WorldWideScience

Sample records for integrated molecular analysis

  1. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles

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    Farshad Farshidfar

    2017-03-01

    Full Text Available Cholangiocarcinoma (CCA is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance.

  2. Massively Parallel, Molecular Analysis Platform Developed Using a CMOS Integrated Circuit With Biological Nanopores

    Science.gov (United States)

    Roever, Stefan

    2012-01-01

    A massively parallel, low cost molecular analysis platform will dramatically change the nature of protein, molecular and genomics research, DNA sequencing, and ultimately, molecular diagnostics. An integrated circuit (IC) with 264 sensors was fabricated using standard CMOS semiconductor processing technology. Each of these sensors is individually controlled with precision analog circuitry and is capable of single molecule measurements. Under electronic and software control, the IC was used to demonstrate the feasibility of creating and detecting lipid bilayers and biological nanopores using wild type α-hemolysin. The ability to dynamically create bilayers over each of the sensors will greatly accelerate pore development and pore mutation analysis. In addition, the noise performance of the IC was measured to be 30fA(rms). With this noise performance, single base detection of DNA was demonstrated using α-hemolysin. The data shows that a single molecule, electrical detection platform using biological nanopores can be operationalized and can ultimately scale to millions of sensors. Such a massively parallel platform will revolutionize molecular analysis and will completely change the field of molecular diagnostics in the future.

  3. Integrating atomistic molecular dynamics simulations, experiments, and network analysis to study protein dynamics

    DEFF Research Database (Denmark)

    Papaleo, Elena

    2015-01-01

    that we observe and the functional properties of these important cellular machines. To make progresses in this direction, we need to improve the physical models used to describe proteins and solvent in molecular dynamics, as well as to strengthen the integration of experiments and simulations to overcome...... with the possibility to validate simulation methods and physical models against a broad range of experimental observables. On the other side, it also allows a complementary and comprehensive view on protein structure and dynamics. What is needed now is a better understanding of the link between the dynamic properties...... simulations with attention to the effects that can be propagated over long distances and are often associated to important biological functions. In this context, approaches inspired by network analysis can make an important contribution to the analysis of molecular dynamics simulations....

  4. Respiromics – An integrative analysis linking mitochondrial bioenergetics to molecular signatures

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    Ellen Walheim

    2018-03-01

    Full Text Available Objective: Energy metabolism is challenged upon nutrient stress, eventually leading to a variety of metabolic diseases that represent a major global health burden. Methods: Here, we combine quantitative mitochondrial respirometry (Seahorse technology and proteomics (LC-MS/MS-based total protein approach to understand how molecular changes translate to changes in mitochondrial energy transduction during diet-induced obesity (DIO in the liver. Results: The integrative analysis reveals that significantly increased palmitoyl-carnitine respiration is supported by an array of proteins enriching lipid metabolism pathways. Upstream of the respiratory chain, the increased capacity for ATP synthesis during DIO associates strongest to mitochondrial uptake of pyruvate, which is routed towards carboxylation. At the respiratory chain, robust increases of complex I are uncovered by cumulative analysis of single subunit concentrations. Specifically, nuclear-encoded accessory subunits, but not mitochondrial-encoded or core units, appear to be permissive for enhanced lipid oxidation. Conclusion: Our integrative analysis, that we dubbed “respiromics”, represents an effective tool to link molecular changes to functional mechanisms in liver energy metabolism, and, more generally, can be applied for mitochondrial analysis in a variety of metabolic and mitochondrial disease models. Keywords: Mitochondria, Respirometry, Proteomics, Mitochondrial pyruvate carrier, Liver disease, Bioenergetics, Obesity, Diabetes

  5. Integrative network analysis unveils convergent molecular pathways in Parkinson's disease and diabetes.

    Science.gov (United States)

    Santiago, Jose A; Potashkin, Judith A

    2013-01-01

    Shared dysregulated pathways may contribute to Parkinson's disease and type 2 diabetes, chronic diseases that afflict millions of people worldwide. Despite the evidence provided by epidemiological and gene profiling studies, the molecular and functional networks implicated in both diseases, have not been fully explored. In this study, we used an integrated network approach to investigate the extent to which Parkinson's disease and type 2 diabetes are linked at the molecular level. Using a random walk algorithm within the human functional linkage network we identified a molecular cluster of 478 neighboring genes closely associated with confirmed Parkinson's disease and type 2 diabetes genes. Biological and functional analysis identified the protein serine-threonine kinase activity, MAPK cascade, activation of the immune response, and insulin receptor and lipid signaling as convergent pathways. Integration of results from microarrays studies identified a blood signature comprising seven genes whose expression is dysregulated in Parkinson's disease and type 2 diabetes. Among this group of genes, is the amyloid precursor protein (APP), previously associated with neurodegeneration and insulin regulation. Quantification of RNA from whole blood of 192 samples from two independent clinical trials, the Harvard Biomarker Study (HBS) and the Prognostic Biomarker Study (PROBE), revealed that expression of APP is significantly upregulated in Parkinson's disease patients compared to healthy controls. Assessment of biomarker performance revealed that expression of APP could distinguish Parkinson's disease from healthy individuals with a diagnostic accuracy of 80% in both cohorts of patients. These results provide the first evidence that Parkinson's disease and diabetes are strongly linked at the molecular level and that shared molecular networks provide an additional source for identifying highly sensitive biomarkers. Further, these results suggest for the first time that

  6. Integrative network analysis unveils convergent molecular pathways in Parkinson's disease and diabetes.

    Directory of Open Access Journals (Sweden)

    Jose A Santiago

    Full Text Available Shared dysregulated pathways may contribute to Parkinson's disease and type 2 diabetes, chronic diseases that afflict millions of people worldwide. Despite the evidence provided by epidemiological and gene profiling studies, the molecular and functional networks implicated in both diseases, have not been fully explored. In this study, we used an integrated network approach to investigate the extent to which Parkinson's disease and type 2 diabetes are linked at the molecular level.Using a random walk algorithm within the human functional linkage network we identified a molecular cluster of 478 neighboring genes closely associated with confirmed Parkinson's disease and type 2 diabetes genes. Biological and functional analysis identified the protein serine-threonine kinase activity, MAPK cascade, activation of the immune response, and insulin receptor and lipid signaling as convergent pathways. Integration of results from microarrays studies identified a blood signature comprising seven genes whose expression is dysregulated in Parkinson's disease and type 2 diabetes. Among this group of genes, is the amyloid precursor protein (APP, previously associated with neurodegeneration and insulin regulation. Quantification of RNA from whole blood of 192 samples from two independent clinical trials, the Harvard Biomarker Study (HBS and the Prognostic Biomarker Study (PROBE, revealed that expression of APP is significantly upregulated in Parkinson's disease patients compared to healthy controls. Assessment of biomarker performance revealed that expression of APP could distinguish Parkinson's disease from healthy individuals with a diagnostic accuracy of 80% in both cohorts of patients.These results provide the first evidence that Parkinson's disease and diabetes are strongly linked at the molecular level and that shared molecular networks provide an additional source for identifying highly sensitive biomarkers. Further, these results suggest for the first

  7. Integrating atomistic molecular dynamics simulations, experiments and network analysis to study protein dynamics: strength in unity

    Directory of Open Access Journals (Sweden)

    Elena ePapaleo

    2015-05-01

    Full Text Available In the last years, we have been observing remarkable improvements in the field of protein dynamics. Indeed, we can now study protein dynamics in atomistic details over several timescales with a rich portfolio of experimental and computational techniques. On one side, this provides us with the possibility to validate simulation methods and physical models against a broad range of experimental observables. On the other side, it also allows a complementary and comprehensive view on protein structure and dynamics. What is needed now is a better understanding of the link between the dynamic properties that we observe and the functional properties of these important cellular machines. To make progresses in this direction, we need to improve the physical models used to describe proteins and solvent in molecular dynamics, as well as to strengthen the integration of experiments and simulations to overcome their own limitations. Moreover, now that we have the means to study protein dynamics in great details, we need new tools to understand the information embedded in the protein ensembles and in their dynamic signature. With this aim in mind, we should enrich the current tools for analysis of biomolecular simulations with attention to the effects that can be propagated over long distances and are often associated to important biological functions. In this context, approaches inspired by network analysis can make an important contribution to the analysis of molecular dynamics simulations.

  8. Integrated network analysis reveals potentially novel molecular mechanisms and therapeutic targets of refractory epilepsies.

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    Hongwei Chu

    Full Text Available Epilepsy is a complex neurological disorder and a significant health problem. The pathogenesis of epilepsy remains obscure in a significant number of patients and the current treatment options are not adequate in about a third of individuals which were known as refractory epilepsies (RE. Network medicine provides an effective approach for studying the molecular mechanisms underlying complex diseases. Here we integrated 1876 disease-gene associations of RE and located those genes to human protein-protein interaction (PPI network to obtain 42 significant RE-associated disease modules. The functional analysis of these disease modules showed novel molecular pathological mechanisms of RE, such as the novel enriched pathways (e.g., "presynaptic nicotinic acetylcholine receptors", "signaling by insulin receptor". Further analysis on the relationships between current drug targets and the RE-related disease genes showed the rational mechanisms of most antiepileptic drugs. In addition, we detected ten potential novel drug targets (e.g., KCNA1, KCNA4-6, KCNC3, KCND2, KCNMA1, CAMK2G, CACNB4 and GRM1 located in three RE related disease modules, which might provide novel insights into the new drug discovery for RE therapy.

  9. Integrative Network Analysis Unveils Convergent Molecular Pathways in Parkinson's Disease and Diabetes

    OpenAIRE

    Santiago, Jose A.; Potashkin, Judith A.

    2013-01-01

    Background Shared dysregulated pathways may contribute to Parkinson's disease and type 2 diabetes, chronic diseases that afflict millions of people worldwide. Despite the evidence provided by epidemiological and gene profiling studies, the molecular and functional networks implicated in both diseases, have not been fully explored. In this study, we used an integrated network approach to investigate the extent to which Parkinson's disease and type 2 diabetes are linked at the molecular level. ...

  10. Detectable states, cycle fluxes, and motility scaling of molecular motor kinesin: An integrative kinetic graph theory analysis

    Science.gov (United States)

    Ren, Jie

    2017-12-01

    The process by which a kinesin motor couples its ATPase activity with concerted mechanical hand-over-hand steps is a foremost topic of molecular motor physics. Two major routes toward elucidating kinesin mechanisms are the motility performance characterization of velocity and run length, and single-molecular state detection experiments. However, these two sets of experimental approaches are largely uncoupled to date. Here, we introduce an integrative motility state analysis based on a theorized kinetic graph theory for kinesin, which, on one hand, is validated by a wealth of accumulated motility data, and, on the other hand, allows for rigorous quantification of state occurrences and chemomechanical cycling probabilities. An interesting linear scaling for kinesin motility performance across species is discussed as well. An integrative kinetic graph theory analysis provides a powerful tool to bridge motility and state characterization experiments, so as to forge a unified effort for the elucidation of the working mechanisms of molecular motors.

  11. Integrating molecular QTL data into genome-wide genetic association analysis: Probabilistic assessment of enrichment and colocalization.

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    Xiaoquan Wen

    2017-03-01

    Full Text Available We propose a novel statistical framework for integrating the result from molecular quantitative trait loci (QTL mapping into genome-wide genetic association analysis of complex traits, with the primary objectives of quantitatively assessing the enrichment of the molecular QTLs in complex trait-associated genetic variants and the colocalizations of the two types of association signals. We introduce a natural Bayesian hierarchical model that treats the latent association status of molecular QTLs as SNP-level annotations for candidate SNPs of complex traits. We detail a computational procedure to seamlessly perform enrichment, fine-mapping and colocalization analyses, which is a distinct feature compared to the existing colocalization analysis procedures in the literature. The proposed approach is computationally efficient and requires only summary-level statistics. We evaluate and demonstrate the proposed computational approach through extensive simulation studies and analyses of blood lipid data and the whole blood eQTL data from the GTEx project. In addition, a useful utility from our proposed method enables the computation of expected colocalization signals using simple characteristics of the association data. Using this utility, we further illustrate the importance of enrichment analysis on the ability to discover colocalized signals and the potential limitations of currently available molecular QTL data. The software pipeline that implements the proposed computation procedures, enloc, is freely available at https://github.com/xqwen/integrative.

  12. Uncovering the molecular secrets of inflammatory breast cancer biology: an integrated analysis of three distinct affymetrix gene expression datasets.

    Science.gov (United States)

    Van Laere, Steven J; Ueno, Naoto T; Finetti, Pascal; Vermeulen, Peter; Lucci, Anthony; Robertson, Fredika M; Marsan, Melike; Iwamoto, Takayuki; Krishnamurthy, Savitri; Masuda, Hiroko; van Dam, Peter; Woodward, Wendy A; Viens, Patrice; Cristofanilli, Massimo; Birnbaum, Daniel; Dirix, Luc; Reuben, James M; Bertucci, François

    2013-09-01

    Inflammatory breast cancer (IBC) is a poorly characterized form of breast cancer. So far, the results of expression profiling in IBC are inconclusive due to various reasons including limited sample size. Here, we present the integration of three Affymetrix expression datasets collected through the World IBC Consortium allowing us to interrogate the molecular profile of IBC using the largest series of IBC samples ever reported. Affymetrix profiles (HGU133-series) from 137 patients with IBC and 252 patients with non-IBC (nIBC) were analyzed using unsupervised and supervised techniques. Samples were classified according to the molecular subtypes using the PAM50-algorithm. Regression models were used to delineate IBC-specific and molecular subtype-independent changes in gene expression, pathway, and transcription factor activation. Four robust IBC-sample clusters were identified, associated with the different molecular subtypes (Pmolecular subtype-independent 79-gene signature, which held independent prognostic value in a series of 871 nIBCs. Functional analysis revealed attenuated TGF-β signaling in IBC. We show that IBC is transcriptionally heterogeneous and that all molecular subtypes described in nIBC are detectable in IBC, albeit with a different frequency. The molecular profile of IBC, bearing molecular traits of aggressive breast tumor biology, shows attenuation of TGF-β signaling, potentially explaining the metastatic potential of IBC tumor cells in an unexpected manner. ©2013 AACR.

  13. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles

    DEFF Research Database (Denmark)

    Farshidfar, Farshad; Zheng, Siyuan; Gingras, Marie-Claude

    2017-01-01

    Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahep...

  14. Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis.

    Science.gov (United States)

    Thompson, Eric M; Hielscher, Thomas; Bouffet, Eric; Remke, Marc; Luu, Betty; Gururangan, Sridharan; McLendon, Roger E; Bigner, Darell D; Lipp, Eric S; Perreault, Sebastien; Cho, Yoon-Jae; Grant, Gerald; Kim, Seung-Ki; Lee, Ji Yeoun; Rao, Amulya A Nageswara; Giannini, Caterina; Li, Kay Ka Wai; Ng, Ho-Keung; Yao, Yu; Kumabe, Toshihiro; Tominaga, Teiji; Grajkowska, Wieslawa A; Perek-Polnik, Marta; Low, David C Y; Seow, Wan Tew; Chang, Kenneth T E; Mora, Jaume; Pollack, Ian F; Hamilton, Ronald L; Leary, Sarah; Moore, Andrew S; Ingram, Wendy J; Hallahan, Andrew R; Jouvet, Anne; Fèvre-Montange, Michelle; Vasiljevic, Alexandre; Faure-Conter, Cecile; Shofuda, Tomoko; Kagawa, Naoki; Hashimoto, Naoya; Jabado, Nada; Weil, Alexander G; Gayden, Tenzin; Wataya, Takafumi; Shalaby, Tarek; Grotzer, Michael; Zitterbart, Karel; Sterba, Jaroslav; Kren, Leos; Hortobágyi, Tibor; Klekner, Almos; László, Bognár; Pócza, Tímea; Hauser, Peter; Schüller, Ulrich; Jung, Shin; Jang, Woo-Youl; French, Pim J; Kros, Johan M; van Veelen, Marie-Lise C; Massimi, Luca; Leonard, Jeffrey R; Rubin, Joshua B; Vibhakar, Rajeev; Chambless, Lola B; Cooper, Michael K; Thompson, Reid C; Faria, Claudia C; Carvalho, Alice; Nunes, Sofia; Pimentel, José; Fan, Xing; Muraszko, Karin M; López-Aguilar, Enrique; Lyden, David; Garzia, Livia; Shih, David J H; Kijima, Noriyuki; Schneider, Christian; Adamski, Jennifer; Northcott, Paul A; Kool, Marcel; Jones, David T W; Chan, Jennifer A; Nikolic, Ana; Garre, Maria Luisa; Van Meir, Erwin G; Osuka, Satoru; Olson, Jeffrey J; Jahangiri, Arman; Castro, Brandyn A; Gupta, Nalin; Weiss, William A; Moxon-Emre, Iska; Mabbott, Donald J; Lassaletta, Alvaro; Hawkins, Cynthia E; Tabori, Uri; Drake, James; Kulkarni, Abhaya; Dirks, Peter; Rutka, James T; Korshunov, Andrey; Pfister, Stefan M; Packer, Roger J; Ramaswamy, Vijay; Taylor, Michael D

    2016-04-01

    Patients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner. We retrospectively identified patients who had a histological diagnosis of medulloblastoma and complete data about extent of resection and survival from centres participating in the Medulloblastoma Advanced Genomics International Consortium. We collected from resections done between April, 1997, and February, 2013, at 35 international institutions. We established medulloblastoma subgroup affiliation by gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. We classified extent of resection on the basis of postoperative imaging as gross total resection (no residual tumour), near-total resection (30 Gy vs no craniospinal irradiation). The primary analysis outcome was the effect of extent of resection by molecular subgroup and the effects of other clinical variables on overall and progression-free survival. We included 787 patients with medulloblastoma (86 with WNT tumours, 242 with SHH tumours, 163 with group 3 tumours, and 296 with group 4 tumours) in our multivariable Cox models of progression-free and overall survival. We found that the prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. We identified a progression-free survival benefit for gross total resection over sub-total resection (hazard ratio [HR] 1·45, 95% CI 1·07-1·96, p=0·16) but no overall survival benefit (HR 1·23, 0·87-1·72, p=0·24). We saw no progression-free survival or overall survival

  15. Novel insights into systemic autoimmune rheumatic diseases using shared molecular signatures and an integrative analysis.

    Science.gov (United States)

    Hudson, Marie; Bernatsky, Sasha; Colmegna, Ines; Lora, Maximilien; Pastinen, Tomi; Klein Oros, Kathleen; Greenwood, Celia M T

    2017-06-03

    We undertook this study to identify DNA methylation signatures of three systemic autoimmune rheumatic diseases (SARDs), namely rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, compared to healthy controls. Using a careful design to minimize confounding, we restricted our study to subjects with incident disease and performed our analyses on purified CD4 + T cells, key effector cells in SARD. We identified differentially methylated (using the Illumina Infinium HumanMethylation450 BeadChip array) and expressed (using the Illumina TruSeq stranded RNA-seq protocol) sites between cases and controls, and investigated the biological significance of this SARD signature using gene annotation databases. We recruited 13 seropositive rheumatoid arthritis, 19 systemic sclerosis, 12 systemic lupus erythematosus subjects, and 8 healthy controls. We identified 33 genes that were both differentially methylated and expressed (26 over- and 7 under-expressed) in SARD cases versus controls. The most highly overexpressed gene was CD1C (log fold change in expression = 1.85, adjusted P value = 0.009). In functional analysis (Ingenuity Pathway Analysis), the top network identified was lipid metabolism, molecular transport, small molecule biochemistry. The top canonical pathways included the mitochondrial L-carnitine shuttle pathway (P = 5E-03) and PTEN signaling (P = 8E-03). The top upstream regulator was HNF4A (P = 3E-05). This novel SARD signature contributes to ongoing work to further our understanding of the molecular mechanisms underlying SARD and provides novel targets of interest.

  16. Integrative Bioinformatic Analysis of Transcriptomic Data Identifies Conserved Molecular Pathways Underlying Ionizing Radiation-Induced Bystander Effects (RIBE

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    Constantinos Yeles

    2017-11-01

    Full Text Available Ionizing radiation-induced bystander effects (RIBE encompass a number of effects with potential for a plethora of damages in adjacent non-irradiated tissue. The cascade of molecular events is initiated in response to the exposure to ionizing radiation (IR, something that may occur during diagnostic or therapeutic medical applications. In order to better investigate these complex response mechanisms, we employed a unified framework integrating statistical microarray analysis, signal normalization, and translational bioinformatics functional analysis techniques. This approach was applied to several microarray datasets from Gene Expression Omnibus (GEO related to RIBE. The analysis produced lists of differentially expressed genes, contrasting bystander and irradiated samples versus sham-irradiated controls. Furthermore, comparative molecular analysis through BioInfoMiner, which integrates advanced statistical enrichment and prioritization methodologies, revealed discrete biological processes, at the cellular level. For example, the negative regulation of growth, cellular response to Zn2+-Cd2+, and Wnt and NIK/NF-kappaB signaling, thus refining the description of the phenotypic landscape of RIBE. Our results provide a more solid understanding of RIBE cell-specific response patterns, especially in the case of high-LET radiations, like α-particles and carbon-ions.

  17. GenFlow: generic flow for integration, management and analysis of molecular biology data

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    Marcio Katsumi Oikawa

    2004-01-01

    Full Text Available A large number of DNA sequencing projects all over the world have yielded a fantastic amount of data, whose analysis is, currently, a big challenge for computational biology. The limiting step in this task is the integration of large volumes of data stored in highly heterogeneous repositories of genomic and cDNA sequences, as well as gene expression results. Solving this problem requires automated analytical tools to optimize operations and efficiently generate knowledge. This paper presents an information flow model , called GenFlow, that can tackle this analytical task.

  18. Analysis of fast boundary-integral approximations for modeling electrostatic contributions of molecular binding

    Science.gov (United States)

    Kreienkamp, Amelia B.; Liu, Lucy Y.; Minkara, Mona S.; Knepley, Matthew G.; Bardhan, Jaydeep P.; Radhakrishnan, Mala L.

    2013-01-01

    We analyze and suggest improvements to a recently developed approximate continuum-electrostatic model for proteins. The model, called BIBEE/I (boundary-integral based electrostatics estimation with interpolation), was able to estimate electrostatic solvation free energies to within a mean unsigned error of 4% on a test set of more than 600 proteins—a significant improvement over previous BIBEE models. In this work, we tested the BIBEE/I model for its capability to predict residue-by-residue interactions in protein–protein binding, using the widely studied model system of trypsin and bovine pancreatic trypsin inhibitor (BPTI). Finding that the BIBEE/I model performs surprisingly less well in this task than simpler BIBEE models, we seek to explain this behavior in terms of the models’ differing spectral approximations of the exact boundary-integral operator. Calculations of analytically solvable systems (spheres and tri-axial ellipsoids) suggest two possibilities for improvement. The first is a modified BIBEE/I approach that captures the asymptotic eigenvalue limit correctly, and the second involves the dipole and quadrupole modes for ellipsoidal approximations of protein geometries. Our analysis suggests that fast, rigorous approximate models derived from reduced-basis approximation of boundary-integral equations might reach unprecedented accuracy, if the dipole and quadrupole modes can be captured quickly for general shapes. PMID:24466561

  19. Integrated analysis of the molecular action of Vorinostat identifies epi-sensitised targets for combination therapy.

    Science.gov (United States)

    Hay, Jodie F; Lappin, Katrina; Liberante, Fabio; Kettyle, Laura M; Matchett, Kyle B; Thompson, Alexander; Mills, Ken I

    2017-09-15

    Several histone deacetylase inhibitors including Vorinostat have received FDA approval for the treatment of haematological malignancies. However, data from these trials indicate that Vorinostat has limited efficacy as a monotherapy, prompting the need for rational design of combination therapies. A number of epi-sensitised pathways, including sonic hedgehog (SHH), were identified in AML cells by integration of global patterns of histone H3 lysine 9 (H3K9) acetylation with transcriptomic analysis following Vorinostat-treatment. Direct targeting of the SHH pathway with SANT-1, following Vorinostat induced epi-sensitisation, resulted in synergistic cell death of AML cells. In addition, xenograft studies demonstrated that combination therapy induced a marked reduction in leukemic burden compared to control or single agents. Together, the data supports epi-sensitisation as a potential component of the strategy for the rational development of combination therapies in AML.

  20. MelanomaDB: a Web Tool for Integrative Analysis of Melanoma Genomic Information to Identify Disease-Associated Molecular Pathways

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    Alexander Joseph Trevarton

    2013-07-01

    Full Text Available Despite on-going research, metastatic melanoma survival rates remain low and treatment options are limited. Researchers can now access a rapidly growing amount of molecular and clinical information about melanoma. This information is becoming difficult to assemble and interpret due to its dispersed nature, yet as it grows it becomes increasingly valuable for understanding melanoma. Integration of this information into a comprehensive resource to aid rational experimental design and patient stratification is needed. As an initial step in this direction, we have assembled a web-accessible melanoma database, MelanomaDB, which incorporates clinical and molecular data from publically available sources, which will be regularly updated as new information becomes available. This database allows complex links to be drawn between many different aspects of melanoma biology: genetic changes (e.g. mutations in individual melanomas revealed by DNA sequencing, associations between gene expression and patient survival, data concerning drug targets, biomarkers, druggability and clinical trials, as well as our own statistical analysis of relationships between molecular pathways and clinical parameters that have been produced using these data sets. The database is freely available at http://genesetdb.auckland.ac.nz/melanomadb/about.html . A subset of the information in the database can also be accessed through a freely available web application in the Illumina genomic cloud computing platform BaseSpace at http://www.biomatters.com/apps/melanoma-profiler-for-research . This illustrates dysregulation of specific signalling pathways, both across 310 exome-sequenced melanomas and in individual tumours and identifies novel features about the distribution of somatic variants in melanoma. We suggest that this database can provide a context in which to interpret the tumour molecular profiles of individual melanoma patients relative to biological information and available

  1. An integrated analysis of molecular acclimation to high light in the marine diatom Phaeodactylum tricornutum

    DEFF Research Database (Denmark)

    Nymark, Marianne; Valle, Kristin C; Brembu, Tore

    2009-01-01

    Photosynthetic diatoms are exposed to rapid and unpredictable changes in irradiance and spectral quality, and must be able to acclimate their light harvesting systems to varying light conditions. Molecular mechanisms behind light acclimation in diatoms are largely unknown. We set out to investiga...

  2. Mathematical analysis of the boundary-integral based electrostatics estimation approximation for molecular solvation: exact results for spherical inclusions.

    Science.gov (United States)

    Bardhan, Jaydeep P; Knepley, Matthew G

    2011-09-28

    We analyze the mathematically rigorous BIBEE (boundary-integral based electrostatics estimation) approximation of the mixed-dielectric continuum model of molecular electrostatics, using the analytically solvable case of a spherical solute containing an arbitrary charge distribution. Our analysis, which builds on Kirkwood's solution using spherical harmonics, clarifies important aspects of the approximation and its relationship to generalized Born models. First, our results suggest a new perspective for analyzing fast electrostatic models: the separation of variables between material properties (the dielectric constants) and geometry (the solute dielectric boundary and charge distribution). Second, we find that the eigenfunctions of the reaction-potential operator are exactly preserved in the BIBEE model for the sphere, which supports the use of this approximation for analyzing charge-charge interactions in molecular binding. Third, a comparison of BIBEE to the recent GBε theory suggests a modified BIBEE model capable of predicting electrostatic solvation free energies to within 4% of a full numerical Poisson calculation. This modified model leads to a projection-framework understanding of BIBEE and suggests opportunities for future improvements. © 2011 American Institute of Physics

  3. Next-generation phage display: integrating and comparing available molecular tools to enable cost-effective high-throughput analysis.

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    Emmanuel Dias-Neto

    2009-12-01

    Full Text Available Combinatorial phage display has been used in the last 20 years in the identification of protein-ligands and protein-protein interactions, uncovering relevant molecular recognition events. Rate-limiting steps of combinatorial phage display library selection are (i the counting of transducing units and (ii the sequencing of the encoded displayed ligands. Here, we adapted emerging genomic technologies to minimize such challenges.We gained efficiency by applying in tandem real-time PCR for rapid quantification to enable bacteria-free phage display library screening, and added phage DNA next-generation sequencing for large-scale ligand analysis, reporting a fully integrated set of high-throughput quantitative and analytical tools. The approach is far less labor-intensive and allows rigorous quantification; for medical applications, including selections in patients, it also represents an advance for quantitative distribution analysis and ligand identification of hundreds of thousands of targeted particles from patient-derived biopsy or autopsy in a longer timeframe post library administration. Additional advantages over current methods include increased sensitivity, less variability, enhanced linearity, scalability, and accuracy at much lower cost. Sequences obtained by qPhage plus pyrosequencing were similar to a dataset produced from conventional Sanger-sequenced transducing-units (TU, with no biases due to GC content, codon usage, and amino acid or peptide frequency. These tools allow phage display selection and ligand analysis at >1,000-fold faster rate, and reduce costs approximately 250-fold for generating 10(6 ligand sequences.Our analyses demonstrates that whereas this approach correlates with the traditional colony-counting, it is also capable of a much larger sampling, allowing a faster, less expensive, more accurate and consistent analysis of phage enrichment. Overall, qPhage plus pyrosequencing is superior to TU-counting plus Sanger

  4. Integrated Modules Analysis to Explore the Molecular Mechanisms of Phlegm-Stasis Cementation Syndrome with Ischemic Heart Disease

    Science.gov (United States)

    Xu, Wei-Ming; Yang, Kuo; Jiang, Li-Jie; Hu, Jing-Qing; Zhou, Xue-Zhong

    2018-01-01

    Background: Ischemic heart disease (IHD) has been the leading cause of death for several decades globally, IHD patients usually hold the symptoms of phlegm-stasis cementation syndrome (PSCS) as significant complications. However, the underlying molecular mechanisms of PSCS complicated with IHD have not yet been fully elucidated. Materials and Methods: Network medicine methods were utilized to elucidate the underlying molecular mechanisms of IHD phenotypes. Firstly, high-quality IHD-associated genes from both human curated disease-gene association database and biomedical literatures were integrated. Secondly, the IHD disease modules were obtained by dissecting the protein-protein interaction (PPI) topological modules in the String V9.1 database and the mapping of IHD-associated genes to the PPI topological modules. After that, molecular functional analyses (e.g., Gene Ontology and pathway enrichment analyses) for these IHD disease modules were conducted. Finally, the PSCS syndrome modules were identified by mapping the PSCS related symptom-genes to the IHD disease modules, which were further validated by both pharmacological and physiological evidences derived from published literatures. Results: The total of 1,056 high-quality IHD-associated genes were integrated and evaluated. In addition, eight IHD disease modules (the PPI sub-networks significantly relevant to IHD) were identified, in which two disease modules were relevant to PSCS syndrome (i.e., two PSCS syndrome modules). These two modules had enriched pathways on Toll-like receptor signaling pathway (hsa04620) and Renin-angiotensin system (hsa04614), with the molecular functions of angiotensin maturation (GO:0002003) and response to bacterium (GO:0009617), which had been validated by classical Chinese herbal formulas-related targets, IHD-related drug targets, and the phenotype features derived from human phenotype ontology (HPO) and published biomedical literatures. Conclusion: A network medicine

  5. Integrated Modules Analysis to Explore the Molecular Mechanisms of Phlegm-Stasis Cementation Syndrome with Ischemic Heart Disease

    Directory of Open Access Journals (Sweden)

    Wei-Ming Xu

    2018-01-01

    Full Text Available Background: Ischemic heart disease (IHD has been the leading cause of death for several decades globally, IHD patients usually hold the symptoms of phlegm-stasis cementation syndrome (PSCS as significant complications. However, the underlying molecular mechanisms of PSCS complicated with IHD have not yet been fully elucidated.Materials and Methods: Network medicine methods were utilized to elucidate the underlying molecular mechanisms of IHD phenotypes. Firstly, high-quality IHD-associated genes from both human curated disease-gene association database and biomedical literatures were integrated. Secondly, the IHD disease modules were obtained by dissecting the protein-protein interaction (PPI topological modules in the String V9.1 database and the mapping of IHD-associated genes to the PPI topological modules. After that, molecular functional analyses (e.g., Gene Ontology and pathway enrichment analyses for these IHD disease modules were conducted. Finally, the PSCS syndrome modules were identified by mapping the PSCS related symptom-genes to the IHD disease modules, which were further validated by both pharmacological and physiological evidences derived from published literatures.Results: The total of 1,056 high-quality IHD-associated genes were integrated and evaluated. In addition, eight IHD disease modules (the PPI sub-networks significantly relevant to IHD were identified, in which two disease modules were relevant to PSCS syndrome (i.e., two PSCS syndrome modules. These two modules had enriched pathways on Toll-like receptor signaling pathway (hsa04620 and Renin-angiotensin system (hsa04614, with the molecular functions of angiotensin maturation (GO:0002003 and response to bacterium (GO:0009617, which had been validated by classical Chinese herbal formulas-related targets, IHD-related drug targets, and the phenotype features derived from human phenotype ontology (HPO and published biomedical literatures.Conclusion: A network medicine

  6. Integrated Modules Analysis to Explore the Molecular Mechanisms of Phlegm-Stasis Cementation Syndrome with Ischemic Heart Disease.

    Science.gov (United States)

    Xu, Wei-Ming; Yang, Kuo; Jiang, Li-Jie; Hu, Jing-Qing; Zhou, Xue-Zhong

    2018-01-01

    Background: Ischemic heart disease (IHD) has been the leading cause of death for several decades globally, IHD patients usually hold the symptoms of phlegm-stasis cementation syndrome (PSCS) as significant complications. However, the underlying molecular mechanisms of PSCS complicated with IHD have not yet been fully elucidated. Materials and Methods: Network medicine methods were utilized to elucidate the underlying molecular mechanisms of IHD phenotypes. Firstly, high-quality IHD-associated genes from both human curated disease-gene association database and biomedical literatures were integrated. Secondly, the IHD disease modules were obtained by dissecting the protein-protein interaction (PPI) topological modules in the String V9.1 database and the mapping of IHD-associated genes to the PPI topological modules. After that, molecular functional analyses (e.g., Gene Ontology and pathway enrichment analyses) for these IHD disease modules were conducted. Finally, the PSCS syndrome modules were identified by mapping the PSCS related symptom-genes to the IHD disease modules, which were further validated by both pharmacological and physiological evidences derived from published literatures. Results: The total of 1,056 high-quality IHD-associated genes were integrated and evaluated. In addition, eight IHD disease modules (the PPI sub-networks significantly relevant to IHD) were identified, in which two disease modules were relevant to PSCS syndrome (i.e., two PSCS syndrome modules). These two modules had enriched pathways on Toll-like receptor signaling pathway (hsa04620) and Renin-angiotensin system (hsa04614), with the molecular functions of angiotensin maturation (GO:0002003) and response to bacterium (GO:0009617), which had been validated by classical Chinese herbal formulas-related targets, IHD-related drug targets, and the phenotype features derived from human phenotype ontology (HPO) and published biomedical literatures. Conclusion: A network medicine

  7. Integrated biochemical, molecular genetic, and bioacoustical analysis of mesoscale variability of the euphausiid Nematoscelis difficilis in the California Current

    Science.gov (United States)

    Bucklin, Ann; Wiebe, Peter H.; Smolenack, Sara B.; Copley, Nancy J.; Clarke, M. Elizabeth

    2002-03-01

    Integrated assessment of the euphausiid Nematoscelis difficilis (Crustacea; Euphausiacea) and the zooplankton assemblage of the California Current was designed to investigate individual, population, and community responses to mesoscale variability in biological and physical characters of the ocean. Zooplankton samples and observational data were collected along a cross-shelf transect of the California Current in association with the California Cooperative Fisheries Investigations (CalCOFI) Survey during October 1996. The transect crossed three domains defined by temperature and salinity: nearshore, mid-Current, and offshore. Individual N. difficilis differed in physiological condition along the transect, with higher size-corrected concentrations of four central metabolic enzymes (citrate synthetase, hexokinase, lactate dehydrogenase (LDH), and phosphoglucose isomerase (PGI)) for euphausiids collected in nearshore waters than in mid-Current and offshore waters. There was little variation in the DNA sequences of the genes encoding PGI and LDH (all DNA changes were either silent or heterozygous base substitutions), suggesting that differences in enzyme concentration did not result from underlying molecular genetic variation. The population genetic makeup of N. difficilis varied from sample to sample based on haplotype frequencies of mitochondrial cytochrome oxidase I (mtCOI; P=0.029). There were significant differences between pooled nearshore and offshore samples, based on allele frequencies at two sites of common substitutions in the mtCOI sequence ( P=0.020 and 0.026). Silhouette and bioacoustical backscattering measurements of the zooplankton assemblage of the top 100 m showed marked diel vertical migration of the scattering layer, of which euphausiids were a small but significant fraction. The biochemical and molecular assays are used as indices of complex physiological (i.e., growth and condition) and genetic (i.e., mortality) processes; the bioacoustical

  8. Integrated Molecular and Cellular Biophysics

    CERN Document Server

    Raicu, Valerica

    2008-01-01

    This book integrates concepts and methods from physics, biology, biochemistry and physical chemistry into a standalone, unitary text of biophysics that aims to provide a quantitative description of structures and processes occurring in living matter. The book introduces graduate physics students and physicists interested in biophysics research to 'classical' as well as emerging areas of biophysics. The advanced undergraduate physics students and the life scientists are also invited to join in, by building on their knowledge of basic physics. Essential notions of biochemistry and biology are introduced, as necessary, throughout the book, while the reader's familiarity with basic knowledge of physics is assumed. Topics covered include interactions between biological molecules, physical chemistry of phospholipids association into bilayer membranes, DNA and protein structure and folding, passive and active electrical properties of the cell membrane, classical as well as fractal aspects of reaction kinetics and di...

  9. Integrated molecular analysis of tumor biopsies on sequential CTLA-4 and PD-1 blockade reveals markers of response and resistance

    Science.gov (United States)

    Roh, Whijae; Chen, Pei-Ling; Reuben, Alexandre; Spencer, Christine N.; Prieto, Peter A.; Miller, John P.; Gopalakrishnan, Vancheswaran; Wang, Feng; Cooper, Zachary A.; Reddy, Sangeetha M.; Gumbs, Curtis; Little, Latasha; Chang, Qing; Chen, Wei-Shen; Wani, Khalida; Petaccia De Macedo, Mariana; Chen, Eveline; Austin-Breneman, Jacob L.; Jiang, Hong; Roszik, Jason; Tetzlaff, Michael T.; Davies, Michael A.; Gershenwald, Jeffrey E.; Tawbi, Hussein; Lazar, Alexander J.; Hwu, Patrick; Hwu, Wen-Jen; Diab, Adi; Glitza, Isabella C.; Patel, Sapna P.; Woodman, Scott E.; Amaria, Rodabe N.; Prieto, Victor G.; Hu, Jianhua; Sharma, Padmanee; Allison, James P.; Chin, Lynda; Zhang, Jianhua; Wargo, Jennifer A.; Futreal, P. Andrew

    2018-01-01

    Immune checkpoint blockade produces clinical benefit in many patients. However better biomarkers of response are still needed, and mechanisms of resistance remain incompletely understood. To address this, we recently studied a cohort of melanoma patients treated with sequential checkpoint blockade against cytotoxic T lymphocyte antigen-4 (CTLA-4) followed by programmed death receptor-1 (PD-1), and identified immune markers of response and resistance. Building on these studies, we performed deep molecular profiling including T-cell receptor sequencing (TCR-seq) and whole exome sequencing (WES) within the same cohort, and demonstrated that a more clonal T cell repertoire was predictive of response to PD-1 but not CTLA-4 blockade. Analysis of copy number alterations identified a higher burden of copy number loss in non-responders to CTLA-4 and PD-1 blockade and found that it was associated with decreased expression of genes in immune-related pathways. The effect of mutational load and burden of copy number loss on response was non-redundant, suggesting the potential utility of a combinatorial biomarker to optimize patient care with checkpoint blockade therapy. PMID:28251903

  10. Integrated multiscale modeling of molecular computing devices

    International Nuclear Information System (INIS)

    Cummings, Peter T; Leng Yongsheng

    2005-01-01

    Molecular electronics, in which single organic molecules are designed to perform the functions of transistors, diodes, switches and other circuit elements used in current siliconbased microelecronics, is drawing wide interest as a potential replacement technology for conventional silicon-based lithographically etched microelectronic devices. In addition to their nanoscopic scale, the additional advantage of molecular electronics devices compared to silicon-based lithographically etched devices is the promise of being able to produce them cheaply on an industrial scale using wet chemistry methods (i.e., self-assembly from solution). The design of molecular electronics devices, and the processes to make them on an industrial scale, will require a thorough theoretical understanding of the molecular and higher level processes involved. Hence, the development of modeling techniques for molecular electronics devices is a high priority from both a basic science point of view (to understand the experimental studies in this field) and from an applied nanotechnology (manufacturing) point of view. Modeling molecular electronics devices requires computational methods at all length scales - electronic structure methods for calculating electron transport through organic molecules bonded to inorganic surfaces, molecular simulation methods for determining the structure of self-assembled films of organic molecules on inorganic surfaces, mesoscale methods to understand and predict the formation of mesoscale patterns on surfaces (including interconnect architecture), and macroscopic scale methods (including finite element methods) for simulating the behavior of molecular electronic circuit elements in a larger integrated device. Here we describe a large Department of Energy project involving six universities and one national laboratory aimed at developing integrated multiscale methods for modeling molecular electronics devices. The project is funded equally by the Office of Basic

  11. An Integrative Analysis of Foot-and-Mouth Disease Virus Carriers in Vietnam Achieved Through Targeted Surveillance and Molecular Epidemiology.

    Science.gov (United States)

    de Carvalho Ferreira, H C; Pauszek, S J; Ludi, A; Huston, C L; Pacheco, J M; Le, V T; Nguyen, P T; Bui, H H; Nguyen, T D; Nguyen, T; Nguyen, T T; Ngo, L T; Do, D H; Rodriguez, L; Arzt, J

    2017-04-01

    Foot-and-mouth disease (FMD) is a major constraint to transboundary trade in animal products, yet much of its natural ecology and epidemiology in endemic regions is still poorly understood. To address this gap, a multidisciplinary, molecular and conventional epidemiological approach was applied to an investigation of endemic FMD in Vietnam. Within the study space, it was found that 22.3% of sampled ruminants had previously been infected with FMD virus (FMDV), of which 10.8% were persistent, asymptomatic carriers (2.4% of the total population). Descriptive data collected from targeted surveillance and a farm questionnaire showed a significantly lower prevalence of FMDV infection for dairy farms. In contrast, farms of intermediate size and/or history of infection in 2010 were at increased risk of FMD exposure. At the individual animal level, buffalo had the highest exposure risk (over cattle), and there was spatial heterogeneity in exposure risk at the commune level. Conversely, carrier prevalence was higher for beef cattle, suggesting lower susceptibility of buffalo to persistent FMDV infection. To characterize virus strains currently circulating in Vietnam, partial FMDV genomic (VP1) sequences from carrier animals collected between 2012 and 2013 (N = 27) and from FMDV outbreaks between 2009 and 2013 (N = 79) were compared by phylogenetic analysis. Sequence analysis suggested that within the study period, there were two apparent novel introductions of serotype A viruses and that the dominant lineage of serotype O in Vietnam shifted from SEA/Mya-98 to ME-SA/PanAsia. FMDV strains shared close ancestors with FMDV from other South-East Asian countries indicating substantial transboundary movement of the predominant circulating strains. Close genetic relationships were observed between carrier and outbreak viruses, which may suggest that asymptomatic carriers of FMDV contribute to regional disease persistence. Multiple viral sequences obtained from carrier cattle

  12. Molecular analysis of thymoma.

    Directory of Open Access Journals (Sweden)

    Sunil Badve

    Full Text Available Histologic classification of thymomas has significant limitations with respect to both subtype definitions and consistency. In order to better understand the biology of the disease processes, we performed whole genome gene expression analysis. RNA was extracted from fresh frozen tumors from 34 patients with thymomas and followup data was available. Using the Illumina BeadStudio® platform and Human Ref-8 Beadchip, gene expression data was analyzed with Partek Genomics Suite®, and Ingenuity Pathways Analysis (IPA. Unsupervised clustering of gene expression data, representing one of the largest series in literature, resulted in identification of four molecular clusters of tumors (C1-C4, which correlated with histology (P = 0.002. However, neither histology nor clusters correlated with clinical outcomes. Correlation of gene expression data with clinical data showed that a number of genes were associated with either advanced stage at diagnosis or development of recurrence or metastases. The top pathways associated with metastases were amino acid metabolisms, biosynthesis of steroids and glycosphingolipids, cell cycle checkpoint proteins and Notch signaling. The differential expression of some of the top genes related to both metastases and stage was confirmed by RT-PCR in all cases of metastases and matched nonmetastatic cases. A number of potential candidates for therapeutics were also identified.

  13. Molecular analysis of an integrative conjugative element, ICEH, present in the chromosome of different strains of Mycoplasma hyopneumoniae

    Directory of Open Access Journals (Sweden)

    Paulo Marcos Pinto

    2007-01-01

    Full Text Available Diversification of bacterial species and pathotypes is largely caused by lateral gene transfer (LGT of diverse mobile DNA elements such as plasmids, phages, transposons and genomic islands. Thus, acquisition of new phenotypes by LGT is very important for bacterial evolution and relationship with hosts. This paper reports a 23 kb region containing fourteen CDSs with similarity to the previous described Integrative Conjugal Element of Mycoplasma fermentans (ICEF. This element, named ICEH, is present as one copy at distinct integration sites in the chromosome of 7448 and 232 pathogenic strains and is absent in the type strain J (non-pathogenic. Notable differences in the nucleotide composition of the insertion sites were detected, and could be correlated to a lack of specificity of the ICEH integrase. Although present in strains of the same organism, the ICEH elements are more divergent than the typical similarity between other chromosomal locus of Mycoplasma hyopneunomiae, suggesting an accelerated evolution of these constins or an ongoing process of degeneration, while maintaining conservation of the tra genes. An extrachromosomal form of this element had been detected in the 7448 strain, suggesting a possible involvement in its mobilization and transference of CDSs to new hosts.

  14. Exploring RNA structure by integrative molecular modelling

    DEFF Research Database (Denmark)

    Masquida, Benoît; Beckert, Bertrand; Jossinet, Fabrice

    2010-01-01

    RNA molecular modelling is adequate to rapidly tackle the structure of RNA molecules. With new structured RNAs constituting a central class of cellular regulators discovered every year, the need for swift and reliable modelling methods is more crucial than ever. The pragmatic method based...... on interactive all-atom molecular modelling relies on the observation that specific structural motifs are recurrently found in RNA sequences. Once identified by a combination of comparative sequence analysis and biochemical data, the motifs composing the secondary structure of a given RNA can be extruded...

  15. Microelectromechanical systems integrating molecular spin crossover actuators

    Energy Technology Data Exchange (ETDEWEB)

    Manrique-Juarez, Maria D. [LCC, CNRS and Université de Toulouse, UPS, INP, F-31077 Toulouse (France); LAAS, CNRS and Université de Toulouse, INSA, UPS, F-31077 Toulouse (France); Rat, Sylvain; Salmon, Lionel; Molnár, Gábor; Bousseksou, Azzedine, E-mail: liviu.nicu@laas.fr, E-mail: azzedine.bousseksou@lcc-toulouse.fr [LCC, CNRS and Université de Toulouse, UPS, INP, F-31077 Toulouse (France); Mathieu, Fabrice; Saya, Daisuke; Séguy, Isabelle; Leïchlé, Thierry; Nicu, Liviu, E-mail: liviu.nicu@laas.fr, E-mail: azzedine.bousseksou@lcc-toulouse.fr [LAAS, CNRS and Université de Toulouse, INSA, UPS, F-31077 Toulouse (France)

    2016-08-08

    Silicon MEMS cantilevers coated with a 200 nm thin layer of the molecular spin crossover complex [Fe(H{sub 2}B(pz){sub 2}){sub 2}(phen)] (H{sub 2}B(pz){sub 2} = dihydrobis(pyrazolyl)borate and phen = 1,10-phenantroline) were actuated using an external magnetic field and their resonance frequency was tracked by means of integrated piezoresistive detection. The light-induced spin-state switching of the molecules from the ground low spin to the metastable high spin state at 10 K led to a well-reproducible shift of the cantilever's resonance frequency (Δf{sub r} = −0.52 Hz). Control experiments at different temperatures using coated as well as uncoated devices along with simple calculations support the assignment of this effect to the spin transition. This latter translates into changes in mechanical behavior of the cantilever due to the strong spin-state/lattice coupling. A guideline for the optimization of device parameters is proposed so as to efficiently harness molecular scale movements for large-scale mechanical work, thus paving the road for nanoelectromechanical systems (NEMS) actuators based on molecular materials.

  16. Integrated molecular analysis of Tamoxifen-resistant invasive lobular breast cancer cells identifies MAPK and GRM/mGluR signaling as therapeutic vulnerabilities.

    Science.gov (United States)

    Stires, Hillary; Heckler, Mary M; Fu, Xiaoyong; Li, Zhao; Grasso, Catherine S; Quist, Michael J; Lewis, Joseph A; Klimach, Uwe; Zwart, Alan; Mahajan, Akanksha; Győrffy, Balázs; Cavalli, Luciane R; Riggins, Rebecca B

    2018-08-15

    Invasive lobular breast cancer (ILC) is an understudied malignancy with distinct clinical, pathological, and molecular features that distinguish it from the more common invasive ductal carcinoma (IDC). Mounting evidence suggests that estrogen receptor-alpha positive (ER+) ILC has a poor response to Tamoxifen (TAM), but the mechanistic drivers of this are undefined. In the current work, we comprehensively characterize the SUM44/LCCTam ILC cell model system through integrated analysis of gene expression, copy number, and mutation, with the goal of identifying actionable alterations relevant to clinical ILC that can be co-targeted along with ER to improve treatment outcomes. We show that TAM has several distinct effects on the transcriptome of LCCTam cells, that this resistant cell model has acquired copy number alterations and mutations that impinge on MAPK and metabotropic glutamate receptor (GRM/mGluR) signaling networks, and that pharmacological inhibition of either improves or restores the growth-inhibitory actions of endocrine therapy. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Integrated genetic analysis microsystems

    International Nuclear Information System (INIS)

    Lagally, Eric T; Mathies, Richard A

    2004-01-01

    With the completion of the Human Genome Project and the ongoing DNA sequencing of the genomes of other animals, bacteria, plants and others, a wealth of new information about the genetic composition of organisms has become available. However, as the demand for sequence information grows, so does the workload required both to generate this sequence and to use it for targeted genetic analysis. Microfabricated genetic analysis systems are well poised to assist in the collection and use of these data through increased analysis speed, lower analysis cost and higher parallelism leading to increased assay throughput. In addition, such integrated microsystems may point the way to targeted genetic experiments on single cells and in other areas that are otherwise very difficult. Concomitant with these advantages, such systems, when fully integrated, should be capable of forming portable systems for high-speed in situ analyses, enabling a new standard in disciplines such as clinical chemistry, forensics, biowarfare detection and epidemiology. This review will discuss the various technologies available for genetic analysis on the microscale, and efforts to integrate them to form fully functional robust analysis devices. (topical review)

  18. Integrated RNA-Seq and sRNA-Seq Analysis Identifies Chilling and Freezing Responsive Key Molecular Players and Pathways in Tea Plant (Camellia sinensis)

    Science.gov (United States)

    Zheng, Chao; Zhao, Lei; Wang, Yu; Shen, Jiazhi; Zhang, Yinfei; Jia, Sisi; Li, Yusheng; Ding, Zhaotang

    2015-01-01

    Tea [Camellia sinensis (L) O. Kuntze, Theaceae] is one of the most popular non-alcoholic beverages worldwide. Cold stress is one of the most severe abiotic stresses that limit tea plants’ growth, survival and geographical distribution. However, the genetic regulatory network and signaling pathways involved in cold stress responses in tea plants remain unearthed. Using RNA-Seq, DGE and sRNA-Seq technologies, we performed an integrative analysis of miRNA and mRNA expression profiling and their regulatory network of tea plants under chilling (4℃) and freezing (-5℃) stress. Differentially expressed (DE) miRNA and mRNA profiles were obtained based on fold change analysis, miRNAs and target mRNAs were found to show both coherent and incoherent relationships in the regulatory network. Furthermore, we compared several key pathways (e.g., ‘Photosynthesis’), GO terms (e.g., ‘response to karrikin’) and transcriptional factors (TFs, e.g., DREB1b/CBF1) which were identified as involved in the early chilling and/or freezing response of tea plants. Intriguingly, we found that karrikins, a new group of plant growth regulators, and β-primeverosidase (BPR), a key enzyme functionally relevant with the formation of tea aroma might play an important role in both early chilling and freezing response of tea plants. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis further confirmed the results from RNA-Seq and sRNA-Seq analysis. This is the first study to simultaneously profile the expression patterns of both miRNAs and mRNAs on a genome-wide scale to elucidate the molecular mechanisms of early responses of tea plants to cold stress. In addition to gaining a deeper insight into the cold resistant characteristics of tea plants, we provide a good case study to analyse mRNA/miRNA expression and profiling of non-model plant species using next-generation sequencing technology. PMID:25901577

  19. A new species of Tometes Valenciennes 1850 (Characiformes: Serrasalmidae from Tocantins-Araguaia River Basin based on integrative analysis of molecular and morphological data.

    Directory of Open Access Journals (Sweden)

    Marcelo C Andrade

    Full Text Available A new large serrasalmid species of Tometes is described from the Tocantins-Araguaia River Basin. Tometes siderocarajensis sp. nov. is currently found in the rapids of the Itacaiúnas River Basin, and formerly inhabited the lower Tocantins River. The new species can be distinguished from all congeners, except from T. ancylorhynchus, by the presence of lateral space between 1st and 2nd premaxillary teeth, and by the absence of lateral cusps in these two teeth. However, T. siderocarajensis sp. nov. can be differentiated from syntopic congener T. ancylorhynchus by an entirely black with mottled red body in live specimens, densely pigmented pelvic fins with a high concentration of dark chromatophores, and the presence of 39 to 41 rows of circumpeduncular scales (vs. silvery body coloration with slightly reddish overtones on middle flank during breeding period in live specimens, hyaline to slightly pale coloration on distalmost region of pelvic fins, and 30 to 36 rows of circumpeduncular scales. Additionally, molecular sequence shows that T. siderocarajensis sp. nov. is reciprocally monophyletic, and diagnosable from all congeners by having two autapomorphic molecular characters in the mitochondrial gene COI. The phylogenetic reconstruction still show that T. siderocarajensis sp. nov. is closely related to T. trilobatus. This is the first molecular study using an integrative taxonomic approach based on morphological and molecular sequence data for all described species of Tometes. These findings increase the number of formally described species of Tometes to seven. A key to the Tometes species is provided.

  20. Molecular integrals for slater type orbitals using coulomb sturmians

    DEFF Research Database (Denmark)

    Avery, James Emil; Avery, John Scales

    2014-01-01

    The use of Slater type orbitals in molecular calculations is hindered by the slowness of integral evaluation. In the present paper, we introduce a method for overcoming this problem by expanding STO's in terms of Coulomb Sturmians, for which the problem of evaluating molecular integrals rapidly has...

  1. Numerical solution of boundary-integral equations for molecular electrostatics.

    Science.gov (United States)

    Bardhan, Jaydeep P

    2009-03-07

    Numerous molecular processes, such as ion permeation through channel proteins, are governed by relatively small changes in energetics. As a result, theoretical investigations of these processes require accurate numerical methods. In the present paper, we evaluate the accuracy of two approaches to simulating boundary-integral equations for continuum models of the electrostatics of solvation. The analysis emphasizes boundary-element method simulations of the integral-equation formulation known as the apparent-surface-charge (ASC) method or polarizable-continuum model (PCM). In many numerical implementations of the ASC/PCM model, one forces the integral equation to be satisfied exactly at a set of discrete points on the boundary. We demonstrate in this paper that this approach to discretization, known as point collocation, is significantly less accurate than an alternative approach known as qualocation. Furthermore, the qualocation method offers this improvement in accuracy without increasing simulation time. Numerical examples demonstrate that electrostatic part of the solvation free energy, when calculated using the collocation and qualocation methods, can differ significantly; for a polypeptide, the answers can differ by as much as 10 kcal/mol (approximately 4% of the total electrostatic contribution to solvation). The applicability of the qualocation discretization to other integral-equation formulations is also discussed, and two equivalences between integral-equation methods are derived.

  2. Conformation analysis of trehalose. Molecular dynamics simulation and molecular mechanics

    International Nuclear Information System (INIS)

    Donnamaira, M.C.; Howard, E.I.; Grigera, J.R.

    1992-09-01

    Conformational analysis of the disaccharide trehalose is done by molecular dynamics and molecular mechanics. In spite of the different force fields used in each case, comparison between the molecular dynamics trajectories of the torsional angles of glycosidic linkage and energy conformational map shows a good agreement between both methods. By molecular dynamics it is observed a moderate mobility of the glycosidic linkage. The demands of computer time is comparable in both cases. (author). 6 refs, 4 figs

  3. Integrated molecular landscape of Parkinson's disease

    NARCIS (Netherlands)

    Klemann, C.J.H.M.; Martens, G.J.; Sharma, M.; Martens, M.B.; Isacson, O.; Gasser, T.; Visser, J.E.; Poelmans, G.J.V.

    2017-01-01

    Parkinson's disease is caused by a complex interplay of genetic and environmental factors. Although a number of independent molecular pathways and processes have been associated with familial Parkinson's disease, a common mechanism underlying especially sporadic Parkinson's disease is still largely

  4. Exploring Nuclear Photorelaxation of Pyranine in Aqueous Solution: an Integrated Ab-Initio Molecular Dynamics and Time Resolved Vibrational Analysis Approach.

    Science.gov (United States)

    Chiariello, Maria Gabriella; Rega, Nadia

    2018-03-22

    Advances in time-resolved vibrational spectroscopy techniques provided a new stimulus for understanding the transient molecular dynamics triggered by the electronic excitation. The detailed interpretation of such time-dependent spectroscopic signals is a challenging task from both experimental and theoretical points of view. We simulated and analyzed the transient photorelaxation of the pyranine photoacid in aqueous solution, with special focus on structural parameters and low frequency skeleton modes that are possibly preparatory for the photoreaction occurring at later time, as suggested by experimental spectroscopic studies. To this aim, we adopted an accurate computational protocol that combines excited state ab initio molecular dynamics within an hybrid quantum mechanical/molecular mechanics framework and a time-resolved vibrational analysis based on the Wavelet transform. According to our results, the main nuclear relaxation on the excited potential energy surface is completed in about 500 fs, in agreement with experimental data. The rearrangement of C-C bonds occurs according to a complex vibrational dynamics, showing oscillatory patterns that are out of phase and modulated by modes below 200 cm -1 . We also analyzed in both the ground and the excited state the evolution of some structural parameters involved in excited state proton transfer reaction, namely, those involving the pyranine and the water molecule hydrogen bonded to the phenolic O-H group. Both the hydrogen bond distance and the intermolecular orientation are optimized in the excited state, resulting in a tighter proton donor-acceptor couple. Indeed, we found evidence that collective low frequency skeleton modes, such as the out of plane wagging at 108 cm -1 and the deformation at 280 cm -1 , are photoactivated by the ultrafast part of the relaxation and modulate the pyranine-water molecule rearrangement, favoring the preparatory step for the photoreactivity.

  5. Fast Electron Repulsion Integrals for Molecular Coulomb Sturmians

    DEFF Research Database (Denmark)

    Avery, James Emil

    2013-01-01

    A new method is presented for calculating interelectron repulsion integrals for molecular Coulomb Sturmian basis sets. This makes use of an expansion of densities in terms of 2k-Sturmians, and the interelectron repulsion integrals are then calculated by a method based on the theory of hyperspheri......A new method is presented for calculating interelectron repulsion integrals for molecular Coulomb Sturmian basis sets. This makes use of an expansion of densities in terms of 2k-Sturmians, and the interelectron repulsion integrals are then calculated by a method based on the theory...... of hyperspherical harmonics. A rudimentary software library has been implemented and preliminary benchmarks indicate very good performance: On average 40 ns, or approximately 80 clock cycles, per electron repulsion integral. This makes molecular Coulomb Sturmians competitive with Gaussian type orbitals in terms...

  6. Integrated physiological, biochemical and molecular analysis identifies important traits and mechanisms associated with differential response of rice genotypes to elevated temperature

    Directory of Open Access Journals (Sweden)

    Boghireddy eSailaja

    2015-11-01

    Full Text Available In changing climate, heat stress caused by high temperature poses a serious threat to rice cultivation. A multiple organizational analysis at physiological, biochemical and molecular level is required to fully understand the impact of elevated temperature in rice. This study was aimed at deciphering the elevated temperature response in eleven popular and mega rice cultivars widely grown in India. Physiological and biochemical traits specifically membrane thermostability (MTS, antioxidants, and photosynthesis were studied at vegetative and reproductive phases which were used to establish a correlation with grain yield under stress. Several useful traits in different genotypes were identified which will be important resource to develop high temperature tolerant rice cultivars. Interestingly, Nagina22 emerged as best performer in terms of yield as well as expression of physiological and biochemical traits at elevated temperature. It showed lesser relative injury, lesser reduction in chlorophyll content, increased super oxide dismutase, catalase and peroxidase activity, lesser reduction in net photosynthetic rate (PN, high transpiration rate (E and other photosynthetic/ fluorescence parameters contributing to least reduction in spikelet fertility and grain yield at elevated temperature. Further, expression of 14 genes including heat shock transcription factors and heat shock proteins was analyzed in Nagina22 (tolerant and Vandana (susceptible at flowering phase, strengthening the fact that N22 performs better at molecular level also during elevated temperature. This study shows that elevated temperature response is complex and involves multiple biological processes which are needed to be characterized to address the challenges of future climate extreme conditions.

  7. Numerical computation of molecular integrals via optimized (vectorized) FORTRAN code

    International Nuclear Information System (INIS)

    Scott, T.C.; Grant, I.P.; Saunders, V.R.

    1997-01-01

    The calculation of molecular properties based on quantum mechanics is an area of fundamental research whose horizons have always been determined by the power of state-of-the-art computers. A computational bottleneck is the numerical calculation of the required molecular integrals to sufficient precision. Herein, we present a method for the rapid numerical evaluation of molecular integrals using optimized FORTRAN code generated by Maple. The method is based on the exploitation of common intermediates and the optimization can be adjusted to both serial and vectorized computations. (orig.)

  8. An Integrated Molecular Database on Indian Insects.

    Science.gov (United States)

    Pratheepa, Maria; Venkatesan, Thiruvengadam; Gracy, Gandhi; Jalali, Sushil Kumar; Rangheswaran, Rajagopal; Antony, Jomin Cruz; Rai, Anil

    2018-01-01

    MOlecular Database on Indian Insects (MODII) is an online database linking several databases like Insect Pest Info, Insect Barcode Information System (IBIn), Insect Whole Genome sequence, Other Genomic Resources of National Bureau of Agricultural Insect Resources (NBAIR), Whole Genome sequencing of Honey bee viruses, Insecticide resistance gene database and Genomic tools. This database was developed with a holistic approach for collecting information about phenomic and genomic information of agriculturally important insects. This insect resource database is available online for free at http://cib.res.in. http://cib.res.in/.

  9. Drug Repositioning by Kernel-Based Integration of Molecular Structure, Molecular Activity, and Phenotype Data

    Science.gov (United States)

    Wang, Yongcui; Chen, Shilong; Deng, Naiyang; Wang, Yong

    2013-01-01

    Computational inference of novel therapeutic values for existing drugs, i.e., drug repositioning, offers the great prospect for faster and low-risk drug development. Previous researches have indicated that chemical structures, target proteins, and side-effects could provide rich information in drug similarity assessment and further disease similarity. However, each single data source is important in its own way and data integration holds the great promise to reposition drug more accurately. Here, we propose a new method for drug repositioning, PreDR (Predict Drug Repositioning), to integrate molecular structure, molecular activity, and phenotype data. Specifically, we characterize drug by profiling in chemical structure, target protein, and side-effects space, and define a kernel function to correlate drugs with diseases. Then we train a support vector machine (SVM) to computationally predict novel drug-disease interactions. PreDR is validated on a well-established drug-disease network with 1,933 interactions among 593 drugs and 313 diseases. By cross-validation, we find that chemical structure, drug target, and side-effects information are all predictive for drug-disease relationships. More experimentally observed drug-disease interactions can be revealed by integrating these three data sources. Comparison with existing methods demonstrates that PreDR is competitive both in accuracy and coverage. Follow-up database search and pathway analysis indicate that our new predictions are worthy of further experimental validation. Particularly several novel predictions are supported by clinical trials databases and this shows the significant prospects of PreDR in future drug treatment. In conclusion, our new method, PreDR, can serve as a useful tool in drug discovery to efficiently identify novel drug-disease interactions. In addition, our heterogeneous data integration framework can be applied to other problems. PMID:24244318

  10. An Integrated Biochemistry Laboratory, Including Molecular Modeling

    Science.gov (United States)

    Hall, Adele J. Wolfson Mona L.; Branham, Thomas R.

    1996-11-01

    ) experience with methods of protein purification; (iii) incorporation of appropriate controls into experiments; (iv) use of basic statistics in data analysis; (v) writing papers and grant proposals in accepted scientific style; (vi) peer review; (vii) oral presentation of results and proposals; and (viii) introduction to molecular modeling. Figure 1 illustrates the modular nature of the lab curriculum. Elements from each of the exercises can be separated and treated as stand-alone exercises, or combined into short or long projects. We have been able to offer the opportunity to use sophisticated molecular modeling in the final module through funding from an NSF-ILI grant. However, many of the benefits of the research proposal can be achieved with other computer programs, or even by literature survey alone. Figure 1.Design of project-based biochemistry laboratory. Modules (projects, or portions of projects) are indicated as boxes. Each of these can be treated independently, or used as part of a larger project. Solid lines indicate some suggested paths from one module to the next. The skills and knowledge required for protein purification and design are developed in three units: (i) an introduction to critical assays needed to monitor degree of purification, including an evaluation of assay parameters; (ii) partial purification by ion-exchange techniques; and (iii) preparation of a grant proposal on protein design by mutagenesis. Brief descriptions of each of these units follow, with experimental details of each project at the end of this paper. Assays for Lysozyme Activity and Protein Concentration (4 weeks) The assays mastered during the first unit are a necessary tool for determining the purity of the enzyme during the second unit on purification by ion exchange. These assays allow an introduction to the concept of specific activity (units of enzyme activity per milligram of total protein) as a measure of purity. In this first sequence, students learn a turbidimetric assay

  11. Integrated metagenomics and molecular ecological network analysis of bacterial community composition during the phytoremediation of cadmium-contaminated soils by bioenergy crops.

    Science.gov (United States)

    Chen, Zhaojin; Zheng, Yuan; Ding, Chuanyu; Ren, Xuemin; Yuan, Jian; Sun, Feng; Li, Yuying

    2017-11-01

    Two energy crops (maize and soybean) were used in the remediation of cadmium-contaminated soils. These crops were used because they are fast growing, have a large biomass and are good sources for bioenergy production. The total accumulation of cadmium in maize and soybean plants was 393.01 and 263.24μg pot -1 , respectively. The rhizosphere bacterial community composition was studied by MiSeq sequencing. Phylogenetic analysis was performed using 16S rRNA gene sequences. The rhizosphere bacteria were divided into 33 major phylogenetic groups according to phyla. The dominant phylogenetic groups included Proteobacteria, Acidobacteria, Actinobacteria, Gemmatimonadetes, and Bacteroidetes. Based on principal component analysis (PCA) and unweighted pair group with arithmetic mean (UPGMA) analysis, we found that the bacterial community was influenced by cadmium addition and bioenergy cropping. Three molecular ecological networks were constructed for the unplanted, soybean- and maize-planted bacterial communities grown in 50mgkg -1 cadmium-contaminated soils. The results indicated that bioenergy cropping increased the complexity of the bacterial community network as evidenced by a higher total number of nodes, the average geodesic distance (GD), the modularity and a shorter geodesic distance. Proteobacteria and Acidobacteria were the keystone bacteria connecting different co-expressed operational taxonomic units (OTUs). The results showed that bioenergy cropping altered the topological roles of individual OTUs and keystone populations. This is the first study to reveal the effects of bioenergy cropping on microbial interactions in the phytoremediation of cadmium-contaminated soils by network reconstruction. This method can greatly enhance our understanding of the mechanisms of plant-microbe-metal interactions in metal-polluted ecosystems. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Hybrid CMOS/Molecular Integrated Circuits

    Science.gov (United States)

    Stan, M. R.; Rose, G. S.; Ziegler, M. M.

    CMOS silicon technologies are likely to run out of steam in the next 10-15 years despite revolutionary advances in the past few decades. Molecular and other nanoscale technologies show significant promise but it is unlikely that they will completely replace CMOS, at least in the near term. This chapter explores opportunities for using CMOS and nanotechnology to enhance and complement each other in hybrid circuits. As an example of such a hybrid CMOS/nano system, a nanoscale programmable logic array (PLA) based on majority logic is described along with its supplemental CMOS circuitry. It is believed that such systems will be able to sustain the historical advances in the semiconductor industry while addressing manufacturability, yield, power, cost, and performance challenges.

  13. Direct characterization of the energy level alignments and molecular components in an organic hetero-junction by integrated photoemission spectroscopy and reflection electron energy loss spectroscopy analysis.

    Science.gov (United States)

    Yun, Dong-Jin; Shin, Weon-Ho; Bulliard, Xavier; Park, Jong Hwan; Kim, Seyun; Chung, Jae Gwan; Kim, Yongsu; Heo, Sung; Kim, Seong Heon

    2016-08-26

    A novel, direct method for the characterization of the energy level alignments at bulk-heterojunction (BHJ)/electrode interfaces on the basis of electronic spectroscopy measurements is proposed. The home-made in situ photoemission system is used to perform x-ray/ultraviolet photoemission spectroscopy (XPS/UPS), reflection electron energy loss spectroscopy (REELS) and inverse photoemission spectroscopy of organic-semiconductors (OSCs) deposited onto a Au substrate. Through this analysis system, we are able to obtain the electronic structures of a boron subphthalocyanine chloride:fullerene (SubPC:C60) BHJ and those of the separate OSC/electrode structures (SubPC/Au and C60/Au). Morphology and chemical composition analyses confirm that the original SubPC and C60 electronic structures remain unchanged in the electrodes prepared. Using this technique, we ascertain that the position and area of the nearest peak to the Fermi energy (EF = 0 eV) in the UPS (REELS) spectra of SubPC:C60 BHJ provide information on the highest occupied molecular orbital level (optical band gap) and combination ratio of the materials, respectively. Thus, extracting the adjusted spectrum from the corresponding SubPC:C60 BHJ UPS (REELS) spectrum reveals its electronic structure, equivalent to that of the C60 materials. This novel analytical approach allows complete energy-level determination for each combination ratio by separating its electronic structure information from the BHJ spectrum.

  14. DNA-Enabled Integrated Molecular Systems for Computation and Sensing

    Science.gov (United States)

    2014-05-21

    Computational devices can be chemically conjugated to different strands of DNA that are then self-assembled according to strict Watson − Crick binding rules... DNA -Enabled Integrated Molecular Systems for Computation and Sensing Craig LaBoda,† Heather Duschl,† and Chris L. Dwyer*,†,‡ †Department of...guided folding of DNA , inspired by nature, allows designs to manipulate molecular-scale processes unlike any other material system. Thus, DNA can be

  15. Molecular annotation of integrative feeding neural circuits.

    Science.gov (United States)

    Pérez, Cristian A; Stanley, Sarah A; Wysocki, Robert W; Havranova, Jana; Ahrens-Nicklas, Rebecca; Onyimba, Frances; Friedman, Jeffrey M

    2011-02-02

    The identity of higher-order neurons and circuits playing an associative role to control feeding is unknown. We injected pseudorabies virus, a retrograde tracer, into masseter muscle, salivary gland, and tongue of BAC-transgenic mice expressing GFP in specific neural populations and identified several CNS regions that project multisynaptically to the periphery. MCH and orexin neurons were identified in the lateral hypothalamus, and Nurr1 and Cnr1 in the amygdala and insular/rhinal cortices. Cholera toxin β tracing showed that insular Nurr1(+) and Cnr1(+) neurons project to the amygdala or lateral hypothalamus, respectively. Finally, we show that cortical Cnr1(+) neurons show increased Cnr1 mRNA and c-Fos expression after fasting, consistent with a possible role for Cnr1(+) neurons in feeding. Overall, these studies define a general approach for identifying specific molecular markers for neurons in complex neural circuits. These markers now provide a means for functional studies of specific neuronal populations in feeding or other complex behaviors. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. RESEARCH NOTE Molecular genetic analysis of consanguineous ...

    Indian Academy of Sciences (India)

    Navya

    Molecular genetic analysis of consanguineous families with primary microcephaly ... Translational Research Institute, Academic Health System, Hamad Medical ..... bridging the gap between homozygosity mapping and deep sequencing.

  17. Accurate Kirkwood-Buff Integrals from Molecular Dynamics Simulations

    DEFF Research Database (Denmark)

    Wedberg, Nils Hejle Rasmus Ingemar; O'Connell, John P.; Peters, Günther H.J.

    2010-01-01

    A method is proposed for obtaining thermodynamic properties via Kirkwood–Buff (KB) integrals from molecular simulations. In order to ensure that the KB integration converges, the pair distribution function is extrapolated to large distances using the extension method of Verlet, which enforces...... of state fitted to simulation results. Good agreement is achieved for both fluids at densities larger than 1.5 times the critical density....

  18. Identification of molecular candidates and interaction networks via integrative toxicogenomic analysis in a human cell line following low-dose exposure to the carcinogenic metals cadmium and nickel.

    Science.gov (United States)

    Kwon, Jee Young; Weon, Jong-Il; Koedrith, Preeyaporn; Park, Kang-Sik; Kim, Im Soon; Seo, Young Rok

    2013-09-01

    Cadmium and nickel have been classified as carcinogenic to humans by the World Health Organization's International Agency for Research on Cancer. Given their prevalence in the environment, the fact that cadmium and nickel may cause diseases including cancer even at low doses is a cause for concern. However, the exact mechanisms underlying the toxicological effects induced by low-dose exposure to cadmium and nickel remain to be elucidated. Furthermore, it has recently been recognized that integrative analysis of DNA, mRNA and proteins is required to discover biomarkers and signaling networks relevant to human toxicant exposure. In the present study, we examined the deleterious effects of chronic low-dose exposure of either cadmium or nickel on global profiling of DNA copy number variation, mRNA and proteins. Array comparative genomic hybridization, gene expression microarray and functional proteomics were conducted, and a bioinformatics tool, which predicted signaling pathways, was applied to integrate data for each heavy metal separately and together. We found distinctive signaling networks associated with subchronic low-dose exposure to cadmium and nickel, and identified pathways common to both. ACTB, HSP90AA1, HSPA5 and HSPA8, which are key mediators of pathways related to apoptosis, proliferation and neoplastic processes, were key mediators of the same pathways in low-dose nickel and cadmium exposure in particular. CASP-associated signaling pathways involving CASP3, CASP7 and CASP9 were observed in cadmium-exposed cells. We found that HSP90AA1, one of the main modulators, interacted with HIF1A, AR and BCL2 in nickel-exposed cells. Interestingly, we found that HSP90AA1 was involved in the BCL2-associated apoptotic pathway in the nickel-only data, whereas this gene interacted with several genes functioning in CASP-associated apoptotic signaling in the cadmium-only data. Additionally, JUN and FASN were main modulators in nickel-responsive signaling pathways. Our

  19. Integrating molecular diagnostics into histopathology training: the Belfast model.

    Science.gov (United States)

    Flynn, C; James, J; Maxwell, P; McQuaid, S; Ervine, A; Catherwood, M; Loughrey, M B; McGibben, D; Somerville, J; McManus, D T; Gray, M; Herron, B; Salto-Tellez, M

    2014-07-01

    Molecular medicine is transforming modern clinical practice, from diagnostics to therapeutics. Discoveries in research are being incorporated into the clinical setting with increasing rapidity. This transformation is also deeply changing the way we practise pathology. The great advances in cell and molecular biology which have accelerated our understanding of the pathogenesis of solid tumours have been embraced with variable degrees of enthusiasm by diverse medical professional specialties. While histopathologists have not been prompt to adopt molecular diagnostics to date, the need to incorporate molecular pathology into the training of future histopathologists is imperative. Our goal is to create, within an existing 5-year histopathology training curriculum, the structure for formal substantial teaching of molecular diagnostics. This specialist training has two main goals: (1) to equip future practising histopathologists with basic knowledge of molecular diagnostics and (2) to create the option for those interested in a subspecialty experience in tissue molecular diagnostics to pursue this training. It is our belief that this training will help to maintain in future the role of the pathologist at the centre of patient care as the integrator of clinical, morphological and molecular information. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  20. Integrative pathway knowledge bases as a tool for systems molecular medicine.

    Science.gov (United States)

    Liang, Mingyu

    2007-08-20

    There exists a sense of urgency to begin to generate a cohesive assembly of biomedical knowledge as the pace of knowledge accumulation accelerates. The urgency is in part driven by the emergence of systems molecular medicine that emphasizes the combination of systems analysis and molecular dissection in the future of medical practice and research. A potentially powerful approach is to build integrative pathway knowledge bases that link organ systems function with molecules.

  1. Integration of next-generation sequencing in clinical diagnostic molecular pathology laboratories for analysis of solid tumours; an expert opinion on behalf of IQN Path ASBL

    NARCIS (Netherlands)

    Deans, Zandra C.; Costa, Jose Luis; Cree, Ian; Dequeker, Els; Edsjo, Anders; Henderson, Shirley; Hummel, Michael; Ligtenberg, Marjolijn J. L.; Loddo, Marco; Machado, Jose Carlos; Marchetti, Antonio; Marquis, Katherine; Mason, Joanne; Normanno, Nicola; Rouleau, Etienne; Schuuring, Ed; Snelson, Keeda-Marie; Thunnissen, Erik; Tops, Bastiaan; Williams, Gareth; van Krieken, Han; Hall, Jacqueline A.

    The clinical demand for mutation detection within multiple genes from a single tumour sample requires molecular diagnostic laboratories to develop rapid, high-throughput, highly sensitive, accurate and parallel testing within tight budget constraints. To meet this demand, many laboratories employ

  2. Integration of next-generation sequencing in clinical diagnostic molecular pathology laboratories for analysis of solid tumours; an expert opinion on behalf of IQN Path ASBL

    NARCIS (Netherlands)

    Deans, Z.C.; Costa, J.L.; Cree, I.; Dequeker, E.; Edsjo, A.; Henderson, S.; Hummel, M.; Ligtenberg, M.J.L.; Loddo, M.; Machado, J.C.; Marchetti, A.; Marquis, K.; Mason, J.; Normanno, N.; Rouleau, E.; Schuuring, E.; Snelson, K.M.; Thunnissen, E.; Tops, B.B.; Williams, G.; Krieken, H. van; Hall, J.A.

    2017-01-01

    The clinical demand for mutation detection within multiple genes from a single tumour sample requires molecular diagnostic laboratories to develop rapid, high-throughput, highly sensitive, accurate and parallel testing within tight budget constraints. To meet this demand, many laboratories employ

  3. HBV DNA Integration: Molecular Mechanisms and Clinical Implications

    Science.gov (United States)

    Tu, Thomas; Budzinska, Magdalena A.; Shackel, Nicholas A.; Urban, Stephan

    2017-01-01

    Chronic infection with the Hepatitis B Virus (HBV) is a major cause of liver-related morbidity and mortality. One peculiar observation in cells infected with HBV (or with closely‑related animal hepadnaviruses) is the presence of viral DNA integration in the host cell genome, despite this form being a replicative dead-end for the virus. The frequent finding of somatic integration of viral DNA suggests an evolutionary benefit for the virus; however, the mechanism of integration, its functions, and the clinical implications remain unknown. Here we review the current body of knowledge of HBV DNA integration, with particular focus on the molecular mechanisms and its clinical implications (including the possible consequences of replication-independent antigen expression and its possible role in hepatocellular carcinoma). HBV DNA integration is likely to influence HBV replication, persistence, and pathogenesis, and so deserves greater attention in future studies. PMID:28394272

  4. Integrated transcriptomic and proteomic analysis of the molecular cargo of extracellular vesicles derived from porcine adipose tissue-derived mesenchymal stem cells

    OpenAIRE

    Eirin, Alfonso; Zhu, Xiang-Yang; Puranik, Amrutesh S.; Woollard, John R.; Tang, Hui; Dasari, Surendra; Lerman, Amir; van Wijnen, Andre J.; Lerman, Lilach O.

    2017-01-01

    Background Mesenchymal stromal/stem cell (MSC) transplantation is a promising therapy for tissue regeneration. Extracellular vesicles (EVs) released by MSCs act as their paracrine effectors by delivering proteins and genetic material to recipient cells. To assess how their cargo mediates biological processes that drive their therapeutic effects, we integrated miRNA, mRNA, and protein expression data of EVs from porcine adipose tissue-derived MSCs. Methods Simultaneous expression profiles of m...

  5. Integrative cluster analysis in bioinformatics

    CERN Document Server

    Abu-Jamous, Basel; Nandi, Asoke K

    2015-01-01

    Clustering techniques are increasingly being put to use in the analysis of high-throughput biological datasets. Novel computational techniques to analyse high throughput data in the form of sequences, gene and protein expressions, pathways, and images are becoming vital for understanding diseases and future drug discovery. This book details the complete pathway of cluster analysis, from the basics of molecular biology to the generation of biological knowledge. The book also presents the latest clustering methods and clustering validation, thereby offering the reader a comprehensive review o

  6. Total Correlation Function Integrals and Isothermal Compressibilities from Molecular Simulations

    DEFF Research Database (Denmark)

    Wedberg, Rasmus; Peters, Günther H.j.; Abildskov, Jens

    2008-01-01

    Generation of thermodynamic data, here compressed liquid density and isothermal compressibility data, using molecular dynamics simulations is investigated. Five normal alkane systems are simulated at three different state points. We compare two main approaches to isothermal compressibilities: (1...... in approximately the same amount of time. This suggests that computation of total correlation function integrals is a route to isothermal compressibility, as accurate and fast as well-established benchmark techniques. A crucial step is the integration of the radial distribution function. To obtain sensible results...

  7. The Center for Integrated Molecular Brain Imaging (Cimbi) database

    DEFF Research Database (Denmark)

    Knudsen, Gitte M.; Jensen, Peter S.; Erritzoe, David

    2016-01-01

    We here describe a multimodality neuroimaging containing data from healthy volunteers and patients, acquired within the Lundbeck Foundation Center for Integrated Molecular Brain Imaging (Cimbi) in Copenhagen, Denmark. The data is of particular relevance for neurobiological research questions rela...... currently contains blood and in some instances saliva samples from about 500 healthy volunteers and 300 patients with e.g., major depression, dementia, substance abuse, obesity, and impulsive aggression. Data continue to be added to the Cimbi database and biobank....

  8. Wavelet Analysis for Molecular Dynamics

    Science.gov (United States)

    2015-06-01

    Our method takes as input the topology and sparsity of the bonding structure of a molecular system, and returns a hierarchical set of system-specific...problems, such as modeling crack initiation and propagation, or interfacial phenomena. In the present work, we introduce a wavelet-based approach to extend...Several functional forms are common for angle poten- tials complicating not only implementation but also choice of approximation. In all cases, the

  9. Integrated piping structural analysis system

    International Nuclear Information System (INIS)

    Motoi, Toshio; Yamadera, Masao; Horino, Satoshi; Idehata, Takamasa

    1979-01-01

    Structural analysis of the piping system for nuclear power plants has become larger in scale and in quantity. In addition, higher quality analysis is regarded as of major importance nowadays from the point of view of nuclear plant safety. In order to fulfill to the above requirements, an integrated piping structural analysis system (ISAP-II) has been developed. Basic philosophy of this system is as follows: 1. To apply the date base system. All information is concentrated. 2. To minimize the manual process in analysis, evaluation and documentation. Especially to apply the graphic system as much as possible. On the basis of the above philosophy four subsystems were made. 1. Data control subsystem. 2. Analysis subsystem. 3. Plotting subsystem. 4. Report subsystem. Function of the data control subsystem is to control all information of the data base. Piping structural analysis can be performed by using the analysis subsystem. Isometric piping drawing and mode shape, etc. can be plotted by using the plotting subsystem. Total analysis report can be made without the manual process through the reporting subsystem. (author)

  10. PathSys: integrating molecular interaction graphs for systems biology

    Directory of Open Access Journals (Sweden)

    Raval Alpan

    2006-02-01

    Full Text Available Abstract Background The goal of information integration in systems biology is to combine information from a number of databases and data sets, which are obtained from both high and low throughput experiments, under one data management scheme such that the cumulative information provides greater biological insight than is possible with individual information sources considered separately. Results Here we present PathSys, a graph-based system for creating a combined database of networks of interaction for generating integrated view of biological mechanisms. We used PathSys to integrate over 14 curated and publicly contributed data sources for the budding yeast (S. cerevisiae and Gene Ontology. A number of exploratory questions were formulated as a combination of relational and graph-based queries to the integrated database. Thus, PathSys is a general-purpose, scalable, graph-data warehouse of biological information, complete with a graph manipulation and a query language, a storage mechanism and a generic data-importing mechanism through schema-mapping. Conclusion Results from several test studies demonstrate the effectiveness of the approach in retrieving biologically interesting relations between genes and proteins, the networks connecting them, and of the utility of PathSys as a scalable graph-based warehouse for interaction-network integration and a hypothesis generator system. The PathSys's client software, named BiologicalNetworks, developed for navigation and analyses of molecular networks, is available as a Java Web Start application at http://brak.sdsc.edu/pub/BiologicalNetworks.

  11. Interactive analysis of systems biology molecular expression data

    Directory of Open Access Journals (Sweden)

    Prabhakar Sunil

    2008-02-01

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

  12. Integrated analysis of hematopoietic differentiation outcomes and molecular characterization reveals unbiased differentiation capacity and minor transcriptional memory in HPC/HSC-iPSCs.

    Science.gov (United States)

    Gao, Shuai; Hou, Xinfeng; Jiang, Yonghua; Xu, Zijian; Cai, Tao; Chen, Jiajie; Chang, Gang

    2017-01-23

    Transcription factor-mediated reprogramming can reset the epigenetics of somatic cells into a pluripotency compatible state. Recent studies show that induced pluripotent stem cells (iPSCs) always inherit starting cell-specific characteristics, called epigenetic memory, which may be advantageous, as directed differentiation into specific cell types is still challenging; however, it also may be unpredictable when uncontrollable differentiation occurs. In consideration of biosafety in disease modeling and personalized medicine, the availability of high-quality iPSCs which lack a biased differentiation capacity and somatic memory could be indispensable. Herein, we evaluate the hematopoietic differentiation capacity and somatic memory state of hematopoietic progenitor and stem cell (HPC/HSC)-derived-iPSCs (HPC/HSC-iPSCs) using a previously established sequential reprogramming system. We found that HPC/HSCs are amenable to being reprogrammed into iPSCs with unbiased differentiation capacity to hematopoietic progenitors and mature hematopoietic cells. Genome-wide analyses revealed that no global epigenetic memory was detectable in HPC/HSC-iPSCs, but only a minor transcriptional memory of HPC/HSCs existed in a specific tetraploid complementation (4 N)-incompetent HPC/HSC-iPSC line. However, the observed minor transcriptional memory had no influence on the hematopoietic differentiation capacity, indicating the reprogramming of the HPC/HSCs was nearly complete. Further analysis revealed the correlation of minor transcriptional memory with the aberrant distribution of H3K27me3. This work provides a comprehensive framework for obtaining high-quality iPSCs from HPC/HSCs with unbiased hematopoietic differentiation capacity and minor transcriptional memory.

  13. Analytic solution of integral equations for molecular fluids

    International Nuclear Information System (INIS)

    Cummings, P.T.

    1984-01-01

    We review some recent progress in the analytic solution of integral equations for molecular fluids. The site-site Ornstein-Zernike (SSOZ) equation with approximate closures appropriate to homonuclear diatomic fluids both with and without attractive dispersion-like interactions has recently been solved in closed form analytically. In this paper, the close relationship between the SSOZ equation for homonuclear dumbells and the usual Ornstein-Zernike (OZ) equation for atomic fluids is carefully elucidated. This relationship is a key motivation for the analytic solutions of the SSOZ equation that have been obtained to date. (author)

  14. IVSPlat 1.0: an integrated virtual screening platform with a molecular graphical interface.

    Science.gov (United States)

    Sun, Yin Xue; Huang, Yan Xin; Li, Feng Li; Wang, Hong Yan; Fan, Cong; Bao, Yong Li; Sun, Lu Guo; Ma, Zhi Qiang; Kong, Jun; Li, Yu Xin

    2012-01-05

    The virtual screening (VS) of lead compounds using molecular docking and pharmacophore detection is now an important tool in drug discovery. VS tasks typically require a combination of several software tools and a molecular graphics system. Thus, the integration of all the requisite tools in a single operating environment could reduce the complexity of running VS experiments. However, only a few freely available integrated software platforms have been developed. A free open-source platform, IVSPlat 1.0, was developed in this study for the management and automation of VS tasks. We integrated several VS-related programs into a molecular graphics system to provide a comprehensive platform for the solution of VS tasks based on molecular docking, pharmacophore detection, and a combination of both methods. This tool can be used to visualize intermediate and final results of the VS execution, while also providing a clustering tool for the analysis of VS results. A case study was conducted to demonstrate the applicability of this platform. IVSPlat 1.0 provides a plug-in-based solution for the management, automation, and visualization of VS tasks. IVSPlat 1.0 is an open framework that allows the integration of extra software to extend its functionality and modified versions can be freely distributed. The open source code and documentation are available at http://kyc.nenu.edu.cn/IVSPlat/.

  15. A systems biology-based approach to uncovering the molecular mechanisms underlying the effects of dragon's blood tablet in colitis, involving the integration of chemical analysis, ADME prediction, and network pharmacology.

    Directory of Open Access Journals (Sweden)

    Haiyu Xu

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

  16. Molecular Assemblies, Genes and Genomics Integrated Efficiently (MAGGIE)

    Energy Technology Data Exchange (ETDEWEB)

    Baliga, Nitin S

    2011-05-26

    Final report on MAGGIE. We set ambitious goals to model the functions of individual organisms and their community from molecular to systems scale. These scientific goals are driving the development of sophisticated algorithms to analyze large amounts of experimental measurements made using high throughput technologies to explain and predict how the environment influences biological function at multiple scales and how the microbial systems in turn modify the environment. By experimentally evaluating predictions made using these models we will test the degree to which our quantitative multiscale understanding wilt help to rationally steer individual microbes and their communities towards specific tasks. Towards this end we have made substantial progress towards understanding evolution of gene families, transcriptional structures, detailed structures of keystone molecular assemblies (proteins and complexes), protein interactions, biological networks, microbial interactions, and community structure. Using comparative analysis we have tracked the evolutionary history of gene functions to understand how novel functions evolve. One level up, we have used proteomics data, high-resolution genome tiling microarrays, and 5' RNA sequencing to revise genome annotations, discover new genes including ncRNAs, and map dynamically changing operon structures of five model organisms: For Desulfovibrio vulgaris Hildenborough, Pyrococcus furiosis, Sulfolobus solfataricus, Methanococcus maripaludis and Haiobacterium salinarum NROL We have developed machine learning algorithms to accurately identify protein interactions at a near-zero false positive rate from noisy data generated using tagfess complex purification, TAP purification, and analysis of membrane complexes. Combining other genome-scale datasets produced by ENIGMA (in particular, microarray data) and available from literature we have been able to achieve a true positive rate as high as 65% at almost zero false positives

  17. Integrated sequence analysis. Final report

    International Nuclear Information System (INIS)

    Andersson, K.; Pyy, P.

    1998-02-01

    The NKS/RAK subprojet 3 'integrated sequence analysis' (ISA) was formulated with the overall objective to develop and to test integrated methodologies in order to evaluate event sequences with significant human action contribution. The term 'methodology' denotes not only technical tools but also methods for integration of different scientific disciplines. In this report, we first discuss the background of ISA and the surveys made to map methods in different application fields, such as man machine system simulation software, human reliability analysis (HRA) and expert judgement. Specific event sequences were, after the surveys, selected for application and testing of a number of ISA methods. The event sequences discussed in the report were cold overpressure of BWR, shutdown LOCA of BWR, steam generator tube rupture of a PWR and BWR disturbed signal view in the control room after an external event. Different teams analysed these sequences by using different ISA and HRA methods. Two kinds of results were obtained from the ISA project: sequence specific and more general findings. The sequence specific results are discussed together with each sequence description. The general lessons are discussed under a separate chapter by using comparisons of different case studies. These lessons include areas ranging from plant safety management (design, procedures, instrumentation, operations, maintenance and safety practices) to methodological findings (ISA methodology, PSA,HRA, physical analyses, behavioural analyses and uncertainty assessment). Finally follows a discussion about the project and conclusions are presented. An interdisciplinary study of complex phenomena is a natural way to produce valuable and innovative results. This project came up with structured ways to perform ISA and managed to apply the in practice. The project also highlighted some areas where more work is needed. In the HRA work, development is required for the use of simulators and expert judgement as

  18. Toward an integrative molecular approach to wildlife disease.

    Science.gov (United States)

    DeCandia, Alexandra L; Dobson, Andrew P; vonHoldt, Bridgett M

    2018-01-29

    Pathogens pose serious threats to human health, agricultural investment, and biodiversity conservation through the emergence of zoonoses, spillover to domestic livestock, and epizootic outbreaks. As such, wildlife managers are often tasked with mitigating the negative effects of disease. Yet, parasites form a major component of biodiversity that often persist. This is due to logistical challenges of implementing management strategies and to insufficient understanding of host-parasite dynamics. We advocate for an inclusive understanding of molecular diversity in driving parasite infection and variable host disease states in wildlife systems. More specifically, we examine the roles of genetic, epigenetic, and commensal microbial variation in disease pathogenesis. These include mechanisms underlying parasite virulence and host resistance and tolerance, and the development, regulation, and parasite subversion of immune pathways, among other processes. Case studies of devil facial tumor disease in Tasmanian devils (Sarcophilus harrisii) and chytridiomycosis in globally distributed amphibians exemplify the broad range of questions that can be addressed by examining different facets of molecular diversity. For particularly complex systems, integrative molecular analyses present a promising frontier that can provide critical insights necessary to elucidate disease dynamics operating across scales. These insights enable more accurate risk assessment, reconstruction of transmission pathways, discernment of optimal intervention strategies, and development of more effective and ecologically sound treatments that minimize damage to the host population and environment. Such measures are crucial when mitigating threats posed by wildlife disease to humans, domestic animals, and species of conservation concern. © 2018 Society for Conservation Biology.

  19. VitisNet: "Omics" integration through grapevine molecular networks.

    Directory of Open Access Journals (Sweden)

    Jérôme Grimplet

    Full Text Available BACKGROUND: Genomic data release for the grapevine has increased exponentially in the last five years. The Vitis vinifera genome has been sequenced and Vitis EST, transcriptomic, proteomic, and metabolomic tools and data sets continue to be developed. The next critical challenge is to provide biological meaning to this tremendous amount of data by annotating genes and integrating them within their biological context. We have developed and validated a system of Grapevine Molecular Networks (VitisNet. METHODOLOGY/PRINCIPAL FINDINGS: The sequences from the Vitis vinifera (cv. Pinot Noir PN40024 genome sequencing project and ESTs from the Vitis genus have been paired and the 39,424 resulting unique sequences have been manually annotated. Among these, 13,145 genes have been assigned to 219 networks. The pathway sets include 88 "Metabolic", 15 "Genetic Information Processing", 12 "Environmental Information Processing", 3 "Cellular Processes", 21 "Transport", and 80 "Transcription Factors". The quantitative data is loaded onto molecular networks, allowing the simultaneous visualization of changes in the transcriptome, proteome, and metabolome for a given experiment. CONCLUSIONS/SIGNIFICANCE: VitisNet uses manually annotated networks in SBML or XML format, enabling the integration of large datasets, streamlining biological functional processing, and improving the understanding of dynamic processes in systems biology experiments. VitisNet is grounded in the Vitis vinifera genome (currently at 8x coverage and can be readily updated with subsequent updates of the genome or biochemical discoveries. The molecular network files can be dynamically searched by pathway name or individual genes, proteins, or metabolites through the MetNet Pathway database and web-portal at http://metnet3.vrac.iastate.edu/. All VitisNet files including the manual annotation of the grape genome encompassing pathway names, individual genes, their genome identifier, and chromosome

  20. Efficient stochastic thermostatting of path integral molecular dynamics.

    Science.gov (United States)

    Ceriotti, Michele; Parrinello, Michele; Markland, Thomas E; Manolopoulos, David E

    2010-09-28

    The path integral molecular dynamics (PIMD) method provides a convenient way to compute the quantum mechanical structural and thermodynamic properties of condensed phase systems at the expense of introducing an additional set of high frequency normal modes on top of the physical vibrations of the system. Efficiently sampling such a wide range of frequencies provides a considerable thermostatting challenge. Here we introduce a simple stochastic path integral Langevin equation (PILE) thermostat which exploits an analytic knowledge of the free path integral normal mode frequencies. We also apply a recently developed colored noise thermostat based on a generalized Langevin equation (GLE), which automatically achieves a similar, frequency-optimized sampling. The sampling efficiencies of these thermostats are compared with that of the more conventional Nosé-Hoover chain (NHC) thermostat for a number of physically relevant properties of the liquid water and hydrogen-in-palladium systems. In nearly every case, the new PILE thermostat is found to perform just as well as the NHC thermostat while allowing for a computationally more efficient implementation. The GLE thermostat also proves to be very robust delivering a near-optimum sampling efficiency in all of the cases considered. We suspect that these simple stochastic thermostats will therefore find useful application in many future PIMD simulations.

  1. Integrated sequence analysis. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Andersson, K.; Pyy, P

    1998-02-01

    The NKS/RAK subprojet 3 `integrated sequence analysis` (ISA) was formulated with the overall objective to develop and to test integrated methodologies in order to evaluate event sequences with significant human action contribution. The term `methodology` denotes not only technical tools but also methods for integration of different scientific disciplines. In this report, we first discuss the background of ISA and the surveys made to map methods in different application fields, such as man machine system simulation software, human reliability analysis (HRA) and expert judgement. Specific event sequences were, after the surveys, selected for application and testing of a number of ISA methods. The event sequences discussed in the report were cold overpressure of BWR, shutdown LOCA of BWR, steam generator tube rupture of a PWR and BWR disturbed signal view in the control room after an external event. Different teams analysed these sequences by using different ISA and HRA methods. Two kinds of results were obtained from the ISA project: sequence specific and more general findings. The sequence specific results are discussed together with each sequence description. The general lessons are discussed under a separate chapter by using comparisons of different case studies. These lessons include areas ranging from plant safety management (design, procedures, instrumentation, operations, maintenance and safety practices) to methodological findings (ISA methodology, PSA,HRA, physical analyses, behavioural analyses and uncertainty assessment). Finally follows a discussion about the project and conclusions are presented. An interdisciplinary study of complex phenomena is a natural way to produce valuable and innovative results. This project came up with structured ways to perform ISA and managed to apply the in practice. The project also highlighted some areas where more work is needed. In the HRA work, development is required for the use of simulators and expert judgement as

  2. Integrative Workflows for Metagenomic Analysis

    Directory of Open Access Journals (Sweden)

    Efthymios eLadoukakis

    2014-11-01

    Full Text Available The rapid evolution of all sequencing technologies, described by the term Next Generation Sequencing (NGS, have revolutionized metagenomic analysis. They constitute a combination of high-throughput analytical protocols, coupled to delicate measuring techniques, in order to potentially discover, properly assemble and map allelic sequences to the correct genomes, achieving particularly high yields for only a fraction of the cost of traditional processes (i.e. Sanger. From a bioinformatic perspective, this boils down to many gigabytes of data being generated from each single sequencing experiment, rendering the management or even the storage, critical bottlenecks with respect to the overall analytical endeavor. The enormous complexity is even more aggravated by the versatility of the processing steps available, represented by the numerous bioinformatic tools that are essential, for each analytical task, in order to fully unveil the genetic content of a metagenomic dataset. These disparate tasks range from simple, nonetheless non-trivial, quality control of raw data to exceptionally complex protein annotation procedures, requesting a high level of expertise for their proper application or the neat implementation of the whole workflow. Furthermore, a bioinformatic analysis of such scale, requires grand computational resources, imposing as the sole realistic solution, the utilization of cloud computing infrastructures. In this review article we discuss different, integrative, bioinformatic solutions available, which address the aforementioned issues, by performing a critical assessment of the available automated pipelines for data management, quality control and annotation of metagenomic data, embracing various, major sequencing technologies and applications.

  3. Integrated Radiation Analysis and Design Tools

    Data.gov (United States)

    National Aeronautics and Space Administration — The Integrated Radiation Analysis and Design Tools (IRADT) Project develops and maintains an integrated tool set that collects the current best practices, databases,...

  4. A Systems Approach to Refine Disease Taxonomy by Integrating Phenotypic and Molecular Networks

    Directory of Open Access Journals (Sweden)

    Xuezhong Zhou

    2018-05-01

    Full Text Available The International Classification of Diseases (ICD relies on clinical features and lags behind the current understanding of the molecular specificity of disease pathobiology, necessitating approaches that incorporate growing biomedical data for classifying diseases to meet the needs of precision medicine. Our analysis revealed that the heterogeneous molecular diversity of disease chapters and the blurred boundary between disease categories in ICD should be further investigated. Here, we propose a new classification of diseases (NCD by developing an algorithm that predicts the additional categories of a disease by integrating multiple networks consisting of disease phenotypes and their molecular profiles. With statistical validations from phenotype-genotype associations and interactome networks, we demonstrate that NCD improves disease specificity owing to its overlapping categories and polyhierarchical structure. Furthermore, NCD captures the molecular diversity of diseases and defines clearer boundaries in terms of both phenotypic similarity and molecular associations, establishing a rational strategy to reform disease taxonomy. Keywords: Disease taxonomy, Network medicine, Disease phenotypes, Molecular profiles, Precision medicine

  5. TREEFINDER: a powerful graphical analysis environment for molecular phylogenetics

    Directory of Open Access Journals (Sweden)

    von Haeseler Arndt

    2004-06-01

    Full Text Available Abstract Background Most analysis programs for inferring molecular phylogenies are difficult to use, in particular for researchers with little programming experience. Results TREEFINDER is an easy-to-use integrative platform-independent analysis environment for molecular phylogenetics. In this paper the main features of TREEFINDER (version of April 2004 are described. TREEFINDER is written in ANSI C and Java and implements powerful statistical approaches for inferring gene tree and related analyzes. In addition, it provides a user-friendly graphical interface and a phylogenetic programming language. Conclusions TREEFINDER is a versatile framework for analyzing phylogenetic data across different platforms that is suited both for exploratory as well as advanced studies.

  6. Integrated minicomputer alpha analysis system

    International Nuclear Information System (INIS)

    Vasilik, D.G.; Coy, D.E.; Seamons, M.; Henderson, R.W.; Romero, L.L.; Thomson, D.A.

    1978-01-01

    Approximately 1,000 stack and occupation air samples from plutonium and uranium facilities at LASL are analyzed daily. The concentrations of radio-nuclides in air are determined by measuring absolute alpha activities of particulates collected on air sample filter media. The Integrated Minicomputer Pulse system (IMPULSE) is an interface between many detectors of extremely simple design and a Digital Equipment Corporation (DEC) PDP-11/04 minicomputer. The detectors are photomultiplier tubes faced with zinc sulfide (ZnS). The average detector background is approximately 0.07 cpm. The IMPULSE system includes two mainframes, each of which can hold up to 64 detectors. The current hardware configuration includes 64 detectors in one mainframe and 40 detectors in the other. Each mainframe contains a minicomputer with 28K words of Random Access Memory. One minicomputer controls the detectors in both mainframes. A second computer was added for fail-safe redundancy and to support other laboratory computer requirements. The main minicomputer includes a dual floppy disk system and a dual DEC 'RK05' disk system for mass storage. The RK05 facilitates report generation and trend analysis. The IMPULSE hardware provides for passage of data from the detectors to the computer, and for passage of status and control information from the computer to the detector stations

  7. Molecular activation analysis for chemical species studies

    International Nuclear Information System (INIS)

    Chai Zhifang; Mao Xueying; Wang Yuqi; Sun Jingxin; Qian Qingfang; Hou Xiaolin; Zhang Peiqun; Chen Chunying; Feng Weiyu; Ding Wenjun; Li Xiaolin; Li Chunsheng; Dai Xiongxin

    2001-01-01

    The Molecular Activation Analysis (MAA) mainly refers to an activation analysis method that is able to provide information about the chemical species of elements in systems of interest, though its exact definition has remained to be assigned. Its development is strongly stimulated by the urgent need to know the chemical species of elements, because the bulk contents or concentrations are often insignificant for judging biological, environmental or geochemical effects of elements. In this paper, the features, methodology and limitation of MAA were outlined. Further, the up-to-date MAA progress made in our laboratory was introduced as well. (author)

  8. Integration of a Radiosensitivity Molecular Signature Into the Assessment of Local Recurrence Risk in Breast Cancer

    International Nuclear Information System (INIS)

    Torres-Roca, Javier F.; Fulp, William J.; Caudell, Jimmy J.; Servant, Nicolas; Bollet, Marc A.; Vijver, Marc van de; Naghavi, Arash O.; Harris, Eleanor E.; Eschrich, Steven A.

    2015-01-01

    Purpose: Recently, we developed radiosensitivity (RSI), a clinically validated molecular signature that estimates tumor radiosensitivity. In the present study, we tested whether integrating RSI with the molecular subtype refines the classification of local recurrence (LR) risk in breast cancer. Methods and Materials: RSI and molecular subtype were evaluated in 343 patients treated with breast-conserving therapy that included whole-breast radiation therapy with or without a tumor bed boost (dose range 45-72 Gy). The follow-up period for patients without recurrence was 10 years. The clinical endpoint was LR-free survival. Results: Although RSI did not uniformly predict for LR across the entire cohort, combining RSI and the molecular subtype identified a subpopulation with an increased risk of LR: triple negative (TN) and radioresistant (reference TN-radioresistant, hazard ratio [HR] 0.37, 95% confidence interval [CI] 0.15-0.92, P=.02). TN patients who were RSI-sensitive/intermediate had LR rates similar to those of luminal (LUM) patients (HR 0.86, 95% CI 0.47-1.57, P=.63). On multivariate analysis, combined RSI and molecular subtype (P=.004) and age (P=.001) were the most significant predictors of LR. In contrast, integrating RSI into the LUM subtype did not identify additional risk groups. We hypothesized that radiation dose escalation was affecting radioresistance in the LUM subtype and serving as a confounder. An increased radiation dose decreased LR only in the luminal-resistant (LUM-R) subset (HR 0.23, 95% CI 0.05-0.98, P=.03). On multivariate analysis, the radiation dose was an independent variable only in the LUMA/B-RR subset (HR 0.025, 95% CI 0.001-0.946, P=.046), along with age (P=.008), T stage (P=.004), and chemotherapy (P=.008). Conclusions: The combined molecular subtype–RSI identified a novel molecular subpopulation (TN and radioresistant) with an increased risk of LR after breast-conserving therapy. We propose that the combination of RSI and

  9. Integration of a Radiosensitivity Molecular Signature Into the Assessment of Local Recurrence Risk in Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Torres-Roca, Javier F., E-mail: javier.torresroca@moffitt.org [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Department of Chemical Biology and Molecular Medicine, Moffitt Cancer Center, Tampa, Florida (United States); Fulp, William J. [Department of Bioinformatics, Moffitt Cancer Center, Tampa, Florida (United States); Department of Biostatistics, Moffitt Cancer Center, Tampa, Florida (United States); Caudell, Jimmy J. [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Servant, Nicolas [Institut Curie, INSERM U900, Paris (France); Mines ParisTech, Paris (France); Bollet, Marc A. [Institut Curie, INSERM U900, Paris (France); Vijver, Marc van de [Netherlands Cancer Institute, Amsterdam (Netherlands); Naghavi, Arash O. [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Harris, Eleanor E. [East Carolina University, Greensborough, North Carolina (United States); Eschrich, Steven A. [Department of Bioinformatics, Moffitt Cancer Center, Tampa, Florida (United States)

    2015-11-01

    Purpose: Recently, we developed radiosensitivity (RSI), a clinically validated molecular signature that estimates tumor radiosensitivity. In the present study, we tested whether integrating RSI with the molecular subtype refines the classification of local recurrence (LR) risk in breast cancer. Methods and Materials: RSI and molecular subtype were evaluated in 343 patients treated with breast-conserving therapy that included whole-breast radiation therapy with or without a tumor bed boost (dose range 45-72 Gy). The follow-up period for patients without recurrence was 10 years. The clinical endpoint was LR-free survival. Results: Although RSI did not uniformly predict for LR across the entire cohort, combining RSI and the molecular subtype identified a subpopulation with an increased risk of LR: triple negative (TN) and radioresistant (reference TN-radioresistant, hazard ratio [HR] 0.37, 95% confidence interval [CI] 0.15-0.92, P=.02). TN patients who were RSI-sensitive/intermediate had LR rates similar to those of luminal (LUM) patients (HR 0.86, 95% CI 0.47-1.57, P=.63). On multivariate analysis, combined RSI and molecular subtype (P=.004) and age (P=.001) were the most significant predictors of LR. In contrast, integrating RSI into the LUM subtype did not identify additional risk groups. We hypothesized that radiation dose escalation was affecting radioresistance in the LUM subtype and serving as a confounder. An increased radiation dose decreased LR only in the luminal-resistant (LUM-R) subset (HR 0.23, 95% CI 0.05-0.98, P=.03). On multivariate analysis, the radiation dose was an independent variable only in the LUMA/B-RR subset (HR 0.025, 95% CI 0.001-0.946, P=.046), along with age (P=.008), T stage (P=.004), and chemotherapy (P=.008). Conclusions: The combined molecular subtype–RSI identified a novel molecular subpopulation (TN and radioresistant) with an increased risk of LR after breast-conserving therapy. We propose that the combination of RSI and

  10. Problems in mathematical analysis III integration

    CERN Document Server

    Kaczor, W J

    2003-01-01

    We learn by doing. We learn mathematics by doing problems. This is the third volume of Problems in Mathematical Analysis. The topic here is integration for real functions of one real variable. The first chapter is devoted to the Riemann and the Riemann-Stieltjes integrals. Chapter 2 deals with Lebesgue measure and integration. The authors include some famous, and some not so famous, integral inequalities related to Riemann integration. Many of the problems for Lebesgue integration concern convergence theorems and the interchange of limits and integrals. The book closes with a section on Fourier series, with a concentration on Fourier coefficients of functions from particular classes and on basic theorems for convergence of Fourier series. The book is primarily geared toward students in analysis, as a study aid, for problem-solving seminars, or for tutorials. It is also an excellent resource for instructors who wish to incorporate problems into their lectures. Solutions for the problems are provided in the boo...

  11. The Vehicle Integrated Performance Analysis Experience: Reconnecting With Technical Integration

    Science.gov (United States)

    McGhee, D. S.

    2006-01-01

    Very early in the Space Launch Initiative program, a small team of engineers at MSFC proposed a process for performing system-level assessments of a launch vehicle. Aimed primarily at providing insight and making NASA a smart buyer, the Vehicle Integrated Performance Analysis (VIPA) team was created. The difference between the VIPA effort and previous integration attempts is that VIPA a process using experienced people from various disciplines, which focuses them on a technically integrated assessment. The foundations of VIPA s process are described. The VIPA team also recognized the need to target early detailed analysis toward identifying significant systems issues. This process is driven by the T-model for technical integration. VIPA s approach to performing system-level technical integration is discussed in detail. The VIPA process significantly enhances the development and monitoring of realizable project requirements. VIPA s assessment validates the concept s stated performance, identifies significant issues either with the concept or the requirements, and then reintegrates these issues to determine impacts. This process is discussed along with a description of how it may be integrated into a program s insight and review process. The VIPA process has gained favor with both engineering and project organizations for being responsive and insightful

  12. Integrated logistic support analysis system

    International Nuclear Information System (INIS)

    Carnicero Iniguez, E.J.; Garcia de la Sen, R.

    1993-01-01

    Integrating logic support into a system results in a large volume of information having to be managed which can only be achieved with the help of computer applications. Both past experience and growing needs in such tasks have led Emperesarios Agrupados to undertake an ambitious development project which is described in this paper. (author)

  13. Analysis of integrated energy systems

    International Nuclear Information System (INIS)

    Matsuhashi, Takaharu; Kaya, Yoichi; Komiyama, Hiroshi; Hayashi, Taketo; Yasukawa, Shigeru.

    1988-01-01

    World attention is now attracted to the concept of Novel Horizontally Integrated Energy System (NHIES). In NHIES, all fossil fuels are fist converted into CO and H 2 . Potential environmental contaminants such as sulfur are removed during this process. CO turbines are mainly used to generate electric power. Combustion is performed in pure oxygen produced through air separation, making it possible to completely prevent the formation of thermal NOx. Thus, NHIES would release very little amount of such substances that would contribute to acid rain. In this system, the intermediate energy sources of CO, H 2 and O 2 are integrated horizontally. They are combined appropriately to produce a specific form of final energy source. The integration of intermediate energy sources can provide a wide variety of final energy sources, allowing any type of fossil fuel to serve as an alternative to other types of fossil fuel. Another feature of NHIES is the positive use of nuclear fuel to reduce the formation of CO 2 . Studies are under way in Japan to develop a new concept of integrated energy system. These studies are especially aimed at decreased overall efficiency and introduction of new liquid fuels that are high in conversion efficiency. Considerations are made on the final form of energy source, robust control, acid fallout, and CO 2 reduction. (Nogami, K.)

  14. Integrative Analysis of Omics Big Data.

    Science.gov (United States)

    Yu, Xiang-Tian; Zeng, Tao

    2018-01-01

    The diversity and huge omics data take biology and biomedicine research and application into a big data era, just like that popular in human society a decade ago. They are opening a new challenge from horizontal data ensemble (e.g., the similar types of data collected from different labs or companies) to vertical data ensemble (e.g., the different types of data collected for a group of person with match information), which requires the integrative analysis in biology and biomedicine and also asks for emergent development of data integration to address the great changes from previous population-guided to newly individual-guided investigations.Data integration is an effective concept to solve the complex problem or understand the complicate system. Several benchmark studies have revealed the heterogeneity and trade-off that existed in the analysis of omics data. Integrative analysis can combine and investigate many datasets in a cost-effective reproducible way. Current integration approaches on biological data have two modes: one is "bottom-up integration" mode with follow-up manual integration, and the other one is "top-down integration" mode with follow-up in silico integration.This paper will firstly summarize the combinatory analysis approaches to give candidate protocol on biological experiment design for effectively integrative study on genomics and then survey the data fusion approaches to give helpful instruction on computational model development for biological significance detection, which have also provided newly data resources and analysis tools to support the precision medicine dependent on the big biomedical data. Finally, the problems and future directions are highlighted for integrative analysis of omics big data.

  15. Penalized differential pathway analysis of integrative oncogenomics studies.

    Science.gov (United States)

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

    2014-04-01

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

  16. Molecular DNA Analysis in Forensic Identification.

    Science.gov (United States)

    Dumache, Raluca; Ciocan, Veronica; Muresan, Camelia; Enache, Alexandra

    2016-01-01

    Serological and biochemical identification methods used in forensics have several major disadvantages, such as: long time in processing biological sample and lack of sensitivity and specificity. In the last 30 years, DNA molecular analysis has become an important tool in forensic investigations. DNA profiling is based on the short tandem repeats (STR) and aids in human identification from biological samples. Forensic genetics, can provide information on the events which occurred at the crime scene or to supplement other methods of forensic identification. Currently, the methods used in identification are based on polymerase chain reaction (PCR) analyses. This method analyses the autosomal STRs, the Y-chromosome, and the mitochondrial DNA. Correlation of biological samples present at the crime scene with identification, selection, and the probative value factor is therefore the first aspect to be taken into consideration in the forensic genetic analysis. In the last decade, because of the advances in the field of molecular biology, new biomarkers such as: microRNAs (miR), messenger RNA (mRNA), and DNA methylation have been studied and proposed to be used in the forensic identifications of body fluids.

  17. Containment integrity analysis under accidents

    International Nuclear Information System (INIS)

    Lin Chengge; Zhao Ruichang; Liu Zhitao

    2010-01-01

    Containment integrity analyses for current nuclear power plants (NPPs) mainly focus on the internal pressure caused by design basis accidents (DBAs). In addition to the analyses of containment pressure response caused by DBAs, the behavior of containment during severe accidents (SAs) are also evaluated for AP1000 NPP. Since the conservatism remains in the assumptions,boundary conditions and codes, margin of the results of containment integrity analyses may be overestimated. Along with the improvements of the knowledge to the phenomena and process of relevant accidents, the margin overrated can be appropriately reduced by using the best estimate codes combined with the uncertainty methods, which could be beneficial to the containment design and construction of large passive plants (LPP) in China. (authors)

  18. Integrative biological analysis for neuropsychopharmacology.

    Science.gov (United States)

    Emmett, Mark R; Kroes, Roger A; Moskal, Joseph R; Conrad, Charles A; Priebe, Waldemar; Laezza, Fernanda; Meyer-Baese, Anke; Nilsson, Carol L

    2014-01-01

    Although advances in psychotherapy have been made in recent years, drug discovery for brain diseases such as schizophrenia and mood disorders has stagnated. The need for new biomarkers and validated therapeutic targets in the field of neuropsychopharmacology is widely unmet. The brain is the most complex part of human anatomy from the standpoint of number and types of cells, their interconnections, and circuitry. To better meet patient needs, improved methods to approach brain studies by understanding functional networks that interact with the genome are being developed. The integrated biological approaches--proteomics, transcriptomics, metabolomics, and glycomics--have a strong record in several areas of biomedicine, including neurochemistry and neuro-oncology. Published applications of an integrated approach to projects of neurological, psychiatric, and pharmacological natures are still few but show promise to provide deep biological knowledge derived from cells, animal models, and clinical materials. Future studies that yield insights based on integrated analyses promise to deliver new therapeutic targets and biomarkers for personalized medicine.

  19. Optimized acoustic biochip integrated with microfluidics for biomarkers detection in molecular diagnostics.

    Science.gov (United States)

    Papadakis, G; Friedt, J M; Eck, M; Rabus, D; Jobst, G; Gizeli, E

    2017-09-01

    The development of integrated platforms incorporating an acoustic device as the detection element requires addressing simultaneously several challenges of technological and scientific nature. The present work was focused on the design of a microfluidic module, which, combined with a dual or array type Love wave acoustic chip could be applied to biomedical applications and molecular diagnostics. Based on a systematic study we optimized the mechanics of the flow cell attachment and the sealing material so that fluidic interfacing/encapsulation would impose minimal losses to the acoustic wave. We have also investigated combinations of operating frequencies with waveguide materials and thicknesses for maximum sensitivity during the detection of protein and DNA biomarkers. Within our investigations neutravidin was used as a model protein biomarker and unpurified PCR amplified Salmonella DNA as the model genetic target. Our results clearly indicate the need for experimental verification of the optimum engineering and analytical parameters, in order to develop commercially viable systems for integrated analysis. The good reproducibility of the signal together with the ability of the array biochip to detect multiple samples hold promise for the future use of the integrated system in a Lab-on-a-Chip platform for application to molecular diagnostics.

  20. Integrating reliability analysis and design

    International Nuclear Information System (INIS)

    Rasmuson, D.M.

    1980-10-01

    This report describes the Interactive Reliability Analysis Project and demonstrates the advantages of using computer-aided design systems (CADS) in reliability analysis. Common cause failure problems require presentations of systems, analysis of fault trees, and evaluation of solutions to these. Results have to be communicated between the reliability analyst and the system designer. Using a computer-aided design system saves time and money in the analysis of design. Computer-aided design systems lend themselves to cable routing, valve and switch lists, pipe routing, and other component studies. At EG and G Idaho, Inc., the Applicon CADS is being applied to the study of water reactor safety systems

  1. Molecular Composition Analysis of Distant Targets

    Science.gov (United States)

    Hughes, Gary B.; Lubin, Philip

    2017-01-01

    This document is the Final Report for NASA Innovative Advanced Concepts (NIAC) Phase I Grant 15-NIAC16A-0145, titled Molecular Composition Analysis of Distant Targets. The research was focused on developing a system concept for probing the molecular composition of cold solar system targets, such as Asteroids, Comets, Planets and Moons from a distant vantage, for example from a spacecraft that is orbiting the target (Hughes et al., 2015). The orbiting spacecraft is equipped with a high-power laser, which is run by electricity from photovoltaic panels. The laser is directed at a spot on the target. Materials on the surface of the target are heated by the laser beam, and begin to melt and then evaporate, forming a plume of asteroid molecules in front of the heated spot. The heated spot glows, producing blackbody illumination that is visible from the spacecraft, via a path through the evaporated plume. As the blackbody radiation from the heated spot passes through the plume of evaporated material, molecules in the plume absorb radiation in a manner that is specific to the rotational and vibrational characteristics of the specific molecules. A spectrometer aboard the spacecraft is used to observe absorption lines in the blackbody signal. The pattern of absorption can be used to estimate the molecular composition of materials in the plume, which originated on the target. Focusing on a single spot produces a borehole, and shallow subsurface profiling of the targets bulk composition is possible. At the beginning of the Phase I research, the estimated Technology Readiness Level (TRL) of the system was TRL-1. During the Phase I research, an end-to-end theoretical model of the sensor system was developed from first principles. The model includes laser energy and optical propagation, target heating, melting and evaporation of target material, plume density, thermal radiation from the heated spot, molecular cross section of likely asteroid materials, and estimation of the

  2. Integrating Molecular Computation and Material Production in an Artificial Subcellular Matrix

    DEFF Research Database (Denmark)

    Fellermann, Harold; Hadorn, Maik; Bönzli, Eva

    Living systems are unique in that they integrate molecular recognition and information processing with material production on the molecular scale. Pre- dominant locus of this integration is the cellular matrix, where a multitude of biochemical reactions proceed simultaneously in highly compartmen......Living systems are unique in that they integrate molecular recognition and information processing with material production on the molecular scale. Pre- dominant locus of this integration is the cellular matrix, where a multitude of biochemical reactions proceed simultaneously in highly...... compartmentalized re- action compartments that interact and get delivered through vesicle trafficking. The European Commission funded project MatchIT (Matrix for Chemical IT) aims at creating an artificial cellular matrix that seamlessly integrates infor- mation processing and material production in much the same...

  3. Cellular and molecular mechanisms of HIV-1 integration targeting.

    Science.gov (United States)

    Engelman, Alan N; Singh, Parmit K

    2018-07-01

    Integration is central to HIV-1 replication and helps mold the reservoir of cells that persists in AIDS patients. HIV-1 interacts with specific cellular factors to target integration to interior regions of transcriptionally active genes within gene-dense regions of chromatin. The viral capsid interacts with several proteins that are additionally implicated in virus nuclear import, including cleavage and polyadenylation specificity factor 6, to suppress integration into heterochromatin. The viral integrase protein interacts with transcriptional co-activator lens epithelium-derived growth factor p75 to principally position integration within gene bodies. The integrase additionally senses target DNA distortion and nucleotide sequence to help fine-tune the specific phosphodiester bonds that are cleaved at integration sites. Research into virus-host interactions that underlie HIV-1 integration targeting has aided the development of a novel class of integrase inhibitors and may help to improve the safety of viral-based gene therapy vectors.

  4. Molecular activation analysis for chemical speciation studies

    International Nuclear Information System (INIS)

    Chai-Chifang

    1998-01-01

    The term of Molecular Activation Analysis (MAA) refers to an activation analysis method that is able to provide information about the chemical species of elements in system of interests, though its definition has remained to be assigned. Its development is strongly stimulated by the urgent need to know the chemical species of elements, because the total concentrations are often without any meaning when assessing health or environmental risks of trace elements.In practice, the MAA is a combination of conventional instrumental or radiochemical activation analysis and physical, chemical or biochemical separation techniques. The MAA is able to play a particular role in speciation studies. However, the critical point in the MAA is that it is not permitted to change the primitive chemical species of elements in systems, or the change has to be under control; in the meantime it is not allowed to form the 'new artifact' originally not present in systems. Some practical examples of MAA for chemical species research performed recently in our laboratory will be presented as follows: Chemical species of platinum group elements in sediment; Chemical species of iodine in marine algae; Chemical species of mercury in human tissues; Chemical species of selenium in corn; Chemical species of rare earth elements in natural plant, etc. The merits and limitations of MAA will be described as well. (author)

  5. Integral data analysis for resonance parameters determination

    International Nuclear Information System (INIS)

    Larson, N.M.; Leal, L.C.; Derrien, H.

    1997-09-01

    Neutron time-of-flight experiments have long been used to determine resonance parameters. Those resonance parameters have then been used in calculations of integral quantities such as Maxwellian averages or resonance integrals, and results of those calculations in turn have been used as a criterion for acceptability of the resonance analysis. However, the calculations were inadequate because covariances on the parameter values were not included in the calculations. In this report an effort to correct for that deficiency is documented: (1) the R-matrix analysis code SAMMY has been modified to include integral quantities of importance, (2) directly within the resonance parameter analysis, and (3) to determine the best fit to both differential (microscopic) and integral (macroscopic) data simultaneously. This modification was implemented because it is expected to have an impact on the intermediate-energy range that is important for criticality safety applications

  6. Integrative data analysis of male reproductive disorders

    DEFF Research Database (Denmark)

    Edsgard, Stefan Daniel

    of such data in conjunction with data from publicly available repositories. This thesis presents an introduction to disease genetics and molecular systems biology, followed by four studies that each provide detailed clues to the etiology of male reproductive disorders. Finally, a fifth study illustrates......-wide association data with respect to copy number variation and show that the aggregated effect of rare variants can influence the risk for testicular cancer. Paper V provides an example of the application of RNA-Seq for expression analysis of a species with an unsequenced genome. We analysed the plant...... of this thesis is the identification of the molecular basis of male reproductive disorders, with a special focus on testicular cancer. To this end, clinical samples were characterized by microarraybased transcription and genomic variation assays and molecular entities were identified by computational analysis...

  7. Preliminary Integrated Safety Analysis Status Report

    International Nuclear Information System (INIS)

    Gwyn, D.

    2001-01-01

    This report provides the status of the potential Monitored Geologic Repository (MGR) Integrated Safety Analysis (EA) by identifying the initial work scope scheduled for completion during the ISA development period, the schedules associated with the tasks identified, safety analysis issues encountered, and a summary of accomplishments during the reporting period. This status covers the period from October 1, 2000 through March 30, 2001

  8. International Space Station Configuration Analysis and Integration

    Science.gov (United States)

    Anchondo, Rebekah

    2016-01-01

    Ambitious engineering projects, such as NASA's International Space Station (ISS), require dependable modeling, analysis, visualization, and robotics to ensure that complex mission strategies are carried out cost effectively, sustainably, and safely. Learn how Booz Allen Hamilton's Modeling, Analysis, Visualization, and Robotics Integration Center (MAVRIC) team performs engineering analysis of the ISS Configuration based primarily on the use of 3D CAD models. To support mission planning and execution, the team tracks the configuration of ISS and maintains configuration requirements to ensure operational goals are met. The MAVRIC team performs multi-disciplinary integration and trade studies to ensure future configurations meet stakeholder needs.

  9. Molecular analysis of waxy mutants in rice

    International Nuclear Information System (INIS)

    Yatou, O.; Amano, E.

    1990-01-01

    Full text: The 'waxy' gene is a structural gene coding a glycosyl transferase which synthesises amylose in the endosperm tissue. 'Non-waxy' rice cultivars have an active gene and their amylose content is 18-25% depending upon gene performance and modifier genes. In 'waxy' rice, no amylose is found because the enzyme is absent. In mutants induced by gamma rays, neutrons, EI or EMS, amylose content ranged from 0 to 20%, i.e. there are intermediate phenotypes as well. Some of them had the same amount of the enzyme as a 'non-waxy' cultivar, even fully 'waxy' mutants showed a certain amount of the enzyme. This suggests that in mutants there may be no structural change in the enzyme gene but the enzyme produced might be less active. By molecular analysis of the mutants' genes it was found that only two mutants induced by thermal neutrons show structural alterations, the changes in other mutants are either too small to be detected by Southern analysis or are outside the structural gene in question. (author)

  10. Property Integration - A New Approach for Simultaneous Solution of Process and Molecular Design Problems

    DEFF Research Database (Denmark)

    The objective of this paper is to introduce the new concept of property integration. It is based on tracking and integrating properties throughout the process. This is made possible by exploiting the unique features at the interface of process and molecular design. Recently developed clustering...... concepts are employed to identify optimal properties without commitment to specific species. Subsequently, group contribution methods and molecular design techniques are employed to solve the reverse property prediction problem to design molecules possessing the optimal properties....

  11. Polymer Molecular Weight Analysis by [Superscript 1]H NMR Spectroscopy

    Science.gov (United States)

    Izunobi, Josephat U.; Higginbotham, Clement L.

    2011-01-01

    The measurement and analysis of molecular weight and molecular weight distribution remain matters of fundamental importance for the characterization and physical properties of polymers. Gel permeation chromatography (GPC) is the most routinely used method for the molecular weight determination of polymers whereas matrix-assisted laser…

  12. Symplectic integrators for large scale molecular dynamics simulations: A comparison of several explicit methods

    International Nuclear Information System (INIS)

    Gray, S.K.; Noid, D.W.; Sumpter, B.G.

    1994-01-01

    We test the suitability of a variety of explicit symplectic integrators for molecular dynamics calculations on Hamiltonian systems. These integrators are extremely simple algorithms with low memory requirements, and appear to be well suited for large scale simulations. We first apply all the methods to a simple test case using the ideas of Berendsen and van Gunsteren. We then use the integrators to generate long time trajectories of a 1000 unit polyethylene chain. Calculations are also performed with two popular but nonsymplectic integrators. The most efficient integrators of the set investigated are deduced. We also discuss certain variations on the basic symplectic integration technique

  13. Integrability of dynamical systems algebra and analysis

    CERN Document Server

    Zhang, Xiang

    2017-01-01

    This is the first book to systematically state the fundamental theory of integrability and its development of ordinary differential equations with emphasis on the Darboux theory of integrability and local integrability together with their applications. It summarizes the classical results of Darboux integrability and its modern development together with their related Darboux polynomials and their applications in the reduction of Liouville and elementary integrabilty and in the center—focus problem, the weakened Hilbert 16th problem on algebraic limit cycles and the global dynamical analysis of some realistic models in fields such as physics, mechanics and biology. Although it can be used as a textbook for graduate students in dynamical systems, it is intended as supplementary reading for graduate students from mathematics, physics, mechanics and engineering in courses related to the qualitative theory, bifurcation theory and the theory of integrability of dynamical systems.

  14. Strategic Analysis of Technology Integration at Allstream

    OpenAIRE

    Brown, Jeff

    2011-01-01

    Innovation has been defined as the combination of invention and commercialization. Invention without commercialization is rarely, if ever, profitable. For the purposes of this paper the definition of innovation will be further expanded into the concept of technology integration. Successful technology integration not only includes new technology introduction, but also the operationalization of the new technology within each business unit of the enterprise. This paper conducts an analysis of Al...

  15. Integrated Molecular Imaging and Therapy for Breast Cancer

    National Research Council Canada - National Science Library

    Panchapakesan, Balaji

    2008-01-01

    ...) and NIR dosing of cancer cells using SWCNT. While previous studies have shown the transport of DNA into cells using nanotubes, in this study we show multi-component molecular targeting of both IGF1R and Her2 surface markers in cancer cells...

  16. Multiple time step integrators in ab initio molecular dynamics

    International Nuclear Information System (INIS)

    Luehr, Nathan; Martínez, Todd J.; Markland, Thomas E.

    2014-01-01

    Multiple time-scale algorithms exploit the natural separation of time-scales in chemical systems to greatly accelerate the efficiency of molecular dynamics simulations. Although the utility of these methods in systems where the interactions are described by empirical potentials is now well established, their application to ab initio molecular dynamics calculations has been limited by difficulties associated with splitting the ab initio potential into fast and slowly varying components. Here we present two schemes that enable efficient time-scale separation in ab initio calculations: one based on fragment decomposition and the other on range separation of the Coulomb operator in the electronic Hamiltonian. We demonstrate for both water clusters and a solvated hydroxide ion that multiple time-scale molecular dynamics allows for outer time steps of 2.5 fs, which are as large as those obtained when such schemes are applied to empirical potentials, while still allowing for bonds to be broken and reformed throughout the dynamics. This permits computational speedups of up to 4.4x, compared to standard Born-Oppenheimer ab initio molecular dynamics with a 0.5 fs time step, while maintaining the same energy conservation and accuracy

  17. Molecular integrals for exponential-type orbitals using hyperspherical harmonics

    DEFF Research Database (Denmark)

    Avery, James Emil; Avery, John Scales

    2015-01-01

    -dimensional hypersphere. Using this projection, Fock was able to show that the Fourier transforms of Coulomb Sturmian basis functions are very simply related to four-dimensional hyperspherical harmonics.With the help of Fock's relationships and the theory of hyperspherical harmonics we are able to evaluate molecular...

  18. The molecular turn in psychiatry: a philosophical analysis.

    Science.gov (United States)

    Rudnick, Abraham

    2002-06-01

    Biological psychiatry has been dominated by a psychopharmacologically-driven neurotransmitter dysfunction paradigm. The objective of this paper is to explore a reductionist assumption underlying this paradigm, and to suggest an improvement on it. The methods used are conceptual analysis with a comparative approach, particularly using illustrations from the history of both biological psychiatry and molecular biology. The results are that complete reduction to physicochemical explanations is not fruitful, at least in the initial stages of research in the medical and life sciences, and that an appropriate (non-reducible) integrative principle--addressing a property of the whole system under study--is required for each domain of research. This is illustrated in Pauling's use of a topological integrative principle for the discovery of the functioning of proteins and in Watson and Crick's use of the notion of a genetic code as an integrative principle for the discovery of the structure of genes. The neurotransmitter dysfunction paradigm addresses single molecules and their neural pathways, yet their interactions within the CNS as a whole seem most pertinent to mental disorders such as schizophrenia. The lack within biological psychiatry of an integrative principle addressing a property of the CNS as a whole may be responsible for the empirical failure of orthomolecular psychiatry, as well as for the central role that serendipity has played in the study of mental disorders, which is dominated by the neurotransmitter paradigm. The conclusion is that research in biological psychiatry may benefit from using, at least initially, some integrative principle(s) addressing a property of the CNS as a whole, such as connectionism or a hierarchical notion.

  19. Revealing molecular mechanisms by integrating high-dimensional functional screens with protein interaction data.

    Directory of Open Access Journals (Sweden)

    Angela Simeone

    2014-09-01

    Full Text Available Functional genomics screens using multi-parametric assays are powerful approaches for identifying genes involved in particular cellular processes. However, they suffer from problems like noise, and often provide little insight into molecular mechanisms. A bottleneck for addressing these issues is the lack of computational methods for the systematic integration of multi-parametric phenotypic datasets with molecular interactions. Here, we present Integrative Multi Profile Analysis of Cellular Traits (IMPACT. The main goal of IMPACT is to identify the most consistent phenotypic profile among interacting genes. This approach utilizes two types of external information: sets of related genes (IMPACT-sets and network information (IMPACT-modules. Based on the notion that interacting genes are more likely to be involved in similar functions than non-interacting genes, this data is used as a prior to inform the filtering of phenotypic profiles that are similar among interacting genes. IMPACT-sets selects the most frequent profile among a set of related genes. IMPACT-modules identifies sub-networks containing genes with similar phenotype profiles. The statistical significance of these selections is subsequently quantified via permutations of the data. IMPACT (1 handles multiple profiles per gene, (2 rescues genes with weak phenotypes and (3 accounts for multiple biases e.g. caused by the network topology. Application to a genome-wide RNAi screen on endocytosis showed that IMPACT improved the recovery of known endocytosis-related genes, decreased off-target effects, and detected consistent phenotypes. Those findings were confirmed by rescreening 468 genes. Additionally we validated an unexpected influence of the IGF-receptor on EGF-endocytosis. IMPACT facilitates the selection of high-quality phenotypic profiles using different types of independent information, thereby supporting the molecular interpretation of functional screens.

  20. Analysis Method for Integrating Components of Product

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jun Ho [Inzest Co. Ltd, Seoul (Korea, Republic of); Lee, Kun Sang [Kookmin Univ., Seoul (Korea, Republic of)

    2017-04-15

    This paper presents some of the methods used to incorporate the parts constituting a product. A new relation function concept and its structure are introduced to analyze the relationships of component parts. This relation function has three types of information, which can be used to establish a relation function structure. The relation function structure of the analysis criteria was established to analyze and present the data. The priority components determined by the analysis criteria can be integrated. The analysis criteria were divided based on their number and orientation, as well as their direct or indirect characteristic feature. This paper presents a design algorithm for component integration. This algorithm was applied to actual products, and the components inside the product were integrated. Therefore, the proposed algorithm was used to conduct research to improve the brake discs for bicycles. As a result, an improved product similar to the related function structure was actually created.

  1. Analysis Method for Integrating Components of Product

    International Nuclear Information System (INIS)

    Choi, Jun Ho; Lee, Kun Sang

    2017-01-01

    This paper presents some of the methods used to incorporate the parts constituting a product. A new relation function concept and its structure are introduced to analyze the relationships of component parts. This relation function has three types of information, which can be used to establish a relation function structure. The relation function structure of the analysis criteria was established to analyze and present the data. The priority components determined by the analysis criteria can be integrated. The analysis criteria were divided based on their number and orientation, as well as their direct or indirect characteristic feature. This paper presents a design algorithm for component integration. This algorithm was applied to actual products, and the components inside the product were integrated. Therefore, the proposed algorithm was used to conduct research to improve the brake discs for bicycles. As a result, an improved product similar to the related function structure was actually created.

  2. Integrative genome-wide expression profiling identifies three distinct molecular subgroups of renal cell carcinoma with different patient outcome

    Directory of Open Access Journals (Sweden)

    Beleut Manfred

    2012-07-01

    Full Text Available Abstract Background Renal cell carcinoma (RCC is characterized by a number of diverse molecular aberrations that differ among individuals. Recent approaches to molecularly classify RCC were based on clinical, pathological as well as on single molecular parameters. As a consequence, gene expression patterns reflecting the sum of genetic aberrations in individual tumors may not have been recognized. In an attempt to uncover such molecular features in RCC, we used a novel, unbiased and integrative approach. Methods We integrated gene expression data from 97 primary RCC of different pathologic parameters, 15 RCC metastases as well as 34 cancer cell lines for two-way nonsupervised hierarchical clustering using gene groups suggested by the PANTHER Classification System. We depicted the genomic landscape of the resulted tumor groups by means of Single Nuclear Polymorphism (SNP technology. Finally, the achieved results were immunohistochemically analyzed using a tissue microarray (TMA composed of 254 RCC. Results We found robust, genome wide expression signatures, which split RCC into three distinct molecular subgroups. These groups remained stable even if randomly selected gene sets were clustered. Notably, the pattern obtained from RCC cell lines was clearly distinguishable from that of primary tumors. SNP array analysis demonstrated differing frequencies of chromosomal copy number alterations among RCC subgroups. TMA analysis with group-specific markers showed a prognostic significance of the different groups. Conclusion We propose the existence of characteristic and histologically independent genome-wide expression outputs in RCC with potential biological and clinical relevance.

  3. Integration, warehousing, and analysis strategies of Omics data.

    Science.gov (United States)

    Gedela, Srinubabu

    2011-01-01

    "-Omics" is a current suffix for numerous types of large-scale biological data generation procedures, which naturally demand the development of novel algorithms for data storage and analysis. With next generation genome sequencing burgeoning, it is pivotal to decipher a coding site on the genome, a gene's function, and information on transcripts next to the pure availability of sequence information. To explore a genome and downstream molecular processes, we need umpteen results at the various levels of cellular organization by utilizing different experimental designs, data analysis strategies and methodologies. Here comes the need for controlled vocabularies and data integration to annotate, store, and update the flow of experimental data. This chapter explores key methodologies to merge Omics data by semantic data carriers, discusses controlled vocabularies as eXtensible Markup Languages (XML), and provides practical guidance, databases, and software links supporting the integration of Omics data.

  4. An integrated acquisition, display, and analysis system

    International Nuclear Information System (INIS)

    Ahmad, T.; Huckins, R.J.

    1987-01-01

    The design goal of the ND9900/Genuie was to integrate a high performance data acquisition and display subsystem with a state-of-the-art 32-bit supermicrocomputer. This was achieved by integrating a Digital Equipment Corporation MicroVAX II CPU board with acquisition and display controllers via the Q-bus. The result is a tightly coupled processing and analysis system for Pulse Height Analysis and other applications. The system architecture supports distributed processing, so that acquisition and display functions are semi-autonomous, making the VAX concurrently available for applications programs

  5. A combined reaction class approach with integrated molecular orbital+molecular orbital (IMOMO) methodology: A practical tool for kinetic modeling

    International Nuclear Information System (INIS)

    Truong, Thanh N.; Maity, Dilip K.; Truong, Thanh-Thai T.

    2000-01-01

    We present a new practical computational methodology for predicting thermal rate constants of reactions involving large molecules or a large number of elementary reactions in the same class. This methodology combines the integrated molecular orbital+molecular orbital (IMOMO) approach with our recently proposed reaction class models for tunneling. With the new methodology, we show that it is possible to significantly reduce the computational cost by several orders of magnitude while compromising the accuracy in the predicted rate constants by less than 40% over a wide range of temperatures. Another important result is that the computational cost increases only slightly as the system size increases. (c) 2000 American Institute of Physics

  6. Integrating molecular markers into the World Health Organization classification of CNS tumors: a survey of the neuro-oncology community.

    Science.gov (United States)

    Aldape, Kenneth; Nejad, Romina; Louis, David N; Zadeh, Gelareh

    2017-03-01

    Molecular markers provide important biological and clinical information related to the classification of brain tumors, and the integration of relevant molecular parameters into brain tumor classification systems has been a widely discussed topic in neuro-oncology over the past decade. With recent advances in the development of clinically relevant molecular signatures and the 2016 World Health Organization (WHO) update, the views of the neuro-oncology community on such changes would be informative for implementing this process. A survey with 8 questions regarding molecular markers in tumor classification was sent to an email list of Society for Neuro-Oncology members and attendees of prior meetings (n=5065). There were 403 respondents. Analysis was performed using whole group response, based on self-reported subspecialty. The survey results show overall strong support for incorporating molecular knowledge into the classification and clinical management of brain tumors. Across all 7 subspecialty groups, ≥70% of respondents agreed to this integration. Interestingly, some variability is seen among subspecialties, notably with lowest support from neuropathologists, which may reflect their roles in implementing such diagnostic technologies. Based on a survey provided to the neuro-oncology community, we report strong support for the integration of molecular markers into the WHO classification of brain tumors, as well as for using an integrated "layered" diagnostic format. While membership from each specialty showed support, there was variation by specialty in enthusiasm regarding proposed changes. The initial results of this survey influenced the deliberations underlying the 2016 WHO classification of tumors of the central nervous system. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.

  7. Abel integral equations analysis and applications

    CERN Document Server

    Gorenflo, Rudolf

    1991-01-01

    In many fields of application of mathematics, progress is crucially dependent on the good flow of information between (i) theoretical mathematicians looking for applications, (ii) mathematicians working in applications in need of theory, and (iii) scientists and engineers applying mathematical models and methods. The intention of this book is to stimulate this flow of information. In the first three chapters (accessible to third year students of mathematics and physics and to mathematically interested engineers) applications of Abel integral equations are surveyed broadly including determination of potentials, stereology, seismic travel times, spectroscopy, optical fibres. In subsequent chapters (requiring some background in functional analysis) mapping properties of Abel integral operators and their relation to other integral transforms in various function spaces are investi- gated, questions of existence and uniqueness of solutions of linear and nonlinear Abel integral equations are treated, and for equatio...

  8. Molecular Analysis Research at Community College of Philadelphia

    Science.gov (United States)

    2015-09-21

    YOUR FORM TO THE ABOVE ADDRESS. Community College of Philadelphia Community College of Philadelphia 1700 Spring Garden Street Philadelphia, PA 19130...Approved for Public Release; Distribution Unlimited Final Report: Molecular Analysis Research at Community College of Philadelphia The views, opinions...Molecular Analysis Research at Community College of Philadelphia Report Title AXIMA Assurance mass spectrometer, Leica DMI-8 fluorescent microscope

  9. Nonlinear structural analysis using integrated force method

    Indian Academy of Sciences (India)

    A new formulation termed the Integrated Force Method (IFM) was proposed by Patnaik ... nated ``Structure (nY m)'' where (nY m) are the force and displacement degrees of ..... Patnaik S N, Yadagiri S 1976 Frequency analysis of structures.

  10. Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas

    NARCIS (Netherlands)

    Liu, Yang; Sethi, Nilay S; Hinoue, Toshinori; Schneider, Barbara G; Cherniack, Andrew D; Sanchez-Vega, Francisco; Seoane, Jose A; Farshidfar, Farshad; Bowlby, Reanne; Islam, Mirazul; Kim, Jaegil; Chatila, Walid; Akbani, Rehan; Kanchi, Rupa S; Rabkin, Charles S; Willis, Joseph E; Wang, Kenneth K; McCall, Shannon J; Mishra, Lopa; Ojesina, Akinyemi I; Bullman, Susan; Pedamallu, Chandra Sekhar; Lazar, Alexander J; Sakai, Ryo; Thorsson, Vésteinn; Bass, Adam J; Laird, Peter W; de Krijger, RR

    2018-01-01

    We analyzed 921 adenocarcinomas of the esophagus, stomach, colon, and rectum to examine shared and distinguishing molecular characteristics of gastrointestinal tract adenocarcinomas (GIACs). Hypermutated tumors were distinct regardless of cancer type and comprised those enriched for

  11. Molecular Composition Analysis of Distant Targets

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose a system capable of probing the molecular composition of cold solar system targets such as asteroids, comets, planets and moons from a distant vantage....

  12. Integration of molecular pathology, epidemiology and social science for global precision medicine.

    Science.gov (United States)

    Nishi, Akihiro; Milner, Danny A; Giovannucci, Edward L; Nishihara, Reiko; Tan, Andy S; Kawachi, Ichiro; Ogino, Shuji

    2016-01-01

    The precision medicine concept and the unique disease principle imply that each patient has unique pathogenic processes resulting from heterogeneous cellular genetic and epigenetic alterations and interactions between cells (including immune cells) and exposures, including dietary, environmental, microbial and lifestyle factors. As a core method field in population health science and medicine, epidemiology is a growing scientific discipline that can analyze disease risk factors and develop statistical methodologies to maximize utilization of big data on populations and disease pathology. The evolving transdisciplinary field of molecular pathological epidemiology (MPE) can advance biomedical and health research by linking exposures to molecular pathologic signatures, enhancing causal inference and identifying potential biomarkers for clinical impact. The MPE approach can be applied to any diseases, although it has been most commonly used in neoplastic diseases (including breast, lung and colorectal cancers) because of availability of various molecular diagnostic tests. However, use of state-of-the-art genomic, epigenomic and other omic technologies and expensive drugs in modern healthcare systems increases racial, ethnic and socioeconomic disparities. To address this, we propose to integrate molecular pathology, epidemiology and social science. Social epidemiology integrates the latter two fields. The integrative social MPE model can embrace sociology, economics and precision medicine, address global health disparities and inequalities, and elucidate biological effects of social environments, behaviors and networks. We foresee advancements of molecular medicine, including molecular diagnostics, biomedical imaging and targeted therapeutics, which should benefit individuals in a global population, by means of an interdisciplinary approach of integrative MPE and social health science.

  13. Molecular analysis of pancreatic cyst fluid changes clinical management.

    Science.gov (United States)

    Arner, David M; Corning, Brooke E; Ahmed, Ali M; Ho, Henry C; Weinbaum, Bradley J; Siddiqui, Uzma; Aslanian, Harry; Adams, Reid B; Bauer, Todd W; Wang, Andrew Y; Shami, Vanessa M; Sauer, Bryan G

    2018-01-01

    DNA molecular analysis has been suggested as a tool to evaluate pancreatic cysts. This study assesses whether the addition of DNA molecular analysis alters clinical management. This is a retrospective review of 46 consecutive patients who underwent EUS-FNA of pancreatic cysts with DNA molecular analysis at two major academic institutions. Cases were presented to two pancreaticobiliary surgeons first without and then with DNA molecular analysis data. The primary outcome was the frequency with which clinical management was altered with the addition of DNA molecular analysis. Forty-six patients with a mean age of 62.0 (±13.4) years and mean cyst size of 3.2 (±2.3) cm were included in the study. Cyst carcinoembryonic antigen (CEA) was available in 30 patients and ranged from 0.4 to 15,927 ng/mL. DNA molecular analysis was described as benign in 23 (50%), statistically indolent in 13 (28%), statistically higher risk in 9 (20%), and indeterminate in 1 (2%). Surgeon #1 changed the management in 13/46 cases (28%) and surgeon #2 changed the management in 12/46 cases (26%) with the addition of DNA molecular analysis. When organized by CEA concentration, those with an intermediate CEA (45-800 ng/mL) or without a CEA concentration had a management changed more frequently (40%) compared to all others (P molecular analysis alters the clinical management of pancreatic cystic lesions most often when CEA levels are intermediate (45-800 ng/mL) or when no CEA concentration is available. Use of DNA molecular analysis can be considered in this cohort. Further study of molecular markers in pancreatic cystic lesions is recommended.

  14. A Liouville-operator derived measure-preserving integrator for molecular dynamics simulations in the isothermal-isobaric ensemble

    International Nuclear Information System (INIS)

    Tuckerman, Mark E; Alejandre, Jose; Lopez-Rendon, Roberto; Jochim, Andrea L; Martyna, Glenn J

    2006-01-01

    The constant-pressure, constant-temperature (NPT) molecular dynamics approach is re-examined from the viewpoint of deriving a new measure-preserving reversible geometric integrator for the equations of motion. The underlying concepts of non-Hamiltonian phase-space analysis, measure-preserving integrators and the symplectic property for Hamiltonian systems are briefly reviewed. In addition, current measure-preserving schemes for the constant-volume, constant-temperature ensemble are also reviewed. A new geometric integrator for the NPT method is presented, is shown to preserve the correct phase-space volume element and is demonstrated to perform well in realistic examples. Finally, a multiple time-step version of the integrator is presented for treating systems with motion on several time scales

  15. Diffuse Gliomas for Nonneuropathologists: The New Integrated Molecular Diagnostics.

    Science.gov (United States)

    Lee, Sunhee C

    2018-05-18

    Diffuse gliomas comprise the bulk of "brain cancer" in adults. The recent update to the 4th edition of the World Health Organization's classification of tumors of the central nervous system reflects an unprecedented change in the landscape of the diagnosis and management of diffuse gliomas that will affect all those involved in the management and care of patients. Of the recently discovered gene alterations, mutations in the Krebs cycle enzymes isocitrate dehydrogenases (IDHs) 1 and 2 have fundamentally changed the way the gliomas are understood and classified. Incorporating information on a few genetic parameters (IDH, ATRX and/or p53, and chromosome 1p19q codeletion), a relatively straightforward diagnostic algorithm has been generated with robust and reproducible results that correlate with patients' survival far better than relying on conventional histology alone. Evidence also supports the conclusion that the vast majority of diffuse gliomas without IDH mutations (IDH-wild-type astrocytomas) behave like IDH-wild-type glioblastomas ("molecular GBM"). Together, these changes reflect a big shift in the practice of diagnostic neuropathology in which tumor risk stratification aligns better with molecular information than histology/grading. The purpose of this review is to provide the readers with a brief synopsis of the changes in the 2016 World Health Organization update with an emphasis on diffuse gliomas and to summarize key gene abnormalities on which these classifications are based. Practical points involved in day-to-day diagnostic workup are also discussed, along with a comparison of the various diagnostic tests, including immunohistochemistry, with an emphasis on targeted next-generation sequencing panel technology as a future universal approach.

  16. Integrating neural network technology and noise analysis

    International Nuclear Information System (INIS)

    Uhrig, R.E.; Oak Ridge National Lab., TN

    1995-01-01

    The integrated use of neural network and noise analysis technologies offers advantages not available by the use of either technology alone. The application of neural network technology to noise analysis offers an opportunity to expand the scope of problems where noise analysis is useful and unique ways in which the integration of these technologies can be used productively. The two-sensor technique, in which the responses of two sensors to an unknown driving source are related, is used to demonstration such integration. The relationship between power spectral densities (PSDs) of accelerometer signals is derived theoretically using noise analysis to demonstrate its uniqueness. This relationship is modeled from experimental data using a neural network when the system is working properly, and the actual PSD of one sensor is compared with the PSD of that sensor predicted by the neural network using the PSD of the other sensor as an input. A significant deviation between the actual and predicted PSDs indicate that system is changing (i.e., failing). Experiments carried out on check values and bearings illustrate the usefulness of the methodology developed. (Author)

  17. Penalized differential pathway analysis of integrative oncogenomics studies

    NARCIS (Netherlands)

    van Wieringen, W.N.; van de Wiel, M.A.

    2014-01-01

    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

  18. Trade-offs in thermal adaptation: the need for a molecular to ecological integration.

    Science.gov (United States)

    Pörtner, Hans O; Bennett, Albert F; Bozinovic, Francisco; Clarke, Andrew; Lardies, Marco A; Lucassen, Magnus; Pelster, Bernd; Schiemer, Fritz; Stillman, Jonathon H

    2006-01-01

    Through functional analyses, integrative physiology is able to link molecular biology with ecology as well as evolutionary biology and is thereby expected to provide access to the evolution of molecular, cellular, and organismic functions; the genetic basis of adaptability; and the shaping of ecological patterns. This paper compiles several exemplary studies of thermal physiology and ecology, carried out at various levels of biological organization from single genes (proteins) to ecosystems. In each of those examples, trade-offs and constraints in thermal adaptation are addressed; these trade-offs and constraints may limit species' distribution and define their level of fitness. For a more comprehensive understanding, the paper sets out to elaborate the functional and conceptual connections among these independent studies and the various organizational levels addressed. This effort illustrates the need for an overarching concept of thermal adaptation that encompasses molecular, organellar, cellular, and whole-organism information as well as the mechanistic links between fitness, ecological success, and organismal physiology. For this data, the hypothesis of oxygen- and capacity-limited thermal tolerance in animals provides such a conceptual framework and allows interpreting the mechanisms of thermal limitation of animals as relevant at the ecological level. While, ideally, evolutionary studies over multiple generations, illustrated by an example study in bacteria, are necessary to test the validity of such complex concepts and underlying hypotheses, animal physiology frequently is constrained to functional studies within one generation. Comparisons of populations in a latitudinal cline, closely related species from different climates, and ontogenetic stages from riverine clines illustrate how evolutionary information can still be gained. An understanding of temperature-dependent shifts in energy turnover, associated with adjustments in aerobic scope and performance

  19. Intracellular Chemistry: Integrating Molecular Inorganic Catalysts with Living Systems.

    Science.gov (United States)

    Ngo, Anh H; Bose, Sohini; Do, Loi H

    2018-03-23

    This concept article focuses on the rapid growth of intracellular chemistry dedicated to the integration of small-molecule metal catalysts with living cells and organisms. Although biological systems contain a plethora of biomolecules that can deactivate inorganic species, researchers have shown that small-molecule metal catalysts could be engineered to operate in heterogeneous aqueous environments. Synthetic intracellular reactions have recently been reported for olefin hydrogenation, hydrolysis/oxidative cleavage, azide-alkyne cycloaddition, allylcarbamate cleavage, C-C bond cross coupling, and transfer hydrogenation. Other promising targets for new biocompatible reaction discovery will also be discussed, with a special emphasis on how such innovations could lead to the development of novel technologies and chemical tools. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. [Integrated health care organizations: guideline for analysis].

    Science.gov (United States)

    Vázquez Navarrete, M Luisa; Vargas Lorenzo, Ingrid; Farré Calpe, Joan; Terraza Núñez, Rebeca

    2005-01-01

    There has been a tendency recently to abandon competition and to introduce policies that promote collaboration between health providers as a means of improving the efficiency of the system and the continuity of care. A number of countries, most notably the United States, have experienced the integration of health care providers to cover the continuum of care of a defined population. Catalonia has witnessed the steady emergence of increasing numbers of integrated health organisations (IHO) but, unlike the United States, studies on health providers' integration are scarce. As part of a research project currently underway, a guide was developed to study Catalan IHOs, based on a classical literature review and the development of a theoretical framework. The guide proposes analysing the IHO's performance in relation to their final objectives of improving the efficiency and continuity of health care by an analysis of the integration type (based on key characteristics); external elements (existence of other suppliers, type of services' payment mechanisms); and internal elements (model of government, organization and management) that influence integration. Evaluation of the IHO's performance focuses on global strategies and results on coordination of care and efficiency. Two types of coordination are evaluated: information coordination and coordination of care management. Evaluation of the efficiency of the IHO refers to technical and allocative efficiency. This guide may have to be modified for use in the Catalan context.

  1. Integration of molecular typing results into tuberculosis surveillance in Germany-A pilot study.

    Science.gov (United States)

    Andrés, Marta; Göhring-Zwacka, Elke; Fiebig, Lena; Priwitzer, Martin; Richter, Elvira; Rüsch-Gerdes, Sabine; Haas, Walter; Niemann, Stefan; Brodhun, Bonita

    2017-01-01

    An integrated molecular surveillance for tuberculosis (TB) improves the understanding of ongoing TB transmission by combining molecular typing and epidemiological data. However, the implementation of an integrated molecular surveillance for TB is complex and requires thoughtful consideration of feasibility, demand, public health benefits and legal issues. We aimed to pilot the integration of molecular typing results between 2008 and 2010 in the German Federal State of Baden-Württemberg (population 10.88 Million) as preparation for a nationwide implementation. Culture positive TB cases were typed by IS6110 DNA fingerprinting and results were integrated into routine notification data. Demographic and clinical characteristics of cases and clusters were described and new epidemiological links detected after integrating typing data were calculated. Furthermore, a cross-sectional survey was performed among local public health offices to evaluate their perception and experiences. Overall, typing results were available for 83% of notified culture positive TB cases, out of which 25% were clustered. Age Germany (OR = 2.01, 95% CI: 1.44-2.80) were associated with clustering. At cluster level, molecular typing information allowed the identification of previously unknown epidemiological links in 11% of the clusters. In 59% of the clusters it was not possible to identify any epidemiological link. Clusters extending over different counties were less likely to have epidemiological links identified among their cases (OR = 11.53, 95% CI: 3.48-98.23). The majority of local public health offices found molecular typing useful for their work. Our study illustrates the feasibility of integrating typing data into the German TB notification system and depicts its added public health value as complementary strategy in TB surveillance, especially to uncover transmission events among geographically separated TB patients. It also emphasizes that special efforts are required to strengthen the

  2. Molecular marker analysis of 'Shatangju' and 'Wuzishatangju ...

    African Journals Online (AJOL)

    'Wuzishatangju'(Citrus reticulata Blanco) is an excellent cultivar derived from a bud sport of a seedy 'Shatangju' cultivar found in Guangdong Province in the 1980s. In this study, six molecular markers including random amplified polymorphic DNA (RAPD), inter-simple sequence repeat (ISSR), simple sequence repeat (SSR) ...

  3. Integrated tools for control-system analysis

    Science.gov (United States)

    Ostroff, Aaron J.; Proffitt, Melissa S.; Clark, David R.

    1989-01-01

    The basic functions embedded within a user friendly software package (MATRIXx) are used to provide a high level systems approach to the analysis of linear control systems. Various control system analysis configurations are assembled automatically to minimize the amount of work by the user. Interactive decision making is incorporated via menu options and at selected points, such as in the plotting section, by inputting data. There are five evaluations such as the singular value robustness test, singular value loop transfer frequency response, Bode frequency response, steady-state covariance analysis, and closed-loop eigenvalues. Another section describes time response simulations. A time response for random white noise disturbance is available. The configurations and key equations used for each type of analysis, the restrictions that apply, the type of data required, and an example problem are described. One approach for integrating the design and analysis tools is also presented.

  4. An integrated system for genetic analysis

    Directory of Open Access Journals (Sweden)

    Duan Xiao

    2006-04-01

    Full Text Available Abstract Background Large-scale genetic mapping projects require data management systems that can handle complex phenotypes and detect and correct high-throughput genotyping errors, yet are easy to use. Description We have developed an Integrated Genotyping System (IGS to meet this need. IGS securely stores, edits and analyses genotype and phenotype data. It stores information about DNA samples, plates, primers, markers and genotypes generated by a genotyping laboratory. Data are structured so that statistical genetic analysis of both case-control and pedigree data is straightforward. Conclusion IGS can model complex phenotypes and contain genotypes from whole genome association studies. The database makes it possible to integrate genetic analysis with data curation. The IGS web site http://bioinformatics.well.ox.ac.uk/project-igs.shtml contains further information.

  5. Integrated Reliability and Risk Analysis System (IRRAS)

    International Nuclear Information System (INIS)

    Russell, K.D.; McKay, M.K.; Sattison, M.B.; Skinner, N.L.; Wood, S.T.; Rasmuson, D.M.

    1992-01-01

    The Integrated Reliability and Risk Analysis System (IRRAS) is a state-of-the-art, microcomputer-based probabilistic risk assessment (PRA) model development and analysis tool to address key nuclear plant safety issues. IRRAS is an integrated software tool that gives the user the ability to create and analyze fault trees and accident sequences using a microcomputer. This program provides functions that range from graphical fault tree construction to cut set generation and quantification. Version 1.0 of the IRRAS program was released in February of 1987. Since that time, many user comments and enhancements have been incorporated into the program providing a much more powerful and user-friendly system. This version has been designated IRRAS 4.0 and is the subject of this Reference Manual. Version 4.0 of IRRAS provides the same capabilities as Version 1.0 and adds a relational data base facility for managing the data, improved functionality, and improved algorithm performance

  6. PHIDIAS: a pathogen-host interaction data integration and analysis system

    OpenAIRE

    Xiang, Zuoshuang; Tian, Yuying; He, Yongqun

    2007-01-01

    The Pathogen-Host Interaction Data Integration and Analysis System (PHIDIAS) is a web-based database system that serves as a centralized source to search, compare, and analyze integrated genome sequences, conserved domains, and gene expression data related to pathogen-host interactions (PHIs) for pathogen species designated as high priority agents for public health and biological security. In addition, PHIDIAS allows submission, search and analysis of PHI genes and molecular networks curated ...

  7. Integrity Analysis of Damaged Steam Generator Tubes

    International Nuclear Information System (INIS)

    Stanic, D.

    1998-01-01

    Variety of degradation mechanisms affecting steam generator tubes makes steam generators as one of the critical components in the nuclear power plants. Depending of their nature, degradation mechanisms cause different types of damages. It requires performance of extensive integrity analysis in order to access various conditions of crack behavior under operating and accidental conditions. Development and application of advanced eddy current techniques for steam generator examination provide good characterization of found damages. Damage characteristics (shape, orientation and dimensions) may be defined and used for further evaluation of damage influence on tube integrity. In comparison with experimental and analytical methods, numerical methods are also efficient tools for integrity assessment. Application of finite element methods provides relatively simple modeling of different type of damages and simulation of various operating conditions. The stress and strain analysis may be performed for elastic and elasto-plastic state with good ability for visual presentation of results. Furthermore, the fracture mechanics parameters may be calculated. Results obtained by numerical analysis supplemented with experimental results are the base for definition of alternative plugging criteria which may significantly reduce the number of plugged tubes. (author)

  8. The integrated microbial genome resource of analysis.

    Science.gov (United States)

    Checcucci, Alice; Mengoni, Alessio

    2015-01-01

    Integrated Microbial Genomes and Metagenomes (IMG) is a biocomputational system that allows to provide information and support for annotation and comparative analysis of microbial genomes and metagenomes. IMG has been developed by the US Department of Energy (DOE)-Joint Genome Institute (JGI). IMG platform contains both draft and complete genomes, sequenced by Joint Genome Institute and other public and available genomes. Genomes of strains belonging to Archaea, Bacteria, and Eukarya domains are present as well as those of viruses and plasmids. Here, we provide some essential features of IMG system and case study for pangenome analysis.

  9. Integrated analysis of genetic data with R

    Directory of Open Access Journals (Sweden)

    Zhao Jing

    2006-01-01

    Full Text Available Abstract Genetic data are now widely available. There is, however, an apparent lack of concerted effort to produce software systems for statistical analysis of genetic data compared with other fields of statistics. It is often a tremendous task for end-users to tailor them for particular data, especially when genetic data are analysed in conjunction with a large number of covariates. Here, R http://www.r-project.org, a free, flexible and platform-independent environment for statistical modelling and graphics is explored as an integrated system for genetic data analysis. An overview of some packages currently available for analysis of genetic data is given. This is followed by examples of package development and practical applications. With clear advantages in data management, graphics, statistical analysis, programming, internet capability and use of available codes, it is a feasible, although challenging, task to develop it into an integrated platform for genetic analysis; this will require the joint efforts of many researchers.

  10. [Ginseng prescription rules and molecular mechanism in treating coronary heart disease based on data mining and integrative pharmacology].

    Science.gov (United States)

    Li, Sen; Tang, Shi-Huan; Liu, Jin-Ling; Su, Jin; He, Fu-Yuan

    2018-04-01

    The ancient dragon Materia Medica, Compendium of Materia Medica and other works recorded that the main effect of ginseng is tonifying qi. It is reported that the main active ingredient of ginseng is ginsenoside. Modern studies have found that ginseng mono saponins are effective for cardiovascular related diseases. This paper preliminary clarified the efficacy of traditional ginseng-nourishing qi and cardiovascular disease through the traditional Chinese medicine (TCM) inheritance auxiliary platform and integration platform of association of pharmacology. With the help of TCM inheritance auxiliary platform-analysis of "Chinese medicine database", Chinese medicine treatment of modern diseases that ginseng rules, so the traditional effect associated with modern medicine and pharmacology; application integration platform enrichment analysis on the target of drug and gene function, metabolic pathway, to further explore the molecular mechanism of ginseng in the treatment of coronary heart disease, aimed at mining the molecular mechanism of ginseng in the treatment of coronary heart disease. Chinese medicine containing ginseng 307 prescriptions, 87 kinds of disease indications, western medicine disease Chinese medicine therapy for ginseng main coronary heart disease; analysis of molecular mechanism of ginseng pharmacology integration platform for the treatment of coronary heart disease. Ginsenosides(Ra₁, Ra₂, Rb₁, Rb₂, Rg₁, Ro) bind these targets, PRKAA1, PRKAA2, NDUFA4, COX5B, UQCRC1, affect chemokines, non-alcoholic fatty liver, gonadotropin, carbon metabolism, glucose metabolism and other pathways to treat coronary heart disease indirectly. The molecular mechanism of Panax ginseng's multi-component, multi-target and synergistic action is preliminarily elucidated in this paper. Copyright© by the Chinese Pharmaceutical Association.

  11. Advancing Alternative Analysis: Integration of Decision Science

    DEFF Research Database (Denmark)

    Malloy, Timothy F; Zaunbrecher, Virginia M; Batteate, Christina

    2016-01-01

    Decision analysis-a systematic approach to solving complex problems-offers tools and frameworks to support decision making that are increasingly being applied to environmental challenges. Alternatives analysis is a method used in regulation and product design to identify, compare, and evaluate......, and civil society and included experts in toxicology, decision science, alternatives assessment, engineering, and law and policy. Participants were divided into two groups and prompted with targeted questions. Throughout the workshop, the groups periodically came together in plenary sessions to reflect......) engaging the systematic development and evaluation of decision approaches and tools; (2) using case studies to advance the integration of decision analysis into alternatives analysis; (3) supporting transdisciplinary research; and (4) supporting education and outreach efforts....

  12. A genetic analysis of segregation distortion revealed by molecular ...

    Indian Academy of Sciences (India)

    Journal of Genetics, Vol. 90, No. ... Segregation analysis was based on 64 molecular markers, including 26 .... FHB of RIL populations was controlled by quantitative trait ... The authors acknowledge financial support by the National Basic.

  13. Phenotypic and molecular genetic analysis of Pyruvate Kinase ...

    African Journals Online (AJOL)

    Phenotypic and molecular genetic analysis of Pyruvate Kinase deficiency in a Tunisian family. Jaouani Mouna, Hamdi Nadia, Chaouch Leila, Kalai Miniar, Mellouli Fethi, Darragi Imen, Boudriga Imen, Chaouachi Dorra, Bejaoui Mohamed, Abbes Salem ...

  14. MOLECULAR ANALYSIS OF HUMAN SPERMATOZOA: POTENTIAL FOR INFERTILITY RESEARCH

    Science.gov (United States)

    Gordon Research Conference: Mammalian Gametogenesis and Embryogenesis New London, CT, July 1-6, 2000Molecular Analysis of Human Spermatozoa: Potential for Infertility ResearchDavid Miller 1, David Dix2, Robert Reid 3, Stephen A Krawetz 3 1Reproductive ...

  15. Integration and segregation in auditory scene analysis

    Science.gov (United States)

    Sussman, Elyse S.

    2005-03-01

    Assessment of the neural correlates of auditory scene analysis, using an index of sound change detection that does not require the listener to attend to the sounds [a component of event-related brain potentials called the mismatch negativity (MMN)], has previously demonstrated that segregation processes can occur without attention focused on the sounds and that within-stream contextual factors influence how sound elements are integrated and represented in auditory memory. The current study investigated the relationship between the segregation and integration processes when they were called upon to function together. The pattern of MMN results showed that the integration of sound elements within a sound stream occurred after the segregation of sounds into independent streams and, further, that the individual streams were subject to contextual effects. These results are consistent with a view of auditory processing that suggests that the auditory scene is rapidly organized into distinct streams and the integration of sequential elements to perceptual units takes place on the already formed streams. This would allow for the flexibility required to identify changing within-stream sound patterns, needed to appreciate music or comprehend speech..

  16. Integration of molecular typing results into tuberculosis surveillance in Germany—A pilot study

    Science.gov (United States)

    Fiebig, Lena; Priwitzer, Martin; Richter, Elvira; Rüsch-Gerdes, Sabine; Haas, Walter; Niemann, Stefan; Brodhun, Bonita

    2017-01-01

    An integrated molecular surveillance for tuberculosis (TB) improves the understanding of ongoing TB transmission by combining molecular typing and epidemiological data. However, the implementation of an integrated molecular surveillance for TB is complex and requires thoughtful consideration of feasibility, demand, public health benefits and legal issues. We aimed to pilot the integration of molecular typing results between 2008 and 2010 in the German Federal State of Baden-Württemberg (population 10.88 Million) as preparation for a nationwide implementation. Culture positive TB cases were typed by IS6110 DNA fingerprinting and results were integrated into routine notification data. Demographic and clinical characteristics of cases and clusters were described and new epidemiological links detected after integrating typing data were calculated. Furthermore, a cross-sectional survey was performed among local public health offices to evaluate their perception and experiences. Overall, typing results were available for 83% of notified culture positive TB cases, out of which 25% were clustered. Age typing information allowed the identification of previously unknown epidemiological links in 11% of the clusters. In 59% of the clusters it was not possible to identify any epidemiological link. Clusters extending over different counties were less likely to have epidemiological links identified among their cases (OR = 11.53, 95% CI: 3.48–98.23). The majority of local public health offices found molecular typing useful for their work. Our study illustrates the feasibility of integrating typing data into the German TB notification system and depicts its added public health value as complementary strategy in TB surveillance, especially to uncover transmission events among geographically separated TB patients. It also emphasizes that special efforts are required to strengthen the communication between local public health offices in different counties to enhance TB control

  17. Molecular Diagnostic Analysis of Outbreak Scenarios

    Science.gov (United States)

    Morsink, M. C.; Dekter, H. E.; Dirks-Mulder, A.; van Leeuwen, W. B.

    2012-01-01

    In the current laboratory assignment, technical aspects of the polymerase chain reaction (PCR) are integrated in the context of six different bacterial outbreak scenarios. The "Enterobacterial Repetitive Intergenic Consensus Sequence" (ERIC) PCR was used to analyze different outbreak scenarios. First, groups of 2-4 students determined optimal…

  18. Integrated framework for dynamic safety analysis

    International Nuclear Information System (INIS)

    Kim, Tae Wan; Karanki, Durga R.

    2012-01-01

    In the conventional PSA (Probabilistic Safety Assessment), detailed plant simulations by independent thermal hydraulic (TH) codes are used in the development of accident sequence models. Typical accidents in a NPP involve complex interactions among process, safety systems, and operator actions. As independent TH codes do not have the models of operator actions and full safety systems, they cannot literally simulate the integrated and dynamic interactions of process, safety systems, and operator responses. Offline simulation with pre decided states and time delays may not model the accident sequences properly. Moreover, when stochastic variability in responses of accident models is considered, defining all the combinations for simulations will be cumbersome task. To overcome some of these limitations of conventional safety analysis approach, TH models are coupled with the stochastic models in the dynamic event tree (DET) framework, which provides flexibility to model the integrated response due to better communication as all the accident elements are in the same model. The advantages of this framework also include: Realistic modeling in dynamic scenarios, comprehensive results, integrated approach (both deterministic and probabilistic models), and support for HRA (Human Reliability Analysis)

  19. The rise of a novel classification system for endometrial carcinoma; integration of molecular subclasses.

    Science.gov (United States)

    McAlpine, Jessica; Leon-Castillo, Alicia; Bosse, Tjalling

    2018-04-01

    Endometrial cancer is a clinically heterogeneous disease and it is becoming increasingly clear that this heterogeneity may be a function of the diversity of the underlying molecular alterations. Recent large-scale genomic studies have revealed that endometrial cancer can be divided into at least four distinct molecular subtypes, with well-described underlying genomic aberrations. These subtypes can be reliably delineated and carry significant prognostic as well as predictive information; embracing and incorporating them into clinical practice is thus attractive. The road towards the integration of molecular features into current classification systems is not without obstacles. Collaborative studies engaging research teams from across the world are working to define pragmatic assays, improve risk stratification systems by combining molecular features and traditional clinicopathological parameters, and determine how molecular classification can be optimally utilized to direct patient care. Pathologists and clinicians caring for women with endometrial cancer need to engage with and understand the possibilities and limitations of this new approach, because integration of molecular classification of endometrial cancers is anticipated to become an essential part of gynaecological pathology practice. This review will describe the challenges in current systems of endometrial carcinoma classification, the evolution of new molecular technologies that define prognostically distinct molecular subtypes, and potential applications of molecular classification as a step towards precision medicine and refining care for individuals with the most common gynaecological cancer in the developed world. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  20. Differential amplicons (ΔAmp)—a new molecular method to assess RNA integrity

    Czech Academy of Sciences Publication Activity Database

    Bjorkman, J.; Švec, David; Kubista, Mikael; Sjöback, R.

    2016-01-01

    Roč. 6, Jan 2016 (2016), s. 4-12 ISSN 2214-7535 R&D Projects: GA ČR GA13-02154S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : RNA integrity * RNA quality * Endogenous RNase resistant marker Subject RIV: EB - Genetics ; Molecular Biology

  1. Effects of Quantum Nuclear Delocalisation on NMR Parameters from Path Integral Molecular Dynamics

    Czech Academy of Sciences Publication Activity Database

    Dračínský, Martin; Hodgkinson, P.

    2014-01-01

    Roč. 20, č. 8 (2014), s. 2201-2207 ISSN 0947-6539 Grant - others:Seventh Framework Programme of the European Union(XE) FP7-299242 People Institutional support: RVO:61388963 Keywords : density functional calculations * isotope effects * NMR spectroscopy * nuclear delocalisation * path integral molecular dynamics Subject RIV: CC - Organic Chemistry Impact factor: 5.731, year: 2014

  2. Formalizing the definition of meta-analysis in Molecular Ecology.

    Science.gov (United States)

    ArchMiller, Althea A; Bauer, Eric F; Koch, Rebecca E; Wijayawardena, Bhagya K; Anil, Ammu; Kottwitz, Jack J; Munsterman, Amelia S; Wilson, Alan E

    2015-08-01

    Meta-analysis, the statistical synthesis of pertinent literature to develop evidence-based conclusions, is relatively new to the field of molecular ecology, with the first meta-analysis published in the journal Molecular Ecology in 2003 (Slate & Phua 2003). The goal of this article is to formalize the definition of meta-analysis for the authors, editors, reviewers and readers of Molecular Ecology by completing a review of the meta-analyses previously published in this journal. We also provide a brief overview of the many components required for meta-analysis with a more specific discussion of the issues related to the field of molecular ecology, including the use and statistical considerations of Wright's FST and its related analogues as effect sizes in meta-analysis. We performed a literature review to identify articles published as 'meta-analyses' in Molecular Ecology, which were then evaluated by at least two reviewers. We specifically targeted Molecular Ecology publications because as a flagship journal in this field, meta-analyses published in Molecular Ecology have the potential to set the standard for meta-analyses in other journals. We found that while many of these reviewed articles were strong meta-analyses, others failed to follow standard meta-analytical techniques. One of these unsatisfactory meta-analyses was in fact a secondary analysis. Other studies attempted meta-analyses but lacked the fundamental statistics that are considered necessary for an effective and powerful meta-analysis. By drawing attention to the inconsistency of studies labelled as meta-analyses, we emphasize the importance of understanding the components of traditional meta-analyses to fully embrace the strengths of quantitative data synthesis in the field of molecular ecology. © 2015 John Wiley & Sons Ltd.

  3. Integrating health and environmental impact analysis

    DEFF Research Database (Denmark)

    Reis, S; Morris, G.; Fleming, L. E.

    2015-01-01

    which addresses human activity in all its social, economic and cultural complexity. The new approach must be integral to, and interactive, with the natural environment. We see the continuing failure to truly integrate human health and environmental impact analysis as deeply damaging, and we propose...... while equally emphasizing the health of the environment, and the growing calls for 'ecological public health' as a response to global environmental concerns now suffusing the discourse in public health. More revolution than evolution, ecological public health will demand new perspectives regarding...... the interconnections among society, the economy, the environment and our health and well-being. Success must be built on collaborations between the disparate scientific communities of the environmental sciences and public health as well as interactions with social scientists, economists and the legal profession...

  4. Advancing Alternative Analysis: Integration of Decision Science.

    Science.gov (United States)

    Malloy, Timothy F; Zaunbrecher, Virginia M; Batteate, Christina M; Blake, Ann; Carroll, William F; Corbett, Charles J; Hansen, Steffen Foss; Lempert, Robert J; Linkov, Igor; McFadden, Roger; Moran, Kelly D; Olivetti, Elsa; Ostrom, Nancy K; Romero, Michelle; Schoenung, Julie M; Seager, Thomas P; Sinsheimer, Peter; Thayer, Kristina A

    2017-06-13

    Decision analysis-a systematic approach to solving complex problems-offers tools and frameworks to support decision making that are increasingly being applied to environmental challenges. Alternatives analysis is a method used in regulation and product design to identify, compare, and evaluate the safety and viability of potential substitutes for hazardous chemicals. We assessed whether decision science may assist the alternatives analysis decision maker in comparing alternatives across a range of metrics. A workshop was convened that included representatives from government, academia, business, and civil society and included experts in toxicology, decision science, alternatives assessment, engineering, and law and policy. Participants were divided into two groups and were prompted with targeted questions. Throughout the workshop, the groups periodically came together in plenary sessions to reflect on other groups' findings. We concluded that the further incorporation of decision science into alternatives analysis would advance the ability of companies and regulators to select alternatives to harmful ingredients and would also advance the science of decision analysis. We advance four recommendations: a ) engaging the systematic development and evaluation of decision approaches and tools; b ) using case studies to advance the integration of decision analysis into alternatives analysis; c ) supporting transdisciplinary research; and d ) supporting education and outreach efforts. https://doi.org/10.1289/EHP483.

  5. Structural integrity analysis of a steam turbine

    International Nuclear Information System (INIS)

    Villagarcia, Maria P.

    1997-01-01

    One of the most critical components of a power utility is the rotor of the steam turbine. Catastrophic failures of the last decades have promoted the development of life assessment procedures for rotors. The present study requires the knowledge of operating conditions, component geometry, the properties of materials, history of the component, size, location and nature of the existing flaws. The aim of the present work is the obtention of a structural integrity analysis procedure for a steam turbine rotor, taking into account the above-mentioned parameters. In this procedure, a stress thermal analysis by finite elements is performed initially, in order to obtain the temperature and stress distribution for a subsequent analysis by fracture mechanics. The risk of a fast fracture due to flaws in the central zone of the rotor is analyzed. The procedure is applied to an operating turbine: the main steam turbine of the Atucha I nuclear power utility. (author)

  6. A taxonomy of integral reaction path analysis

    Energy Technology Data Exchange (ETDEWEB)

    Grcar, Joseph F.; Day, Marcus S.; Bell, John B.

    2004-12-23

    W. C. Gardiner observed that achieving understanding through combustion modeling is limited by the ability to recognize the implications of what has been computed and to draw conclusions about the elementary steps underlying the reaction mechanism. This difficulty can be overcome in part by making better use of reaction path analysis in the context of multidimensional flame simulations. Following a survey of current practice, an integral reaction flux is formulated in terms of conserved scalars that can be calculated in a fully automated way. Conditional analyses are then introduced, and a taxonomy for bidirectional path analysis is explored. Many examples illustrate the resulting path analysis and uncover some new results about nonpremixed methane-air laminar jets.

  7. The ASDEX integrated data analysis system AIDA

    International Nuclear Information System (INIS)

    Grassie, K.; Gruber, O.; Kardaun, O.; Kaufmann, M.; Lackner, K.; Martin, P.; Mast, K.F.; McCarthy, P.J.; Mertens, V.; Pohl, D.; Rang, U.; Wunderlich, R.

    1989-11-01

    Since about two years, the ASDEX integrated data analysis system (AIDA), which combines the database (DABA) and the statistical analysis system (SAS), is successfully in operation. Besides a considerable, but meaningful, reduction of the 'raw' shot data, it offers the advantage of carefully selected and precisely defined datasets, which are easily accessible for informative tabular data overviews (DABA), and multi-shot analysis (SAS). Even rather complicated, statistical analyses can be performed efficiently within this system. In this report, we want to summarise AIDA's main features, give some details on its set-up and on the physical models which have been used for the derivation of the processed data. We also give short introduction how to use DABA and SAS. (orig.)

  8. Integration of Molecular Pathology, Epidemiology, and Social Science for Global Precision Medicine

    Science.gov (United States)

    Nishi, Akihiro; Milner, Danny A; Giovannucci, Edward L.; Nishihara, Reiko; Tan, Andy S.; Kawachi, Ichiro; Ogino, Shuji

    2015-01-01

    Summary The precision medicine concept and the unique disease principle imply that each patient has unique pathogenic processes resulting from heterogeneous cellular genetic and epigenetic alterations, and interactions between cells (including immune cells) and exposures, including dietary, environmental, microbial, and lifestyle factors. As a core method field in population health science and medicine, epidemiology is a growing scientific discipline that can analyze disease risk factors, and develop statistical methodologies to maximize utilization of big data on populations and disease pathology. The evolving transdisciplinary field of molecular pathological epidemiology (MPE) can advance biomedical and health research by linking exposures to molecular pathologic signatures, enhancing causal inference, and identifying potential biomarkers for clinical impact. The MPE approach can be applied to any diseases, although it has been most commonly used in neoplastic diseases (including breast, lung and colorectal cancers) because of availability of various molecular diagnostic tests. However, use of state-of-the-art genomic, epigenomic and other omic technologies and expensive drugs in modern healthcare systems increases racial, ethnic and socioeconomic disparities. To address this, we propose to integrate molecular pathology, epidemiology, and social science. Social epidemiology integrates the latter two fields. The integrative social MPE model can embrace sociology, economics and precision medicine, address global health disparities and inequalities, and elucidate biological effects of social environments, behaviors, and networks. We foresee advancements of molecular medicine, including molecular diagnostics, biomedical imaging, and targeted therapeutics, which should benefit individuals in a global population, by means of an interdisciplinary approach of integrative MPE and social health science. PMID:26636627

  9. An analytical procedure to evaluate electronic integrals for molecular quantum mechanical calculations

    International Nuclear Information System (INIS)

    Mundim, Kleber C.

    2004-01-01

    Full text: We propose an alternative methodology for the calculation of electronic integrals, through an analytical function based on the generalized Gaussian function (q Gaussian), where a single q Gaussian replaces the usual linear combination of Gaussian functions for different basis set. Moreover, the integrals become analytical functions of the interatomic distances. Therefore, when estimating certain quantities such as molecular energy, g Gaussian avoid new calculations of the integrals: they are simply another value of the corresponding function. The procedure proposed here is particularly advantageous, when compared with the usual one, because it reduces drastically the number of two-electronic integrals used in the construction of the Fock matrix, enabling the use of the quantum mechanics in the description of macro-molecular systems. This advantage increases when the size of the molecular systems become larger and more complex. While in the usual approach CPU time increases with n4, in the one proposed here the CPU time scales linearly with n. This catastrophic dependence of the rank the Hamiltonian or Fock matrix with n4 two-electron integrals is a severe bottleneck for petaFLOPS computing time. Its is important to emphasize that this methodology is equally applicable to systems of any sizes, including biomolecules, solid materials and solutions, within the HF, post-HF and DFT theories. (author)

  10. Dynamical analysis of highly excited molecular spectra

    Energy Technology Data Exchange (ETDEWEB)

    Kellman, M.E. [Univ. of Oregon, Eugene (United States)

    1993-12-01

    The goal of this program is new methods for analysis of spectra and dynamics of highly excited vibrational states of molecules. In these systems, strong mode coupling and anharmonicity give rise to complicated classical dynamics, and make the simple normal modes analysis unsatisfactory. New methods of spectral analysis, pattern recognition, and assignment are sought using techniques of nonlinear dynamics including bifurcation theory, phase space classification, and quantization of phase space structures. The emphasis is chaotic systems and systems with many degrees of freedom.

  11. Accelerated sampling by infinite swapping of path integral molecular dynamics with surface hopping

    Science.gov (United States)

    Lu, Jianfeng; Zhou, Zhennan

    2018-02-01

    To accelerate the thermal equilibrium sampling of multi-level quantum systems, the infinite swapping limit of a recently proposed multi-level ring polymer representation is investigated. In the infinite swapping limit, the ring polymer evolves according to an averaged Hamiltonian with respect to all possible surface index configurations of the ring polymer and thus connects the surface hopping approach to the mean-field path-integral molecular dynamics. A multiscale integrator for the infinite swapping limit is also proposed to enable efficient sampling based on the limiting dynamics. Numerical results demonstrate the huge improvement of sampling efficiency of the infinite swapping compared with the direct simulation of path-integral molecular dynamics with surface hopping.

  12. Accelerator physics analysis with an integrated toolkit

    International Nuclear Information System (INIS)

    Holt, J.A.; Michelotti, L.; Satogata, T.

    1992-08-01

    Work is in progress on an integrated software toolkit for linear and nonlinear accelerator design, analysis, and simulation. As a first application, ''beamline'' and ''MXYZPTLK'' (differential algebra) class libraries, were used with an X Windows graphics library to build an user-friendly, interactive phase space tracker which, additionally, finds periodic orbits. This program was used to analyse a theoretical lattice which contains octupoles and decapoles to find the 20th order, stable and unstable periodic orbits and to explore the local phase space structure

  13. XML-based approaches for the integration of heterogeneous bio-molecular data.

    Science.gov (United States)

    Mesiti, Marco; Jiménez-Ruiz, Ernesto; Sanz, Ismael; Berlanga-Llavori, Rafael; Perlasca, Paolo; Valentini, Giorgio; Manset, David

    2009-10-15

    The today's public database infrastructure spans a very large collection of heterogeneous biological data, opening new opportunities for molecular biology, bio-medical and bioinformatics research, but raising also new problems for their integration and computational processing. In this paper we survey the most interesting and novel approaches for the representation, integration and management of different kinds of biological data by exploiting XML and the related recommendations and approaches. Moreover, we present new and interesting cutting edge approaches for the appropriate management of heterogeneous biological data represented through XML. XML has succeeded in the integration of heterogeneous biomolecular information, and has established itself as the syntactic glue for biological data sources. Nevertheless, a large variety of XML-based data formats have been proposed, thus resulting in a difficult effective integration of bioinformatics data schemes. The adoption of a few semantic-rich standard formats is urgent to achieve a seamless integration of the current biological resources.

  14. The Integral A Crux for Analysis

    CERN Document Server

    Krantz, Steven G

    2011-01-01

    This book treats all of the most commonly used theories of the integral. After motivating the idea of integral, we devote a full chapter to the Riemann integral and the next to the Lebesgue integral. Another chapter compares and contrasts the two theories. The concluding chapter offers brief introductions to the Henstock integral, the Daniell integral, the Stieltjes integral, and other commonly used integrals. The purpose of this book is to provide a quick but accurate (and detailed) introduction to all aspects of modern integration theory. It should be accessible to any student who has had ca

  15. Integr8: enhanced inter-operability of European molecular biology databases.

    Science.gov (United States)

    Kersey, P J; Morris, L; Hermjakob, H; Apweiler, R

    2003-01-01

    The increasing production of molecular biology data in the post-genomic era, and the proliferation of databases that store it, require the development of an integrative layer in database services to facilitate the synthesis of related information. The solution of this problem is made more difficult by the absence of universal identifiers for biological entities, and the breadth and variety of available data. Integr8 was modelled using UML (Universal Modelling Language). Integr8 is being implemented as an n-tier system using a modern object-oriented programming language (Java). An object-relational mapping tool, OJB, is being used to specify the interface between the upper layers and an underlying relational database. The European Bioinformatics Institute is launching the Integr8 project. Integr8 will be an automatically populated database in which we will maintain stable identifiers for biological entities, describe their relationships with each other (in accordance with the central dogma of biology), and store equivalences between identified entities in the source databases. Only core data will be stored in Integr8, with web links to the source databases providing further information. Integr8 will provide the integrative layer of the next generation of bioinformatics services from the EBI. Web-based interfaces will be developed to offer gene-centric views of the integrated data, presenting (where known) the links between genome, proteome and phenotype.

  16. Correlation analysis of the Taurus molecular cloud complex

    International Nuclear Information System (INIS)

    Kleiner, S.C.

    1985-01-01

    Autocorrelation and power spectrum methods were applied to the analysis of the density and velocity structure of the Taurus Complex and Heiles Cloud 2 as traced out by 13 CO J = 1 → 0 molecular line observations obtained with the 14m antenna of the Five College Radio Astronomy Observatory. Statistically significant correlations in the spacing of density fluctuations within the Taurus Complex and Heiles 2 were uncovered. The length scales of the observed correlations correspond in magnitude to the Jeans wavelengths characterizing gravitational instabilities with (i) interstellar atomic hydrogen gas for the case of the Taurus complex, and (ii) molecular hydrogen for Heiles 2. The observed correlations may be the signatures of past and current gravitational instabilities frozen into the structure of the molecular gas. The appendices provide a comprehensive description of the analytical and numerical methods developed for the correlation analysis of molecular clouds

  17. Fragrance analysis using molecular and biochemical methods in ...

    African Journals Online (AJOL)

    admin

    Biochemical analysis of aroma was performed with the 1.7% KOH solution and molecular analysis of aroma was carried out with microsatellite markers present on chromosome 8 (BAD2, BADEX7-5, SCUSSR1) to determine the extent of association between trait, marker and chromosome 8. Among these markers, BAD2 ...

  18. Molecular responses and expression analysis of genes in a ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-06-17

    Jun 17, 2009 ... Molecular responses and expression analysis of genes in a xerophytic desert shrub Haloxylon ammodendron .... physiological determination and cDNA-AFLP analysis, three groups of seeds were sowed in pots with sand and .... HaDR27. U. 234. PDR-like ABC transporter. AT1G59870. HaDR28. U. 135.

  19. Parallel processing of structural integrity analysis codes

    International Nuclear Information System (INIS)

    Swami Prasad, P.; Dutta, B.K.; Kushwaha, H.S.

    1996-01-01

    Structural integrity analysis forms an important role in assessing and demonstrating the safety of nuclear reactor components. This analysis is performed using analytical tools such as Finite Element Method (FEM) with the help of digital computers. The complexity of the problems involved in nuclear engineering demands high speed computation facilities to obtain solutions in reasonable amount of time. Parallel processing systems such as ANUPAM provide an efficient platform for realising the high speed computation. The development and implementation of software on parallel processing systems is an interesting and challenging task. The data and algorithm structure of the codes plays an important role in exploiting the parallel processing system capabilities. Structural analysis codes based on FEM can be divided into two categories with respect to their implementation on parallel processing systems. The first category codes such as those used for harmonic analysis, mechanistic fuel performance codes need not require the parallelisation of individual modules of the codes. The second category of codes such as conventional FEM codes require parallelisation of individual modules. In this category, parallelisation of equation solution module poses major difficulties. Different solution schemes such as domain decomposition method (DDM), parallel active column solver and substructuring method are currently used on parallel processing systems. Two codes, FAIR and TABS belonging to each of these categories have been implemented on ANUPAM. The implementation details of these codes and the performance of different equation solvers are highlighted. (author). 5 refs., 12 figs., 1 tab

  20. Office of Integrated Assessment and Policy Analysis

    International Nuclear Information System (INIS)

    Parzyck, D.C.

    1980-01-01

    The mission of the Office of Integrated Assessments and Policy Analysis (OIAPA) is to examine current and future policies related to the development and use of energy technologies. The principal ongoing research activity to date has focused on the impacts of several energy sources, including coal, oil shale, solar, and geothermal, from the standpoint of the Resource Conservation and Recovery Act. An additional project has recently been initiated on an evaluation of impacts associated with the implementation of the Toxic Substances Control Act. The impacts of the Resource Conservation and Recovery Act and the Toxic Substances Control Act on energy supply constitute the principal research focus of OIAPA for the near term. From these studies a research approach will be developed to identify certain common elements in the regulatory evaluation cycle as a means of evaluating subsequent environmental, health, and socioeconomic impact. It is planned that an integrated assessment team examine studies completed or underway on the following aspects of major regulations: health, risk assessment, testing protocols, environment control cost/benefits, institutional structures, and facility siting. This examination would assess the methodologies used, determine the general applicability of such studies, and present in a logical form information that appears to have broad general application. A suggested action plan for the State of Tennessee on radioactive and hazardous waste management is outlined

  1. Integrating Data Transformation in Principal Components Analysis

    KAUST Repository

    Maadooliat, Mehdi

    2015-01-02

    Principal component analysis (PCA) is a popular dimension reduction method to reduce the complexity and obtain the informative aspects of high-dimensional datasets. When the data distribution is skewed, data transformation is commonly used prior to applying PCA. Such transformation is usually obtained from previous studies, prior knowledge, or trial-and-error. In this work, we develop a model-based method that integrates data transformation in PCA and finds an appropriate data transformation using the maximum profile likelihood. Extensions of the method to handle functional data and missing values are also developed. Several numerical algorithms are provided for efficient computation. The proposed method is illustrated using simulated and real-world data examples.

  2. Toward molecular trait-based ecology through integration of biogeochemical, geographical and metagenomic data

    DEFF Research Database (Denmark)

    Raes, Jeroen; Letunic, Ivica; Yamada, Takuji

    2011-01-01

    Using metagenomic 'parts lists' to infer global patterns on microbial ecology remains a significant challenge. To deduce important ecological indicators such as environmental adaptation, molecular trait dispersal, diversity variation and primary production from the gene pool of an ecosystem, we...... integrated 25 ocean metagenomes with geographical, meteorological and geophysicochemical data. We find that climatic factors (temperature, sunlight) are the major determinants of the biomolecular repertoire of each sample and the main limiting factor on functional trait dispersal (absence of biogeographic...... provincialism). Molecular functional richness and diversity show a distinct latitudinal gradient peaking at 20° N and correlate with primary production. The latter can also be predicted from the molecular functional composition of an environmental sample. Together, our results show that the functional community...

  3. Integration of metabolomics and proteomics in molecular plant physiology--coping with the complexity by data-dimensionality reduction.

    Science.gov (United States)

    Weckwerth, Wolfram

    2008-02-01

    In recent years, genomics has been extended to functional genomics. Toward the characterization of organisms or species on the genome level, changes on the metabolite and protein level have been shown to be essential to assign functions to genes and to describe the dynamic molecular phenotype. Gas chromatography (GC) and liquid chromatography coupled to mass spectrometry (GC- and LC-MS) are well suited for the fast and comprehensive analysis of ultracomplex metabolite samples. For the integration of metabolite profiles with quantitative protein profiles, a high throughput (HTP) shotgun proteomics approach using LC-MS and label-free quantification of unique proteins in a complex protein digest is described. Multivariate statistics are applied to examine sample pattern recognition based on data-dimensionality reduction and biomarker identification in plant systems biology. The integration of the data reveal multiple correlative biomarkers providing evidence for an increase of information in such holistic approaches. With computational simulation of metabolic networks and experimental measurements, it can be shown that biochemical regulation is reflected by metabolite network dynamics measured in a metabolomics approach. Examples in molecular plant physiology are presented to substantiate the integrative approach.

  4. Molecular Eigensolution Symmetry Analysis and Fine Structure

    Directory of Open Access Journals (Sweden)

    William G. Harter

    2013-01-01

    Full Text Available Spectra of high-symmetry molecules contain fine and superfine level cluster structure related to J-tunneling between hills and valleys on rovibronic energy surfaces (RES. Such graphic visualizations help disentangle multi-level dynamics, selection rules, and state mixing effects including widespread violation of nuclear spin symmetry species. A review of RES analysis compares it to that of potential energy surfaces (PES used in Born-Oppenheimer approximations. Both take advantage of adiabatic coupling in order to visualize Hamiltonian eigensolutions. RES of symmetric and D2 asymmetric top rank-2-tensor Hamiltonians are compared with Oh spherical top rank-4-tensor fine-structure clusters of 6-fold and 8-fold tunneling multiplets. Then extreme 12-fold and 24-fold multiplets are analyzed by RES plots of higher rank tensor Hamiltonians. Such extreme clustering is rare in fundamental bands but prevalent in hot bands, and analysis of its superfine structure requires more efficient labeling and a more powerful group theory. This is introduced using elementary examples involving two groups of order-6 (C6 and D3~C3v, then applied to families of Oh clusters in SF6 spectra and to extreme clusters.

  5. Molecular thermal transistor: Dimension analysis and mechanism

    Science.gov (United States)

    Behnia, S.; Panahinia, R.

    2018-04-01

    Recently, large challenge has been spent to realize high efficient thermal transistors. Outstanding properties of DNA make it as an excellent nano material in future technologies. In this paper, we introduced a high efficient DNA based thermal transistor. The thermal transistor operates when the system shows an increase in the thermal flux despite of decreasing temperature gradient. This is what called as negative differential thermal resistance (NDTR). Based on multifractal analysis, we could distinguish regions with NDTR state from non-NDTR state. Moreover, Based on dimension spectrum of the system, it is detected that NDTR state is accompanied by ballistic transport regime. The generalized correlation sum (analogous to specific heat) shows that an irregular decrease in the specific heat induces an increase in the mean free path (mfp) of phonons. This leads to the occurrence of NDTR.

  6. Online molecular image repository and analysis system: A multicenter collaborative open-source infrastructure for molecular imaging research and application.

    Science.gov (United States)

    Rahman, Mahabubur; Watabe, Hiroshi

    2018-05-01

    Molecular imaging serves as an important tool for researchers and clinicians to visualize and investigate complex biochemical phenomena using specialized instruments; these instruments are either used individually or in combination with targeted imaging agents to obtain images related to specific diseases with high sensitivity, specificity, and signal-to-noise ratios. However, molecular imaging, which is a multidisciplinary research field, faces several challenges, including the integration of imaging informatics with bioinformatics and medical informatics, requirement of reliable and robust image analysis algorithms, effective quality control of imaging facilities, and those related to individualized disease mapping, data sharing, software architecture, and knowledge management. As a cost-effective and open-source approach to address these challenges related to molecular imaging, we develop a flexible, transparent, and secure infrastructure, named MIRA, which stands for Molecular Imaging Repository and Analysis, primarily using the Python programming language, and a MySQL relational database system deployed on a Linux server. MIRA is designed with a centralized image archiving infrastructure and information database so that a multicenter collaborative informatics platform can be built. The capability of dealing with metadata, image file format normalization, and storing and viewing different types of documents and multimedia files make MIRA considerably flexible. With features like logging, auditing, commenting, sharing, and searching, MIRA is useful as an Electronic Laboratory Notebook for effective knowledge management. In addition, the centralized approach for MIRA facilitates on-the-fly access to all its features remotely through any web browser. Furthermore, the open-source approach provides the opportunity for sustainable continued development. MIRA offers an infrastructure that can be used as cross-boundary collaborative MI research platform for the rapid

  7. Proteomic-Biostatistic Integrated Approach for Finding the Underlying Molecular Determinants of Hypertension in Human Plasma.

    Science.gov (United States)

    Gajjala, Prathibha R; Jankowski, Vera; Heinze, Georg; Bilo, Grzegorz; Zanchetti, Alberto; Noels, Heidi; Liehn, Elisa; Perco, Paul; Schulz, Anna; Delles, Christian; Kork, Felix; Biessen, Erik; Narkiewicz, Krzysztof; Kawecka-Jaszcz, Kalina; Floege, Juergen; Soranna, Davide; Zidek, Walter; Jankowski, Joachim

    2017-08-01

    Despite advancements in lowering blood pressure, the best approach to lower it remains controversial because of the lack of information on the molecular basis of hypertension. We, therefore, performed plasma proteomics of plasma from patients with hypertension to identify molecular determinants detectable in these subjects but not in controls and vice versa. Plasma samples from hypertensive subjects (cases; n=118) and controls (n=85) from the InGenious HyperCare cohort were used for this study and performed mass spectrometric analysis. Using biostatistical methods, plasma peptides specific for hypertension were identified, and a model was developed using least absolute shrinkage and selection operator logistic regression. The underlying peptides were identified and sequenced off-line using matrix-assisted laser desorption ionization orbitrap mass spectrometry. By comparison of the molecular composition of the plasma samples, 27 molecular determinants were identified differently expressed in cases from controls. Seventy percent of the molecular determinants selected were found to occur less likely in hypertensive patients. In cross-validation, the overall R 2 was 0.434, and the area under the curve was 0.891 with 95% confidence interval 0.8482 to 0.9349, P hypertensive patients were found to be -2.007±0.3568 and 3.383±0.2643, respectively, P hypertensives and normotensives. The identified molecular determinants may be the starting point for further studies to clarify the molecular causes of hypertension. © 2017 American Heart Association, Inc.

  8. Molecular analysis of deep subsurface bacteria

    International Nuclear Information System (INIS)

    Jimenez Baez, L.E.

    1989-09-01

    Deep sediments samples from site C10a, in Appleton, and sites, P24, P28, and P29, at the Savannah River Site (SRS), near Aiken, South Carolina were studied to determine their microbial community composition, DNA homology and mol %G+C. Different geological formations with great variability in hydrogeological parameters were found across the depth profile. Phenotypic identification of deep subsurface bacteria underestimated the bacterial diversity at the three SRS sites, since bacteria with the same phenotype have different DNA composition and less than 70% DNA homology. Total DNA hybridization and mol %G+C analysis of deep sediment bacterial isolates suggested that each formation is comprised of different microbial communities. Depositional environment was more important than site and geological formation on the DNA relatedness between deep subsurface bacteria, since more 70% of bacteria with 20% or more of DNA homology came from the same depositional environments. Based on phenotypic and genotypic tests Pseudomonas spp. and Acinetobacter spp.-like bacteria were identified in 85 million years old sediments. This suggests that these microbial communities might have been adapted during a long period of time to the environmental conditions of the deep subsurface

  9. Personalizing Chinese medicine by integrating molecular features of diseases and herb ingredient information: application to acute myeloid leukemia.

    Science.gov (United States)

    Huang, Lin; Li, Haichang; Xie, Duoli; Shi, Tieliu; Wen, Chengping

    2017-06-27

    Traditional Chinese Medicine (TCM) has been widely used as a complementary medicine in Acute Myeloid Leukemia (AML) treatment. In this study, we proposed a new classification of Chinese Medicines (CMs) by integrating the latest discoveries in disease molecular mechanisms and traditional medicine theory. We screened out a set of chemical compounds on basis of AML differential expression genes and chemical-protein interactions and then mapped them to Traditional Chinese Medicine Integrated Database. 415 CMs contain those compounds and they were categorized into 8 groups according to the Traditional Chinese Pharmacology. Pathway analysis and synthetic lethality gene pairs were applied to analyze the dissimilarity, generality and intergroup relations of different groups. We defined hub CM pairs and alternative CM groups based on the analysis result and finally proposed a formula to form an effective anti-AML prescription which combined the hub CM pairs with alternative CMs according to patients' molecular features. Our method of formulating CMs based on patients' stratification provides novel insights into the new usage of conventional CMs and will promote TCM modernization.

  10. Qualitative Analysis of Integration Adapter Modeling

    OpenAIRE

    Ritter, Daniel; Holzleitner, Manuel

    2015-01-01

    Integration Adapters are a fundamental part of an integration system, since they provide (business) applications access to its messaging channel. However, their modeling and configuration remain under-represented. In previous work, the integration control and data flow syntax and semantics have been expressed in the Business Process Model and Notation (BPMN) as a semantic model for message-based integration, while adapter and the related quality of service modeling were left for further studi...

  11. Fabrication of reproducible, integration-compatible hybrid molecular/si electronics.

    Science.gov (United States)

    Yu, Xi; Lovrinčić, Robert; Kraynis, Olga; Man, Gabriel; Ely, Tal; Zohar, Arava; Toledano, Tal; Cahen, David; Vilan, Ayelet

    2014-12-29

    Reproducible molecular junctions can be integrated within standard CMOS technology. Metal-molecule-semiconductor junctions are fabricated by direct Si-C binding of hexadecane or methyl-styrene onto oxide-free H-Si(111) surfaces, with the lateral size of the junctions defined by an etched SiO2 well and with evaporated Pb as the top contact. The current density, J, is highly reproducible with a standard deviation in log(J) of 0.2 over a junction diameter change from 3 to 100 μm. Reproducibility over such a large range indicates that transport is truly across the molecules and does not result from artifacts like edge effects or defects in the molecular monolayer. Device fabrication is tested for two n-Si doping levels. With highly doped Si, transport is dominated by tunneling and reveals sharp conductance onsets at room temperature. Using the temperature dependence of current across medium-doped n-Si, the molecular tunneling barrier can be separated from the Si-Schottky one, which is a 0.47 eV, in agreement with the molecular-modified surface dipole and quite different from the bare Si-H junction. This indicates that Pb evaporation does not cause significant chemical changes to the molecules. The ability to manufacture reliable devices constitutes important progress toward possible future hybrid Si-based molecular electronics. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. PHIDIAS- Pathogen Host Interaction Data Integration and Analysis

    Indian Academy of Sciences (India)

    PHIDIAS- Pathogen Host Interaction Data Integration and Analysis- allows searching of integrated genome sequences, conserved domains and gene expressions data related to pathogen host interactions in high priority agents for public health and security ...

  13. Molecular analysis of Ku redox regulation

    Directory of Open Access Journals (Sweden)

    Shatilla Andrea

    2009-08-01

    Full Text Available Abstract Background DNA double-strand breaks (DSBs can occur in response to ionizing radiation (IR, radiomimetic agents and from endogenous DNA-damaging reactive oxygen metabolites. Unrepaired or improperly repaired DSBs are potentially the most lethal form of DNA damage and can result in chromosomal translocations and contribute to the development of cancer. The principal mechanism for the repair of DSBs in humans is non-homologous end-joining (NHEJ. Ku is a key member of the NHEJ pathway and plays an important role in the recognition step when it binds to free DNA termini. Ku then stimulates the assembly and activation of other NHEJ components. DNA binding of Ku is regulated by redox conditions and evidence from our laboratory has demonstrated that Ku undergoes structural changes when oxidized that results in a reduction in DNA binding activity. The C-terminal domain and cysteine 493 of Ku80 were investigated for their contribution to redox regulation of Ku. Results We effectively removed the C-terminal domain of Ku80 generating a truncation mutant and co-expressed this variant with wild type Ku70 in an insect cell system to create a Ku70/80ΔC heterodimer. We also generated two single amino acid variants of Cys493, replacing this amino acid with either an alanine (C493A or a serine (C493S, and over-expressed the variant proteins in SF9 insect cells in complex with wild type Ku70. Neither the truncation nor the amino acid substitutions alters protein expression or stability as determined by SDS-PAGE and Western blot analysis. We show that the C493 mutations do not alter the ability of Ku to bind duplex DNA in vitro under reduced conditions while truncation of the Ku80 C-terminus slightly reduced DNA binding affinity. Diamide oxidation of cysteines was shown to inhibit DNA binding similarly for both the wild-type and all variant proteins. Interestingly, differential DNA binding activity following re-reduction was observed for the Ku70/80

  14. Analysis of the normal optical, Michel and molecular potentials on ...

    Indian Academy of Sciences (India)

    6. — journal of. June 2016 physics pp. 1275–1286. Analysis of the normal ... the levels are obtained for the three optical potentials to estimate the quality ... The experimental angular distribution data for the 40Ca(6Li, d)44Ti reaction .... analysed using the normal optical, Michel and molecular potentials within the framework.

  15. Molecular characterization and expression analysis of fat mass and ...

    Indian Academy of Sciences (India)

    Keywords. fat mass and obesity-associated gene (FTO); rabbit; mRNA expression patterns; sequence analysis; Oryctolagus cuniculus. ... In this work, the molecular characterization and expression features of rabbit (Oryctolagus cuniculus) FTO cDNA were analysed. The rabbit FTO cDNA with a size of 2158 bp was cloned, ...

  16. Fragrance analysis using molecular and biochemical methods in ...

    African Journals Online (AJOL)

    For molecular and biochemical analysis of aroma, a mapping population comprising 208 recombinant inbred lines (RILs) derived from a diverse cross between CSR10 and Taraori Basmati through Single seed descent (SSD) method was used. RILs are among the best mapping populations, which provide a novel material ...

  17. A Molecular Iodine Spectral Data Set for Rovibronic Analysis

    Science.gov (United States)

    Williamson, J. Charles; Kuntzleman, Thomas S.; Kafader, Rachael A.

    2013-01-01

    A data set of 7,381 molecular iodine vapor rovibronic transitions between the X and B electronic states has been prepared for an advanced undergraduate spectroscopic analysis project. Students apply standard theoretical techniques to these data and determine the values of three X-state constants (image omitted) and four B-state constants (image…

  18. Total and Direct Correlation Function Integrals from Molecular Simulation of Binary Systems

    DEFF Research Database (Denmark)

    Wedberg, Nils Hejle Rasmus Ingemar; O’Connell, John P.; Peters, Günther H.J.

    2011-01-01

    The possibility for obtaining derivative properties for mixtures from integrals of spatial total and direct correlation functions obtained from molecular dynamics simulations is explored. Theoretically well-supported methods are examined to extend simulation radial distribution functions to long...... are consistent with an excess Helmholtz energy model fitted to available simulations. In addition, simulations of water/methanol and water/t-butanol mixtures have been carried out. The method yields results for partial molar volumes, activity coefficient derivatives, and individual correlation function integrals...... in reasonable agreement with smoothed experimental data. The proposed method for obtaining correlation function integrals is shown to perform at least as well as or better than two previously published approaches....

  19. Migration in Deltas: An Integrated Analysis

    Science.gov (United States)

    Nicholls, Robert J.; Hutton, Craig W.; Lazar, Attila; Adger, W. Neil; Allan, Andrew; Arto, Inaki; Vincent, Katharine; Rahman, Munsur; Salehin, Mashfiqus; Sugata, Hazra; Ghosh, Tuhin; Codjoe, Sam; Appeaning-Addo, Kwasi

    2017-04-01

    Deltas and low-lying coastal regions have long been perceived as vulnerable to global sea-level rise, with the potential for mass displacement of exposed populations. The assumption of mass displacement of populations in deltas requires a comprehensive reassessment in the light of present and future migration in deltas, including the potential role of adaptation to influence these decisions. At present, deltas are subject to multiple drivers of environmental change and often have high population densities as they are accessible and productive ecosystems. Climate change, catchment management, subsidence and land cover change drive environmental change across all deltas. Populations in deltas are also highly mobile, with significant urbanization trends and the growth of large cities and mega-cities within or adjacent to deltas across Asia and Africa. Such migration is driven primarily by economic opportunity, yet environmental change in general, and climate change in particular, are likely to play an increasing direct and indirect role in future migration trends. The policy challenges centre on the role of migration within regional adaptation strategies to climate change; the protection of vulnerable populations; and the future of urban settlements within deltas. This paper reviews current knowledge on migration and adaptation to environmental change to discern specific issues pertinent to delta regions. It develops a new integrated methodology to assess present and future migration in deltas using the Volta delta in Ghana, Mahanadi delta in India and Ganges-Brahmaputra-Meghna delta across India and Bangladesh. The integrated method focuses on: biophysical changes and spatial distribution of vulnerability; demographic changes and migration decision-making using multiple methods and data; macro-economic trends and scenarios in the deltas; and the policies and governance structures that constrain and enable adaptation. The analysis is facilitated by a range of

  20. Importance and pitfalls of molecular analysis to parasite epidemiology.

    Science.gov (United States)

    Constantine, Clare C

    2003-08-01

    Molecular tools are increasingly being used to address questions about parasite epidemiology. Parasites represent a diverse group and they might not fit traditional population genetic models. Testing hypotheses depends equally on correct sampling, appropriate tool and/or marker choice, appropriate analysis and careful interpretation. All methods of analysis make assumptions which, if violated, make the results invalid. Some guidelines to avoid common pitfalls are offered here.

  1. Conformational analysis of oligosaccharides and polysaccharides using molecular dynamics simulations.

    Science.gov (United States)

    Frank, Martin

    2015-01-01

    Complex carbohydrates usually have a large number of rotatable bonds and consequently a large number of theoretically possible conformations can be generated (combinatorial explosion). The application of systematic search methods for conformational analysis of carbohydrates is therefore limited to disaccharides and trisaccharides in a routine analysis. An alternative approach is to use Monte-Carlo methods or (high-temperature) molecular dynamics (MD) simulations to explore the conformational space of complex carbohydrates. This chapter describes how to use MD simulation data to perform a conformational analysis (conformational maps, hydrogen bonds) of oligosaccharides and how to build realistic 3D structures of large polysaccharides using Conformational Analysis Tools (CAT).

  2. Integration of pharmacology, molecular pathology, and population data science to support precision gastrointestinal oncology.

    Science.gov (United States)

    Ogino, Shuji; Jhun, Iny; Mata, Douglas A; Soong, Thing Rinda; Hamada, Tsuyoshi; Liu, Li; Nishihara, Reiko; Giannakis, Marios; Cao, Yin; Manson, JoAnn E; Nowak, Jonathan A; Chan, Andrew T

    2017-01-01

    Precision medicine has a goal of customizing disease prevention and treatment strategies. Under the precision medicine paradigm, each patient has unique pathologic processes resulting from cellular genomic, epigenomic, proteomic, and metabolomic alterations, which are influenced by pharmacological, environmental, microbial, dietary, and lifestyle factors. Hence, to realize the promise of precision medicine, multi-level research methods that can comprehensively analyze many of these variables are needed. In order to address this gap, the integrative field of molecular pathology and population data science (i.e., molecular pathological epidemiology) has been developed to enable such multi-level analyses, especially in gastrointestinal cancer research. Further integration of pharmacology can improve our understanding of drug effects, and inform decision-making of drug use at both the individual and population levels. Such integrative research demonstrated potential benefits of aspirin in colorectal carcinoma with PIK3CA mutations, providing the basis for new clinical trials. Evidence also suggests that HPGD (15-PDGH) expression levels in normal colon and the germline rs6983267 polymorphism that relates to tumor CTNNB1 (β-catenin)/ WNT signaling status may predict the efficacy of aspirin for cancer chemoprevention. As immune checkpoint blockade targeting the CD274 (PD-L1)/ PDCD1 (PD-1) pathway for microsatellite instability-high (or mismatch repair-deficient) metastatic gastrointestinal or other tumors has become standard of care, potential modifying effects of dietary, lifestyle, microbial, and environmental factors on immunotherapy need to be studied to further optimize treatment strategies. With its broad applicability, our integrative approach can provide insights into the interactive role of medications, exposures, and molecular pathology, and guide the development of precision medicine.

  3. Integration of risk analysis, land use planning, and cost analysis

    International Nuclear Information System (INIS)

    Rajen, G.; Sanchez, G.

    1994-01-01

    The Department of Energy (DOE) and the Pueblo of San Ildefonso (Pueblo), which is a sovereign Indian tribe, have often been involved in adversarial situations regarding the Los Alamos National Laboratory (LANL). The Pueblo shares a common boundary with the LANL. This paper describes an on-going project that could alter the DOE and the Pueblo's relationship to one of cooperation; and unite the DOE and the Pueblo in a Pollution Prevention/Waste Minimization, and Integrated Risk Analysis and Land Use Planning effort

  4. MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms.

    Science.gov (United States)

    Kumar, Sudhir; Stecher, Glen; Li, Michael; Knyaz, Christina; Tamura, Koichiro

    2018-06-01

    The Molecular Evolutionary Genetics Analysis (Mega) software implements many analytical methods and tools for phylogenomics and phylomedicine. Here, we report a transformation of Mega to enable cross-platform use on Microsoft Windows and Linux operating systems. Mega X does not require virtualization or emulation software and provides a uniform user experience across platforms. Mega X has additionally been upgraded to use multiple computing cores for many molecular evolutionary analyses. Mega X is available in two interfaces (graphical and command line) and can be downloaded from www.megasoftware.net free of charge.

  5. IMP: Integrated method for power analysis

    Energy Technology Data Exchange (ETDEWEB)

    1989-03-01

    An integrated, easy to use, economical package of microcomputer programs has been developed which can be used by small hydro developers to evaluate potential sites for small scale hydroelectric plants in British Columbia. The programs enable evaluation of sites located far from the nearest stream gauging station, for which streamflow data are not available. For each of the province's 6 hydrologic regions, a streamflow record for one small watershed is provided in the data base. The program can then be used to generate synthetic streamflow records and to compare results obtained by the modelling procedure with the actual data. The program can also be used to explore the significance of modelling parameters and to develop a detailed appreciation for the accuracy which can be obtained under various circumstances. The components of the program are an atmospheric model of precipitation; a watershed model that will generate a continuous series of streamflow data, based on information from the atmospheric model; a flood frequency analysis system that uses site-specific topographic data plus information from the atmospheric model to generate a flood frequency curve; a hydroelectric power simulation program which determines daily energy output for a run-of-river or reservoir storage site based on selected generation facilities and the time series generated in the watershed model; and a graphic analysis package that provides direct visualization of data and modelling results. This report contains a description of the programs, a user guide, the theory behind the model, the modelling methodology, and results from a workshop that reviewed the program package. 32 refs., 16 figs., 18 tabs.

  6. K West integrated water treatment system subproject safety analysis document

    International Nuclear Information System (INIS)

    SEMMENS, L.S.

    1999-01-01

    This Accident Analysis evaluates unmitigated accident scenarios, and identifies Safety Significant and Safety Class structures, systems, and components for the K West Integrated Water Treatment System

  7. K West integrated water treatment system subproject safety analysis document

    Energy Technology Data Exchange (ETDEWEB)

    SEMMENS, L.S.

    1999-02-24

    This Accident Analysis evaluates unmitigated accident scenarios, and identifies Safety Significant and Safety Class structures, systems, and components for the K West Integrated Water Treatment System.

  8. Integrating health and environmental impact analysis.

    Science.gov (United States)

    Reis, S; Morris, G; Fleming, L E; Beck, S; Taylor, T; White, M; Depledge, M H; Steinle, S; Sabel, C E; Cowie, H; Hurley, F; Dick, J McP; Smith, R I; Austen, M

    2015-10-01

    Scientific investigations have progressively refined our understanding of the influence of the environment on human health, and the many adverse impacts that human activities exert on the environment, from the local to the planetary level. Nonetheless, throughout the modern public health era, health has been pursued as though our lives and lifestyles are disconnected from ecosystems and their component organisms. The inadequacy of the societal and public health response to obesity, health inequities, and especially global environmental and climate change now calls for an ecological approach which addresses human activity in all its social, economic and cultural complexity. The new approach must be integral to, and interactive, with the natural environment. We see the continuing failure to truly integrate human health and environmental impact analysis as deeply damaging, and we propose a new conceptual model, the ecosystems-enriched Drivers, Pressures, State, Exposure, Effects, Actions or 'eDPSEEA' model, to address this shortcoming. The model recognizes convergence between the concept of ecosystems services which provides a human health and well-being slant to the value of ecosystems while equally emphasizing the health of the environment, and the growing calls for 'ecological public health' as a response to global environmental concerns now suffusing the discourse in public health. More revolution than evolution, ecological public health will demand new perspectives regarding the interconnections among society, the economy, the environment and our health and well-being. Success must be built on collaborations between the disparate scientific communities of the environmental sciences and public health as well as interactions with social scientists, economists and the legal profession. It will require outreach to political and other stakeholders including a currently largely disengaged general public. The need for an effective and robust science-policy interface has

  9. Integration of Chinese medicine with Western medicine could lead to future medicine: molecular module medicine.

    Science.gov (United States)

    Zhang, Chi; Zhang, Ge; Chen, Ke-ji; Lu, Ai-ping

    2016-04-01

    The development of an effective classification method for human health conditions is essential for precise diagnosis and delivery of tailored therapy to individuals. Contemporary classification of disease systems has properties that limit its information content and usability. Chinese medicine pattern classification has been incorporated with disease classification, and this integrated classification method became more precise because of the increased understanding of the molecular mechanisms. However, we are still facing the complexity of diseases and patterns in the classification of health conditions. With continuing advances in omics methodologies and instrumentation, we are proposing a new classification approach: molecular module classification, which is applying molecular modules to classifying human health status. The initiative would be precisely defining the health status, providing accurate diagnoses, optimizing the therapeutics and improving new drug discovery strategy. Therefore, there would be no current disease diagnosis, no disease pattern classification, and in the future, a new medicine based on this classification, molecular module medicine, could redefine health statuses and reshape the clinical practice.

  10. Automated Analysis and Classification of Histological Tissue Features by Multi-Dimensional Microscopic Molecular Profiling.

    Directory of Open Access Journals (Sweden)

    Daniel P Riordan

    Full Text Available Characterization of the molecular attributes and spatial arrangements of cells and features within complex human tissues provides a critical basis for understanding processes involved in development and disease. Moreover, the ability to automate steps in the analysis and interpretation of histological images that currently require manual inspection by pathologists could revolutionize medical diagnostics. Toward this end, we developed a new imaging approach called multidimensional microscopic molecular profiling (MMMP that can measure several independent molecular properties in situ at subcellular resolution for the same tissue specimen. MMMP involves repeated cycles of antibody or histochemical staining, imaging, and signal removal, which ultimately can generate information analogous to a multidimensional flow cytometry analysis on intact tissue sections. We performed a MMMP analysis on a tissue microarray containing a diverse set of 102 human tissues using a panel of 15 informative antibody and 5 histochemical stains plus DAPI. Large-scale unsupervised analysis of MMMP data, and visualization of the resulting classifications, identified molecular profiles that were associated with functional tissue features. We then directly annotated H&E images from this MMMP series such that canonical histological features of interest (e.g. blood vessels, epithelium, red blood cells were individually labeled. By integrating image annotation data, we identified molecular signatures that were associated with specific histological annotations and we developed statistical models for automatically classifying these features. The classification accuracy for automated histology labeling was objectively evaluated using a cross-validation strategy, and significant accuracy (with a median per-pixel rate of 77% per feature from 15 annotated samples for de novo feature prediction was obtained. These results suggest that high-dimensional profiling may advance the

  11. Noise analysis of switched integrator preamplifiers

    International Nuclear Information System (INIS)

    Sun Hongbo; Li Yulan; Zhu Weibin

    2004-01-01

    The main noise sources of switched integrator preamplifiers are discussed, and their noise performance are given combined PSpice simulation and experiments on them. Then, some practical methods on how to reduce noise of preamplifiers in two different integrator modes are provided. (authors)

  12. Social Ecological Model Analysis for ICT Integration

    Science.gov (United States)

    Zagami, Jason

    2013-01-01

    ICT integration of teacher preparation programmes was undertaken by the Australian Teaching Teachers for the Future (TTF) project in all 39 Australian teacher education institutions and highlighted the need for guidelines to inform systemic ICT integration approaches. A Social Ecological Model (SEM) was used to positively inform integration…

  13. Molecular radiotherapy: The NUKFIT software for calculating the time-integrated activity coefficient

    Energy Technology Data Exchange (ETDEWEB)

    Kletting, P.; Schimmel, S.; Luster, M. [Klinik für Nuklearmedizin, Universität Ulm, Ulm 89081 (Germany); Kestler, H. A. [Research Group Bioinformatics and Systems Biology, Institut für Neuroinformatik, Universität Ulm, Ulm 89081 (Germany); Hänscheid, H.; Fernández, M.; Lassmann, M. [Klinik für Nuklearmedizin, Universität Würzburg, Würzburg 97080 (Germany); Bröer, J. H.; Nosske, D. [Bundesamt für Strahlenschutz, Fachbereich Strahlenschutz und Gesundheit, Oberschleißheim 85764 (Germany); Glatting, G. [Medical Radiation Physics/Radiation Protection, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167 (Germany)

    2013-10-15

    Purpose: Calculation of the time-integrated activity coefficient (residence time) is a crucial step in dosimetry for molecular radiotherapy. However, available software is deficient in that it is either not tailored for the use in molecular radiotherapy and/or does not include all required estimation methods. The aim of this work was therefore the development and programming of an algorithm which allows for an objective and reproducible determination of the time-integrated activity coefficient and its standard error.Methods: The algorithm includes the selection of a set of fitting functions from predefined sums of exponentials and the choice of an error model for the used data. To estimate the values of the adjustable parameters an objective function, depending on the data, the parameters of the error model, the fitting function and (if required and available) Bayesian information, is minimized. To increase reproducibility and user-friendliness the starting values are automatically determined using a combination of curve stripping and random search. Visual inspection, the coefficient of determination, the standard error of the fitted parameters, and the correlation matrix are provided to evaluate the quality of the fit. The functions which are most supported by the data are determined using the corrected Akaike information criterion. The time-integrated activity coefficient is estimated by analytically integrating the fitted functions. Its standard error is determined assuming Gaussian error propagation. The software was implemented using MATLAB.Results: To validate the proper implementation of the objective function and the fit functions, the results of NUKFIT and SAAM numerical, a commercially available software tool, were compared. The automatic search for starting values was successfully tested for reproducibility. The quality criteria applied in conjunction with the Akaike information criterion allowed the selection of suitable functions. Function fit

  14. Path integral centroid molecular dynamics simulations of semiinfinite slab and bulk liquid of para-hydrogen

    Energy Technology Data Exchange (ETDEWEB)

    Kinugawa, Kenichi [Nara Women`s Univ., Nara (Japan). Dept. of Chemistry

    1998-10-01

    It has been unsuccessful to solve a set of time-dependent Schroedinger equations numerically for many-body quantum systems which involve, e.g., a number of hydrogen molecules, protons, and excess electrons at a low temperature, where quantum effect evidently appears. This undesirable situation is fatal for the investigation of real low-temperature chemical systems because they are essentially composed of many quantum degrees of freedom. However, if we use a new technique called `path integral centroid molecular dynamics (CMD) simulation` proposed by Cao and Voth in 1994, the real-time semi-classical dynamics of many degrees of freedom can be computed by utilizing the techniques already developed in the traditional classical molecular dynamics (MD) simulations. Therefore, the CMD simulation is expected to be very powerful tool for the quantum dynamics studies or real substances. (J.P.N.)

  15. PHIDIAS: a pathogen-host interaction data integration and analysis system.

    Science.gov (United States)

    Xiang, Zuoshuang; Tian, Yuying; He, Yongqun

    2007-01-01

    The Pathogen-Host Interaction Data Integration and Analysis System (PHIDIAS) is a web-based database system that serves as a centralized source to search, compare, and analyze integrated genome sequences, conserved domains, and gene expression data related to pathogen-host interactions (PHIs) for pathogen species designated as high priority agents for public health and biological security. In addition, PHIDIAS allows submission, search and analysis of PHI genes and molecular networks curated from peer-reviewed literature. PHIDIAS is publicly available at http://www.phidias.us.

  16. Systematic study of imidazoles inhibiting IDO1 via the integration of molecular mechanics and quantum mechanics calculations.

    Science.gov (United States)

    Zou, Yi; Wang, Fang; Wang, Yan; Guo, Wenjie; Zhang, Yihua; Xu, Qiang; Lai, Yisheng

    2017-05-05

    Indoleamine 2,3-dioxygenase 1 (IDO1) is regarded as an attractive target for cancer immunotherapy. To rationalize the detailed interactions between IDO1 and its inhibitors at the atomic level, an integrated computational approach by combining molecular mechanics and quantum mechanics methods was employed in this report. Specifically, the binding modes of 20 inhibitors was initially investigated using the induced fit docking (IFD) protocol, which outperformed other two docking protocols in terms of correctly predicting ligand conformations. Secondly, molecular dynamics (MD) simulations and MM/PBSA free energy calculations were employed to determine the dynamic binding process and crucial residues were confirmed through close contact analysis, hydrogen-bond analysis and binding free energy decomposition calculations. Subsequent quantum mechanics and nonbonding interaction analysis were carried out to provide in-depth explanations on the critical role of those key residues, and Arg231 and 7-propionate of the heme group were major contributors to ligand binding, which lowed a great amount of interaction energy. We anticipate that these findings will be valuable for enzymatic studies and rational drug design. Copyright © 2017. Published by Elsevier Masson SAS.

  17. Molecular pathological epidemiology of epigenetics: emerging integrative science to analyze environment, host, and disease.

    Science.gov (United States)

    Ogino, Shuji; Lochhead, Paul; Chan, Andrew T; Nishihara, Reiko; Cho, Eunyoung; Wolpin, Brian M; Meyerhardt, Jeffrey A; Meissner, Alexander; Schernhammer, Eva S; Fuchs, Charles S; Giovannucci, Edward

    2013-04-01

    Epigenetics acts as an interface between environmental/exogenous factors, cellular responses, and pathological processes. Aberrant epigenetic signatures are a hallmark of complex multifactorial diseases (including neoplasms and malignancies such as leukemias, lymphomas, sarcomas, and breast, lung, prostate, liver, and colorectal cancers). Epigenetic signatures (DNA methylation, mRNA and microRNA expression, etc) may serve as biomarkers for risk stratification, early detection, and disease classification, as well as targets for therapy and chemoprevention. In particular, DNA methylation assays are widely applied to formalin-fixed, paraffin-embedded archival tissue specimens as clinical pathology tests. To better understand the interplay between etiological factors, cellular molecular characteristics, and disease evolution, the field of 'molecular pathological epidemiology (MPE)' has emerged as an interdisciplinary integration of 'molecular pathology' and 'epidemiology'. In contrast to traditional epidemiological research including genome-wide association studies (GWAS), MPE is founded on the unique disease principle, that is, each disease process results from unique profiles of exposomes, epigenomes, transcriptomes, proteomes, metabolomes, microbiomes, and interactomes in relation to the macroenvironment and tissue microenvironment. MPE may represent a logical evolution of GWAS, termed 'GWAS-MPE approach'. Although epigenome-wide association study attracts increasing attention, currently, it has a fundamental problem in that each cell within one individual has a unique, time-varying epigenome. Having a similar conceptual framework to systems biology, the holistic MPE approach enables us to link potential etiological factors to specific molecular pathology, and gain novel pathogenic insights on causality. The widespread application of epigenome (eg, methylome) analyses will enhance our understanding of disease heterogeneity, epigenotypes (CpG island methylator

  18. 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

  19. 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

  20. Evaluation of Kirkwood-Buff integrals via finite size scaling: a large scale molecular dynamics study

    Science.gov (United States)

    Dednam, W.; Botha, A. E.

    2015-01-01

    Solvation of bio-molecules in water is severely affected by the presence of co-solvent within the hydration shell of the solute structure. Furthermore, since solute molecules can range from small molecules, such as methane, to very large protein structures, it is imperative to understand the detailed structure-function relationship on the microscopic level. For example, it is useful know the conformational transitions that occur in protein structures. Although such an understanding can be obtained through large-scale molecular dynamic simulations, it is often the case that such simulations would require excessively large simulation times. In this context, Kirkwood-Buff theory, which connects the microscopic pair-wise molecular distributions to global thermodynamic properties, together with the recently developed technique, called finite size scaling, may provide a better method to reduce system sizes, and hence also the computational times. In this paper, we present molecular dynamics trial simulations of biologically relevant low-concentration solvents, solvated by aqueous co-solvent solutions. In particular we compare two different methods of calculating the relevant Kirkwood-Buff integrals. The first (traditional) method computes running integrals over the radial distribution functions, which must be obtained from large system-size NVT or NpT simulations. The second, newer method, employs finite size scaling to obtain the Kirkwood-Buff integrals directly by counting the particle number fluctuations in small, open sub-volumes embedded within a larger reservoir that can be well approximated by a much smaller simulation cell. In agreement with previous studies, which made a similar comparison for aqueous co-solvent solutions, without the additional solvent, we conclude that the finite size scaling method is also applicable to the present case, since it can produce computationally more efficient results which are equivalent to the more costly radial distribution

  1. Evaluation of Kirkwood-Buff integrals via finite size scaling: a large scale molecular dynamics study

    International Nuclear Information System (INIS)

    Dednam, W; Botha, A E

    2015-01-01

    Solvation of bio-molecules in water is severely affected by the presence of co-solvent within the hydration shell of the solute structure. Furthermore, since solute molecules can range from small molecules, such as methane, to very large protein structures, it is imperative to understand the detailed structure-function relationship on the microscopic level. For example, it is useful know the conformational transitions that occur in protein structures. Although such an understanding can be obtained through large-scale molecular dynamic simulations, it is often the case that such simulations would require excessively large simulation times. In this context, Kirkwood-Buff theory, which connects the microscopic pair-wise molecular distributions to global thermodynamic properties, together with the recently developed technique, called finite size scaling, may provide a better method to reduce system sizes, and hence also the computational times. In this paper, we present molecular dynamics trial simulations of biologically relevant low-concentration solvents, solvated by aqueous co-solvent solutions. In particular we compare two different methods of calculating the relevant Kirkwood-Buff integrals. The first (traditional) method computes running integrals over the radial distribution functions, which must be obtained from large system-size NVT or NpT simulations. The second, newer method, employs finite size scaling to obtain the Kirkwood-Buff integrals directly by counting the particle number fluctuations in small, open sub-volumes embedded within a larger reservoir that can be well approximated by a much smaller simulation cell. In agreement with previous studies, which made a similar comparison for aqueous co-solvent solutions, without the additional solvent, we conclude that the finite size scaling method is also applicable to the present case, since it can produce computationally more efficient results which are equivalent to the more costly radial distribution

  2. CFD Analysis for Advanced Integrated Head Assembly

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Won Ho; Kang, Tae Kyo; Cho, Yeon Ho; Kim, Hyun Min [KEPCO Engineering and Construction Co., Daejeon (Korea, Republic of)

    2016-10-15

    The Integrated Head Assembly (IHA) is permanently installed on the reactor vessel closure head during the normal plant operation and refueling operation. It consists of a number of systems and components such as the head lifting system, seismic support system, Control Element Drive Mechanism (CEDM) cooling system, cable support system, cooling shroud assemblies. With the operating experiences of the IHA, the needs for the design change to the current APR1400 IHA arouse to improve the seismic resistance and to accommodate the convenient maintenance. In this paper, the effects of the design changes were rigorously studied for the various sizes of the inlet openings to assure the proper cooling of the CEDMs. And the system pressure differentials and required flow rate for the CEDM cooling fan were analyzed regarding the various operating conditions for determining the capacity of the fan. As a part of the design process of the AIHA, the number of air inlets and baffle regions are reduced by simplifying the design of the APR1400 IHA. The design change of the baffle regions has been made such that the maximum possible space are occupied inside the IHA cooling shroud shell while avoiding the interference with CEDMs. So, only the air inlet opening was studied for the design change to supply a sufficient cooling air flow for each CEDM. The size and location of the air inlets in middle cooling shroud assembly were determined by the CFD analyses of the AIHA. And the case CFD analyses were performed depending on the ambient air temperature and fan operating conditions. The size of the air inlet openings is increased by comparison with the initial AIHA design, and it is confirmed that the cooling air flow rate for each CEDM meet the design requirement of 800 SCFM ± 10% with the increased air inlets. At the initial analysis, the fan outlet flow rate was assumed as 48.3 lbm/s, but the result revealed that the less outflow rate at the fan is enough to meet the design requirement

  3. Balancing an accurate representation of the molecular surface in generalized Born formalisms with integrator stability in molecular dynamics simulations

    Czech Academy of Sciences Publication Activity Database

    Chocholoušová, Jana; Feig, M.

    2006-01-01

    Roč. 27, č. 6 (2006), s. 719-729 ISSN 0192-8651 Keywords : molecular surface * generalized Born formalisms * molecular dynamic simulations Subject RIV: CC - Organic Chemistry Impact factor: 4.893, year: 2006

  4. Integrating open-source software applications to build molecular dynamics systems.

    Science.gov (United States)

    Allen, Bruce M; Predecki, Paul K; Kumosa, Maciej

    2014-04-05

    Three open-source applications, NanoEngineer-1, packmol, and mis2lmp are integrated using an open-source file format to quickly create molecular dynamics (MD) cells for simulation. The three software applications collectively make up the open-source software (OSS) suite known as MD Studio (MDS). The software is validated through software engineering practices and is verified through simulation of the diglycidyl ether of bisphenol-a and isophorone diamine (DGEBA/IPD) system. Multiple simulations are run using the MDS software to create MD cells, and the data generated are used to calculate density, bulk modulus, and glass transition temperature of the DGEBA/IPD system. Simulation results compare well with published experimental and numerical results. The MDS software prototype confirms that OSS applications can be analyzed against real-world research requirements and integrated to create a new capability. Copyright © 2014 Wiley Periodicals, Inc.

  5. Ab initio path-integral molecular dynamics and the quantum nature of hydrogen bonds

    International Nuclear Information System (INIS)

    Feng Yexin; Chen Ji; Wang Enge; Li Xin-Zheng

    2016-01-01

    The hydrogen bond (HB) is an important type of intermolecular interaction, which is generally weak, ubiquitous, and essential to life on earth. The small mass of hydrogen means that many properties of HBs are quantum mechanical in nature. In recent years, because of the development of computer simulation methods and computational power, the influence of nuclear quantum effects (NQEs) on the structural and energetic properties of some hydrogen bonded systems has been intensively studied. Here, we present a review of these studies by focussing on the explanation of the principles underlying the simulation methods, i.e., the ab initio path-integral molecular dynamics. Its extension in combination with the thermodynamic integration method for the calculation of free energies will also be introduced. We use two examples to show how this influence of NQEs in realistic systems is simulated in practice. (topical review)

  6. Sensitivity Analysis for Design Optimization Integrated Software Tools, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The objective of this proposed project is to provide a new set of sensitivity analysis theory and codes, the Sensitivity Analysis for Design Optimization Integrated...

  7. Molecular radiotherapy: the NUKFIT software for calculating the time-integrated activity coefficient.

    Science.gov (United States)

    Kletting, P; Schimmel, S; Kestler, H A; Hänscheid, H; Luster, M; Fernández, M; Bröer, J H; Nosske, D; Lassmann, M; Glatting, G

    2013-10-01

    Calculation of the time-integrated activity coefficient (residence time) is a crucial step in dosimetry for molecular radiotherapy. However, available software is deficient in that it is either not tailored for the use in molecular radiotherapy and/or does not include all required estimation methods. The aim of this work was therefore the development and programming of an algorithm which allows for an objective and reproducible determination of the time-integrated activity coefficient and its standard error. The algorithm includes the selection of a set of fitting functions from predefined sums of exponentials and the choice of an error model for the used data. To estimate the values of the adjustable parameters an objective function, depending on the data, the parameters of the error model, the fitting function and (if required and available) Bayesian information, is minimized. To increase reproducibility and user-friendliness the starting values are automatically determined using a combination of curve stripping and random search. Visual inspection, the coefficient of determination, the standard error of the fitted parameters, and the correlation matrix are provided to evaluate the quality of the fit. The functions which are most supported by the data are determined using the corrected Akaike information criterion. The time-integrated activity coefficient is estimated by analytically integrating the fitted functions. Its standard error is determined assuming Gaussian error propagation. The software was implemented using MATLAB. To validate the proper implementation of the objective function and the fit functions, the results of NUKFIT and SAAM numerical, a commercially available software tool, were compared. The automatic search for starting values was successfully tested for reproducibility. The quality criteria applied in conjunction with the Akaike information criterion allowed the selection of suitable functions. Function fit parameters and their standard

  8. Morphology is dead – long live morphology! Integrating MorphoEvoDevo into molecular EvoDevo and phylogenomics

    Directory of Open Access Journals (Sweden)

    Andreas eWanninger

    2015-05-01

    Full Text Available Morphology, the description and analysis of organismal form, is one of the oldest biological disciplines that has significantly contributed to our understanding as to how animals function and how the overwhelming diversity of phenotypes evolved. The early discovery that comparative studies of morphogenesis add to our understanding of the evolutionary history and interrelationships of organisms led to the formulation of highly influential evolutionary principles, including Haeckel’s theory of recapitulation or Hatschek’s trochozoon-hypothesis, and established the intellectual foundation of a research area today termed EvoDevo. While the rapid integration of molecular techniques into systematics, phylogenetics, and developmental biology from the 1980s onwards made some consider morphology as having little to contribute to evolutionary research, methodological progress together with a revived focus on morphogenesis has resulted in an unexpected renaissance of evolutionary developmental morphology, here termed MorphoEvoDevo. Herein, I briefly summarize some classical landmark contributions and progress achieved by studies using the MorphoEvoDevo approach. I will focus on the role of morphology in modern evolutionary biology, especially with respect to the molecular-driven approaches such as phylogenetics and developmental genetics. I argue that, while MorphoEvoDevo may well survive as an independent field of research, in times of increased competition for funding it will significantly profit from integration of the molecular disciplines into research programs with a strong emphasis on morphology. After all, morphological data are indispensable for reconstruction of phenotypic ground patterns and character evolution, and only a holistic approach incorporating all major subdisciplines of the evolutionary biosciences may ultimately result in a deep understanding, from molecules to ecosystems, of the driving forces that have shaped our organismal

  9. Game analysis of product-service integration

    Directory of Open Access Journals (Sweden)

    Heping Zhong

    2014-10-01

    Full Text Available Purpose: This paper aims at defining the value creation mechanism and income distribution strategies of product-service integration in order to promote product-service integration of a firm.Design/methodology/approach: This paper conducts researches quantitatively on the coordination mechanism of product-service integration by using game theory, and uses the methods of Shapley value and Equal growth rate to further discuss income distribution strategies of product-service integration.Findings: Product-service integration increases the total income of a firm and the added value of the income decreases as the unit price demand variation coefficient of products and services increases, while decreases as the marginal cost of products increases, decreases as the marginal cost of services increases. Moreover, the findings suggest that both income distribution strategies of product-service integration based on Shapley value method and Equal growth rate method can make the product department and service department of a firm win-win and realize the pareto improvement. The choice of what kind of distribution strategy to coordinate the actions between departments depends on the department playing dominant role in the firm. Generally speaking, for a firm at the center of market, when the product department is the main contributor to firm income, the service department will choose the income distribution strategy of product-service integration based on Shapley value method; when the service department is the main contributor to firm income, the service department will choose the income distribution strategy of product-service integration based on Equal growth rate method.Research limitations/implications: This paper makes some strict assumptions such as complete information, risk neutral, linear cost function and so on and the discussion is limited to the simple relationship between product department and service department.Practical implications: Product

  10. Accommodating error analysis in comparison and clustering of molecular fingerprints.

    OpenAIRE

    Salamon, H.; Segal, M. R.; Ponce de Leon, A.; Small, P. M.

    1998-01-01

    Molecular epidemiologic studies of infectious diseases rely on pathogen genotype comparisons, which usually yield patterns comprising sets of DNA fragments (DNA fingerprints). We use a highly developed genotyping system, IS6110-based restriction fragment length polymorphism analysis of Mycobacterium tuberculosis, to develop a computational method that automates comparison of large numbers of fingerprints. Because error in fragment length measurements is proportional to fragment length and is ...

  11. Advanced Concept Architecture Design and Integrated Analysis (ACADIA)

    Science.gov (United States)

    2017-11-03

    1 Advanced Concept Architecture Design and Integrated Analysis (ACADIA) Submitted to the National Institute of Aerospace (NIA) on...Research Report 20161001 - 20161030 Advanced Concept Architecture Design and Integrated Analysis (ACADIA) W911NF-16-2-0229 8504Cedric Justin, Youngjun

  12. Integrating fire management analysis into land management planning

    Science.gov (United States)

    Thomas J. Mills

    1983-01-01

    The analysis of alternative fire management programs should be integrated into the land and resource management planning process, but a single fire management analysis model cannot meet all planning needs. Therefore, a set of simulation models that are analytically separate from integrated land management planning models are required. The design of four levels of fire...

  13. Integration Strategy Is a Key Step in Network-Based Analysis and Dramatically Affects Network Topological Properties and Inferring Outcomes

    Science.gov (United States)

    Jin, Nana; Wu, Deng; Gong, Yonghui; Bi, Xiaoman; Jiang, Hong; Li, Kongning; Wang, Qianghu

    2014-01-01

    An increasing number of experiments have been designed to detect intracellular and intercellular molecular interactions. Based on these molecular interactions (especially protein interactions), molecular networks have been built for using in several typical applications, such as the discovery of new disease genes and the identification of drug targets and molecular complexes. Because the data are incomplete and a considerable number of false-positive interactions exist, protein interactions from different sources are commonly integrated in network analyses to build a stable molecular network. Although various types of integration strategies are being applied in current studies, the topological properties of the networks from these different integration strategies, especially typical applications based on these network integration strategies, have not been rigorously evaluated. In this paper, systematic analyses were performed to evaluate 11 frequently used methods using two types of integration strategies: empirical and machine learning methods. The topological properties of the networks of these different integration strategies were found to significantly differ. Moreover, these networks were found to dramatically affect the outcomes of typical applications, such as disease gene predictions, drug target detections, and molecular complex identifications. The analysis presented in this paper could provide an important basis for future network-based biological researches. PMID:25243127

  14. Tools for integrated sequence-structure analysis with UCSF Chimera

    Directory of Open Access Journals (Sweden)

    Huang Conrad C

    2006-07-01

    Full Text Available Abstract Background Comparing related structures and viewing the structures in the context of sequence alignments are important tasks in protein structure-function research. While many programs exist for individual aspects of such work, there is a need for interactive visualization tools that: (a provide a deep integration of sequence and structure, far beyond mapping where a sequence region falls in the structure and vice versa; (b facilitate changing data of one type based on the other (for example, using only sequence-conserved residues to match structures, or adjusting a sequence alignment based on spatial fit; (c can be used with a researcher's own data, including arbitrary sequence alignments and annotations, closely or distantly related sets of proteins, etc.; and (d interoperate with each other and with a full complement of molecular graphics features. We describe enhancements to UCSF Chimera to achieve these goals. Results The molecular graphics program UCSF Chimera includes a suite of tools for interactive analyses of sequences and structures. Structures automatically associate with sequences in imported alignments, allowing many kinds of crosstalk. A novel method is provided to superimpose structures in the absence of a pre-existing sequence alignment. The method uses both sequence and secondary structure, and can match even structures with very low sequence identity. Another tool constructs structure-based sequence alignments from superpositions of two or more proteins. Chimera is designed to be extensible, and mechanisms for incorporating user-specific data without Chimera code development are also provided. Conclusion The tools described here apply to many problems involving comparison and analysis of protein structures and their sequences. Chimera includes complete documentation and is intended for use by a wide range of scientists, not just those in the computational disciplines. UCSF Chimera is free for non-commercial use and is

  15. Density functional calculations of potential energy surface and charge transfer integrals in molecular triphenylene derivative HAT6

    NARCIS (Netherlands)

    Zbiri, M.; Johnson, M.R.; Kearley, G.J.; Mulder, F.M.

    2009-01-01

    We investigate the effect of structural fluctuations on charge transfer integrals, overlap integrals, and site energies in a system of two stacked molecular 2,3,6,7,10,11-hexakishexyloxytriphenylene (HAT6), which is a model system for conducting devices in organic photocell applications. A density

  16. Identification of a New Mullet Species Complex Based on an Integrative Molecular and Cytogenetic Investigation of Mugil hospes (Mugilidae: Mugiliformes).

    Science.gov (United States)

    Nirchio, Mauro; Paim, Fabilene G; Milana, Valentina; Rossi, Anna R; Oliveira, Claudio

    2018-01-01

    Mullets are very common fishes included in the family Mugilidae, (Mugiliformes), which are characterized by both a remarkably uniform external morphology and internal anatomy. Recently, within this family, different species complexes were molecularly identified within Mugil , a genus which is characterized by lineages that sometimes show very different karyotypes. Here we report the results of cytogenetic and molecular analyses conducted on Mugil hospes , commonly known as the hospe mullet, from Ecuador. The study aims to verify whether the original described species from the Pacific Ocean corresponds to that identified in the Atlantic Ocean, and to identify species-specific chromosome markers that can add new comparative data about Mugilidae karyotype evolution. The karyotype of M. hospes from Ecuador is composed of 48 acrocentric chromosomes and shows two active nucleolar organizer regions (NORs). In situ hybridization, using different types of repetitive sequences (rDNAs, U1 snDNA, telomeric repeats) as probes, identified species-specific chromosome markers that have been compared with those of other species of the genus Mugil . Cytochrome c oxidase subunit I (COI) sequence analysis shows only 92-93% similarity with sequences previously deposited under this species name in GenBank, all of which were from the Atlantic Ocean. Phylogenetic reconstructions indicate the presence of three well-supported hospe mullet lineages whose molecular divergence is compatible with the presence of distinct species. Indeed, the first lineage includes samples from Ecuador, whereas the other two lineages include the Atlantic samples and correspond to M. brevirostris from Brazil and Mugil sp. R from Belize/Venezuela. Results here provided reiterate the pivotal importance of an integrative molecular and cytogenetic approach in the reconstruction of the relationships within Mugilidae.

  17. Identification of a New Mullet Species Complex Based on an Integrative Molecular and Cytogenetic Investigation of Mugil hospes (Mugilidae: Mugiliformes

    Directory of Open Access Journals (Sweden)

    Mauro Nirchio

    2018-02-01

    Full Text Available Mullets are very common fishes included in the family Mugilidae, (Mugiliformes, which are characterized by both a remarkably uniform external morphology and internal anatomy. Recently, within this family, different species complexes were molecularly identified within Mugil, a genus which is characterized by lineages that sometimes show very different karyotypes. Here we report the results of cytogenetic and molecular analyses conducted on Mugil hospes, commonly known as the hospe mullet, from Ecuador. The study aims to verify whether the original described species from the Pacific Ocean corresponds to that identified in the Atlantic Ocean, and to identify species-specific chromosome markers that can add new comparative data about Mugilidae karyotype evolution. The karyotype of M. hospes from Ecuador is composed of 48 acrocentric chromosomes and shows two active nucleolar organizer regions (NORs. In situ hybridization, using different types of repetitive sequences (rDNAs, U1 snDNA, telomeric repeats as probes, identified species-specific chromosome markers that have been compared with those of other species of the genus Mugil. Cytochrome c oxidase subunit I (COI sequence analysis shows only 92–93% similarity with sequences previously deposited under this species name in GenBank, all of which were from the Atlantic Ocean. Phylogenetic reconstructions indicate the presence of three well-supported hospe mullet lineages whose molecular divergence is compatible with the presence of distinct species. Indeed, the first lineage includes samples from Ecuador, whereas the other two lineages include the Atlantic samples and correspond to M. brevirostris from Brazil and Mugil sp. R from Belize/Venezuela. Results here provided reiterate the pivotal importance of an integrative molecular and cytogenetic approach in the reconstruction of the relationships within Mugilidae.

  18. Engineering integrated digital circuits with allosteric ribozymes for scaling up molecular computation and diagnostics.

    Science.gov (United States)

    Penchovsky, Robert

    2012-10-19

    Here we describe molecular implementations of integrated digital circuits, including a three-input AND logic gate, a two-input multiplexer, and 1-to-2 decoder using allosteric ribozymes. Furthermore, we demonstrate a multiplexer-decoder circuit. The ribozymes are designed to seek-and-destroy specific RNAs with a certain length by a fully computerized procedure. The algorithm can accurately predict one base substitution that alters the ribozyme's logic function. The ability to sense the length of RNA molecules enables single ribozymes to be used as platforms for multiple interactions. These ribozymes can work as integrated circuits with the functionality of up to five logic gates. The ribozyme design is universal since the allosteric and substrate domains can be altered to sense different RNAs. In addition, the ribozymes can specifically cleave RNA molecules with triplet-repeat expansions observed in genetic disorders such as oculopharyngeal muscular dystrophy. Therefore, the designer ribozymes can be employed for scaling up computing and diagnostic networks in the fields of molecular computing and diagnostics and RNA synthetic biology.

  19. Application of atomic absorption in molecular analysis (spectrophotometry)

    International Nuclear Information System (INIS)

    Baliza, S.V.; Soledade, L.E.B.

    1981-01-01

    The apparatus of atomic absorption has been considered by all the experts in chemical analysis as one of the most important equipments in actual utilization in such field. Among its several applications one should emphasize direct and indirect metals analyses using flame, graphite furnace, cold vapor generator,... Besides such known applications, the authors have developed at the R and D Center of CSN a patent pendent method for the utilization of such equipment for molecular analysis, in substitution of a sophisticated and specific apparatus. (Author) [pt

  20. Fully 3D printed integrated reactor array for point-of-care molecular diagnostics.

    Science.gov (United States)

    Kadimisetty, Karteek; Song, Jinzhao; Doto, Aoife M; Hwang, Young; Peng, Jing; Mauk, Michael G; Bushman, Frederic D; Gross, Robert; Jarvis, Joseph N; Liu, Changchun

    2018-06-30

    Molecular diagnostics that involve nucleic acid amplification tests (NAATs) are crucial for prevention and treatment of infectious diseases. In this study, we developed a simple, inexpensive, disposable, fully 3D printed microfluidic reactor array that is capable of carrying out extraction, concentration and isothermal amplification of nucleic acids in variety of body fluids. The method allows rapid molecular diagnostic tests for infectious diseases at point of care. A simple leak-proof polymerization strategy was developed to integrate flow-through nucleic acid isolation membranes into microfluidic devices, yielding a multifunctional diagnostic platform. Static coating technology was adopted to improve the biocompatibility of our 3D printed device. We demonstrated the suitability of our device for both end-point colorimetric qualitative detection and real-time fluorescence quantitative detection. We applied our diagnostic device to detection of Plasmodium falciparum in plasma samples and Neisseria meningitides in cerebrospinal fluid (CSF) samples by loop-mediated, isothermal amplification (LAMP) within 50 min. The detection limits were 100 fg for P. falciparum and 50 colony-forming unit (CFU) for N. meningitidis per reaction, which are comparable to that of benchtop instruments. This rapid and inexpensive 3D printed device has great potential for point-of-care molecular diagnosis of infectious disease in resource-limited settings. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Real analysis measure theory, integration, and Hilbert spaces

    CERN Document Server

    Stein, Elias M

    2005-01-01

    Real Analysis is the third volume in the Princeton Lectures in Analysis, a series of four textbooks that aim to present, in an integrated manner, the core areas of analysis. Here the focus is on the development of measure and integration theory, differentiation and integration, Hilbert spaces, and Hausdorff measure and fractals. This book reflects the objective of the series as a whole: to make plain the organic unity that exists between the various parts of the subject, and to illustrate the wide applicability of ideas of analysis to other fields of mathematics and science. After

  2. Semantic web for integrated network analysis in biomedicine.

    Science.gov (United States)

    Chen, Huajun; Ding, Li; Wu, Zhaohui; Yu, Tong; Dhanapalan, Lavanya; Chen, Jake Y

    2009-03-01

    The Semantic Web technology enables integration of heterogeneous data on the World Wide Web by making the semantics of data explicit through formal ontologies. In this article, we survey the feasibility and state of the art of utilizing the Semantic Web technology to represent, integrate and analyze the knowledge in various biomedical networks. We introduce a new conceptual framework, semantic graph mining, to enable researchers to integrate graph mining with ontology reasoning in network data analysis. Through four case studies, we demonstrate how semantic graph mining can be applied to the analysis of disease-causal genes, Gene Ontology category cross-talks, drug efficacy analysis and herb-drug interactions analysis.

  3. Integrated risk analysis of global climate change

    International Nuclear Information System (INIS)

    Shlyakhter, Alexander; Wilson, Richard; Valverde A, L.J. Jr.

    1995-01-01

    This paper discusses several factors that should be considered in integrated risk analyses of global climate change. We begin by describing how the problem of global climate change can be subdivided into largely independent parts that can be linked together in an analytically tractable fashion. Uncertainty plays a central role in integrated risk analyses of global climate change. Accordingly, we consider various aspects of uncertainty as they relate to the climate change problem. We also consider the impacts of these uncertainties on various risk management issues, such as sequential decision strategies, value of information, and problems of interregional and intergenerational equity. (author)

  4. Packaged integrated opto-fluidic solution for harmful fluid analysis

    Science.gov (United States)

    Allenet, T.; Bucci, D.; Geoffray, F.; Canto, F.; Couston, L.; Jardinier, E.; Broquin, J.-E.

    2016-02-01

    Advances in nuclear fuel reprocessing have led to a surging need for novel chemical analysis tools. In this paper, we present a packaged lab-on-chip approach with co-integration of optical and micro-fluidic functions on a glass substrate as a solution. A chip was built and packaged to obtain light/fluid interaction in order for the entire device to make spectral measurements using the photo spectroscopy absorption principle. The interaction between the analyte solution and light takes place at the boundary between a waveguide and a fluid micro-channel thanks to the evanescent part of the waveguide's guided mode that propagates into the fluid. The waveguide was obtained via ion exchange on a glass wafer. The input and the output of the waveguides were pigtailed with standard single mode optical fibers. The micro-scale fluid channel was elaborated with a lithography procedure and hydrofluoric acid wet etching resulting in a 150+/-8 μm deep channel. The channel was designed with fluidic accesses, in order for the chip to be compatible with commercial fluidic interfaces/chip mounts. This allows for analyte fluid in external capillaries to be pumped into the device through micro-pipes, hence resulting in a fully packaged chip. In order to produce this co-integrated structure, two substrates were bonded. A study of direct glass wafer-to-wafer molecular bonding was carried-out to improve detector sturdiness and durability and put forward a bonding protocol with a bonding surface energy of γ>2.0 J.m-2. Detector viability was shown by obtaining optical mode measurements and detecting traces of 1.2 M neodymium (Nd) solute in 12+/-1 μL of 0.01 M and pH 2 nitric acid (HNO3) solvent by obtaining an absorption peak specific to neodymium at 795 nm.

  5. Integrated watershed analysis: adapting to changing times

    Science.gov (United States)

    Gordon H. Reeves

    2013-01-01

    Resource managers are increasingly required to conduct integrated analyses of aquatic and terrestrial ecosystems before undertaking any activities. Th ere are a number of research studies on the impacts of management actions on these ecosystems, as well as a growing body of knowledge about ecological processes that aff ect them, particularly aquatic ecosystems, which...

  6. Relay Feedback Analysis for Double Integral Plants

    Directory of Open Access Journals (Sweden)

    Zhen Ye

    2011-01-01

    Full Text Available Double integral plants under relay feedback are studied. Complete results on the uniqueness of solutions, existence, and stability of the limit cycles are established using the point transformation method. Analytical expressions are also given for determining the amplitude and period of a limit cycle from the plant parameters.

  7. Accommodating error analysis in comparison and clustering of molecular fingerprints.

    Science.gov (United States)

    Salamon, H; Segal, M R; Ponce de Leon, A; Small, P M

    1998-01-01

    Molecular epidemiologic studies of infectious diseases rely on pathogen genotype comparisons, which usually yield patterns comprising sets of DNA fragments (DNA fingerprints). We use a highly developed genotyping system, IS6110-based restriction fragment length polymorphism analysis of Mycobacterium tuberculosis, to develop a computational method that automates comparison of large numbers of fingerprints. Because error in fragment length measurements is proportional to fragment length and is positively correlated for fragments within a lane, an align-and-count method that compensates for relative scaling of lanes reliably counts matching fragments between lanes. Results of a two-step method we developed to cluster identical fingerprints agree closely with 5 years of computer-assisted visual matching among 1,335 M. tuberculosis fingerprints. Fully documented and validated methods of automated comparison and clustering will greatly expand the scope of molecular epidemiology.

  8. Differential amplicons (ΔAmp)-a new molecular method to assess RNA integrity.

    Science.gov (United States)

    Björkman, J; Švec, D; Lott, E; Kubista, M; Sjöback, R

    2016-01-01

    Integrity of the mRNA in clinical samples has major impact on the quality of measured expression levels. This is independent of the measurement technique being next generation sequencing (NGS), Quantitative real-time PCR (qPCR) or microarray profiling. If mRNA is highly degraded or damaged, measured data will be very unreliable and the whole study is likely a waste of time and money. It is therefore common strategy to test the quality of RNA in samples before conducting large and costly studies. Most methods today to assess the quality of RNA are ignorant to the nature of the RNA and, therefore, reflect the integrity of ribosomal RNA, which is the dominant species, rather than of mRNAs, microRNAs and long non-coding RNAs, which usually are the species of interest. Here, we present a novel molecular approach to assess the quality of the targeted RNA species by measuring the differential amplification (ΔAmp) of an Endogenous RNase Resistant (ERR) marker relative to a reference gene, optionally combined with the measurement of two amplicons of different lengths. The combination reveals any mRNA degradation caused by ribonucleases as well as physical, chemical or UV damage. ΔAmp has superior sensitivity to common microfluidic electrophoretic methods, senses the integrity of the actual targeted RNA species, and allows for a smoother and more cost efficient workflow.

  9. Differential amplicons (ΔAmp—a new molecular method to assess RNA integrity

    Directory of Open Access Journals (Sweden)

    J. Björkman

    2016-01-01

    Full Text Available Integrity of the mRNA in clinical samples has major impact on the quality of measured expression levels. This is independent of the measurement technique being next generation sequencing (NGS, Quantitative real-time PCR (qPCR or microarray profiling. If mRNA is highly degraded or damaged, measured data will be very unreliable and the whole study is likely a waste of time and money. It is therefore common strategy to test the quality of RNA in samples before conducting large and costly studies. Most methods today to assess the quality of RNA are ignorant to the nature of the RNA and, therefore, reflect the integrity of ribosomal RNA, which is the dominant species, rather than of mRNAs, microRNAs and long non-coding RNAs, which usually are the species of interest. Here, we present a novel molecular approach to assess the quality of the targeted RNA species by measuring the differential amplification (ΔAmp of an Endogenous RNase Resistant (ERR marker relative to a reference gene, optionally combined with the measurement of two amplicons of different lengths. The combination reveals any mRNA degradation caused by ribonucleases as well as physical, chemical or UV damage. ΔAmp has superior sensitivity to common microfluidic electrophoretic methods, senses the integrity of the actual targeted RNA species, and allows for a smoother and more cost efficient workflow.

  10. Harnessing Integrative Omics to Facilitate Molecular Imaging of the Human Epidermal Growth Factor Receptor Family for Precision Medicine.

    Science.gov (United States)

    Pool, Martin; de Boer, H Rudolf; Hooge, Marjolijn N Lub-de; van Vugt, Marcel A T M; de Vries, Elisabeth G E

    2017-01-01

    Cancer is a growing problem worldwide. The cause of death in cancer patients is often due to treatment-resistant metastatic disease. Many molecularly targeted anticancer drugs have been developed against 'oncogenic driver' pathways. However, these treatments are usually only effective in properly selected patients. Resistance to molecularly targeted drugs through selective pressure on acquired mutations or molecular rewiring can hinder their effectiveness. This review summarizes how molecular imaging techniques can potentially facilitate the optimal implementation of targeted agents. Using the human epidermal growth factor receptor (HER) family as a model in (pre)clinical studies, we illustrate how molecular imaging may be employed to characterize whole body target expression as well as monitor drug effectiveness and the emergence of tumor resistance. We further discuss how an integrative omics discovery platform could guide the selection of 'effect sensors' - new molecular imaging targets - which are dynamic markers that indicate treatment effectiveness or resistance.

  11. Integration of video and radiation analysis data

    International Nuclear Information System (INIS)

    Menlove, H.O.; Howell, J.A.; Rodriguez, C.A.; Eccleston, G.W.; Beddingfield, D.; Smith, J.E.; Baumgart, C.W.

    1995-01-01

    For the past several years, the integration of containment and surveillance (C/S) with nondestructive assay (NDA) sensors for monitoring the movement of nuclear material has focused on the hardware and communications protocols in the transmission network. Little progress has been made in methods to utilize the combined C/S and NDA data for safeguards and to reduce the inspector time spent in nuclear facilities. One of the fundamental problems in the integration of the combined data is that the two methods operate in different dimensions. The C/S video data is spatial in nature; whereas, the NDA sensors provide radiation levels versus time data. The authors have introduced a new method to integrate spatial (digital video) with time (radiation monitoring) information. This technology is based on pattern recognition by neural networks, provides significant capability to analyze complex data, and has the ability to learn and adapt to changing situations. This technique has the potential of significantly reducing the frequency of inspection visits to key facilities without a loss of safeguards effectiveness

  12. Integration of Design and Control through Model Analysis

    DEFF Research Database (Denmark)

    Russel, Boris Mariboe; Henriksen, Jens Peter; Jørgensen, Sten Bay

    2002-01-01

    A systematic computer aided analysis of the process model is proposed as a pre-solution step for integration of design and control problems. The process model equations are classified in terms of balance equations, constitutive equations and conditional equations. Analysis of the phenomena models...... (structure selection) issues for the integrated problems are considered. (C) 2002 Elsevier Science Ltd. All rights reserved....... representing the constitutive equations identify the relationships between the important process and design variables, which help to understand, define and address some of the issues related to integration of design and control. Furthermore, the analysis is able to identify a set of process (control) variables...

  13. MutAid: Sanger and NGS Based Integrated Pipeline for Mutation Identification, Validation and Annotation in Human Molecular Genetics.

    Directory of Open Access Journals (Sweden)

    Ram Vinay Pandey

    Full Text Available Traditional Sanger sequencing as well as Next-Generation Sequencing have been used for the identification of disease causing mutations in human molecular research. The majority of currently available tools are developed for research and explorative purposes and often do not provide a complete, efficient, one-stop solution. As the focus of currently developed tools is mainly on NGS data analysis, no integrative solution for the analysis of Sanger data is provided and consequently a one-stop solution to analyze reads from both sequencing platforms is not available. We have therefore developed a new pipeline called MutAid to analyze and interpret raw sequencing data produced by Sanger or several NGS sequencing platforms. It performs format conversion, base calling, quality trimming, filtering, read mapping, variant calling, variant annotation and analysis of Sanger and NGS data under a single platform. It is capable of analyzing reads from multiple patients in a single run to create a list of potential disease causing base substitutions as well as insertions and deletions. MutAid has been developed for expert and non-expert users and supports four sequencing platforms including Sanger, Illumina, 454 and Ion Torrent. Furthermore, for NGS data analysis, five read mappers including BWA, TMAP, Bowtie, Bowtie2 and GSNAP and four variant callers including GATK-HaplotypeCaller, SAMTOOLS, Freebayes and VarScan2 pipelines are supported. MutAid is freely available at https://sourceforge.net/projects/mutaid.

  14. MutAid: Sanger and NGS Based Integrated Pipeline for Mutation Identification, Validation and Annotation in Human Molecular Genetics.

    Science.gov (United States)

    Pandey, Ram Vinay; Pabinger, Stephan; Kriegner, Albert; Weinhäusel, Andreas

    2016-01-01

    Traditional Sanger sequencing as well as Next-Generation Sequencing have been used for the identification of disease causing mutations in human molecular research. The majority of currently available tools are developed for research and explorative purposes and often do not provide a complete, efficient, one-stop solution. As the focus of currently developed tools is mainly on NGS data analysis, no integrative solution for the analysis of Sanger data is provided and consequently a one-stop solution to analyze reads from both sequencing platforms is not available. We have therefore developed a new pipeline called MutAid to analyze and interpret raw sequencing data produced by Sanger or several NGS sequencing platforms. It performs format conversion, base calling, quality trimming, filtering, read mapping, variant calling, variant annotation and analysis of Sanger and NGS data under a single platform. It is capable of analyzing reads from multiple patients in a single run to create a list of potential disease causing base substitutions as well as insertions and deletions. MutAid has been developed for expert and non-expert users and supports four sequencing platforms including Sanger, Illumina, 454 and Ion Torrent. Furthermore, for NGS data analysis, five read mappers including BWA, TMAP, Bowtie, Bowtie2 and GSNAP and four variant callers including GATK-HaplotypeCaller, SAMTOOLS, Freebayes and VarScan2 pipelines are supported. MutAid is freely available at https://sourceforge.net/projects/mutaid.

  15. Molecular biogeography: towards an integrated framework for conserving pan-African biodiversity.

    Directory of Open Access Journals (Sweden)

    Yoshan Moodley

    2007-05-01

    Full Text Available Biogeographic models partition ecologically similar species assemblages into discrete ecoregions. However, the history, relationship and interactions between these regions and their assemblages have rarely been explored.Here we develop a taxon-based approach that explicitly utilises molecular information to compare ecoregion history and status, which we exemplify using a continentally distributed mammalian species: the African bushbuck (Tragelaphus scriptus. We reveal unprecedented levels of genetic diversity and structure in this species and show that ecoregion biogeographic history better explains the distribution of molecular variation than phenotypic similarity or geography. We extend these data to explore ecoregion connectivity, identify core habitats and infer ecological affinities from them.This analysis defines 28 key biogeographic regions for sub-Saharan Africa, and provides a valuable framework for the incorporation of genetic and biogeographic information into a more widely applicable model for the conservation of continental biodiversity.

  16. Molecular Isotopic Distribution Analysis (MIDAs) with adjustable mass accuracy.

    Science.gov (United States)

    Alves, Gelio; Ogurtsov, Aleksey Y; Yu, Yi-Kuo

    2014-01-01

    In this paper, we present Molecular Isotopic Distribution Analysis (MIDAs), a new software tool designed to compute molecular isotopic distributions with adjustable accuracies. MIDAs offers two algorithms, one polynomial-based and one Fourier-transform-based, both of which compute molecular isotopic distributions accurately and efficiently. The polynomial-based algorithm contains few novel aspects, whereas the Fourier-transform-based algorithm consists mainly of improvements to other existing Fourier-transform-based algorithms. We have benchmarked the performance of the two algorithms implemented in MIDAs with that of eight software packages (BRAIN, Emass, Mercury, Mercury5, NeutronCluster, Qmass, JFC, IC) using a consensus set of benchmark molecules. Under the proposed evaluation criteria, MIDAs's algorithms, JFC, and Emass compute with comparable accuracy the coarse-grained (low-resolution) isotopic distributions and are more accurate than the other software packages. For fine-grained isotopic distributions, we compared IC, MIDAs's polynomial algorithm, and MIDAs's Fourier transform algorithm. Among the three, IC and MIDAs's polynomial algorithm compute isotopic distributions that better resemble their corresponding exact fine-grained (high-resolution) isotopic distributions. MIDAs can be accessed freely through a user-friendly web-interface at http://www.ncbi.nlm.nih.gov/CBBresearch/Yu/midas/index.html.

  17. Integrative taxonomy by molecular species delimitation: multi-locus data corroborate a new species of Balkan Drusinae micro-endemics.

    Science.gov (United States)

    Vitecek, Simon; Kučinić, Mladen; Previšić, Ana; Živić, Ivana; Stojanović, Katarina; Keresztes, Lujza; Bálint, Miklós; Hoppeler, Felicitas; Waringer, Johann; Graf, Wolfram; Pauls, Steffen U

    2017-06-06

    Taxonomy offers precise species identification and delimitation and thus provides basic information for biological research, e.g. through assessment of species richness. The importance of molecular taxonomy, i.e., the identification and delimitation of taxa based on molecular markers, has increased in the past decade. Recently developed exploratory tools now allow estimating species-level diversity in multi-locus molecular datasets. Here we use molecular species delimitation tools that either quantify differences in intra- and interspecific variability of loci, or divergence times within and between species, or perform coalescent species tree inference to estimate species-level entities in molecular genetic datasets. We benchmark results from these methods against 14 morphologically readily differentiable species of a well-defined subgroup of the diverse Drusinae subfamily (Trichoptera, Limnephilidae). Using a 3798 bp (6 loci) molecular data set we aim to corroborate a geographically isolated new species by integrating comparative morphological studies and molecular taxonomy. Our results indicate that only multi-locus species delimitation provides taxonomically relevant information. The data further corroborate the new species Drusus zivici sp. nov. We provide differential diagnostic characters and describe the male, female and larva of this new species and discuss diversity patterns of Drusinae in the Balkans. We further discuss potential and significance of molecular species delimitation. Finally we argue that enhancing collaborative integrative taxonomy will accelerate assessment of global diversity and completion of reference libraries for applied fields, e.g., conservation and biomonitoring.

  18. Path integral molecular dynamics for exact quantum statistics of multi-electronic-state systems.

    Science.gov (United States)

    Liu, Xinzijian; Liu, Jian

    2018-03-14

    An exact approach to compute physical properties for general multi-electronic-state (MES) systems in thermal equilibrium is presented. The approach is extended from our recent progress on path integral molecular dynamics (PIMD), Liu et al. [J. Chem. Phys. 145, 024103 (2016)] and Zhang et al. [J. Chem. Phys. 147, 034109 (2017)], for quantum statistical mechanics when a single potential energy surface is involved. We first define an effective potential function that is numerically favorable for MES-PIMD and then derive corresponding estimators in MES-PIMD for evaluating various physical properties. Its application to several representative one-dimensional and multi-dimensional models demonstrates that MES-PIMD in principle offers a practical tool in either of the diabatic and adiabatic representations for studying exact quantum statistics of complex/large MES systems when the Born-Oppenheimer approximation, Condon approximation, and harmonic bath approximation are broken.

  19. Six Years of Monitoring of the Sgr B2 Molecular Cloud with INTEGRAL

    Science.gov (United States)

    Terrier, R.; Bélanger, G.; Ponti, G.; Trap, G.; Goldwurm, A.; Decourchelle, A.

    2009-05-01

    Several molecular clouds around the Galactic Centre (GC) emit strong neutral iron fluorescence line at 6.4 keV, as well as hard X-ray emission up to 100 keV. The origin of this emission has long been a matter of controversy: irradiation by low energy cosmic ray electrons or X-rays emitted by a nearby flaring source in the central region. A recent evidence for time variability in the iron line intensity that has been detected in the Sgr B2 cloud favors the reflexion scenario. We present here the data obtained after 6 years of INTEGRAL monitoring of the GC. In particular, we show a lightcurve of Sgr B2 that reveals a decrease in the hard X-ray flux over the last years and discuss its implications. We finally discuss perspectives with Simbol-X.

  20. Vapor-solid-solid grown Ge nanowires at integrated circuit compatible temperature by molecular beam epitaxy

    Science.gov (United States)

    Zhu, Zhongyunshen; Song, Yuxin; Zhang, Zhenpu; Sun, Hao; Han, Yi; Li, Yaoyao; Zhang, Liyao; Xue, Zhongying; Di, Zengfeng; Wang, Shumin

    2017-09-01

    We demonstrate Au-assisted vapor-solid-solid (VSS) growth of Ge nanowires (NWs) by molecular beam epitaxy at the substrate temperature of ˜180 °C, which is compatible with the temperature window for Si-based integrated circuit. Low temperature grown Ge NWs hold a smaller size, similar uniformity, and better fit with Au tips in diameter, in contrast to Ge NWs grown at around or above the eutectic temperature of Au-Ge alloy in the vapor-liquid-solid (VLS) growth. Six ⟨110⟩ growth orientations were observed on Ge (110) by the VSS growth at ˜180 °C, differing from only one vertical growth direction of Ge NWs by the VLS growth at a high temperature. The evolution of NWs dimension and morphology from the VLS growth to the VSS growth is qualitatively explained by analyzing the mechanism of the two growth modes.

  1. Integrated structural biology and molecular ecology of N-cycling enzymes from ammonia-oxidizing archaea.

    Science.gov (United States)

    Tolar, Bradley B; Herrmann, Jonathan; Bargar, John R; van den Bedem, Henry; Wakatsuki, Soichi; Francis, Christopher A

    2017-10-01

    Knowledge of the molecular ecology and environmental determinants of ammonia-oxidizing organisms is critical to understanding and predicting the global nitrogen (N) and carbon cycles, but an incomplete biochemical picture hinders in vitro studies of N-cycling enzymes. Although an integrative structural and dynamic characterization at the atomic scale would advance our understanding of function tremendously, structural knowledge of key N-cycling enzymes from ecologically relevant ammonia oxidizers is unfortunately extremely limited. Here, we discuss the challenges and opportunities for examining the ecology of ammonia-oxidizing organisms, particularly uncultivated Thaumarchaeota, through (meta)genome-driven structural biology of the enzymes ammonia monooxygenase (AMO) and nitrite reductase (NirK). © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  2. Integration of molecular machines into supramolecular materials: actuation between equilibrium polymers and crystal-like gels.

    Science.gov (United States)

    Mariani, Giacomo; Goujon, Antoine; Moulin, Emilie; Rawiso, Michel; Giuseppone, Nicolas; Buhler, Eric

    2017-11-30

    In this article, the dynamic structure of complex supramolecular polymers composed of bistable [c2]daisy chain rotaxanes as molecular machines that are linked by ureidopyrimidinones (Upy) as recognition moieties was studied. pH actuation of the integrated mechanically active rotaxanes controls the contraction/extension of the polymer chains as well as their physical reticulation. Small-angle neutron and X-ray scattering were used to study in-depth the nanostructure of the contracted and extended polymer aggregates in toluene solution. The supramolecular polymers comprising contracted nanomachines were found to be equilibrium polymers with a mass that is concentration dependent in dilute and semidilute regimes. Surprisingly, the extended polymers form a gel network with a crystal-like internal structure that is independent of concentration and reminiscent of a pearl-necklace network.

  3. Analysis of Optimal Operation of an Energy Integrated Distillation Plant

    DEFF Research Database (Denmark)

    Li, Hong Wen; Hansen, C.A.; Gani, Rafiqul

    2003-01-01

    The efficiency of manufacturing systems can be significantly increased through diligent application of control based on mathematical models thereby enabling more tight integration of decision making with systems operation. In the present paper analysis of optimal operation of an energy integrated...

  4. Integrated program of using of Probabilistic Safety Analysis in Spain

    International Nuclear Information System (INIS)

    1998-01-01

    Since 25 June 1986, when the CSN (Nuclear Safety Conseil) approve the Integrated Program of Probabilistic Safety Analysis, this program has articulated the main activities of CSN. This document summarize the activities developed during these years and reviews the Integrated programme

  5. Analysis of integrated video and radiation data

    International Nuclear Information System (INIS)

    Howell, J.A.; Menlove, H.O.; Rodriguez, C.A.; Beddingfield, D.; Vasil, A.

    1995-01-01

    We have developed prototype software for a facility-monitoring application that will detect anomalous activity in a nuclear facility. The software, which forms the basis of a simple model, automatically reviews and analyzes integrated safeguards data from continuous unattended monitoring systems. This technology, based on pattern recognition by neural networks, provides significant capability to analyze complex data and has the ability to learn and adapt to changing situations. It is well suited for large automated facilities, reactors, spent-fuel storage facilities, reprocessing plants, and nuclear material storage vaults

  6. Signal integrity analysis on discontinuous microstrip line

    International Nuclear Information System (INIS)

    Qiao, Qingyang; Dai, Yawen; Chen, Zipeng

    2013-01-01

    In high speed PCB design, microstirp lines were used to control the impedance, however, the discontinuous microstrip line can cause signal integrity problems. In this paper, we use the transmission line theory to study the characteristics of microstrip lines. Research results indicate that the discontinuity such as truncation, gap and size change result in the problems such as radiation, reflection, delay and ground bounce. We change the discontinuities to distributed parameter circuits, analysed the steady-state response and transient response and the phase delay. The transient response cause radiation and voltage jump.

  7. Advantages of Integrative Data Analysis for Developmental Research

    Science.gov (United States)

    Bainter, Sierra A.; Curran, Patrick J.

    2015-01-01

    Amid recent progress in cognitive development research, high-quality data resources are accumulating, and data sharing and secondary data analysis are becoming increasingly valuable tools. Integrative data analysis (IDA) is an exciting analytical framework that can enhance secondary data analysis in powerful ways. IDA pools item-level data across…

  8. Integrating survey and molecular approaches to better understand wildlife disease ecology.

    Directory of Open Access Journals (Sweden)

    Brendan D Cowled

    Full Text Available Infectious wildlife diseases have enormous global impacts, leading to human pandemics, global biodiversity declines and socio-economic hardship. Understanding how infection persists and is transmitted in wildlife is critical for managing diseases, but our understanding is limited. Our study aim was to better understand how infectious disease persists in wildlife populations by integrating genetics, ecology and epidemiology approaches. Specifically, we aimed to determine whether environmental or host factors were stronger drivers of Salmonella persistence or transmission within a remote and isolated wild pig (Sus scrofa population. We determined the Salmonella infection status of wild pigs. Salmonella isolates were genotyped and a range of data was collected on putative risk factors for Salmonella transmission. We a priori identified several plausible biological hypotheses for Salmonella prevalence (cross sectional study design versus transmission (molecular case series study design and fit the data to these models. There were 543 wild pig Salmonella observations, sampled at 93 unique locations. Salmonella prevalence was 41% (95% confidence interval [CI]: 37-45%. The median Salmonella DICE coefficient (or Salmonella genetic similarity was 52% (interquartile range [IQR]: 42-62%. Using the traditional cross sectional prevalence study design, the only supported model was based on the hypothesis that abundance of available ecological resources determines Salmonella prevalence in wild pigs. In the molecular study design, spatial proximity and herd membership as well as some individual risk factors (sex, condition score and relative density determined transmission between pigs. Traditional cross sectional surveys and molecular epidemiological approaches are complementary and together can enhance understanding of disease ecology: abundance of ecological resources critical for wildlife influences Salmonella prevalence, whereas Salmonella transmission is

  9. Integrating Survey and Molecular Approaches to Better Understand Wildlife Disease Ecology

    Science.gov (United States)

    Cowled, Brendan D.; Ward, Michael P.; Laffan, Shawn W.; Galea, Francesca; Garner, M. Graeme; MacDonald, Anna J.; Marsh, Ian; Muellner, Petra; Negus, Katherine; Quasim, Sumaiya; Woolnough, Andrew P.; Sarre, Stephen D.

    2012-01-01

    Infectious wildlife diseases have enormous global impacts, leading to human pandemics, global biodiversity declines and socio-economic hardship. Understanding how infection persists and is transmitted in wildlife is critical for managing diseases, but our understanding is limited. Our study aim was to better understand how infectious disease persists in wildlife populations by integrating genetics, ecology and epidemiology approaches. Specifically, we aimed to determine whether environmental or host factors were stronger drivers of Salmonella persistence or transmission within a remote and isolated wild pig (Sus scrofa) population. We determined the Salmonella infection status of wild pigs. Salmonella isolates were genotyped and a range of data was collected on putative risk factors for Salmonella transmission. We a priori identified several plausible biological hypotheses for Salmonella prevalence (cross sectional study design) versus transmission (molecular case series study design) and fit the data to these models. There were 543 wild pig Salmonella observations, sampled at 93 unique locations. Salmonella prevalence was 41% (95% confidence interval [CI]: 37–45%). The median Salmonella DICE coefficient (or Salmonella genetic similarity) was 52% (interquartile range [IQR]: 42–62%). Using the traditional cross sectional prevalence study design, the only supported model was based on the hypothesis that abundance of available ecological resources determines Salmonella prevalence in wild pigs. In the molecular study design, spatial proximity and herd membership as well as some individual risk factors (sex, condition score and relative density) determined transmission between pigs. Traditional cross sectional surveys and molecular epidemiological approaches are complementary and together can enhance understanding of disease ecology: abundance of ecological resources critical for wildlife influences Salmonella prevalence, whereas Salmonella transmission is driven by

  10. Protein Nano-Object Integrator: Generating atomic-style objects for use in molecular biophysics

    Science.gov (United States)

    Smith, Nicholas David Fenimore

    As researchers obtain access to greater and greater amounts of computational power, focus has shifted towards modeling macroscopic objects while still maintaining atomic-level details. The Protein Nano-Object Integrator (ProNOI) presented here has been designed to provide a streamlined solution for creating and designing macro-scale objects with atomic-level details to be used in molecular simulations and tools. To accomplish this, two different interfaces were developed: a Protein Data Bank (PDB), PDB-focused interface for generating regularly-shaped three-dimensional atomic objects and a 2D image-based interface for tracing images with irregularly shaped objects and then extracting three-dimensional models from these images. Each interface is dependent upon the C++ backend utility for generating the objects and ensures that the output is consistent across each program. The objects are exported in a standard PDB format which allows for the visualization and manipulation of the objects via standard tools available in Molecular Computational Biophysics.

  11. A comparison between integral equation theory and molecular dynamics simulations of dense, flexible polymer liquids

    International Nuclear Information System (INIS)

    Curro, J.G.; Schweizer, K.S.; Grest, G.S.; Kremer, K.; Corporate Research Science Laboratory, Exxon Research and Engineering Company, Annandale, New Jersey 08801; Institut fur Festkorperforschung der Kernforschungsanlage Julich, D-5170 Julich, Federal Republic of Germany)

    1989-01-01

    Recently we (J.G.C. and K.S.S.) formulated a tractable ''reference interaction site model'' (RISM) integral equation theory of flexible polymer liquids. The purpose of this paper is to compare the results of the theory with recent molecular dynamics simulations (G.S.G. and K.K.) on dense chain liquids of degree of polymerization N=50 and 200. Specific comparisons were made between theory and simulation for the intramolecular structure factor ω(k) and the intermolecular radial distribution function g(r) in the liquid. In particular it was possible to independently test the assumptions inherent in the RISM theory and the additional ideality approximation that was made in the initial application of the theory. This comparison was accomplished by calculating the intermolecular g(r) using the simulated intramolecular structure factor, as well as, ω(k) derived from a freely jointed chain model.The RISM theory results, using the simulated ω(k), were found to be in excellent agreement, over all length scales, with the g(r) from molecular dynamics simulations. The theoretical predictions using the ''ideal'' intramolecular structure factor tended to underestimate g(r) near contact, indicating local intramolecular expansion of the chains. This local expansion can be incorporated into the theory self consistently by including the effects of the ''medium induced'' potential on the intramolecular structure

  12. Molecular evolution in court: analysis of a large hepatitis C virus outbreak from an evolving source.

    Science.gov (United States)

    González-Candelas, Fernando; Bracho, María Alma; Wróbel, Borys; Moya, Andrés

    2013-07-19

    Molecular phylogenetic analyses are used increasingly in the epidemiological investigation of outbreaks and transmission cases involving rapidly evolving RNA viruses. Here, we present the results of such an analysis that contributed to the conviction of an anesthetist as being responsible for the infection of 275 of his patients with hepatitis C virus. We obtained sequences of the NS5B and E1-E2 regions in the viral genome for 322 patients suspected to have been infected by the doctor, and for 44 local, unrelated controls. The analysis of 4,184 cloned sequences of the E1-E2 region allowed us to exclude 47 patients from the outbreak. A subset of patients had known dates of infection. We used these data to calibrate a relaxed molecular clock and to determine a rough estimate of the time of infection for each patient. A similar analysis led to an estimate for the time of infection of the source. The date turned out to be 10 years before the detection of the outbreak. The number of patients infected was small at first, but it increased substantially in the months before the detection of the outbreak. We have developed a procedure to integrate molecular phylogenetic reconstructions of rapidly evolving viral populations into a forensic setting adequate for molecular epidemiological analysis of outbreaks and transmission events. We applied this procedure to a large outbreak of hepatitis C virus caused by a single source and the results obtained played a key role in the trial that led to the conviction of the suspected source.

  13. Integrated care: a comprehensive bibliometric analysis and literature review

    Directory of Open Access Journals (Sweden)

    Xiaowei Sun

    2014-06-01

    Full Text Available Introduction: Integrated care could not only fix up fragmented health care but also improve the continuity of care and the quality of life. Despite the volume and variety of publications, little is known about how ‘integrated care’ has developed. There is a need for a systematic bibliometric analysis on studying the important features of the integrated care literature.Aim: To investigate the growth pattern, core journals and jurisdictions and identify the key research domains of integrated care.Methods: We searched Medline/PubMed using the search strategy ‘(delivery of health care, integrated [MeSH Terms] OR integrated care [Title/Abstract]’ without time and language limits. Second, we extracted the publishing year, journals, jurisdictions and keywords of the retrieved articles. Finally, descriptive statistical analysis by the Bibliographic Item Co-occurrence Matrix Builder and hierarchical clustering by SPSS were used.Results: As many as 9090 articles were retrieved. Results included: (1 the cumulative numbers of the publications on integrated care rose perpendicularly after 1993; (2 all documents were recorded by 1646 kinds of journals. There were 28 core journals; (3 the USA is the predominant publishing country; and (4 there are six key domains including: the definition/models of integrated care, interdisciplinary patient care team, disease management for chronically ill patients, types of health care organizations and policy, information system integration and legislation/jurisprudence.Discussion and conclusion: Integrated care literature has been most evident in developed countries. International Journal of Integrated Care is highly recommended in this research area. The bibliometric analysis and identification of publication hotspots provides researchers and practitioners with core target journals, as well as an overview of the field for further research in integrated care.

  14. An operator expansion technique for path integral analysis

    International Nuclear Information System (INIS)

    Tsvetkov, I.V.

    1995-01-01

    A new method of path integral analysis in the framework of a power series technique is presented. The method is based on the operator expansion of an exponential. A regular procedure to calculate the correction terms is found. (orig.)

  15. Analysis of Price Variation and Market Integration of Prosopis ...

    African Journals Online (AJOL)

    Analysis of Price Variation and Market Integration of Prosopis Africana (guill. ... select five markets based on the presence of traders selling the commodity in the markets ... T- test result showed that Prosopis africana seed trade is profitable and ...

  16. Integrating Data Transformation in Principal Components Analysis

    KAUST Repository

    Maadooliat, Mehdi; Huang, Jianhua Z.; Hu, Jianhua

    2015-01-01

    Principal component analysis (PCA) is a popular dimension reduction method to reduce the complexity and obtain the informative aspects of high-dimensional datasets. When the data distribution is skewed, data transformation is commonly used prior

  17. Integrative Transcriptomic and Metabonomic Molecular Profiling of Colonic Mucosal Biopsies Indicates a Unique Molecular Phenotype for Ulcerative Colitis

    DEFF Research Database (Denmark)

    Rantalainen, Mattias; Bjerrum, Jacob Tveiten; Olsen, Jørgen

    2015-01-01

    characterized the molecular phenotype of ulcerative colitis through transcriptomic and metabonomic profiling of colonic mucosal biopsies from patients and controls. We have characterized the extent to which metabonomic and transcriptomic molecular phenotypes are associated with ulcerative colitis versus...... transcriptomic and metabonomic data have previously been shown to predict the clinical course of ulcerative colitis and related clinical phenotypes, indicating that molecular phenotypes reveal molecular changes associated with the disease. Our analyses indicate that variables of both transcriptomics...... and metabonomics are associated with disease case and control status, that a large proportion of transcripts are associated with at least one metabolite in mucosal colonic biopsies, and that multiple pathways are connected to disease-related metabolites and transcripts....

  18. Implementation of force distribution analysis for molecular dynamics simulations

    Directory of Open Access Journals (Sweden)

    Seifert Christian

    2011-04-01

    Full Text Available Abstract Background The way mechanical stress is distributed inside and propagated by proteins and other biopolymers largely defines their function. Yet, determining the network of interactions propagating internal strain remains a challenge for both, experiment and theory. Based on molecular dynamics simulations, we developed force distribution analysis (FDA, a method that allows visualizing strain propagation in macromolecules. Results To be immediately applicable to a wide range of systems, FDA was implemented as an extension to Gromacs, a commonly used package for molecular simulations. The FDA code comes with an easy-to-use command line interface and can directly be applied to every system built using Gromacs. We provide an additional R-package providing functions for advanced statistical analysis and presentation of the FDA data. Conclusions Using FDA, we were able to explain the origin of mechanical robustness in immunoglobulin domains and silk fibers. By elucidating propagation of internal strain upon ligand binding, we previously also successfully revealed the functionality of a stiff allosteric protein. FDA thus has the potential to be a valuable tool in the investigation and rational design of mechanical properties in proteins and nano-materials.

  19. Delineation of Chondroid Lipoma: An Immunohistochemical and Molecular Biological Analysis

    Science.gov (United States)

    de Vreeze, Ronald S. A.; van Coevorden, Frits; Boerrigter, Lucie; Nederlof, Petra M.; Haas, Rick L.; Bras, Johannes; Rosenwald, Andreas; Mentzel, Thomas; de Jong, Daphne

    2011-01-01

    Aims. Chondroid lipoma (CL) is a benign tumor that mimics a variety of soft tissue tumors and is characterized by translocation t(11;16). Here, we analyze CL and its histological mimics. Methods. CL (n = 4) was compared to a variety of histological mimics (n = 83) for morphological aspects and immunohistochemical features including cyclinD1(CCND1). Using FISH analysis, CCND1 and FUS were investigated as potential translocation partners. Results. All CLs were strongly positive for CCND1. One of 4 myoepitheliomas, CCND1, was positive. In well-differentiated lipomatous tumors and in chondrosarcomas, CCND1 was frequently expressed, but all myxoid liposarcomas were negative. FISH analysis did not give support for direct involvement of CCND1 and FUS as translocation partners. Conclusions. Chondroid lipoma is extremely rare and has several and more prevalent histological mimics. The differential diagnosis of chondroid lipomas can be unraveled using immunohistochemical and molecular support. PMID:21559269

  20. Molecular activation analysis for organo-halogen contaminants in yogurt

    International Nuclear Information System (INIS)

    Zhang Hong; Chai Zhifang

    2004-01-01

    The concentrations of total halogen (TX), extractable organo-halogen (EOX), extractable persistent organo-halogen (EPOX), organo-chlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in 18 different yogurt specimens of 14 brands from Beijing, Tianjin, Shanghai, Guangzhou and Shijiazhuang were determined by epithermal neutron activation analysis (ENAA), molecular activation analysis (MAA) and GC-Mass Spectrometry (GC-MS), respectively. The results indicated that the halogen in yogurt mainly existed as inorganic species and non-extractable organo-halogen compounds. About 1/3 to 1/4 of EOX was EPOX. Further, EOCl and EPOCl were the main organo-halogen species in yogurt. The average concentration of the unknown organo-chlorine was 96% of the EPOCl. HCHs and DDTs were still the main contaminants of OCPs in the yogurt of interest. Also, PCB202, PCB103 and PCB208 were the main contaminants of PCBs. (authors)

  1. Molecular analysis of radiation-induced mutations in vitro

    International Nuclear Information System (INIS)

    Kronenberg, A.

    1996-01-01

    This review will focus on the nature of specific locus mutations detected in mammalian cells exposed in vitro to different types of ionizing radiations. Ionizing radiation has been shown to produce a wide variety of heritable alterations in DNA. These range from single base pair substitutions to stable loss or translocation of large portions of whole chromosomes. Data will be reviewed for certain test systems that reveal different mutation spectra. Techniques for the analysis of molecular alterations include applications of the polymerase chain reaction, some of which may be coupled with DNA sequence analysis, and a variety of hybridization-based techniques. The complexity of large scale rearrangements is approached with cytogenetic techniques including high resolution banding and various applications of the fluorescence in situ hybridization (FISH) technique. Radiation-induced mutant frequencies and mutation spectra are a function of the linkage constraints on the recovery of viable mutants for a given locus and test system. 44 refs

  2. Accurate and efficient integration for molecular dynamics simulations at constant temperature and pressure

    Science.gov (United States)

    Lippert, Ross A.; Predescu, Cristian; Ierardi, Douglas J.; Mackenzie, Kenneth M.; Eastwood, Michael P.; Dror, Ron O.; Shaw, David E.

    2013-10-01

    In molecular dynamics simulations, control over temperature and pressure is typically achieved by augmenting the original system with additional dynamical variables to create a thermostat and a barostat, respectively. These variables generally evolve on timescales much longer than those of particle motion, but typical integrator implementations update the additional variables along with the particle positions and momenta at each time step. We present a framework that replaces the traditional integration procedure with separate barostat, thermostat, and Newtonian particle motion updates, allowing thermostat and barostat updates to be applied infrequently. Such infrequent updates provide a particularly substantial performance advantage for simulations parallelized across many computer processors, because thermostat and barostat updates typically require communication among all processors. Infrequent updates can also improve accuracy by alleviating certain sources of error associated with limited-precision arithmetic. In addition, separating the barostat, thermostat, and particle motion update steps reduces certain truncation errors, bringing the time-average pressure closer to its target value. Finally, this framework, which we have implemented on both general-purpose and special-purpose hardware, reduces software complexity and improves software modularity.

  3. Magnetic particles for in vitro molecular diagnosis: From sample preparation to integration into microsystems.

    Science.gov (United States)

    Tangchaikeeree, Tienrat; Polpanich, Duangporn; Elaissari, Abdelhamid; Jangpatarapongsa, Kulachart

    2017-10-01

    Colloidal magnetic particles (MPs) have been developed in association with molecular diagnosis for several decades. MPs have the great advantage of easy manipulation using a magnet. In nucleic acid detection, these particles can act as a capture support for rapid and simple biomolecule separation. The surfaces of MPs can be modified by coating with various polymer materials to provide functionalization for different applications. The use of MPs enhances the sensitivity and specificity of detection due to the specific activity on the surface of the particles. Practical applications of MPs demonstrate greater efficiency than conventional methods. Beyond traditional detection, MPs have been successfully adopted as a smart carrier in microfluidic and lab-on-a-chip biosensors. The versatility of MPs has enabled their integration into small single detection units. MPs-based biosensors can facilitate rapid and highly sensitive detection of very small amounts of a sample. In this review, the application of MPs to the detection of nucleic acids, from sample preparation to analytical readout systems, is described. State-of-the-art integrated microsystems containing microfluidic and lab-on-a-chip biosensors for the nucleic acid detection are also addressed. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. The Eukaryotic Cell Originated in the Integration and Redistribution of Hyperstructures from Communities of Prokaryotic Cells Based on Molecular Complementarity

    Directory of Open Access Journals (Sweden)

    Vic Norris

    2009-06-01

    Full Text Available In the “ecosystems-first” approach to the origins of life, networks of non-covalent assemblies of molecules (composomes, rather than individual protocells, evolved under the constraints of molecular complementarity. Composomes evolved into the hyperstructures of modern bacteria. We extend the ecosystems-first approach to explain the origin of eukaryotic cells through the integration of mixed populations of bacteria. We suggest that mutualism and symbiosis resulted in cellular mergers entailing the loss of redundant hyperstructures, the uncoupling of transcription and translation, and the emergence of introns and multiple chromosomes. Molecular complementarity also facilitated integration of bacterial hyperstructures to perform cytoskeletal and movement functions.

  5. Cost benefit analysis of power plant database integration

    International Nuclear Information System (INIS)

    Wilber, B.E.; Cimento, A.; Stuart, R.

    1988-01-01

    A cost benefit analysis of plant wide data integration allows utility management to evaluate integration and automation benefits from an economic perspective. With this evaluation, the utility can determine both the quantitative and qualitative savings that can be expected from data integration. The cost benefit analysis is then a planning tool which helps the utility to develop a focused long term implementation strategy that will yield significant near term benefits. This paper presents a flexible cost benefit analysis methodology which is both simple to use and yields accurate, verifiable results. Included in this paper is a list of parameters to consider, a procedure for performing the cost savings analysis, and samples of this procedure when applied to a utility. A case study is presented involving a specific utility where this procedure was applied. Their uses of the cost-benefit analysis are also described

  6. Development of data analysis tool for combat system integration

    Directory of Open Access Journals (Sweden)

    Seung-Chun Shin

    2013-03-01

    Full Text Available System integration is an important element for the construction of naval combat ships. In particular, because impeccable combat system integration together with the sensors and weapons can ensure the combat capability and survivability of the ship, the integrated performance of the combat system should be verified and validated whether or not it fulfills the requirements of the end user. In order to conduct systematic verification and validation, a data analysis tool is requisite. This paper suggests the Data Extraction, Recording and Analysis Tool (DERAT for the data analysis of the integrated performance of the combat system, including the functional definition, architecture and effectiveness of the DERAT by presenting the test results.

  7. Integrative miRNA and mRNA analysis in penile carcinomas reveals markers and pathways with potential clinical impact

    DEFF Research Database (Denmark)

    Kuasne, Hellen; Barros-Filho, Mateus Camargo; Busso-Lopes, Ariane F

    2017-01-01

    Penile carcinoma (PeCa) is an important public health issue in poor and developing countries, and has only recently been explored in terms of genetic and epigenetic studies. Integrative data analysis is a powerful method for the identification of molecular drivers involved in cancer development...

  8. Integrated systems analysis of the PIUS reactor

    Energy Technology Data Exchange (ETDEWEB)

    Fullwood, F.; Kroeger, P.; Higgins, J. [Brookhaven National Lab., Upton, NY (United States)] [and others

    1993-11-01

    Results are presented of a systems failure analysis of the PIUS plant systems that are used during normal reactor operation and postulated accidents. This study was performed to provide the NRC with an understanding of the behavior of the plant. The study applied two diverse failure identification methods, Failure Modes Effects & Criticality Analysis (FMECA) and Hazards & Operability (HAZOP) to the plant systems, supported by several deterministic analyses. Conventional PRA methods were also used along with a scheme for classifying events by initiator frequency and combinations of failures. Principal results of this study are: (a) an extensive listing of potential event sequences, grouped in categories that can be used by the NRC, (b) identification of support systems that are important to safety, and (c) identification of key operator actions.

  9. Integrated systems analysis of the PIUS reactor

    International Nuclear Information System (INIS)

    Fullwood, F.; Kroeger, P.; Higgins, J.

    1993-11-01

    Results are presented of a systems failure analysis of the PIUS plant systems that are used during normal reactor operation and postulated accidents. This study was performed to provide the NRC with an understanding of the behavior of the plant. The study applied two diverse failure identification methods, Failure Modes Effects ampersand Criticality Analysis (FMECA) and Hazards ampersand Operability (HAZOP) to the plant systems, supported by several deterministic analyses. Conventional PRA methods were also used along with a scheme for classifying events by initiator frequency and combinations of failures. Principal results of this study are: (a) an extensive listing of potential event sequences, grouped in categories that can be used by the NRC, (b) identification of support systems that are important to safety, and (c) identification of key operator actions

  10. Molecular analysis of precursor lesions in familial pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Tatjana Crnogorac-Jurcevic

    Full Text Available With less than a 5% survival rate pancreatic adenocarcinoma (PDAC is almost uniformly lethal. In order to make a significant impact on survival of patients with this malignancy, it is necessary to diagnose the disease early, when curative surgery is still possible. Detailed knowledge of the natural history of the disease and molecular events leading to its progression is therefore critical.We have analysed the precursor lesions, PanINs, from prophylactic pancreatectomy specimens of patients from four different kindreds with high risk of familial pancreatic cancer who were treated for histologically proven PanIN-2/3. Thus, the material was procured before pancreatic cancer has developed, rather than from PanINs in a tissue field that already contains cancer. Genome-wide transcriptional profiling using such unique specimens was performed. Bulk frozen sections displaying the most extensive but not microdissected PanIN-2/3 lesions were used in order to obtain the holistic view of both the precursor lesions and their microenvironment. A panel of 76 commonly dysregulated genes that underlie neoplastic progression from normal pancreas to PanINs and PDAC were identified. In addition to shared genes some differences between the PanINs of individual families as well as between the PanINs and PDACs were also seen. This was particularly pronounced in the stromal and immune responses.Our comprehensive analysis of precursor lesions without the invasive component provides the definitive molecular proof that PanIN lesions beget cancer from a molecular standpoint. We demonstrate the need for accumulation of transcriptomic changes during the progression of PanIN to PDAC, both in the epithelium and in the surrounding stroma. An identified 76-gene signature of PDAC progression presents a rich candidate pool for the development of early diagnostic and/or surveillance markers as well as potential novel preventive/therapeutic targets for both familial and sporadic

  11. An integrated platform for biomolecule interaction analysis

    Science.gov (United States)

    Jan, Chia-Ming; Tsai, Pei-I.; Chou, Shin-Ting; Lee, Shu-Sheng; Lee, Chih-Kung

    2013-02-01

    We developed a new metrology platform which can detect real-time changes in both a phase-interrogation mode and intensity mode of a SPR (surface plasmon resonance). We integrated a SPR and ellipsometer to a biosensor chip platform to create a new biomolecular interaction measurement mechanism. We adopted a conductive ITO (indium-tinoxide) film to the bio-sensor platform chip to expand the dynamic range and improve measurement accuracy. The thickness of the conductive film and the suitable voltage constants were found to enhance performance. A circularly polarized ellipsometry configuration was incorporated into the newly developed platform to measure the label-free interactions of recombinant human C-reactive protein (CRP) with immobilized biomolecule target monoclonal human CRP antibody at various concentrations. CRP was chosen as it is a cardiovascular risk biomarker and is an acute phase reactant as well as a specific prognostic indicator for inflammation. We found that the sensitivity of a phaseinterrogation SPR is predominantly dependent on the optimization of the sample incidence angle. The effect of the ITO layer effective index under DC and AC effects as well as an optimal modulation were experimentally performed and discussed. Our experimental results showed that the modulated dynamic range for phase detection was 10E-2 RIU based on a current effect and 10E-4 RIU based on a potential effect of which a 0.55 (°/RIU) measurement was found by angular-interrogation. The performance of our newly developed metrology platform was characterized to have a higher sensitivity and less dynamic range when compared to a traditional full-field measurement system.

  12. An analysis of 3D particle path integration algorithms

    International Nuclear Information System (INIS)

    Darmofal, D.L.; Haimes, R.

    1996-01-01

    Several techniques for the numerical integration of particle paths in steady and unsteady vector (velocity) fields are analyzed. Most of the analysis applies to unsteady vector fields, however, some results apply to steady vector field integration. Multistep, multistage, and some hybrid schemes are considered. It is shown that due to initialization errors, many unsteady particle path integration schemes are limited to third-order accuracy in time. Multistage schemes require at least three times more internal data storage than multistep schemes of equal order. However, for timesteps within the stability bounds, multistage schemes are generally more accurate. A linearized analysis shows that the stability of these integration algorithms are determined by the eigenvalues of the local velocity tensor. Thus, the accuracy and stability of the methods are interpreted with concepts typically used in critical point theory. This paper shows how integration schemes can lead to erroneous classification of critical points when the timestep is finite and fixed. For steady velocity fields, we demonstrate that timesteps outside of the relative stability region can lead to similar integration errors. From this analysis, guidelines for accurate timestep sizing are suggested for both steady and unsteady flows. In particular, using simulation data for the unsteady flow around a tapered cylinder, we show that accurate particle path integration requires timesteps which are at most on the order of the physical timescale of the flow

  13. Integrating human factors into process hazard analysis

    International Nuclear Information System (INIS)

    Kariuki, S.G.; Loewe, K.

    2007-01-01

    A comprehensive process hazard analysis (PHA) needs to address human factors. This paper describes an approach that systematically identifies human error in process design and the human factors that influence its production and propagation. It is deductive in nature and therefore considers human error as a top event. The combinations of different factors that may lead to this top event are analysed. It is qualitative in nature and is used in combination with other PHA methods. The method has an advantage because it does not look at the operator error as the sole contributor to the human failure within a system but a combination of all underlying factors

  14. Integrative Genomic Analysis of Complex traits

    DEFF Research Database (Denmark)

    Ehsani, Ali Reza

    In the last decade rapid development in biotechnologies has made it possible to extract extensive information about practically all levels of biological organization. An ever-increasing number of studies are reporting miltilayered datasets on the entire DNA sequence, transceroption, protein...... expression, and metabolite abundance of more and more populations in a multitude of invironments. However, a solid model for including all of this complex information in one analysis, to disentangle genetic variation and the underlying genetic architecture of complex traits and diseases, has not yet been...

  15. Sparse multivariate factor analysis regression models and its applications to integrative genomics analysis.

    Science.gov (United States)

    Zhou, Yan; Wang, Pei; Wang, Xianlong; Zhu, Ji; Song, Peter X-K

    2017-01-01

    The multivariate regression model is a useful tool to explore complex associations between two kinds of molecular markers, which enables the understanding of the biological pathways underlying disease etiology. For a set of correlated response variables, accounting for such dependency can increase statistical power. Motivated by integrative genomic data analyses, we propose a new methodology-sparse multivariate factor analysis regression model (smFARM), in which correlations of response variables are assumed to follow a factor analysis model with latent factors. This proposed method not only allows us to address the challenge that the number of association parameters is larger than the sample size, but also to adjust for unobserved genetic and/or nongenetic factors that potentially conceal the underlying response-predictor associations. The proposed smFARM is implemented by the EM algorithm and the blockwise coordinate descent algorithm. The proposed methodology is evaluated and compared to the existing methods through extensive simulation studies. Our results show that accounting for latent factors through the proposed smFARM can improve sensitivity of signal detection and accuracy of sparse association map estimation. We illustrate smFARM by two integrative genomics analysis examples, a breast cancer dataset, and an ovarian cancer dataset, to assess the relationship between DNA copy numbers and gene expression arrays to understand genetic regulatory patterns relevant to the disease. We identify two trans-hub regions: one in cytoband 17q12 whose amplification influences the RNA expression levels of important breast cancer genes, and the other in cytoband 9q21.32-33, which is associated with chemoresistance in ovarian cancer. © 2016 WILEY PERIODICALS, INC.

  16. Classical and quantum analysis of a hetero-triatomic molecular Bose-Einstein condensate model

    International Nuclear Information System (INIS)

    Tonel, A.P.; Kuhn, C.C.N.; Foerster, A.; Santos, G.; Roditi, I.; Santos, Z.V.T.

    2014-11-01

    We investigate an integrable Hamiltonian modelling a hetero-triatomic-molecular Bose-Einstein condensate. This model describes a mixture of two species of atoms in different proportions, which can combine to form a triatomic molecule. Beginning with a classical analysis, we determine the fixed points of the system. Bifurcations of these points separate the parameter space into different regions. Three distinct scenarios are found, varying with the atomic population imbalance. This result suggests the ground state properties of the quantum model exhibits a sensitivity on the atomic population imbalance, which is confirmed by a quantum analysis using different approaches, such as the ground-state expectation values, the behaviour of the quantum dynamics, the energy gap and the ground state fidelity. (author)

  17. Network-based integration of molecular and physiological data elucidates regulatory mechanisms underlying adaptation to high-fat diet

    NARCIS (Netherlands)

    Derous, D.; Kelder, T.; Schothorst, E.M. van; Erk, M. van; Voigt, A.; Klaus, S.; Keijer, J.; Radonjic, M.

    2015-01-01

    Health is influenced by interplay of molecular, physiological and environmental factors. To effectively maintain health and prevent disease, health-relevant relations need to be understood at multiple levels of biological complexity. Network-based methods provide a powerful platform for integration

  18. Project analysis and integration economic analyses summary

    Science.gov (United States)

    Macomber, H. L.

    1986-01-01

    An economic-analysis summary was presented for the manufacture of crystalline-silicon modules involving silicon ingot/sheet, growth, slicing, cell manufacture, and module assembly. Economic analyses provided: useful quantitative aspects for complex decision-making to the Flat-plate Solar Array (FSA) Project; yardsticks for design and performance to industry; and demonstration of how to evaluate and understand the worth of research and development both to JPL and other government agencies and programs. It was concluded that future research and development funds for photovoltaics must be provided by the Federal Government because the solar industry today does not reap enough profits from its present-day sales of photovoltaic equipment.

  19. Integrative analysis of metabolomics and transcriptomics data

    DEFF Research Database (Denmark)

    Brink-Jensen, Kasper; Bak, Søren; Jørgensen, Kirsten

    2013-01-01

    ) measurements from the same samples, to identify genes controlling the production of metabolites. Due to the high dimensionality of both LC-MS and DNA microarray data, dimension reduction and variable selection are key elements of the analysis. Our proposed approach starts by identifying the basis functions......The abundance of high-dimensional measurements in the form of gene expression and mass spectroscopy calls for models to elucidate the underlying biological system. For widely studied organisms like yeast, it is possible to incorporate prior knowledge from a variety of databases, an approach used...... ("building blocks") that constitute the output from a mass spectrometry experiment. Subsequently, the weights of these basis functions are related to the observations from the corresponding gene expression data in order to identify which genes are associated with specific patterns seen in the metabolite data...

  20. Genetic diversity analysis of common beans based on molecular markers

    Directory of Open Access Journals (Sweden)

    Homar R. Gill-Langarica

    Full Text Available A core collection of the common bean (Phaseolus vulgaris L., representing genetic diversity in the entire Mexican holding, is kept at the INIFAP (Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias, Mexico Germplasm Bank. After evaluation, the genetic structure of this collection (200 accessions was compared with that of landraces from the states of Oaxaca, Chiapas and Veracruz (10 genotypes from each, as well as a further 10 cultivars, by means of four amplified fragment length polymorphisms (AFLP +3/+3 primer combinations and seven simple sequence repeats (SSR loci, in order to define genetic diversity, variability and mutual relationships. Data underwent cluster (UPGMA and molecular variance (AMOVA analyses. AFLP analysis produced 530 bands (88.5% polymorphic while SSR primers amplified 174 alleles, all polymorphic (8.2 alleles per locus. AFLP indicated that the highest genetic diversity was to be found in ten commercial-seed classes from two major groups of accessions from Central Mexico and Chiapas, which seems to be an important center of diversity in the south. A third group included genotypes from Nueva Granada, Mesoamerica, Jalisco and Durango races. Here, SSR analysis indicated a reduced number of shared haplotypes among accessions, whereas the highest genetic components of AMOVA variation were found within accessions. Genetic diversity observed in the common-bean core collection represents an important sample of the total Phaseolus genetic variability at the main Germplasm Bank of INIFAP. Molecular marker strategies could contribute to a better understanding of the genetic structure of the core collection as well as to its improvement and validation.

  1. Genetic diversity analysis of common beans based on molecular markers

    Directory of Open Access Journals (Sweden)

    Homar R. Gill-Langarica

    2011-01-01

    Full Text Available A core collection of the common bean (Phaseolus vulgaris L., representing genetic diversity in the entire Mexican holding, is kept at the INIFAP (Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias, Mexico Germplasm Bank. After evaluation, the genetic structure of this collection (200 accessions was compared with that of landraces from the states of Oaxaca, Chiapas and Veracruz (10 genotypes from each, as well as a further 10 cultivars, by means of four amplified fragment length polymorphisms (AFLP +3/+3 primer combinations and seven simple sequence repeats (SSR loci, in order to define genetic diversity, variability and mutual relationships. Data underwent cluster (UPGMA and molecular variance (AMOVA analyses. AFLP analysis produced 530 bands (88.5% polymorphic while SSR primers amplified 174 alleles, all polymorphic (8.2 alleles per locus. AFLP indicated that the highest genetic diversity was to be found in ten commercial-seed classes from two major groups of accessions from Central Mexico and Chiapas, which seems to be an important center of diversity in the south. A third group included genotypes from Nueva Granada, Mesoamerica, Jalisco and Durango races. Here, SSR analysis indicated a reduced number of shared haplotypes among accessions, whereas the highest genetic components of AMOVA variation were found within accessions. Genetic diversity observed in the common-bean core collection represents an important sample of the total Phaseolus genetic variability at the main Germplasm Bank of INIFAP. Molecular marker strategies could contribute to a better understanding of the genetic structure of the core collection as well as to its improvement and validation.

  2. Genetic diversity of popcorn genotypes using molecular analysis.

    Science.gov (United States)

    Resh, F S; Scapim, C A; Mangolin, C A; Machado, M F P S; do Amaral, A T; Ramos, H C C; Vivas, M

    2015-08-19

    In this study, we analyzed dominant molecular markers to estimate the genetic divergence of 26 popcorn genotypes and evaluate whether using various dissimilarity coefficients with these dominant markers influences the results of cluster analysis. Fifteen random amplification of polymorphic DNA primers produced 157 amplified fragments, of which 65 were monomorphic and 92 were polymorphic. To calculate the genetic distances among the 26 genotypes, the complements of the Jaccard, Dice, and Rogers and Tanimoto similarity coefficients were used. A matrix of Dij values (dissimilarity matrix) was constructed, from which the genetic distances among genotypes were represented in a more simplified manner as a dendrogram generated using the unweighted pair-group method with arithmetic average. Clusters determined by molecular analysis generally did not group material from the same parental origin together. The largest genetic distance was between varieties 17 (UNB-2) and 18 (PA-091). In the identification of genotypes with the smallest genetic distance, the 3 coefficients showed no agreement. The 3 dissimilarity coefficients showed no major differences among their grouping patterns because agreement in determining the genotypes with large, medium, and small genetic distances was high. The largest genetic distances were observed for the Rogers and Tanimoto dissimilarity coefficient (0.74), followed by the Jaccard coefficient (0.65) and the Dice coefficient (0.48). The 3 coefficients showed similar estimations for the cophenetic correlation coefficient. Correlations among the matrices generated using the 3 coefficients were positive and had high magnitudes, reflecting strong agreement among the results obtained using the 3 evaluated dissimilarity coefficients.

  3. Genetic diversity analysis of common beans based on molecular markers.

    Science.gov (United States)

    Gill-Langarica, Homar R; Muruaga-Martínez, José S; Vargas-Vázquez, M L Patricia; Rosales-Serna, Rigoberto; Mayek-Pérez, Netzahualcoyotl

    2011-10-01

    A core collection of the common bean (Phaseolus vulgaris L.), representing genetic diversity in the entire Mexican holding, is kept at the INIFAP (Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias, Mexico) Germplasm Bank. After evaluation, the genetic structure of this collection (200 accessions) was compared with that of landraces from the states of Oaxaca, Chiapas and Veracruz (10 genotypes from each), as well as a further 10 cultivars, by means of four amplified fragment length polymorphisms (AFLP) +3/+3 primer combinations and seven simple sequence repeats (SSR) loci, in order to define genetic diversity, variability and mutual relationships. Data underwent cluster (UPGMA) and molecular variance (AMOVA) analyses. AFLP analysis produced 530 bands (88.5% polymorphic) while SSR primers amplified 174 alleles, all polymorphic (8.2 alleles per locus). AFLP indicated that the highest genetic diversity was to be found in ten commercial-seed classes from two major groups of accessions from Central Mexico and Chiapas, which seems to be an important center of diversity in the south. A third group included genotypes from Nueva Granada, Mesoamerica, Jalisco and Durango races. Here, SSR analysis indicated a reduced number of shared haplotypes among accessions, whereas the highest genetic components of AMOVA variation were found within accessions. Genetic diversity observed in the common-bean core collection represents an important sample of the total Phaseolus genetic variability at the main Germplasm Bank of INIFAP. Molecular marker strategies could contribute to a better understanding of the genetic structure of the core collection as well as to its improvement and validation.

  4. Vertically Integrated Seismological Analysis II : Inference

    Science.gov (United States)

    Arora, N. S.; Russell, S.; Sudderth, E.

    2009-12-01

    Methods for automatically associating detected waveform features with hypothesized seismic events, and localizing those events, are a critical component of efforts to verify the Comprehensive Test Ban Treaty (CTBT). As outlined in our companion abstract, we have developed a hierarchical model which views detection, association, and localization as an integrated probabilistic inference problem. In this abstract, we provide more details on the Markov chain Monte Carlo (MCMC) methods used to solve this inference task. MCMC generates samples from a posterior distribution π(x) over possible worlds x by defining a Markov chain whose states are the worlds x, and whose stationary distribution is π(x). In the Metropolis-Hastings (M-H) method, transitions in the Markov chain are constructed in two steps. First, given the current state x, a candidate next state x‧ is generated from a proposal distribution q(x‧ | x), which may be (more or less) arbitrary. Second, the transition to x‧ is not automatic, but occurs with an acceptance probability—α(x‧ | x) = min(1, π(x‧)q(x | x‧)/π(x)q(x‧ | x)). The seismic event model outlined in our companion abstract is quite similar to those used in multitarget tracking, for which MCMC has proved very effective. In this model, each world x is defined by a collection of events, a list of properties characterizing those events (times, locations, magnitudes, and types), and the association of each event to a set of observed detections. The target distribution π(x) = P(x | y), the posterior distribution over worlds x given the observed waveform data y at all stations. Proposal distributions then implement several types of moves between worlds. For example, birth moves create new events; death moves delete existing events; split moves partition the detections for an event into two new events; merge moves combine event pairs; swap moves modify the properties and assocations for pairs of events. Importantly, the rules for

  5. Development of safety analysis technology for integral reactor

    Energy Technology Data Exchange (ETDEWEB)

    Sim, Suk K.; Song, J. H.; Chung, Y. J. and others

    1999-03-01

    Inherent safety features and safety system characteristics of the SMART integral reactor are investigated in this study. Performance and safety of the SMART conceptual design have been evaluated and confirmed through the performance and safety analyses using safety analysis system codes as well as a preliminary performance and safety analysis methodology. SMART design base events and their acceptance criteria are identified to develop a preliminary PIRT for the SMART integral reactor. Using the preliminary PIRT, a set of experimental program for the thermal hydraulic separate effect tests and the integral effect tests was developed for the thermal hydraulic model development and the system code validation. Safety characteristics as well as the safety issues of the integral reactor has been identified during the study, which will be used to resolve the safety issues and guide the regulatory criteria for the integral reactor. The results of the performance and safety analyses performed during the study were used to feedback for the SMART conceptual design. The performance and safety analysis code systems as well as the preliminary safety analysis methodology developed in this study will be validated as the SMART design evolves. The performance and safety analysis technology developed during the study will be utilized for the SMART basic design development. (author)

  6. Overcoming barriers to integrating economic analysis into risk assessment.

    Science.gov (United States)

    Hoffmann, Sandra

    2011-09-01

    Regulatory risk analysis is designed to provide decisionmakers with a clearer understanding of how policies are likely to affect risk. The systems that produce risk are biological, physical, and social and economic. As a result, risk analysis is an inherently interdisciplinary task. Yet in practice, risk analysis has been interdisciplinary in only limited ways. Risk analysis could provide more accurate assessments of risk if there were better integration of economics and other social sciences into risk assessment itself. This essay examines how discussions about risk analysis policy have influenced the roles of various disciplines in risk analysis. It explores ways in which integrated bio/physical-economic modeling could contribute to more accurate assessments of risk. It reviews examples of the kind of integrated economics-bio/physical modeling that could be used to enhance risk assessment. The essay ends with a discussion of institutional barriers to greater integration of economic modeling into risk assessment and provides suggestions on how these might be overcome. © 2011 Society for Risk Analysis.

  7. Reactivity of etoricoxib based on computational study of molecular orbitals, molecular electrostatic potential surface and Mulliken charge analysis

    Science.gov (United States)

    Sachdeva, Ritika; Soni, Abhinav; Singh, V. P.; Saini, G. S. S.

    2018-05-01

    Etoricoxib is one of the selective cyclooxygenase inhibitor drug which plays a significant role in the pharmacological management of arthritis and pain. The theoretical investigation of its reactivity is done using Density Functional Theory calculations. Molecular Electrostatic Potential Surface of etoricoxib and its Mulliken atomic charge distribution are used for the prediction of its electrophilic and nucleophilic sites. The detailed analysis of its frontier molecular orbitals is also done.

  8. A network analysis of leadership theory : the infancy of integration.

    OpenAIRE

    Meuser, J. D.; Gardner, W. L.; Dinh, J. E.; Hu, J.; Liden, R. C.; Lord, R. G.

    2016-01-01

    We investigated the status of leadership theory integration by reviewing 14 years of published research (2000 through 2013) in 10 top journals (864 articles). The authors of these articles examined 49 leadership approaches/theories, and in 293 articles, 3 or more of these leadership approaches were included in their investigations. Focusing on these articles that reflected relatively extensive integration, we applied an inductive approach and used graphic network analysis as a guide for drawi...

  9. Integrated analysis of oxide nuclear fuel sintering

    International Nuclear Information System (INIS)

    Baranov, V.; Kuzmin, R.; Tenishev, A.; Timoshin, I.; Khlunov, A.; Ivanov, A.; Petrov, I.

    2011-01-01

    Dilatometric and thermal-gravimetric investigations have been carried out for the sintering process of oxide nuclear fuel in gaseous Ar - 8% H 2 atmosphere at temperatures up to 1600 0 C. The pressed compacts were fabricated under real production conditions of the OAO MSZ with application of two different technologies, so called 'dry' and 'wet' technologies. Effects of the grain size growth after the heating to different temperatures were observed. In order to investigate the effects produced by rate of heating on properties of sintered fuel pellets, the heating rates were varied from 1 to 8 0 C per minute. Time of isothermal overexposure at maximal temperature (1600 0 C) was about 8 hours. Real production conditions were imitated. The results showed that the sintering process of the fuel pellets produced by two technologies differs. The samples sintered under different heating rates were studied with application of scanning electronic microscopy analysis for determination of mean grain size. A simulation of heating profile for industrial furnaces was performed to reduce the beam cycles and estimate the effects of variation of the isothermal overexposure temperatures. Based on this data, an optimization of the sintering conditions was performed in operations terms of OAO MSZ. (authors)

  10. Integrated Network Analysis and Effective Tools in Plant Systems Biology

    Directory of Open Access Journals (Sweden)

    Atsushi eFukushima

    2014-11-01

    Full Text Available One of the ultimate goals in plant systems biology is to elucidate the genotype-phenotype relationship in plant cellular systems. Integrated network analysis that combines omics data with mathematical models has received particular attention. Here we focus on the latest cutting-edge computational advances that facilitate their combination. We highlight (1 network visualization tools, (2 pathway analyses, (3 genome-scale metabolic reconstruction, and (4 the integration of high-throughput experimental data and mathematical models. Multi-omics data that contain the genome, transcriptome, proteome, and metabolome and mathematical models are expected to integrate and expand our knowledge of complex plant metabolisms.

  11. Momentum integral network method for thermal-hydraulic transient analysis

    International Nuclear Information System (INIS)

    Van Tuyle, G.J.

    1983-01-01

    A new momentum integral network method has been developed, and tested in the MINET computer code. The method was developed in order to facilitate the transient analysis of complex fluid flow and heat transfer networks, such as those found in the balance of plant of power generating facilities. The method employed in the MINET code is a major extension of a momentum integral method reported by Meyer. Meyer integrated the momentum equation over several linked nodes, called a segment, and used a segment average pressure, evaluated from the pressures at both ends. Nodal mass and energy conservation determined nodal flows and enthalpies, accounting for fluid compression and thermal expansion

  12. Study on integrated design and analysis platform of NPP

    International Nuclear Information System (INIS)

    Lu Dongsen; Gao Zuying; Zhou Zhiwei

    2001-01-01

    Many calculation software have been developed to nuclear system's design and safety analysis, such as structure design software, fuel design and manage software, thermal hydraulic analysis software, severe accident simulation software, etc. This study integrates those software to a platform, develops visual modeling tool for Retran, NGFM90. And in this platform, a distribution calculation method is also provided for couple calculation between different software. The study will improve the design and analysis of NPP

  13. Bioinformatic Integration of Molecular Networks and Major Pathways Involved in Mice Cochlear and Vestibular Supporting Cells.

    Science.gov (United States)

    Requena, Teresa; Gallego-Martinez, Alvaro; Lopez-Escamez, Jose A

    2018-01-01

    Background : Cochlear and vestibular epithelial non-hair cells (ENHCs) are the supporting elements of the cellular architecture in the organ of Corti and the vestibular neuroepithelium in the inner ear. Intercellular and cell-extracellular matrix interactions are essential to prevent an abnormal ion redistribution leading to hearing and vestibular loss. The aim of this study is to define the main pathways and molecular networks in the mouse ENHCs. Methods : We retrieved microarray and RNA-seq datasets from mouse epithelial sensory and non-sensory cells from gEAR portal (http://umgear.org/index.html) and obtained gene expression fold-change between ENHCs and non-epithelial cells (NECs) against HCs for each gene. Differentially expressed genes (DEG) with a log2 fold change between 1 and -1 were discarded. The remaining genes were selected to search for interactions using Ingenuity Pathway Analysis and STRING platform. Specific molecular networks for ENHCs in the cochlea and the vestibular organs were generated and significant pathways were identified. Results : Between 1723 and 1559 DEG were found in the mouse cochlear and vestibular tissues, respectively. Six main pathways showed enrichment in the supporting cells in both tissues: (1) "Inhibition of Matrix Metalloproteases"; (2) "Calcium Transport I"; (3) "Calcium Signaling"; (4) "Leukocyte Extravasation Signaling"; (5) "Signaling by Rho Family GTPases"; and (6) "Axonal Guidance Si". In the mouse cochlea, ENHCs showed a significant enrichment in 18 pathways highlighting "axonal guidance signaling (AGS)" ( p = 4.37 × 10 -8 ) and "RhoGDI Signaling" ( p = 3.31 × 10 -8 ). In the vestibular dataset, there were 20 enriched pathways in ENHCs, the most significant being "Leukocyte Extravasation Signaling" ( p = 8.71 × 10 -6 ), "Signaling by Rho Family GTPases" ( p = 1.20 × 10 -5 ) and "Calcium Signaling" ( p = 1.20 × 10 -5 ). Among the top ranked networks, the most biologically significant network contained the

  14. Determination of the protonation state of the Asp dyad: conventional molecular dynamics versus thermodynamic integration.

    Science.gov (United States)

    Huang, Jinfeng; Zhu, Yali; Sun, Bin; Yao, Yuan; Liu, Junjun

    2016-03-01

    The protonation state of the Asp dyad is important as it can reveal enzymatic mechanisms, and the information this provides can be used in the development of drugs for proteins such as memapsin 2 (BACE-1), HIV-1 protease, and rennin. Conventional molecular dynamics (MD) simulations have been successfully used to determine the preferred protonation state of the Asp dyad. In the present work, we demonstrate that the results obtained from conventional MD simulations can be greatly influenced by the particular force field applied or the values used for control parameters. In principle, free-energy changes between possible protonation states can be used to determine the protonation state. We show that protonation state prediction by the thermodynamic integration (TI) method is insensitive to force field version or to the cutoff for calculating nonbonded interactions (a control parameter). In the present study, the protonation state of the Asp dyad predicted by TI calculations was the same regardless of the force field and cutoff value applied. Contrary to the intuition that conventional MD is more efficient, our results clearly show that the TI method is actually more efficient and more reliable for determining the protonation state of the Asp dyad.

  15. Molecular characterization and function of tenomodulin, a marker of tendons and ligaments that integrate musculoskeletal components

    Directory of Open Access Journals (Sweden)

    Chisa Shukunami, DDS, PhD

    2016-11-01

    Full Text Available Tendons and ligaments are dense fibrous bands of connective tissue that integrate musculoskeletal components in vertebrates. Tendons connect skeletal muscles to the bone and function as mechanical force transmitters, whereas ligaments bind adjacent bones together to stabilize joints and restrict unwanted joint movement. Fibroblasts residing in tendons and ligaments are called tenocytes and ligamentocytes, respectively. Tenomodulin (Tnmd is a type II transmembrane glycoprotein that is expressed at high levels in tenocytes and ligamentocytes, and is also present in periodontal ligament cells and tendon stem/progenitor cells. Tnmd is related to chondromodulin-1 (Chm1, a cartilage-derived angiogenesis inhibitor, and both Tnmd and Chm1 are expressed in the CD31− avascular mesenchyme. The conserved C-terminal hydrophobic domain of these proteins, which is characterized by the eight Cys residues to form four disulfide bonds, may have an anti-angiogenic function. This review highlights the molecular characterization and function of Tnmd, a specific marker of tendons and ligaments.

  16. Integrated failure probability estimation based on structural integrity analysis and failure data: Natural gas pipeline case

    International Nuclear Information System (INIS)

    Dundulis, Gintautas; Žutautaitė, Inga; Janulionis, Remigijus; Ušpuras, Eugenijus; Rimkevičius, Sigitas; Eid, Mohamed

    2016-01-01

    In this paper, the authors present an approach as an overall framework for the estimation of the failure probability of pipelines based on: the results of the deterministic-probabilistic structural integrity analysis (taking into account loads, material properties, geometry, boundary conditions, crack size, and defected zone thickness), the corrosion rate, the number of defects and failure data (involved into the model via application of Bayesian method). The proposed approach is applied to estimate the failure probability of a selected part of the Lithuanian natural gas transmission network. The presented approach for the estimation of integrated failure probability is a combination of several different analyses allowing us to obtain: the critical crack's length and depth, the failure probability of the defected zone thickness, dependency of the failure probability on the age of the natural gas transmission pipeline. A model's uncertainty analysis and uncertainty propagation analysis are performed, as well. - Highlights: • Degradation mechanisms of natural gas transmission pipelines. • Fracture mechanic analysis of the pipe with crack. • Stress evaluation of the pipe with critical crack. • Deterministic-probabilistic structural integrity analysis of gas pipeline. • Integrated estimation of pipeline failure probability by Bayesian method.

  17. Direct integration multiple collision integral transport analysis method for high energy fusion neutronics

    International Nuclear Information System (INIS)

    Koch, K.R.

    1985-01-01

    A new analysis method specially suited for the inherent difficulties of fusion neutronics was developed to provide detailed studies of the fusion neutron transport physics. These studies should provide a better understanding of the limitations and accuracies of typical fusion neutronics calculations. The new analysis method is based on the direct integration of the integral form of the neutron transport equation and employs a continuous energy formulation with the exact treatment of the energy angle kinematics of the scattering process. In addition, the overall solution is analyzed in terms of uncollided, once-collided, and multi-collided solution components based on a multiple collision treatment. Furthermore, the numerical evaluations of integrals use quadrature schemes that are based on the actual dependencies exhibited in the integrands. The new DITRAN computer code was developed on the Cyber 205 vector supercomputer to implement this direct integration multiple-collision fusion neutronics analysis. Three representative fusion reactor models were devised and the solutions to these problems were studied to provide suitable choices for the numerical quadrature orders as well as the discretized solution grid and to understand the limitations of the new analysis method. As further verification and as a first step in assessing the accuracy of existing fusion-neutronics calculations, solutions obtained using the new analysis method were compared to typical multigroup discrete ordinates calculations

  18. IMG: the integrated microbial genomes database and comparative analysis system

    Science.gov (United States)

    Markowitz, Victor M.; Chen, I-Min A.; Palaniappan, Krishna; Chu, Ken; Szeto, Ernest; Grechkin, Yuri; Ratner, Anna; Jacob, Biju; Huang, Jinghua; Williams, Peter; Huntemann, Marcel; Anderson, Iain; Mavromatis, Konstantinos; Ivanova, Natalia N.; Kyrpides, Nikos C.

    2012-01-01

    The Integrated Microbial Genomes (IMG) system serves as a community resource for comparative analysis of publicly available genomes in a comprehensive integrated context. IMG integrates publicly available draft and complete genomes from all three domains of life with a large number of plasmids and viruses. IMG provides tools and viewers for analyzing and reviewing the annotations of genes and genomes in a comparative context. IMG's data content and analytical capabilities have been continuously extended through regular updates since its first release in March 2005. IMG is available at http://img.jgi.doe.gov. Companion IMG systems provide support for expert review of genome annotations (IMG/ER: http://img.jgi.doe.gov/er), teaching courses and training in microbial genome analysis (IMG/EDU: http://img.jgi.doe.gov/edu) and analysis of genomes related to the Human Microbiome Project (IMG/HMP: http://www.hmpdacc-resources.org/img_hmp). PMID:22194640

  19. MDWeb and MDMoby: an integrated web-based platform for molecular dynamics simulations.

    Science.gov (United States)

    Hospital, Adam; Andrio, Pau; Fenollosa, Carles; Cicin-Sain, Damjan; Orozco, Modesto; Gelpí, Josep Lluís

    2012-05-01

    MDWeb and MDMoby constitute a web-based platform to help access to molecular dynamics (MD) in the standard and high-throughput regime. The platform provides tools to prepare systems from PDB structures mimicking the procedures followed by human experts. It provides inputs and can send simulations for three of the most popular MD packages (Amber, NAMD and Gromacs). Tools for analysis of trajectories, either provided by the user or retrieved from our MoDEL database (http://mmb.pcb.ub.es/MoDEL) are also incorporated. The platform has two ways of access, a set of web-services based on the BioMoby framework (MDMoby), programmatically accessible and a web portal (MDWeb). http://mmb.irbbarcelona.org/MDWeb; additional information and methodology details can be found at the web site ( http://mmb.irbbarcelona.org/MDWeb/help.php)

  20. Integrated structural biology to unravel molecular mechanisms of protein-RNA recognition.

    Science.gov (United States)

    Schlundt, Andreas; Tants, Jan-Niklas; Sattler, Michael

    2017-04-15

    Recent advances in RNA sequencing technologies have greatly expanded our knowledge of the RNA landscape in cells, often with spatiotemporal resolution. These techniques identified many new (often non-coding) RNA molecules. Large-scale studies have also discovered novel RNA binding proteins (RBPs), which exhibit single or multiple RNA binding domains (RBDs) for recognition of specific sequence or structured motifs in RNA. Starting from these large-scale approaches it is crucial to unravel the molecular principles of protein-RNA recognition in ribonucleoprotein complexes (RNPs) to understand the underlying mechanisms of gene regulation. Structural biology and biophysical studies at highest possible resolution are key to elucidate molecular mechanisms of RNA recognition by RBPs and how conformational dynamics, weak interactions and cooperative binding contribute to the formation of specific, context-dependent RNPs. While large compact RNPs can be well studied by X-ray crystallography and cryo-EM, analysis of dynamics and weak interaction necessitates the use of solution methods to capture these properties. Here, we illustrate methods to study the structure and conformational dynamics of protein-RNA complexes in solution starting from the identification of interaction partners in a given RNP. Biophysical and biochemical techniques support the characterization of a protein-RNA complex and identify regions relevant in structural analysis. Nuclear magnetic resonance (NMR) is a powerful tool to gain information on folding, stability and dynamics of RNAs and characterize RNPs in solution. It provides crucial information that is complementary to the static pictures derived from other techniques. NMR can be readily combined with other solution techniques, such as small angle X-ray and/or neutron scattering (SAXS/SANS), electron paramagnetic resonance (EPR), and Förster resonance energy transfer (FRET), which provide information about overall shapes, internal domain

  1. Functional Analysis of OMICs Data and Small Molecule Compounds in an Integrated "Knowledge-Based" Platform.

    Science.gov (United States)

    Dubovenko, Alexey; Nikolsky, Yuri; Rakhmatulin, Eugene; Nikolskaya, Tatiana

    2017-01-01

    Analysis of NGS and other sequencing data, gene variants, gene expression, proteomics, and other high-throughput (OMICs) data is challenging because of its biological complexity and high level of technical and biological noise. One way to deal with both problems is to perform analysis with a high fidelity annotated knowledgebase of protein interactions, pathways, and functional ontologies. This knowledgebase has to be structured in a computer-readable format and must include software tools for managing experimental data, analysis, and reporting. Here, we present MetaCore™ and Key Pathway Advisor (KPA), an integrated platform for functional data analysis. On the content side, MetaCore and KPA encompass a comprehensive database of molecular interactions of different types, pathways, network models, and ten functional ontologies covering human, mouse, and rat genes. The analytical toolkit includes tools for gene/protein list enrichment analysis, statistical "interactome" tool for the identification of over- and under-connected proteins in the dataset, and a biological network analysis module made up of network generation algorithms and filters. The suite also features Advanced Search, an application for combinatorial search of the database content, as well as a Java-based tool called Pathway Map Creator for drawing and editing custom pathway maps. Applications of MetaCore and KPA include molecular mode of action of disease research, identification of potential biomarkers and drug targets, pathway hypothesis generation, analysis of biological effects for novel small molecule compounds and clinical applications (analysis of large cohorts of patients, and translational and personalized medicine).

  2. Mathematical analysis of compressive/tensile molecular and nuclear structures

    Science.gov (United States)

    Wang, Dayu

    Mathematical analysis in chemistry is a fascinating and critical tool to explain experimental observations. In this dissertation, mathematical methods to present chemical bonding and other structures for many-particle systems are discussed at different levels (molecular, atomic, and nuclear). First, the tetrahedral geometry of single, double, or triple carbon-carbon bonds gives an unsatisfying demonstration of bond lengths, compared to experimental trends. To correct this, Platonic solids and Archimedean solids were evaluated as atoms in covalent carbon or nitrogen bond systems in order to find the best solids for geometric fitting. Pentagonal solids, e.g. the dodecahedron and icosidodecahedron, give the best fit with experimental bond lengths; an ideal pyramidal solid which models covalent bonds was also generated. Second, the macroscopic compression/tension architectural approach was applied to forces at the molecular level, considering atomic interactions as compressive (repulsive) and tensile (attractive) forces. Two particle interactions were considered, followed by a model of the dihydrogen molecule (H2; two protons and two electrons). Dihydrogen was evaluated as two different types of compression/tension structures: a coaxial spring model and a ring model. Using similar methods, covalent diatomic molecules (made up of C, N, O, or F) were evaluated. Finally, the compression/tension model was extended to the nuclear level, based on the observation that nuclei with certain numbers of protons/neutrons (magic numbers) have extra stability compared to other nucleon ratios. A hollow spherical model was developed that combines elements of the classic nuclear shell model and liquid drop model. Nuclear structure and the trend of the "island of stability" for the current and extended periodic table were studied.

  3. Molecular analysis of radiation-induced experimental tumors in mice

    International Nuclear Information System (INIS)

    Niwa, O.; Muto, M.; Suzuki, F.

    1992-01-01

    Molecular analysis was made on mouse tumors induced by radiation and chemicals. Expression of oncogenes was studied in 12 types of 178 mouse tumors. Southern blotting was done on tumors in which overexpression of oncogenes was noted. Amplification of the myc oncogene was found in chemically induced sarcomas, but not those induced by radiations. Radiogenic thymomas were studied in detail. These thymomas were induced in two different ways. The first was thymomas induced by direct irradiation of F1 mice between C57BL/6NxC3H/He. Southern analysis of DNA revealed deletion of specific minisatellite bands in these tumors. DNA from directly induced thymomas induced focus formation when transfected into normal Golden hamster cells. The mouse K-ras oncogene was detected in these transformants. The second type of thymomas was induced by X-irradiation of thymectomized B10.thy1.2 mice in which normal thymus from congenic B10,thy1.1. mice was grafted. Thymomas of the donor origin was analysed by transfection and the transformants by DNA from those indirectly induced thymomas did not contain activated ras oncogenes. (author)

  4. MDAnalysis: a toolkit for the analysis of molecular dynamics simulations.

    Science.gov (United States)

    Michaud-Agrawal, Naveen; Denning, Elizabeth J; Woolf, Thomas B; Beckstein, Oliver

    2011-07-30

    MDAnalysis is an object-oriented library for structural and temporal analysis of molecular dynamics (MD) simulation trajectories and individual protein structures. It is written in the Python language with some performance-critical code in C. It uses the powerful NumPy package to expose trajectory data as fast and efficient NumPy arrays. It has been tested on systems of millions of particles. Many common file formats of simulation packages including CHARMM, Gromacs, Amber, and NAMD and the Protein Data Bank format can be read and written. Atoms can be selected with a syntax similar to CHARMM's powerful selection commands. MDAnalysis enables both novice and experienced programmers to rapidly write their own analytical tools and access data stored in trajectories in an easily accessible manner that facilitates interactive explorative analysis. MDAnalysis has been tested on and works for most Unix-based platforms such as Linux and Mac OS X. It is freely available under the GNU General Public License from http://mdanalysis.googlecode.com. Copyright © 2011 Wiley Periodicals, Inc.

  5. Molecular Characterization and Expression Analysis of Equine ( Gene in Horse (

    Directory of Open Access Journals (Sweden)

    Ki-Duk Song

    2014-05-01

    Full Text Available The objective of this study was to determine the molecular characteristics of the horse vascular endothelial growth factor alpha gene (VEGFα by constructing a phylogenetic tree, and to investigate gene expression profiles in tissues and blood leukocytes after exercise for development of suitable biomarkers. Using published amino acid sequences of other vertebrate species (human, chimpanzee, mouse, rat, cow, pig, chicken and dog, we constructed a phylogenetic tree which showed that equine VEGFα belonged to the same clade of the pig VEGFα. Analysis for synonymous (Ks and non-synonymous substitution ratios (Ka revealed that the horse VEGFα underwent positive selection. RNA was extracted from blood samples before and after exercise and different tissue samples of three horses. Expression analyses using reverse transcription-polymerase chain reaction (RT-PCR and quantitative-polymerase chain reaction (qPCR showed ubiquitous expression of VEGFα mRNA in skeletal muscle, kidney, thyroid, lung, appendix, colon, spinal cord, and heart tissues. Analysis of differential expression of VEGFα gene in blood leukocytes after exercise indicated a unimodal pattern. These results will be useful in developing biomarkers that can predict the recovery capacity of racing horses.

  6. Integrative sparse principal component analysis of gene expression data.

    Science.gov (United States)

    Liu, Mengque; Fan, Xinyan; Fang, Kuangnan; Zhang, Qingzhao; Ma, Shuangge

    2017-12-01

    In the analysis of gene expression data, dimension reduction techniques have been extensively adopted. The most popular one is perhaps the PCA (principal component analysis). To generate more reliable and more interpretable results, the SPCA (sparse PCA) technique has been developed. With the "small sample size, high dimensionality" characteristic of gene expression data, the analysis results generated from a single dataset are often unsatisfactory. Under contexts other than dimension reduction, integrative analysis techniques, which jointly analyze the raw data of multiple independent datasets, have been developed and shown to outperform "classic" meta-analysis and other multidatasets techniques and single-dataset analysis. In this study, we conduct integrative analysis by developing the iSPCA (integrative SPCA) method. iSPCA achieves the selection and estimation of sparse loadings using a group penalty. To take advantage of the similarity across datasets and generate more accurate results, we further impose contrasted penalties. Different penalties are proposed to accommodate different data conditions. Extensive simulations show that iSPCA outperforms the alternatives under a wide spectrum of settings. The analysis of breast cancer and pancreatic cancer data further shows iSPCA's satisfactory performance. © 2017 WILEY PERIODICALS, INC.

  7. A hybrid approach to device integration on a genetic analysis platform

    International Nuclear Information System (INIS)

    Brennan, Des; Justice, John; Aherne, Margaret; Galvin, Paul; Jary, Dorothee; Kurg, Ants; Berik, Evgeny; Macek, Milan

    2012-01-01

    Point-of-care (POC) systems require significant component integration to implement biochemical protocols associated with molecular diagnostic assays. Hybrid platforms where discrete components are combined in a single platform are a suitable approach to integration, where combining multiple device fabrication steps on a single substrate is not possible due to incompatible or costly fabrication steps. We integrate three devices each with a specific system functionality: (i) a silicon electro-wetting-on-dielectric (EWOD) device to move and mix sample and reagent droplets in an oil phase, (ii) a polymer microfluidic chip containing channels and reservoirs and (iii) an aqueous phase glass microarray for fluorescence microarray hybridization detection. The EWOD device offers the possibility of fully integrating on-chip sample preparation using nanolitre sample and reagent volumes. A key challenge is sample transfer from the oil phase EWOD device to the aqueous phase microarray for hybridization detection. The EWOD device, waveguide performance and functionality are maintained during the integration process. An on-chip biochemical protocol for arrayed primer extension (APEX) was implemented for single nucleotide polymorphism (SNiP) analysis. The prepared sample is aspirated from the EWOD oil phase to the aqueous phase microarray for hybridization. A bench-top instrumentation system was also developed around the integrated platform to drive the EWOD electrodes, implement APEX sample heating and image the microarray after hybridization. (paper)

  8. Train integrity detection risk analysis based on PRISM

    Science.gov (United States)

    Wen, Yuan

    2018-04-01

    GNSS based Train Integrity Monitoring System (TIMS) is an effective and low-cost detection scheme for train integrity detection. However, as an external auxiliary system of CTCS, GNSS may be influenced by external environments, such as uncertainty of wireless communication channels, which may lead to the failure of communication and positioning. In order to guarantee the reliability and safety of train operation, a risk analysis method of train integrity detection based on PRISM is proposed in this article. First, we analyze the risk factors (in GNSS communication process and the on-board communication process) and model them. Then, we evaluate the performance of the model in PRISM based on the field data. Finally, we discuss how these risk factors influence the train integrity detection process.

  9. Strategic Integration of Multiple Bioinformatics Resources for System Level Analysis of Biological Networks.

    Science.gov (United States)

    D'Souza, Mark; Sulakhe, Dinanath; Wang, Sheng; Xie, Bing; Hashemifar, Somaye; Taylor, Andrew; Dubchak, Inna; Conrad Gilliam, T; Maltsev, Natalia

    2017-01-01

    Recent technological advances in genomics allow the production of biological data at unprecedented tera- and petabyte scales. Efficient mining of these vast and complex datasets for the needs of biomedical research critically depends on a seamless integration of the clinical, genomic, and experimental information with prior knowledge about genotype-phenotype relationships. Such experimental data accumulated in publicly available databases should be accessible to a variety of algorithms and analytical pipelines that drive computational analysis and data mining.We present an integrated computational platform Lynx (Sulakhe et al., Nucleic Acids Res 44:D882-D887, 2016) ( http://lynx.cri.uchicago.edu ), a web-based database and knowledge extraction engine. It provides advanced search capabilities and a variety of algorithms for enrichment analysis and network-based gene prioritization. It gives public access to the Lynx integrated knowledge base (LynxKB) and its analytical tools via user-friendly web services and interfaces. The Lynx service-oriented architecture supports annotation and analysis of high-throughput experimental data. Lynx tools assist the user in extracting meaningful knowledge from LynxKB and experimental data, and in the generation of weighted hypotheses regarding the genes and molecular mechanisms contributing to human phenotypes or conditions of interest. The goal of this integrated platform is to support the end-to-end analytical needs of various translational projects.

  10. Argentinean integrated small reactor design and scale economy analysis of integrated reactor

    International Nuclear Information System (INIS)

    Florido, P. C.; Bergallo, J. E.; Ishida, M. V.

    2000-01-01

    This paper describes the design of CAREM, which is Argentinean integrated small reactor project and the scale economy analysis results of integrated reactor. CAREM project consists on the development, design and construction of a small nuclear power plant. CAREM is an advanced reactor conceived with new generation design solutions and standing on the large experience accumulated in the safe operation of Light Water Reactors. The CAREM is an indirect cycle reactor with some distinctive and characteristic features that greatly simplify the reactor and also contribute to a highly level of safety: integrated primary cooling system, self pressurized, primary cooling by natural circulation and safety system relying on passive features. For a fully doupled economic evaluation of integrated reactors done by IREP (Integrated Reactor Evaluation Program) code transferred to IAEA, CAREM have been used as a reference point. The results shows that integrated reactors become competitive with power larger than 200MWe with Argentinean cheapest electricity option. Due to reactor pressure vessel construction limit, low pressure drop steam generator are used to reach power output of 200MWe for natural circulation. For forced circulation, 300MWe can be achieved. (author)

  11. Development of Probabilistic Structural Analysis Integrated with Manufacturing Processes

    Science.gov (United States)

    Pai, Shantaram S.; Nagpal, Vinod K.

    2007-01-01

    An effort has been initiated to integrate manufacturing process simulations with probabilistic structural analyses in order to capture the important impacts of manufacturing uncertainties on component stress levels and life. Two physics-based manufacturing process models (one for powdered metal forging and the other for annular deformation resistance welding) have been linked to the NESSUS structural analysis code. This paper describes the methodology developed to perform this integration including several examples. Although this effort is still underway, particularly for full integration of a probabilistic analysis, the progress to date has been encouraging and a software interface that implements the methodology has been developed. The purpose of this paper is to report this preliminary development.

  12. Integration of rocket turbine design and analysis through computer graphics

    Science.gov (United States)

    Hsu, Wayne; Boynton, Jim

    1988-01-01

    An interactive approach with engineering computer graphics is used to integrate the design and analysis processes of a rocket engine turbine into a progressive and iterative design procedure. The processes are interconnected through pre- and postprocessors. The graphics are used to generate the blade profiles, their stacking, finite element generation, and analysis presentation through color graphics. Steps of the design process discussed include pitch-line design, axisymmetric hub-to-tip meridional design, and quasi-three-dimensional analysis. The viscous two- and three-dimensional analysis codes are executed after acceptable designs are achieved and estimates of initial losses are confirmed.

  13. INS integrated motion analysis for autonomous vehicle navigation

    Science.gov (United States)

    Roberts, Barry; Bazakos, Mike

    1991-01-01

    The use of inertial navigation system (INS) measurements to enhance the quality and robustness of motion analysis techniques used for obstacle detection is discussed with particular reference to autonomous vehicle navigation. The approach to obstacle detection used here employs motion analysis of imagery generated by a passive sensor. Motion analysis of imagery obtained during vehicle travel is used to generate range measurements to points within the field of view of the sensor, which can then be used to provide obstacle detection. Results obtained with an INS integrated motion analysis approach are reviewed.

  14. Integrating computer programs for engineering analysis and design

    Science.gov (United States)

    Wilhite, A. W.; Crisp, V. K.; Johnson, S. C.

    1983-01-01

    The design of a third-generation system for integrating computer programs for engineering and design has been developed for the Aerospace Vehicle Interactive Design (AVID) system. This system consists of an engineering data management system, program interface software, a user interface, and a geometry system. A relational information system (ARIS) was developed specifically for the computer-aided engineering system. It is used for a repository of design data that are communicated between analysis programs, for a dictionary that describes these design data, for a directory that describes the analysis programs, and for other system functions. A method is described for interfacing independent analysis programs into a loosely-coupled design system. This method emphasizes an interactive extension of analysis techniques and manipulation of design data. Also, integrity mechanisms exist to maintain database correctness for multidisciplinary design tasks by an individual or a team of specialists. Finally, a prototype user interface program has been developed to aid in system utilization.

  15. Integrative taxonomy of ciliates: Assessment of molecular phylogenetic content and morphological homology testing.

    Science.gov (United States)

    Vďačný, Peter

    2017-10-01

    The very diverse and comparatively complex morphology of ciliates has given rise to numerous taxonomic concepts. However, the information content of the utilized molecular markers has seldom been explored prior to phylogenetic analyses and taxonomic decisions. Likewise, robust testing of morphological homology statements and the apomorphic nature of diagnostic characters of ciliate taxa is rarely carried out. Four phylogenetic techniques that may help address these issues are reviewed. (1) Split spectrum analysis serves to determine the exact number and quality of nucleotide positions supporting individual nodes in phylogenetic trees and to discern long-branch artifacts that cause spurious phylogenies. (2) Network analysis can depict all possible evolutionary trajectories inferable from the dataset and locate and measure the conflict between them. (3) A priori likelihood mapping tests the suitability of data for reconstruction of a well resolved tree, visualizes the tree-likeness of quartets, and assesses the support of an internal branch of a given tree topology. (4) Reconstruction of ancestral morphologies can be applied for analyzing homology and apomorphy statements without circular reasoning. Since these phylogenetic tools are rarely used, their principles and interpretation are introduced and exemplified using various groups of ciliates. Finally, environmental sequencing data are discussed in this light. Copyright © 2017 The Author. Published by Elsevier GmbH.. All rights reserved.

  16. Integration of heterogeneous molecular networks to unravel gene-regulation in Mycobacterium tuberculosis.

    Science.gov (United States)

    van Dam, Jesse C J; Schaap, Peter J; Martins dos Santos, Vitor A P; Suárez-Diez, María

    2014-09-26

    Different methods have been developed to infer regulatory networks from heterogeneous omics datasets and to construct co-expression networks. Each algorithm produces different networks and efforts have been devoted to automatically integrate them into consensus sets. However each separate set has an intrinsic value that is diluted and partly lost when building a consensus network. Here we present a methodology to generate co-expression networks and, instead of a consensus network, we propose an integration framework where the different networks are kept and analysed with additional tools to efficiently combine the information extracted from each network. We developed a workflow to efficiently analyse information generated by different inference and prediction methods. Our methodology relies on providing the user the means to simultaneously visualise and analyse the coexisting networks generated by different algorithms, heterogeneous datasets, and a suite of analysis tools. As a show case, we have analysed the gene co-expression networks of Mycobacterium tuberculosis generated using over 600 expression experiments. Regarding DNA damage repair, we identified SigC as a key control element, 12 new targets for LexA, an updated LexA binding motif, and a potential mismatch repair system. We expanded the DevR regulon with 27 genes while identifying 9 targets wrongly assigned to this regulon. We discovered 10 new genes linked to zinc uptake and a new regulatory mechanism for ZuR. The use of co-expression networks to perform system level analysis allows the development of custom made methodologies. As show cases we implemented a pipeline to integrate ChIP-seq data and another method to uncover multiple regulatory layers. Our workflow is based on representing the multiple types of information as network representations and presenting these networks in a synchronous framework that allows their simultaneous visualization while keeping specific associations from the different

  17. Analysis and Modeling of Integrated Magnetics for LLC resonant Converters

    DEFF Research Database (Denmark)

    Li, Mingxiao; Ouyang, Ziwei; Zhao, Bin

    2017-01-01

    Shunt-inserted transformers are widely used toobtain high leakage inductance. This paper investigates thismethod in depth to make it applicable to integrate resonantinductor for the LLC resonant converters. The analysis andmodel of magnetizing inductance and leakage inductance forshunt...... transformers can provide a significantdifference. The way to obtain the desirable magnetizing andleakage inductance value for LLC resonant converters issimplified by the creation of air gaps together with a magneticshunt. The calculation and relation are validated by finiteelement analysis (FEA) simulations...

  18. Integrated dynamic modeling and management system mission analysis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, A.K.

    1994-12-28

    This document summarizes the mission analysis performed on the Integrated Dynamic Modeling and Management System (IDMMS). The IDMMS will be developed to provide the modeling and analysis capability required to understand the TWRS system behavior in terms of the identified TWRS performance measures. The IDMMS will be used to demonstrate in a verified and validated manner the satisfactory performance of the TWRS system configuration and assurance that the requirements have been satisfied.

  19. Integrated dynamic modeling and management system mission analysis

    International Nuclear Information System (INIS)

    Lee, A.K.

    1994-01-01

    This document summarizes the mission analysis performed on the Integrated Dynamic Modeling and Management System (IDMMS). The IDMMS will be developed to provide the modeling and analysis capability required to understand the TWRS system behavior in terms of the identified TWRS performance measures. The IDMMS will be used to demonstrate in a verified and validated manner the satisfactory performance of the TWRS system configuration and assurance that the requirements have been satisfied

  20. Heater-Integrated Cantilevers for Nano-Samples Thermogravimetric Analysis

    OpenAIRE

    Toffoli, Valeria; Carrato, Sergio; Lee, Dongkyu; Jeon, Sangmin; Lazzarino, Marco

    2013-01-01

    The design and characteristics of a micro-system for thermogravimetric analysis (TGA) in which heater, temperature sensor and mass sensor are integrated into a single device are presented. The system consists of a suspended cantilever that incorporates a microfabricated resistor, used as both heater and thermometer. A three-dimensional finite element analysis was used to define the structure parameters. TGA sensors were fabricated by standard microlithographic techniques and tested using mill...

  1. Elucidating the Aβ42 Anti-Aggregation Mechanism of Action of Tramiprosate in Alzheimer's Disease: Integrating Molecular Analytical Methods, Pharmacokinetic and Clinical Data.

    Science.gov (United States)

    Kocis, Petr; Tolar, Martin; Yu, Jeremy; Sinko, William; Ray, Soumya; Blennow, Kaj; Fillit, Howard; Hey, John A

    2017-06-01

    Amyloid beta (Aβ) oligomers play a critical role in the pathogenesis of Alzheimer's disease (AD) and represent a promising target for drug development. Tramiprosate is a small-molecule Aβ anti-aggregation agent that was evaluated in phase III clinical trials for AD but did not meet the primary efficacy endpoints; however, a pre-specified subgroup analysis revealed robust, sustained, and clinically meaningful cognitive and functional effects in patients with AD homozygous for the ε4 allele of apolipoprotein E4 (APOE4/4 homozygotes), who carry an increased risk for the disease. Therefore, to build on this important efficacy attribute and to further improve its pharmaceutical properties, we have developed a prodrug of tramiprosate ALZ-801 that is in advanced stages of clinical development. To elucidate how tramiprosate works, we investigated its molecular mechanism of action (MOA) and the translation to observed clinical outcomes. The two main objectives of this research were to (1) elucidate and characterize the MOA of tramiprosate via an integrated application of three independent molecular methodologies and (2) present an integrated translational analysis that links the MOA, conformation of the target, stoichiometry, and pharmacokinetic dose exposure to the observed clinical outcome in APOE4/4 homozygote subjects. We used three molecular analytical methods-ion mobility spectrometry-mass spectrometry (IMS-MS), nuclear magnetic resonance (NMR), and molecular dynamics-to characterize the concentration-related interactions of tramiprosate versus Aβ42 monomers and the resultant conformational alterations affecting aggregation into oligomers. The molecular stoichiometry of the tramiprosate versus Aβ42 interaction was further analyzed in the context of clinical pharmacokinetic dose exposure and central nervous system Aβ42 levels (i.e., pharmacokinetic-pharmacodynamic translation in humans). We observed a multi-ligand interaction of tramiprosate with monomeric Aβ42

  2. On the Integration of Digital Design and Analysis Tools

    DEFF Research Database (Denmark)

    Klitgaard, Jens; Kirkegaard, Poul Henning

    2006-01-01

    The aim of this research is to look into integrated digital design and analysis tools in order to find out if it is suited for use by architects and designers or only by specialists and technicians - and if not, then to look at what can be done to make them more available to architects and design...

  3. Multi-criteria decision analysis integrated with GIS for radio ...

    African Journals Online (AJOL)

    Multi-criteria decision analysis integrated with GIS for radio astronomical observatory site selection in peninsular of Malaysia. R Umar, Z.Z. Abidin, Z.A. Ibrahim, M.K.A. Kamarudin, S.N. Hazmin, A Endut, H Juahir ...

  4. Integrated analysis for genotypic adaptation in rice | Das | African ...

    African Journals Online (AJOL)

    Integrated analysis for genotypic adaptation in rice. S Das, RC Misra, MC Pattnaik, SK Sinha. Abstract. Development of varieties with high yield potential coupled with wide adaptability is an important plant breeding objective. The presence of genotype by environment (GxE) interaction plays a crucial role in determining the ...

  5. Integration of Design and Control Through Model Analysis

    DEFF Research Database (Denmark)

    Russel, Boris Mariboe; Henriksen, Jens Peter; Jørgensen, Sten Bay

    2000-01-01

    of the phenomena models representing the process model identify the relationships between the important process and design variables, which help to understand, define and address some of the issues related to integration of design and control issues. The model analysis is highlighted through examples involving...... processes with mass and/or energy recycle. (C) 2000 Elsevier Science Ltd. All rights reserved....

  6. Sex Change in Clownfish: Molecular Insights from Transcriptome Analysis

    KAUST Repository

    Casas, Laura

    2016-10-17

    Sequential hermaphroditism is a unique reproductive strategy among teleosts that is displayed mainly in fish species living in the coral reef environment. The reproductive biology of hermaphrodites has long been intriguing; however, very little is known about the molecular pathways underlying their sex change. Here, we provide the first de novo transcriptome analyses of a hermaphrodite teleost´s undergoing sex change in its natural environment. Our study has examined relative gene expression across multiple groups—rather than just two contrasting conditions— and has allowed us to explore the differential expression patterns throughout the whole process. Our analysis has highlighted the rapid and complex genomic response of the brain associated with sex change, which is subsequently transmitted to the gonads, identifying a large number of candidate genes, some well-known and some novel, involved in the process. The present study provides strong evidence of the importance of the sex steroidogenic machinery during sex change in clownfish, with the aromatase gene playing a central role, both in the brain and the gonad. This work constitutes the first genome-wide study in a social sex-changing species and provides insights into the genetic mechanism governing social sex change and gonadal restructuring in protandrous hermaphrodites.

  7. Molecular genetic analysis of phosphomannomutase genes in Triticum monococcum

    Institute of Scientific and Technical Information of China (English)

    Chunmei; Yu; Xinyan; Liu; Qian; Zhang; Xinyu; He; Wan; Huai; Baohua; Wang; Yunying; Cao; Rong; Zhou

    2015-01-01

    In higher plants, phosphomannomutase(PMM) is essential for synthesizing the antioxidant ascorbic acid through the Smirnoff–Wheeler pathway. Previously, we characterized six PMM genes(Ta PMM-A1, A2, B1, B2, D1 and D2) in common wheat(Triticum aestivum, AABBDD).Here, we report a molecular genetic analysis of PMM genes in Triticum monococcum(AmAm), a diploid wheat species whose Amgenome is closely related to the A genome of common wheat. Two distinct PMM genes, Tm PMM-1 and Tm PMM-2, were found in T. monococcum. The coding region of Tm PMM-1 was intact and highly conserved. In contrast, two main Tm PMM-2 alleles were identified, with Tm PMM-2a possessing an intact coding sequence and Tm PMM-2b being a pseudogene. The transcript level of Tm PMM-2a was much higher than that of Tm PMM-2b, and a bacterially expressed Tm PMM-2a recombinant protein displayed relatively high PMM activity. In general, the total transcript level of PMM was substantially higher in accessions carrying Tm PMM-1 and Tm PMM-2a than those harboring Tm PMM-1 and Tm PMM-2b. However, total PMM protein and activity levels did not differ drastically between the two genotypes. This work provides new information on PMM genes in T. monococcum and expands our understanding on Triticeae PMM genes, which may aid further functional and applied studies of PMM in crop plants.

  8. Enhancing yeast transcription analysis through integration of heterogeneous data

    DEFF Research Database (Denmark)

    Grotkjær, Thomas; Nielsen, Jens

    2004-01-01

    of Saccharomyces cerevisiae whole genome transcription data. A special focus is on the quantitative aspects of normalisation and mathematical modelling approaches, since they are expected to play an increasing role in future DNA microarray analysis studies. Data analysis is exemplified with cluster analysis......DNA microarray technology enables the simultaneous measurement of the transcript level of thousands of genes. Primary analysis can be done with basic statistical tools and cluster analysis, but effective and in depth analysis of the vast amount of transcription data requires integration with data...... from several heterogeneous data Sources, such as upstream promoter sequences, genome-scale metabolic models, annotation databases and other experimental data. In this review, we discuss how experimental design, normalisation, heterogeneous data and mathematical modelling can enhance analysis...

  9. MEGA-CC: computing core of molecular evolutionary genetics analysis program for automated and iterative data analysis.

    Science.gov (United States)

    Kumar, Sudhir; Stecher, Glen; Peterson, Daniel; Tamura, Koichiro

    2012-10-15

    There is a growing need in the research community to apply the molecular evolutionary genetics analysis (MEGA) software tool for batch processing a large number of datasets and to integrate it into analysis workflows. Therefore, we now make available the computing core of the MEGA software as a stand-alone executable (MEGA-CC), along with an analysis prototyper (MEGA-Proto). MEGA-CC provides users with access to all the computational analyses available through MEGA's graphical user interface version. This includes methods for multiple sequence alignment, substitution model selection, evolutionary distance estimation, phylogeny inference, substitution rate and pattern estimation, tests of natural selection and ancestral sequence inference. Additionally, we have upgraded the source code for phylogenetic analysis using the maximum likelihood methods for parallel execution on multiple processors and cores. Here, we describe MEGA-CC and outline the steps for using MEGA-CC in tandem with MEGA-Proto for iterative and automated data analysis. http://www.megasoftware.net/.

  10. Gene hunting: molecular analysis of the chicken genome

    NARCIS (Netherlands)

    Crooijmans, R.P.M.A.

    2000-01-01

    This dissertation describes the development of molecular tools to identify genes that are involved in production and health traits in poultry. To unravel the chicken genome, fluorescent molecular markers (microsatellite markers) were developed and optimized to perform high throughput

  11. The Silica-Water Interface from the Analysis of Molecular Dynamic Simulations

    KAUST Repository

    Lardhi, Sheikha F.

    2013-05-01

    Surface chemistry is an emerging field that can give detailed insight about the elec- tronic properties and the interaction of complex material surfaces with their neigh- bors. This is for both solid-solid and solid-liquid interfaces. Among the latter class, the silica-water interface plays a major role in nature. Silica is among the most abundant materials on earth, as well in advanced technological applications such as catalysis and nanotechnology. This immediately indicates the relevance of a detailed understanding of the silica-water interface. In this study, we investigate the details of this interaction at microscopic level by analyzing trajectories obtained with ab initio molecular dynamic simulations. The system we consider consists of bulk liquid water confined between two β-cristobalite silica surfaces. The molecular dynamics were generated with the CP2K, an ab initio molecular dynamic simulation tool. The simulations are 25 picoseconds long, and the CP2K program was run on 64 cores on a supercomputer cluster. During the simulations the program integrates Newton’s equations of motion for the system and generates the trajectory for analysis. For analysis, we focused on the following properties that characterize the silica water interface. We calculated the density profile of the water layers from the silica surface, and we also calculated the radial distribution function (RDF) of the hydrogen bond at the silanols on the silica surface. The main focus of this thesis is to write the programs for calculating the atom density profile and the RDF from the generated MD trajectories. The atomic probability density profile shows that water is strongly adsorbed on the (001) cristobalite surface, while the RDF indicates differently ad- sorbed water molecules in the first adsorption layer. As final remark, the protocol and the tools developed in this thesis can be applied to the study of basically any crystal-water interface.

  12. Integration of End-User Cloud Storage for CMS Analysis

    CERN Document Server

    Riahi, Hassen; Álvarez Ayllón, Alejandro; Balcas, Justas; Ciangottini, Diego; Hernández, José M; Keeble, Oliver; Magini, Nicolò; Manzi, Andrea; Mascetti, Luca; Mascheroni, Marco; Tanasijczuk, Andres Jorge; Vaandering, Eric Wayne

    2018-01-01

    End-user Cloud storage is increasing rapidly in popularity in research communities thanks to the collaboration capabilities it offers, namely synchronisation and sharing. CERN IT has implemented a model of such storage named, CERNBox, integrated with the CERN AuthN and AuthZ services. To exploit the use of the end-user Cloud storage for the distributed data analysis activity, the CMS experiment has started the integration of CERNBox as a Grid resource. This will allow CMS users to make use of their own storage in the Cloud for their analysis activities as well as to benefit from synchronisation and sharing capabilities to achieve results faster and more effectively. It will provide an integration model of Cloud storages in the Grid, which is implemented and commissioned over the world’s largest computing Grid infrastructure, Worldwide LHC Computing Grid (WLCG). In this paper, we present the integration strategy and infrastructure changes needed in order to transparently integrate end-user Cloud storage with...

  13. A new approach to calculate charge carrier transport mobility in organic molecular crystals from imaginary time path integral simulations

    International Nuclear Information System (INIS)

    Song, Linze; Shi, Qiang

    2015-01-01

    We present a new non-perturbative method to calculate the charge carrier mobility using the imaginary time path integral approach, which is based on the Kubo formula for the conductivity, and a saddle point approximation to perform the analytic continuation. The new method is first tested using a benchmark calculation from the numerical exact hierarchical equations of motion method. Imaginary time path integral Monte Carlo simulations are then performed to explore the temperature dependence of charge carrier delocalization and mobility in organic molecular crystals (OMCs) within the Holstein and Holstein-Peierls models. The effects of nonlocal electron-phonon interaction on mobility in different charge transport regimes are also investigated

  14. Application of Stochastic Sensitivity Analysis to Integrated Force Method

    Directory of Open Access Journals (Sweden)

    X. F. Wei

    2012-01-01

    Full Text Available As a new formulation in structural analysis, Integrated Force Method has been successfully applied to many structures for civil, mechanical, and aerospace engineering due to the accurate estimate of forces in computation. Right now, it is being further extended to the probabilistic domain. For the assessment of uncertainty effect in system optimization and identification, the probabilistic sensitivity analysis of IFM was further investigated in this study. A set of stochastic sensitivity analysis formulation of Integrated Force Method was developed using the perturbation method. Numerical examples are presented to illustrate its application. Its efficiency and accuracy were also substantiated with direct Monte Carlo simulations and the reliability-based sensitivity method. The numerical algorithm was shown to be readily adaptable to the existing program since the models of stochastic finite element and stochastic design sensitivity are almost identical.

  15. A Key Event Path Analysis Approach for Integrated Systems

    Directory of Open Access Journals (Sweden)

    Jingjing Liao

    2012-01-01

    Full Text Available By studying the key event paths of probabilistic event structure graphs (PESGs, a key event path analysis approach for integrated system models is proposed. According to translation rules concluded from integrated system architecture descriptions, the corresponding PESGs are constructed from the colored Petri Net (CPN models. Then the definitions of cycle event paths, sequence event paths, and key event paths are given. Whereafter based on the statistic results after the simulation of CPN models, key event paths are found out by the sensitive analysis approach. This approach focuses on the logic structures of CPN models, which is reliable and could be the basis of structured analysis for discrete event systems. An example of radar model is given to characterize the application of this approach, and the results are worthy of trust.

  16. Integrative Analysis of Metabolic Models – from Structure to Dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Hartmann, Anja, E-mail: hartmann@ipk-gatersleben.de [Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Gatersleben (Germany); Schreiber, Falk [Monash University, Melbourne, VIC (Australia); Martin-Luther-University Halle-Wittenberg, Halle (Germany)

    2015-01-26

    The characterization of biological systems with respect to their behavior and functionality based on versatile biochemical interactions is a major challenge. To understand these complex mechanisms at systems level modeling approaches are investigated. Different modeling formalisms allow metabolic models to be analyzed depending on the question to be solved, the biochemical knowledge and the availability of experimental data. Here, we describe a method for an integrative analysis of the structure and dynamics represented by qualitative and quantitative metabolic models. Using various formalisms, the metabolic model is analyzed from different perspectives. Determined structural and dynamic properties are visualized in the context of the metabolic model. Interaction techniques allow the exploration and visual analysis thereby leading to a broader understanding of the behavior and functionality of the underlying biological system. The System Biology Metabolic Model Framework (SBM{sup 2} – Framework) implements the developed method and, as an example, is applied for the integrative analysis of the crop plant potato.

  17. Construction of an integrated database to support genomic sequence analysis

    Energy Technology Data Exchange (ETDEWEB)

    Gilbert, W.; Overbeek, R.

    1994-11-01

    The central goal of this project is to develop an integrated database to support comparative analysis of genomes including DNA sequence data, protein sequence data, gene expression data and metabolism data. In developing the logic-based system GenoBase, a broader integration of available data was achieved due to assistance from collaborators. Current goals are to easily include new forms of data as they become available and to easily navigate through the ensemble of objects described within the database. This report comments on progress made in these areas.

  18. Containment integrity analysis with SAMPSON/DCRA module

    International Nuclear Information System (INIS)

    Hosoda, Seigo; Shirakawa, Noriyuki; Naitoh, Masanori

    2006-01-01

    The integrity of PWR containment under a severe accident is analyzed using the debris concrete reaction analysis code. If core fuels melt through the pressure vessel and the debris accumulates on the reactor cavity of a lower part of containment, its temperature continues to rise due to decay heat and the debris ablates the concrete floor. In case that cooling water is issued into the containment cavity and the amount of debris is limited to 30% of core fuels, our analyses showed that the debris could be cooled and frozen so that integrity of containment could hold. (author)

  19. From gene to structure: Lactobacillus bulgaricus D-lactate dehydrogenase from yogurt as an integrated curriculum model for undergraduate molecular biology and biochemistry laboratory courses.

    Science.gov (United States)

    Lawton, Jeffrey A; Prescott, Noelle A; Lawton, Ping X

    2018-05-01

    We have developed an integrated, project-oriented curriculum for undergraduate molecular biology and biochemistry laboratory courses spanning two semesters that is organized around the ldhA gene from the yogurt-fermenting bacterium Lactobacillus bulgaricus, which encodes the enzyme d-lactate dehydrogenase. The molecular biology module, which consists of nine experiments carried out over eleven sessions, begins with the isolation of genomic DNA from L. bulgaricus in yogurt and guides students through the process of cloning the ldhA gene into a prokaryotic expression vector, followed by mRNA isolation and characterization of recombinant gene expression levels using RT-PCR. The biochemistry module, which consists of nine experiments carried out over eight sessions, begins with overexpression of the cloned ldhA gene and guides students through the process of affinity purification, biochemical characterization of the purified LdhA protein, and analysis of enzyme kinetics using various substrates and an inhibitor, concluding with a guided inquiry investigation of structure-function relationships in the three-dimensional structure of LdhA using molecular visualization software. Students conclude by writing a paper describing their work on the project, formatted as a manuscript to be submitted for publication in a scientific journal. Overall, this curriculum, with its emphasis on experiential learning, provides hands-on training with a variety of common laboratory techniques in molecular biology and biochemistry and builds experience with the process of scientific reasoning, along with reinforcement of essential transferrable skills such as critical thinking, information literacy, and written communication, all within the framework of an extended project having the look and feel of a research experience. © 2018 by The International Union of Biochemistry and Molecular Biology, 46(3):270-278, 2018. © 2018 The International Union of Biochemistry and Molecular Biology.

  20. Path integral molecular dynamics within the grand canonical-like adaptive resolution technique: Simulation of liquid water

    Energy Technology Data Exchange (ETDEWEB)

    Agarwal, Animesh, E-mail: animesh@zedat.fu-berlin.de; Delle Site, Luigi, E-mail: dellesite@fu-berlin.de [Institute for Mathematics, Freie Universität Berlin, Berlin (Germany)

    2015-09-07

    Quantum effects due to the spatial delocalization of light atoms are treated in molecular simulation via the path integral technique. Among several methods, Path Integral (PI) Molecular Dynamics (MD) is nowadays a powerful tool to investigate properties induced by spatial delocalization of atoms; however, computationally this technique is very demanding. The above mentioned limitation implies the restriction of PIMD applications to relatively small systems and short time scales. One of the possible solutions to overcome size and time limitation is to introduce PIMD algorithms into the Adaptive Resolution Simulation Scheme (AdResS). AdResS requires a relatively small region treated at path integral level and embeds it into a large molecular reservoir consisting of generic spherical coarse grained molecules. It was previously shown that the realization of the idea above, at a simple level, produced reasonable results for toy systems or simple/test systems like liquid parahydrogen. Encouraged by previous results, in this paper, we show the simulation of liquid water at room conditions where AdResS, in its latest and more accurate Grand-Canonical-like version (GC-AdResS), is merged with two of the most relevant PIMD techniques available in the literature. The comparison of our results with those reported in the literature and/or with those obtained from full PIMD simulations shows a highly satisfactory agreement.

  1. Analysis of T-DNA integration and generative segregation in transgenic winter triticale (x Triticosecale Wittmack

    Directory of Open Access Journals (Sweden)

    Hensel Goetz

    2012-09-01

    Full Text Available Abstract Background While the genetic transformation of the major cereal crops has become relatively routine, to date only a few reports were published on transgenic triticale, and robust data on T-DNA integration and segregation have not been available in this species. Results Here, we present a comprehensive analysis of stable transgenic winter triticale cv. Bogo carrying the selectable marker gene HYGROMYCIN PHOSPHOTRANSFERASE (HPT and a synthetic green fluorescent protein gene (gfp. Progeny of four independent transgenic plants were comprehensively investigated with regard to the number of integrated T-DNA copies, the number of plant genomic integration loci, the integrity and functionality of individual T-DNA copies, as well as the segregation of transgenes in T1 and T2 generations, which also enabled us to identify homozygous transgenic lines. The truncation of some integrated T-DNAs at their left end along with the occurrence of independent segregation of multiple T-DNAs unintendedly resulted in a single-copy segregant that is selectable marker-free and homozygous for the gfp gene. The heritable expression of gfp driven by the maize UBI-1 promoter was demonstrated by confocal laser scanning microscopy. Conclusions The used transformation method is a valuable tool for the genetic engineering of triticale. Here we show that comprehensive molecular analyses are required for the correct interpretation of phenotypic data collected from the transgenic plants.

  2. Deciphering the Origin of the 2012 Cholera Epidemic in Guinea by Integrating Epidemiological and Molecular Analyses

    Science.gov (United States)

    Rebaudet, Stanislas; Mengel, Martin A.; Koivogui, Lamine; Moore, Sandra; Mutreja, Ankur; Kande, Yacouba; Yattara, Ousmane; Sarr Keita, Véronique; Njanpop-Lafourcade, Berthe-Marie; Fournier, Pierre-Edouard; Garnotel, Eric; Keita, Sakoba; Piarroux, Renaud

    2014-01-01

    Cholera is typically considered endemic in West Africa, especially in the Republic of Guinea. However, a three-year lull period was observed from 2009 to 2011, before a new epidemic struck the country in 2012, which was officially responsible for 7,350 suspected cases and 133 deaths. To determine whether cholera re-emerged from the aquatic environment or was rather imported due to human migration, a comprehensive epidemiological and molecular survey was conducted. A spatiotemporal analysis of the national case databases established Kaback Island, located off the southern coast of Guinea, as the initial focus of the epidemic in early February. According to the field investigations, the index case was found to be a fisherman who had recently arrived from a coastal district of neighboring Sierra Leone, where a cholera outbreak had recently occurred. MLVA-based genotype mapping of 38 clinical Vibrio cholerae O1 El Tor isolates sampled throughout the epidemic demonstrated a progressive genetic diversification of the strains from a single genotype isolated on Kaback Island in February, which correlated with spatial epidemic spread. Whole-genome sequencing characterized this strain as an “atypical” El Tor variant. Furthermore, genome-wide SNP-based phylogeny analysis grouped the Guinean strain into a new clade of the third wave of the seventh pandemic, distinct from previously analyzed African strains and directly related to a Bangladeshi isolate. Overall, these results highly suggest that the Guinean 2012 epidemic was caused by a V. cholerae clone that was likely imported from Sierra Leone by an infected individual. These results indicate the importance of promoting the cross-border identification and surveillance of mobile and vulnerable populations, including fishermen, to prevent, detect and control future epidemics in the region. Comprehensive epidemiological investigations should be expanded to better understand cholera dynamics and improve disease control

  3. Gastric Cancer Associated Genes Identified by an Integrative Analysis of Gene Expression Data

    Directory of Open Access Journals (Sweden)

    Bing Jiang

    2017-01-01

    Full Text Available Gastric cancer is one of the most severe complex diseases with high morbidity and mortality in the world. The molecular mechanisms and risk factors for this disease are still not clear since the cancer heterogeneity caused by different genetic and environmental factors. With more and more expression data accumulated nowadays, we can perform integrative analysis for these data to understand the complexity of gastric cancer and to identify consensus players for the heterogeneous cancer. In the present work, we screened the published gene expression data and analyzed them with integrative tool, combined with pathway and gene ontology enrichment investigation. We identified several consensus differentially expressed genes and these genes were further confirmed with literature mining; at last, two genes, that is, immunoglobulin J chain and C-X-C motif chemokine ligand 17, were screened as novel gastric cancer associated genes. Experimental validation is proposed to further confirm this finding.

  4. Personal microbiome analysis improves student engagement and interest in Immunology, Molecular Biology, and Genomics undergraduate courses

    Science.gov (United States)

    Bridgewater, Laura C.; Jensen, Jamie L.; Breakwell, Donald P.; Nielsen, Brent L.; Johnson, Steven M.

    2018-01-01

    A critical area of emphasis for science educators is the identification of effective means of teaching and engaging undergraduate students. Personal microbiome analysis is a means of identifying the microbial communities found on or in our body. We hypothesized the use of personal microbiome analysis in the classroom could improve science education by making courses more applied and engaging for undergraduate students. We determined to test this prediction in three Brigham Young University undergraduate courses: Immunology, Advanced Molecular Biology Laboratory, and Genomics. These three courses have a two-week microbiome unit and students during the 2016 semester students could submit their own personal microbiome kit or use the demo data, whereas during the 2017 semester students were given access to microbiome data from an anonymous individual. The students were surveyed before, during, and after the human microbiome unit to determine whether analyzing their own personal microbiome data, compared to analyzing demo microbiome data, impacted student engagement and interest. We found that personal microbiome analysis significantly enhanced the engagement and interest of students while completing microbiome assignments, the self-reported time students spent researching the microbiome during the two week microbiome unit, and the attitudes of students regarding the course overall. Thus, we found that integrating personal microbiome analysis in the classroom was a powerful means of improving student engagement and interest in undergraduate science courses. PMID:29641525

  5. Plant-wide integrated equipment monitoring and analysis system

    International Nuclear Information System (INIS)

    Morimoto, C.N.; Hunter, T.A.; Chiang, S.C.

    2004-01-01

    A nuclear power plant equipment monitoring system monitors plant equipment and reports deteriorating equipment conditions. The more advanced equipment monitoring systems can also provide information for understanding the symptoms and diagnosing the root cause of a problem. Maximizing the equipment availability and minimizing or eliminating consequential damages are the ultimate goals of equipment monitoring systems. GE Integrated Equipment Monitoring System (GEIEMS) is designed as an integrated intelligent monitoring and analysis system for plant-wide application for BWR plants. This approach reduces system maintenance efforts and equipment monitoring costs and provides information for integrated planning. This paper describes GEIEMS and how the current system is being upgraded to meet General Electric's vision for plant-wide decision support. (author)

  6. STINGRAY: system for integrated genomic resources and analysis.

    Science.gov (United States)

    Wagner, Glauber; Jardim, Rodrigo; Tschoeke, Diogo A; Loureiro, Daniel R; Ocaña, Kary A C S; Ribeiro, Antonio C B; Emmel, Vanessa E; Probst, Christian M; Pitaluga, André N; Grisard, Edmundo C; Cavalcanti, Maria C; Campos, Maria L M; Mattoso, Marta; Dávila, Alberto M R

    2014-03-07

    The STINGRAY system has been conceived to ease the tasks of integrating, analyzing, annotating and presenting genomic and expression data from Sanger and Next Generation Sequencing (NGS) platforms. STINGRAY includes: (a) a complete and integrated workflow (more than 20 bioinformatics tools) ranging from functional annotation to phylogeny; (b) a MySQL database schema, suitable for data integration and user access control; and (c) a user-friendly graphical web-based interface that makes the system intuitive, facilitating the tasks of data analysis and annotation. STINGRAY showed to be an easy to use and complete system for analyzing sequencing data. While both Sanger and NGS platforms are supported, the system could be faster using Sanger data, since the large NGS datasets could potentially slow down the MySQL database usage. STINGRAY is available at http://stingray.biowebdb.org and the open source code at http://sourceforge.net/projects/stingray-biowebdb/.

  7. microsatellite analysis of the correlation between molecular and ...

    African Journals Online (AJOL)

    Administrator

    3Northeast Normal University, Laboratory of Plant Molecular Epigenetics, Changchun China, Zip 130024 ... grounds. Furthermore, recent evidences that the environment can influence the ..... Forty Coffee Varieties Assessed by RAPD. Markers ...

  8. Analysis of Time Reversible Born-Oppenheimer Molecular Dynamics

    Directory of Open Access Journals (Sweden)

    Lin Lin

    2013-12-01

    Full Text Available We analyze the time reversible Born-Oppenheimer molecular dynamics (TRBOMD scheme, which preserves the time reversibility of the Born-Oppenheimer molecular dynamics even with non-convergent self-consistent field iteration. In the linear response regime, we derive the stability condition, as well as the accuracy of TRBOMD for computing physical properties, such as the phonon frequency obtained from the molecular dynamics simulation. We connect and compare TRBOMD with Car-Parrinello molecular dynamics in terms of accuracy and stability. We further discuss the accuracy of TRBOMD beyond the linear response regime for non-equilibrium dynamics of nuclei. Our results are demonstrated through numerical experiments using a simplified one-dimensional model for Kohn-Sham density functional theory.

  9. Highly distinct chromosomal structures in cowpea (Vigna unguiculata), as revealed by molecular cytogenetic analysis.

    Science.gov (United States)

    Iwata-Otsubo, Aiko; Lin, Jer-Young; Gill, Navdeep; Jackson, Scott A

    2016-05-01

    Cowpea (Vigna unguiculata (L.) Walp) is an important legume, particularly in developing countries. However, little is known about its genome or chromosome structure. We used molecular cytogenetics to characterize the structure of pachytene chromosomes to advance our knowledge of chromosome and genome organization of cowpea. Our data showed that cowpea has highly distinct chromosomal structures that are cytologically visible as brightly DAPI-stained heterochromatic regions. Analysis of the repetitive fraction of the cowpea genome present at centromeric and pericentromeric regions confirmed that two retrotransposons are major components of pericentromeric regions and that a 455-bp tandem repeat is found at seven out of 11 centromere pairs in cowpea. These repeats likely evolved after the divergence of cowpea from common bean and form chromosomal structure unique to cowpea. The integration of cowpea genetic and physical chromosome maps reveals potential regions of suppressed recombination due to condensed heterochromatin and a lack of pairing in a few chromosomal termini. This study provides fundamental knowledge on cowpea chromosome structure and molecular cytogenetics tools for further chromosome studies.

  10. An Integrated Solution for Performing Thermo-fluid Conjugate Analysis

    Science.gov (United States)

    Kornberg, Oren

    2009-01-01

    A method has been developed which integrates a fluid flow analyzer and a thermal analyzer to produce both steady state and transient results of 1-D, 2-D, and 3-D analysis models. The Generalized Fluid System Simulation Program (GFSSP) is a one dimensional, general purpose fluid analysis code which computes pressures and flow distributions in complex fluid networks. The MSC Systems Improved Numerical Differencing Analyzer (MSC.SINDA) is a one dimensional general purpose thermal analyzer that solves network representations of thermal systems. Both GFSSP and MSC.SINDA have graphical user interfaces which are used to build the respective model and prepare it for analysis. The SINDA/GFSSP Conjugate Integrator (SGCI) is a formbase graphical integration program used to set input parameters for the conjugate analyses and run the models. The contents of this paper describes SGCI and its thermo-fluids conjugate analysis techniques and capabilities by presenting results from some example models including the cryogenic chill down of a copper pipe, a bar between two walls in a fluid stream, and a solid plate creating a phase change in a flowing fluid.

  11. Analysis of Waste Isolation Pilot Plant Samples: Integrated Summary Report

    Energy Technology Data Exchange (ETDEWEB)

    Britt, Phillip F [ORNL

    2015-03-01

    Analysis of Waste Isolation Pilot Plant Samples: Integrated Summary Report. Summaries of conclusions, analytical processes, and analytical results. Analysis of samples taken from the Waste Isolation Pilot Plant (WIPP) near Carlsbad, New Mexico in support of the WIPP Technical Assessment Team (TAT) activities to determine to the extent feasible the mechanisms and chemical reactions that may have resulted in the breach of at least one waste drum and release of waste material in WIPP Panel 7 Room 7 on February 14, 2014. This report integrates and summarizes the results contained in three separate reports, described below, and draws conclusions based on those results. Chemical and Radiochemical Analyses of WIPP Samples R-15 C5 SWB and R16 C-4 Lip; PNNL-24003, Pacific Northwest National Laboratory, December 2014 Analysis of Waste Isolation Pilot Plant (WIPP) Underground and MgO Samples by the Savannah River National Laboratory (SRNL); SRNL-STI-2014-00617; Savannah River National Laboratory, December 2014 Report for WIPP UG Sample #3, R15C5 (9/3/14); LLNL-TR-667015; Lawrence Livermore National Laboratory, January 2015 This report is also contained in the Waste Isolation Pilot Plant Technical Assessment Team Report; SRNL-RP-2015-01198; Savannah River National Laboratory, March 17, 2015, as Appendix C: Analysis Integrated Summary Report.

  12. Molecular analysis of the oral microbiota of dental diseases

    OpenAIRE

    Kanasi, Eleni

    2008-01-01

    Traditionally, bacterial culture has been used for bacterial detection, allowing study of living microorganisms. Molecular methods are rapid and allow simultaneous identification of numerous species and uncultivated phylotypes. The objective of this doctoral thesis was to investigate the role of the oral microbiota, including poorly characterized and uncultivated bacteria, in dental caries and periodontitis, by comprehensive molecular, clinical, and statistical methods. The microbiota of 275 ...

  13. Vehicle Integrated Performance Analysis, the VIPA Experience: Reconnecting with Technical Integration

    Science.gov (United States)

    McGhee, David S.

    2005-01-01

    Today's NASA is facing significant challenges and changes. The Exploration initiative indicates a large increase in projects with limited increase in budget. The Columbia report has criticized NASA for its lack of insight and technical integration impacting its ability to provide safety. The Aldridge report is advocating NASA find new ways of doing business. Very early in the Space Launch Initiative (SLI) program a small team of engineers at MSFC were asked to propose a process for performing a system level assessment of a launch vehicle. The request was aimed primarily at providing insight and making NASA a "smart buyer." Out of this effort the VIPA team was created. The difference between the VIPA effort and many integration attempts is that VIPA focuses on using experienced people from various disciplines and a process which focuses them on a technically integrated assessment. Most previous attempts have focused on developing an all encompassing software tool. In addition, VIPA anchored its process formulation in the experience of its members and in early developmental Space Shuttle experience. The primary reference for this is NASA-TP-2001-210092, "Launch Vehicle Design Process: Characterization, Technical Integration, and Lessons Learned," and discussions with its authors. The foundations of VIPA's process are described. The VIPA team also recognized the need to drive detailed analysis earlier in the design process. Analyses and techniques typically done in later design phases, are brought forward using improved computing technology. The intent is to allow the identification of significant sensitivities, trades, and design issues much earlier in the program. This process is driven by the T-model for Technical Integration described in the aforementioned reference. VIPA's approach to performing system level technical integration is discussed in detail. Proposed definitions are offered to clarify this discussion and the general systems integration dialog. VIPA

  14. Integrative pathway dissection of molecular mechanisms of moxLDL-induced vascular smooth muscle phenotype transformation

    Directory of Open Access Journals (Sweden)

    Karagiannis George S

    2013-01-01

    Full Text Available Abstract Background Atherosclerosis (AT is a chronic inflammatory disease characterized by the accumulation of inflammatory cells, lipoproteins and fibrous tissue in the walls of arteries. AT is the primary cause of heart attacks and stroke and is the leading cause of death in Western countries. To date, the pathogenesis of AT is not well-defined. Studies have shown that the dedifferentiation of contractile and quiescent vascular smooth muscle cells (SMC to the proliferative, migratory and synthetic phenotype in the intima is pivotal for the onset and progression of AT. To further delineate the mechanisms underlying the pathogenesis of AT, we analyzed the early molecular pathways and networks involved in the SMC phenotype transformation. Methods Quiescent human coronary artery SMCs were treated with minimally-oxidized LDL (moxLDL, for 3 hours and 21 hours, respectively. Transcriptomic data was generated for both time-points using microarrays and was subjected to pathway analysis using Gene Set Enrichment Analysis, GeneMANIA and Ingenuity software tools. Gene expression heat maps and pathways enriched in differentially expressed genes were compared to identify functional biological themes to elucidate early and late molecular mechanisms of moxLDL-induced SMC dedifferentiation. Results Differentially expressed genes were found to be enriched in cholesterol biosynthesis, inflammatory cytokines, chemokines, growth factors, cell cycle control and myogenic contraction themes. These pathways are consistent with inflammatory responses, cell proliferation, migration and ECM production, which are characteristic of SMC dedifferentiation. Furthermore, up-regulation of cholesterol synthesis and dysregulation of cholesterol metabolism was observed in moxLDL-induced SMC. These observations are consistent with the accumulation of cholesterol and oxidized cholesterol esters, which induce proinflammatory reactions during atherogenesis. Our data implicate for the

  15. Spatial and molecular resolution of diffuse malignant mesothelioma heterogeneity by integrating label-free FTIR imaging, laser capture microdissection and proteomics

    Science.gov (United States)

    Großerueschkamp, Frederik; Bracht, Thilo; Diehl, Hanna C.; Kuepper, Claus; Ahrens, Maike; Kallenbach-Thieltges, Angela; Mosig, Axel; Eisenacher, Martin; Marcus, Katrin; Behrens, Thomas; Brüning, Thomas; Theegarten, Dirk; Sitek, Barbara; Gerwert, Klaus

    2017-03-01

    Diffuse malignant mesothelioma (DMM) is a heterogeneous malignant neoplasia manifesting with three subtypes: epithelioid, sarcomatoid and biphasic. DMM exhibit a high degree of spatial heterogeneity that complicates a thorough understanding of the underlying different molecular processes in each subtype. We present a novel approach to spatially resolve the heterogeneity of a tumour in a label-free manner by integrating FTIR imaging and laser capture microdissection (LCM). Subsequent proteome analysis of the dissected homogenous samples provides in addition molecular resolution. FTIR imaging resolves tumour subtypes within tissue thin-sections in an automated and label-free manner with accuracy of about 85% for DMM subtypes. Even in highly heterogeneous tissue structures, our label-free approach can identify small regions of interest, which can be dissected as homogeneous samples using LCM. Subsequent proteome analysis provides a location specific molecular characterization. Applied to DMM subtypes, we identify 142 differentially expressed proteins, including five protein biomarkers commonly used in DMM immunohistochemistry panels. Thus, FTIR imaging resolves not only morphological alteration within tissue but it resolves even alterations at the level of single proteins in tumour subtypes. Our fully automated workflow FTIR-guided LCM opens new avenues collecting homogeneous samples for precise and predictive biomarkers from omics studies.

  16. A molecular phylogenetic analysis of the Scarabaeinae (dung beetles).

    Science.gov (United States)

    Monaghan, Michael T; Inward, Daegan J G; Hunt, Toby; Vogler, Alfried P

    2007-11-01

    The dung beetles (Scarabaeinae) include ca. 5000 species and exhibit a diverse array of morphologies and behaviors. This variation presumably reflects the adaptation to a diversity of food types and the different strategies used to avoid competition for vertebrate dung, which is the primary breeding environment for most species. The current classification gives great weight to the major behavioral types, separating the ball rollers and the tunnelers, but existing phylogenetic studies have been based on limited taxonomic or biogeographic sampling and have been contradictory. Here, we present a molecular phylogenetic analysis of 214 species of Scarabaeinae, representing all 12 traditionally recognized tribes and six biogeographical regions, using partial gene sequences from one nuclear (28S) and two mitochondrial (cox1, rrnL) genes. Length variation in 28S (588-621 bp) and rrnL (514-523 bp) was subjected to a thorough evaluation of alternative alignments, gap-coding methods, and tree searches using model-based (Bayesian and likelihood), maximum parsimony, and direct optimization analyses. The small-bodied, non-dung-feeding Sarophorus+Coptorhina were basal in all reconstructions. These were closely related to rolling Odontoloma+Dicranocara, suggesting an early acquisition of rolling behavior. Smaller tribes and most genera were monophyletic, while Canthonini and Dichotomiini each consisted of multiple paraphyletic lineages at hierarchical levels equivalent to the smaller tribes. Plasticity of rolling and tunneling was evidenced by a lack of monophyly (S-H test, p > 0.05) and several reversals within clades. The majority of previously unrecognized clades were geographical, including the well-supported Neotropical Phanaeini+Eucraniini, and a large Australian clade of rollers as well as tunneling Coptodactyla and Demarziella. Only three lineages, Gymnopleurini, Copris+Microcopris and Onthophagus, were widespread and therefore appear to be dispersive at a global scale. A

  17. INTEGRATION OF FACILITY MODELING CAPABILITIES FOR NUCLEAR NONPROLIFERATION ANALYSIS

    Energy Technology Data Exchange (ETDEWEB)

    Gorensek, M.; Hamm, L.; Garcia, H.; Burr, T.; Coles, G.; Edmunds, T.; Garrett, A.; Krebs, J.; Kress, R.; Lamberti, V.; Schoenwald, D.; Tzanos, C.; Ward, R.

    2011-07-18

    Developing automated methods for data collection and analysis that can facilitate nuclear nonproliferation assessment is an important research area with significant consequences for the effective global deployment of nuclear energy. Facility modeling that can integrate and interpret observations collected from monitored facilities in order to ascertain their functional details will be a critical element of these methods. Although improvements are continually sought, existing facility modeling tools can characterize all aspects of reactor operations and the majority of nuclear fuel cycle processing steps, and include algorithms for data processing and interpretation. Assessing nonproliferation status is challenging because observations can come from many sources, including local and remote sensors that monitor facility operations, as well as open sources that provide specific business information about the monitored facilities, and can be of many different types. Although many current facility models are capable of analyzing large amounts of information, they have not been integrated in an analyst-friendly manner. This paper addresses some of these facility modeling capabilities and illustrates how they could be integrated and utilized for nonproliferation analysis. The inverse problem of inferring facility conditions based on collected observations is described, along with a proposed architecture and computer framework for utilizing facility modeling tools. After considering a representative sampling of key facility modeling capabilities, the proposed integration framework is illustrated with several examples.

  18. Integration of facility modeling capabilities for nuclear nonproliferation analysis

    International Nuclear Information System (INIS)

    Garcia, Humberto; Burr, Tom; Coles, Garill A.; Edmunds, Thomas A.; Garrett, Alfred; Gorensek, Maximilian; Hamm, Luther; Krebs, John; Kress, Reid L.; Lamberti, Vincent; Schoenwald, David; Tzanos, Constantine P.; Ward, Richard C.

    2012-01-01

    Developing automated methods for data collection and analysis that can facilitate nuclear nonproliferation assessment is an important research area with significant consequences for the effective global deployment of nuclear energy. Facility modeling that can integrate and interpret observations collected from monitored facilities in order to ascertain their functional details will be a critical element of these methods. Although improvements are continually sought, existing facility modeling tools can characterize all aspects of reactor operations and the majority of nuclear fuel cycle processing steps, and include algorithms for data processing and interpretation. Assessing nonproliferation status is challenging because observations can come from many sources, including local and remote sensors that monitor facility operations, as well as open sources that provide specific business information about the monitored facilities, and can be of many different types. Although many current facility models are capable of analyzing large amounts of information, they have not been integrated in an analyst-friendly manner. This paper addresses some of these facility modeling capabilities and illustrates how they could be integrated and utilized for nonproliferation analysis. The inverse problem of inferring facility conditions based on collected observations is described, along with a proposed architecture and computer framework for utilizing facility modeling tools. After considering a representative sampling of key facility modeling capabilities, the proposed integration framework is illustrated with several examples.

  19. Integration Of Facility Modeling Capabilities For Nuclear Nonproliferation Analysis

    International Nuclear Information System (INIS)

    Gorensek, M.; Hamm, L.; Garcia, H.; Burr, T.; Coles, G.; Edmunds, T.; Garrett, A.; Krebs, J.; Kress, R.; Lamberti, V.; Schoenwald, D.; Tzanos, C.; Ward, R.

    2011-01-01

    Developing automated methods for data collection and analysis that can facilitate nuclear nonproliferation assessment is an important research area with significant consequences for the effective global deployment of nuclear energy. Facility modeling that can integrate and interpret observations collected from monitored facilities in order to ascertain their functional details will be a critical element of these methods. Although improvements are continually sought, existing facility modeling tools can characterize all aspects of reactor operations and the majority of nuclear fuel cycle processing steps, and include algorithms for data processing and interpretation. Assessing nonproliferation status is challenging because observations can come from many sources, including local and remote sensors that monitor facility operations, as well as open sources that provide specific business information about the monitored facilities, and can be of many different types. Although many current facility models are capable of analyzing large amounts of information, they have not been integrated in an analyst-friendly manner. This paper addresses some of these facility modeling capabilities and illustrates how they could be integrated and utilized for nonproliferation analysis. The inverse problem of inferring facility conditions based on collected observations is described, along with a proposed architecture and computer framework for utilizing facility modeling tools. After considering a representative sampling of key facility modeling capabilities, the proposed integration framework is illustrated with several examples.

  20. Identification of differentially expressed genes and signaling pathways in ovarian cancer by integrated bioinformatics analysis

    Directory of Open Access Journals (Sweden)

    Yang X

    2018-03-01

    Full Text Available Xiao Yang,1 Shaoming Zhu,2 Li Li,3 Li Zhang,1 Shu Xian,1 Yanqing Wang,1 Yanxiang Cheng1 1Department of Obstetrics and Gynecology, 2Department of Urology, Renmin Hospital of Wuhan University, 3Department of Pharmacology, Wuhan University Health Science Center, Wuhan, Hubei, People’s Republic of China Background: The mortality rate associated with ovarian cancer ranks the highest among gynecological malignancies. However, the cause and underlying molecular events of ovarian cancer are not clear. Here, we applied integrated bioinformatics to identify key pathogenic genes involved in ovarian cancer and reveal potential molecular mechanisms. Results: The expression profiles of GDS3592, GSE54388, and GSE66957 were downloaded from the Gene Expression Omnibus (GEO database, which contained 115 samples, including 85 cases of ovarian cancer samples and 30 cases of normal ovarian samples. The three microarray datasets were integrated to obtain differentially expressed genes (DEGs and were deeply analyzed by bioinformatics methods. The gene ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG pathway enrichments of DEGs were performed by DAVID and KOBAS online analyses, respectively. The protein–protein interaction (PPI networks of the DEGs were constructed from the STRING database. A total of 190 DEGs were identified in the three GEO datasets, of which 99 genes were upregulated and 91 genes were downregulated. GO analysis showed that the biological functions of DEGs focused primarily on regulating cell proliferation, adhesion, and differentiation and intracellular signal cascades. The main cellular components include cell membranes, exosomes, the cytoskeleton, and the extracellular matrix. The molecular functions include growth factor activity, protein kinase regulation, DNA binding, and oxygen transport activity. KEGG pathway analysis showed that these DEGs were mainly involved in the Wnt signaling pathway, amino acid metabolism, and the

  1. Combination and Integration of Qualitative and Quantitative Analysis

    Directory of Open Access Journals (Sweden)

    Philipp Mayring

    2001-02-01

    Full Text Available In this paper, I am going to outline ways of combining qualitative and quantitative steps of analysis on five levels. On the technical level, programs for the computer-aided analysis of qualitative data offer various combinations. Where the data are concerned, the employment of categories (for instance by using qualitative content analysis allows for combining qualitative and quantitative forms of data analysis. On the individual level, the creation of types and the inductive generalisation of cases allow for proceeding from individual case material to quantitative generalisations. As for research design, different models can be distinguished (preliminary study, generalisation, elaboration, triangulation which combine qualitative and quantitative steps of analysis. Where the logic of research is concerned, it can be shown that an extended process model which combined qualitative and quantitative research can be appropriate and thus lead to an integration of the two approaches. URN: urn:nbn:de:0114-fqs010162

  2. Inertial navigation sensor integrated motion analysis for autonomous vehicle navigation

    Science.gov (United States)

    Roberts, Barry; Bhanu, Bir

    1992-01-01

    Recent work on INS integrated motion analysis is described. Results were obtained with a maximally passive system of obstacle detection (OD) for ground-based vehicles and rotorcraft. The OD approach involves motion analysis of imagery acquired by a passive sensor in the course of vehicle travel to generate range measurements to world points within the sensor FOV. INS data and scene analysis results are used to enhance interest point selection, the matching of the interest points, and the subsequent motion-based computations, tracking, and OD. The most important lesson learned from the research described here is that the incorporation of inertial data into the motion analysis program greatly improves the analysis and makes the process more robust.

  3. Sparse Group Penalized Integrative Analysis of Multiple Cancer Prognosis Datasets

    Science.gov (United States)

    Liu, Jin; Huang, Jian; Xie, Yang; Ma, Shuangge

    2014-01-01

    SUMMARY In cancer research, high-throughput profiling studies have been extensively conducted, searching for markers associated with prognosis. Because of the “large d, small n” characteristic, results generated from the analysis of a single dataset can be unsatisfactory. Recent studies have shown that integrative analysis, which simultaneously analyzes multiple datasets, can be more effective than single-dataset analysis and classic meta-analysis. In most of existing integrative analysis, the homogeneity model has been assumed, which postulates that different datasets share the same set of markers. Several approaches have been designed to reinforce this assumption. In practice, different datasets may differ in terms of patient selection criteria, profiling techniques, and many other aspects. Such differences may make the homogeneity model too restricted. In this study, we assume the heterogeneity model, under which different datasets are allowed to have different sets of markers. With multiple cancer prognosis datasets, we adopt the AFT (accelerated failure time) model to describe survival. This model may have the lowest computational cost among popular semiparametric survival models. For marker selection, we adopt a sparse group MCP (minimax concave penalty) approach. This approach has an intuitive formulation and can be computed using an effective group coordinate descent algorithm. Simulation study shows that it outperforms the existing approaches under both the homogeneity and heterogeneity models. Data analysis further demonstrates the merit of heterogeneity model and proposed approach. PMID:23938111

  4. Simulation analysis of globally integrated logistics and recycling strategies

    Energy Technology Data Exchange (ETDEWEB)

    Song, S.J.; Hiroshi, K. [Hiroshima Inst. of Tech., Graduate School of Mechanical Systems Engineering, Dept. of In formation and Intelligent Systems Engineering, Hiroshima (Japan)

    2004-07-01

    This paper focuses on the optimal analysis of world-wide recycling activities associated with managing the logistics and production activities in global manufacturing whose activities stretch across national boundaries. Globally integrated logistics and recycling strategies consist of the home country and two free trading economic blocs, NAFTA and ASEAN, where significant differences are found in production and disassembly cost, tax rates, local content rules and regulations. Moreover an optimal analysis of globally integrated value-chain was developed by applying simulation optimization technique as a decision-making tool. The simulation model was developed and analyzed by using ProModel packages, and the results help to identify some of the appropriate conditions required to make well-performed logistics and recycling plans in world-wide collaborated manufacturing environment. (orig.)

  5. LLIMAS: Revolutionizing integrating modeling and analysis at MIT Lincoln Laboratory

    Science.gov (United States)

    Doyle, Keith B.; Stoeckel, Gerhard P.; Rey, Justin J.; Bury, Mark E.

    2017-08-01

    MIT Lincoln Laboratory's Integrated Modeling and Analysis Software (LLIMAS) enables the development of novel engineering solutions for advanced prototype systems through unique insights into engineering performance and interdisciplinary behavior to meet challenging size, weight, power, environmental, and performance requirements. LLIMAS is a multidisciplinary design optimization tool that wraps numerical optimization algorithms around an integrated framework of structural, thermal, optical, stray light, and computational fluid dynamics analysis capabilities. LLIMAS software is highly extensible and has developed organically across a variety of technologies including laser communications, directed energy, photometric detectors, chemical sensing, laser radar, and imaging systems. The custom software architecture leverages the capabilities of existing industry standard commercial software and supports the incorporation of internally developed tools. Recent advances in LLIMAS's Structural-Thermal-Optical Performance (STOP), aeromechanical, and aero-optical capabilities as applied to Lincoln prototypes are presented.

  6. Computational Approaches for Integrative Analysis of the Metabolome and Microbiome

    Directory of Open Access Journals (Sweden)

    Jasmine Chong

    2017-11-01

    Full Text Available The study of the microbiome, the totality of all microbes inhabiting the host or an environmental niche, has experienced exponential growth over the past few years. The microbiome contributes functional genes and metabolites, and is an important factor for maintaining health. In this context, metabolomics is increasingly applied to complement sequencing-based approaches (marker genes or shotgun metagenomics to enable resolution of microbiome-conferred functionalities associated with health. However, analyzing the resulting multi-omics data remains a significant challenge in current microbiome studies. In this review, we provide an overview of different computational approaches that have been used in recent years for integrative analysis of metabolome and microbiome data, ranging from statistical correlation analysis to metabolic network-based modeling approaches. Throughout the process, we strive to present a unified conceptual framework for multi-omics integration and interpretation, as well as point out potential future directions.

  7. Sensitivity Analysis Based on Markovian Integration by Parts Formula

    Directory of Open Access Journals (Sweden)

    Yongsheng Hang

    2017-10-01

    Full Text Available Sensitivity analysis is widely applied in financial risk management and engineering; it describes the variations brought by the changes of parameters. Since the integration by parts technique for Markov chains is well developed in recent years, in this paper we apply it for computation of sensitivity and show the closed-form expressions for two commonly-used time-continuous Markovian models. By comparison, we conclude that our approach outperforms the existing technique of computing sensitivity on Markovian models.

  8. Corporate Disclosure, Materiality, and Integrated Report: An Event Study Analysis

    OpenAIRE

    Maria Cleofe Giorgino; Enrico Supino; Federico Barnabè

    2017-01-01

    Within the extensive literature investigating the impacts of corporate disclosure in supporting the sustainable growth of an organization, few studies have included in the analysis the materiality issue referred to the information being disclosed. This article aims to address this gap, exploring the effect produced on capital markets by the publication of a recent corporate reporting tool, Integrated Report (IR). The features of this tool are that it aims to represent the multidimensional imp...

  9. Process Integration Analysis of an Industrial Hydrogen Production Process

    OpenAIRE

    Stolten, Detlef; Grube, Thomas; Tock, Laurence; Maréchal, François; Metzger, Christian; Arpentinier, Philippe

    2010-01-01

    The energy efficiency of an industrial hydrogen production process using steam methane reforming (SMR) combined with the water gas shift reaction (WGS) is analyzed using process integration techniques based on heat cascade calculation and pinch analysis with the aim of identifying potential measures to enhance the process performance. The challenge is to satisfy the high temperature heat demand of the SMR reaction by minimizing the consumption of natural gas to feed the combustion and to expl...

  10. Building-integrated renewable energy policy analysis in China

    Institute of Scientific and Technical Information of China (English)

    姚春妮; 郝斌

    2009-01-01

    With the dramatic development of renewable energy all over the world,and for purpose of adjusting energy structure,the Ministry of Construction of China plans to promote the large scale application of renewable energy in buildings. In order to ensure the validity of policy-making,this work firstly exerts a method to do cost-benefit analysis for three kinds of technologies such as building-integrated solar hot water (BISHW) system,building-integrated photovoltaic (BIPV) technology and ground water heat pump (GWHP). Through selecting a representative city of every climate region,the analysis comes into different results for different climate regions in China and respectively different suggestion for policy-making. On the analysis basis,the Ministry of Construction (MOC) and the Ministry of Finance of China (MOF) united to start-up Building-integrated Renewable Energy Demonstration Projects (BIREDP) in 2006. In the demonstration projects,renewable energy takes place of traditional energy to supply the domestic hot water,electricity,air-conditioning and heating. Through carrying out the demonstration projects,renewable energy related market has been expanded. More and more relative companies and local governments take the opportunity to promote the large scale application of renewable energy in buildings.

  11. Lectures on functional analysis and the Lebesgue integral

    CERN Document Server

    Komornik, Vilmos

    2016-01-01

    This textbook, based on three series of lectures held by the author at the University of Strasbourg, presents functional analysis in a non-traditional way by generalizing elementary theorems of plane geometry to spaces of arbitrary dimension. This approach leads naturally to the basic notions and theorems. Most results are illustrated by the small ℓp spaces. The Lebesgue integral, meanwhile, is treated via the direct approach of Frigyes Riesz, whose constructive definition of measurable functions leads to optimal, clear-cut versions of the classical theorems of Fubini-Tonelli and Radon-Nikodým. Lectures on Functional Analysis and the Lebesgue Integral presents the most important topics for students, with short, elegant proofs. The exposition style follows the Hungarian mathematical tradition of Paul Erdős and others. The order of the first two parts, functional analysis and the Lebesgue integral, may be reversed. In the third and final part they are combined to study various spaces of continuous and integ...

  12. A hybrid framework of first principles molecular orbital calculations and a three-dimensional integral equation theory for molecular liquids: Multi-center molecular Ornstein-Zernike self-consistent field approach

    Science.gov (United States)

    Kido, Kentaro; Kasahara, Kento; Yokogawa, Daisuke; Sato, Hirofumi

    2015-07-01

    In this study, we reported the development of a new quantum mechanics/molecular mechanics (QM/MM)-type framework to describe chemical processes in solution by combining standard molecular-orbital calculations with a three-dimensional formalism of integral equation theory for molecular liquids (multi-center molecular Ornstein-Zernike (MC-MOZ) method). The theoretical procedure is very similar to the 3D-reference interaction site model self-consistent field (RISM-SCF) approach. Since the MC-MOZ method is highly parallelized for computation, the present approach has the potential to be one of the most efficient procedures to treat chemical processes in solution. Benchmark tests to check the validity of this approach were performed for two solute (solute water and formaldehyde) systems and a simple SN2 reaction (Cl- + CH3Cl → ClCH3 + Cl-) in aqueous solution. The results for solute molecular properties and solvation structures obtained by the present approach were in reasonable agreement with those obtained by other hybrid frameworks and experiments. In particular, the results of the proposed approach are in excellent agreements with those of 3D-RISM-SCF.

  13. A hybrid framework of first principles molecular orbital calculations and a three-dimensional integral equation theory for molecular liquids: Multi-center molecular Ornstein–Zernike self-consistent field approach

    International Nuclear Information System (INIS)

    Kido, Kentaro; Kasahara, Kento; Yokogawa, Daisuke; Sato, Hirofumi

    2015-01-01

    In this study, we reported the development of a new quantum mechanics/molecular mechanics (QM/MM)-type framework to describe chemical processes in solution by combining standard molecular-orbital calculations with a three-dimensional formalism of integral equation theory for molecular liquids (multi-center molecular Ornstein–Zernike (MC-MOZ) method). The theoretical procedure is very similar to the 3D-reference interaction site model self-consistent field (RISM-SCF) approach. Since the MC-MOZ method is highly parallelized for computation, the present approach has the potential to be one of the most efficient procedures to treat chemical processes in solution. Benchmark tests to check the validity of this approach were performed for two solute (solute water and formaldehyde) systems and a simple S N 2 reaction (Cl − + CH 3 Cl → ClCH 3 + Cl − ) in aqueous solution. The results for solute molecular properties and solvation structures obtained by the present approach were in reasonable agreement with those obtained by other hybrid frameworks and experiments. In particular, the results of the proposed approach are in excellent agreements with those of 3D-RISM-SCF

  14. A hybrid framework of first principles molecular orbital calculations and a three-dimensional integral equation theory for molecular liquids: multi-center molecular Ornstein-Zernike self-consistent field approach.

    Science.gov (United States)

    Kido, Kentaro; Kasahara, Kento; Yokogawa, Daisuke; Sato, Hirofumi

    2015-07-07

    In this study, we reported the development of a new quantum mechanics/molecular mechanics (QM/MM)-type framework to describe chemical processes in solution by combining standard molecular-orbital calculations with a three-dimensional formalism of integral equation theory for molecular liquids (multi-center molecular Ornstein-Zernike (MC-MOZ) method). The theoretical procedure is very similar to the 3D-reference interaction site model self-consistent field (RISM-SCF) approach. Since the MC-MOZ method is highly parallelized for computation, the present approach has the potential to be one of the most efficient procedures to treat chemical processes in solution. Benchmark tests to check the validity of this approach were performed for two solute (solute water and formaldehyde) systems and a simple SN2 reaction (Cl(-) + CH3Cl → ClCH3 + Cl(-)) in aqueous solution. The results for solute molecular properties and solvation structures obtained by the present approach were in reasonable agreement with those obtained by other hybrid frameworks and experiments. In particular, the results of the proposed approach are in excellent agreements with those of 3D-RISM-SCF.

  15. Density functional theory, comparative vibrational spectroscopic studies, highest occupied molecular orbital and lowest unoccupied molecular orbital analysis of Linezolid

    Science.gov (United States)

    Rajalakshmi, K.; Gunasekaran, S.; Kumaresan, S.

    2015-06-01

    The Fourier transform infrared spectra and Fourier transform Raman spectra of Linezolid have been recorded in the regions 4,000-400 and 4,000-100 cm-1, respectively. Utilizing the observed Fourier transform infrared spectra and Fourier transform Raman spectra data, a complete vibrational assignment and analysis of the fundamental modes of the compound have been carried out. The optimum molecular geometry, harmonic vibrational frequencies, infrared intensities and Raman scattering activities, have been calculated by density functional theory with 6-31G(d,p), 6-311G(d,p) and M06-2X/6-31G(d,p) levels. The difference between the observed and scaled wavenumber values of most of the fundamentals is very small. A detailed interpretation of the infrared and Raman spectra of Linezolid is reported. Mulliken's net charges have also been calculated. Ultraviolet-visible spectrum of the title molecule has also been calculated using time-dependent density functional method. Besides, molecular electrostatic potential, highest occupied molecular orbital and lowest unoccupied molecular orbital analysis and several thermodynamic properties have been performed by the density functional theoretical method.

  16. Heater-Integrated Cantilevers for Nano-Samples Thermogravimetric Analysis

    Directory of Open Access Journals (Sweden)

    Valeria Toffoli

    2013-12-01

    Full Text Available The design and characteristics of a micro-system for thermogravimetric analysis (TGA in which heater, temperature sensor and mass sensor are integrated into a single device are presented. The system consists of a suspended cantilever that incorporates a microfabricated resistor, used as both heater and thermometer. A three-dimensional finite element analysis was used to define the structure parameters. TGA sensors were fabricated by standard microlithographic techniques and tested using milli-Q water and polyurethane microcapsule. The results demonstrated that our approach provides a faster and more sensitive TGA with respect to commercial systems.

  17. Heater-Integrated Cantilevers for Nano-Samples Thermogravimetric Analysis

    Science.gov (United States)

    Toffoli, Valeria; Carrato, Sergio; Lee, Dongkyu; Jeon, Sangmin; Lazzarino, Marco

    2013-01-01

    The design and characteristics of a micro-system for thermogravimetric analysis (TGA) in which heater, temperature sensor and mass sensor are integrated into a single device are presented. The system consists of a suspended cantilever that incorporates a microfabricated resistor, used as both heater and thermometer. A three-dimensional finite element analysis was used to define the structure parameters. TGA sensors were fabricated by standard microlithographic techniques and tested using milli-Q water and polyurethane microcapsule. The results demonstrated that our approach provides a faster and more sensitive TGA with respect to commercial systems.

  18. All-organic microelectromechanical systems integrating specific molecular recognition--a new generation of chemical sensors.

    Science.gov (United States)

    Ayela, Cédric; Dubourg, Georges; Pellet, Claude; Haupt, Karsten

    2014-09-03

    Cantilever-type all-organic microelectromechanical systems based on molecularly imprinted polymers for specific analyte recognition are used as chemical sensors. They are produced by a simple spray-coating-shadow-masking process. Analyte binding to the cantilever generates a measurable change in its resonance frequency. This allows label-free detection by direct mass sensing of low-molecular-weight analytes at nanomolar concentrations. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Structural integrity analysis of an INPP building under external loading

    International Nuclear Information System (INIS)

    Dundulis, G.; Karalevicius, R.; Uspuras, E.; Kulak, R.F.; Marchertas, A.

    2005-01-01

    After the terrorist attacks in New York and Washington D. C. using civil airplanes, the evaluation of civil airplane crashes into civil and NPP structures has become very important. The interceptions of many terrorists' communications reveal that the use of commandeered commercial aircraft is still a major part of their plans for destruction. Aircraft crash or other flying objects in the territory of the Ignalina Nuclear Power Plant (INPP) represents a concern to the plant. Aircraft traveling at high velocity have a destructive potential. The aircraft crash may damage the roof and walls of buildings, pipelines, electric motors, cases of power supplies, power cables of electricity transmission and other elements and systems, which are important for safety. Therefore, the evaluation of the structural response to an of aircraft crash is important and was selected for analysis. The structural integrity analysis due to the effects of an aircraft crash on an NPP building structure is the subject of this paper. The finite element method was used for the structural analysis of a typical Ignalina NPP building. The structural integrity analysis was performed for a portion of the ALS using the dynamic loading of an aircraft crash impact model. The computer code NEPTUNE was used for this analysis. The local effects caused by impact of the aircraft's engine on the building wall were evaluated independently by using an empirical formula. (authors)

  20. Irreversible thermodynamic analysis and application for molecular heat engines

    Science.gov (United States)

    Lucia, Umberto; Açıkkalp, Emin

    2017-09-01

    Is there a link between the macroscopic approach to irreversibility and microscopic behaviour of the systems? Consumption of free energy keeps the system away from a stable equilibrium. Entropy generation results from the redistribution of energy, momentum, mass and charge. This concept represents the essence of the thermodynamic approach to irreversibility. Irreversibility is the result of the interaction between systems and their environment. The aim of this paper is to determine lost works in a molecular engine and compare results with macro (classical) heat engines. Firstly, irreversible thermodynamics are reviewed for macro and molecular cycles. Secondly, irreversible thermodynamics approaches are applied for a quantum heat engine with -1/2 spin system. Finally, lost works are determined for considered system and results show that macro and molecular heat engines obey same limitations. Moreover, a quantum thermodynamic approach is suggested in order to explain the results previously obtained from an atomic viewpoint.

  1. Calcium-deficiency assessment and biomarker identification by an integrated urinary metabonomics analysis

    Science.gov (United States)

    2013-01-01

    Background Calcium deficiency is a global public-health problem. Although the initial stage of calcium deficiency can lead to metabolic alterations or potential pathological changes, calcium deficiency is difficult to diagnose accurately. Moreover, the details of the molecular mechanism of calcium deficiency remain somewhat elusive. To accurately assess and provide appropriate nutritional intervention, we carried out a global analysis of metabolic alterations in response to calcium deficiency. Methods The metabolic alterations associated with calcium deficiency were first investigated in a rat model, using urinary metabonomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis. Correlations between dietary calcium intake and the biomarkers identified from the rat model were further analyzed to confirm the potential application of these biomarkers in humans. Results Urinary metabolic-profiling analysis could preliminarily distinguish between calcium-deficient and non-deficient rats after a 2-week low-calcium diet. We established an integrated metabonomics strategy for identifying reliable biomarkers of calcium deficiency using a time-course analysis of discriminating metabolites in a low-calcium diet experiment, repeating the low-calcium diet experiment and performing a calcium-supplement experiment. In total, 27 biomarkers were identified, including glycine, oxoglutaric acid, pyrophosphoric acid, sebacic acid, pseudouridine, indoxyl sulfate, taurine, and phenylacetylglycine. The integrated urinary metabonomics analysis, which combined biomarkers with regular trends of change (types A, B, and C), could accurately assess calcium-deficient rats at different stages and clarify the dynamic pathophysiological changes and molecular mechanism of calcium deficiency in detail. Significant correlations between calcium intake and two biomarkers, pseudouridine (Pearson

  2. Molecular tools for carotenogenesis analysis in the zygomycete Mucor circinelloides.

    Science.gov (United States)

    Torres-Martínez, Santiago; Ruiz-Vázquez, Rosa M; Garre, Victoriano; López-García, Sergio; Navarro, Eusebio; Vila, Ana

    2012-01-01

    The carotene producer fungus Mucor circinelloides is the zygomycete more amenable to genetic manipulations by using molecular tools. Since the initial development of an effective procedure of genetic transformation, more than two decades ago, the availability of new molecular approaches such as gene replacement techniques and gene expression inactivation by RNA silencing, in addition to the sequencing of its genome, has made Mucor a valuable organism for the study of a number of processes. Here we describe in detail the main techniques and methods currently used to manipulate M. circinelloides, including transformation, gene replacement, gene silencing, RNAi, and immunoprecipitation.

  3. Data driven linear algebraic methods for analysis of molecular pathways: application to disease progression in shock/trauma.

    Science.gov (United States)

    McGuire, Mary F; Sriram Iyengar, M; Mercer, David W

    2012-04-01

    Although trauma is the leading cause of death for those below 45years of age, there is a dearth of information about the temporal behavior of the underlying biological mechanisms in those who survive the initial trauma only to later suffer from syndromes such as multiple organ failure. Levels of serum cytokines potentially affect the clinical outcomes of trauma; understanding how cytokine levels modulate intra-cellular signaling pathways can yield insights into molecular mechanisms of disease progression and help to identify targeted therapies. However, developing such analyses is challenging since it necessitates the integration and interpretation of large amounts of heterogeneous, quantitative and qualitative data. Here we present the Pathway Semantics Algorithm (PSA), an algebraic process of node and edge analyses of evoked biological pathways over time for in silico discovery of biomedical hypotheses, using data from a prospective controlled clinical study of the role of cytokines in multiple organ failure (MOF) at a major US trauma center. A matrix algebra approach was used in both the PSA node and PSA edge analyses with different matrix configurations and computations based on the biomedical questions to be examined. In the edge analysis, a percentage measure of crosstalk called XTALK was also developed to assess cross-pathway interference. In the node/molecular analysis of the first 24h from trauma, PSA uncovered seven molecules evoked computationally that differentiated outcomes of MOF or non-MOF (NMOF), of which three molecules had not been previously associated with any shock/trauma syndrome. In the edge/molecular interaction analysis, PSA examined four categories of functional molecular interaction relationships--activation, expression, inhibition, and transcription--and found that the interaction patterns and crosstalk changed over time and outcome. The PSA edge analysis suggests that a diagnosis, prognosis or therapy based on molecular interaction

  4. Molecular analysis of high-grade serous ovarian carcinoma with and without associated serous tubal intra-epithelial carcinoma.

    Science.gov (United States)

    Ducie, Jennifer; Dao, Fanny; Considine, Michael; Olvera, Narciso; Shaw, Patricia A; Kurman, Robert J; Shih, Ie-Ming; Soslow, Robert A; Cope, Leslie; Levine, Douglas A

    2017-10-17

    Many high-grade serous carcinomas (HGSCs) of the pelvis are thought to originate in the distal portion of the fallopian tube. Serous tubal intra-epithelial carcinoma (STIC) lesions are the putative precursor to HGSC and identifiable in ~ 50% of advanced stage cases. To better understand the molecular etiology of HGSCs, we report a multi-center integrated genomic analysis of advanced stage tumors with and without STIC lesions and normal tissues. The most significant focal DNA SCNAs were shared between cases with and without STIC lesions. The RNA sequence and the miRNA data did not identify any clear separation between cases with and without STIC lesions. HGSCs had molecular profiles more similar to normal fallopian tube epithelium than ovarian surface epithelium or peritoneum. The data suggest that the molecular features of HGSCs with and without associated STIC lesions are mostly shared, indicating a common biologic origin, likely to be the distal fallopian tube among all cases.High-grade serous carcinomas (HGSCs) are associated with precursor lesions (STICs) in the fallopian epithelium in only half of the cases. Here the authors report the molecular analysis of HGSCs with and without associated STICs and show similar profiles supporting a common origin for all HGSCs.

  5. Integration of facility modeling capabilities for nuclear nonproliferation analysis

    International Nuclear Information System (INIS)

    Burr, Tom; Gorensek, M.B.; Krebs, John; Kress, Reid L.; Lamberti, Vincent; Schoenwald, David; Ward, Richard C.

    2012-01-01

    Developing automated methods for data collection and analysis that can facilitate nuclearnonproliferation assessment is an important research area with significant consequences for the effective global deployment of nuclear energy. Facilitymodeling that can integrate and interpret observations collected from monitored facilities in order to ascertain their functional details will be a critical element of these methods. Although improvements are continually sought, existing facilitymodeling tools can characterize all aspects of reactor operations and the majority of nuclear fuel cycle processing steps, and include algorithms for data processing and interpretation. Assessing nonproliferation status is challenging because observations can come from many sources, including local and remote sensors that monitor facility operations, as well as open sources that provide specific business information about the monitored facilities, and can be of many different types. Although many current facility models are capable of analyzing large amounts of information, they have not been integrated in an analyst-friendly manner. This paper addresses some of these facilitymodelingcapabilities and illustrates how they could be integrated and utilized for nonproliferationanalysis. The inverse problem of inferring facility conditions based on collected observations is described, along with a proposed architecture and computer framework for utilizing facilitymodeling tools. After considering a representative sampling of key facilitymodelingcapabilities, the proposed integration framework is illustrated with several examples.

  6. An integrative genomic and transcriptomic analysis reveals potential targets associated with cell proliferation in uterine leiomyomas.

    Directory of Open Access Journals (Sweden)

    Priscila Daniele Ramos Cirilo

    Full Text Available Uterine Leiomyomas (ULs are the most common benign tumours affecting women of reproductive age. ULs represent a major problem in public health, as they are the main indication for hysterectomy. Approximately 40-50% of ULs have non-random cytogenetic abnormalities, and half of ULs may have copy number alterations (CNAs. Gene expression microarrays studies have demonstrated that cell proliferation genes act in response to growth factors and steroids. However, only a few genes mapping to CNAs regions were found to be associated with ULs.We applied an integrative analysis using genomic and transcriptomic data to identify the pathways and molecular markers associated with ULs. Fifty-one fresh frozen specimens were evaluated by array CGH (JISTIC and gene expression microarrays (SAM. The CONEXIC algorithm was applied to integrate the data.The integrated analysis identified the top 30 significant genes (P<0.01, which comprised genes associated with cancer, whereas the protein-protein interaction analysis indicated a strong association between FANCA and BRCA1. Functional in silico analysis revealed target molecules for drugs involved in cell proliferation, including FGFR1 and IGFBP5. Transcriptional and protein analyses showed that FGFR1 (P = 0.006 and P<0.01, respectively and IGFBP5 (P = 0.0002 and P = 0.006, respectively were up-regulated in the tumours when compared with the adjacent normal myometrium.The integrative genomic and transcriptomic approach indicated that FGFR1 and IGFBP5 amplification, as well as the consequent up-regulation of the protein products, plays an important role in the aetiology of ULs and thus provides data for potential drug therapies development to target genes associated with cellular proliferation in ULs.

  7. Calculation of two-center one-electron molecular integrals with STOs. [BICEN

    Energy Technology Data Exchange (ETDEWEB)

    Rico, J.F.; Lopez, R.; Paniagua, M.; Ramirez, G. (Universidad Autonoma de Madrid (Spain). Dept. de Quimica Fisica y Quimica Cuantica)

    1991-05-01

    A program for the calculation of two-center one-electron integrals (overlap, nuclear attraction and kinetic energy) between real Slater-type orbitals (STOs) is reported. The integrals are obtained by recursion over simple auxiliary matrices, whose elements are calculated in terms of further auxiliary functions evaluated in a quick and accurate way. (orig.).

  8. Calculation of two-center one-electron molecular integrals with STOs

    International Nuclear Information System (INIS)

    Rico, J.F.; Lopez, R.; Paniagua, M.; Ramirez, G.

    1991-01-01

    A program for the calculation of two-center one-electron integrals (overlap, nuclear attraction and kinetic energy) between real Slater-type orbitals (STOs) is reported. The integrals are obtained by recursion over simple auxiliary matrices, whose elements are calculated in terms of further auxiliary functions evaluated in a quick and accurate way. (orig.)

  9. Molecular cloning, structural analysis and expression of a zinc ...

    African Journals Online (AJOL)

    The results of prokaryotic expression of ZnBP and overexpression of the ZnBP gene in A. thaliana improve our understanding of the function of this gene. Future studies should investigate the molecular mechanisms involved in gland morphogenesis in cotton. Key words: Gossypium hirsutum, pigment gland, zinc binding ...

  10. RAPD-PCR molecular analysis of the threatened Cabrera's vole ...

    African Journals Online (AJOL)

    Optimal management and conservation programs of the threatened Cabrera's vole require investigating potential molecular genetic markers in the genomic background, if the few remaining fragile populations are to ... The results described Cabrera's vole populations as a single genetic unit with slightly restricted gene flow.

  11. Molecular analysis of cross-bacterial contamination detected in ...

    African Journals Online (AJOL)

    ... the isolate Delftia acidovorans BP(R2) and it is also coupled to protein with molecular weight 25-26 KDa. As well as, this bacterial contamination was the reason for the false positive results observed during the detection of HCV infections. Journal of Applied Sciences and Environmental Management Vol. 9(1) 2005: 5-10.

  12. Molecular Analysis of Multi-Drug Resistance (MDR) in ...

    African Journals Online (AJOL)

    This review therefore brings to light some of the processes involved in molecular typing of Mycobacterium tuberculosis strains like the use of restriction fragment length polymorphism (RFLP) and spoligotyping, which have become valuable tools in the epidemiology of tuberculosis, identification of genotypes and ...

  13. Cryogenic Collection of Complete Subsurface Samples for Molecular Biological Analysis

    Science.gov (United States)

    2012-05-01

    276.5318.1568 Moser, D. P., J. K. Fredrickson, D. R. Geist, E. V. Arntzen, A. D. Peacock , S.-M. W. Li, T. Spadoni, et al. (2003). Biogeochemical...Influencing Amplification Efficiency and Allele Drop-out in Single Cell PCR: Implications for Preimplantation Genetic Diagnosis. Molecular Human Reproduction

  14. Molecular Analysis of AFP and HSA Interactions with PTEN Protein

    Directory of Open Access Journals (Sweden)

    Mingyue Zhu

    2015-01-01

    Full Text Available Human cytoplasmic alpha-fetoprotein (AFP has been classified as a member of the albuminoid gene family. The protein sequence of AFP has significant homology to that of human serum albumin (HSA, but its biological characteristics are vastly different from HSA. The AFP functions as a regulator in the phosphatidylinositol 3-kinase (PI3K/protein kinase B (AKT pathway, but HSA plays a key role as a transport protein. To probe their molecular mechanisms, we have applied colocalization, coimmunoprecipitation (co-IP, and molecular docking approaches to analyze the differences between AFP and HSA. The data from colocalization and co-IP displayed a strong interaction between AFP and PTEN (phosphatase and tensin homolog, demonstrating that AFP did bind to PTEN, but HSA did not. The molecular docking study further showed that the AFP domains I and III could contact with PTEN. In silicon substitutions of AFP binding site residues at position 490M/K and 105L/R corresponding to residues K490 and R105 in HSA resulted in steric clashes with PTEN residues R150 and K46, respectively. These steric clashes may explain the reason why HSA cannot bind to PTEN. Ultimately, the experimental results and the molecular modeling data from the interactions of AFP and HSA with PTEN will help us to identify targets for designing drugs and vaccines against human hepatocellular carcinoma.

  15. Thermodynamic Models from Fluctuation Solution Theory Analysis of Molecular Simulations

    DEFF Research Database (Denmark)

    Christensen, Steen; Peters, Günther H.j.; Hansen, Flemming Yssing

    2007-01-01

    Fluctuation solution theory (FST) is employed to analyze results of molecular dynamics (MD) simulations of liquid mixtures. The objective is to generate parameters for macroscopic GE-models, here the modified Margules model. We present a strategy for choosing the number of parameters included...

  16. Molecular analysis of candidate probiotic effector molecules of Lactobacillus plantarum

    NARCIS (Netherlands)

    Remus, D.M.

    2012-01-01

    Probiotics are health-promoting microorganisms that exert their beneficial effects in several ways. While it is known that probiotic bacteria interact with cells of the host gastrointestinal tractand modulate cell-signaling responses by which they might promote health, the underlying molecular

  17. Molecular analysis of mutants of the Neurospora adenylosuccinate ...

    Indian Academy of Sciences (India)

    2012-08-07

    Aug 7, 2012 ... and mutants induced with X-ray, UV or chemical mutagens. ... We have sequenced the ad-8 locus from 13 of these mutants and identified the molecular nature ..... mutants in yeast by selection for constitutive behavior in pig-.

  18. A molecular cytogenetic analysis of introgression in Alstroemeria

    NARCIS (Netherlands)

    Kamstra, S.A.

    1999-01-01

    This thesis describes the results of a molecular cytogenetic investigation of the process of introgression in Alstroemeria . The aim of this study was to transfer chromosomes or genes from one Alstroemeria species into another. For this, two

  19. Molecular dynamic analysis of the structure of dendrimers

    Energy Technology Data Exchange (ETDEWEB)

    Canetta, E.; Maino, G. E-mail: maino@bologna.enea.it

    2004-01-01

    We present main results of molecular dynamics simulations that we have carried out in order to investigate structural properties of polyamidoamine (PAMAM) dendrimers. Obtained data confirm the PAMAM dendrimer structure proposed by experiments, performed by means of X-ray scattering (SAXS) and quasi-elastic light scattering (QELS) techniques.

  20. Molecular dynamic analysis of the structure of dendrimers

    International Nuclear Information System (INIS)

    Canetta, E.; Maino, G.

    2004-01-01

    We present main results of molecular dynamics simulations that we have carried out in order to investigate structural properties of polyamidoamine (PAMAM) dendrimers. Obtained data confirm the PAMAM dendrimer structure proposed by experiments, performed by means of X-ray scattering (SAXS) and quasi-elastic light scattering (QELS) techniques

  1. Molecular responses and expression analysis of genes in a ...

    African Journals Online (AJOL)

    Haloxylon ammodendron (C.A Mey.) Bunge is a xero-halophytic desert shrub with excellent drought resistance and salt tolerance. To decipher the molecular responses involved in its drought resistance, the cDNA-AFLP (amplified fragment length polymorphism) technique was employed to identify genes expressed ...

  2. Molecular characterization and expression analysis of a hepcidin ...

    African Journals Online (AJOL)

    Jane

    2011-08-03

    Aug 3, 2011 ... the liver, intestine and brain were 2.4, 1.5 and 2-fold increase, respectively, compared with the control animals after 5 days .... (sex change) of RFE attracted more attention (Cheng et al., 2003 ...... Molecular Biology. New York: ...

  3. Physiological response, molecular analysis and water use efficiency ...

    African Journals Online (AJOL)

    With a view to study the effects of irrigation scheduling on the water use efficiency and physiological response and molecular basis of maize hybrids of different maturity groups, a field experiment was conducted at Water Management Research Center (WMRC), Belvatagi, University of Agricultural Sciences, Dharwad, India ...

  4. Comparative molecular analysis of old olive ( Olea europaea L ...

    African Journals Online (AJOL)

    We compared the genetic profiles of six old olive cultivars from an Eastern Mediterranean Region of Turkey to 15 modern Turkish olive cultivars from different geographical origins. The RAPD profiles successfully clarified the molecular relationships among the genotypes tested. Seventeen RAPD primers generated 153 ...

  5. Molecular analysis of childhood primitive neuroectodermal tumors defines markers associated with poor outcome

    DEFF Research Database (Denmark)

    Scheurlen, W G; Schwabe, G C; Joos, S

    1998-01-01

    PURPOSE: The diagnostic and prognostic significance of well-defined molecular markers was investigated in childhood primitive neuroectodermal tumors (PNET). MATERIALS AND METHODS: Using microsatellite analysis, Southern blot analysis, and fluorescence in situ hybridization (FISH), 30 primary tumors......: In our study, amplification of c-myc was a poor-prognosis marker in PNET. LOH of chromosome 17p was associated with metastatic disease. Molecular analysis of primary tumors using these markers may be useful for stratification of children with PNET in future prospective studies. The other aberrations...... investigated were not of significant prognostic value, but may provide an entry point for future large-scale molecular studies....

  6. Integrated situational awareness for cyber attack detection, analysis, and mitigation

    Science.gov (United States)

    Cheng, Yi; Sagduyu, Yalin; Deng, Julia; Li, Jason; Liu, Peng

    2012-06-01

    Real-time cyberspace situational awareness is critical for securing and protecting today's enterprise networks from various cyber threats. When a security incident occurs, network administrators and security analysts need to know what exactly has happened in the network, why it happened, and what actions or countermeasures should be taken to quickly mitigate the potential impacts. In this paper, we propose an integrated cyberspace situational awareness system for efficient cyber attack detection, analysis and mitigation in large-scale enterprise networks. Essentially, a cyberspace common operational picture will be developed, which is a multi-layer graphical model and can efficiently capture and represent the statuses, relationships, and interdependencies of various entities and elements within and among different levels of a network. Once shared among authorized users, this cyberspace common operational picture can provide an integrated view of the logical, physical, and cyber domains, and a unique visualization of disparate data sets to support decision makers. In addition, advanced analyses, such as Bayesian Network analysis, will be explored to address the information uncertainty, dynamic and complex cyber attack detection, and optimal impact mitigation issues. All the developed technologies will be further integrated into an automatic software toolkit to achieve near real-time cyberspace situational awareness and impact mitigation in large-scale computer networks.

  7. Measure and integral an introduction to real analysis

    CERN Document Server

    Wheeden, Richard L

    2015-01-01

    Now considered a classic text on the topic, Measure and Integral: An Introduction to Real Analysis provides an introduction to real analysis by first developing the theory of measure and integration in the simple setting of Euclidean space, and then presenting a more general treatment based on abstract notions characterized by axioms and with less geometric content.Published nearly forty years after the first edition, this long-awaited Second Edition also:Studies the Fourier transform of functions in the spaces L1, L2, and Lp, 1 p Shows the Hilbert transform to be a bounded operator on L2, as an application of the L2 theory of the Fourier transform in the one-dimensional caseCovers fractional integration and some topics related to mean oscillation properties of functions, such as the classes of Hölder continuous functions and the space of functions of bounded mean oscillationDerives a subrepresentation formula, which in higher dimensions plays a role roughly similar to the one played by the fundamental theor...

  8. Integrative Analysis of Cancer Diagnosis Studies with Composite Penalization

    Science.gov (United States)

    Liu, Jin; Huang, Jian; Ma, Shuangge

    2013-01-01

    Summary In cancer diagnosis studies, high-throughput gene profiling has been extensively conducted, searching for genes whose expressions may serve as markers. Data generated from such studies have the “large d, small n” feature, with the number of genes profiled much larger than the sample size. Penalization has been extensively adopted for simultaneous estimation and marker selection. Because of small sample sizes, markers identified from the analysis of single datasets can be unsatisfactory. A cost-effective remedy is to conduct integrative analysis of multiple heterogeneous datasets. In this article, we investigate composite penalization methods for estimation and marker selection in integrative analysis. The proposed methods use the minimax concave penalty (MCP) as the outer penalty. Under the homogeneity model, the ridge penalty is adopted as the inner penalty. Under the heterogeneity model, the Lasso penalty and MCP are adopted as the inner penalty. Effective computational algorithms based on coordinate descent are developed. Numerical studies, including simulation and analysis of practical cancer datasets, show satisfactory performance of the proposed methods. PMID:24578589

  9. Molecular analysis of MECP2 gene in Egyptian patients with Rett ...

    African Journals Online (AJOL)

    Molecular analysis of MECP2 gene in Egyptian patients with Rett syndrome. ... Egyptian Journal of Medical Human Genetics ... This study represents one of the limited MECP2 molecular analyses done on Egyptian patients with RTT, in which direct sequencing of MECP2 coding region in 10 female Egyptian patients ...

  10. Methodology for dimensional variation analysis of ITER integrated systems

    International Nuclear Information System (INIS)

    Fuentes, F. Javier; Trouvé, Vincent; Cordier, Jean-Jacques; Reich, Jens

    2016-01-01

    Highlights: • Tokamak dimensional management methodology, based on 3D variation analysis, is presented. • Dimensional Variation Model implementation workflow is described. • Methodology phases are described in detail. The application of this methodology to the tolerance analysis of ITER Vacuum Vessel is presented. • Dimensional studies are a valuable tool for the assessment of Tokamak PCR (Project Change Requests), DR (Deviation Requests) and NCR (Non-Conformance Reports). - Abstract: The ITER machine consists of a large number of complex systems highly integrated, with critical functional requirements and reduced design clearances to minimize the impact in cost and performances. Tolerances and assembly accuracies in critical areas could have a serious impact in the final performances, compromising the machine assembly and plasma operation. The management of tolerances allocated to part manufacture and assembly processes, as well as the control of potential deviations and early mitigation of non-compliances with the technical requirements, is a critical activity on the project life cycle. A 3D tolerance simulation analysis of ITER Tokamak machine has been developed based on 3DCS dedicated software. This integrated dimensional variation model is representative of Tokamak manufacturing functional tolerances and assembly processes, predicting accurate values for the amount of variation on critical areas. This paper describes the detailed methodology to implement and update the Tokamak Dimensional Variation Model. The model is managed at system level. The methodology phases are illustrated by its application to the Vacuum Vessel (VV), considering the status of maturity of VV dimensional variation model. The following topics are described in this paper: • Model description and constraints. • Model implementation workflow. • Management of input and output data. • Statistical analysis and risk assessment. The management of the integration studies based on

  11. Methodology for dimensional variation analysis of ITER integrated systems

    Energy Technology Data Exchange (ETDEWEB)

    Fuentes, F. Javier, E-mail: FranciscoJavier.Fuentes@iter.org [ITER Organization, Route de Vinon-sur-Verdon—CS 90046, 13067 St Paul-lez-Durance (France); Trouvé, Vincent [Assystem Engineering & Operation Services, rue J-M Jacquard CS 60117, 84120 Pertuis (France); Cordier, Jean-Jacques; Reich, Jens [ITER Organization, Route de Vinon-sur-Verdon—CS 90046, 13067 St Paul-lez-Durance (France)

    2016-11-01

    Highlights: • Tokamak dimensional management methodology, based on 3D variation analysis, is presented. • Dimensional Variation Model implementation workflow is described. • Methodology phases are described in detail. The application of this methodology to the tolerance analysis of ITER Vacuum Vessel is presented. • Dimensional studies are a valuable tool for the assessment of Tokamak PCR (Project Change Requests), DR (Deviation Requests) and NCR (Non-Conformance Reports). - Abstract: The ITER machine consists of a large number of complex systems highly integrated, with critical functional requirements and reduced design clearances to minimize the impact in cost and performances. Tolerances and assembly accuracies in critical areas could have a serious impact in the final performances, compromising the machine assembly and plasma operation. The management of tolerances allocated to part manufacture and assembly processes, as well as the control of potential deviations and early mitigation of non-compliances with the technical requirements, is a critical activity on the project life cycle. A 3D tolerance simulation analysis of ITER Tokamak machine has been developed based on 3DCS dedicated software. This integrated dimensional variation model is representative of Tokamak manufacturing functional tolerances and assembly processes, predicting accurate values for the amount of variation on critical areas. This paper describes the detailed methodology to implement and update the Tokamak Dimensional Variation Model. The model is managed at system level. The methodology phases are illustrated by its application to the Vacuum Vessel (VV), considering the status of maturity of VV dimensional variation model. The following topics are described in this paper: • Model description and constraints. • Model implementation workflow. • Management of input and output data. • Statistical analysis and risk assessment. The management of the integration studies based on

  12. Double path integral method for obtaining the mobility of the one-dimensional charge transport in molecular chain.

    Science.gov (United States)

    Yoo-Kong, Sikarin; Liewrian, Watchara

    2015-12-01

    We report on a theoretical investigation concerning the polaronic effect on the transport properties of a charge carrier in a one-dimensional molecular chain. Our technique is based on the Feynman's path integral approach. Analytical expressions for the frequency-dependent mobility and effective mass of the carrier are obtained as functions of electron-phonon coupling. The result exhibits the crossover from a nearly free particle to a heavily trapped particle. We find that the mobility depends on temperature and decreases exponentially with increasing temperature at low temperature. It exhibits large polaronic-like behaviour in the case of weak electron-phonon coupling. These results agree with the phase transition (A.S. Mishchenko et al., Phys. Rev. Lett. 114, 146401 (2015)) of transport phenomena related to polaron motion in the molecular chain.

  13. Technology integrated teaching in Malaysian schools: GIS, a SWOT analysis

    Directory of Open Access Journals (Sweden)

    Habibah Lateh, vasugiammai muniandy

    2011-08-01

    , articles and proceeding papers. Researches had been continuously done in integrating GIS into Geography syllabus. Thus, this article describes and discusses the barriers and opportunities of implementing GIS in schools with a deep focus of how GIS could enhance the process of teaching and learning geography. The purpose of the study is to determine the effectiveness of GIS in enhancing students’ interest towards the subject. Barriers that might limit the implementation of GIS in schools also briefly discussedin this article. The capabilities of GIS in schools and teaching with GIS is also a part of this article. SWOT analysis is used to find the strength, threaten, opportunities and weakness of GIS to be integrated in Malaysian schools. A content analysis was performed using articles from local and abroad publications regarding technology integration and GIS. Conference proceedings were also analyzed. This content analysis included 35 articles selected from ICT and GIS publication in Malaysia and abroad. The content analysis was done in order to identify the barriers of trying GIS in schools in Malaysia. Thus, this article discusses strengths, weaknesses, opportunities and threatens. The future of GIS in Malaysian Schools has been added into the conclusion.

  14. Analysis on working pressure selection of ACME integral test facility

    International Nuclear Information System (INIS)

    Chen Lian; Chang Huajian; Li Yuquan; Ye Zishen; Qin Benke

    2011-01-01

    An integral effects test facility, advanced core cooling mechanism experiment facility (ACME) was designed to verify the performance of the passive safety system and validate its safety analysis codes of a pressurized water reactor power plant. Three test facilities for AP1000 design were introduced and review was given. The problems resulted from the different working pressures of its test facilities were analyzed. Then a detailed description was presented on the working pressure selection of ACME facility as well as its characteristics. And the approach of establishing desired testing initial condition was discussed. The selected 9.3 MPa working pressure covered almost all important passive safety system enables the ACME to simulate the LOCAs with the same pressure and property similitude as the prototype. It's expected that the ACME design would be an advanced core cooling integral test facility design. (authors)

  15. Application of symplectic integrator to numerical fluid analysis

    International Nuclear Information System (INIS)

    Tanaka, Nobuatsu

    2000-01-01

    This paper focuses on application of the symplectic integrator to numerical fluid analysis. For the purpose, we introduce Hamiltonian particle dynamics to simulate fluid behavior. The method is based on both the Hamiltonian formulation of a system and the particle methods, and is therefore called Hamiltonian Particle Dynamics (HPD). In this paper, an example of HPD applications, namely the behavior of incompressible inviscid fluid, is solved. In order to improve accuracy of HPD with respect to space, CIVA, which is a highly accurate interpolation method, is combined, but the combined method is subject to problems in that the invariants of the system are not conserved in a long-time computation. For solving the problems, symplectic time integrators are introduced and the effectiveness is confirmed by numerical analyses. (author)

  16. New Biogeographic insight into Bauhinia s.l. (Leguminosae): integration from fossil records and molecular analyses.

    Science.gov (United States)

    Meng, Hong-Hu; Jacques, Frédéric Mb; Su, Tao; Huang, Yong-Jiang; Zhang, Shi-Tao; Ma, Hong-Jie; Zhou, Zhe-Kun

    2014-08-10

    Given that most species that have ever existed on earth are extinct, it stands to reason that the evolutionary history can be better understood with fossil taxa. Bauhinia is a typical genus of pantropical intercontinental disjunction among the Asian, African, and American continents. Geographic distribution patterns are better recognized when fossil records and molecular sequences are combined in the analyses. Here, we describe a new macrofossil species of Bauhinia from the Upper Miocene Xiaolongtan Formation in Wenshan County, Southeast Yunnan, China, and elucidate the biogeographic significance through the analyses of molecules and fossils. Morphometric analysis demonstrates that the leaf shapes of B. acuminata, B. championii, B. chalcophylla, B. purpurea, and B. podopetala closely resemble the leaf shapes of the new finding fossil. Phylogenetic relationships among the Bauhinia species were reconstructed using maximum parsimony and Bayesian inference, which inferred that species in Bauhinia species are well-resolved into three main groups. Divergence times were estimated by the Bayesian Markov chain Monte Carlo (MCMC) method under a relaxed clock, and inferred that the stem diversification time of Bauhinia was ca. 62.7 Ma. The Asian lineage first diverged at ca. 59.8 Ma, followed by divergence of the Africa lineage starting during the late Eocene, whereas that of the neotropical lineage starting during the middle Miocene. Hypotheses relying on vicariance or continental history to explain pantropical disjunct distributions are dismissed because they require mostly Palaeogene and older tectonic events. We suggest that Bauhinia originated in the middle Paleocene in Laurasia, probably in Asia, implying a possible Tethys Seaway origin or an "Out of Tropical Asia", and dispersal of legumes. Its present pantropical disjunction resulted from disruption of the boreotropical flora by climatic cooling after the Paleocene-Eocene Thermal Maximum (PETM). North Atlantic land

  17. Spectroscopic analysis and molecular docking of imidazole derivatives and investigation of its reactive properties by DFT and molecular dynamics simulations

    Science.gov (United States)

    Thomas, Renjith; Hossain, Mossaraf; Mary, Y. Sheena; Resmi, K. S.; Armaković, Stevan; Armaković, Sanja J.; Nanda, Ashis Kumar; Ranjan, Vivek Kumar; Vijayakumar, G.; Van Alsenoy, C.

    2018-04-01

    Solvent-free synthesis pathway for obtaining two imidazole derivatives (2-chloro-1-(4-methoxyphenyl)-4,5-dimethyl-1H-imidazole (CLMPDI) and 1-(4-bromophenyl)-2-chloro-4,5-dimethyl-1H-imidazole (BPCLDI) has been reported in this work, followed by detailed experimental and computational spectroscopic characterization and reactivity study. Spectroscopic methods encompassed IR, FT-Raman and NMR techniques, with the mutual comparison of experimentally and computationally obtained results at DFT/B3LYP level of theory. Reactivity study based on DFT calculations encompassed molecular orbitals analysis, followed by calculations of molecular electrostatic potential (MEP) and average local ionization energy (ALIE) values, Fukui functions and bond dissociation energies (BDE). Additionally, the stability of title molecules in water has been investigated via molecular dynamics (MD) simulations, while interactivity with aspulvinonedimethylallyl transferase protein has been evaluated by molecular docking procedure. CLMPDI compound showed antimicrobial activity against all four bacterial strain in both gram positive and gram negative bacteria while, BPCLDI showed only in gram positive bacteria, Staphylococcus Aureus (MTCC1144). The first order hyperpolarizability of CLMPDI and BPCLDI are 20.15 and 6.10 times that of the standard NLO material urea.

  18. Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas.

    Science.gov (United States)

    Brat, Daniel J; Verhaak, Roel G W; Aldape, Kenneth D; Yung, W K Alfred; Salama, Sofie R; Cooper, Lee A D; Rheinbay, Esther; Miller, C Ryan; Vitucci, Mark; Morozova, Olena; Robertson, A Gordon; Noushmehr, Houtan; Laird, Peter W; Cherniack, Andrew D; Akbani, Rehan; Huse, Jason T; Ciriello, Giovanni; Poisson, Laila M; Barnholtz-Sloan, Jill S; Berger, Mitchel S; Brennan, Cameron; Colen, Rivka R; Colman, Howard; Flanders, Adam E; Giannini, Caterina; Grifford, Mia; Iavarone, Antonio; Jain, Rajan; Joseph, Isaac; Kim, Jaegil; Kasaian, Katayoon; Mikkelsen, Tom; Murray, Bradley A; O'Neill, Brian Patrick; Pachter, Lior; Parsons, Donald W; Sougnez, Carrie; Sulman, Erik P; Vandenberg, Scott R; Van Meir, Erwin G; von Deimling, Andreas; Zhang, Hailei; Crain, Daniel; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Penny, Robert; Shelton, Troy; Sherman, Mark; Yena, Peggy; Black, Aaron; Bowen, Jay; Dicostanzo, Katie; Gastier-Foster, Julie; Leraas, Kristen M; Lichtenberg, Tara M; Pierson, Christopher R; Ramirez, Nilsa C; Taylor, Cynthia; Weaver, Stephanie; Wise, Lisa; Zmuda, Erik; Davidsen, Tanja; Demchok, John A; Eley, Greg; Ferguson, Martin L; Hutter, Carolyn M; Mills Shaw, Kenna R; Ozenberger, Bradley A; Sheth, Margi; Sofia, Heidi J; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean Claude; Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Jensen, Mark A; Liu, Jia; Pihl, Todd; Raman, Rohini; Wan, Yunhu; Wu, Ye; Ally, Adrian; Auman, J Todd; Balasundaram, Miruna; Balu, Saianand; Baylin, Stephen B; Beroukhim, Rameen; Bootwalla, Moiz S; Bowlby, Reanne; Bristow, Christopher A; Brooks, Denise; Butterfield, Yaron; Carlsen, Rebecca; Carter, Scott; Chin, Lynda; Chu, Andy; Chuah, Eric; Cibulskis, Kristian; Clarke, Amanda; Coetzee, Simon G; Dhalla, Noreen; Fennell, Tim; Fisher, Sheila; Gabriel, Stacey; Getz, Gad; Gibbs, Richard; Guin, Ranabir; Hadjipanayis, Angela; Hayes, D Neil; Hinoue, Toshinori; Hoadley, Katherine; Holt, Robert A; Hoyle, Alan P; Jefferys, Stuart R; Jones, Steven; Jones, Corbin D; Kucherlapati, Raju; Lai, Phillip H; Lander, Eric; Lee, Semin; Lichtenstein, Lee; Ma, Yussanne; Maglinte, Dennis T; Mahadeshwar, Harshad S; Marra, Marco A; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew L; Mieczkowski, Piotr A; Moore, Richard A; Mose, Lisle E; Mungall, Andrew J; Pantazi, Angeliki; Parfenov, Michael; Park, Peter J; Parker, Joel S; Perou, Charles M; Protopopov, Alexei; Ren, Xiaojia; Roach, Jeffrey; Sabedot, Thaís S; Schein, Jacqueline; Schumacher, Steven E; Seidman, Jonathan G; Seth, Sahil; Shen, Hui; Simons, Janae V; Sipahimalani, Payal; Soloway, Matthew G; Song, Xingzhi; Sun, Huandong; Tabak, Barbara; Tam, Angela; Tan, Donghui; Tang, Jiabin; Thiessen, Nina; Triche, Timothy; Van Den Berg, David J; Veluvolu, Umadevi; Waring, Scot; Weisenberger, Daniel J; Wilkerson, Matthew D; Wong, Tina; Wu, Junyuan; Xi, Liu; Xu, Andrew W; Yang, Lixing; Zack, Travis I; Zhang, Jianhua; Aksoy, B Arman; Arachchi, Harindra; Benz, Chris; Bernard, Brady; Carlin, Daniel; Cho, Juok; DiCara, Daniel; Frazer, Scott; Fuller, Gregory N; Gao, JianJiong; Gehlenborg, Nils; Haussler, David; Heiman, David I; Iype, Lisa; Jacobsen, Anders; Ju, Zhenlin; Katzman, Sol; Kim, Hoon; Knijnenburg, Theo; Kreisberg, Richard Bailey; Lawrence, Michael S; Lee, William; Leinonen, Kalle; Lin, Pei; Ling, Shiyun; Liu, Wenbin; Liu, Yingchun; Liu, Yuexin; Lu, Yiling; Mills, Gordon; Ng, Sam; Noble, Michael S; Paull, Evan; Rao, Arvind; Reynolds, Sheila; Saksena, Gordon; Sanborn, Zack; Sander, Chris; Schultz, Nikolaus; Senbabaoglu, Yasin; Shen, Ronglai; Shmulevich, Ilya; Sinha, Rileen; Stuart, Josh; Sumer, S Onur; Sun, Yichao; Tasman, Natalie; Taylor, Barry S; Voet, Doug; Weinhold, Nils; Weinstein, John N; Yang, Da; Yoshihara, Kosuke; Zheng, Siyuan; Zhang, Wei; Zou, Lihua; Abel, Ty; Sadeghi, Sara; Cohen, Mark L; Eschbacher, Jenny; Hattab, Eyas M; Raghunathan, Aditya; Schniederjan, Matthew J; Aziz, Dina; Barnett, Gene; Barrett, Wendi; Bigner, Darell D; Boice, Lori; Brewer, Cathy; Calatozzolo, Chiara; Campos, Benito; Carlotti, Carlos Gilberto; Chan, Timothy A; Cuppini, Lucia; Curley, Erin; Cuzzubbo, Stefania; Devine, Karen; DiMeco, Francesco; Duell, Rebecca; Elder, J Bradley; Fehrenbach, Ashley; Finocchiaro, Gaetano; Friedman, William; Fulop, Jordonna; Gardner, Johanna; Hermes, Beth; Herold-Mende, Christel; Jungk, Christine; Kendler, Ady; Lehman, Norman L; Lipp, Eric; Liu, Ouida; Mandt, Randy; McGraw, Mary; Mclendon, Roger; McPherson, Christopher; Neder, Luciano; Nguyen, Phuong; Noss, Ardene; Nunziata, Raffaele; Ostrom, Quinn T; Palmer, Cheryl; Perin, Alessandro; Pollo, Bianca; Potapov, Alexander; Potapova, Olga; Rathmell, W Kimryn; Rotin, Daniil; Scarpace, Lisa; Schilero, Cathy; Senecal, Kelly; Shimmel, Kristen; Shurkhay, Vsevolod; Sifri, Suzanne; Singh, Rosy; Sloan, Andrew E; Smolenski, Kathy; Staugaitis, Susan M; Steele, Ruth; Thorne, Leigh; Tirapelli, Daniela P C; Unterberg, Andreas; Vallurupalli, Mahitha; Wang, Yun; Warnick, Ronald; Williams, Felicia; Wolinsky, Yingli; Bell, Sue; Rosenberg, Mara; Stewart, Chip; Huang, Franklin; Grimsby, Jonna L; Radenbaugh, Amie J; Zhang, Jianan

    2015-06-25

    Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have highly variable clinical behavior that is not adequately predicted on the basis of histologic class. Some are indolent; others quickly progress to glioblastoma. The uncertainty is compounded by interobserver variability in histologic diagnosis. Mutations in IDH, TP53, and ATRX and codeletion of chromosome arms 1p and 19q (1p/19q codeletion) have been implicated as clinically relevant markers of lower-grade gliomas. We performed genomewide analyses of 293 lower-grade gliomas from adults, incorporating exome sequence, DNA copy number, DNA methylation, messenger RNA expression, microRNA expression, and targeted protein expression. These data were integrated and tested for correlation with clinical outcomes. Unsupervised clustering of mutations and data from RNA, DNA-copy-number, and DNA-methylation platforms uncovered concordant classification of three robust, nonoverlapping, prognostically significant subtypes of lower-grade glioma that were captured more accurately by IDH, 1p/19q, and TP53 status than by histologic class. Patients who had lower-grade gliomas with an IDH mutation and 1p/19q codeletion had the most favorable clinical outcomes. Their gliomas harbored mutations in CIC, FUBP1, NOTCH1, and the TERT promoter. Nearly all lower-grade gliomas with IDH mutations and no 1p/19q codeletion had mutations in TP53 (94%) and ATRX inactivation (86%). The large majority of lower-grade gliomas without an IDH mutation had genomic aberrations and clinical behavior strikingly similar to those found in primary glioblastoma. The integration of genomewide data from multiple platforms delineated three molecular classes of lower-grade gliomas that were more concordant with IDH, 1p/19q, and TP53 status than with histologic class. Lower-grade gliomas with an IDH mutation either had 1p/19q codeletion or carried a TP53 mutation. Most

  19. Towards Breath Gas Analysis Based on Millimeter-Wave Molecular Spectroscopy

    Science.gov (United States)

    Rothbart, Nick; Hübers, Heinz-Wilhelm; Schmalz, Klaus; Borngräber, Johannes; Kissinger, Dietmar

    2018-03-01

    Breath gas analysis is a promising non-invasive tool for medical diagnosis as there are thousands of Volatile Organic Compounds (VOCs) in human breath that can be used as health monitoring markers. Millimeter-wave/terahertz molecular spectroscopy is highly suitable for breath gas analysis due to unique fingerprint spectra of many VOCs in that frequency range. We present our recent work on sensor systems for gas spectroscopy based on integrated transmitters (TX) and receivers (RX) fabricated in IHP's 0.13 μm SiGe BiCMOS technology. For a single-band system, spectroscopic measurements and beam profiles are presented. The frequency is tuned by direct voltage-frequency tuning and by a fractional-n PLL, respectively. The spectroscopic system includes a folded gas absorption cell with gas pre-concentration abilities demonstrating the detection of a 50 ppm mixture of ethanol in ambient air corresponding to a minimum detectable concentration of 260 ppb. Finally, the design of a 3-band system covering frequencies from 225 to 273 GHz is introduced.

  20. Integration of heterogeneous molecular networks to unravel gene-regulation in Mycobacterium tuberculosis

    NARCIS (Netherlands)

    Dam, van J.C.J.; Schaap, P.J.; Martins dos Santos, V.A.P.; Suarez Diez, M.

    2014-01-01

    Background: Different methods have been developed to infer regulatory networks from heterogeneous omics datasets and to construct co-expression networks. Each algorithm produces different networks and efforts have been devoted to automatically integrate them into consensus sets. However each

  1. Integrated information system for analysis of nuclear power plants

    International Nuclear Information System (INIS)

    Galperin, A.

    1994-01-01

    Performing complicated engineering analyses of a nuclear power plant requires storage and manipulation of a large amount of information, both data and knowledge. This information is characterized by its multidisciplinary nature, complexity, and diversity. The problems caused by inefficient and lengthy manual operations involving the data flow management within the frame-work of the safety-related analysis of a power plant can be solved by applying the computer aided engineering principles. These principles are the basis of the design of an integrated information storage system (IRIS). The basic idea is to create a computerized environment, which includes both database and functional capabilities. Consideration and analysis of the data types and required data manipulation capabilities as well as operational requirements, resulted in the choice of an object-oriented data-base management system (OODBMS) as a development platform for solving the software engineering problems. Several advantages of OODBMSs over conventional relations database systems were found of crucial importance, especially providing the necessary flexibility for different data types and extensibility potential. A detailed design of a data model is produced for the plant technical data and for the storage of analysis results. The overall system architecture was designed to assure the feasibility of integrating database capabilities with procedures and functions written in conventional algorithmic programming languages

  2. Vertically integrated analysis of human DNA. Final technical report

    Energy Technology Data Exchange (ETDEWEB)

    Olson, M.

    1997-10-01

    This project has been oriented toward improving the vertical integration of the sequential steps associated with the large-scale analysis of human DNA. The central focus has been on an approach to the preparation of {open_quotes}sequence-ready{close_quotes} maps, which is referred to as multiple-complete-digest (MCD) mapping, primarily directed at cosmid clones. MCD mapping relies on simple experimental steps, supported by advanced image-analysis and map-assembly software, to produce extremely accurate restriction-site and clone-overlap maps. We believe that MCD mapping is one of the few high-resolution mapping systems that has the potential for high-level automation. Successful automation of this process would be a landmark event in genome analysis. Once other higher organisms, paving the way for cost-effective sequencing of these genomes. Critically, MCD mapping has the potential to provide built-in quality control for sequencing accuracy and to make possible a highly integrated end product even if there are large numbers of discontinuities in the actual sequence.

  3. DESIGN ANALYSIS OF ELECTRICAL MACHINES THROUGH INTEGRATED NUMERICAL APPROACH

    Directory of Open Access Journals (Sweden)

    ARAVIND C.V.

    2016-02-01

    Full Text Available An integrated design platform for the newer type of machines is presented in this work. The machine parameters are evaluated out using developed modelling tool. With the machine parameters, the machine is modelled using computer aided tool. The designed machine is brought to simulation tool to perform electromagnetic and electromechanical analysis. In the simulation, conditions setting are performed to setup the materials, meshes, rotational speed and the excitation circuit. Electromagnetic analysis is carried out to predict the behavior of the machine based on the movement of flux in the machines. Besides, electromechanical analysis is carried out to analyse the speed-torque characteristic, the current-torque characteristic and the phase angle-torque characteristic. After all the results are analysed, the designed machine is used to generate S block function that is compatible with MATLAB/SIMULINK tool for the dynamic operational characteristics. This allows the integration of existing drive system into the new machines designed in the modelling tool. An example of the machine design is presented to validate the usage of such a tool.

  4. Using Biocatalysis to Integrate Organic Chemistry into a Molecular Biology Laboratory Course

    Science.gov (United States)

    Beers, Mande; Archer, Crystal; Feske, Brent D.; Mateer, Scott C.

    2012-01-01

    Current cutting-edge biomedical investigation requires that the researcher have an operational understanding of several diverse disciplines. Biocatalysis is a field of science that operates at the crossroads of organic chemistry, biochemistry, microbiology, and molecular biology, and provides an excellent model for interdisciplinary research. We…

  5. The Need for Novel Informatics Tools for Integrating and Planning Research in Molecular and Cellular Cognition

    Science.gov (United States)

    Silva, Alcino J.; Müller, Klaus-Robert

    2015-01-01

    The sheer volume and complexity of publications in the biological sciences are straining traditional approaches to research planning. Nowhere is this problem more serious than in molecular and cellular cognition, since in this neuroscience field, researchers routinely use approaches and information from a variety of areas in neuroscience and other…

  6. An Integrated Visualization and Basic Molecular Modeling Laboratory for First-Year Undergraduate Medicinal Chemistry

    Science.gov (United States)

    Hayes, Joseph M.

    2014-01-01

    A 3D model visualization and basic molecular modeling laboratory suitable for first-year undergraduates studying introductory medicinal chemistry is presented. The 2 h practical is embedded within a series of lectures on drug design, target-drug interactions, enzymes, receptors, nucleic acids, and basic pharmacokinetics. Serving as a teaching aid…

  7. Molecular malaria diagnostics: A systematic review and meta-analysis.

    Science.gov (United States)

    Roth, Johanna M; Korevaar, Daniël A; Leeflang, Mariska M G; Mens, Pètra F

    2016-01-01

    Accurate diagnosis of malaria is essential for identification and subsequent treatment of the disease. Currently, microscopy and rapid diagnostic tests are the most commonly used diagnostics, next to treatment based on clinical signs only. These tests are easy to deploy, but have a relatively high detection limit. With declining prevalence in many areas, there is an increasing need for more sensitive diagnostics. Molecular tools may be a suitable alternative, although costs and technical requirements currently hamper their implementation in resource limited settings. A range of (near) point-of-care diagnostics is therefore under development, including simplifications in sample preparation, amplification and/or read-out of the test. Accuracy data, in combination with technical characteristics, are essential in determining which molecular test, if any, would be the most promising to be deployed. This review presents a comprehensive overview of the currently available molecular malaria diagnostics, ranging from well-known tests to platforms in early stages of evaluation, and systematically evaluates their published accuracy. No important difference in accuracy was found between the most commonly used PCR-based assays (conventional, nested and real-time PCR), with most of them having high sensitivity and specificity, implying that there are no reasons other than practical ones to choose one technique over the other. Loop-mediated isothermal amplification and other (novel) diagnostics appear to be highly accurate as well, with some offering potential to be used in resource-limited settings.

  8. Solid waste integrated cost analysis model: 1991 project year report

    Energy Technology Data Exchange (ETDEWEB)

    1991-01-01

    The purpose of the City of Houston's 1991 Solid Waste Integrated Cost Analysis Model (SWICAM) project was to continue the development of a computerized cost analysis model. This model is to provide solid waste managers with tool to evaluate the dollar cost of real or hypothetical solid waste management choices. Those choices have become complicated by the implementation of Subtitle D of the Resources Conservation and Recovery Act (RCRA) and the EPA's Integrated Approach to managing municipal solid waste;. that is, minimize generation, maximize recycling, reduce volume (incinerate), and then bury (landfill) only the remainder. Implementation of an integrated solid waste management system involving all or some of the options of recycling, waste to energy, composting, and landfilling is extremely complicated. Factors such as hauling distances, markets, and prices for recyclable, costs and benefits of transfer stations, and material recovery facilities must all be considered. A jurisdiction must determine the cost impacts of implementing a number of various possibilities for managing, handling, processing, and disposing of waste. SWICAM employs a single Lotus 123 spreadsheet to enable a jurisdiction to predict or assess the costs of its waste management system. It allows the user to select his own process flow for waste material and to manipulate the model to include as few or as many options as he or she chooses. The model will calculate the estimated cost for those choices selected. The user can then change the model to include or exclude waste stream components, until the mix of choices suits the user. Graphs can be produced as a visual communication aid in presenting the results of the cost analysis. SWICAM also allows future cost projections to be made.

  9. Molecular-beam epitaxial growth and ion-beam analysis systems for functional materials research

    International Nuclear Information System (INIS)

    Takeshita, H.; Aoki, Y.; Yamamoto, S.; Naramoto, H.

    1992-01-01

    Experimental systems for molecular beam epitaxial growth and ion beam analysis have been designed and constructed for the research of inorganic functional materials such as thin films and superlattices. (author)

  10. An Integrated Analysis of Changes in Water Stress in Europe

    DEFF Research Database (Denmark)

    Henrichs, T.; Lehner, B.; Alcamo, J.

    2002-01-01

    Future changes in water availability with climate change and changes in water use due to socio-economic development are to occur in parallel. In an integrated analysis we bring together these aspects of global change in a consistent manner, and analyse the water stress situation in Europe. We find...... that today high water stress exists in one-fifth of European river basin area. Under a scenario projection, increases in water use throughout Eastern Europe are accompanied by decreases in water availability in most of Southern Europe--combining these trends leads to a marked increase in water stress...

  11. Case for integral core-disruptive accident analysis

    International Nuclear Information System (INIS)

    Luck, L.B.; Bell, C.R.

    1985-01-01

    Integral analysis is an approach used at the Los Alamos National Laboratory to cope with the broad multiplicity of accident paths and complex phenomena that characterize the transition phase of core-disruptive accident progression in a liquid-metal-cooled fast breeder reactor. The approach is based on the combination of a reference calculation, which is intended to represent a band of similar accident paths, and associated system- and separate-effect studies, which are designed to determine the effect of uncertainties. Results are interpreted in the context of a probabilistic framework. The approach was applied successfully in two studies; illustrations from the Clinch River Breeder Reactor licensing assessment are included

  12. Integrated polymer waveguides for absorbance detection in chemical analysis systems

    DEFF Research Database (Denmark)

    Mogensen, Klaus Bo; El-Ali, Jamil; Wolff, Anders

    2003-01-01

    A chemical analysis system for absorbance detection with integrated polymer waveguides is reported for the first time. The fabrication procedure relies on structuring of a single layer of the photoresist SU-8, so both the microfluidic channel network and the optical components, which include planar....... The emphasis of this paper is on the signal-to-noise ratio of the detection and its relation to the sensitivity. Two absorbance cells with an optical path length of 100 μm and 1000 μm were characterized and compared in terms of sensitivity, limit of detection and effective path length for measurements...

  13. Apportioning sources of organic matter in streambed sediments: An integrated molecular and compound-specific stable isotope approach

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, Richard J., E-mail: Richard.J.Cooper@uea.ac.uk [School of Environmental Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ (United Kingdom); Pedentchouk, Nikolai; Hiscock, Kevin M.; Disdle, Paul [School of Environmental Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ (United Kingdom); Krueger, Tobias [IRI THESys, Humboldt University, 10099 Berlin (Germany); Rawlins, Barry G. [British Geological Survey, Keyworth, Nottingham NG12 5GG (United Kingdom)

    2015-07-01

    apportionment of organic matter sources. Median organic matter contributions ranged from 22% to 52% for trees, 29% to 50% for herbaceous perennials, 17% to 34% for C{sub 3} graminoids and 3% to 7% for C{sub 4} graminoids. The results presented here clearly demonstrate the effectiveness of an integrated molecular and stable isotope analysis for quantitatively apportioning, with uncertainty, plant-specific organic matter contributions to streambed sediments via a Bayesian mixing model approach. - Highlights: • Organic contributions from trees, herbs and C{sub 3}/C{sub 4} graminoids are apportioned. • δ{sup 2}H provides strong discrimination between plant functional types. • δ{sup 13}C provides strong contrasts between C{sub 3} and C{sub 4} plants. • δ{sup 2}H and δ{sup 13}C values could not differentiate aquatic and terrestrial species. • n-Alkane ratios compliment isotopic discrimination.

  14. Integrated Modeling for the James Webb Space Telescope (JWST) Project: Structural Analysis Activities

    Science.gov (United States)

    Johnston, John; Mosier, Mark; Howard, Joe; Hyde, Tupper; Parrish, Keith; Ha, Kong; Liu, Frank; McGinnis, Mark

    2004-01-01

    This paper presents viewgraphs about structural analysis activities and integrated modeling for the James Webb Space Telescope (JWST). The topics include: 1) JWST Overview; 2) Observatory Structural Models; 3) Integrated Performance Analysis; and 4) Future Work and Challenges.

  15. Application of Deep Learning in Automated Analysis of Molecular Images in Cancer: A Survey

    Science.gov (United States)

    Xue, Yong; Chen, Shihui; Liu, Yong

    2017-01-01

    Molecular imaging enables the visualization and quantitative analysis of the alterations of biological procedures at molecular and/or cellular level, which is of great significance for early detection of cancer. In recent years, deep leaning has been widely used in medical imaging analysis, as it overcomes the limitations of visual assessment and traditional machine learning techniques by extracting hierarchical features with powerful representation capability. Research on cancer molecular images using deep learning techniques is also increasing dynamically. Hence, in this paper, we review the applications of deep learning in molecular imaging in terms of tumor lesion segmentation, tumor classification, and survival prediction. We also outline some future directions in which researchers may develop more powerful deep learning models for better performance in the applications in cancer molecular imaging. PMID:29114182

  16. Integrated omics analysis of specialized metabolism in medicinal plants.

    Science.gov (United States)

    Rai, Amit; Saito, Kazuki; Yamazaki, Mami

    2017-05-01

    Medicinal plants are a rich source of highly diverse specialized metabolites with important pharmacological properties. Until recently, plant biologists were limited in their ability to explore the biosynthetic pathways of these metabolites, mainly due to the scarcity of plant genomics resources. However, recent advances in high-throughput large-scale analytical methods have enabled plant biologists to discover biosynthetic pathways for important plant-based medicinal metabolites. The reduced cost of generating omics datasets and the development of computational tools for their analysis and integration have led to the elucidation of biosynthetic pathways of several bioactive metabolites of plant origin. These discoveries have inspired synthetic biology approaches to develop microbial systems to produce bioactive metabolites originating from plants, an alternative sustainable source of medicinally important chemicals. Since the demand for medicinal compounds are increasing with the world's population, understanding the complete biosynthesis of specialized metabolites becomes important to identify or develop reliable sources in the future. Here, we review the contributions of major omics approaches and their integration to our understanding of the biosynthetic pathways of bioactive metabolites. We briefly discuss different approaches for integrating omics datasets to extract biologically relevant knowledge and the application of omics datasets in the construction and reconstruction of metabolic models. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  17. Integrative analysis of the mitochondrial proteome in yeast.

    Directory of Open Access Journals (Sweden)

    Holger Prokisch

    2004-06-01

    Full Text Available In this study yeast mitochondria were used as a model system to apply, evaluate, and integrate different genomic approaches to define the proteins of an organelle. Liquid chromatography mass spectrometry applied to purified mitochondria identified 546 proteins. By expression analysis and comparison to other proteome studies, we demonstrate that the proteomic approach identifies primarily highly abundant proteins. By expanding our evaluation to other types of genomic approaches, including systematic deletion phenotype screening, expression profiling, subcellular localization studies, protein interaction analyses, and computational predictions, we show that an integration of approaches moves beyond the limitations of any single approach. We report the success of each approach by benchmarking it against a reference set of known mitochondrial proteins, and predict approximately 700 proteins associated with the mitochondrial organelle from the integration of 22 datasets. We show that a combination of complementary approaches like deletion phenotype screening and mass spectrometry can identify over 75% of the known mitochondrial proteome. These findings have implications for choosing optimal genome-wide approaches for the study of other cellular systems, including organelles and pathways in various species. Furthermore, our systematic identification of genes involved in mitochondrial function and biogenesis in yeast expands the candidate genes available for mapping Mendelian and complex mitochondrial disorders in humans.

  18. Integral Transport Analysis Results for Ions Flowing Through Neutral Gas

    Science.gov (United States)

    Emmert, Gilbert; Santarius, John

    2017-10-01

    Results of a computational model for the flow of energetic ions and neutrals through a background neutral gas will be presented. The method models reactions as creating a new source of ions or neutrals if the energy or charge state of the resulting particle is changed. For a given source boundary condition, the creation and annihilation of the various species is formulated as a 1-D Volterra integral equation that can quickly be solved numerically by finite differences. The present work focuses on multiple-pass, 1-D ion flow through neutral gas and a nearly transparent, concentric anode and cathode pair in spherical, cylindrical, or linear geometry. This has been implemented as a computer code for atomic (3He, 3He +, 3He + +) and molecular (D, D2, D-, D +, D2 +, D3 +) ion and neutral species, and applied to modeling inertial-electrostatic connement (IEC) devices. The code yields detailed energy spectra of the various ions and energetic neutral species. Calculations for several University of Wisconsin IEC and ion implantation devices will be presented. Research supported by US Dept. of Homeland Security Grant 2015-DN-077-ARI095, Dept. of Energy Grant DE-FG02-04ER54745, and the Grainger Foundation.

  19. Prognostic value of Ki-67 index in adult medulloblastoma after accounting for molecular subgroup: a retrospective clinical and molecular analysis.

    Science.gov (United States)

    Zhao, Fu; Zhang, Jing; Li, Peng; Zhou, Qiangyi; Zhang, Shun; Zhao, Chi; Wang, Bo; Yang, Zhijun; Li, Chunde; Liu, Pinan

    2018-04-23

    Medulloblastoma (MB) is a rare primary brain tumor in adults. We previously evaluated that combining both clinical and molecular classification could improve current risk stratification for adult MB. In this study, we aimed to identify the prognostic value of Ki-67 index in adult MB. Ki-67 index of 51 primary adult MBs was reassessed using a computer-based image analysis (Image-Pro Plus). All patients were followed up ranging from 12 months up to 15 years. Gene expression profiling and immunochemistry were used to establish the molecular subgroups in adult MB. Combined risk stratification models were designed based on clinical characteristics, molecular classification and Ki-67 index, and identified by multivariable Cox proportional hazards analysis. In our cohort, the mean Ki-67 value was 30.0 ± 11.3% (range 6.56-63.55%). The average Ki-67 value was significantly higher in LC/AMB than in CMB and DNMB (P = .001). Among three molecular subgroups, Group 4-tumors had the highest average Ki-67 value compared with WNT- and SHH-tumors (P = .004). Patients with Ki-67 index large than 30% displayed poorer overall survival (OS) and progression free survival (PFS) than those with Ki-67 less than 30% (OS: P = .001; PFS: P = .006). Ki-67 index (i.e. > 30%, < 30%) was identified as an independent significant prognostic factor (OS: P = .017; PFS: P = .024) by using multivariate Cox proportional hazards model. In conclusion, Ki-67 index can be considered as a valuable independent prognostic biomarker for adult patients with MB.

  20. Analysis of small molecular phase in coal involved in pyrolysis and solvent extraction by PGC

    Energy Technology Data Exchange (ETDEWEB)

    Jie Feng; Wen-Ying Li; Ke-Chang Xie [Taiyuan University of Technology, Taiyuan (China). Key Laboratory of Coal Science and Technology

    2004-06-01

    The small molecular phase, which strongly affects coal's reactivity, is the main part of the structure unit in coal. At present, its composition and structure features have not been clearly understood. In this paper, a flash pyrolysis technique with on-line GC (PGC) was used to investigate the properties of the small molecular phase from six kinds of rank coal in China. Experiments were divided into two parts: one is PGC of parent coal; another is PGC of coal extracts from NMP + CS{sub 2} (75:1) solvent extraction at 373 K. Results show that the small molecular phase mainly consists of C12-C16 compounds that could be integrally released when the heating rate was greater than 10 K/ms and the final pyrolysis temperature was 1373 K; other compounds may be the products of decomposition and polymerization from this small molecular phase during pyrolysis. 13 refs., 7 figs., 1 tab.

  1. Molecular cloning, expression and computational analysis of a water ...

    African Journals Online (AJOL)

    User

    2012-11-06

    Nov 6, 2012 ... analysis of a water stress inducible copper-containing ... Although, in slico analysis of the protein have indicated its probable structure and functions, further ..... based on protein data bank (PDB) template c1ksiA which.

  2. Integrated intelligent instruments using supercritical fluid technology for soil analysis

    International Nuclear Information System (INIS)

    Liebman, S.A.; Phillips, C.; Fitzgerald, W.; Levy, E.J.

    1994-01-01

    Contaminated soils pose a significant challenge for characterization and remediation programs that require rapid, accurate and comprehensive data in the field or laboratory. Environmental analyzers based on supercritical fluid (SF) technology have been designed and developed for meeting these global needs. The analyzers are designated the CHAMP Systems (Chemical Hazards Automated Multimedia Processors). The prototype instrumentation features SF extraction (SFE) and on-line capillary gas chromatographic (GC) analysis with chromatographic and/or spectral identification detectors, such as ultra-violet, Fourier transform infrared and mass spectrometers. Illustrations are given for a highly automated SFE-capillary GC/flame ionization (FID) configuration to provide validated screening analysis for total extractable hydrocarbons within ca. 5--10 min, as well as a full qualitative/quantitative analysis in 25--30 min. Data analysis using optional expert system and neural networks software is demonstrated for test gasoline and diesel oil mixtures in this integrated intelligent instrument approach to trace organic analysis of soils and sediments

  3. Integrative Analysis of Prognosis Data on Multiple Cancer Subtypes

    Science.gov (United States)

    Liu, Jin; Huang, Jian; Zhang, Yawei; Lan, Qing; Rothman, Nathaniel; Zheng, Tongzhang; Ma, Shuangge

    2014-01-01

    Summary In cancer research, profiling studies have been extensively conducted, searching for genes/SNPs associated with prognosis. Cancer is diverse. Examining the similarity and difference in the genetic basis of multiple subtypes of the same cancer can lead to a better understanding of their connections and distinctions. Classic meta-analysis methods analyze each subtype separately and then compare analysis results across subtypes. Integrative analysis methods, in contrast, analyze the raw data on multiple subtypes simultaneously and can outperform meta-analysis methods. In this study, prognosis data on multiple subtypes of the same cancer are analyzed. An AFT (accelerated failure time) model is adopted to describe survival. The genetic basis of multiple subtypes is described using the heterogeneity model, which allows a gene/SNP to be associated with prognosis of some subtypes but not others. A compound penalization method is developed to identify genes that contain important SNPs associated with prognosis. The proposed method has an intuitive formulation and is realized using an iterative algorithm. Asymptotic properties are rigorously established. Simulation shows that the proposed method has satisfactory performance and outperforms a penalization-based meta-analysis method and a regularized thresholding method. An NHL (non-Hodgkin lymphoma) prognosis study with SNP measurements is analyzed. Genes associated with the three major subtypes, namely DLBCL, FL, and CLL/SLL, are identified. The proposed method identifies genes that are different from alternatives and have important implications and satisfactory prediction performance. PMID:24766212

  4. Integrated Data Analysis (IDCA) Program - PETN Class 4 Standard

    Energy Technology Data Exchange (ETDEWEB)

    Sandstrom, Mary M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Brown, Geoffrey W. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Preston, Daniel N. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Pollard, Colin J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Warner, Kirstin F. [Naval Surface Warfare Center (NSWC), Indian Head, MD (United States). Indian Head Division; Sorensen, Daniel N. [Naval Surface Warfare Center (NSWC), Indian Head, MD (United States). Indian Head Division; Remmers, Daniel L. [Naval Surface Warfare Center (NSWC), Indian Head, MD (United States). Indian Head Division; Shelley, Timothy J. [Air Force Research Lab. (AFRL), Tyndall AFB, FL (United States); Reyes, Jose A. [Applied Research Associates, Tyndall AFB, FL (United States); Phillips, Jason J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hsu, Peter C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Reynolds, John G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2012-08-01

    The Integrated Data Collection Analysis (IDCA) program is conducting a proficiency study for Small- Scale Safety and Thermal (SSST) testing of homemade explosives (HMEs). Described here are the results for impact, friction, electrostatic discharge, and differential scanning calorimetry analysis of PETN Class 4. The PETN was found to have: 1) an impact sensitivity (DH50) range of 6 to 12 cm, 2) a BAM friction sensitivity (F50) range 7 to 11 kg, TIL (0/10) of 3.7 to 7.2 kg, 3) a ABL friction sensitivity threshold of 5 or less psig at 8 fps, 4) an ABL ESD sensitivity threshold of 0.031 to 0.326 j/g, and 5) a thermal sensitivity of an endothermic feature with Tmin = ~ 141 °C, and a exothermic feature with a Tmax = ~205°C.

  5. Integrated Data Collection Analysis (IDCA) Program — Ammonium Nitrate

    Energy Technology Data Exchange (ETDEWEB)

    Sandstrom, Mary M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Brown, Geoffrey W. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Preston, Daniel N. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Pollard, Colin J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Warner, Kirstin F. [Naval Surface Warfare Center (NSWC), Indian Head, MD (United States). Indian Head Division; Sorensen, Daniel N. [Naval Surface Warfare Center (NSWC), Indian Head, MD (United States). Indian Head Division; Remmers, Daniel L. [Naval Surface Warfare Center (NSWC), Indian Head, MD (United States). Indian Head Division; Phillips, Jason J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Shelley, Timothy J. [Bureau of Alcohol, Tobacco and Firearms, Redstone Arsenal, AL (United States); Reyes, Jose A. [Applied Research Associates, Tyndall AFB, FL (United States); Hsu, Peter C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Reynolds, John G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2013-05-17

    The Integrated Data Collection Analysis (IDCA) program is conducting a proficiency study for Small- Scale Safety and Thermal (SSST) testing of homemade explosives (HMEs). Described here are the results for impact, friction, electrostatic discharge, and differential scanning calorimetry analysis of ammonium nitrate (AN). AN was tested, in most cases, as both received from manufacturer and dried/sieved. The participants found the AN to be: 1) insensitive in Type 12A impact testing (although with a wide range of values), 2) completely insensitive in BAM friction testing, 3) less sensitive than the RDX standard in ABL friction testing, 4) less sensitive than RDX in ABL ESD testing, and 5) less sensitive than RDX and PETN in DSC thermal analyses.

  6. An integrated economic and distributional analysis of energy policies

    International Nuclear Information System (INIS)

    Labandeira, Xavier; Labeaga, Jose M.; Rodriguez, Miguel

    2009-01-01

    Most public policies, particularly those in the energy sphere, have not only efficiency but also distributional effects. However, there is a trade-off between modelling approaches suitable for calculating those impacts on the economy. For the former most of the studies have been conducted with general equilibrium models, whereas partial equilibrium models represent the main approach for distributional analysis. This paper proposes a methodology to simultaneously carry out an analysis of the distributional and efficiency consequences of changes in energy taxation. In order to do so, we have integrated a microeconomic household demand model and a computable general equilibrium model for the Spanish economy. We illustrate the advantages of this approach by simulating a revenue-neutral reform in Spanish indirect taxation, with a large increase of energy taxes that serve an environmental purpose. The results show that the reforms bring about significant efficiency and distributional effects, in some cases counterintuitive, and demonstrate the academic and social utility of this approximation. (author)

  7. An integrated economic and distributional analysis of energy policies

    Energy Technology Data Exchange (ETDEWEB)

    Labandeira, Xavier [Facultade de CC. Economicas, University of Vigo, 36310 Vigo (Spain); Labeaga, Jose M. [Instituto de Estudios Fiscales, Avda. Cardenal Herrera Oria 378, 28035 Madrid (Spain); Rodriguez, Miguel [Facultade de CC. Empresariais e Turismo, University of Vigo, 32004 Ourense (Spain)

    2009-12-15

    Most public policies, particularly those in the energy sphere, have not only efficiency but also distributional effects. However, there is a trade-off between modelling approaches suitable for calculating those impacts on the economy. For the former most of the studies have been conducted with general equilibrium models, whereas partial equilibrium models represent the main approach for distributional analysis. This paper proposes a methodology to simultaneously carry out an analysis of the distributional and efficiency consequences of changes in energy taxation. In order to do so, we have integrated a microeconomic household demand model and a computable general equilibrium model for the Spanish economy. We illustrate the advantages of this approach by simulating a revenue-neutral reform in Spanish indirect taxation, with a large increase of energy taxes that serve an environmental purpose. The results show that the reforms bring about significant efficiency and distributional effects, in some cases counterintuitive, and demonstrate the academic and social utility of this approximation. (author)

  8. Simulation analysis for integrated evaluation of technical and commercial risk

    International Nuclear Information System (INIS)

    Gutleber, D.S.; Heiberger, E.M.; Morris, T.D.

    1995-01-01

    Decisions to invest in oil- and gasfield acquisitions or participating interests often are based on the perceived ability to enhance the economic value of the underlying asset. A multidisciplinary approach integrating reservoir engineering, operations and drilling, and deal structuring with Monte Carlo simulation modeling can overcome weaknesses of deterministic analysis and significantly enhance investment decisions. This paper discusses the use of spreadsheets and Monte Carlo simulation to generate probabilistic outcomes for key technical and economic parameters for ultimate identification of the economic volatility and value of potential deal concepts for a significant opportunity. The approach differs from a simple risk analysis for an individual well by incorporating detailed, full-field simulations that vary the reservoir parameters, capital and operating cost assumptions, and schedules on timing in the framework of various deal structures

  9. Molecular Laser Spectroscopy as a Tool for Gas Analysis Applications

    Directory of Open Access Journals (Sweden)

    Javis Anyangwe Nwaboh

    2011-01-01

    Full Text Available We have used the traceable infrared laser spectrometric amount fraction measurement (TILSAM method to perform absolute concentration measurements of molecular species using three laser spectroscopic techniques. We report results performed by tunable diode laser absorption spectroscopy (TDLAS, quantum cascade laser absorption spectroscopy (QCLAS, and cavity ring down spectroscopy (CRDS, all based on the TILSAM methodology. The measured results of the different spectroscopic techniques are in agreement with respective gravimetric values, showing that the TILSAM method is feasible with all different techniques. We emphasize the data quality objectives given by traceability issues and uncertainty analyses.

  10. Designing molecular complexes using free-energy derivatives from liquid-state integral equation theory

    International Nuclear Information System (INIS)

    Mrugalla, Florian; Kast, Stefan M

    2016-01-01

    Complex formation between molecules in solution is the key process by which molecular interactions are translated into functional systems. These processes are governed by the binding or free energy of association which depends on both direct molecular interactions and the solvation contribution. A design goal frequently addressed in pharmaceutical sciences is the optimization of chemical properties of the complex partners in the sense of minimizing their binding free energy with respect to a change in chemical structure. Here, we demonstrate that liquid-state theory in the form of the solute–solute equation of the reference interaction site model provides all necessary information for such a task with high efficiency. In particular, computing derivatives of the potential of mean force (PMF), which defines the free-energy surface of complex formation, with respect to potential parameters can be viewed as a means to define a direction in chemical space toward better binders. We illustrate the methodology in the benchmark case of alkali ion binding to the crown ether 18-crown-6 in aqueous solution. In order to examine the validity of the underlying solute–solute theory, we first compare PMFs computed by different approaches, including explicit free-energy molecular dynamics simulations as a reference. Predictions of an optimally binding ion radius based on free-energy derivatives are then shown to yield consistent results for different ion parameter sets and to compare well with earlier, orders-of-magnitude more costly explicit simulation results. This proof-of-principle study, therefore, demonstrates the potential of liquid-state theory for molecular design problems. (paper)

  11. Integrating Pavement Crack Detection and Analysis Using Autonomous Unmanned Aerial Vehicle Imagery

    Science.gov (United States)

    2015-03-27

    INTEGRATING PAVEMENT CRACK DETECTION AND ANALYSIS USING AUTONOMOUS UNMANNED AERIAL VEHICLE...protection in the United States. AFIT-ENV-MS-15-M-195 INTEGRATING PAVEMENT CRACK DETECTION AND ANALYSIS USING AUTONOMOUS UNMANNED AERIAL...APPROVED FOR PUBLIC RELEASE; DISTRIBUTION UNLIMITED. AFIT-ENV-MS-15-M-195 INTEGRATING PAVEMENT CRACK DETECTION AND ANALYSIS USING AUTONOMOUS

  12. Sensitivity Analysis of the Integrated Medical Model for ISS Programs

    Science.gov (United States)

    Goodenow, D. A.; Myers, J. G.; Arellano, J.; Boley, L.; Garcia, Y.; Saile, L.; Walton, M.; Kerstman, E.; Reyes, D.; Young, M.

    2016-01-01

    Sensitivity analysis estimates the relative contribution of the uncertainty in input values to the uncertainty of model outputs. Partial Rank Correlation Coefficient (PRCC) and Standardized Rank Regression Coefficient (SRRC) are methods of conducting sensitivity analysis on nonlinear simulation models like the Integrated Medical Model (IMM). The PRCC method estimates the sensitivity using partial correlation of the ranks of the generated input values to each generated output value. The partial part is so named because adjustments are made for the linear effects of all the other input values in the calculation of correlation between a particular input and each output. In SRRC, standardized regression-based coefficients measure the sensitivity of each input, adjusted for all the other inputs, on each output. Because the relative ranking of each of the inputs and outputs is used, as opposed to the values themselves, both methods accommodate the nonlinear relationship of the underlying model. As part of the IMM v4.0 validation study, simulations are available that predict 33 person-missions on ISS and 111 person-missions on STS. These simulated data predictions feed the sensitivity analysis procedures. The inputs to the sensitivity procedures include the number occurrences of each of the one hundred IMM medical conditions generated over the simulations and the associated IMM outputs: total quality time lost (QTL), number of evacuations (EVAC), and number of loss of crew lives (LOCL). The IMM team will report the results of using PRCC and SRRC on IMM v4.0 predictions of the ISS and STS missions created as part of the external validation study. Tornado plots will assist in the visualization of the condition-related input sensitivities to each of the main outcomes. The outcomes of this sensitivity analysis will drive review focus by identifying conditions where changes in uncertainty could drive changes in overall model output uncertainty. These efforts are an integral

  13. Integration of molecular imaging in treatment planning and delivery of modern radiotherapy

    International Nuclear Information System (INIS)

    Jacob, V.; Wilkens, J.J.

    2011-01-01

    Among various imaging modalities currently available, positron emission tomography (PET) has the potential to visualize processes on a molecular level. Molecular imaging, often also referred to as functional or biological imaging, brought a new dimension to diagnostics and therapy of cancer by providing images of metabolism and other processes in the human body and in tumours. PET was first applied for diagnostics and staging of various tumours with high diagnostic precision. Modern radiotherapy asks increasingly for individualized treatment strategies, taking molecular imaging into account. Technical developments over the last years, in particular methods to register various imaging modalities within software packages for treatment planning and target delineation, facilitated the use of PET imaging in radiotherapy. In order to exploit the full potential of modern high-precision radiotherapy, exact imaging procedures are necessary, for example for precise target volume definition. In the long run, concepts employing an inhomogeneous dose prescription based on biological imaging may become routine in clinical applications, leading to individualized, biologically adaptive therapy. (orig.)

  14. Multi - band Persistent Scatterer Interferometry data integration for landslide analysis

    Science.gov (United States)

    Bianchini, Silvia; Mateos, Rosa; Mora, Oscar; García, Inma; Sánchez, Ciscu; Sanabria, Margarita; López, Maite; Mulas, Joaquin; Hernández, Mario; Herrera, Gerardo

    2013-04-01

    We present a methodology to perform a geomorphological assessment of ground movements over wide areas, by improving Persistent Scatterer Interferometry (PSI) analysis for landslide studies. The procedure relies on the integrated use of multi-band EO data acquired by different satellite sensors in different time intervals, to provide a detailed investigation of ground displacements. The methodology, throughout the cross-comparison and integration of PS data in different microwave bands (ALOS in L-band, ERS1/2 and ENVISAT in C-band, COSMOSKY-MED in X-band), is applied on the Tramontana Range in the northwestern part of Mallorca island (Spain), extensively affected by mass movements across time, especially during the last years. We increase the confidence degree of the available interferometric data and we homogenize all PS targets by implementing and classifying them through common criteria. Therefore, PSI results are combined with geo-thematic data and pre-existing landslide inventories of the study area, in order to improve the landslide database, providing additional information on the detected ground displacements. The results of this methodology are used to elaborate landslide activity maps, permitting to jointly exploit heterogeneous PS data for analyzing landslides at regional scale. Moreover, from a geomorphological perspective, the proposed approach exploits the implemented PS data to achieve a reliable spatial analysis of movement rates, whatever referred to certain landslide phenomena or to other natural processes, in order to perform ground motion activity maps within a wide area.

  15. Integrated severe accident containment analysis with the CONTAIN computer code

    International Nuclear Information System (INIS)

    Bergeron, K.D.; Williams, D.C.; Rexroth, P.E.; Tills, J.L.

    1985-12-01

    Analysis of physical and radiological conditions iunside the containment building during a severe (core-melt) nuclear reactor accident requires quantitative evaluation of numerous highly disparate yet coupled phenomenologies. These include two-phase thermodynamics and thermal-hydraulics, aerosol physics, fission product phenomena, core-concrete interactions, the formation and combustion of flammable gases, and performance of engineered safety features. In the past, this complexity has meant that a complete containment analysis would require application of suites of separate computer codes each of which would treat only a narrower subset of these phenomena, e.g., a thermal-hydraulics code, an aerosol code, a core-concrete interaction code, etc. In this paper, we describe the development and some recent applications of the CONTAIN code, which offers an integrated treatment of the dominant containment phenomena and the interactions among them. We describe the results of a series of containment phenomenology studies, based upon realistic accident sequence analyses in actual plants. These calculations highlight various phenomenological effects that have potentially important implications for source term and/or containment loading issues, and which are difficult or impossible to treat using a less integrated code suite

  16. Integrative analysis to select cancer candidate biomarkers to targeted validation

    Science.gov (United States)

    Heberle, Henry; Domingues, Romênia R.; Granato, Daniela C.; Yokoo, Sami; Canevarolo, Rafael R.; Winck, Flavia V.; Ribeiro, Ana Carolina P.; Brandão, Thaís Bianca; Filgueiras, Paulo R.; Cruz, Karen S. P.; Barbuto, José Alexandre; Poppi, Ronei J.; Minghim, Rosane; Telles, Guilherme P.; Fonseca, Felipe Paiva; Fox, Jay W.; Santos-Silva, Alan R.; Coletta, Ricardo D.; Sherman, Nicholas E.; Paes Leme, Adriana F.

    2015-01-01

    Targeted proteomics has flourished as the method of choice for prospecting for and validating potential candidate biomarkers in many diseases. However, challenges still remain due to the lack of standardized routines that can prioritize a limited number of proteins to be further validated in human samples. To help researchers identify candidate biomarkers that best characterize their samples under study, a well-designed integrative analysis pipeline, comprising MS-based discovery, feature selection methods, clustering techniques, bioinformatic analyses and targeted approaches was performed using discovery-based proteomic data from the secretomes of three classes of human cell lines (carcinoma, melanoma and non-cancerous). Three feature selection algorithms, namely, Beta-binomial, Nearest Shrunken Centroids (NSC), and Support Vector Machine-Recursive Features Elimination (SVM-RFE), indicated a panel of 137 candidate biomarkers for carcinoma and 271 for melanoma, which were differentially abundant between the tumor classes. We further tested the strength of the pipeline in selecting candidate biomarkers by immunoblotting, human tissue microarrays, label-free targeted MS and functional experiments. In conclusion, the proposed integrative analysis was able to pre-qualify and prioritize candidate biomarkers from discovery-based proteomics to targeted MS. PMID:26540631

  17. Integrated modeling and analysis methodology for precision pointing applications

    Science.gov (United States)

    Gutierrez, Homero L.

    2002-07-01

    Space-based optical systems that perform tasks such as laser communications, Earth imaging, and astronomical observations require precise line-of-sight (LOS) pointing. A general approach is described for integrated modeling and analysis of these types of systems within the MATLAB/Simulink environment. The approach can be applied during all stages of program development, from early conceptual design studies to hardware implementation phases. The main objective is to predict the dynamic pointing performance subject to anticipated disturbances and noise sources. Secondary objectives include assessing the control stability, levying subsystem requirements, supporting pointing error budgets, and performing trade studies. The integrated model resides in Simulink, and several MATLAB graphical user interfaces (GUI"s) allow the user to configure the model, select analysis options, run analyses, and process the results. A convenient parameter naming and storage scheme, as well as model conditioning and reduction tools and run-time enhancements, are incorporated into the framework. This enables the proposed architecture to accommodate models of realistic complexity.

  18. Integrated dynamic landscape analysis and modeling system (IDLAMS) : installation manual.

    Energy Technology Data Exchange (ETDEWEB)

    Li, Z.; Majerus, K. A.; Sundell, R. C.; Sydelko, P. J.; Vogt, M. C.

    1999-02-24

    The Integrated Dynamic Landscape Analysis and Modeling System (IDLAMS) is a prototype, integrated land management technology developed through a joint effort between Argonne National Laboratory (ANL) and the US Army Corps of Engineers Construction Engineering Research Laboratories (USACERL). Dr. Ronald C. Sundell, Ms. Pamela J. Sydelko, and Ms. Kimberly A. Majerus were the principal investigators (PIs) for this project. Dr. Zhian Li was the primary software developer. Dr. Jeffrey M. Keisler, Mr. Christopher M. Klaus, and Mr. Michael C. Vogt developed the decision analysis component of this project. It was developed with funding support from the Strategic Environmental Research and Development Program (SERDP), a land/environmental stewardship research program with participation from the US Department of Defense (DoD), the US Department of Energy (DOE), and the US Environmental Protection Agency (EPA). IDLAMS predicts land conditions (e.g., vegetation, wildlife habitats, and erosion status) by simulating changes in military land ecosystems for given training intensities and land management practices. It can be used by military land managers to help predict the future ecological condition for a given land use based on land management scenarios of various levels of training intensity. It also can be used as a tool to help land managers compare different land management practices and further determine a set of land management activities and prescriptions that best suit the needs of a specific military installation.

  19. The practical implementation of integrated safety management for nuclear safety analysis and fire hazards analysis documentation

    International Nuclear Information System (INIS)

    COLLOPY, M.T.

    1999-01-01

    In 1995 Mr. Joseph DiNunno of the Defense Nuclear Facilities Safety Board issued an approach to describe the concept of an integrated safety management program which incorporates hazard and safety analysis to address a multitude of hazards affecting the public, worker, property, and the environment. Since then the U S . Department of Energy (DOE) has adopted a policy to systematically integrate safety into management and work practices at all levels so that missions can be completed while protecting the public, worker, and the environment. While the DOE and its contractors possessed a variety of processes for analyzing fire hazards at a facility, activity, and job; the outcome and assumptions of these processes have not always been consistent for similar types of hazards within the safety analysis and the fire hazard analysis. Although the safety analysis and the fire hazard analysis are driven by different DOE Orders and requirements, these analyses should not be entirely independent and their preparation should be integrated to ensure consistency of assumptions, consequences, design considerations, and other controls. Under the DOE policy to implement an integrated safety management system, identification of hazards must be evaluated and agreed upon to ensure that the public. the workers. and the environment are protected from adverse consequences. The DOE program and contractor management need a uniform, up-to-date reference with which to plan. budget, and manage nuclear programs. It is crucial that DOE understand the hazards and risks necessarily to authorize the work needed to be performed. If integrated safety management is not incorporated into the preparation of the safety analysis and the fire hazard analysis, inconsistencies between assumptions, consequences, design considerations, and controls may occur that affect safety. Furthermore, confusion created by inconsistencies may occur in the DOE process to grant authorization of the work. In accordance with

  20. Design and construction of a first-generation high-throughput integrated robotic molecular biology platform for bioenergy applications.

    Science.gov (United States)

    Hughes, Stephen R; Butt, Tauseef R; Bartolett, Scott; Riedmuller, Steven B; Farrelly, Philip

    2011-08-01

    The molecular biological techniques for plasmid-based assembly and cloning of gene open reading frames are essential for elucidating the function of the proteins encoded by the genes. High-throughput integrated robotic molecular biology platforms that have the capacity to rapidly clone and express heterologous gene open reading frames in bacteria and yeast and to screen large numbers of expressed proteins for optimized function are an important technology for improving microbial strains for biofuel production. The process involves the production of full-length complementary DNA libraries as a source of plasmid-based clones to express the desired proteins in active form for determination of their functions. Proteins that were identified by high-throughput screening as having desired characteristics are overexpressed in microbes to enable them to perform functions that will allow more cost-effective and sustainable production of biofuels. Because the plasmid libraries are composed of several thousand unique genes, automation of the process is essential. This review describes the design and implementation of an automated integrated programmable robotic workcell capable of producing complementary DNA libraries, colony picking, isolating plasmid DNA, transforming yeast and bacteria, expressing protein, and performing appropriate functional assays. These operations will allow tailoring microbial strains to use renewable feedstocks for production of biofuels, bioderived chemicals, fertilizers, and other coproducts for profitable and sustainable biorefineries. Published by Elsevier Inc.

  1. Integration of a zebrafish research project into a molecular biology course to support critical thinking and course content goals.

    Science.gov (United States)

    Felzien, Lisa K

    2016-11-12

    Engaging undergraduates in research is essential for teaching them to think like scientists, and it has become a desired component of classroom and laboratory instruction. Research projects that span an entire semester expose students to a variety of concepts and techniques and allow students to use experiments to learn scientific principles, understand why specific techniques are applicable, critically analyze varied data, and examine how experimentation leads to acquiring knowledge. To provide an experience with these features, a semester long research project was integrated into a combined lecture and laboratory course, Molecular Biology. The project utilized the zebrafish model to examine gene expression during embryonic development and required students to develop and test hypotheses about the timing of expression of previously uncharacterized genes. The main goals for the project were to provide opportunities for students to develop critical thinking skills required for conducting research and to support the content goals of the course. To determine whether these goals were met, student performance on the steps of the project and related pre-test and post-test questions was examined. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(6):565-573, 2016. © 2016 The International Union of Biochemistry and Molecular Biology.

  2. The pathology of familial breast cancer: Immunohistochemistry and molecular analysis

    International Nuclear Information System (INIS)

    Osin, Pinchas P; Lakhani, Sunil R

    1999-01-01

    Extensive studies of BRCA1- and BRCA2-associated breast tumours have been carried out in the few years since the identification of these familial breast cancer predisposing genes. The morphological studies suggest that BRCA1 tumours differ from BRCA2 tumours and from sporadic breast cancers. Recent progress in immunohistochemistry and molecular biology techniques has enabled in-depth investigation of molecular pathology of these tumours. Studies to date have investigated issues such as steroid hormone receptor expression, mutation status of tumour suppressor genes TP53 and c-erbB2, and expression profiles of cell cycle proteins p21, p27 and cyclin D 1 . Despite relative paucity of data, strong evidence of unique biological characteristics of BRCA1-associated breast cancer is accumulating. BRCA1-associated tumours appear to show an increased frequency of TP53 mutations, frequent p53 protein stabilization and absence of imunoreactivity for steroid hormone receptors. Further studies of larger number of samples of both BRCA1- and BRCA2-associated tumours are necessary to clarify and confirm these observations

  3. A Concise Review on Multi-Omics Data Integration for Terroir Analysis in Vitis vinifera

    Directory of Open Access Journals (Sweden)

    Pastor Jullian Fabres

    2017-06-01

    Full Text Available Vitis vinifera (grapevine is one of the most important fruit crops, both for fresh consumption and wine and spirit production. The term terroir is frequently used in viticulture and the wine industry to relate wine sensory attributes to its geographic origin. Although, it can be cultivated in a wide range of environments, differences in growing conditions have a significant impact on fruit traits that ultimately affect wine quality. Understanding how fruit quality and yield are controlled at a molecular level in grapevine in response to environmental cues has been a major driver of research. Advances in the area of genomics, epigenomics, transcriptomics, proteomics and metabolomics, have significantly increased our knowledge on the abiotic regulation of yield and quality in many crop species, including V. vinifera. The integrated analysis of multiple ‘omics’ can give us the opportunity to better understand how plants modulate their response to different environments. However, ‘omics’ technologies provide a large amount of biological data and its interpretation is not always straightforward, especially when different ‘omic’ results are combined. Here we examine the current strategies used to integrate multi-omics, and how these have been used in V. vinifera. In addition, we also discuss the importance of including epigenomics data when integrating omics data as epigenetic mechanisms could play a major role as an intermediary between the environment and the genome.

  4. Strategies for integrated analysis of genetic, epigenetic and gene expression variation in cancer: addressing the challenges

    Directory of Open Access Journals (Sweden)

    Louise Bruun Thingholm

    2016-02-01

    Full Text Available The development and progression of cancer, a collection of diseases with complex genetic architectures, is facilitated by the interplay of multiple etiological factors. This complexity challenges the traditional single-platform study design and calls for an integrated approach to data analysis. However, integration of heterogeneous measurements of biological variation is a non-trivial exercise due to the diversity of the human genome and the variety of output data formats and genome coverage obtained from the commonly used molecular platforms. This review article will provide an introduction to integration strategies used for analyzing genetic risk factors for cancer. We critically examine the ability of these strategies to handle the complexity of the human genome and also accommodate information about the biological and functional interactions between the elements that have been measured – making the assessment of disease risk against a composite genomic factor possible. The focus of this review is to provide an overview and introduction to the main strategies and to discuss where there is a need for further development.

  5. Pteros: fast and easy to use open-source C++ library for molecular analysis.

    Science.gov (United States)

    Yesylevskyy, Semen O

    2012-07-15

    An open-source Pteros library for molecular modeling and analysis of molecular dynamics trajectories for C++ programming language is introduced. Pteros provides a number of routine analysis operations ranging from reading and writing trajectory files and geometry transformations to structural alignment and computation of nonbonded interaction energies. The library features asynchronous trajectory reading and parallel execution of several analysis routines, which greatly simplifies development of computationally intensive trajectory analysis algorithms. Pteros programming interface is very simple and intuitive while the source code is well documented and easily extendible. Pteros is available for free under open-source Artistic License from http://sourceforge.net/projects/pteros/. Copyright © 2012 Wiley Periodicals, Inc.

  6. Integrated Software Environment for Pressurized Thermal Shock Analysis

    Directory of Open Access Journals (Sweden)

    Dino Araneo

    2011-01-01

    Full Text Available The present paper describes the main features and an application to a real Nuclear Power Plant (NPP of an Integrated Software Environment (in the following referred to as “platform” developed at University of Pisa (UNIPI to perform Pressurized Thermal Shock (PTS analysis. The platform is written in Java for the portability and it implements all the steps foreseen in the methodology developed at UNIPI for the deterministic analysis of PTS scenarios. The methodology starts with the thermal hydraulic analysis of the NPP with a system code (such as Relap5-3D and Cathare2, during a selected transient scenario. The results so obtained are then processed to provide boundary conditions for the next step, that is, a CFD calculation. Once the system pressure and the RPV wall temperature are known, the stresses inside the RPV wall can be calculated by mean a Finite Element (FE code. The last step of the methodology is the Fracture Mechanics (FM analysis, using weight functions, aimed at evaluating the stress intensity factor (KI at crack tip to be compared with the critical stress intensity factor KIc. The platform automates all these steps foreseen in the methodology once the user specifies a number of boundary conditions at the beginning of the simulation.

  7. SEURAT: visual analytics for the integrated analysis of microarray data.

    Science.gov (United States)

    Gribov, Alexander; Sill, Martin; Lück, Sonja; Rücker, Frank; Döhner, Konstanze; Bullinger, Lars; Benner, Axel; Unwin, Antony

    2010-06-03

    In translational cancer research, gene expression data is collected together with clinical data and genomic data arising from other chip based high throughput technologies. Software tools for the joint analysis of such high dimensional data sets together with clinical data are required. We have developed an open source software tool which provides interactive visualization capability for the integrated analysis of high-dimensional gene expression data together with associated clinical data, array CGH data and SNP array data. The different data types are organized by a comprehensive data manager. Interactive tools are provided for all graphics: heatmaps, dendrograms, barcharts, histograms, eventcharts and a chromosome browser, which displays genetic variations along the genome. All graphics are dynamic and fully linked so that any object selected in a graphic will be highlighted in all other graphics. For exploratory data analysis the software provides unsupervised data analytics like clustering, seriation algorithms and biclustering algorithms. The SEURAT software meets the growing needs of researchers to perform joint analysis of gene expression, genomical and clinical data.

  8. SEURAT: Visual analytics for the integrated analysis of microarray data

    Directory of Open Access Journals (Sweden)

    Bullinger Lars

    2010-06-01

    Full Text Available Abstract Background In translational cancer research, gene expression data is collected together with clinical data and genomic data arising from other chip based high throughput technologies. Software tools for the joint analysis of such high dimensional data sets together with clinical data are required. Results We have developed an open source software tool which provides interactive visualization capability for the integrated analysis of high-dimensional gene expression data together with associated clinical data, array CGH data and SNP array data. The different data types are organized by a comprehensive data manager. Interactive tools are provided for all graphics: heatmaps, dendrograms, barcharts, histograms, eventcharts and a chromosome browser, which displays genetic variations along the genome. All graphics are dynamic and fully linked so that any object selected in a graphic will be highlighted in all other graphics. For exploratory data analysis the software provides unsupervised data analytics like clustering, seriation algorithms and biclustering algorithms. Conclusions The SEURAT software meets the growing needs of researchers to perform joint analysis of gene expression, genomical and clinical data.

  9. Transient flow analysis of integrated valve opening process

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Xinming; Qin, Benke; Bo, Hanliang, E-mail: bohl@tsinghua.edu.cn; Xu, Xingxing

    2017-03-15

    Highlights: • The control rod hydraulic driving system (CRHDS) is a new type of built-in control rod drive technology and the integrated valve (IV) is the key control component. • The transient flow experiment induced by IV is conducted and the test results are analyzed to get its working mechanism. • The theoretical model of IV opening process is established and applied to get the changing rule of the transient flow characteristic parameters. - Abstract: The control rod hydraulic driving system (CRHDS) is a new type of built-in control rod drive technology and the IV is the key control component. The working principle of integrated valve (IV) is analyzed and the IV hydraulic experiment is conducted. There is transient flow phenomenon in the valve opening process. The theoretical model of IV opening process is established by the loop system control equations and boundary conditions. The valve opening boundary condition equation is established based on the IV three dimensional flow field analysis results and the dynamic analysis of the valve core movement. The model calculation results are in good agreement with the experimental results. On this basis, the model is used to analyze the transient flow under high temperature condition. The peak pressure head is consistent with the one under room temperature and the pressure fluctuation period is longer than the one under room temperature. Furthermore, the changing rule of pressure transients with the fluid and loop structure parameters is analyzed. The peak pressure increases with the flow rate and the peak pressure decreases with the increase of the valve opening time. The pressure fluctuation period increases with the loop pipe length and the fluctuation amplitude remains largely unchanged under different equilibrium pressure conditions. The research results lay the base for the vibration reduction analysis of the CRHDS.

  10. Molecular evolution and diversification of snake toxin genes, revealed by analysis of intron sequences.

    Science.gov (United States)

    Fujimi, T J; Nakajyo, T; Nishimura, E; Ogura, E; Tsuchiya, T; Tamiya, T

    2003-08-14

    The genes encoding erabutoxin (short chain neurotoxin) isoforms (Ea, Eb, and Ec), LsIII (long chain neurotoxin) and a novel long chain neurotoxin pseudogene were cloned from a Laticauda semifasciata genomic library. Short and long chain neurotoxin genes were also cloned from the genome of Laticauda laticaudata, a closely related species of L. semifasciata, by PCR. A putative matrix attached region (MAR) sequence was found in the intron I of the LsIII gene. Comparative analysis of 11 structurally relevant snake toxin genes (three-finger-structure toxins) revealed the molecular evolution of these toxins. Three-finger-structure toxin genes diverged from a common ancestor through two types of evolutionary pathways (long and short types), early in the course of evolution. At a later stage of evolution in each gene, the accumulation of mutations in the exons, especially exon II, by accelerated evolution may have caused the increased diversification in their functions. It was also revealed that the putative MAR sequence found in the LsIII gene was integrated into the gene after the species-level divergence.

  11. High-resolution monitoring of marine protists based on an observation strategy integrating automated on-board filtration and molecular analyses

    Science.gov (United States)

    Metfies, Katja; Schroeder, Friedhelm; Hessel, Johanna; Wollschläger, Jochen; Micheller, Sebastian; Wolf, Christian; Kilias, Estelle; Sprong, Pim; Neuhaus, Stefan; Frickenhaus, Stephan; Petersen, Wilhelm

    2016-11-01

    Information on recent biomass distribution and biogeography of photosynthetic marine protists with adequate temporal and spatial resolution is urgently needed to better understand the consequences of environmental change for marine ecosystems. Here we introduce and review a molecular-based observation strategy for high-resolution assessment of these protists in space and time. It is the result of extensive technology developments, adaptations and evaluations which are documented in a number of different publications, and the results of the recently completed field testing which are introduced in this paper. The observation strategy is organized at four different levels. At level 1, samples are collected at high spatiotemporal resolution using the remotely controlled automated filtration system AUTOFIM. Resulting samples can either be preserved for later laboratory analyses, or directly subjected to molecular surveillance of key species aboard the ship via an automated biosensor system or quantitative polymerase chain reaction (level 2). Preserved samples are analyzed at the next observational levels in the laboratory (levels 3 and 4). At level 3 this involves molecular fingerprinting methods for a quick and reliable overview of differences in protist community composition. Finally, selected samples can be used to generate a detailed analysis of taxonomic protist composition via the latest next generation sequencing technology (NGS) at level 4. An overall integrated dataset of the results based on the different analyses provides comprehensive information on the diversity and biogeography of protists, including all related size classes. At the same time the cost of the observation is optimized with respect to analysis effort and time.

  12. Integrated electrocoagulation-electrooxidation process for the treatment of soluble coffee effluent: Optimization of COD degradation and operation time analysis.

    Science.gov (United States)

    Ibarra-Taquez, Harold N; GilPavas, Edison; Blatchley, Ernest R; Gómez-García, Miguel-Ángel; Dobrosz-Gómez, Izabela

    2017-09-15

    Soluble coffee production generates wastewater containing complex mixtures of organic macromolecules. In this work, a sequential Electrocoagulation-Electrooxidation (EC-EO) process, using aluminum and graphite electrodes, was proposed as an alternative way for the treatment of soluble coffee effluent. Process operational parameters were optimized, achieving total decolorization, as well as 74% and 63.5% of COD and TOC removal, respectively. The integrated EC-EO process yielded a highly oxidized (AOS = 1.629) and biocompatible (BOD 5 /COD ≈ 0.6) effluent. The Molecular Weight Distribution (MWD) analysis showed that during the EC-EO process, EC effectively decomposed contaminants with molecular weight in the range of 10-30 kDa. In contrast, EO was quite efficient in mineralization of contaminants with molecular weight higher than 30 kDa. A kinetic analysis allowed determination of the time required to meet Colombian permissible discharge limits. Finally, a comprehensive operational cost analysis was performed. The integrated EC-EO process was demonstrated as an efficient alternative for the treatment of industrial effluents resulting from soluble coffee production. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Performance Analysis of a Photovoltaic-Thermal Integrated System

    International Nuclear Information System (INIS)

    Radziemska, E.

    2009-01-01

    The present commercial photovoltaic solar cells (PV) converts solar energy into electricity with a relatively low efficiency, less than 20%. More than 80% of the absorbed solar energy is dumped to the surroundings again after photovoltaic conversion. Hybrid PV/T systems consist of PV modules coupled with the heat extraction devices. The PV/T collectors generate electric power and heat simultaneously. Stabilizing temperature of photovoltaic modules at low level is highly desirable to obtain efficiency increase. The total efficiency of 60-80% can be achieved with the whole PV/T system provided that the T system is operated near ambient temperature. The value of the low-T heat energy is typically much smaller than the value of the PV electricity. The PV/T systems can exist in many designs, but the most common models are with the use of water or air as a working fuid. Efficiency is the most valuable parameter for the economic analysis. It has substantial meaning in the case of installations with great nominal power, as air-cooled Building Integrated Photovoltaic Systems (BIPV). In this paper the performance analysis of a hybrid PV/T system is presented: an energetic analysis as well as an exergetic analysis. Exergy is always destroyed when a process involves a temperature change. This destruction is proportional to the entropy increase of the system together with its surroundings the destroyed exergy has been called energy. Exergy analysis identifies the location, the magnitude, and the sources of thermodynamic inefficiencies in a system. This information, which cannot be provided by other means (e.g., an energy analysis), is very useful for the improvement and cost-effectiveness of the system. Calculations were carried out for the tested water-cooled ASE-100-DGL-SM Solar watt module.

  14. Performance Analysis of a Photovoltaic-Thermal Integrated System

    Directory of Open Access Journals (Sweden)

    Ewa Radziemska

    2009-01-01

    Full Text Available The present commercial photovoltaic solar cells (PV converts solar energy into electricity with a relatively low efficiency, less than 20%. More than 80% of the absorbed solar energy is dumped to the surroundings again after photovoltaic conversion. Hybrid PV/T systems consist of PV modules coupled with the heat extraction devices. The PV/T collectors generate electric power and heat simultaneously. Stabilizing temperature of photovoltaic modules at low level is higly desirable to obtain efficiency increase. The total efficiency of 60–80% can be achieved with the whole PV/T system provided that the T system is operated near ambient temperature. The value of the low-T heat energy is typically much smaller than the value of the PV electricity. The PV/T systems can exist in many designs, but the most common models are with the use of water or air as a working fuid. Efficiency is the most valuable parameter for the economic analysis. It has substantial meaning in the case of installations with great nominal power, as air-cooled Building Integrated Photovoltaic Systems (BIPV. In this paper the performance analysis of a hybrid PV/T system is presented: an energetic analysis as well as an exergetic analysis. Exergy is always destroyed when a process involves a temperature change. This destruction is proportional to the entropy increase of the system together with its surroundings—the destroyed exergy has been called anergy. Exergy analysis identifies the location, the magnitude, and the sources of thermodynamic inefficiences in a system. This information, which cannot be provided by other means (e.g., an energy analysis, is very useful for the improvement and cost-effictiveness of the system. Calculations were carried out for the tested water-cooled ASE-100-DGL-SM Solarwatt module.

  15. PEA: an integrated R toolkit for plant epitranscriptome analysis.

    Science.gov (United States)

    Zhai, Jingjing; Song, Jie; Cheng, Qian; Tang, Yunjia; Ma, Chuang

    2018-05-29

    The epitranscriptome, also known as chemical modifications of RNA (CMRs), is a newly discovered layer of gene regulation, the biological importance of which emerged through analysis of only a small fraction of CMRs detected by high-throughput sequencing technologies. Understanding of the epitranscriptome is hampered by the absence of computational tools for the systematic analysis of epitranscriptome sequencing data. In addition, no tools have yet been designed for accurate prediction of CMRs in plants, or to extend epitranscriptome analysis from a fraction of the transcriptome to its entirety. Here, we introduce PEA, an integrated R toolkit to facilitate the analysis of plant epitranscriptome data. The PEA toolkit contains a comprehensive collection of functions required for read mapping, CMR calling, motif scanning and discovery, and gene functional enrichment analysis. PEA also takes advantage of machine learning technologies for transcriptome-scale CMR prediction, with high prediction accuracy, using the Positive Samples Only Learning algorithm, which addresses the two-class classification problem by using only positive samples (CMRs), in the absence of negative samples (non-CMRs). Hence PEA is a versatile epitranscriptome analysis pipeline covering CMR calling, prediction, and annotation, and we describe its application to predict N6-methyladenosine (m6A) modifications in Arabidopsis thaliana. Experimental results demonstrate that the toolkit achieved 71.6% sensitivity and 73.7% specificity, which is superior to existing m6A predictors. PEA is potentially broadly applicable to the in-depth study of epitranscriptomics. PEA Docker image is available at https://hub.docker.com/r/malab/pea, source codes and user manual are available at https://github.com/cma2015/PEA. chuangma2006@gmail.com. Supplementary data are available at Bioinformatics online.

  16. HTGR-INTEGRATED COAL TO LIQUIDS PRODUCTION ANALYSIS

    Energy Technology Data Exchange (ETDEWEB)

    Anastasia M Gandrik; Rick A Wood

    2010-10-01

    As part of the DOE’s Idaho National Laboratory (INL) nuclear energy development mission, the INL is leading a program to develop and design a high temperature gas-cooled reactor (HTGR), which has been selected as the base design for the Next Generation Nuclear Plant. Because an HTGR operates at a higher temperature, it can provide higher temperature process heat, more closely matched to chemical process temperatures, than a conventional light water reactor. Integrating HTGRs into conventional industrial processes would increase U.S. energy security and potentially reduce greenhouse gas emissions (GHG), particularly CO2. This paper focuses on the integration of HTGRs into a coal to liquids (CTL) process, for the production of synthetic diesel fuel, naphtha, and liquefied petroleum gas (LPG). The plant models for the CTL processes were developed using Aspen Plus. The models were constructed with plant production capacity set at 50,000 barrels per day of liquid products. Analysis of the conventional CTL case indicated a potential need for hydrogen supplementation from high temperature steam electrolysis (HTSE), with heat and power supplied by the HTGR. By supplementing the process with an external hydrogen source, the need to “shift” the syngas using conventional water-gas shift reactors was eliminated. HTGR electrical power generation efficiency was set at 40%, a reactor size of 600 MWth was specified, and it was assumed that heat in the form of hot helium could be delivered at a maximum temperature of 700°C to the processes. Results from the Aspen Plus model were used to perform a preliminary economic analysis and a life cycle emissions assessment. The following conclusions were drawn when evaluating the nuclear assisted CTL process against the conventional process: • 11 HTGRs (600 MWth each) are required to support production of a 50,000 barrel per day CTL facility. When compared to conventional CTL production, nuclear integration decreases coal

  17. HTGR-Integrated Coal To Liquids Production Analysis

    International Nuclear Information System (INIS)

    Gandrik, Anastasia M.; Wood, Rick A.

    2010-01-01

    As part of the DOE's Idaho National Laboratory (INL) nuclear energy development mission, the INL is leading a program to develop and design a high temperature gas-cooled reactor (HTGR), which has been selected as the base design for the Next Generation Nuclear Plant. Because an HTGR operates at a higher temperature, it can provide higher temperature process heat, more closely matched to chemical process temperatures, than a conventional light water reactor. Integrating HTGRs into conventional industrial processes would increase U.S. energy security and potentially reduce greenhouse gas emissions (GHG), particularly CO2. This paper focuses on the integration of HTGRs into a coal to liquids (CTL) process, for the production of synthetic diesel fuel, naphtha, and liquefied petroleum gas (LPG). The plant models for the CTL processes were developed using Aspen Plus. The models were constructed with plant production capacity set at 50,000 barrels per day of liquid products. Analysis of the conventional CTL case indicated a potential need for hydrogen supplementation from high temperature steam electrolysis (HTSE), with heat and power supplied by the HTGR. By supplementing the process with an external hydrogen source, the need to 'shift' the syngas using conventional water-gas shift reactors was eliminated. HTGR electrical power generation efficiency was set at 40%, a reactor size of 600 MWth was specified, and it was assumed that heat in the form of hot helium could be delivered at a maximum temperature of 700 C to the processes. Results from the Aspen Plus model were used to perform a preliminary economic analysis and a life cycle emissions assessment. The following conclusions were drawn when evaluating the nuclear assisted CTL process against the conventional process: (1) 11 HTGRs (600 MWth each) are required to support production of a 50,000 barrel per day CTL facility. When compared to conventional CTL production, nuclear integration decreases coal consumption by 66

  18. Metabolome Integrated Analysis of High-Temperature Response in Pinus radiata

    Directory of Open Access Journals (Sweden)

    Mónica Escandón

    2018-04-01

    Full Text Available The integrative omics approach is crucial to identify the molecular mechanisms underlying high-temperature response in non-model species. Based on future scenarios of heat increase, Pinus radiata plants were exposed to a temperature of 40°C for a period of 5 days, including recovered plants (30 days after last exposure to 40°C in the analysis. The analysis of the metabolome using complementary mass spectrometry techniques (GC-MS and LC-Orbitrap-MS allowed the reliable quantification of 2,287 metabolites. The analysis of identified metabolites and highlighter metabolic pathways across heat time exposure reveal the dynamism of the metabolome in relation to high-temperature response in P. radiata, identifying the existence of a turning point (on day 3 at which P. radiata plants changed from an initial stress response program (shorter-term response to an acclimation one (longer-term response. Furthermore, the integration of metabolome and physiological measurements, which cover from the photosynthetic state to hormonal profile, suggests a complex metabolic pathway interaction network related to heat-stress response. Cytokinins (CKs, fatty acid metabolism and flavonoid and terpenoid biosynthesis were revealed as the most important pathways involved in heat-stress response in P. radiata, with zeatin riboside (ZR and isopentenyl adenosine (iPA as the key hormones coordinating these multiple and complex interactions. On the other hand, the integrative approach allowed elucidation of crucial metabolic mechanisms involved in heat response in P. radiata, as well as the identification of thermotolerance metabolic biomarkers (L-phenylalanine, hexadecanoic acid, and dihydromyricetin, crucial metabolites which can reschedule the metabolic strategy to adapt to high temperature.

  19. III-nitride integration on ferroelectric materials of lithium niobate by molecular beam epitaxy

    International Nuclear Information System (INIS)

    Namkoong, Gon; Lee, Kyoung-Keun; Madison, Shannon M.; Henderson, Walter; Ralph, Stephen E.; Doolittle, W. Alan

    2005-01-01

    Integration of III-nitride electrical devices on the ferroelectric material lithium niobate (LiNbO 3 ) has been demonstrated. As a ferroelectric material, lithium niobate has a polarization which may provide excellent control of the polarity of III-nitrides. However, while high temperature, 1000 deg. C, thermal treatments produce atomically smooth surfaces, improving adhesion of GaN epitaxial layers on lithium niobate, repolarization of the substrate in local domains occurs. These effects result in multi domains of mixed polarization in LiNbO 3 , producing inversion domains in subsequent GaN epilayers. However, it is found that AlN buffer layers suppress inversion domains of III-nitrides. Therefore, two-dimensional electron gases in AlGaN/GaN heterojunction structures are obtained. Herein, the demonstration of the monolithic integration of high power devices with ferroelectric materials presents possibilities to control LiNbO 3 modulators on compact optoelectronic/electronic chips

  20. Chemical Approach to Biological Safety: Molecular-Level Control of an Integrated Zinc Finger Nuclease

    DEFF Research Database (Denmark)

    Németh, Eszter; Asaka, Masamitsu N; Kato, Kohsuke

    2018-01-01

    circular dichroism spectroscopy, and nano-electrospray ionisation mass spectrometry. In situ intramolecular activation of the nuclease domain was observed, resulting in specific cleavage of DNA with moderate activity. This study represents a new approach to AN design through integrated nucleases consisting......Application of artificial nucleases (ANs) in genome editing is still hindered by their cytotoxicity related to off-target cleavages. This problem can be targeted by regulation of the nuclease domain. Here, we provide an experimental survey of computationally designed integrated zinc finger...... nucleases, constructed by linking the inactivated catalytic centre and the allosteric activator sequence of the colicin E7 nuclease domain to the two opposite termini of a zinc finger array. DNA specificity and metal binding were confirmed by electrophoretic mobility shift assays, synchrotron radiation...