Pathway analysis: State of the art

Directory of Open Access Journals (Sweden)

Miguel Angel eGarcía-Campos

2015-12-01

Full Text Available Pathway analysis is a set of widely used tools for research in life sciences intended to give meaning to high-throughput biological data. The methodology of these tools settles in the gathering and usage of knowledge that comprise biomolecular functioning, coupled with statistical testing and other algorithms. Despite their wide employment, pathway analysis foundations and overall background may not be fully understood, leading to misinterpretation of analysis results. This review attempts to comprise the fundamental knowledge to take into consideration when using pathway analysis as a hypothesis generation tool. We discuss the key elements that are part of these methodologies, their capabilities and current deficiencies. We also present an overview of current and all-time popular methods, highlighting different classes across them. In doing so, we show the exploding diversity of methods that pathway analysis encompasses, point out commonly overlooked caveats, and direct attention to a potential new class of methods that attempt to zoom the analysis scope to the sample scale.

IPAD: the Integrated Pathway Analysis Database for Systematic Enrichment Analysis.

Science.gov (United States)

Zhang, Fan; Drabier, Renee

2012-01-01

Next-Generation Sequencing (NGS) technologies and Genome-Wide Association Studies (GWAS) generate millions of reads and hundreds of datasets, and there is an urgent need for a better way to accurately interpret and distill such large amounts of data. Extensive pathway and network analysis allow for the discovery of highly significant pathways from a set of disease vs. healthy samples in the NGS and GWAS. Knowledge of activation of these processes will lead to elucidation of the complex biological pathways affected by drug treatment, to patient stratification studies of new and existing drug treatments, and to understanding the underlying anti-cancer drug effects. There are approximately 141 biological human pathway resources as of Jan 2012 according to the Pathguide database. However, most currently available resources do not contain disease, drug or organ specificity information such as disease-pathway, drug-pathway, and organ-pathway associations. Systematically integrating pathway, disease, drug and organ specificity together becomes increasingly crucial for understanding the interrelationships between signaling, metabolic and regulatory pathway, drug action, disease susceptibility, and organ specificity from high-throughput omics data (genomics, transcriptomics, proteomics and metabolomics). We designed the Integrated Pathway Analysis Database for Systematic Enrichment Analysis (IPAD, http://bioinfo.hsc.unt.edu/ipad), defining inter-association between pathway, disease, drug and organ specificity, based on six criteria: 1) comprehensive pathway coverage; 2) gene/protein to pathway/disease/drug/organ association; 3) inter-association between pathway, disease, drug, and organ; 4) multiple and quantitative measurement of enrichment and inter-association; 5) assessment of enrichment and inter-association analysis with the context of the existing biological knowledge and a "gold standard" constructed from reputable and reliable sources; and 6) cross-linking of

Pathway analysis of IMC

DEFF Research Database (Denmark)

Skrypnyuk, Nataliya; Nielson, Flemming; Pilegaard, Henrik

2009-01-01

We present the ongoing work on the pathway analysis of a stochastic calculus. Firstly we present a particular stochastic calculus that we have chosen for our modeling - the Interactive Markov Chains calculus, IMC for short. After that we specify a few restrictions that we have introduced into the...... into the syntax of IMC in order to make our analysis feasible. Finally we describe the analysis itself together with several theoretical results that we have proved for it.......We present the ongoing work on the pathway analysis of a stochastic calculus. Firstly we present a particular stochastic calculus that we have chosen for our modeling - the Interactive Markov Chains calculus, IMC for short. After that we specify a few restrictions that we have introduced...

Critical Role of the Sphingolipid Pathway in Stroke: a Review of Current Utility and Potential Therapeutic Targets.

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Sun, Na; Keep, Richard F; Hua, Ya; Xi, Guohua

2016-10-01

Sphingolipids are a series of cell membrane-derived lipids which act as signaling molecules and play a critical role in cell death and survival, proliferation, recognition, and migration. Sphingosine-1-phosphate acts as a key signaling molecule and regulates lymphocyte trafficking, glial cell activation, vasoconstriction, endothelial barrier function, and neuronal death pathways which plays a critical role in numerous neurological conditions. Stroke is a second leading cause of death all over the world and effective therapies are still in great demand, including ischemic stroke and hemorrhagic stroke as well as poststroke repair. Significantly, sphingolipid activities change after stroke and correlate with stroke outcome, which has promoted efforts to testify whether the sphingolipid pathway could be a novel therapeutic target in stroke. The sphingolipid metabolic pathway, the connection between the pathway and stroke, as well as therapeutic interventions to manipulate the pathway to reduce stroke-induced brain injury are discussed in this review.

Association between mutations of critical pathway genes and survival outcomes according to the tumor location in colorectal cancer.

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Lee, Dae-Won; Han, Sae-Won; Cha, Yongjun; Bae, Jeong Mo; Kim, Hwang-Phill; Lyu, Jaemyun; Han, Hyojun; Kim, Hyoki; Jang, Hoon; Bang, Duhee; Huh, Iksoo; Park, Taesung; Won, Jae-Kyung; Jeong, Seung-Yong; Park, Kyu Joo; Kang, Gyeong Hoon; Kim, Tae-You

2017-09-15

Colorectal cancer (CRC) develops through the alteration of several critical pathways. This study was aimed at evaluating the influence of critical pathways on survival outcomes for patients with CRC. Targeted next-generation sequencing of 40 genes included in the 5 critical pathways of CRC (WNT, P53, RTK-RAS, phosphatidylinositol-4,5-bisphosphate 3-kinase [PI3K], and transforming growth factor β [TGF-β]) was performed for 516 patients with stage III or high-risk stage II CRC treated with surgery followed by adjuvant fluoropyrimidine and oxaliplatin chemotherapy. The associations between critical pathway mutations and relapse-free survival (RFS) and overall survival were analyzed. The associations were further analyzed according to the tumor location. The mutation rates for the WNT, P53, RTK-RAS, PI3K, and TGF-β pathways were 84.5%, 69.0%, 60.7%, 30.0%, and 28.9%, respectively. A mutation in the PI3K pathway was associated with longer RFS (adjusted hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.36-0.99), whereas a mutation in the RTK-RAS pathway was associated with shorter RFS (adjusted HR, 1.60; 95% CI, 1.01-2.52). Proximal tumors showed a higher mutation rate than distal tumors, and the mutation profile was different according to the tumor location. The mutation rates of Kirsten rat sarcoma viral oncogene homolog (KRAS), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA), and B-Raf proto-oncogene serine/threonine kinase (BRAF) were higher in proximal tumors, and the mutation rates of adenomatous polyposis coli (APC), tumor protein 53 (TP53), and neuroblastoma RAS viral oncogene homolog (NRAS) were higher in distal tumors. The better RFS with the PI3K pathway mutation was significant only for proximal tumors, and the worse RFS with the RTK-RAS pathway mutation was significant only for distal tumors. A PI3K pathway mutation was associated with better RFS for CRC patients treated with adjuvant chemotherapy, and an RTK

Critical Analysis of Multimodal Discourse

DEFF Research Database (Denmark)

van Leeuwen, Theo

2013-01-01

This is an encyclopaedia article which defines the fields of critical discourse analysis and multimodality studies, argues that within critical discourse analysis more attention should be paid to multimodality, and within multimodality to critical analysis, and ends reviewing a few examples of re...

Identification of cell proliferation, immune response and cell migration as critical pathways in a prognostic signature for HER2+:ERα- breast cancer.

Directory of Open Access Journals (Sweden)

Jeffrey C Liu

Full Text Available Multi-gene prognostic signatures derived from primary tumor biopsies can guide clinicians in designing an appropriate course of treatment. Identifying genes and pathways most essential to a signature performance may facilitate clinical application, provide insights into cancer progression, and uncover potentially new therapeutic targets. We previously developed a 17-gene prognostic signature (HTICS for HER2+:ERα- breast cancer patients, using genes that are differentially expressed in tumor initiating cells (TICs versus non-TICs from MMTV-Her2/neu mammary tumors. Here we probed the pathways and genes that underlie the prognostic power of HTICS.We used Leave-One Out, Data Combination Test, Gene Set Enrichment Analysis (GSEA, Correlation and Substitution analyses together with Receiver Operating Characteristic (ROC and Kaplan-Meier survival analysis to identify critical biological pathways within HTICS. Publically available cohorts with gene expression and clinical outcome were used to assess prognosis. NanoString technology was used to detect gene expression in formalin-fixed paraffin embedded (FFPE tissues.We show that three major biological pathways: cell proliferation, immune response, and cell migration, drive the prognostic power of HTICS, which is further tuned by Homeostatic and Glycan metabolic signalling. A 6-gene minimal Core that retained a significant prognostic power, albeit less than HTICS, also comprised the proliferation/immune/migration pathways. Finally, we developed NanoString probes that could detect expression of HTICS genes and their substitutions in FFPE samples.Our results demonstrate that the prognostic power of a signature is driven by the biological processes it monitors, identify cell proliferation, immune response and cell migration as critical pathways for HER2+:ERα- cancer progression, and defines substitutes and Core genes that should facilitate clinical application of HTICS.

Implementing critical pathways and a multidisciplinary team approach to cardiovascular disease management.

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Peterson, Eric D; Albert, Nancy M; Amin, Alpesh; Patterson, J Herbert; Fonarow, Gregg C

2008-09-08

According to several medical registries, there is a need to improve the care of post-myocardial infarction (MI) patients, especially those with left ventricular dysfunction (LVD) and heart failure. This can potentially be achieved by implementing disease management programs, which include critical pathways, patient education, and multidisciplinary hospital teams. Currently, algorithms for critical pathways, including discharge processes, are lacking for post-MI LVD patients. Such schemes can increase the use of evidence-based medicines proved to reduce mortality. Educational programs are aimed at increasing patients' awareness of their condition, promoting medication compliance, and encouraging the adoption of healthy behaviors; such programs have been shown to be effective in improving outcomes of post-MI LVD patients. Reductions in all-cause hospitalizations and medical costs as well as improved survival rates have been observed when a multidisciplinary team (a nurse, a pharmacist, and a hospitalist) is engaged in patient care. In addition, the use of the "pay for performance" method, which can be advantageous for patients, physicians, and hospitals, may potentially improve the care of post-MI patients with LVD.

Ventral aspect of the visual form pathway is not critical for the perception of biological motion

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Gilaie-Dotan, Sharon; Saygin, Ayse Pinar; Lorenzi, Lauren J.; Rees, Geraint; Behrmann, Marlene

2015-01-01

Identifying the movements of those around us is fundamental for many daily activities, such as recognizing actions, detecting predators, and interacting with others socially. A key question concerns the neurobiological substrates underlying biological motion perception. Although the ventral “form” visual cortex is standardly activated by biologically moving stimuli, whether these activations are functionally critical for biological motion perception or are epiphenomenal remains unknown. To address this question, we examined whether focal damage to regions of the ventral visual cortex, resulting in significant deficits in form perception, adversely affects biological motion perception. Six patients with damage to the ventral cortex were tested with sensitive point-light display paradigms. All patients were able to recognize unmasked point-light displays and their perceptual thresholds were not significantly different from those of three different control groups, one of which comprised brain-damaged patients with spared ventral cortex (n > 50). Importantly, these six patients performed significantly better than patients with damage to regions critical for biological motion perception. To assess the necessary contribution of different regions in the ventral pathway to biological motion perception, we complement the behavioral findings with a fine-grained comparison between the lesion location and extent, and the cortical regions standardly implicated in biological motion processing. This analysis revealed that the ventral aspects of the form pathway (e.g., fusiform regions, ventral extrastriate body area) are not critical for biological motion perception. We hypothesize that the role of these ventral regions is to provide enhanced multiview/posture representations of the moving person rather than to represent biological motion perception per se. PMID:25583504

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

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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

Genome-wide analysis of a Wnt1-regulated transcriptional network implicates neurodegenerative pathways.

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Wexler, Eric M; Rosen, Ezra; Lu, Daning; Osborn, Gregory E; Martin, Elizabeth; Raybould, Helen; Geschwind, Daniel H

2011-10-04

Wnt proteins are critical to mammalian brain development and function. The canonical Wnt signaling pathway involves the stabilization and nuclear translocation of β-catenin; however, Wnt also signals through alternative, noncanonical pathways. To gain a systems-level, genome-wide view of Wnt signaling, we analyzed Wnt1-stimulated changes in gene expression by transcriptional microarray analysis in cultured human neural progenitor (hNP) cells at multiple time points over a 72-hour time course. We observed a widespread oscillatory-like pattern of changes in gene expression, involving components of both the canonical and the noncanonical Wnt signaling pathways. A higher-order, systems-level analysis that combined independent component analysis, waveform analysis, and mutual information-based network construction revealed effects on pathways related to cell death and neurodegenerative disease. Wnt effectors were tightly clustered with presenilin1 (PSEN1) and granulin (GRN), which cause dominantly inherited forms of Alzheimer's disease and frontotemporal dementia (FTD), respectively. We further explored a potential link between Wnt1 and GRN and found that Wnt1 decreased GRN expression by hNPs. Conversely, GRN knockdown increased WNT1 expression, demonstrating that Wnt and GRN reciprocally regulate each other. Finally, we provided in vivo validation of the in vitro findings by analyzing gene expression data from individuals with FTD. These unbiased and genome-wide analyses provide evidence for a connection between Wnt signaling and the transcriptional regulation of neurodegenerative disease genes.

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

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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

Applying critical analysis - main methods

Directory of Open Access Journals (Sweden)

Miguel Araujo Alonso

2012-02-01

Full Text Available What is the usefulness of critical appraisal of literature? Critical analysis is a fundamental condition for the correct interpretation of any study that is subject to review. In epidemiology, in order to learn how to read a publication, we must be able to analyze it critically. Critical analysis allows us to check whether a study fulfills certain previously established methodological inclusion and exclusion criteria. This is frequently used in conducting systematic reviews although eligibility criteria are generally limited to the study design. Critical analysis of literature and be done implicitly while reading an article, as in reading for personal interest, or can be conducted in a structured manner, using explicit and previously established criteria. The latter is done when formally reviewing a topic.

Safety assessment for deep underground disposal vault-pathways analysis

International Nuclear Information System (INIS)

Lyon, R.B.; Rosinger, E.L.J.

1980-01-01

The concept verification phase of the Canadian programme for the disposal of nuclear fuel waste encompasses a period of about three years before the start of site selection. During this time, the methodology for Environmental and Safety Assessment studies is being developed by focusing on a model site. Pathways analysis is an important component of these studies. It involves the prediction of the rate at which radionuclides might be released from a disposal vault and travel through the geosphere and biosphere to reach man. The pathways analysis studies cover three major topics: geosphere pathways analysis, biosphere pathways analysis and potentially-disruptive-phenomena analysis. Geosphere pathways analysis includes a total systems analysis, using the computer program GARD2, vault analysis, which considers container failure and waste leaching, hydrogeological modelling and geochemical modelling. Biosphere pathways analysis incorporates a compartmental modelling approach using the computer program RAMM, and a food chain analysis using the computer program FOOD II. Potentially-disruptive-phenomena analysis involves the estimation of the probability and consequences of events such as earthquakes which might reduce the effectiveness of the barriers preventing the release of radionuclides. The current stage of development of the required methodology and data is discussed in each of the three areas and preliminary results are presented. (author)

Identification of Key Pathways and Genes in Advanced Coronary Atherosclerosis Using Bioinformatics Analysis

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Xiaowen Tan

2017-01-01

Full Text Available Background. Coronary artery atherosclerosis is a chronic inflammatory disease. This study aimed to identify the key changes of gene expression between early and advanced carotid atherosclerotic plaque in human. Methods. Gene expression dataset GSE28829 was downloaded from Gene Expression Omnibus (GEO, including 16 advanced and 13 early stage atherosclerotic plaque samples from human carotid. Differentially expressed genes (DEGs were analyzed. Results. 42,450 genes were obtained from the dataset. Top 100 up- and downregulated DEGs were listed. Functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG identification were performed. The result of functional and pathway enrichment analysis indicted that the immune system process played a critical role in the progression of carotid atherosclerotic plaque. Protein-protein interaction (PPI networks were performed either. Top 10 hub genes were identified from PPI network and top 6 modules were inferred. These genes were mainly involved in chemokine signaling pathway, cell cycle, B cell receptor signaling pathway, focal adhesion, and regulation of actin cytoskeleton. Conclusion. The present study indicated that analysis of DEGs would make a deeper understanding of the molecular mechanisms of atherosclerosis development and they might be used as molecular targets and diagnostic biomarkers for the treatment of atherosclerosis.

Primary Metabolic Pathways and Metabolic Flux Analysis

DEFF Research Database (Denmark)

Villadsen, John

2015-01-01

his chapter introduces the metabolic flux analysis (MFA) or stoichiometry-based MFA, and describes the quantitative basis for MFA. It discusses the catabolic pathways in which free energy is produced to drive the cell-building anabolic pathways. An overview of these primary pathways provides...... the reader who is primarily trained in the engineering sciences with atleast a preliminary introduction to biochemistry and also shows how carbon is drained off the catabolic pathways to provide precursors for cell mass building and sometimes for important industrial products. The primary pathways...... to be examined in the following are: glycolysis, primarily by the EMP pathway, but other glycolytic pathways is also mentioned; fermentative pathways in which the redox generated in the glycolytic reactions are consumed; reactions in the tricarboxylic acid (TCA) cycle, which produce biomass precursors and redox...

A systems biology approach for pathway level analysis

OpenAIRE

Draghici, Sorin; Khatri, Purvesh; Tarca, Adi Laurentiu; Amin, Kashyap; Done, Arina; Voichita, Calin; Georgescu, Constantin; Romero, Roberto

2007-01-01

A common challenge in the analysis of genomics data is trying to understand the underlying phenomenon in the context of all complex interactions taking place on various signaling pathways. A statistical approach using various models is universally used to identify the most relevant pathways in a given experiment. Here, we show that the existing pathway analysis methods fail to take into consideration important biological aspects and may provide incorrect results in certain situations. By usin...

Final report on the Pathway Analysis Task

International Nuclear Information System (INIS)

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

1993-04-01

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

Final report on the Pathway Analysis Task

Energy Technology Data Exchange (ETDEWEB)

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

1993-04-01

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

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)

Cleanup standards and pathways analysis methods

International Nuclear Information System (INIS)

Devgun, J.S.

1993-01-01

Remediation of a radioactively contaminated site requires that certain regulatory criteria be met before the site can be released for unrestricted future use. Since the ultimate objective of remediation is to protect the public health and safety, residual radioactivity levels remaining at a site after cleanup must be below certain preset limits or meet acceptable dose or risk criteria. Release of a decontaminated site requires proof that the radiological data obtained from the site meet the regulatory criteria for such a release. Typically release criteria consist of a composite of acceptance limits that depend on the radionuclides, the media in which they are present, and federal and local regulations. In recent years, the US Department of Energy (DOE) has developed a pathways analysis model to determine site-specific soil activity concentration guidelines for radionuclides that do not have established generic acceptance limits. The DOE pathways analysis computer code (developed by Argonne National Laboratory for the DOE) is called RESRAD (Gilbert et al. 1989). Similar efforts have been initiated by the US Nuclear Regulatory Commission (NRC) to develop and use dose-related criteria based on genetic pathways analyses rather than simplistic numerical limits on residual radioactivity. The focus of this paper is radionuclide contaminated soil. Cleanup standards are reviewed, pathways analysis methods are described, and an example is presented in which RESRAD was used to derive cleanup guidelines

Historical emissions critical for mapping decarbonization pathways

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Majkut, J.; Kopp, R. E.; Sarmiento, J. L.; Oppenheimer, M.

2016-12-01

Policymakers have set a goal of limiting temperature increase from human influence on the climate. This motivates the identification of decarbonization pathways to stabilize atmospheric concentrations of CO2. In this context, the future behavior of CO2 sources and sinks define the CO2 emissions necessary to meet warming thresholds with specified probabilities. We adopt a simple model of the atmosphere-land-ocean carbon balance to reflect uncertainty in how natural CO2 sinks will respond to increasing atmospheric CO2 and temperature. Bayesian inversion is used to estimate the probability distributions of selected parameters of the carbon model. Prior probability distributions are chosen to reflect the behavior of CMIP5 models. We then update these prior distributions by running historical simulations of the global carbon cycle and inverting with observationally-based inventories and fluxes of anthropogenic carbon in the ocean and atmosphere. The result is a best-estimate of historical CO2 sources and sinks and a model of how CO2 sources and sinks will vary in the future under various emissions scenarios, with uncertainty. By linking the carbon model to a simple climate model, we calculate emissions pathways and carbon budgets consistent with meeting specific temperature thresholds and identify key factors that contribute to remaining uncertainty. In particular, we show how the assumed history of CO2 emissions from land use change (LUC) critically impacts estimates of the strength of the land CO2 sink via CO2 fertilization. Different estimates of historical LUC emissions taken from the literature lead to significantly different parameterizations of the carbon system. High historical CO2 emissions from LUC lead to a more robust CO2 fertilization effect, significantly lower future atmospheric CO2 concentrations, and an increased amount of CO2 that can be emitted to satisfy temperature stabilization targets. Thus, in our model, historical LUC emissions have a

Proteomics and pathway analysis identifies JNK signaling as critical for high linear energy transfer radiation-induced apoptosis in non-small lung cancer cells.

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Ståhl, Sara; Fung, Eva; Adams, Christopher; Lengqvist, Johan; Mörk, Birgitta; Stenerlöw, Bo; Lewensohn, Rolf; Lehtiö, Janne; Zubarev, Roman; Viktorsson, Kristina

2009-05-01

During the past decade, we have witnessed an explosive increase in generation of large proteomics data sets, not least in cancer research. There is a growing need to extract and correctly interpret information from such data sets to generate biologically relevant hypotheses. A pathway search engine (PSE) has recently been developed as a novel tool intended to meet these requirements. Ionizing radiation (IR) is an anticancer treatment modality that triggers multiple signal transduction networks. In this work, we show that high linear energy transfer (LET) IR induces apoptosis in a non-small cell lung cancer cell line, U-1810, whereas low LET IR does not. PSE was applied to study changes in pathway status between high and low LET IR to find pathway candidates of importance for high LET-induced apoptosis. Such pathways are potential clinical targets, and they were further validated in vitro. We used an unsupervised shotgun proteomics approach where high resolution mass spectrometry coupled to nanoflow liquid chromatography determined the identity and relative abundance of expressed proteins. Based on the proteomics data, PSE suggested the JNK pathway (p = 6.10(-6)) as a key event in response to high LET IR. In addition, the Fas pathway was found to be activated (p = 3.10(-5)) and the p38 pathway was found to be deactivated (p = 0.001) compared with untreated cells. Antibody-based analyses confirmed that high LET IR caused an increase in phosphorylation of JNK. Moreover pharmacological inhibition of JNK blocked high LET-induced apoptotic signaling. In contrast, neither an activation of p38 nor a role for p38 in high LET IR-induced apoptotic signaling was found. We conclude that, in contrast to conventional low LET IR, high LET IR can trigger activation of the JNK pathway, which in turn is critical for induction of apoptosis in these cells. Thus PSE predictions were largely confirmed, and PSE was proven to be a useful hypothesis-generating tool.

Criticality Analysis of SAMOP Subcritical Assembly

International Nuclear Information System (INIS)

Tegas-Sutondo; Syarip; Triwulan-Tjiptono

2005-01-01

A critically analysis has been performed for homogenous system of uranyl nitrate solution, as part of a preliminary design assessment on neutronic aspect of SAMOP sub-critical assembly. The analysis is intended to determine some critical parameters such as the minimum of critical dimension and critical mass for the desired concentration. As the basis of this analysis, it has been defined a fuel system with an enrichment of 20% for cylindrical geometry of both bare and graphite reflected of 30 cm thickness. The MCNP code has been utilized for this purpose, for variation of concentrations ranging from 150 g/l to 500 g/l. It is found that the best concentration giving the minimum geometrical dimension is around 400 g/l, for both the bare and reflected systems. Whilst the best one, of minimum critical mass is corresponding to the concentration of around 200 g/l with critical mass around 14.1 kg and 4.2 kg for the bare and reflected systems respectively. Based on the result of calculations, it is concluded that by taking into consideration of the critical limit, the SAMOP subcritical assembly is neutronically can be made. (author)

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

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Wufeng Fan

2017-01-01

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

Separate enrichment analysis of pathways for up- and downregulated genes.

Science.gov (United States)

Hong, Guini; Zhang, Wenjing; Li, Hongdong; Shen, Xiaopei; Guo, Zheng

2014-03-06

Two strategies are often adopted for enrichment analysis of pathways: the analysis of all differentially expressed (DE) genes together or the analysis of up- and downregulated genes separately. However, few studies have examined the rationales of these enrichment analysis strategies. Using both microarray and RNA-seq data, we show that gene pairs with functional links in pathways tended to have positively correlated expression levels, which could result in an imbalance between the up- and downregulated genes in particular pathways. We then show that the imbalance could greatly reduce the statistical power for finding disease-associated pathways through the analysis of all-DE genes. Further, using gene expression profiles from five types of tumours, we illustrate that the separate analysis of up- and downregulated genes could identify more pathways that are really pertinent to phenotypic difference. In conclusion, analysing up- and downregulated genes separately is more powerful than analysing all of the DE genes together.

A strategy for evaluating pathway analysis methods.

Science.gov (United States)

Yu, Chenggang; Woo, Hyung Jun; Yu, Xueping; Oyama, Tatsuya; Wallqvist, Anders; Reifman, Jaques

2017-10-13

Researchers have previously developed a multitude of methods designed to identify biological pathways associated with specific clinical or experimental conditions of interest, with the aim of facilitating biological interpretation of high-throughput data. Before practically applying such pathway analysis (PA) methods, we must first evaluate their performance and reliability, using datasets where the pathways perturbed by the conditions of interest have been well characterized in advance. However, such 'ground truths' (or gold standards) are often unavailable. Furthermore, previous evaluation strategies that have focused on defining 'true answers' are unable to systematically and objectively assess PA methods under a wide range of conditions. In this work, we propose a novel strategy for evaluating PA methods independently of any gold standard, either established or assumed. The strategy involves the use of two mutually complementary metrics, recall and discrimination. Recall measures the consistency of the perturbed pathways identified by applying a particular analysis method to an original large dataset and those identified by the same method to a sub-dataset of the original dataset. In contrast, discrimination measures specificity-the degree to which the perturbed pathways identified by a particular method to a dataset from one experiment differ from those identifying by the same method to a dataset from a different experiment. We used these metrics and 24 datasets to evaluate six widely used PA methods. The results highlighted the common challenge in reliably identifying significant pathways from small datasets. Importantly, we confirmed the effectiveness of our proposed dual-metric strategy by showing that previous comparative studies corroborate the performance evaluations of the six methods obtained by our strategy. Unlike any previously proposed strategy for evaluating the performance of PA methods, our dual-metric strategy does not rely on any ground truth

Pathway Processor 2.0: a web resource for pathway-based analysis of high-throughput data.

Science.gov (United States)

Beltrame, Luca; Bianco, Luca; Fontana, Paolo; Cavalieri, Duccio

2013-07-15

Pathway Processor 2.0 is a web application designed to analyze high-throughput datasets, including but not limited to microarray and next-generation sequencing, using a pathway centric logic. In addition to well-established methods such as the Fisher's test and impact analysis, Pathway Processor 2.0 offers innovative methods that convert gene expression into pathway expression, leading to the identification of differentially regulated pathways in a dataset of choice. Pathway Processor 2.0 is available as a web service at http://compbiotoolbox.fmach.it/pathwayProcessor/. Sample datasets to test the functionality can be used directly from the application. duccio.cavalieri@fmach.it Supplementary data are available at Bioinformatics online.

minepath.org: a free interactive pathway analysis web server.

Science.gov (United States)

Koumakis, Lefteris; Roussos, Panos; Potamias, George

2017-07-03

( www.minepath.org ) is a web-based platform that elaborates on, and radically extends the identification of differentially expressed sub-paths in molecular pathways. Besides the network topology, the underlying MinePath algorithmic processes exploit exact gene-gene molecular relationships (e.g. activation, inhibition) and are able to identify differentially expressed pathway parts. Each pathway is decomposed into all its constituent sub-paths, which in turn are matched with corresponding gene expression profiles. The highly ranked, and phenotype inclined sub-paths are kept. Apart from the pathway analysis algorithm, the fundamental innovation of the MinePath web-server concerns its advanced visualization and interactive capabilities. To our knowledge, this is the first pathway analysis server that introduces and offers visualization of the underlying and active pathway regulatory mechanisms instead of genes. Other features include live interaction, immediate visualization of functional sub-paths per phenotype and dynamic linked annotations for the engaged genes and molecular relations. The user can download not only the results but also the corresponding web viewer framework of the performed analysis. This feature provides the flexibility to immediately publish results without publishing source/expression data, and get all the functionality of a web based pathway analysis viewer. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Simplified analysis for liquid pathway studies

International Nuclear Information System (INIS)

Codell, R.B.

1984-08-01

The analysis of the potential contamination of surface water via groundwater contamination from severe nuclear accidents is routinely calculated during licensing reviews. This analysis is facilitated by the methods described in this report, which is codified into a BASIC language computer program, SCREENLP. This program performs simplified calculations for groundwater and surface water transport and calculates population doses to potential users for the contaminated water irrespective of possible mitigation methods. The results are then compared to similar analyses performed using data for the generic sites in NUREG-0440, Liquid Pathway Generic Study, to determine if the site being investigated would pose any unusual liquid pathway hazards

Assessment of SRS radiological liquid and airborne contaminants and pathways

International Nuclear Information System (INIS)

Jannik, G.T.

1997-04-01

This report compiles and documents the radiological critical-contaminant/critical-pathway analysis performed for SRS. The analysis covers radiological releases to the atmosphere and to surface water, which are the principal media that carry contaminants off site. During routine operations at SRS, limited amounts of radionuclides are released to the environment through atmospheric and/or liquid pathways. These releases potentially result in exposure to offsite people. Though the groundwater beneath an estimated 5 to 10 percent of SRS has been contaminated by radionuclides, there is no evidence that groundwater contaminated with these constituents has migrated offsite (Arnett, 1996). Therefore, with the notable exception of radiological source terms originating from shallow surface water migration into site streams, onsite groundwater was not considered as a potential exposure pathway to offsite people

Proteomics and Pathway Analysis Identifies JNK Signaling as Critical for High Linear Energy Transfer Radiation-induced Apoptosis in Non-small Lung Cancer Cells*S⃞

Science.gov (United States)

Ståhl, Sara; Fung, Eva; Adams, Christopher; Lengqvist, Johan; Mörk, Birgitta; Stenerlöw, Bo; Lewensohn, Rolf; Lehtiö, Janne; Zubarev, Roman; Viktorsson, Kristina

2009-01-01

During the past decade, we have witnessed an explosive increase in generation of large proteomics data sets, not least in cancer research. There is a growing need to extract and correctly interpret information from such data sets to generate biologically relevant hypotheses. A pathway search engine (PSE) has recently been developed as a novel tool intended to meet these requirements. Ionizing radiation (IR) is an anticancer treatment modality that triggers multiple signal transduction networks. In this work, we show that high linear energy transfer (LET) IR induces apoptosis in a non-small cell lung cancer cell line, U-1810, whereas low LET IR does not. PSE was applied to study changes in pathway status between high and low LET IR to find pathway candidates of importance for high LET-induced apoptosis. Such pathways are potential clinical targets, and they were further validated in vitro. We used an unsupervised shotgun proteomics approach where high resolution mass spectrometry coupled to nanoflow liquid chromatography determined the identity and relative abundance of expressed proteins. Based on the proteomics data, PSE suggested the JNK pathway (p = 6·10−6) as a key event in response to high LET IR. In addition, the Fas pathway was found to be activated (p = 3·10−5) and the p38 pathway was found to be deactivated (p = 0.001) compared with untreated cells. Antibody-based analyses confirmed that high LET IR caused an increase in phosphorylation of JNK. Moreover pharmacological inhibition of JNK blocked high LET-induced apoptotic signaling. In contrast, neither an activation of p38 nor a role for p38 in high LET IR-induced apoptotic signaling was found. We conclude that, in contrast to conventional low LET IR, high LET IR can trigger activation of the JNK pathway, which in turn is critical for induction of apoptosis in these cells. Thus PSE predictions were largely confirmed, and PSE was proven to be a useful hypothesis-generating tool. PMID:19168796

ComPath: comparative enzyme analysis and annotation in pathway/subsystem contexts

Directory of Open Access Journals (Sweden)

Kim Sun

2008-03-01

Full Text Available Abstract Background Once a new genome is sequenced, one of the important questions is to determine the presence and absence of biological pathways. Analysis of biological pathways in a genome is a complicated task since a number of biological entities are involved in pathways and biological pathways in different organisms are not identical. Computational pathway identification and analysis thus involves a number of computational tools and databases and typically done in comparison with pathways in other organisms. This computational requirement is much beyond the capability of biologists, so information systems for reconstructing, annotating, and analyzing biological pathways are much needed. We introduce a new comparative pathway analysis workbench, ComPath, which integrates various resources and computational tools using an interactive spreadsheet-style web interface for reliable pathway analyses. Results ComPath allows users to compare biological pathways in multiple genomes using a spreadsheet style web interface where various sequence-based analysis can be performed either to compare enzymes (e.g. sequence clustering and pathways (e.g. pathway hole identification, to search a genome for de novo prediction of enzymes, or to annotate a genome in comparison with reference genomes of choice. To fill in pathway holes or make de novo enzyme predictions, multiple computational methods such as FASTA, Whole-HMM, CSR-HMM (a method of our own introduced in this paper, and PDB-domain search are integrated in ComPath. Our experiments show that FASTA and CSR-HMM search methods generally outperform Whole-HMM and PDB-domain search methods in terms of sensitivity, but FASTA search performs poorly in terms of specificity, detecting more false positive as E-value cutoff increases. Overall, CSR-HMM search method performs best in terms of both sensitivity and specificity. Gene neighborhood and pathway neighborhood (global network visualization tools can be used

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.

PathwaySplice: An R package for unbiased pathway analysis of alternative splicing in RNA-Seq data.

Science.gov (United States)

Yan, Aimin; Ban, Yuguang; Gao, Zhen; Chen, Xi; Wang, Lily

2018-04-24

Pathway analysis of alternative splicing would be biased without accounting for the different number of exons or junctions associated with each gene, because genes with higher number of exons or junctions are more likely to be included in the "significant" gene list in alternative splicing. We present PathwaySplice, an R package that (1) Performs pathway analysis that explicitly adjusts for the number of exons or junctions associated with each gene; (2) Visualizes selection bias due to different number of exons or junctions for each gene and formally tests for presence of bias using logistic regression; (3) Supports gene sets based on the Gene Ontology terms, as well as more broadly defined gene sets (e.g. MSigDB) or user defined gene sets; (4) Identifies the significant genes driving pathway significance and (5) Organizes significant pathways with an enrichment map, where pathways with large number of overlapping genes are grouped together in a network graph. https://bioconductor.org/packages/release/bioc/html/PathwaySplice.html. lily.wangg@gmail.com, xi.steven.chen@gmail.com.

Pan-cancer analysis of TCGA data reveals notable signaling pathways

International Nuclear Information System (INIS)

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

2015-01-01

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

Self-organized criticality in a network of interacting neurons

NARCIS (Netherlands)

Cowan, J.D.; Neuman, J.; Kiewiet, B.; van Drongelen, W.

2013-01-01

This paper contains an analysis of a simple neural network that exhibits self-organized criticality. Such criticality follows from the combination of a simple neural network with an excitatory feedback loop that generates bistability, in combination with an anti-Hebbian synapse in its input pathway.

RaMP: A Comprehensive Relational Database of Metabolomics Pathways for Pathway Enrichment Analysis of Genes and Metabolites.

Science.gov (United States)

Zhang, Bofei; Hu, Senyang; Baskin, Elizabeth; Patt, Andrew; Siddiqui, Jalal K; Mathé, Ewy A

2018-02-22

The value of metabolomics in translational research is undeniable, and metabolomics data are increasingly generated in large cohorts. The functional interpretation of disease-associated metabolites though is difficult, and the biological mechanisms that underlie cell type or disease-specific metabolomics profiles are oftentimes unknown. To help fully exploit metabolomics data and to aid in its interpretation, analysis of metabolomics data with other complementary omics data, including transcriptomics, is helpful. To facilitate such analyses at a pathway level, we have developed RaMP (Relational database of Metabolomics Pathways), which combines biological pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, WikiPathways, and the Human Metabolome DataBase (HMDB). To the best of our knowledge, an off-the-shelf, public database that maps genes and metabolites to biochemical/disease pathways and can readily be integrated into other existing software is currently lacking. For consistent and comprehensive analysis, RaMP enables batch and complex queries (e.g., list all metabolites involved in glycolysis and lung cancer), can readily be integrated into pathway analysis tools, and supports pathway overrepresentation analysis given a list of genes and/or metabolites of interest. For usability, we have developed a RaMP R package (https://github.com/Mathelab/RaMP-DB), including a user-friendly RShiny web application, that supports basic simple and batch queries, pathway overrepresentation analysis given a list of genes or metabolites of interest, and network visualization of gene-metabolite relationships. The package also includes the raw database file (mysql dump), thereby providing a stand-alone downloadable framework for public use and integration with other tools. In addition, the Python code needed to recreate the database on another system is also publicly available (https://github.com/Mathelab/RaMP-BackEnd). Updates for databases in RaMP will be

Intermittent Domestic Water Supply: A Critical Review and Analysis of Causal-Consequential Pathways

Directory of Open Access Journals (Sweden)

S. E. Galaitsi

2016-06-01

Full Text Available Communities in many parts of the world, especially in developing countries, face obstacles in supplying continuous water to household consumers. Authorities often cite water scarcity as the cause, but we demonstrate that environmental constraints constitute only one aspect of a multi-dimensional problem. By asking what causes intermittent domestic water supply, this literature review (129 articles identifies 47 conditions of intermittent systems and the causal-consequential pathways between them that can reinforce intermittency. These pathways span several disciplines including engineering, government administration and anthropology, and when viewed together they (1 emphasize the human drivers of intermittency; (2 suggest generalized interventions; and (3 reveal a gap in the literature in terms of meaningful categorizations of the reliability of intermittent supplies. Based on the reliability of consumers’ water access, we propose three categories of intermittency—predictable, irregular, and unreliable—to facilitate comparisons between case studies and transfers of solutions.

Preclosure Criticality Analysis Process Report

International Nuclear Information System (INIS)

Thomas, D.A.

1999-01-01

The design approach for criticality of the disposal container and waste package will be dictated by existing regulatory requirements. This conclusion is based on the fact that preclosure operations and facilities have significant similarities to existing facilities and operations currently regulated by the NRC. The major difference would be the use of a risk-informed approach with burnup credit. This approach could reduce licensing delays and costs of the repository. The probability of success for this proposed seamless licensing strategy is increased, since there is precedence of regulation (10 CFR Part 63 and NUREG 1520) and commercial precedence for allowing burnup credit at sites similar to Yucca Mountain during preclosure. While NUREG 1520 is not directly applicable to a facility for handling spent nuclear fuel, the risk-informed approach to criticality analysis in NUREG 1520 is considered indicative of how the NRC will approach risk-informed criticality analysis at spent fuel facilities in the future. The types of design basis events which must be considered during the criticality safety analysis portion of the Integrated Safety Analysis (ISA) are those events which result in unanticipated moderation, loss of neutron absorber, geometric changes in the critical system, or administrative errors in waste form placement (loading) of the disposal container. The specific events to be considered must be based on the review of the system's design, as discussed in Section 3.2. A transition of licensing approach (e.g., deterministic versus risk-informed, performance-based) is not obvious and will require analysis. For commercial spent nuclear fuel, the probability of interspersed moderation may be low enough to allow nearly the same Critical Limit for both preclosure and postclosure, though an administrative margin will be applied to preclosure and possibly not to postclosure. Similarly the Design Basis Events for the waste package may be incredible and therefore not

Preclosure Criticality Analysis Process Report

International Nuclear Information System (INIS)

Thomas, D.A.

1999-01-01

The design approach for criticality of the disposal container and waste package will be dictated by existing regulatory requirements. This conclusion is based on the fact that preclosure operations and facilities have significant similarities to existing facilities and operations currently regulated by the NRC. The major difference would be the use of a risk-informed approach with burnup credit. This approach could reduce licensing delays and costs of the repository. The probability of success for this proposed seamless licensing strategy is increased, since there is precedence of regulation (10 CFR Part 63 and NUREG 1520) and commercial precedence for allowing burnup credit at sites similar to Yucca Mountain during preclosure. While NUREG 1520 is not directly applicable to a facility for handling spent nuclear fuel, the risk-informed approach to criticality analysis in NUREG 1520 is considered indicative of how the NRC will approach risk-informed criticality analysis at spent fuel facilities in the future. The types of design basis events which must be considered during the criticality safety analysis portion of the Integrated Safety Analysis (ISA) are those events which result in unanticipated moderation, loss of neutron absorber, geometric changes in the critical system, or administrative errors in waste form placement (loading) of the disposal container. The specific events to be considered must be based on the review of the system's design, as discussed in Section 3.2. A transition of licensing approach (e.g., deterministic versus risk-informed, performance-based) is not obvious and will require analysis. For commercial spent nuclear fuel, the probability of interspersed moderation may be low enough to allow nearly the same Critical Limit for both preclosure and postclosure, though an administrative margin will be applied to preclosure and possibly not to postclosure. Similarly the Design Basis Events for the waste package may be incredible and therefore not

PyPathway: Python Package for Biological Network Analysis and Visualization.

Science.gov (United States)

Xu, Yang; Luo, Xiao-Chun

2018-05-01

Life science studies represent one of the biggest generators of large data sets, mainly because of rapid sequencing technological advances. Biological networks including interactive networks and human curated pathways are essential to understand these high-throughput data sets. Biological network analysis offers a method to explore systematically not only the molecular complexity of a particular disease but also the molecular relationships among apparently distinct phenotypes. Currently, several packages for Python community have been developed, such as BioPython and Goatools. However, tools to perform comprehensive network analysis and visualization are still needed. Here, we have developed PyPathway, an extensible free and open source Python package for functional enrichment analysis, network modeling, and network visualization. The network process module supports various interaction network and pathway databases such as Reactome, WikiPathway, STRING, and BioGRID. The network analysis module implements overrepresentation analysis, gene set enrichment analysis, network-based enrichment, and de novo network modeling. Finally, the visualization and data publishing modules enable users to share their analysis by using an easy web application. For package availability, see the first Reference.

Microbial Disruption of Autophagy Alters Expression of the RISC Component AGO2, a Critical Regulator of the miRNA Silencing Pathway.

Science.gov (United States)

Sibony, Michal; Abdullah, Majd; Greenfield, Laura; Raju, Deepa; Wu, Ted; Rodrigues, David M; Galindo-Mata, Esther; Mascarenhas, Heidi; Philpott, Dana J; Silverberg, Mark S; Jones, Nicola L

2015-12-01

Autophagy is implicated in Crohn's disease (CD) pathogenesis. Recent evidence suggests autophagy regulates the microRNA (miRNA)-induced silencing complex (miRISC). Therefore, autophagy may play a novel role in CD by regulating expression of miRISC, thereby altering miRNA silencing. As microbes associated with CD can alter autophagy, we hypothesized that microbial disruption of autophagy affects the critical miRISC component AGO2. AGO2 expression was assessed in epithelial and immune cells, and intestinal organoids with disrupted autophagy. Microarray technology was used to determine the expression of downstream miRNAs in cells with defective autophagy. Increased AGO2 was detected in autophagy-deficient ATG5-/- and ATG16-/- mouse embryonic fibroblast cells (MEFs) in comparison with wild-type MEFs. Chemical agents and VacA toxin, which disrupt autophagy, increased AGO2 expression in MEFs, epithelial cells lines, and human monocytes, respectively. Increased AGO2 was also detected in ATG7-/- intestinal organoids, in comparison with wild-type organoids. Five miRNAs were differentially expressed in autophagy-deficient MEFs. Pathway enrichment analysis of the differentially expressed miRNAs implicated signaling pathways previously associated with CD. Taken together, our results suggest that autophagy is involved in the regulation of the critical miRISC component AGO2 in epithelial and immune cells and primary intestinal epithelial cells. We propose a mechanism by which autophagy alters miRNA expression, which likely impacts the regulation of CD-associated pathways. Furthermore, as enteric microbial products can manipulate autophagy and AGO2, our findings suggest a novel mechanism by which enteric microbes could influence miRNA to promote disease.

Nano hydroxyapatite-blasted titanium surface affects pre-osteoblast morphology by modulating critical intracellular pathways.

Science.gov (United States)

Bezerra, Fábio; Ferreira, Marcel R; Fontes, Giselle N; da Costa Fernandes, Célio Jr; Andia, Denise C; Cruz, Nilson C; da Silva, Rodrigo A; Zambuzzi, Willian F

2017-08-01

Although, intracellular signaling pathways are proposed to predict the quality of cell-surface relationship, this study addressed pre-osteoblast behavior in response to nano hydroxyapatite (HA)-blasted titanium (Ti) surface by exploring critical intracellular pathways and pre-osteoblast morphological change. Physicochemical properties were evaluated by atomic force microscopy (AFM) and wettability considering water contact angle of three differently texturized Ti surfaces: Machined (Mac), Dual acid-etching (DAE), and nano hydroxyapatite-blasted (nHA). The results revealed critical differences in surface topography, impacting the water contact angle and later the osteoblast performance. In order to evaluate the effect of those topographical characteristics on biological responses, we have seeded pre-osteoblast cells on the Ti discs for up to 4 h and subjected the cultures to biological analysis. First, we have observed pre-osteoblasts morphological changes resulting from the interaction with the Ti texturized surfaces whereas the cells cultured on nHA presented a more advanced spreading process when compared with the cells cultured on the other surfaces. These results argued us for analyzing the molecular machinery and thus, we have shown that nHA promoted a lower Bax/Bcl2 ratio, suggesting an interesting anti-apoptotic effect, maybe explained by the fact that HA is a natural element present in bone composition. Thereafter, we investigated the potential effect of those surfaces on promoting pre-osteoblast adhesion and survival signaling by performing crystal violet and immunoblotting approaches, respectively. Our results showed that nHA promoted a higher pre-osteoblast adhesion supported by up-modulating FAK and Src activations, both signaling transducers involved during eukaryotic cell adhesion. Also, we have shown Ras-Erk stimulation by the all evaluated surfaces. Finally, we showed that all Ti-texturing surfaces were able to promote osteoblast differentiation

Network Expansion and Pathway Enrichment Analysis towards Biologically Significant Findings from Microarrays

Directory of Open Access Journals (Sweden)

Wu Xiaogang

2012-06-01

Full Text Available In many cases, crucial genes show relatively slight changes between groups of samples (e.g. normal vs. disease, and many genes selected from microarray differential analysis by measuring the expression level statistically are also poorly annotated and lack of biological significance. In this paper, we present an innovative approach - network expansion and pathway enrichment analysis (NEPEA for integrative microarray analysis. We assume that organized knowledge will help microarray data analysis in significant ways, and the organized knowledge could be represented as molecular interaction networks or biological pathways. Based on this hypothesis, we develop the NEPEA framework based on network expansion from the human annotated and predicted protein interaction (HAPPI database, and pathway enrichment from the human pathway database (HPD. We use a recently-published microarray dataset (GSE24215 related to insulin resistance and type 2 diabetes (T2D as case study, since this study provided a thorough experimental validation for both genes and pathways identified computationally from classical microarray analysis and pathway analysis. We perform our NEPEA analysis for this dataset based on the results from the classical microarray analysis to identify biologically significant genes and pathways. Our findings are not only consistent with the original findings mostly, but also obtained more supports from other literatures.

ACRR fuel storage racks criticality safety analysis

International Nuclear Information System (INIS)

Bodette, D.E.; Naegeli, R.E.

1997-10-01

This document presents the criticality safety analysis for a new fuel storage rack to support modification of the Annular Core Research Reactor for production of molybdenum-99 at Sandia National Laboratories, Technical Area V facilities. Criticality calculations with the MCNP code investigated various contingencies for the criticality control parameters. Important contingencies included mix of fuel element types stored, water density due to air bubbles or water level for the over-moderated racks, interaction with existing fuel storage racks and fuel storage holsters in the fuel storage pool, neutron absorption of planned rack design and materials, and criticality changes due to manufacturing tolerances or damage. Some limitations or restrictions on use of the new fuel storage rack for storage operations were developed through the criticality analysis and are required to meet the double contingency requirements of criticality safety. As shown in the analysis, this system will remain subcritical under all credible upset conditions. Administrative controls are necessary for loading, moving, and handling the storage rack as well as for control of operations around it. 21 refs., 16 figs., 4 tabs

Sensitivity Analysis of Criticality for Different Nuclear Fuel Shapes

Energy Technology Data Exchange (ETDEWEB)

Kang, Hyun Sik; Jang, Misuk; Kim, Seoung Rae [NESS, Daejeon (Korea, Republic of)

2016-10-15

Rod-type nuclear fuel was mainly developed in the past, but recent study has been extended to plate-type nuclear fuel. Therefore, this paper reviews the sensitivity of criticality according to different shapes of nuclear fuel types. Criticality analysis was performed using MCNP5. MCNP5 is well-known Monte Carlo codes for criticality analysis and a general-purpose Monte Carlo N-Particle code that can be used for neutron, photon, electron or coupled neutron / photon / electron transport, including the capability to calculate eigenvalues for critical systems. We performed the sensitivity analysis of criticality for different fuel shapes. In sensitivity analysis for simple fuel shapes, the criticality is proportional to the surface area. But for fuel Assembly types, it is not proportional to the surface area. In sensitivity analysis for intervals between plates, the criticality is greater as the interval increases, but if the interval is greater than 8mm, it showed an opposite trend that the criticality decrease by a larger interval. As a result, it has failed to obtain the logical content to be described in common for all cases. The sensitivity analysis of Criticality would be always required whenever subject to be analyzed is changed.

Sensitivity Analysis of Criticality for Different Nuclear Fuel Shapes

International Nuclear Information System (INIS)

Kang, Hyun Sik; Jang, Misuk; Kim, Seoung Rae

2016-01-01

Rod-type nuclear fuel was mainly developed in the past, but recent study has been extended to plate-type nuclear fuel. Therefore, this paper reviews the sensitivity of criticality according to different shapes of nuclear fuel types. Criticality analysis was performed using MCNP5. MCNP5 is well-known Monte Carlo codes for criticality analysis and a general-purpose Monte Carlo N-Particle code that can be used for neutron, photon, electron or coupled neutron / photon / electron transport, including the capability to calculate eigenvalues for critical systems. We performed the sensitivity analysis of criticality for different fuel shapes. In sensitivity analysis for simple fuel shapes, the criticality is proportional to the surface area. But for fuel Assembly types, it is not proportional to the surface area. In sensitivity analysis for intervals between plates, the criticality is greater as the interval increases, but if the interval is greater than 8mm, it showed an opposite trend that the criticality decrease by a larger interval. As a result, it has failed to obtain the logical content to be described in common for all cases. The sensitivity analysis of Criticality would be always required whenever subject to be analyzed is changed

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

Sustainable development goals for health promotion: a critical frame analysis.

Science.gov (United States)

Spencer, Grace; Corbin, J Hope; Miedema, Esther

2018-05-25

The Sustainable Development Goals (SDGs) lay the foundations for supporting global health and international development work for the next 15 years. Thirty years ago, the Ottawa Charter defined health promotion and outlined key principles for global action on health, including the importance of advocating, enabling and mediating for health equity. Advocacy underscores a human right to health and suggests political action to support its attainment. Enabling speaks to health promotion's focus on the empowerment of people and communities to take control over their health and aspirations. Mediation draws attention to the critical intersectoral partnerships required to address health and social inequities. Underpinned by this approach, the aim of this paper is to consider how key health promotion principles, namely, rights, empowerment and partnership feature (and are framed) within the SDGs and to consider how these framings may shape future directions for health promotion. To that end, a critical frame analysis of the Transforming Our World document was conducted. The analysis interrogated varying uses and meanings of partnerships, empowerment and rights (and their connections) within the SDGs. The analysis here presents three framings from the SDGs: (1) a moral code for global action on (in)equity; (2) a future orientation to address global issues yet devoid of history; and (3) a reductionist framing of health as the absence of disease. These framings raise important questions about the underpinning values of the SDGs and pathways to health equity - offering both challenges and opportunities for defining the nature and scope of health promotion.

Dysregulated Pathway Identification of Alzheimer's Disease Based on Internal Correlation Analysis of Genes and Pathways.

Science.gov (United States)

Kong, Wei; Mou, Xiaoyang; Di, Benteng; Deng, Jin; Zhong, Ruxing; Wang, Shuaiqun

2017-11-20

Dysregulated pathway identification is an important task which can gain insight into the underlying biological processes of disease. Current pathway-identification methods focus on a set of co-expression genes and single pathways and ignore the correlation between genes and pathways. The method proposed in this study, takes into account the internal correlations not only between genes but also pathways to identifying dysregulated pathways related to Alzheimer's disease (AD), the most common form of dementia. In order to find the significantly differential genes for AD, mutual information (MI) is used to measure interdependencies between genes other than expression valves. Then, by integrating the topology information from KEGG, the significant pathways involved in the feature genes are identified. Next, the distance correlation (DC) is applied to measure the pairwise pathway crosstalks since DC has the advantage of detecting nonlinear correlations when compared to Pearson correlation. Finally, the pathway pairs with significantly different correlations between normal and AD samples are known as dysregulated pathways. The molecular biology analysis demonstrated that many dysregulated pathways related to AD pathogenesis have been discovered successfully by the internal correlation detection. Furthermore, the insights of the dysregulated pathways in the development and deterioration of AD will help to find new effective target genes and provide important theoretical guidance for drug design. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Critical groups - basic concepts

International Nuclear Information System (INIS)

Carter, M.W.

1992-01-01

The potential exposure pathways from the land application site to man are presented. It is emphasised that the critical group is not necessary the population group closest to the source. It could be the group impact by the most significant pathways(s). Only by assessing the importance of each of these pathways and then combining them can a proper choice of critical group be made. It would be wrong to select a critical group on the basis that it seems the most probable one, before the pathways have been properly assessed. A calculation in Carter (1983) suggested that for the operating mine site, the annual doses to an Aboriginal person, a service worker and a local housewife, were all about the same and were in the range 0.1 to 0.2 mSv per year. Thus it may be that for the land application area, the critical group turns out to be non-Aboriginal rather than the expected Aboriginal group. 6 refs., 3 figs

The Liverpool Care Pathway for the Dying Patient: a critical analysis of its rise, demise and legacy in England [version 2; referees: 2 approved

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Jane Seymour

2018-04-01

Full Text Available Background: The Liverpool Care Pathway for the Dying Patient (‘LCP’ was an integrated care pathway (ICP recommended by successive governments in England and Wales to improve end-of-life care. It was discontinued in 2014 following mounting criticism and a national review.  Understanding the problems encountered in the roll out of the LCP has crucial importance for future policy making in end of life care. We provide an in-depth account of LCP development and implementation with explanatory theoretical perspectives. We address three critical questions: 1 why and how did the LCP come to prominence as a vehicle of policy and practice? 2 what factors contributed to its demise? 3 what immediate implications and lessons resulted from its withdrawal? Methods: We use primary and secondary sources in the public domain to assemble a critical and historical review. We also draw on the ‘boundary object’ concept and on wider analyses of the use of ICPs. Results: The rapidity of transfer and translation of the LCP reflected uncritical enthusiasm for ICPs in the early 2000s. While the LCP had some weaknesses in its formulation and implementation, it became the bearer of responsibility for all aspects of NHS end-of-life care. It exposed fault lines in the NHS, provided a platform for debates about the ‘evidence’ required to underpin innovations in palliative care and became a conduit of discord about ‘good’ or ‘bad’ practice in care of the dying. It also fostered a previously unseen critique of assumptions within palliative care. Conclusions: In contrast to most observers of the LCP story who refer to the dangers of scaling up clinical interventions without an evidence base, we call for greater assessment of the wider risks and more careful consideration of the unintended consequences that might result from the roll out of new end-of-life interventions.

Application of the critical pathway and integrated case teaching method to nursing orientation.

Science.gov (United States)

Goodman, D

1997-01-01

Nursing staff development programs must be responsive to current changes in healthcare. New nursing staff must be prepared to manage continuous change and to function competently in clinical practice. The orientation pathway, based on a case management model, is used as a structure for the orientation phase of staff development. The integrated case is incorporated as a teaching strategy in orientation. The integrated case method is based on discussion and analysis of patient situations with emphasis on role modeling and integration of theory and skill. The orientation pathway and integrated case teaching method provide a useful framework for orientation of new staff. Educators, preceptors and orientees find the structure provided by the orientation pathway very useful. Orientation that is developed, implemented and evaluated based on a case management model with the use of an orientation pathway and incorporation of an integrated case teaching method provides a standardized structure for orientation of new staff. This approach is designed for the adult learner, promotes conceptual reasoning, and encourages the social and contextual basis for continued learning.

Teaching For Art Criticism: Incorporating Feldman’s Critical Analysis Learning Model In Students’ Studio Practice

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Maithreyi Subramaniam

2016-01-01

Full Text Available This study adopted 30 first year graphic design students’ artwork, with critical analysis using Feldman’s model of art criticism. Data were analyzed quantitatively; descriptive statistical techniques were employed. The scores were viewed in the form of mean score and frequencies to determine students’ performances in their critical ability. Pearson Correlation Coefficient was used to find out the correlation between students’ studio practice and art critical ability scores. The findings showed most students performed slightly better than average in the critical analyses and performed best in selecting analysis among the four dimensions assessed. In the context of the students’ studio practice and critical ability, findings showed there are some connections between the students’ art critical ability and studio practice.

Pathway analysis for alternate low-level waste disposal methods

International Nuclear Information System (INIS)

Rao, R.R.; Kozak, M.W.; McCord, J.T.; Olague, N.E.

1992-01-01

The purpose of this paper is to evaluate a complete set of environmental pathways for disposal options and conditions that the Nuclear Regulatory Commission (NRC) may analyze for a low-level radioactive waste (LLW) license application. The regulations pertaining In the past, shallow-land burial has been used for the disposal of low-level radioactive waste. However, with the advent of the State Compact system of LLW disposal, many alternative technologies may be used. The alternative LLW disposal facilities include below- ground vault, tumulus, above-ground vault, shaft, and mine disposal This paper will form the foundation of an update of the previously developed Sandia National Laboratories (SNL)/NRC LLW performance assessment methodology. Based on the pathway assessment for alternative disposal methods, a determination will be made about whether the current methodology can satisfactorily analyze the pathways and phenomena likely to be important for the full range of potential disposal options. We have attempted to be conservative in keeping pathways in the lists that may usually be of marginal importance. In this way we can build confidence that we have spanned the range of cases likely to be encountered at a real site. Results of the pathway assessment indicate that disposal methods can be categorized in groupings based on their depth of disposal. For the deep disposal options of shaft and mine disposal, the key pathways are identical. The shallow disposal options, such as tumulus, shallow-land, and below-ground vault disposal also may be grouped together from a pathway analysis perspective. Above-ground vault disposal cannot be grouped with any of the other disposal options. The pathway analysis shows a definite trend concerning depth of disposal. The above-ground option has the largest number of significant pathways. As the waste becomes more isolated, the number of significant pathways is reduced. Similar to shallow-land burial, it was found that for all

Identifying novel glioma associated pathways based on systems biology level meta-analysis.

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Hu, Yangfan; Li, Jinquan; Yan, Wenying; Chen, Jiajia; Li, Yin; Hu, Guang; Shen, Bairong

2013-01-01

With recent advances in microarray technology, including genomics, proteomics, and metabolomics, it brings a great challenge for integrating this "-omics" data to analysis complex disease. Glioma is an extremely aggressive and lethal form of brain tumor, and thus the study of the molecule mechanism underlying glioma remains very important. To date, most studies focus on detecting the differentially expressed genes in glioma. However, the meta-analysis for pathway analysis based on multiple microarray datasets has not been systematically pursued. In this study, we therefore developed a systems biology based approach by integrating three types of omics data to identify common pathways in glioma. Firstly, the meta-analysis has been performed to study the overlapping of signatures at different levels based on the microarray gene expression data of glioma. Among these gene expression datasets, 12 pathways were found in GeneGO database that shared by four stages. Then, microRNA expression profiles and ChIP-seq data were integrated for the further pathway enrichment analysis. As a result, we suggest 5 of these pathways could be served as putative pathways in glioma. Among them, the pathway of TGF-beta-dependent induction of EMT via SMAD is of particular importance. Our results demonstrate that the meta-analysis based on systems biology level provide a more useful approach to study the molecule mechanism of complex disease. The integration of different types of omics data, including gene expression microarrays, microRNA and ChIP-seq data, suggest some common pathways correlated with glioma. These findings will offer useful potential candidates for targeted therapeutic intervention of glioma.

Inwardly Rectifying Potassium (Kir) Channels Represent a Critical Ion Conductance Pathway in the Nervous Systems of Insects.

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Chen, Rui; Swale, Daniel R

2018-01-25

A complete understanding of the physiological pathways critical for proper function of the insect nervous system is still lacking. The recent development of potent and selective small-molecule modulators of insect inward rectifier potassium (Kir) channels has enabled the interrogation of the physiological role and toxicological potential of Kir channels within various insect tissue systems. Therefore, we aimed to highlight the physiological and functional role of neural Kir channels the central nervous system, muscular system, and neuromuscular system through pharmacological and genetic manipulations. Our data provide significant evidence that Drosophila neural systems rely on the inward conductance of K + ions for proper function since pharmacological inhibition and genetic ablation of neural Kir channels yielded dramatic alterations of the CNS spike discharge frequency and broadening and reduced amplitude of the evoked EPSP at the neuromuscular junction. Based on these data, we conclude that neural Kir channels in insects (1) are critical for proper function of the insect nervous system, (2) represents an unexplored physiological pathway that is likely to shape the understanding of neuronal signaling, maintenance of membrane potentials, and maintenance of the ionic balance of insects, and (3) are capable of inducing acute toxicity to insects through neurological poisoning.

Pathview Web: user friendly pathway visualization and data integration.

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Luo, Weijun; Pant, Gaurav; Bhavnasi, Yeshvant K; Blanchard, Steven G; Brouwer, Cory

2017-07-03

Pathway analysis is widely used in omics studies. Pathway-based data integration and visualization is a critical component of the analysis. To address this need, we recently developed a novel R package called Pathview. Pathview maps, integrates and renders a large variety of biological data onto molecular pathway graphs. Here we developed the Pathview Web server, as to make pathway visualization and data integration accessible to all scientists, including those without the special computing skills or resources. Pathview Web features an intuitive graphical web interface and a user centered design. The server not only expands the core functions of Pathview, but also provides many useful features not available in the offline R package. Importantly, the server presents a comprehensive workflow for both regular and integrated pathway analysis of multiple omics data. In addition, the server also provides a RESTful API for programmatic access and conveniently integration in third-party software or workflows. Pathview Web is openly and freely accessible at https://pathview.uncc.edu/. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Uncertainty analysis in Monte Carlo criticality computations

International Nuclear Information System (INIS)

Qi Ao

2011-01-01

Highlights: ► Two types of uncertainty methods for k eff Monte Carlo computations are examined. ► Sampling method has the least restrictions on perturbation but computing resources. ► Analytical method is limited to small perturbation on material properties. ► Practicality relies on efficiency, multiparameter applicability and data availability. - Abstract: Uncertainty analysis is imperative for nuclear criticality risk assessments when using Monte Carlo neutron transport methods to predict the effective neutron multiplication factor (k eff ) for fissionable material systems. For the validation of Monte Carlo codes for criticality computations against benchmark experiments, code accuracy and precision are measured by both the computational bias and uncertainty in the bias. The uncertainty in the bias accounts for known or quantified experimental, computational and model uncertainties. For the application of Monte Carlo codes for criticality analysis of fissionable material systems, an administrative margin of subcriticality must be imposed to provide additional assurance of subcriticality for any unknown or unquantified uncertainties. Because of a substantial impact of the administrative margin of subcriticality on economics and safety of nuclear fuel cycle operations, recently increasing interests in reducing the administrative margin of subcriticality make the uncertainty analysis in criticality safety computations more risk-significant. This paper provides an overview of two most popular k eff uncertainty analysis methods for Monte Carlo criticality computations: (1) sampling-based methods, and (2) analytical methods. Examples are given to demonstrate their usage in the k eff uncertainty analysis due to uncertainties in both neutronic and non-neutronic parameters of fissionable material systems.

Gene expression meta-analysis identifies metastatic pathways and transcription factors in breast cancer

International Nuclear Information System (INIS)

Thomassen, Mads; Tan, Qihua; Kruse, Torben A

2008-01-01

Metastasis is believed to progress in several steps including different pathways but the determination and understanding of these mechanisms is still fragmentary. Microarray analysis of gene expression patterns in breast tumors has been used to predict outcome in recent studies. Besides classification of outcome, these global expression patterns may reflect biological mechanisms involved in metastasis of breast cancer. Our purpose has been to investigate pathways and transcription factors involved in metastasis by use of gene expression data sets. We have analyzed 8 publicly available gene expression data sets. A global approach, 'gene set enrichment analysis' as well as an approach focusing on a subset of significantly differently regulated genes, GenMAPP, has been applied to rank pathway gene sets according to differential regulation in metastasizing tumors compared to non-metastasizing tumors. Meta-analysis has been used to determine overrepresentation of pathways and transcription factors targets, concordant deregulated in metastasizing breast tumors, in several data sets. The major findings are up-regulation of cell cycle pathways and a metabolic shift towards glucose metabolism reflected in several pathways in metastasizing tumors. Growth factor pathways seem to play dual roles; EGF and PDGF pathways are decreased, while VEGF and sex-hormone pathways are increased in tumors that metastasize. Furthermore, migration, proteasome, immune system, angiogenesis, DNA repair and several signal transduction pathways are associated to metastasis. Finally several transcription factors e.g. E2F, NFY, and YY1 are identified as being involved in metastasis. By pathway meta-analysis many biological mechanisms beyond major characteristics such as proliferation are identified. Transcription factor analysis identifies a number of key factors that support central pathways. Several previously proposed treatment targets are identified and several new pathways that may

Criticality analysis of a spent fuel shipping cask

International Nuclear Information System (INIS)

Pena, J.

1984-01-01

Criticality analysis for a system yields to the determination of the multiplication factor. Should such analysis be performed for a spent fuel shipping cask some standards must be accomplished. In this study a sample design is analyzed and criticality results are presented. (author)

GenMAPP 2: new features and resources for pathway analysis

Directory of Open Access Journals (Sweden)

Dahlquist Kam D

2007-06-01

Full Text Available Abstract Background Microarray technologies have evolved rapidly, enabling biologists to quantify genome-wide levels of gene expression, alternative splicing, and sequence variations for a variety of species. Analyzing and displaying these data present a significant challenge. Pathway-based approaches for analyzing microarray data have proven useful for presenting data and for generating testable hypotheses. Results To address the growing needs of the microarray community we have released version 2 of Gene Map Annotator and Pathway Profiler (GenMAPP, a new GenMAPP database schema, and integrated resources for pathway analysis. We have redesigned the GenMAPP database to support multiple gene annotations and species as well as custom species database creation for a potentially unlimited number of species. We have expanded our pathway resources by utilizing homology information to translate pathway content between species and extending existing pathways with data derived from conserved protein interactions and coexpression. We have implemented a new mode of data visualization to support analysis of complex data, including time-course, single nucleotide polymorphism (SNP, and splicing. GenMAPP version 2 also offers innovative ways to display and share data by incorporating HTML export of analyses for entire sets of pathways as organized web pages. Conclusion GenMAPP version 2 provides a means to rapidly interrogate complex experimental data for pathway-level changes in a diverse range of organisms.

Identification of hydrologic and geochemical pathways using high frequency sampling, REE aqueous sampling and soil characterization at Koiliaris Critical Zone Observatory, Crete

Energy Technology Data Exchange (ETDEWEB)

Moraetis, Daniel, E-mail: moraetis@mred.tuc.gr [Department of Environmental Engineering, Technical University of Crete, 73100 Chania (Greece); Stamati, Fotini; Kotronakis, Manolis; Fragia, Tasoula; Paranychnianakis, Nikolaos; Nikolaidis, Nikolaos P. [Department of Environmental Engineering, Technical University of Crete, 73100 Chania (Greece)

2011-06-15

Highlights: > Identification of hydrological and geochemical pathways within a complex watershed. > Water increased N-NO{sub 3} concentration and E.C. values during flash flood events. > Soil degradation and impact on water infiltration within the Koiliaris watershed. > Analysis of Rare Earth Elements in water bodies for identification of karstic water. - Abstract: Koiliaris River watershed is a Critical Zone Observatory that represents severely degraded soils due to intensive agricultural activities and biophysical factors. It has typical Mediterranean soils under the imminent threat of desertification which is expected to intensify due to projected climate change. High frequency hydro-chemical monitoring with targeted sampling for Rare Earth Elements (REE) analysis of different water bodies and geochemical characterization of soils were used for the identification of hydrologic and geochemical pathways. The high frequency monitoring of water chemical data highlighted the chemical alterations of water in Koiliaris River during flash flood events. Soil physical and chemical characterization surveys were used to identify erodibility patterns within the watershed and the influence of soils on surface and ground water chemistry. The methodology presented can be used to identify the impacts of degraded soils to surface and ground water quality as well as in the design of methods to minimize the impacts of land use practices.

Academic provenance: Investigation of pathways that lead students into the geosciences

Science.gov (United States)

Houlton, Heather R.

Pathways that lead students into the geosciences as a college major have not been fully explored in the current literature, despite the recent studies on the "geoscience pipeline model." Anecdotal evidence suggests low quality geoscience curriculum in K-12 education, lack of visibility of the discipline and lack of knowledge about geoscience careers contribute to low geoscience enrollments at universities. This study investigated the reasons why college students decided to major in the geosciences. Students' interests, experiences, motivations and desired future careers were examined to develop a pathway model. In addition, self-efficacy was used to inform pathway analyses, as it is an influential factor in academic major and career choice. These results and interpretations have strong implications for recruitment and retention in academia and industry. A semi-structured interview protocol was developed, which was informed by John Flanagan's critical incident theory. The responses to this interview were used to identify common experiences that diverse students shared for reasons they became geoscience majors. Researchers used self-efficacy theory by Alfred Bandura to assess students' pathways. Seventeen undergraduate geoscience majors from two U.S. Midwest research universities were sampled for cross-comparison and analysis. Qualitative analyses led to the development of six categorical steps for the geoscience pathway. The six pathway steps are: innate attributes/interest sources, pre-college critical incidents, college critical incidents, current/near future goals, expected career attributes and desired future careers. Although, how students traversed through each step was unique for individuals, similar patterns were identified between different populations in our participants: Natives, Immigrants and Refugees. In addition, critical incidents were found to act on behavior in two different ways: to support and confirm decision-making behavior (supportive critical

Bioinformatics analysis of RNA-seq data revealed critical genes in colon adenocarcinoma.

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Xi, W-D; Liu, Y-J; Sun, X-B; Shan, J; Yi, L; Zhang, T-T

2017-07-01

RNA-seq data of colon adenocarcinoma (COAD) were analyzed with bioinformatics tools to discover critical genes in the disease. Relevant small molecule drugs, transcription factors (TFs) and microRNAs (miRNAs) were also investigated. RNA-seq data of COAD were downloaded from The Cancer Genome Atlas (TCGA). Differential analysis was performed with package edgeR. False positive discovery (FDR) 1 were set as the cut-offs to screen out differentially expressed genes (DEGs). Gene coexpression network was constructed with package Ebcoexpress. GO enrichment analysis was performed for the DEGs in the gene coexpression network with DAVID. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was also performed for the genes with KOBASS 2.0. Modules were identified with MCODE of Cytoscape. Relevant small molecules drugs were predicted by Connectivity map. Relevant miRNAs and TFs were searched by WebGestalt. A total of 457 DEGs, including 255 up-regulated and 202 down-regulated genes, were identified from 437 COAD and 39 control samples. A gene coexpression network was constructed containing 40 DEGs and 101 edges. The genes were mainly associated with collagen fibril organization, extracellular matrix organization and translation. Two modules were identified from the gene coexpression network, which were implicated in muscle contraction and extracellular matrix organization, respectively. Several critical genes were disclosed, such as MYH11, COL5A2 and ribosomal proteins. Nine relevant small molecule drugs were identified, such as scriptaid and STOCK1N-35874. Accordingly, a total of 17 TFs and 10 miRNAs related to COAD were acquired, such as ETS2, NFAT, AP4, miR-124A, MiR-9, miR-96 and let-7. Several critical genes and relevant drugs, TFs and miRNAs were revealed in COAD. These findings could advance the understanding of the disease and benefit therapy development.

Teaching for Art Criticism: Incorporating Feldman's Critical Analysis Learning Model in Students' Studio Practice

Science.gov (United States)

Subramaniam, Maithreyi; Hanafi, Jaffri; Putih, Abu Talib

2016-01-01

This study adopted 30 first year graphic design students' artwork, with critical analysis using Feldman's model of art criticism. Data were analyzed quantitatively; descriptive statistical techniques were employed. The scores were viewed in the form of mean score and frequencies to determine students' performances in their critical ability.…

Critical pathway studies for selected radionuclides. Part of a coordinated programme on environmental monitoring for radiological protection in Asia and the Far East

International Nuclear Information System (INIS)

Bhat, I.S.

1980-04-01

The programme carried out critical pathway studies for selected radionuclides ( 60 Co, 63 Ni, 59 Fe, 54 Mn, sup(110m)Ag, 106 Ru and 144 Ce) and assessed population exposure in the vicinity of Tarapur Atomic Power Station. The following topics are covered under the programme. (i) Demographic study of dietary habits and consumption data for Tarapur population. (ii) Concentration and accumulation of radionuclides in food products. (iii) Determination of radionuclides in sea water, silt, marine algae and marine organisms at Tarapur Atomic Power Station (TAPS) Site. (iv) Behaviour of radionuclides released to marine environment. (v) Evaluation of critical exposure pathway. (vi) Population exposure in the vicinity of Tarapur Atomic Power Station

Definition of critical periods for Hedgehog pathway antagonist-induced holoprosencephaly, cleft lip, and cleft palate.

Directory of Open Access Journals (Sweden)

Galen W Heyne

Full Text Available The Hedgehog (Hh signaling pathway mediates multiple spatiotemporally-specific aspects of brain and face development. Genetic and chemical disruptions of the pathway are known to result in an array of structural malformations, including holoprosencephaly (HPE, clefts of the lip with or without cleft palate (CL/P, and clefts of the secondary palate only (CPO. Here, we examined patterns of dysmorphology caused by acute, stage-specific Hh signaling inhibition. Timed-pregnant wildtype C57BL/6J mice were administered a single dose of the potent pathway antagonist vismodegib at discrete time points between gestational day (GD 7.0 and 10.0, an interval approximately corresponding to the 15th to 24th days of human gestation. The resultant pattern of facial and brain dysmorphology was dependent upon stage of exposure. Insult between GD7.0 and GD8.25 resulted in HPE, with peak incidence following exposure at GD7.5. Unilateral clefts of the lip extending into the primary palate were also observed, with peak incidence following exposure at GD8.875. Insult between GD9.0 and GD10.0 resulted in CPO and forelimb abnormalities. We have previously demonstrated that Hh antagonist-induced cleft lip results from deficiency of the medial nasal process and show here that CPO is associated with reduced growth of the maxillary-derived palatal shelves. By defining the critical periods for the induction of HPE, CL/P, and CPO with fine temporal resolution, these results provide a mechanism by which Hh pathway disruption can result in "non-syndromic" orofacial clefting, or HPE with or without co-occurring clefts. This study also establishes a novel and tractable mouse model of human craniofacial malformations using a single dose of a commercially available and pathway-specific drug.

Integrated In Silico Analysis of Pathway Designs for Synthetic Photo-Electro-Autotrophy.

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Michael Volpers

Full Text Available The strong advances in synthetic biology enable the engineering of novel functions and complex biological features in unprecedented ways, such as implementing synthetic autotrophic metabolism into heterotrophic hosts. A key challenge for the sustainable production of fuels and chemicals entails the engineering of synthetic autotrophic organisms that can effectively and efficiently fix carbon dioxide by using sustainable energy sources. This challenge involves the integration of carbon fixation and energy uptake systems. A variety of carbon fixation pathways and several types of photosystems and other energy uptake systems can be chosen and, potentially, modularly combined to design synthetic autotrophic metabolism. Prior to implementation, these designs can be evaluated by the combination of several computational pathway analysis techniques. Here we present a systematic, integrated in silico analysis of photo-electro-autotrophic pathway designs, consisting of natural and synthetic carbon fixation pathways, a proton-pumping rhodopsin photosystem for ATP regeneration and an electron uptake pathway. We integrated Flux Balance Analysis of the heterotrophic chassis Escherichia coli with kinetic pathway analysis and thermodynamic pathway analysis (Max-min Driving Force. The photo-electro-autotrophic designs are predicted to have a limited potential for anaerobic, autotrophic growth of E. coli, given the relatively low ATP regenerating capacity of the proton pumping rhodopsin photosystems and the high ATP maintenance of E. coli. If these factors can be tackled, our analysis indicates the highest growth potential for the natural reductive tricarboxylic acid cycle and the synthetic pyruvate synthase-pyruvate carboxylate -glyoxylate bicycle. Both carbon fixation cycles are very ATP efficient, while maintaining fast kinetics, which also results in relatively low estimated protein costs for these pathways. Furthermore, the synthetic bicycles are highly

Disposal criticality analysis methodology for fissile waste forms

International Nuclear Information System (INIS)

Davis, J.W.; Gottlieb, P.

1998-03-01

A general methodology has been developed to evaluate the criticality potential of the wide range of waste forms planned for geologic disposal. The range of waste forms include commercial spent fuel, high level waste, DOE spent fuel (including highly enriched), MOX using weapons grade plutonium, and immobilized plutonium. The disposal of these waste forms will be in a container with sufficiently thick corrosion resistant barriers to prevent water penetration for up to 10,000 years. The criticality control for DOE spent fuel is primarily provided by neutron absorber material incorporated into the basket holding the individual assemblies. For the immobilized plutonium, the neutron absorber material is incorporated into the waste form itself. The disposal criticality analysis methodology includes the analysis of geochemical and physical processes that can breach the waste package and affect the waste forms within. The basic purpose of the methodology is to guide the criticality control features of the waste package design, and to demonstrate that the final design meets the criticality control licensing requirements. The methodology can also be extended to the analysis of criticality consequences (primarily increased radionuclide inventory), which will support the total performance assessment for the respository

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

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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

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

Rethinking Critical Mathematics: A Comparative Analysis of Critical, Reform, and Traditional Geometry Instructional Texts

Science.gov (United States)

Brantlinger, Andrew

2011-01-01

This paper presents findings from a comparative analysis of three similar secondary geometry texts, one critical unit, one standards-based reform unit, and one specialist chapter. I developed the critical unit as I took the tenets of critical mathematics (CM) and substantiated them in printed curricular materials in which to teach as part of a…

Genetic variants in two pathways influence serum urate levels and gout risk: a systematic pathway analysis.

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Dong, Zheng; Zhou, Jingru; Xu, Xia; Jiang, Shuai; Li, Yuan; Zhao, Dongbao; Yang, Chengde; Ma, Yanyun; Wang, Yi; He, Hongjun; Ji, Hengdong; Zhang, Juan; Yuan, Ziyu; Yang, Yajun; Wang, Xiaofeng; Pang, Yafei; Jin, Li; Zou, Hejian; Wang, Jiucun

2018-03-01

The aims of this study were to identify candidate pathways associated with serum urate and to explore the genetic effect of those pathways on the risk of gout. Pathway analysis of the loci identified in genome-wide association studies (GWASs) showed that the ion transmembrane transporter activity pathway (GO: 0015075) and the secondary active transmembrane transporter activity pathway (GO: 0015291) were both associated with serum urate concentrations, with P FDR values of 0.004 and 0.007, respectively. In a Chinese population of 4,332 individuals, the two pathways were also found to be associated with serum urate (P FDR  = 1.88E-05 and 3.44E-04, separately). In addition, these two pathways were further associated with the pathogenesis of gout (P FDR  = 1.08E-08 and 2.66E-03, respectively) in the Chinese population and a novel gout-associated gene, SLC17A2, was identified (OR = 0.83, P FDR  = 0.017). The mRNA expression of candidate genes also showed significant differences among different groups at pathway level. The present study identified two transmembrane transporter activity pathways (GO: 0015075 and GO: 0015291) were associations with serum urate concentrations and the risk of gout. SLC17A2 was identified as a novel gene that influenced the risk of gout.

TSLP signaling pathway map: a platform for analysis of TSLP-mediated signaling.

Science.gov (United States)

Zhong, Jun; Sharma, Jyoti; Raju, Rajesh; Palapetta, Shyam Mohan; Prasad, T S Keshava; Huang, Tai-Chung; Yoda, Akinori; Tyner, Jeffrey W; van Bodegom, Diederik; Weinstock, David M; Ziegler, Steven F; Pandey, Akhilesh

2014-01-01

Thymic stromal lymphopoietin (TSLP) is a four-helix bundle cytokine that plays a critical role in the regulation of immune responses and in the differentiation of hematopoietic cells. TSLP signals through a heterodimeric receptor complex consisting of an interleukin-7 receptor α chain and a unique TSLP receptor (TSLPR) [also known as cytokine receptor-like factor 2 (CRLF2)]. Cellular targets of TSLP include dendritic cells, B cells, mast cells, regulatory T (Treg) cells and CD4+ and CD8+ T cells. The TSLP/TSLPR axis can activate multiple signaling transduction pathways including the JAK/STAT pathway and the PI-3 kinase pathway. Aberrant TSLP/TSLPR signaling has been associated with a variety of human diseases including asthma, atopic dermatitis, nasal polyposis, inflammatory bowel disease, eosinophilic eosophagitis and, most recently, acute lymphoblastic leukemia. A centralized resource of the TSLP signaling pathway cataloging signaling events is not yet available. In this study, we present a literature-annotated resource of reactions in the TSLP signaling pathway. This pathway map is publicly available through NetPath (http://www.netpath.org/), an open access signal transduction pathway resource developed previously by our group. This map includes 236 molecules and 252 reactions that are involved in TSLP/TSLPR signaling pathway. We expect that the TSLP signaling pathway map will provide a rich resource to study the biology of this important cytokine as well as to identify novel therapeutic targets for diseases associated with dysregulated TSLP/TSLPR signaling. Database URL: http://www.netpath.org/pathways?path_id=NetPath_24.

Analysis of Critical Parts and Materials

Science.gov (United States)

1980-12-01

1 1 1% 1% 1% 1% Large Orders Manual Ordering of Some Critical Parts Order Spares with Original Order Incentives Belter Capital Investment...demand 23 Large orders 24 Long lead procurement funding (including raw materials, facility funding) 25 Manpower analysis and training 26 Manual ... ordering of some critical parts 27 More active role in schedule negotiation 28 Multiple source procurements 29 Multi-year program funding 30 Order

Dynamical analysis of critical assembly CC-1

International Nuclear Information System (INIS)

Aleman Fernandez, J.R.

1990-01-01

The computer code CC-1, elaborated for the analysis of transients in Critical Assemblies is described. The results by the program are compared with the ones presented in the Safety Report for the Critical Assembly of ''La Quebrada'' Nuclear Research Centre (CIN). 7 refs

Biomarker Identification and Pathway Analysis by Serum Metabolomics of Lung Cancer

Directory of Open Access Journals (Sweden)

Yingrong Chen

2015-01-01

Full Text Available Lung cancer is one of the most common causes of cancer death, for which no validated tumor biomarker is sufficiently accurate to be useful for diagnosis. Additionally, the metabolic alterations associated with the disease are unclear. In this study, we investigated the construction, interaction, and pathways of potential lung cancer biomarkers using metabolomics pathway analysis based on the Kyoto Encyclopedia of Genes and Genomes database and the Human Metabolome Database to identify the top altered pathways for analysis and visualization. We constructed a diagnostic model using potential serum biomarkers from patients with lung cancer. We assessed their specificity and sensitivity according to the area under the curve of the receiver operator characteristic (ROC curves, which could be used to distinguish patients with lung cancer from normal subjects. The pathway analysis indicated that sphingolipid metabolism was the top altered pathway in lung cancer. ROC curve analysis indicated that glycerophospho-N-arachidonoyl ethanolamine (GpAEA and sphingosine were potential sensitive and specific biomarkers for lung cancer diagnosis and prognosis. Compared with the traditional lung cancer diagnostic biomarkers carcinoembryonic antigen and cytokeratin 19 fragment, GpAEA and sphingosine were as good or more appropriate for detecting lung cancer. We report our identification of potential metabolic diagnostic and prognostic biomarkers of lung cancer and clarify the metabolic alterations in lung cancer.

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Directory of Open Access Journals (Sweden)

Zhongqi Ge

2018-04-01

Full Text Available Summary: Protein ubiquitination is a dynamic and reversible process of adding single ubiquitin molecules or various ubiquitin chains to target proteins. Here, using multidimensional omic data of 9,125 tumor samples across 33 cancer types from The Cancer Genome Atlas, we perform comprehensive molecular characterization of 929 ubiquitin-related genes and 95 deubiquitinase genes. Among them, we systematically identify top somatic driver candidates, including mutated FBXW7 with cancer-type-specific patterns and amplified MDM2 showing a mutually exclusive pattern with BRAF mutations. Ubiquitin pathway genes tend to be upregulated in cancer mediated by diverse mechanisms. By integrating pan-cancer multiomic data, we identify a group of tumor samples that exhibit worse prognosis. These samples are consistently associated with the upregulation of cell-cycle and DNA repair pathways, characterized by mutated TP53, MYC/TERT amplification, and APC/PTEN deletion. Our analysis highlights the importance of the ubiquitin pathway in cancer development and lays a foundation for developing relevant therapeutic strategies. : Ge et al. analyze a cohort of 9,125 TCGA samples across 33 cancer types to provide a comprehensive characterization of the ubiquitin pathway. They detect somatic driver candidates in the ubiquitin pathway and identify a cluster of patients with poor survival, highlighting the importance of this pathway in cancer development. Keywords: ubiquitin pathway, pan-cancer analysis, The Cancer Genome Atlas, tumor subtype, cancer prognosis, therapeutic targets, biomarker, FBXW7

Does College Teach Critical Thinking? A Meta-Analysis

Science.gov (United States)

Huber, Christopher R.; Kuncel, Nathan R.

2016-01-01

Educators view critical thinking as an essential skill, yet it remains unclear how effectively it is being taught in college. This meta-analysis synthesizes research on gains in critical thinking skills and attitudinal dispositions over various time frames in college. The results suggest that both critical thinking skills and dispositions improve…

SCALE 5: Powerful new criticality safety analysis tools

International Nuclear Information System (INIS)

Bowman, Stephen M.; Hollenbach, Daniel F.; Dehart, Mark D.; Rearden, Bradley T.; Gauld, Ian C.; Goluoglu, Sedat

2003-01-01

Version 5 of the SCALE computer software system developed at Oak Ridge National Laboratory, scheduled for release in December 2003, contains several significant new modules and sequences for criticality safety analysis and marks the most important update to SCALE in more than a decade. This paper highlights the capabilities of these new modules and sequences, including continuous energy flux spectra for processing multigroup problem-dependent cross sections; one- and three-dimensional sensitivity and uncertainty analyses for criticality safety evaluations; two-dimensional flexible mesh discrete ordinates code; automated burnup-credit analysis sequence; and one-dimensional material distribution optimization for criticality safety. (author)

Computational methods for nuclear criticality safety analysis

International Nuclear Information System (INIS)

Maragni, M.G.

1992-01-01

Nuclear criticality safety analyses require the utilization of methods which have been tested and verified against benchmarks results. In this work, criticality calculations based on the KENO-IV and MCNP codes are studied aiming the qualification of these methods at the IPEN-CNEN/SP and COPESP. The utilization of variance reduction techniques is important to reduce the computer execution time, and several of them are analysed. As practical example of the above methods, a criticality safety analysis for the storage tubes for irradiated fuel elements from the IEA-R1 research has been carried out. This analysis showed that the MCNP code is more adequate for problems with complex geometries, and the KENO-IV code shows conservative results when it is not used the generalized geometry option. (author)

Teaching For Art Criticism: Incorporating Feldman’s Critical Analysis Learning Model In Students’ Studio Practice

OpenAIRE

Maithreyi Subramaniam; Jaffri Hanafi; Abu Talib Putih

2016-01-01

This study adopted 30 first year graphic design students’ artwork, with critical analysis using Feldman’s model of art criticism. Data were analyzed quantitatively; descriptive statistical techniques were employed. The scores were viewed in the form of mean score and frequencies to determine students’ performances in their critical ability. Pearson Correlation Coefficient was used to find out the correlation between students’ studio practice and art critical ability scores. The...

Pathway Analysis of miR-181a in Hypopharyngeal Squamous Cell ...

African Journals Online (AJOL)

syakima

2012-03-15

Mar 15, 2012 ... Key words: MicroRNA, head and neck cancer, miR-181a, pathway analysis, luciferase assay, FaDu cell line, transfection ..... prostate carcinoma and glioblastoma cells. Nucleic Acids .... WNT pathway in oral cancer: epigenetic.

RIP2 Is a Critical Regulator for NLRs Signaling and MHC Antigen Presentation but Not for MAPK and PI3K/Akt Pathways.

Science.gov (United States)

Wu, Xiao Man; Chen, Wen Qin; Hu, Yi Wei; Cao, Lu; Nie, Pin; Chang, Ming Xian

2018-01-01

RIP2 is an adaptor protein which is essential for the activation of NF-κB and NOD1- and NOD2-dependent signaling. Although NOD-RIP2 axis conservatively existed in the teleost, the function of RIP2 was only reported in zebrafish, goldfish, and rainbow trout in vitro . Very little is known about the role and mechanisms of piscine NOD-RIP2 axis in vivo . Our previous study showed the protective role of zebrafish NOD1 in larval survival through CD44a-mediated activation of PI3K-Akt signaling. In this study, we examined whether RIP2 was required for larval survival with or without pathogen infection, and determined the signaling pathways modulated by RIP2. Based on our previous report and the present study, our data demonstrated that NOD1-RIP2 axis was important for larval survival in the early ontogenesis. Similar to NOD1, RIP2 deficiency significantly affected immune system processes. The significantly enriched pathways were mainly involved in immune system, such as "Antigen processing and presentation" and "NOD-like receptor signaling pathway" and so on. Furthermore, both transcriptome analysis and qRT-PCR revealed that RIP2 was a critical regulator for expression of NLRs (NOD-like receptors) and those genes involved in MHC antigen presentation. Different from NOD1, the present study showed that NOD1, but not RIP2 deficiency significantly impaired protein levels of MAPK pathways. Although RIP2 deficiency also significantly impaired the expression of CD44a, the downstream signaling of CD44a-Lck-PI3K-Akt pathway remained unchanged. Collectively, our works highlight the similarity and discrepancy of NOD1 and RIP2 in the regulation of immune signaling pathways in the zebrafish early ontogenesis, and confirm the crucial role of RIP2 in NLRs signaling and MHC antigen presentation, but not for MAPK and PI3K/Akt pathways.

Energy pathway analysis - a hydrogen fuel cycle framework for system studies

International Nuclear Information System (INIS)

Badin, J.S.; Tagore, S.

1997-01-01

An analytical framework has been developed that can be used to estimate a range of life-cycle costs and impacts that result from the incremental production, storage, transport, and use of different fuels or energy carriers, such as hydrogen, electricity, natural gas, and gasoline. This information is used in a comparative analysis of energy pathways. The pathways provide the U.S. Department of Energy (DOE) with an indication of near-, mid-, and long-term technologies that have the greatest potential for advancement and can meet the cost goals. The methodology and conceptual issues are discussed. Also presented are results for selected pathways from the E3 (Energy, Economics, Emissions) Pathway Analysis Model. This model will be expanded to consider networks of pathways and to be compatible with a linear programming optimization processor. Scenarios and sets of constraints (energy demands, sources, emissions) will be defined so the effects on energy transformation activities included in the solution and on the total optimized system cost can be investigated. This evaluation will be used as a guide to eliminate technically feasible pathways if they are not cost effective or do not meet the threshold requirements for the market acceptance. (Author)

PathNet: a tool for pathway analysis using topological information

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Dutta Bhaskar

2012-09-01

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

In-depth analysis of accidental criticality in a reprocessing plant

International Nuclear Information System (INIS)

Thomas, W.; Gmal, B.

1989-01-01

An in-depth-analysis including probabilistic considerations has been performed for a potential criticality excursion in two large vessels in a planned reprocessing plant. Criticality safety of these components is based on limitation of uranium and plutonium concentration. The main intention of this study was to investigate the potential and probable magnitude of a criticality in greater detail and to detect possible weaknesses of criticality safety provisions. The results of the analysis show, that the calculated probability of less than 5 · 10 -4 /a a for a criticality excursion in the most relevant rework tank may be further reduced. The peak power rework tank may be further reduced by design modifications. The peak power and total fissions of the critical excursion as assessed in a preceding analysis for licensing are conservative by factors of 10 and 4, respectively

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.

Pathway analysis of kidney cancer using proteomics and metabolic profiling

Directory of Open Access Journals (Sweden)

Fiehn Oliver

2006-11-01

Full Text Available Abstract Background Renal cell carcinoma (RCC is the sixth leading cause of cancer death and is responsible for 11,000 deaths per year in the US. Approximately one-third of patients present with disease which is already metastatic and for which there is currently no adequate treatment, and no biofluid screening tests exist for RCC. In this study, we have undertaken a comprehensive proteomic analysis and subsequently a pathway and network approach to identify biological processes involved in clear cell RCC (ccRCC. We have used these data to investigate urinary markers of RCC which could be applied to high-risk patients, or to those being followed for recurrence, for early diagnosis and treatment, thereby substantially reducing mortality of this disease. Results Using 2-dimensional electrophoresis and mass spectrometric analysis, we identified 31 proteins which were differentially expressed with a high degree of significance in ccRCC as compared to adjacent non-malignant tissue, and we confirmed some of these by immunoblotting, immunohistochemistry, and comparison to published transcriptomic data. When evaluated by several pathway and biological process analysis programs, these proteins are demonstrated to be involved with a high degree of confidence (p values Conclusion Extensive pathway and network analysis allowed for the discovery of highly significant pathways from a set of clear cell RCC samples. Knowledge of activation of these processes will lead to novel assays identifying their proteomic and/or metabolomic signatures in biofluids of patient at high risk for this disease; we provide pilot data for such a urinary bioassay. Furthermore, we demonstrate how the knowledge of networks, processes, and pathways altered in kidney cancer may be used to influence the choice of optimal therapy.

Competing endogenous RNA network analysis identifies critical genes among the different breast cancer subtypes.

Science.gov (United States)

Chen, Juan; Xu, Juan; Li, Yongsheng; Zhang, Jinwen; Chen, Hong; Lu, Jianping; Wang, Zishan; Zhao, Xueying; Xu, Kang; Li, Yixue; Li, Xia; Zhang, Yan

2017-02-07

Although competing endogenous RNAs (ceRNAs) have been implicated in many solid tumors, their roles in breast cancer subtypes are not well understood. We therefore generated a ceRNA network for each subtype based on the significance of both, positive co-expression and the shared miRNAs, in the corresponding subtype miRNA dys-regulatory network, which was constructed based on negative regulations between differentially expressed miRNAs and targets. All four subtype ceRNA networks exhibited scale-free architecture and showed that the common ceRNAs were at the core of the networks. Furthermore, the common ceRNA hubs had greater connectivity than the subtype-specific hubs. Functional analysis of the common subtype ceRNA hubs highlighted factors involved in proliferation, MAPK signaling pathways and tube morphogenesis. Subtype-specific ceRNA hubs highlighted unique subtype-specific pathways, like the estrogen response and inflammatory pathways in the luminal subtypes or the factors involved in the coagulation process that participates in the basal-like subtype. Ultimately, we identified 29 critical subtype-specific ceRNA hubs that characterized the different breast cancer subtypes. Our study thus provides new insight into the common and specific subtype ceRNA interactions that define the different categories of breast cancer and enhances our understanding of the pathology underlying the different breast cancer subtypes, which can have prognostic and therapeutic implications in the future.

Critical analysis of emerging forest biorefinery (FBR) technologies for ethanol production

International Nuclear Information System (INIS)

Cohen, J.; Janssen, M.; Chambost, V.; Stuart, P.

2010-01-01

This article provided a literature review of emerging technologies for ethanol production in Canada. A multi-criteria decision making (MCDM) panel was used to weigh critical metrics for evaluating the potential of emerging forest biorefinery technologies for bio-ethanol production. The 3-step methodology identified key factors for evaluating technology pathways. Key factors were applied to a group of selected technologies in order to collect data. All previous criteria were weighted through the MCDM panel in order to rank the technologies, which included biochemical pathway and thermochemical pathway production processes. Criteria included return on investment; feedstock flexibility; technology risk; energy and integration; products and revenue diversification; potential for additional products; and potential environmental impact. The study showed that techno-economic criteria are the most important barriers to the implementation of ethanol biorefineries. While thermochemical processes are economically feasible and provide greater flexibility, biochemical refining processes may provide for the development of other value-added products. 21 refs., 3 tabs., 7 figs.

Critical analysis of emerging forest biorefinery (FBR) technologies for ethanol production

Energy Technology Data Exchange (ETDEWEB)

Cohen, J.; Janssen, M.; Chambost, V.; Stuart, P. [Ecole Polytechnique, Montreal, PQ (Canada). Dept. de Genie Chimique. Design Engineering Chair in Process Integration

2010-05-15

This article provided a literature review of emerging technologies for ethanol production in Canada. A multi-criteria decision making (MCDM) panel was used to weigh critical metrics for evaluating the potential of emerging forest biorefinery technologies for bio-ethanol production. The 3-step methodology identified key factors for evaluating technology pathways. Key factors were applied to a group of selected technologies in order to collect data. All previous criteria were weighted through the MCDM panel in order to rank the technologies, which included biochemical pathway and thermochemical pathway production processes. Criteria included return on investment; feedstock flexibility; technology risk; energy and integration; products and revenue diversification; potential for additional products; and potential environmental impact. The study showed that techno-economic criteria are the most important barriers to the implementation of ethanol biorefineries. While thermochemical processes are economically feasible and provide greater flexibility, biochemical refining processes may provide for the development of other value-added products. 21 refs., 3 tabs., 7 figs.

An RNA-Based Fluorescent Biosensor for High-Throughput Analysis of the cGAS-cGAMP-STING Pathway.

Science.gov (United States)

Bose, Debojit; Su, Yichi; Marcus, Assaf; Raulet, David H; Hammond, Ming C

2016-12-22

In mammalian cells, the second messenger (2'-5',3'-5') cyclic guanosine monophosphate-adenosine monophosphate (2',3'-cGAMP), is produced by the cytosolic DNA sensor cGAMP synthase (cGAS), and subsequently bound by the stimulator of interferon genes (STING) to trigger interferon response. Thus, the cGAS-cGAMP-STING pathway plays a critical role in pathogen detection, as well as pathophysiological conditions including cancer and autoimmune disorders. However, studying and targeting this immune signaling pathway has been challenging due to the absence of tools for high-throughput analysis. We have engineered an RNA-based fluorescent biosensor that responds to 2',3'-cGAMP. The resulting "mix-and-go" cGAS activity assay shows excellent statistical reliability as a high-throughput screening (HTS) assay and distinguishes between direct and indirect cGAS inhibitors. Furthermore, the biosensor enables quantitation of 2',3'-cGAMP in mammalian cell lysates. We envision this biosensor-based assay as a resource to study the cGAS-cGAMP-STING pathway in the context of infectious diseases, cancer immunotherapy, and autoimmune diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

PRECLOSURE CRITICALITY ANALYSIS PROCESS REPORT

International Nuclear Information System (INIS)

Danise, A.E.

2004-01-01

This report describes a process for performing preclosure criticality analyses for a repository at Yucca Mountain, Nevada. These analyses will be performed from the time of receipt of fissile material until permanent closure of the repository (preclosure period). The process describes how criticality safety analyses will be performed for various configurations of waste in or out of waste packages that could occur during preclosure as a result of normal operations or event sequences. The criticality safety analysis considers those event sequences resulting in unanticipated moderation, loss of neutron absorber, geometric changes, or administrative errors in waste form placement (loading) of the waste package. The report proposes a criticality analyses process for preclosure to allow a consistent transition from preclosure to postclosure, thereby possibly reducing potential cost increases and delays in licensing of Yucca Mountain. The proposed approach provides the advantage of using a parallel regulatory framework for evaluation of preclosure and postclosure performance and is consistent with the U.S. Nuclear Regulatory Commission's approach of supporting risk-informed, performance-based regulation for fuel cycle facilities, ''Yucca Mountain Review Plan, Final Report'', and 10 CFR Part 63. The criticality-related criteria for ensuring subcriticality are also described as well as which guidance documents will be utilized. Preclosure operations and facilities have significant similarities to existing facilities and operations currently regulated by the U.S. Nuclear Regulatory Commission; therefore, the design approach for preclosure criticality safety will be dictated by existing regulatory requirements while using a risk-informed approach with burnup credit for in-package operations

Utilization of the MCNP-3A code for criticality safety analysis

International Nuclear Information System (INIS)

Maragni, M.G.; Moreira, J.M.L.

1996-01-01

In the last decade, Brazil started to operate facilities for processing and storing uranium in different forms. The necessity of criticality safety analysis appeared in the design phase of the uranium pilot process plants and also in the licensing of transportation and storage of fissile materials. The 2-MW research reactor and the Angra I power plant also required criticality safety assessments because their spent-fuel storage was approaching full-capacity utilization. The criticality safety analysis in Brazil has been based on KENO IV code calculations, which present some difficulties for correct geometry representation. The MCNP-3A code is not reported to be used frequently for criticality safety analysis in Brazil, but its good geometry representation makes it a possible tool for treating problems of complex geometry. A set of benchmark tests was performed to verify its applicability for criticality safety analysis in Brazil. This paper presents several benchmark tests aimed at selecting a set of options available in the MCNP-3A code that would be adequate for criticality safety analysis. The MCNP-3A code is also compared with the KENO-IV code regarding its performance for criticality safety analysis

Empowerment in critical care - a concept analysis.

Science.gov (United States)

Wåhlin, Ingrid

2017-03-01

The purpose of this paper was to analyse how the concept of empowerment is defined in the scientific literature in relation to critical care. As empowerment is a mutual process affecting all individuals involved, the perspectives of not only patients and next of kin but also staff were sought. A literature review and a concept analysis based on Walker and Avant's analysis procedure were used to identify the basic elements of empowerment in critical care. Twenty-two articles with a focus on critical care were discovered and included in the investigation. A mutual and supportive relationship, knowledge, skills, power within oneself and self-determination were found to be the common attributes of empowerment in critical care. The results could be adapted and used for all parties involved in critical care - whether patients, next of kin or staff - as these defining attributes are assumed to be universal to all three groups, even if the more specific content of each attribute varies between groups and individuals. Even if empowerment is only sparsely used in relation to critical care, it appears to be a very useful concept in this context. The benefits of improving empowerment are extensive: decreased levels of distress and strain, increased sense of coherence and control over situation, and personal and/or professional development and growth, together with increased comfort and inner satisfaction. © 2016 The Authors. Scandinavian Journal of Caring Sciences published by John Wiley & Sons Ltd on behalf of Nordic College.

Pathway analysis concepts for radiological impact assessment

International Nuclear Information System (INIS)

Moroney, J.R.

1992-06-01

The concepts underlying exposure pathways analysis are outlined with reference to the features of the two broad types of radionuclide transport models now in use - dynamic and steady-state - and the methods for constructing and developing them. By way of illustration, representative radiation doses are estimated for the four main exposure pathways likely to be involved in the land application of effluent water from Retention Pond 2 of Ranger Uranium Mines. These include: external irradiation by 226 Ra and natural uranium (Un at) in soil, ingestion of 226 Ra and Un at in food, inhalation of 222 Rn daughter products from 226 Rn in soil, and inhalation of 226 Ra and Un at in airborne dust resuspended from soil. Consideration has been given to local residents pursuing a traditional lifestyle on conclusion of the land application program. Because of the possible importance of the contribution from resuspended dust, currently available data are explored in refining the methodology for the pathway and developing a more appropriate model for it. 37 refs., 9 tabs., 6 figs

The Liverpool Care Pathway for the Dying Patient: a critical analysis of its rise, demise and legacy in England [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Jane Seymour

2018-02-01

Full Text Available Background: The Liverpool Care Pathway for the Dying Patient (‘the LCP’ was an integrated care pathway (ICP recommended by successive governments in England and Wales to improve end-of-life care, using insights from hospice and palliative care. It was discontinued in 2014 following mounting criticism and a national review.  The ensuing debate among clinicians polarised between ‘blaming’ of the LCP and regret at its removal. Employing the concept of ‘boundary objects’, we aimed to address three questions: 1 why and how did the LCP come to prominence as a vehicle of policy and practice 2 what factors contributed to its demise? 3 what immediate implications and lessons resulted from its withdrawal? Methods: We use primary and secondary sources in the public domain to assemble a critical and historical review. Results: The rapidity of transfer and translation of the LCP reflected uncritical enthusiasm for ICPs in the early 2000s. The subsequent LCP ‘scandal’ demonstrated the power of social media in creating knowledge, as well as conflicting perceptions about end-of-life interventions. While the LCP had some weaknesses in its formulation and implementation, it became the bearer of responsibility for all aspects of NHS end-of-life care. This was beyond its original remit. It exposed fault lines in the NHS, provided a platform for debates about the ‘evidence’ required to underpin innovations in palliative care and became a conduit of discord about ‘good’ or ‘bad’ practice in care of the dying. It also fostered a previously unseen critique of assumptions within palliative care.  Conclusions:  In contrast to most observers of the LCP story who refer to the dangers of scaling up clinical interventions without an evidence base, we call for greater assessment of the wider risks and more careful consideration of the unintended consequences that might result from the roll out of new end-of-life interventions.

Deep-ocean disposal of high-activity nuclear wastes: a conservative assessment of the seafood critical pathway

International Nuclear Information System (INIS)

Baxter, M.S.; Economides, B.

1984-01-01

This paper applies conventional 'worst-case' assumptions to modelling the effects of possible future disposal of high-activity wastes in the oceans. It otherwise uses previously published and generally accepted data to assess the possible intakes of the waste nuclides via consumption of seaweeds, molluscs, crustaceans, plankton and fish. Model-predicted intakes for critical groups generally exceed ICRP-recommended limits, with 244 Cm, 241 Am and 137 Cs being the most potentially hazardous nuclides. The various seafood consumption pathways are found to rank, in decreasing order of potential hazard, as seaweeds > molluscs > plankton > fish > crustaceans. (Auth.)

Stimulation of the Salicylic Acid Pathway Aboveground Recruits Entomopathogenic Nematodes Belowground.

Directory of Open Access Journals (Sweden)

Camila Cramer Filgueiras

Full Text Available Plant defense pathways play a critical role in mediating tritrophic interactions between plants, herbivores, and natural enemies. While the impact of plant defense pathway stimulation on natural enemies has been extensively explored aboveground, belowground ramifications of plant defense pathway stimulation are equally important in regulating subterranean pests and still require more attention. Here we investigate the effect of aboveground stimulation of the salicylic acid pathway through foliar application of the elicitor methyl salicylate on belowground recruitment of the entomopathogenic nematode, Steinernema diaprepesi. Also, we implicate a specific root-derived volatile that attracts S. diaprepesi belowground following aboveground plant stimulation by an elicitor. In four-choice olfactometer assays, citrus plants treated with foliar applications of methyl salicylate recruited S. diaprepesi in the absence of weevil feeding as compared with negative controls. Additionally, analysis of root volatile profiles of citrus plants receiving foliar application of methyl salicylate revealed production of d-limonene, which was absent in negative controls. The entomopathogenic nematode S. diaprepesi was recruited to d-limonene in two-choice olfactometer trials. These results reinforce the critical role of plant defense pathways in mediating tritrophic interactions, suggest a broad role for plant defense pathway signaling belowground, and hint at sophisticated plant responses to pest complexes.

Stimulation of the Salicylic Acid Pathway Aboveground Recruits Entomopathogenic Nematodes Belowground

Science.gov (United States)

Filgueiras, Camila Cramer; Willett, Denis S.; Junior, Alcides Moino; Pareja, Martin; Borai, Fahiem El; Dickson, Donald W.; Stelinski, Lukasz L.; Duncan, Larry W.

2016-01-01

Plant defense pathways play a critical role in mediating tritrophic interactions between plants, herbivores, and natural enemies. While the impact of plant defense pathway stimulation on natural enemies has been extensively explored aboveground, belowground ramifications of plant defense pathway stimulation are equally important in regulating subterranean pests and still require more attention. Here we investigate the effect of aboveground stimulation of the salicylic acid pathway through foliar application of the elicitor methyl salicylate on belowground recruitment of the entomopathogenic nematode, Steinernema diaprepesi. Also, we implicate a specific root-derived volatile that attracts S. diaprepesi belowground following aboveground plant stimulation by an elicitor. In four-choice olfactometer assays, citrus plants treated with foliar applications of methyl salicylate recruited S. diaprepesi in the absence of weevil feeding as compared with negative controls. Additionally, analysis of root volatile profiles of citrus plants receiving foliar application of methyl salicylate revealed production of d-limonene, which was absent in negative controls. The entomopathogenic nematode S. diaprepesi was recruited to d-limonene in two-choice olfactometer trials. These results reinforce the critical role of plant defense pathways in mediating tritrophic interactions, suggest a broad role for plant defense pathway signaling belowground, and hint at sophisticated plant responses to pest complexes. PMID:27136916

Effect of curcumin on aged Drosophila melanogaster: a pathway prediction analysis.

Science.gov (United States)

Zhang, Zhi-guo; Niu, Xu-yan; Lu, Ai-ping; Xiao, Gary Guishan

2015-02-01

To re-analyze the data published in order to explore plausible biological pathways that can be used to explain the anti-aging effect of curcumin. Microarray data generated from other study aiming to investigate effect of curcumin on extending lifespan of Drosophila melanogaster were further used for pathway prediction analysis. The differentially expressed genes were identified by using GeneSpring GX with a criterion of 3.0-fold change. Two Cytoscape plugins including BisoGenet and molecular complex detection (MCODE) were used to establish the protein-protein interaction (PPI) network based upon differential genes in order to detect highly connected regions. The function annotation clustering tool of Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for pathway analysis. A total of 87 genes expressed differentially in D. melanogaster melanogaster treated with curcumin were identified, among which 50 were up-regulated significantly and 37 were remarkably down-regulated in D. melanogaster melanogaster treated with curcumin. Based upon these differential genes, PPI network was constructed with 1,082 nodes and 2,412 edges. Five highly connected regions in PPI networks were detected by MCODE algorithm, suggesting anti-aging effect of curcumin may be underlined through five different pathways including Notch signaling pathway, basal transcription factors, cell cycle regulation, ribosome, Wnt signaling pathway, and p53 pathway. Genes and their associated pathways in D. melanogaster melanogaster treated with anti-aging agent curcumin were identified using PPI network and MCODE algorithm, suggesting that curcumin may be developed as an alternative therapeutic medicine for treating aging-associated diseases.

The pain, depression, disability pathway in those with low back pain: a moderation analysis of health locus of control.

Science.gov (United States)

Campbell, Paul; Hope, Kate; Dunn, Kate M

2017-01-01

Low back pain (LBP) is common, impacts on the individual and society, and is a major health concern. Psychological consequences of LBP, such as depression, are significant barriers to recovery, but mechanisms for the development of depression are less well understood. One potential mechanism is the individual's health locus of control (HLoC), that is, perception of the level of control an individual has over their health. The objective of this study is to investigate the moderation effect of HLoC on the pain-depression-disability pathway in those with LBP. The design is a nested cross-sectional analysis of two existing cohorts of patients (n=637) who had previously consulted their primary care physician about LBP. Measures were taken of HLoC, pain intensity and interference, depression, disability, and bothersomeness. Structural Equation Modeling analysis was applied to two path models that examined the pain to depression to disability pathway moderated by the HLoC constructs of Internality and Externality, respectively. Critical ratio (CR) difference tests were applied to the coefficients using pairwise comparisons. The results show that both models had an acceptable model fit and pathways were significant. CR tests indicated a significant moderation effect, with stronger pathway coefficients for depression for those who report low Internality (β 0.48), compared to those with high Internality (β 0.28). No moderation effects were found within the Externality model. HLoC Internality significantly moderates the pain-depression pathway in those with LBP, meaning that those who have a low perception of control report greater levels of depression. HLoC may signify depression among people with LBP, and could potentially be a target for intervention.

Mathematical Teaching Strategies: Pathways to Critical Thinking and Metacognition

OpenAIRE

Su, Hui Fang Huang " Ricci, Frederick A; Mnatsakanian, Mamikon

2015-01-01

A teacher that emphasizes reasoning, logic and validity gives their students access to mathematics as an effective way of practicing critical thinking. All students have the ability to enhance and expand their critical thinking when learning mathematics. Students can develop this ability when confronting mathematical problems, identifying possible solutions and evaluating and justifying their reasons for the results, thereby allowing students to become confident critical thinkers. Critical th...

Critical Discourse Analysis and Leadership

Science.gov (United States)

Arriaza, Gilberto

2015-01-01

This article outlines the need of infusing critical discourse analysis into the preparation and support of prospective school leaders. It argues that in the process of school transformation, the school leader must possess the ability to self-reflect on his/her language and understand the potential power of language as a means that may support or…

Fundamentals of critical analysis: the concept of validity and analysis essentials

Directory of Open Access Journals (Sweden)

Miguel Araujo Alonso

2012-01-01

Full Text Available Critical analysis of literature is an assessment process that allows the reader to get an idea of potential error in the results of a study, errors arising either from bias or confusion. Critical analysis attempts to establish whether the study meets expected criteria or methodological conditions. There are many checklists available that are commonly used to guide this analysis, but filling out a checklist is not tantamount to critical appraisal. Internal validity is defined as the extent to which a research finding actually represents the true relationship between exposure and outcome, considering the unique conditions in which the study was carried out. Attention must be given to the inclusion and exclusion criteria that were used, on the sampling methods, on the baseline characteristics of the patients that were enrolled in the study. External validity refers to the possibility of generalizing conclusions beyond the study sample or the study population. External validity includes population validity and ecological validity. Lastly, the article covers potential threats to external validity that must be considered when analyzing a study.

Criticality safety analysis of Hanford Waste Tank 241-101-SY

International Nuclear Information System (INIS)

Perry, R.T.; Sapir, J.L.; Krohn, B.J.

1993-01-01

As part of a safety assessment for proposed pump mixing operations to mitigate episodic gas releases in Tank 241-101-SY at the Hanford Site, Richland, Washington, a criticality safety analysis was made using the Sn transport code ONEDANT. The tank contains approximately one million gallons of waste and an estimated 910 G of plutonium. the criticality analysis considers reconfiguration and underestimation of plutonium content. The results indicate that Tank SY-101 does not present a criticality hazard. These methods are also used in criticality analyses of other Hanford tanks

A Pathway-Centered Analysis of Pig Domestication and Breeding in Eurasia

Directory of Open Access Journals (Sweden)

Jordi Leno-Colorado

2017-07-01

Full Text Available Ascertaining the molecular and physiological basis of domestication and breeding is an active area of research. Due to the current wide distribution of its wild ancestor, the wild boar, the pig (Sus scrofa is an excellent model to study these processes, which occurred independently in East Asia and Europe ca. 9000 yr ago. Analyzing genome variability patterns in terms of metabolic pathways is attractive since it considers the impact of interrelated functions of genes, in contrast to genome-wide scans that treat genes or genome windows in isolation. To that end, we studied 40 wild boars and 123 domestic pig genomes from Asia and Europe when metabolic pathway was the unit of analysis. We computed statistical significance for differentiation (Fst and linkage disequilibrium (nSL statistics at the pathway level. In terms of Fst, we found 21 and 12 pathways significantly differentiated at a q-value 10 significant pathways (in terms of Fst, comprising genes involved in the transduction of a large number of signals, like phospholipase PCLB1, which is expressed in the brain, or ITPR3, which has an important role in taste transduction. In terms of nSL, significant pathways were mainly related to reproductive performance (ovarian steroidogenesis, a similarly important target trait during domestication and modern animal breeding. Different levels of recombination cannot explain these results, since we found no correlation between Fst and recombination rate. However, we did find an increased ratio of deleterious mutations in domestic vs. wild populations, suggesting a relaxed functional constraint associated with the domestication and breeding processes. Purifying selection was, nevertheless, stronger in significantly differentiated pathways than in random pathways, mainly in Europe. We conclude that pathway analysis facilitates the biological interpretation of genome-wide studies. Notably, in the case of pig, behavior played an important role, among other

A Pathway-Centered Analysis of Pig Domestication and Breeding in Eurasia.

Science.gov (United States)

Leno-Colorado, Jordi; Hudson, Nick J; Reverter, Antonio; Pérez-Enciso, Miguel

2017-07-05

Ascertaining the molecular and physiological basis of domestication and breeding is an active area of research. Due to the current wide distribution of its wild ancestor, the wild boar, the pig ( Sus scrofa ) is an excellent model to study these processes, which occurred independently in East Asia and Europe ca. 9000 yr ago. Analyzing genome variability patterns in terms of metabolic pathways is attractive since it considers the impact of interrelated functions of genes, in contrast to genome-wide scans that treat genes or genome windows in isolation. To that end, we studied 40 wild boars and 123 domestic pig genomes from Asia and Europe when metabolic pathway was the unit of analysis. We computed statistical significance for differentiation (Fst) and linkage disequilibrium (nSL) statistics at the pathway level. In terms of Fst, we found 21 and 12 pathways significantly differentiated at a q -value 10 significant pathways (in terms of Fst), comprising genes involved in the transduction of a large number of signals, like phospholipase PCLB1, which is expressed in the brain, or ITPR3, which has an important role in taste transduction. In terms of nSL, significant pathways were mainly related to reproductive performance (ovarian steroidogenesis), a similarly important target trait during domestication and modern animal breeding. Different levels of recombination cannot explain these results, since we found no correlation between Fst and recombination rate. However, we did find an increased ratio of deleterious mutations in domestic vs. wild populations, suggesting a relaxed functional constraint associated with the domestication and breeding processes. Purifying selection was, nevertheless, stronger in significantly differentiated pathways than in random pathways, mainly in Europe. We conclude that pathway analysis facilitates the biological interpretation of genome-wide studies. Notably, in the case of pig, behavior played an important role, among other physiological

Gluconeogenesis: An ancient biochemical pathway with a new twist

OpenAIRE

Miyamoto, Tetsuya; Amrein, Hubert

2017-01-01

Synthesis of sugars from simple carbon sources is critical for survival of animals under limited nutrient availability. Thus, sugar-synthesizing enzymes should be present across the entire metazoan spectrum. Here, we explore the evolution of glucose and trehalose synthesis using a phylogenetic analysis of enzymes specific for the two pathways. Our analysis reveals that the production of trehalose is the more ancestral biochemical process, found in single cell organisms and primitive metazoans...

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

Science.gov (United States)

Li, Chaoxing; Liu, Li; Dinu, Valentin

2018-01-01

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

Endocrine-disrupting Chemicals: Review of Toxicological Mechanisms Using Molecular Pathway Analysis

Science.gov (United States)

Yang, Oneyeol; Kim, Hye Lim; Weon, Jong-Il; Seo, Young Rok

2015-01-01

Endocrine disruptors are known to cause harmful effects to human through various exposure routes. These chemicals mainly appear to interfere with the endocrine or hormone systems. As importantly, numerous studies have demonstrated that the accumulation of endocrine disruptors can induce fatal disorders including obesity and cancer. Using diverse biological tools, the potential molecular mechanisms related with these diseases by exposure of endocrine disruptors. Recently, pathway analysis, a bioinformatics tool, is being widely used to predict the potential mechanism or biological network of certain chemicals. In this review, we initially summarize the major molecular mechanisms involved in the induction of the above mentioned diseases by endocrine disruptors. Additionally, we provide the potential markers and signaling mechanisms discovered via pathway analysis under exposure to representative endocrine disruptors, bisphenol, diethylhexylphthalate, and nonylphenol. The review emphasizes the importance of pathway analysis using bioinformatics to finding the specific mechanisms of toxic chemicals, including endocrine disruptors. PMID:25853100

Critical Analysis of a Website: A Critique based on Critical Applied Linguistics and Critical Discourse Analysis

Directory of Open Access Journals (Sweden)

Rina Agustina

2013-05-01

Full Text Available E-learning was easily found through browsing internet, which was mostly free of charge and provided various learning materials. Spellingcity.com was one of e-learning websites for teaching and learning English to learn spelling, vocabulary and writing, which offered various games and activities for young learners, 6 until 8 year old learners in particular. Having considered those constraints, this paper aimed to analyse the website from two different views: (1 critical applied linguistics  (CAL aspects and (2 critical  discourse analysis (CDA. After analysing the website using CAL and CDA, it was found that the website was adequate for beginner, in which it provided fun learning through games as well as challenged learners’ to test their vocabulary. Despite of these strengths, there were several issues required further thinking in terms of learners’ broad knowledge, such as, some of learning materials focused on states in America. It was quite difficult for EFL learners if they did not have adequate general knowledge. Thus, the findings implied that the website could be used as a supporting learning material, which accompanied textbooks and vocabulary exercise books.

Life Cycle Greenhouse Gas Analysis of Multiple Vehicle Fuel Pathways in China

Directory of Open Access Journals (Sweden)

Tianduo Peng

2017-11-01

Full Text Available The Tsinghua University Life Cycle Analysis Model (TLCAM is applied to calculate the life cycle fossil energy consumption and greenhouse gas (GHG emissions for more than 20 vehicle fuel pathways in China. In addition to conventional gasoline and diesel, these include coal- and gas-based vehicle fuels, and electric vehicle (EV pathways. The results indicate the following. (1 China’s current dependence on coal and relative low-efficiency processes limits the potential for most alternative fuel pathways to decrease energy consumption and emissions; (2 Future low-carbon electricity pathways offer more obvious advantages, with coal-based pathways needing to adopt carbon dioxide capture and storage technology to compete; (3 A well-to-wheels analysis of the fossil energy consumption of vehicles fueled by compressed natural gas and liquefied natural gas (LNG showed that they are comparable to conventional gasoline vehicles. However, importing rather than domestically producing LNG for vehicle use can decrease domestic GHG emissions by 35% and 31% compared with those of conventional gasoline and diesel vehicles, respectively; (4 The manufacturing and recovery of battery and vehicle in the EV analysis has significant impact on the overall ability of EVs to decrease fossil energy consumption and GHG emissions from ICEVs.

Development of the criticality accident analysis code, AGNES

International Nuclear Information System (INIS)

Nakajima, Ken

1989-01-01

In the design works for the facilities which handle nuclear fuel, the evaluation of criticality accidents cannot be avoided even if their possibility is as small as negligible. In particular in the system using solution fuel like uranyl nitrate, solution has the property easily becoming dangerous form, and all the past criticality accidents occurred in the case of solution, therefore, the evaluation of criticality accidents becomes the most important item of safety analysis. When a criticality accident occurred in a solution fuel system, due to the generation and movement of radiolysis gas voids, the oscillation of power output and pressure pulses are observed. In order to evaluate the effect of criticality accidents, these output oscillation and pressure pulses must be calculated accurately. For this purpose, the development of the dynamic characteristic code AGNES (Accidentally Generated Nuclear Excursion Simulation code) was carried out. The AGNES is the reactor dynamic characteristic code having two independent void models. Modified energy model and pressure model, and as the benchmark calculation of the AGNES code, the results of the experimental analysis on the CRAC experiment are reported. (K.I.)

Risk and Interdependencies in Critical Infrastructures A Guideline for Analysis

CERN Document Server

Utne, Ingrid; Vatn, Jørn

2012-01-01

Today’s society is completely dependent on critical networks such as  water supply, sewage, electricity, ICT and transportation. Risk and vulnerability analyses are needed to grasp the impact of threats and hazards. However, these become quite complex as there are strong interdependencies both within and between infrastructure systems. Risk and Interdependencies in Critical Infrastructures: A  guideline for analysis provides methods for analyzing risks and interdependencies of critical infrastructures.  A number of analysis approaches are described and are adapted to each of these infrastructures. Various approaches are also revised, and all are supported by several examples and illustrations. Particular emphasis is given to the analysis of various interdependencies that often exist between the infrastructures.  Risk and Interdependencies in Critical Infrastructures: A  guideline for analysis provides a good tool to identify the hazards that are threatening your infrastructures, and will enhance the un...

Screening Analysis of Criticality Features, Events, and Processes for License Application

International Nuclear Information System (INIS)

J.A. McClure

2004-01-01

This report documents the screening analysis of postclosure criticality features, events, and processes. It addresses the probability of criticality events resulting from degradation processes as well as disruptive events (i.e., seismic, rock fall, and igneous). Probability evaluations are performed utilizing the configuration generator described in ''Configuration Generator Model'', a component of the methodology from ''Disposal Criticality Analysis Methodology Topical Report''. The total probability per package of criticality is compared against the regulatory probability criterion for inclusion of events established in 10 CFR 63.114(d) (consider only events that have at least one chance in 10,000 of occurring over 10,000 years). The total probability of criticality accounts for the evaluation of identified potential critical configurations of all baselined commercial and U.S. Department of Energy spent nuclear fuel waste form and waste package combinations, both internal and external to the waste packages. This criticality screening analysis utilizes available information for the 21-Pressurized Water Reactor Absorber Plate, 12-Pressurized Water Reactor Absorber Plate, 44-Boiling Water Reactor Absorber Plate, 24-Boiling Water Reactor Absorber Plate, and the 5-Defense High-Level Radioactive Waste/U.S. Department of Energy Short waste package types. Where defensible, assumptions have been made for the evaluation of the following waste package types in order to perform a complete criticality screening analysis: 21-Pressurized Water Reactor Control Rod, 5-Defense High-Level Radioactive Waste/U.S. Department of Energy Long, and 2-Multi-Canister Overpack/2-Defense High-Level Radioactive Waste package types. The inputs used to establish probabilities for this analysis report are based on information and data generated for the Total System Performance Assessment for the License Application, where available. This analysis report determines whether criticality is to be

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

Understanding pathways of exposure using site-specific habits surveys, particularly new pathways and methodologies

International Nuclear Information System (INIS)

Grzechnik, M.; McTaggart, K.; Clyne, F.

2006-01-01

Full text of publication follows: UK policy on the control of radiation exposure via routine discharges from nuclear licensed sites has long been based on ICRP recommendations that embody the principles of justification of practices, optimisation of protection, and dose limitation. Radiological protection of the public is based on the concept of a critical group of individuals. This group is defined as those people who, as a result of the area they reside and their habits, receive the highest radiation dose due to the operations of a site. Therefore, if the dose to this critical group is acceptable in relation to relevant dose limits and constraints, then other members of the public will receive lower doses. Thus, the principle of critical groups provides overall protection for the public. Surveys to determine local habits involve an integrated methodology, whereby the potential radioactive exposure pathways from liquid and gaseous discharges and direct radiation from the site are investigated. Surveys to identify these habits must be undertaken rigorously for consistency, and have been known to reveal unexpected pathways of radiation exposure. Pathways typically include consumption of local foodstuffs and external exposure. Furthermore, a number of critical groups ma y be identified within a single survey area if the habits of one group do not adequately describe those of the other inhabitants of the area. Survey preparation involves the initial identification of high producers and consumers of local foods in a geographically defined area surrounding the nuclear facility. Pathways can be broken down into three general groups, which include exposure arising from; 1) Terrestrial (gaseous) discharges surveyed within 5 km of the site 2) Direct radiation surveyed within 1 km of the site 3) Aquatic (liquid) discharges surveyed within local areas affected by the discharges, including seas, rivers and sewage works. The survey fieldwork involves interviewing members of the

Critical feature analysis of a radiotherapy machine

International Nuclear Information System (INIS)

Rae, Andrew; Jackson, Daniel; Ramanan, Prasad; Flanz, Jay; Leyman, Didier

2005-01-01

The software implementation of the emergency shutdown feature in a major radiotherapy system was analyzed, using a directed form of code review based on module dependences. Dependences between modules are labelled by particular assumptions; this allows one to trace through the code, and identify those fragments responsible for critical features. An 'assumption tree' is constructed in parallel, showing the assumptions which each module makes about others. The root of the assumption tree is the critical feature of interest, and its leaves represent assumptions which, if not valid, might cause the critical feature to fail. The analysis revealed some unexpected assumptions that motivated improvements to the code

21 CFR 120.8 - Hazard Analysis and Critical Control Point (HACCP) plan.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Hazard Analysis and Critical Control Point (HACCP... SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION HAZARD ANALYSIS AND CRITICAL CONTROL POINT (HACCP) SYSTEMS General Provisions § 120.8 Hazard Analysis and Critical Control Point (HACCP) plan. (a) HACCP plan. Each...

Challenges in the vulnerability and risk analysis of critical infrastructures

International Nuclear Information System (INIS)

Zio, Enrico

2016-01-01

The objective of this paper is to provide a systematic view on the problem of vulnerability and risk analysis of critical infrastructures. Reflections are made on the inherent complexities of these systems, related challenges are identified and possible ways forward for their analysis and management are indicated. Specifically: the framework of vulnerability and risk analysis is examined in relation to its application for the protection and resilience of critical infrastructures; it is argued that the complexity of these systems is a challenging characteristic, which calls for the integration of different modeling perspectives and new approaches of analysis; examples of are given in relation to the Internet and, particularly, the electric power grid, as representative of critical infrastructures and the associated complexity; the integration of different types of analyses and methods of system modeling is put forward for capturing the inherent structural and dynamic complexities of critical infrastructures and eventually evaluating their vulnerability and risk characteristics, so that decisions on protections and resilience actions can be taken with the required confidence. - Highlights: • The problem of the protection and resilience of CIs is the focus of the work. • The vulnerability and risk analysis framework for this is critically examined. • The complexity of CIs is presented as a challenge for system modeling and analysis. • The integration of different modeling perspectives of analysis is put forward as a solution. • The extension of the analysis framework to new methods for dealing with surprises and black swans is advocated.

Mutational Analysis of a Peripheral Pathway for Phospholipid Transport in ATP8A2

DEFF Research Database (Denmark)

Mogensen, Louise; Mikkelsen, Stine; Gantzel, Rasmus

2017-01-01

for conservation of classical transport elements from P2-ATPases. Moreover, T108 located at the exoplasmic end of M2 is critical to ATPase activity and lipid substrate affinity indicating that this residue could be part of an entry gate of the peripheral pathway. Overall, several findings in our study...

Searching for scientific literacy and critical pedagogy in socioscientific curricula: A critical discourse analysis

Science.gov (United States)

Cummings, Kristina M.

The omnipresence of science and technology in our society require the development of a critical and scientifically literate citizenry. However, the inclusion of socioscientific issues, which are open-ended controversial issues informed by both science and societal factors such as politics, economics, and ethics, do not guarantee the development of these skills. The purpose of this critical discourse analysis is to identify and analyze the discursive strategies used in intermediate science texts and curricula that address socioscientific topics and the extent to which the discourses are designed to promote or suppress the development of scientific literacy and a critical pedagogy. Three curricula that address the issue of energy and climate change were analyzed using Gee's (2011) building tasks and inquiry tools. The curricula were written by an education organization entitled PreSEES, a corporate-sponsored group called NEED, and a non-profit organization named Oxfam. The analysis found that the PreSEES and Oxfam curricula elevated the significance of climate change and the NEED curriculum deemphasized the issue. The PreSEES and Oxfam curricula promoted the development of scientific literacy while the NEED curricula suppressed its development. The PreSEES and Oxfam curricula both promoted the development of the critical pedagogy; however, only the Oxfam curricula provided authentic opportunities to enact sociopolitical change. The NEED curricula suppressed the development of critical pedagogy. From these findings, the following conclusions were drawn. When socioscientific issues are presented with the development of scientific literacy and critical pedagogy, the curricula allow students to develop fact-based opinions about the issue. However, curricula that address socioscientific issues without the inclusion of these skills minimize the significance of the issue and normalize the hegemonic worldview promoted by the curricula's authors. Based on these findings

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

International Nuclear Information System (INIS)

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

1983-01-01

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

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

International Nuclear Information System (INIS)

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

1984-01-01

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

Criticality safety analysis for plutonium dissolver using silver mediated electrolytic oxidation method

International Nuclear Information System (INIS)

Umeda, Miki; Sugikawa, Susumu; Nakamura, Kazuhito; Egashira, Tetsurou

1998-08-01

Design and construction of a plutonium dissolver using silver mediated electrolytic oxidation method are promoted in NUCEF. Criticality safety analysis for the plutonium dissolver is described in this report. The electrolytic plutonium dissolver consists of connection pipes and three pots for MOX powder supply, circulation and electrolysis. The criticality control for the dissolver is made by geometrically safe shape with mass limitation. Monte Carlo code KENO-IV using MGCL-137 library based on ENDF/B-IV was used for the criticality safety analysis for the plutonium dissolver. Considering the required size for construction and criticality safety, diameter of pot and distance between two pots were determined. On this condition, the criticality safety analysis for the plutonium dissolver with connection pipes was carried out. As the result of the criticality safety analysis, an effective neutron multiplication factor keff of 0.91 was obtained and the criticality safety of the plutonium dissolver was confirmed on the basis of criteria of ≤0.95. (author)

Integrated bioinformatics analysis reveals key candidate genes and pathways in breast cancer.

Science.gov (United States)

Wang, Yuzhi; Zhang, Yi; Huang, Qian; Li, Chengwen

2018-04-19

Breast cancer (BC) is the leading malignancy in women worldwide, yet relatively little is known about the genes and signaling pathways involved in BC tumorigenesis and progression. The present study aimed to elucidate potential key candidate genes and pathways in BC. Five gene expression profile data sets (GSE22035, GSE3744, GSE5764, GSE21422 and GSE26910) were downloaded from the Gene Expression Omnibus (GEO) database, which included data from 113 tumorous and 38 adjacent non‑tumorous tissue samples. Differentially expressed genes (DEGs) were identified using t‑tests in the limma R package. These DEGs were subsequently investigated by pathway enrichment analysis and a protein‑protein interaction (PPI) network was constructed. The most significant module from the PPI network was selected for pathway enrichment analysis. In total, 227 DEGs were identified, of which 82 were upregulated and 145 were downregulated. Pathway enrichment analysis results revealed that the upregulated DEGs were mainly enriched in 'cell division', the 'proteinaceous extracellular matrix (ECM)', 'ECM structural constituents' and 'ECM‑receptor interaction', whereas downregulated genes were mainly enriched in 'response to drugs', 'extracellular space', 'transcriptional activator activity' and the 'peroxisome proliferator‑activated receptor signaling pathway'. The PPI network contained 174 nodes and 1,257 edges. DNA topoisomerase 2‑a, baculoviral inhibitor of apoptosis repeat‑containing protein 5, cyclin‑dependent kinase 1, G2/mitotic‑specific cyclin‑B1 and kinetochore protein NDC80 homolog were identified as the top 5 hub genes. Furthermore, the genes in the most significant module were predominantly involved in 'mitotic nuclear division', 'mid‑body', 'protein binding' and 'cell cycle'. In conclusion, the DEGs, relative pathways and hub genes identified in the present study may aid in understanding of the molecular mechanisms underlying BC progression and provide

Critical importance of the de novo pyrimidine biosynthesis pathway for Trypanosoma cruzi growth in the mammalian host cell cytoplasm

International Nuclear Information System (INIS)

Hashimoto, Muneaki; Morales, Jorge; Fukai, Yoshihisa; Suzuki, Shigeo; Takamiya, Shinzaburo; Tsubouchi, Akiko; Inoue, Syou; Inoue, Masayuki; Kita, Kiyoshi; Harada, Shigeharu; Tanaka, Akiko; Aoki, Takashi; Nara, Takeshi

2012-01-01

Highlights: ► We established Trypanosoma cruzi lacking the gene for carbamoyl phosphate synthetase II. ► Disruption of the cpsII gene significantly reduced the growth of epimastigotes. ► In particular, the CPSII-null mutant severely retarded intracellular growth. ► The de novo pyrimidine pathway is critical for the parasite growth in the host cell. -- Abstract: The intracellular parasitic protist Trypanosoma cruzi is the causative agent of Chagas disease in Latin America. In general, pyrimidine nucleotides are supplied by both de novo biosynthesis and salvage pathways. While epimastigotes—an insect form—possess both activities, amastigotes—an intracellular replicating form of T. cruzi—are unable to mediate the uptake of pyrimidine. However, the requirement of de novo pyrimidine biosynthesis for parasite growth and survival has not yet been elucidated. Carbamoyl-phosphate synthetase II (CPSII) is the first and rate-limiting enzyme of the de novo biosynthetic pathway, and increased CPSII activity is associated with the rapid proliferation of tumor cells. In the present study, we showed that disruption of the T. cruzicpsII gene significantly reduced parasite growth. In particular, the growth of amastigotes lacking the cpsII gene was severely suppressed. Thus, the de novo pyrimidine pathway is important for proliferation of T. cruzi in the host cell cytoplasm and represents a promising target for chemotherapy against Chagas disease.

Cognitive systems engineering analysis of the JCO criticality accident

International Nuclear Information System (INIS)

Tanabe, Fumiya; Yamaguchi, Yukichi

2000-01-01

The JCO Criticality Accident is analyzed with a framework based on cognitive systems engineering. With the framework, analysis is conducted integrally both from the system viewpoint and actors viewpoint. The occupational chemical risk was important as safety constraint for the actors as well as the nuclear risk, which is due to criticality accident, to the public and to actors. The inappropriate actor's mental model of the work system played a critical role and several factors (e.g. poor training and education, lack of information on criticality safety control in the procedures and instructions, and lack of warning signs at workplace) contributed to form and shape the mental model. Based on the analysis, several countermeasures, such as warning signs, information system for supporting actors and improved training and education, are derived to prevent such an accident. (author)

Analysis of strain distribution and critical current of superconductors based on a strain-critical current measurement system

International Nuclear Information System (INIS)

Liu Fang; Wu Yu; Long Feng

2010-01-01

Based on Pacman device which is widely used to investigate the axial strain dependence of the critical current in superconductors, the finite element analysis method is employed to carry out the force analysis of the spring and the superconducting strand, thereby the axial and lateral strain distributions of the superconducting strand are obtained. According to the two extreme assumptions(low inter-filament resistance and high inter-filament resistance), the effects of the strain homogeneity at the cross section of the superconductor on the critical current is analyzed combined with the Nb 3 Sn deviatoric strain-critical current scaling law. (authors)

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

Directory of Open Access Journals (Sweden)

Chaoxing Li

2018-04-01

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

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

International Nuclear Information System (INIS)

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

2017-01-01

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

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

Science.gov (United States)

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

2017-03-09

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

Developmental transcriptomic analyses for mechanistic insights into critical pathways involved in embryogenesis of pelagic mahi-mahi (Coryphaena hippurus.

Directory of Open Access Journals (Sweden)

Elvis Genbo Xu

Full Text Available Mahi-mahi (Coryphaena hippurus is a commercially and ecologically important species of fish occurring in tropical and temperate waters worldwide. Understanding early life events is crucial for predicting effects of environmental stress, which is largely restricted by a lack of genetic resources regarding expression of early developmental genes and regulation of pathways. The need for anchoring developmental stages to transcriptional activities is highlighted by increasing evidence on the impacts of recurrent worldwide oil spills in this sensitive species during early development. By means of high throughput sequencing, we characterized the developmental transcriptome of mahi-mahi at three critical developmental stages, from pharyngula embryonic stage (24 hpf to 48 hpf yolk-sac larva (transition 1, and to 96 hpf free-swimming larva (transition 2. With comparative analysis by multiple bioinformatic tools, a larger number of significantly altered genes and more diverse gene ontology terms were observed during transition 2 than transition 1. Cellular and tissue development terms were more significantly enriched in transition 1, while metabolism related terms were more enriched in transition 2, indicating a switch progressing from general embryonic development to metabolism during the two transitions. Special focus was given on the most significant common canonical pathways (e.g. calcium signaling, glutamate receptor signaling, cAMP response element-binding protein signaling, cardiac β-adrenergic signaling, etc. and expression of developmental genes (e.g. collagens, myosin, notch, glutamate metabotropic receptor etc., which were associated with morphological changes of nervous, muscular, and cardiovascular system. These data will provide an important basis for understanding embryonic development and identifying molecular mechanisms of abnormal development in fish species.

Criticality analysis in uranium enrichment plant

International Nuclear Information System (INIS)

Okamoto, Tsuyoshi; Kiyose, Ryohei

1977-01-01

In a large scale uranium enrichment plant, uranium inventory in cascade rooms is not very large in quantity, but the facilities dealing with the largest quantity of uranium in that process are the UF 6 gas supply system and the blending system for controlling the product concentration. When UF 6 spills out of these systems, the enriched uranium is accumulated, and the danger of criticality accident is feared. If a NaF trap is placed at the forestage of waste gas treatment system, plenty of UF 6 and HF are adsorbed together in the NaF trap. Thus, here is the necessity of checking the safety against criticality. Various assumptions were made to perform the computation surveying the criticality of the system composed of UF 6 and HF adsorbed on NaF traps with WIMS code (transport analysis). The minimum critical radius resulted in about 53 cm in case of 3.5% enriched fuel for light water reactors. The optimum volume ratio of fissile material in the double salt UF 6 .2NaF and NaF.HF is about 40 vol. %. While, criticality survey computation was also made for the annular NaF trap having the central cooling tube, and it was found that the effect of cooling tube radius did not decrease the multiplication factor up to the cooling tube radius of about 5 cm. (Wakatsuki, Y.)

α-Cut method based importance measure for criticality analysis in fuzzy probability – Based fault tree analysis

International Nuclear Information System (INIS)

Purba, Julwan Hendry; Sony Tjahyani, D.T.; Widodo, Surip; Tjahjono, Hendro

2017-01-01

Highlights: •FPFTA deals with epistemic uncertainty using fuzzy probability. •Criticality analysis is important for reliability improvement. •An α-cut method based importance measure is proposed for criticality analysis in FPFTA. •The α-cut method based importance measure utilises α-cut multiplication, α-cut subtraction, and area defuzzification technique. •Benchmarking confirm that the proposed method is feasible for criticality analysis in FPFTA. -- Abstract: Fuzzy probability – based fault tree analysis (FPFTA) has been recently developed and proposed to deal with the limitations of conventional fault tree analysis. In FPFTA, reliabilities of basic events, intermediate events and top event are characterized by fuzzy probabilities. Furthermore, the quantification of the FPFTA is based on fuzzy multiplication rule and fuzzy complementation rule to propagate uncertainties from basic event to the top event. Since the objective of the fault tree analysis is to improve the reliability of the system being evaluated, it is necessary to find the weakest path in the system. For this purpose, criticality analysis can be implemented. Various importance measures, which are based on conventional probabilities, have been developed and proposed for criticality analysis in fault tree analysis. However, not one of those importance measures can be applied for criticality analysis in FPFTA, which is based on fuzzy probability. To be fully applied in nuclear power plant probabilistic safety assessment, FPFTA needs to have its corresponding importance measure. The objective of this study is to develop an α-cut method based importance measure to evaluate and rank the importance of basic events for criticality analysis in FPFTA. To demonstrate the applicability of the proposed measure, a case study is performed and its results are then benchmarked to the results generated by the four well known importance measures in conventional fault tree analysis. The results

Validating analysis methodologies used in burnup credit criticality calculations

International Nuclear Information System (INIS)

Brady, M.C.; Napolitano, D.G.

1992-01-01

The concept of allowing reactivity credit for the depleted (or burned) state of pressurized water reactor fuel in the licensing of spent fuel facilities introduces a new challenge to members of the nuclear criticality community. The primary difference in this analysis approach is the technical ability to calculate spent fuel compositions (or inventories) and to predict their effect on the system multiplication factor. Isotopic prediction codes are used routinely for in-core physics calculations and the prediction of radiation source terms for both thermal and shielding analyses, but represent an innovation for criticality specialists. This paper discusses two methodologies currently being developed to specifically evaluate isotopic composition and reactivity for the burnup credit concept. A comprehensive approach to benchmarking and validating the methods is also presented. This approach involves the analysis of commercial reactor critical data, fuel storage critical experiments, chemical assay isotopic data, and numerical benchmark calculations

Waste-to-wheel analysis of anaerobic-digestion-based renewable natural gas pathways with the GREET model

International Nuclear Information System (INIS)

Han, J.; Mintz, M.; Wang, M.

2011-01-01

In 2009, manure management accounted for 2,356 Gg or 107 billion standard cubic ft of methane (CH 4 ) emissions in the United States, equivalent to 0.5% of U.S. natural gas (NG) consumption. Owing to the high global warming potential of methane, capturing and utilizing this methane source could reduce greenhouse gas (GHG) emissions. The extent of that reduction depends on several factors - most notably, how much of this manure-based methane can be captured, how much GHG is produced in the course of converting it to vehicular fuel, and how much GHG was produced by the fossil fuel it might displace. A life-cycle analysis was conducted to quantify these factors and, in so doing, assess the impact of converting methane from animal manure into renewable NG (RNG) and utilizing the gas in vehicles. Several manure-based RNG pathways were characterized in the GREET (Greenhouse gases, Regulated Emissions, and Energy use in Transportation) model, and their fuel-cycle energy use and GHG emissions were compared to petroleum-based pathways as well as to conventional fossil NG pathways. Results show that despite increased total energy use, both fossil fuel use and GHG emissions decline for most RNG pathways as compared with fossil NG and petroleum. However, GHG emissions for RNG pathways are highly dependent on the specifics of the reference case, as well as on the process energy emissions and methane conversion factors assumed for the RNG pathways. The most critical factors are the share of flared controllable CH 4 and the quantity of CH 4 lost during NG extraction in the reference case, the magnitude of N 2 O lost in the anaerobic digestion (AD) process and in AD residue, and the amount of carbon sequestered in AD residue. In many cases, data for these parameters are limited and uncertain. Therefore, more research is needed to gain a better understanding of the range and magnitude of environmental benefits from converting animal manure to RNG via AD.

Waste-to-wheel analysis of anaerobic-digestion-based renewable natural gas pathways with the GREET model.

Energy Technology Data Exchange (ETDEWEB)

Han, J.; Mintz, M.; Wang, M. (Energy Systems)

2011-12-14

In 2009, manure management accounted for 2,356 Gg or 107 billion standard cubic ft of methane (CH{sub 4}) emissions in the United States, equivalent to 0.5% of U.S. natural gas (NG) consumption. Owing to the high global warming potential of methane, capturing and utilizing this methane source could reduce greenhouse gas (GHG) emissions. The extent of that reduction depends on several factors - most notably, how much of this manure-based methane can be captured, how much GHG is produced in the course of converting it to vehicular fuel, and how much GHG was produced by the fossil fuel it might displace. A life-cycle analysis was conducted to quantify these factors and, in so doing, assess the impact of converting methane from animal manure into renewable NG (RNG) and utilizing the gas in vehicles. Several manure-based RNG pathways were characterized in the GREET (Greenhouse gases, Regulated Emissions, and Energy use in Transportation) model, and their fuel-cycle energy use and GHG emissions were compared to petroleum-based pathways as well as to conventional fossil NG pathways. Results show that despite increased total energy use, both fossil fuel use and GHG emissions decline for most RNG pathways as compared with fossil NG and petroleum. However, GHG emissions for RNG pathways are highly dependent on the specifics of the reference case, as well as on the process energy emissions and methane conversion factors assumed for the RNG pathways. The most critical factors are the share of flared controllable CH{sub 4} and the quantity of CH{sub 4} lost during NG extraction in the reference case, the magnitude of N{sub 2}O lost in the anaerobic digestion (AD) process and in AD residue, and the amount of carbon sequestered in AD residue. In many cases, data for these parameters are limited and uncertain. Therefore, more research is needed to gain a better understanding of the range and magnitude of environmental benefits from converting animal manure to RNG via AD.

Critical analysis of science textbooks evaluating instructional effectiveness

CERN Document Server

2013-01-01

The critical analysis of science textbooks is vital in improving teaching and learning at all levels in the subject, and this volume sets out a range of academic perspectives on how that analysis should be done. Each chapter focuses on an aspect of science textbook appraisal, with coverage of everything from theoretical and philosophical underpinnings, methodological issues, and conceptual frameworks for critical analysis, to practical techniques for evaluation. Contributions from many of the most distinguished scholars in the field give this collection its sure-footed contemporary relevance, reflecting the international standards of UNESCO as well as leading research organizations such as the American Association for the Advancement of Science (whose Project 2061 is an influential waypoint in developing protocols for textbook analysis). Thus the book shows how to gauge aspects of textbooks such as their treatment of controversial issues, graphical depictions, scientific historiography, vocabulary usage, acc...

IL-1β, But Not Programed Death-1 and Programed Death Ligand Pathway, Is Critical for the Human Th17 Response to Mycobacterium tuberculosis

Science.gov (United States)

Stephen-Victor, Emmanuel; Sharma, Varun Kumar; Das, Mrinmoy; Karnam, Anupama; Saha, Chaitrali; Lecerf, Maxime; Galeotti, Caroline; Kaveri, Srinivas V.; Bayry, Jagadeesh

2016-01-01

The programed death-1 (PD-1)–programed death ligand-1 (PD-L1) and PD-L2 co-inhibitory pathway has been implicated in the evasion strategies of Mycobacterium tuberculosis. Specifically, M. tuberculosis-induced PD-L1 orchestrates expansion of regulatory T cells and suppression of Th1 response. However, the role of PD pathway in regulating Th17 response to M. tuberculosis has not been investigated. In the present report, we demonstrate that M. tuberculosis and M. tuberculosis-derived antigen fractions have differential abilities to mediate human monocyte- and dendritic cell (DC)-mediated Th17 response and were independent of expression of PD-L1 or PD-L2 on aforementioned antigen-presenting cells. Importantly, we observed that blockade of PD-L1 or PD-1 did not significantly modify either the frequencies of Th17 cells or the production of IL-17 from CD4+ T cells though IFN-γ response was significantly enhanced. On the contrary, IL-1β from monocytes and DCs were critical for the Th17 response to M. tuberculosis. Together, our results indicate that IL-1β, but not members of the programed death pathway, is critical for human Th17 response to M. tuberculosis. PMID:27867382

IL-1β but not programmed death-1 and programmed death-ligand pathway is critical for the human Th17 response to M. tuberculosis

Directory of Open Access Journals (Sweden)

Emmanuel Stephen-Victor

2016-11-01

Full Text Available The programmed death-1 (PD-1- programmed death ligand-1 (PD-L1 and PD-L2 co-inhibitory pathway has been implicated in the evasion strategies of Mycobacterium tuberculosis. Specifically, M. tuberculosis-induced PD-L1 orchestrates expansion of regulatory T cells (Tregs and suppression of Th1 response. However, the role of PD pathway in regulating Th17 response to M. tuberculosis has not been investigated. In the present report, we demonstrate that M. tuberculosis and M. tuberculosis-derived antigen fractions have differential abilities to mediate human monocyte and dendritic cell (DC-mediated Th17 response and were independent of expression of PD-L1 or PD-L2 on aforementioned antigen-presenting cells. Importantly, we observed that blockade of PD-L1 or PD-1 did not significantly modify either the frequencies of Th17 cells or the production of IL-17 from CD4+ T cells though IFN-γ response was significantly enhanced. On the contrary, IL-1β from monocytes and DCs were critical for the Th17 response to M. tuberculosis. Together, our results indicate that IL-1β but not members of the programmed death pathway is critical for human Th17 response to M. tuberculosis

American Offensive Funny Riddles: A Critical Metaphor Analysis

Directory of Open Access Journals (Sweden)

Ahmed Sahib Jabir Mubarak

2018-01-01

Full Text Available The paradox in the offensive humor lies in the assumption that what evokes laughter can be harmful for someone. Linguistically, the offense can be expressed directly and indirectly, additionally, humor, including riddles is one of the most effective ways to show offense or aggression toward someone. Humor, on the other hand, is mostly expressed indirectly. Metaphoric forms are said to be one of the most appealing strategies of humor language. The present study aims at applying a critical metaphor analysis of some randomly selected American offensive humorous riddles related to various aspects of offense like race and nation. In this approach to critical discourse analysis, the cognitive aspect is added for the sake of analyzing figurative forms like metaphor which is considered as an important part of ideology. Thus, critical metaphor analysis covers both social and cognitive aspects. It is concluded that offensive jokes (namely funny riddles can be used as a tool to measure the aggressiveness towards certain social aspects like race; on the other hand, metaphors afford indications of facets of power, inequality and people ideologies in American society.

A novel approach to select differential pathways associated with hypertrophic cardiomyopathy based on gene co‑expression analysis.

Science.gov (United States)

Chen, Xiao-Min; Feng, Ming-Jun; Shen, Cai-Jie; He, Bin; Du, Xian-Feng; Yu, Yi-Bo; Liu, Jing; Chu, Hui-Min

2017-07-01

The present study was designed to develop a novel method for identifying significant pathways associated with human hypertrophic cardiomyopathy (HCM), based on gene co‑expression analysis. The microarray dataset associated with HCM (E‑GEOD‑36961) was obtained from the European Molecular Biology Laboratory‑European Bioinformatics Institute database. Informative pathways were selected based on the Reactome pathway database and screening treatments. An empirical Bayes method was utilized to construct co‑expression networks for informative pathways, and a weight value was assigned to each pathway. Differential pathways were extracted based on weight threshold, which was calculated using a random model. In order to assess whether the co‑expression method was feasible, it was compared with traditional pathway enrichment analysis of differentially expressed genes, which were identified using the significance analysis of microarrays package. A total of 1,074 informative pathways were screened out for subsequent investigations and their weight values were also obtained. According to the threshold of weight value of 0.01057, 447 differential pathways, including folding of actin by chaperonin containing T‑complex protein 1 (CCT)/T‑complex protein 1 ring complex (TRiC), purine ribonucleoside monophosphate biosynthesis and ubiquinol biosynthesis, were obtained. Compared with traditional pathway enrichment analysis, the number of pathways obtained from the co‑expression approach was increased. The results of the present study demonstrated that this method may be useful to predict marker pathways for HCM. The pathways of folding of actin by CCT/TRiC and purine ribonucleoside monophosphate biosynthesis may provide evidence of the underlying molecular mechanisms of HCM, and offer novel therapeutic directions for HCM.

Disposal criticality analysis for immobilized plutonium: Internal configurations

International Nuclear Information System (INIS)

Gottlieb, P.; Massari, J.R.; Cloke, P.L.

1998-03-01

The analysis for immobilized Pu follows the disposal criticality analysis methodology. In this study the focus is on determining the range of chemical compositions of the configurations which can occur following the aqueous degradation processes, particularly with respect to the concentrations of uranium, plutonium, and the principal neutron absorber, gadolinium. The principal analysis tool is a mass balance program that computes the amounts of plutonium, uranium, gadolinium, and chromium in solution as a function of time with inputs from a range of possible waste form dissolution rates, stainless steel corrosion rates, and compound solubilities for the neutronically significant elements. For the waste forms and degradation modes considered here, it is possible to preclude the possibility of criticality by maintaining a plutonium loading limit. Since the presence of hafnium is shown to increase this loading limit, the defense-in-depth policy would suggest the maximization of the amount of Hf as a backup criticality control material. At the end of 1997, after this study was completed, the ceramic waste form was downselected and a new formulation was developed, with the amount of Hf increased to the point where internal criticality may no longer be possible. In addition, recent calculations indicate that GdPO 4 is insoluble over a much broader range of pH than is Gd 2 O 3 , so that its use as the Gd carrier in the waste form would provide an extra margin of defense-in-depth

Monte Carlo criticality analysis for dissolvers with neutron poison

International Nuclear Information System (INIS)

Yu, Deshun; Dong, Xiufang; Pu, Fuxiang.

1987-01-01

Criticality analysis for dissolvers with neutron poison is given on the basis of Monte Carlo method. In Monte Carlo calculations of thermal neutron group parameters for fuel pieces, neutron transport length is determined in terms of maximum cross section approach. A set of related effective multiplication factors (K eff ) are calculated by Monte Carlo method for the three cases. Related numerical results are quite useful for the design and operation of this kind of dissolver in the criticality safety analysis. (author)

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

Directory of Open Access Journals (Sweden)

Robin I. Oosterholt

2017-03-01

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

Using Proteomics To Elucidate Critical Signaling Pathways

KAUST Repository

Ahmed, Heba

2012-11-01

Despite important advances in the therapy of acute myeloid leukemia (AML) the majority of patients will die from their disease (Appelbaum, Rowe, Radich, & Dick, 2001). Characterization of the aberrant molecular pathways responsible for this malignancy provides a platform to discover alternative treatments to help alter the fate of patients. AML is characterized by a blockage in the differentiation of myeloid cells resulting in the accumulation of highly proliferating immature hematopoietic cells. Since treatments such as chemotherapy rarely destroy the leukemic cells entirely, differentiation induction therapy has become a very attractive treatment option. Interestingly, previous experiments have shown that ligation of CD44, a cell surface glycoprotein strongly expressed on all AML cells, with anti-CD44 monoclonal antibodies (mAbs) could reverse this block in differentiation of leukemic blasts regardless of the AML subtype. To expand the understanding of the cellular regulation and circuitry involved, we aim to apply quantitative phosphoproteomics to monitor dynamic changes in phosphorylation state in response to anti-CD44 treatment. Protein phosphorylation and dephosphorylation is a highly controlled biochemical process that responds to various intracellular and extracellular stimuli. As phosphorylation is a dynamic process, quantification of these phosphorylation events would be vastly insightful. The main objective of this project is to determine the differentiation-dependent phosphoproteome of AML cells upon treatment of cells with the anti-CD44 mAb.In these experiments, optimization of protein extraction, phosphopeptide enrichment and data processing and analysis has been achieved. The primary results show successful phosphoproteome extraction complemented with efficient phosphopeptide enrichment and informative data processing. Further quantification with stable isotope labeling techniques is anticipated to provide candidates for targeted therapy.

Critical parameters for isobutane determined by the image analysis

Energy Technology Data Exchange (ETDEWEB)

Masui, G. [Center for Multiscale Mechanics and Mechanical Systems, Keio University, Hiyoshi 3-14-1, Kohoku-ku, Yokohama 223-8522 (Japan); Honda, Y. [Center for Multiscale Mechanics and Mechanical Systems, Keio University, Hiyoshi 3-14-1, Kohoku-ku, Yokohama 223-8522 (Japan); Uematsu, M. [Center for Multiscale Mechanics and Mechanical Systems, Keio University, Hiyoshi 3-14-1, Kohoku-ku, Yokohama 223-8522 (Japan)]. E-mail: uematsu@mech.keio.ac.jp

2006-12-15

(p, {rho}, T) Measurements and visual observations of the meniscus for isobutane were carried out carefully in the critical region over the range of temperatures: -15 mK {<=} (T - T {sub c}) {<=} 35 mK, and of densities: -7.5 kg . m{sup -3} {<=} ({rho} - {rho} {sub c}) {<=} 7.5 kg . m{sup -3} by a metal-bellows volumometer with an optical cell. Vapor pressures were also measured at T = (310, 405, 406, 407, and 407.5) K. The critical point of T {sub c} and {rho} {sub c} was determined by the image analysis of the critical opalescence which is proposed in this study. The critical pressure p {sub c} was determined to be the pressure measurement at the critical point. Comparisons of the critical parameters with values given in the literature are presented.

Critical parameters for isobutane determined by the image analysis

International Nuclear Information System (INIS)

Masui, G.; Honda, Y.; Uematsu, M.

2006-01-01

(p, ρ, T) Measurements and visual observations of the meniscus for isobutane were carried out carefully in the critical region over the range of temperatures: -15 mK ≤ (T - T c ) ≤ 35 mK, and of densities: -7.5 kg . m -3 ≤ (ρ - ρ c ) ≤ 7.5 kg . m -3 by a metal-bellows volumometer with an optical cell. Vapor pressures were also measured at T = (310, 405, 406, 407, and 407.5) K. The critical point of T c and ρ c was determined by the image analysis of the critical opalescence which is proposed in this study. The critical pressure p c was determined to be the pressure measurement at the critical point. Comparisons of the critical parameters with values given in the literature are presented

Metabolic-flux analysis of hydrogen production pathway in Citrobacter amalonaticus Y19

Energy Technology Data Exchange (ETDEWEB)

Oh, You-Kwan; Kim, Mi-Sun [Bioenergy Research Center, Korea Institute of Energy Research, Daejeon 305-343 (Korea); Kim, Heung-Joo; Park, Sunghoon [Department of Chemical and Biochemical Engineering and Institute for Environmental Technology and Industry, Pusan National University, Busan 609-735 (Korea); Ryu, Dewey D.Y. [Biochemical Engineering Program, Department of Chemical Engineering and Material Science, University of California, Davis, CA 95616 (United States)

2008-03-15

For the newly isolated chemoheterotrophic bacterium Citrobacter amalonaticus Y19, anaerobic glucose metabolism and hydrogen (H{sub 2}) production pathway were studied using batch cultivation and an in silico metabolic-flux analysis. Batch cultivation was conducted under varying initial glucose concentration between 1.5 and 9.5 g/L with quantitative measurement of major metabolites to obtain accurate carbon material balance. The metabolic flux of Y19 was analyzed using a metabolic-pathway model which was constructed from 81 biochemical reactions. The linear optimization program MetaFluxNet was employed for the analysis. When the specific growth rate of cells was chosen as an objective function, the model described the batch culture characteristics of Ci. amalonaticus Y19 reasonably well. When the specific H{sub 2} production rate was selected as an objective function, on the other hand, the achievable maximal H{sub 2} production yield (8.7molH{sub 2}/mol glucose) and the metabolic pathway enabling the high H{sub 2} yield were identified. The pathway involved non-native NAD(P)-linked hydrogenase and H{sub 2} production from NAD(P)H which were supplied at a high rate from glucose degradation through the pentose phosphate pathway. (author)

Integrated data analysis reveals potential drivers and pathways disrupted by DNA methylation in papillary thyroid carcinomas

DEFF Research Database (Denmark)

Beltrami, Caroline Moraes; Dos Reis, Mariana Bisarro; Barros-Filho, Mateus Camargo

2017-01-01

and positive correlation, respectively. Genes showing negative correlation underlined FGF and retinoic acid signaling as critical canonical pathways disrupted by DNA methylation in PTC. BRAF mutation was detected in 68% (28 of 41) of the tumors, which presented a higher level of demethylation (95...

Synthetic lethality between gene defects affecting a single non-essential molecular pathway with reversible steps.

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Andrei Zinovyev

2013-04-01

Full Text Available Systematic analysis of synthetic lethality (SL constitutes a critical tool for systems biology to decipher molecular pathways. The most accepted mechanistic explanation of SL is that the two genes function in parallel, mutually compensatory pathways, known as between-pathway SL. However, recent genome-wide analyses in yeast identified a significant number of within-pathway negative genetic interactions. The molecular mechanisms leading to within-pathway SL are not fully understood. Here, we propose a novel mechanism leading to within-pathway SL involving two genes functioning in a single non-essential pathway. This type of SL termed within-reversible-pathway SL involves reversible pathway steps, catalyzed by different enzymes in the forward and backward directions, and kinetic trapping of a potentially toxic intermediate. Experimental data with recombinational DNA repair genes validate the concept. Mathematical modeling recapitulates the possibility of kinetic trapping and revealed the potential contributions of synthetic, dosage-lethal interactions in such a genetic system as well as the possibility of within-pathway positive masking interactions. Analysis of yeast gene interaction and pathway data suggests broad applicability of this novel concept. These observations extend the canonical interpretation of synthetic-lethal or synthetic-sick interactions with direct implications to reconstruct molecular pathways and improve therapeutic approaches to diseases such as cancer.

Pathway-based Analysis of the Hidden Genetic Heterogeneities in Cancers

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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.

Sensitivity analysis of critical experiment with direct perturbation compared to TSUNAMI-3D sensitivity analysis

International Nuclear Information System (INIS)

Barber, A. D.; Busch, R.

2009-01-01

The goal of this work is to obtain sensitivities from direct uncertainty analysis calculation and correlate those calculated values with the sensitivities produced from TSUNAMI-3D (Tools for Sensitivity and Uncertainty Analysis Methodology Implementation in Three Dimensions). A full sensitivity analysis is performed on a critical experiment to determine the overall uncertainty of the experiment. Small perturbation calculations are performed for all known uncertainties to obtain the total uncertainty of the experiment. The results from a critical experiment are only known as well as the geometric and material properties. The goal of this relationship is to simplify the uncertainty quantification process in assessing a critical experiment, while still considering all of the important parameters. (authors)

Applications of probabilistic risk analysis in nuclear criticality safety design

International Nuclear Information System (INIS)

Chang, J.K.

1992-01-01

Many documents have been prepared that try to define the scope of the criticality analysis and that suggest adding probabilistic risk analysis (PRA) to the deterministic safety analysis. The report of the US Department of Energy (DOE) AL 5481.1B suggested that an accident is credible if the occurrence probability is >1 x 10 -6 /yr. The draft DOE 5480 safety analysis report suggested that safety analyses should include the application of methods such as deterministic safety analysis, risk assessment, reliability engineering, common-cause failure analysis, human reliability analysis, and human factor safety analysis techniques. The US Nuclear Regulatory Commission (NRC) report NRC SG830.110 suggested that major safety analysis methods should include but not be limited to risk assessment, reliability engineering, and human factor safety analysis. All of these suggestions have recommended including PRA in the traditional criticality analysis

Validation of the Continuous-Energy Monte Carlo Criticality-Safety Analysis System MVP and JENDL-3.2 Using the Internationally Evaluated Criticality Benchmarks

International Nuclear Information System (INIS)

Mitake, Susumu

2003-01-01

Validation of the continuous-energy Monte Carlo criticality-safety analysis system, comprising the MVP code and neutron cross sections based on JENDL-3.2, was examined using benchmarks evaluated in the 'International Handbook of Evaluated Criticality Safety Benchmark Experiments'. Eight experiments (116 configurations) for the plutonium solution and plutonium-uranium mixture systems performed at Valduc, Battelle Pacific Northwest Laboratories, and other facilities were selected and used in the studies. The averaged multiplication factors calculated with MVP and MCNP-4B using the same neutron cross-section libraries based on JENDL-3.2 were in good agreement. Based on methods provided in the Japanese nuclear criticality-safety handbook, the estimated criticality lower-limit multiplication factors to be used as a subcriticality criterion for the criticality-safety evaluation of nuclear facilities were obtained. The analysis proved the applicability of the MVP code to the criticality-safety analysis of nuclear fuel facilities, particularly to the analysis of systems fueled with plutonium and in homogeneous and thermal-energy conditions

The c-Jun N-terminal kinase pathway is critical for cell transformation by the latent membrane protein 1 of Epstein-Barr virus

International Nuclear Information System (INIS)

Kutz, Helmut; Reisbach, Gilbert; Schultheiss, Ute; Kieser, Arnd

2008-01-01

The latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) transforms cells activating signal transduction pathways such as NF-κB, PI3-kinase, or c-Jun N-terminal kinase (JNK). Here, we investigated the functional role of the LMP1-induced JNK pathway in cell transformation. Expression of a novel dominant-negative JNK1 allele caused a block of proliferation in LMP1-transformed Rat1 fibroblasts. The JNK-specific inhibitor SP600125 reproduced this effect in Rat1-LMP1 cells and efficiently interfered with proliferation of EBV-transformed lymphoblastoid cells (LCLs). Inhibition of the LMP1-induced JNK pathway in LCLs caused the downregulation of c-Jun and Cdc2, the essential G2/M cell cycle kinase, which was accompanied by a cell cycle arrest of LCLs at G2/M phase transition. Moreover, SP600125 retarded tumor growth of LCLs in a xenograft model in SCID mice. Our data support a critical role of the LMP1-induced JNK pathway for proliferation of LMP1-transformed cells and characterize JNK as a potential target for intervention against EBV-induced malignancies

Benchmarking criticality analysis of TRIGA fuel storage racks.

Science.gov (United States)

Robinson, Matthew Loren; DeBey, Timothy M; Higginbotham, Jack F

2017-01-01

A criticality analysis was benchmarked to sub-criticality measurements of the hexagonal fuel storage racks at the United States Geological Survey TRIGA MARK I reactor in Denver. These racks, which hold up to 19 fuel elements each, are arranged at 0.61m (2 feet) spacings around the outer edge of the reactor. A 3-dimensional model was created of the racks using MCNP5, and the model was verified experimentally by comparison to measured subcritical multiplication data collected in an approach to critical loading of two of the racks. The validated model was then used to show that in the extreme condition where the entire circumference of the pool was lined with racks loaded with used fuel the storage array is subcritical with a k value of about 0.71; well below the regulatory limit of 0.8. A model was also constructed of the rectangular 2×10 fuel storage array used in many other TRIGA reactors to validate the technique against the original TRIGA licensing sub-critical analysis performed in 1966. The fuel used in this study was standard 20% enriched (LEU) aluminum or stainless steel clad TRIGA fuel. Copyright © 2016. Published by Elsevier Ltd.

Mathematical Teaching Strategies: Pathways to Critical Thinking and Metacognition

Science.gov (United States)

Su, Hui Fang Huang; Ricci, Frederick A.; Mnatsakanian, Mamikon

2016-01-01

A teacher that emphasizes reasoning, logic and validity gives their students access to mathematics as an effective way of practicing critical thinking. All students have the ability to enhance and expand their critical thinking when learning mathematics. Students can develop this ability when confronting mathematical problems, identifying possible…

Computational methods for criticality safety analysis within the scale system

International Nuclear Information System (INIS)

Parks, C.V.; Petrie, L.M.; Landers, N.F.; Bucholz, J.A.

1986-01-01

The criticality safety analysis capabilities within the SCALE system are centered around the Monte Carlo codes KENO IV and KENO V.a, which are both included in SCALE as functional modules. The XSDRNPM-S module is also an important tool within SCALE for obtaining multiplication factors for one-dimensional system models. This paper reviews the features and modeling capabilities of these codes along with their implementation within the Criticality Safety Analysis Sequences (CSAS) of SCALE. The CSAS modules provide automated cross-section processing and user-friendly input that allow criticality safety analyses to be done in an efficient and accurate manner. 14 refs., 2 figs., 3 tabs

Meta-Analysis of Placental Transcriptome Data Identifies a Novel Molecular Pathway Related to Preeclampsia.

Science.gov (United States)

van Uitert, Miranda; Moerland, Perry D; Enquobahrie, Daniel A; Laivuori, Hannele; van der Post, Joris A M; Ris-Stalpers, Carrie; Afink, Gijs B

2015-01-01

Studies using the placental transcriptome to identify key molecules relevant for preeclampsia are hampered by a relatively small sample size. In addition, they use a variety of bioinformatics and statistical methods, making comparison of findings challenging. To generate a more robust preeclampsia gene expression signature, we performed a meta-analysis on the original data of 11 placenta RNA microarray experiments, representing 139 normotensive and 116 preeclamptic pregnancies. Microarray data were pre-processed and analyzed using standardized bioinformatics and statistical procedures and the effect sizes were combined using an inverse-variance random-effects model. Interactions between genes in the resulting gene expression signature were identified by pathway analysis (Ingenuity Pathway Analysis, Gene Set Enrichment Analysis, Graphite) and protein-protein associations (STRING). This approach has resulted in a comprehensive list of differentially expressed genes that led to a 388-gene meta-signature of preeclamptic placenta. Pathway analysis highlights the involvement of the previously identified hypoxia/HIF1A pathway in the establishment of the preeclamptic gene expression profile, while analysis of protein interaction networks indicates CREBBP/EP300 as a novel element central to the preeclamptic placental transcriptome. In addition, there is an apparent high incidence of preeclampsia in women carrying a child with a mutation in CREBBP/EP300 (Rubinstein-Taybi Syndrome). The 388-gene preeclampsia meta-signature offers a vital starting point for further studies into the relevance of these genes (in particular CREBBP/EP300) and their concomitant pathways as biomarkers or functional molecules in preeclampsia. This will result in a better understanding of the molecular basis of this disease and opens up the opportunity to develop rational therapies targeting the placental dysfunction causal to preeclampsia.

SCALE system cross-section validation for criticality safety analysis

International Nuclear Information System (INIS)

Hathout, A.M.; Westfall, R.M.; Dodds, H.L. Jr.

1980-01-01

The purpose of this study is to test selected data from three cross-section libraries for use in the criticality safety analysis of UO 2 fuel rod lattices. The libraries, which are distributed with the SCALE system, are used to analyze potential criticality problems which could arise in the industrial fuel cycle for PWR and BWR reactors. Fuel lattice criticality problems could occur in pool storage, dry storage with accidental moderation, shearing and dissolution of irradiated elements, and in fuel transport and storage due to inadequate packing and shipping cask design. The data were tested by using the SCALE system to analyze 25 recently performed critical experiments

Pathway Analysis of Metabolic Syndrome Using a Genome-Wide Association Study of Korea Associated Resource (KARE Cohorts

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Unjin Shim

2014-12-01

Full Text Available Metabolic syndrome (MetS is a complex disorder related to insulin resistance, obesity, and inflammation. Genetic and environmental factors also contribute to the development of MetS, and through genome-wide association studies (GWASs, important susceptibility loci have been identified. However, GWASs focus more on individual single-nucleotide polymorphisms (SNPs, explaining only a small portion of genetic heritability. To overcome this limitation, pathway analyses are being applied to GWAS datasets. The aim of this study is to elucidate the biological pathways involved in the pathogenesis of MetS through pathway analysis. Cohort data from the Korea Associated Resource (KARE was used for analysis, which include 8,842 individuals (age, 52.2 ± 8.9 years; body mass index, 24.6 ± 3.2 kg/m2. A total of 312,121 autosomal SNPs were obtained after quality control. Pathway analysis was conducted using Meta-analysis Gene-Set Enrichment of Variant Associations (MAGENTA to discover the biological pathways associated with MetS. In the discovery phase, SNPs from chromosome 12, including rs11066280, rs2074356, and rs12229654, were associated with MetS (p < 5 × 10-6, and rs11066280 satisfied the Bonferroni-corrected cutoff (unadjusted p < 1.38 × 10-7, Bonferroni-adjusted p < 0.05. Through pathway analysis, biological pathways, including electron carrier activity, signaling by platelet-derived growth factor (PDGF, the mitogen-activated protein kinase kinase kinase cascade, PDGF binding, peroxisome proliferator-activated receptor (PPAR signaling, and DNA repair, were associated with MetS. Through pathway analysis of MetS, pathways related with PDGF, mitogen-activated protein kinase, and PPAR signaling, as well as nucleic acid binding, protein secretion, and DNA repair, were identified. Further studies will be needed to clarify the genetic pathogenesis leading to MetS.

Analysis of Membrane Protein Topology in the Plant Secretory Pathway.

Science.gov (United States)

Guo, Jinya; Miao, Yansong; Cai, Yi

2017-01-01

Topology of membrane proteins provides important information for the understanding of protein function and intermolecular associations. Integrate membrane proteins are generally transported from endoplasmic reticulum (ER) to Golgi and downstream compartments in the plant secretory pathway. Here, we describe a simple method to study membrane protein topology along the plant secretory pathway by transiently coexpressing a fluorescent protein (XFP)-tagged membrane protein and an ER export inhibitor protein, ARF1 (T31N), in tobacco BY-2 protoplast. By fractionation, microsome isolation, and trypsin digestion, membrane protein topology could be easily detected by either direct confocal microscopy imaging or western-blot analysis using specific XFP antibodies. A similar strategy in determining membrane protein topology could be widely adopted and applied to protein analysis in a broad range of eukaryotic systems, including yeast cells and mammalian cells.

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...

New enhancements to SCALE for criticality safety analysis

International Nuclear Information System (INIS)

Hollenbach, D.F.; Bowman, S.M.; Petrie, L.M.; Parks, C.V.

1995-01-01

As the speed, available memory, and reliability of computer hardware increases and the cost decreases, the complexity and usability of computer software will increase, taking advantage of the new hardware capabilities. Computer programs today must be more flexible and user friendly than those of the past. Within available resources, the SCALE staff at Oak Ridge National Laboratory (ORNL) is committed to upgrading its computer codes to keep pace with the current level of technology. This paper examines recent additions and enhancements to the criticality safety analysis sections of the SCALE code package. These recent additions and enhancements made to SCALE can be divided into nine categories: (1) new analytical computer codes, (2) new cross-section libraries, (3) new criticality search sequences, (4) enhanced graphical capabilities, (5) additional KENO enhancements, (6) enhanced resonance processing capabilities, (7) enhanced material information processing capabilities, (8) portability of the SCALE code package, and (9) other minor enhancements, modifications, and corrections to SCALE. Each of these additions and enhancements to the criticality safety analysis capabilities of the SCALE code system are discussed below

Critical evaluation of substitution of natural gas by biogas

International Nuclear Information System (INIS)

Behrendt, F.

2009-01-01

Biogas use in Germany's distribution grid is regulated by the federal integrated energy and climate program. The key measures that influence the biogas feed-in include core regulation; changes to the act grating feed-in preference for electricity generated from renewable energies; regulation for heat supply from renewable energies; and regulations regarding biofuels. A critical evaluation of substitution of natural gas by biogas was presented. Specific topics that were discussed included aims and measures; potential; usage pathways for biogas; efficiency criteria of usage pathways; and location analysis. The presentation also discussed the parameters of raw biogas and regular distribution grid; a process chain for biogas upgrading; and criteria for process evaluation. It was concluded that costs and environmental relevance of biogas-processing can be compared over the complete life cycle for various pathways and configurations. This represented an excellent and very flexible planning tool. Subsidies and related measures could be focussed on the most efficient pathways. tabs., figs.

Pathways to Medical Home Recognition: A Qualitative Comparative Analysis of the PCMH Transformation Process.

Science.gov (United States)

Mendel, Peter; Chen, Emily K; Green, Harold D; Armstrong, Courtney; Timbie, Justin W; Kress, Amii M; Friedberg, Mark W; Kahn, Katherine L

2017-12-15

To understand the process of practice transformation by identifying pathways for attaining patient-centered medical home (PCMH) recognition. The CMS Federally Qualified Health Center (FQHC) Advanced Primary Care Practice Demonstration was designed to help FQHCs achieve NCQA Level 3 PCMH recognition and improve patient outcomes. We used a stratified random sample of 20 (out of 503) participating sites for this analysis. We developed a conceptual model of structural, cultural, and implementation factors affecting PCMH transformation based on literature and initial qualitative interview themes. We then used conventional cross-case analysis, followed by qualitative comparative analysis (QCA), a cross-case method based on Boolean logic algorithms, to systematically identify pathways (i.e., combinations of factors) associated with attaining-or not attaining-Level 3 recognition. Site-level indicators were derived from semistructured interviews with site leaders at two points in time (mid- and late-implementation) and administrative data collected prior to and during the demonstration period. The QCA results identified five distinct pathways to attaining PCMH recognition and four distinct pathways to not attaining recognition by the end of the demonstration. Across these pathways, one condition (change leader capacity) was common to all pathways for attaining recognition, and another (previous improvement or recognition experience) was absent in all pathways for not attaining recognition. In general, sites could compensate for deficiencies in one factor with capacity in others, but they needed a threshold of strengths in cultural and implementation factors to attain PCMH recognition. Future efforts at primary care transformation should take into account multiple pathways sites may pursue. Sites should be assessed on key cultural and implementation factors, in addition to structural components, in order to differentiate interventions and technical assistance. © Health

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

Directory of Open Access Journals (Sweden)

Zhike Zi

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

Genome wide expression analysis in HPV16 Cervical Cancer: identification of altered metabolic pathways

Directory of Open Access Journals (Sweden)

Salcedo Mauricio

2007-09-01

Full Text Available Abstract Background Cervical carcinoma (CC is a leading cause of death among women worldwide. Human papilloma virus (HPV is a major etiological factor in CC and HPV 16 is the more frequent viral type present. Our aim was to characterize metabolic pathways altered in HPV 16 tumor samples by means of transcriptome wide analysis and bioinformatics tools for visualizing expression data in the context of KEGG biological pathways. Results We found 2,067 genes significantly up or down-modulated (at least 2-fold in tumor clinical samples compared to normal tissues, representing ~3.7% of analyzed genes. Cervical carcinoma was associated with an important up-regulation of Wnt signaling pathway, which was validated by in situ hybridization in clinical samples. Other up-regulated pathways were those of calcium signaling and MAPK signaling, as well as cell cycle-related genes. There was down-regulation of focal adhesion, TGF-β signaling, among other metabolic pathways. Conclusion This analysis of HPV 16 tumors transcriptome could be useful for the identification of genes and molecular pathways involved in the pathogenesis of cervical carcinoma. Understanding the possible role of these proteins in the pathogenesis of CC deserves further studies.

Proliferation Resistance: Acquisition/Diversion Pathway Analysis for the DUPIC Fuel Cycle

International Nuclear Information System (INIS)

Ko, Won Il; Chang, Hong Lae; Song, Dae Yong; Lee, Ho Hee; Kwon, Eun Ha; Jeong, Chang Joon; Kim, Ho Dong

2009-07-01

Within the International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO), a methodology for evaluating proliferation resistance (INPRO PR methodology) has been developed. However, it remains to develop the methodology to evaluate User Requirements (UR) 4 regarding multiplicity and robustness of barriers against proliferation - innovative nuclear energy systems should incorporate multiple proliferation resistance features and measures. Since this requires an acquisition/diversion pathway analysis, this report describes a systematic approach developed for the identification and analysis of pathways for the acquisition of weapons-usable nuclear material using the DUPIC fuel cycle system. At the first step, the objectives of the proliferation were identified, including the quality and quantity of the material, the time required to acquire the material for the proliferation, thr capability of the potential proliferant country, etc. At the second step, the possible strategies, which the potential proliferant country could adopt, were identified: undeclared removal of nuclear material from the fuel cycle facilities; and further treatment of the diverted nuclear materials needed to acquire weapons-usable materials. At the final step, a systematic approach to select the plausible pathways for the acquisition/diversion of nuclear material during the whole fuel cycle has been developed. The coarse material diversion pathways for the DUPIC fuel cycle and the approach developed was reviewed and discussed at the experts meeting at the IAEA for its appropriateness and comprehensiveness

Critical Analysis of Boko Haram Insurgency

Science.gov (United States)

2017-06-09

insurgency, which poses a threat and problem to the Nigerian government. This research will consult and refer to materials, books , internet, articles, and...this paper recommends the government of Nigeria use efforts to defeat the group focused on; socio economic development, improved intelligence network...College or any other governmental agency. ( References to this study should include the foregoing statement.) iv ABSTRACT A CRITICAL ANALYSIS OF

Critical parameters for propane determined by the image analysis

Energy Technology Data Exchange (ETDEWEB)

Honda, Y.; Sato, T. [Center for Multiscale Mechanics and Mechanical Systems, Keio University, Hiyoshi 3-14-1, Kohoku-ku, Yokohama 223-8522 (Japan); Uematsu, M. [Center for Multiscale Mechanics and Mechanical Systems, Keio University, Hiyoshi 3-14-1, Kohoku-ku, Yokohama 223-8522 (Japan)], E-mail: uematsu@mech.keio.ac.jp

2008-02-15

The (p, {rho}, T) measurements and visual observations of the meniscus for propane were carried out carefully in the critical region over the range of temperatures: -60 mK {<=} (T - T{sub c}) {<=} 40 mK and of densities: -4 kg . m{sup -3} {<=} ({rho} - {rho}{sub c}) {<=} 6 kg . m{sup -3} by a metal-bellows volumometer with an optical cell. Vapour pressures were also measured at T = (320.000, 343.132, 369.000, and 369.625) K. The critical point of T{sub c}, {rho}{sub c}, and p{sub c} was determined by the image analysis of the critical opalescence. Comparisons of the critical parameters with values given in the literature are presented.

Critical parameters for propane determined by the image analysis

International Nuclear Information System (INIS)

Honda, Y.; Sato, T.; Uematsu, M.

2008-01-01

The (p, ρ, T) measurements and visual observations of the meniscus for propane were carried out carefully in the critical region over the range of temperatures: -60 mK ≤ (T - T c ) ≤ 40 mK and of densities: -4 kg . m -3 ≤ (ρ - ρ c ) ≤ 6 kg . m -3 by a metal-bellows volumometer with an optical cell. Vapour pressures were also measured at T = (320.000, 343.132, 369.000, and 369.625) K. The critical point of T c , ρ c , and p c was determined by the image analysis of the critical opalescence. Comparisons of the critical parameters with values given in the literature are presented

Pathway-based factor analysis of gene expression data produces highly heritable phenotypes that associate with age.

Science.gov (United States)

Anand Brown, Andrew; Ding, Zhihao; Viñuela, Ana; Glass, Dan; Parts, Leopold; Spector, Tim; Winn, John; Durbin, Richard

2015-03-09

Statistical factor analysis methods have previously been used to remove noise components from high-dimensional data prior to genetic association mapping and, in a guided fashion, to summarize biologically relevant sources of variation. Here, we show how the derived factors summarizing pathway expression can be used to analyze the relationships between expression, heritability, and aging. We used skin gene expression data from 647 twins from the MuTHER Consortium and applied factor analysis to concisely summarize patterns of gene expression to remove broad confounding influences and to produce concise pathway-level phenotypes. We derived 930 "pathway phenotypes" that summarized patterns of variation across 186 KEGG pathways (five phenotypes per pathway). We identified 69 significant associations of age with phenotype from 57 distinct KEGG pathways at a stringent Bonferroni threshold ([Formula: see text]). These phenotypes are more heritable ([Formula: see text]) than gene expression levels. On average, expression levels of 16% of genes within these pathways are associated with age. Several significant pathways relate to metabolizing sugars and fatty acids; others relate to insulin signaling. We have demonstrated that factor analysis methods combined with biological knowledge can produce more reliable phenotypes with less stochastic noise than the individual gene expression levels, which increases our power to discover biologically relevant associations. These phenotypes could also be applied to discover associations with other environmental factors. Copyright © 2015 Brown et al.

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.

Comparative Criticality Analysis of Two Monte Carlo Codes on Centrifugal Atomizer: MCNPS and SCALE

International Nuclear Information System (INIS)

Kang, H-S; Jang, M-S; Kim, S-R; Park, J-M; Kim, K-N

2015-01-01

There are two well-known Monte Carlo codes for criticality analysis, MCNP5 and SCALE. MCNP5 is a general-purpose Monte Carlo N-Particle code that can be used for neutron, photon, electron or coupled neutron / photon / electron transport, including the capability to calculate eigenvalues for critical system as a main analysis code. SCALE provides a comprehensive, verified and validated, user-friendly tool set for criticality safety, reactor physics, radiation shielding, radioactive source term characterization, and sensitivity and uncertainty analysis. SCALE was conceived and funded by US NRC to perform standardized computer analysis for licensing evaluation and is used widely in the world. We performed a validation test of MCNP5 and a comparative analysis of Monte Carlo codes, MCNP5 and SCALE, in terms of the critical analysis of centrifugal atomizer. In the criticality analysis using MCNP5 code, we obtained the statistically reliable results by using a large number of source histories per cycle and performing of uncertainty analysis

Comparative Criticality Analysis of Two Monte Carlo Codes on Centrifugal Atomizer: MCNPS and SCALE

Energy Technology Data Exchange (ETDEWEB)

Kang, H-S; Jang, M-S; Kim, S-R [NESS, Daejeon (Korea, Republic of); Park, J-M; Kim, K-N [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2015-10-15

There are two well-known Monte Carlo codes for criticality analysis, MCNP5 and SCALE. MCNP5 is a general-purpose Monte Carlo N-Particle code that can be used for neutron, photon, electron or coupled neutron / photon / electron transport, including the capability to calculate eigenvalues for critical system as a main analysis code. SCALE provides a comprehensive, verified and validated, user-friendly tool set for criticality safety, reactor physics, radiation shielding, radioactive source term characterization, and sensitivity and uncertainty analysis. SCALE was conceived and funded by US NRC to perform standardized computer analysis for licensing evaluation and is used widely in the world. We performed a validation test of MCNP5 and a comparative analysis of Monte Carlo codes, MCNP5 and SCALE, in terms of the critical analysis of centrifugal atomizer. In the criticality analysis using MCNP5 code, we obtained the statistically reliable results by using a large number of source histories per cycle and performing of uncertainty analysis.

Meta-Analysis of Placental Transcriptome Data Identifies a Novel Molecular Pathway Related to Preeclampsia.

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Miranda van Uitert

Full Text Available Studies using the placental transcriptome to identify key molecules relevant for preeclampsia are hampered by a relatively small sample size. In addition, they use a variety of bioinformatics and statistical methods, making comparison of findings challenging. To generate a more robust preeclampsia gene expression signature, we performed a meta-analysis on the original data of 11 placenta RNA microarray experiments, representing 139 normotensive and 116 preeclamptic pregnancies. Microarray data were pre-processed and analyzed using standardized bioinformatics and statistical procedures and the effect sizes were combined using an inverse-variance random-effects model. Interactions between genes in the resulting gene expression signature were identified by pathway analysis (Ingenuity Pathway Analysis, Gene Set Enrichment Analysis, Graphite and protein-protein associations (STRING. This approach has resulted in a comprehensive list of differentially expressed genes that led to a 388-gene meta-signature of preeclamptic placenta. Pathway analysis highlights the involvement of the previously identified hypoxia/HIF1A pathway in the establishment of the preeclamptic gene expression profile, while analysis of protein interaction networks indicates CREBBP/EP300 as a novel element central to the preeclamptic placental transcriptome. In addition, there is an apparent high incidence of preeclampsia in women carrying a child with a mutation in CREBBP/EP300 (Rubinstein-Taybi Syndrome. The 388-gene preeclampsia meta-signature offers a vital starting point for further studies into the relevance of these genes (in particular CREBBP/EP300 and their concomitant pathways as biomarkers or functional molecules in preeclampsia. This will result in a better understanding of the molecular basis of this disease and opens up the opportunity to develop rational therapies targeting the placental dysfunction causal to preeclampsia.

Cytogenomic Integrative Network Analysis of the Critical Region Associated with Wolf-Hirschhorn Syndrome

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Thiago Corrêa

2018-01-01

Full Text Available Deletions in the 4p16.3 region are associated with Wolf-Hirschhorn syndrome (WHS, a contiguous gene deletion syndrome involving variable size deletions. In this study, we perform a cytogenomic integrative analysis combining classical cytogenetic methods, fluorescence in situ hybridization (FISH, chromosomal microarray analysis (CMA, and systems biology strategies, to establish the cytogenomic profile involving the 4p16.3 critical region and suggest WHS-related intracellular cell signaling cascades. The cytogenetic and clinical patient profiles were evaluated. We characterized 12 terminal deletions, one interstitial deletion, two ring chromosomes, and one classical translocation 4;8. CMA allowed delineation of the deletions, which ranged from 3.7 to 25.6 Mb with breakpoints from 4p16.3 to 4p15.33. Furthermore, the smallest region of overlapping (SRO encompassed seven genes in a terminal region of 330 kb in the 4p16.3 region, suggesting a region of susceptibility to convulsions and microcephaly. Therefore, molecular interaction networks and topological analysis were performed to understand these WHS-related symptoms. Our results suggest that specific cell signaling pathways including dopamine receptor, NAD+ nucleosidase activity, and fibroblast growth factor-activated receptor activity are associated with the diverse pathological WHS phenotypes and their symptoms. Additionally, we identified 29 hub-bottlenecks (H-B nodes with a major role in WHS.

Partnering for Research: A Critical Discourse Analysis

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Irving, Catherine J.; English, Leona M.

2008-01-01

Using a critical discourse analysis, informed by poststructuralist theory, we explore the research phenomenon of coerced partnership. This lens allows us to pay attention to the social relations of power operating in knowledge generation processes, especially as they affect feminist researchers in adult education. We propose an alternative vision…

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...

Uncovering transcription factor and microRNA risk regulatory pathways associated with osteoarthritis by network analysis.

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Song, Zhenhua; Zhang, Chi; He, Lingxiao; Sui, Yanfang; Lin, Xiafei; Pan, Jingjing

2018-05-01

Osteoarthritis (OA) is the most common form of joint disease. The development of inflammation have been considered to play a key role during the progression of OA. Regulatory pathways are known to play crucial roles in many pathogenic processes. Thus, deciphering these risk regulatory pathways is critical for elucidating the mechanisms underlying OA. We constructed an OA-specific regulatory network by integrating comprehensive curated transcription and post-transcriptional resource involving transcription factor (TF) and microRNA (miRNA). To deepen our understanding of underlying molecular mechanisms of OA, we developed an integrated systems approach to identify OA-specific risk regulatory pathways. In this study, we identified 89 significantly differentially expressed genes between normal and inflamed areas of OA patients. We found the OA-specific regulatory network was a standard scale-free network with small-world properties. It significant enriched many immune response-related functions including leukocyte differentiation, myeloid differentiation and T cell activation. Finally, 141 risk regulatory pathways were identified based on OA-specific regulatory network, which contains some known regulator of OA. The risk regulatory pathways may provide clues for the etiology of OA and be a potential resource for the discovery of novel OA-associated disease genes. Copyright © 2018 Elsevier Inc. All rights reserved.

Gluconeogenesis: An ancient biochemical pathway with a new twist.

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Miyamoto, Tetsuya; Amrein, Hubert

2017-07-03

Synthesis of sugars from simple carbon sources is critical for survival of animals under limited nutrient availability. Thus, sugar-synthesizing enzymes should be present across the entire metazoan spectrum. Here, we explore the evolution of glucose and trehalose synthesis using a phylogenetic analysis of enzymes specific for the two pathways. Our analysis reveals that the production of trehalose is the more ancestral biochemical process, found in single cell organisms and primitive metazoans, but also in insects. The gluconeogenic-specific enzyme glucose-6-phosphatase (G6Pase) first appears in Cnidaria, but is also present in Echinodermata, Mollusca and Vertebrata. Intriguingly, some species of nematodes and arthropods possess the genes for both pathways. Moreover, expression data from Drosophila suggests that G6Pase and, hence, gluconeogenesis, initially had a neuronal function. We speculate that in insects-and possibly in some vertebrates-gluconeogenesis may be used as a means of neuronal signaling.

Extending in silico mechanism-of-action analysis by annotating targets with pathways: application to cellular cytotoxicity readouts.

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Liggi, Sonia; Drakakis, Georgios; Koutsoukas, Alexios; Cortes-Ciriano, Isidro; Martínez-Alonso, Patricia; Malliavin, Thérèse E; Velazquez-Campoy, Adrian; Brewerton, Suzanne C; Bodkin, Michael J; Evans, David A; Glen, Robert C; Carrodeguas, José Alberto; Bender, Andreas

2014-01-01

An in silico mechanism-of-action analysis protocol was developed, comprising molecule bioactivity profiling, annotation of predicted targets with pathways and calculation of enrichment factors to highlight targets and pathways more likely to be implicated in the studied phenotype. The method was applied to a cytotoxicity phenotypic endpoint, with enriched targets/pathways found to be statistically significant when compared with 100 random datasets. Application on a smaller apoptotic set (10 molecules) did not allowed to obtain statistically relevant results, suggesting that the protocol requires modification such as analysis of the most frequently predicted targets/annotated pathways. Pathway annotations improved the mechanism-of-action information gained by target prediction alone, allowing a better interpretation of the predictions and providing better mapping of targets onto pathways.

Analysis of Stomatal Patterning in Selected Mutants of MAPK Pathways

KAUST Repository

Felemban, Abrar

2016-05-01

Stomata are cellular valves in plants that play an essential role in the regulation of gas exchange and are distributed in the epidermis of aerial organs. In Arabidopsis thaliana, stomatal production and development are coordinated by the mitogen-activated protein kinase (MAPK) signalling pathway, which modulates a variety of other processes, including cell proliferation, regulation of cytokinesis, programed cell death, and response to abiotic and biotic stress. The environment also plays a role in stomatal development, by influencing the frequency at which stomata develop in leaves. This thesis presents an analysis of stomatal development in Arabidopsis mutants in two MAPK pathways: MEKK1-MKK1/MKK2-MPK4, and MAP3K17/18-MKK3. Obtained results demonstrate the effect of stress conditions on stomatal development and specify the involvement of analysed MAPK in stomatal patterning. First, both analysed pathways modulate stomatal patterning in Arabidopsis cotyledons. Second, plant growth-promoting bacteria tested enhance stomatal density and affect guard cell morphology. Third, the sucrose or mannitol treatment increases defects in stomatal patterning. Finally, salt stress or high temperature can suppress stomatal defects in mutants of the MEKK1-MKK1/MKK2-MPK4 pathway.

Critical Discourse Analysis in Literacy Education: A Review of the Literature

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Rogers, Rebecca; Schaenen, Inda

2014-01-01

This article is a critical, integrative literature review of scholarship in literacy studies from 2004 to 2012 that draws on critical discourse analysis (CDA). We discuss key issues, trends, and criticisms in the field. Our methodology was carried out in three stages. First, we searched educational databases to locate literacy-focused CDA…

Disposal criticality analysis for aluminum-based DOE fuels

International Nuclear Information System (INIS)

Davis, J.W.; Gottlieb, P.

1997-11-01

This paper describes the disposal criticality analysis for canisters containing aluminum-based Department of Energy fuels from research reactors. Different canisters were designed for disposal of highly enriched uranium (HEU) and medium enriched uranium (MEU) fuel. In addition to the standard criticality concerns in storage and transportation, such as flooding, the disposal criticality analysis must consider the degradation of the fuel and components within the waste package. Massachusetts Institute of Technology (MIT) U-Al fuel with 93.5% enriched uranium and Oak Ridge Research Reactor (ORR) U-Si-Al fuel with 21% enriched uranium are representative of the HEU and MEU fuel inventories, respectively. Conceptual canister designs with 64 MIT assemblies (16/layer, 4 layers) or 40 ORR assemblies (10/layer, 4 layers) were developed for these fuel types. Borated stainless steel plates were incorporated into a stainless steel internal basket structure within a 439 mm OD, 15 mm thick XM-19 canister shell. The Codisposal waste package contains 5 HLW canisters (represented by 5 Defense Waste Processing Facility canisters from the Savannah River Site) with the fuel canister placed in the center. It is concluded that without the presence of a fairly insoluble neutron absorber, the long-term action of infiltrating water can lead to a small, but significant, probability of criticality for both the HEU and MEU fuels. The use of 1.5kg of Gd distributed throughout the MIT fuel and the use of carbon steels for the structural basket or 1.1 kg of Gd distributed in the ORR fuel will reduce the probability of criticality to virtually zero for both fuels

Science education as a pathway to teaching language literacy: a critical book review

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Tolbert, Sara

2011-03-01

In this paper, I present a critical review of the recent book, Science Education as a Pathway to Teaching Language Literacy, edited by Alberto J. Rodriguez. This volume is a timely collection of essays in which the authors bring to attention both the successes and challenges of integrating science instruction with literacy instruction (and vice versa). Although several themes in the book merit further attention, a central unifying issue throughout all of the chapters is the task of designing instruction which (1) gives students access to the dominant Discourses in science and literacy, (2) builds on students' lived experiences, and (3) connects new material to socially and culturally relevant contexts in both science and literacy instruction— all within the high stakes testing realities of teachers and students in public schools. In this review, I illustrate how the authors of these essays effectively address this formidable challenge through research that `ascends to the concrete'. I also discuss where we could build on the work of the authors to integrate literacy and science instruction with the purpose of `humanizing and democratizing' science education in K-12 classrooms.

Pathway and network-based analysis of genome-wide association studies and RT-PCR validation in polycystic ovary syndrome.

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Shen, Haoran; Liang, Zhou; Zheng, Saihua; Li, Xuelian

2017-11-01

The purpose of this study was to identify promising candidate genes and pathways in polycystic ovary syndrome (PCOS). Microarray dataset GSE345269 obtained from the Gene Expression Omnibus database includes 7 granulosa cell samples from PCOS patients, and 3 normal granulosa cell samples. Differentially expressed genes (DEGs) were screened between PCOS and normal samples. Pathway enrichment analysis was conducted for DEGs using ClueGO and CluePedia plugin of Cytoscape. A Reactome functional interaction (FI) network of the DEGs was built using ReactomeFIViz, and then network modules were extracted, followed by pathway enrichment analysis for the modules. Expression of DEGs in granulosa cell samples was measured using quantitative RT-PCR. A total of 674 DEGs were retained, which were significantly enriched with inflammation and immune-related pathways. Eight modules were extracted from the Reactome FI network. Pathway enrichment analysis revealed significant pathways of each module: module 0, Regulation of RhoA activity and Signaling by Rho GTPases pathways shared ARHGAP4 and ARHGAP9; module 2, GlycoProtein VI-mediated activation cascade pathway was enriched with RHOG; module 3, Thromboxane A2 receptor signaling, Chemokine signaling pathway, CXCR4-mediated signaling events pathways were enriched with LYN, the hub gene of module 3. Results of RT-PCR confirmed the finding of the bioinformatic analysis that ARHGAP4, ARHGAP9, RHOG and LYN were significantly upregulated in PCOS. RhoA-related pathways, GlycoProtein VI-mediated activation cascade pathway, ARHGAP4, ARHGAP9, RHOG and LYN may be involved in the pathogenesis of PCOS.

Penalized differential pathway analysis of integrative oncogenomics studies.

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

2014-04-01

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

Critical incident analysis through narrative reflective practice: A case study

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Thomas S. C. Farrell

2013-01-01

Full Text Available Teachers can reflect on their practices by articulating and exploring incidents they consider critical to themselves or others. By talking about these critical incidents, teachers can make better sense of seemingly random experiences that occur in their teaching because they hold the real inside knowledge, especially personal intuitive knowledge, expertise and experience that is based on their accumulated years as language educators teaching in schools and classrooms. This paper is about one such critical incident analysis that an ESL teacher in Canada revealed to her critical friend and how both used McCabe’s (2002 narrative framework for analyzing an important critical incident that occurred in the teacher’s class.

Large-scale transcriptome analysis reveals arabidopsis metabolic pathways are frequently influenced by different pathogens.

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Jiang, Zhenhong; He, Fei; Zhang, Ziding

2017-07-01

Through large-scale transcriptional data analyses, we highlighted the importance of plant metabolism in plant immunity and identified 26 metabolic pathways that were frequently influenced by the infection of 14 different pathogens. Reprogramming of plant metabolism is a common phenomenon in plant defense responses. Currently, a large number of transcriptional profiles of infected tissues in Arabidopsis (Arabidopsis thaliana) have been deposited in public databases, which provides a great opportunity to understand the expression patterns of metabolic pathways during plant defense responses at the systems level. Here, we performed a large-scale transcriptome analysis based on 135 previously published expression samples, including 14 different pathogens, to explore the expression pattern of Arabidopsis metabolic pathways. Overall, metabolic genes are significantly changed in expression during plant defense responses. Upregulated metabolic genes are enriched on defense responses, and downregulated genes are enriched on photosynthesis, fatty acid and lipid metabolic processes. Gene set enrichment analysis (GSEA) identifies 26 frequently differentially expressed metabolic pathways (FreDE_Paths) that are differentially expressed in more than 60% of infected samples. These pathways are involved in the generation of energy, fatty acid and lipid metabolism as well as secondary metabolite biosynthesis. Clustering analysis based on the expression levels of these 26 metabolic pathways clearly distinguishes infected and control samples, further suggesting the importance of these metabolic pathways in plant defense responses. By comparing with FreDE_Paths from abiotic stresses, we find that the expression patterns of 26 FreDE_Paths from biotic stresses are more consistent across different infected samples. By investigating the expression correlation between transcriptional factors (TFs) and FreDE_Paths, we identify several notable relationships. Collectively, the current study

ANALYSIS OF THE PRODUCTION OF KNOWLEDGE AND INTERDISCIPLINARY PERSPECTIVE: CRITICAL ANNOTATIONS

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Kátia Oliver Sá

2014-06-01

Full Text Available The work raises critical notes on the analysis of knowledge production starting from elements of reality that feeds the logic that prevails in the world of capital and the production of scientific knowledge. Points to the critical analysis process in interdisciplinary perspective backed on the historical conception of the philosophical tradition, considering fundamentals of dialectical method to the concrete elements in scientific thinking.

Criticality Analysis Of TCA Critical Lattices With MNCP-4C Monte Carlo Calculation

International Nuclear Information System (INIS)

Zuhair

2002-01-01

The use of uranium-plutonium mixed oxide (MOX) fuel in electric generation light water reactor (PWR, BWR) is being planned in Japan. Therefore, the accuracy evaluations of neutronic analysis code for MOX cores have been employed by many scientists and reactor physicists. Benchmark evaluations for TCA was done using various calculation methods. The Monte Carlo become the most reliable method to predict criticality of various reactor types. In this analysis, the MCNP-4C code was chosen because various superiorities the code has. All in all, the MCNP-4C calculation for TCA core with 38 MOX critical lattice configurations gave the results with high accuracy. The JENDL-3.2 library showed significantly closer results to the ENDF/B-V. The k eff values calculated with the ENDF/B-VI library gave underestimated results. The ENDF/B-V library gave the best estimation. It can be concluded that MCNP-4C calculation, especially with ENDF/B-V and JENDL-3.2 libraries, for MOX fuel utilized NPP design in reactor core is the best choice

Transcriptome Analysis of Manganese-deficient Chlamydomonas reinhardtii Provides Insight on the Chlorophyll Biosynthesis Pathway

Energy Technology Data Exchange (ETDEWEB)

Lockhart, Ainsley; Zvenigorodsky, Natasha; Pedraza, Mary Ann; Lindquist, Erika

2011-08-11

The biosynthesis of chlorophyll and other tetrapyrroles is a vital but poorly understood process. Recent genomic advances with the unicellular green algae Chlamydomonas reinhardtii have created opportunity to more closely examine the mechanisms of the chlorophyll biosynthesis pathway via transcriptome analysis. Manganese is a nutrient of interest for complex reactions because of its multiple stable oxidation states and role in molecular oxygen coordination. C. reinhardtii was cultured in Manganese-deplete Tris-acetate-phosphate (TAP) media for 24 hours and used to create cDNA libraries for sequencing using Illumina TruSeq technology. Transcriptome analysis provided intriguing insight on possible regulatory mechanisms in the pathway. Evidence supports similarities of GTR (Glutamyl-tRNA synthase) to its Chlorella vulgaris homolog in terms of Mn requirements. Data was also suggestive of Mn-related compensatory up-regulation for pathway proteins CHLH1 (Manganese Chelatase), GUN4 (Magnesium chelatase activating protein), and POR1 (Light-dependent protochlorophyllide reductase). Intriguingly, data suggests possible reciprocal expression of oxygen dependent CPX1 (coproporphyrinogen III oxidase) and oxygen independent CPX2. Further analysis using RT-PCR could provide compelling evidence for several novel regulatory mechanisms in the chlorophyll biosynthesis pathway.

Report on the Oak Ridge sewage sludge land-farming experience. Part II. Pathways analysis

International Nuclear Information System (INIS)

Oakes, T.W.; Ohnesorge, W.F.; Daniels, K.L.; Braunstein, H.M.; Kitchings, J.T.; Alexander, W.A.

1984-08-01

The data presented in Part I was used to analyze the potential hazard to humans from the transport of radioactive material from the sludge disposal area into the surrounding environment. A number of environmental pathways were examined to determine the possible radiation dose that humans might incur if radionuclides from the disposal site were concentrated in an environmental medium other than soil. Subsequent to the data assessment, calculations were made to delineate the potential dose received from exposure to five different environmental pathways: (a) direct radiation from the field; (b) inhalation of dust emissions from the sludge disposal area; (c) ingestion of water resulting from radionuclides being leached from the soil and transported via surface runoff into Melton Hill Lake; (d) ingestion of fish caught in Melton Hill Lake; and (e) ingestion of deer meat from animals which might graze on the contaminated site. Results of analyses from these four pathways showed the total annual exposure to be 4.2 mrem to the endostial cells (critical organ) and 1.1 mrem to the total body. 5 references, 7 tables

Multidisciplinary critical discourse analysis: a plea for diversity

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Teun A. van Dijk

2013-12-01

Full Text Available This text is a Brazilian Portuguese version of the chapter from the book “Methods of Critical Discourse Analysis”. The author outlines a Critical Discourse Analysis framework while presents a synthesis of its thinking about the some possible relations between Discourse and Society. The author’s theorical horizon embraces features since the structuralist paradigm to the socio-cognitivo one. At last, the reader can realize an early presentation of the author’s Theory of Context (2001 categories of a theory of context which was published seven years later.

Critical Roles of the Direct GABAergic Pallido-cortical Pathway in Controlling Absence Seizures

Science.gov (United States)

Li, Min; Ma, Tao; Wu, Shengdun; Ma, Jingling; Cui, Yan; Xia, Yang; Xu, Peng; Yao, Dezhong

2015-01-01

The basal ganglia (BG), serving as an intermediate bridge between the cerebral cortex and thalamus, are believed to play crucial roles in controlling absence seizure activities generated by the pathological corticothalamic system. Inspired by recent experiments, here we systematically investigate the contribution of a novel identified GABAergic pallido-cortical pathway, projecting from the globus pallidus externa (GPe) in the BG to the cerebral cortex, to the control of absence seizures. By computational modelling, we find that both increasing the activation of GPe neurons and enhancing the coupling strength of the inhibitory pallido-cortical pathway can suppress the bilaterally synchronous 2–4 Hz spike and wave discharges (SWDs) during absence seizures. Appropriate tuning of several GPe-related pathways may also trigger the SWD suppression, through modulating the activation level of GPe neurons. Furthermore, we show that the previously discovered bidirectional control of absence seizures due to the competition between other two BG output pathways also exists in our established model. Importantly, such bidirectional control is shaped by the coupling strength of this direct GABAergic pallido-cortical pathway. Our work suggests that the novel identified pallido-cortical pathway has a functional role in controlling absence seizures and the presented results might provide testable hypotheses for future experimental studies. PMID:26496656

Atmospheric Pathway Screening Analysis for Saltstone Disposal Facility Vault 4

International Nuclear Information System (INIS)

COOK, JAMES

2004-01-01

A sequential screening process using a methodology developed by the National Council on Radiation Protection and Measurements, professional judgment and process knowledge has been used to produce a list of radionuclides requiring detailed analysis to derive disposal limits for the Saltstone Disposal Facility based on the atmospheric pathway

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

Science.gov (United States)

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

2012-01-01

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

Post-operative endophthalmitis: the application of hazard analysis critical control points (HACCP) to an infection control problem.

Science.gov (United States)

Baird, D R; Henry, M; Liddell, K G; Mitchell, C M; Sneddon, J G

2001-09-01

Hazard analysis critical control points (HACCP) is a quality assurance system widely used in the food industry to ensure safety. We adopted the HACCP approach when conventional infection control measures had failed to solve an ongoing problem with an increased incidence of postoperative endophthalmitis, and our ophthalmology unit was threatened with permanent cessation of intraocular surgery. Although time-consuming, the result was an entirely new set of protocols for the care of patients undergoing intraocular surgery, the development of an integrated care pathway, and a comprehensive and robust audit programme, which enabled intraocular surgery to continue in a new spirit of confidence. HACCP methodology has so far been little used in healthcare, but it might be usefully applied to a variety of apparently intractable infection control problems. Copyright 2001 The Hospital Infection Society.

Enhancement of Nucleoside Production in Hirsutella sinensis Based on Biosynthetic Pathway Analysis

Science.gov (United States)

Liu, Zhi-Qiang; Zhang, Bo; Lin, Shan; Baker, Peter James; Chen, Mao-Sheng; Xue, Ya-Ping; Wu, Hui; Xu, Feng; Yuan, Shui-Jin; Teng, Yi; Wu, Ling-Fang

2017-01-01

To enhance nucleoside production in Hirsutella sinensis, the biosynthetic pathways of purine and pyrimidine nucleosides were constructed and verified. The differential expression analysis showed that purine nucleoside phosphorylase, inosine monophosphate dehydrogenase, and guanosine monophosphate synthase genes involved in purine nucleotide biosynthesis were significantly upregulated 16.56-fold, 8-fold, and 5.43-fold, respectively. Moreover, dihydroorotate dehydrogenase, uridine nucleosidase, uridine/cytidine monophosphate kinase, and inosine triphosphate pyrophosphatase genes participating in pyrimidine nucleoside biosynthesis were upregulated 4.53-fold, 10.63-fold, 4.26-fold, and 5.98-fold, respectively. To enhance the nucleoside production, precursors for synthesis of nucleosides were added based on the analysis of biosynthetic pathways. Uridine and cytidine contents, respectively, reached 5.04 mg/g and 3.54 mg/g when adding 2 mg/mL of ribose, resulting in an increase of 28.6% and 296% compared with the control, respectively. Meanwhile, uridine and cytidine contents, respectively, reached 10.83 mg/g 2.12 mg/g when adding 0.3 mg/mL of uracil, leading to an increase of 176.3% and 137.1%, respectively. This report indicated that fermentation regulation was an effective way to enhance the nucleoside production in H. sinensis based on biosynthetic pathway analysis. PMID:29333435

Microarray analysis reveals genetic pathways modulated by tipifarnib in acute myeloid leukemia

International Nuclear Information System (INIS)

Raponi, Mitch; Belly, Robert T; Karp, Judith E; Lancet, Jeffrey E; Atkins, David; Wang, Yixin

2004-01-01

Farnesyl protein transferase inhibitors (FTIs) were originally developed to inhibit oncogenic ras, however it is now clear that there are several other potential targets for this drug class. The FTI tipifarnib (ZARNESTRA™, R115777) has recently demonstrated clinical responses in adults with refractory and relapsed acute leukemias. This study was conducted to identify genetic markers and pathways that are regulated by tipifarnib in acute myeloid leukemia (AML). Tipifarnib-mediated gene expression changes in 3 AML cell lines and bone marrow samples from two patients with AML were analyzed on a cDNA microarray containing approximately 7000 human genes. Pathways associated with these expression changes were identified using the Ingenuity Pathway Analysis tool. The expression analysis identified a common set of genes that were regulated by tipifarnib in three leukemic cell lines and in leukemic blast cells isolated from two patients who had been treated with tipifarnib. Association of modulated genes with biological functional groups identified several pathways affected by tipifarnib including cell signaling, cytoskeletal organization, immunity, and apoptosis. Gene expression changes were verified in a subset of genes using real time RT-PCR. Additionally, regulation of apoptotic genes was found to correlate with increased Annexin V staining in the THP-1 cell line but not in the HL-60 cell line. The genetic networks derived from these studies illuminate some of the biological pathways affected by FTI treatment while providing a proof of principle for identifying candidate genes that might be used as surrogate biomarkers of drug activity

Integration of multiple networks and pathways identifies cancer driver genes in pan-cancer analysis.

Science.gov (United States)

Cava, Claudia; Bertoli, Gloria; Colaprico, Antonio; Olsen, Catharina; Bontempi, Gianluca; Castiglioni, Isabella

2018-01-06

Modern high-throughput genomic technologies represent a comprehensive hallmark of molecular changes in pan-cancer studies. Although different cancer gene signatures have been revealed, the mechanism of tumourigenesis has yet to be completely understood. Pathways and networks are important tools to explain the role of genes in functional genomic studies. However, few methods consider the functional non-equal roles of genes in pathways and the complex gene-gene interactions in a network. We present a novel method in pan-cancer analysis that identifies de-regulated genes with a functional role by integrating pathway and network data. A pan-cancer analysis of 7158 tumour/normal samples from 16 cancer types identified 895 genes with a central role in pathways and de-regulated in cancer. Comparing our approach with 15 current tools that identify cancer driver genes, we found that 35.6% of the 895 genes identified by our method have been found as cancer driver genes with at least 2/15 tools. Finally, we applied a machine learning algorithm on 16 independent GEO cancer datasets to validate the diagnostic role of cancer driver genes for each cancer. We obtained a list of the top-ten cancer driver genes for each cancer considered in this study. Our analysis 1) confirmed that there are several known cancer driver genes in common among different types of cancer, 2) highlighted that cancer driver genes are able to regulate crucial pathways.

Literature mining, gene-set enrichment and pathway analysis for target identification in Behçet's disease.

Science.gov (United States)

Wilson, Paul; Larminie, Christopher; Smith, Rona

2016-01-01

To use literature mining to catalogue Behçet's associated genes, and advanced computational methods to improve the understanding of the pathways and signalling mechanisms that lead to the typical clinical characteristics of Behçet's patients. To extend this technique to identify potential treatment targets for further experimental validation. Text mining methods combined with gene enrichment tools, pathway analysis and causal analysis algorithms. This approach identified 247 human genes associated with Behçet's disease and the resulting disease map, comprising 644 nodes and 19220 edges, captured important details of the relationships between these genes and their associated pathways, as described in diverse data repositories. Pathway analysis has identified how Behçet's associated genes are likely to participate in innate and adaptive immune responses. Causal analysis algorithms have identified a number of potential therapeutic strategies for further investigation. Computational methods have captured pertinent features of the prominent disease characteristics presented in Behçet's disease and have highlighted NOD2, ICOS and IL18 signalling as potential therapeutic strategies.

Conceptual and critical analysis of the Implicit Leadership Theory

OpenAIRE

Hernández Avilés, Omar David; García Ramos, Tania

2013-01-01

The purpose of this essay is to present a conceptual and critical analysis of the Implicit Leadership Theory (ILT). The objectives are: 1) explaining the main concepts of the ILT; 2) explaining the main processes of the ILT; 3) identifying constructivist assumptions in the ILT; 4) identifying constructionist assumptions in the ILT, and 5) analyzing critically theoretical assumptions of the ILT. At analyzing constructivism and constructionism assumptions in the ILP, the constructivist leadersh...

A concept analysis of critical thinking: A guide for nurse educators.

Science.gov (United States)

Von Colln-Appling, Christina; Giuliano, Danielle

2017-02-01

In research literature, the concept of critical thinking has been widely utilized in nursing education. However, critical thinking has been defined and evaluated using a variety of methods. This paper presents a concept analysis to define and clarify the concept of critical thinking to provide a deeper understanding of how critical thinking can be incorporated into nursing education through the use of simulation exercises. A theoretical definition and sample cases were developed to illuminate the concept as well as a discussion of the antecedents, consequences, and empirical referents of critical thinking. Copyright © 2016 Elsevier Ltd. All rights reserved.

Interleukin-2 signaling pathway analysis by quantitative phosphoproteomics

DEFF Research Database (Denmark)

Osinalde, Nerea; Moss, Helle; Arrizabalaga, Onetsine

2011-01-01

among which 79 were found with increased abundance in the tyrosine-phosphorylated complexes, including several previously not reported IL-2 downstream effectors. Combinatorial site-specific phosphoproteomic analysis resulted in identification of 99 phosphorylated sites mapping to the identified proteins...... with increased abundance in the tyrosine-phosphorylated complexes, of which 34 were not previously described. In addition, chemical inhibition of the identified IL-2-mediated JAK, PI3K and MAPK signaling pathways, resulted in distinct alteration on the IL-2 dependent proliferation....

Potential impacts of ENDF/B-V on critical experiment analysis based on ZEBRA-8 criticals

Energy Technology Data Exchange (ETDEWEB)

Choong, T S

1982-06-01

The ZEBRA-8 series of null-zone measurements featured a different neutron spectrum for each assembly. The experiments were designed for the purpose of basic data testing. The series cover a range of spectra both harder and softer than that for the LMFBR. The potential impacts of the newly released ENDF/BV cross section library on LMFBR critical exeriment analysis are discussed based on analysis of ZEBRA-8 series.

Defining critical success factors in TOD implementation using rough set analysis

NARCIS (Netherlands)

Thomas, R.; Bertolini, L.

2017-01-01

This paper defines critical success conditions in transit-oriented development (TOD), evaluating the impact of practices, policies, and governance models on implementation. As part of a meta-analysis of 11 international case studies, 16 critical success factors were developed and validated using

Criticality safety analysis for mockup facility

International Nuclear Information System (INIS)

Shin, Young Joon; Shin, Hee Sung; Kim, Ik Soo; Oh, Seung Chul; Ro, Seung Gy; Bae, Kang Mok

2000-03-01

Benchmark calculations for SCALE4.4 CSAS6 module have been performed for 31 UO 2 fuel, 15MOX fuel and 10 metal material criticality experiments and then calculation biases of the SCALE 4.4 CSAS6 module have been revealed to be 0.00982, 0.00579 and 0.02347, respectively. When CSAS6 is applied to the criticality safety analysis for the mockup facility in which several kinds of nuclear material components are included, the calculation bias of CSAS6 is conservatively taken to be 0.02347. With the aid of this benchmarked code system, criticality safety analyses for the mockup facility at normal and hypothetical accidental conditions have been carried out. It appears that the maximum K eff is 0.28356 well below than the critical limit, K eff =0.95 at normal condition. In a hypothetical accidental condition, the maximum K eff is found to be 0.73527 much lower than the subcritical limit. For another hypothetical accidental condition the nuclear material leaks out of container and spread or lump in the floor, it was assumed that the nuclear material is shaped into a slab and water exists in the empty space of the nuclear material. K eff has been calculated as function of slab thickness and the volume ratio of water to nuclear material. The result shows that the K eff increases as the water volume ratio increases. It is also revealed that the K eff reaches to the maximum value when water if filled in the empty space of nuclear material. The maximum K eff value is 0.93960 lower than the subcritical limit

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.

Method of critical power prediction based on film flow model coupled with subchannel analysis

International Nuclear Information System (INIS)

Tomiyama, Akio; Yokomizo, Osamu; Yoshimoto, Yuichiro; Sugawara, Satoshi.

1988-01-01

A new method was developed to predict critical powers for a wide variety of BWR fuel bundle designs. This method couples subchannel analysis with a liquid film flow model, instead of taking the conventional way which couples subchannel analysis with critical heat flux correlations. Flow and quality distributions in a bundle are estimated by the subchannel analysis. Using these distributions, film flow rates along fuel rods are then calculated with the film flow model. Dryout is assumed to occur where one of the film flows disappears. This method is expected to give much better adaptability to variations in geometry, heat flux, flow rate and quality distributions than the conventional methods. In order to verify the method, critical power data under BWR conditions were analyzed. Measured and calculated critical powers agreed to within ±7%. Furthermore critical power data for a tight-latticed bundle obtained by LeTourneau et al. were compared with critical powers calculated by the present method and two conventional methods, CISE correlation and subchannel analysis coupled with the CISE correlation. It was confirmed that the present method can predict critical powers more accurately than the conventional methods. (author)

Cloning and Expression Analysis of MEP Pathway Enzyme-encoding Genes in Osmanthus fragrans

Directory of Open Access Journals (Sweden)

Chen Xu

2016-09-01

Full Text Available The 2-C-methyl-d-erythritol 4-phosphate (MEP pathway is responsible for the biosynthesis of many crucial secondary metabolites, such as carotenoids, monoterpenes, plastoquinone, and tocopherols. In this study, we isolated and identified 10 MEP pathway genes in the important aromatic plant sweet osmanthus (Osmanthus fragrans. Multiple sequence alignments revealed that 10 MEP pathway genes shared high identities with other reported proteins. The genes showed distinctive expression profiles in various tissues, or at different flower stages and diel time points. The qRT-PCR results demonstrated that these genes were highly expressed in inflorescences, which suggested a tissue-specific transcript pattern. Our results also showed that OfDXS1, OfDXS2, and OfHDR1 had a clear diurnal oscillation pattern. The isolation and expression analysis provides a strong foundation for further research on the MEP pathway involved in gene function and molecular evolution, and improves our understanding of the molecular mechanism underlying this pathway in plants.

Risk analysis of critical infrastructures emphasizing electricity supply and interdependencies

International Nuclear Information System (INIS)

Kjølle, G.H.; Utne, I.B.; Gjerde, O.

2012-01-01

Failures in critical infrastructures can cause major damage to society. Wide-area interruptions (blackouts) in the electricity supply system have severe impacts on societal critical functions and other critical infrastructures, but there is no agreed-upon framework on how to analyze and predict the reliability of electricity supply. Thus, there is a need for an approach to cross-sector risk analyses, which facilitates risk analysis of outages in the electricity supply system and enables investigation of cascading failures and consequences in other infrastructures. This paper presents such an approach, which includes contingency analysis (power flow) and reliability analysis of power systems, as well as use of a cascade diagram for investigating interdependencies. A case study was carried out together with the Emergency Preparedness Group in the city of Oslo, Norway and the network company Hafslund Nett. The case study results highlight the need for cross-sector analyses by showing that the total estimated societal costs are substantially higher when cascading effects and consequences to other infrastructures are taken into account compared to only considering the costs of electricity interruptions as seen by the network company. The approach is a promising starting point for cross-sector risk analysis of electricity supply interruptions and consequences for dependent infrastructures.

Metabolic pathway analysis and kinetic studies for production of nattokinase in Bacillus subtilis.

Science.gov (United States)

Unrean, Pornkamol; Nguyen, Nhung H A

2013-01-01

We have constructed a reaction network model of Bacillus subtilis. The model was analyzed using a pathway analysis tool called elementary mode analysis (EMA). The analysis tool was used to study the network capabilities and the possible effects of altered culturing conditions on the production of a fibrinolytic enzyme, nattokinase (NK) by B. subtilis. Based on all existing metabolic pathways, the maximum theoretical yield for NK synthesis in B. subtilis under different substrates and oxygen availability was predicted and the optimal culturing condition for NK production was identified. To confirm model predictions, experiments were conducted by testing these culture conditions for their influence on NK activity. The optimal culturing conditions were then applied to batch fermentation, resulting in high NK activity. The EMA approach was also applied for engineering B. subtilis metabolism towards the most efficient pathway for NK synthesis by identifying target genes for deletion and overexpression that enable the cell to produce NK at the maximum theoretical yield. The consistency between experiments and model predictions proves the feasibility of EMA being used to rationally design culture conditions and genetic manipulations for the efficient production of desired products.

Reuse-centric Requirements Analysis with Task Models, Scenarios, and Critical Parameters

Directory of Open Access Journals (Sweden)

Cyril Montabert

2007-02-01

Full Text Available This paper outlines a requirements-analysis process that unites task models, scenarios, and critical parameters to exploit and generate reusable knowledge at the requirements phase. Through the deployment of a critical-parameter-based approach to task modeling, the process yields the establishment of an integrative and formalized model issued from scenarios that can be used for requirements characterization. Furthermore, not only can this entity serve as interface to a knowledge repository relying on a critical-parameter-based taxonomy to support reuse but its characterization in terms of critical parameters also allows the model to constitute a broader reuse solution. We discuss our vision for a user-centric and reuse-centric approach to requirements analysis, present previous efforts implicated with this line of work, and state the revisions brought to extend the reuse potential and effectiveness of a previous iteration of a requirements tool implementing such process. Finally, the paper describes the sequence and nature of the activities involved with the conduct of our proposed requirements-analysis technique, concluding by previewing ongoing work in the field that will explore the feasibility for designers to use our approach.

Association genetics and transcriptome analysis reveal a gibberellin-responsive pathway involved in regulating photosynthesis.

Science.gov (United States)

Xie, Jianbo; Tian, Jiaxing; Du, Qingzhang; Chen, Jinhui; Li, Ying; Yang, Xiaohui; Li, Bailian; Zhang, Deqiang

2016-05-01

Gibberellins (GAs) regulate a wide range of important processes in plant growth and development, including photosynthesis. However, the mechanism by which GAs regulate photosynthesis remains to be understood. Here, we used multi-gene association to investigate the effect of genes in the GA-responsive pathway, as constructed by RNA sequencing, on photosynthesis, growth, and wood property traits, in a population of 435 Populus tomentosa By analyzing changes in the transcriptome following GA treatment, we identified many key photosynthetic genes, in agreement with the observed increase in measurements of photosynthesis. Regulatory motif enrichment analysis revealed that 37 differentially expressed genes related to photosynthesis shared two essential GA-related cis-regulatory elements, the GA response element and the pyrimidine box. Thus, we constructed a GA-responsive pathway consisting of 47 genes involved in regulating photosynthesis, including GID1, RGA, GID2, MYBGa, and 37 photosynthetic differentially expressed genes. Single nucleotide polymorphism (SNP)-based association analysis showed that 142 SNPs, representing 40 candidate genes in this pathway, were significantly associated with photosynthesis, growth, and wood property traits. Epistasis analysis uncovered interactions between 310 SNP-SNP pairs from 37 genes in this pathway, revealing possible genetic interactions. Moreover, a structural gene-gene matrix based on a time-course of transcript abundances provided a better understanding of the multi-gene pathway affecting photosynthesis. The results imply a functional role for these genes in mediating photosynthesis, growth, and wood properties, demonstrating the potential of combining transcriptome-based regulatory pathway construction and genetic association approaches to detect the complex genetic networks underlying quantitative traits. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights

Software criticality analysis of COTS/SOUP

Energy Technology Data Exchange (ETDEWEB)

Bishop, Peter; Bloomfield, Robin; Clement, Tim; Guerra, Sofia

2003-09-01

This paper describes the Software Criticality Analysis (SCA) approach that was developed to support the justification of using commercial off-the-shelf software (COTS) in a safety-related system. The primary objective of SCA is to assess the importance to safety of the software components within the COTS and to show there is segregation between software components with different safety importance. The approach taken was a combination of Hazops based on design documents and on a detailed analysis of the actual code (100 kloc). Considerable effort was spent on validation and ensuring the conservative nature of the results. The results from reverse engineering from the code showed that results based only on architecture and design documents would have been misleading.

Software criticality analysis of COTS/SOUP

International Nuclear Information System (INIS)

Bishop, Peter; Bloomfield, Robin; Clement, Tim; Guerra, Sofia

2003-01-01

This paper describes the Software Criticality Analysis (SCA) approach that was developed to support the justification of using commercial off-the-shelf software (COTS) in a safety-related system. The primary objective of SCA is to assess the importance to safety of the software components within the COTS and to show there is segregation between software components with different safety importance. The approach taken was a combination of Hazops based on design documents and on a detailed analysis of the actual code (100 kloc). Considerable effort was spent on validation and ensuring the conservative nature of the results. The results from reverse engineering from the code showed that results based only on architecture and design documents would have been misleading

Regulation of dual glycolytic pathways for fructose metabolism in heterofermentative Lactobacillus panis PM1.

Science.gov (United States)

Kang, Tae Sun; Korber, Darren R; Tanaka, Takuji

2013-12-01

Lactobacillus panis PM1 belongs to the group III heterofermentative lactobacilli that use the 6-phosphogluconate/phosphoketolase (6-PG/PK) pathway as their central metabolic pathway and are reportedly unable to grow on fructose as a sole carbon source. We isolated a variant PM1 strain capable of sporadic growth on fructose medium and observed its distinctive characteristics of fructose metabolism. The end product pattern was different from what is expected in typical group III lactobacilli using the 6-PG/PK pathway (i.e., more lactate, less acetate, and no mannitol). In addition, in silico analysis revealed the presence of genes encoding most of critical enzymes in the Embden-Meyerhof (EM) pathway. These observations indicated that fructose was metabolized via two pathways. Fructose metabolism in the PM1 strain was influenced by the activities of two enzymes, triosephosphate isomerase (TPI) and glucose 6-phosphate isomerase (PGI). A lack of TPI resulted in the intracellular accumulation of dihydroxyacetone phosphate (DHAP) in PM1, the toxicity of which caused early growth cessation during fructose fermentation. The activity of PGI was enhanced by the presence of glyceraldehyde 3-phosphate (GAP), which allowed additional fructose to enter into the 6-PG/PK pathway to avoid toxicity by DHAP. Exogenous TPI gene expression shifted fructose metabolism from heterolactic to homolactic fermentation, indicating that TPI enabled the PM1 strain to mainly use the EM pathway for fructose fermentation. These findings clearly demonstrate that the balance in the accumulation of GAP and DHAP determines the fate of fructose metabolism and the activity of TPI plays a critical role during fructose fermentation via the EM pathway in L. panis PM1.

A threat analysis framework as applied to critical infrastructures in the Energy Sector.

Energy Technology Data Exchange (ETDEWEB)

Michalski, John T.; Duggan, David Patrick

2007-09-01

The need to protect national critical infrastructure has led to the development of a threat analysis framework. The threat analysis framework can be used to identify the elements required to quantify threats against critical infrastructure assets and provide a means of distributing actionable threat information to critical infrastructure entities for the protection of infrastructure assets. This document identifies and describes five key elements needed to perform a comprehensive analysis of threat: the identification of an adversary, the development of generic threat profiles, the identification of generic attack paths, the discovery of adversary intent, and the identification of mitigation strategies.

Religious Education in Russia: A Comparative and Critical Analysis

Science.gov (United States)

Blinkova, Alexandra; Vermeer, Paul

2018-01-01

RE in Russia has been recently introduced as a compulsory regular school subject during the last year of elementary school. The present study offers a critical analysis of the current practice of Russian RE by comparing it with RE in Sweden, Denmark and Britain. This analysis shows that Russian RE is ambivalent. Although it is based on a…

Ensemble Modeling for Robustness Analysis in engineering non-native metabolic pathways.

Science.gov (United States)

Lee, Yun; Lafontaine Rivera, Jimmy G; Liao, James C

2014-09-01

Metabolic pathways in cells must be sufficiently robust to tolerate fluctuations in expression levels and changes in environmental conditions. Perturbations in expression levels may lead to system failure due to the disappearance of a stable steady state. Increasing evidence has suggested that biological networks have evolved such that they are intrinsically robust in their network structure. In this article, we presented Ensemble Modeling for Robustness Analysis (EMRA), which combines a continuation method with the Ensemble Modeling approach, for investigating the robustness issue of non-native pathways. EMRA investigates a large ensemble of reference models with different parameters, and determines the effects of parameter drifting until a bifurcation point, beyond which a stable steady state disappears and system failure occurs. A pathway is considered to have high bifurcational robustness if the probability of system failure is low in the ensemble. To demonstrate the utility of EMRA, we investigate the bifurcational robustness of two synthetic central metabolic pathways that achieve carbon conservation: non-oxidative glycolysis and reverse glyoxylate cycle. With EMRA, we determined the probability of system failure of each design and demonstrated that alternative designs of these pathways indeed display varying degrees of bifurcational robustness. Furthermore, we demonstrated that target selection for flux improvement should consider the trade-offs between robustness and performance. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

SCALE-4 analysis of pressurized water reactor critical configurations. Volume 1: Summary

International Nuclear Information System (INIS)

DeHart, M.D.

1995-03-01

The requirements of ANSI/ANS 8.1 specify that calculational methods for away-from-reactor criticality safety analyses be validated against experimental measurements. If credit is to be taken for the reduced reactivity of burned or spent fuel relative to its original fresh composition, it is necessary to benchmark computational methods used in determining such reactivity worth against spent fuel reactivity measurements. This report summarizes a portion of the ongoing effort to benchmark away-from-reactor criticality analysis methods using critical configurations from commercial pressurized water reactors (PWR). The analysis methodology utilized for all calculations in this report is based on the modules and data associated with the SCALE-4 code system. Each of the five volumes comprising this report provides an overview of the methodology applied. Subsequent volumes also describe in detail the approach taken in performing criticality calculations for these PWR configurations: Volume 2 describes criticality calculations for the Tennessee Valley Authority's Sequoyah Unit 2 reactor for Cycle 3; Volume 3 documents the analysis of Virginia Power's Surry Unit 1 reactor for the Cycle 2 core; Volume 4 documents the calculations performed based on GPU Nuclear Corporation's Three Mile Island Unit 1 Cycle 5 core; and, lastly, Volume 5 describes the analysis of Virginia Power's North Anna Unit 1 Cycle 5 core. Each of the reactor-specific volumes provides the details of calculations performed to determine the effective multiplication factor for each reactor core for one or more critical configurations using the SCALE-4 system; these results are summarized in this volume. Differences between the core designs and their possible impact on the criticality calculations are also discussed. Finally, results are presented for additional analyses performed to verify that solutions were sufficiently converged

Critical analysis of industrial electron accelerators

Energy Technology Data Exchange (ETDEWEB)

Korenev, S. E-mail: sergey_korenev@steris.com

2004-10-01

The critical analysis of electron linacs for industrial applications (degradation of PTFE, curing of composites, modification of materials, sterilization and others) is considered in this report. Main physical requirements for industrial electron accelerators consist in the variations of beam parameters, such as kinetic energy and beam power. Questions for regulation of these beam parameters are considered. The level of absorbed dose in the irradiated product and throughput determines the main parameters of electron accelerator. The type of ideal electron linac for industrial applications is discussed.

Critical analysis of industrial electron accelerators

Science.gov (United States)

Korenev, S.

2004-09-01

The critical analysis of electron linacs for industrial applications (degradation of PTFE, curing of composites, modification of materials, sterlization and others) is considered in this report. Main physical requirements for industrial electron accelerators consist in the variations of beam parameters, such as kinetic energy and beam power. Questions for regulation of these beam parameters are considered. The level of absorbed dose in the irradiated product and throughput determines the main parameters of electron accelerator. The type of ideal electron linac for industrial applications is discussed.

Critical analysis of industrial electron accelerators

International Nuclear Information System (INIS)

Korenev, S.

2004-01-01

The critical analysis of electron linacs for industrial applications (degradation of PTFE, curing of composites, modification of materials, sterilization and others) is considered in this report. Main physical requirements for industrial electron accelerators consist in the variations of beam parameters, such as kinetic energy and beam power. Questions for regulation of these beam parameters are considered. The level of absorbed dose in the irradiated product and throughput determines the main parameters of electron accelerator. The type of ideal electron linac for industrial applications is discussed

Hazard analysis and critical control point (HACCP) history and conceptual overview.

Science.gov (United States)

Hulebak, Karen L; Schlosser, Wayne

2002-06-01

The concept of Hazard Analysis and Critical Control Point (HACCP) is a system that enables the production of safe meat and poultry products through the thorough analysis of production processes, identification of all hazards that are likely to occur in the production establishment, the identification of critical points in the process at which these hazards may be introduced into product and therefore should be controlled, the establishment of critical limits for control at those points, the verification of these prescribed steps, and the methods by which the processing establishment and the regulatory authority can monitor how well process control through the HACCP plan is working. The history of the development of HACCP is reviewed, and examples of practical applications of HACCP are described.

Kinetic analysis of sub-prompt-critical reactor assemblies

International Nuclear Information System (INIS)

Das, S.

1992-01-01

Neutronic analysis of safety-related kinetics problems in experimental neutron multiplying assemblies has been carried out using a sub-prompt-critical reactor model. The model is based on the concept of a sub-prompt-critical nuclear reactor and the concept of instantaneous neutron multiplication in a reactor system. Computations of reactor power, period and reactivity using the model show excellent agreement with results obtained from exact kinetics method. Analytic expressions for the energy released in a controlled nuclear power excursion are derived. Application of the model to a Pulsed Fast Reactor gives its sensitivity between 4 and 5. (author). 6 refs., 4 figs., 1 tab

A Method to Evaluate Critical Factors for Successful Implementation of Clinical Pathways.

Science.gov (United States)

Dong, W; Huang, Z

2015-01-01

Clinical pathways (CPs) have been viewed as a multidisciplinary tool to improve the quality and efficiency of evidence-based care. Despite widespread enthusiasm for CPs, research has shown that many CP initiatives are unsuccessful. To this end, this study provides a methodology to evaluate critical success factors (CSFs) that can aid healthcare organizations to achieve successful CP implementation. This study presents a new approach to evaluate CP implementation CSFs, with the aims being: (1) to identify CSFs for implementation of CPs through a comprehensive literature review and interviews with collaborative experts; (2) to use a filed study data with a robust fuzzy DEMATEL (the decision making trial and evaluation laboratory) approach to visualize the structure of complicated causal relationships between CSFs and obtain the influence level of these factors. The filed study data is provided by ten clinical experts of a Chinese hospital. 23 identified CSF factors which are initially identified through a review of the literature and interviews with collaborative experts. Then, a number of direct and indirect relationships are derived from the data such that different perceptions can be integrated into a compromised cause and effect model of CP implementation. The results indicate that the proposed approach can systematically evaluate CSFs and realize the importance of each factor such that the most common causes of failure of CP implementation could be eliminated or avoided. Therefore, the tool proposed would help healthcare organizations to manage CP implementation in a more effective and proactive way.

Critical experiments analysis by ABBN-90 constant system

Energy Technology Data Exchange (ETDEWEB)

Tsiboulia, A.; Nikolaev, M.N.; Golubev, V. [Institute of Physics and Power Engineering, Obninsk (Russian Federation)] [and others

1997-06-01

The ABBN-90 is a new version of the well-known Russian group-constant system ABBN. Included constants were calculated based on files of evaluated nuclear data from the BROND-2, ENDF/B-VI, and JENDL-3 libraries. The ABBN-90 is intended for the calculation of different types of nuclear reactors and radiation shielding. Calculations of criticality safety and reactivity accidents are also provided by using this constant set. Validation of the ABBN-90 set was made by using a computerized bank of evaluated critical experiments. This bank includes the results of experiments conducted in Russia and abroad of compact spherical assemblies with different reflectors, fast critical assemblies, and fuel/water-solution criticalities. This report presents the results of the calculational analysis of the whole collection of critical experiments. All calculations were produced with the ABBN-90 group-constant system. Revealed discrepancies between experimental and calculational results and their possible reasons are discussed. The codes and archives INDECS system is also described. This system includes three computerized banks: LEMEX, which consists of evaluated experiments and their calculational results; LSENS, which consists of sensitivity coefficients; and LUND, which consists of group-constant covariance matrices. The INDECS system permits us to estimate the accuracy of neutronics calculations. A discussion of the reliability of such estimations is finally presented. 16 figs.

Analysis of the criticality safety of a nuclear fuel deposit

International Nuclear Information System (INIS)

Landeyro, P.A.; Mincarini, M.

1987-01-01

In the present work a safety analysis from criticality accidents of nuclear fuel deposits is performed. The analysis is performed utilizing two methods derived from different physical principes: 1) superficial density method, obtained from experimental research; 2) solid angle method, derived from transport theory

Interaction, Critical Thinking, and Social Network Analysis (SNA in Online Courses

Directory of Open Access Journals (Sweden)

Joan Thormann

2013-07-01

Full Text Available This study tried to ascertain a possible relationship between the number of student moderators (1, 2, and 3, online interactions, and critical thinking of K-12 educators enrolled in an online course that was taught from a constructivist approach. The course topic was use of technology in special education. Social network analysis (SNA and measures of critical thinking (Newman, Webb, & Cochrane, 1995 were used to research and assess if there was a difference in interaction and critical thinking between 1, 2, or 3 student moderators who facilitated a forum discussion of an assignment in an online course. The same course was repeated over three years. Each year either 1, 2, or 3 students moderated. The analysis indicated more discussion per non-moderating student with the three student moderated group. Using SNA we found that there was only one noticeable difference among the three groups which was in the value of network centralization. Using critical thinking measures the three student moderator group scored higher in five of the eight critical thinking categories. Variations in instructor presence in the online courses may have influenced these findings.

Phytohormone signaling pathway analysis method for comparing hormone responses in plant-pest interactions

Directory of Open Access Journals (Sweden)

Studham Matthew E

2012-07-01

Full Text Available Abstract Background Phytohormones mediate plant defense responses to pests and pathogens. In particular, the hormones jasmonic acid, ethylene, salicylic acid, and abscisic acid have been shown to dictate and fine-tune defense responses, and identification of the phytohormone components of a particular defense response is commonly used to characterize it. Identification of phytohormone regulation is particularly important in transcriptome analyses. Currently there is no computational tool to determine the relative activity of these hormones that can be applied to transcriptome analyses in soybean. Findings We developed a pathway analysis method that provides a broad measure of the activation or suppression of individual phytohormone pathways based on changes in transcript expression of pathway-related genes. The magnitude and significance of these changes are used to determine a pathway score for a phytohormone for a given comparison in a microarray experiment. Scores for individual hormones can then be compared to determine the dominant phytohormone in a given defense response. To validate this method, it was applied to publicly available data from previous microarray experiments that studied the response of soybean plants to Asian soybean rust and soybean cyst nematode. The results of the analyses for these experiments agreed with our current understanding of the role of phytohormones in these defense responses. Conclusions This method is useful in providing a broad measure of the relative induction and suppression of soybean phytohormones during a defense response. This method could be used as part of microarray studies that include individual transcript analysis, gene set analysis, and other methods for a comprehensive defense response characterization.

Live-cell microscopy reveals small molecule inhibitor effects on MAPK pathway dynamics.

Directory of Open Access Journals (Sweden)

Daniel J Anderson

Full Text Available Oncogenic mutations in the mitogen activated protein kinase (MAPK pathway are prevalent in human tumors, making this pathway a target of drug development efforts. Recently, ATP-competitive Raf inhibitors were shown to cause MAPK pathway activation via Raf kinase priming in wild-type BRaf cells and tumors, highlighting the need for a thorough understanding of signaling in the context of small molecule kinase inhibitors. Here, we present critical improvements in cell-line engineering and image analysis coupled with automated image acquisition that allow for the simultaneous identification of cellular localization of multiple MAPK pathway components (KRas, CRaf, Mek1 and Erk2. We use these assays in a systematic study of the effect of small molecule inhibitors across the MAPK cascade either as single agents or in combination. Both Raf inhibitor priming as well as the release from negative feedback induced by Mek and Erk inhibitors cause translocation of CRaf to the plasma membrane via mechanisms that are additive in pathway activation. Analysis of Erk activation and sub-cellular localization upon inhibitor treatments reveals differential inhibition and activation with the Raf inhibitors AZD628 and GDC0879 respectively. Since both single agent and combination studies of Raf and Mek inhibitors are currently in the clinic, our assays provide valuable insight into their effects on MAPK signaling in live cells.

Comparative expression pathway analysis of human and canine mammary tumors

Directory of Open Access Journals (Sweden)

Marconato Laura

2009-03-01

Full Text Available Abstract Background Spontaneous tumors in dog have been demonstrated to share many features with their human counterparts, including relevant molecular targets, histological appearance, genetics, biological behavior and response to conventional treatments. Mammary tumors in dog therefore provide an attractive alternative to more classical mouse models, such as transgenics or xenografts, where the tumour is artificially induced. To assess the extent to which dog tumors represent clinically significant human phenotypes, we performed the first genome-wide comparative analysis of transcriptional changes occurring in mammary tumors of the two species, with particular focus on the molecular pathways involved. Results We analyzed human and dog gene expression data derived from both tumor and normal mammary samples. By analyzing the expression levels of about ten thousand dog/human orthologous genes we observed a significant overlap of genes deregulated in the mammary tumor samples, as compared to their normal counterparts. Pathway analysis of gene expression data revealed a great degree of similarity in the perturbation of many cancer-related pathways, including the 'PI3K/AKT', 'KRAS', 'PTEN', 'WNT-beta catenin' and 'MAPK cascade'. Moreover, we show that the transcriptional relationships between different gene signatures observed in human breast cancer are largely maintained in the canine model, suggesting a close interspecies similarity in the network of cancer signalling circuitries. Conclusion Our data confirm and further strengthen the value of the canine mammary cancer model and open up new perspectives for the evaluation of novel cancer therapeutics and the development of prognostic and diagnostic biomarkers to be used in clinical studies.

21 CFR 123.6 - Hazard analysis and Hazard Analysis Critical Control Point (HACCP) plan.

Science.gov (United States)

2010-04-01

... Control Point (HACCP) plan. 123.6 Section 123.6 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Provisions § 123.6 Hazard analysis and Hazard Analysis Critical Control Point (HACCP) plan. (a) Hazard... fish or fishery product being processed in the absence of those controls. (b) The HACCP plan. Every...

Using Formal Concept Analysis to Create Pathways through Museum Collections

DEFF Research Database (Denmark)

Wray, Tim; Eklund, Peter

2014-01-01

This paper presents A Place for Art - an iPad app that allows users to explore an art collection via semantically linked pathways that are generated using Formal Concept Analysis. The app embraces the information seeking approach of exploration and is based on the idea that showing context...... and relationships among objects in a museum collection augments an interpretive experience. The fundamental interaction metaphor inherent in A Place for Art relies on Formal Concept Analysis so the interface has embedded within it the semantic clustering features of machine learning in artificial intelligence....

Thermodynamics of metabolic pathways for penicillin production: Analysis of thermodynamic feasibility and free energy changes during fed-batch cultivation

DEFF Research Database (Denmark)

Pissarra, P.D.; Nielsen, Jens Bredal

1997-01-01

This paper describes the thermodynamic analysis of pathways related to penicillin production in Penicillium chrysogenum. First a thermodynamic feasibility analysis is performed of the L-lysine pathway of which one of the precursors for penicillin biosynthesis (alpha-aminoadipic acid......) is an intermediate. It is found that the L-lysine pathway in P. chrysogenum is thermodynamically feasible and that the calculated standard Gibbs free energy values of the two enzymes controlling the pathway flux indicate that they operate far from equilibrium. It is therefore proposed that the regulation of alpha......-aminoadipate reductase by lysine is important to maintain a high concentration of alpha-aminoadipate in order to direct the carbon flux to penicillin production. Secondly the changes in Gibbs free energy in the penicillin biosynthetic pathway during fed-batch cultivation were studied. The analysis showed that all...

Dual pathways to prospective remembering

Science.gov (United States)

McDaniel, Mark A.; Umanath, Sharda; Einstein, Gilles O.; Waldum, Emily R.

2015-01-01

According to the multiprocess framework (McDaniel and Einstein, 2000), the cognitive system can support prospective memory (PM) retrieval through two general pathways. One pathway depends on top–down attentional control processes that maintain activation of the intention and/or monitor the environment for the triggering or target cues that indicate that the intention should be executed. A second pathway depends on (bottom–up) spontaneous retrieval processes, processes that are often triggered by a PM target cue; critically, spontaneous retrieval is assumed not to require monitoring or active maintenance of the intention. Given demand characteristics associated with experimental settings, however, participants are often inclined to monitor, thereby potentially masking discovery of bottom–up spontaneous retrieval processes. In this article, we discuss parameters of laboratory PM paradigms to discourage monitoring and review recent behavioral evidence from such paradigms that implicate spontaneous retrieval in PM. We then re-examine the neuro-imaging evidence from the lens of the multiprocess framework and suggest some critical modifications to existing neuro-cognitive interpretations of the neuro-imaging results. These modifications illuminate possible directions and refinements for further neuro-imaging investigations of PM. PMID:26236213

Dual Pathways to Prospective Remembering

Directory of Open Access Journals (Sweden)

Mark A Mcdaniel

2015-07-01

Full Text Available According to the multiprocess framework (McDaniel & Einstein, 2000, the cognitive system can support prospective memory (PM retrieval through two general pathways. One pathway depends on top-down attentional control processes that maintain activation of the intention and/or monitor the environment for the triggering or target cues that indicate that the intention should be executed. A second pathway depends on (bottom-up spontaneous retrieval processes, processes that are often triggered by a PM target cue; critically spontaneous retrieval is assumed to not require monitoring or active maintenance of the intention. Given demand characteristics associated with experimental settings, however, participants are often inclined to monitor, thereby potentially masking discovery of bottom-up spontaneous retrieval processes. In this article, we discuss parameters of laboratory PM paradigms to discourage monitoring and review recent behavioral evidence from such paradigms that implicate spontaneous retrieval in PM. We then re-examine the neuro-imaging evidence from the lens of the multiprocess framework and suggest some critical modifications to existing neuro-cognitive interpretations of the neuro-imaging results. These modifications illuminate possible directions and refinements for further neuro-imaging investigations of PM.

Protein design for pathway engineering.

Science.gov (United States)

Eriksen, Dawn T; Lian, Jiazhang; Zhao, Huimin

2014-02-01

Design and construction of biochemical pathways has increased the complexity of biosynthetically-produced compounds when compared to single enzyme biocatalysis. However, the coordination of multiple enzymes can introduce a complicated set of obstacles to overcome in order to achieve a high titer and yield of the desired compound. Metabolic engineering has made great strides in developing tools to optimize the flux through a target pathway, but the inherent characteristics of a particular enzyme within the pathway can still limit the productivity. Thus, judicious protein design is critical for metabolic and pathway engineering. This review will describe various strategies and examples of applying protein design to pathway engineering to optimize the flux through the pathway. The proteins can be engineered for altered substrate specificity/selectivity, increased catalytic activity, reduced mass transfer limitations through specific protein localization, and reduced substrate/product inhibition. Protein engineering can also be expanded to design biosensors to enable high through-put screening and to customize cell signaling networks. These strategies have successfully engineered pathways for significantly increased productivity of the desired product or in the production of novel compounds. Copyright © 2013 Elsevier Inc. All rights reserved.

Life cycle analysis of transportation fuel pathways

Energy Technology Data Exchange (ETDEWEB)

NONE

2012-02-24

The purpose of this work is to improve the understanding of the concept of life cycle analysis (LCA) of transportation fuels and some of its pertinent issues among non-technical people, senior managers, and policy makers. This work should provide some guidance to nations considering LCA-based policies and to people who are affected by existing policies or those being developed. While the concept of employing LCA to evaluate fuel options is simple and straightforward, the act of putting the concept into practice is complex and fraught with issues. Policy makers need to understand the limitations inherent in carrying out LCA work for transportation fuel systems. For many systems, even those that have been employed for a 100 years, there is a lack of sound data on the performance of those systems. Comparisons between systems should ideally be made using the same tool, so that differences caused by system boundaries, allocation processes, and temporal issues can be minimized (although probably not eliminated). Comparing the results for fuel pathway 1 from tool A to those of fuel system 2 from tool B introduces significant uncertainty into the results. There is also the question of the scale of system changes. LCA will give more reliable estimates when it is used to examine small changes in transportation fuel pathways than when used to estimate large scale changes that replace current pathways with completely new pathways. Some LCA tools have been developed recently primarily for regulatory purposes. These tools may deviate from ISO principles in order to facilitate simplicity and ease of use. In a regulatory environment, simplicity and ease of use are worthy objectives and in most cases there is nothing inherently wrong with this approach, particularly for assessing relative performance. However, the results of these tools should not be confused with, or compared to, the results that are obtained from a more complex and rigorous ISO compliant LCA. It should be

Microarray analysis reveals key genes and pathways in Tetralogy of Fallot

Science.gov (United States)

He, Yue-E; Qiu, Hui-Xian; Jiang, Jian-Bing; Wu, Rong-Zhou; Xiang, Ru-Lian; Zhang, Yuan-Hai

2017-01-01

The aim of the present study was to identify key genes that may be involved in the pathogenesis of Tetralogy of Fallot (TOF) using bioinformatics methods. The GSE26125 microarray dataset, which includes cardiovascular tissue samples derived from 16 children with TOF and five healthy age-matched control infants, was downloaded from the Gene Expression Omnibus database. Differential expression analysis was performed between TOF and control samples to identify differentially expressed genes (DEGs) using Student's t-test, and the R/limma package, with a log2 fold-change of >2 and a false discovery rate of <0.01 set as thresholds. The biological functions of DEGs were analyzed using the ToppGene database. The ReactomeFIViz application was used to construct functional interaction (FI) networks, and the genes in each module were subjected to pathway enrichment analysis. The iRegulon plugin was used to identify transcription factors predicted to regulate the DEGs in the FI network, and the gene-transcription factor pairs were then visualized using Cytoscape software. A total of 878 DEGs were identified, including 848 upregulated genes and 30 downregulated genes. The gene FI network contained seven function modules, which were all comprised of upregulated genes. Genes enriched in Module 1 were enriched in the following three neurological disorder-associated signaling pathways: Parkinson's disease, Alzheimer's disease and Huntington's disease. Genes in Modules 0, 3 and 5 were dominantly enriched in pathways associated with ribosomes and protein translation. The Xbox binding protein 1 transcription factor was demonstrated to be involved in the regulation of genes encoding the subunits of cytoplasmic and mitochondrial ribosomes, as well as genes involved in neurodegenerative disorders. Therefore, dysfunction of genes involved in signaling pathways associated with neurodegenerative disorders, ribosome function and protein translation may contribute to the pathogenesis of TOF

Critical Thinking Development in Pharmacy Education: A Meta-Analysis

Directory of Open Access Journals (Sweden)

Michael J Peeters

2016-03-01

Full Text Available Objective: The investigators aimed to summarize prior studies of critical thinking development among pharmacy students, using the California Critical Thinking Skills Test (CCTST, Health Sciences Reasoning Test (HSRT, and Defining Issues Test (DIT. Methods: Independently, two investigators (KLZ, MJP systematically searched available literature using PubMed, Google Scholar, ERIC, PsychInfo, as well as pharmacy education conference abstracts in American Journal of Pharmaceutical Education. Their search terms were ‘pharmacy’, and [‘critical thinking’, ‘HSRT’, ‘CCTST’, and ‘DIT’]. Studies included were those that investigated pharmacy students, used one of the tests (CCTST, HSRT, DIT, and used a longitudinal design with test administration at two or more time-points for the same subjects (i.e., development. On review, the CCTST and HSRT seem more foundational to analytical/critical thinking, while the DIT appears to measure moral/complex thinking. Summarizing used meta-analysis with Cohen’s d and random-effects modelling. Results: Five studies involved thinking development with 10 separate cohorts for meta-analysis (8 cohorts for CCTST, 2 for DIT, and 0 for HSRT. At 5 institutions, 407 and 1148 students were included (CCTST and DIT, respectively. For the CCTST, the overall effect was 0.33 (0.19-0.47 95%CI with some heterogeneity among study cohorts (I2=52%. For the DIT, the overall effect was -0.23 (-0.83-0.37 95%CI with considerable heterogeneity between study cohorts (I2=95%. For the CCTST and DIT, some studies showed effect-sizes greater than 0.5. Meta-analysis of the HSRT could not be conducted (i.e., 0 studies found. Implications: While measuring different aspects of “critical thinking”, the CCTST and DIT showed responsiveness to change and appear to be promising measures of cognitive development. These tests should be used in further well-designed research studies that explore strategies for improving cognitive

Lessons and challenges from adaptation pathways planning applications

Science.gov (United States)

Haasnoot, M.; Lawrence, J.; Kwakkel, J. H.; Walker, W.; Timmermans, J.; Bloemen, P.; Thissen, W.

2015-12-01

Planning for adaptation to dynamic risks (e.g., because of climate change) is a critical need. The concept of 'adaptive policies' is receiving increasing attention as a way of performing strategic planning that is able to address many of the inherent challenges of uncertainty and dynamic change. Several approaches for developing adaptive policies are available in the literature. One approach, for which several applications already exist, is Dynamic Adaptive Policy Pathways (DAPP). Pathway maps enable policy analysts, decision makers, and stakeholders to recognize potential 'locked-in' situations and to assess the flexibility, robustness, and efficacy of decision alternatives. Most of the applications of DAPP have been in deltas, coastal cities, or floodplains, often within the context of climate change adaptation. In this talk, we describe the DAPP approach and present a framework for designing signposts as adaptation signals, together with an illustrative application for the Rhine River in the Netherlands. We also draw lessons and challenges from pathways applications that differ in environment, culture, and institutional context. For example, the Dutch Delta Programme has used pathways to identify short-term decisions and long-term policy options. In Bangladesh, an application is in its early phase. Steps before generating pathways - such as long- term thinking in multiple possible futures and acknowledging uncertainties - are already a big challenge there. In New Zealand, the 'Sustainable Delta Game' has been used as the catalyst for pathways thinking by two local councils. This has led to its application in decision making for coastal and flood risk management and economic analysis of policy options.

The identification of critical groups

International Nuclear Information System (INIS)

Hunt, G.J.; Shepherd, J.G.

1980-01-01

The criteria for critical group identification are summarized and the extent to which they are satisfied by possible numerical methods are examined, drawing on UK experience in dose estimation within a system for setting controls on liquid radioactive waste discharges from major nuclear installations. The nature of the exposure pathway is an important factor in identifying an appropriate method. It is held that there is a greater uncertainty in estimating individual exposure from internal exposure than that from external exposure due to the greater relevance of metabolic variations. Accordingly different methods are proposed for numerical treatment of data associated with internal exposure pathways compared with external exposure pathways. (H.K.)

Analysis of the IPEN/MB-01 critical unit based on criticality experiments

International Nuclear Information System (INIS)

Santos, Adimir dos; Yamaguchi, Mitsuo; Ferreira, Carlos Roberto; Yoriyaz, Helio

1995-01-01

The analysis of the critical loading of the IPEN/MB-01 was performed by using several reactor cell methodologies. The results obtained by using the coupled NJOY/AMPX-II/HAMMER-TECHNION shows the good quality of the available nuclear data files as well as the methodologies in the Reactor Physics area. The original HAMMER system shows results that are well as the methodologies in the Reactor Physics area. The original HAMMER system shows results that are well outside of the desired quality for a cell code. (author), 15 refs, 3 figs, 5 tabs

Quantifying tight-gas sandstone permeability via critical path analysis

Science.gov (United States)

Rock permeability has been actively investigated over the past several decades by the geosciences community. However, its accurate estimation still presents significant technical challenges, especially in spatially complex rocks. In this letter, we apply critical path analysis (CPA) to estimate perm...

Assembly of inflammation-related genes for pathway-focused genetic analysis.

Directory of Open Access Journals (Sweden)

Matthew J Loza

2007-10-01

Full Text Available Recent identifications of associations between novel variants in inflammation-related genes and several common diseases emphasize the need for systematic evaluations of these genes in disease susceptibility. Considering that many genes are involved in the complex inflammation responses and many genetic variants in these genes have the potential to alter the functions and expression of these genes, we assembled a list of key inflammation-related genes to facilitate the identification of genetic associations of diseases with an inflammation-related etiology. We first reviewed various phases of inflammation responses, including the development of immune cells, sensing of danger, influx of cells to sites of insult, activation and functional responses of immune and non-immune cells, and resolution of the immune response. Assisted by the Ingenuity Pathway Analysis, we then identified 17 functional sub-pathways that are involved in one or multiple phases. This organization would greatly increase the chance of detecting gene-gene interactions by hierarchical clustering of genes with their functional closeness in a pathway. Finally, as an example application, we have developed tagging single nucleotide polymorphism (tSNP arrays for populations of European and African descent to capture all the common variants of these key inflammation-related genes. Assays of these tSNPs have been designed and assembled into two Affymetrix ParAllele customized chips, one each for European (12,011 SNPs and African (21,542 SNPs populations. These tSNPs have greater coverage for these inflammation-related genes compared to the existing genome-wide arrays, particularly in the African population. These tSNP arrays can facilitate systematic evaluation of inflammation pathways in disease susceptibility. For additional applications, other genotyping platforms could also be employed. For existing genome-wide association data, this list of key inflammation-related genes and

Genetic analysis of pathway regulation for enhancing branched-chain amino acid biosynthesis in plants

KAUST Repository

Chen, Hao

2010-08-01

The branched-chain amino acids (BCAAs) valine, leucine and isoleucine are essential amino acids that play critical roles in animal growth and development. Animals cannot synthesize these amino acids and must obtain them from their diet. Plants are the ultimate source of these essential nutrients, and they synthesize BCAAs through a conserved pathway that is inhibited by its end products. This feedback inhibition has prevented scientists from engineering plants that accumulate high levels of BCAAs by simply over-expressing the respective biosynthetic genes. To identify components critical for this feedback regulation, we performed a genetic screen for Arabidopsis mutants that exhibit enhanced resistance to BCAAs. Multiple dominant allelic mutations in the VALINE-TOLERANT 1 (VAT1) gene were identified that conferred plant resistance to valine inhibition. Map-based cloning revealed that VAT1 encodes a regulatory subunit of acetohydroxy acid synthase (AHAS), the first committed enzyme in the BCAA biosynthesis pathway. The VAT1 gene is highly expressed in young, rapidly growing tissues. When reconstituted with the catalytic subunit in vitro, the vat1 mutant-containing AHAS holoenzyme exhibits increased resistance to valine. Importantly, transgenic plants expressing the mutated vat1 gene exhibit valine tolerance and accumulate higher levels of BCAAs. Our studies not only uncovered regulatory characteristics of plant AHAS, but also identified a method to enhance BCAA accumulation in crop plants that will significantly enhance the nutritional value of food and feed. © 2010 Blackwell Publishing Ltd.

Supplement to the Disposal Criticality Analysis Methodology

International Nuclear Information System (INIS)

Thomas, D.A.

1999-01-01

The methodology for evaluating criticality potential for high-level radioactive waste and spent nuclear fuel after the repository is sealed and permanently closed is described in the Disposal Criticality Analysis Methodology Topical Report (DOE 1998b). The topical report provides a process for validating various models that are contained in the methodology and states that validation will be performed to support License Application. The Supplement to the Disposal Criticality Analysis Methodology provides a summary of data and analyses that will be used for validating these models and will be included in the model validation reports. The supplement also summarizes the process that will be followed in developing the model validation reports. These reports will satisfy commitments made in the topical report, and thus support the use of the methodology for Site Recommendation and License Application. It is concluded that this report meets the objective of presenting additional information along with references that support the methodology presented in the topical report and can be used both in validation reports and in answering request for additional information received from the Nuclear Regulatory Commission concerning the topical report. The data and analyses summarized in this report and presented in the references are not sufficient to complete a validation report. However, this information will provide a basis for several of the validation reports. Data from several references in this report have been identified with TBV-1349. Release of the TBV governing this data is required prior to its use in quality affecting activities and for use in analyses affecting procurement, construction, or fabrication. Subsequent to the initiation of TBV-1349, DOE issued a concurrence letter (Mellington 1999) approving the request to identify information taken from the references specified in Section 1.4 as accepted data

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

Science.gov (United States)

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

2017-05-24

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

Sensitivity analysis of intracellular signaling pathway kinetics predicts targets for stem cell fate control.

Directory of Open Access Journals (Sweden)

Alborz Mahdavi

2007-07-01

Full Text Available Directing stem cell fate requires knowledge of how signaling networks integrate temporally and spatially segregated stimuli. We developed and validated a computational model of signal transducer and activator of transcription-3 (Stat3 pathway kinetics, a signaling network involved in embryonic stem cell (ESC self-renewal. Our analysis identified novel pathway responses; for example, overexpression of the receptor glycoprotein-130 results in reduced pathway activation and increased ESC differentiation. We used a systematic in silico screen to identify novel targets and protein interactions involved in Stat3 activation. Our analysis demonstrates that signaling activation and desensitization (the inability to respond to ligand restimulation is regulated by balancing the activation state of a distributed set of parameters including nuclear export of Stat3, nuclear phosphatase activity, inhibition by suppressor of cytokine signaling, and receptor trafficking. This knowledge was used to devise a temporally modulated ligand delivery strategy that maximizes signaling activation and leads to enhanced ESC self-renewal.

Comprehensive analysis of schizophrenia-associated loci highlights ion channel pathways and biologically plausible candidate causal genes

DEFF Research Database (Denmark)

Pers, Tune H; Timshel, Pascal; Ripke, Stephan

2016-01-01

Over 100 associated genetic loci have been robustly associated with schizophrenia. Gene prioritization and pathway analysis have focused on a priori hypotheses and thus may have been unduly influenced by prior assumptions and missed important causal genes and pathways. Using a data-driven approac...

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

Science.gov (United States)

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

2012-01-01

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

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

Directory of Open Access Journals (Sweden)

Eva Chovancova

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

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

Science.gov (United States)

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

2012-01-01

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

New design procedure development of future reactor critical power estimation. (1) Practical design-by-analysis method for BWR critical power design correlation

International Nuclear Information System (INIS)

Yamamoto, Yasushi; Mitsutake, Toru

2007-01-01

For present BWR fuels, the full mock-up thermal-hydraulic test, such as the critical power measurement test, pressure drop measurement test and so on, has been needed. However, the full mock-up test required the high costs and large-scale test facility. At present, there are only a few test facilities to perform the full mock-up thermal-hydraulic test in the world. Moreover, for future BWR, the bundle size tends to be larger, because of reducing the plant construction costs and minimizing the routine check period. For instance, AB1600, improved ABWR, was proposed from Toshiba, whose bundle size was 1.2 times larger than the conventional BWR fuel size. It is too expensive and far from realistic to perform the full mock-up thermal-hydraulic test for such a large size fuel bundle. The new design procedure is required to realize the large scale bundle design development, especially for the future reactor. Therefore, the new design procedure, Practical Design-by-Analysis (PDBA) method, has been developed. This new procedure consists of the partial mock-up test and numerical analysis. At present, the subchannel analysis method based on three-fluid two-phase flow model only is a realistic choice. Firstly, the partial mock-up test is performed, for instance, the 1/4 partial mock-up bundle. Then, the first-step critical power correlation coefficients are evaluated with the measured data. The input data, such as the spacer effect model coefficient, on the subchannel analysis are also estimated with the data. Next, the radial power effect on the critical power of the full-bundle size was estimated with the subchannel analysis. Finally, the critical power correlation is modified by the subchannel analysis results. In the present study, the critical power correlation of the conventional 8x8 BWR fuel was developed with the PDBA method by 4x4 partial mock-up tests and the subchannel analysis code. The accuracy of the estimated critical power was 3.8%. The several themes remain to

Análisis de criticidad personalizados // Analysis of Criticity Personalized

Directory of Open Access Journals (Sweden)

A. M. del Castillo-Serpa

2009-09-01

Full Text Available En la actualidad existen diferentes enfoques del mantenimiento con los cuales se ha logrado muybuenos resultados a nivel mundial, ejemplo de esto es el Mantenimiento Centrado en laConfiabilidad (RCM, el cual constituye un sistema avanzado de gestión, que con una correctaimplementación garantiza la eficiencia y eficacia del mantenimiento. Basado en un análisis desistemas previo, resulta conveniente definir los niveles de criticidad de los diferentes equipos, deque consta cada sistema. Se impone la necesidad de desarrollar una metodología para el análisis dela criticidad, para ser aplicada en diferentes instalaciones, que incluye la obtención de unaexpresión matemática, que basada en ciertos criterios de evaluación analice la criticidad particularen cada caso sometido a este proceso.En este trabajo se verifica la factibilidad de la metodología propuesta, con el objetivo de realizar elanálisis de sistemas y el análisis de criticidad de forma personalizada.Se muestran los resultados de la expresión matemática obtenida en cada caso, y su validación. Laaplicación de esta metodología ha permitido direccionar los recursos de mantenimiento hacia lossubsistemas de mayor criticidad, mejorando significativamente la relación costo beneficio en estaactividad, así como la obtención de un software que automatiza este análisis.Palabras claves: confiabilidad, diagnóstico, mantenimiento, criticidad.______________________________________________________________________________AbstractAt the present time different focuses of the maintenance exist with which has been achieved verygood results at world level, example of this it is the Centered Maintenance in the Dependability(RCM, which constitutes an advanced system of administration that guarantees the efficiency andeffectiveness of the maintenance with a correct implementation. Based on a previous analysis ofsystems, it is convenient to define the levels of criticity of the different teams

Rehabilitative skilled forelimb training enhances axonal remodeling in the corticospinal pathway but not the brainstem-spinal pathways after photothrombotic stroke in the primary motor cortex.

Science.gov (United States)

Okabe, Naohiko; Himi, Naoyuki; Maruyama-Nakamura, Emi; Hayashi, Norito; Narita, Kazuhiko; Miyamoto, Osamu

2017-01-01

Task-specific rehabilitative training is commonly used for chronic stroke patients. Axonal remodeling is believed to be one mechanism underlying rehabilitation-induced functional recovery, and significant roles of the corticospinal pathway have previously been demonstrated. Brainstem-spinal pathways, as well as the corticospinal tract, have been suggested to contribute to skilled motor function and functional recovery after brain injury. However, whether axonal remodeling in the brainstem-spinal pathways is a critical component for rehabilitation-induced functional recovery is not known. In this study, rats were subjected to photothrombotic stroke in the caudal forelimb area of the primary motor cortex and received rehabilitative training with a skilled forelimb reaching task for 4 weeks. After completion of the rehabilitative training, the retrograde tracer Fast blue was injected into the contralesional lower cervical spinal cord. Fast blue-positive cells were counted in 32 brain areas located in the cerebral cortex, hypothalamus, midbrain, pons, and medulla oblongata. Rehabilitative training improved motor performance in the skilled forelimb reaching task but not in the cylinder test, ladder walk test, or staircase test, indicating that rehabilitative skilled forelimb training induced task-specific recovery. In the histological analysis, rehabilitative training significantly increased the number of Fast blue-positive neurons in the ipsilesional rostral forelimb area and secondary sensory cortex. However, rehabilitative training did not alter the number of Fast blue-positive neurons in any areas of the brainstem. These results indicate that rehabilitative skilled forelimb training enhances axonal remodeling selectively in the corticospinal pathway, which suggests a critical role of cortical plasticity, rather than brainstem plasticity, in task-specific recovery after subtotal motor cortex destruction.

Criticality Model

International Nuclear Information System (INIS)

Alsaed, A.

2004-01-01

The ''Disposal Criticality Analysis Methodology Topical Report'' (YMP 2003) presents the methodology for evaluating potential criticality situations in the monitored geologic repository. As stated in the referenced Topical Report, the detailed methodology for performing the disposal criticality analyses will be documented in model reports. Many of the models developed in support of the Topical Report differ from the definition of models as given in the Office of Civilian Radioactive Waste Management procedure AP-SIII.10Q, ''Models'', in that they are procedural, rather than mathematical. These model reports document the detailed methodology necessary to implement the approach presented in the Disposal Criticality Analysis Methodology Topical Report and provide calculations utilizing the methodology. Thus, the governing procedure for this type of report is AP-3.12Q, ''Design Calculations and Analyses''. The ''Criticality Model'' is of this latter type, providing a process evaluating the criticality potential of in-package and external configurations. The purpose of this analysis is to layout the process for calculating the criticality potential for various in-package and external configurations and to calculate lower-bound tolerance limit (LBTL) values and determine range of applicability (ROA) parameters. The LBTL calculations and the ROA determinations are performed using selected benchmark experiments that are applicable to various waste forms and various in-package and external configurations. The waste forms considered in this calculation are pressurized water reactor (PWR), boiling water reactor (BWR), Fast Flux Test Facility (FFTF), Training Research Isotope General Atomic (TRIGA), Enrico Fermi, Shippingport pressurized water reactor, Shippingport light water breeder reactor (LWBR), N-Reactor, Melt and Dilute, and Fort Saint Vrain Reactor spent nuclear fuel (SNF). The scope of this analysis is to document the criticality computational method. The criticality

Critical Action as a Pathway to Social Mobility among Marginalized Youth

Science.gov (United States)

Rapa, Luke J.; Diemer, Matthew A.; Bañales, Josefina

2018-01-01

Marginalized youth's development occurs in contexts rife with racialized, gendered, and socioeconomic social identity threats and barriers to social mobility. An emergent line of inquiry suggests critical action--a component of critical consciousness, defined as engaging in individual or collective social action to produce social change--may…

Genome-wide transcriptome analysis of hippocampus in rats indicated that TLR/NLR signaling pathway was involved in the pathogenisis of depressive disorder induced by chronic restraint stress.

Science.gov (United States)

Wang, Yu; Jiang, Huili; Meng, Hong; Lu, Jun; Li, Jing; Zhang, Xuhui; Yang, Xinjing; Zhao, Bingcong; Sun, Yang; Bao, Tuya

2017-09-01

Data from clinical investigations and laboratory fundings have provided preliminary evidence for the effectiveness and safety of acupuncture therapy in depression. However, the mechanisms underlying the antidepressant response of acupuncture are not fully elucidated. To elucidate the potential effects of acupuncture for depression on the hippocampal genome-wide transcriptome at the molecular level, we evaluated the transcriptomic profile of depression rats under treatment of acupuncture, and fluoxetine. We identified a very significant effect of acupucture intervention, with 107 genes differentially expressed in acupuncture vs. model group; while 41 genes between fluoxetine vs. model group. Notably, the 54 differentially expressed genes between acupuncture and fluoxetine showed the significantly different effect between acupuncture and fluoxetine. Through GO (gene ontology) functional term and KEGG (kyoto encyclopedia of genes and genomes) pathway analysis, we identified that the upregulation of gene sets were related to inflammatory response, innate immunity and immune response. We found that toll-like receptor signalling pathway and NOD like receptor signalling pathway were associated with the function of inflammatory response, innate immunity and immune response. Importantly, acupuncture reversed the upregulation of gene sets that were related to inflammatory response, innate immunity and immune response (including toll-like receptor signalling pathway and NOD like receptor signalling pathway), which might be critical for the pathogenesis of depression and provide evidence for the antidepressive effects of acupuncture by regulating inflammatory response, innate immunity and immune response via toll-like receptor signalling pathway and NOD like receptor signalling pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

I Frankenstein: from media critical reception to the semiological analysis

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João Marcos Mateus Kogawa

2017-10-01

Full Text Available In 2014, the movie I, Frankenstein was released. This movie has raised some comments from the media criticism, among which we list some to be object of our analysis. The analysis of critical statements reveals a discourse based on the axes of morality, profitability, traditionalism and temporality that produces a disqualification sense, which means that the movie is something that ‘hurts’ the notion of ‘classic’. From this demonstration, this paper questions the claims that the new Frankenstein should respond to a tradition opened by Mary Shelley to point some senses that re-construct the contemporary myth. Therefore, the new Frankenstein requires an interrelationship between technical apparatus - 3D technology - and a contemporary myth - an ideal of consumption facing interactivity.

Uncertainties in criticality analysis which affect the storage and transportation of LWR fuel

International Nuclear Information System (INIS)

Napolitani, D.G.

1989-01-01

Satisfying the design criteria for subcriticality with uncertainties affects: the capacity of LWR storage arrays, maximum allowable enrichment, minimum allowable burnup and economics of various storage options. There are uncertainties due to: calculational method, data libraries, geometric limitations, modelling bias, the number and quality of benchmarks performed and mechanical uncertainties in the array. Yankee Atomic Electric Co. (YAEC) has developed and benchmarked methods to handle: high density storage rack designs, pin consolidation, low density moderation and burnup credit. The uncertainties associated with such criticality analysis are quantified on the basis of clean criticals, power reactor criticals and intercomparison of independent analysis methods

Selection and Evaluation of Media for Behavioral Health Interventions Employing Critical Media Analysis.

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Wilson, Patrick A; Cherenack, Emily M; Jadwin-Cakmak, Laura; Harper, Gary W

2018-01-01

Although a growing number of psychosocial health promotion interventions use the critical analysis of media to facilitate behavior change, no specific guidelines exist to assist researchers and practitioners in the selection and evaluation of culturally relevant media stimuli for intervention development. Mobilizing Our Voices for Empowerment is a critical consciousness-based health enhancement intervention for HIV-positive Black young gay/bisexual men that employs the critical analysis of popular media. In the process of developing and testing this intervention, feedback on media stimuli was collected from youth advisory board members (n = 8), focus group participants (n = 19), intervention participants (n = 40), and intervention facilitators (n = 6). A thematic analysis of qualitative data resulted in the identification of four key attributes of media stimuli and participants' responses to media stimuli that are important to consider when selecting and evaluating media stimuli for use in behavioral health interventions employing the critical analysis of media: comprehension, relevance, emotionality, and action. These four attributes are defined and presented as a framework for evaluating media, and adaptable tools are provided based on this framework to guide researchers and practitioners in the selection and evaluation of media for similar interventions.

Impact on mortality of prompt admission to critical care for deteriorating ward patients: an instrumental variable analysis using critical care bed strain.

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Harris, Steve; Singer, Mervyn; Sanderson, Colin; Grieve, Richard; Harrison, David; Rowan, Kathryn

2018-05-07

To estimate the effect of prompt admission to critical care on mortality for deteriorating ward patients. We performed a prospective cohort study of consecutive ward patients assessed for critical care. Prompt admissions (within 4 h of assessment) were compared to a 'watchful waiting' cohort. We used critical care strain (bed occupancy) as a natural randomisation event that would predict prompt transfer to critical care. Strain was classified as low, medium or high (2+, 1 or 0 empty beds). This instrumental variable (IV) analysis was repeated for the subgroup of referrals with a recommendation for critical care once assessed. Risk-adjusted 90-day survival models were also constructed. A total of 12,380 patients from 48 hospitals were available for analysis. There were 2411 (19%) prompt admissions (median delay 1 h, IQR 1-2) and 9969 (81%) controls; 1990 (20%) controls were admitted later (median delay 11 h, IQR 6-26). Prompt admissions were less frequent (p care. In the risk-adjust survival model, 90-day mortality was similar. After allowing for unobserved prognostic differences between the groups, we find that prompt admission to critical care leads to lower 90-day mortality for patients assessed and recommended to critical care.

Analysis of criticality experiments at SHE

International Nuclear Information System (INIS)

Takano, Makoto; Doi, Takeshi; Hirano, Mitsumasa; Shindo, Ryuichi; Oomura, Hiroshi

1982-03-01

In the report, the criticality experiments, which were conducted for the core configurations of Semi-Homogeneous Experimental Assembly (SHE)-8,12,13,14, are analyzed for the purpose of verifying the computer codes and calculational methods employed in the nuclear design of VHTR. The codes, DELIGHT-5 and CITATION calculate the neutron spectrum and the effective multiplication factor respectively. Each system of SHE is modeled by twodimensional R-Z, Triangular and threedimensional Triangular-Z geometries. Various effects such as axial buckling, modeling and the difference between diffusion and transport are also taken into account. Calculated values of effective multiplication factor show the disagreement of 1 - 3% from the values of experiments approximately. Therefore the analysis is considered to be inadequate to the verification and more precise analysis is required with the emphasis on how to model the system, condense the group constants and guess the buckling value for spectrum calculation. (author)

Do Instructional Interventions Influence College Students' Critical Thinking Skills? A Meta-Analysis

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Niu, Lian; Behar-Horenstein, Linda S.; Garvan, Cyndi W.

2013-01-01

Promoting students' critical thinking skills is an important task of higher education. Colleges and universities have designed various instructional interventions to enhance students' critical thinking skills. Empirical studies have yielded inconsistent results in terms of the effects of such interventions. This meta-analysis presents a synthesis…

A Simple Geotracer Compositional Correlation Analysis Reveals Oil Charge and Migration Pathways

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Yang, Yunlai; Arouri, Khaled

2016-03-01

A novel approach, based on geotracer compositional correlation analysis is reported, which reveals the oil charge sequence and migration pathways for five oil fields in Saudi Arabia. The geotracers utilised are carbazoles, a family of neutral pyrrolic nitrogen compounds known to occur naturally in crude oils. The approach is based on the concept that closely related fields, with respect to filling sequence, will show a higher carbazole compositional correlation, than those fields that are less related. That is, carbazole compositional correlation coefficients can quantify the charge and filling relationships among different fields. Consequently, oil migration pathways can be defined based on the established filling relationships. The compositional correlation coefficients of isomers of C1 and C2 carbazoles, and benzo[a]carbazole for all different combination pairs of the five fields were found to vary extremely widely (0.28 to 0.94). A wide range of compositional correlation coefficients allows adequate differentiation of separate filling relationships. Based on the established filling relationships, three distinct migration pathways were inferred, with each apparently being charged from a different part of a common source kitchen. The recognition of these charge and migration pathways will greatly aid the search for new accumulations.

A Simple Geotracer Compositional Correlation Analysis Reveals Oil Charge and Migration Pathways.

Science.gov (United States)

Yang, Yunlai; Arouri, Khaled

2016-03-11

A novel approach, based on geotracer compositional correlation analysis is reported, which reveals the oil charge sequence and migration pathways for five oil fields in Saudi Arabia. The geotracers utilised are carbazoles, a family of neutral pyrrolic nitrogen compounds known to occur naturally in crude oils. The approach is based on the concept that closely related fields, with respect to filling sequence, will show a higher carbazole compositional correlation, than those fields that are less related. That is, carbazole compositional correlation coefficients can quantify the charge and filling relationships among different fields. Consequently, oil migration pathways can be defined based on the established filling relationships. The compositional correlation coefficients of isomers of C1 and C2 carbazoles, and benzo[a]carbazole for all different combination pairs of the five fields were found to vary extremely widely (0.28 to 0.94). A wide range of compositional correlation coefficients allows adequate differentiation of separate filling relationships. Based on the established filling relationships, three distinct migration pathways were inferred, with each apparently being charged from a different part of a common source kitchen. The recognition of these charge and migration pathways will greatly aid the search for new accumulations.

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

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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

Critical Education for Systemic Change: A World-Systems Analysis Perspective

Science.gov (United States)

Griffiths, Tom G.

2015-01-01

This paper both draws on, and seeks to apply, world-systems analysis to a broad, critical education project that builds mass schooling's potential contribution to the process of world-systemic change. In short, this is done by first setting out the world-systems analysis account of the current state, and period of transition, of the capitalist…

Analysis of Critical Thinking Skills on The Topic of Static Fluid

Science.gov (United States)

Puspita, I.; Kaniawati, I.; Suwarma, I. R.

2017-09-01

This study aimed to know the critical thinking skills profil of senior high school students. This research using a descriptive study to analysis student test results of critical thinking skill of 40 students XI grade in one of the senior high school in Bogor District. The method used is survey research with sample determined by purposive sampling technique. The instrument used is test of critical thinking skill by 5 indicators on static fluid topics. Questions consist of 11 set. It is has been developed by researcher and validated by experts. The results showed students critical thinking skills are still low. Is almost every indicator of critical thinking skills only reaches less than 30%. 28% for elementary clarification, 10% for the basic for decisions/basic support, 6% for inference, 6% for advanced clarification, 4% for strategies and tactics.

Computational Chemical Synthesis Analysis and Pathway Design

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Fan Feng

2018-06-01

Full Text Available With the idea of retrosynthetic analysis, which was raised in the 1960s, chemical synthesis analysis and pathway design have been transformed from a complex problem to a regular process of structural simplification. This review aims to summarize the developments of computer-assisted synthetic analysis and design in recent years, and how machine-learning algorithms contributed to them. LHASA system started the pioneering work of designing semi-empirical reaction modes in computers, with its following rule-based and network-searching work not only expanding the databases, but also building new approaches to indicating reaction rules. Programs like ARChem Route Designer replaced hand-coded reaction modes with automatically-extracted rules, and programs like Chematica changed traditional designing into network searching. Afterward, with the help of machine learning, two-step models which combine reaction rules and statistical methods became the main stream. Recently, fully data-driven learning methods using deep neural networks which even do not require any prior knowledge, were applied into this field. Up to now, however, these methods still cannot replace experienced human organic chemists due to their relatively low accuracies. Future new algorithms with the aid of powerful computational hardware will make this topic promising and with good prospects.

Maintaining scale as a realiable computational system for criticality safety analysis

International Nuclear Information System (INIS)

Bowmann, S.M.; Parks, C.V.; Martin, S.K.

1995-01-01

Accurate and reliable computational methods are essential for nuclear criticality safety analyses. The SCALE (Standardized Computer Analyses for Licensing Evaluation) computer code system was originally developed at Oak Ridge National Laboratory (ORNL) to enable users to easily set up and perform criticality safety analyses, as well as shielding, depletion, and heat transfer analyses. Over the fifteen-year life of SCALE, the mainstay of the system has been the criticality safety analysis sequences that have featured the KENO-IV and KENO-V.A Monte Carlo codes and the XSDRNPM one-dimensional discrete-ordinates code. The criticality safety analysis sequences provide automated material and problem-dependent resonance processing for each criticality calculation. This report details configuration management which is essential because SCALE consists of more than 25 computer codes (referred to as modules) that share libraries of commonly used subroutines. Changes to a single subroutine in some cases affect almost every module in SCALE exclamation point Controlled access to program source and executables and accurate documentation of modifications are essential to maintaining SCALE as a reliable code system. The modules and subroutine libraries in SCALE are programmed by a staff of approximately ten Code Managers. The SCALE Software Coordinator maintains the SCALE system and is the only person who modifies the production source, executables, and data libraries. All modifications must be authorized by the SCALE Project Leader prior to implementation

SECOND WASTE PACKAGE PROBABILISTIC CRITICALITY ANALYSIS: GENERATION AND EVALUATION OF INTERNAL CRITICIALITY CONFIGURATIONS

Energy Technology Data Exchange (ETDEWEB)

P. Gottlieb, J.R. Massari, J.K. McCoy

1996-03-27

This analysis is prepared by the Mined Geologic Disposal System (MGDS) Waste Package Development (WPD) department to provide an evaluation of the criticality potential within a waste package having sonic or all of its contents degraded by corrosion and removal of neutron absorbers. This analysis is also intended to provide an estimate of the consequences of any internal criticality, particularly in terms of any increase in radionuclide inventory. These consequence estimates will be used as part of the WPD input to the Total System Performance Assessment. The ultimate objective of this analysis is to augment the information gained from the Initial Waste Package Probabilistic Criticality Analyses (Ref. 5.8 and 5.9, hereafter referred to as IPA) to a degree which will support preliminary waste package design recommendations intended to reduce the risk of waste package criticality and the risk to total repository system performance posed by the consequences of any criticality. The IPA evaluated the criticality potential under the assumption that the waste package basket retained its structural integrity, so that the assemblies retained their initial separation, even when the neutron absorbers had been leached from the basket. This analysis is based on the more realistic condition that removal of the neutron absorbers is a consequence of the corrosion of the steel in which they are contained, which has the additional consequence of reducing the structural support between assemblies. The result is a set of more reactive configurations having a smaller spacing between assemblies, or no inter-assembly spacing at all. Another difference from the IPA is the minimal attention to probabilistic evaluation given in this study. Although the IPA covered a time horizon to 100,000 years, the lack of consideration of basket degradation modes made it primarily applicable to the first 10,000 years. In contrast, this study, by focusing on the degraded modes of the basket, is primarily

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.”

Beyond Mirrors and Windows: A Critical Content Analysis of Latinx Children's Books

Science.gov (United States)

Braden, Eliza G.; Rodriguez, Sanjuana C.

2016-01-01

This critical content analysis examines the representation of Latinx characters in 15 picture books published in 2013 and identified by Children's Cooperative Book Center (CCBC) as having significant Latinx content. The theoretical framework undergirding this study is Critical Race Theory (Ladson-Billings, 1998; Solórzano & Yosso, 2002;…

Dexter energy transfer pathways.

Science.gov (United States)

Skourtis, Spiros S; Liu, Chaoren; Antoniou, Panayiotis; Virshup, Aaron M; Beratan, David N

2016-07-19

Energy transfer with an associated spin change of the donor and acceptor, Dexter energy transfer, is critically important in solar energy harvesting assemblies, damage protection schemes of photobiology, and organometallic opto-electronic materials. Dexter transfer between chemically linked donors and acceptors is bridge mediated, presenting an enticing analogy with bridge-mediated electron and hole transfer. However, Dexter coupling pathways must convey both an electron and a hole from donor to acceptor, and this adds considerable richness to the mediation process. We dissect the bridge-mediated Dexter coupling mechanisms and formulate a theory for triplet energy transfer coupling pathways. Virtual donor-acceptor charge-transfer exciton intermediates dominate at shorter distances or higher tunneling energy gaps, whereas virtual intermediates with an electron and a hole both on the bridge (virtual bridge excitons) dominate for longer distances or lower energy gaps. The effects of virtual bridge excitons were neglected in earlier treatments. The two-particle pathway framework developed here shows how Dexter energy-transfer rates depend on donor, bridge, and acceptor energetics, as well as on orbital symmetry and quantum interference among pathways.

Multi-variant pathway association analysis reveals the importance of genetic determinants of estrogen metabolism in breast and endometrial cancer susceptibility.

Directory of Open Access Journals (Sweden)

Yen Ling Low

2010-07-01

Full Text Available Despite the central role of estrogen exposure in breast and endometrial cancer development and numerous studies of genes in the estrogen metabolic pathway, polymorphisms within the pathway have not been consistently associated with these cancers. We posit that this is due to the complexity of multiple weak genetic effects within the metabolic pathway that can only be effectively detected through multi-variant analysis. We conducted a comprehensive association analysis of the estrogen metabolic pathway by interrogating 239 tagSNPs within 35 genes of the pathway in three tumor samples. The discovery sample consisted of 1,596 breast cancer cases, 719 endometrial cancer cases, and 1,730 controls from Sweden; and the validation sample included 2,245 breast cancer cases and 1,287 controls from Finland. We performed admixture maximum likelihood (AML-based global tests to evaluate the cumulative effect from multiple SNPs within the whole metabolic pathway and three sub-pathways for androgen synthesis, androgen-to-estrogen conversion, and estrogen removal. In the discovery sample, although no single polymorphism was significant after correction for multiple testing, the pathway-based AML global test suggested association with both breast (p(global = 0.034 and endometrial (p(global = 0.052 cancers. Further testing revealed the association to be focused on polymorphisms within the androgen-to-estrogen conversion sub-pathway, for both breast (p(global = 0.008 and endometrial cancer (p(global = 0.014. The sub-pathway association was validated in the Finnish sample of breast cancer (p(global = 0.015. Further tumor subtype analysis demonstrated that the association of the androgen-to-estrogen conversion sub-pathway was confined to postmenopausal women with sporadic estrogen receptor positive tumors (p(global = 0.0003. Gene-based AML analysis suggested CYP19A1 and UGT2B4 to be the major players within the sub-pathway. Our study indicates that the composite

Analysis of PIK3CA Mutations and Activation Pathways in Triple Negative Breast Cancer.

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Paolo Cossu-Rocca

Full Text Available Triple Negative Breast Cancer (TNBC accounts for 12-24% of all breast carcinomas, and shows worse prognosis compared to other breast cancer subtypes. Molecular studies demonstrated that TNBCs are a heterogeneous group of tumors with different clinical and pathologic features, prognosis, genetic-molecular alterations and treatment responsivity. The PI3K/AKT is a major pathway involved in the regulation of cell survival and proliferation, and is the most frequently altered pathway in breast cancer, apparently with different biologic impact on specific cancer subtypes. The most common genetic abnormality is represented by PIK3CA gene activating mutations, with an overall frequency of 20-40%. The aims of our study were to investigate PIK3CA gene mutations on a large series of TNBC, to perform a wider analysis on genetic alterations involving PI3K/AKT and BRAF/RAS/MAPK pathways and to correlate the results with clinical-pathologic data.PIK3CA mutation analysis was performed by using cobas® PIK3CA Mutation Test. EGFR, AKT1, BRAF, and KRAS genes were analyzed by sequencing. Immunohistochemistry was carried out to identify PTEN loss and to investigate for PI3K/AKT pathways components.PIK3CA mutations were detected in 23.7% of TNBC, whereas no mutations were identified in EGFR, AKT1, BRAF, and KRAS genes. Moreover, we observed PTEN loss in 11.3% of tumors. Deregulation of PI3K/AKT pathways was revealed by consistent activation of pAKT and p-p44/42 MAPK in all PIK3CA mutated TNBC.Our data shows that PIK3CA mutations and PI3K/AKT pathway activation are common events in TNBC. A deeper investigation on specific TNBC genomic abnormalities might be helpful in order to select patients who would benefit from current targeted therapy strategies.

Analysis of PIK3CA Mutations and Activation Pathways in Triple Negative Breast Cancer.

Science.gov (United States)

Cossu-Rocca, Paolo; Orrù, Sandra; Muroni, Maria Rosaria; Sanges, Francesca; Sotgiu, Giovanni; Ena, Sara; Pira, Giovanna; Murgia, Luciano; Manca, Alessandra; Uras, Maria Gabriela; Sarobba, Maria Giuseppina; Urru, Silvana; De Miglio, Maria Rosaria

2015-01-01

Triple Negative Breast Cancer (TNBC) accounts for 12-24% of all breast carcinomas, and shows worse prognosis compared to other breast cancer subtypes. Molecular studies demonstrated that TNBCs are a heterogeneous group of tumors with different clinical and pathologic features, prognosis, genetic-molecular alterations and treatment responsivity. The PI3K/AKT is a major pathway involved in the regulation of cell survival and proliferation, and is the most frequently altered pathway in breast cancer, apparently with different biologic impact on specific cancer subtypes. The most common genetic abnormality is represented by PIK3CA gene activating mutations, with an overall frequency of 20-40%. The aims of our study were to investigate PIK3CA gene mutations on a large series of TNBC, to perform a wider analysis on genetic alterations involving PI3K/AKT and BRAF/RAS/MAPK pathways and to correlate the results with clinical-pathologic data. PIK3CA mutation analysis was performed by using cobas® PIK3CA Mutation Test. EGFR, AKT1, BRAF, and KRAS genes were analyzed by sequencing. Immunohistochemistry was carried out to identify PTEN loss and to investigate for PI3K/AKT pathways components. PIK3CA mutations were detected in 23.7% of TNBC, whereas no mutations were identified in EGFR, AKT1, BRAF, and KRAS genes. Moreover, we observed PTEN loss in 11.3% of tumors. Deregulation of PI3K/AKT pathways was revealed by consistent activation of pAKT and p-p44/42 MAPK in all PIK3CA mutated TNBC. Our data shows that PIK3CA mutations and PI3K/AKT pathway activation are common events in TNBC. A deeper investigation on specific TNBC genomic abnormalities might be helpful in order to select patients who would benefit from current targeted therapy strategies.

A knowledge-based T2-statistic to perform pathway analysis for quantitative proteomic data.

Science.gov (United States)

Lai, En-Yu; Chen, Yi-Hau; Wu, Kun-Pin

2017-06-01

Approaches to identify significant pathways from high-throughput quantitative data have been developed in recent years. Still, the analysis of proteomic data stays difficult because of limited sample size. This limitation also leads to the practice of using a competitive null as common approach; which fundamentally implies genes or proteins as independent units. The independent assumption ignores the associations among biomolecules with similar functions or cellular localization, as well as the interactions among them manifested as changes in expression ratios. Consequently, these methods often underestimate the associations among biomolecules and cause false positives in practice. Some studies incorporate the sample covariance matrix into the calculation to address this issue. However, sample covariance may not be a precise estimation if the sample size is very limited, which is usually the case for the data produced by mass spectrometry. In this study, we introduce a multivariate test under a self-contained null to perform pathway analysis for quantitative proteomic data. The covariance matrix used in the test statistic is constructed by the confidence scores retrieved from the STRING database or the HitPredict database. We also design an integrating procedure to retain pathways of sufficient evidence as a pathway group. The performance of the proposed T2-statistic is demonstrated using five published experimental datasets: the T-cell activation, the cAMP/PKA signaling, the myoblast differentiation, and the effect of dasatinib on the BCR-ABL pathway are proteomic datasets produced by mass spectrometry; and the protective effect of myocilin via the MAPK signaling pathway is a gene expression dataset of limited sample size. Compared with other popular statistics, the proposed T2-statistic yields more accurate descriptions in agreement with the discussion of the original publication. We implemented the T2-statistic into an R package T2GA, which is available at https

Triple phase boundary specific pathway analysis for quantitative characterization of solid oxide cell electrode microstructure

DEFF Research Database (Denmark)

Jørgensen, Peter Stanley; Ebbehøj, Søren Lyng; Hauch, Anne

2015-01-01

of the pathways through which they can be reached. New methods for performing TPB specific pathway analysis on 3D image data are introduced, analyzing the pathway properties of each TPB site in the electrode structure. The methods seek to provide additional information beyond whether the TPB sites are percolating......The density and percolation of Triple phase boundary sites are important quantities in analyzing microstructures of solid oxide fuel cell electrodes from tomography data. However, these measures do not provide descriptions of the quality of the TPB sites in terms of the length and radius...... or not by also analyzing the pathway length to the TPB sites and the bottleneck radius of the pathway. We show how these methods can be utilized in quantifying and relating the TPB specific results to cell test data of an electrode reduction protocol study for Ni/Scandia-and-Yttria-doped-Zirconia (Ni...

Parallel imaging of Drosophila embryos for quantitative analysis of genetic perturbations of the Ras pathway

Directory of Open Access Journals (Sweden)

Yogesh Goyal

2017-07-01

Full Text Available The Ras pathway patterns the poles of the Drosophila embryo by downregulating the levels and activity of a DNA-binding transcriptional repressor Capicua (Cic. We demonstrate that the spatiotemporal pattern of Cic during this signaling event can be harnessed for functional studies of mutations in the Ras pathway in human diseases. Our approach relies on a new microfluidic device that enables parallel imaging of Cic dynamics in dozens of live embryos. We found that although the pattern of Cic in early embryos is complex, it can be accurately approximated by a product of one spatial profile and one time-dependent amplitude. Analysis of these functions of space and time alone reveals the differential effects of mutations within the Ras pathway. Given the highly conserved nature of Ras-dependent control of Cic, our approach provides new opportunities for functional analysis of multiple sequence variants from developmental abnormalities and cancers.

A gene pathway analysis highlights the role of cellular adhesion molecules in multiple sclerosis susceptibility

DEFF Research Database (Denmark)

Damotte, V; Guillot-Noel, L; Patsopoulos, N A

2014-01-01

adhesion molecule (CAMs) biological pathway using Cytoscape software. This network is a strong candidate, as it is involved in the crossing of the blood-brain barrier by the T cells, an early event in MS pathophysiology, and is used as an efficient therapeutic target. We drew up a list of 76 genes...... in interaction with other genes as a group. Pathway analysis is an alternative way to highlight such group of genes. Using SNP association P-values from eight multiple sclerosis (MS) GWAS data sets, we performed a candidate pathway analysis for MS susceptibility by considering genes interacting in the cell...... belonging to the CAM network. We highlighted 64 networks enriched with CAM genes with low P-values. Filtering by a percentage of CAM genes up to 50% and rejecting enriched signals mainly driven by transcription factors, we highlighted five networks associated with MS susceptibility. One of them, constituted...

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

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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.

Examining Bilingual Children's Gender Ideologies through Critical Discourse Analysis

Science.gov (United States)

Martinez-Roldan, Carmen M.

2005-01-01

This article presents a case study of young bilingual students' discussions of literature in a second-grade Spanish/English bilingual classroom in the US. Sociocultural, critical, and Chicana feminist perspectives informed an analysis of the ways the children worked at understanding, marking, and resisting gender boundaries. This critical…

The Potential Unity of Critical Thinking and Values Analysis.

Science.gov (United States)

Browne, M. Neil

Metaphorically, the head and the heart represent different decision-making strategies. The disjunction between these two cultures is both sharp and unnecessary. The conflict between rationality and emotion is much broader than the tension between critical thinking and values analysis, but the assumptions responsible for the mutual awkwardness of…

Computational Methods for Sensitivity and Uncertainty Analysis in Criticality Safety

International Nuclear Information System (INIS)

Broadhead, B.L.; Childs, R.L.; Rearden, B.T.

1999-01-01

Interest in the sensitivity methods that were developed and widely used in the 1970s (the FORSS methodology at ORNL among others) has increased recently as a result of potential use in the area of criticality safety data validation procedures to define computational bias, uncertainties and area(s) of applicability. Functional forms of the resulting sensitivity coefficients can be used as formal parameters in the determination of applicability of benchmark experiments to their corresponding industrial application areas. In order for these techniques to be generally useful to the criticality safety practitioner, the procedures governing their use had to be updated and simplified. This paper will describe the resulting sensitivity analysis tools that have been generated for potential use by the criticality safety community

Molecular pathways involved in neuronal cell adhesion and membrane scaffolding contribute to schizophrenia and bipolar disorder susceptibility.

LENUS (Irish Health Repository)

O'Dushlaine, C

2011-03-01

Susceptibility to schizophrenia and bipolar disorder may involve a substantial, shared contribution from thousands of common genetic variants, each of small effect. Identifying whether risk variants map to specific molecular pathways is potentially biologically informative. We report a molecular pathway analysis using the single-nucleotide polymorphism (SNP) ratio test, which compares the ratio of nominally significant (P<0.05) to nonsignificant SNPs in a given pathway to identify the \\'enrichment\\' for association signals. We applied this approach to the discovery (the International Schizophrenia Consortium (n=6909)) and validation (Genetic Association Information Network (n=2729)) of schizophrenia genome-wide association study (GWAS) data sets. We investigated each of the 212 experimentally validated pathways described in the Kyoto Encyclopaedia of Genes and Genomes in the discovery sample. Nominally significant pathways were tested in the validation sample, and five pathways were found to be significant (P=0.03-0.001); only the cell adhesion molecule (CAM) pathway withstood conservative correction for multiple testing. Interestingly, this pathway was also significantly associated with bipolar disorder (Wellcome Trust Case Control Consortium (n=4847)) (P=0.01). At a gene level, CAM genes associated in all three samples (NRXN1 and CNTNAP2), which were previously implicated in specific language disorder, autism and schizophrenia. The CAM pathway functions in neuronal cell adhesion, which is critical for synaptic formation and normal cell signaling. Similar pathways have also emerged from a pathway analysis of autism, suggesting that mechanisms involved in neuronal cell adhesion may contribute broadly to neurodevelopmental psychiatric phenotypes.

Functional Crosstalk between the PP2A and SUMO Pathways Revealed by Analysis of STUbL Suppressor, razor 1-1.

Directory of Open Access Journals (Sweden)

Minghua Nie

2016-07-01

Full Text Available Posttranslational modifications (PTMs provide dynamic regulation of the cellular proteome, which is critical for both normal cell growth and for orchestrating rapid responses to environmental stresses, e.g. genotoxins. Key PTMs include ubiquitin, the Small Ubiquitin-like MOdifier SUMO, and phosphorylation. Recently, SUMO-targeted ubiquitin ligases (STUbLs were found to integrate signaling through the SUMO and ubiquitin pathways. In general, STUbLs are recruited to target proteins decorated with poly-SUMO chains to ubiquitinate them and drive either their extraction from protein complexes, and/or their degradation at the proteasome. In fission yeast, reducing or preventing the formation of SUMO chains can circumvent the essential and DNA damage response functions of STUbL. This result indicates that whilst some STUbL "targets" have been identified, the crucial function of STUbL is to antagonize SUMO chain formation. Herein, by screening for additional STUbL suppressors, we reveal crosstalk between the serine/threonine phosphatase PP2A-Pab1B55 and the SUMO pathway. A hypomorphic Pab1B55 mutant not only suppresses STUbL dysfunction, but also mitigates the phenotypes associated with deletion of the SUMO protease Ulp2, or mutation of the STUbL cofactor Rad60. Together, our results reveal a novel role for PP2A-Pab1B55 in modulating SUMO pathway output, acting in parallel to known critical regulators of SUMOylation homeostasis. Given the broad evolutionary functional conservation of the PP2A and SUMO pathways, our results could be relevant to the ongoing attempts to therapeutically target these factors.

Functional analysis of the MAPK pathways in fungi.

Science.gov (United States)

Martínez-Soto, Domingo; Ruiz-Herrera, José

The Mitogen-Activated Protein Kinase (MAPK) signaling pathways constitute one of the most important and evolutionarily conserved mechanisms for the perception of extracellular information in all the eukaryotic organisms. The MAPK pathways are involved in the transfer to the cell of the information perceived from extracellular stimuli, with the final outcome of activation of different transcription factors that regulate gene expression in response to them. In all species of fungi, the MAPK pathways have important roles in their physiology and development; e.g. cell cycle control, mating, morphogenesis, response to different stresses, resistance to UV radiation and to temperature changes, cell wall assembly and integrity, degradation of cellular organelles, virulence, cell-cell signaling, fungus-plant interaction, and response to damage-associated molecular patterns (DAMPs). Considering the importance of the phylogenetically conserved MAPK pathways in fungi, an updated review of the knowledge on them is discussed in this article. This information reveals their importance, their distribution in fungal species evolutionarily distant and with different lifestyles, their organization and function, and the interactions occurring between different MAPK pathways, and with other signaling pathways, for the regulation of the most complex cellular processes. Copyright © 2017 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.

Benchmarking pathway interaction network for colorectal cancer to identify dysregulated pathways

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Q. Wang

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

Comparative transcriptome analysis on the synthesis pathway of honey bee (Apis mellifera) mandibular gland secretions.

Science.gov (United States)

Wu, YuQi; Zheng, HuoQing; Corona, Miguel; Pirk, Christian; Meng, Fei; Zheng, YuFei; Hu, FuLiang

2017-07-03

Secretions from mandibular glands (MGs) have important caste-specific functions that are associated with the social evolution of honey bees. To gain insights into the molecular architecture underlying these caste differences, we compared the gene expression patterns of MGs from queens, queenright workers (WQRs) and queenless workers (WQLs) using high-throughput RNA-sequencing technology. In total, we identified 46 candidate genes associated with caste-specific biosynthesis of fatty acid pheromones in the MG, including members of cytochrome P450 (CYP450) family and genes involved in fatty acid β-oxidation and ω-oxidation. For further identification of the CYP450s genes involved in the biosynthesis of MG secretions, we analyzed by means of qPCR, the expression levels of six of the CYP450 genes most abundantly expressed in the transcriptome analysis across different castes, ages, tasks and tissues. Our analysis revealed that CYP6AS8 and CYP6AS11, the most abundantly expressed CYP450 genes in worker and queen MGs, respectively, are selectively expressed in the MGs of workers and queens compared to other tissues. These results suggest that these genes might be responsible for the critical bifurcated hydroxylation process in the biosynthesis pathway. Our study contributes to the description of the molecular basis for the biosynthesis of fatty acid-derived pheromones in the MGs.

Fission reactor critical experiments and analysis

International Nuclear Information System (INIS)

Anon.

1977-01-01

Work accomplished in support of nonweapons programs by LASL Group Q-14 is described. Included are efforts in basic critical measurements, nuclear criticality safety, a plasma core critical assembly, and reactivity coefficient measurements

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.

Risk analysis of hematopoietic stem cell transplant process: failure mode, effect, and criticality analysis and hazard analysis critical control point methods integration based on guidelines to good manufacturing practice for medicinal product ANNEX 20 (February 2008).

Science.gov (United States)

Gianassi, S; Bisin, S; Bindi, B; Spitaleri, I; Bambi, F

2010-01-01

The collection and handling of hematopoietic stem cells (HSCs) must meet high quality requirements. An integrated Quality Risk Management can help to identify and contain potential risks related to HSC production. Risk analysis techniques allow one to "weigh" identified hazards, considering the seriousness of their effects, frequency, and detectability, seeking to prevent the most harmful hazards. The Hazard Analysis Critical Point, recognized as the most appropriate technique to identify risks associated with physical, chemical, and biological hazards for cellular products, consists of classifying finished product specifications and limits of acceptability, identifying all off-specifications, defining activities that can cause them, and finally establishing both a monitoring system for each Critical Control Point and corrective actions for deviations. The severity of possible effects on patients, as well as the occurrence and detectability of critical parameters, are measured on quantitative scales (Risk Priority Number [RPN]). Risk analysis was performed with this technique on manipulation process of HPC performed at our blood center. The data analysis showed that hazards with higher values of RPN with greater impact on the process are loss of dose and tracking; technical skills of operators and manual transcription of data were the most critical parameters. Problems related to operator skills are handled by defining targeted training programs, while other critical parameters can be mitigated with the use of continuous control systems. The blood center management software was completed by a labeling system with forms designed to be in compliance with standards in force and by starting implementation of a cryopreservation management module. Copyright 2010 Elsevier Inc. All rights reserved.

Exploration of molecular pathways mediating electric field-directed Schwann cell migration by RNA-Seq

Science.gov (United States)

Yao, Li; Li, Yongchao; Knapp, Jennifer; Smith, Peter

2015-01-01

In peripheral nervous systems, Schwann cells wrap around axons of motor and sensory neurons to form the myelin sheath. Following spinal cord injury, Schwann cells regenerate and migrate to the lesion and are involved in the spinal cord regeneration process. Transplantation of Schwann cells into injured neural tissue results in enhanced spinal axonal regeneration. Effective directional migration of Schwann cells is critical in the neural regeneration process. In this study, we report that Schwann cells migrate anodally in an applied electric field (EF). The directedness and displacement of anodal migration increased significantly when the strength of the EF increased from 50 mV/mm to 200 mV/mm. The EF did not significantly affect the cell migration speed. To explore the genes and signaling pathways that regulate cell migration in EFs, we performed a comparative analysis of differential gene expression between cells stimulated with an EF (100 mV/mm) and those without using next-generation RNA sequencing, verified by RT-qPCR. Based on the cut-off criteria (FC > 1.2, q cells versus EF-stimulated cells. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis found that compared to the control group, 21 pathways are down-regulated, while 10 pathways are up-regulated. Differentially expressed genes participate in multiple cellular signaling pathways involved in the regulation of cell migration, including pathways of regulation of actin cytoskeleton, focal adhesion, and PI3K-Akt. PMID:25557037

Autoclave nuclear criticality safety analysis

Energy Technology Data Exchange (ETDEWEB)

D`Aquila, D.M. [Martin Marietta Energy Systems, Inc., Piketon, OH (United States); Tayloe, R.W. Jr. [Battelle, Columbus, OH (United States)

1991-12-31

Steam-heated autoclaves are used in gaseous diffusion uranium enrichment plants to heat large cylinders of UF{sub 6}. Nuclear criticality safety for these autoclaves is evaluated. To enhance criticality safety, systems are incorporated into the design of autoclaves to limit the amount of water present. These safety systems also increase the likelihood that any UF{sub 6} inadvertently released from a cylinder into an autoclave is not released to the environment. Up to 140 pounds of water can be held up in large autoclaves. This mass of water is sufficient to support a nuclear criticality when optimally combined with 125 pounds of UF{sub 6} enriched to 5 percent U{sup 235}. However, water in autoclaves is widely dispersed as condensed droplets and vapor, and is extremely unlikely to form a critical configuration with released UF{sub 6}.

Analysis of the impact of correlated benchmark experiments on the validation of codes for criticality safety analysis

International Nuclear Information System (INIS)

Bock, M.; Stuke, M.; Behler, M.

2013-01-01

The validation of a code for criticality safety analysis requires the recalculation of benchmark experiments. The selected benchmark experiments are chosen such that they have properties similar to the application case that has to be assessed. A common source of benchmark experiments is the 'International Handbook of Evaluated Criticality Safety Benchmark Experiments' (ICSBEP Handbook) compiled by the 'International Criticality Safety Benchmark Evaluation Project' (ICSBEP). In order to take full advantage of the information provided by the individual benchmark descriptions for the application case, the recommended procedure is to perform an uncertainty analysis. The latter is based on the uncertainties of experimental results included in most of the benchmark descriptions. They can be performed by means of the Monte Carlo sampling technique. The consideration of uncertainties is also being introduced in the supplementary sheet of DIN 25478 'Application of computer codes in the assessment of criticality safety'. However, for a correct treatment of uncertainties taking into account the individual uncertainties of the benchmark experiments is insufficient. In addition, correlations between benchmark experiments have to be handled correctly. For example, these correlations can arise due to different cases of a benchmark experiment sharing the same components like fuel pins or fissile solutions. Thus, manufacturing tolerances of these components (e.g. diameter of the fuel pellets) have to be considered in a consistent manner in all cases of the benchmark experiment. At the 2012 meeting of the Expert Group on 'Uncertainty Analysis for Criticality Safety Assessment' (UACSA) of the OECD/NEA a benchmark proposal was outlined that aimed for the determination of the impact on benchmark correlations on the estimation of the computational bias of the neutron multiplication factor (k eff ). The analysis presented here is based on this proposal. (orig.)

Environmental radiological surveillance in perspective: the relative importance of environmental media as a function of effluent pathway and radionuclides

International Nuclear Information System (INIS)

Denham, D.H.

1977-10-01

Most published guidelines for environmental surveillance emphasize the collection and analysis of specific media (e.g. air, water, milk, direct radiation) without total regard for the potential dose impact of the radionuclides expected in or actually present in the effluent streams from nuclear facilities. To determine the relative importance of medium/nuclide combinations in environmental surveillance, the experience at major ERDA sites and at operating nuclear power plants was reviewed. Typical release rates for nuclide groupings (tritium, noble gases, radioiodine, mixed fission or activation products, and transuranics) in those effluent streams were followed through various environmental pathways. By using this scheme the environmental medium which is most prominent in the critical dose pathway to man was determined. It was also possible to determine points of short-or long-term contaminant accumulation. Following these calculations, each medium was ranked for a given nuclide/effluent pathway combination providing the relative importance of sampling specific environmental media with emphasis on the radiation dose to a critical population group. Finally, the results of these environmental pathway studies are presented in tabular form to provide ready reference for environmental surveillance program design or evaluation

Teaching Blended Content Analysis and Critically Vigilant Media Consumption

Science.gov (United States)

Harris, Christopher S.

2015-01-01

The semester-long activity described herein uses an integrated instructional approach to media studies to introduce students to the research method of qualitative content analysis and help them become more critically vigilant media consumers. The goal is to increase students' media literacy by guiding them in the design of an exploratory…

A study of software safety analysis system for safety-critical software

International Nuclear Information System (INIS)

Chang, H. S.; Shin, H. K.; Chang, Y. W.; Jung, J. C.; Kim, J. H.; Han, H. H.; Son, H. S.

2004-01-01

The core factors and requirements for the safety-critical software traced and the methodology adopted in each stage of software life cycle are presented. In concept phase, Failure Modes and Effects Analysis (FMEA) for the system has been performed. The feasibility evaluation of selected safety parameter was performed and Preliminary Hazards Analysis list was prepared using HAZOP(Hazard and Operability) technique. And the check list for management control has been produced via walk-through technique. Based on the evaluation of the check list, activities to be performed in requirement phase have been determined. In the design phase, hazard analysis has been performed to check the safety capability of the system with regard to safety software algorithm using Fault Tree Analysis (FTA). In the test phase, the test items based on FMEA have been checked for fitness guided by an accident scenario. The pressurizer low pressure trip algorithm has been selected to apply FTA method to software safety analysis as a sample. By applying CASE tool, the requirements traceability of safety critical system has been enhanced during all of software life cycle phases

Discovery of new candidate genes for rheumatoid arthritis through integration of genetic association data with expression pathway analysis.

Science.gov (United States)

Shchetynsky, Klementy; Diaz-Gallo, Lina-Marcella; Folkersen, Lasse; Hensvold, Aase Haj; Catrina, Anca Irinel; Berg, Louise; Klareskog, Lars; Padyukov, Leonid

2017-02-02

Here we integrate verified signals from previous genetic association studies with gene expression and pathway analysis for discovery of new candidate genes and signaling networks, relevant for rheumatoid arthritis (RA). RNA-sequencing-(RNA-seq)-based expression analysis of 377 genes from previously verified RA-associated loci was performed in blood cells from 5 newly diagnosed, non-treated patients with RA, 7 patients with treated RA and 12 healthy controls. Differentially expressed genes sharing a similar expression pattern in treated and untreated RA sub-groups were selected for pathway analysis. A set of "connector" genes derived from pathway analysis was tested for differential expression in the initial discovery cohort and validated in blood cells from 73 patients with RA and in 35 healthy controls. There were 11 qualifying genes selected for pathway analysis and these were grouped into two evidence-based functional networks, containing 29 and 27 additional connector molecules. The expression of genes, corresponding to connector molecules was then tested in the initial RNA-seq data. Differences in the expression of ERBB2, TP53 and THOP1 were similar in both treated and non-treated patients with RA and an additional nine genes were differentially expressed in at least one group of patients compared to healthy controls. The ERBB2, TP53. THOP1 expression profile was successfully replicated in RNA-seq data from peripheral blood mononuclear cells from healthy controls and non-treated patients with RA, in an independent collection of samples. Integration of RNA-seq data with findings from association studies, and consequent pathway analysis implicate new candidate genes, ERBB2, TP53 and THOP1 in the pathogenesis of RA.

Boundary conditions for pathways, safety analysis and basic criteria for low-level radiation waste site selection

International Nuclear Information System (INIS)

Saverot, P.

1994-01-01

There are three successive periods in the life of a disposal facility: the operating period, the institutional control period and the unrestricted site access period. The purpose of safety analysis of the disposal facility is to ensure that the radiological impacts for each period in the life of the facility are acceptable under all circumstances. Founded on a deterministic approach, this analysis leads to a determination of the maximum quantity of each radionuclide present in the facility at the beginning of the institutional control period in order for the impacts to be considered acceptable. Safety analysis involves the calculation of the radiological impacts of a given radiological inventory under a selected scenario, from all plausible scenarios of radionuclide migration to the environment in both normal and accident conditions, and taking into account other specified variables. The calculation itself involves an assessment of the quantities of radionuclides that could be released to the environment under the specific scenario selected and following identified pathways, and a determination of the resultant exposure, both internal and external, to the public. An iterative approach is used in the performance of pathways analyses. If the pathways analyses result in unacceptable radiological impacts, either the radiological inventory of the site is reduced or barrier characteristics not previously factored into the analysis are taken into account. New pathways analyses are then performed until the results are within the acceptable range. Once accepted by the safety authorities, the radiological inventory becomes the radiological capacity, which is the approved quantities of specific radionuclides that may be disposed of at the site. The following elaborates on the boundary conditions used in safety analyses and describes the types of pathways analyses performed for a LLW disposal facility

Pareto analysis of critical factors affecting technical institution evaluation

Directory of Open Access Journals (Sweden)

Victor Gambhir

2012-08-01

Full Text Available With the change of education policy in 1991, more and more technical institutions are being set up in India. Some of these institutions provide quality education, but others are merely concentrating on quantity. These stakeholders are in a state of confusion about decision to select the best institute for their higher educational studies. Although various agencies including print media provide ranking of these institutions every year, but their results are controversial and biased. In this paper, the authors have made an endeavor to find the critical factors for technical institution evaluation from literature survey. A Pareto analysis has also been performed to find the intensity of these critical factors in evaluation. This will not only help the stake holders in taking right decisions but will also help the management of institutions in benchmarking for identifying the most important critical areas to improve the existing system. This will in turn help Indian economy.

In Silico Analysis of Putrefaction Pathways in Bacteria and Its Implication in Colorectal Cancer

Directory of Open Access Journals (Sweden)

Harrisham Kaur

2017-11-01

Full Text Available Fermentation of undigested proteins in human gastrointestinal tract (gut by the resident microbiota, a process called bacterial putrefaction, can sometimes disrupt the gut homeostasis. In this process, essential amino acids (e.g., histidine, tryptophan, etc. that are required by the host may be utilized by the gut microbes. In addition, some of the products of putrefaction, like ammonia, putrescine, cresol, indole, phenol, etc., have been implicated in the disease pathogenesis of colorectal cancer (CRC. We have investigated bacterial putrefaction pathways that are known to be associated with such metabolites. Results of the comprehensive in silico analysis of the selected putrefaction pathways across bacterial genomes revealed presence of these pathways in limited bacterial groups. Majority of these bacteria are commonly found in human gut. These include Bacillus, Clostridium, Enterobacter, Escherichia, Fusobacterium, Salmonella, etc. Interestingly, while pathogens utilize almost all the analyzed pathways, commensals prefer putrescine and H2S production pathways for metabolizing the undigested proteins. Further, comparison of the putrefaction pathways in the gut microbiomes of healthy, carcinoma and adenoma datasets indicate higher abundances of putrefying bacteria in the carcinoma stage of CRC. The insights obtained from the present study indicate utilization of possible microbiome-based therapies to minimize the adverse effects of gut microbiome in enteric diseases.

A cost effective approach for criticality accident analysis of a DOE SNF storage facility

International Nuclear Information System (INIS)

Garrett, R.L.; Couture, G.F.; Gough, S.T.

1997-01-01

This paper presents the methodologies used to derive criticality accident analyses for a spent nuclear fuel receipt, storage, handling, and shipping facility. Two criticality events are considered: process-induced and Natural Phenomena Hazards (NPH)-induced. The criticality analyses required the development of: (1) the frequency at which each sceanario occurred, (2) the estimated number of fissions for each scenario, and (3) the consequences associated with each criticality scenario. A fault tree analysis was performed to quantify the frequency of criticality due to process-induced events. For the frequency analysis of NPH-induced criticality, a probabilistic approach was employed. To estimate the consequences of a criticality event, the resulting fission yield was determined using a probabilistic approach. For estimating the source term, a 95% amount of overall conservatism was targeted. This methodology applied to the facility criticality scenarios indicated that: (1) the 95th percentile yield levels from the historical yield distributions are approximately 5 x 10 17 fissions and 5 x 10 18 fissions for internal event and NPH-induced criticality event, respectively; and (2) using probabilistic Latin Hypercube Sampling, the downwind 95th percentile dose to a receptor at the US DOE reservation boundary is 2.2 mrem. This estimate is compared to the bounding dose of 1.4 rem. 4 refs., 1 fig

Ecological literacy materials for use in elementary schools: A critical analysis

Science.gov (United States)

Chambers, Joan Maureen

My research is a critical examination of environmental science education resources for use in Alberta schools. I examine both the resources and the processes by which these resources are developed by diverse groups. My inquiry is guided by the following question: What is the nature of the discourse of ecological literacy in the promotion and content of teaching materials in elementary schools in Alberta? This critical analysis centres on the discourses, language, and perspectives (both hidden and overt) of these resources and processes; the manifestation of political agendas; existing relations; and the inclusion or exclusion of alternate views. Framed within critical theory and an ecosocial construct, my methodology employs critical discourse analysis and hermeneutic interpretation. I analyse selected environmental science resources produced for the elementary classroom by government and nongovernment organizations. I also interview the producers and/or writers of these instructional resources to provide the perspectives of some of the developers of these materials. The findings illustrate how the discursive management of the view of nature, human-nature relationships, uncertainty, multiple perspectives, and dimensions of ecological literacy in materials for schools offer students a particular perspective. These ecological and science discourses act to shape their personal relationships with nature and notions of environmental responsibility and consciousness. This research is necessary because, particularly in Alberta, corporate interests have the potential to impact school curricula. The study points to a need for a critical appraisal of resources for schools produced by the environmental science community.

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.

Sensitivity and uncertainty analysis of the PATHWAY radionuclide transport model

International Nuclear Information System (INIS)

Otis, M.D.

1983-01-01

Procedures were developed for the uncertainty and sensitivity analysis of a dynamic model of radionuclide transport through human food chains. Uncertainty in model predictions was estimated by propagation of parameter uncertainties using a Monte Carlo simulation technique. Sensitivity of model predictions to individual parameters was investigated using the partial correlation coefficient of each parameter with model output. Random values produced for the uncertainty analysis were used in the correlation analysis for sensitivity. These procedures were applied to the PATHWAY model which predicts concentrations of radionuclides in foods grown in Nevada and Utah and exposed to fallout during the period of atmospheric nuclear weapons testing in Nevada. Concentrations and time-integrated concentrations of iodine-131, cesium-136, and cesium-137 in milk and other foods were investigated. 9 figs., 13 tabs

Nuclear critical safety analysis for UX-30 transport of freight package

International Nuclear Information System (INIS)

Quan Yanhui; Zhou Qi; Yin Shenggui

2014-01-01

The nuclear critical safety analysis and evaluation for UX-30 transport freight package in the natural condition and accident condition were carried out with MONK-9A code and MCNP code. Firstly, the critical benchmark experiment data of public in international were selected, and the deflection and subcritical limiting value with MONK-9A code and MCNP code in calculating same material form were validated and confirmed. Secondly, the neutron efficiency multiplication factors in the natural condition and accident condition were calculated and analyzed, and the safety in transport process was evaluated by taking conservative suppose of nuclear critical safety. The calculation results show that the max value of k eff for UX-30 transport freight package is less than the subcritical limiting value, and the UX-30 transport freight package is in the state of subcritical safety. Moreover, the critical safety index (CSI) for UX-30 package can define zero based on the definition of critical safety index. (authors)

Investigating a multigene prognostic assay based on significant pathways for Luminal A breast cancer through gene expression profile analysis.

Science.gov (United States)

Gao, Haiyan; Yang, Mei; Zhang, Xiaolan

2018-04-01

The present study aimed to investigate potential recurrence-risk biomarkers based on significant pathways for Luminal A breast cancer through gene expression profile analysis. Initially, the gene expression profiles of Luminal A breast cancer patients were downloaded from The Cancer Genome Atlas database. The differentially expressed genes (DEGs) were identified using a Limma package and the hierarchical clustering analysis was conducted for the DEGs. In addition, the functional pathways were screened using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and rank ratio calculation. The multigene prognostic assay was exploited based on the statistically significant pathways and its prognostic function was tested using train set and verified using the gene expression data and survival data of Luminal A breast cancer patients downloaded from the Gene Expression Omnibus. A total of 300 DEGs were identified between good and poor outcome groups, including 176 upregulated genes and 124 downregulated genes. The DEGs may be used to effectively distinguish Luminal A samples with different prognoses verified by hierarchical clustering analysis. There were 9 pathways screened as significant pathways and a total of 18 DEGs involved in these 9 pathways were identified as prognostic biomarkers. According to the survival analysis and receiver operating characteristic curve, the obtained 18-gene prognostic assay exhibited good prognostic function with high sensitivity and specificity to both the train and test samples. In conclusion the 18-gene prognostic assay including the key genes, transcription factor 7-like 2, anterior parietal cortex and lymphocyte enhancer factor-1 may provide a new method for predicting outcomes and may be conducive to the promotion of precision medicine for Luminal A breast cancer.

The Biological Connection Markup Language: a SBGN-compliant format for visualization, filtering and analysis of biological pathways.

Science.gov (United States)

Beltrame, Luca; Calura, Enrica; Popovici, Razvan R; Rizzetto, Lisa; Guedez, Damariz Rivero; Donato, Michele; Romualdi, Chiara; Draghici, Sorin; Cavalieri, Duccio

2011-08-01

Many models and analysis of signaling pathways have been proposed. However, neither of them takes into account that a biological pathway is not a fixed system, but instead it depends on the organism, tissue and cell type as well as on physiological, pathological and experimental conditions. The Biological Connection Markup Language (BCML) is a format to describe, annotate and visualize pathways. BCML is able to store multiple information, permitting a selective view of the pathway as it exists and/or behave in specific organisms, tissues and cells. Furthermore, BCML can be automatically converted into data formats suitable for analysis and into a fully SBGN-compliant graphical representation, making it an important tool that can be used by both computational biologists and 'wet lab' scientists. The XML schema and the BCML software suite are freely available under the LGPL for download at http://bcml.dc-atlas.net. They are implemented in Java and supported on MS Windows, Linux and OS X.

Data mining and pathway analysis of glucose-6-phosphate dehydrogenase with natural language processing

Science.gov (United States)

Chen, Long; Zhang, Chunhua; Wang, Yanling; Li, Yuqian; Han, Qiaoqiao; Yang, Huixin; Zhu, Yuechun

2017-01-01

Human glucose-6-phosphate dehydrogenase (G6PD) is a crucial enzyme in the pentose phosphate pathway, and serves an important role in biosynthesis and the redox balance. G6PD deficiency is a major cause of neonatal jaundice and acute hemolyticanemia, and recently, G6PD has been associated with diseases including inflammation and cancer. The aim of the present study was to conduct a search of the National Center for Biotechnology Information PubMed library for articles discussing G6PD. Genes that were identified to be associated with G6PD were recorded, and the frequency at which each gene appeared was calculated. Gene ontology (GO), pathway and network analyses were then performed. A total of 98 G6PD-associated genes and 33 microRNAs (miRNAs) that potentially regulate G6PD were identified. The 98 G6PD-associated genes were then sub-classified into three functional groups by GO analysis, followed by analysis of function, pathway, network, and disease association. Out of the 47 signaling pathways identified, seven were significantly correlated with G6PD-associated genes. At least two out of four independent programs identified the 33 miRNAs that were predicted to target G6PD. miR-1207-5P, miR-1 and miR-125a-5p were predicted by all four software programs to target G6PD. The results of the present study revealed that dysregulation of G6PD was associated with cancer, autoimmune diseases, and oxidative stress-induced disorders. These results revealed the potential roles of G6PD-regulated signaling and metabolic pathways in the etiology of these diseases. PMID:28627690

Redundancy control in pathway databases (ReCiPa): an application for improving gene-set enrichment analysis in Omics studies and "Big data" biology.

Science.gov (United States)

Vivar, Juan C; Pemu, Priscilla; McPherson, Ruth; Ghosh, Sujoy

2013-08-01

Abstract Unparalleled technological advances have fueled an explosive growth in the scope and scale of biological data and have propelled life sciences into the realm of "Big Data" that cannot be managed or analyzed by conventional approaches. Big Data in the life sciences are driven primarily via a diverse collection of 'omics'-based technologies, including genomics, proteomics, metabolomics, transcriptomics, metagenomics, and lipidomics. Gene-set enrichment analysis is a powerful approach for interrogating large 'omics' datasets, leading to the identification of biological mechanisms associated with observed outcomes. While several factors influence the results from such analysis, the impact from the contents of pathway databases is often under-appreciated. Pathway databases often contain variously named pathways that overlap with one another to varying degrees. Ignoring such redundancies during pathway analysis can lead to the designation of several pathways as being significant due to high content-similarity, rather than truly independent biological mechanisms. Statistically, such dependencies also result in correlated p values and overdispersion, leading to biased results. We investigated the level of redundancies in multiple pathway databases and observed large discrepancies in the nature and extent of pathway overlap. This prompted us to develop the application, ReCiPa (Redundancy Control in Pathway Databases), to control redundancies in pathway databases based on user-defined thresholds. Analysis of genomic and genetic datasets, using ReCiPa-generated overlap-controlled versions of KEGG and Reactome pathways, led to a reduction in redundancy among the top-scoring gene-sets and allowed for the inclusion of additional gene-sets representing possibly novel biological mechanisms. Using obesity as an example, bioinformatic analysis further demonstrated that gene-sets identified from overlap-controlled pathway databases show stronger evidence of prior association

Genome-Based Construction of the Metabolic Pathways of Orientia tsutsugamushi and Comparative Analysis within the Rickettsiales Order

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Chan-Ki Min

2008-01-01

Full Text Available Orientia tsutsugamushi, the causative agent of scrub typhus, is an obligate intracellular bacterium that belongs to the order of Rickettsiales. Recently, we have reported that O. tsutsugamushi has a unique genomic structure, consisting of highly repetitive sequences, and suggested that it may provide valuable insight into the evolution of intracellular bacteria. Here, we have used genomic information to construct the major metabolic pathways of O. tsutsugamushi and performed a comparative analysis of the metabolic genes and pathways of O. tsutsugamushi with other members of the Rickettsiales order. While O. tsutsugamushi has the largest genome among the members of this order, mainly due to the presence of repeated sequences, its metabolic pathways have been highly streamlined. Overall, the metabolic pathways of O. tsutsugamushi were similar to Rickettsia but there were notable differences in several pathways including carbohydrate metabolism, the TCA cycle, and the synthesis of cell wall components as well as in the transport systems. Our results will provide a useful guide to the postgenomic analysis of O. tsutsugamushi and lead to a better understanding of the virulence and physiology of this intracellular pathogen.

The Construction of Cultural Values and Beliefs in Chinese Language Textbooks: A Critical Discourse Analysis

Science.gov (United States)

Liu, Yongbing

2005-01-01

This article examines the discourses of cultural values and beliefs constructed in Chinese language textbooks currently used for primary school students nationwide in China. By applying story grammar analysis in the framework of critical discourse analysis, the article critically investigates how the discourses are constructed and what ideological…

Summary of the Supplemental Model Reports Supporting the Disposal Criticality Analysis Methodology Topical Report

International Nuclear Information System (INIS)

Brownson, D. A.

2002-01-01

The Department of Energy (DOE) Office of Civilian Radioactive Waste Management (OCRWM) has committed to a series of model reports documenting the methodology to be utilized in the Disposal Criticality Analysis Methodology Topical Report (YMP 2000). These model reports detail and provide validation of the methodology to be utilized for criticality analyses related to: (1) Waste form/waste package degradation; (2) Waste package isotopic inventory; (3) Criticality potential of degraded waste form/waste package configurations (effective neutron multiplication factor); (4) Probability of criticality (for each potential critical configuration as well as total event); and (5) Criticality consequences. This purpose of this summary report is to provide a status of the model reports and a schedule for their completion. This report also provides information relative to the model report content and validation. The model reports and their revisions are being generated as a result of: (1) Commitments made in the Disposal Criticality Analysis Methodology Topical Report (YMP 2000); (2) Open Items from the Safety Evaluation Report (Reamer 2000); (3) Key Technical Issue agreements made during DOE/U.S. Nuclear Regulatory Commission (NRC) Technical Exchange Meeting (Reamer and Williams 2000); and (4) NRC requests for additional information (Schlueter 2002)

Gene expression meta-analysis identifies metastatic pathways and transcription factors in breast cancer

DEFF Research Database (Denmark)

Thomassen, Mads; Tan, Qihua; Kruse, Torben

2008-01-01

ABSTRACT: BACKGROUND: Metastasis is believed to progress in several steps including different pathways but the determination and understanding of these mechanisms is still fragmentary. Microarray analysis of gene expression patterns in breast tumors has been used to predict outcome in recent stud...

Simulation of reactor noise analysis measurement for light-water critical assembly TCA using MCNP-DSP

International Nuclear Information System (INIS)

Yamamoto, Toshihiro; Sakurai, Kiyoshi; Tonoike, Kotaro; Miyoshi, Yoshinori

2001-01-01

Reactor noise analysis methods using Monte Carlo technique have been proposed and developed in the field of nuclear criticality safety. The Monte Carlo simulation for noise analysis can be made by simulating physical phenomena in the course of neutron transport in a nuclear fuel as practically as possible. MCNP-DSP was developed by T. Valentine of ORNL for this purpose and it is a modified version of MCNP-4A. The authors applied this code to frequency analysis measurements performed in light-water critical assembly TCA. Prompt neutron generation times for critical and subcritical cores were measured by doing the frequency analysis of detector signals. The Monte Carlo simulations for these experiments were carried out using MCNP-DSP, and prompt neutron generation times were calculated. (author)

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.

The Analysis of SBWR Critical Power Bundle Using Cobrag Code

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Yohannes Sardjono

2013-03-01

Full Text Available The coolant mechanism of SBWR is similar with the Dodewaard Nuclear Power Plant (NPP in the Netherlands that first went critical in 1968. The similarity of both NPP is cooled by natural convection system. These coolant concept is very related with same parameters on fuel bundle design especially fuel bundle length, core pressure drop and core flow rate as well as critical power bundle. The analysis was carried out by using COBRAG computer code. COBRAG computer code is GE Company proprietary. Basically COBRAG computer code is a tool to solve compressible three-dimensional, two fluid, three field equations for two phase flow. The three fields are the vapor field, the continuous liquid field, and the liquid drop field. This code has been applied to analyses model flow and heat transfer within the reactor core. This volume describes the finitevolume equations and the numerical solution methods used to solve these equations. This analysis of same parameters has been done i.e.; inlet sub cooling 20 BTU/lbm and 40 BTU/lbm, 1000 psi pressure and R-factor is 1.038, mass flux are 0.5 Mlb/hr.ft2, 0.75 Mlb/hr.ft2, 1.00 Mlb/hr.ft2 and 1.25 Mlb/hr.ft2. Those conditions based on history operation of some type of the cell fuel bundle line at GE Nuclear Energy. According to the results, it can be concluded that SBWR critical power bundle is 10.5 % less than current BWR critical power bundle with length reduction of 12 ft to 9 ft.

Critical reflection activation analysis - a new near-surface probe

International Nuclear Information System (INIS)

Gunn, J.M.F.; Trohidou, K.N.

1988-09-01

We propose a new surface analytic technique, Critical Reflection Activation Analysis (CRAA). This technique allows accurate depth profiling of impurities ≤ 100A beneath a surface. The depth profile of the impurity is simply related to the induced activity as a function of the angle of reflection. We argue that the technique is practical and estimate its accuracy. (author)

Somatic ACE regulates self-renewal of mouse spermatogonial stem cells via the MAPK signaling pathway.

Science.gov (United States)

Gao, Tingting; Zhao, Xin; Liu, Chenchen; Shao, Binbin; Zhang, Xi; Li, Kai; Cai, Jinyang; Wang, Su; Huang, Xiaoyan

2018-05-24

Spermatogonial stem cell (SSC) self-renewal is an indispensable part of spermatogenesis. Angiotensin I-converting enzyme (ACE) is a zinc dipeptidyl carboxypeptidase that plays a critical role in regulation of the renin-angiotensin system. Here, we used RT-PCR and Western blot analysis to confirm that somatic ACE (sACE) but not testicular ACE (tACE) is highly expressed in mouse testis before postpartum day 7 and in cultured SSCs. Our results revealed that sACE is located on the membrane of SSCs. Treating cultured SSCs with the ACE competitive inhibitor captopril was found to inhibit sACE activity, and significantly reduced the proliferation rate of SSCs. Microarray analysis identified 651 genes with significant differential expression. KEGG pathway analysis showed that these differentially expressed genes are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway and cell cycle. sACE was found to play an important role in SSC self-renewal via the regulation of MAPK-dependent cell proliferation.

Integrative Analysis of Gene Expression Data Including an Assessment of Pathway Enrichment for Predicting Prostate Cancer

Directory of Open Access Journals (Sweden)

Pingzhao Hu

2006-01-01

Full Text Available Background: Microarray technology has been previously used to identify genes that are differentially expressed between tumour and normal samples in a single study, as well as in syntheses involving multiple studies. When integrating results from several Affymetrix microarray datasets, previous studies summarized probeset-level data, which may potentially lead to a loss of information available at the probe-level. In this paper, we present an approach for integrating results across studies while taking probe-level data into account. Additionally, we follow a new direction in the analysis of microarray expression data, namely to focus on the variation of expression phenotypes in predefined gene sets, such as pathways. This targeted approach can be helpful for revealing information that is not easily visible from the changes in the individual genes. Results: We used a recently developed method to integrate Affymetrix expression data across studies. The idea is based on a probe-level based test statistic developed for testing for differentially expressed genes in individual studies. We incorporated this test statistic into a classic random-effects model for integrating data across studies. Subsequently, we used a gene set enrichment test to evaluate the significance of enriched biological pathways in the differentially expressed genes identified from the integrative analysis. We compared statistical and biological significance of the prognostic gene expression signatures and pathways identified in the probe-level model (PLM with those in the probeset-level model (PSLM. Our integrative analysis of Affymetrix microarray data from 110 prostate cancer samples obtained from three studies reveals thousands of genes significantly correlated with tumour cell differentiation. The bioinformatics analysis, mapping these genes to the publicly available KEGG database, reveals evidence that tumour cell differentiation is significantly associated with many

Analysis of aromatic catabolic pathways in Pseudomonas putida KT 2440 using a combined proteomic approach: 2-DE/MS and cleavable isotope-coded affinity tag analysis.

Science.gov (United States)

Kim, Young Hwan; Cho, Kun; Yun, Sung-Ho; Kim, Jin Young; Kwon, Kyung-Hoon; Yoo, Jong Shin; Kim, Seung Il

2006-02-01

Proteomic analysis of Pseudomonas putida KT2440 cultured in monocyclic aromatic compounds was performed using 2-DE/MS and cleavable isotope-coded affinity tag (ICAT) to determine whether proteins involved in aromatic compound degradation pathways were altered as predicted by genomic analysis (Jiménez et al., Environ Microbiol. 2002, 4, 824-841). Eighty unique proteins were identified by 2-DE/MS or MS/MS analysis from P. putida KT2440 cultured in the presence of six different organic compounds. Benzoate dioxygenase (BenA, BenD) and catechol 1,2-dioxygenase (CatA) were induced by benzoate. Protocatechuate 3,4-dixoygenase (PcaGH) was induced by p-hydroxybenzoate and vanilline. beta-Ketoadipyl CoA thiolase (PcaF) and 3-oxoadipate enol-lactone hydrolase (PcaD) were induced by benzoate, p-hydroxybenzoate and vanilline, suggesting that benzoate, p-hydroxybenzoate and vanilline were degraded by different dioxygenases and then converged in the same beta-ketoadipate degradation pathway. An additional 110 proteins, including 19 proteins from 2-DE analysis, were identified by cleavable ICAT analysis for benzoate-induced proteomes, which complemented the 2-DE results. Phenylethylamine exposure induced beta-ketoacyl CoA thiolase (PhaD) and ring-opening enzyme (PhaL), both enzymes of the phenylacetate (pha) biodegradation pathway. Phenylalanine induced 4-hydroxyphenyl-pyruvate dioxygenase (Hpd) and homogentisate 1,2-dioxygenase (HmgA), key enzymes in the homogentisate degradation pathway. Alkyl hydroperoxide reductase (AphC) was induced under all aromatic compounds conditions. These results suggest that proteome analysis complements and supports predictive information obtained by genomic sequence analysis.

Simulated front crawl swimming performance related to critical speed and critical power.

Science.gov (United States)

Toussaint, H M; Wakayoshi, K; Hollander, A P; Ogita, F

1998-01-01

Competitive pool swimming events range in distance from 50 to 1500 m. Given the difference in performance times (+/- 23-1000 s), the contribution of the aerobic and anaerobic energy systems changes considerably with race distance. In training practice the regression line between swimming distance and time (Distance = critical velocity x time + anaerobic swimming capacity) is used to determine the individual capacity of the aerobic and anaerobic metabolic pathways. Although there is confidence that critical velocity and anaerobic swimming capacity are fitness measures that separate aerobic and anaerobic components, a firm theoretical basis for the interpretation of these results does not exist. The purpose of this study was to evaluate the critical power concept and anaerobic swimming capacity as measures of the aerobic and anaerobic capacity using a modeling approach. A systems model was developed that relates the mechanics and energetics involved in front crawl swimming performance. From actual swimming flume measurements, the time dependent aerobic and anaerobic energy release was modeled. Data derived from the literature were used to relate the energy cost of front crawl swimming to swimming velocity. A balance should exist between the energy cost to swim a distance in a certain time and the concomitant aerobic and anaerobic energy release. The ensuing model was used to predict performance times over a range of distances (50-1500 m) and to calculate the regression line between swimming distance and time. Using a sensitivity analysis, it was demonstrated that the critical velocity is indicative for the capacity of the aerobic energy system. Estimates of the anaerobic swimming capacity, however, were influenced by variations in both anaerobic and aerobic energy release. Therefore, it was concluded that the anaerobic swimming capacity does not provide a reliable estimate of the anaerobic capacity.

Environmental radiological surveillance in perspective: the relative importance of environmental media as a function of effluent pathway and radionuclides

International Nuclear Information System (INIS)

Denham, D.H.

1977-01-01

Most published guidelines for environmental surveillance emphasize the collection and analysis of specific media (e.g. air, water, milk, direct radiation) without total regard for the potential dose impact of the radionuclides expected in or actually present in the effluent streams FR-om nuclear facilities. To determine the relative importance of medium/nuclide combinations in environmental surveillance, the experience at major ERDA sites and at operating nuclear power plants was reviewed. Typical release rates for nuclide groupings (tritium, noble gases, radioiodine, mixed fission or activation products, and transuranics) in those effluent streams were followed through various environmental pathways. By using this scheme the environmental medium which is most prominent in the critical dose pathway to man was determined. It was also possible to determine points of short-or long-term contaminant accumulation. Following these combination providing the relative importance of sampling specific environmental media with emphasis on the radiation dose to a critical population group. Finally, the results of these environmental pathway studies are presented in tabular form to provide ready reference for environmental surveillance program design or evaluation

Fast critical experiments in FCA and their analysis

International Nuclear Information System (INIS)

Hirota, Jitsuya

1984-02-01

JAERI Fast Critical Facility FCA went critical for the first time in April, 1967. Since then, critical experiments and their analysis were carried out on thirty-five assemblies until march, 1982. This report summarizes many achievements obtained in these fifteen years and points out disagreements observed between the calculation and experiment for further studies. A series of mock-up experiments for Experimental Fast Reactor JOYO, a theoretical and numerical study of adjustment of group constants by using integral data and a development of proton-recoil counter system for fast neutron spectrum measurement won high praise. Studies of Doppler effect of structural materials, effect of fission product accumulation on sodium-void worth, axially heterogeneous core and actinide cross sections attracted world-side attention. Significant contributions were also made to Prototype Fast Breeder Reactor MONJU through the partial mock-up experiments. Disagreements between the calculation and experiment were observed in the following items; reaction rate distribution and reactivity worth of B 4 C absorber in radial blanket, central reactivity worth in core with reflector, plate/pin fuel heterogeneity effect on criticality, sodium-void effect in central core region, Doppler effect of structural materials, core neutron spectrum near large resonances of iron and oxygen, effect of fission product accumulation on sodium-void worth, physics property of heterogeneous core, reactivity change resulted from fuel slumping and so on. Further efforts should be made to solve these disagreements through recalculating the experimental results with newly developed data and methods and carrying out the experiments intended to identify the cause of disagreement. (author)

Criticality safety analysis of a calciner exit chute

International Nuclear Information System (INIS)

Haught, C.F.; Basoglu, B.; Brewer, R.W.; Hollenback, D.F.; Wilkinson, A.D.; Dodds, H.L.

1994-01-01

Calcination of uranyl nitrate into uranium oxide is part of normal operations of some enrichment plants. Typically, a calciner discharges uranium oxide powder (U 3 O 8 ) into an exit chute that directs the powder into a receiving can located in a glove box. One possible scenario for a criticality accident is the exit chute becoming blocked with powder near its discharge. The blockage restricts the flow of powder causing the exit chute to become filled with the powder. If blockage does occur, the height of the powder could reach a level that would not be safe from a criticality point of view. In this analysis, the subcritical height limit is examined for 98% enriched U 3 O 8 in the exit chute with full water reflection and optimal water moderation. The height limit for ensuring criticality safety during such an accumulation is 28.2 cm above the top of the discharge pipe at the bottom of the chute. Chute design variations are also evaluated with full water reflection and optimal water moderation. Subcritical configurations for the exit chute variation are developed, but the configurations are not safe when combined with the calciner. To ensure criticality safety, modifications must be made to the calciner tube or safety measures must be implemented if these designs are to be utilized with 98% enriched material. A geometrically safe configuration for the exit chute is developed for a blockage of 20% enriched powder with full water reflection and optimal water moderation, and this configuration is safe when combined with the existing calciner

Gendered Pathways to Burnout: Results from the SALVEO Study.

Science.gov (United States)

Beauregard, Nancy; Marchand, Alain; Bilodeau, Jaunathan; Durand, Pierre; Demers, Andrée; Haines, Victor Y

2018-02-19

Burnout is a pervasive mental health problem in the workforce, with mounting evidence suggesting ties with occupational and safety outcomes such as work injuries, critical events and musculoskeletal disorders. While environmental [work and non-work, work-to-family conflict (WFC)] and individual (personality) pathways to burnout are well documented, little is known about how gender comes to influence such associative patterns. The aim of the study consisted in examining gendered pathways to burnout. Data were derived from the SALVEO study, a cross-sectional study of 2026 workers from 63 workplaces from the province of Québec (Canada). Data were analyzed using multilevel path analysis. Direct effects of gendered pathways were evidenced for work (e.g. decision latitude) and non-work (e.g. child-related strains) environmental pathways, as well as for individual pathways (i.e. internal locus of control). Indirect effects of gendered pathways were also evidenced, with women reporting higher levels of burnout compared to men due to lower levels of decision latitude and of self-esteem, as well as higher levels of WFC. Women also reported lower burnout levels through investing more time into domestic tasks, which could represent a recovery strategy to highly demanding work. WFC further mediated the associations between working hours and burnout, as well as the between irregular work schedules and burnout. These result suggest than men distinctively reported higher levels of burnout due to the specific nature of their work contract negatively impacting on WFC, and incidentally, on their mental health. Study results supported our hypotheses positing that gender distinctively shapes environmental and individual pathways to burnout. OHS prevention efforts striving for better mental health outcomes in the workforce could relevantly be informed by a gendered approach to burnout.

Critical assessment of human metabolic pathway databases: a stepping stone for future integration

Directory of Open Access Journals (Sweden)

Stobbe Miranda D

2011-10-01

Full Text Available Abstract Background Multiple pathway databases are available that describe the human metabolic network and have proven their usefulness in many applications, ranging from the analysis and interpretation of high-throughput data to their use as a reference repository. However, so far the various human metabolic networks described by these databases have not been systematically compared and contrasted, nor has the extent to which they differ been quantified. For a researcher using these databases for particular analyses of human metabolism, it is crucial to know the extent of the differences in content and their underlying causes. Moreover, the outcomes of such a comparison are important for ongoing integration efforts. Results We compared the genes, EC numbers and reactions of five frequently used human metabolic pathway databases. The overlap is surprisingly low, especially on reaction level, where the databases agree on 3% of the 6968 reactions they have combined. Even for the well-established tricarboxylic acid cycle the databases agree on only 5 out of the 30 reactions in total. We identified the main causes for the lack of overlap. Importantly, the databases are partly complementary. Other explanations include the number of steps a conversion is described in and the number of possible alternative substrates listed. Missing metabolite identifiers and ambiguous names for metabolites also affect the comparison. Conclusions Our results show that each of the five networks compared provides us with a valuable piece of the puzzle of the complete reconstruction of the human metabolic network. To enable integration of the networks, next to a need for standardizing the metabolite names and identifiers, the conceptual differences between the databases should be resolved. Considerable manual intervention is required to reach the ultimate goal of a unified and biologically accurate model for studying the systems biology of human metabolism. Our comparison

Performance management in healthcare: a critical analysis.

Science.gov (United States)

Hewko, Sarah J; Cummings, Greta G

2016-01-01

Purpose - The purpose of this paper is to explore the underlying theoretical assumptions and implications of current micro-level performance management and evaluation (PME) practices, specifically within health-care organizations. PME encompasses all activities that are designed and conducted to align employee outputs with organizational goals. Design/methodology/approach - PME, in the context of healthcare, is analyzed through the lens of critical theory. Specifically, Habermas' theory of communicative action is used to highlight some of the questions that arise in looking critically at PME. To provide a richer definition of key theoretical concepts, the authors conducted a preliminary, exploratory hermeneutic semantic analysis of the key words "performance" and "management" and of the term "performance management". Findings - Analysis reveals that existing micro-level PME systems in health-care organizations have the potential to create a workforce that is compliant, dependent, technically oriented and passive, and to support health-care systems in which inequalities and power imbalances are perpetually reinforced. Practical implications - At a time when the health-care system is under increasing pressure to provide high-quality, affordable services with fewer resources, it may be wise to investigate new sector-specific ways of evaluating and managing performance. Originality/value - In this paper, written for health-care leaders and health human resource specialists, the theoretical assumptions and implications of current PME practices within health-care organizations are explored. It is hoped that readers will be inspired to support innovative PME practices within their organizations that encourage peak performance among health-care professionals.

Acknowledging the Infrasystem: A Critical Feminist Analysis of Systems Theory.

Science.gov (United States)

Creedon, Pamela J.

1993-01-01

Examines the absence of a critical feminist perspective in the application of systems theory as a unifying model for public relations. Describes an unacknowledged third system, the infrasystem, that constructs both suprasystem and subsystem interactions. Concludes with a case analysis of sport as illustration. (HB)

Heading in the right direction: thermodynamics-based network analysis and pathway engineering.

Science.gov (United States)

Ataman, Meric; Hatzimanikatis, Vassily

2015-12-01

Thermodynamics-based network analysis through the introduction of thermodynamic constraints in metabolic models allows a deeper analysis of metabolism and guides pathway engineering. The number and the areas of applications of thermodynamics-based network analysis methods have been increasing in the last ten years. We review recent applications of these methods and we identify the areas that such analysis can contribute significantly, and the needs for future developments. We find that organisms with multiple compartments and extremophiles present challenges for modeling and thermodynamics-based flux analysis. The evolution of current and new methods must also address the issues of the multiple alternatives in flux directionalities and the uncertainties and partial information from analytical methods. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Study of Critical Eco-Linguistic in Green Discourse: Prospective Eco-Linguistic Analysis

Directory of Open Access Journals (Sweden)

Tommi Yuniawan

2017-10-01

Full Text Available Eco-linguistic studies are influenced by one of the other interdisciplinary sciences, namely critical discourse analysis. The combination of these two sciences is called critical eco-linguistic studies. Critical eco-linguistic examines the discourse about the environment and various forms of discourse and their ideology which concerns people and the environment. The environmental discourse with all its manifestations (oral text, written text is called green discourse. To that end, critical eco-linguistic dictates the linguistic aspects contained in the green discourse. Utilization of lingual units in green discourse will affect the sense and logic of people involved in the discourse, ie the writers and readers or the speakers and the speakers. What is recorded in their cognition, will affect their attitudes and actions to the environment. If green discourse is constructive, then their attitude and actions to the environment are constructive. Conversely, if green discourse is more destructive and exploitative, then their attitudes and actions towards the environment will also be affected towards destruction and exploitation. For this reason, critical eco-linguistic studies in green discourse deserve to be given space as a form of prospective eco-linguistic analysis.

Development and implementation of a critical pathway for prevention of adverse reactions to contrast media for computed tomography

International Nuclear Information System (INIS)

Jang, Keun Jo; Kweon, Dae Cheol; Kim, Myeong Goo; Yoo, Beong Gyu

2007-01-01

The purpose of this study is to develop a critical pathway (CP) for the prevention of adverse reactions to contrast media for computed tomography. The CP was developed and implemented by a multidisciplinary group is Seoul National University Hospital. The CP was applied to CT patients. Patients who underwent CT scanning were included in the CP group from March in 2004. The satisfaction of the patients with CP was compared with non-CP groups. We also investigated the degree of satisfaction among the radiological technologists and nurses. The degree of patient satisfaction with the care process increased patient information (24%), prevention of adverse reactions to contrast media (19%), pre-cognitive effect of adverse reactions to contrast media (39%) and information degree of adverse reactions to contrast media (19%). This CP program can be used as one of the patient care tools for reducing the adverse reactions to contrast media and increasing the efficiency of care process in CT examination settings

Development and implementation of a critical pathway for prevention of adverse reactions to contrast media for computed tomography

Energy Technology Data Exchange (ETDEWEB)

Jang, Keun Jo [Presbyterian Medical Center, Seoul (Korea, Republic of); Kweon, Dae Cheol; Kim, Myeong Goo [Seoul National University Hospital, Seoul (Korea, Republic of); Yoo, Beong Gyu [Wonkwang Health Science College, Iksan (Korea, Republic of)

2007-03-15

The purpose of this study is to develop a critical pathway (CP) for the prevention of adverse reactions to contrast media for computed tomography. The CP was developed and implemented by a multidisciplinary group is Seoul National University Hospital. The CP was applied to CT patients. Patients who underwent CT scanning were included in the CP group from March in 2004. The satisfaction of the patients with CP was compared with non-CP groups. We also investigated the degree of satisfaction among the radiological technologists and nurses. The degree of patient satisfaction with the care process increased patient information (24%), prevention of adverse reactions to contrast media (19%), pre-cognitive effect of adverse reactions to contrast media (39%) and information degree of adverse reactions to contrast media (19%). This CP program can be used as one of the patient care tools for reducing the adverse reactions to contrast media and increasing the efficiency of care process in CT examination settings.

BeHealthy Charities Aid Foundation Program, Russia: a Program Impact Pathways (PIP) analysis.

Science.gov (United States)

Mukhina, Marina; Novikova, Irina

2014-09-01

In 2007, the Charities Aid Foundation Branch in Russia, under the initiative of and with financial support from the Mondelēz International Foundation and Mondelēz International, launched the charitable BeHealthy Program. The program's main focus is the implementation of four interrelated activities: conducting lessons for schoolchildren on healthy nutrition, with an emphasis on breakfast; healthy cooking lessons with children; cultivating nutritional plants; and providing conditions to encourage children to engage in more physical activity. The program serves more than 13,000 children attending public schools in the Leningrad (Lomonosovskii District), Vladimir, and Novgorod regions. BeHealthy provides funding for schools and comprehensive educational materials to help schoolchildren develop habits of healthy nutrition and physical activity, as well as consulting and expert support for school staff and other key stakeholders. The program brings in experts on program implementation and training for teachers. Curriculum support also includes printed and Web-based healthy lifestyle educational materials on best practices and positive experience, as well as meetings and conferences with school representatives and local authorities. One of the biggest challenges for program managers is to fully understand the complexities of the program, and why and how it is expected to induce changes in healthy lifestyle behaviors of the schoolchildren. For more comprehensive understanding, we performed a Program Impact Pathways (PIP) analysis to identify Critical Quality Control Points (CCPs) and a suite of core indicators of the program's impact on healthy lifestyles. The findings were presented at the Healthy Life-styles Program Evaluation Workshop held in Granada, Spain, 13-14 September 2013, under the auspices of the Mondelēz International Foundation. First, we developed an updated logic model based on how the program was executed. We then translated the logic model into a PIP

Using root cause analysis to promote critical thinking in final year Bachelor of Midwifery students.

Science.gov (United States)

Carter, Amanda G; Sidebotham, Mary; Creedy, Debra K; Fenwick, Jennifer; Gamble, Jenny

2014-06-01

Midwives require well developed critical thinking to practice autonomously. However, multiple factors impinge on students' deep learning in the clinical context. Analysis of actual case scenarios using root cause analysis may foster students' critical thinking and application of 'best practice' principles in complex clinical situations. To examine the effectiveness of an innovative teaching strategy involving root cause analysis to develop students' perceptions of their critical thinking abilities. A descriptive, mixed methods design was used. Final 3rd year undergraduate midwifery students (n=22) worked in teams to complete and present an assessment item based on root cause analysis. The cases were adapted from coroners' reports. After graduation, 17 (77%) students evaluated the course using a standard university assessment tool. In addition 12 (54%) students provided specific feedback on the teaching strategy using a 16-item survey tool based on the domain concepts of Educational Acceptability, Educational Impact, and Preparation for Practice. Survey responses were on a 5-point Likert scale and analysed using descriptive statistics. Open-ended responses were analysed using content analysis. The majority of students perceived the course and this teaching strategy positively. The domain mean scores were high for Educational Acceptability (mean=4.3, SD=.49) and Educational Impact (mean=4.19, SD=.75) but slightly lower for Preparation for Practice (mean=3.7, SD=.77). Overall student responses to each item were positive with no item mean less than 3.42. Students found the root cause analysis challenging and time consuming but reported development of critical thinking skills about the complexity of practice, clinical governance and risk management principles. Analysing complex real life clinical cases to determine a root cause enhanced midwifery students' perceptions of their critical thinking. Teaching and assessment strategies to promote critical thinking need to be

A Demonstrative Analysis of News Articles Using Fairclough’s Critical Discourse Analysis Framework

Directory of Open Access Journals (Sweden)

Roy Randy Y. Briones

2017-07-01

Full Text Available This paper attempts to demonstrate Norman Fairclough’s Critical Discourse Analysis (CDA framework by conducting internal and external level analyses on two online news articles that report on the Moro Islamic Liberation Front’s (MILF submission of its findings on the “Mamasapano Incident” that happened in the Philippines in 2015. In performing analyses using this framework, the social context and background for these texts, as well as the relationship between the internal discourse features and the external social practices and structures in which the texts were produced are thoroughly examined. As a result, it can be noted that from the texts’ internal discourse features, the news articles portray ideological and social distinctions among social actors such as the Philippine Senate, the SAF troopers, the MILF, the MILF fighters, and the civilians. Moreover, from the viewpoint of the texts as being external social practices, the texts maintain institutional identities as news reports, but they also reveal some evaluative stance as exemplified by the adjectival phrases that the writers employed. Having both the internal and external features examined, it can be said that the way these texts were written seems to portray power relations that exist between the Philippine government and the MILF. Key words: Critical Discourse Analysis, discourse analysis, news articles, social practices, social structures, power relations

Note of the methodological flaws in the paper entitled "Polymorphisms in IL-4/IL-13 pathway genes and glioma risk: an updated meta-analysis".

Science.gov (United States)

Wang, Ting-Ting; Li, Jin-Mei; Zhou, Dong

2016-01-01

With great interest, we read the paper "Polymorphisms in IL-4/IL-13 pathway genes and glioma risk: an updated meta-analysis" (by Chen PQ et al.) [1], which has reached important conclusions about the relationship between polymorphisms in interleukin (IL)-4/IL-13 pathway genes and glioma risk. Through quantitative analysis, the meta-analysis found no association between IL-4/IL-13 pathway genetic polymorphisms and glioma risk (Chen et al. in Tumor Biol 36:121-127, 2015). The meta-analysis is the most comprehensive study of polymorphisms in the IL-4/IL-13 pathway and glioma risk. Nevertheless, some deficiencies still exist in this meta-analysis that we would like to raise.

The Digital Single Market and Legal Certainty : A Critical Analysis

NARCIS (Netherlands)

Castermans, A.G.; Graaff, de R.; Haentjens, M.; Colombi, Ciacchi A.

2016-01-01

This chapter critically examines the CESL from the viewpoint of its capability to provide legal certainty for commercial actors. This chapter’s analysis focuses on three important stages in the life cycle of a contract, seen from a business perspective: the scope rules that determine whether the

Thinking Critically about Critical Thinking: Integrating Online Tools to Promote Critical Thinking

OpenAIRE

B. Jean Mandernach, PhD

2006-01-01

The value and importance of critical thinking is clearly established; the challenge for instructors lies in successfully promoting students’ critical thinking skills within the confines of a traditional classroom experience. Since instructors are faced with limited student contact time to meet their instructional objectives and facilitate learning, they are often forced to make instructional decisions between content coverage, depth of understanding, and critical analysis of course material. ...

Winding through the WNT pathway during cellular development and demise.

Science.gov (United States)

Li, F; Chong, Z Z; Maiese, K

2006-01-01

In slightly over a period of twenty years, our comprehension of the cellular and molecular mechanisms that govern the Wnt signaling pathway continue to unfold. The Wnt proteins were initially implicated in viral carcinogenesis experiments associated with mammary tumors, but since this period investigations focusing on the Wnt pathways and their transmembrane receptors termed Frizzled have been advanced to demonstrate the critical nature of Wnt for the development of a variety of cell populations as well as the potential of the Wnt pathway to avert apoptotic injury. In particular, Wnt signaling plays a significant role in both the cardiovascular and nervous systems during embryonic cell patterning, proliferation, differentiation, and orientation. Furthermore, modulation of Wnt signaling under specific cellular influences can either promote or prevent the early and late stages of apoptotic cellular injury in neurons, endothelial cells, vascular smooth muscle cells, and cardiomyocytes. A number of downstream signal transduction pathways can mediate the biological response of the Wnt proteins that include Dishevelled, beta-catenin, intracellular calcium, protein kinase C, Akt, and glycogen synthase kinase-3beta. Interestingly, these cellular cascades of the Wnt-Frizzled pathways can participate in several neurodegenerative, vascular, and cardiac disorders and may be closely integrated with the function of trophic factors. Identification of the critical elements that modulate the Wnt-Frizzled signaling pathway should continue to unlock the potential of Wnt pathway for the development of new therapeutic options against neurodegenerative and vascular diseases.

HIF-VEGF pathways are critical for chronic otitis media in Junbo and Jeff mouse mutants.

Directory of Open Access Journals (Sweden)

Michael T Cheeseman

2011-10-01

Full Text Available Otitis media with effusion (OME is the commonest cause of hearing loss in children, yet the underlying genetic pathways and mechanisms involved are incompletely understood. Ventilation of the middle ear with tympanostomy tubes is the commonest surgical procedure in children and the best treatment for chronic OME, but the mechanism by which they work remains uncertain. As hypoxia is a common feature of inflamed microenvironments, moderation of hypoxia may be a significant contributory mechanism. We have investigated the occurrence of hypoxia and hypoxia-inducible factor (HIF mediated responses in Junbo and Jeff mouse mutant models, which develop spontaneous chronic otitis media. We found that Jeff and Junbo mice labeled in vivo with pimonidazole showed cellular hypoxia in inflammatory cells in the bulla lumen, and in Junbo the middle ear mucosa was also hypoxic. The bulla fluid inflammatory cell numbers were greater and the upregulation of inflammatory gene networks were more pronounced in Junbo than Jeff. Hif-1α gene expression was elevated in bulla fluid inflammatory cells, and there was upregulation of its target genes including Vegfa in Junbo and Jeff. We therefore investigated the effects in Junbo of small-molecule inhibitors of VEGFR signaling (PTK787, SU-11248, and BAY 43-9006 and destabilizing HIF by inhibiting its chaperone HSP90 with 17-DMAG. We found that both classes of inhibitor significantly reduced hearing loss and the occurrence of bulla fluid and that VEGFR inhibitors moderated angiogenesis and lymphangiogenesis in the inflamed middle ear mucosa. The effectiveness of HSP90 and VEGFR signaling inhibitors in suppressing OM in the Junbo model implicates HIF-mediated VEGF as playing a pivotal role in OM pathogenesis. Our analysis of the Junbo and Jeff mutants highlights the role of hypoxia and HIF-mediated pathways, and we conclude that targeting molecules in HIF-VEGF signaling pathways has therapeutic potential in the treatment of

Developing group investigation-based book on numerical analysis to increase critical thinking student’s ability

Science.gov (United States)

Maharani, S.; Suprapto, E.

2018-03-01

Critical thinking is very important in Mathematics; it can make student more understanding mathematics concept. Critical thinking is also needed in numerical analysis. The Numerical analysis's book is not yet including critical thinking in them. This research aims to develop group investigation-based book on numerical analysis to increase critical thinking student’s ability, to know the quality of the group investigation-based book on numerical analysis is valid, practical, and effective. The research method is Research and Development (R&D) with the subject are 30 student college department of Mathematics education at Universitas PGRI Madiun. The development model used is 4-D modified to 3-D until the stage development. The type of data used is descriptive qualitative data. Instruments used are sheets of validation, test, and questionnaire. Development results indicate that group investigation-based book on numerical analysis in the category of valid a value 84.25%. Students response to the books very positive, so group investigation-based book on numerical analysis category practical, i.e., 86.00%. The use of group investigation-based book on numerical analysis has been meeting the completeness criteria classical learning that is 84.32 %. Based on research result of this study concluded that group investigation-based book on numerical analysis is feasible because it meets the criteria valid, practical, and effective. So, the book can be used by every mathematics academician. The next research can be observed that book based group investigation in other subjects.

A critical analysis of the biological impacts of plasticizers on wildlife

Science.gov (United States)

Oehlmann, Jörg; Schulte-Oehlmann, Ulrike; Kloas, Werner; Jagnytsch, Oana; Lutz, Ilka; Kusk, Kresten O.; Wollenberger, Leah; Santos, Eduarda M.; Paull, Gregory C.; Van Look, Katrien J. W.; Tyler, Charles R.

2009-01-01

This review provides a critical analysis of the biological effects of the most widely used plasticizers, including dibutyl phthalate, diethylhexyl phthalate, dimethyl phthalate, butyl benzyl phthalate and bisphenol A (BPA), on wildlife, with a focus on annelids (both aquatic and terrestrial), molluscs, crustaceans, insects, fish and amphibians. Moreover, the paper provides novel data on the biological effects of some of these plasticizers in invertebrates, fish and amphibians. Phthalates and BPA have been shown to affect reproduction in all studied animal groups, to impair development in crustaceans and amphibians and to induce genetic aberrations. Molluscs, crustaceans and amphibians appear to be especially sensitive to these compounds, and biological effects are observed at environmentally relevant exposures in the low ng l−1 to µg l−1 range. In contrast, most effects in fish (except for disturbance in spermatogenesis) occur at higher concentrations. Most plasticizers appear to act by interfering with the functioning of various hormone systems, but some phthalates have wider pathways of disruption. Effect concentrations of plasticizers in laboratory experiments coincide with measured environmental concentrations, and thus there is a very real potential for effects of these chemicals on some wildlife populations. The most striking gaps in our current knowledge on the impacts of plasticizers on wildlife are the lack of data for long-term exposures to environmentally relevant concentrations and their ecotoxicity when part of complex mixtures. Furthermore, the hazard of plasticizers has been investigated in annelids, molluscs and arthropods only, and given the sensitivity of some invertebrates, effects assessments are warranted in other invertebrate phyla. PMID:19528055

Disposal criticality analysis methodology's principal isotope burnup credit

International Nuclear Information System (INIS)

Doering, T.W.; Thomas, D.A.

2001-01-01

This paper presents the burnup credit aspects of the United States Department of Energy Yucca Mountain Project's methodology for performing criticality analyses for commercial light-water-reactor fuel. The disposal burnup credit methodology uses a 'principal isotope' model, which takes credit for the reduced reactivity associated with the build-up of the primary principal actinides and fission products in irradiated fuel. Burnup credit is important to the disposal criticality analysis methodology and to the design of commercial fuel waste packages. The burnup credit methodology developed for disposal of irradiated commercial nuclear fuel can also be applied to storage and transportation of irradiated commercial nuclear fuel. For all applications a series of loading curves are developed using a best estimate methodology and depending on the application, an additional administrative safety margin may be applied. The burnup credit methodology better represents the 'true' reactivity of the irradiated fuel configuration, and hence the real safety margin, than do evaluations using the 'fresh fuel' assumption. (author)

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.

TEGS-CN: A Statistical Method for Pathway Analysis of Genome-wide Copy Number Profile.

Science.gov (United States)

Huang, Yen-Tsung; Hsu, Thomas; Christiani, David C

2014-01-01

The effects of copy number alterations make up a significant part of the tumor genome profile, but pathway analyses of these alterations are still not well established. We proposed a novel method to analyze multiple copy numbers of genes within a pathway, termed Test for the Effect of a Gene Set with Copy Number data (TEGS-CN). TEGS-CN was adapted from TEGS, a method that we previously developed for gene expression data using a variance component score test. With additional development, we extend the method to analyze DNA copy number data, accounting for different sizes and thus various numbers of copy number probes in genes. The test statistic follows a mixture of X (2) distributions that can be obtained using permutation with scaled X (2) approximation. We conducted simulation studies to evaluate the size and the power of TEGS-CN and to compare its performance with TEGS. We analyzed a genome-wide copy number data from 264 patients of non-small-cell lung cancer. With the Molecular Signatures Database (MSigDB) pathway database, the genome-wide copy number data can be classified into 1814 biological pathways or gene sets. We investigated associations of the copy number profile of the 1814 gene sets with pack-years of cigarette smoking. Our analysis revealed five pathways with significant P values after Bonferroni adjustment (number data, and causal mechanisms of the five pathways require further study.

Sensitivity analysis of critical experiments with evaluated nuclear data libraries

International Nuclear Information System (INIS)

Fujiwara, D.; Kosaka, S.

2008-01-01

Criticality benchmark testing was performed with evaluated nuclear data libraries for thermal, low-enriched uranium fuel rod applications. C/E values for k eff were calculated with the continuous-energy Monte Carlo code MVP2 and its libraries generated from Endf/B-VI.8, Endf/B-VII.0, JENDL-3.3 and JEFF-3.1. Subsequently, the observed k eff discrepancies between libraries were decomposed to specify the source of difference in the nuclear data libraries using sensitivity analysis technique. The obtained sensitivity profiles are also utilized to estimate the adequacy of cold critical experiments to the boiling water reactor under hot operating condition. (authors)

Scale-4 analysis of pressurized water reactor critical configurations: Volume 5, North Anna Unit 1 Cycle 5

International Nuclear Information System (INIS)

Bowman, S.M.; Suto, T.

1996-10-01

ANSI/ANS 8.1 requires that calculational methods for away-from- reactor (AFR) criticality safety analyses be validated against experiment. This report summarizes part of the ongoing effort to benchmark AFR criticality analysis methods using selected critical configurations from commercial PWRs. Codes and data in the SCALE-4 code system were used. This volume documents the SCALE system analysis of one reactor critical configuration for North Anna Unit 1 Cycle 5. The KENO V.a criticality calculations for the North Anna 1 Cycle 5 beginning-of-cycle model yielded a value for k eff of 1. 0040±0.0005

Washing and chilling as critical control points in pork slaughter hazard analysis and critical control point (HACCP) systems.

Science.gov (United States)

Bolton, D J; Pearce, R A; Sheridan, J J; Blair, I S; McDowell, D A; Harrington, D

2002-01-01

The aim of this research was to examine the effects of preslaughter washing, pre-evisceration washing, final carcass washing and chilling on final carcass quality and to evaluate these operations as possible critical control points (CCPs) within a pork slaughter hazard analysis and critical control point (HACCP) system. This study estimated bacterial numbers (total viable counts) and the incidence of Salmonella at three surface locations (ham, belly and neck) on 60 animals/carcasses processed through a small commercial pork abattoir (80 pigs d(-1)). Significant reductions (P HACCP in pork slaughter plants. This research will provide a sound scientific basis on which to develop and implement effective HACCP in pork abattoirs.

Criticism versus stylistics: an analysis of their areas of overlap and ...

African Journals Online (AJOL)

Criticism versus stylistics: an analysis of their areas of overlap and contrast. ... AFRREV LALIGENS: An International Journal of Language, Literature and Gender Studies ... in a number of areas, a great deal of discrepancy exists between them.

Content Analysis in Computer-Mediated Communication: Analyzing Models for Assessing Critical Thinking through the Lens of Social Constructivism

Science.gov (United States)

Buraphadeja, Vasa; Dawson, Kara

2008-01-01

This article reviews content analysis studies aimed to assess critical thinking in computer-mediated communication. It also discusses theories and content analysis models that encourage critical thinking skills in asynchronous learning environments and reviews theories and factors that may foster critical thinking skills and new knowledge…

Identity and representation in Russia's regions: Adopting a critical theory perspective

Directory of Open Access Journals (Sweden)

Andrey Makarychev

2012-07-01

Full Text Available In this paper, the author seeks to find pathways of extrapolating the critical potential of post-structuralist reasoning to the study of Russia's domestic regions' policies. He argues that ideas, norms and rhetorical frames are important ideational arguments to explain policy outcomes in specific Russia's region and in the whole system of Russian federalism. Analysis of Russian regionalism, therefore, can be enriched by engaging with and adopting the new concepts and tools bringing attention to the power of regional identities as exemplified by different types of discourses.

Branching points for transition pathways: assessing responses of actors to challenges on pathways to a low carbon future

International Nuclear Information System (INIS)

Foxon, Timothy J.; Pearson, Peter J.G.; Arapostathis, Stathis; Carlsson-Hyslop, Anna; Thornton, Judith

2013-01-01

This paper describes initial analysis of branching points on a set of transition pathways to a UK low carbon electricity future by 2050. As described in other papers in this special issue, we are exploring and analysing a set of core transition pathways, based on alternative governance patterns in which the ‘logics’ of market actors, government actors and civil society actors, respectively dominate. This core pathway analysis is enhanced by analyses of branching points within and across the pathways, which informs how competition between different logics plays out at key decision points. Branching points are defined as key decision points at which choices made by actors, in response to internal or external stresses or triggers, determine whether and in what ways the pathway is followed. A set of initial branching points for our three core transition pathways is identified through project and stakeholder workshops, and drawing on analysis of actors’ choices and responses at past branching points in energy system transitions. The potential responses of the actors are identified at these branching points, and risk mitigation strategies are formulated for the dominant actors to reinforce that pathway, as well as opportunities for actors to move away from the pathway. - Highlights: Transition Pathways is analysing three potential pathways to a low carbon future. ► Stresses lead to branching points, where actors make choices, creating pathways. ► These choices may lead to path-dependency. ► Differences in governance logics within transition pathways are also analysed. ► Studying branching points adds theoretical understanding and policy relevance to TP.

Pathway modeling of microarray data: A case study of pathway activity changes in the testis following in utero exposure to dibutyl phthalate (DBP)

International Nuclear Information System (INIS)