural abundance and labelled isotope approaches, to N 2 O production pathways quantification. It identifies the limitations and potential problems with these approaches, as well as improvement opportunities. We conclude that, while the capabilities of isotope technology have been largely recognized, the quantification of N 2 O production pathways with isotope technology in WWTS require further improvement, particularly in relation to its accuracy and reliability. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Model of an Integrated Immune System Pathway in Homo sapiens and Its Interaction with Superantigen Producing Expression Regulatory Pathway in Staphylococcus aureus: Comparing Behavior of Pathogen Perturbed and Unperturbed Pathway

Science.gov (United States)

Tomar, Namrata; De, Rajat K.

2013-01-01

Response of an immune system to a pathogen attack depends on the balance between the host immune defense and the virulence of the pathogen. Investigation of molecular interactions between the proteins of a host and a pathogen helps in identifying the pathogenic proteins. It is necessary to understand the dynamics of a normally behaved host system to evaluate the capacity of its immune system upon pathogen attack. In this study, we have compared the behavior of an unperturbed and pathogen perturbed host system. Moreover, we have developed a formalism under Flux Balance Analysis (FBA) for the optimization of conflicting objective functions. We have constructed an integrated pathway system, which includes Staphylococcal Superantigen (SAg) expression regulatory pathway and TCR signaling pathway of Homo sapiens. We have implemented the method on this pathway system and observed the behavior of host signaling molecules upon pathogen attack. The entire study has been divided into six different cases, based on the perturbed/unperturbed conditions. In other words, we have investigated unperturbed and pathogen perturbed human TCR signaling pathway, with different combinations of optimization of concentrations of regulatory and signaling molecules. One of these cases has aimed at finding out whether minimization of the toxin production in a pathogen leads to the change in the concentration levels of the proteins coded by TCR signaling pathway genes in the infected host. Based on the computed results, we have hypothesized that the balance between TCR signaling inhibitory and stimulatory molecules can keep TCR signaling system into resting/stimulating state, depending upon the perturbation. The proposed integrated host-pathogen interaction pathway model has accurately reflected the experimental evidences, which we have used for validation purpose. The significance of this kind of investigation lies in revealing the susceptible interaction points that can take back the

Identification of core pathways based on attractor and crosstalk in ischemic stroke.

Science.gov (United States)

Diao, Xiufang; Liu, Aijuan

2018-02-01

Ischemic stroke is a leading cause of mortality and disability around the world. It is an important task to identify dysregulated pathways which infer molecular and functional insights existing in high-throughput experimental data. Gene expression profile of E-GEOD-16561 was collected. Pathways were obtained from the database of Kyoto Encyclopedia of Genes and Genomes and Retrieval of Interacting Genes was used to download protein-protein interaction sets. Attractor and crosstalk approaches were applied to screen dysregulated pathways. A total of 20 differentially expressed genes were identified in ischemic stroke. Thirty-nine significant differential pathways were identified according to Ppathways were identified with RPpathways were identified with impact factor >250. On the basis of the three criteria, 11 significant dysfunctional pathways were identified. Among them, Epstein-Barr virus infection was the most significant differential pathway. In conclusion, with the method based on attractor and crosstalk, significantly dysfunctional pathways were identified. These pathways are expected to provide molecular mechanism of ischemic stroke and represents a novel potential therapeutic target for ischemic stroke treatment.

New approaches in agent-based modeling of complex financial systems

Science.gov (United States)

Chen, Ting-Ting; Zheng, Bo; Li, Yan; Jiang, Xiong-Fei

2017-12-01

Agent-based modeling is a powerful simulation technique to understand the collective behavior and microscopic interaction in complex financial systems. Recently, the concept for determining the key parameters of agent-based models from empirical data instead of setting them artificially was suggested. We first review several agent-based models and the new approaches to determine the key model parameters from historical market data. Based on the agents' behaviors with heterogeneous personal preferences and interactions, these models are successful in explaining the microscopic origination of the temporal and spatial correlations of financial markets. We then present a novel paradigm combining big-data analysis with agent-based modeling. Specifically, from internet query and stock market data, we extract the information driving forces and develop an agent-based model to simulate the dynamic behaviors of complex financial systems.

A data fusion based approach for damage detection in linear systems

Directory of Open Access Journals (Sweden)

Ernesto Grande

2014-07-01

Full Text Available The aim of the present paper is to propose innovative approaches able to improve the capability of classical damage indicators in detecting the damage position in linear systems. In particular, starting from classical indicators based on the change of the flexibility matrix and on the change of the modal strain energy, the proposed approaches consider two data fusion procedures both based on the Dempster-Shafer theory. Numerical applications are reported in the paper in order to assess the reliability of the proposed approaches considering different damage scenarios, different sets of modes of vibration and the presence of errors affecting the accounted modes of vibrations.

A fuzzy-logic-based approach to qualitative safety modelling for marine systems

International Nuclear Information System (INIS)

Sii, H.S.; Ruxton, Tom; Wang Jin

2001-01-01

Safety assessment based on conventional tools (e.g. probability risk assessment (PRA)) may not be well suited for dealing with systems having a high level of uncertainty, particularly in the feasibility and concept design stages of a maritime or offshore system. By contrast, a safety model using fuzzy logic approach employing fuzzy IF-THEN rules can model the qualitative aspects of human knowledge and reasoning processes without employing precise quantitative analyses. A fuzzy-logic-based approach may be more appropriately used to carry out risk analysis in the initial design stages. This provides a tool for working directly with the linguistic terms commonly used in carrying out safety assessment. This research focuses on the development and representation of linguistic variables to model risk levels subjectively. These variables are then quantified using fuzzy sets. In this paper, the development of a safety model using fuzzy logic approach for modelling various design variables for maritime and offshore safety based decision making in the concept design stage is presented. An example is used to illustrate the proposed approach

Modelling and simulation of electrical energy systems through a complex systems approach using agent-based models

Energy Technology Data Exchange (ETDEWEB)

Kremers, Enrique

2013-10-01

Complexity science aims to better understand the processes of both natural and man-made systems which are composed of many interacting entities at different scales. A disaggregated approach is proposed for simulating electricity systems, by using agent-based models coupled to continuous ones. The approach can help in acquiring a better understanding of the operation of the system itself, e.g. on emergent phenomena or scale effects; as well as in the improvement and design of future smart grids.

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

Pivotal role of the muscle-contraction pathway in cryptorchidism and evidence for genomic connections with cardiomyopathy pathways in RASopathies

KAUST Repository

Cannistraci, Carlo

2013-02-14

Background: Cryptorchidism is the most frequent congenital disorder in male children; however the genetic causes of cryptorchidism remain poorly investigated. Comparative integratomics combined with systems biology approach was employed to elucidate genetic factors and molecular pathways underlying testis descent. Methods. Literature mining was performed to collect genomic loci associated with cryptorchidism in seven mammalian species. Information regarding the collected candidate genes was stored in MySQL relational database. Genomic view of the loci was presented using Flash GViewer web tool (http://gmod.org/wiki/Flashgviewer/). DAVID Bioinformatics Resources 6.7 was used for pathway enrichment analysis. Cytoscape plug-in PiNGO 1.11 was employed for protein-network-based prediction of novel candidate genes. Relevant protein-protein interactions were confirmed and visualized using the STRING database (version 9.0). Results. The developed cryptorchidism gene atlas includes 217 candidate loci (genes, regions involved in chromosomal mutations, and copy number variations) identified at the genomic, transcriptomic, and proteomic level. Human orthologs of the collected candidate loci were presented using a genomic map viewer. The cryptorchidism gene atlas is freely available online: http://www.integratomics-time.com/cryptorchidism/. Pathway analysis suggested the presence of twelve enriched pathways associated with the list of 179 literature-derived candidate genes. Additionally, a list of 43 network-predicted novel candidate genes was significantly associated with four enriched pathways. Joint pathway analysis of the collected and predicted candidate genes revealed the pivotal importance of the muscle-contraction pathway in cryptorchidism and evidence for genomic associations with cardiomyopathy pathways in RASopathies. Conclusions: The developed gene atlas represents an important resource for the scientific community researching genetics of cryptorchidism. The

Security of Heterogeneous Content in Cloud Based Library Information Systems Using an Ontology Based Approach

Directory of Open Access Journals (Sweden)

Mihai DOINEA

2014-01-01

Full Text Available As in any domain that involves the use of software, the library information systems take advantages of cloud computing. The paper highlights the main aspect of cloud based systems, describing some public solutions provided by the most important players on the market. Topics related to content security in cloud based services are tackled in order to emphasize the requirements that must be met by these types of systems. A cloud based implementation of an Information Library System is presented and some adjacent tools that are used together with it to provide digital content and metadata links are described. In a cloud based Information Library System security is approached by means of ontologies. Aspects such as content security in terms of digital rights are presented and a methodology for security optimization is proposed.

The Multimedia Environmental Pollutant Assessment System (MEPAS reg-sign): Completely-Stirred Tank Reactor (CSTR) formulations for the wetland pathway

International Nuclear Information System (INIS)

McDonald, J.P.; van der Aa, N.G.F.M.; Whelan, G.

1997-06-01

The Multimedia Environmental Pollutant Assessment System (MEPAS) is a physics-based environmental analysis code integrating source-term, fate, and exposure models for concentration, dose, or risk endpoints. Developed by Pacific Northwest National Laboratory for the US Department of Energy, MEPAS is designed for site-specific assessments using readily available information. Endpoints are computed for chemical and radioactive pollutants. For human health impacts, risks are computed for radioactive and hazardous carcinogens, and hazard quotients for noncarcinogens. This system has wide applicability to environmental problems using air, groundwater, surface-water, overland, wetland, and exposure models. MEPAS enables users to simulate release of contaminants from a source; transport of contaminants through the air, groundwater, surface-water, overland, or wetland pathways; and transfer of contaminants through food chains and exposure pathways to the exposed individual or population. Whenever available and appropriate, guidance and/or models from the US Environmental Protection Agency, International Commission on Radiological Protection, and National Council on Radiation Protection and Measurements were used to facilitate compatibility and acceptance. Although based on relatively standard transport and exposure computation approaches, MEPAS uniquely integrated these approaches into a single system, providing a consistent basis for evaluating health impacts for a large number of problems and sites. Implemented on a desktop computer, a user-friendly platform allows the user to define the problem, input the required data, and execute the appropriate models. This document describes the mathematical formulations for the Completely-Stirred Tank Reactor (CSTR) component of MEPAS as applied to the wetland pathway

A diagnostic expert system for NPP based on hybrid knowledge approach

International Nuclear Information System (INIS)

Yang, Joon On; Chang, Soon Heung

1989-01-01

This paper describes a diagnostic expert system, HYPOSS (Hybrid Knowledge Based Plant Operation Supporting System), which has been developed to support operators' decision making during the transients of nuclear power plant. HYPOSS adopts the hybrid knowledge approach which combines shallow and deep knowledge to couple the merits of both approaches. In HYPOSS, four types of knowledge are used according to the steps of diagnosis procedure: structural, functional, behavioral and heuristic knowledge. The structural and functional knowledge is represented by three fundamental primitives and five types of functions respectively. The behavioral knowledge is represented using constraints. The inference procedure is based on the human problem solving behavior modeled in HYPOSS. For the validation of HYPOSS, several tests have been performed based on the data produced by a plant simulator. The results of validation studies showed a good applicability of HYPOSS to the anomaly diagnosis of nuclear power plant

Industrial cloud-based cyber-physical systems the IMC-AESOP approach

CERN Document Server

Bangemann, Thomas; Karnouskos, Stamatis; Delsing, Jerker; Stluka, Petr; Harrison, Robert; Jammes, Francois; Lastra, Jose

2014-01-01

This book presents cutting-edge emerging technologies and approaches in the areas of service-oriented architectures, intelligent devices, and cloud-based cyber-physical systems. It provides a clear view on their applicability to the management and automation of manufacturing and process industries. It offers a holistic view of future industrial cyber-physical systems and their industrial usage, and also depicts technologies and architectures as well as a migration approach and engineering tools based on these. By providing a careful balance between the theory and the practical aspects, this book has been authored by several experts from academia and industry, thereby offering a valuable understanding of the vision, the domain, the processes and the results of the research. It has several illustrations and tables to clearly exemplify the concepts and results examined in the text, and these are supported by four real-life case-studies. We are witnessing rapid advances in the industrial automation, mainly driven...

An approach to build a knowledge base for reactor diagnostic system using statistical method

International Nuclear Information System (INIS)

Yokobayashi, Masao; Matsumoto, Kiyoshi; Kohsaka, Atsuo

1988-01-01

In the development of a rule-based expert system, one of the key issues is how to acquire knowledge and to build a knowledge base. When the knowledge base of DISKET was built, which is an expert system for nuclear reactor accident diagnosis developed in Japan Atomic Energy Research Institute, several problems have been experienced. To write rules is a time-consuming task, and it was difficult to keep the objectivity and consistency of rules as the number of rules increased. Certainty factors must be determined often according to engineering judgement, i.e. empirically or intuitively. A systematic approach was attempted to cope with these difficulties and to build efficiently an objective knowledge base. The approach described in this paper is based on the concept that a prototype knowledge base, colloquially speaking an initial guess, should first be generated in a systematic way, then it is modified or improved by human experts for practical use. Factor analysis was used as the systematic way. DISKET system, the procedure of building a knowledge base, and the verification of the approach are reported. (Kako, I.)

Model of the Russian Federation Construction Innovation System: An Integrated Participatory Systems Approach

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Emiliya Suprun

2016-08-01

Full Text Available This research integrates systemic and participatory techniques to model the Russian Federation construction innovation system. Understanding this complex construction innovation system and determining the best levers for enhancing it require the dynamic modelling of a number of factors, such as flows of resources and activities, policies, uncertainty and time. To build the foundations for such a dynamic model, the employed study method utilised an integrated stakeholder-based participatory approach coupled with structural analysis (MICMAC—Matrice d'Impacts Croisés Multiplication Appliquée à un Classement Cross-Impact Matrix. This method identified the key factors of the Russian Federation construction innovation system, their causal relationship (i.e., influence/dependence map and, ultimately, a causal loop diagram. The generated model reveals pathways to improving construction innovation in the Russian Federation and underpins the future development of an operationalised system dynamics model.

Prediction of novel synthetic pathways for the production of desired chemicals

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Park Jin

2010-03-01

Full Text Available Abstract Background There have been several methods developed for the prediction of synthetic metabolic pathways leading to the production of desired chemicals. In these approaches, novel pathways were predicted based on chemical structure changes, enzymatic information, and/or reaction mechanisms, but the approaches generating a huge number of predicted results are difficult to be applied to real experiments. Also, some of these methods focus on specific pathways, and thus are limited to expansion to the whole metabolism. Results In the present study, we propose a system framework employing a retrosynthesis model with a prioritization scoring algorithm. This new strategy allows deducing the novel promising pathways for the synthesis of a desired chemical together with information on enzymes involved based on structural changes and reaction mechanisms present in the system database. The prioritization scoring algorithm employing Tanimoto coefficient and group contribution method allows examination of structurally qualified pathways to recognize which pathway is more appropriate. In addition, new concepts of binding site covalence, estimation of pathway distance and organism specificity were taken into account to identify the best synthetic pathway. Parameters of these factors can be evolutionarily optimized when a newly proven synthetic pathway is registered. As the proofs of concept, the novel synthetic pathways for the production of isobutanol, 3-hydroxypropionate, and butyryl-CoA were predicted. The prediction shows a high reliability, in which experimentally verified synthetic pathways were listed within the top 0.089% of the identified pathway candidates. Conclusions It is expected that the system framework developed in this study would be useful for the in silico design of novel metabolic pathways to be employed for the efficient production of chemicals, fuels and materials.

A Hospital Nursing Adverse Events Reporting System Project: An Approach Based on the Systems Development Life Cycle.

Science.gov (United States)

Cao, Yingjuan; Ball, Marion

2017-01-01

Based on the System Development Life Cycle, a hospital based nursing adverse event reporting system was developed and implemented which integrated with the current Hospital Information System (HIS). Besides the potitive outcomes in terms of timeliness and efficiency, this approach has brought an enormous change in how the nurses report, analyze and respond to the adverse events.

Creating Agent-Based Energy Transition Management Models That Can Uncover Profitable Pathways to Climate Change Mitigation

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Auke Hoekstra

2017-01-01

Full Text Available The energy domain is still dominated by equilibrium models that underestimate both the dangers and opportunities related to climate change. In reality, climate and energy systems contain tipping points, feedback loops, and exponential developments. This paper describes how to create realistic energy transition management models: quantitative models that can discover profitable pathways from fossil fuels to renewable energy. We review the literature regarding agent-based economics, disruptive innovation, and transition management and determine the following requirements. Actors must be detailed, heterogeneous, interacting, learning, and strategizing. Technology should be represented as a detailed and heterogeneous portfolio that can develop in a bottom-up manner, using endogenous feedback loops. Assumptions about discount rates and the social cost of carbon should be configurable. The model should contain interactions between the global, national, local, and individual level. A review of modelling techniques shows that equilibrium models are unsuitable and that system dynamics and discrete event simulation are too limited. The agent-based approach is found to be uniquely suited for the complex adaptive sociotechnical systems that must be modelled. But the choice for agent-based models does not mean a rejection of other approaches because they can be accommodated within the agent-based framework. We conclude with practical guidelines.

A Process Mining Based Service Composition Approach for Mobile Information Systems

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Chengxi Huang

2017-01-01

Full Text Available Due to the growing trend in applying big data and cloud computing technologies in information systems, it is becoming an important issue to handle the connection between large scale of data and the associated business processes in the Internet of Everything (IoE environment. Service composition as a widely used phase in system development has some limits when the complexity of relationship among data increases. Considering the expanding scale and the variety of devices in mobile information systems, a process mining based service composition approach is proposed in this paper in order to improve the adaptiveness and efficiency of compositions. Firstly, a preprocessing is conducted to extract existing service execution information from server-side logs. Then process mining algorithms are applied to discover the overall event sequence with preprocessed data. After that, a scene-based service composition is applied to aggregate scene information and relocate services of the system. Finally, a case study that applied the work in mobile medical application proves that the approach is practical and valuable in improving service composition adaptiveness and efficiency.

Innovative Approach to Implementation of FPGA-based NPP Instrumentation and Control Systems

Energy Technology Data Exchange (ETDEWEB)

Andrashov, Anton; Kharchenko, Vyacheslav; Sklyar, Volodymir [Centre for Safety Infrastructure-Oriented Research and Analysis, Kharkov (Ukraine); SIORA Alexander [Research and Production Corporation Radiy, Kirovograd (Ukraine)

2011-08-15

Advantages of application of Field Programmable Gates Arrays (FPGA) technology for implementation of Instrumentation and Control (I and C) systems for Nuclear Power Plants (NPP) are outlined. Specific features of FPGA technology in the context of cyber security threats for NPPs I and C systems are analyzed. Description of FPGA-based platform used for implementation of different safety I and C systems for NPPs is presented. Typical architecture of NPPs safety I and C system based on the platform, as well as approach to implementation of I and C systems using FPGA-based platform are discussed. Data on implementation experience of application of the platform for NPP safety I and C systems modernization projects are finalizing the paper.

Innovative approach to implementation of FPGA-based NPP instrumentation and control systems

International Nuclear Information System (INIS)

Andrashov, Anton; Kharchenko, Vyacheslav; Sklyar, Volodymir; Siora, Alexander

2011-01-01

Advantages of application of Field Programmable Gates Arrays (FPGA) technology for implementation of Instrumentation and Control (I and C) systems for Nuclear Power Plants (NPP) are outlined. Specific features of FPGA technology in the context of cyber security threats for NPPs I and C systems are analyzed. Description of FPGA-based platform used for implementation of different safety I and C systems for NPPs is presented. Typical architecture of NPPs safety I and C system based on the platform, as well as approach to implementation of I and C systems using FPGA-based platform are discussed. Data on implementation experience of application of the platform for NPP safety I and C systems modernization projects are finalizing the paper. (author)

Innovative Approach to Implementation of FPGA-based NPP Instrumentation and Control Systems

International Nuclear Information System (INIS)

Andrashov, Anton; Kharchenko, Vyacheslav; Sklyar, Volodymir; SIORA Alexander

2011-01-01

Advantages of application of Field Programmable Gates Arrays (FPGA) technology for implementation of Instrumentation and Control (I and C) systems for Nuclear Power Plants (NPP) are outlined. Specific features of FPGA technology in the context of cyber security threats for NPPs I and C systems are analyzed. Description of FPGA-based platform used for implementation of different safety I and C systems for NPPs is presented. Typical architecture of NPPs safety I and C system based on the platform, as well as approach to implementation of I and C systems using FPGA-based platform are discussed. Data on implementation experience of application of the platform for NPP safety I and C systems modernization projects are finalizing the paper

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

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Sudin eBhattacharya

2012-12-01

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

A pathway-based network analysis of hypertension-related genes

Science.gov (United States)

Wang, Huan; Hu, Jing-Bo; Xu, Chuan-Yun; Zhang, De-Hai; Yan, Qian; Xu, Ming; Cao, Ke-Fei; Zhang, Xu-Sheng

2016-02-01

Complex network approach has become an effective way to describe interrelationships among large amounts of biological data, which is especially useful in finding core functions and global behavior of biological systems. Hypertension is a complex disease caused by many reasons including genetic, physiological, psychological and even social factors. In this paper, based on the information of biological pathways, we construct a network model of hypertension-related genes of the salt-sensitive rat to explore the interrelationship between genes. Statistical and topological characteristics show that the network has the small-world but not scale-free property, and exhibits a modular structure, revealing compact and complex connections among these genes. By the threshold of integrated centrality larger than 0.71, seven key hub genes are found: Jun, Rps6kb1, Cycs, Creb312, Cdk4, Actg1 and RT1-Da. These genes should play an important role in hypertension, suggesting that the treatment of hypertension should focus on the combination of drugs on multiple genes.

User Interface Requirements for Web-Based Integrated Care Pathways: Evidence from the Evaluation of an Online Care Pathway Investigation Tool.

Science.gov (United States)

Balatsoukas, Panos; Williams, Richard; Davies, Colin; Ainsworth, John; Buchan, Iain

2015-11-01

Integrated care pathways (ICPs) define a chronological sequence of steps, most commonly diagnostic or treatment, to be followed in providing care for patients. Care pathways help to ensure quality standards are met and to reduce variation in practice. Although research on the computerisation of ICP progresses, there is still little knowledge on what are the requirements for designing user-friendly and usable electronic care pathways, or how users (normally health care professionals) interact with interfaces that support design, analysis and visualisation of ICPs. The purpose of the study reported in this paper was to address this gap by evaluating the usability of a novel web-based tool called COCPIT (Collaborative Online Care Pathway Investigation Tool). COCPIT supports the design, analysis and visualisation of ICPs at the population level. In order to address the aim of this study, an evaluation methodology was designed based on heuristic evaluations and a mixed method usability test. The results showed that modular visualisation and direct manipulation of information related to the design and analysis of ICPs is useful for engaging and stimulating users. However, designers should pay attention to issues related to the visibility of the system status and the match between the system and the real world, especially in relation to the display of statistical information about care pathways and the editing of clinical information within a care pathway. The paper concludes with recommendations for interface design.

Power System Event Ranking Using a New Linear Parameter-Varying Modeling with a Wide Area Measurement System-Based Approach

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Mohammad Bagher Abolhasani Jabali

2017-07-01

Full Text Available Detecting critical power system events for Dynamic Security Assessment (DSA is required for reliability improvement. The approach proposed in this paper investigates the effects of events on dynamic behavior during nonlinear system response while common approaches use steady-state conditions after events. This paper presents some new and enhanced indices for event ranking based on time-domain simulation and polytopic linear parameter-varying (LPV modeling of a power system. In the proposed approach, a polytopic LPV representation is generated via linearization about some points of the nonlinear dynamic behavior of power system using wide-area measurement system (WAMS concepts and then event ranking is done based on the frequency response of the system models on the vertices. Therefore, the nonlinear behaviors of the system in the time of fault occurrence are considered for events ranking. The proposed algorithm is applied to a power system using nonlinear simulation. The comparison of the results especially in different fault conditions shows the advantages of the proposed approach and indices.

Cost-effectiveness analysis of a system-based approach for managing neonatal jaundice and preventing kernicterus in Ontario

Science.gov (United States)

Xie, Bin; da Silva, Orlando; Zaric, Greg

2012-01-01

OBJECTIVE: To evaluate the incremental cost-effectiveness of a system-based approach for the management of neonatal jaundice and the prevention of kernicterus in term and late-preterm (≥35 weeks) infants, compared with the traditional practice based on visual inspection and selected bilirubin testing. STUDY DESIGN: Two hypothetical cohorts of 150,000 term and late-preterm neonates were used to compare the costs and outcomes associated with the use of a system-based or traditional practice approach. Data for the evaluation were obtained from the case costing centre at a large teaching hospital in Ontario, supplemented by data from the literature. RESULTS: The per child cost for the system-based approach cohort was $176, compared with $173 in the traditional practice cohort. The higher cost associated with the system-based cohort reflects increased costs for predischarge screening and treatment and increased postdischarge follow-up visits. These costs are partially offset by reduced costs from fewer emergency room visits, hospital readmissions and kernicterus cases. Compared with the traditional approach, the cost to prevent one kernicterus case using the system-based approach was $570,496, the cost per life year gained was $26,279, and the cost per quality-adjusted life year gained was $65,698. CONCLUSION: The cost to prevent one kernicterus case using the system-based approach is much lower than previously reported in the literature. PMID:23277747

Cost-effectiveness analysis of a system-based approach for managing neonatal jaundice and preventing kernicterus in Ontario.

Science.gov (United States)

Xie, Bin; da Silva, Orlando; Zaric, Greg

2012-01-01

To evaluate the incremental cost-effectiveness of a system-based approach for the management of neonatal jaundice and the prevention of kernicterus in term and late-preterm (≥35 weeks) infants, compared with the traditional practice based on visual inspection and selected bilirubin testing. Two hypothetical cohorts of 150,000 term and late-preterm neonates were used to compare the costs and outcomes associated with the use of a system-based or traditional practice approach. Data for the evaluation were obtained from the case costing centre at a large teaching hospital in Ontario, supplemented by data from the literature. The per child cost for the system-based approach cohort was $176, compared with $173 in the traditional practice cohort. The higher cost associated with the system-based cohort reflects increased costs for predischarge screening and treatment and increased postdischarge follow-up visits. These costs are partially offset by reduced costs from fewer emergency room visits, hospital readmissions and kernicterus cases. Compared with the traditional approach, the cost to prevent one kernicterus case using the system-based approach was $570,496, the cost per life year gained was $26,279, and the cost per quality-adjusted life year gained was $65,698. The cost to prevent one kernicterus case using the system-based approach is much lower than previously reported in the literature.

Systems Pharmacological Approach of Pulsatillae Radix on Treating Crohn’s Disease

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Su Yeon Suh

2017-01-01

Full Text Available In East Asian traditional medicine, Pulsatillae Radix (PR is widely used to treat amoebic dysentery and renowned for its anti-inflammatory effects. This study aimed to confirm evidence regarding the potential therapeutic effect of PR on Crohn’s disease using a system network level based in silico approach. Study results showed that the compounds in PR are highly connected to Crohn’s disease related pathways, biological processes, and organs, and these findings were confirmed by compound-target network, target-pathway network, and gene ontology analysis. Most compounds in PR have been reported to possess anti-inflammatory, anticancer, and antioxidant effects, and we found that these compounds interact with multiple targets in a synergetic way. Furthermore, the mRNA expressions of genes targeted by PR are elevated significantly in immunity-related organ tissues, small intestine, and colon. Our results suggest that the anti-inflammatory and repair and immune system enhancing effects of PR might have therapeutic impact on Crohn’s disease.

MinePath: Mining for Phenotype Differential Sub-paths in Molecular Pathways

Science.gov (United States)

Koumakis, Lefteris; Kartsaki, Evgenia; Chatzimina, Maria; Zervakis, Michalis; Vassou, Despoina; Marias, Kostas; Moustakis, Vassilis; Potamias, George

2016-01-01

Pathway analysis methodologies couple traditional gene expression analysis with knowledge encoded in established molecular pathway networks, offering a promising approach towards the biological interpretation of phenotype differentiating genes. Early pathway analysis methodologies, named as gene set analysis (GSA), view pathways just as plain lists of genes without taking into account either the underlying pathway network topology or the involved gene regulatory relations. These approaches, even if they achieve computational efficiency and simplicity, consider pathways that involve the same genes as equivalent in terms of their gene enrichment characteristics. Most recent pathway analysis approaches take into account the underlying gene regulatory relations by examining their consistency with gene expression profiles and computing a score for each profile. Even with this approach, assessing and scoring single-relations limits the ability to reveal key gene regulation mechanisms hidden in longer pathway sub-paths. We introduce MinePath, a pathway analysis methodology that addresses and overcomes the aforementioned problems. MinePath facilitates the decomposition of pathways into their constituent sub-paths. Decomposition leads to the transformation of single-relations to complex regulation sub-paths. Regulation sub-paths are then matched with gene expression sample profiles in order to evaluate their functional status and to assess phenotype differential power. Assessment of differential power supports the identification of the most discriminant profiles. In addition, MinePath assess the significance of the pathways as a whole, ranking them by their p-values. Comparison results with state-of-the-art pathway analysis systems are indicative for the soundness and reliability of the MinePath approach. In contrast with many pathway analysis tools, MinePath is a web-based system (www.minepath.org) offering dynamic and rich pathway visualization functionality, with the

The future use of pathway analysis in IAEA safeguards

International Nuclear Information System (INIS)

Budlong Sylvester, Kory; Pilat, J.; Murphy, Chantell

2013-01-01

Pathway analysis has the potential to play an important role in the development of a safeguards system that is more information driven, leveraging all the information available to the International Atomic Energy Agency (IAEA). Pathway analysis should be seen as an extension of traditional hypothesis testing used by the Agency in the past. The most attractive pathways based on the assessed capabilities of a given state can be identified and used in the development of state-level safeguards approaches. This ranking of pathways can be revised based on evidence of pathway use, or preparations for use, allowing limited safeguards resources to flow to the areas of highest concern. The possible uses of pathway analysis in the implementation of the IAEA's state-level concept are described along with implementation issues that will likely arise. The paper is followed by the slides of the presentation. (authors)

Characterization of p38 MAPK isoforms for drug resistance study using systems biology approach.

Science.gov (United States)

Peng, Huiming; Peng, Tao; Wen, Jianguo; Engler, David A; Matsunami, Risë K; Su, Jing; Zhang, Le; Chang, Chung-Che Jeff; Zhou, Xiaobo

2014-07-01

p38 mitogen-activated protein kinase activation plays an important role in resistance to chemotherapeutic cytotoxic drugs in treating multiple myeloma (MM). However, how the p38 mitogen-activated protein kinase signaling pathway is involved in drug resistance, in particular the roles that the various p38 isoforms play, remains largely unknown. To explore the underlying mechanisms, we developed a novel systems biology approach by integrating liquid chromatography-mass spectrometry and reverse phase protein array data from human MM cell lines with computational pathway models in which the unknown parameters were inferred using a proposed novel algorithm called modularized factor graph. New mechanisms predicted by our models suggest that combined activation of various p38 isoforms may result in drug resistance in MM via regulating the related pathways including extracellular signal-regulated kinase (ERK) pathway and NFкB pathway. ERK pathway regulating cell growth is synergistically regulated by p38δ isoform, whereas nuclear factor kappa B (NFкB) pathway regulating cell apoptosis is synergistically regulated by p38α isoform. This finding that p38δ isoform promotes the phosphorylation of ERK1/2 in MM cells treated with bortezomib was validated by western blotting. Based on the predicted mechanisms, we further screened drug combinations in silico and found that a promising drug combination targeting ERK1/2 and NFκB might reduce the effects of drug resistance in MM cells. This study provides a framework of a systems biology approach to studying drug resistance and drug combination selection. RPPA experimental Data and Matlab source codes of modularized factor graph for parameter estimation are freely available online at http://ctsb.is.wfubmc.edu/publications/modularized-factor-graph.php. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A Model-free Approach to Fault Detection of Continuous-time Systems Based on Time Domain Data

Institute of Scientific and Technical Information of China (English)

Ping Zhang; Steven X. Ding

2007-01-01

In this paper, a model-free approach is presented to design an observer-based fault detection system of linear continuoustime systems based on input and output data in the time domain. The core of the approach is to directly identify parameters of the observer-based residual generator based on a numerically reliable data equation obtained by filtering and sampling the input and output signals.

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.

Semantic Mining based on graph theory and ontologies. Case Study: Cell Signaling Pathways

Directory of Open Access Journals (Sweden)

Carlos R. Rangel

2016-08-01

Full Text Available In this paper we use concepts from graph theory and cellular biology represented as ontologies, to carry out semantic mining tasks on signaling pathway networks. Specifically, the paper describes the semantic enrichment of signaling pathway networks. A cell signaling network describes the basic cellular activities and their interactions. The main contribution of this paper is in the signaling pathway research area, it proposes a new technique to analyze and understand how changes in these networks may affect the transmission and flow of information, which produce diseases such as cancer and diabetes. Our approach is based on three concepts from graph theory (modularity, clustering and centrality frequently used on social networks analysis. Our approach consists into two phases: the first uses the graph theory concepts to determine the cellular groups in the network, which we will call them communities; the second uses ontologies for the semantic enrichment of the cellular communities. The measures used from the graph theory allow us to determine the set of cells that are close (for example, in a disease, and the main cells in each community. We analyze our approach in two cases: TGF-ß and the Alzheimer Disease.

Integrating eQTL data with GWAS summary statistics in pathway-based analysis with application to schizophrenia.

Science.gov (United States)

Wu, Chong; Pan, Wei

2018-04-01

Many genetic variants affect complex traits through gene expression, which can be exploited to boost statistical power and enhance interpretation in genome-wide association studies (GWASs) as demonstrated by the transcriptome-wide association study (TWAS) approach. Furthermore, due to polygenic inheritance, a complex trait is often affected by multiple genes with similar functions as annotated in gene pathways. Here, we extend TWAS from gene-based analysis to pathway-based analysis: we integrate public pathway collections, expression quantitative trait locus (eQTL) data and GWAS summary association statistics (or GWAS individual-level data) to identify gene pathways associated with complex traits. The basic idea is to weight the SNPs of the genes in a pathway based on their estimated cis-effects on gene expression, then adaptively test for association of the pathway with a GWAS trait by effectively aggregating possibly weak association signals across the genes in the pathway. The P values can be calculated analytically and thus fast. We applied our proposed test with the KEGG and GO pathways to two schizophrenia (SCZ) GWAS summary association data sets, denoted by SCZ1 and SCZ2 with about 20,000 and 150,000 subjects, respectively. Most of the significant pathways identified by analyzing the SCZ1 data were reproduced by the SCZ2 data. Importantly, we identified 15 novel pathways associated with SCZ, such as GABA receptor complex (GO:1902710), which could not be uncovered by the standard single SNP-based analysis or gene-based TWAS. The newly identified pathways may help us gain insights into the biological mechanism underlying SCZ. Our results showcase the power of incorporating gene expression information and gene functional annotations into pathway-based association testing for GWAS. © 2018 WILEY PERIODICALS, INC.

A critique of the molecular target-based drug discovery paradigm based on principles of metabolic control: advantages of pathway-based discovery.

Science.gov (United States)

Hellerstein, Marc K

2008-01-01

Contemporary drug discovery and development (DDD) is dominated by a molecular target-based paradigm. Molecular targets that are potentially important in disease are physically characterized; chemical entities that interact with these targets are identified by ex vivo high-throughput screening assays, and optimized lead compounds enter testing as drugs. Contrary to highly publicized claims, the ascendance of this approach has in fact resulted in the lowest rate of new drug approvals in a generation. The primary explanation for low rates of new drugs is attrition, or the failure of candidates identified by molecular target-based methods to advance successfully through the DDD process. In this essay, I advance the thesis that this failure was predictable, based on modern principles of metabolic control that have emerged and been applied most forcefully in the field of metabolic engineering. These principles, such as the robustness of flux distributions, address connectivity relationships in complex metabolic networks and make it unlikely a priori that modulating most molecular targets will have predictable, beneficial functional outcomes. These same principles also suggest, however, that unexpected therapeutic actions will be common for agents that have any effect (i.e., that complexity can be exploited therapeutically). A potential operational solution (pathway-based DDD), based on observability rather than predictability, is described, focusing on emergent properties of key metabolic pathways in vivo. Recent examples of pathway-based DDD are described. In summary, the molecular target-based DDD paradigm is built on a naïve and misleading model of biologic control and is not heuristically adequate for advancing the mission of modern therapeutics. New approaches that take account of and are built on principles described by metabolic engineers are needed for the next generation of DDD.

Advances in Piezoelectric Systems: An Application-Based Approach

DEFF Research Database (Denmark)

Zsurzsan, Tiberiu-Gabriel

with their low manufacturing costs and high robustness has enabled wide-spread usage in applications ranging from simple spark lighters or pressure sensors to much more complicated energy harvesting systems and piezoelectric transformers. One governing property of piezoelectric devices is the existence....... These three distinct behaviors encountered in any piezoelectric device represents the ba- sis of discussion in the thesis. Therefore the present PhD dissertation is an application-based approach to researching all three behaviors individually, while nding solutions to the challenges encountered along the way...... bidirectional operation of a self-oscillating converter. Feasibility of using the converter in an MRI scanner is demonstrated. The third and nal behavior researched is the resistive behavior. This is widely encountered since most piezoelectric motors, ultrasonic baths and some energy harvesting systems operate...

Understanding alternative fluxes/effluxes through comparative metabolic pathway analysis of phylum actinobacteria using a simplified approach.

Science.gov (United States)

Verma, Mansi; Lal, Devi; Saxena, Anjali; Anand, Shailly; Kaur, Jasvinder; Kaur, Jaspreet; Lal, Rup

2013-12-01

Actinobacteria are known for their diverse metabolism and physiology. Some are dreadful human pathogens whereas some constitute the natural flora for human gut. Therefore, the understanding of metabolic pathways is a key feature for targeting the pathogenic bacteria without disturbing the symbiotic ones. A big challenge faced today is multiple drug resistance by Mycobacterium and other pathogens that utilize alternative fluxes/effluxes. With the availability of genome sequence, it is now feasible to conduct the comparative in silico analysis. Here we present a simplified approach to compare metabolic pathways so that the species specific enzyme may be traced and engineered for future therapeutics. The analyses of four key carbohydrate metabolic pathways, i.e., glycolysis, pyruvate metabolism, tri carboxylic acid cycle and pentose phosphate pathway suggest the presence of alternative fluxes. It was found that the upper pathway of glycolysis was highly variable in the actinobacterial genomes whereas lower glycolytic pathway was highly conserved. Likewise, pentose phosphate pathway was well conserved in contradiction to TCA cycle, which was found to be incomplete in majority of actinobacteria. The clustering based on presence and absence of genes of these metabolic pathways clearly revealed that members of different genera shared identical pathways and, therefore, provided an easy method to identify the metabolic similarities/differences between pathogenic and symbiotic organisms. The analyses could identify isoenzymes and some key enzymes that were found to be missing in some pathogenic actinobacteria. The present work defines a simple approach to explore the effluxes in four metabolic pathways within the phylum actinobacteria. The analysis clearly reflects that actinobacteria exhibit diverse routes for metabolizing substrates. The pathway comparison can help in finding the enzymes that can be used as drug targets for pathogens without effecting symbiotic organisms

A four stage approach for ontology-based health information system design.

Science.gov (United States)

Kuziemsky, Craig E; Lau, Francis

2010-11-01

To describe and illustrate a four stage methodological approach to capture user knowledge in a biomedical domain area, use that knowledge to design an ontology, and then implement and evaluate the ontology as a health information system (HIS). A hybrid participatory design-grounded theory (GT-PD) method was used to obtain data and code them for ontology development. Prototyping was used to implement the ontology as a computer-based tool. Usability testing evaluated the computer-based tool. An empirically derived domain ontology and set of three problem-solving approaches were developed as a formalized model of the concepts and categories from the GT coding. The ontology and problem-solving approaches were used to design and implement a HIS that tested favorably in usability testing. The four stage approach illustrated in this paper is useful for designing and implementing an ontology as the basis for a HIS. The approach extends existing ontology development methodologies by providing an empirical basis for theory incorporated into ontology design. Copyright © 2010 Elsevier B.V. All rights reserved.

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.

A corpus-based approach to generalising a chatbot system

OpenAIRE

Abu Shawar, Bayan; Atwell, Eric

2003-01-01

International research in NLP is dominated by work on English. NLP techniques and systems can be ported to other natural languages, but this is generally a labour-intensive task, requiring scarce computational and linguistic expertise; hence minority languages are poorly represented in NLP technology. We present an automated approach to porting an NLP technology, the AIML-based chatbot, to new languages, by using a corpus in the target language to retrain the chatbot. We have s...

Model-Based Systems Engineering Approach to Managing Mass Margin

Science.gov (United States)

Chung, Seung H.; Bayer, Todd J.; Cole, Bjorn; Cooke, Brian; Dekens, Frank; Delp, Christopher; Lam, Doris

2012-01-01

When designing a flight system from concept through implementation, one of the fundamental systems engineering tasks ismanaging the mass margin and a mass equipment list (MEL) of the flight system. While generating a MEL and computing a mass margin is conceptually a trivial task, maintaining consistent and correct MELs and mass margins can be challenging due to the current practices of maintaining duplicate information in various forms, such as diagrams and tables, and in various media, such as files and emails. We have overcome this challenge through a model-based systems engineering (MBSE) approach within which we allow only a single-source-of-truth. In this paper we describe the modeling patternsused to capture the single-source-of-truth and the views that have been developed for the Europa Habitability Mission (EHM) project, a mission concept study, at the Jet Propulsion Laboratory (JPL).

Microbial production of natural and non-natural flavonoids: Pathway engineering, directed evolution and systems/synthetic biology.

Science.gov (United States)

Pandey, Ramesh Prasad; Parajuli, Prakash; Koffas, Mattheos A G; Sohng, Jae Kyung

2016-01-01

In this review, we address recent advances made in pathway engineering, directed evolution, and systems/synthetic biology approaches employed in the production and modification of flavonoids from microbial cells. The review is divided into two major parts. In the first, various metabolic engineering and system/synthetic biology approaches used for production of flavonoids and derivatives are discussed broadly. All the manipulations/engineering accomplished on the microorganisms since 2000 are described in detail along with the biosynthetic pathway enzymes, their sources, structures of the compounds, and yield of each product. In the second part of the review, post-modifications of flavonoids by four major reactions, namely glycosylations, methylations, hydroxylations and prenylations using recombinant strains are described. Copyright © 2016 Elsevier Inc. All rights reserved.

A decision support system based on hybrid knowledge approach for nuclear power plant operation

International Nuclear Information System (INIS)

Yang, J.O.; Chang, S.H.

1991-01-01

This paper describes a diagnostic expert system, HYPOSS (Hybrid Knowledge Based Plant Operation Supporting System), which has been developed to support operators' decision making during the transients of nuclear power plant. HYPOSS adopts the hybrid knowledge approach which combines shallow and deep knowledge to couple the merits of both approaches. In HYPOSS, four types of knowledge are used according to the steps of diagnosis procedure: structural, functional, behavioral and heuristic knowledge. Frames and rules are adopted to represent the various knowledge types. Rule-based deduction and abduction are used for shallow and deep knowledge based reasoning respectively. The event-based operational guidelines are provided to the operator according to the diagnosed results

A method for integrating and ranking the evidence for biochemical pathways by mining reactions from text

Science.gov (United States)

Miwa, Makoto; Ohta, Tomoko; Rak, Rafal; Rowley, Andrew; Kell, Douglas B.; Pyysalo, Sampo; Ananiadou, Sophia

2013-01-01

Motivation: To create, verify and maintain pathway models, curators must discover and assess knowledge distributed over the vast body of biological literature. Methods supporting these tasks must understand both the pathway model representations and the natural language in the literature. These methods should identify and order documents by relevance to any given pathway reaction. No existing system has addressed all aspects of this challenge. Method: We present novel methods for associating pathway model reactions with relevant publications. Our approach extracts the reactions directly from the models and then turns them into queries for three text mining-based MEDLINE literature search systems. These queries are executed, and the resulting documents are combined and ranked according to their relevance to the reactions of interest. We manually annotate document-reaction pairs with the relevance of the document to the reaction and use this annotation to study several ranking methods, using various heuristic and machine-learning approaches. Results: Our evaluation shows that the annotated document-reaction pairs can be used to create a rule-based document ranking system, and that machine learning can be used to rank documents by their relevance to pathway reactions. We find that a Support Vector Machine-based system outperforms several baselines and matches the performance of the rule-based system. The success of the query extraction and ranking methods are used to update our existing pathway search system, PathText. Availability: An online demonstration of PathText 2 and the annotated corpus are available for research purposes at http://www.nactem.ac.uk/pathtext2/. Contact: makoto.miwa@manchester.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online. PMID:23813008

Systemic approaches to biodegradation.

Science.gov (United States)

Trigo, Almudena; Valencia, Alfonso; Cases, Ildefonso

2009-01-01

Biodegradation, the ability of microorganisms to remove complex chemicals from the environment, is a multifaceted process in which many biotic and abiotic factors are implicated. The recent accumulation of knowledge about the biochemistry and genetics of the biodegradation process, and its categorization and formalization in structured databases, has recently opened the door to systems biology approaches, where the interactions of the involved parts are the main subject of study, and the system is analysed as a whole. The global analysis of the biodegradation metabolic network is beginning to produce knowledge about its structure, behaviour and evolution, such as its free-scale structure or its intrinsic robustness. Moreover, these approaches are also developing into useful tools such as predictors for compounds' degradability or the assisted design of artificial pathways. However, it is the environmental application of high-throughput technologies from the genomics, metagenomics, proteomics and metabolomics that harbours the most promising opportunities to understand the biodegradation process, and at the same time poses tremendous challenges from the data management and data mining point of view.

Optimal inverse magnetorheological damper modeling using shuffled frog-leaping algorithm–based adaptive neuro-fuzzy inference system approach

Directory of Open Access Journals (Sweden)

Xiufang Lin

2016-08-01

Full Text Available Magnetorheological dampers have become prominent semi-active control devices for vibration mitigation of structures which are subjected to severe loads. However, the damping force cannot be controlled directly due to the inherent nonlinear characteristics of the magnetorheological dampers. Therefore, for fully exploiting the capabilities of the magnetorheological dampers, one of the challenging aspects is to develop an accurate inverse model which can appropriately predict the input voltage to control the damping force. In this article, a hybrid modeling strategy combining shuffled frog-leaping algorithm and adaptive-network-based fuzzy inference system is proposed to model the inverse dynamic characteristics of the magnetorheological dampers for improving the modeling accuracy. The shuffled frog-leaping algorithm is employed to optimize the premise parameters of the adaptive-network-based fuzzy inference system while the consequent parameters are tuned by a least square estimation method, here known as shuffled frog-leaping algorithm-based adaptive-network-based fuzzy inference system approach. To evaluate the effectiveness of the proposed approach, the inverse modeling results based on the shuffled frog-leaping algorithm-based adaptive-network-based fuzzy inference system approach are compared with those based on the adaptive-network-based fuzzy inference system and genetic algorithm–based adaptive-network-based fuzzy inference system approaches. Analysis of variance test is carried out to statistically compare the performance of the proposed methods and the results demonstrate that the shuffled frog-leaping algorithm-based adaptive-network-based fuzzy inference system strategy outperforms the other two methods in terms of modeling (training accuracy and checking accuracy.

Optimal processing pathway for the production of biodiesel from microalgal biomass: A superstructure based approach

DEFF Research Database (Denmark)

Rizwan, Muhammad; Lee, Jay H.; Gani, Rafiqul

2013-01-01

In this study, we propose a mixed integer nonlinear programming (MINLP) model for superstructure based optimization of biodiesel production from microalgal biomass. The proposed superstructure includes a number of major processing steps for the production of biodiesel from microalgal biomass......, such as the harvesting of microalgal biomass, pretreatments including drying and cell disruption of harvested biomass, lipid extraction, transesterification, and post-transesterfication purification. The proposed model is used to find the optimal processing pathway among the large number of potential pathways that exist...... for the production of biodiesel from microalgae. The proposed methodology is tested by implementing on a specific case with different choices of objective functions. The MINLP model is implemented and solved in GAMS using a database built in Excel. The results from the optimization are analyzed...

Metric-based approach and tool for modeling the I and C system using Markov chains

International Nuclear Information System (INIS)

Butenko, Valentyna; Kharchenko, Vyacheslav; Odarushchenko, Elena; Butenko, Dmitriy

2015-01-01

Markov's chains (MC) are well-know and widely applied in dependability and performability analysis of safety-critical systems, because of the flexible representation of system components dependencies and synchronization. There are few radblocks for greater application of the MC: accounting the additional system components increases the model state-space and complicates analysis; the non-numerically sophisticated user may find it difficult to decide between the variety of numerical methods to determine the most suitable and accurate for their application. Thus obtaining the high accurate and trusted modeling results becomes a nontrivial task. In this paper, we present the metric-based approach for selection of the applicable solution approach, based on the analysis of MCs stiffness, decomposability, sparsity and fragmentedness. Using this selection procedure the modeler can provide the verification of earlier obtained results. The presented approach was implemented in utility MSMC, which supports the MC construction, metric-based analysis, recommendations shaping and model solution. The model can be exported to the wall-known off-the-shelf mathematical packages for verification. The paper presents the case study of the industrial NPP I and C system, manufactured by RPC Radiy. The paper shows an application of metric-based approach and MSMC fool for dependability and safety analysis of RTS, and procedure of results verification. (author)

RAMM: a system of computer programs for radionuclide pathway analysis calculations

International Nuclear Information System (INIS)

Lyon, R.B.

1976-09-01

A generalized system of computer programs, designated RAMM (Radioactive Materials Management) system, has been developed to assist in the analysis of the movement of radionuclides through the environment to man. RAMM incorporates the GASP IV continuous/discrete simulation system. A nodal approach is used whereby the system to be analyzed is split up into parts small enough that the distribution of nuclides within the node may be taken to be homogeneous. Pathways are defined between nodes, and appropriate transfer coefficients are input or generated. Output includes the time dependent contents of the nodes and dose rates, integrated doses and dose commitments of selected nodes. (author)

Toward a Model-Based Approach to Flight System Fault Protection

Science.gov (United States)

Day, John; Murray, Alex; Meakin, Peter

2012-01-01

Fault Protection (FP) is a distinct and separate systems engineering sub-discipline that is concerned with the off-nominal behavior of a system. Flight system fault protection is an important part of the overall flight system systems engineering effort, with its own products and processes. As with other aspects of systems engineering, the FP domain is highly amenable to expression and management in models. However, while there are standards and guidelines for performing FP related analyses, there are not standards or guidelines for formally relating the FP analyses to each other or to the system hardware and software design. As a result, the material generated for these analyses are effectively creating separate models that are only loosely-related to the system being designed. Development of approaches that enable modeling of FP concerns in the same model as the system hardware and software design enables establishment of formal relationships that has great potential for improving the efficiency, correctness, and verification of the implementation of flight system FP. This paper begins with an overview of the FP domain, and then continues with a presentation of a SysML/UML model of the FP domain and the particular analyses that it contains, by way of showing a potential model-based approach to flight system fault protection, and an exposition of the use of the FP models in FSW engineering. The analyses are small examples, inspired by current real-project examples of FP analyses.

On Anticipatory Development of Dual Education Based on the Systemic Approach

Science.gov (United States)

Alshynbayeva, Zhuldyz; Sarbassova, Karlygash; Galiyeva, Temir; Kaltayeva, Gulnara; Bekmagambetov, Aidos

2016-01-01

The article addresses separate theoretical and methodical aspects of the anticipatory development of dual education in the Republic of Kazakhstan based on the systemic approach. It states the need to develop orientating basis of prospective professional activities in students. We define the concepts of anticipatory cognition and anticipatory…

Systems Biology Approach to Bioremediation of Nitroaromatics: Constraint-Based Analysis of 2,4,6-Trinitrotoluene Biotransformation by Escherichia coli

Directory of Open Access Journals (Sweden)

Maryam Iman

2017-08-01

Full Text Available Microbial remediation of nitroaromatic compounds (NACs is a promising environmentally friendly and cost-effective approach to the removal of these life-threating agents. Escherichia coli (E. coli has shown remarkable capability for the biotransformation of 2,4,6-trinitro-toluene (TNT. Efforts to develop E. coli as an efficient TNT degrading biocatalyst will benefit from holistic flux-level description of interactions between multiple TNT transforming pathways operating in the strain. To gain such an insight, we extended the genome-scale constraint-based model of E. coli to account for a curated version of major TNT transformation pathways known or evidently hypothesized to be active in E. coli in present of TNT. Using constraint-based analysis (CBA methods, we then performed several series of in silico experiments to elucidate the contribution of these pathways individually or in combination to the E. coli TNT transformation capacity. Results of our analyses were validated by replicating several experimentally observed TNT degradation phenotypes in E. coli cultures. We further used the extended model to explore the influence of process parameters, including aeration regime, TNT concentration, cell density, and carbon source on TNT degradation efficiency. We also conducted an in silico metabolic engineering study to design a series of E. coli mutants capable of degrading TNT at higher yield compared with the wild-type strain. Our study, therefore, extends the application of CBA to bioremediation of nitroaromatics and demonstrates the usefulness of this approach to inform bioremediation research.

Language pathway tracking: comparing nTMS-based DTI fiber tracking with a cubic ROIs-based protocol.

Science.gov (United States)

Negwer, Chiara; Sollmann, Nico; Ille, Sebastian; Hauck, Theresa; Maurer, Stefanie; Kirschke, Jan S; Ringel, Florian; Meyer, Bernhard; Krieg, Sandro M

2017-03-01

OBJECTIVE Diffusion tensor imaging (DTI) fiber tracking (FT) has been widely used in glioma surgery in recent years. It can provide helpful information about subcortical structures, especially in patients with eloquent space-occupying lesions. This study compared the newly developed navigated transcranial magnetic stimulation (nTMS)-based DTI FT of language pathways with the most reproducible protocol for language pathway tractography, using cubic regions of interest (ROIs) for the arcuate fascicle. METHODS Thirty-seven patients with left-sided perisylvian lesions underwent language mapping by repetitive nTMS. DTI FT was performed using the cubic ROIs-based protocol and the authors' nTMS-based DTI FT approach. The same minimal fiber length and fractional anisotropy were chosen (50 mm and 0.2, respectively). Both protocols were performed with standard clinical tractography software. RESULTS Both methods visualized language-related fiber tracts (i.e., corticonuclear tract, arcuate fascicle, uncinate fascicle, superior longitudinal fascicle, inferior longitudinal fascicle, arcuate fibers, commissural fibers, corticothalamic fibers, and frontooccipital fascicle) in all 37 patients. Using the cubic ROIs-based protocol, 39.9% of these language-related fiber tracts were detected in the examined patients, as opposed to 76.0% when performing nTMS-based DTI FT. For specifically tracking the arcuate fascicle, however, the cubic ROIs-based approach showed better results (97.3% vs 75.7% with nTMS-based DTI FT). CONCLUSIONS The cubic ROIs-based protocol was designed for arcuate fascicle tractography, and this study shows that it is still useful for this intention. However, superior results were obtained using the nTMS-based DTI FT for visualization of other language-related fiber tracts.

Quantitative assessment of key parameters in qualitative vulnerability methods applied in karst systems based on an integrated numerical modelling approach

Science.gov (United States)

Doummar, Joanna; Kassem, Assaad

2017-04-01

In the framework of a three-year PEER (USAID/NSF) funded project, flow in a Karst system in Lebanon (Assal) dominated by snow and semi arid conditions was simulated and successfully calibrated using an integrated numerical model (MIKE-She 2016) based on high resolution input data and detailed catchment characterization. Point source infiltration and fast flow pathways were simulated by a bypass function and a high conductive lens respectively. The approach consisted of identifying all the factors used in qualitative vulnerability methods (COP, EPIK, PI, DRASTIC, GOD) applied in karst systems and to assess their influence on recharge signals in the different hydrological karst compartments (Atmosphere, Unsaturated zone and Saturated zone) based on the integrated numerical model. These parameters are usually attributed different weights according to their estimated impact on Groundwater vulnerability. The aim of this work is to quantify the importance of each of these parameters and outline parameters that are not accounted for in standard methods, but that might play a role in the vulnerability of a system. The spatial distribution of the detailed evapotranspiration, infiltration, and recharge signals from atmosphere to unsaturated zone to saturated zone was compared and contrasted among different surface settings and under varying flow conditions (e.g., in varying slopes, land cover, precipitation intensity, and soil properties as well point source infiltration). Furthermore a sensitivity analysis of individual or coupled major parameters allows quantifying their impact on recharge and indirectly on vulnerability. The preliminary analysis yields a new methodology that accounts for most of the factors influencing vulnerability while refining the weights attributed to each one of them, based on a quantitative approach.

A structural systems biology approach for quantifying the systemic consequences of missense mutations in proteins.

Directory of Open Access Journals (Sweden)

Tammy M K Cheng

Full Text Available Gauging the systemic effects of non-synonymous single nucleotide polymorphisms (nsSNPs is an important topic in the pursuit of personalized medicine. However, it is a non-trivial task to understand how a change at the protein structure level eventually affects a cell's behavior. This is because complex information at both the protein and pathway level has to be integrated. Given that the idea of integrating both protein and pathway dynamics to estimate the systemic impact of missense mutations in proteins remains predominantly unexplored, we investigate the practicality of such an approach by formulating mathematical models and comparing them with experimental data to study missense mutations. We present two case studies: (1 interpreting systemic perturbation for mutations within the cell cycle control mechanisms (G2 to mitosis transition for yeast; (2 phenotypic classification of neuron-related human diseases associated with mutations within the mitogen-activated protein kinase (MAPK pathway. We show that the application of simplified mathematical models is feasible for understanding the effects of small sequence changes on cellular behavior. Furthermore, we show that the systemic impact of missense mutations can be effectively quantified as a combination of protein stability change and pathway perturbation.

A Study on Satellite Diagnostic Expert Systems Using Case-Based Approach

Directory of Open Access Journals (Sweden)

Young-Tack Park

1997-06-01

Full Text Available Many research works are on going to monitor and diagnose diverse malfunctions of satellite systems as the complexity and number of satellites increase. Currently, many works on monitoring and diagnosis are carried out by human experts but there are needs to automate much of the routine works of them. Hence, it is necessary to study on using expert systems which can assist human experts routine work by doing automatically, thereby allow human experts devote their expertise more critical and important areas of monitoring and diagnosis. In this paper, we are employing artificial intelligence techniques to model human experts' knowledge and inference the constructed knowledge. Especially, case-based approaches are used to construct a knowledge base to model human expert capabilities which use previous typical exemplars. We have designed and implemented a prototype case-based system for diagnosing satellite malfunctions using cases. Our system remembers typical failure cases and diagnoses a current malfunction by indexing the case base. Diverse methods are used to build a more user friendly interface which allows human experts can build a knowledge base in as easy way.

Imprecise system reliability and component importance based on survival signature

International Nuclear Information System (INIS)

Feng, Geng; Patelli, Edoardo; Beer, Michael; Coolen, Frank P.A.

2016-01-01

The concept of the survival signature has recently attracted increasing attention for performing reliability analysis on systems with multiple types of components. It opens a new pathway for a structured approach with high computational efficiency based on a complete probabilistic description of the system. In practical applications, however, some of the parameters of the system might not be defined completely due to limited data, which implies the need to take imprecisions of component specifications into account. This paper presents a methodology to include explicitly the imprecision, which leads to upper and lower bounds of the survival function of the system. In addition, the approach introduces novel and efficient component importance measures. By implementing relative importance index of each component without or with imprecision, the most critical component in the system can be identified depending on the service time of the system. Simulation method based on survival signature is introduced to deal with imprecision within components, which is precise and efficient. Numerical example is presented to show the applicability of the approach for systems. - Highlights: • Survival signature is a novel way for system reliability and component importance • High computational efficiency based on a complete description of system. • Include explicitly the imprecision, which leads to bounds of the survival function. • A novel relative importance index is proposed as importance measure. • Allows to identify critical components depending on the service time of the system.

A knowledge-based approach to the design of integrated renewable energy systems

Energy Technology Data Exchange (ETDEWEB)

Ramakumar, R.; Abouzahr, I. (Oklahoma State Univ., Stillwater, OK (United States). Engineering Energy Lab.); Ashenayi, K. (Dept. of Electrical Engineering, Univ. of Tulsa, Tulsa, OK (United States))

1992-12-01

Integrated Renewable Energy Systems (IRES) utilize two or more renewable energy resources and end-use technologies to supply a variety of energy needs, often in a stand-alone mode. A knowledge-based design approach that minimizes the total capital cost at a pre-selected reliability level is presented. The reliability level is quantified by the loss of power supply probability (LPSP). The procedure includes some resource-need matching based on economics, the quality of energy needed, and the characteristics of the resource. A detailed example is presented in this paper and discussed to illustrate the usefullness of the design approach.

The evolution of the pathway and its role in improving patient care.

Science.gov (United States)

Mould, G; Bowers, J; Ghattas, M

2010-10-01

Redesign in healthcare has increased the focus on the needs of the patient. The redesign process typically involves a review of current practice using the patient pathway before considering possible improvements. The patient pathway can serve various roles, and it may be mapped in different ways using a variety of media. This paper reviews the evolution of the patient pathway comparing the merits of different media. Simple approaches to mapping pathways can be most useful. However, experience in the redesign of Unscheduled Care in NHS Fife suggests that computer-based, hierarchical pathway models using stylised icons offer many advantages. Such approaches can increase the effectiveness of pathways in the redesign process, providing both the detail and the system view in an accessible graphical form. This enhanced capability helps staff analyse current practice and visualise and assess redesign options. In addition, the pathway can fulfil new roles as a training tool and an effective basis for organising knowledge about patient care.

Agent-Based Modeling in Molecular Systems Biology.

Science.gov (United States)

Soheilypour, Mohammad; Mofrad, Mohammad R K

2018-06-08

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

A port-Hamiltonian approach to image-based visual servo control for dynamic systems

NARCIS (Netherlands)

Mahony, R.; Stramigioli, Stefano

2012-01-01

This paper introduces a port-Hamiltonian framework for the design of image-based visual servo control for dynamic mechanical systems. The approach taken introduces the concept of an image effort and provides an interpretation of energy exchange between the dynamics of the physical system and virtual

Assessment of multi-version NPP I and C systems safety. Metric-based approach, technique and tool

International Nuclear Information System (INIS)

Kharchenko, Vyacheslav; Volkovoy, Andrey; Bakhmach, Eugenii; Siora, Alexander; Duzhyi, Vyacheslav

2011-01-01

The challenges related to problem of assessment of actual diversity level and evaluation of diversity-oriented NPP I and C systems safety are analyzed. There are risks of inaccurate assessment and problems of insufficient decreasing probability of CCFs. CCF probability of safety-critical systems may be essentially decreased due to application of several different types of diversity (multi-diversity). Different diversity types of FPGA-based NPP I and C systems, general approach and stages of diversity and safety assessment as a whole are described. Objectives of the report are: (a) analysis of the challenges caused by use of diversity approach in NPP I and C systems in context of FPGA and other modern technologies application; (b) development of multi-version NPP I and C systems assessment technique and tool based on check-list and metric-oriented approach; (c) case-study of the technique: assessment of multi-version FPGA-based NPP I and C developed by use of Radiy TM Platform. (author)

Stabilization of nonlinear systems using sampled-data output-feedback fuzzy controller based on polynomial-fuzzy-model-based control approach.

Science.gov (United States)

Lam, H K

2012-02-01

This paper investigates the stability of sampled-data output-feedback (SDOF) polynomial-fuzzy-model-based control systems. Representing the nonlinear plant using a polynomial fuzzy model, an SDOF fuzzy controller is proposed to perform the control process using the system output information. As only the system output is available for feedback compensation, it is more challenging for the controller design and system analysis compared to the full-state-feedback case. Furthermore, because of the sampling activity, the control signal is kept constant by the zero-order hold during the sampling period, which complicates the system dynamics and makes the stability analysis more difficult. In this paper, two cases of SDOF fuzzy controllers, which either share the same number of fuzzy rules or not, are considered. The system stability is investigated based on the Lyapunov stability theory using the sum-of-squares (SOS) approach. SOS-based stability conditions are obtained to guarantee the system stability and synthesize the SDOF fuzzy controller. Simulation examples are given to demonstrate the merits of the proposed SDOF fuzzy control approach.

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

An integrated approach to preventing cardiovascular disease: community-based approaches, health system initiatives, and public health policy.

Science.gov (United States)

Karwalajtys, Tina; Kaczorowski, Janusz

2010-01-01

Cardiovascular disease (CVD) is largely the product of interactions among modifiable risk factors that are common in developed nations and increasingly of concern in developing countries. Hypertension is an important precursor to the development of CVD, and although detection and treatment rates have improved in recent years in some jurisdictions, effective strategies and policies supporting a shift in distribution of risk factors at the population level remain paramount. Challenges in managing cardiovascular health more effectively include factors at the patient, provider, and system level. Strategies to reduce hypertension and CVD should be population based, incorporate multilevel, multicomponent, and socioenvironmental approaches, and integrate community resources with public health and clinical care. There is an urgent need to improve monitoring and management of risk factors through community-wide, primary care-linked initiatives, increase the evidence base for community-based prevention strategies, further develop and evaluate promising program components, and develop new approaches to support healthy lifestyle behaviors in diverse age, socioeconomic, and ethnocultural groups. Policy and system changes are critical to reduce risk in populations, including legislation and public education to reduce dietary sodium and trans-fatty acids, food pricing policies, and changes to health care delivery systems to explicitly support prevention and management of CVD.

Mass spectrometry-based metabolomics: applications to biomarker and metabolic pathway research.

Science.gov (United States)

Zhang, Aihua; Sun, Hui; Yan, Guangli; Wang, Ping; Wang, Xijun

2016-01-01

Mass spectrometry-based metabolomics has become increasingly popular in molecular medicine. High-definition mass spectrometry (MS), coupled with pattern recognition methods, have been carried out to obtain comprehensive metabolite profiling and metabolic pathway of large biological datasets. This sets the scene for a new and powerful diagnostic approach. Analysis of the key metabolites in body fluids has become an important part of improving disease diagnosis. With technological advances in analytical techniques, the ability to measure low-molecular-weight metabolites in bio-samples provides a powerful platform for identifying metabolites that are uniquely correlated with a specific human disease. MS-based metabolomics can lead to enhanced understanding of disease mechanisms and to new diagnostic markers and has a strong potential to contribute to improving early diagnosis of diseases. This review will highlight the importance and benefit with certain characteristic examples of MS-metabolomics for identifying metabolic pathways and metabolites that accurately screen for potential diagnostic biomarkers of diseases. Copyright © 2015 John Wiley & Sons, Ltd.

Adverse Outcome Pathways can drive non-animal approaches for safety assessment.

Science.gov (United States)

Burden, Natalie; Sewell, Fiona; Andersen, Melvin E; Boobis, Alan; Chipman, J Kevin; Cronin, Mark T D; Hutchinson, Thomas H; Kimber, Ian; Whelan, Maurice

2015-09-01

Adverse Outcome Pathways (AOPs) provide an opportunity to develop new and more accurate safety assessment processes for drugs and other chemicals, and may ultimately play an important role in regulatory decision making. Not only can the development and application of AOPs pave the way for the development of improved evidence-based approaches for hazard and risk assessment, there is also the promise of a significant impact on animal welfare, with a reduced reliance on animal-based methods. The establishment of a useable and coherent knowledge framework under which AOPs will be developed and applied has been a first critical step towards realizing this opportunity. This article explores how the development of AOPs under this framework, and their application in practice, could benefit the science and practice of safety assessment, while in parallel stimulating a move away from traditional methods towards an increased acceptance of non-animal approaches. We discuss here the key areas where current, and future initiatives should be focused to enable the translation of AOPs into routine chemical safety assessment, and lasting 3Rs benefits. © 2015 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd.

De novo pathway-based biomarker identification

DEFF Research Database (Denmark)

Alcaraz, Nicolas; List, Markus; Batra, Richa

2017-01-01

in a large cohort of breast cancer samples from The Cancer Genome Atlas (TCGA) revealed that MGs are considerably more stable than SG models, while also providing valuable insight into the cancer hallmarks that drive them. In addition, when tested on an independent benchmark non-TCGA dataset, MG features......Gene expression profiles have been extensively discussed as an aid to guide the therapy by predicting disease outcome for the patients suffering from complex diseases, such as cancer. However, prediction models built upon single-gene (SG) features show poor stability and performance on independent...... on their molecular subtypes can provide a detailed view of the disease and lead to more personalized therapies. We propose and discuss a novel MG approach based on de novo pathways, which for the first time have been used as features in a multi-class setting to predict cancer subtypes. Comprehensive evaluation...

Toward a risk-based approach to the assessment of the surety of information systems

Energy Technology Data Exchange (ETDEWEB)

Wyss, G.D.; Fletcher, S.K.; Halbgewachs, R.D.; Jansma, R.M.; Lim, J.J.; Murphy, M.; Sands, P.D.

1995-03-01

Traditional approaches to the assessment of information systems have treated system security, system reliability, data integrity, and application functionality as separate disciplines. However, each areas requirements and solutions have a profound impact on the successful implementation of the other areas. A better approach is to assess the ``surety`` of an information system, which is defined as ensuring the ``correct`` operation of an information system by incorporating appropriate levels of safety, functionality, confidentiality, availability, and integrity. Information surety examines the combined impact of design alternatives on all of these areas. We propose a modelling approach that combines aspects of fault trees and influence diagrams for assessing information surety requirements under a risk assessment framework. This approach allows tradeoffs to be based on quantitative importance measures such as risk reduction while maintaining the modelling flexibility of the influence diagram paradigm. This paper presents an overview of the modelling method and a sample application problem.

IoT-Based Information System for Healthcare Application: Design Methodology Approach

Directory of Open Access Journals (Sweden)

Damian Dziak

2017-06-01

Full Text Available Over the last few decades, life expectancy has increased significantly. However, elderly people who live on their own often need assistance due to mobility difficulties, symptoms of dementia or other health problems. In such cases, an autonomous supporting system may be helpful. This paper proposes the Internet of Things (IoT-based information system for indoor and outdoor use. Since the conducted survey of related works indicated a lack of methodological approaches to the design process, therefore a Design Methodology (DM, which approaches the design target from the perspective of the stakeholders, contracting authorities and potential users, is introduced. The implemented solution applies the three-axial accelerometer and magnetometer, Pedestrian Dead Reckoning (PDR, thresholding and the decision trees algorithm. Such an architecture enables the localization of a monitored person within four room-zones with accuracy; furthermore, it identifies falls and the activities of lying, standing, sitting and walking. Based on the identified activities, the system classifies current activities as normal, suspicious or dangerous, which is used to notify the healthcare staff about possible problems. The real-life scenarios validated the high robustness of the proposed solution. Moreover, the test results satisfied both stakeholders and future users and ensured further cooperation with the project.

A Multi-Model Approach for System Diagnosis

DEFF Research Database (Denmark)

Niemann, Hans Henrik; Poulsen, Niels Kjølstad; Bækgaard, Mikkel Ask Buur

2007-01-01

A multi-model approach for system diagnosis is presented in this paper. The relation with fault diagnosis as well as performance validation is considered. The approach is based on testing a number of pre-described models and find which one is the best. It is based on an active approach......,i.e. an auxiliary input to the system is applied. The multi-model approach is applied on a wind turbine system....

Sensitivity analysis approaches applied to systems biology models.

Science.gov (United States)

Zi, Z

2011-11-01

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

A procurement-based pathway for promoting public health: innovative purchasing approaches for state and local government agencies.

Science.gov (United States)

Noonan, Kathleen; Miller, Dorothy; Sell, Katherine; Rubin, David

2013-11-01

Through their purchasing powers, government agencies can play a critical role in leveraging markets to create healthier foods. In the United States, state and local governments are implementing creative approaches to procuring healthier foods, moving beyond the traditional regulatory relationship between government and vendors. They are forging new partnerships between government, non-profits, and researchers to increase healthier purchasing. On the basis of case examples, this article proposes a pathway in which state and local government agencies can use the procurement cycle to improve healthy eating.

Two-Component Systems of Mycobacterium tuberculosis—Structure-Based Approaches

DEFF Research Database (Denmark)

Tucker, Paul; Nowak, Elzbieta; Morth, Jens Preben

2007-01-01

Mycobacterium tuberculosis contains few two‐component systems compared to many other bacteria, possibly because it has more serine/threonine signaling pathways. Even so, these two‐component systems appear to play an important role in early intracellular survival of the pathogen as well as in aspe...

TRWG developmental pathway for biospecimen-based assessment modalities

Energy Technology Data Exchange (ETDEWEB)

Translational Research Working Group; Srivastava, Sudhir; Gray, Joe W.; Reid, Brian J.; Grad, Oren; Greenwood, Addison; Hawk, Ernest T.

2008-09-03

The Translational Research Working Group (TRWG) was created as a national initiative to evaluate the current status of NCI's investment in translational research and envision its future. The TRWG conceptualized translational research as a set of six developmental processes or pathways focused on various clinical goals. One of those pathways describes the development of biospecimen-based assays that utilize biomarkers for the detection, diagnosis, prognosis, and assessment of response to cancer treatment. The biospecimen-based assessment modality (BM) pathway was conceived not as comprehensive description of the corresponding real-world processes, but rather as a tool designed to facilitate movement of a candidate assay through the translational process to the point where it can be handed off for definitive clinical testing. This paper introduces the pathway in the context of prior work and discusses key challenges associated with the biomarker development process in light of the pathway.

Nanotubule and Tour Molecule Based Molecular Electronics: Suggestion for a Hybrid Approach

Science.gov (United States)

Srivastava, Deepak; Saini, Subhash (Technical Monitor)

1998-01-01

Recent experimental and theoretical attempts and results indicate two distinct broad pathways towards future molecular electronic devices and architectures. The first is the approach via Tour type ladder molecules and their junctions which can be fabricated with solution phase chemical approaches. Second are fullerenes or nanotubules and their junctions which may have better conductance, switching and amplifying characteristics but can not be made through well controlled and defined chemical means. A hybrid approach combining the two pathways to take advantage of the characteristics of both is suggested. Dimension and scale of such devices would be somewhere in between isolated molecule and nanotubule based devices but it maybe possible to use self-assembly towards larger functional and logicalunits.

Pathway-based approaches for assessment of real-time exposure to an estrogenic wastewater treatment plant effluent on fathead minnow reproduction

Science.gov (United States)

Cavallin, Jenna E.; Jensen, Kathleen M.; Kahl, Michael D.; Villeneuve, Daniel L.; Lee, Kathy E.; Schroeder, Anthony L.; Mayasich, Joe; Eid, Evan P.; Nelson, Krysta R.; Milsk, Rebecca Y.; Blackwell, Brett R.; Berninger, Jason P.; LaLone, Carlie A.; Blanskma, Chad; Jicha, Terri M.; Elonen, Colleen M.; Johnson, Rodney C.; Ankley, Gerald T.

2016-01-01

Wastewater treatment plant (WWTP) effluents are known contributors of chemical mixtures into the environment. Of particular concern are endocrine-disrupting compounds, such as estrogens, which can affect the hypothalamic-pituitary-gonadal axis function in exposed organisms. The present study examined reproductive effects in fathead minnows exposed for 21 d to a historically estrogenic WWTP effluent. Fathead minnow breeding pairs were held in control water or 1 of 3 effluent concentrations (5%, 20%, and 100%) in a novel onsite, flow-through system providing real-time exposure. The authors examined molecular and biochemical endpoints representing key events along adverse outcome pathways linking estrogen receptor activation and other molecular initiating events to reproductive impairment. In addition, the authors used chemical analysis of the effluent to construct a chemical-gene interaction network to aid in targeted gene expression analyses and identifying potentially impacted biological pathways. Cumulative fecundity was significantly reduced in fish exposed to 100% effluent but increased in those exposed to 20% effluent, the approximate dilution factor in the receiving waters. Plasma vitellogenin concentrations in males increased in a dose-dependent manner with effluent concentration; however, male fertility was not impacted. Although in vitro analyses, analytical chemistry, and biomarker responses confirmed the effluent was estrogenic, estrogen receptor agonists were unlikely the primary driver of impaired reproduction. The results provide insights into the significance of pathway-based effects with regard to predicting adverse reproductive outcomes.

An approach to build knowledge base for reactor accident diagnostic system using statistical method

International Nuclear Information System (INIS)

Kohsaka, Atsuo; Yokobayashi, Masao; Matsumoto, Kiyoshi; Fujii, Minoru

1988-01-01

In the development of a rule based expert system, one of key issues is how to build a knowledge base (KB). A systematic approach has been attempted for building an objective KB efficiently. The approach is based on the concept that a prototype KB should first be generated in a systematic way and then it is to be modified and/or improved by expert for practical use. The statistical method, Factor Analysis, was applied to build a prototype KB for the JAERI expert system DISKET using source information obtained from a PWR simulator. The prototype KB was obtained and the inference with this KB was performed against several types of transients. In each diagnosis, the transient type was well identified. From this study, it is concluded that the statistical method used is useful for building a prototype knowledge base. (author)

Advanced control approach for hybrid systems based on solid oxide fuel cells

International Nuclear Information System (INIS)

Ferrari, Mario L.

2015-01-01

Highlights: • Advanced new control system for SOFC based hybrid plants. • Proportional–Integral approach with feed-forward technology. • Good control of fuel cell temperature. • All critical properties maintained inside safe conditions. - Abstract: This paper shows a new advanced control approach for operations in hybrid systems equipped with solid oxide fuel cell technology. This new tool, which combines feed-forward and standard proportional–integral techniques, controls the system during load changes avoiding failures and stress conditions detrimental to component life. This approach was selected to combine simplicity and good control performance. Moreover, the new approach presented in this paper eliminates the need for mass flow rate meters and other expensive probes, as usually required for a commercial plant. Compared to previous works, better performance is achieved in controlling fuel cell temperature (maximum gradient significantly lower than 3 K/min), reducing the pressure gap between cathode and anode sides (at least a 30% decrease during transient operations), and generating a higher safe margin (at least a 10% increase) for the Steam-to-Carbon Ratio. This new control system was developed and optimized using a hybrid system transient model implemented, validated and tested within previous works. The plant, comprising the coupling of a tubular solid oxide fuel cell stack with a microturbine, is equipped with a bypass valve able to connect the compressor outlet with the turbine inlet duct for rotational speed control. Following model development and tuning activities, several operative conditions were considered to show the new control system increased performance compared to previous tools (the same hybrid system model was used with the new control approach). Special attention was devoted to electrical load steps and ramps considering significant changes in ambient conditions

Fuzzy OLAP association rules mining-based modular reinforcement learning approach for multiagent systems.

Science.gov (United States)

Kaya, Mehmet; Alhajj, Reda

2005-04-01

Multiagent systems and data mining have recently attracted considerable attention in the field of computing. Reinforcement learning is the most commonly used learning process for multiagent systems. However, it still has some drawbacks, including modeling other learning agents present in the domain as part of the state of the environment, and some states are experienced much less than others, or some state-action pairs are never visited during the learning phase. Further, before completing the learning process, an agent cannot exhibit a certain behavior in some states that may be experienced sufficiently. In this study, we propose a novel multiagent learning approach to handle these problems. Our approach is based on utilizing the mining process for modular cooperative learning systems. It incorporates fuzziness and online analytical processing (OLAP) based mining to effectively process the information reported by agents. First, we describe a fuzzy data cube OLAP architecture which facilitates effective storage and processing of the state information reported by agents. This way, the action of the other agent, not even in the visual environment. of the agent under consideration, can simply be predicted by extracting online association rules, a well-known data mining technique, from the constructed data cube. Second, we present a new action selection model, which is also based on association rules mining. Finally, we generalize not sufficiently experienced states, by mining multilevel association rules from the proposed fuzzy data cube. Experimental results obtained on two different versions of a well-known pursuit domain show the robustness and effectiveness of the proposed fuzzy OLAP mining based modular learning approach. Finally, we tested the scalability of the approach presented in this paper and compared it with our previous work on modular-fuzzy Q-learning and ordinary Q-learning.

A Participatory Design Approach for a Mobile App-Based Personal Response System

Science.gov (United States)

Song, Donggil; Oh, Eun Young

2016-01-01

This study reports on a participatory design approach including the design, development, implementation, and evaluation of a mobile app-based personal response system (PRS). The first cycle formulated initial design principles through context and needs analysis; the second utilized the collaboration with instructors and experts embodying specific…

Pathway-based analysis of a melanoma genome-wide association study: analysis of genes related to tumour-immunosuppression.

Directory of Open Access Journals (Sweden)

Nils Schoof

Full Text Available Systemic immunosuppression is a risk factor for melanoma, and sunburn-induced immunosuppression is thought to be causal. Genes in immunosuppression pathways are therefore candidate melanoma-susceptibility genes. If variants within these genes individually have a small effect on disease risk, the association may be undetected in genome-wide association (GWA studies due to low power to reach a high significance level. Pathway-based approaches have been suggested as a method of incorporating a priori knowledge into the analysis of GWA studies. In this study, the association of 1113 single nucleotide polymorphisms (SNPs in 43 genes (39 genomic regions related to immunosuppression have been analysed using a gene-set approach in 1539 melanoma cases and 3917 controls from the GenoMEL consortium GWA study. The association between melanoma susceptibility and the whole set of tumour-immunosuppression genes, and also predefined functional subgroups of genes, was considered. The analysis was based on a measure formed by summing the evidence from the most significant SNP in each gene, and significance was evaluated empirically by case-control label permutation. An association was found between melanoma and the complete set of genes (p(emp=0.002, as well as the subgroups related to the generation of tolerogenic dendritic cells (p(emp=0.006 and secretion of suppressive factors (p(emp=0.0004, thus providing preliminary evidence of involvement of tumour-immunosuppression gene polymorphisms in melanoma susceptibility. The analysis was repeated on a second phase of the GenoMEL study, which showed no evidence of an association. As one of the first attempts to replicate a pathway-level association, our results suggest that low power and heterogeneity may present challenges.

Systems-wide metabolic pathway engineering in Corynebacterium glutamicum for bio-based production of diaminopentane.

Science.gov (United States)

Kind, Stefanie; Jeong, Weol Kyu; Schröder, Hartwig; Wittmann, Christoph

2010-07-01

In the present work the Gram-positive bacterium Corynebacterium glutamicum was engineered into an efficient, tailor-made production strain for diaminopentane (cadaverine), a highly attractive building block for bio-based polyamides. The engineering comprised expression of lysine decarboxylase (ldcC) from Escherichia coli, catalyzing the conversion of lysine into diaminopentane, and systems-wide metabolic engineering of central supporting pathways. Substantially re-designing the metabolism yielded superior strains with desirable properties such as (i) the release from unwanted feedback regulation at the level of aspartokinase and pyruvate carboxylase by introducing the point mutations lysC311 and pycA458, (ii) an optimized supply of the key precursor oxaloacetate by amplifying the anaplerotic enzyme, pyruvate carboxylase, and deleting phosphoenolpyruvate carboxykinase which otherwise removes oxaloacetate, (iii) enhanced biosynthetic flux via combined amplification of aspartokinase, dihydrodipicolinate reductase, diaminopimelate dehydrogenase and diaminopimelate decarboxylase, and (iv) attenuated flux into the threonine pathway competing with production by the leaky mutation hom59 in the homoserine dehydrogenase gene. Lysine decarboxylase proved to be a bottleneck for efficient production, since its in vitro activity and in vivo flux were closely correlated. To achieve an optimal strain having only stable genomic modifications, the combination of the strong constitutive C. glutamicum tuf promoter and optimized codon usage allowed efficient genome-based ldcC expression and resulted in a high diaminopentane yield of 200 mmol mol(-1). By supplementing the medium with 1 mgL(-1) pyridoxal, the cofactor of lysine decarboxylase, the yield was increased to 300 mmol mol(-1). In the production strain obtained, lysine secretion was almost completely abolished. Metabolic analysis, however, revealed substantial formation of an as yet unknown by-product. It was identified as an

A novel bi-level meta-analysis approach: applied to biological pathway analysis.

Science.gov (United States)

Nguyen, Tin; Tagett, Rebecca; Donato, Michele; Mitrea, Cristina; Draghici, Sorin

2016-02-01

The accumulation of high-throughput data in public repositories creates a pressing need for integrative analysis of multiple datasets from independent experiments. However, study heterogeneity, study bias, outliers and the lack of power of available methods present real challenge in integrating genomic data. One practical drawback of many P-value-based meta-analysis methods, including Fisher's, Stouffer's, minP and maxP, is that they are sensitive to outliers. Another drawback is that, because they perform just one statistical test for each individual experiment, they may not fully exploit the potentially large number of samples within each study. We propose a novel bi-level meta-analysis approach that employs the additive method and the Central Limit Theorem within each individual experiment and also across multiple experiments. We prove that the bi-level framework is robust against bias, less sensitive to outliers than other methods, and more sensitive to small changes in signal. For comparative analysis, we demonstrate that the intra-experiment analysis has more power than the equivalent statistical test performed on a single large experiment. For pathway analysis, we compare the proposed framework versus classical meta-analysis approaches (Fisher's, Stouffer's and the additive method) as well as against a dedicated pathway meta-analysis package (MetaPath), using 1252 samples from 21 datasets related to three human diseases, acute myeloid leukemia (9 datasets), type II diabetes (5 datasets) and Alzheimer's disease (7 datasets). Our framework outperforms its competitors to correctly identify pathways relevant to the phenotypes. The framework is sufficiently general to be applied to any type of statistical meta-analysis. The R scripts are available on demand from the authors. sorin@wayne.edu Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e

Understanding images using knowledge based approach

International Nuclear Information System (INIS)

Tascini, G.

1985-01-01

This paper presents an approach to image understanding focusing on low level image processing and proposes a rule-based approach as part of larger knowledge-based system. The general system has a yerarchical structure that comprises several knowledge-based layers. The main idea is to confine at the lower level the domain independent knowledge and to reserve the higher levels for the domain dependent knowledge, that is for the interpretation

Purinergic signaling pathways in endocrine system.

Science.gov (United States)

Bjelobaba, Ivana; Janjic, Marija M; Stojilkovic, Stanko S

2015-09-01

Adenosine-5'-triphosphate is released by neuroendocrine, endocrine, and other cell types and acts as an extracellular agonist for ligand-gated P2X cationic channels and G protein-coupled P2Y receptors in numerous organs and tissues, including the endocrine system. The breakdown of ATP by ectonucleotidases not only terminates its extracellular messenger functions, but also provides a pathway for the generation of two additional agonists: adenosine 5'-diphosphate, acting via some P2Y receptors, and adenosine, a native agonist for G protein-coupled adenosine receptors, also expressed in the endocrine system. This article provides a review of purinergic signaling pathways in the hypothalamic magnocellular neurosecretory cells and neurohypophysis, hypothalamic parvocellular neuroendocrine system, adenohypophysis, and effector glands organized in five axes: hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-growth hormone, and hypothalamic-pituitary-prolactin. We attempted to summarize current knowledge of purinergic receptor subtypes expressed in the endocrine system, including their roles in intracellular signaling, hormone secretion, and other cell functions. We also briefly review the release mechanism for adenosine-5'-triphosphate by neuroendocrine, endocrine and surrounding cells, the enzymes involved in adenosine-5'-triphosphate hydrolysis to adenosine-5'-diphosphate and adenosine, and the relevance of this pathway for sequential activation of receptors and termination of signaling. Published by Elsevier B.V.

Purinergic Signaling Pathways in Endocrine System

Science.gov (United States)

Bjelobaba, Ivana; Janjic, Marija M.; Stojilkovic, Stanko S.

2015-01-01

Adenosine-5′-triphosphate is released by neuroendocrine, endocrine, and other cell types and acts as an extracellular agonist for ligand-gated P2X cationic channels and G protein-coupled P2Y receptors in numerous organs and tissues, including the endocrine system. The breakdown of ATP by ectonucleotidases not only terminates its extracellular messenger functions, but also provides a pathway for the generation of two additional agonists: adenosine 5′-diphosphate, acting via some P2Y receptors, and adenosine, a native agonist for G protein-coupled adenosine receptors, also expressed in the endocrine system. This article provides a review of purinergic signaling pathways in the hypothalamic magnocellular neurosecretory cells and neurohypophysis, hypothalamic parvocellular neuroendocrine system, adenohypophysis, and effector glands organized in five axes: hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-growth hormone, and hypothalamic-pituitary-prolactin. We attempted to summarize current knowledge of purinergic receptor subtypes expressed in the endocrine system, including their roles in intracellular signaling, hormone secretion, and other cell functions. We also briefly review the release mechanism for adenosine-5′-triphosphate by neuroendocrine, endocrine and surrounding cells, the enzymes involved in adenosine-5′-triphosphate hydrolysis to adenosine-5′-diphosphate and adenosine, and the relevance of this pathway for sequential activation of receptors and termination of signaling. PMID:25960051

A systems approach to traditional oriental medicine

DEFF Research Database (Denmark)

Kim, Hyun Uk; Ryu, Jae Yong; Lee, Jong Ok

2015-01-01

Analyzing structural similarities between compounds derived from traditional oriental medicine and human metabolites is a systems-based approach that can help identify mechanisms of action and suggest approaches to reduce toxicity.......Analyzing structural similarities between compounds derived from traditional oriental medicine and human metabolites is a systems-based approach that can help identify mechanisms of action and suggest approaches to reduce toxicity....

Assessing Viability and Sustainability: a Systems-based Approach for Deriving Comprehensive Indicator Sets

Directory of Open Access Journals (Sweden)

Hartmut Bossel

2002-01-01

Full Text Available Performance assessment in holistic approaches such as integrated natural resource management has to deal with a complex set of interacting and self-organizing natural and human systems and agents, all pursuing their own "interests" while also contributing to the development of the total system. Performance indicators must therefore reflect the viability of essential component systems as well as their contributions to the viability and performance of other component systems and the total system under study. A systems-based derivation of a comprehensive set of performance indicators first requires the identification of essential component systems, their mutual (often hierarchical or reciprocal relationships, and their contributions to the performance of other component systems and the total system. The second step consists of identifying the indicators that represent the viability states of the component systems and the contributions of these component systems to the performance of the total system. The search for performance indicators is guided by the realization that essential interests (orientations or orientors of systems and actors are shaped by both their characteristic functions and the fundamental and general properties of their system environments (e.g., normal environmental state, scarcity of resources, variety, variability, change, other coexisting systems. To be viable, a system must devote an essential minimum amount of attention to satisfying the "basic orientors" that respond to the properties of its environment. This fact can be used to define comprehensive and system-specific sets of performance indicators that reflect all important concerns. Often, qualitative indicators and the study of qualitative systems are sufficient for reliable performance assessments. However, this approach can also be formalized for quantitative computer-assisted assessment. Examples are presented of indicator sets for the sustainable development of

A PetriNet-Based Approach for Supporting Traceability in Cyber-Physical Manufacturing Systems.

Science.gov (United States)

Huang, Jiwei; Zhu, Yeping; Cheng, Bo; Lin, Chuang; Chen, Junliang

2016-03-17

With the growing popularity of complex dynamic activities in manufacturing processes, traceability of the entire life of every product has drawn significant attention especially for food, clinical materials, and similar items. This paper studies the traceability issue in cyber-physical manufacturing systems from a theoretical viewpoint. Petri net models are generalized for formulating dynamic manufacturing processes, based on which a detailed approach for enabling traceability analysis is presented. Models as well as algorithms are carefully designed, which can trace back the lifecycle of a possibly contaminated item. A practical prototype system for supporting traceability is designed, and a real-life case study of a quality control system for bee products is presented to validate the effectiveness of the approach.

Scientific Opportunities for Monitoring at Environmental Remediation Sites (SOMERS): Integrated Systems-Based Approaches to Monitoring

Energy Technology Data Exchange (ETDEWEB)

Bunn, Amoret L.; Wellman, Dawn M.; Deeb, Rula A.; Hawley, Elizabeth L.; Truex, Michael J.; Peterson, Mark; Freshley, Mark D.; Pierce, Eric M.; McCord, John; Young, Michael H.; Gilmore, Tyler J.; Miller, Rick; Miracle, Ann L.; Kaback, Dawn; Eddy-Dilek, Carol; Rossabi, Joe; Lee, Michelle H.; Bush, Richard P.; Beam , Paul; Chamberlain, G. M.; Marble, Justin; Whitehurst, Latrincy; Gerdes, Kurt D.; Collazo, Yvette

2012-05-15

Through an inter-disciplinary effort, DOE is addressing a need to advance monitoring approaches from sole reliance on cost- and labor-intensive point-source monitoring to integrated systems-based approaches such as flux-based approaches and the use of early indicator parameters. Key objectives include identifying current scientific, technical and implementation opportunities and challenges, prioritizing science and technology strategies to meet current needs within the DOE complex for the most challenging environments, and developing an integrated and risk-informed monitoring framework.

Chemogenomics profiling of drug targets of peptidoglycan biosynthesis pathway in Leptospira interrogans by virtual screening approaches.

Science.gov (United States)

Bhattacharjee, Biplab; Simon, Rose Mary; Gangadharaiah, Chaithra; Karunakar, Prashantha

2013-06-28

Leptospirosis is a worldwide zoonosis of global concern caused by Leptospira interrogans. The availability of ligand libraries has facilitated the search for novel drug targets using chemogenomics approaches, compared with the traditional method of drug discovery, which is time consuming and yields few leads with little intracellular information for guiding target selection. Recent subtractive genomics studies have revealed the putative drug targets in peptidoglycan biosynthesis pathways in Leptospira interrogans. Aligand library for the murD ligase enzyme in the peptidoglycan pathway has also been identified. Our approach in this research involves screening of the pre-existing ligand library of murD with related protein family members in the putative drug target assembly in the peptidoglycan biosynthesis pathway. A chemogenomics approach has been implemented here, which involves screening of known ligands of a protein family having analogous domain architecture for identification of leads for existing druggable protein family members. By means of this approach, one murC and one murF inhibitor were identified, providing a platform for developing an antileptospirosis drug targeting the peptidoglycan biosynthesis pathway. Given that the peptidoglycan biosynthesis pathway is exclusive to bacteria, the in silico identified mur ligase inhibitors are expected to be broad-spectrum Gram-negative inhibitors if synthesized and tested in in vitro and in vivo assays.

V&V Plan for FPGA-based ESF-CCS Using System Engineering Approach.

Science.gov (United States)

Maerani, Restu; Mayaka, Joyce; El Akrat, Mohamed; Cheon, Jung Jae

2018-02-01

Instrumentation and Control (I&C) systems play an important role in maintaining the safety of Nuclear Power Plant (NPP) operation. However, most current I&C safety systems are based on Programmable Logic Controller (PLC) hardware, which is difficult to verify and validate, and is susceptible to software common cause failure. Therefore, a plan for the replacement of the PLC-based safety systems, such as the Engineered Safety Feature - Component Control System (ESF-CCS), with Field Programmable Gate Arrays (FPGA) is needed. By using a systems engineering approach, which ensures traceability in every phase of the life cycle, from system requirements, design implementation to verification and validation, the system development is guaranteed to be in line with the regulatory requirements. The Verification process will ensure that the customer and stakeholder’s needs are satisfied in a high quality, trustworthy, cost efficient and schedule compliant manner throughout a system’s entire life cycle. The benefit of the V&V plan is to ensure that the FPGA based ESF-CCS is correctly built, and to ensure that the measurement of performance indicators has positive feedback that “do we do the right thing” during the re-engineering process of the FPGA based ESF-CCS.

Systems-level mechanisms of action of Panax ginseng: a network pharmacological approach.

Science.gov (United States)

Park, Sa-Yoon; Park, Ji-Hun; Kim, Hyo-Su; Lee, Choong-Yeol; Lee, Hae-Jeung; Kang, Ki Sung; Kim, Chang-Eop

2018-01-01

Panax ginseng has been used since ancient times based on the traditional Asian medicine theory and clinical experiences, and currently, is one of the most popular herbs in the world. To date, most of the studies concerning P. ginseng have focused on specific mechanisms of action of individual constituents. However, in spite of many studies on the molecular mechanisms of P. ginseng , it still remains unclear how multiple active ingredients of P. ginseng interact with multiple targets simultaneously, giving the multidimensional effects on various conditions and diseases. In order to decipher the systems-level mechanism of multiple ingredients of P. ginseng , a novel approach is needed beyond conventional reductive analysis. We aim to review the systems-level mechanism of P. ginseng by adopting novel analytical framework-network pharmacology. Here, we constructed a compound-target network of P. ginseng using experimentally validated and machine learning-based prediction results. The targets of the network were analyzed in terms of related biological process, pathways, and diseases. The majority of targets were found to be related with primary metabolic process, signal transduction, nitrogen compound metabolic process, blood circulation, immune system process, cell-cell signaling, biosynthetic process, and neurological system process. In pathway enrichment analysis of targets, mainly the terms related with neural activity showed significant enrichment and formed a cluster. Finally, relative degrees analysis for the target-disease association of P. ginseng revealed several categories of related diseases, including respiratory, psychiatric, and cardiovascular diseases.

Integrating physically based simulators with Event Detection Systems: Multi-site detection approach.

Science.gov (United States)

Housh, Mashor; Ohar, Ziv

2017-03-01

The Fault Detection (FD) Problem in control theory concerns of monitoring a system to identify when a fault has occurred. Two approaches can be distinguished for the FD: Signal processing based FD and Model-based FD. The former concerns of developing algorithms to directly infer faults from sensors' readings, while the latter uses a simulation model of the real-system to analyze the discrepancy between sensors' readings and expected values from the simulation model. Most contamination Event Detection Systems (EDSs) for water distribution systems have followed the signal processing based FD, which relies on analyzing the signals from monitoring stations independently of each other, rather than evaluating all stations simultaneously within an integrated network. In this study, we show that a model-based EDS which utilizes a physically based water quality and hydraulics simulation models, can outperform the signal processing based EDS. We also show that the model-based EDS can facilitate the development of a Multi-Site EDS (MSEDS), which analyzes the data from all the monitoring stations simultaneously within an integrated network. The advantage of the joint analysis in the MSEDS is expressed by increased detection accuracy (higher true positive alarms and fewer false alarms) and shorter detection time. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Systems Biology Approach Reveals Converging Molecular Mechanisms that Link Different POPs to Common Metabolic Diseases.

Science.gov (United States)

Ruiz, Patricia; Perlina, Ally; Mumtaz, Moiz; Fowler, Bruce A

2016-07-01

A number of epidemiological studies have identified statistical associations between persistent organic pollutants (POPs) and metabolic diseases, but testable hypotheses regarding underlying molecular mechanisms to explain these linkages have not been published. We assessed the underlying mechanisms of POPs that have been associated with metabolic diseases; three well-known POPs [2,3,7,8-tetrachlorodibenzodioxin (TCDD), 2,2´,4,4´,5,5´-hexachlorobiphenyl (PCB 153), and 4,4´-dichlorodiphenyldichloroethylene (p,p´-DDE)] were studied. We used advanced database search tools to delineate testable hypotheses and to guide laboratory-based research studies into underlying mechanisms by which this POP mixture could produce or exacerbate metabolic diseases. For our searches, we used proprietary systems biology software (MetaCore™/MetaDrug™) to conduct advanced search queries for the underlying interactions database, followed by directional network construction to identify common mechanisms for these POPs within two or fewer interaction steps downstream of their primary targets. These common downstream pathways belong to various cytokine and chemokine families with experimentally well-documented causal associations with type 2 diabetes. Our systems biology approach allowed identification of converging pathways leading to activation of common downstream targets. To our knowledge, this is the first study to propose an integrated global set of step-by-step molecular mechanisms for a combination of three common POPs using a systems biology approach, which may link POP exposure to diseases. Experimental evaluation of the proposed pathways may lead to development of predictive biomarkers of the effects of POPs, which could translate into disease prevention and effective clinical treatment strategies. Ruiz P, Perlina A, Mumtaz M, Fowler BA. 2016. A systems biology approach reveals converging molecular mechanisms that link different POPs to common metabolic diseases. Environ

Mining pathway associations for disease-related pathway activity analysis based on gene expression and methylation data.

Science.gov (United States)

Lee, Hyeonjeong; Shin, Miyoung

2017-01-01

The problem of discovering genetic markers as disease signatures is of great significance for the successful diagnosis, treatment, and prognosis of complex diseases. Even if many earlier studies worked on identifying disease markers from a variety of biological resources, they mostly focused on the markers of genes or gene-sets (i.e., pathways). However, these markers may not be enough to explain biological interactions between genetic variables that are related to diseases. Thus, in this study, our aim is to investigate distinctive associations among active pathways (i.e., pathway-sets) shown each in case and control samples which can be observed from gene expression and/or methylation data. The pathway-sets are obtained by identifying a set of associated pathways that are often active together over a significant number of class samples. For this purpose, gene expression or methylation profiles are first analyzed to identify significant (active) pathways via gene-set enrichment analysis. Then, regarding these active pathways, an association rule mining approach is applied to examine interesting pathway-sets in each class of samples (case or control). By doing so, the sets of associated pathways often working together in activity profiles are finally chosen as our distinctive signature of each class. The identified pathway-sets are aggregated into a pathway activity network (PAN), which facilitates the visualization of differential pathway associations between case and control samples. From our experiments with two publicly available datasets, we could find interesting PAN structures as the distinctive signatures of breast cancer and uterine leiomyoma cancer, respectively. Our pathway-set markers were shown to be superior or very comparable to other genetic markers (such as genes or gene-sets) in disease classification. Furthermore, the PAN structure, which can be constructed from the identified markers of pathway-sets, could provide deeper insights into

Coordinated Ramping of Dorsal Striatal Pathways preceding Food Approach and Consumption.

Science.gov (United States)

London, Tanisha D; Licholai, Julia A; Szczot, Ilona; Ali, Mohamed A; LeBlanc, Kimberly H; Fobbs, Wambura C; Kravitz, Alexxai V

2018-04-04

The striatum controls food-related actions and consumption and is linked to feeding disorders, including obesity and anorexia nervosa. Two populations of neurons project from the striatum: direct pathway medium spiny neurons and indirect pathway medium spiny neurons. The selective contribution of direct pathway medium spiny neurons and indirect pathway medium spiny neurons to food-related actions and consumption remains unknown. Here, we used in vivo electrophysiology and fiber photometry in mice (of both sexes) to record both spiking activity and pathway-specific calcium activity of dorsal striatal neurons during approach to and consumption of food pellets. While electrophysiology revealed complex task-related dynamics across neurons, population calcium was enhanced during approach and inhibited during consumption in both pathways. We also observed ramping changes in activity that preceded both pellet-directed actions and spontaneous movements. These signals were heterogeneous in the spiking units, with neurons exhibiting either increasing or decreasing ramps. In contrast, the population calcium signals were homogeneous, with both pathways having increasing ramps of activity for several seconds before actions were initiated. An analysis comparing population firing rates to population calcium signals also revealed stronger ramping dynamics in the calcium signals than in the spiking data. In a second experiment, we trained the mice to perform an action sequence to evaluate when the ramping signals terminated. We found that the ramping signals terminated at the beginning of the action sequence, suggesting they may reflect upcoming actions and not preconsumption activity. Plasticity of such mechanisms may underlie disorders that alter action selection, such as drug addiction or obesity. SIGNIFICANCE STATEMENT Alterations in striatal function have been linked to pathological consumption in disorders, such as obesity and drug addiction. We recorded spiking and

A Systems Approach to Nitrogen Delivery

Energy Technology Data Exchange (ETDEWEB)

Goins, Bobby [Y-12 National Security Complex, Oak Ridge, TN (United States)

2017-10-23

A systems based approach will be used to evaluate the nitrogen delivery process. This approach involves principles found in Lean, Reliability, Systems Thinking, and Requirements. This unique combination of principles and thought process yields a very in depth look into the system to which it is applied. By applying a systems based approach to the nitrogen delivery process there should be improvements in cycle time, efficiency, and a reduction in the required number of personnel needed to sustain the delivery process. This will in turn reduce the amount of demurrage charges that the site incurs. In addition there should be less frustration associated with the delivery process.

A Systems Approach to Nitrogen Delivery

Energy Technology Data Exchange (ETDEWEB)

Goins, Bobby [Y-12 National Security Complex, Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States)

2017-10-17

A systems based approach will be used to evaluate the nitrogen delivery process. This approach involves principles found in Lean, Reliability, Systems Thinking, and Requirements. This unique combination of principles and thought process yields a very in depth look into the system to which it is applied. By applying a systems based approach to the nitrogen delivery process there should be improvements in cycle time, efficiency, and a reduction in the required number of personnel needed to sustain the delivery process. This will in turn reduce the amount of demurrage charges that the site incurs. In addition there should be less frustration associated with the delivery process.

An overview of bioinformatics methods for modeling biological pathways in yeast.

Science.gov (United States)

Hou, Jie; Acharya, Lipi; Zhu, Dongxiao; Cheng, Jianlin

2016-03-01

The advent of high-throughput genomics techniques, along with the completion of genome sequencing projects, identification of protein-protein interactions and reconstruction of genome-scale pathways, has accelerated the development of systems biology research in the yeast organism Saccharomyces cerevisiae In particular, discovery of biological pathways in yeast has become an important forefront in systems biology, which aims to understand the interactions among molecules within a cell leading to certain cellular processes in response to a specific environment. While the existing theoretical and experimental approaches enable the investigation of well-known pathways involved in metabolism, gene regulation and signal transduction, bioinformatics methods offer new insights into computational modeling of biological pathways. A wide range of computational approaches has been proposed in the past for reconstructing biological pathways from high-throughput datasets. Here we review selected bioinformatics approaches for modeling biological pathways inS. cerevisiae, including metabolic pathways, gene-regulatory pathways and signaling pathways. We start with reviewing the research on biological pathways followed by discussing key biological databases. In addition, several representative computational approaches for modeling biological pathways in yeast are discussed. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Risk-based decision-making regarding mixed waste disposal systems

International Nuclear Information System (INIS)

Roberds, W.J.

1991-01-01

This paper reports on an efficient approach that has been developed for making rational and defensible decisions among a variety of options (e.g., remedial actions, engineered barriers designs/operational controls, inventory limitations, site investigations and research) for mixed-waste disposal systems, which consist of multiple interacting sites (active, inactive and/or future) with multiple pathways. Such decisions are based on maximizing the satisfaction of identified objectives (including the reliability vis a vis specified criteria), explicitly considering tradeoffs among objectives as well as uncertainties in the consequences of any option

Delay-Dependent Exponential Optimal Synchronization for Nonidentical Chaotic Systems via Neural-Network-Based Approach

Directory of Open Access Journals (Sweden)

Feng-Hsiag Hsiao

2013-01-01

Full Text Available A novel approach is presented to realize the optimal exponential synchronization of nonidentical multiple time-delay chaotic (MTDC systems via fuzzy control scheme. A neural-network (NN model is first constructed for the MTDC system. Then, a linear differential inclusion (LDI state-space representation is established for the dynamics of the NN model. Based on this LDI state-space representation, a delay-dependent exponential stability criterion of the error system derived in terms of Lyapunov's direct method is proposed to guarantee that the trajectories of the slave system can approach those of the master system. Subsequently, the stability condition of this criterion is reformulated into a linear matrix inequality (LMI. According to the LMI, a fuzzy controller is synthesized not only to realize the exponential synchronization but also to achieve the optimal performance by minimizing the disturbance attenuation level at the same time. Finally, a numerical example with simulations is given to demonstrate the effectiveness of our approach.

Unity-Based Diversity: System Approach to Defining Information

Directory of Open Access Journals (Sweden)

Yixin Zhong

2011-07-01

Full Text Available What is information? This is the first question that information science should answer clearly. However, the definitions of information have been so diversified that people are questioning if there is any unity among the diversity, leading to a suspicion on whether it is possible to establish a unified theory of information or not. To answer this question, a system approach to defining information is introduced in this paper. It is proved that the unity of information definitions can be maintained with this approach. As a by-product, an important concept, the information eco-system, was also achieved.

A modified artificial immune system based pattern recognition approach -- an application to clinic diagnostics

Science.gov (United States)

Zhao, Weixiang; Davis, Cristina E.

2011-01-01

Objective This paper introduces a modified artificial immune system (AIS)-based pattern recognition method to enhance the recognition ability of the existing conventional AIS-based classification approach and demonstrates the superiority of the proposed new AIS-based method via two case studies of breast cancer diagnosis. Methods and materials Conventionally, the AIS approach is often coupled with the k nearest neighbor (k-NN) algorithm to form a classification method called AIS-kNN. In this paper we discuss the basic principle and possible problems of this conventional approach, and propose a new approach where AIS is integrated with the radial basis function – partial least square regression (AIS-RBFPLS). Additionally, both the two AIS-based approaches are compared with two classical and powerful machine learning methods, back-propagation neural network (BPNN) and orthogonal radial basis function network (Ortho-RBF network). Results The diagnosis results show that: (1) both the AIS-kNN and the AIS-RBFPLS proved to be a good machine leaning method for clinical diagnosis, but the proposed AIS-RBFPLS generated an even lower misclassification ratio, especially in the cases where the conventional AIS-kNN approach generated poor classification results because of possible improper AIS parameters. For example, based upon the AIS memory cells of “replacement threshold = 0.3”, the average misclassification ratios of two approaches for study 1 are 3.36% (AIS-RBFPLS) and 9.07% (AIS-kNN), and the misclassification ratios for study 2 are 19.18% (AIS-RBFPLS) and 28.36% (AIS-kNN); (2) the proposed AIS-RBFPLS presented its robustness in terms of the AIS-created memory cells, showing a smaller standard deviation of the results from the multiple trials than AIS-kNN. For example, using the result from the first set of AIS memory cells as an example, the standard deviations of the misclassification ratios for study 1 are 0.45% (AIS-RBFPLS) and 8.71% (AIS-kNN) and those for

A PetriNet-Based Approach for Supporting Traceability in Cyber-Physical Manufacturing Systems

Directory of Open Access Journals (Sweden)

Jiwei Huang

2016-03-01

Full Text Available With the growing popularity of complex dynamic activities in manufacturing processes, traceability of the entire life of every product has drawn significant attention especially for food, clinical materials, and similar items. This paper studies the traceability issue in cyber-physical manufacturing systems from a theoretical viewpoint. Petri net models are generalized for formulating dynamic manufacturing processes, based on which a detailed approach for enabling traceability analysis is presented. Models as well as algorithms are carefully designed, which can trace back the lifecycle of a possibly contaminated item. A practical prototype system for supporting traceability is designed, and a real-life case study of a quality control system for bee products is presented to validate the effectiveness of the approach.

Practice and effectiveness of web-based problem-based learning approach in a large class-size system: A comparative study.

Science.gov (United States)

Ding, Yongxia; Zhang, Peili

2018-06-12

Problem-based learning (PBL) is an effective and highly efficient teaching approach that is extensively applied in education systems across a variety of countries. This study aimed to investigate the effectiveness of web-based PBL teaching pedagogies in large classes. The cluster sampling method was used to separate two college-level nursing student classes (graduating class of 2013) into two groups. The experimental group (n = 162) was taught using a web-based PBL teaching approach, while the control group (n = 166) was taught using conventional teaching methods. We subsequently assessed the satisfaction of the experimental group in relation to the web-based PBL teaching mode. This assessment was performed following comparison of teaching activity outcomes pertaining to exams and self-learning capacity between the two groups. When compared with the control group, the examination scores and self-learning capabilities were significantly higher in the experimental group (P web-based PBL teaching approach. In a large class-size teaching environment, the web-based PBL teaching approach appears to be more optimal than traditional teaching methods. These results demonstrate the effectiveness of web-based teaching technologies in problem-based learning. Copyright © 2018. Published by Elsevier Ltd.

NemaPath: online exploration of KEGG-based metabolic pathways for nematodes

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Wang Zhengyuan

2008-11-01

Full Text Available Abstract Background Nematode.net http://www.nematode.net is a web-accessible resource for investigating gene sequences from parasitic and free-living nematode genomes. Beyond the well-characterized model nematode C. elegans, over 500,000 expressed sequence tags (ESTs and nearly 600,000 genome survey sequences (GSSs have been generated from 36 nematode species as part of the Parasitic Nematode Genomics Program undertaken by the Genome Center at Washington University School of Medicine. However, these sequencing data are not present in most publicly available protein databases, which only include sequences in Swiss-Prot. Swiss-Prot, in turn, relies on GenBank/Embl/DDJP for predicted proteins from complete genomes or full-length proteins. Description Here we present the NemaPath pathway server, a web-based pathway-level visualization tool for navigating putative metabolic pathways for over 30 nematode species, including 27 parasites. The NemaPath approach consists of two parts: 1 a backend tool to align and evaluate nematode genomic sequences (curated EST contigs against the annotated Kyoto Encyclopedia of Genes and Genomes (KEGG protein database; 2 a web viewing application that displays annotated KEGG pathway maps based on desired confidence levels of primary sequence similarity as defined by a user. NemaPath also provides cross-referenced access to nematode genome information provided by other tools available on Nematode.net, including: detailed NemaGene EST cluster information; putative translations; GBrowse EST cluster views; links from nematode data to external databases for corresponding synonymous C. elegans counterparts, subject matches in KEGG's gene database, and also KEGG Ontology (KO identification. Conclusion The NemaPath server hosts metabolic pathway mappings for 30 nematode species and is available on the World Wide Web at http://nematode.net/cgi-bin/keggview.cgi. The nematode source sequences used for the metabolic pathway

A model-data based systems approach to process intensification

DEFF Research Database (Denmark)

Gani, Rafiqul

. Their developments, however, are largely due to experiment based trial and error approaches and while they do not require validation, they can be time consuming and resource intensive. Also, one may ask, can a truly new intensified unit operation be obtained in this way? An alternative two-stage approach is to apply...... a model-based synthesis method to systematically generate and evaluate alternatives in the first stage and an experiment-model based validation in the second stage. In this way, the search for alternatives is done very quickly, reliably and systematically over a wide range, while resources are preserved...... for focused validation of only the promising candidates in the second-stage. This approach, however, would be limited to intensification based on “known” unit operations, unless the PI process synthesis/design is considered at a lower level of aggregation, namely the phenomena level. That is, the model-based...

A new infusion pathway intactness monitoring system.

Science.gov (United States)

Ogawa, Hidekuni; Yonezawa, Yoshiharu; Maki, Hiromichi; Ninomiya, Ishio; Sata, Koji; Hamada, Shingo; Caldwell, W Morton

2006-01-01

A new infusion pathway monitoring system has been developed for hospital and home use. The system consists of linear integrated circuits and a low-power 8-bit single chip microcomputer which constantly monitors the infusion pathway intactness. An AC (alternating current) voltage is induced on the patient's body by electrostatic coupling from the normal 100 volt, 60 Hz AC power line wiring field in the patient's room. The induced AC voltage can be recorded by a main electrode wrapped around the infusion polyvinyl chloride tube. A reference electrode is wrapped on the electrode to monitor the AC voltage around the main electrode. If the injection needle or infusion tube becomes detached, then the system detects changes in the induced AC voltages and alerts the nursing station, via the nurse call system or PHS (personal handy phone system).

Systemic-Functional Approach to Utilities Supplys

Directory of Open Access Journals (Sweden)

Nikolay I. Komkov

2017-01-01

Full Text Available Purpose: the purpose of the article consists in statement of management approach to development of utilities supply processes based on conflict situations decision – making search. It had appeared in the period of the transition from the planned and directive management to market development. Methods: the research methodology is based on the system analysis of full life cycle processes functioning, forecasting of complex systems development, mathematical modeling of processes of services supply and innovative and investment projects modeling as well as development of supplying services processes. Results: the results of the work are concentrated in the presentation of systemic-functional approach to managing the development of processes of municipal services, able to resolve conflict situations in this sphere. Conclusions and Relevance: the traditional management approach on the basis of elimination of "bottlenecks" and emergencies prevailing within planned and directive system at its transformation in the market conditions has led to accumulation of conflict situations and unsolvable problems. The offered systemic-functional approach based on forecasting of full life cycle of the modernized processes and the services providing systems allows to consider costs of modernization, prime cost and quality of the rendered services. 

Ontology modeling for generation of clinical pathways

Directory of Open Access Journals (Sweden)

Jasmine Tehrani

2012-12-01

Full Text Available Purpose: Increasing costs of health care, fuelled by demand for high quality, cost-effective healthcare has drove hospitals to streamline their patient care delivery systems. One such systematic approach is the adaptation of Clinical Pathways (CP as a tool to increase the quality of healthcare delivery. However, most organizations still rely on are paper-based pathway guidelines or specifications, which have limitations in process management and as a result can influence patient safety outcomes. In this paper, we present a method for generating clinical pathways based on organizational semiotics by capturing knowledge from syntactic, semantic and pragmatic to social level. Design/methodology/approach: The proposed modeling approach to generation of CPs adopts organizational semiotics and enables the generation of semantically rich representation of CP knowledge. Semantic Analysis Method (SAM is applied to explicitly represent the semantics of the concepts, their relationships and patterns of behavior in terms of an ontology chart. Norm Analysis Method (NAM is adopted to identify and formally specify patterns of behavior and rules that govern the actions identified on the ontology chart. Information collected during semantic and norm analysis is integrated to guide the generation of CPs using best practice represented in BPMN thus enabling the automation of CP. Findings: This research confirms the necessity of taking into consideration social aspects in designing information systems and automating CP. The complexity of healthcare processes can be best tackled by analyzing stakeholders, which we treat as social agents, their goals and patterns of action within the agent network. Originality/value: The current modeling methods describe CPs from a structural aspect comprising activities, properties and interrelationships. However, these methods lack a mechanism to describe possible patterns of human behavior and the conditions under which the

Multi-criteria decision analysis of energy system transformation pathways: A case study for Switzerland

International Nuclear Information System (INIS)

Volkart, Kathrin; Weidmann, Nicolas; Bauer, Christian; Hirschberg, Stefan

2017-01-01

Two recent political decisions are expected to frame the development of the Swiss energy system in the coming decades: the nuclear phase-out and the greenhouse gas (GHG) emission reduction target. To accomplish both of them, low-carbon technologies based on renewable energy and Carbon Capture and Storage (CCS) are expected to gain importance. The objective of the present work is to support prospective Swiss energy policy-making by providing a detailed sustainability analysis of possible energy system transformation pathways. For this purpose, the results of the scenario quantification with an energy system model are coupled with multi-criteria sustainability analysis. Two climate protection and one reference scenario are addressed, and the trade-offs between the scenarios are analysed based on a set of 12 interdisciplinary indicators. Implementing a stringent climate policy in Switzerland is associated with co-benefits such as less fossil resource use, less fatalities in severe accidents in the energy sector, less societal conflicts and higher resource autonomy. The availability and implementation of CCS allows for achieving the GHG emission reduction target at lower costs, but at the expense of a more fossil fuel-based energy system. - Highlights: • Three energy system transformation pathways for Switzerland are analysed. • A set of policy-relevant sustainability indicators are quantified for each pathway. • Implementing a stringent climate policy in Switzerland is associated with co-benefits. • In the CCS scenario fossil fuel use increases, but the total system costs are lower. • Fossil-fuelled transport substantially contributes to most of the addressed criteria.

Pathways, Networks and Systems Medicine Conferences

Energy Technology Data Exchange (ETDEWEB)

Nadeau, Joseph H. [Pacific Northwest Research Institute

2013-11-25

The 6th Pathways, Networks and Systems Medicine Conference was held at the Minoa Palace Conference Center, Chania, Crete, Greece (16-21 June 2008). The Organizing Committee was composed of Joe Nadeau (CWRU, Cleveland), Rudi Balling (German Research Centre, Brauschweig), David Galas (Institute for Systems Biology, Seattle), Lee Hood (Institute for Systems Biology, Seattle), Diane Isonaka (Seattle), Fotis Kafatos (Imperial College, London), John Lambris (Univ. Pennsylvania, Philadelphia),Harris Lewin (Univ. of Indiana, Urbana-Champaign), Edison Liu (Genome Institute of Singapore, Singapore), and Shankar Subramaniam (Univ. California, San Diego). A total of 101 individuals from 21 countries participated in the conference: USA (48), Canada (5), France (5), Austria (4), Germany (3), Italy (3), UK (3), Greece (2), New Zealand (2), Singapore (2), Argentina (1), Australia (1), Cuba (1), Denmark (1), Japan (1), Mexico (1), Netherlands (1), Spain (1), Sweden (1), Switzerland (1). With respect to speakers, 29 were established faculty members and 13 were graduate students or postdoctoral fellows. With respect to gender representation, among speakers, 13 were female and 28 were male, and among all participants 43 were female and 58 were male. Program these included the following topics: Cancer Pathways and Networks (Day 1), Metabolic Disease Networks (Day 2), Day 3 ? Organs, Pathways and Stem Cells (Day 3), and Day 4 ? Inflammation, Immunity, Microbes and the Environment (Day 4). Proceedings of the Conference were not published.

A design approach for systems based on magnetic pulse compression

International Nuclear Information System (INIS)

Praveen Kumar, D. Durga; Mitra, S.; Senthil, K.; Sharma, D. K.; Rajan, Rehim N.; Sharma, Archana; Nagesh, K. V.; Chakravarthy, D. P.

2008-01-01

A design approach giving the optimum number of stages in a magnetic pulse compression circuit and gain per stage is given. The limitation on the maximum gain per stage is discussed. The total system volume minimization is done by considering the energy storage capacitor volume and magnetic core volume at each stage. At the end of this paper, the design of a magnetic pulse compression based linear induction accelerator of 200 kV, 5 kA, and 100 ns with a repetition rate of 100 Hz is discussed with its experimental results

Information theory based approaches to cellular signaling.

Science.gov (United States)

Waltermann, Christian; Klipp, Edda

2011-10-01

Cells interact with their environment and they have to react adequately to internal and external changes such changes in nutrient composition, physical properties like temperature or osmolarity and other stresses. More specifically, they must be able to evaluate whether the external change is significant or just in the range of noise. Based on multiple external parameters they have to compute an optimal response. Cellular signaling pathways are considered as the major means of information perception and transmission in cells. Here, we review different attempts to quantify information processing on the level of individual cells. We refer to Shannon entropy, mutual information, and informal measures of signaling pathway cross-talk and specificity. Information theory in systems biology has been successfully applied to identification of optimal pathway structures, mutual information and entropy as system response in sensitivity analysis, and quantification of input and output information. While the study of information transmission within the framework of information theory in technical systems is an advanced field with high impact in engineering and telecommunication, its application to biological objects and processes is still restricted to specific fields such as neuroscience, structural and molecular biology. However, in systems biology dealing with a holistic understanding of biochemical systems and cellular signaling only recently a number of examples for the application of information theory have emerged. This article is part of a Special Issue entitled Systems Biology of Microorganisms. Copyright © 2011 Elsevier B.V. All rights reserved.

Local energy developments based on spatial and systemic approaches

NARCIS (Netherlands)

Manickam, Anu

Local energy developments from a spatial and systemic approach are highlighted using examples from a Dutch case study. Developments in energy systems included interconnectedness of contextual factors and systems responses. The need to explore both the contextual factors and systemic aspects are

Integrated Systems-Based Approach for Reaching Acceptable End Points for Groundwater - 13629

International Nuclear Information System (INIS)

Lee, M. Hope; Wellman, Dawn; Truex, Mike; Freshley, Mark D.; Sorenson, Kent S. Jr.; Wymore, Ryan

2013-01-01

The sheer mass and nature of contaminated materials at DOE and DoD sites, makes it impractical to completely restore these sites to pre-disposal conditions. DOE faces long-term challenges, particularly with developing monitoring and end state approaches for clean-up that are protective of the environment, technically based and documented, sustainable, and most importantly cost effective. Integrated systems-based monitoring approaches (e.g., tools for characterization and monitoring, multi-component strategies, geophysical modeling) could provide novel approaches and a framework to (a) define risk-informed endpoints and/or conditions that constitute completion of cleanup and (b) provide the understanding for implementation of advanced scientific approaches to meet cleanup goals. Multi-component strategies which combine site conceptual models, biological, chemical, and physical remediation strategies, as well as iterative review and optimization have proven successful at several DOE sites. Novel tools such as enzyme probes and quantitative PCR for DNA and RNA, and innovative modeling approaches for complex subsurface environments, have been successful at facilitating the reduced operation or shutdown of pump and treat facilities and transition of clean-up activities into monitored natural attenuation remedies. Integrating novel tools with site conceptual models and other lines of evidence to characterize, optimize, and monitor long term remedial approaches for complex contaminant plumes are critical for transitioning active remediation into cost effective, yet technically defensible endpoint strategies. (authors)

Localism and energy: Negotiating approaches to embedding resilience in energy systems

International Nuclear Information System (INIS)

O'Brien, Geoff; Hope, Alex

2010-01-01

Tensions are evident in energy policy objectives between centralised top-down interconnected energy systems and localised distributed approaches. Examination of these tensions indicates that a localised approach can address a systemic problem of interconnected systems; namely vulnerability. The challenge for energy policy is to realise the interrelated goals of energy security, climate and environmental targets and social and economic issues such as fuel poverty, whilst mitigating vulnerability. The effectiveness of conventional approaches is debatable. A transition to a low carbon pathway should focus on resilience, counter to vulnerability. This article draws from on-going work which evaluates the energy aspects of a Private Finance Initiative (PFI) project to refurbish and re-build a local authority's entire stock of sheltered accommodation to high environmental standards. Initial findings suggest that whereas more conventional procurement processes tend to increase systemic vulnerability, a user focussed process driven through PFI competitive dialogue is beginning to motivate some developers to adopt innovative approaches to energy system development.

Supporting transitions in medical career pathways: the role of simulation-based education.

Science.gov (United States)

Cleland, Jennifer; Patey, Rona; Thomas, Ian; Walker, Kenneth; O'Connor, Paul; Russ, Stephanie

2016-01-01

Transitions, or periods of change, in medical career pathways can be challenging episodes, requiring the transitioning clinician to take on new roles and responsibilities, adapt to new cultural dynamics, change behaviour patterns, and successfully manage uncertainty. These intensive learning periods present risks to patient safety. Simulation-based education (SBE) is a pedagogic approach that allows clinicians to practise their technical and non-technical skills in a safe environment to increase preparedness for practice. In this commentary, we present the potential uses, strengths, and limitations of SBE for supporting transitions across medical career pathways, discussing educational utility, outcome and process evaluation, and cost and value, and introduce a new perspective on considering the gains from SBE. We provide case-study examples of the application of SBE to illustrate these points and stimulate discussion.

A rapid pathway toward a superb gene delivery system: programming structural and functional diversity into a supramolecular nanoparticle library.

Science.gov (United States)

Wang, Hao; Liu, Kan; Chen, Kuan-Ju; Lu, Yujie; Wang, Shutao; Lin, Wei-Yu; Guo, Feng; Kamei, Ken-ichiro; Chen, Yi-Chun; Ohashi, Minori; Wang, Mingwei; Garcia, Mitch André; Zhao, Xing-Zhong; Shen, Clifton K-F; Tseng, Hsian-Rong

2010-10-26

Nanoparticles are regarded as promising transfection reagents for effective and safe delivery of nucleic acids into a specific type of cells or tissues providing an alternative manipulation/therapy strategy to viral gene delivery. However, the current process of searching novel delivery materials is limited due to conventional low-throughput and time-consuming multistep synthetic approaches. Additionally, conventional approaches are frequently accompanied with unpredictability and continual optimization refinements, impeding flexible generation of material diversity creating a major obstacle to achieving high transfection performance. Here we have demonstrated a rapid developmental pathway toward highly efficient gene delivery systems by leveraging the powers of a supramolecular synthetic approach and a custom-designed digital microreactor. Using the digital microreactor, broad structural/functional diversity can be programmed into a library of DNA-encapsulated supramolecular nanoparticles (DNA⊂SNPs) by systematically altering the mixing ratios of molecular building blocks and a DNA plasmid. In vitro transfection studies with DNA⊂SNPs library identified the DNA⊂SNPs with the highest gene transfection efficiency, which can be attributed to cooperative effects of structures and surface chemistry of DNA⊂SNPs. We envision such a rapid developmental pathway can be adopted for generating nanoparticle-based vectors for delivery of a variety of loads.

Mechatronic System Design Based On An Optimisation Approach

DEFF Research Database (Denmark)

Andersen, Torben Ole; Pedersen, Henrik Clemmensen; Hansen, Michael Rygaard

The envisaged objective of this paper project is to extend the current state of the art regarding the design of complex mechatronic systems utilizing an optimisation approach. We propose to investigate a novel framework for mechatronic system design. The novelty and originality being the use...... of optimisation techniques. The methods used to optimise/design within the classical disciplines will be identified and extended to mechatronic system design....

Pathway discovery in metabolic networks by subgraph extraction.

Science.gov (United States)

Faust, Karoline; Dupont, Pierre; Callut, Jérôme; van Helden, Jacques

2010-05-01

Subgraph extraction is a powerful technique to predict pathways from biological networks and a set of query items (e.g. genes, proteins, compounds, etc.). It can be applied to a variety of different data types, such as gene expression, protein levels, operons or phylogenetic profiles. In this article, we investigate different approaches to extract relevant pathways from metabolic networks. Although these approaches have been adapted to metabolic networks, they are generic enough to be adjusted to other biological networks as well. We comparatively evaluated seven sub-network extraction approaches on 71 known metabolic pathways from Saccharomyces cerevisiae and a metabolic network obtained from MetaCyc. The best performing approach is a novel hybrid strategy, which combines a random walk-based reduction of the graph with a shortest paths-based algorithm, and which recovers the reference pathways with an accuracy of approximately 77%. Most of the presented algorithms are available as part of the network analysis tool set (NeAT). The kWalks method is released under the GPL3 license.

SNMP-SI: A Network Management Tool Based on Slow Intelligence System Approach

Science.gov (United States)

Colace, Francesco; de Santo, Massimo; Ferrandino, Salvatore

The last decade has witnessed an intense spread of computer networks that has been further accelerated with the introduction of wireless networks. Simultaneously with, this growth has increased significantly the problems of network management. Especially in small companies, where there is no provision of personnel assigned to these tasks, the management of such networks is often complex and malfunctions can have significant impacts on their businesses. A possible solution is the adoption of Simple Network Management Protocol. Simple Network Management Protocol (SNMP) is a standard protocol used to exchange network management information. It is part of the Transmission Control Protocol/Internet Protocol (TCP/IP) protocol suite. SNMP provides a tool for network administrators to manage network performance, find and solve network problems, and plan for network growth. SNMP has a big disadvantage: its simple design means that the information it deals with is neither detailed nor well organized enough to deal with the expanding modern networking requirements. Over the past years much efforts has been given to improve the lack of Simple Network Management Protocol and new frameworks has been developed: A promising approach involves the use of Ontology. This is the starting point of this paper where a novel approach to the network management based on the use of the Slow Intelligence System methodologies and Ontology based techniques is proposed. Slow Intelligence Systems is a general-purpose systems characterized by being able to improve performance over time through a process involving enumeration, propagation, adaptation, elimination and concentration. Therefore, the proposed approach aims to develop a system able to acquire, according to an SNMP standard, information from the various hosts that are in the managed networks and apply solutions in order to solve problems. To check the feasibility of this model first experimental results in a real scenario are showed.

Discover binding pathways using the sliding binding-box docking approach: application to binding pathways of oseltamivir to avian influenza H5N1 neuraminidase

Science.gov (United States)

Tran, Diem-Trang T.; Le, Ly T.; Truong, Thanh N.

2013-08-01

Drug binding and unbinding are transient processes which are hardly observed by experiment and difficult to analyze by computational techniques. In this paper, we employed a cost-effective method called "pathway docking" in which molecular docking was used to screen ligand-receptor binding free energy surface to reveal possible paths of ligand approaching protein binding pocket. A case study was applied on oseltamivir, the key drug against influenza a virus. The equilibrium pathways identified by this method are found to be similar to those identified in prior studies using highly expensive computational approaches.

Selection of personalized patient therapy through the use of knowledge-based computational models that identify tumor-driving signal transduction pathways.

Science.gov (United States)

Verhaegh, Wim; van Ooijen, Henk; Inda, Márcia A; Hatzis, Pantelis; Versteeg, Rogier; Smid, Marcel; Martens, John; Foekens, John; van de Wiel, Paul; Clevers, Hans; van de Stolpe, Anja

2014-06-01

Increasing knowledge about signal transduction pathways as drivers of cancer growth has elicited the development of "targeted drugs," which inhibit aberrant signaling pathways. They require a companion diagnostic test that identifies the tumor-driving pathway; however, currently available tests like estrogen receptor (ER) protein expression for hormonal treatment of breast cancer do not reliably predict therapy response, at least in part because they do not adequately assess functional pathway activity. We describe a novel approach to predict signaling pathway activity based on knowledge-based Bayesian computational models, which interpret quantitative transcriptome data as the functional output of an active signaling pathway, by using expression levels of transcriptional target genes. Following calibration on only a small number of cell lines or cohorts of patient data, they provide a reliable assessment of signaling pathway activity in tumors of different tissue origin. As proof of principle, models for the canonical Wnt and ER pathways are presented, including initial clinical validation on independent datasets from various cancer types. ©2014 American Association for Cancer Research.

An Approach for State Observation in Dynamical Systems Based on the Twisting Algorithm

DEFF Research Database (Denmark)

Schmidt, Lasse; Andersen, Torben Ole; Pedersen, Henrik C.

2013-01-01

This paper discusses a novel approach for state estimation in dynamical systems, with the special focus on hydraulic valve-cylinder drives. The proposed observer structure is based on the framework of the so-called twisting algorithm. This algorithm utilizes the sign of the state being the target...

Approach to developing reliable space reactor power systems

International Nuclear Information System (INIS)

Mondt, J.F.; Shinbrot, C.H.

1991-01-01

The Space Reactor Power System Project is in the engineering development phase of a three-phase program. During Phase II, the Engineering Development Phase, the SP-100 Project has defined and is pursuing a new approach to developing reliable power systems. The approach to developing such a system during the early technology phase is described in this paper along with some preliminary examples to help explain the approach. Developing reliable components to meet space reactor power system requirements is based on a top down systems approach which includes a point design based on a detailed technical specification of a 100 kW power system

Fractionated stereotactic radiosurgery for patients with skull base metastases from systemic cancer involving the anterior visual pathway

International Nuclear Information System (INIS)

Minniti, Giuseppe; Osti, Mattia Falchetto; Maurizi Enrici, Riccardo; Esposito, Vincenzo; Clarke, Enrico; Scaringi, Claudia; Bozzao, Alessandro; Falco, Teresa; De Sanctis, Vitaliana; Enrici, Maurizio Maurizi; Valeriani, Maurizio

2014-01-01

To analyze the tumor control, survival outcomes, and toxicity after stereotactic radiosurgery (SRS) for skull base metastases from systemic cancer involving the anterior visual pathway. We have analyzed 34 patients (23 females and 11 males, median age 59 years) who underwent multi-fraction SRS for a skull base metastasis compressing or in close proximity of optic nerves and chiasm. All metastases were treated with frameless LINAC-based multi-fraction SRS in 5 daily fractions of 5 Gy each. Local control, distant failure, and overall survival were estimated using the Kaplan-Meier method calculated from the time of SRS. Prognostic variables were assessed using log-rank and Cox regression analyses. At a median follow-up of 13 months (range, 2–36.5 months), twenty-five patients had died and 9 were alive. The 1-year and 2-year local control rates were 89% and 72%, and respective actuarial survival rates were 63% and 30%. Four patients recurred with a median time to progression of 12 months (range, 6–27 months), and 17 patients had new brain metastases at distant brain sites. The 1-year and 2-year distant failure rates were 50% and 77%, respectively. On multivariate analysis, a Karnofsky performance status (KPS) >70 and the absence of extracranial metastases were prognostic factors associated with lower distant failure rates and longer survival. After multi-fraction SRS, 15 (51%) out of 29 patients had a clinical improvement of their preexisting cranial deficits. No patients developed radiation-induced optic neuropathy during the follow-up. Multi-fraction SRS (5 x 5 Gy) is a safe treatment option associated with good local control and improved cranial nerve symptoms for patients with a skull base metastasis involving the anterior visual pathway

Improving operating room turnover time: a systems based approach.

Science.gov (United States)

Bhatt, Ankeet S; Carlson, Grant W; Deckers, Peter J

2014-12-01

Operating room (OR) turnover time (TT) has a broad and significant impact on hospital administrators, providers, staff and patients. Our objective was to identify current problems in TT management and implement a consistent, reproducible process to reduce average TT and process variability. Initial observations of TT were made to document the existing process at a 511 bed, 24 OR, academic medical center. Three control groups, including one consisting of Orthopedic and Vascular Surgery, were used to limit potential confounders such as case acuity/duration and equipment needs. A redesigned process based on observed issues, focusing on a horizontally structured, systems-based approach has three major interventions: developing consistent criteria for OR readiness, utilizing parallel processing for patient and room readiness, and enhancing perioperative communication. Process redesign was implemented in Orthopedics and Vascular Surgery. Comparisons of mean and standard deviation of TT were made using an independent 2-tailed t-test. Using all surgical specialties as controls (n = 237), mean TT (hh:mm:ss) was reduced by 0:20:48 min (95 % CI, 0:10:46-0:30:50), from 0:44:23 to 0:23:25, a 46.9 % reduction. Standard deviation of TT was reduced by 0:10:32 min, from 0:16:24 to 0:05:52 and frequency of TT≥30 min was reduced from 72.5to 11.7 %. P systems-based focus should drive OR TT design.

METHODOLOGICAL APPROACH TO ANALYSIS AND EVALUATION OF INFORMATION PROTECTION IN INFORMATION SYSTEMS BASED ON VULNERABILITY DANGER

Directory of Open Access Journals (Sweden)

Y. M. Krotiuk

2008-01-01

Full Text Available The paper considers a methodological approach to an analysis and estimation of information security in the information systems which is based on the analysis of vulnerabilities and an extent of their hazard. By vulnerability hazard it is meant a complexity of its operation as a part of an information system. The required and sufficient vulnerability operational conditions  have  been  determined in the paper. The paper proposes a generalized model for attack realization which is used as a basis for construction of an attack realization model for an operation of a particular vulnerability. A criterion for estimation of information protection in the information systems which is based on the estimation of vulnerability hazard is formulated in the paper. The proposed approach allows to obtain a quantitative estimation of the information system security on the basis of the proposed schemes on realization of typical attacks for the distinguished classes of vulnerabilities.The methodical approach is used for choosing variants to be applied for realization of protection mechanisms in the information systems as well as for estimation of information safety in the operating information systems.

Integrated system fault diagnostics utilising digraph and fault tree-based approaches

International Nuclear Information System (INIS)

Bartlett, L.M.; Hurdle, E.E.; Kelly, E.M.

2009-01-01

With the growing intolerance to failures within systems, the issue of fault diagnosis has become ever prevalent. Information concerning these possible failures can help to minimise the disruption to the functionality of the system by allowing quick rectification. Traditional approaches to fault diagnosis within engineering systems have focused on sequential testing procedures and real-time mechanisms. Both methods have been predominantly limited to single fault causes. Latest approaches also consider the issue of multiple faults in reflection to the characteristics of modern day systems designed for high reliability. In addition, a diagnostic capability is required in real time and for changeable system functionality. This paper focuses on two approaches which have been developed to cater for the demands of diagnosis within current engineering systems, namely application of the fault tree analysis technique and the method of digraphs. Both use a comparative approach to consider differences between actual system behaviour and that expected. The procedural guidelines are discussed for each method, with an experimental aircraft fuel system used to test and demonstrate the features of the techniques. The effectiveness of the approaches is compared and their future potential highlighted

Optimized swimmer tracking system based on a novel multi-related-targets approach

Science.gov (United States)

Benarab, D.; Napoléon, T.; Alfalou, A.; Verney, A.; Hellard, P.

2017-02-01

Robust tracking is a crucial step in automatic swimmer evaluation from video sequences. We designed a robust swimmer tracking system using a new multi-related-targets approach. The main idea is to consider the swimmer as a bloc of connected subtargets that advance at the same speed. If one of the subtargets is partially or totally occluded, it can be localized by knowing the position of the others. In this paper, we first introduce the two-dimensional direct linear transformation technique that we used to calibrate the videos. Then, we present the classical tracking approach based on dynamic fusion. Next, we highlight the main contribution of our work, which is the multi-related-targets tracking approach. This approach, the classical head-only approach and the ground truth are then compared, through testing on a database of high-level swimmers in training, national and international competitions (French National Championships, Limoges 2015, and World Championships, Kazan 2015). Tracking percentage and the accuracy of the instantaneous speed are evaluated and the findings show that our new appraoach is significantly more accurate than the classical approach.

Protocol for a multicentre, multistage, prospective study in China using system-based approaches for consistent improvement in surgical safety.

Science.gov (United States)

Yu, Xiaochu; Jiang, Jingmei; Liu, Changwei; Shen, Keng; Wang, Zixing; Han, Wei; Liu, Xingrong; Lin, Guole; Zhang, Ye; Zhang, Ying; Ma, Yufen; Bo, Haixin; Zhao, Yupei

2017-06-15

Surgical safety has emerged as a crucial global health issue in the past two decades. Although several safety-enhancing tools are available, the pace of large-scale improvement remains slow, especially in developing countries such as China. The present project (Modern Surgery and Anesthesia Safety Management System Construction and Promotion) aims to develop and validate system-based integrated approaches for reducing perioperative deaths and complications using a multicentre, multistage design. The project involves collection of clinical and outcome information for 1 20 000 surgical inpatients at four regionally representative academic/teaching general hospitals in China during three sequential stages: preparation and development, effectiveness validation and improvement of implementation for promotion. These big data will provide the evidence base for the formulation, validation and improvement processes of a system-based stratified safety intervention package covering the entire surgical pathway. Attention will be directed to managing inherent patient risks and regulating medical safety behaviour. Information technology will facilitate data collection and intervention implementation, provide supervision mechanisms and guarantee transfer of key patient safety messages between departments and personnel. Changes in rates of deaths, surgical complications during hospitalisation, length of stay, system adoption and implementation rates will be analysed to evaluate effectiveness and efficiency. This study was approved by the institutional review boards of Peking Union Medical College Hospital, First Hospital of China Medical University, Qinghai Provincial People's Hospital, Xiangya Hospital Central South University and the Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences. Study findings will be disseminated via peer-reviewed journals, conference presentations and patent papers. © Article author(s) (or their employer(s) unless otherwise

Towards a mechanism-based approach to pain management in osteoarthritis.

Science.gov (United States)

Malfait, Anne-Marie; Schnitzer, Thomas J

2013-11-01

Pain is the defining symptom of osteoarthritis (OA), yet available treatment options, of which NSAIDs are the most common, provide inadequate pain relief and are associated with serious health risks when used long term. Chronic pain pathways are subject to complex levels of control and modulation, both in the periphery and in the central nervous system. Ongoing clinical and basic research is uncovering how these pathways operate in OA. Indeed, clinical investigation into the types of pain associated with progressive OA, the presence of central sensitization, the correlation with structural changes in the joint, and the efficacy of novel analgesics affords new insights into the pathophysiology of OA pain. Moreover, studies in disease-specific animal models enable the unravelling of the cellular and molecular pathways involved. We expect that increased understanding of the mechanisms by which chronic OA-associated pain is generated and maintained will offer opportunities for targeting and improving the safety of analgesia. In addition, using clinical and genetic approaches, it might become possible to identify subsets of patients with pain of different pathophysiology, thus enabling a tailored approach to pain management.

A network-based biomarker approach for molecular investigation and diagnosis of lung cancer

Directory of Open Access Journals (Sweden)

Chen Bor-Sen

2011-01-01

Full Text Available Abstract Background Lung cancer is the leading cause of cancer deaths worldwide. Many studies have investigated the carcinogenic process and identified the biomarkers for signature classification. However, based on the research dedicated to this field, there is no highly sensitive network-based method for carcinogenesis characterization and diagnosis from the systems perspective. Methods In this study, a systems biology approach integrating microarray gene expression profiles and protein-protein interaction information was proposed to develop a network-based biomarker for molecular investigation into the network mechanism of lung carcinogenesis and diagnosis of lung cancer. The network-based biomarker consists of two protein association networks constructed for cancer samples and non-cancer samples. Results Based on the network-based biomarker, a total of 40 significant proteins in lung carcinogenesis were identified with carcinogenesis relevance values (CRVs. In addition, the network-based biomarker, acting as the screening test, proved to be effective in diagnosing smokers with signs of lung cancer. Conclusions A network-based biomarker using constructed protein association networks is a useful tool to highlight the pathways and mechanisms of the lung carcinogenic process and, more importantly, provides potential therapeutic targets to combat cancer.

An Agent Based Software Approach towards Building Complex Systems

Directory of Open Access Journals (Sweden)

Latika Kharb

2015-08-01

Full Text Available Agent-oriented techniques represent an exciting new means of analyzing, designing and building complex software systems. They have the potential to significantly improve current practice in software engineering and to extend the range of applications that can feasibly be tackled. Yet, to date, there have been few serious attempts to cast agent systems as a software engineering paradigm. This paper seeks to rectify this omission. Specifically, points to be argued include:firstly, the conceptual apparatus of agent-oriented systems is well-suited to building software solutions for complex systems and secondly, agent-oriented approaches represent a genuine advance over the current state of the art for engineering complex systems. Following on from this view, the major issues raised by adopting an agentoriented approach to software engineering are highlighted and discussed in this paper.

Managing care pathways combining SNOMED CT, archetypes and an electronic guideline system.

Science.gov (United States)

Bernstein, Knut; Andersen, Ulrich

2008-01-01

Today electronic clinical guideline systems exist, but they are not well integrated with electronic health records. This paper thus proposes that the patient's "position" in the pathway during the patient journey should be made visible to all involved healthcare parties and the patient. This requires that the generic knowledge, which is represented in the guidelines, is combined with the patient specific information - and then made accessible for all relevant parties. In addition to the decision support provided by the guideline system documentation support can be provided by templates based on archetypes. This paper provides a proposal for how the guideline system and the EHR can be integrated by the use of archetypes and SNOMED CT. SNOMED CT provides the common reference terminology and the semantic links between the systems. The proposal also includes the use of a National Patient Index for storing data about the patient's position in the pathway and for sharing this information by all involved parties.

Biotransformation pathways of fluorotelomer-based polyfluoroalkyl substances: a review.

Science.gov (United States)

Butt, Craig M; Muir, Derek C G; Mabury, Scott A

2014-02-01

The study reviews the current state of knowledge regarding the biotransformation of fluorotelomer-based compounds, with a focus on compounds that ultimately degrade to form perfluoroalkyl carboxylates (PFCAs). Most metabolism studies have been performed with either microbial systems or rats and mice, and comparatively few studies have used fish models. Furthermore, biotransformation studies thus far have predominately used the 8:2 fluorotelomer alcohol (FTOH) as the substrate. However, there have been an increasing number of studies investigating 6:2 FTOH biotransformation as a result of industry's transition to shorter-chain fluorotelomer chemistry. Studies with the 8:2 FTOH metabolism universally show the formation of perfluorooctanoate (PFOA) and, to a smaller fraction, perfluorononanoate (PFNA) and lower-chain-length PFCAs. In general, the overall yield of PFOA is low, presumably because of the multiple branches in the biotransformation pathways, including conjugation reactions in animal systems. There have been a few studies of non-FTOH biotransformation, which include polyfluoroalkyl phosphates (PAPs), 8:2 fluorotelomer acrylate (8:2 FTAC), and fluorotelomer carboxylates (FTCAs, FTUCAs). The PAPs compounds and 8:2 FTAC were shown to be direct precursors to FTOHs and thus follow similar degradation pathways. © 2013 SETAC.

Real-Time Fault Detection Approach for Nonlinear Systems and its Asynchronous T-S Fuzzy Observer-Based Implementation.

Science.gov (United States)

Li, Linlin; Ding, Steven X; Qiu, Jianbin; Yang, Ying

2017-02-01

This paper is concerned with a real-time observer-based fault detection (FD) approach for a general type of nonlinear systems in the presence of external disturbances. To this end, in the first part of this paper, we deal with the definition and the design condition for an L ∞ / L 2 type of nonlinear observer-based FD systems. This analytical framework is fundamental for the development of real-time nonlinear FD systems with the aid of some well-established techniques. In the second part, we address the integrated design of the L ∞ / L 2 observer-based FD systems by applying Takagi-Sugeno (T-S) fuzzy dynamic modeling technique as the solution tool. This fuzzy observer-based FD approach is developed via piecewise Lyapunov functions, and can be applied to the case that the premise variables of the FD system is nonsynchronous with the premise variables of the fuzzy model of the plant. In the end, a case study on the laboratory setup of three-tank system is given to show the efficiency of the proposed results.

A Systems Thinking Approach to Engineering Challenges of Military Systems-of-Systems

Science.gov (United States)

2016-09-01

as part of organizational thinking , processes and practice; and 2) an adequate SoSE practice supporting environment created and used to enable SoS...UNCLASSIFIED UNCLLASIFIED A Systems Thinking Approach to Engineering Challenges of Military Systems-of-Systems Pin Chen and Mark...their products and outcomes. This report introduces a systems thinking -based approach, SoS thinking , which offers a language and a thoughtful process

When Success Is the Only Option: Designing Competency-Based Pathways for Next Generation Learning

Science.gov (United States)

Sturgis, Chris; Patrick, Susan

2010-01-01

This exploration into competency-based innovation at the school, district, and state levels suggests that competency-based pathways are a re-engineering of this nation's education system around learning--a re-engineering designed for success in which failure is no longer viable. This discussion draws on interviews and site visits with innovators…

A systems biology approach to study glucose repression in the yeast Saccharomyces cerevisiae

DEFF Research Database (Denmark)

Westergaard, Steen Lund; Soberano de Oliveira, Ana Paula; Bro, Christoffer

2007-01-01

in repression of a wide range of genes involved to utilization of alternative carbon sources. In this work, we applied a systems biology approach to study the interaction between these two pathways. Through genome-wide transcription analysis of strains with disruption of HXK2, GRR1, MIG1, the combination of MIG......1 and MIG2, and the parentel strain, we identified 393 genes to have significantly changed expression levels. To identify co-regulation patterns in the different strains we applied principal component analysis. Disruption of either GRR1 or HXK2 were both found to have profound effects...... reporter metabolites, and found that there is a high degree of consistency between the identified reporter metabolites and the physiological effects observed in the different mutants . Our systems biology approach points to close interaction between the two pathways, and our metabolism driven analysis...

A systems biology approach for miRNA-mRNA expression patterns analysis in non-small cell lung cancer.

Science.gov (United States)

Najafi, Ali; Tavallaei, Mahmood; Hosseini, Sayed Mostafa

2016-01-01

Non-small cell lung cancers (NSCLCs) is a prevalent and heterogeneous subtype of lung cancer accounting for 85 percent of patients. MicroRNAs (miRNAs), a class of small endogenous non-coding RNAs, incorporate into regulation of gene expression post-transcriptionally. Therefore, deregulation of miRNAs' expression has provided further layers of complexity to the molecular etiology and pathogenesis of different diseases and malignancies. Although, until now considerable number of studies has been carried out to illuminate this complexity in NSCLC, they have remained less effective in their goal due to lack of a holistic and integrative systems biology approach which considers all natural elaborations of miRNAs' function. It is able to reliably nominate most affected signaling pathways and therapeutic target genes by deregulated miRNAs during a particular pathological condition. Herein, we utilized a holistic systems biology approach, based on appropriate re-analyses of microarray datasets followed by reliable data filtering, to analyze integrative and combinatorial deregulated miRNA-mRNA interaction network in NSCLC, aiming to ascertain miRNA-dysregulated signaling pathway and potential therapeutic miRNAs and mRNAs which represent a lion' share during various aspects of NSCLC's pathogenesis. Our systems biology approach introduced and nominated 1) important deregulated miRNAs in NSCLCs compared with normal tissue 2) significant and confident deregulated mRNAs which were anti-correlatively targeted by deregulated miRNA in NSCLCs and 3) dysregulated signaling pathways in association with deregulated miRNA-mRNAs interactions in NSCLCs. These results introduce possible mechanism of function of deregulated miRNAs and mRNAs in NSCLC that could be used as potential therapeutic targets.

An integrated approach to preventing cardiovascular disease: community-based approaches, health system initiatives, and public health policy

Directory of Open Access Journals (Sweden)

Tina Karwalajtys

2010-09-01

Full Text Available Tina Karwalajtys1, Janusz Kaczorowski2,31Department of Family Medicine, McMaster University, Hamilton, ON, Canada; 2Primary Care & Community Research, Child & Family Research Institute, Vancouver, BC, Canada; 3Department of Family Practice, University of British Columbia, Vancouver, BC, CanadaAbstract: Cardiovascular disease (CVD is largely the product of interactions among modifiable risk factors that are common in developed nations and increasingly of concern in developing countries. Hypertension is an important precursor to the development of CVD, and although detection and treatment rates have improved in recent years in some jurisdictions, effective strategies and policies supporting a shift in distribution of risk factors at the population level remain paramount. Challenges in managing cardiovascular health more effectively include factors at the patient, provider, and system level. Strategies to reduce hypertension and CVD should be population based, incorporate multilevel, multicomponent, and socioenvironmental approaches, and integrate community resources with public health and clinical care. There is an urgent need to improve monitoring and management of risk factors through community-wide, primary care-linked initiatives, increase the evidence base for community-based prevention strategies, further develop and evaluate promising program components, and develop new approaches to support healthy lifestyle behaviors in diverse age, socioeconomic, and ethnocultural groups. Policy and system changes are critical to reduce risk in populations, including legislation and public education to reduce dietary sodium and trans-fatty acids, food pricing policies, and changes to health care delivery systems to explicitly support prevention and management of CVD.Keywords: risk factors, blood pressure determination, community health services, community health planning, public health practice

A complementarity-based approach to phase in finite-dimensional quantum systems

International Nuclear Information System (INIS)

Klimov, A B; Sanchez-Soto, L L; Guise, H de

2005-01-01

We develop a comprehensive theory of phase for finite-dimensional quantum systems. The only physical requirement we impose is that phase is complementary to amplitude. To implement this complementarity we use the notion of mutually unbiased bases, which exist for dimensions that are powers of a prime. For a d-dimensional system (qudit) we explicitly construct d+1 classes of maximally commuting operators, each one consisting of d-1 operators. One of these classes consists of diagonal operators that represent amplitudes (or inversions). By finite Fourier transformation, it is mapped onto ladder operators that can be appropriately interpreted as phase variables. We discuss examples of qubits and qutrits, and show how these results generalize previous approaches

NeuroVRAC--a comprehensive approach to virtual reality-based neurological assessment and treatment systems.

Science.gov (United States)

Valvoda, Jakob T; Assenmacher, Ingo; Dohle, Christian; Kuhlen, Torsten; Bischof, Christian

2003-01-01

We describe a comprehensive software-oriented approach to virtual reality-based neuroscientific systems in order to establish an easy to use framework for neuroscientific assessment and treatment. We have defined a process model and implemented the NeuroVRAC authoring tool for design and execution of experiments in virtual environments. Our system enables the modeling of virtual world objects and the definition of events, which are used to control the experimental process. We have included the virtual test person concept to enhance the sense of presence during the execution of virtual reality-based neuroscientific experiments.

Methodological approaches based on business rules

Directory of Open Access Journals (Sweden)

Anca Ioana ANDREESCU

2008-01-01

Full Text Available Business rules and business processes are essential artifacts in defining the requirements of a software system. Business processes capture business behavior, while rules connect processes and thus control processes and business behavior. Traditionally, rules are scattered inside application code. This approach makes it very difficult to change rules and shorten the life cycle of the software system. Because rules change more quickly than the application itself, it is desirable to externalize the rules and move them outside the application. This paper analyzes and evaluates three well-known business rules approaches. It also outlines some critical factors that have to be taken into account in the decision to introduce business rules facilities in a software system. Based on the concept of explicit manipulation of business rules in a software system, the need for a general approach based on business rules is discussed.

Decision Making in Complex Systems The DeciMaS Agent-based Interdisciplinary Framework Approach

CERN Document Server

Sokolova, Marina V

2012-01-01

The study of complex systems attracts the attention of many researchers in diverse fields. Complex systems are characterized by a high number of entities and a high degree of interactions. One of the most important features is that they do not involve a central organizing authority, but the various elements that make up the systems are self-organized. Moreover, some complex systems possess an emergency priority: climate change and sustainable development research, studies of public health, ecosystem habitats, epidemiology, and medicine, among others. Unfortunately, a great number of today’s overlapping approaches fail to meet the needs of decision makers when managing complex domains. Indeed, the design of complex systems often requires the integration of a number of artificial intelligence tools and techniques. The problem can be viewed in terms of goals, states, and actions, choosing the best action to move the system toward its desired state or behavior. This is why agent-based approaches are used to mod...

Metabolic reconstruction of Setaria italica: a systems biology approach for integrating tissue-specific omics and pathway analysis of bioenergy grasses

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Cristiana Gomes De Oliveira Dal'molin

2016-08-01

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

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

Science.gov (United States)

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

2016-01-01

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

FREQUENT SUBGRAPH MINING OF PERSONALIZED SIGNALING PATHWAY NETWORKS GROUPS PATIENTS WITH FREQUENTLY DYSREGULATED DISEASE PATHWAYS AND PREDICTS PROGNOSIS.

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Durmaz, Arda; Henderson, Tim A D; Brubaker, Douglas; Bebek, Gurkan

2017-01-01

Large scale genomics studies have generated comprehensive molecular characterization of numerous cancer types. Subtypes for many tumor types have been established; however, these classifications are based on molecular characteristics of a small gene sets with limited power to detect dysregulation at the patient level. We hypothesize that frequent graph mining of pathways to gather pathways functionally relevant to tumors can characterize tumor types and provide opportunities for personalized therapies. In this study we present an integrative omics approach to group patients based on their altered pathway characteristics and show prognostic differences within breast cancer (p network-based classifier algorithms and showed that our unsupervised approach generates more robust and biologically relevant clustering whereas previous approaches failed to report specific functions for similar patient groups or classify patients into prognostic groups. These results could serve as a means to improve prognosis for future cancer patients, and to provide opportunities for improved treatment options and personalized interventions. The proposed novel graph mining approach is able to integrate PPI networks with gene expression in a biologically sound approach and cluster patients in to clinically distinct groups. We have utilized breast cancer and glioblastoma multiforme datasets from microarray and RNA-Seq platforms and identified disease mechanisms differentiating samples. Supplementary methods, figures, tables and code are available at https://github.com/bebeklab/dysprog.

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

Development of field programmable gate array-based reactor trip functions using systems engineering approach

Energy Technology Data Exchange (ETDEWEB)

Jung, Jae Cheon; Ahmed, Ibrahim [Nuclear Power Plant Engineering, KEPCO International Nuclear Graduate School, Ulsan (Korea, Republic of)

2016-08-15

Design engineering process for field programmable gate array (FPGA)-based reactor trip functions are developed in this work. The process discussed in this work is based on the systems engineering approach. The overall design process is effectively implemented by combining with design and implementation processes. It transforms its overall development process from traditional V-model to Y-model. This approach gives the benefit of concurrent engineering of design work with software implementation. As a result, it reduces development time and effort. The design engineering process consisted of five activities, which are performed and discussed: needs/systems analysis; requirement analysis; functional analysis; design synthesis; and design verification and validation. Those activities are used to develop FPGA-based reactor bistable trip functions that trigger reactor trip when the process input value exceeds the setpoint. To implement design synthesis effectively, a model-based design technique is implied. The finite-state machine with data path structural modeling technique together with very high speed integrated circuit hardware description language and the Aldec Active-HDL tool are used to design, model, and verify the reactor bistable trip functions for nuclear power plants.

Prioritizing Acquisition Pathways in the State Level Concept

Energy Technology Data Exchange (ETDEWEB)

Murphy, Chantell L. [Los Alamos National Laboratory; Budlong-Sylvester, Kory [Los Alamos National Laboratory; Pilat, Joseph F. [Los Alamos National Laboratory

2012-06-27

The International Atomic Energy Agency's (IAEA) Department of Safeguards has launched a project to further develop the State-level concept for the planning, implementation, and evaluation of safeguards activities. In order to further evolve the safeguards system an emphasis is placed on integrating inspection-related activities and the State evaluation process to draw safeguards conclusions in the most efficient way. The credible implementation of acquisition pathway analysis is central to the success of the IAEA's State-level concept. NNSA's Office of Nuclear Safeguards and Security (NA-241) The Next Generation Safeguards Initiative (NGSI) is sponsoring Los Alamos National Laboratory (LANL) to produce a study that will examine the use of acquisition pathway analysis in: (1) Developing a State-specific, State-level approach (SLA) and Annual Implementation Plan (AIP); (2) Maximizing the utility of the physical model; and (3) Supporting resource allocation decisions through a pathway prioritization. To deal with the challenge of developing an effective and efficient SLA, this study looks at: (1) Prioritizing proliferation pathways based on an assessment of a State's capabilities and assumed proliferation strategies; and (2) Relevant State behavior (e.g., transparency, cooperation, etc.) while avoiding subjective judgments about States themselves. The study makes use of case studies and concrete examples in order to illustrate how new concepts and approaches will be implemented, and how they may differ from more traditional safeguards approaches.

Calculating systems-scale energy efficiency and net energy returns: A bottom-up matrix-based approach

International Nuclear Information System (INIS)

Brandt, Adam R.; Dale, Michael; Barnhart, Charles J.

2013-01-01

In this paper we expand the work of Brandt and Dale (2011) on ERRs (energy return ratios) such as EROI (energy return on investment). This paper describes a “bottom-up” mathematical formulation which uses matrix-based computations adapted from the LCA (life cycle assessment) literature. The framework allows multiple energy pathways and flexible inclusion of non-energy sectors. This framework is then used to define a variety of ERRs that measure the amount of energy supplied by an energy extraction and processing pathway compared to the amount of energy consumed in producing the energy. ERRs that were previously defined in the literature are cast in our framework for calculation and comparison. For illustration, our framework is applied to include oil production and processing and generation of electricity from PV (photovoltaic) systems. Results show that ERR values will decline as system boundaries expand to include more processes. NERs (net energy return ratios) tend to be lower than GERs (gross energy return ratios). External energy return ratios (such as net external energy return, or NEER (net external energy ratio)) tend to be higher than their equivalent total energy return ratios. - Highlights: • An improved bottom-up mathematical method for computing net energy return metrics is developed. • Our methodology allows arbitrary numbers of interacting processes acting as an energy system. • Our methodology allows much more specific and rigorous definition of energy return ratios such as EROI or NER

A Gene Module-Based eQTL Analysis Prioritizing Disease Genes and Pathways in Kidney Cancer

Directory of Open Access Journals (Sweden)

Mary Qu Yang

Full Text Available Clear cell renal cell carcinoma (ccRCC is the most common and most aggressive form of renal cell cancer (RCC. The incidence of RCC has increased steadily in recent years. The pathogenesis of renal cell cancer remains poorly understood. Many of the tumor suppressor genes, oncogenes, and dysregulated pathways in ccRCC need to be revealed for improvement of the overall clinical outlook of the disease. Here, we developed a systems biology approach to prioritize the somatic mutated genes that lead to dysregulation of pathways in ccRCC. The method integrated multi-layer information to infer causative mutations and disease genes. First, we identified differential gene modules in ccRCC by coupling transcriptome and protein-protein interactions. Each of these modules consisted of interacting genes that were involved in similar biological processes and their combined expression alterations were significantly associated with disease type. Then, subsequent gene module-based eQTL analysis revealed somatic mutated genes that had driven the expression alterations of differential gene modules. Our study yielded a list of candidate disease genes, including several known ccRCC causative genes such as BAP1 and PBRM1, as well as novel genes such as NOD2, RRM1, CSRNP1, SLC4A2, TTLL1 and CNTN1. The differential gene modules and their driver genes revealed by our study provided a new perspective for understanding the molecular mechanisms underlying the disease. Moreover, we validated the results in independent ccRCC patient datasets. Our study provided a new method for prioritizing disease genes and pathways. Keywords: ccRCC, Causative mutation, Pathways, Protein-protein interaction, Gene module, eQTL

An optimization model for metabolic pathways.

Science.gov (United States)

Planes, F J; Beasley, J E

2009-10-15

Different mathematical methods have emerged in the post-genomic era to determine metabolic pathways. These methods can be divided into stoichiometric methods and path finding methods. In this paper we detail a novel optimization model, based upon integer linear programming, to determine metabolic pathways. Our model links reaction stoichiometry with path finding in a single approach. We test the ability of our model to determine 40 annotated Escherichia coli metabolic pathways. We show that our model is able to determine 36 of these 40 pathways in a computationally effective manner.

Application of Adverse Outcome Pathways to U.S. EPA's Endocrine Disruptor Screening Program.

Science.gov (United States)

Browne, Patience; Noyes, Pamela D; Casey, Warren M; Dix, David J

2017-09-01

The U.S. EPA's Endocrine Disruptor Screening Program (EDSP) screens and tests environmental chemicals for potential effects in estrogen, androgen, and thyroid hormone pathways, and it is one of the only regulatory programs designed around chemical mode of action. This review describes the EDSP's use of adverse outcome pathway (AOP) and toxicity pathway frameworks to organize and integrate diverse biological data for evaluating the endocrine activity of chemicals. Using these frameworks helps to establish biologically plausible links between endocrine mechanisms and apical responses when those end points are not measured in the same assay. Pathway frameworks can facilitate a weight of evidence determination of a chemical's potential endocrine activity, identify data gaps, aid study design, direct assay development, and guide testing strategies. Pathway frameworks also can be used to evaluate the performance of computational approaches as alternatives for low-throughput and animal-based assays and predict downstream key events. In cases where computational methods can be validated based on performance, they may be considered as alternatives to specific assays or end points. A variety of biological systems affect apical end points used in regulatory risk assessments, and without mechanistic data, an endocrine mode of action cannot be determined. Because the EDSP was designed to consider mode of action, toxicity pathway and AOP concepts are a natural fit. Pathway frameworks have diverse applications to endocrine screening and testing. An estrogen pathway example is presented, and similar approaches are being used to evaluate alternative methods and develop predictive models for androgen and thyroid pathways. https://doi.org/10.1289/EHP1304.

Novel "CHASER" pathway for the management of pericardial disease.

Science.gov (United States)

Argulian, Edgar; Halpern, Dan G; Aziz, Emad F; Uretsky, Seth; Chaudhry, Farooq; Herzog, Eyal

2011-06-01

The diagnosis and management of pericardial disease are very challenging for clinicians. The evidence base in this field is relatively scarce compared with other disease entities in cardiology. In this article, we outline a unified, stepwise pathway-based approach for the management of pericardial disease. We used the "CHASER" acronym to define the entry points into the pathway. These include chest pain, hypotension or arrest, shortness of breath, echocardiographic or other imaging finding of pericardial effusion, and right-predominant heart failure. We propose a score for the assessment of pericardial effusion that is composed of the following 3 parameters: the etiology of the effusion, the size of the effusion, and the echocardiographic assessment of hemodynamic parameters. The score is applied to clinically stable patients with pericardial effusion to quantify the necessity of pericardial effusion drainage. A stepwise, pathway-based approach to the management of pericardial disease is intended to provide guidance for clinicians in decision-making and a patient-tailored evidence-based approach to medical and surgical therapy for pericardial disease. The pathway for the management of pericardial disease is the ninth project to be incorporated into the "Advanced Cardiac Admission Program" at Saint Luke's Roosevelt Hospital Center of Columbia University in New York. Further studies should focus on the validation of the feasibility, efficacy, and reliability of this pathway.

A Catchment Systems Engineering (CSE) approach to managing intensively farmed land

Science.gov (United States)

Jonczyk, Jennine; Quinn, Paul; Barber, Nicholas; Wilkinson, Mark; ODonnell, Greg

2014-05-01

Rural land management practices can have a significant impact on the hydrological and nutrient dynamics within a catchment which can dramatically alter the way it processes water, exacerbating nutrient losses from the system. A collaborative and holistic approach for managing potential conflicts between land management activity for food production alongside the aspiration to achieve good water quality and the need to make space for water can ensure the long-term sustainability of our agricultural catchments. Catchment System Engineering (CSE) is an interventionist approach to altering the catchment scale runoff regime through the manipulation of hydrological flow pathways throughout the catchment. By targeting hydrological flow pathways at source, such as overland flow, field drain and ditch function, a significant component of the runoff generation can be managed, greatly reducing erosive soil losses. Coupled with management of farm nutrients at source many runoff attenuation features or measures can be co-located to achieve benefits for water quality. Examples of community-led mitigation measures using the CSE approach will be presented from two catchments in Northumberland, Northern England, that demonstrate the generic framework for identification of multipurpose features that slow, store and filter runoff at strategic locations in the landscape. Measures include within-field barriers, edge of field traps and within-field sediment filters and sediment traps which demonstrate how sediment can be trapped locally (including silt and clay fractions) and be recovered for use back on the land. Deliverables from this CSE approach includes the reduction of downstream flood risk and capturing of sediment and associated nutrients. The CSE approach allows for a more natural flood and nutrient management approach which helps to restore vital catchment functions to re-establish a healthy catchment system.

An approach to build a knowledge base for reactor accident diagnostic expert system

International Nuclear Information System (INIS)

Yoshida, K.; Fujii, M.; Fujiki, K.; Yokobayashi, M.; Kohsaka, A.; Aoyagi, T.; Hirota, Y.

1987-01-01

In the development of a rule based expert system, one of the key issues is how to acquire knowledge and to build knowledge base (KB). On building the KB of DISKET, which is an expert system for nuclear reactor accident diagnosis developed in JAERI, several problems have been experienced as follows. To write rules is a time consuming task, and it is difficult to keep the objectivity and consistency of rules as the number of rules increase. Further, certainty factors (CFs) must be often determined according to engineering judgment, i.e., empirically or intuitively. A systematic approach was attempted to handle these difficulties and to build an objective KB efficiently. The approach described in this paper is based on the concept that a prototype KB, colloquially speaking an initial guess, should first be generated in a systematic way and then is to be modified and/or improved by human experts for practical use. Statistical methods, principally Factor Analysis, were used as the systematic way to build a prototype KB for the DISKET using a PWR plant simulator data. The source information is a number of data obtained from the simulation of transients, such as the status of components and annunciator etc., and major process parameters like pressures, temperatures and so on

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

of HCC are HCC subtype-associated specifically. In conclusion, PoTRA is a new approach to explore and discover pathways involved in cancer. PoTRA can be used as a complement to other existing methods to broaden our understanding of the biological mechanisms behind cancer at the system-level.

A Novel Relevance Feedback Approach Based on Similarity Measure Modification in an X-Ray Image Retrieval System Based on Fuzzy Representation Using Fuzzy Attributed Relational Graph

Directory of Open Access Journals (Sweden)

Hossien Pourghassem

2011-04-01

Full Text Available Relevance feedback approaches is used to improve the performance of content-based image retrieval systems. In this paper, a novel relevance feedback approach based on similarity measure modification in an X-ray image retrieval system based on fuzzy representation using fuzzy attributed relational graph (FARG is presented. In this approach, optimum weight of each feature in feature vector is calculated using similarity rate between query image and relevant and irrelevant images in user feedback. The calculated weight is used to tune fuzzy graph matching algorithm as a modifier parameter in similarity measure. The standard deviation of the retrieved image features is applied to calculate the optimum weight. The proposed image retrieval system uses a FARG for representation of images, a fuzzy matching graph algorithm as similarity measure and a semantic classifier based on merging scheme for determination of the search space in image database. To evaluate relevance feedback approach in the proposed system, a standard X-ray image database consisting of 10000 images in 57 classes is used. The improvement of the evaluation parameters shows proficiency and efficiency of the proposed system.

A Model-Based Approach to Engineering Behavior of Complex Aerospace Systems

Science.gov (United States)

Ingham, Michel; Day, John; Donahue, Kenneth; Kadesch, Alex; Kennedy, Andrew; Khan, Mohammed Omair; Post, Ethan; Standley, Shaun

2012-01-01

One of the most challenging yet poorly defined aspects of engineering a complex aerospace system is behavior engineering, including definition, specification, design, implementation, and verification and validation of the system's behaviors. This is especially true for behaviors of highly autonomous and intelligent systems. Behavior engineering is more of an art than a science. As a process it is generally ad-hoc, poorly specified, and inconsistently applied from one project to the next. It uses largely informal representations, and results in system behavior being documented in a wide variety of disparate documents. To address this problem, JPL has undertaken a pilot project to apply its institutional capabilities in Model-Based Systems Engineering to the challenge of specifying complex spacecraft system behavior. This paper describes the results of the work in progress on this project. In particular, we discuss our approach to modeling spacecraft behavior including 1) requirements and design flowdown from system-level to subsystem-level, 2) patterns for behavior decomposition, 3) allocation of behaviors to physical elements in the system, and 4) patterns for capturing V&V activities associated with behavioral requirements. We provide examples of interesting behavior specification patterns, and discuss findings from the pilot project.

Prioritizing Candidate Disease Metabolites Based on Global Functional Relationships between Metabolites in the Context of Metabolic Pathways

Science.gov (United States)

Yang, Haixiu; Xu, Yanjun; Han, Junwei; Li, Jing; Su, Fei; Zhang, Yunpeng; Zhang, Chunlong; Li, Dongguo; Li, Xia

2014-01-01

Identification of key metabolites for complex diseases is a challenging task in today's medicine and biology. A special disease is usually caused by the alteration of a series of functional related metabolites having a global influence on the metabolic network. Moreover, the metabolites in the same metabolic pathway are often associated with the same or similar disease. Based on these functional relationships between metabolites in the context of metabolic pathways, we here presented a pathway-based random walk method called PROFANCY for prioritization of candidate disease metabolites. Our strategy not only takes advantage of the global functional relationships between metabolites but also sufficiently exploits the functionally modular nature of metabolic networks. Our approach proved successful in prioritizing known metabolites for 71 diseases with an AUC value of 0.895. We also assessed the performance of PROFANCY on 16 disease classes and found that 4 classes achieved an AUC value over 0.95. To investigate the robustness of the PROFANCY, we repeated all the analyses in two metabolic networks and obtained similar results. Then we applied our approach to Alzheimer's disease (AD) and found that a top ranked candidate was potentially related to AD but had not been reported previously. Furthermore, our method was applicable to prioritize the metabolites from metabolomic profiles of prostate cancer. The PROFANCY could identify prostate cancer related-metabolites that are supported by literatures but not considered to be significantly differential by traditional differential analysis. We also developed a freely accessible web-based and R-based tool at http://bioinfo.hrbmu.edu.cn/PROFANCY. PMID:25153931

Risk-based configuration control system: Analysis and approaches

International Nuclear Information System (INIS)

Samanta, P.K.; Kim, I.S.; Vesely, W.E.; Lofgren, E.V.

1989-01-01

This paper presents an evaluation of the configuration risks associated with the operation of a nuclear power plant and the approaches to control these risks using risk-based configuration control considerations. In that context, the actual and maximum potential configuration risks at a plant are analyzed and the alternative types criteria for a risk-based configuration control systems are described. The risk-based configuration calculations which are studied here focus on the core-melt frequency impacts from given plant configurations. By calculating the core-melt frequency for given configurations, the configurations which cause large core-melt frequency increases can be identified and controlled. The duration time in which the configuration can exist can then be limited or the core-melt frequency level associated with the configuration can be reduced by various actions. Furthermore, maintenances and tests can be scheduled to avoid the configurations which cause large core-melt frequency increases. Present technical specifications do not control many of these configurations which can cause large core-melt frequency increases but instead focus on many risk-unimportant allowed outage times. Hence, risk-based configuration management can be effectively used to reduce core-melt frequency associated risks at a plant and at the same time can provide flexibility in plant operation. The alternative strategies for controlling the core-melt frequency and other risk contributions include: (1) controlling the increased risk level which is associated with the configuration; (2) controlling the individual configuration risk which is associated with a given duration of a configuration; (3) controlling the time period configuration risk from configurations which occur in a time period

Bifurcation-based approach reveals synergism and optimal combinatorial perturbation.

Science.gov (United States)

Liu, Yanwei; Li, Shanshan; Liu, Zengrong; Wang, Ruiqi

2016-06-01

Cells accomplish the process of fate decisions and form terminal lineages through a series of binary choices in which cells switch stable states from one branch to another as the interacting strengths of regulatory factors continuously vary. Various combinatorial effects may occur because almost all regulatory processes are managed in a combinatorial fashion. Combinatorial regulation is crucial for cell fate decisions because it may effectively integrate many different signaling pathways to meet the higher regulation demand during cell development. However, whether the contribution of combinatorial regulation to the state transition is better than that of a single one and if so, what the optimal combination strategy is, seem to be significant issue from the point of view of both biology and mathematics. Using the approaches of combinatorial perturbations and bifurcation analysis, we provide a general framework for the quantitative analysis of synergism in molecular networks. Different from the known methods, the bifurcation-based approach depends only on stable state responses to stimuli because the state transition induced by combinatorial perturbations occurs between stable states. More importantly, an optimal combinatorial perturbation strategy can be determined by investigating the relationship between the bifurcation curve of a synergistic perturbation pair and the level set of a specific objective function. The approach is applied to two models, i.e., a theoretical multistable decision model and a biologically realistic CREB model, to show its validity, although the approach holds for a general class of biological systems.

Cultural pathways through universal development.

Science.gov (United States)

Greenfield, Patricia M; Keller, Heidi; Fuligni, Andrew; Maynard, Ashley

2003-01-01

We focus our review on three universal tasks of human development: relationship formation, knowledge acquisition, and the balance between autonomy and relatedness at adolescence. We present evidence that each task can be addressed through two deeply different cultural pathways through development: the pathways of independence and interdependence. Whereas core theories in developmental psychology are universalistic in their intentions, they in fact presuppose the independent pathway of development. Because the independent pathway is therefore well-known in psychology, we focus a large part of our review on empirically documenting the alternative, interdependent pathway for each developmental task. We also present three theoretical approaches to culture and development: the ecocultural, the sociohistorical, and the cultural values approach. We argue that an understanding of cultural pathways through human development requires all three approaches. We review evidence linking values (cultural values approach), ecological conditions (ecocultural approach), and socialization practices (sociohistorical approach) to cultural pathways through universal developmental tasks.

Surface inspection system for industrial components based on shape from shading minimization approach

Science.gov (United States)

Kotan, Muhammed; Öz, Cemil

2017-12-01

An inspection system using estimated three-dimensional (3-D) surface characteristics information to detect and classify the faults to increase the quality control on the frequently used industrial components is proposed. Shape from shading (SFS) is one of the basic and classic 3-D shape recovery problems in computer vision. In our application, we developed a system using Frankot and Chellappa SFS method based on the minimization of the selected basis function. First, the specialized image acquisition system captured the images of the component. To eliminate noise, wavelet transform is applied to the taken images. Then, estimated gradients were used to obtain depth and surface profiles. Depth information was used to determine and classify the surface defects. Also, a comparison made with some linearization-based SFS algorithms was discussed. The developed system was applied to real products and the results indicated that using SFS approaches is useful and various types of defects can easily be detected in a short period of time.

A molecular systems approach to modelling human skin pigmentation: identifying underlying pathways and critical components.

Science.gov (United States)

Raghunath, Arathi; Sambarey, Awanti; Sharma, Neha; Mahadevan, Usha; Chandra, Nagasuma

2015-04-29

Ultraviolet radiations (UV) serve as an environmental stress for human skin, and result in melanogenesis, with the pigment melanin having protective effects against UV induced damage. This involves a dynamic and complex regulation of various biological processes that results in the expression of melanin in the outer most layers of the epidermis, where it can exert its protective effect. A comprehensive understanding of the underlying cross talk among different signalling molecules and cell types is only possible through a systems perspective. Increasing incidences of both melanoma and non-melanoma skin cancers necessitate the need to better comprehend UV mediated effects on skin pigmentation at a systems level, so as to ultimately evolve knowledge-based strategies for efficient protection and prevention of skin diseases. A network model for UV-mediated skin pigmentation in the epidermis was constructed and subjected to shortest path analysis. Virtual knock-outs were carried out to identify essential signalling components. We describe a network model for UV-mediated skin pigmentation in the epidermis. The model consists of 265 components (nodes) and 429 directed interactions among them, capturing the manner in which one component influences the other and channels information. Through shortest path analysis, we identify novel signalling pathways relevant to pigmentation. Virtual knock-outs or perturbations of specific nodes in the network have led to the identification of alternate modes of signalling as well as enabled determining essential nodes in the process. The model presented provides a comprehensive picture of UV mediated signalling manifesting in human skin pigmentation. A systems perspective helps provide a holistic purview of interconnections and complexity in the processes leading to pigmentation. The model described here is extensive yet amenable to expansion as new data is gathered. Through this study, we provide a list of important proteins essential

Analysis and classification of oncology activities on the way to workflow based single source documentation in clinical information systems.

Science.gov (United States)

Wagner, Stefan; Beckmann, Matthias W; Wullich, Bernd; Seggewies, Christof; Ries, Markus; Bürkle, Thomas; Prokosch, Hans-Ulrich

2015-12-22

Today, cancer documentation is still a tedious task involving many different information systems even within a single institution and it is rarely supported by appropriate documentation workflows. In a comprehensive 14 step analysis we compiled diagnostic and therapeutic pathways for 13 cancer entities using a mixed approach of document analysis, workflow analysis, expert interviews, workflow modelling and feedback loops. These pathways were stepwise classified and categorized to create a final set of grouped pathways and workflows including electronic documentation forms. A total of 73 workflows for the 13 entities based on 82 paper documentation forms additionally to computer based documentation systems were compiled in a 724 page document comprising 130 figures, 94 tables and 23 tumour classifications as well as 12 follow-up tables. Stepwise classification made it possible to derive grouped diagnostic and therapeutic pathways for the three major classes - solid entities with surgical therapy - solid entities with surgical and additional therapeutic activities and - non-solid entities. For these classes it was possible to deduct common documentation workflows to support workflow-guided single-source documentation. Clinical documentation activities within a Comprehensive Cancer Center can likely be realized in a set of three documentation workflows with conditional branching in a modern workflow supporting clinical information system.

A knowledge-based approach to identification and adaptation in dynamical systems control

Science.gov (United States)

Glass, B. J.; Wong, C. M.

1988-01-01

Artificial intelligence techniques are applied to the problems of model form and parameter identification of large-scale dynamic systems. The object-oriented knowledge representation is discussed in the context of causal modeling and qualitative reasoning. Structured sets of rules are used for implementing qualitative component simulations, for catching qualitative discrepancies and quantitative bound violations, and for making reconfiguration and control decisions that affect the physical system. These decisions are executed by backward-chaining through a knowledge base of control action tasks. This approach was implemented for two examples: a triple quadrupole mass spectrometer and a two-phase thermal testbed. Results of tests with both of these systems demonstrate that the software replicates some or most of the functionality of a human operator, thereby reducing the need for a human-in-the-loop in the lower levels of control of these complex systems.

Risk-based configuration control system: Analysis and approaches

International Nuclear Information System (INIS)

Samanta, P.K.; Kim, I.S.; Lofgren, E.V.; Vesely, W.E.

1990-01-01

This paper presents an analysis of risks associated with component outage configurations during power operation of a nuclear power plant and discusses approaches and strategies for developing a risk-based configuration control system. A configuration, as used here, is a set of component states. The objective of risk-based configuration control is to detect and control plant configurations using a risk-perspective. The configuration contributions to core-melt frequency and core-melt probability are studied for two plants. Large core-melt frequency can be caused by configurations and there are a number of such configurations that are not currently controlled by technical specifications. However, the expected frequency of occurrence of the impacting configurations is small and the actual core-melt probability contributions are also generally small. Effective strategies and criteria for controlling configuration risks are presented. Such control strategies take into consideration the risks associated with configurations, the nature and characteristics of the configuration risks, and also the practical considerations such as adequate repair times and/or options to transfer to low risk configurations. Alternative types of criteria are discussed that are not overly restrictive to result in unnecessary plant shutdown, but rather motivates effective test and maintenance practices that control risk-significant configurations to allow continued operation with an adequate margin to meet challenges to safety

Risk-based configuration control system: Analysis and approaches

International Nuclear Information System (INIS)

Samanta, P.K.; Vesely, W.E.; Kim, I.S.; Lofgren, E.V.

1989-01-01

This paper presents an analysis of risks associated with component outage configurations during power operation of a nuclear power plant and discusses approaches and strategies for developing a risk-based configuration control system. A configuration, as used here, is a set of component states. The objective of risk-based configuration control is to detect and control plant configurations using a risk-perspective. The configuration contributions to core-melt frequency and core-melt probability are studied for two plants. Large core-melt frequency can be caused by configurations and there are a number of such configurations that are not currently controlled by technical specifications. However, the expected frequency of occurrence of the impacting configurations is small and the actual core-melt probability contributions are also generally small. Effective strategies and criteria for controlling configuration risks are presented. Such control strategies take into consideration the risks associated with configurations, the nature and characteristics of the configuration risks, and also the practical considerations such as adequate repair times and/or options to transfer to low risk configurations. Alternative types of criteria are discussed that are not overly restrictive to result in unnecessary plant shutdown, but rather motivates effective tests and maintenance practices that control; risk-significant configurations to allow continued operation with an adequate margin to meet challenges to safety. 3 refs., 7 figs., 2 tabs

Hi-Jack: a novel computational framework for pathway-based inference of host–pathogen interactions

KAUST Repository

Kleftogiannis, Dimitrios A.

2015-03-09

Motivation: Pathogens infect their host and hijack the host machinery to produce more progeny pathogens. Obligate intracellular pathogens, in particular, require resources of the host to replicate. Therefore, infections by these pathogens lead to alterations in the metabolism of the host, shifting in favor of pathogen protein production. Some computational identification of mechanisms of host-pathogen interactions have been proposed, but it seems the problem has yet to be approached from the metabolite-hijacking angle. Results: We propose a novel computational framework, Hi-Jack, for inferring pathway-based interactions between a host and a pathogen that relies on the idea of metabolite hijacking. Hi-Jack searches metabolic network data from hosts and pathogens, and identifies candidate reactions where hijacking occurs. A novel scoring function ranks candidate hijacked reactions and identifies pathways in the host that interact with pathways in the pathogen, as well as the associated frequent hijacked metabolites. We also describe host-pathogen interaction principles that can be used in the future for subsequent studies. Our case study on Mycobacterium tuberculosis (Mtb) revealed pathways in human-e.g. carbohydrate metabolism, lipids metabolism and pathways related to amino acids metabolism-that are likely to be hijacked by the pathogen. In addition, we report interesting potential pathway interconnections between human and Mtb such as linkage of human fatty acid biosynthesis with Mtb biosynthesis of unsaturated fatty acids, or linkage of human pentose phosphate pathway with lipopolysaccharide biosynthesis in Mtb. © The Author 2015. Published by Oxford University Press. All rights reserved.

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

Pathway-based analysis of genome-wide siRNA screens reveals the regulatory landscape of APP processing.

Directory of Open Access Journals (Sweden)

Luiz Miguel Camargo

Full Text Available The progressive aggregation of Amyloid-β (Aβ in the brain is a major trait of Alzheimer's Disease (AD. Aβ is produced as a result of proteolytic processing of the β-amyloid precursor protein (APP. Processing of APP is mediated by multiple enzymes, resulting in the production of distinct peptide products: the non-amyloidogenic peptide sAPPα and the amyloidogenic peptides sAPPβ, Aβ40, and Aβ42. Using a pathway-based approach, we analyzed a large-scale siRNA screen that measured the production of different APP proteolytic products. Our analysis identified many of the biological processes/pathways that are known to regulate APP processing and have been implicated in AD pathogenesis, as well as revealing novel regulatory mechanisms. Furthermore, we also demonstrate that some of these processes differentially regulate APP processing, with some mechanisms favouring production of certain peptide species over others. For example, synaptic transmission having a bias towards regulating Aβ40 production over Aβ42 as well as processes involved in insulin and pancreatic biology having a bias for sAPPβ production over sAPPα. In addition, some of the pathways identified as regulators of APP processing contain genes (CLU, BIN1, CR1, PICALM, TREM2, SORL1, MEF2C, DSG2, EPH1A recently implicated with AD through genome wide association studies (GWAS and associated meta-analysis. In addition, we provide supporting evidence and a deeper mechanistic understanding of the role of diabetes in AD. The identification of these processes/pathways, their differential impact on APP processing, and their relationships to each other, provide a comprehensive systems biology view of the "regulatory landscape" of APP.

Formal verification of dynamic hybrid systems: a NuSMV-based model checking approach

Directory of Open Access Journals (Sweden)

Xu Zhi

2018-01-01

Full Text Available Software security is an important and challenging research topic in developing dynamic hybrid embedded software systems. Ensuring the correct behavior of these systems is particularly difficult due to the interactions between the continuous subsystem and the discrete subsystem. Currently available security analysis methods for system risks have been limited, as they rely on manual inspections of the individual subsystems under simplifying assumptions. To improve this situation, a new approach is proposed that is based on the symbolic model checking tool NuSMV. A dual PID system is used as an example system, for which the logical part and the computational part of the system are modeled in a unified manner. Constraints are constructed on the controlled object, and a counter-example path is ultimately generated, indicating that the hybrid system can be analyzed by the model checking tool.

Potential pyrolysis pathway assessment for microalgae-based aviation fuel based on energy conversion efficiency and life cycle

International Nuclear Information System (INIS)

Guo, Fang; Wang, Xin; Yang, Xiaoyi

2017-01-01

Highlights: • High lipid content in microalgae increases energy conversion efficiency. • Indirect pathway has the highest mass ratio, energy ratio and energy efficiency. • The Isochrysis indirect pathway produces most kerosene component precursor. • The Isochrysis indirect pyrolysis pathway shows the best performance in LCA. - Abstract: Although the research of microalgae pyrolysis has been conducted for many years, there is a lack of investigations on energy efficiency and life cycle assessment. In this study, we investigated the biocrude yield and energy efficiency of direct pyrolysis, microalgae residue pyrolysis after lipid extraction (indirect pyrolysis), and different microalgae co-pyrolysis. This research also investigated the life cycle assessment of the three different pyrolysis pathways. A system boundary of Well-to-Wake (WTWa) was defined and included sub-process models, such as feedstock production, fuel production and pump-to-wheels (PTW) stages. The pathway of Isochrysis indirect pyrolysis shows the best performance in the mass ratio and energy ratio, produces the most kerosene component precursor, has the lowest WTWa total energy input, fossil fuel consumption and greenhouse gas emissions, and resultes in the best energy efficiency. All the evidence indicates that Isochrysis R2 pathway is a potential and optimal pyrolysis pathway to liquid biofuels. The mass ratio of pyrolysis biocrude is shown to be the decisive factor for different microalgae species. The sensitivity analysis results also indicates that the life cycle indicators are particularly sensitive to the mass ratio of pyrolysis biocrude for microalgae-based hydrotreated pyrolysis aviation fuel.

Pathway-based outlier method reveals heterogeneous genomic structure of autism in blood transcriptome.

Science.gov (United States)

Campbell, Malcolm G; Kohane, Isaac S; Kong, Sek Won

2013-09-24

Decades of research strongly suggest that the genetic etiology of autism spectrum disorders (ASDs) is heterogeneous. However, most published studies focus on group differences between cases and controls. In contrast, we hypothesized that the heterogeneity of the disorder could be characterized by identifying pathways for which individuals are outliers rather than pathways representative of shared group differences of the ASD diagnosis. Two previously published blood gene expression data sets--the Translational Genetics Research Institute (TGen) dataset (70 cases and 60 unrelated controls) and the Simons Simplex Consortium (Simons) dataset (221 probands and 191 unaffected family members)--were analyzed. All individuals of each dataset were projected to biological pathways, and each sample's Mahalanobis distance from a pooled centroid was calculated to compare the number of case and control outliers for each pathway. Analysis of a set of blood gene expression profiles from 70 ASD and 60 unrelated controls revealed three pathways whose outliers were significantly overrepresented in the ASD cases: neuron development including axonogenesis and neurite development (29% of ASD, 3% of control), nitric oxide signaling (29%, 3%), and skeletal development (27%, 3%). Overall, 50% of cases and 8% of controls were outliers in one of these three pathways, which could not be identified using group comparison or gene-level outlier methods. In an independently collected data set consisting of 221 ASD and 191 unaffected family members, outliers in the neurogenesis pathway were heavily biased towards cases (20.8% of ASD, 12.0% of control). Interestingly, neurogenesis outliers were more common among unaffected family members (Simons) than unrelated controls (TGen), but the statistical significance of this effect was marginal (Chi squared P < 0.09). Unlike group difference approaches, our analysis identified the samples within the case and control groups that manifested each expression

Junction detection and pathway selection

Science.gov (United States)

Peck, Alex N.; Lim, Willie Y.; Breul, Harry T.

1992-02-01

The ability to detect junctions and make choices among the possible pathways is important for autonomous navigation. In our script-based navigation approach where a journey is specified as a script of high-level instructions, actions are frequently referenced to junctions, e.g., `turn left at the intersection.' In order for the robot to carry out these kind of instructions, it must be able (1) to detect an intersection (i.e., an intersection of pathways), (2) know that there are several possible pathways it can take, and (3) pick the pathway consistent with the high level instruction. In this paper we describe our implementation of the ability to detect junctions in an indoor environment, such as corners, T-junctions and intersections, using sonar. Our approach uses a combination of partial scan of the local environment and recognition of sonar signatures of certain features of the junctions. In the case where the environment is known, we use additional sensor information (such as compass bearings) to help recognize the specific junction. In general, once a junction is detected and its type known, the number of possible pathways can be deduced and the correct pathway selected. Then the appropriate behavior for negotiating the junction is activated.

SMARTPHONE-BASED APPROACH TO ADVANCED DRIVER ASSISTANCE SYSTEM (ADAS RESEARCH AND DEVELOPMENT

Directory of Open Access Journals (Sweden)

I. B. Lashkov

2015-11-01

Full Text Available Subject of Research.The paper deals with findings and presents asmartphone-based approach to advanced driver assistance system (ADAS research and development.The approach is based on the data of smartphone cameras and sensors. The line of researchis associated with the developmentof mobile advanced driver assistance system (ADAS. Method.The proposedapproach isbased on the use of driver'sand vehicle behavior ontologies. Current ADAS systems can be divided into two main categories according to the method of implementation: mobile applications, manually installed by the driver from the application stores, and safetyhardware and softwaresystems,integrated into vehicles by manufacturesor in the automotive service centers.Mobile application installed on the smartphone uses the built-in rear and front-facing cameras and sensors to monitor both the road and vehicles ahead, and at the same time the driver in order to prevent traffic collisions. The service consists of components for objects recognition in the images obtained with cameras, and components for traffic situation analysis. Main Results. The driver safety mobile application has been developedfor the use on mobile phones.The mobile phone is mounted on the windshield of a car.In case of dangerous event occurrence, the application engine will make an audible or vibration signal to inform the driver to be concentratedand more vigilant. For example, road obstacles, rear-end and stationary vehicle accidents are the most common accident types.The mobile application detects whether a crash is imminent by computing the ‘Time To Contact’ (TTC taking into account host vehicle speed, relative speed and relative acceleration.If the driver doesn’t maintain safe minimum distance with the car immediately ahead, the mobile application will alert the driver by displaying an attention icon with an audible alert. The dual-camera sensing application is designed to help the drivers increase the trip safety

Introducing care pathway commissioning to primary dental care: measuring performance.

Science.gov (United States)

Harris, R; Bridgman, C; Ahmad, M; Bowes, L; Haley, R; Saleem, S; Singh, R; Taylor, S

2011-12-09

Care pathways have been used in a variety of ways: firstly to support quality improvement through standardising clinical processes, but also for secondary purposes, by purchasers of healthcare, to monitor activity and health outcomes and to commission services. This paper focuses on reporting a secondary use of care pathways: to commission and monitor performance of primary dental care services. Findings of a project involving three dental practices implementing a system based on rating patients according to their risk of disease and need for care are outlined. Data from surgery-based clinical databases and interviews from commissioners and providers are reported. The use of both process and outcome key performance indicators in this context is discussed, as well as issues which arise such as attributability of outcome measures and strategic approaches to improving quality of care.

[Comparison of ablation of left-sided accessory pathway by atrial septal and retrograde arterial approach].

Science.gov (United States)

Zhu, J G; Bao, Z Y; Gu, X

2017-03-07

Objective: To compare the advantages and disadvantages of radiofrequency ablation of left-sided accessory pathways by via atrial septal approach with retrograde through aortic approach. Methods: A total of 184 patients of left-side accessory pathways were treated in Taizhou People's Hospital and the Subei People's Hospital from March 2012 to August 2015.A total of 103 cases were treated by aortic retrograde approach as through arterial group, 81 cases were treated by punctured atrial septal to left atrial for mapping and ablation as through atrial septal group.Comparison of ablation procedure time, total and pathways of different parts(subgroup) at instant success and relapse rates, safety (serious complications), and statistics other complications in operation and postoperative. Results: Through arterial group and through atrial septal group were no significant difference ( P >0.05) in the ablation procedure time((25±18 ) vs (22±15)min ), instant success(98.1% vs 97.5%) and relapse rates(1.0% vs 1.2%), security(1 vs 0 case). There was no statistical difference in septal part subgroups (all P >0.05) in the ablation procedure time((22±18)vs (25±19)min), instant success(91.7% vs 89.9 %) and relapse rates(0 vs 11.1%); posterior wall subgroup had no statistical difference in the ablation procedure time((18±15)vs (16±12)min), instant success(100% vs 100 %) and relapse rates(0 vs 0)(all P >0.05); side wall subgroup had no statistical difference in the ablation procedure time((29±20)vs (21±18) min), instant success (98.3% vs 98.1%)and relapse rates(1.7% vs 0%)(all P >0.05). Conclusion: Ablation of left-sided accessory pathways by transseptal approach and transaortic approach has no statistical difference in the procedure time, instant success and relapse rates, security.In a particular case, there is a certain complementarity between the two methods.

A Distributed Approach to System-Level Prognostics

Science.gov (United States)

Daigle, Matthew J.; Bregon, Anibal; Roychoudhury, Indranil

2012-01-01

Prognostics, which deals with predicting remaining useful life of components, subsystems, and systems, is a key technology for systems health management that leads to improved safety and reliability with reduced costs. The prognostics problem is often approached from a component-centric view. However, in most cases, it is not specifically component lifetimes that are important, but, rather, the lifetimes of the systems in which these components reside. The system-level prognostics problem can be quite difficult due to the increased scale and scope of the prognostics problem and the relative Jack of scalability and efficiency of typical prognostics approaches. In order to address these is ues, we develop a distributed solution to the system-level prognostics problem, based on the concept of structural model decomposition. The system model is decomposed into independent submodels. Independent local prognostics subproblems are then formed based on these local submodels, resul ting in a scalable, efficient, and flexible distributed approach to the system-level prognostics problem. We provide a formulation of the system-level prognostics problem and demonstrate the approach on a four-wheeled rover simulation testbed. The results show that the system-level prognostics problem can be accurately and efficiently solved in a distributed fashion.

Seeking kinetic pathways relevant to the structural evolution of metal nanoparticles

International Nuclear Information System (INIS)

Haldar, Paramita; Chatterjee, Abhijit

2015-01-01

Understanding the kinetic pathways that cause metal nanoparticles to structurally evolve over time is essential for predicting their shape and size distributions and catalytic properties. Consequently, we need detailed kinetic models that can provide such information. Most kinetic Monte Carlo models used for metal systems contain a fixed catalogue of atomic moves; the catalogue is largely constructed based on our physical understanding of the material. In some situations, it is possible that an incorrect picture of the overall dynamics is obtained when kinetic pathways that are relevant to the dynamics are missing from the catalogue. Hence, a computational framework that can systematically determine the relevant pathways is required. This work intends to fulfil this requirement. Examples involving an Ag nanoparticle are studied to illustrate how molecular dynamics (MD) calculations can be employed to find the relevant pathways in a system. Since pathways that are unlikely to be selected at short timescales can become relevant at longer times, the accuracy of the catalogue is maintained by continually seeking these pathways using MD. We discuss various aspects of our approach, namely, defining the relevance of atomic moves to the dynamics and determining when additional MD is required to ensure the desired accuracy, as well as physical insights into the Ag nanoparticle. (paper)

Genome Wide Association Study of SNP-, Gene-, and Pathway-based Approaches to Identify Genes Influencing Susceptibility to Staphylococcus aureus Infections

Directory of Open Access Journals (Sweden)

Zhan eYe

2014-05-01

Full Text Available Background: We conducted a genome-wide association study (GWAS to identify specific genetic variants that underlie susceptibility to disease caused by Staphylococcus aureus in humans. Methods: Cases (n=309 and controls (n=2,925 were genotyped at 508,921 single nucleotide polymorphisms (SNPs. Cases had at least one laboratory and clinician confirmed disease caused by S. aureus whereas controls did not. R-package (for SNP association, EIGENSOFT (to estimate and adjust for population stratification and gene- (VEGAS and pathway-based (DAVID, PANTHER, and Ingenuity Pathway Analysis analyses were performed.Results: No SNP reached genome-wide significance. Four SNPs exceeded the pConclusion: We identified potential susceptibility genes for S. aureus diseases in this preliminary study but confirmation by other studies is needed. The observed associations could be relevant given the complexity of S. aureus as a pathogen and its ability to exploit multiple biological pathways to cause infections in humans.

Rule-based modeling: a computational approach for studying biomolecular site dynamics in cell signaling systems

Science.gov (United States)

Chylek, Lily A.; Harris, Leonard A.; Tung, Chang-Shung; Faeder, James R.; Lopez, Carlos F.

2013-01-01

Rule-based modeling was developed to address the limitations of traditional approaches for modeling chemical kinetics in cell signaling systems. These systems consist of multiple interacting biomolecules (e.g., proteins), which themselves consist of multiple parts (e.g., domains, linear motifs, and sites of phosphorylation). Consequently, biomolecules that mediate information processing generally have the potential to interact in multiple ways, with the number of possible complexes and post-translational modification states tending to grow exponentially with the number of binary interactions considered. As a result, only large reaction networks capture all possible consequences of the molecular interactions that occur in a cell signaling system, which is problematic because traditional modeling approaches for chemical kinetics (e.g., ordinary differential equations) require explicit network specification. This problem is circumvented through representation of interactions in terms of local rules. With this approach, network specification is implicit and model specification is concise. Concise representation results in a coarse graining of chemical kinetics, which is introduced because all reactions implied by a rule inherit the rate law associated with that rule. Coarse graining can be appropriate if interactions are modular, and the coarseness of a model can be adjusted as needed. Rules can be specified using specialized model-specification languages, and recently developed tools designed for specification of rule-based models allow one to leverage powerful software engineering capabilities. A rule-based model comprises a set of rules, which can be processed by general-purpose simulation and analysis tools to achieve different objectives (e.g., to perform either a deterministic or stochastic simulation). PMID:24123887

Rule-based modeling: a computational approach for studying biomolecular site dynamics in cell signaling systems.

Science.gov (United States)

Chylek, Lily A; Harris, Leonard A; Tung, Chang-Shung; Faeder, James R; Lopez, Carlos F; Hlavacek, William S

2014-01-01

Rule-based modeling was developed to address the limitations of traditional approaches for modeling chemical kinetics in cell signaling systems. These systems consist of multiple interacting biomolecules (e.g., proteins), which themselves consist of multiple parts (e.g., domains, linear motifs, and sites of phosphorylation). Consequently, biomolecules that mediate information processing generally have the potential to interact in multiple ways, with the number of possible complexes and posttranslational modification states tending to grow exponentially with the number of binary interactions considered. As a result, only large reaction networks capture all possible consequences of the molecular interactions that occur in a cell signaling system, which is problematic because traditional modeling approaches for chemical kinetics (e.g., ordinary differential equations) require explicit network specification. This problem is circumvented through representation of interactions in terms of local rules. With this approach, network specification is implicit and model specification is concise. Concise representation results in a coarse graining of chemical kinetics, which is introduced because all reactions implied by a rule inherit the rate law associated with that rule. Coarse graining can be appropriate if interactions are modular, and the coarseness of a model can be adjusted as needed. Rules can be specified using specialized model-specification languages, and recently developed tools designed for specification of rule-based models allow one to leverage powerful software engineering capabilities. A rule-based model comprises a set of rules, which can be processed by general-purpose simulation and analysis tools to achieve different objectives (e.g., to perform either a deterministic or stochastic simulation). © 2013 Wiley Periodicals, Inc.

Spectrally-balanced chromatic approach-lighting system

Science.gov (United States)

Chase, W. D.

1977-01-01

Approach lighting system employing combinations of red and blue lights reduces problem of color-based optical illusions. System exploits inherent chromatic aberration of eye to create three-dimensional effect, giving pilot visual clues of position.

Automated tool for virtual screening and pharmacology-based pathway prediction and analysis

Directory of Open Access Journals (Sweden)

Sugandh Kumar

2017-10-01

Full Text Available The virtual screening is an effective tool for the lead identification in drug discovery. However, there are limited numbers of crystal structures available as compared to the number of biological sequences which makes (Structure Based Drug Discovery SBDD a difficult choice. The current tool is an attempt to automate the protein structure modelling and automatic virtual screening followed by pharmacology-based prediction and analysis. Starting from sequence(s, this tool automates protein structure modelling, binding site identification, automated docking, ligand preparation, post docking analysis and identification of hits in the biological pathways that can be modulated by a group of ligands. This automation helps in the characterization of ligands selectivity and action of ligands on a complex biological molecular network as well as on individual receptor. The judicial combination of the ligands binding different receptors can be used to inhibit selective biological pathways in a disease. This tool also allows the user to systemically investigate network-dependent effects of a drug or drug candidate.

An engineering approach to knowledge-based systems, the alarm processing and diagnostic system

International Nuclear Information System (INIS)

Mah, E.; Damon, L.

1992-01-01

The number of alarms that may be initiated during transients or accidents in nuclear-generating control rooms may temporarily exceed an operator's ability to assimilate and respond. This phenomenon is characterized as Cognitive Overload. The Alarm Processing and Diagnostic System (APDS) was designed to deal with this problem through a unique and operationally sensitive method of alarm prioritization and filtration. The approach taken attempts to parallel the operator's situation assessment methodology when dealing with transient conditions. A strong criteria for the development methodology employed was its ultimate acceptance by parties engaged in the operation of nuclear power facilities. As such, the methodology used had to be easily understood and consistent with the acceptance standards of nuclear power. This necessitated the verifiable practices found in engineering design. While APDS remains rooted in artificial intelligence or expert systems, it goes beyond the paradigm of rules and inferencing to an object-oriented structure that allows traditional and well-documented engineering-based decision methods to be applied. These features have important consequences when considering final acceptance, implementation, and maintenance. 3 refs., 1 tab

Sensitivity of Base-Isolated Systems to Ground Motion Characteristics: A Stochastic Approach

International Nuclear Information System (INIS)

Kaya, Yavuz; Safak, Erdal

2008-01-01

Base isolators dissipate energy through their nonlinear behavior when subjected to earthquake-induced loads. A widely used base isolation system for structures involves installing lead-rubber bearings (LRB) at the foundation level. The force-deformation behavior of LRB isolators can be modeled by a bilinear hysteretic model. This paper investigates the effects of ground motion characteristics on the response of bilinear hysteretic oscillators by using a stochastic approach. Ground shaking is characterized by its power spectral density function (PSDF), which includes corner frequency, seismic moment, moment magnitude, and site effects as its parameters. The PSDF of the oscillator response is calculated by using the equivalent-linearization techniques of random vibration theory for hysteretic nonlinear systems. Knowing the PSDF of the response, we can calculate the mean square and the expected maximum response spectra for a range of natural periods and ductility values. The results show that moment magnitude is a critical factor determining the response. Site effects do not seem to have a significant influence

System-on-a-Chip Based Nano Star Tracker and Its Real-Time Image Processing Approach

OpenAIRE

Wei, Minsong; Bao, Jingyu; Xing, Fei; Liu, Zengyi; Sun, Ting; You, Zheng

2016-01-01

The star tracker is one of the most accurate components for satellite attitude determination. With the development of the nano star tracker, it is compatible for application on small satellites. However, the drawback in dynamic property of nano star tracker has limited its extensive applications. The principal objective of this study is to introduce a system-on-a-chip (SOC) based nano star tracker with enhanced dynamic property. A morphology based image processing approach was realized based ...

A practical approach for active camera coordination based on a fusion-driven multi-agent system

Science.gov (United States)

Bustamante, Alvaro Luis; Molina, José M.; Patricio, Miguel A.

2014-04-01

In this paper, we propose a multi-agent system architecture to manage spatially distributed active (or pan-tilt-zoom) cameras. Traditional video surveillance algorithms are of no use for active cameras, and we have to look at different approaches. Such multi-sensor surveillance systems have to be designed to solve two related problems: data fusion and coordinated sensor-task management. Generally, architectures proposed for the coordinated operation of multiple cameras are based on the centralisation of management decisions at the fusion centre. However, the existence of intelligent sensors capable of decision making brings with it the possibility of conceiving alternative decentralised architectures. This problem is approached by means of a MAS, integrating data fusion as an integral part of the architecture for distributed coordination purposes. This paper presents the MAS architecture and system agents.

Identifying pathways affected by cancer mutations.

Science.gov (United States)

Iengar, Prathima

2017-12-16

Mutations in 15 cancers, sourced from the COSMIC Whole Genomes database, and 297 human pathways, arranged into pathway groups based on the processes they orchestrate, and sourced from the KEGG pathway database, have together been used to identify pathways affected by cancer mutations. Genes studied in ≥15, and mutated in ≥10 samples of a cancer have been considered recurrently mutated, and pathways with recurrently mutated genes have been considered affected in the cancer. Novel doughnut plots have been presented which enable visualization of the extent to which pathways and genes, in each pathway group, are targeted, in each cancer. The 'organismal systems' pathway group (including organism-level pathways; e.g., nervous system) is the most targeted, more than even the well-recognized signal transduction, cell-cycle and apoptosis, and DNA repair pathway groups. The important, yet poorly-recognized, role played by the group merits attention. Pathways affected in ≥7 cancers yielded insights into processes affected. Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical Transformation Motifs --- Modelling Pathways as Integer Hyperflows

DEFF Research Database (Denmark)

Andersen, Jakob L.; Flamm, Christoph; Merkle, Daniel

2018-01-01

analysis are discussed in detail. To demonstrate the applicability of the mathematical framework to real-life problems we first explore the design space of possible non-oxidative glycolysis pathways and show that recent manually designed pathways can be further optimised. We then use a model of sugar...... chemistry to investigate pathways in the autocatalytic formose process. A graph transformation-based approach is used to automatically generate the reaction networks of interest....

System Topology Optimization - An Approach to System Design of Electro-Hydraulic-Mechanical Systems

DEFF Research Database (Denmark)

Andersen, T. O.; Hansen, M. R.; Conrad, Finn

2003-01-01

The current paper presents an approach to system design of combined electro-hydraulic-mechanical systems. The approach is based on the concurrent handling of the topology as well as the design parameters of the mechanical, hydraulic and controller sub- systems, respectively. Based on an initial...... design the procedure attempts to find the optimal topology and the related parameters. The topology considerations comprise the type of hydraulic pump, the employment of knee linkages or not as well as the type of hydraulic actuators. The design variables also include the signals to the proportional...... valve in a number of predefined load cases as well as the hydraulic and mechanical parameters....

A Remote Sensing Approach for Regional-Scale Mapping of Agricultural Land-Use Systems Based on NDVI Time Series

Directory of Open Access Journals (Sweden)

Beatriz Bellón

2017-06-01

Full Text Available In response to the need for generic remote sensing tools to support large-scale agricultural monitoring, we present a new approach for regional-scale mapping of agricultural land-use systems (ALUS based on object-based Normalized Difference Vegetation Index (NDVI time series analysis. The approach consists of two main steps. First, to obtain relatively homogeneous land units in terms of phenological patterns, a principal component analysis (PCA is applied to an annual MODIS NDVI time series, and an automatic segmentation is performed on the resulting high-order principal component images. Second, the resulting land units are classified into the crop agriculture domain or the livestock domain based on their land-cover characteristics. The crop agriculture domain land units are further classified into different cropping systems based on the correspondence of their NDVI temporal profiles with the phenological patterns associated with the cropping systems of the study area. A map of the main ALUS of the Brazilian state of Tocantins was produced for the 2013–2014 growing season with the new approach, and a significant coherence was observed between the spatial distribution of the cropping systems in the final ALUS map and in a reference map extracted from the official agricultural statistics of the Brazilian Institute of Geography and Statistics (IBGE. This study shows the potential of remote sensing techniques to provide valuable baseline spatial information for supporting agricultural monitoring and for large-scale land-use systems analysis.

Soft systems methodology as a systemic approach to nuclear safety management

International Nuclear Information System (INIS)

Vieira Neto, Antonio S.; Guilhen, Sabine N.; Rubin, Gerson A.; Caldeira Filho, Jose S.; Camargo, Iara M.C.

2017-01-01

Safety approach currently adopted by nuclear installations is built almost exclusively upon analytical methodologies based, mainly, on the belief that the properties of a system, such as its safety, are given by its constituent parts. This approach, however, does not properly address the complex dynamic interactions between technical, human and organizational factors occurring within and outside the organization. After the accident at Fukushima Daiichi nuclear power plant in March 2011, experts of the International Atomic Energy Agency (IAEA) recommended a systemic approach as a complementary perspective to nuclear safety. The aim of this paper is to present an overview of the systems thinking approach and its potential use for structuring socio technical problems involved in the safety of nuclear installations, highlighting the methodologies related to the soft systems thinking, in particular the Soft Systems Methodology (SSM). The implementation of a systemic approach may thus result in a more holistic picture of the system by the complex dynamic interactions between technical, human and organizational factors. (author)

Soft systems methodology as a systemic approach to nuclear safety management

Energy Technology Data Exchange (ETDEWEB)

Vieira Neto, Antonio S.; Guilhen, Sabine N.; Rubin, Gerson A.; Caldeira Filho, Jose S.; Camargo, Iara M.C., E-mail: asvneto@ipen.br, E-mail: snguilhen@ipen.br, E-mail: garubin@ipen.br, E-mail: jscaldeira@ipen.br, E-mail: icamargo@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNE-SP), Sao Paulo, SP (Brazil)

2017-07-01

Safety approach currently adopted by nuclear installations is built almost exclusively upon analytical methodologies based, mainly, on the belief that the properties of a system, such as its safety, are given by its constituent parts. This approach, however, does not properly address the complex dynamic interactions between technical, human and organizational factors occurring within and outside the organization. After the accident at Fukushima Daiichi nuclear power plant in March 2011, experts of the International Atomic Energy Agency (IAEA) recommended a systemic approach as a complementary perspective to nuclear safety. The aim of this paper is to present an overview of the systems thinking approach and its potential use for structuring socio technical problems involved in the safety of nuclear installations, highlighting the methodologies related to the soft systems thinking, in particular the Soft Systems Methodology (SSM). The implementation of a systemic approach may thus result in a more holistic picture of the system by the complex dynamic interactions between technical, human and organizational factors. (author)

A combined Component-Based Approach for the Design of Distributed Software Systems

NARCIS (Netherlands)

Guareis de farias, Cléver; Ferreira Pires, Luis; van Sinderen, Marten J.; Quartel, Dick; Yang, H.; Gupta, S.

2001-01-01

Component-based software development enables the construction of software artefacts by assembling binary units of production, distribution and deployment, the so-called components. Several approaches to component-based development have been proposed recently. Most of these approaches are based on

Interacting with mobile devices by fusion eye and hand gestures recognition systems based on decision tree approach

Science.gov (United States)

Elleuch, Hanene; Wali, Ali; Samet, Anis; Alimi, Adel M.

2017-03-01

Two systems of eyes and hand gestures recognition are used to control mobile devices. Based on a real-time video streaming captured from the device's camera, the first system recognizes the motion of user's eyes and the second one detects the static hand gestures. To avoid any confusion between natural and intentional movements we developed a system to fuse the decision coming from eyes and hands gesture recognition systems. The phase of fusion was based on decision tree approach. We conducted a study on 5 volunteers and the results that our system is robust and competitive.

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

significant pathways in subtypes of HCC are HCC subtype-associated specifically. In conclusion, PoTRA is a new approach to explore and discover pathways involved in cancer. PoTRA can be used as a complement to other existing methods to broaden our understanding of the biological mechanisms behind cancer at the system-level.

User-based and Cognitive Approaches to Knowledge Organization

DEFF Research Database (Denmark)

Hjørland, Birger

2013-01-01

’s PageRank are not based on the empirical studies of users. In knowledge organization, the Book House System is one example of a system based on user studies. In cognitive science the important WordNet database is claimed to be based on psychological research. This article considers such examples......In the 1970s and 1980s, forms of user-based and cognitive approaches to knowledge organization came to the forefront as part of the overall development in library and information science and in the broader society. The specific nature of userbased approaches is their basis in the empirical studies...

Modeling of non-steroidal anti-inflammatory drug effect within signaling pathways and miRNA-regulation pathways.

Directory of Open Access Journals (Sweden)

Jian Li

Full Text Available To date, it is widely recognized that Non-Steroidal Anti-Inflammatory Drugs (NSAIDs can exert considerable anti-tumor effects regarding many types of cancers. The prolonged use of NSAIDs is highly associated with diverse side effects. Therefore, tailoring down the NSAID application onto individual patients has become a necessary and relevant step towards personalized medicine. This study conducts the systemsbiological approach to construct a molecular model (NSAID model containing a cyclooxygenase (COX-pathway and its related signaling pathways. Four cancer hallmarks are integrated into the model to reflect different developmental aspects of tumorigenesis. In addition, a Flux-Comparative-Analysis (FCA based on Petri net is developed to transfer the dynamic properties (including drug responsiveness of individual cellular system into the model. The gene expression profiles of different tumor-types with available drug-response information are applied to validate the predictive ability of the NSAID model. Moreover, two therapeutic developmental strategies, synthetic lethality and microRNA (miRNA biomarker discovery, are investigated based on the COX-pathway. In conclusion, the result of this study demonstrates that the NSAID model involving gene expression, gene regulation, signal transduction, protein interaction and other cellular processes, is able to predict the individual cellular responses for different therapeutic interventions (such as NS-398 and COX-2 specific siRNA inhibition. This strongly indicates that this type of model is able to reflect the physiological, developmental and pathological processes of an individual. The approach of miRNA biomarker discovery is demonstrated for identifying miRNAs with oncogenic and tumor suppressive functions for individual cell lines of breast-, colon- and lung-tumor. The achieved results are in line with different independent studies that investigated miRNA biomarker related to diagnostics of cancer

A new approach to hand-based authentication

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Amayeh, G.; Bebis, G.; Erol, A.; Nicolescu, M.

2007-04-01

Hand-based authentication is a key biometric technology with a wide range of potential applications both in industry and government. Traditionally, hand-based authentication is performed by extracting information from the whole hand. To account for hand and finger motion, guidance pegs are employed to fix the position and orientation of the hand. In this paper, we consider a component-based approach to hand-based verification. Our objective is to investigate the discrimination power of different parts of the hand in order to develop a simpler, faster, and possibly more accurate and robust verification system. Specifically, we propose a new approach which decomposes the hand in different regions, corresponding to the fingers and the back of the palm, and performs verification using information from certain parts of the hand only. Our approach operates on 2D images acquired by placing the hand on a flat lighting table. Using a part-based representation of the hand allows the system to compensate for hand and finger motion without using any guidance pegs. To decompose the hand in different regions, we use a robust methodology based on morphological operators which does not require detecting any landmark points on the hand. To capture the geometry of the back of the palm and the fingers in suffcient detail, we employ high-order Zernike moments which are computed using an effcient methodology. The proposed approach has been evaluated on a database of 100 subjects with 10 images per subject, illustrating promising performance. Comparisons with related approaches using the whole hand for verification illustrate the superiority of the proposed approach. Moreover, qualitative comparisons with state-of-the-art approaches indicate that the proposed approach has comparable or better performance.

Capability-based computer systems

CERN Document Server

Levy, Henry M

2014-01-01

Capability-Based Computer Systems focuses on computer programs and their capabilities. The text first elaborates capability- and object-based system concepts, including capability-based systems, object-based approach, and summary. The book then describes early descriptor architectures and explains the Burroughs B5000, Rice University Computer, and Basic Language Machine. The text also focuses on early capability architectures. Dennis and Van Horn's Supervisor; CAL-TSS System; MIT PDP-1 Timesharing System; and Chicago Magic Number Machine are discussed. The book then describes Plessey System 25

Energy demand projections based on an uncertain dynamic system modeling approach

International Nuclear Information System (INIS)

Dong, S.

2000-01-01

Today, China has become the world's second largest pollution source of CO 2 . Owing to coal-based energy consumption, it is estimated that 85--90% of the SO 2 and CO 2 emission of China results from coal use. With high economic growth and increasing environmental concerns, China's energy consumption in the next few decades has become an issue of active concern. Forecasting of energy demand over long periods, however, is getting more complex and uncertain. It is believed that the economic and energy systems are chaotic and nonlinear. Traditional linear system modeling, used mostly in energy demand forecasts, therefore, is not a useful approach. In view of uncertainty and imperfect information about future economic growth and energy development, an uncertain dynamic system model, which has the ability to incorporate and absorb the nature of an uncertain system with imperfect or incomplete information, is developed. Using the model, the forecasting of energy demand in the next 25 years is provided. The model predicts that China's energy demand in 2020 will be about 2,700--3,000 Mtce, coal demand 3,500 Mt, increasing by 128% and 154%, respectively, compared with that of 1995

How new concepts become universal scientific approaches: insights from citation network analysis of agent-based complex systems science.

Science.gov (United States)

Vincenot, Christian E

2018-03-14

Progress in understanding and managing complex systems comprised of decision-making agents, such as cells, organisms, ecosystems or societies, is-like many scientific endeavours-limited by disciplinary boundaries. These boundaries, however, are moving and can actively be made porous or even disappear. To study this process, I advanced an original bibliometric approach based on network analysis to track and understand the development of the model-based science of agent-based complex systems (ACS). I analysed research citations between the two communities devoted to ACS research, namely agent-based (ABM) and individual-based modelling (IBM). Both terms refer to the same approach, yet the former is preferred in engineering and social sciences, while the latter prevails in natural sciences. This situation provided a unique case study for grasping how a new concept evolves distinctly across scientific domains and how to foster convergence into a universal scientific approach. The present analysis based on novel hetero-citation metrics revealed the historical development of ABM and IBM, confirmed their past disjointedness, and detected their progressive merger. The separation between these synonymous disciplines had silently opposed the free flow of knowledge among ACS practitioners and thereby hindered the transfer of methodological advances and the emergence of general systems theories. A surprisingly small number of key publications sparked the ongoing fusion between ABM and IBM research. Beside reviews raising awareness of broad-spectrum issues, generic protocols for model formulation and boundary-transcending inference strategies were critical means of science integration. Accessible broad-spectrum software similarly contributed to this change. From the modelling viewpoint, the discovery of the unification of ABM and IBM demonstrates that a wide variety of systems substantiate the premise of ACS research that microscale behaviours of agents and system-level dynamics

Enriched pathways for major depressive disorder identified from a genome-wide association study.

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Kao, Chung-Feng; Jia, Peilin; Zhao, Zhongming; Kuo, Po-Hsiu

2012-11-01

Major depressive disorder (MDD) has caused a substantial burden of disease worldwide with moderate heritability. Despite efforts through conducting numerous association studies and now, genome-wide association (GWA) studies, the success of identifying susceptibility loci for MDD has been limited, which is partially attributed to the complex nature of depression pathogenesis. A pathway-based analytic strategy to investigate the joint effects of various genes within specific biological pathways has emerged as a powerful tool for complex traits. The present study aimed to identify enriched pathways for depression using a GWA dataset for MDD. For each gene, we estimated its gene-wise p value using combined and minimum p value, separately. Canonical pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and BioCarta were used. We employed four pathway-based analytic approaches (gene set enrichment analysis, hypergeometric test, sum-square statistic, sum-statistic). We adjusted for multiple testing using Benjamini & Hochberg's method to report significant pathways. We found 17 significantly enriched pathways for depression, which presented low-to-intermediate crosstalk. The top four pathways were long-term depression (p⩽1×10-5), calcium signalling (p⩽6×10-5), arrhythmogenic right ventricular cardiomyopathy (p⩽1.6×10-4) and cell adhesion molecules (p⩽2.2×10-4). In conclusion, our comprehensive pathway analyses identified promising pathways for depression that are related to neurotransmitter and neuronal systems, immune system and inflammatory response, which may be involved in the pathophysiological mechanisms underlying depression. We demonstrated that pathway enrichment analysis is promising to facilitate our understanding of complex traits through a deeper interpretation of GWA data. Application of this comprehensive analytic strategy in upcoming GWA data for depression could validate the findings reported in this study.

A new infusion pathway monitoring system utilizing electrostatic induced potential.

Science.gov (United States)

Maki, Hiromichi; Yonezawa, Yoshiharu; Ogawa, Hidekuni; Ninomiya, Ishio; Sada, Kouji; Hamada, Shingo; Hahn, Alien W; Caldwell, W Morton

2006-01-01

We have developed a new infusion pathway monitoring system employing linear integrated circuits and a low-power 8-bit single chip microcomputer. The system is available for hospital and home use and it constantly monitors the intactness of the pathway. The sensor is an electro-conductive polymer electrode wrapped around the infusion polyvinyl chloride infusion tube. This records an AC (alternating current) voltage induced on the patient's body by electrostatic coupling from the normal 100 volt, 60 Hz AC power line wiring field in the patient's room. If the injection needle or infusion tube becomes detached, then the system detects changes in the induced AC voltage and alerts the nursing station, via the nurse call system or PHS (personal handy phone System).

Evolution of JAK-STAT pathway components: mechanisms and role in immune system development.

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Clifford Liongue

Full Text Available BACKGROUND: Lying downstream of a myriad of cytokine receptors, the Janus kinase (JAK-Signal transducer and activator of transcription (STAT pathway is pivotal for the development and function of the immune system, with additional important roles in other biological systems. To gain further insight into immune system evolution, we have performed a comprehensive bioinformatic analysis of the JAK-STAT pathway components, including the key negative regulators of this pathway, the SH2-domain containing tyrosine phosphatase (SHP, Protein inhibitors against Stats (PIAS, and Suppressor of cytokine signaling (SOCS proteins across a diverse range of organisms. RESULTS: Our analysis has demonstrated significant expansion of JAK-STAT pathway components co-incident with the emergence of adaptive immunity, with whole genome duplication being the principal mechanism for generating this additional diversity. In contrast, expansion of upstream cytokine receptors appears to be a pivotal driver for the differential diversification of specific pathway components. CONCLUSION: Diversification of JAK-STAT pathway components during early vertebrate development occurred concurrently with a major expansion of upstream cytokine receptors and two rounds of whole genome duplications. This produced an intricate cell-cell communication system that has made a significant contribution to the evolution of the immune system, particularly the emergence of adaptive immunity.

A proposed clinical research support career pathway for noninvestigators.

Science.gov (United States)

Smith, Sheree; Gullick, Janice; Ballard, Jacqueline; Perry, Lin

2018-03-08

To discuss the international experience of clinical research support for noninvestigator roles and to propose a new pathway for Australia, to promote a sustainable research support workforce capable of delivering high-quality clinical research. Noninvestigator research support roles are currently characterized by an ad hoc approach to training, with limited role delineation and perceived professional isolation with implications for study completion rates and participant safety. A focused approach to developing and implementing research support pathways has improved patient recruitment, study completion, job satisfaction, and research governance. The Queensland and New South Wales state-based Nurses' Awards, the Australian Qualifications Framework, and a University Professional (Research) Staff Award. Research nurses in the clinical environment improve study coordination, adherence to study protocol, patient safety, and clinical care. A career pathway that guides education and outlines position descriptions and skill sets would enhance development of the research support workforce. This pathway could contribute to changing the patient outcomes through coordination and study completion of high-quality research. A wide consultative approach is required to determine a cost-effective and feasible approach to implementation and evaluation of the proposed pathway. © 2018 John Wiley & Sons Australia, Ltd.

Model based approach to Study the Impact of Biofuels on the Sustainability of an Ecological System

Science.gov (United States)

The importance and complexity of sustainability has been well recognized and a formal study of sustainability based on system theory approaches is imperative as many of the relationships between various components of the ecosystem could be nonlinear, intertwined and non intuitive...

Non-fragile observer-based output feedback control for polytopic uncertain system under distributed model predictive control approach

Science.gov (United States)

Zhu, Kaiqun; Song, Yan; Zhang, Sunjie; Zhong, Zhaozhun

2017-07-01

In this paper, a non-fragile observer-based output feedback control problem for the polytopic uncertain system under distributed model predictive control (MPC) approach is discussed. By decomposing the global system into some subsystems, the computation complexity is reduced, so it follows that the online designing time can be saved.Moreover, an observer-based output feedback control algorithm is proposed in the framework of distributed MPC to deal with the difficulties in obtaining the states measurements. In this way, the presented observer-based output-feedback MPC strategy is more flexible and applicable in practice than the traditional state-feedback one. What is more, the non-fragility of the controller has been taken into consideration in favour of increasing the robustness of the polytopic uncertain system. After that, a sufficient stability criterion is presented by using Lyapunov-like functional approach, meanwhile, the corresponding control law and the upper bound of the quadratic cost function are derived by solving an optimisation subject to convex constraints. Finally, some simulation examples are employed to show the effectiveness of the method.

Yeast glucose pathways converge on the transcriptional regulation of trehalose biosynthesis

Directory of Open Access Journals (Sweden)

Apweiler Eva

2012-06-01

Full Text Available Abstract Background Cellular glucose availability is crucial for the functioning of most biological processes. Our understanding of the glucose regulatory system has been greatly advanced by studying the model organism Saccharomyces cerevisiae, but many aspects of this system remain elusive. To understand the organisation of the glucose regulatory system, we analysed 91 deletion mutants of the different glucose signalling and metabolic pathways in Saccharomyces cerevisiae using DNA microarrays. Results In general, the mutations do not induce pathway-specific transcriptional responses. Instead, one main transcriptional response is discerned, which varies in direction to mimic either a high or a low glucose response. Detailed analysis uncovers established and new relationships within and between individual pathways and their members. In contrast to signalling components, metabolic components of the glucose regulatory system are transcriptionally more frequently affected. A new network approach is applied that exposes the hierarchical organisation of the glucose regulatory system. Conclusions The tight interconnection between the different pathways of the glucose regulatory system is reflected by the main transcriptional response observed. Tps2 and Tsl1, two enzymes involved in the biosynthesis of the storage carbohydrate trehalose, are predicted to be the most downstream transcriptional components. Epistasis analysis of tps2Δ double mutants supports this prediction. Although based on transcriptional changes only, these results suggest that all changes in perceived glucose levels ultimately lead to a shift in trehalose biosynthesis.

A complex systems approach to planning, optimization and decision making for energy networks

International Nuclear Information System (INIS)

Beck, Jessica; Kempener, Ruud; Cohen, Brett; Petrie, Jim

2008-01-01

This paper explores a new approach to planning and optimization of energy networks, using a mix of global optimization and agent-based modeling tools. This approach takes account of techno-economic, environmental and social criteria, and engages explicitly with inherent network complexity in terms of the autonomous decision-making capability of individual agents within the network, who may choose not to act as economic rationalists. This is an important consideration from the standpoint of meeting sustainable development goals. The approach attempts to set targets for energy planning, by determining preferred network development pathways through multi-objective optimization. The viability of such plans is then explored through agent-based models. The combined approach is demonstrated for a case study of regional electricity generation in South Africa, with biomass as feedstock

Consensus statement understanding health and malnutrition through a systems approach: the ENOUGH program for early life.

Science.gov (United States)

Kaput, Jim; van Ommen, Ben; Kremer, Bas; Priami, Corrado; Monteiro, Jacqueline Pontes; Morine, Melissa; Pepping, Fre; Diaz, Zoey; Fenech, Michael; He, Yiwu; Albers, Ruud; Drevon, Christian A; Evelo, Chris T; Hancock, Robert E W; Ijsselmuiden, Carel; Lumey, L H; Minihane, Anne-Marie; Muller, Michael; Murgia, Chiara; Radonjic, Marijana; Sobral, Bruno; West, Keith P

2014-01-01

Nutrition research, like most biomedical disciplines, adopted and often uses experimental approaches based on Beadle and Tatum's one gene-one polypeptide hypothesis, thereby reducing biological processes to single reactions or pathways. Systems thinking is needed to understand the complexity of health and disease processes requiring measurements of physiological processes, as well as environmental and social factors, which may alter the expression of genetic information. Analysis of physiological processes with omics technologies to assess systems' responses has only become available over the past decade and remains costly. Studies of environmental and social conditions known to alter health are often not connected to biomedical research. While these facts are widely accepted, developing and conducting comprehensive research programs for health are often beyond financial and human resources of single research groups. We propose a new research program on essential nutrients for optimal underpinning of growth and health (ENOUGH) that will use systems approaches with more comprehensive measurements and biostatistical analysis of the many biological and environmental factors that influence undernutrition. Creating a knowledge base for nutrition and health is a necessary first step toward developing solutions targeted to different populations in diverse social and physical environments for the two billion undernourished people in developed and developing economies.

An examination of cross-cultural systems implementing evidence-based assessment and intervention approaches

Directory of Open Access Journals (Sweden)

Murray Laura K

2006-01-01

Full Text Available Implementation of evidence-based assessment and intervention approaches for youth with behavioral and/or emotional problems is rising to recognition worldwide. Feasibility research is critical to examine what characteristics of systems allow for success or barriers to the implementation of evidence-based practices into real-world settings, especially when working cross-culturally. This paper briefly reviews the experience of 4 international sites to understand how the overall structure and specific site variables directed the implementation of the World Health Organization and the World Psychiatry Association project. Discussion includes a thematic summary of the successes and challenges experienced by the sites, and future directions of feasibility studies.

Systems Pharmacology-Based Approach of Connecting Disease Genes in Genome-Wide Association Studies with Traditional Chinese Medicine.

Science.gov (United States)

Kim, Jihye; Yoo, Minjae; Shin, Jimin; Kim, Hyunmin; Kang, Jaewoo; Tan, Aik Choon

2018-01-01

Traditional Chinese medicine (TCM) originated in ancient China has been practiced over thousands of years for treating various symptoms and diseases. However, the molecular mechanisms of TCM in treating these diseases remain unknown. In this study, we employ a systems pharmacology-based approach for connecting GWAS diseases with TCM for potential drug repurposing and repositioning. We studied 102 TCM components and their target genes by analyzing microarray gene expression experiments. We constructed disease-gene networks from 2558 GWAS studies. We applied a systems pharmacology approach to prioritize disease-target genes. Using this bioinformatics approach, we analyzed 14,713 GWAS disease-TCM-target gene pairs and identified 115 disease-gene pairs with q value < 0.2. We validated several of these GWAS disease-TCM-target gene pairs with literature evidence, demonstrating that this computational approach could reveal novel indications for TCM. We also develop TCM-Disease web application to facilitate the traditional Chinese medicine drug repurposing efforts. Systems pharmacology is a promising approach for connecting GWAS diseases with TCM for potential drug repurposing and repositioning. The computational approaches described in this study could be easily expandable to other disease-gene network analysis.

Vision-Based Geo-Monitoring - A New Approach for an Automated System

Science.gov (United States)

Wagner, A.; Reiterer, A.; Wasmeier, P.; Rieke-Zapp, D.; Wunderlich, T.

2012-04-01

: (1) combining two measurement systems and measuring object points by spatial intersection, or (2) using one measurement system and combining image-based techniques with the integrated distance measurement unit. Beside the system configuration, the detection of features inside the captured images can be done on the basis of different approaches, e.g. template-, edge-, and/or point-based methods. Our system is able to select a suitable algorithm based on different object characteristics, such as object geometry, texture, behaviour, etc. The long-term objective is the research, development and installation of a fully-automated measurement system, including a data analysis and interpretation component. Acknowledgments: The presented research has been supported by the Alexander von Humboldt Foundation, and by the European Sciences Foundation (ESF).

Development of an open platform system for environmental pathway analysis

International Nuclear Information System (INIS)

LePoire, D. J.; Arnish, J. J.; Gnanapragasam, E.; Chen, S. Y.

2001-01-01

Most existing computer codes for environmental pathway modeling have been developed to satisfy a specific objective (e.g., perform analyses to demonstrate regulatory compliance). These codes were written in various computer languages and software environments over time and often are not mutually compatible. In recent years, largely driven by advancements in industrial software development, a new concept based on ''modularization'' has emerged. This approach entails the development of common ''modules,'' or components, that can be shared by and used in different applications that have certain common needs. For instance, an air dispersion model can be written as a common component to be shared by several different applications, each with the need to model air dispersion of some material release. When this concept is fully developed, modeling applications would become an exercise of selecting, integrating, and applying a consistent combination of appropriate pre-existing modules for a specific problem. Although modularization holds promising advantages over the traditional approach, a number of issues do exist. These issues must be fully addressed and resolved before the approach can be accepted as a new paradigm for environmental modeling. This paper discusses these issues and provides recommendations and a course of actions for future development

Assessing Natural Direct and Indirect Effects Through Multiple Pathways

DEFF Research Database (Denmark)

Lange, T; Rasmussen, M; Thygesen, Lau Caspar

2014-01-01

. The approach is an extension of the natural effect models proposed by Lange et al. (Am J Epidemiol. 2012;176(3):190-195). By allowing the analysis of distinct multiple pathways, the suggested approach adds to the capabilities of modern mediation techniques. Furthermore, the approach can be implemented using......Within the fields of epidemiology, interventions research and social sciences researchers are often faced with the challenge of decomposing the effect of an exposure into different causal pathways working through defined mediator variables. The goal of such analyses is often to understand...... the mechanisms of the system or to suggest possible interventions. The case of a single mediator, thus implying only 2 causal pathways (direct and indirect) from exposure to outcome, has been extensively studied. By using the framework of counterfactual variables, researchers have established theoretical...

Bioreactors to influence stem cell fate: augmentation of mesenchymal stem cell signaling pathways via dynamic culture systems.

Science.gov (United States)

Yeatts, Andrew B; Choquette, Daniel T; Fisher, John P

2013-02-01

Mesenchymal stem cells (MSCs) are a promising cell source for bone and cartilage tissue engineering as they can be easily isolated from the body and differentiated into osteoblasts and chondrocytes. A cell based tissue engineering strategy using MSCs often involves the culture of these cells on three-dimensional scaffolds; however the size of these scaffolds and the cell population they can support can be restricted in traditional static culture. Thus dynamic culture in bioreactor systems provides a promising means to culture and differentiate MSCs in vitro. This review seeks to characterize key MSC differentiation signaling pathways and provides evidence as to how dynamic culture is augmenting these pathways. Following an overview of dynamic culture systems, discussion will be provided on how these systems can effectively modify and maintain important culture parameters including oxygen content and shear stress. Literature is reviewed for both a highlight of key signaling pathways and evidence for regulation of these signaling pathways via dynamic culture systems. The ability to understand how these culture systems are affecting MSC signaling pathways could lead to a shear or oxygen regime to direct stem cell differentiation. In this way the efficacy of in vitro culture and differentiation of MSCs on three-dimensional scaffolds could be greatly increased. Bioreactor systems have the ability to control many key differentiation stimuli including mechanical stress and oxygen content. The further integration of cell signaling investigations within dynamic culture systems will lead to a quicker realization of the promise of tissue engineering and regenerative medicine. This article is part of a Special Issue entitled Biochemistry of Stem Cells. Copyright © 2012 Elsevier B.V. All rights reserved.

Hierarchical structure of biological systems: a bioengineering approach.

Science.gov (United States)

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

2014-01-01

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

A novel genetic score approach using instruments to investigate interactions between pathways and environment: application to air pollution.

Directory of Open Access Journals (Sweden)

Marie-Abele Bind

Full Text Available Air pollution has been associated with increased systemic inflammation markers. We developed a new pathway analysis approach to investigate whether gene variants within relevant pathways (oxidative stress, endothelial function, and metal processing modified the association between particulate air pollution and fibrinogen, C-reactive protein (CRP, intercellular adhesion molecule-1 (ICAM-1, and vascular cell adhesion molecule-1 (VCAM-1. Our study population consisted of 822 elderly participants of the Normative Aging Study (1999-2011. To investigate the role of biological mechanisms and to reduce the number of comparisons in the analysis, we created pathway-specific scores using gene variants related to each pathway. To select the most appropriate gene variants, we used the least absolute shrinkage and selection operator (Lasso to relate independent outcomes representative of each pathway (8-hydroxydeoxyguanosine for oxidative stress, augmentation index for endothelial function, and patella lead for metal processing to gene variants. A high genetic score corresponds to a higher allelic risk profile. We fit mixed-effects models to examine modification by the genetic score of the weekly air pollution association with the outcome. Among participants with higher genetic scores within the oxidative stress pathway, we observed significant associations between particle number and fibrinogen, while we did not find any association among participants with lower scores (p(interaction = 0.04. Compared to individuals with low genetic scores of metal processing gene variants, participants with higher scores had greater effects of particle number on fibrinogen (p(interaction = 0.12, CRP (p(interaction = 0.02, and ICAM-1 (pinteraction = 0.08. This two-stage penalization method is easy to implement and can be used for large-scale genetic applications.

GWAS-based pathway analysis differentiates between fluid and crystallized intelligence.

Science.gov (United States)

Christoforou, A; Espeseth, T; Davies, G; Fernandes, C P D; Giddaluru, S; Mattheisen, M; Tenesa, A; Harris, S E; Liewald, D C; Payton, A; Ollier, W; Horan, M; Pendleton, N; Haggarty, P; Djurovic, S; Herms, S; Hoffman, P; Cichon, S; Starr, J M; Lundervold, A; Reinvang, I; Steen, V M; Deary, I J; Le Hellard, S

2014-09-01

Cognitive abilities vary among people. About 40-50% of this variability is due to general intelligence (g), which reflects the positive correlation among individuals' scores on diverse cognitive ability tests. g is positively correlated with many life outcomes, such as education, occupational status and health, motivating the investigation of its underlying biology. In psychometric research, a distinction is made between general fluid intelligence (gF) - the ability to reason in novel situations - and general crystallized intelligence (gC) - the ability to apply acquired knowledge. This distinction is supported by developmental and cognitive neuroscience studies. Classical epidemiological studies and recent genome-wide association studies (GWASs) have established that these cognitive traits have a large genetic component. However, no robust genetic associations have been published thus far due largely to the known polygenic nature of these traits and insufficient sample sizes. Here, using two GWAS datasets, in which the polygenicity of gF and gC traits was previously confirmed, a gene- and pathway-based approach was undertaken with the aim of characterizing and differentiating their genetic architecture. Pathway analysis, using genes selected on the basis of relaxed criteria, revealed notable differences between these two traits. gF appeared to be characterized by genes affecting the quantity and quality of neurons and therefore neuronal efficiency, whereas long-term depression (LTD) seemed to underlie gC. Thus, this study supports the gF-gC distinction at the genetic level and identifies functional annotations and pathways worthy of further investigation. © 2014 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.

The "parallel pathway": a novel nutritional and metabolic approach to cancer patients.

Science.gov (United States)

Muscaritoli, Maurizio; Molfino, Alessio; Gioia, Gianfranco; Laviano, Alessandro; Rossi Fanelli, Filippo

2011-04-01

Cancer-associated malnutrition results from a deadly combination of anorexia, which leads to reduced food intake, and derangements of host metabolism inducing body weight loss, and hindering its reversal with nutrient supplementation. Cancer patients often experience both anorexia and weight loss, contributing to the onset of the clinical feature named as anorexia-cachexia syndrome. This condition has a negative impact upon patients' nutritional status. The pathogenesis of the anorexia-cachexia syndrome is multifactorial, and is related to: tumour-derived factors, host-derived factors inducing metabolic derangements, and side effects of anticancer therapies. In addition, the lack of awareness of cancer patients' nutritional issues and status by many oncologists, frequently results in progressive weight loss going undiagnosed until it becomes severe. The critical involvement of host inflammatory response in the development of weight loss, and, in particular, lean body mass depletion, limits the response to the provision of standard nutrition support. A novel nutritional and metabolic approach, named "parallel pathway", has been devised that may help maintain or improve nutritional status, and prevent or delay the onset of cancer cachexia. Such an approach may improve tolerance to aggressive anticancer therapies, and ameliorate the functional capacity and quality of life even in advanced disease stages. The "parallel pathway" implies a multiprofessional and multimodal approach aimed at ensuring early, appropriate and continuous nutritional and metabolic support to cancer patients in any phase of their cancer journey.

A genomic pathway approach to a complex disease: axon guidance and Parkinson disease.

Directory of Open Access Journals (Sweden)

Timothy G Lesnick

2007-06-01

Full Text Available While major inroads have been made in identifying the genetic causes of rare Mendelian disorders, little progress has been made in the discovery of common gene variations that predispose to complex diseases. The single gene variants that have been shown to associate reproducibly with complex diseases typically have small effect sizes or attributable risks. However, the joint actions of common gene variants within pathways may play a major role in predisposing to complex diseases (the paradigm of complex genetics. The goal of this study was to determine whether polymorphism in a candidate pathway (axon guidance predisposed to a complex disease (Parkinson disease [PD]. We mined a whole-genome association dataset and identified single nucleotide polymorphisms (SNPs that were within axon-guidance pathway genes. We then constructed models of axon-guidance pathway SNPs that predicted three outcomes: PD susceptibility (odds ratio = 90.8, p = 4.64 x 10(-38, survival free of PD (hazards ratio = 19.0, p = 5.43 x 10(-48, and PD age at onset (R(2 = 0.68, p = 1.68 x 10(-51. By contrast, models constructed from thousands of random selections of genomic SNPs predicted the three PD outcomes poorly. Mining of a second whole-genome association dataset and mining of an expression profiling dataset also supported a role for many axon-guidance pathway genes in PD. These findings could have important implications regarding the pathogenesis of PD. This genomic pathway approach may also offer insights into other complex diseases such as Alzheimer disease, diabetes mellitus, nicotine and alcohol dependence, and several cancers.

performance-based approach to design and evaluation of nuclear security systems for Brazilian nuclear facilities

Energy Technology Data Exchange (ETDEWEB)

Tavares, Renato L. A.; Filho, Josélio S. M., E-mail: renato.tavares@cnen.gov.br, E-mail: joselio@cnen.gov.br [Comissão Nacional de Energia Nuclear (CNEN), Rio de Janeiro, RJ (Brazil). Diretoria de Radioproteção e Segurança Nuclear. Divisão de Normas e Segurança Física; Fontes, Gladson S.; Fiel, J.C.B., E-mail: gsfontes@hotmail.com, E-mail: fiel@ime.eb.br [Instituto Militar de Engenharia (SE-7/IME), Rio de Janeiro, RJ (Brazil). Seção de Engenharia Nuclear

2017-07-01

This study presents an application of a performance-based approach to definition of requirements, design and evaluation of physical protection systems for nuclear facilities. Such approach considers a probabilistic analysis of the threat, equipment, systems and response forces used to prevent, dissuade and detain malicious acts against the integrity of facilities and the nuclear materials inside them. Nowadays, in the context of Brazilian nuclear facilities licensing, a mostly prescriptive approach is adopted, which despite having advantages such as simplified inspections and homogeneous regulatory requisites amid different fuel cycle facility types, does not consider evolution, dynamism and capacities of external or internal threats to facilities and to Brazilian Nuclear Program itself, neither provides metrics to evaluate system performance facing such threats. In order to preserve actual plans and systems confidentiality, a facility hypothetical model is created, including a research reactor and a waste storage facility. It is expected that the methodology and results obtained in this study serve in the future as a basis to Brazilian nuclear operators, in elaboration process of their Physical Protection Plans, which must comply with future regulation CNEN-NN 2.01, a revision of CNEN-NE 2.01, once that regulation will include performance requisites. (author)

performance-based approach to design and evaluation of nuclear security systems for Brazilian nuclear facilities

International Nuclear Information System (INIS)

Tavares, Renato L. A.; Filho, Josélio S. M.; Fontes, Gladson S.; Fiel, J.C.B.

2017-01-01

This study presents an application of a performance-based approach to definition of requirements, design and evaluation of physical protection systems for nuclear facilities. Such approach considers a probabilistic analysis of the threat, equipment, systems and response forces used to prevent, dissuade and detain malicious acts against the integrity of facilities and the nuclear materials inside them. Nowadays, in the context of Brazilian nuclear facilities licensing, a mostly prescriptive approach is adopted, which despite having advantages such as simplified inspections and homogeneous regulatory requisites amid different fuel cycle facility types, does not consider evolution, dynamism and capacities of external or internal threats to facilities and to Brazilian Nuclear Program itself, neither provides metrics to evaluate system performance facing such threats. In order to preserve actual plans and systems confidentiality, a facility hypothetical model is created, including a research reactor and a waste storage facility. It is expected that the methodology and results obtained in this study serve in the future as a basis to Brazilian nuclear operators, in elaboration process of their Physical Protection Plans, which must comply with future regulation CNEN-NN 2.01, a revision of CNEN-NE 2.01, once that regulation will include performance requisites. (author)

Rule based systems for big data a machine learning approach

CERN Document Server

Liu, Han; Cocea, Mihaela

2016-01-01

The ideas introduced in this book explore the relationships among rule based systems, machine learning and big data. Rule based systems are seen as a special type of expert systems, which can be built by using expert knowledge or learning from real data. The book focuses on the development and evaluation of rule based systems in terms of accuracy, efficiency and interpretability. In particular, a unified framework for building rule based systems, which consists of the operations of rule generation, rule simplification and rule representation, is presented. Each of these operations is detailed using specific methods or techniques. In addition, this book also presents some ensemble learning frameworks for building ensemble rule based systems.

Proteomics-based network analysis characterizes biological processes and pathways activated by preconditioned mesenchymal stem cells in cardiac repair mechanisms.

Science.gov (United States)

Di Silvestre, Dario; Brambilla, Francesca; Scardoni, Giovanni; Brunetti, Pietro; Motta, Sara; Matteucci, Marco; Laudanna, Carlo; Recchia, Fabio A; Lionetti, Vincenzo; Mauri, Pierluigi

2017-05-01

We have demonstrated that intramyocardial delivery of human mesenchymal stem cells preconditioned with a hyaluronan mixed ester of butyric and retinoic acid (MSCp + ) is more effective in preventing the decay of regional myocardial contractility in a swine model of myocardial infarction (MI). However, the understanding of the role of MSCp + in proteomic remodeling of cardiac infarcted tissue is not complete. We therefore sought to perform a comprehensive analysis of the proteome of infarct remote (RZ) and border zone (BZ) of pigs treated with MSCp + or unconditioned stem cells. Heart tissues were analyzed by MudPIT and differentially expressed proteins were selected by a label-free approach based on spectral counting. Protein profiles were evaluated by using PPI networks and their topological analysis. The proteomic remodeling was largely prevented in MSCp + group. Extracellular proteins involved in fibrosis were down-regulated, while energetic pathways were globally up-regulated. Cardioprotectant pathways involved in the production of keto acid metabolites were also activated. Additionally, we found that new hub proteins support the cardioprotective phenotype characterizing the left ventricular BZ treated with MSCp + . In fact, the up-regulation of angiogenic proteins NCL and RAC1 can be explained by the increase of capillary density induced by MSCp + . Our results show that angiogenic pathways appear to be uniquely positioned to integrate signaling with energetic pathways involving cardiac repair. Our findings prompt the use of proteomics-based network analysis to optimize new approaches preventing the post-ischemic proteomic remodeling that may underlie the limited self-repair ability of adult heart. Copyright © 2017 Elsevier B.V. All rights reserved.

Studying Sensing-Based Systems

DEFF Research Database (Denmark)

Kjærgaard, Mikkel Baun

2013-01-01

Recent sensing-based systems involve a multitude of users, devices, and places. These types of systems challenge existing approaches for conducting valid system evaluations. Here, the author discusses such evaluation challenges and revisits existing system evaluation methodologies....

A Review of Pathway-Based Analysis Tools That Visualize Genetic Variants

Directory of Open Access Journals (Sweden)

Elisa Cirillo

2017-11-01

Full Text Available Pathway analysis is a powerful method for data analysis in genomics, most often applied to gene expression analysis. It is also promising for single-nucleotide polymorphism (SNP data analysis, such as genome-wide association study data, because it allows the interpretation of variants with respect to the biological processes in which the affected genes and proteins are involved. Such analyses support an interactive evaluation of the possible effects of variations on function, regulation or interaction of gene products. Current pathway analysis software often does not support data visualization of variants in pathways as an alternate method to interpret genetic association results, and specific statistical methods for pathway analysis of SNP data are not combined with these visualization features. In this review, we first describe the visualization options of the tools that were identified by a literature review, in order to provide insight for improvements in this developing field. Tool evaluation was performed using a computational epistatic dataset of gene–gene interactions for obesity risk. Next, we report the necessity to include in these tools statistical methods designed for the pathway-based analysis with SNP data, expressly aiming to define features for more comprehensive pathway-based analysis tools. We conclude by recognizing that pathway analysis of genetic variations data requires a sophisticated combination of the most useful and informative visual aspects of the various tools evaluated.

Reconstructing biochemical pathways from time course data.

Science.gov (United States)

Srividhya, Jeyaraman; Crampin, Edmund J; McSharry, Patrick E; Schnell, Santiago

2007-03-01

Time series data on biochemical reactions reveal transient behavior, away from chemical equilibrium, and contain information on the dynamic interactions among reacting components. However, this information can be difficult to extract using conventional analysis techniques. We present a new method to infer biochemical pathway mechanisms from time course data using a global nonlinear modeling technique to identify the elementary reaction steps which constitute the pathway. The method involves the generation of a complete dictionary of polynomial basis functions based on the law of mass action. Using these basis functions, there are two approaches to model construction, namely the general to specific and the specific to general approach. We demonstrate that our new methodology reconstructs the chemical reaction steps and connectivity of the glycolytic pathway of Lactococcus lactis from time course experimental data.

Systems Bioinformatics: increasing precision of computational diagnostics and therapeutics through network-based approaches.

Science.gov (United States)

Oulas, Anastasis; Minadakis, George; Zachariou, Margarita; Sokratous, Kleitos; Bourdakou, Marilena M; Spyrou, George M

2017-11-27

Systems Bioinformatics is a relatively new approach, which lies in the intersection of systems biology and classical bioinformatics. It focuses on integrating information across different levels using a bottom-up approach as in systems biology with a data-driven top-down approach as in bioinformatics. The advent of omics technologies has provided the stepping-stone for the emergence of Systems Bioinformatics. These technologies provide a spectrum of information ranging from genomics, transcriptomics and proteomics to epigenomics, pharmacogenomics, metagenomics and metabolomics. Systems Bioinformatics is the framework in which systems approaches are applied to such data, setting the level of resolution as well as the boundary of the system of interest and studying the emerging properties of the system as a whole rather than the sum of the properties derived from the system's individual components. A key approach in Systems Bioinformatics is the construction of multiple networks representing each level of the omics spectrum and their integration in a layered network that exchanges information within and between layers. Here, we provide evidence on how Systems Bioinformatics enhances computational therapeutics and diagnostics, hence paving the way to precision medicine. The aim of this review is to familiarize the reader with the emerging field of Systems Bioinformatics and to provide a comprehensive overview of its current state-of-the-art methods and technologies. Moreover, we provide examples of success stories and case studies that utilize such methods and tools to significantly advance research in the fields of systems biology and systems medicine. © The Author 2017. Published by Oxford University Press.

Nutritional Systems Biology

DEFF Research Database (Denmark)

Jensen, Kasper

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

Design of Adaptive Policy Pathways under Deep Uncertainties

Science.gov (United States)

Babovic, Vladan

2013-04-01

The design of large-scale engineering and infrastructural systems today is growing in complexity. Designers need to consider sociotechnical uncertainties, intricacies, and processes in the long- term strategic deployment and operations of these systems. In this context, water and spatial management is increasingly challenged not only by climate-associated changes such as sea level rise and increased spatio-temporal variability of precipitation, but also by pressures due to population growth and particularly accelerating rate of urbanisation. Furthermore, high investment costs and long term-nature of water-related infrastructure projects requires long-term planning perspective, sometimes extending over many decades. Adaptation to such changes is not only determined by what is known or anticipated at present, but also by what will be experienced and learned as the future unfolds, as well as by policy responses to social and water events. As a result, a pathway emerges. Instead of responding to 'surprises' and making decisions on ad hoc basis, exploring adaptation pathways into the future provide indispensable support in water management decision-making. In this contribution, a structured approach for designing a dynamic adaptive policy based on the concepts of adaptive policy making and adaptation pathways is introduced. Such an approach provides flexibility which allows change over time in response to how the future unfolds, what is learned about the system, and changes in societal preferences. The introduced flexibility provides means for dealing with complexities of adaptation under deep uncertainties. It enables engineering systems to change in the face of uncertainty to reduce impacts from downside scenarios while capitalizing on upside opportunities. This contribution presents comprehensive framework for development and deployment of adaptive policy pathway framework, and demonstrates its performance under deep uncertainties on a case study related to urban

Model-based system engineering approach for the Euclid mission to manage scientific and technical complexity

Science.gov (United States)

Lorenzo Alvarez, Jose; Metselaar, Harold; Amiaux, Jerome; Saavedra Criado, Gonzalo; Gaspar Venancio, Luis M.; Salvignol, Jean-Christophe; Laureijs, René J.; Vavrek, Roland

2016-08-01

In the last years, the system engineering field is coming to terms with a paradigm change in the approach for complexity management. Different strategies have been proposed to cope with highly interrelated systems, system of systems and collaborative system engineering have been proposed and a significant effort is being invested into standardization and ontology definition. In particular, Model Based System Engineering (MBSE) intends to introduce methodologies for a systematic system definition, development, validation, deployment, operation and decommission, based on logical and visual relationship mapping, rather than traditional 'document based' information management. The practical implementation in real large-scale projects is not uniform across fields. In space science missions, the usage has been limited to subsystems or sample projects with modeling being performed 'a-posteriori' in many instances. The main hurdle for the introduction of MBSE practices in new projects is still the difficulty to demonstrate their added value to a project and whether their benefit is commensurate with the level of effort required to put them in place. In this paper we present the implemented Euclid system modeling activities, and an analysis of the benefits and limitations identified to support in particular requirement break-down and allocation, and verification planning at mission level.

Redox and Ionic Homeostasis Regulations against Oxidative, Salinity and Drought Stress in Wheat (A Systems Biology Approach

Directory of Open Access Journals (Sweden)

Zahid Hussain Shah

2017-10-01

Full Text Available Systems biology and omics has provided a comprehensive understanding about the dynamics of the genome, metabolome, transcriptome, and proteome under stress. In wheat, abiotic stresses trigger specific networks of pathways involved in redox and ionic homeostasis as well as osmotic balance. These networks are considerably more complicated than those in model plants, and therefore, counter models are proposed by unifying the approaches of omics and stress systems biology. Furthermore, crosstalk among these pathways is monitored by the regulation and streaming of transcripts and genes. In this review, we discuss systems biology and omics as a promising tool to study responses to oxidative, salinity, and drought stress in wheat.

A systems integration approach to the optimum operation and scheduling of biocide usage and discharge for seawater cooling systems

KAUST Repository

Mahfouz, Abdullah Bin

2012-01-01

The objective of this work is to develop a systematic approach to the optimal design and integration of seawater cooling systems in industrial facilities along with the usage and discharge of biocides. Specifically, the paper will address the following tasks: 1 identification of the reaction pathways for the biocide from the mixing basin to the discharge points 2 kinetic modelling of the biocide and by-products throughout the process 3 a process integration framework to provide a holistic approach to optimising the design and operation of the seawater cooling systems, along with the dosage and discharge systems. A hierarchical procedure is developed to first identify design modifications for heat integration and energy efficiency. Then, a multi-period, multi-segment optimisation formulation is developed and solved to identify the optimal operation and scheduling of biocide usage and discharge. A case study is solved to illustrate the applicability of the devised approach.

A new approach for sizing stand alone photovoltaic systems based in neural networks

Energy Technology Data Exchange (ETDEWEB)

Hontoria, L.; Aguilera, J. [Universidad de Jaen, Dept. de Electronica, Jaen (Spain); Zufiria, P. [UPM Ciudad Universitaria, Dept. de Matematica Aplicada a las Tecnologias de la Informacion, Madrid (Spain)

2005-02-01

Several methods for sizing stand alone photovoltaic (pv) systems has been developed. The more simplistic are called intuitive methods. They are a useful tool for a first approach in sizing stand alone photovoltaic systems. Nevertheless they are very inaccurate. Analytical methods use equations to describe the pv system size as a function of reliability. These ones are more accurate than the previous ones but they are also not accurate enough for sizing of high reliability. In a third group there are methods which use system simulations. These ones are called numerical methods. Many of the analytical methods employ the concept of reliability of the system or the complementary term: loss of load probability (LOLP). In this paper an improvement for obtaining LOLP curves based on the neural network called Multilayer Perceptron (MLP) is presented. A unique MLP for many locations of Spain has been trained and after the training, the MLP is able to generate LOLP curves for any value and location. (Author)

Alternative approaches to risk-based technical specifications

International Nuclear Information System (INIS)

Atefi, B.; Gallagher, D.W.; Liner, R.T.; Lofgren, E.V.

1987-01-01

Four alternative risk-based approaches to Technical Specifications are identified. These are: a Probabilistic Risk Assessment (PRA) oriented approach; a reliability goal-oriented approach; an approach based on configuration control; a data-oriented approach. Based on preliminary results, the PRA-oriented approach, which has been developed further than the other approaches, seems to offer a logical, quantitative basis for setting Allowed Outage Times (AOTs) and Surveillance Test Intervals (STIs) for some plant components and systems. The most attractive feature of this approach is that it directly links the AOTs and STIs with the risk associated with the operation of the plant. This would focus the plant operator's and the regulatory agency's attention on the most risk-significant components of the plant. A series of practical issues related to the level of detail and content of the plant PRAs, requirements for the review of these PRAs, and monitoring cf the plant's performance by the regulatory agency must be resolved before the approach could be implemented. Future efforts will examine the other three approaches and their practicality before firm conclusions are drawn regarding the viability of any of these approaches

Introducing Systems Approaches

Science.gov (United States)

Reynolds, Martin; Holwell, Sue

Systems Approaches to Managing Change brings together five systems approaches to managing complex issues, each having a proven track record of over 25 years. The five approaches are: System Dynamics (SD) developed originally in the late 1950s by Jay Forrester Viable Systems Model (VSM) developed originally in the late 1960s by Stafford Beer Strategic Options Development and Analysis (SODA: with cognitive mapping) developed originally in the 1970s by Colin Eden Soft Systems Methodology (SSM) developed originally in the 1970s by Peter Checkland Critical Systems Heuristics (CSH) developed originally in the late 1970s by Werner Ulrich

A Database Approach to Content-based XML retrieval

NARCIS (Netherlands)

Hiemstra, Djoerd

2003-01-01

This paper describes a rst prototype system for content-based retrieval from XML data. The system's design supports both XPath queries and complex information retrieval queries based on a language modelling approach to information retrieval. Evaluation using the INEX benchmark shows that it is

An Approach for the Assessment of System Upset Resilience

Science.gov (United States)

Torres-Pomales, Wilfredo

2013-01-01

This report describes an approach for the assessment of upset resilience that is applicable to systems in general, including safety-critical, real-time systems. For this work, resilience is defined as the ability to preserve and restore service availability and integrity under stated conditions of configuration, functional inputs and environmental conditions. To enable a quantitative approach, we define novel system service degradation metrics and propose a new mathematical definition of resilience. These behavioral-level metrics are based on the fundamental service classification criteria of correctness, detectability, symmetry and persistence. This approach consists of a Monte-Carlo-based stimulus injection experiment, on a physical implementation or an error-propagation model of a system, to generate a system response set that can be characterized in terms of dimensional error metrics and integrated to form an overall measure of resilience. We expect this approach to be helpful in gaining insight into the error containment and repair capabilities of systems for a wide range of conditions.

A framework for managing runoff and pollution in the rural landscape using a Catchment Systems Engineering approach.

Science.gov (United States)

Wilkinson, M E; Quinn, P F; Barber, N J; Jonczyk, J

2014-01-15

Intense farming plays a key role in increasing local scale runoff and erosion rates, resulting in water quality issues and flooding problems. There is potential for agricultural management to become a major part of improved strategies for controlling runoff. Here, a Catchment Systems Engineering (CSE) approach has been explored to solve the above problem. CSE is an interventionist approach to altering the catchment scale runoff regime through the manipulation of hydrological flow pathways throughout the catchment. By targeting hydrological flow pathways at source, such as overland flow, field drain and ditch function, a significant component of the runoff generation can be managed in turn reducing soil nutrient losses. The Belford catchment (5.7 km(2)) is a catchment scale study for which a CSE approach has been used to tackle a number of environmental issues. A variety of Runoff Attenuation Features (RAFs) have been implemented throughout the catchment to address diffuse pollution and flooding issues. The RAFs include bunds disconnecting flow pathways, diversion structures in ditches to spill and store high flows, large wood debris structure within the channel, and riparian zone management. Here a framework for applying a CSE approach to the catchment is shown in a step by step guide to implementing mitigation measures in the Belford Burn catchment. The framework is based around engagement with catchment stakeholders and uses evidence arising from field science. Using the framework, the flooding issue has been addressed at the catchment scale by altering the runoff regime. Initial findings suggest that RAFs have functioned as designed to reduce/attenuate runoff locally. However, evidence suggested that some RAFs needed modification and new RAFs be created to address diffuse pollution issues during storm events. Initial findings from these modified RAFs are showing improvements in sediment trapping capacities and reductions in phosphorus, nitrate and suspended

Metabolic adaptation of a human pathogen during chronic infections - a systems biology approach

DEFF Research Database (Denmark)

Thøgersen, Juliane Charlotte

modeling to uncover how human pathogens adapt to the human host. Pseudomonas aeruginosa infections in cystic fibrosis patients are used as a model system for under-­‐ standing these adaptation processes. The exploratory systems biology approach facilitates identification of important phenotypes...... by classical molecular biology approaches where genes and reactions typically are investigated in a one to one relationship. This thesis is an example of how mathematical approaches and modeling can facilitate new biologi-­‐ cal understanding and provide new surprising ideas to important biological processes....... and metabolic pathways that are necessary or related to establishment of chronic infections. Archetypal analysis showed to be successful in extracting relevant phenotypes from global gene expression da-­‐ ta. Furthermore, genome-­‐scale metabolic modeling showed to be useful in connecting the genotype...

Beta-irradiation used for systemic radioimmunotherapy induces apoptosis and activates apoptosis pathways in leukaemia cells

International Nuclear Information System (INIS)

Friesen, Claudia; Lubatschofski, Annelie; Debatin, Klaus-Michael; Kotzerke, Joerg; Buchmann, Inga; Reske, Sven N.

2003-01-01

Beta-irradiation used for systemic radioimmunotherapy (RIT) is a promising treatment approach for high-risk leukaemia and lymphoma. In bone marrow-selective radioimmunotherapy, beta-irradiation is applied using iodine-131, yttrium-90 or rhenium-188 labelled radioimmunoconjugates. However, the mechanisms by which beta-irradiation induces cell death are not understood at the molecular level. Here, we report that beta-irradiation induced apoptosis and activated apoptosis pathways in leukaemia cells depending on doses, time points and dose rates. After beta-irradiation, upregulation of CD95 ligand and CD95 receptor was detected and activation of caspases resulting in apoptosis was found. These effects were completely blocked by the broad-range caspase inhibitor zVAD-fmk. In addition, irradiation-mediated mitochondrial damage resulted in perturbation of mitochondrial membrane potential, caspase-9 activation and cytochrome c release. Bax, a death-promoting protein, was upregulated and Bcl-x L , a death-inhibiting protein, was downregulated. We also found higher apoptosis rates and earlier activation of apoptosis pathways after gamma-irradiation in comparison to beta-irradiation at the same dose rate. Furthermore, irradiation-resistant cells were cross-resistant to CD95 and CD95-resistant cells were cross-resistant to irradiation, indicating that CD95 and irradiation used, at least in part, identical effector pathways. These findings demonstrate that beta-irradiation induces apoptosis and activates apoptosis pathways in leukaemia cells using both mitochondrial and death receptor pathways. Understanding the timing, sequence and molecular pathways of beta-irradiation-mediated apoptosis may allow rational adjustment of chemo- and radiotherapeutic strategies. (orig.)

Folding pathways explored with artificial potential functions

International Nuclear Information System (INIS)

Ulutaş, B; Bozma, I; Haliloglu, T

2009-01-01

This paper considers the generation of trajectories to a given protein conformation and presents a novel approach based on artificial potential functions—originally proposed for multi-robot navigation. The artificial potential function corresponds to a simplified energy model, but with the novelty that—motivated by work on robotic navigation—a nonlinear compositional scheme of constructing the energy model is adapted instead of an additive formulation. The artificial potential naturally gives rise to a dynamic system for the protein structure that ensures collision-free motion to an equilibrium point. In cases where the equilibrium point is the native conformation, the motion trajectory corresponds to the folding pathway. This framework is used to investigate folding in a variety of protein structures, and the results are compared with those of other approaches including experimental studies

Effect of overall feedback inhibition in unbranched biosynthetic pathways.

Science.gov (United States)

Alves, R; Savageau, M A

2000-11-01

We have determined the effects of control by overall feedback inhibition on the systemic behavior of unbranched metabolic pathways with an arbitrary pattern of other feedback inhibitions by using a recently developed numerical generalization of Mathematically Controlled Comparisons, a method for comparing the function of alternative molecular designs. This method allows the rigorous determination of the changes in systemic properties that can be exclusively attributed to overall feedback inhibition. Analytical results show that the unbranched pathway can achieve the same steady-state flux, concentrations, and logarithmic gains with respect to changes in substrate, with or without overall feedback inhibition. The analytical approach also shows that control by overall feedback inhibition amplifies the regulation of flux by the demand for end product while attenuating the sensitivity of the concentrations to the same demand. This approach does not provide a clear answer regarding the effect of overall feedback inhibition on the robustness, stability, and transient time of the pathway. However, the generalized numerical method we have used does clarify the answers to these questions. On average, an unbranched pathway with control by overall feedback inhibition is less sensitive to perturbations in the values of the parameters that define the system. The difference in robustness can range from a few percent to fifty percent or more, depending on the length of the pathway and on the metabolite one considers. On average, overall feedback inhibition decreases the stability margins by a minimal amount (typically less than 5%). Finally, and again on average, stable systems with overall feedback inhibition respond faster to fluctuations in the metabolite concentrations. Taken together, these results show that control by overall feedback inhibition confers several functional advantages upon unbranched pathways. These advantages provide a rationale for the prevalence of this

Modelling and Analysis of Biochemical Signalling Pathway Cross-talk

Directory of Open Access Journals (Sweden)

Robin Donaldson

2010-02-01

Full Text Available Signalling pathways are abstractions that help life scientists structure the coordination of cellular activity. Cross-talk between pathways accounts for many of the complex behaviours exhibited by signalling pathways and is often critical in producing the correct signal-response relationship. Formal models of signalling pathways and cross-talk in particular can aid understanding and drive experimentation. We define an approach to modelling based on the concept that a pathway is the (synchronising parallel composition of instances of generic modules (with internal and external labels. Pathways are then composed by (synchronising parallel composition and renaming; different types of cross-talk result from different combinations of synchronisation and renaming. We define a number of generic modules in PRISM and five types of cross-talk: signal flow, substrate availability, receptor function, gene expression and intracellular communication. We show that Continuous Stochastic Logic properties can both detect and distinguish the types of cross-talk. The approach is illustrated with small examples and an analysis of the cross-talk between the TGF-b/BMP, WNT and MAPK pathways.

Constructing phylogenetic trees using interacting pathways.

Science.gov (United States)

Wan, Peng; Che, Dongsheng

2013-01-01

Phylogenetic trees are used to represent evolutionary relationships among biological species or organisms. The construction of phylogenetic trees is based on the similarities or differences of their physical or genetic features. Traditional approaches of constructing phylogenetic trees mainly focus on physical features. The recent advancement of high-throughput technologies has led to accumulation of huge amounts of biological data, which in turn changed the way of biological studies in various aspects. In this paper, we report our approach of building phylogenetic trees using the information of interacting pathways. We have applied hierarchical clustering on two domains of organisms-eukaryotes and prokaryotes. Our preliminary results have shown the effectiveness of using the interacting pathways in revealing evolutionary relationships.

A System-Wide Approach to Identify the Mechanisms of Barnacle Attachment: Toward the Discovery of New Antifouling Compounds

KAUST Repository

Al-Aqeel, Sarah

2015-01-01

, cuticle development, and eggshell formation, and down-regulation of genes in the nitric oxide pathway, which stimulates the swimming and feeding responses of marine invertebrates. This system-wide integrated approach elucidated the development

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.

Bio-optical data integration based on a 4 D database system approach

Science.gov (United States)

Imai, N. N.; Shimabukuro, M. H.; Carmo, A. F. C.; Alcantara, E. H.; Rodrigues, T. W. P.; Watanabe, F. S. Y.

2015-04-01

Bio-optical characterization of water bodies requires spatio-temporal data about Inherent Optical Properties and Apparent Optical Properties which allow the comprehension of underwater light field aiming at the development of models for monitoring water quality. Measurements are taken to represent optical properties along a column of water, and then the spectral data must be related to depth. However, the spatial positions of measurement may differ since collecting instruments vary. In addition, the records should not refer to the same wavelengths. Additional difficulty is that distinct instruments store data in different formats. A data integration approach is needed to make these large and multi source data sets suitable for analysis. Thus, it becomes possible, even automatically, semi-empirical models evaluation, preceded by preliminary tasks of quality control. In this work it is presented a solution, in the stated scenario, based on spatial - geographic - database approach with the adoption of an object relational Database Management System - DBMS - due to the possibilities to represent all data collected in the field, in conjunction with data obtained by laboratory analysis and Remote Sensing images that have been taken at the time of field data collection. This data integration approach leads to a 4D representation since that its coordinate system includes 3D spatial coordinates - planimetric and depth - and the time when each data was taken. It was adopted PostgreSQL DBMS extended by PostGIS module to provide abilities to manage spatial/geospatial data. It was developed a prototype which has the mainly tools an analyst needs to prepare the data sets for analysis.

Integrated pathway-based transcription regulation network mining and visualization based on gene expression profiles.

Science.gov (United States)

Kibinge, Nelson; Ono, Naoaki; Horie, Masafumi; Sato, Tetsuo; Sugiura, Tadao; Altaf-Ul-Amin, Md; Saito, Akira; Kanaya, Shigehiko

2016-06-01

Conventionally, workflows examining transcription regulation networks from gene expression data involve distinct analytical steps. There is a need for pipelines that unify data mining and inference deduction into a singular framework to enhance interpretation and hypotheses generation. We propose a workflow that merges network construction with gene expression data mining focusing on regulation processes in the context of transcription factor driven gene regulation. The pipeline implements pathway-based modularization of expression profiles into functional units to improve biological interpretation. The integrated workflow was implemented as a web application software (TransReguloNet) with functions that enable pathway visualization and comparison of transcription factor activity between sample conditions defined in the experimental design. The pipeline merges differential expression, network construction, pathway-based abstraction, clustering and visualization. The framework was applied in analysis of actual expression datasets related to lung, breast and prostrate cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Hanford Site Composite Analysis Technical Approach Description: Groundwater Pathway Dose Calculation.

Energy Technology Data Exchange (ETDEWEB)

Morgans, D. L. [CH2M Hill Plateau Remediation Company, Richland, WA (United States); Lindberg, S. L. [Intera Inc., Austin, TX (United States)

2017-09-20

The purpose of this technical approach document (TAD) is to document the assumptions, equations, and methods used to perform the groundwater pathway radiological dose calculations for the revised Hanford Site Composite Analysis (CA). DOE M 435.1-1, states, “The composite analysis results shall be used for planning, radiation protection activities, and future use commitments to minimize the likelihood that current low-level waste disposal activities will result in the need for future corrective or remedial actions to adequately protect the public and the environment.”

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.

Modeling of nitrous oxide production by autotrophic ammonia-oxidizing bacteria with multiple production pathways.

Science.gov (United States)

Ni, Bing-Jie; Peng, Lai; Law, Yingyu; Guo, Jianhua; Yuan, Zhiguo

2014-04-01

Autotrophic ammonia oxidizing bacteria (AOB) have been recognized as a major contributor to N2O production in wastewater treatment systems. However, so far N2O models have been proposed based on a single N2O production pathway by AOB, and there is still a lack of effective approach for the integration of these models. In this work, an integrated mathematical model that considers multiple production pathways is developed to describe N2O production by AOB. The pathways considered include the nitrifier denitrification pathway (N2O as the final product of AOB denitrification with NO2(-) as the terminal electron acceptor) and the hydroxylamine (NH2OH) pathway (N2O as a byproduct of incomplete oxidation of NH2OH to NO2(-)). In this model, the oxidation and reduction processes are modeled separately, with intracellular electron carriers introduced to link the two types of processes. The model is calibrated and validated using experimental data obtained with two independent nitrifying cultures. The model satisfactorily describes the N2O data from both systems. The model also predicts shifts of the dominating pathway at various dissolved oxygen (DO) and nitrite levels, consistent with previous hypotheses. This unified model is expected to enhance our ability to predict N2O production by AOB in wastewater treatment systems under varying operational conditions.

SLS Navigation Model-Based Design Approach

Science.gov (United States)

Oliver, T. Emerson; Anzalone, Evan; Geohagan, Kevin; Bernard, Bill; Park, Thomas

2018-01-01

The SLS Program chose to implement a Model-based Design and Model-based Requirements approach for managing component design information and system requirements. This approach differs from previous large-scale design efforts at Marshall Space Flight Center where design documentation alone conveyed information required for vehicle design and analysis and where extensive requirements sets were used to scope and constrain the design. The SLS Navigation Team has been responsible for the Program-controlled Design Math Models (DMMs) which describe and represent the performance of the Inertial Navigation System (INS) and the Rate Gyro Assemblies (RGAs) used by Guidance, Navigation, and Controls (GN&C). The SLS Navigation Team is also responsible for the navigation algorithms. The navigation algorithms are delivered for implementation on the flight hardware as a DMM. For the SLS Block 1-B design, the additional GPS Receiver hardware is managed as a DMM at the vehicle design level. This paper provides a discussion of the processes and methods used to engineer, design, and coordinate engineering trades and performance assessments using SLS practices as applied to the GN&C system, with a particular focus on the Navigation components. These include composing system requirements, requirements verification, model development, model verification and validation, and modeling and analysis approaches. The Model-based Design and Requirements approach does not reduce the effort associated with the design process versus previous processes used at Marshall Space Flight Center. Instead, the approach takes advantage of overlap between the requirements development and management process, and the design and analysis process by efficiently combining the control (i.e. the requirement) and the design mechanisms. The design mechanism is the representation of the component behavior and performance in design and analysis tools. The focus in the early design process shifts from the development and

Liquid pathways generic studies; results, interpretation, and design implications