WorldWideScience

Sample records for integration target site

  1. Retroviral DNA integration: viral and cellular determinants of target-site selection.

    Directory of Open Access Journals (Sweden)

    Mary K Lewinski

    2006-06-01

    Full Text Available Retroviruses differ in their preferences for sites for viral DNA integration in the chromosomes of infected cells. Human immunodeficiency virus (HIV integrates preferentially within active transcription units, whereas murine leukemia virus (MLV integrates preferentially near transcription start sites and CpG islands. We investigated the viral determinants of integration-site selection using HIV chimeras with MLV genes substituted for their HIV counterparts. We found that transferring the MLV integrase (IN coding region into HIV (to make HIVmIN caused the hybrid to integrate with a specificity close to that of MLV. Addition of MLV gag (to make HIVmGagmIN further increased the similarity of target-site selection to that of MLV. A chimeric virus with MLV Gag only (HIVmGag displayed targeting preferences different from that of both HIV and MLV, further implicating Gag proteins in targeting as well as IN. We also report a genome-wide analysis indicating that MLV, but not HIV, favors integration near DNase I-hypersensitive sites (i.e., +/- 1 kb, and that HIVmIN and HIVmGagmIN also favored integration near these features. These findings reveal that IN is the principal viral determinant of integration specificity; they also reveal a new role for Gag-derived proteins, and strengthen models for integration targeting based on tethering of viral IN proteins to host proteins.

  2. Integrative Analysis of CRISPR/Cas9 Target Sites in the Human HBB Gene

    Directory of Open Access Journals (Sweden)

    Yumei Luo

    2015-01-01

    Full Text Available Recently, the clustered regularly interspaced short palindromic repeats (CRISPR system has emerged as a powerful customizable artificial nuclease to facilitate precise genetic correction for tissue regeneration and isogenic disease modeling. However, previous studies reported substantial off-target activities of CRISPR system in human cells, and the enormous putative off-target sites are labor-intensive to be validated experimentally, thus motivating bioinformatics methods for rational design of CRISPR system and prediction of its potential off-target effects. Here, we describe an integrative analytical process to identify specific CRISPR target sites in the human β-globin gene (HBB and predict their off-target effects. Our method includes off-target analysis in both coding and noncoding regions, which was neglected by previous studies. It was found that the CRISPR target sites in the introns have fewer off-target sites in the coding regions than those in the exons. Remarkably, target sites containing certain transcriptional factor motif have enriched binding sites of relevant transcriptional factor in their off-target sets. We also found that the intron sites have fewer SNPs, which leads to less variation of CRISPR efficiency in different individuals during clinical applications. Our studies provide a standard analytical procedure to select specific CRISPR targets for genetic correction.

  3. Retroviral DNA integration: ASLV, HIV, and MLV show distinct target site preferences.

    Directory of Open Access Journals (Sweden)

    Rick S Mitchell

    2004-08-01

    Full Text Available The completion of the human genome sequence has made possible genome-wide studies of retroviral DNA integration. Here we report an analysis of 3,127 integration site sequences from human cells. We compared retroviral vectors derived from human immunodeficiency virus (HIV, avian sarcoma-leukosis virus (ASLV, and murine leukemia virus (MLV. Effects of gene activity on integration targeting were assessed by transcriptional profiling of infected cells. Integration by HIV vectors, analyzed in two primary cell types and several cell lines, strongly favored active genes. An analysis of the effects of tissue-specific transcription showed that it resulted in tissue-specific integration targeting by HIV, though the effect was quantitatively modest. Chromosomal regions rich in expressed genes were favored for HIV integration, but these regions were found to be interleaved with unfavorable regions at CpG islands. MLV vectors showed a strong bias in favor of integration near transcription start sites, as reported previously. ASLV vectors showed only a weak preference for active genes and no preference for transcription start regions. Thus, each of the three retroviruses studied showed unique integration site preferences, suggesting that virus-specific binding of integration complexes to chromatin features likely guides site selection.

  4. An integrated CRISPR Bombyx mori genome editing system with improved efficiency and expanded target sites.

    Science.gov (United States)

    Ma, Sanyuan; Liu, Yue; Liu, Yuanyuan; Chang, Jiasong; Zhang, Tong; Wang, Xiaogang; Shi, Run; Lu, Wei; Xia, Xiaojuan; Zhao, Ping; Xia, Qingyou

    2017-04-01

    Genome editing enabled unprecedented new opportunities for targeted genomic engineering of a wide variety of organisms ranging from microbes, plants, animals and even human embryos. The serial establishing and rapid applications of genome editing tools significantly accelerated Bombyx mori (B. mori) research during the past years. However, the only CRISPR system in B. mori was the commonly used SpCas9, which only recognize target sites containing NGG PAM sequence. In the present study, we first improve the efficiency of our previous established SpCas9 system by 3.5 folds. The improved high efficiency was also observed at several loci in both BmNs cells and B. mori embryos. Then to expand the target sites, we showed that two newly discovered CRISPR system, SaCas9 and AsCpf1, could also induce highly efficient site-specific genome editing in BmNs cells, and constructed an integrated CRISPR system. Genome-wide analysis of targetable sites was further conducted and showed that the integrated system cover 69,144,399 sites in B. mori genome, and one site could be found in every 6.5 bp. The efficiency and resolution of this CRISPR platform will probably accelerate both fundamental researches and applicable studies in B. mori, and perhaps other insects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Comprehensive profiling of retroviral integration sites using target enrichment methods from historical koala samples without an assembled reference genome

    Directory of Open Access Journals (Sweden)

    Pin Cui

    2016-03-01

    Full Text Available Background. Retroviral integration into the host germline results in permanent viral colonization of vertebrate genomes. The koala retrovirus (KoRV is currently invading the germline of the koala (Phascolarctos cinereus and provides a unique opportunity for studying retroviral endogenization. Previous analysis of KoRV integration patterns in modern koalas demonstrate that they share integration sites primarily if they are related, indicating that the process is currently driven by vertical transmission rather than infection. However, due to methodological challenges, KoRV integrations have not been comprehensively characterized. Results. To overcome these challenges, we applied and compared three target enrichment techniques coupled with next generation sequencing (NGS and a newly customized sequence-clustering based computational pipeline to determine the integration sites for 10 museum Queensland and New South Wales (NSW koala samples collected between the 1870s and late 1980s. A secondary aim of this study sought to identify common integration sites across modern and historical specimens by comparing our dataset to previously published studies. Several million sequences were processed, and the KoRV integration sites in each koala were characterized. Conclusions. Although the three enrichment methods each exhibited bias in integration site retrieval, a combination of two methods, Primer Extension Capture and hybridization capture is recommended for future studies on historical samples. Moreover, identification of integration sites shows that the proportion of integration sites shared between any two koalas is quite small.

  6. Retroviral integration: Site matters

    Science.gov (United States)

    Demeulemeester, Jonas; De Rijck, Jan

    2015-01-01

    Here, we review genomic target site selection during retroviral integration as a multistep process in which specific biases are introduced at each level. The first asymmetries are introduced when the virus takes a specific route into the nucleus. Next, by co‐opting distinct host cofactors, the integration machinery is guided to particular chromatin contexts. As the viral integrase captures a local target nucleosome, specific contacts introduce fine‐grained biases in the integration site distribution. In vivo, the established population of proviruses is subject to both positive and negative selection, thereby continuously reshaping the integration site distribution. By affecting stochastic proviral expression as well as the mutagenic potential of the virus, integration site choice may be an inherent part of the evolutionary strategies used by different retroviruses to maximise reproductive success. PMID:26293289

  7. Fidelity of target site duplication and sequence preference during integration of xenotropic murine leukemia virus-related virus.

    Directory of Open Access Journals (Sweden)

    Sanggu Kim

    Full Text Available Xenotropic murine leukemia virus (MLV-related virus (XMRV is a new human retrovirus associated with prostate cancer and chronic fatigue syndrome. The causal relationship of XMRV infection to human disease and the mechanism of pathogenicity have not been established. During retrovirus replication, integration of the cDNA copy of the viral RNA genome into the host cell chromosome is an essential step and involves coordinated joining of the two ends of the linear viral DNA into staggered sites on target DNA. Correct integration produces proviruses that are flanked by a short direct repeat, which varies from 4 to 6 bp among the retroviruses but is invariant for each particular retrovirus. Uncoordinated joining of the two viral DNA ends into target DNA can cause insertions, deletions, or other genomic alterations at the integration site. To determine the fidelity of XMRV integration, cells infected with XMRV were clonally expanded and DNA sequences at the viral-host DNA junctions were determined and analyzed. We found that a majority of the provirus ends were correctly processed and flanked by a 4-bp direct repeat of host DNA. A weak consensus sequence was also detected at the XMRV integration sites. We conclude that integration of XMRV DNA involves a coordinated joining of two viral DNA ends that are spaced 4 bp apart on the target DNA and proceeds with high fidelity.

  8. A genome-wide analysis of lentivector integration sites using targeted sequence capture and next generation sequencing technology.

    Science.gov (United States)

    Ustek, Duran; Sirma, Sema; Gumus, Ergun; Arikan, Muzaffer; Cakiris, Aris; Abaci, Neslihan; Mathew, Jaicy; Emrence, Zeliha; Azakli, Hulya; Cosan, Fulya; Cakar, Atilla; Parlak, Mahmut; Kursun, Olcay

    2012-10-01

    One application of next-generation sequencing (NGS) is the targeted resequencing of interested genes which has not been used in viral integration site analysis of gene therapy applications. Here, we combined targeted sequence capture array and next generation sequencing to address the whole genome profiling of viral integration sites. Human 293T and K562 cells were transduced with a HIV-1 derived vector. A custom made DNA probe sets targeted pLVTHM vector used to capture lentiviral vector/human genome junctions. The captured DNA was sequenced using GS FLX platform. Seven thousand four hundred and eighty four human genome sequences flanking the long terminal repeats (LTR) of pLVTHM fragment sequences matched with an identity of at least 98% and minimum 50 bp criteria in both cells. In total, 203 unique integration sites were identified. The integrations in both cell lines were totally distant from the CpG islands and from the transcription start sites and preferentially located in introns. A comparison between the two cell lines showed that the lentiviral-transduced DNA does not have the same preferred regions in the two different cell lines. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Target site preference of subgroup C Rous sarcoma virus integration into the chicken DNA

    Czech Academy of Sciences Publication Activity Database

    Reinišová, Markéta; Pavlíček, Adam; Divina, Petr; Geryk, Josef; Plachý, Jiří; Hejnar, Jiří

    2008-01-01

    Roč. 1, - (2008), s. 6-12 ISSN 1875-693X R&D Projects: GA ČR(CZ) GA204/07/1030 Institutional research plan: CEZ:AV0Z50520514 Keywords : retroviral integration * integration preference * RSV Subject RIV: EB - Genetics ; Molecular Biology

  10. From heat integration targets toward implementation – A TSA (total site analysis)-based design approach for heat recovery systems in industrial clusters

    International Nuclear Information System (INIS)

    Hackl, Roman; Harvey, Simon

    2015-01-01

    The European process industry is facing major challenges to decrease production costs. One strategy to achieve this is by increasing energy efficiency. Single chemical processes are often well-integrated and the tools to target and design such measures are well developed. Site-wide heat integration based on total site analysis tools can be used to identify opportunities to further increase energy efficiency. However, the methodology has to be developed further in order to enable identification of practical heat integration measures in a systematic way. Designing site-wide heat recovery systems across an industrial cluster is complex and involves aspects apart from thermal process and utility flows. This work presents a method for designing a roadmap of heat integration investments based on total site analysis. The method is applied to a chemical cluster in Sweden. The results of the case study show that application of the proposed method can achieve up to 42% of the previously targeted hot utility savings of 129 MW. A roadmap of heat integration systems is suggested, ranging from less complex systems that achieve a minor share of the heat recovery potential to sophisticated, strongly interdependent systems demanding large investments and a high level of collaboration. - Highlights: • Methodology focused on the practical implementation of site-wide heat recovery. • Algorithm to determine a roadmap of heat integration investments. • Case study: 42% hot utility savings potential at a pay-back period of 3.9y.

  11. Integrating risks at contaminated sites

    International Nuclear Information System (INIS)

    MacDonell, M.; Habegger, L.; Nieves, L.; Schreiber, Z.; Travis, C.

    2000-01-01

    The U.S. Department of Energy (DOE) is responsible for a number of large sites across the country that were radioactively and chemically contaminated by past nuclear research, development, and production activities. Multiple risk assessments are being conducted for these sites to evaluate current conditions and determine what measures are needed to protect human health and the environment from today through the long term. Integrating the risks associated with multiple contaminants in different environmental media across extensive areas, over time periods that extend beyond 1,000 years, and for a number of different impact categories--from human health and ecological to social and economic--represents a considerable challenge. A central element of these integrated analyses is the ability to reflect key interrelationships among environmental resources and human communities that may be adversely affected by the actions or inactions being considered for a given site. Complicating the already difficult task of integrating many kinds of risk is the importance of reflecting the diverse values and preferences brought to bear by the multiple parties interested in the risk analysis process and outcome. An initial conceptual framework has been developed to provide an organized structure to this risk integration, with the aim of supporting effective environmental management decisions. This paper highlights key issues associated with comprehensive risk integration and offers suggestions developed from preliminary work at a complex DOE site

  12. Targeted integration of genes in Xenopus tropicalis

    DEFF Research Database (Denmark)

    Shi, Zhaoying; Tian, Dandan; Xin, Huhu

    2017-01-01

    With the successful establishment of both targeted gene disruption and integration methods in the true diploid frog Xenopus tropicalis, this excellent vertebrate genetic model now is making a unique contribution to modelling human diseases. Here, we summarize our efforts on establishing homologous...... recombination-mediated targeted integration in Xenopus tropicalis, the usefulness, and limitation of targeted integration via the homology-independent strategy, and future directions on how to further improve targeted gene integration in Xenopus tropicalis....

  13. Enhancers Are Major Targets for Murine Leukemia Virus Vector Integration

    Science.gov (United States)

    De Ravin, Suk See; Su, Ling; Theobald, Narda; Choi, Uimook; Macpherson, Janet L.; Poidinger, Michael; Symonds, Geoff; Pond, Susan M.; Ferris, Andrea L.; Hughes, Stephen H.

    2014-01-01

    ABSTRACT Retroviral vectors have been used in successful gene therapies. However, in some patients, insertional mutagenesis led to leukemia or myelodysplasia. Both the strong promoter/enhancer elements in the long terminal repeats (LTRs) of murine leukemia virus (MLV)-based vectors and the vector-specific integration site preferences played an important role in these adverse clinical events. MLV integration is known to prefer regions in or near transcription start sites (TSS). Recently, BET family proteins were shown to be the major cellular proteins responsible for targeting MLV integration. Although MLV integration sites are significantly enriched at TSS, only a small fraction of the MLV integration sites (integration map of more than one million integration sites from CD34+ hematopoietic stem cells transduced with a clinically relevant MLV-based vector. The integration sites form ∼60,000 tight clusters. These clusters comprise ∼1.9% of the genome. The vast majority (87%) of the integration sites are located within histone H3K4me1 islands, a hallmark of enhancers. The majority of these clusters also have H3K27ac histone modifications, which mark active enhancers. The enhancers of some oncogenes, including LMO2, are highly preferred targets for integration without in vivo selection. IMPORTANCE We show that active enhancer regions are the major targets for MLV integration; this means that MLV preferentially integrates in regions that are favorable for viral gene expression in a variety of cell types. The results provide insights for MLV integration target site selection and also explain the high risk of insertional mutagenesis that is associated with gene therapy trials using MLV vectors. PMID:24501411

  14. Total Site Heat Integration Considering Pressure Drops

    Directory of Open Access Journals (Sweden)

    Kew Hong Chew

    2015-02-01

    Full Text Available Pressure drop is an important consideration in Total Site Heat Integration (TSHI. This is due to the typically large distances between the different plants and the flow across plant elevations and equipment, including heat exchangers. Failure to consider pressure drop during utility targeting and heat exchanger network (HEN synthesis may, at best, lead to optimistic energy targets, and at worst, an inoperable system if the pumps or compressors cannot overcome the actual pressure drop. Most studies have addressed the pressure drop factor in terms of pumping cost, forbidden matches or allowable pressure drop constraints in the optimisation of HEN. This study looks at the implication of pressure drop in the context of a Total Site. The graphical Pinch-based TSHI methodology is extended to consider the pressure drop factor during the minimum energy requirement (MER targeting stage. The improved methodology provides a more realistic estimation of the MER targets and valuable insights for the implementation of the TSHI design. In the case study, when pressure drop in the steam distribution networks is considered, the heating and cooling duties increase by 14.5% and 4.5%.

  15. 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.

  16. Drug target ontology to classify and integrate drug discovery data.

    Science.gov (United States)

    Lin, Yu; Mehta, Saurabh; Küçük-McGinty, Hande; Turner, John Paul; Vidovic, Dusica; Forlin, Michele; Koleti, Amar; Nguyen, Dac-Trung; Jensen, Lars Juhl; Guha, Rajarshi; Mathias, Stephen L; Ursu, Oleg; Stathias, Vasileios; Duan, Jianbin; Nabizadeh, Nooshin; Chung, Caty; Mader, Christopher; Visser, Ubbo; Yang, Jeremy J; Bologa, Cristian G; Oprea, Tudor I; Schürer, Stephan C

    2017-11-09

    model for druggable targets including various related information such as protein, gene, protein domain, protein structure, binding site, small molecule drug, mechanism of action, protein tissue localization, disease association, and many other types of information. DTO will further facilitate the otherwise challenging integration and formal linking to biological assays, phenotypes, disease models, drug poly-pharmacology, binding kinetics and many other processes, functions and qualities that are at the core of drug discovery. The first version of DTO is publically available via the website http://drugtargetontology.org/ , Github ( http://github.com/DrugTargetOntology/DTO ), and the NCBO Bioportal ( http://bioportal.bioontology.org/ontologies/DTO ). The long-term goal of DTO is to provide such an integrative framework and to populate the ontology with this information as a community resource.

  17. Comprehensive, integrated, remote sensing at DOE sites

    International Nuclear Information System (INIS)

    Lackey, J.G.; Burson, Z.G.

    1985-01-01

    The Department of Energy has established a program called Comprehensive, Integrated Remote Sensing (CIRS). The overall objective of the program is to provide a state-of-the-art data base of remotely sensed data for all users of such information at large DOE sites. The primary types of remote sensing provided, at present, consist of the following: large format aerial photography, video from aerial platforms, multispectral scanning, and airborne nuclear radiometric surveys. Implementation of the CIRS Program by EG and G Energy Measurements, Inc. began with field operations at the Savannah River Plant in 1982 and is continuing at that DOE site at a level of effort of about $1.5 m per year. Integrated remote sensing studies were subsequently extended to the West Valley Demonstration Project in this summer and fall of 1984. It is expected that the Program will eventually be extended to cover all large DOE sites on a continuing basis

  18. Whole genome resequencing reveals natural target site preferences of transposable elements in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Raquel S Linheiro

    Full Text Available Transposable elements are mobile DNA sequences that integrate into host genomes using diverse mechanisms with varying degrees of target site specificity. While the target site preferences of some engineered transposable elements are well studied, the natural target preferences of most transposable elements are poorly characterized. Using population genomic resequencing data from 166 strains of Drosophila melanogaster, we identified over 8,000 new insertion sites not present in the reference genome sequence that we used to decode the natural target preferences of 22 families of transposable element in this species. We found that terminal inverted repeat transposon and long terminal repeat retrotransposon families present clade-specific target site duplications and target site sequence motifs. Additionally, we found that the sequence motifs at transposable element target sites are always palindromes that extend beyond the target site duplication. Our results demonstrate the utility of population genomics data for high-throughput inference of transposable element targeting preferences in the wild and establish general rules for terminal inverted repeat transposon and long terminal repeat retrotransposon target site selection in eukaryotic genomes.

  19. Characteristics of Food Industry Web Sites and "Advergames" Targeting Children

    Science.gov (United States)

    Culp, Jennifer; Bell, Robert A.; Cassady, Diana

    2010-01-01

    Objective: To assess the content of food industry Web sites targeting children by describing strategies used to prolong their visits and foster brand loyalty; and to document health-promoting messages on these Web sites. Design: A content analysis was conducted of Web sites advertised on 2 children's networks, Cartoon Network and Nickelodeon. A…

  20. Target-site resistance to neonicotinoids.

    Science.gov (United States)

    Crossthwaite, Andrew J; Rendine, Stefano; Stenta, Marco; Slater, Russell

    2014-10-01

    Neonicotinoid insecticides selectively target the invertebrate nicotinic acetylcholine receptor and disrupt excitatory cholinergic neurotransmission. First launched over 20 years ago, their broad pest spectrum, variety of application methods and relatively low risk to nontarget organisms have resulted in this class dominating the insecticide market with global annual sales in excess of $3.5 bn. This remarkable commercial success brings with it conditions in the field that favour selection of resistant phenotypes. A number of important pest species have been identified with mutations at the nicotinic acetylcholine receptor associated with insensitivity to neonicotinoids. The detailed characterization of these mutations has facilitated a greater understanding of the invertebrate nicotinic acetylcholine receptor.

  1. SeedVicious: Analysis of microRNA target and near-target sites.

    Science.gov (United States)

    Marco, Antonio

    2018-01-01

    Here I describe seedVicious, a versatile microRNA target site prediction software that can be easily fitted into annotation pipelines and run over custom datasets. SeedVicious finds microRNA canonical sites plus other, less efficient, target sites. Among other novel features, seedVicious can compute evolutionary gains/losses of target sites using maximum parsimony, and also detect near-target sites, which have one nucleotide different from a canonical site. Near-target sites are important to study population variation in microRNA regulation. Some analyses suggest that near-target sites may also be functional sites, although there is no conclusive evidence for that, and they may actually be target alleles segregating in a population. SeedVicious does not aim to outperform but to complement existing microRNA prediction tools. For instance, the precision of TargetScan is almost doubled (from 11% to ~20%) when we filter predictions by the distance between target sites using this program. Interestingly, two adjacent canonical target sites are more likely to be present in bona fide target transcripts than pairs of target sites at slightly longer distances. The software is written in Perl and runs on 64-bit Unix computers (Linux and MacOS X). Users with no computing experience can also run the program in a dedicated web-server by uploading custom data, or browse pre-computed predictions. SeedVicious and its associated web-server and database (SeedBank) are distributed under the GPL/GNU license.

  2. Integrated Site Model Process Model Report

    International Nuclear Information System (INIS)

    Booth, T.

    2000-01-01

    The Integrated Site Model (ISM) provides a framework for discussing the geologic features and properties of Yucca Mountain, which is being evaluated as a potential site for a geologic repository for the disposal of nuclear waste. The ISM is important to the evaluation of the site because it provides 3-D portrayals of site geologic, rock property, and mineralogic characteristics and their spatial variabilities. The ISM is not a single discrete model; rather, it is a set of static representations that provide three-dimensional (3-D), computer representations of site geology, selected hydrologic and rock properties, and mineralogic-characteristics data. These representations are manifested in three separate model components of the ISM: the Geologic Framework Model (GFM), the Rock Properties Model (RPM), and the Mineralogic Model (MM). The GFM provides a representation of the 3-D stratigraphy and geologic structure. Based on the framework provided by the GFM, the RPM and MM provide spatial simulations of the rock and hydrologic properties, and mineralogy, respectively. Functional summaries of the component models and their respective output are provided in Section 1.4. Each of the component models of the ISM considers different specific aspects of the site geologic setting. Each model was developed using unique methodologies and inputs, and the determination of the modeled units for each of the components is dependent on the requirements of that component. Therefore, while the ISM represents the integration of the rock properties and mineralogy into a geologic framework, the discussion of ISM construction and results is most appropriately presented in terms of the three separate components. This Process Model Report (PMR) summarizes the individual component models of the ISM (the GFM, RPM, and MM) and describes how the three components are constructed and combined to form the ISM

  3. Site descriptive modelling - strategy for integrated evaluation

    International Nuclear Information System (INIS)

    Andersson, Johan

    2003-02-01

    The current document establishes the strategy to be used for achieving sufficient integration between disciplines in producing Site Descriptive Models during the Site Investigation stage. The Site Descriptive Model should be a multidisciplinary interpretation of geology, rock mechanics, thermal properties, hydrogeology, hydrogeochemistry, transport properties and ecosystems using site investigation data from deep bore holes and from the surface as input. The modelling comprise the following iterative steps, evaluation of primary data, descriptive and quantitative modelling (in 3D), overall confidence evaluation. Data are first evaluated within each discipline and then the evaluations are checked between the disciplines. Three-dimensional modelling (i.e. estimating the distribution of parameter values in space and its uncertainty) is made in a sequence, where the geometrical framework is taken from the geological model and in turn used by the rock mechanics, thermal and hydrogeological modelling etc. The three-dimensional description should present the parameters with their spatial variability over a relevant and specified scale, with the uncertainty included in this description. Different alternative descriptions may be required. After the individual discipline modelling and uncertainty assessment a phase of overall confidence evaluation follows. Relevant parts of the different modelling teams assess the suggested uncertainties and evaluate the feedback. These discussions should assess overall confidence by, checking that all relevant data are used, checking that information in past model versions is considered, checking that the different kinds of uncertainty are addressed, checking if suggested alternatives make sense and if there is potential for additional alternatives, and by discussing, if appropriate, how additional measurements (i.e. more data) would affect confidence. The findings as well as the modelling results are to be documented in a Site Description

  4. Characteristics of food industry web sites and "advergames" targeting children.

    Science.gov (United States)

    Culp, Jennifer; Bell, Robert A; Cassady, Diana

    2010-01-01

    To assess the content of food industry Web sites targeting children by describing strategies used to prolong their visits and foster brand loyalty; and to document health-promoting messages on these Web sites. A content analysis was conducted of Web sites advertised on 2 children's networks, Cartoon Network and Nickelodeon. A total of 290 Web pages and 247 unique games on 19 Internet sites were examined. Games, found on 81% of Web sites, were the most predominant promotion strategy used. All games had at least 1 brand identifier, with logos being most frequently used. On average Web sites contained 1 "healthful" message for every 45 exposures to brand identifiers. Food companies use Web sites to extend their television advertising to promote brand loyalty among children. These sites almost exclusively promoted food items high in sugar and fat. Health professionals need to monitor food industry marketing practices used in "new media." Published by Elsevier Inc.

  5. Integrated fate and toxicity assessment for site contaminants

    International Nuclear Information System (INIS)

    MacDonell, Margaret; Peterson, John; Finster, Molly; Douglas, R.

    2007-01-01

    Understanding the fate and toxicity of environmental contaminants is essential to framing practical management decisions. Forms and bioavailable concentrations often change over time due to natural physical, chemical, and biological processes. For some sites, hundreds of contaminants may be of initial interest, and even small projects can involve a substantial number of contaminants. With multiple assessments common, attention to effectiveness and efficiency is important, and integrating fate and toxicity information provides a valuable way to focus the analyses. Fate assessments help identify what forms may be present where and when, while toxicity information indicates what health effects could result if people were exposed. The integration process is illustrated by an application for the Hanford site, to support long-term management decisions for the cesium and strontium capsules. Fate data, health-based benchmarks, and related toxicity information were effectively combined to indicate performance targets for chemicals and radionuclides identified for capsule leachate that could migrate to groundwater. More than 50 relevant benchmarks and toxicity context were identified for 15 of the 17 study contaminants; values for chronic drinking water exposure provided the common basis for selected indicators. For two chemicals, toxicity information was identified from the scientific literature to guide the performance targets. (authors)

  6. A new thermodynamic model for shaftwork targeting on total sites

    Energy Technology Data Exchange (ETDEWEB)

    Sorin, M.; Hammache, A. [CANMET Energy Technology Centre-Varennes, Quebec (Canada)

    2005-05-01

    The purpose of the paper is to introduce a targeting model based on a new thermodynamic insight on cogeneration in general and Rankine cycle in particular. The insight permits to express the ideal shaftwork of a cogeneration unit through the outlet heat load and the difference in Carnot factors between the heat source and heat sink for the given inlet temperature of the heat source. The deviation from the ideal shaftwork to the real one is assessed by using the traditionally turbine isentropic efficiency. Finally the new model allows targeting fuel consumption, cooling requirement and shaftwork production with high accuracy and visualizing then directly as special segments on the T-H diagram. A modified Site Utility Grand Composite Curve (SUGCC) diagram is proposed and compared to the original SUGCC. The shape of the right hand side of the diagram above site pinch is the same, however, below site pinch it is shifted to the left by an amount equal to shaftwork production below site pinch. Above site pinch VHP consumption is also corrected to account for shaftwork production above site pinch that is represented by segments rather than areas on the left hand side of the T-H diagram. (author)

  7. Characteristics of the volatile organic compounds -- Arid Integrated Demonstration Site

    International Nuclear Information System (INIS)

    Last, G.V.; Lenhard, R.J.; Bjornstad, B.N.; Evans, J.C.; Roberson, K.R.; Spane, F.A.; Amonette, J.E.; Rockhold, M.L.

    1991-10-01

    The Volatile Organic Compounds -- Arid Integrated Demonstration Program (VOC-Arid ID) is targeted at demonstration and testing of technologies for the evaluation and cleanup of volatile organic compounds and associated contaminants at arid DOE sites. The initial demonstration site is an area of carbon tetrachloride (CCl 4 ) contamination located near the center of the Hanford Site. The movement of CCl 4 and other volatile organic contaminants in the subsurface is very complex. The problem at the Hanford Site is further complicated by the concurrent discharge of other waste constituents including acids, lard oil, organic phosphates, and transuranic radionuclides. In addition, the subsurface environment is very complex, with large spatial variabilities in hydraulic properties. A thorough understanding of the problem is essential to the selection of appropriate containment, retrieval, and/or in situ remedial technologies. The effectiveness of remedial technologies depends on knowing where the contaminants are, how they are held up in a given physical and chemical subsurface environment; and knowing the physical, chemical, and microbiological changes that are induced by the various remedial technologies

  8. New emissions targeting strategy for site utility of process industries

    International Nuclear Information System (INIS)

    Manesh, Mohamamd Hasan Khoshgoftar; Amidpour, Majid; Hamedi, Mohammad Hosein; Abadi, Sajad Khamis; Ghalami, Hooman

    2013-01-01

    A new procedure for environmental targeting of co-generation system is presented. The proposed method is based on the concepts of pinch technology for total site targeting of fuel, power, steam, environmental impacts and total annualized cost with considering emissions taxes. This approach provides a consistent, general procedure for determining mass flow rates and efficiencies of the applied turbines. This algorithm utilizes the relationship of entropy with enthalpy and isentropic efficiency. Also, the life cycle assessment (LCA) as a well-known tool for analyzing environmental impacts on a wide perspective with reference to a product system and the related environmental and economic impacts have been applied. In this regard, a damage-oriented impact analysis method based on Eco-indicator 99 and footprints analysis was considered. In addition, the present work demonstrates the effect of including both sensible and latent heating of steam in the extended Site Utility Grand Composite Curve (ESUGCC). It is shown that including sensible heating allows for better thermal matching between the processes. Furthermore, the other representation YSUGCC as the other form of Site Utility Grand Composite has been proposed. Two case studies were used to illustrate the usefulness of the new environmental targeting method

  9. Nuclease Target Site Selection for Maximizing On-target Activity and Minimizing Off-target Effects in Genome Editing

    Science.gov (United States)

    Lee, Ciaran M; Cradick, Thomas J; Fine, Eli J; Bao, Gang

    2016-01-01

    The rapid advancement in targeted genome editing using engineered nucleases such as ZFNs, TALENs, and CRISPR/Cas9 systems has resulted in a suite of powerful methods that allows researchers to target any genomic locus of interest. A complementary set of design tools has been developed to aid researchers with nuclease design, target site selection, and experimental validation. Here, we review the various tools available for target selection in designing engineered nucleases, and for quantifying nuclease activity and specificity, including web-based search tools and experimental methods. We also elucidate challenges in target selection, especially in predicting off-target effects, and discuss future directions in precision genome editing and its applications. PMID:26750397

  10. Outreach for Outreach: Targeting social media audiences to promote a NASA kids’ web site

    Science.gov (United States)

    Pham, C. C.

    2009-12-01

    The Space Place is a successful NASA web site that benefits upper elementary school students and educators by providing games, activities, and resources to stimulate interest in science, technology, engineering, and mathematics, as well as to inform the audience of NASA’s contributions. As online social networking grows to be a central component of modern communication, The Space Place has explored the benefits of integrating social networks with the web site to increase awareness of materials the web site offers. This study analyzes the capabilities of social networks, and specifically the demographics of Twitter and Facebook. It then compares these results with the content, audience, and perceived demographics of The Space Place web site. Based upon the demographic results, we identified a target constituency that would benefit from the integration of social networks into The Space Place web site. As a result of this study, a Twitter feed has been established that releases a daily tweet from The Space Place. In addition, a Facebook page has been created to showcase new content and prompt interaction among fans of The Space Place. Currently, plans are under way to populate the Space Place Facebook page. Each social network has been utilized in an effort to spark excitement about the content on The Space Place, as well as to attract followers to the main NASA Space Place web site. To pursue this idea further, a plan has been developed to promote NASA Space Place’s social media tools among the target audience.

  11. An integrated approach to site selection for nuclear power plants

    International Nuclear Information System (INIS)

    Hassan, E.M.A.

    1975-01-01

    A method of analysing and evaluating the large number of factors influencing site selection is proposed, which can interrelate these factors and associated problems in an integrated way and at the same time establish a technique for site evaluation. The objective is to develop an integrated programme that illustrates the complexity and dynamic interrelationships of the various factors to develop an improved understanding of the functions and objectives of siting nuclear power plants and would aim finally at the development of an effective procedure and technique for site evaluation and/or comparative evaluation for making rational site-selection decisions. (author)

  12. Retrotransposons. An RNA polymerase III subunit determines sites of retrotransposon integration.

    Science.gov (United States)

    Bridier-Nahmias, Antoine; Tchalikian-Cosson, Aurélie; Baller, Joshua A; Menouni, Rachid; Fayol, Hélène; Flores, Amando; Saïb, Ali; Werner, Michel; Voytas, Daniel F; Lesage, Pascale

    2015-05-01

    Mobile genetic elements are ubiquitous. Their integration site influences genome stability and gene expression. The Ty1 retrotransposon of the yeast Saccharomyces cerevisiae integrates upstream of RNA polymerase III (Pol III)-transcribed genes, yet the primary determinant of target specificity has remained elusive. Here we describe an interaction between Ty1 integrase and the AC40 subunit of Pol III and demonstrate that AC40 is the predominant determinant targeting Ty1 integration upstream of Pol III-transcribed genes. Lack of an integrase-AC40 interaction dramatically alters target site choice, leading to a redistribution of Ty1 insertions in the genome, mainly to chromosome ends. The mechanism of target specificity allows Ty1 to proliferate and yet minimizes genetic damage to its host. Copyright © 2015, American Association for the Advancement of Science.

  13. Retention of ferrofluid aggregates at the target site during magnetic drug targeting

    Energy Technology Data Exchange (ETDEWEB)

    Asfer, Mohammed, E-mail: asfer786@gmail.com [School of Engineering and Technology, BML Munjal University, Haryana (India); Saroj, Sunil Kumar [Department of Mechanical Engineering, IIT Kanpur, Kanpur (India); Panigrahi, Pradipta Kumar, E-mail: panig@iitk.ac.in [Department of Mechanical Engineering, IIT Kanpur, Kanpur (India)

    2017-08-15

    Highlights: • The present in vitro work reports the retention dynamics of ferrofluid aggregates at the target site against a bulk flow of DI water inside a micro capillary during magnetic drug targeting. • The recirculation zone at the downstream of the aggregate is found to be a function of aggregate height, Reynolds number and the degree of surface roughness of the outer boundary of the aggregate. • The reported results of the present work can be used as a guideline for the better design of MDT technique for in vivo applications. - Abstract: The present study reports the retention dynamics of a ferrofluid aggregate localized at the target site inside a glass capillary (500 × 500 µm{sup 2} square cross section) against a bulk flow of DI water (Re = 0.16 and 0.016) during the process of magnetic drug targeting (MDT). The dispersion dynamics of iron oxide nanoparticles (IONPs) into bulk flow for different initial size of aggregate at the target site is reported using the brightfield visualization technique. The flow field around the aggregate during the retention is evaluated using the µPIV technique. IONPs at the outer boundary experience a higher shear force as compared to the magnetic force, resulting in dispersion of IONPs into the bulk flow downstream to the aggregate. The blockage effect and the roughness of the outer boundary of the aggregate resulting from chain like clustering of IONPs contribute to the flow recirculation at the downstream region of the aggregate. The entrapment of seeding particles inside the chain like clusters of IONPs at the outer boundary of the aggregate reduces the degree of roughness resulting in a streamlined aggregate at the target site at later time. The effect of blockage, structure of the aggregate, and disturbed flow such as recirculation around the aggregate are the primary factors, which must be investigated for the effectiveness of the MDT process for in vivo applications.

  14. TargetMine, an integrated data warehouse for candidate gene prioritisation and target discovery.

    Directory of Open Access Journals (Sweden)

    Yi-An Chen

    Full Text Available Prioritising candidate genes for further experimental characterisation is a non-trivial challenge in drug discovery and biomedical research in general. An integrated approach that combines results from multiple data types is best suited for optimal target selection. We developed TargetMine, a data warehouse for efficient target prioritisation. TargetMine utilises the InterMine framework, with new data models such as protein-DNA interactions integrated in a novel way. It enables complicated searches that are difficult to perform with existing tools and it also offers integration of custom annotations and in-house experimental data. We proposed an objective protocol for target prioritisation using TargetMine and set up a benchmarking procedure to evaluate its performance. The results show that the protocol can identify known disease-associated genes with high precision and coverage. A demonstration version of TargetMine is available at http://targetmine.nibio.go.jp/.

  15. Heat integration and analysis of decarbonised IGCC sites

    Energy Technology Data Exchange (ETDEWEB)

    Ng, K.S.; Lopez, Y.; Campbell, G.M.; Sadhukhan, J. [University of Manchester, Manchester (United Kingdom). School of Chemical Engineering & Analytical Science

    2010-02-15

    Integrated gasification combined cycle (IGCC) power generation systems have become of interest due to their high combined heat and power (CHP) generation efficiency and flexibility to include carbon capture and storage (CCS) in order to reduce CO{sub 2} emissions. However, IGCC's biggest challenge is its high cost of energy production. In this study, decarbonised coal IGCC sites integrated with CCS have been investigated for heat integration and economic value analyses. It is envisaged that the high energy production cost of an IGCC site can be offset by maximising site-wide heat recovery and thereby improving the cost of electricity (COE) of CHP generation. Strategies for designing high efficiency CHP networks have been proposed based on thermodynamic heuristics and pinch theory. Additionally, a comprehensive methodology to determine the COE from a process site has been developed. In this work, we have established thermodynamic and economic comparisons between IGCC sites with and without CCS and a trade-off between the degree of decarbonisation and the COE from the heat integrated IGCC sites. The results show that the COE from the heat integrated decarbonised IGCC sites is significantly lower compared to IGCC sites without heat integration making application of CCS in IGCC sites economically competitive.

  16. HIV integration sites and implications for maintenance of the reservoir.

    Science.gov (United States)

    Symons, Jori; Cameron, Paul U; Lewin, Sharon R

    2018-03-01

    To provide an overview of recent research of how HIV integration relates to productive and latent infection and implications for cure strategies. How and where HIV integrates provides new insights into how HIV persists on antiretroviral therapy (ART). Clonal expansion of infected cells with the same integration site demonstrates that T-cell proliferation is an important factor in HIV persistence, however, the driver of proliferation remains unclear. Clones with identical integration sites harbouring defective provirus can accumulate in HIV-infected individuals on ART and defective proviruses can express RNA and produce protein. HIV integration sites differ in clonally expanded and nonexpanded cells and in latently and productively infected cells and this influences basal and inducible transcription. There is a growing number of cellular proteins that can alter the pattern of integration to favour latency. Understanding these pathways may identify new interventions to eliminate latently infected cells. Using advances in analysing HIV integration sites, T-cell proliferation of latently infected cells is thought to play a major role in HIV persistence. Clonal expansion has been demonstrated with both defective and intact viruses. Production of viral RNA and protein from defective viruses may play a role in driving chronic immune activation. The site of integration may determine the likelihood of proliferation and the degree of basal and induced transcription. Finally, host factors and gene expression at the time of infection may determine the integration site. Together these new insights may lead to novel approaches to elimination of latently infected cells.

  17. Total Site Integration and paper machine technologies; Total site integration ja paperikoneteknologia - PMST 02

    Energy Technology Data Exchange (ETDEWEB)

    Puumalainen, T; Kaijaluoto, S; Tervonen, P; Edelmann, K [VTT Energy, Jyvaeskylae (Finland)

    1999-12-31

    During the last 30 years the production capacity of a paper machine has tripled. The fastest machines of today run over about 1600 m/min, the web width being around 10 m. The desire to further increase the production capacity is leading to more expensive paper machines and to larger buildings, if current pressing and drying techniques are used. New pressing and drying techniques will decrease the need of thermal energy. Closed water cycles reduce the need of secondary heat abundantly available from the dryer section based on cylinder drying. Total Site Integration studies are required when the effect of new process concepts are to be evaluated against energy efficiency and environmental impacts. A proto type tool has been developed and the effect of new paper machine concepts on energy consumption have been analysed. The utilisation possibilities of the surplus energy will be studied later in the course of this project. (orig.)

  18. Total Site Integration and paper machine technologies; Total site integration ja paperikoneteknologia - PMST 02

    Energy Technology Data Exchange (ETDEWEB)

    Puumalainen, T.; Kaijaluoto, S.; Tervonen, P.; Edelmann, K. [VTT Energy, Jyvaeskylae (Finland)

    1998-12-31

    During the last 30 years the production capacity of a paper machine has tripled. The fastest machines of today run over about 1600 m/min, the web width being around 10 m. The desire to further increase the production capacity is leading to more expensive paper machines and to larger buildings, if current pressing and drying techniques are used. New pressing and drying techniques will decrease the need of thermal energy. Closed water cycles reduce the need of secondary heat abundantly available from the dryer section based on cylinder drying. Total Site Integration studies are required when the effect of new process concepts are to be evaluated against energy efficiency and environmental impacts. A proto type tool has been developed and the effect of new paper machine concepts on energy consumption have been analysed. The utilisation possibilities of the surplus energy will be studied later in the course of this project. (orig.)

  19. AAVS1-Targeted Plasmid Integration in AAV Producer Cell Lines.

    Science.gov (United States)

    Luo, Yuxia; Frederick, Amy; Martin, John M; Scaria, Abraham; Cheng, Seng H; Armentano, Donna; Wadsworth, Samuel C; Vincent, Karen A

    2017-06-01

    Adeno-associated virus (AAV) producer cell lines are created via transfection of HeLaS3 cells with a single plasmid containing three components (the vector sequence, the AAV rep and cap genes, and a selectable marker gene). As this plasmid contains both the cis (Rep binding sites) and trans (Rep protein encoded by the rep gene) elements required for site-specific integration, it was predicted that plasmid integration might occur within the AAVS1 locus on human chromosome 19 (chr19). The objective of this study was to investigate whether integration in AAVS1 might be correlated with vector yield. Plasmid integration sites within several independent cell lines were assessed via Southern, fluorescence in situ hybridization (FISH) and PCR analyses. In the Southern analyses, the presence of fragments detected by both rep- and AAVS1-specific probes suggested that for several mid- and high-producing lines, plasmid DNA had integrated into the AAVS1 locus. Analysis with puroR and AAVS1-specific probes suggested that integration in AAVS1 was a more widespread phenomenon. High-producing AAV2-secreted alkaline phosphatase (SEAP) lines (masterwell 82 [MW82] and MW278) were evaluated via FISH using probes specific for the plasmid, AAVS1, and a chr19 marker. FISH analysis detected two plasmid integration sites in MW278 (neither in AAVS1), while a total of three sites were identified in MW82 (two in AAVS1). An inverse PCR assay confirmed integration within AAVS1 for several mid- and high-producing lines. In summary, the FISH, Southern, and PCR data provide evidence of site-specific integration of the plasmid within AAVS1 in several AAV producer cell lines. The data also suggest that integration in AAVS1 is a general phenomenon that is not necessarily restricted to high producers. The results also suggest that plasmid integration within the AAVS1 locus is not an absolute requirement for a high vector yield.

  20. Integrated Propulsion Data System Public Web Site

    Science.gov (United States)

    Hamilton, Kimberly

    2001-01-01

    The Integrated Propulsion Data System's (IPDS) focus is to provide technologically-advanced philosophies of doing business at SSC that will enhance the existing operations, engineering and management strategies and provide insight and metrics to assess their daily impacts, especially as related to the Propulsion Test Directorate testing scenarios for the 21st Century.

  1. Engineered Proteins Program Mammalian Cells to Target Inflammatory Disease Sites.

    Science.gov (United States)

    Qudrat, Anam; Mosabbir, Abdullah Al; Truong, Kevin

    2017-06-22

    Disease sites in atherosclerosis and cancer feature cell masses (e.g., plaques/tumors), a low pH extracellular microenvironment, and various pro-inflammatory cytokines such as tumor necrosis factor α (TNFα). The ability to engineer a cell to seek TNFα sources allows for targeted therapeutic delivery. To accomplish this, here we introduced a system of proteins: an engineered TNFα chimeric receptor (named TNFR1chi), a previously engineered Ca 2+ -activated RhoA (named CaRQ), vesicular stomatitis virus glycoprotein G (VSVG), and thymidine kinase. Upon binding TNFα, TNFR1chi generates a Ca 2+ signal that in turn activates CaRQ-mediated non-apoptotic blebs that allow migration toward the TNFα source. Next, the addition of VSVG, upon low pH induction, causes membrane fusion of the engineered and TNFα source cells. Finally, after ganciclovir treatment cells undergo death via the thymidine kinase suicide mechanism. Hence, we assembled a system of proteins that forms the basis of engineering a cell to target inflammatory disease sites characterized by TNFα secretion and a low-pH microenvironment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Electroless plating technology of integral hohlraum Cu target

    International Nuclear Information System (INIS)

    Liu Jiguang; Fu Qu; Wan Xiaobo; Zhou Lan; Xiao Jiang

    2005-01-01

    The electroless plating method of making integral hohlraum Cu target and corrosion-resistant technology of target's surface were researched. The actual process was as follows, choosing plexiglass (PMMA) as arbor, taking cationic activation and electroless plating Cu on the arbor surface, taking arbor surface passivation and chemical etching by C 6 H 5 N 3 solution. The technology is easy to realize and its cost is lower, so it is of great reference value for fabricating other integral hohlraum metal or alloy targets used for inertial confinement fusion study. (author)

  3. Novel acetylcholinesterase target site for malaria mosquito control.

    Directory of Open Access Journals (Sweden)

    Yuan-Ping Pang

    2006-12-01

    Full Text Available Current anticholinesterase pesticides were developed during World War II and are toxic to mammals because they target a catalytic serine residue of acetylcholinesterases (AChEs in insects and in mammals. A sequence analysis of AChEs from 73 species and a three-dimensional model of a malaria-carrying mosquito (Anopheles gambiae AChE (AgAChE reported here show that C286 and R339 of AgAChE are conserved at the opening of the active site of AChEs in 17 invertebrate and four insect species, respectively. Both residues are absent in the active site of AChEs of human, monkey, dog, cat, cattle, rabbit, rat, and mouse. The 17 invertebrates include house mosquito, Japanese encephalitis mosquito, African malaria mosquito, German cockroach, Florida lancelet, rice leaf beetle, African bollworm, beet armyworm, codling moth, diamondback moth, domestic silkworm, honey bee, oat or wheat aphid, the greenbug, melon or cotton aphid, green peach aphid, and English grain aphid. The four insects are house mosquito, Japanese encephalitis mosquito, African malaria mosquito, and German cockroach. The discovery of the two invertebrate-specific residues enables the development of effective and safer pesticides that target the residues present only in mosquito AChEs rather than the ubiquitous serine residue, thus potentially offering an effective control of mosquito-borne malaria. Anti-AgAChE pesticides can be designed to interact with R339 and subsequently covalently bond to C286. Such pesticides would be toxic to mosquitoes but not to mammals.

  4. Target and Tissue Selectivity Prediction by Integrated Mechanistic Pharmacokinetic-Target Binding and Quantitative Structure Activity Modeling.

    Science.gov (United States)

    Vlot, Anna H C; de Witte, Wilhelmus E A; Danhof, Meindert; van der Graaf, Piet H; van Westen, Gerard J P; de Lange, Elizabeth C M

    2017-12-04

    Selectivity is an important attribute of effective and safe drugs, and prediction of in vivo target and tissue selectivity would likely improve drug development success rates. However, a lack of understanding of the underlying (pharmacological) mechanisms and availability of directly applicable predictive methods complicates the prediction of selectivity. We explore the value of combining physiologically based pharmacokinetic (PBPK) modeling with quantitative structure-activity relationship (QSAR) modeling to predict the influence of the target dissociation constant (K D ) and the target dissociation rate constant on target and tissue selectivity. The K D values of CB1 ligands in the ChEMBL database are predicted by QSAR random forest (RF) modeling for the CB1 receptor and known off-targets (TRPV1, mGlu5, 5-HT1a). Of these CB1 ligands, rimonabant, CP-55940, and Δ 8 -tetrahydrocanabinol, one of the active ingredients of cannabis, were selected for simulations of target occupancy for CB1, TRPV1, mGlu5, and 5-HT1a in three brain regions, to illustrate the principles of the combined PBPK-QSAR modeling. Our combined PBPK and target binding modeling demonstrated that the optimal values of the K D and k off for target and tissue selectivity were dependent on target concentration and tissue distribution kinetics. Interestingly, if the target concentration is high and the perfusion of the target site is low, the optimal K D value is often not the lowest K D value, suggesting that optimization towards high drug-target affinity can decrease the benefit-risk ratio. The presented integrative structure-pharmacokinetic-pharmacodynamic modeling provides an improved understanding of tissue and target selectivity.

  5. Drug target ontology to classify and integrate drug discovery data

    DEFF Research Database (Denmark)

    Lin, Yu; Mehta, Saurabh; Küçük-McGinty, Hande

    2017-01-01

    using a new software tool to auto-generate most axioms from a database while supporting manual knowledge acquisition. A modular, hierarchical implementation facilitate ontology development and maintenance and makes use of various external ontologies, thus integrating the DTO into the ecosystem...... of biomedical ontologies. As a formal OWL-DL ontology, DTO contains asserted and inferred axioms. Modeling data from the Library of Integrated Network-based Cellular Signatures (LINCS) program illustrates the potential of DTO for contextual data integration and nuanced definition of important drug target...... characteristics. DTO has been implemented in the IDG user interface Portal, Pharos and the TIN-X explorer of protein target disease relationships. CONCLUSIONS: DTO was built based on the need for a formal semantic model for druggable targets including various related information such as protein, gene, protein...

  6. Centredale Manor Superfund Site in Rhode Island included on EPA List of Targeted for Immediate Attention

    Science.gov (United States)

    Today, the U.S. Environmental Protection Agency released the list of Superfund sites that Administrator Pruitt has targeted for immediate and intense attention. The Centredale Manor Restoration Project superfund site is one of the 21 sites on the list.

  7. Application of the Integrated Site and Environment Data Management System for LILW Disposal Site

    International Nuclear Information System (INIS)

    Lee, Ji Hoon; Lee, Eun Yong; Kim, Chang Lak

    2007-01-01

    During the last five years, Site Information and Total Environmental data management System(SITES) has been developed. SITES is an integrated program for overall data acquisition, environmental monitoring, and safety analysis. SITES is composed of three main modules, such as site database system (SECURE), safety assessment system (SAINT) and environmental monitoring system (SUDAL). In general, for the safe management of radioactive waste repository, the information of site environment should be collected and managed systematically from the initial site survey. For this, SECURE module manages its data for the site characterization, environmental information, and radioactive environmental information etc. The purpose of SAINT module is to apply and analyze the data from SECURE. SUDAL is developed for environmental monitoring of the radioactive waste repository. Separately, it is ready to open to the public for offering partial information

  8. VISPA2: a scalable pipeline for high-throughput identification and annotation of vector integration sites.

    Science.gov (United States)

    Spinozzi, Giulio; Calabria, Andrea; Brasca, Stefano; Beretta, Stefano; Merelli, Ivan; Milanesi, Luciano; Montini, Eugenio

    2017-11-25

    Bioinformatics tools designed to identify lentiviral or retroviral vector insertion sites in the genome of host cells are used to address the safety and long-term efficacy of hematopoietic stem cell gene therapy applications and to study the clonal dynamics of hematopoietic reconstitution. The increasing number of gene therapy clinical trials combined with the increasing amount of Next Generation Sequencing data, aimed at identifying integration sites, require both highly accurate and efficient computational software able to correctly process "big data" in a reasonable computational time. Here we present VISPA2 (Vector Integration Site Parallel Analysis, version 2), the latest optimized computational pipeline for integration site identification and analysis with the following features: (1) the sequence analysis for the integration site processing is fully compliant with paired-end reads and includes a sequence quality filter before and after the alignment on the target genome; (2) an heuristic algorithm to reduce false positive integration sites at nucleotide level to reduce the impact of Polymerase Chain Reaction or trimming/alignment artifacts; (3) a classification and annotation module for integration sites; (4) a user friendly web interface as researcher front-end to perform integration site analyses without computational skills; (5) the time speedup of all steps through parallelization (Hadoop free). We tested VISPA2 performances using simulated and real datasets of lentiviral vector integration sites, previously obtained from patients enrolled in a hematopoietic stem cell gene therapy clinical trial and compared the results with other preexisting tools for integration site analysis. On the computational side, VISPA2 showed a > 6-fold speedup and improved precision and recall metrics (1 and 0.97 respectively) compared to previously developed computational pipelines. These performances indicate that VISPA2 is a fast, reliable and user-friendly tool for

  9. Liposome as nanocarrier: Site targeted delivery in lung cancer

    Directory of Open Access Journals (Sweden)

    Najeeb Ullah

    2017-08-01

    Full Text Available Lung cancer is fatal and spreading rapidly worldwide. Different clinical strategies are applied to stop this cancer. As the lung is a delicate organ, special clinical applications must be used and nanodrugs delivery systems are the most important applications of all. This review discusses the lung problems such as lung cancer, lung inflammation and bronchi constrictions followed by repetitive intake of some drugs. The objective of this review is to study how nanodrug delivery systems were synthesized and used in lung disorder treatment especially in lung cancer. The authors studied some articles from 1989 to 2015. Liposome encapsulation was done in various ways for the delivery of different drugs such as metaproterenol into liposomes caused bronchodilation, immunoliposomes bearing antibodies for doxorubicin reduced 50% inhibitory effects, radioliposomes with high penetrating ability to peripheral airways, aerosol delivery systems with deep pulmonary deposition, polymeric drug delivery having potential to improve beneficial index of drug, solid lipid liposomes, liposomal gentamicin with altered different clinical susceptibilities of resistance, transferrin conjugated liposomes to deliver cytostatic drugs to site of lungs, anti-inflammatory drugs with mannosylated liposomes, liposomal suspensions with single stranded RNAs and peptide encapsulation of liposomes. This review indicates that many animals perished with intravenous administration of drugs but survived in liposomal targeting groups.

  10. Visualizing multiple inter-organelle contact sites using the organelle-targeted split-GFP system.

    Science.gov (United States)

    Kakimoto, Yuriko; Tashiro, Shinya; Kojima, Rieko; Morozumi, Yuki; Endo, Toshiya; Tamura, Yasushi

    2018-04-18

    Functional integrity of eukaryotic organelles relies on direct physical contacts between distinct organelles. However, the entity of organelle-tethering factors is not well understood due to lack of means to analyze inter-organelle interactions in living cells. Here we evaluate the split-GFP system for visualizing organelle contact sites in vivo and show its advantages and disadvantages. We observed punctate GFP signals from the split-GFP fragments targeted to any pairs of organelles among the ER, mitochondria, peroxisomes, vacuole and lipid droplets in yeast cells, which suggests that these organelles form contact sites with multiple organelles simultaneously although it is difficult to rule out the possibilities that these organelle contacts sites are artificially formed by the irreversible associations of the split-GFP probes. Importantly, split-GFP signals in the overlapped regions of the ER and mitochondria were mainly co-localized with ERMES, an authentic ER-mitochondria tethering structure, suggesting that split-GFP assembly depends on the preexisting inter-organelle contact sites. We also confirmed that the split-GFP system can be applied to detection of the ER-mitochondria contact sites in HeLa cells. We thus propose that the split-GFP system is a potential tool to observe and analyze inter-organelle contact sites in living yeast and mammalian cells.

  11. INR targets and site-level anticoagulation control: results from the Veterans AffaiRs Study to Improve Anticoagulation (VARIA).

    Science.gov (United States)

    Rose, A J; Berlowitz, D R; Miller, D R; Hylek, E M; Ozonoff, A; Zhao, S; Reisman, J I; Ash, A S

    2012-04-01

    Not all clinicians target the same International Normalized Ratio (INR) for patients with a guideline-recommended target range of 2-3. A patient's mean INR value suggests the INR that was actually targeted. We hypothesized that sites would vary by mean INR, and that sites of care with mean values nearest to 2.5 would achieve better anticoagulation control, as measured by per cent time in therapeutic range (TTR). To examine variations among sites in mean INR and the relationship with anticoagulation control in an integrated system of care. We studied 103,897 patients receiving oral anticoagulation with an expected INR target between 2 and 3 at 100 Veterans Health Administration (VA) sites from 1 October 2006 to 30 September 2008. Key site-level variables were: proportion near 2.5 (that is, percentage of patients with mean INR between 2.3 and 2.7) and mean risk-adjusted TTR. Site mean INR ranged from 2.22 to 2.89; proportion near 2.5, from 30 to 64%. Sites' proportions of patients near 2.5, below 2.3 and above 2.7 were consistent from year to year. A 10 percentage point increase in the proportion near 2.5 predicted a 3.8 percentage point increase in risk-adjusted TTR (P < 0.001). Proportion of patients with mean INR near 2.5 is a site-level 'signature' of care and an implicit measure of targeted INR. This proportion varies by site and is strongly associated with site-level TTR. Our study suggests that sites wishing to improve TTR, and thereby improve patient outcomes, should avoid the explicit or implicit pursuit of non-standard INR targets. © 2012 International Society on Thrombosis and Haemostasis.

  12. CERCLA integration with site operations the Fernald experience

    International Nuclear Information System (INIS)

    Coyle, S.W.; Shirley, R.S.; Varchol, B.D.

    1991-01-01

    A major transition in the Fernald Environmental Management Project (FEMP) site mission has occurred over the past few years. The production capabilities formally provided by the FEMP are being transferred to private industry through a vendor qualification program. Environmental compliance and site cleanup are now the primary focus. In line with this program, the production of uranium products at the site was suspended in July 1989 in order to concentrate resources on the environmental mission. Formal termination of the FEMP production mission was accomplished on June 19, 1991. Environmental issues such as stored inventories of process residues materials and equipment are being addressed under the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA). The diversity of these hazards complicates the strategic planning for an integrated site cleanup program. The FEMP is one of the first Department of Energy (DOE) facilities to transition from an active production mission guided by Defense Programs (DP) to an environmental mission guided by Environmental Management (EM) under Leo Duffy. Westinghouse Environmental Management Company of Ohio (WEMCO) has been charged with integrating all site activities to carry out the cleanup. A new management structure has been formulated, and an integration approach initiated. Analyses are under way to evaluate all site activities such as waste management, safe shutdown, product material disposition and routine environmental monitoring in view of CERCLA requirements. Site activities are being broken down into three categories: (a) CERCLA driven - restoration work required under CERCLA, (b) CERCLA covered - other environmental requirements which must be integrated with CERCLA, and (c) CERCLA exempt (if any). The approach to comply with these categorized activities must be negotiated with state and federal regulatory agencies

  13. Integrated radiobioecological monitoring of Semipalatinsk test site: general approach

    International Nuclear Information System (INIS)

    Sejsebaev, A.T.; Shenal', K.; Bakhtin, M.M.; Kadyrova, N.Zh.

    2001-01-01

    This paper presents major research directions and general methodology for establishment of an integrated radio-bio-ecological monitoring system at the territory of the former Semipalatinsk nuclear test site. Also, it briefly provides the first results of monitoring the natural plant and animal populations at STS. (author)

  14. Modification site localization scoring integrated into a search engine.

    Science.gov (United States)

    Baker, Peter R; Trinidad, Jonathan C; Chalkley, Robert J

    2011-07-01

    Large proteomic data sets identifying hundreds or thousands of modified peptides are becoming increasingly common in the literature. Several methods for assessing the reliability of peptide identifications both at the individual peptide or data set level have become established. However, tools for measuring the confidence of modification site assignments are sparse and are not often employed. A few tools for estimating phosphorylation site assignment reliabilities have been developed, but these are not integral to a search engine, so require a particular search engine output for a second step of processing. They may also require use of a particular fragmentation method and are mostly only applicable for phosphorylation analysis, rather than post-translational modifications analysis in general. In this study, we present the performance of site assignment scoring that is directly integrated into the search engine Protein Prospector, which allows site assignment reliability to be automatically reported for all modifications present in an identified peptide. It clearly indicates when a site assignment is ambiguous (and if so, between which residues), and reports an assignment score that can be translated into a reliability measure for individual site assignments.

  15. Integrating Risk Analyses and Tools at the DOE Hanford Site

    International Nuclear Information System (INIS)

    LOBER, R.W.

    2002-01-01

    Risk assessment and environmental impact analysis at the U.S. Department of Energy (DOE) Hanford Site in Washington State has made significant progress in refining the strategy for using risk analysis to support closing of several hundred waste sites plus 149 single-shell tanks at the Hanford Site. A Single-Shell Tank System Closure Work Plan outlines the current basis for closing the single-shell tank systems. An analogous site approach has been developed to address closure of aggregated groups of similar waste sites. Because of the complexity, decision time frames, proximity of non-tank farm waste sites to tank farms, scale, and regulatory considerations, various projects are providing integrated assessments to support risk analyses and decision-making. Projects and the tools that are being developed and applied at Hanford to support retrieval and cleanup decisions include: (1) Life Cycle Model (LCM) and Risk Receptor Model (RRM)--A site-level set of tools to support strategic analyses through scoping level risk management to assess different alternatives and options for tank closure. (2) Systems Assessment Capability for Integrated Groundwater Nadose Zone (SAC) and the Site-Wide Groundwater Model (SWGM)--A site-wide groundwater modeling system coupled with a risk-based uncertainty analysis of inventory, vadose zone, groundwater, and river interactions for evaluating cumulative impacts from individual and aggregate waste sites. (3) Retrieval Performance Evaluation (RPE)--A site-specific, risk-based methodology developed to evaluate performance of waste retrieval, leak detection and closure on a tank-specific basis as a function of past tank Leaks, potential leakage during retrieval operations, and remaining residual waste inventories following completion of retrieval operations. (4) Field Investigation Report (FIR)--A corrective action program to investigate the nature and extent of past tank leaks through characterization activities and assess future impacts to

  16. Targeting relationally integrated project teams for sustainable PPPs

    OpenAIRE

    Kumaraswamy, M. M.; Ling, F. Y. Y.; Anvuur, A. M.; Rahman, M. M.

    2007-01-01

    Purpose – This paper targets the development of comprehensive approaches to prequalifying teams for Public Private Partnerships (PPPs). Design/methodology/approach – Research outcomes from a study into “relationally integrated project teams” (RIPTs) were applied to necessarily longer-term PPP scenarios. A force field model was developed to visualise the importance of stronger relational forces between the many PPP participants for “sustainable RIPTs” (SRITs). A framework was conceptualised to...

  17. Hanford Site waste treatment/storage/disposal integration

    International Nuclear Information System (INIS)

    MCDONALD, K.M.

    1999-01-01

    In 1998 Waste Management Federal Services of Hanford, Inc. began the integration of all low-level waste, mixed waste, and TRU waste-generating activities across the Hanford site. With seven contractors, dozens of generating units, and hundreds of waste streams, integration was necessary to provide acute waste forecasting and planning for future treatment activities. This integration effort provides disposition maps that account for waste from generation, through processing, treatment and final waste disposal. The integration effort covers generating facilities from the present through the life-cycle, including transition and deactivation. The effort is patterned after the very successful DOE Complex EM Integration effort. Although still in the preliminary stages, the comprehensive onsite integration effort has already reaped benefits. These include identifying significant waste streams that had not been forecast, identifying opportunities for consolidating activities and services to accelerate schedule or save money; and identifying waste streams which currently have no path forward in the planning baseline. Consolidation/integration of planned activities may also provide opportunities for pollution prevention and/or avoidance of secondary waste generation. A workshop was held to review the waste disposition maps, and to identify opportunities with potential cost or schedule savings. Another workshop may be held to follow up on some of the long-term integration opportunities. A change to the Hanford waste forecast data call would help to align the Solid Waste Forecast with the new disposition maps

  18. Integrated Targeting and Guidance for Powered Planetary Descent

    Science.gov (United States)

    Azimov, Dilmurat M.; Bishop, Robert H.

    2018-02-01

    This paper presents an on-board guidance and targeting design that enables explicit state and thrust vector control and on-board targeting for planetary descent and landing. These capabilities are developed utilizing a new closed-form solution for the constant thrust arc of the braking phase of the powered descent trajectory. The key elements of proven targeting and guidance architectures, including braking and approach phase quartics, are employed. It is demonstrated that implementation of the proposed solution avoids numerical simulation iterations, thereby facilitating on-board execution of targeting procedures during the descent. It is shown that the shape of the braking phase constant thrust arc is highly dependent on initial mass and propulsion system parameters. The analytic solution process is explicit in terms of targeting and guidance parameters, while remaining generic with respect to planetary body and descent trajectory design. These features increase the feasibility of extending the proposed integrated targeting and guidance design to future cargo and robotic landing missions.

  19. Integrative biology approach identifies cytokine targeting strategies for psoriasis.

    Science.gov (United States)

    Perera, Gayathri K; Ainali, Chrysanthi; Semenova, Ekaterina; Hundhausen, Christian; Barinaga, Guillermo; Kassen, Deepika; Williams, Andrew E; Mirza, Muddassar M; Balazs, Mercedesz; Wang, Xiaoting; Rodriguez, Robert Sanchez; Alendar, Andrej; Barker, Jonathan; Tsoka, Sophia; Ouyang, Wenjun; Nestle, Frank O

    2014-02-12

    Cytokines are critical checkpoints of inflammation. The treatment of human autoimmune disease has been revolutionized by targeting inflammatory cytokines as key drivers of disease pathogenesis. Despite this, there exist numerous pitfalls when translating preclinical data into the clinic. We developed an integrative biology approach combining human disease transcriptome data sets with clinically relevant in vivo models in an attempt to bridge this translational gap. We chose interleukin-22 (IL-22) as a model cytokine because of its potentially important proinflammatory role in epithelial tissues. Injection of IL-22 into normal human skin grafts produced marked inflammatory skin changes resembling human psoriasis. Injection of anti-IL-22 monoclonal antibody in a human xenotransplant model of psoriasis, developed specifically to test potential therapeutic candidates, efficiently blocked skin inflammation. Bioinformatic analysis integrating both the IL-22 and anti-IL-22 cytokine transcriptomes and mapping them onto a psoriasis disease gene coexpression network identified key cytokine-dependent hub genes. Using knockout mice and small-molecule blockade, we show that one of these hub genes, the so far unexplored serine/threonine kinase PIM1, is a critical checkpoint for human skin inflammation and potential future therapeutic target in psoriasis. Using in silico integration of human data sets and biological models, we were able to identify a new target in the treatment of psoriasis.

  20. Site-Specific Integration of Exogenous Genes Using Genome Editing Technologies in Zebrafish

    Directory of Open Access Journals (Sweden)

    Atsuo Kawahara

    2016-05-01

    Full Text Available The zebrafish (Danio rerio is an ideal vertebrate model to investigate the developmental molecular mechanism of organogenesis and regeneration. Recent innovation in genome editing technologies, such as zinc finger nucleases (ZFNs, transcription activator-like effector nucleases (TALENs and the clustered regularly interspaced short palindromic repeats (CRISPR/CRISPR associated protein 9 (Cas9 system, have allowed researchers to generate diverse genomic modifications in whole animals and in cultured cells. The CRISPR/Cas9 and TALEN techniques frequently induce DNA double-strand breaks (DSBs at the targeted gene, resulting in frameshift-mediated gene disruption. As a useful application of genome editing technology, several groups have recently reported efficient site-specific integration of exogenous genes into targeted genomic loci. In this review, we provide an overview of TALEN- and CRISPR/Cas9-mediated site-specific integration of exogenous genes in zebrafish.

  1. 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

  2. Renton's Quendall Terminals on List of EPA Superfund Sites Targeted for Immediate, Intense Attention

    Science.gov (United States)

    EPA released the list of Superfund sites that Administrator Pruitt has targeted for intense and immediate attention, including the Quendall Terminals Site, a former creosote facility on the shore of Lake Washington in Renton, Washington.

  3. CERCLA integration with site operations the Fernald experience

    International Nuclear Information System (INIS)

    Coyle, S.W.; Shirley, R.S.; Varchol, B.D.

    1991-01-01

    A major transition in the Fernald Environmental Management Project (FEMP) site mission has occurred over the past few years. The production capabilities formally provided by the FEMP are being transferred to private industry through a vendor qualification program. Environmental compliance and site cleanup are now the primary focus. In line with this program, the production of uranium products at the site was suspended in July 1989 in order to concentrate resources on the environmental mission. Formal termination of the FEMP production mission was accomplished on June 19, 1991. Environmental issues such as stored inventories of process residues materials and equipment are being addressed under the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA). The diversity of these hazards complicates the strategic planning for an integrated site cleanup program. This paper will discuss the programmatic approach which is being implemented to ensure activities such as waste management, site utility and support services, health and safety programs, and Resource Conservation and Recovery Act (RCRA) programs are being integrated with CERCLA. 6 figs., 3 tabs

  4. Integration of Environmental Compliance at the Savannah River Site - 13024

    Energy Technology Data Exchange (ETDEWEB)

    Hoel, David [United States Department of Energy - Savannah River Operations Office (United States); Griffith, Michael [Savannah River Nuclear Solutions, LLC (United States)

    2013-07-01

    The Savannah River Site (SRS) is a large federal installation hosting diverse missions and multiple organizations with competing regulatory needs. Accordingly, there was a need to integrate environmental compliance strategies to ensure the consistent flow of information between Department of Energy-Savannah River (DOE-SR), the regulatory agencies and other interested parties. In order to meet this objective, DOE and major SRS contractors and tenants have committed to a strategy of collaboratively working together to ensure that a consistent, integrated, and fully coordinated approach to environmental compliance and regulator relationships is maintained. DOE-SR and Savannah River Nuclear Solutions, LLC, the SRS management and operations contractor, have established an environmental compliance integration process that provides for the consistent flow down of requirements to projects, facilities, SRS contractors, and subcontractors as well as the upward flow of information to assist in the early identification and resolution of environmental regulatory issues and enhancement of compliance opportunities. In addition, this process strongly fosters teamwork to collaboratively resolve complex regulatory challenges, promote pollution prevention and waste minimization opportunities to advance site missions in a manner that balances near-term actions with the long-term site vision, while being protective of human health and the environment. Communication tools are being utilized, some with enhancements, to ensure appropriate information is communicated to all levels with environmental responsibility at SRS. SRS internal regulatory integration is accomplished through a variety of informational exchange forums (e.g., Challenges, Opportunities and Resolution (COR) Team, DOE's Joint Site Regulatory Integration Team, and the Senior Environmental Managers Council (SEMC)). SRS communications and problem-solving with the regulatory agencies have been enhanced through formation

  5. Integration of Environmental Compliance at the Savannah River Site - 13024

    International Nuclear Information System (INIS)

    Hoel, David; Griffith, Michael

    2013-01-01

    The Savannah River Site (SRS) is a large federal installation hosting diverse missions and multiple organizations with competing regulatory needs. Accordingly, there was a need to integrate environmental compliance strategies to ensure the consistent flow of information between Department of Energy-Savannah River (DOE-SR), the regulatory agencies and other interested parties. In order to meet this objective, DOE and major SRS contractors and tenants have committed to a strategy of collaboratively working together to ensure that a consistent, integrated, and fully coordinated approach to environmental compliance and regulator relationships is maintained. DOE-SR and Savannah River Nuclear Solutions, LLC, the SRS management and operations contractor, have established an environmental compliance integration process that provides for the consistent flow down of requirements to projects, facilities, SRS contractors, and subcontractors as well as the upward flow of information to assist in the early identification and resolution of environmental regulatory issues and enhancement of compliance opportunities. In addition, this process strongly fosters teamwork to collaboratively resolve complex regulatory challenges, promote pollution prevention and waste minimization opportunities to advance site missions in a manner that balances near-term actions with the long-term site vision, while being protective of human health and the environment. Communication tools are being utilized, some with enhancements, to ensure appropriate information is communicated to all levels with environmental responsibility at SRS. SRS internal regulatory integration is accomplished through a variety of informational exchange forums (e.g., Challenges, Opportunities and Resolution (COR) Team, DOE's Joint Site Regulatory Integration Team, and the Senior Environmental Managers Council (SEMC)). SRS communications and problem-solving with the regulatory agencies have been enhanced through formation of an

  6. Common integration sites of published datasets identified using a graph-based framework

    Directory of Open Access Journals (Sweden)

    Alessandro Vasciaveo

    2016-01-01

    Full Text Available With next-generation sequencing, the genomic data available for the characterization of integration sites (IS has dramatically increased. At present, in a single experiment, several thousand viral integration genome targets can be investigated to define genomic hot spots. In a previous article, we renovated a formal CIS analysis based on a rigid fixed window demarcation into a more stretchy definition grounded on graphs. Here, we present a selection of supporting data related to the graph-based framework (GBF from our previous article, in which a collection of common integration sites (CIS was identified on six published datasets. In this work, we will focus on two datasets, ISRTCGD and ISHIV, which have been previously discussed. Moreover, we show in more detail the workflow design that originates the datasets.

  7. Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies

    Science.gov (United States)

    2017-10-01

    prostate cancer . Cancer Res 70: 7992-8002, 2010 8. Nelson PS: Molecular states underlying an- drogen receptor activation: A framework for thera- peutics...targeting androgen signaling in prostate cancer . J Clin Oncol 30:644-646, 2012 9. Thadani-Mulero M, Nanus DM, Giannakakou P: Androgen receptor on the... prostate cancer . Clin Cancer Res 21:795-807, 2015 17. van Soest RJ, de Morrée ES, Kweldam CF, et al: Targeting the androgen receptor confers in vivo

  8. Integrated approach to planning the remediation of sites undergoing decommissioning

    International Nuclear Information System (INIS)

    2009-01-01

    Responding to the needs of Member States, the IAEA has launched an environmental remediation guidance initiative dealing with the issues of radioactive contamination world wide. Its aim is to collate and disseminate information concerning the key issues affecting environmental remediation of contaminated sites. This IAEA initiative includes the development of documents that report on remediation technologies available, best practices, and information and guidance concerning (a) Strategy development for environmental remediation; (b) Characterization and remediation of contaminated sites and contaminated groundwater; (c) Management of waste and residues from mining and milling of uranium and thorium; (d) Decommissioning of buildings; (e) A database for contaminated sites. The subject of this present report concerns the integration of decommissioning and remediation activities at sites undergoing decommissioning and this fits within the first category of guidance documentation (strategy development). This document addresses key strategic planning issues. It is intended to provide practical advice and complement other reports that focus on decommissioning and remediation at nuclear facilities. The document is designed to encourage site remediation activities that take advantage of synergies with decommissioning in order to reduce the duplication of effort by various parties and minimize adverse impacts on human health, the environment, and costs through the transfer of experience and knowledge. To achieve this objective, the document is designed to help Member States gain perspective by summarizing available information about synergies between decommissioning and remediation, strategic planning and project management and planning tools and techniques to support decision making and remediation. Case studies are also presented as to give concrete examples of the theoretical elements elaborated in the documents. This publication investigates the potential synergies

  9. Multi-target electrochemical biosensing enabled by integrated CMOS electronics

    International Nuclear Information System (INIS)

    Rothe, J; Lewandowska, M K; Heer, F; Frey, O; Hierlemann, A

    2011-01-01

    An integrated electrochemical measurement system, based on CMOS technology, is presented, which allows the detection of several analytes in parallel (multi-analyte) and enables simultaneous monitoring at different locations (multi-site). The system comprises a 576-electrode CMOS sensor chip, an FPGA module for chip control and data processing, and the measurement laptop. The advantages of the highly versatile system are demonstrated by two applications. First, a label-free, hybridization-based DNA sensor is enabled by the possibility of large-scale integration in CMOS technology. Second, the detection of the neurotransmitter choline is presented by assembling the chip with biosensor microprobe arrays. The low noise level enables a limit of detection of, e.g., 0.3 µM choline. The fully integrated system is self-contained: it features cleaning, functionalization and measurement functions without the need for additional electrical equipment. With the power supplied by the laptop, the system is very suitable for on-site measurements

  10. Integrated Patient Education on U.S. Hospital Web Sites.

    Science.gov (United States)

    Huang, Edgar; Wu, Kerong; Edwards, Kelsey

    2016-01-01

    Based on a census of the 2015 Most Wired Hospitals, this content analysis aimed to find out how patient education has been integrated on these best IT hospitals' Web sites to serve the purposes of marketing and meeting online visitors' needs. This study will help hospitals to understand where the weaknesses are in their interactive patient education implementation and come up with a smart integration strategy. The study found that 70% of these hospitals had adopted interactive patient education contents, 76.6% of such contents were from a third-party developer, and only 20% of the hospitals linked their patient education contents to one or more of the hospital's resources while 26% cross-references such contents. The authors concluded that more hospitals should take advantage of modern information communication technology to cross-reference their patient education contents and to integrate such contents into their overall online marketing strategy to benefit patients and themselves.

  11. Lessons learned in the implementation of Integrated Safety Management at DOE Order Compliance Sites vs Necessary and Sufficient Sites

    International Nuclear Information System (INIS)

    Hill, R.L.

    2000-01-01

    This paper summarizes the development and implementation of Integrated Safety Management (ISM) at an Order Compliance Site (Savannah River Site) and a Necessary and Sufficient Site (Nevada Test Site). A discussion of each core safety function of ISM is followed by an example from an Order Compliance Site and a Necessary and Sufficient Site. The Savannah River Site was the first DOE site to have a DOE Headquarters-validated and approved ISM System. The NTS is beginning the process of verification and validation. This paper defines successful strategies for integrating Environment, Safety, and Health management into work under various scenarios

  12. Integration of HIV in the Human Genome: Which Sites Are Preferential? A Genetic and Statistical Assessment

    Science.gov (United States)

    Gonçalves, Juliana; Moreira, Elsa; Sequeira, Inês J.; Rodrigues, António S.; Rueff, José; Brás, Aldina

    2016-01-01

    Chromosomal fragile sites (FSs) are loci where gaps and breaks may occur and are preferential integration targets for some viruses, for example, Hepatitis B, Epstein-Barr virus, HPV16, HPV18, and MLV vectors. However, the integration of the human immunodeficiency virus (HIV) in Giemsa bands and in FSs is not yet completely clear. This study aimed to assess the integration preferences of HIV in FSs and in Giemsa bands using an in silico study. HIV integration positions from Jurkat cells were used and two nonparametric tests were applied to compare HIV integration in dark versus light bands and in FS versus non-FS (NFSs). The results show that light bands are preferential targets for integration of HIV-1 in Jurkat cells and also that it integrates with equal intensity in FSs and in NFSs. The data indicates that HIV displays different preferences for FSs compared to other viruses. The aim was to develop and apply an approach to predict the conditions and constraints of HIV insertion in the human genome which seems to adequately complement empirical data. PMID:27294106

  13. Efficient site-specific integration in Plasmodium falciparum chromosomes mediated by mycobacteriophage Bxb1 integrase.

    Science.gov (United States)

    Nkrumah, Louis J; Muhle, Rebecca A; Moura, Pedro A; Ghosh, Pallavi; Hatfull, Graham F; Jacobs, William R; Fidock, David A

    2006-08-01

    Here we report an efficient, site-specific system of genetic integration into Plasmodium falciparum malaria parasite chromosomes. This is mediated by mycobacteriophage Bxb1 integrase, which catalyzes recombination between an incoming attP and a chromosomal attB site. We developed P. falciparum lines with the attB site integrated into the glutaredoxin-like cg6 gene. Transfection of these attB(+) lines with a dual-plasmid system, expressing a transgene on an attP-containing plasmid together with a drug resistance gene and the integrase on a separate plasmid, produced recombinant parasites within 2 to 4 weeks that were genetically uniform for single-copy plasmid integration. Integrase-mediated recombination resulted in proper targeting of parasite proteins to intra-erythrocytic compartments, including the apicoplast, a plastid-like organelle. Recombinant attB x attP parasites were genetically stable in the absence of drug and were phenotypically homogeneous. This system can be exploited for rapid genetic integration and complementation analyses at any stage of the P. falciparum life cycle, and it illustrates the utility of Bxb1-based integrative recombination for genetic studies of intracellular eukaryotic organisms.

  14. Accelerated Homology-Directed Targeted Integration of Transgenes in Chinese Hamster Ovary Cells Via CRISPR/Cas9 and Fluorescent Enrichment

    DEFF Research Database (Denmark)

    Lee, Jae Seong; Grav, Lise Marie; Pedersen, Lasse Ebdrup

    2016-01-01

    Targeted gene integration into site-specific loci can be achieved in Chinese hamster ovary (CHO) cells via CRISPR/Cas9 genome editing technology and the homology-directed repair (HDR) pathway. The low efficiency of HDR often requires antibiotic selection, which limits targeted integration...

  15. Target Site Recognition by a Diversity-Generating Retroelement

    OpenAIRE

    Guo, Huatao; Tse, Longping V.; Nieh, Angela W.; Czornyj, Elizabeth; Williams, Steven; Oukil, Sabrina; Liu, Vincent B.; Miller, Jeff F.

    2011-01-01

    Diversity-generating retroelements (DGRs) are in vivo sequence diversification machines that are widely distributed in bacterial, phage, and plasmid genomes. They function to introduce vast amounts of targeted diversity into protein-encoding DNA sequences via mutagenic homing. Adenine residues are converted to random nucleotides in a retrotransposition process from a donor template repeat (TR) to a recipient variable repeat (VR). Using the Bordetella bacteriophage BPP-1 element as a prototype...

  16. Carbon tetrachloride contamination, 200 West Area, Hanford Site: Arid Site Integrated Demonstration for remediation of volatile organic compounds

    International Nuclear Information System (INIS)

    Last, G.V.; Rohay, V.J.

    1991-01-01

    The Arid State Integrated Demonstration is a US Department of Energy (DOE) program targeted at the acquisition, development, demonstration, and deployment of technologies for evaluation and cleanup of volatile organic and associated contaminants in soils and ground waters. Several DOE laboratories, universities, and industry will participate in the program. Candidate technologies will be demonstrated in the areas of site characterization; performance prediction, monitoring, and evaluations; contaminant extraction and ex situ treatment; in situ remediations; and site closure and monitoring. The performance of these demonstrated technologies will be compared to baseline technologies and documented to promote the transfer of new technologies to industry for use at DOE facilities. The initial host site is the Hanford Site's 200 West Area. The location of the demonstration contains primarily carbon tetrachloride (CCl 4 ), chloroform, and a variety of associated mixed waste contaminants. Chemical processes used to recover and purify plutonium at Hanford's plutonium finishing plant (Z Plant) resulted in the production of actinide-bearing waste liquid. Both aqueous and organic liquid wastes were generated, and were routinely discharged to subsurface disposal facilities. The primary radionuclide in the waste streams was plutonium, and the primary organic was CCl 4 . This paper contains brief descriptions of the principal CCl 4 waste disposal facilities in Hanford's 200 West Area, associated hydrogeology, existing information on the extent of soil and ground-water contamination, and a conceptual outline of suspected subsurface CCl 4 distributions

  17. SITE-94. Discrete-feature modelling of the Aespoe site: 2. Development of the integrated site-scale model

    Energy Technology Data Exchange (ETDEWEB)

    Geier, J.E. [Golder Associates AB, Uppsala (Sweden)

    1996-12-01

    A 3-dimensional, discrete-feature hydrological model is developed. The model integrates structural and hydrologic data for the Aespoe site, on scales ranging from semi regional fracture zones to individual fractures in the vicinity of the nuclear waste canisters. Hydrologic properties of the large-scale structures are initially estimated from cross-hole hydrologic test data, and automatically calibrated by numerical simulation of network flow, and comparison with undisturbed heads and observed drawdown in selected cross-hole tests. The calibrated model is combined with a separately derived fracture network model, to yield the integrated model. This model is partly validated by simulation of transient responses to a long-term pumping test and a convergent tracer test, based on the LPT2 experiment at Aespoe. The integrated model predicts that discharge from the SITE-94 repository is predominantly via fracture zones along the eastern shore of Aespoe. Similar discharge loci are produced by numerous model variants that explore uncertainty with regard to effective semi regional boundary conditions, hydrologic properties of the site-scale structures, and alternative structural/hydrological interpretations. 32 refs.

  18. SITE-94. Discrete-feature modelling of the Aespoe site: 2. Development of the integrated site-scale model

    International Nuclear Information System (INIS)

    Geier, J.E.

    1996-12-01

    A 3-dimensional, discrete-feature hydrological model is developed. The model integrates structural and hydrologic data for the Aespoe site, on scales ranging from semi regional fracture zones to individual fractures in the vicinity of the nuclear waste canisters. Hydrologic properties of the large-scale structures are initially estimated from cross-hole hydrologic test data, and automatically calibrated by numerical simulation of network flow, and comparison with undisturbed heads and observed drawdown in selected cross-hole tests. The calibrated model is combined with a separately derived fracture network model, to yield the integrated model. This model is partly validated by simulation of transient responses to a long-term pumping test and a convergent tracer test, based on the LPT2 experiment at Aespoe. The integrated model predicts that discharge from the SITE-94 repository is predominantly via fracture zones along the eastern shore of Aespoe. Similar discharge loci are produced by numerous model variants that explore uncertainty with regard to effective semi regional boundary conditions, hydrologic properties of the site-scale structures, and alternative structural/hydrological interpretations. 32 refs

  19. Hanford Site waste management and environmental restoration integration plan

    International Nuclear Information System (INIS)

    Merrick, D.L.

    1990-01-01

    The ''Hanford Site Waste Management and Environmental Restoration Integration Plan'' describes major actions leading to waste disposal and site remediation. The primary purpose of this document is to provide a management tool for use by executives who need to quickly comprehend the waste management and environmental restoration programs. The Waste Management and Environmental Restoration Programs have been divided into missions. Waste Management consists of five missions: double-shell tank (DST) wastes; single-shell tank (SST) wastes (surveillance and interim storage, stabilization, and isolation); encapsulated cesium and strontium; solid wastes; and liquid effluents. Environmental Restoration consists of two missions: past practice units (PPU) (including characterization and assessment of SST wastes) and surplus facilities. For convenience, both aspects of SST wastes are discussed in one place. A general category of supporting activities is also included. 20 refs., 14 figs., 7 tabs

  20. Opportunities for Launch Site Integrated System Health Engineering and Management

    Science.gov (United States)

    Waterman, Robert D.; Langwost, Patricia E.; Waterman, Susan J.

    2005-01-01

    The launch site processing flow involves operations such as functional verification, preflight servicing and launch. These operations often include hazards that must be controlled to protect human life and critical space hardware assets. Existing command and control capabilities are limited to simple limit checking durig automated monitoring. Contingency actions are highly dependent on human recognition, decision making, and execution. Many opportunities for Integrated System Health Engineering and Management (ISHEM) exist throughout the processing flow. This paper will present the current human-centered approach to health management as performed today for the shuttle and space station programs. In addition, it will address some of the more critical ISHEM needs, and provide recommendations for future implementation of ISHEM at the launch site.

  1. Integrated account of method, site selection and programme prior to the site investigation phase

    International Nuclear Information System (INIS)

    2000-12-01

    In order to dispose of the spent nuclear fuel in a safe manner, SKB plans to site a deep repository and an encapsulation plant with associated canister fabrication and transportation system. After an integrated evaluation of feasibility studies and other material, SKB will proceed with investigations of the rock and studies regarding establishment of the deep disposal system in the municipality of Oskarshamn or in Northern Uppland. The plans also include further study of the prospects for a deep repository in the municipality of Nykoeping. In the municipality of Oskarshamn, SKB plans further studies of a siting of the deep repository at Simpevarp. There SKB wants to initiate site investigations with test drilling. For the encapsulation plant, SKB wants to continue studying a siting at CLAB. In Northern Uppland, SKB plans to study two siting alternatives for the deep repository. One is Forsmark in the municipality of Oesthammar, where SKB wants to initiate a site investigation with test drilling. The other is Tierp north of Skutskaer, where SKB intends to start test drilling in an area north of Tierp. First, however, a suitable drilling area with possible transport solutions needs to be defined. This alternative requires the participation of the municipalities of both Tierp and Aelvkarleby. A siting of the encapsulation plant in Northern Uppland will also be studied. For the municipality of Nykoeping, SKB plans to conduct a new safety assessment for the Fjaellveden area, based on data from previous investigations as well as additional studies of how a deep repository could be arranged. SKB will thereby gather data from yet another geographic and geological region beyond those that are prioritized. No test drilling is planned in Nykoeping. The goal of the site investigation phase is to obtain all permits needed to build the planned facilities. It will take an estimated 7 - 8 years to assemble the requisite supporting material, carry out consultations, compile siting

  2. Hanford and Savannah River Site Programmatic and Technical Integration

    International Nuclear Information System (INIS)

    Ramsey, William Gene

    2013-01-01

    Abstract only. The Hanford Site and the Savannah River Site (SRS) were the primary plutonium production facilities within the U.S. nuclear weapons complex. Radioactive wastes were generated as part of these missions and are stored in similar fashion. The majority of radioactivity maintained by the two sites is located in underground carbon steel tanks in the physical form of supernatant, saltcake, or sludge. Disposition of SRS tank waste is ongoing by converting it into glass (pathway for sludge and radionuclides separated from supernatant or dissolved saltcake) or cement (pathway for the decontaminated supernatant and dissolved saltcake). Tank closure activity has also begun at SRS and will continue for the duration of mission. The Hanford tank waste inventory is roughly 2/3rds larger than SRS's by volume- but nominally half the radioactivity. The baseline disposition path includes high-level and low-activity waste vitrification with separate disposition of contact-handled transuranic tank waste. Retrieval of tank waste from aging single shell tanks (SSTs) into double-shell tanks (DSTs) is currently ongoing. As vitrification commences later this decade, Hanford will be in a similar operations mode as SRS. Site integration is increasing as the missions align. The ongoing integration is centered on key issues that impact both sites- regardless of mission timeframe. Three recent workshop exchanges have been held to improve communication with the primary intent of improving operations and technical work organization. The topics of these workshops are as follows: DST space utilization, optimization, and closure; Waste Feed Qualification; and, Cementitious Waste Forms. Key goals for these and future exchanges include aligning research and technology, preparing for joint initiatives (to maximize budgetary value for the customer), and reviewing lessons learned. Each site has played a leading role in the development of technology and operational practices that can be used

  3. Target sites for chemical regulation of strigolactone signaling

    Directory of Open Access Journals (Sweden)

    Hidemitsu eNakamura

    2014-11-01

    Full Text Available Demands for plant growth regulators (chemicals that control plant growth are increasing globally, especially in developing countries. Both positive and negative plant growth regulators are widely used to enhance crop production and to suppress unwanted shoot growth, respectively. Strigolactones (SLs are multifunctional molecules that function as phytohormones, inhibiting shoot branching and also functioning in the rhizospheric communication with symbiotic fungi and parasitic weeds. Therefore, it is anticipated that chemicals that regulate the functions of SLs will be widely used in agricultural applications. Although the SL biosynthetic pathway is not fully understood, it has been demonstrated that beta-carotene isomerases, carotenoid cleavage dioxygenases (CCDs, and a cytochrome P450 monooxygenase are involved in strigolactone biosynthesis. A CCD inhibitor, abamine, which is also an inhibitor of abscisic acid biosynthesis, reduces the levels of SL in several plant species and reduces the germination rate of Orobanche minor seeds grown with tobacco. On the basis of the structure of abamine, several chemicals have been designed to specifically inhibit CCDs during SL synthesis. Cytochrome P450 monooxygenase is another target enzyme in the development of SL biosynthesis inhibitors, and the triazole-derived TIS series of chemicals is known to include SL biosynthesis inhibitors, although their target enzyme has not been identified. Recently, DWARF14 (D14 has been shown to be a receptor for SLs, and the D-ring moiety of SL is essential for its recognition by D14. A variety of SL agonists are currently under development and most agonists commonly contain the D-ring or a D-ring-like moiety. Several research groups have also resolved the crystal structure of D14 in the last two years. It is expected that this information on the D14 structure will be invaluable not only for developing SL agonists with novel structures but also in the design of inhibitors

  4. Integration sites of Epstein-Barr virus genome on chromosomes of human lymphoblastoid cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Wuu, K.D.; Chen, Y.J.; Wang-Wuu, S. [Institute of Genetics, Taipei (Taiwan, Province of China)

    1994-09-01

    Epstein-Barr virus (EBV) is the pathogen of infectious mononucleosis. The viral genome is present in more than 95% of the African cases of Burkitt lymphoma and it is usually maintained in episomal form in the tumor cells. Viral integration has been described only for Nanalwa which is a Burkitt lymphoma cell line lacking episomes. In order to examine the role of EBV in the immortalization of human Blymphocytes, we investigated whether the EBV integration into the human genome is essential. If the integration does occur, we would like to know whether the integration is randomly distributed or whether the viral DNA integrates preferentially at certain sites. Fourteen in vitro immortalized human lymphoblastoid cell lines (LCLs) were examined by fluorescence in situ hybridization (FISH) with a biotinylated EBV BamHI w DNA fragment as probe. The episomal form of EBV DNA was found in all cells of these cell lines, while only about 65% of the cells have the integrated viral DNA. This might suggest that integration is not a pre-requisite for cell immortalization. Although all chromosomes, except Y, have been found with integrated viral genome, chromsomes 1 and 5 are the most frequent EBV DNA carrier (p<0.05). Nine chromosome bands, namely, 1p31, 1q31, 2q32, 3q13, 3q26, 5q14, 6q24, 7q31 and 12q21, are preferential targets for EBV integration (p<0.001). Eighty percent of the total 938 EBV hybridization signals were found to be at G-band-positive area. This suggests that the mechanism of EBV integration might be different from that of the retroviruses, which specifically integrate to G-band-negative areas. Thus, we conclude that the integration of EBV to host genome is non-random and it may have something to do with the structure of chromosome and DNA sequences.

  5. Automating an integrated spatial data-mining model for landfill site selection

    Science.gov (United States)

    Abujayyab, Sohaib K. M.; Ahamad, Mohd Sanusi S.; Yahya, Ahmad Shukri; Ahmad, Siti Zubaidah; Aziz, Hamidi Abdul

    2017-10-01

    An integrated programming environment represents a robust approach to building a valid model for landfill site selection. One of the main challenges in the integrated model is the complicated processing and modelling due to the programming stages and several limitations. An automation process helps avoid the limitations and improve the interoperability between integrated programming environments. This work targets the automation of a spatial data-mining model for landfill site selection by integrating between spatial programming environment (Python-ArcGIS) and non-spatial environment (MATLAB). The model was constructed using neural networks and is divided into nine stages distributed between Matlab and Python-ArcGIS. A case study was taken from the north part of Peninsular Malaysia. 22 criteria were selected to utilise as input data and to build the training and testing datasets. The outcomes show a high-performance accuracy percentage of 98.2% in the testing dataset using 10-fold cross validation. The automated spatial data mining model provides a solid platform for decision makers to performing landfill site selection and planning operations on a regional scale.

  6. Integrative Bioinformatics Approaches for Identification of Drug Targets in Hypertension.

    Science.gov (United States)

    Hemerich, Daiane; van Setten, Jessica; Tragante, Vinicius; Asselbergs, Folkert W

    2018-01-01

    High blood pressure or hypertension is an established risk factor for a myriad of cardiovascular diseases. Genome-wide association studies have successfully found over nine hundred loci that contribute to blood pressure. However, the mechanisms through which these loci contribute to disease are still relatively undetermined as less than 10% of hypertension-associated variants are located in coding regions. Phenotypic cell-type specificity analyses and expression quantitative trait loci show predominant vascular and cardiac tissue involvement for blood pressure-associated variants. Maps of chromosomal conformation and expression quantitative trait loci (eQTL) in critical tissues identified 2,424 genes interacting with blood pressure-associated loci, of which 517 are druggable. Integrating genome, regulome and transcriptome information in relevant cell-types could help to functionally annotate blood pressure associated loci and identify drug targets.

  7. Spallation Neutron Source Second Target Station Integrated Systems Update

    Energy Technology Data Exchange (ETDEWEB)

    Ankner, John Francis [ORNL; An, Ke [ORNL; Blokland, Willem [ORNL; Charlton, Timothy R. [ORNL; Coates, Leighton [ORNL; Dayton, Michael J. [ORNL; Dean, Robert A. [ORNL; Dominguez-Ontiveros, Elvis E. [ORNL; Ehlers, Georg [ORNL; Gallmeier, Franz X. [ORNL; Graves, Van B. [ORNL; Heller, William T. [ORNL; Holmes, Jeffrey A. [ORNL; Huq, Ashfia [ORNL; Lumsden, Mark D. [ORNL; McHargue, William M. [ORNL; McManamy, Thomas J. [ORNL; Plum, Michael A. [ORNL; Rajic, Slobodan [ORNL; Remec, Igor [ORNL; Robertson, Lee [ORNL; Sala, Gabriele [ORNL; Stoica, Alexandru Dan [ORNL; Trotter, Steven M. [ORNL; Winn, Barry L. [ORNL; Abudureyimu, Reheman [ORNL; Rennich, Mark J. [ORNL; Herwig, Kenneth W. [ORNL

    2017-04-01

    The Spallation Neutron Source (SNS) was designed from the beginning to accommodate both an accelerator upgrade to increase the proton power and a second target station (STS). Four workshops were organized in 2013 and 2014 to identify key science areas and challenges where neutrons will play a vital role [1-4]. Participants concluded that the addition of STS to the existing ORNL neutron sources was needed to complement the strengths of High Flux Isotope Reactor (HFIR) and the SNS first target station (FTS). To address the capability gaps identified in the workshops, a study was undertaken to identify instrument concepts that could provide the required new science capabilities. The study outlined 22 instrument concepts and presented an initial science case for STS [5]. These instrument concepts formed the basis of a planning suite of instruments whose requirements determined an initial site layout and moderator selection. An STS Technical Design Report (TDR) documented the STS concept based on those choices [6]. Since issue of the TDR, the STS concept has significantly matured as described in this document.

  8. Demonstration of Eastman Christensen horizontal drilling system -- Integrated Demonstration Site, Savannah River Site

    International Nuclear Information System (INIS)

    1992-12-01

    An innovative horizontal drilling system was used to install two horizontal wells as part of an integrated demonstration project at the Savannah River Site (SRS), Aiken, South Carolina. The SRS is located in south-central South Carolina in the upper Coastal Plain physiographic province. The demonstration site is located near the A/M Area, and is currently known as the Integated Demonstration Site. The Department of Energy's Office of Technology Development initiated an integrated demonstration of innovative technologies for cleanup of volatile organic compounds (VOCS) in soils and groundwater at the SRS in 1989. The overall goal of the program is to demonstrate, at a single location, multiple technologies in the fields of drilling, characterization, monitoring, and remediation. Innovative technologies are compared to one another and to baseline technologies in terms of technical performance and cost effectiveness. Transfer of successfully demonstrated technologies and systems to DOE environmental restoration organizations, to other government agencies, and to industry is a critical part of the program

  9. IFMIF target and test cell - design and integration

    International Nuclear Information System (INIS)

    Heinzel, V.

    2007-01-01

    and shielding and material mutations - Pressure loss and heat transfer for helium cooling in mini channels like in the HFTM and jet cooling for the MFTM - Code for an automatic transfer of the CAD designs to the Monte Carlo code - Calculation for the lithium flow within the nozzle and the target During the 6 years ''Engineering Validation Engineering Design Activity'' phase carried out within the frame of the Broader Approach, FZK has major responsibilities in the design of TTC, in the validation of the helium cooling systems and in various design integration activities. The presentation will give an overview on the design tools, the state of the art of the miniaturised specimens and the design integration during EVEDA. (orig.)

  10. Site-Wide Integrated Water Monitoring - Defining and Implementing Sampling Objectives to Support Site Closure - 13060

    International Nuclear Information System (INIS)

    Wilborn, Bill; Knapp, Kathryn; Farnham, Irene; Marutzky, Sam

    2013-01-01

    The Underground Test Area (UGTA) activity is responsible for assessing and evaluating the effects of the underground nuclear weapons tests on groundwater at the Nevada National Security Site (NNSS), formerly the Nevada Test Site (NTS), and implementing a corrective action closure strategy. The UGTA strategy is based on a combination of characterization, modeling studies, monitoring, and institutional controls (i.e., monitored natural attenuation). The closure strategy verifies through appropriate monitoring activities that contaminants of concern do not exceed the SDWA at the regulatory boundary and that adequate institutional controls are established and administered to ensure protection of the public. Other programs conducted at the NNSS supporting the environmental mission include the Routine Radiological Environmental Monitoring Program (RREMP), Waste Management, and the Infrastructure Program. Given the current programmatic and operational demands for various water-monitoring activities at the same locations, and the ever-increasing resource challenges, cooperative and collaborative approaches to conducting the work are necessary. For this reason, an integrated sampling plan is being developed by the UGTA activity to define sampling and analysis objectives, reduce duplication, eliminate unnecessary activities, and minimize costs. The sampling plan will ensure the right data sets are developed to support closure and efficient transition to long-term monitoring. The plan will include an integrated reporting mechanism for communicating results and integrating process improvements within the UGTA activity as well as between other U.S. Department of Energy (DOE) Programs. (authors)

  11. Repair of oxidative DNA base damage in the host genome influences the HIV integration site sequence preference.

    Directory of Open Access Journals (Sweden)

    Geoffrey R Bennett

    Full Text Available Host base excision repair (BER proteins that repair oxidative damage enhance HIV infection. These proteins include the oxidative DNA damage glycosylases 8-oxo-guanine DNA glycosylase (OGG1 and mutY homolog (MYH as well as DNA polymerase beta (Polβ. While deletion of oxidative BER genes leads to decreased HIV infection and integration efficiency, the mechanism remains unknown. One hypothesis is that BER proteins repair the DNA gapped integration intermediate. An alternative hypothesis considers that the most common oxidative DNA base damages occur on guanines. The subtle consensus sequence preference at HIV integration sites includes multiple G:C base pairs surrounding the points of joining. These observations suggest a role for oxidative BER during integration targeting at the nucleotide level. We examined the hypothesis that BER repairs a gapped integration intermediate by measuring HIV infection efficiency in Polβ null cell lines complemented with active site point mutants of Polβ. A DNA synthesis defective mutant, but not a 5'dRP lyase mutant, rescued HIV infection efficiency to wild type levels; this suggested Polβ DNA synthesis activity is not necessary while 5'dRP lyase activity is required for efficient HIV infection. An alternate hypothesis that BER events in the host genome influence HIV integration site selection was examined by sequencing integration sites in OGG1 and MYH null cells. In the absence of these 8-oxo-guanine specific glycosylases the chromatin elements of HIV integration site selection remain the same as in wild type cells. However, the HIV integration site sequence preference at G:C base pairs is altered at several positions in OGG1 and MYH null cells. Inefficient HIV infection in the absence of oxidative BER proteins does not appear related to repair of the gapped integration intermediate; instead oxidative damage repair may participate in HIV integration site preference at the sequence level.

  12. Commercial integration and partnering at Savannah River Site

    Energy Technology Data Exchange (ETDEWEB)

    Steele, J.R. [Westinghouse Savannah River Co., Aiken, SC (United States); Babione, R.A.; Shikashio, L.A.; Wacaster, A.J.; Paterson, A.D. [SCIENTECH, Inc., Idaho Falls, ID (United States)

    1994-06-01

    Savannah River Site (SRS), particularly the Savannah River Technology Center (SRTC) with the experience from the first successful Integrated Technology Demonstration, can provide an excellent foundation for meeting DOE-EM`s objectives with the new DOE-EM five focus area approach. With this in mind, SRTC established an activity to pursue full commercialization of environmental technologies. This report is an assessment of the status of commercialization at SRS and provides recommendations for enhancement as well as some tools critical to implementation. A review was made of the current situation at SRS with regards to taking technology development to commercial fruition. This was done from the perspective of comparing it to known commercialization models and processes. It was found that SRTC already works through many of the steps in these processes. With integration and action-oriented efforts of the inclusion of business and market factors, SRTC could become an aggressive, successful developer of commercialized technologies. Commercial success criteria tools were developed with regards to integrating them with SRTC selection criteria to ensure that all critical factors are covered in technology commercialization project evaluations. Private investors are very clear that their interest lies in funding commercial enterprises, not merely technologies. Mobilizing private capital is critical to real job growth and long-term economic development. Also, potential industry partners were identified that are willing to be involved with SRS` technology applications and regional development efforts. As another important component to success, regional support organizations were reviewed and evaluated.

  13. Determining Antifungal Target Sites in the Sterol Pathway of the Yeast Candida and Saccharomyces

    National Research Council Canada - National Science Library

    Bard, Martin

    1998-01-01

    ... as in topical infections which lead to significant losses in work-place productivity. The work reported here seeks to identify new target sites in the sterol biosynthetic pathway against which new antifungal compounds might be developed...

  14. Hydrogeological site investigation for the efficient remediation of uranium mining sites -- an integrated approach

    International Nuclear Information System (INIS)

    Biehler, D.; Jaquet, O.; Croise, J.; Lavanchy, J.-M.

    2002-01-01

    The currently practised remediation of former uranium mines in Eastern Germany involves the flooding of underground and open pit mines, and the stabilization of waste rock dumps and tailings ponds, e.g. by dewatering, covering, improving dams, cleaning effluents. This article presents examples demonstrating that the remediation concepts developed and implemented have failed their targets, resulting in uncontrolled flow behaviour and migration of contaminated water, leading to increased costs and additional threats to the environment. A generic series of steps for an improved remediation management with respect to financial efforts and environmental safety are proposed in terms of an integrated approach. (author)

  15. Enhanced targeted integration mediated by translocated I-SceI during the Agrobacterium mediated transformation of yeast.

    Science.gov (United States)

    Rolloos, Martijn; Hooykaas, Paul J J; van der Zaal, Bert J

    2015-02-09

    Agrobacterium mediated transformation (AMT) has been embraced by biotechnologists as the technology of choice to introduce or alter genetic traits of plants. However, in plants it is virtually impossible to predetermine the integration site of the transferred T-strand unless one is able to generate a double stranded break (DSB) in the DNA at the site of interest. In this study, we used the model organism Saccharomyces cerevisiae to investigate whether the Agrobacterium mediated translocation of site-specific endonucleases via the type IV secretion system (T4SS), concomitantly with T-DNA transfer is possible and whether this can improve the gene targeting efficiency. In addition to that, the effect of different chromatin states on targeted integration, was investigated. It was found that Agrobacterium mediated translocation of the homing endonuclease I-SceI has a positive effect on the integration of T-DNA via the homologous repair (HR) pathway. Furthermore, we obtained evidence that nucleosome removal has a positive effect on I-SceI facilitated T-DNA integration by HR. Reversely; inducing nucleosome formation at the site of integration removes the positive effect of translocated I-SceI on T-DNA integration.

  16. Lentivector Integration Sites in Ependymal Cells From a Model of Metachromatic Leukodystrophy: Non-B DNA as a New Factor Influencing Integration

    Science.gov (United States)

    McAllister, Robert G; Liu, Jiahui; Woods, Matthew W; Tom, Sean K; Rupar, C Anthony; Barr, Stephen D

    2014-01-01

    The blood–brain barrier controls the passage of molecules from the blood into the central nervous system (CNS) and is a major challenge for treatment of neurological diseases. Metachromatic leukodystrophy is a neurodegenerative lysosomal storage disease caused by loss of arylsulfatase A (ARSA) activity. Gene therapy via intraventricular injection of a lentiviral vector is a potential approach to rapidly and permanently deliver therapeutic levels of ARSA to the CNS. We present the distribution of integration sites of a lentiviral vector encoding human ARSA (LV-ARSA) in murine brain choroid plexus and ependymal cells, administered via a single intracranial injection into the CNS. LV-ARSA did not exhibit a strong preference for integration in or near actively transcribed genes, but exhibited a strong preference for integration in or near satellite DNA. We identified several genomic hotspots for LV-ARSA integration and identified a consensus target site sequence characterized by two G-quadruplex-forming motifs flanking the integration site. In addition, our analysis identified several other non-B DNA motifs as new factors that potentially influence lentivirus integration, including human immunodeficiency virus type-1 in human cells. Together, our data demonstrate a clinically favorable integration site profile in the murine brain and identify non-B DNA as a potential new host factor that influences lentiviral integration in murine and human cells. PMID:25158091

  17. Target-mediated drug disposition model for drugs with two binding sites that bind to a target with one binding site.

    Science.gov (United States)

    Gibiansky, Leonid; Gibiansky, Ekaterina

    2017-10-01

    The paper extended the TMDD model to drugs with two identical binding sites (2-1 TMDD). The quasi-steady-state (2-1 QSS), quasi-equilibrium (2-1 QE), irreversible binding (2-1 IB), and Michaelis-Menten (2-1 MM) approximations of the model were derived. Using simulations, the 2-1 QSS approximation was compared with the full 2-1 TMDD model. As expected and similarly to the standard TMDD for monoclonal antibodies (mAb), 2-1 QSS predictions were nearly identical to 2-1 TMDD predictions, except for times of fast changes following initiation of dosing, when equilibrium has not yet been reached. To illustrate properties of new equations and approximations, several variations of population PK data for mAbs with soluble (slow elimination of the complex) or membrane-bound (fast elimination of the complex) targets were simulated from a full 2-1 TMDD model and fitted to 2-1 TMDD models, to its approximations, and to the standard (1-1) QSS model. For a mAb with a soluble target, it was demonstrated that the 2-1 QSS model provided nearly identical description of the observed (simulated) free drug and total target concentrations, although there was some minor bias in predictions of unobserved free target concentrations. The standard QSS approximation also provided a good description of the observed data, but was not able to distinguish between free drug concentrations (with no target attached and both binding site free) and partially bound drug concentrations (with one of the binding sites occupied by the target). For a mAb with a membrane-bound target, the 2-1 MM approximation adequately described the data. The 2-1 QSS approximation converged 10 times faster than the full 2-1 TMDD, and its run time was comparable with the standard QSS model.

  18. Predicting success of oligomerized pool engineering (OPEN for zinc finger target site sequences

    Directory of Open Access Journals (Sweden)

    Goodwin Mathew J

    2010-11-01

    Full Text Available Abstract Background Precise and efficient methods for gene targeting are critical for detailed functional analysis of genomes and regulatory networks and for potentially improving the efficacy and safety of gene therapies. Oligomerized Pool ENgineering (OPEN is a recently developed method for engineering C2H2 zinc finger proteins (ZFPs designed to bind specific DNA sequences with high affinity and specificity in vivo. Because generation of ZFPs using OPEN requires considerable effort, a computational method for identifying the sites in any given gene that are most likely to be successfully targeted by this method is desirable. Results Analysis of the base composition of experimentally validated ZFP target sites identified important constraints on the DNA sequence space that can be effectively targeted using OPEN. Using alternate encodings to represent ZFP target sites, we implemented Naïve Bayes and Support Vector Machine classifiers capable of distinguishing "active" targets, i.e., ZFP binding sites that can be targeted with a high rate of success, from those that are "inactive" or poor targets for ZFPs generated using current OPEN technologies. When evaluated using leave-one-out cross-validation on a dataset of 135 experimentally validated ZFP target sites, the best Naïve Bayes classifier, designated ZiFOpT, achieved overall accuracy of 87% and specificity+ of 90%, with an ROC AUC of 0.89. When challenged with a completely independent test set of 140 newly validated ZFP target sites, ZiFOpT performance was comparable in terms of overall accuracy (88% and specificity+ (92%, but with reduced ROC AUC (0.77. Users can rank potentially active ZFP target sites using a confidence score derived from the posterior probability returned by ZiFOpT. Conclusion ZiFOpT, a machine learning classifier trained to identify DNA sequences amenable for targeting by OPEN-generated zinc finger arrays, can guide users to target sites that are most likely to function

  19. Computational design of trimeric influenza-neutralizing proteins targeting the hemagglutinin receptor binding site

    Energy Technology Data Exchange (ETDEWEB)

    Strauch, Eva-Maria; Bernard, Steffen M.; La, David; Bohn, Alan J.; Lee, Peter S.; Anderson, Caitlin E.; Nieusma, Travis; Holstein, Carly A.; Garcia, Natalie K.; Hooper, Kathryn A.; Ravichandran, Rashmi; Nelson, Jorgen W.; Sheffler, William; Bloom, Jesse D.; Lee, Kelly K.; Ward, Andrew B.; Yager, Paul; Fuller, Deborah H.; Wilson, Ian A.; Baker , David (UWASH); (Scripps); (FHCRC)

    2017-06-12

    Many viral surface glycoproteins and cell surface receptors are homo-oligomers1, 2, 3, 4, and thus can potentially be targeted by geometrically matched homo-oligomers that engage all subunits simultaneously to attain high avidity and/or lock subunits together. The adaptive immune system cannot generally employ this strategy since the individual antibody binding sites are not arranged with appropriate geometry to simultaneously engage multiple sites in a single target homo-oligomer. We describe a general strategy for the computational design of homo-oligomeric protein assemblies with binding functionality precisely matched to homo-oligomeric target sites5, 6, 7, 8. In the first step, a small protein is designed that binds a single site on the target. In the second step, the designed protein is assembled into a homo-oligomer such that the designed binding sites are aligned with the target sites. We use this approach to design high-avidity trimeric proteins that bind influenza A hemagglutinin (HA) at its conserved receptor binding site. The designed trimers can both capture and detect HA in a paper-based diagnostic format, neutralizes influenza in cell culture, and completely protects mice when given as a single dose 24 h before or after challenge with influenza.

  20. Nevada National Security Site Integrated Groundwater Sampling Plan, Revision 0

    Energy Technology Data Exchange (ETDEWEB)

    Marutzky, Sam; Farnham, Irene

    2014-10-01

    The purpose of the Nevada National Security Site (NNSS) Integrated Sampling Plan (referred to herein as the Plan) is to provide a comprehensive, integrated approach for collecting and analyzing groundwater samples to meet the needs and objectives of the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Field Office (NNSA/NFO) Underground Test Area (UGTA) Activity. Implementation of this Plan will provide high-quality data required by the UGTA Activity for ensuring public protection in an efficient and cost-effective manner. The Plan is designed to ensure compliance with the UGTA Quality Assurance Plan (QAP). The Plan’s scope comprises sample collection and analysis requirements relevant to assessing the extent of groundwater contamination from underground nuclear testing. This Plan identifies locations to be sampled by corrective action unit (CAU) and location type, sampling frequencies, sample collection methodologies, and the constituents to be analyzed. In addition, the Plan defines data collection criteria such as well-purging requirements, detection levels, and accuracy requirements; identifies reporting and data management requirements; and provides a process to ensure coordination between NNSS groundwater sampling programs for sampling of interest to UGTA. This Plan does not address compliance with requirements for wells that supply the NNSS public water system or wells involved in a permitted activity.

  1. Neurons with two sites of synaptic integration learn invariant representations.

    Science.gov (United States)

    Körding, K P; König, P

    2001-12-01

    Neurons in mammalian cerebral cortex combine specific responses with respect to some stimulus features with invariant responses to other stimulus features. For example, in primary visual cortex, complex cells code for orientation of a contour but ignore its position to a certain degree. In higher areas, such as the inferotemporal cortex, translation-invariant, rotation-invariant, and even view point-invariant responses can be observed. Such properties are of obvious interest to artificial systems performing tasks like pattern recognition. It remains to be resolved how such response properties develop in biological systems. Here we present an unsupervised learning rule that addresses this problem. It is based on a neuron model with two sites of synaptic integration, allowing qualitatively different effects of input to basal and apical dendritic trees, respectively. Without supervision, the system learns to extract invariance properties using temporal or spatial continuity of stimuli. Furthermore, top-down information can be smoothly integrated in the same framework. Thus, this model lends a physiological implementation to approaches of unsupervised learning of invariant-response properties.

  2. Industrial implementation issues of Total Site Heat Integration

    International Nuclear Information System (INIS)

    Chew, Kew Hong; Klemeš, Jiří Jaromír; Wan Alwi, Sharifah Rafidah; Abdul Manan, Zainuddin

    2013-01-01

    Heat Integration has been a well-established energy conservation strategy in the industry. Total Site Heat Integration (TSHI) has received growing interest since its inception in the 90s. The methodology has been used with certain simplifications to solve TSHI problems. This paper investigates the main issues that can influence the practical implementation of TSHI in the industry. The main aim is to provide an assessment and possible guidance for future development and extension of the TSHI methodology from the industrial perspective. Several key issues have been identified as being of vital importance for the industries: design, operation, reliability/availability/maintenance, regulatory/policy and economics. Design issues to consider include plant layout, pressure drop, etc. For operation, issues such as startup and shutdown need to be considered. Reliability, availability and maintenance (RAM) are important as they directly affect the production. Relevant government policy and incentives are also important when considering the options for TSHI. Finally, a TSHI system needs to be economically viable. This paper highlights the key issues to be considered for a successful implementation of TSHI. The impacts of these issues on TS integration are summarised in a matrix, which forms a basis for an improved and closer-to-real-life implementation of the TSHI methodology. Highlights: ► Current TSHI methodology has been used for solving models with certain simplifications. ► Several issues that can influence practical implementation of TSHI are identified. ► Impacts of these issues on safety, environment and economics are evaluated. ► The findings form a basis for an improved and practical implementation of TSHI

  3. Mathematical description of drug-target interactions: application to biologics that bind to targets with two binding sites.

    Science.gov (United States)

    Gibiansky, Leonid; Gibiansky, Ekaterina

    2018-02-01

    The emerging discipline of mathematical pharmacology occupies the space between advanced pharmacometrics and systems biology. A characteristic feature of the approach is application of advance mathematical methods to study the behavior of biological systems as described by mathematical (most often differential) equations. One of the early application of mathematical pharmacology (that was not called this name at the time) was formulation and investigation of the target-mediated drug disposition (TMDD) model and its approximations. The model was shown to be remarkably successful, not only in describing the observed data for drug-target interactions, but also in advancing the qualitative and quantitative understanding of those interactions and their role in pharmacokinetic and pharmacodynamic properties of biologics. The TMDD model in its original formulation describes the interaction of the drug that has one binding site with the target that also has only one binding site. Following the framework developed earlier for drugs with one-to-one binding, this work aims to describe a rigorous approach for working with similar systems and to apply it to drugs that bind to targets with two binding sites. The quasi-steady-state, quasi-equilibrium, irreversible binding, and Michaelis-Menten approximations of the model are also derived. These equations can be used, in particular, to predict concentrations of the partially bound target (RC). This could be clinically important if RC remains active and has slow internalization rate. In this case, introduction of the drug aimed to suppress target activity may lead to the opposite effect due to RC accumulation.

  4. ZFNGenome: A comprehensive resource for locating zinc finger nuclease target sites in model organisms

    Directory of Open Access Journals (Sweden)

    Voytas Daniel F

    2011-01-01

    Full Text Available Abstract Background Zinc Finger Nucleases (ZFNs have tremendous potential as tools to facilitate genomic modifications, such as precise gene knockouts or gene replacements by homologous recombination. ZFNs can be used to advance both basic research and clinical applications, including gene therapy. Recently, the ability to engineer ZFNs that target any desired genomic DNA sequence with high fidelity has improved significantly with the introduction of rapid, robust, and publicly available techniques for ZFN design such as the Oligomerized Pool ENgineering (OPEN method. The motivation for this study is to make resources for genome modifications using OPEN-generated ZFNs more accessible to researchers by creating a user-friendly interface that identifies and provides quality scores for all potential ZFN target sites in the complete genomes of several model organisms. Description ZFNGenome is a GBrowse-based tool for identifying and visualizing potential target sites for OPEN-generated ZFNs. ZFNGenome currently includes a total of more than 11.6 million potential ZFN target sites, mapped within the fully sequenced genomes of seven model organisms; S. cerevisiae, C. reinhardtii, A. thaliana, D. melanogaster, D. rerio, C. elegans, and H. sapiens and can be visualized within the flexible GBrowse environment. Additional model organisms will be included in future updates. ZFNGenome provides information about each potential ZFN target site, including its chromosomal location and position relative to transcription initiation site(s. Users can query ZFNGenome using several different criteria (e.g., gene ID, transcript ID, target site sequence. Tracks in ZFNGenome also provide "uniqueness" and ZiFOpT (Zinc Finger OPEN Targeter "confidence" scores that estimate the likelihood that a chosen ZFN target site will function in vivo. ZFNGenome is dynamically linked to ZiFDB, allowing users access to all available information about zinc finger reagents, such as the

  5. Targeting for energy efficiency and improved energy collaboration between different companies using total site analysis (TSA)

    International Nuclear Information System (INIS)

    Hackl, Roman; Andersson, Eva; Harvey, Simon

    2011-01-01

    Rising fuel prices, increasing costs associated with emissions of green house gases and the threat of global warming make efficient use of energy more and more important. Industrial clusters have the potential to significantly increase energy efficiency by energy collaboration. In this paper Sweden's largest chemical cluster is analysed using the total site analysis (TSA) method. TSA delivers targets for the amount of utility consumed and generated through excess energy recovery by the different processes. The method enables investigation of opportunities to deliver waste heat from one process to another using a common utility system. The cluster consists of 5 chemical companies producing a variety of products, including polyethylene (PE), polyvinyl chloride (PVC), amines, ethylene, oxygen/nitrogen and plasticisers. The companies already work together by exchanging material streams. In this study the potential for energy collaboration is analysed in order to reach an industrial symbiosis. The overall heating and cooling demands of the site are around 442 MW and 953 MW, respectively. 122 MW of heat is produced in boilers and delivered to the processes. TSA is used to stepwise design a site-wide utility system which improves energy efficiency. It is shown that heat recovery in the cluster can be increased by 129 MW, i.e. the current utility demand could be completely eliminated and further 7 MW excess steam can be made available. The proposed retrofitted utility system involves the introduction of a site-wide hot water circuit, increased recovery of low pressure steam and shifting of heating steam pressure to lower levels in a number heat exchangers when possible. Qualitative evaluation of the suggested measures shows that 60 MW of the savings potential could to be achieved with moderate changes to the process utility system corresponding to 50% of the heat produced from purchased fuel in the boilers of the cluster. Further analysis showed that after implementation

  6. Safe genetic modification of cardiac stem cells using a site-specific integration technique.

    Science.gov (United States)

    Lan, Feng; Liu, Junwei; Narsinh, Kazim H; Hu, Shijun; Han, Leng; Lee, Andrew S; Karow, Marisa; Nguyen, Patricia K; Nag, Divya; Calos, Michele P; Robbins, Robert C; Wu, Joseph C

    2012-09-11

    Human cardiac progenitor cells (hCPCs) are a promising cell source for regenerative repair after myocardial infarction. Exploitation of their full therapeutic potential may require stable genetic modification of the cells ex vivo. Safe genetic engineering of stem cells, using facile methods for site-specific integration of transgenes into known genomic contexts, would significantly enhance the overall safety and efficacy of cellular therapy in a variety of clinical contexts. We used the phiC31 site-specific recombinase to achieve targeted integration of a triple fusion reporter gene into a known chromosomal context in hCPCs and human endothelial cells. Stable expression of the reporter gene from its unique chromosomal integration site resulted in no discernible genomic instability or adverse changes in cell phenotype. Namely, phiC31-modified hCPCs were unchanged in their differentiation propensity, cellular proliferative rate, and global gene expression profile when compared with unaltered control hCPCs. Expression of the triple fusion reporter gene enabled multimodal assessment of cell fate in vitro and in vivo using fluorescence microscopy, bioluminescence imaging, and positron emission tomography. Intramyocardial transplantation of genetically modified hCPCs resulted in significant improvement in myocardial function 2 weeks after cell delivery, as assessed by echocardiography (P=0.002) and MRI (P=0.001). We also demonstrated the feasibility and therapeutic efficacy of genetically modifying differentiated human endothelial cells, which enhanced hind limb perfusion (Pmodification system is a safe, efficient tool to enable site-specific integration of reporter transgenes in progenitor and differentiated cell types.

  7. Integrated pathway clusters with coherent biological themes for target prioritisation.

    Directory of Open Access Journals (Sweden)

    Yi-An Chen

    Full Text Available Prioritising candidate genes for further experimental characterisation is an essential, yet challenging task in biomedical research. One way of achieving this goal is to identify specific biological themes that are enriched within the gene set of interest to obtain insights into the biological phenomena under study. Biological pathway data have been particularly useful in identifying functional associations of genes and/or gene sets. However, biological pathway information as compiled in varied repositories often differs in scope and content, preventing a more effective and comprehensive characterisation of gene sets. Here we describe a new approach to constructing biologically coherent gene sets from pathway data in major public repositories and employing them for functional analysis of large gene sets. We first revealed significant overlaps in gene content between different pathways and then defined a clustering method based on the shared gene content and the similarity of gene overlap patterns. We established the biological relevance of the constructed pathway clusters using independent quantitative measures and we finally demonstrated the effectiveness of the constructed pathway clusters in comparative functional enrichment analysis of gene sets associated with diverse human diseases gathered from the literature. The pathway clusters and gene mappings have been integrated into the TargetMine data warehouse and are likely to provide a concise, manageable and biologically relevant means of functional analysis of gene sets and to facilitate candidate gene prioritisation.

  8. Targeted Gene Knock Out Using Nuclease-Assisted Vector Integration: Hemi- and Homozygous Deletion of JAG1.

    Science.gov (United States)

    Gapinske, Michael; Tague, Nathan; Winter, Jackson; Underhill, Gregory H; Perez-Pinera, Pablo

    2018-01-01

    Gene editing technologies are revolutionizing fields such as biomedicine and biotechnology by providing a simple means to manipulate the genetic makeup of essentially any organism. Gene editing tools function by introducing double-stranded breaks at targeted sites within the genome, which the host cells repair preferentially by Non-Homologous End Joining. While the technologies to introduce double-stranded breaks have been extensively optimized, this progress has not been matched by the development of methods to integrate heterologous DNA at the target sites or techniques to detect and isolate cells that harbor the desired modification. We present here a technique for rapid introduction of vectors at target sites in the genome that enables efficient isolation of successfully edited cells.

  9. Integrated site investigation and groundwater monitoring in an urban environment

    Science.gov (United States)

    Weatherl, R. K.

    2017-12-01

    Understanding groundwater dynamics around cities and other areas of human influence is of crucial importance for water resource management and protection, especially in a time of environmental and societal change. The human environment presents a unique challenge in terms of hydrological characterization, as the water cycle is generally artificialized and emissions of treated waste and chemical products into the surface- and groundwater system tend to disrupt the natural aqueous signature in significant ways. This project presents an integrated approach for robust characterization and monitoring of an urban aquifer which is actively exploited for municipal water supply. The study is carried out in the town of Fehraltorf, in the canton of Zürich, Switzerland. This particular town encompasses industrial and agricultural zones in addition to its standard urban setting. A minimal amount of data exist at this site, and the data that do exist are spatially and temporally sparse. Making use of traditional hydrogeological methods alongside evolving and emerging technologies, we aim to identify sources of contamination and to define groundwater flow and solute transport through space and time. Chemical and physical indicator parameters are identified for tracing contaminations including micropollutants and plant nutrients. Wireless sensors are installed for continuous on-line monitoring of essential parameters (electrical conductivity, temperature, water level). A wireless sensor network has previously been installed in the sewer system of the study site, facilitating investigation into interactions between sewer water and groundwater. Our approach illustrates the relations between land use, climate, rainfall dynamics, and the groundwater signature through time. At its conclusion, insights gained from this study will be used by municipal authorities to refine protective zones around pumping wells and to direct resources towards updating practices and replacing

  10. Transcranial sonography: integration into target volume definition for glioblastoma multiforme

    International Nuclear Information System (INIS)

    Vordermark, Dirk; Becker, Georg; Flentje, Michael; Richter, Susanne; Goerttler-Krauspe, Irene; Koelbl, Oliver

    2000-01-01

    Purpose: Recent studies indicate that transcranial sonography (TCS) reliably displays the extension of malignant brain tumors. The effect of integrating TCS into radiotherapy planning for glioblastoma multiforme (GBM) was investigated herein. Methods and Materials: Thirteen patients subtotally resected for GBM underwent TCS during radiotherapy planning and were conventionally treated (54 to 60 Gy). Gross tumor volumes (GTVs) and stereotactic boost planning target volumes (PTVs, 3-mm margin) were created, based on contrast enhancement on computed tomography (CT) only (PTV CT ) or the combined CT and TCS information (PTV CT+TCS ). Noncoplonar conformal treatment plans for both PTVs were compared. Tumor progression patterns and preoperative magnetic resonance imaging (MRI) were related to both PTVs. Results: A sufficient temporal bone window for TCS was present in 11 of 13 patients. GTVs as defined by TCS were considerably larger than the respective CT volumes: Of the composite GTV CT+TCS (median volume 42 ml), 23%, 13%, and 66% (medians) were covered by the overlap of both methods, CT only and TCS only, respectively. Median sizes of PTV CT and PTV CT+TCS were 34 and 74 ml, respectively. Addition of TCS to CT information led to a median increase of the volume irradiated within the 80% isodose by 32 ml (median factor 1.51). PTV CT+TCS volume was at median 24% of a 'conventional' MRI(T2)-based PTV. Of eight progressions analyzed, three and six occurred inside the 80% isodose of the plans for PTV CT and for PTV CT+TCS , respectively. Conclusion: Addition of TCS tumor volume to the contrast-enhancing CT volume in postoperative radiotherapy planning for GBM increases the treated volume by a median factor of 1.5. Since a high frequency of marginal recurrences is reported from dose-escalation trials of this disease, TCS may complement established methods in PTV definition

  11. Selective pressures to maintain attachment site specificity of integrative and conjugative elements.

    Directory of Open Access Journals (Sweden)

    Kayla L Menard

    Full Text Available Integrative and conjugative elements (ICEs are widespread mobile genetic elements that are usually found integrated in bacterial chromosomes. They are important agents of evolution and contribute to the acquisition of new traits, including antibiotic resistances. ICEs can excise from the chromosome and transfer to recipients by conjugation. Many ICEs are site-specific in that they integrate preferentially into a primary attachment site in the bacterial genome. Site-specific ICEs can also integrate into secondary locations, particularly if the primary site is absent. However, little is known about the consequences of integration of ICEs into alternative attachment sites or what drives the apparent maintenance and prevalence of the many ICEs that use a single attachment site. Using ICEBs1, a site-specific ICE from Bacillus subtilis that integrates into a tRNA gene, we found that integration into secondary sites was detrimental to both ICEBs1 and the host cell. Excision of ICEBs1 from secondary sites was impaired either partially or completely, limiting the spread of ICEBs1. Furthermore, induction of ICEBs1 gene expression caused a substantial drop in proliferation and cell viability within three hours. This drop was dependent on rolling circle replication of ICEBs1 that was unable to excise from the chromosome. Together, these detrimental effects provide selective pressure against the survival and dissemination of ICEs that have integrated into alternative sites and may explain the maintenance of site-specific integration for many ICEs.

  12. BIOTIC INTEGRITY OF STREAMS IN THE SAVANNAH RIVER SITE INTEGRATOR OPERABLE UNITS, 1996 TO 2003

    Energy Technology Data Exchange (ETDEWEB)

    Paller, M; Susan Dyer, S

    2004-11-08

    The Savannah River Site (SRS) has been divided into six Integrator Operable Units (IOUs) that correspond to the watersheds of the five major streams on the SRS (Upper Three Runs, Fourmile Branch, Pen Branch, Steel Creek, and Lower Three Runs) and the portions of the Savannah River and Savannah River Swamp associated with the SRS. The streams are the primary integrators within each IOU because they potentially receive, through surface or subsurface drainage, soluble contaminants from all waste sites within their watersheds. If these contaminants reach biologically significant levels, they would be expected to effect the numbers, types, and health of stream organisms. In this study, biological sampling was conducted within each IOU as a measure of the cumulative ecological effects of the waste sites within the IOUs. The use of information from biological sampling to assess environmental quality is often termed bioassessment. The IOU bioassessment program included 38 sites in SRS streams and nine sites in the Savannah River. Sampling was conducted in 1996 to 1998, 2000, and 2003. Four bioassessment methods were used to evaluate ecological conditions in the IOU streams: the Index of Biotic Integrity, the Fish Health Assessment Index, measurement of fish tissue contaminant levels, and two benthic macroinvertebrate indices. The Index of Biotic Integrity (IBI) is an EPA supported method based on comparison of ecologically important and sensitive fish assemblage variables between potentially disturbed and reference (i.e., undisturbed) sites. It is designed to assess the ability of a stream to support a self-sustaining biological community and ecological processes typical of undisturbed, natural conditions. Since many types of contaminants can bioaccumulate, fish tissue contaminant data were used to determine the types of chemicals fish were exposed to and their relative magnitudes among IOUs. The Fish Health Assessment Index (HAI) is an EPA supported method for assessing

  13. Bidirectional Retroviral Integration Site PCR Methodology and Quantitative Data Analysis Workflow.

    Science.gov (United States)

    Suryawanshi, Gajendra W; Xu, Song; Xie, Yiming; Chou, Tom; Kim, Namshin; Chen, Irvin S Y; Kim, Sanggu

    2017-06-14

    Integration Site (IS) assays are a critical component of the study of retroviral integration sites and their biological significance. In recent retroviral gene therapy studies, IS assays, in combination with next-generation sequencing, have been used as a cell-tracking tool to characterize clonal stem cell populations sharing the same IS. For the accurate comparison of repopulating stem cell clones within and across different samples, the detection sensitivity, data reproducibility, and high-throughput capacity of the assay are among the most important assay qualities. This work provides a detailed protocol and data analysis workflow for bidirectional IS analysis. The bidirectional assay can simultaneously sequence both upstream and downstream vector-host junctions. Compared to conventional unidirectional IS sequencing approaches, the bidirectional approach significantly improves IS detection rates and the characterization of integration events at both ends of the target DNA. The data analysis pipeline described here accurately identifies and enumerates identical IS sequences through multiple steps of comparison that map IS sequences onto the reference genome and determine sequencing errors. Using an optimized assay procedure, we have recently published the detailed repopulation patterns of thousands of Hematopoietic Stem Cell (HSC) clones following transplant in rhesus macaques, demonstrating for the first time the precise time point of HSC repopulation and the functional heterogeneity of HSCs in the primate system. The following protocol describes the step-by-step experimental procedure and data analysis workflow that accurately identifies and quantifies identical IS sequences.

  14. Crops with target-site herbicide resistance for Orobanche and Striga control.

    Science.gov (United States)

    Gressel, Jonathan

    2009-05-01

    It is necessary to control root parasitic weeds before or as they attach to the crop. This can only be easily achieved chemically with herbicides that are systemic, or with herbicides that are active in soil. Long-term control can only be attained if the crops do not metabolise the herbicide, i.e. have target-site resistance. Such target-site resistances have allowed foliar applications of herbicides inhibiting enol-pyruvylshikimate phosphate synthase (EPSPS) (glyphosate), acetolactate synthase (ALS) (e.g. chlorsulfuron, imazapyr) and dihydropteroate synthase (asulam) for Orobanche control in experimental conditions with various crops. Large-scale use of imazapyr as a seed dressing of imidazolinone-resistant maize has been commercialised for Striga control. Crops with two target-site resistances will be more resilient to the evolution of resistance in the parasite, if well managed.

  15. Integrated Weed Control for Land Stewardship at Legacy Management's Rocky Flats Site in Colorado - 13086

    International Nuclear Information System (INIS)

    Nelson, Jody K.

    2013-01-01

    insects have been released to assist with control of different target weed species. Monitoring is conducted to evaluate the effectiveness of control efforts and to provide information for future control efforts. The effective implementation of this integrated approach has reduced the infestation levels of many species and has kept several newly discovered invasive species from spreading and becoming larger problems at the site. (authors)

  16. PROSPER: an integrated feature-based tool for predicting protease substrate cleavage sites.

    Directory of Open Access Journals (Sweden)

    Jiangning Song

    Full Text Available The ability to catalytically cleave protein substrates after synthesis is fundamental for all forms of life. Accordingly, site-specific proteolysis is one of the most important post-translational modifications. The key to understanding the physiological role of a protease is to identify its natural substrate(s. Knowledge of the substrate specificity of a protease can dramatically improve our ability to predict its target protein substrates, but this information must be utilized in an effective manner in order to efficiently identify protein substrates by in silico approaches. To address this problem, we present PROSPER, an integrated feature-based server for in silico identification of protease substrates and their cleavage sites for twenty-four different proteases. PROSPER utilizes established specificity information for these proteases (derived from the MEROPS database with a machine learning approach to predict protease cleavage sites by using different, but complementary sequence and structure characteristics. Features used by PROSPER include local amino acid sequence profile, predicted secondary structure, solvent accessibility and predicted native disorder. Thus, for proteases with known amino acid specificity, PROSPER provides a convenient, pre-prepared tool for use in identifying protein substrates for the enzymes. Systematic prediction analysis for the twenty-four proteases thus far included in the database revealed that the features we have included in the tool strongly improve performance in terms of cleavage site prediction, as evidenced by their contribution to performance improvement in terms of identifying known cleavage sites in substrates for these enzymes. In comparison with two state-of-the-art prediction tools, PoPS and SitePrediction, PROSPER achieves greater accuracy and coverage. To our knowledge, PROSPER is the first comprehensive server capable of predicting cleavage sites of multiple proteases within a single substrate

  17. Integral measurements of neutron production in spallation targets

    International Nuclear Information System (INIS)

    Frehaut, J.; Deneuville, D.; Ledoux, X.; Lochard, J.P.; Longuet, J.L.; Petibon, E.; Alrick, K.; Bownan, D.; Cverna, F.; King, N.S.P.; Morgan, G.L.; Greene, G.; Hanson, A.; Snead, L.; Thompson, R.; Ward, T.

    1998-01-01

    Measurements of neutron production for thick iron, tungsten and lead targets of different diameter prototypic for spallation systems have been made at SATURNE in an incident proton energy range from 400 MeV to 2 GeV. TIERCE code system calculations are in good agreement with experiment for iron and large diameter tungsten and lead targets. They overestimate the measured neutron production for tungsten and lead targets for diameter ≤20 cm. (author)

  18. Current Research at the Endeavour Ridge 2000 Integrated Studies Site

    Science.gov (United States)

    Butterfield, D. A.; Kelley, D. S.; Ridge 2000 Community, R.

    2004-12-01

    Integrated geophysical, geological, chemical, and biological studies are being conducted on the Endeavour segment with primary support from NSF, the W.M. Keck Foundation, and NSERC (Canada). The research includes a seismic network, physical and chemical sensors, high-precision mapping and time-series sampling. Several research expeditions have taken place at the Endeavour ISS in the past year. In June 2003, an NSF-sponsored cruise with R.V. al T.G.Thompson/ROV al Jason2 installed microbial incubators in drill-holes in the sides of active sulfide chimneys and sampled rocks, fluids, and microbes in the Mothra and Main Endeavour Field (MEF). In July 2003, with al Thompson/Jason2, an NSF-LEXEN project at Baby Bare on Endeavour east flank conducted sampling through seafloor-penetrating probes, plus time-series sampling of fluids, microbes, and rocks at the MEF. In September 2003, with al Thompson/ROV al ROPOS, the Keck Proto-Neptune project installed a seismic network consisting of 1 broadband and 7 short-period seismometers, installation of chemical/physical sensors and time-series samplers for chemistry and microbiology in the MEF and Clam Bed sites, collection of rocks, fluids, animals, and microbes. In May/June 2004, an NSF-sponsored al Atlantis/Alvin cruise recovered sulfide incubators installed in 2003, redeployed a sulfide incubator, mapped MEF and Mothra vent fields with high-resolution Imagenix sonar, sampled fluids from MEF, Mothra, and Clam Bed, recovered year-long time-series fluid and microbial samplers from MEF and Clam Bed, recovered and installed hot vent temperature-resistivity monitors, cleaned up the MEF and deployed new markers at major sulfide structures. In August 2004, there were two MBARI/Keck-sponsored cruises with R.V. al Western Flyer/ROV al Tiburon. The first cruise completed the seismic network with addition of two more broadband seismometers and serviced all 7 short-period seismometers. al Tiburon then performed microbial and chemical

  19. Analysis and interpretation of geophysical surveys in archaeological sites employing different integrated approach.

    Science.gov (United States)

    Piro, Salvatore; Papale, Enrico; Kucukdemirci, Melda; Zamuner, Daniela

    2017-04-01

    Non-destructive ground surface geophysical prospecting methods are frequently used for the investigation of archaeological sites, where a detailed physical and geometrical reconstructions of hidden volumes is required prior to any excavation work. All methods measure the variations of single physical parameters, therefore if these are used singularly, they could not permit a complete location and characterization of anomalous bodies. The probability of a successful result rapidly increases if a multhimethodological approach is adopted, according to the logic of objective complementarity of information and of global convergence toward a high quality multiparametric imaging of the buried structures. The representation of the static configuration of the bodies in the subsoil and of the space-time evolution of the interaction processes between targets and hosting materials have to be actually considered fundamental elements of primary knowledge in archaeological prospecting. The main effort in geophysical prospecting for archaeology is therefore the integration of different, absolutely non-invasive techniques, especially if managed in view of a ultra-high resolution three-dimensional (3D) tomographic representation mode. Following the above outlined approach, we have integrated geophysical methods which measure the variations of potential field (gradiometric methods) with active methods which measure the variations of physical properties due to the body's geometry and volume (GPR and ERT). In this work, the results obtained during the surveys of three archaeological sites, employing Ground Penetrating Radar (GPR), Electrical Resistivity Tomography (ERT) and Fluxgate Differential Magnetic (FDM) to obtain precise and detailed maps of subsurface bodies, are presented and discussed. The first site, situated in a suburban area between Itri and Fondi, in the Aurunci Natural Regional Park (Central Italy), is characterized by the presence of remains of past human activity

  20. MirZ: an integrated microRNA expression atlas and target prediction resource.

    Science.gov (United States)

    Hausser, Jean; Berninger, Philipp; Rodak, Christoph; Jantscher, Yvonne; Wirth, Stefan; Zavolan, Mihaela

    2009-07-01

    MicroRNAs (miRNAs) are short RNAs that act as guides for the degradation and translational repression of protein-coding mRNAs. A large body of work showed that miRNAs are involved in the regulation of a broad range of biological functions, from development to cardiac and immune system function, to metabolism, to cancer. For most of the over 500 miRNAs that are encoded in the human genome the functions still remain to be uncovered. Identifying miRNAs whose expression changes between cell types or between normal and pathological conditions is an important step towards characterizing their function as is the prediction of mRNAs that could be targeted by these miRNAs. To provide the community the possibility of exploring interactively miRNA expression patterns and the candidate targets of miRNAs in an integrated environment, we developed the MirZ web server, which is accessible at www.mirz.unibas.ch. The server provides experimental and computational biologists with statistical analysis and data mining tools operating on up-to-date databases of sequencing-based miRNA expression profiles and of predicted miRNA target sites in species ranging from Caenorhabditis elegans to Homo sapiens.

  1. Nevada National Security Site Integrated Groundwater Sampling Plan, Revision 1

    Energy Technology Data Exchange (ETDEWEB)

    Farnham, Irene

    2018-03-01

    The purpose is to provide a comprehensive, integrated approach for collecting and analyzing groundwater samples to meet the needs and objectives of the DOE/EM Nevada Program’s UGTA Activity. Implementation of this Plan will provide high-quality data required by the UGTA Activity for ensuring public protection in an efficient and cost-effective manner. The Plan is designed to ensure compliance with the UGTA Quality Assurance Plan (QAP) (NNSA/NFO, 2015); Federal Facility Agreement and Consent Order (FFACO) (1996, as amended); and DOE Order 458.1, Radiation Protection of the Public and the Environment (DOE, 2013). The Plan’s scope comprises sample collection and analysis requirements relevant to assessing both the extent of groundwater contamination from underground nuclear testing and impact of testing on water quality in downgradient communities. This Plan identifies locations to be sampled by CAU and location type, sampling frequencies, sample collection methodologies, and the constituents to be analyzed. In addition, the Plan defines data collection criteria such as well purging, detection levels, and accuracy requirements/recommendations; identifies reporting and data management requirements; and provides a process to ensure coordination between NNSS groundwater sampling programs for sampling analytes of interest to UGTA. Information used in the Plan development—including the rationale for selection of wells, sampling frequency, and the analytical suite—is discussed under separate cover (N-I, 2014) and is not reproduced herein. This Plan does not address compliance for those wells involved in a permitted activity. Sampling and analysis requirements associated with these wells are described in their respective permits and are discussed in NNSS environmental reports (see Section 5.2). In addition, sampling for UGTA CAUs that are in the Closure Report (CR) stage are not included in this Plan. Sampling requirements for these CAUs are described in the CR

  2. Novel and viable acetylcholinesterase target site for developing effective and environmentally safe insecticides.

    Science.gov (United States)

    Pang, Yuan-Ping; Brimijoin, Stephen; Ragsdale, David W; Zhu, Kun Yan; Suranyi, Robert

    2012-04-01

    Insect pests are responsible for human suffering and financial losses worldwide. New and environmentally safe insecticides are urgently needed to cope with these serious problems. Resistance to current insecticides has resulted in a resurgence of insect pests, and growing concerns about insecticide toxicity to humans discourage the use of insecticides for pest control. The small market for insecticides has hampered insecticide development; however, advances in genomics and structural genomics offer new opportunities to develop insecticides that are less dependent on the insecticide market. This review summarizes the literature data that support the hypothesis that an insect-specific cysteine residue located at the opening of the acetylcholinesterase active site is a promising target site for developing new insecticides with reduced off-target toxicity and low propensity for insect resistance. These data are used to discuss the differences between targeting the insect-specific cysteine residue and targeting the ubiquitous catalytic serine residue of acetylcholinesterase from the perspective of reducing off-target toxicity and insect resistance. Also discussed is the prospect of developing cysteine-targeting anticholinesterases as effective and environmentally safe insecticides for control of disease vectors, crop damage, and residential insect pests within the financial confines of the present insecticide market.

  3. Integration of a working site in its regional context

    International Nuclear Information System (INIS)

    Couture, J.

    1986-01-01

    This paper shows how a local representative has felt the decision of construction of the Paluel nuclear power plant and the problems involved, and how it has been tried to resolve them: insertion in the site, reception of the population of this big working site [fr

  4. Molecular characterization of monoclonal antibodies that inhibit acetylcholinesterase by targeting the peripheral site and backdoor region.

    Directory of Open Access Journals (Sweden)

    Yves Bourne

    Full Text Available The inhibition properties and target sites of monoclonal antibodies (mAbs Elec403, Elec408 and Elec410, generated against Electrophorus electricus acetylcholinesterase (AChE, have been defined previously using biochemical and mutagenesis approaches. Elec403 and Elec410, which bind competitively with each other and with the peptidic toxin inhibitor fasciculin, are directed toward distinctive albeit overlapping epitopes located at the AChE peripheral anionic site, which surrounds the entrance of the active site gorge. Elec408, which is not competitive with the other two mAbs nor fasciculin, targets a second epitope located in the backdoor region, distant from the gorge entrance. To characterize the molecular determinants dictating their binding site specificity, we cloned and sequenced the mAbs; generated antigen-binding fragments (Fab retaining the parental inhibition properties; and explored their structure-function relationships using complementary x-ray crystallography, homology modeling and flexible docking approaches. Hypermutation of one Elec403 complementarity-determining region suggests occurrence of antigen-driven selection towards recognition of the AChE peripheral site. Comparative analysis of the 1.9Å-resolution structure of Fab408 and of theoretical models of its Fab403 and Fab410 congeners evidences distinctive surface topographies and anisotropic repartitions of charges, consistent with their respective target sites and inhibition properties. Finally, a validated, data-driven docking model of the Fab403-AChE complex suggests a mode of binding at the PAS that fully correlates with the functional data. This comprehensive study documents the molecular peculiarities of Fab403 and Fab410, as the largest peptidic inhibitors directed towards the peripheral site, and those of Fab408, as the first inhibitor directed toward the backdoor region of an AChE and a unique template for the design of new, specific modulators of AChE catalysis.

  5. Integrated environmental monitoring program at the Hanford Site

    International Nuclear Information System (INIS)

    Jaquish, R.E.

    1990-08-01

    The US Department of Energy's Hanford Site, north of Richland, Washington, has a mission of defense production, waste management, environmental restoration, advanced reactor design, and research development. Environmental programs at Hanford are conducted by Pacific Northwest Laboratory (PNL) and the Westinghouse Hanford Company (WHC). The WHC environmental programs include the compliance and surveillance activities associated with site operations and waste management. The PNL environmental programs address the site-wide and the of-site areas. They include the environmental surveillance and the associated support activities, such as dose calculations, and also the monitoring of environmental conditions to comply with federal and state environmental regulations on wildlife and cultural resources. These are called ''independent environmental programs'' in that they are conducted completely separate from site operations. The Environmental Surveillance and Oversight Program consists of the following projects: surface environmental surveillance; ground-water surveillance; wildlife resources monitoring; cultural resources; dose overview; radiation standards and calibrations; meteorological and climatological services; emergency preparedness

  6. Integrated bird conservation web site in the United States

    Science.gov (United States)

    Roxanne Bogart; Chris Eberly; Elizabeth Martin

    2005-01-01

    In working towards a vision of integrated bird conservation, scientists, conservationists, land managers, and administrators are faced with a variety of scientific, managerial, administrative, and logistical challenges and complexities. The broad scope of integrated bird conservation requires organizations to work together to conserve birds across taxonomic groups,...

  7. Occurrence Prospect of HDR and Target Site Selection Study in Southeastern of China

    Science.gov (United States)

    Lin, W.; Gan, H.

    2017-12-01

    Hot dry rock (HDR) geothermal resource is one of the most important clean energy in future. Site selection a HDR resource is a fundamental work to explore the HDR resources. This paper compiled all the HDR development projects domestic and abroad, and summarized the location of HDR geothermal geological index. After comparing the geological background of HDR in the southeast coastal area of China, Yangjiang Xinzhou in Guangdong province, Leizhou Peninsula area, Lingshui in Hainan province and Huangshadong in Guangzhou were selected from some key potential target area along the southeast coast of China. Deep geothermal field model of the study area is established based on the comprehensive analysis of the target area of deep geothermal geological background and deep thermal anomalies. This paper also compared the hot dry rock resources target locations, and proposed suggestions for the priority exploration target area and exploration scheme.

  8. Immunological Reactivity Using Monoclonal and Polyclonal Antibodies of Autoimmune Thyroid Target Sites with Dietary Proteins

    Directory of Open Access Journals (Sweden)

    Datis Kharrazian

    2017-01-01

    Full Text Available Many hypothyroid and autoimmune thyroid patients experience reactions with specific foods. Additionally, food interactions may play a role in a subset of individuals who have difficulty finding a suitable thyroid hormone dosage. Our study was designed to investigate the potential role of dietary protein immune reactivity with thyroid hormones and thyroid axis target sites. We identified immune reactivity between dietary proteins and target sites on the thyroid axis that includes thyroid hormones, thyroid receptors, enzymes, and transport proteins. We also measured immune reactivity of either target specific monoclonal or polyclonal antibodies for thyroid-stimulating hormone (TSH receptor, 5′deiodinase, thyroid peroxidase, thyroglobulin, thyroxine-binding globulin, thyroxine, and triiodothyronine against 204 purified dietary proteins commonly consumed in cooked and raw forms. Dietary protein determinants included unmodified (raw and modified (cooked and roasted foods, herbs, spices, food gums, brewed beverages, and additives. There were no dietary protein immune reactions with TSH receptor, thyroid peroxidase, and thyroxine-binding globulin. However, specific antigen-antibody immune reactivity was identified with several purified food proteins with triiodothyronine, thyroxine, thyroglobulin, and 5′deiodinase. Laboratory analysis of immunological cross-reactivity between thyroid target sites and dietary proteins is the initial step necessary in determining whether dietary proteins may play a potential immunoreactive role in autoimmune thyroid disease.

  9. Multimedia approach to estimating target cleanup levels for soils at hazardous waste sites

    International Nuclear Information System (INIS)

    Hwang, S.T.

    1990-04-01

    Contaminated soils at hazardous and nuclear waste sites pose a potential threat to human health via transport through environmental media and subsequent human intake. To minimize health risks, it is necessary to identify those risks and ensure that appropriate actions are taken to protect public health. The regulatory process may typically include identification of target cleanup levels and evaluation of the effectiveness of remedial alternatives and the corresponding reduction in risks at a site. The US Environmental Protection Agency (EPA) recommends that exposure assessments be combined with toxicity information to quantify the health risk posed by a specific site. This recommendation then forms the basis for establishing target cleanup levels. An exposure assessment must first identify the chemical concentration in a specific medium (soil, water, air, or food), estimate the exposure potential based on human intake from that media, and then combined with health criteria to estimate the upperbound health risks for noncarcinogens and carcinogens. Estimation of target cleanup levels involves the use of these same principles but can occur in reverse order. The procedure starts from establishing a permissible health effect level and ends with an estimated target cleanup level through an exposure assessment process. 17 refs

  10. Customer Focused Product Design Using Integrated Model of Target Costing, Quality Function Deployment and Value Engineering

    Directory of Open Access Journals (Sweden)

    Hossein Rezaei Dolatabadi

    2013-01-01

    Full Text Available Target costing by integrating customer requirements, technical attributes and cost information into the product design phase and eliminating the non-value added functions, plays a vital role in different phases of the product life cycle. Quality Function Deployment (QFD and Value Engineering (VE are two techniques which can be used for applying target costing, successfully. The purpose of this paper is to propose an integrated model of target costing, QFD and VE to explore the role of target costing in managing product costs while promoting quality specifications meeting customers’ needs. F indings indicate that the integration of target costing, QFD and VE is an essential technique in managing the costs of production process. Findings also imply that integration of the three techniques provides a competitive cost advantage to companies.

  11. Inactivation of Pol θ and C-NHEJ eliminates off-target integration of exogenous DNA.

    Science.gov (United States)

    Zelensky, Alex N; Schimmel, Joost; Kool, Hanneke; Kanaar, Roland; Tijsterman, Marcel

    2017-07-07

    Off-target or random integration of exogenous DNA hampers precise genomic engineering and presents a safety risk in clinical gene therapy strategies. Genetic definition of random integration has been lacking for decades. Here, we show that the A-family DNA polymerase θ (Pol θ) promotes random integration, while canonical non-homologous DNA end joining plays a secondary role; cells double deficient for polymerase θ and canonical non-homologous DNA end joining are devoid of any integration events, demonstrating that these two mechanisms define random integration. In contrast, homologous recombination is not reduced in these cells and gene targeting is improved to 100% efficiency. Such complete reversal of integration outcome, from predominately random integration to exclusively gene targeting, provides a rational way forward to improve the efficacy and safety of DNA delivery and gene correction approaches.Random off-target integration events can impair precise gene targeting and poses a safety risk for gene therapy. Here the authors show that repression of polymerase θ and classical non-homologous recombination eliminates random integration.

  12. Genome-wide search for miRNA-target interactions in Arabidopsis thaliana with an integrated approach

    Directory of Open Access Journals (Sweden)

    Ding Jiandong

    2012-06-01

    Full Text Available Abstract Background MiRNA are about 22nt long small noncoding RNAs that post transcriptionally regulate gene expression in animals, plants and protozoa. Confident identification of MiRNA-Target Interactions (MTI is vital to understand their function. Currently, several integrated computational programs and databases are available for animal miRNAs, the mechanisms of which are significantly different from plant miRNAs. Methods Here we present an integrated MTI prediction and analysis toolkit (imiRTP for Arabidopsis thaliana. It features two important functions: (i combination of several effective plant miRNA target prediction methods provides a sufficiently large MTI candidate set, and (ii different filters allow for an efficient selection of potential targets. The modularity of imiRTP enables the prediction of high quality targets on genome-wide scale. Moreover, predicted MTIs can be presented in various ways, which allows for browsing through the putative target sites as well as conducting simple and advanced analyses. Results Results show that imiRTP could always find high quality candidates compared with single method by choosing appropriate filter and parameter. And we also reveal that a portion of plant miRNA could bind target genes out of coding region. Based on our results, imiRTP could facilitate the further study of Arabidopsis miRNAs in real use. All materials of imiRTP are freely available under a GNU license at (http://admis.fudan.edu.cn/projects/imiRTP.htm.

  13. Targeting Alternative Sites on the Androgen Receptor to Treat Castration-Resistant Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Paul S. Rennie

    2013-06-01

    Full Text Available Recurrent, metastatic prostate cancer continues to be a leading cause of cancer-death in men. The androgen receptor (AR is a modular, ligand-inducible transcription factor that regulates the expression of genes that can drive the progression of this disease, and as a consequence, this receptor is a key therapeutic target for controlling prostate cancer. The current drugs designed to directly inhibit the AR are called anti-androgens, and all act by competing with androgens for binding to the androgen/ligand binding site. Unfortunately, with the inevitable progression of the cancer to castration resistance, many of these drugs become ineffective. However, there are numerous other regulatory sites on this protein that have not been exploited therapeutically. The regulation of AR activity involves a cascade of complex interactions with numerous chaperones, co-factors and co-regulatory proteins, leading ultimately to direct binding of AR dimers to specific DNA androgen response elements within the promoter and enhancers of androgen-regulated genes. As part of the family of nuclear receptors, the AR is organized into modular structural and functional domains with specialized roles in facilitating their inter-molecular interactions. These regions of the AR present attractive, yet largely unexploited, drug target sites for reducing or eliminating androgen signaling in prostate cancers. The design of small molecule inhibitors targeting these specific AR domains is only now being realized and is the culmination of decades of work, including crystallographic and biochemistry approaches to map the shape and accessibility of the AR surfaces and cavities. Here, we review the structure of the AR protein and describe recent advancements in inhibiting its activity with small molecules specifically designed to target areas distinct from the receptor’s androgen binding site. It is anticipated that these new classes of anti-AR drugs will provide an additional

  14. COSMID: A Web-based Tool for Identifying and Validating CRISPR/Cas Off-target Sites

    Directory of Open Access Journals (Sweden)

    Thomas J Cradick

    2014-01-01

    Full Text Available Precise genome editing using engineered nucleases can significantly facilitate biological studies and disease treatment. In particular, clustered regularly interspaced short palindromic repeats (CRISPR with CRISPR-associated (Cas proteins are a potentially powerful tool for modifying a genome by targeted cleavage of DNA sequences complementary to designed guide strand RNAs. Although CRISPR/Cas systems can have on-target cleavage rates close to the transfection rates, they may also have relatively high off-target cleavage at similar genomic sites that contain one or more base pair mismatches, and insertions or deletions relative to the guide strand. We have developed a bioinformatics-based tool, COSMID (CRISPR Off-target Sites with Mismatches, Insertions, and Deletions that searches genomes for potential off-target sites (http://crispr.bme.gatech.edu. Based on the user-supplied guide strand and input parameters, COSMID identifies potential off-target sites with the specified number of mismatched bases and insertions or deletions when compared with the guide strand. For each site, amplification primers optimal for the chosen application are also given as output. This ranked-list of potential off-target sites assists the choice and evaluation of intended target sites, thus helping the design of CRISPR/Cas systems with minimal off-target effects, as well as the identification and quantification of CRISPR/Cas induced off-target cleavage in cells.

  15. Rapid development of stable transgene CHO cell lines by CRISPR/Cas9-mediated site-specific integration into C12orf35.

    Science.gov (United States)

    Zhao, Menglin; Wang, Jiaxian; Luo, Manyu; Luo, Han; Zhao, Meiqi; Han, Lei; Zhang, Mengxiao; Yang, Hui; Xie, Yueqing; Jiang, Hua; Feng, Lei; Lu, Huili; Zhu, Jianwei

    2018-07-01

    Chinese hamster ovary (CHO) cells are the most widely used mammalian hosts for recombinant protein production. However, by conventional random integration strategy, development of a high-expressing and stable recombinant CHO cell line has always been a difficult task due to the heterogenic insertion and its caused requirement of multiple rounds of selection. Site-specific integration of transgenes into CHO hot spots is an ideal strategy to overcome these challenges since it can generate isogenic cell lines with consistent productivity and stability. In this study, we investigated three sites with potential high transcriptional activities: C12orf35, HPRT, and GRIK1, to determine the possible transcriptional hot spots in CHO cells, and further construct a reliable site-specific integration strategy to develop recombinant cell lines efficiently. Genes encoding representative proteins mCherry and anti-PD1 monoclonal antibody were targeted into these three loci respectively through CRISPR/Cas9 technology. Stable cell lines were generated successfully after a single round of selection. In comparison with a random integration control, all the targeted integration cell lines showed higher productivity, among which C12orf35 locus was the most advantageous in both productivity and cell line stability. Binding affinity and N-glycan analysis of the antibody revealed that all batches of product were of similar quality independent on integrated sites. Deep sequencing demonstrated that there was low level of off-target mutations caused by CRISPR/Cas9, but none of them contributed to the development process of transgene cell lines. Our results demonstrated the feasibility of C12orf35 as the target site for exogenous gene integration, and strongly suggested that C12orf35 targeted integration mediated by CRISPR/Cas9 is a reliable strategy for the rapid development of recombinant CHO cell lines.

  16. Protecting important sites for biodiversity contributes to meeting global conservation targets.

    Directory of Open Access Journals (Sweden)

    Stuart H M Butchart

    Full Text Available Protected areas (PAs are a cornerstone of conservation efforts and now cover nearly 13% of the world's land surface, with the world's governments committed to expand this to 17%. However, as biodiversity continues to decline, the effectiveness of PAs in reducing the extinction risk of species remains largely untested. We analyzed PA coverage and trends in species' extinction risk at globally significant sites for conserving birds (10,993 Important Bird Areas, IBAs and highly threatened vertebrates and conifers (588 Alliance for Zero Extinction sites, AZEs (referred to collectively hereafter as 'important sites'. Species occurring in important sites with greater PA coverage experienced smaller increases in extinction risk over recent decades: the increase was half as large for bird species with>50% of the IBAs at which they occur completely covered by PAs, and a third lower for birds, mammals and amphibians restricted to protected AZEs (compared with unprotected or partially protected sites. Globally, half of the important sites for biodiversity conservation remain unprotected (49% of IBAs, 51% of AZEs. While PA coverage of important sites has increased over time, the proportion of PA area covering important sites, as opposed to less important land, has declined (by 0.45-1.14% annually since 1950 for IBAs and 0.79-1.49% annually for AZEs. Thus, while appropriately located PAs may slow the rate at which species are driven towards extinction, recent PA network expansion has under-represented important sites. We conclude that better targeted expansion of PA networks would help to improve biodiversity trends.

  17. First record of target-site-resistance of poverty brome (Bromus sterilis to ACCase inhibitors

    Directory of Open Access Journals (Sweden)

    Dicke, Dominik

    2014-02-01

    Full Text Available In 2011 reduced efficacy of grass weed herbicides to poverty brome (Bromus sterilis was observed in oilseed rape on a site in East Hessen. The field was cultivated by using the ploughless tillage system more than 25 years. The site showed high densities of poverty brome (>1000 plants/m² prior to herbicide treatment. Poverty brome seeds were collected in 2012 in the hessian oilseed rape field and from a site in East Westphalia, where poverty brome appeared at low densities (10 plants/m² and was not suspected to resistance. The seeds were sown in to pots and plants cultivated. The plants were treated with two application rates (normal dose, double dose with herbicides of different HRAC-classes. The time of treatment was adjusted to the best expectable treatment/efficiency conditions of the individual herbicides (see chapter 3. Clear differences in efficacy that were caused by herbicide, the origins of poverty brome and the dosages were recorded via visual rating eight weeks after spraying. The herbicides Agil and Focus Ultra were able to control about 90% of the poverty brome plants of the East Westphalia site origin. However, only 20-30% of the Hessian plants could be knocked out by the same herbicides. The ACCase-gene of single powerty brome leaf samples from the hessian site was analyzed after resistance assessment. A molecular genetic analysis on 7 variable positions identified target site resistance: Isoleucine (Ile was replaced by asparagine (Asn at position 2041.

  18. A Graph Based Framework to Model Virus Integration Sites

    Directory of Open Access Journals (Sweden)

    Raffaele Fronza

    2016-01-01

    Here, we addressed the challenge to: 1 define the notion of CIS on graph models, 2 demonstrate that the structure of CIS enters in the category of scale-free networks and 3 show that our network approach analyzes CIS dynamically in an integrated systems biology framework using the Retroviral Transposon Tagged Cancer Gene Database (RTCGD as a testing dataset.

  19. Integral excitation functions for proton and alpha induced reactions on target elements 22 <= Z <= 28

    International Nuclear Information System (INIS)

    Brinkmann, G.

    1979-01-01

    In the framework of a systematic study which is also important for certain cosmological questions a series of integral excitation functions of p- and α-induced nuclear reactions on target elements 22 [de

  20. Integrative analysis of RUNX1 downstream pathways and target genes

    Directory of Open Access Journals (Sweden)

    Liu Marjorie

    2008-07-01

    Full Text Available Abstract Background The RUNX1 transcription factor gene is frequently mutated in sporadic myeloid and lymphoid leukemia through translocation, point mutation or amplification. It is also responsible for a familial platelet disorder with predisposition to acute myeloid leukemia (FPD-AML. The disruption of the largely unknown biological pathways controlled by RUNX1 is likely to be responsible for the development of leukemia. We have used multiple microarray platforms and bioinformatic techniques to help identify these biological pathways to aid in the understanding of why RUNX1 mutations lead to leukemia. Results Here we report genes regulated either directly or indirectly by RUNX1 based on the study of gene expression profiles generated from 3 different human and mouse platforms. The platforms used were global gene expression profiling of: 1 cell lines with RUNX1 mutations from FPD-AML patients, 2 over-expression of RUNX1 and CBFβ, and 3 Runx1 knockout mouse embryos using either cDNA or Affymetrix microarrays. We observe that our datasets (lists of differentially expressed genes significantly correlate with published microarray data from sporadic AML patients with mutations in either RUNX1 or its cofactor, CBFβ. A number of biological processes were identified among the differentially expressed genes and functional assays suggest that heterozygous RUNX1 point mutations in patients with FPD-AML impair cell proliferation, microtubule dynamics and possibly genetic stability. In addition, analysis of the regulatory regions of the differentially expressed genes has for the first time systematically identified numerous potential novel RUNX1 target genes. Conclusion This work is the first large-scale study attempting to identify the genetic networks regulated by RUNX1, a master regulator in the development of the hematopoietic system and leukemia. The biological pathways and target genes controlled by RUNX1 will have considerable importance in disease

  1. Protecting Important Sites for Biodiversity Contributes to Meeting Global Conservation Targets

    Science.gov (United States)

    Butchart, Stuart H. M.; Scharlemann, Jörn P. W.; Evans, Mike I.; Quader, Suhel; Aricò, Salvatore; Arinaitwe, Julius; Balman, Mark; Bennun, Leon A.; Bertzky, Bastian; Besançon, Charles; Boucher, Timothy M.; Brooks, Thomas M.; Burfield, Ian J.; Burgess, Neil D.; Chan, Simba; Clay, Rob P.; Crosby, Mike J.; Davidson, Nicholas C.; De Silva, Naamal; Devenish, Christian; Dutson, Guy C. L.; Fernández, David F. Día z; Fishpool, Lincoln D. C.; Fitzgerald, Claire; Foster, Matt; Heath, Melanie F.; Hockings, Marc; Hoffmann, Michael; Knox, David; Larsen, Frank W.; Lamoreux, John F.; Loucks, Colby; May, Ian; Millett, James; Molloy, Dominic; Morling, Paul; Parr, Mike; Ricketts, Taylor H.; Seddon, Nathalie; Skolnik, Benjamin; Stuart, Simon N.; Upgren, Amy; Woodley, Stephen

    2012-01-01

    Protected areas (PAs) are a cornerstone of conservation efforts and now cover nearly 13% of the world's land surface, with the world's governments committed to expand this to 17%. However, as biodiversity continues to decline, the effectiveness of PAs in reducing the extinction risk of species remains largely untested. We analyzed PA coverage and trends in species' extinction risk at globally significant sites for conserving birds (10,993 Important Bird Areas, IBAs) and highly threatened vertebrates and conifers (588 Alliance for Zero Extinction sites, AZEs) (referred to collectively hereafter as ‘important sites’). Species occurring in important sites with greater PA coverage experienced smaller increases in extinction risk over recent decades: the increase was half as large for bird species with>50% of the IBAs at which they occur completely covered by PAs, and a third lower for birds, mammals and amphibians restricted to protected AZEs (compared with unprotected or partially protected sites). Globally, half of the important sites for biodiversity conservation remain unprotected (49% of IBAs, 51% of AZEs). While PA coverage of important sites has increased over time, the proportion of PA area covering important sites, as opposed to less important land, has declined (by 0.45–1.14% annually since 1950 for IBAs and 0.79–1.49% annually for AZEs). Thus, while appropriately located PAs may slow the rate at which species are driven towards extinction, recent PA network expansion has under-represented important sites. We conclude that better targeted expansion of PA networks would help to improve biodiversity trends. PMID:22457717

  2. A mathematical model of single target site location by Brownian movement in subcellular compartments.

    Science.gov (United States)

    Kuthan, Hartmut

    2003-03-07

    The location of distinct sites is mandatory for many cellular processes. In the subcompartments of the cell nucleus, only very small numbers of diffusing macromolecules and specific target sites of some types may be present. In this case, we are faced with the Brownian movement of individual macromolecules and their "random search" for single/few specific target sites, rather than bulk-averaged diffusion and multiple sites. In this article, I consider the location of a distant central target site, e.g. a globular protein, by individual macromolecules executing unbiased (i.e. drift-free) random walks in a spherical compartment. For this walk-and-capture model, the closed-form analytic solution of the first passage time probability density function (p.d.f.) has been obtained as well as the first and second moment. In the limit of a large ratio of the radii of the spherical diffusion space and central target, well-known relations for the variance and the first two moments for the exponential p.d.f. were found to hold with high accuracy. These calculations reinforce earlier numerical results and Monte Carlo simulations. A major implication derivable from the model is that non-directed random movement is an effective means for locating single sites in submicron-sized compartments, even when the diffusion coefficients are comparatively small and the diffusing species are present in one copy only. These theoretical conclusions are underscored numerically for effective diffusion constants ranging from 0.5 to 10.0 microm(2) s(-1), which have been reported for a couple of nuclear proteins in their physiological environment. Spherical compartments of submicron size are, for example, the Cajal bodies (size: 0.1-1.0 microm), which are present in 1-5 copies in the cell nucleus. Within a small Cajal body of radius 0.1 microm a single diffusing protein molecule (with D=0.5 microm(2) s(-1)) would encounter a medium-sized protein of radius 2.5 nm within 1 s with a probability near

  3. Integrated planning for nuclear siting - The South African experience

    Energy Technology Data Exchange (ETDEWEB)

    Hobbs, J C.A.; Heidstra, N; Graupner, O F [Eskom, Johannesburg (South Africa); Hambleton-Jones, B [Atomic Energy Corporation of South Africa Ltd., Pellindaba, Pretoria (South Africa)

    1990-06-01

    This paper describes the process involved in the current national programme to identify potential sites for nuclear power development in South Africa. A description is given of the sensitivity studies - the evaluation of the potential perturbations to and opportunities for the biophysical and socioeconomic environments and the suitability studies - the evaluation of environmental influences on geotechnical, safety and financial considerations. This programme is divorced from any decision of whether or not to build further nuclear power station in South Africa. The programme described is a long range land-use planning exercise considered expedient in the face of competition for land that share similar requirements as those of nuclear power station sites. It is also designed to streamline nuclear power station lead times and to make national and regional planners aware of Eskom's requirements in the drafting of their policies and plans. (author)

  4. Integrated planning for nuclear siting - The South African experience

    International Nuclear Information System (INIS)

    Hobbs, J.C.A.; Heidstra, N.; Graupner, O.F.; Hambleton-Jones, B.

    1990-01-01

    This paper describes the process involved in the current national programme to identify potential sites for nuclear power development in South Africa. A description is given of the sensitivity studies - the evaluation of the potential perturbations to and opportunities for the biophysical and socioeconomic environments and the suitability studies - the evaluation of environmental influences on geotechnical, safety and financial considerations. This programme is divorced from any decision of whether or not to build further nuclear power station in South Africa. The programme described is a long range land-use planning exercise considered expedient in the face of competition for land that share similar requirements as those of nuclear power station sites. It is also designed to streamline nuclear power station lead times and to make national and regional planners aware of Eskom's requirements in the drafting of their policies and plans. (author)

  5. High-throughput monitoring of integration site clonality in preclinical and clinical gene therapy studies

    Directory of Open Access Journals (Sweden)

    Frank A Giordano

    Full Text Available Gene transfer to hematopoietic stem cells with integrating vectors not only allows sustained correction of monogenic diseases but also tracking of individual clones in vivo. Quantitative real-time PCR (qPCR has been shown to be an accurate method to quantify individual stem cell clones, yet due to frequently limited amounts of target material (especially in clinical studies, it is not useful for large-scale analyses. To explore whether vector integration site (IS recovery techniques may be suitable to describe clonal contributions if combined with next-generation sequencing techniques, we designed artificial ISs of different sizes which were mixed to simulate defined clonal situations in clinical settings. We subjected all mixes to either linear amplification–mediated PCR (LAM-PCR or nonrestrictive LAM-PCR (nrLAM-PCR, both combined with 454 sequencing. We showed that nrLAM-PCR/454-detected clonality allows estimating qPCR-detected clonality in vitro. We then followed the kinetics of two clones detected in a patient enrolled in a clinical gene therapy trial using both, nrLAM-PCR/454 and qPCR and also saw nrLAM-PCR/454 to correlate to qPCR-measured clonal contributions. The method presented here displays a feasible high-throughput strategy to monitor clonality in clinical gene therapy trials is at hand.

  6. Total site integration of light hydrocarbons separation process

    OpenAIRE

    Ulyev, L.; Vasilyev, M.; Maatouk, A.; Duic, Neven; Khusanovc, Alisher

    2016-01-01

    Ukraine is the largest consumer of hydrocarbons per unit of production in Europe (Ukraine policy review, 2006). The most important point is a reduction of energy consumption in chemical and metallurgical industries as a biggest consumer. This paper deals with energy savings potential of light hydrocarbons separation process. Energy consumption of light hydrocarbons separation process processes typical of Eastern European countries were analysed. Process Integration (PI) was used to perform a ...

  7. An integrated structure- and system-based framework to identify new targets of metabolites and known drugs

    KAUST Repository

    Naveed, Hammad

    2015-08-18

    Motivation: The inherent promiscuity of small molecules towards protein targets impedes our understanding of healthy versus diseased metabolism. This promiscuity also poses a challenge for the pharmaceutical industry as identifying all protein targets is important to assess (side) effects and repositioning opportunities for a drug. Results: Here, we present a novel integrated structure- and system-based approach of drug-target prediction (iDTP) to enable the large-scale discovery of new targets for small molecules, such as pharmaceutical drugs, co-factors and metabolites (collectively called ‘drugs’). For a given drug, our method uses sequence order–independent structure alignment, hierarchical clustering, and probabilistic sequence similarity to construct a probabilistic pocket ensemble (PPE) that captures promiscuous structural features of different binding sites on known targets. A drug’s PPE is combined with an approximation of its delivery profile to reduce false positives. In our cross-validation study, we use iDTP to predict the known targets of eleven drugs, with 63% sensitivity and 81% specificity. We then predicted novel targets for these drugs—two that are of high pharmacological interest, the nuclear receptor PPARγ and the oncogene Bcl-2, were successfully validated through in vitro binding experiments. Our method is broadly applicable for the prediction of protein-small molecule interactions with several novel applications to biological research and drug development.

  8. Glyphosate-Resistant Parthenium hysterophorus in the Caribbean Islands: Non Target Site Resistance and Target Site Resistance in Relation to Resistance Levels.

    Directory of Open Access Journals (Sweden)

    Enzo Bracamonte

    2016-12-01

    of a proline to serine change in Cu-R1, Do-R1 Do-R2. The above-mentioned results indicate that high resistance values are determined by the number of defense mechanisms (target-site and non-target-site resistance possessed by the different P. hysterophorus accessions, concurrently.

  9. Integrating epidemiology, psychology, and economics to achieve HPV vaccination targets.

    Science.gov (United States)

    Basu, Sanjay; Chapman, Gretchen B; Galvani, Alison P

    2008-12-02

    Human papillomavirus (HPV) vaccines provide an opportunity to reduce the incidence of cervical cancer. Optimization of cervical cancer prevention programs requires anticipation of the degree to which the public will adhere to vaccination recommendations. To compare vaccination levels driven by public perceptions with levels that are optimal for maximizing the community's overall utility, we develop an epidemiological game-theoretic model of HPV vaccination. The model is parameterized with survey data on actual perceptions regarding cervical cancer, genital warts, and HPV vaccination collected from parents of vaccine-eligible children in the United States. The results suggest that perceptions of survey respondents generate vaccination levels far lower than those that maximize overall health-related utility for the population. Vaccination goals may be achieved by addressing concerns about vaccine risk, particularly those related to sexual activity among adolescent vaccine recipients. In addition, cost subsidizations and shifts in federal coverage plans may compensate for perceived and real costs of HPV vaccination to achieve public health vaccination targets.

  10. Iron Deprivation Affects Drug Susceptibilities of Mycobacteria Targeting Membrane Integrity

    Directory of Open Access Journals (Sweden)

    Rahul Pal

    2015-01-01

    Full Text Available Multidrug resistance (MDR acquired by Mycobacterium tuberculosis (MTB through continuous deployment of antitubercular drugs warrants immediate search for novel targets and mechanisms. The ability of MTB to sense and become accustomed to changes in the host is essential for survival and confers the basis of infection. A crucial condition that MTB must surmount is iron limitation, during the establishment of infection, since iron is required by both bacteria and humans. This study focuses on how iron deprivation affects drug susceptibilities of known anti-TB drugs in Mycobacterium smegmatis, a “surrogate of MTB.” We showed that iron deprivation leads to enhanced potency of most commonly used first line anti-TB drugs that could be reverted upon iron supplementation. We explored that membrane homeostasis is disrupted upon iron deprivation as revealed by enhanced membrane permeability and hypersensitivity to membrane perturbing agent leading to increased passive diffusion of drug and TEM images showing detectable differences in cell envelope thickness. Furthermore, iron seems to be indispensable to sustain genotoxic stress suggesting its possible role in DNA repair machinery. Taken together, we for the first time established a link between cellular iron and drug susceptibility of mycobacteria suggesting iron as novel determinant to combat MDR.

  11. Scaling Up Renewable Energy Generation: Aligning Targets and Incentives with Grid Integration Considerations, Greening The Grid

    Energy Technology Data Exchange (ETDEWEB)

    Katz, Jessica; Cochran, Jaquelin

    2015-05-27

    Greening the Grid provides technical assistance to energy system planners, regulators, and grid operators to overcome challenges associated with integrating variable renewable energy into the grid. This document, part of a Greening the Grid toolkit, provides power system planners with tips to help secure and sustain investment in new renewable energy generation by aligning renewable energy policy targets and incentives with grid integration considerations.

  12. Thermodynamic Characterization of Hydration Sites from Integral Equation-Derived Free Energy Densities: Application to Protein Binding Sites and Ligand Series.

    Science.gov (United States)

    Güssregen, Stefan; Matter, Hans; Hessler, Gerhard; Lionta, Evanthia; Heil, Jochen; Kast, Stefan M

    2017-07-24

    Water molecules play an essential role for mediating interactions between ligands and protein binding sites. Displacement of specific water molecules can favorably modulate the free energy of binding of protein-ligand complexes. Here, the nature of water interactions in protein binding sites is investigated by 3D RISM (three-dimensional reference interaction site model) integral equation theory to understand and exploit local thermodynamic features of water molecules by ranking their possible displacement in structure-based design. Unlike molecular dynamics-based approaches, 3D RISM theory allows for fast and noise-free calculations using the same detailed level of solute-solvent interaction description. Here we correlate molecular water entities instead of mere site density maxima with local contributions to the solvation free energy using novel algorithms. Distinct water molecules and hydration sites are investigated in multiple protein-ligand X-ray structures, namely streptavidin, factor Xa, and factor VIIa, based on 3D RISM-derived free energy density fields. Our approach allows the semiquantitative assessment of whether a given structural water molecule can potentially be targeted for replacement in structure-based design. Finally, PLS-based regression models from free energy density fields used within a 3D-QSAR approach (CARMa - comparative analysis of 3D RISM Maps) are shown to be able to extract relevant information for the interpretation of structure-activity relationship (SAR) trends, as demonstrated for a series of serine protease inhibitors.

  13. Discrepancy of target sites between clinician and cytopathological reports in head neck fine needle aspiration: Did I miss the target or did the clinician mistake the organ site?

    International Nuclear Information System (INIS)

    Khanlari, Mahsa; Daneshbod, Yahya; Shaterzadeh Yazdi, Hanieh; Shirian, Sadegh; Negahban, Shahrzad; Aledavood, Azita; Oryan, Ahmad; Khademi, Bijan; Daneshbod, Khosrow; Field, Andrew

    2015-01-01

    The diagnostic accuracy of fine needle aspiration cytology (FNAC) of head and neck lesions is relatively high, but cytologic interpretation might be confusing if the sample is lacking typical cytologic features according to labeled site by physician. These errors may have an impact on pathology search engines, healthcare costs or even adverse outcomes. The cytology archive database of multiple institutions in southern Iran and Australia covering the period 2001–2011, were searched using keywords: salivary gland, head, neck, FNAC, and cytology. All the extracted reports were reviewed. The reports which showed discordance between the clinician's impression of the organ involved and subsequent fine needle biopsy request, and the eventual cytological diagnosis were selected. The cytological diagnosis was confirmed by histology or cell block, with assistance from imaging, clinical outcome, physical examination, molecular studies, or microbiological culture. The total number of 10,200 head and neck superficial FNAC were included in the study, from which 48 cases showed discordance between the clinicians request and the actual site of pathology. Apart from the histopathology, the imaging, clinical history, physical examination, immunohistochemical study, microbiologic culture and molecular testing helped to finalize the target organ of pathology in 23, 6, 7, 8, 2, and 1 cases respectively. The commonest discrepancies were for FNAC of “salivary gland” [total: 20 with actual final pathology in: bone (7), soft tissue (5), lymph node (3), odontogenic (3) and skin (2)], “lymph node” [total: 12 with final pathology in: soft tissue (3), skin (3), bone (1) and brain (1)], “soft tissue” [total: 11 with final pathology in: bone (5), skin (2), salivary gland (1), and ocular region (1)] and “skin” [total: 5 with final pathology in: lymph node (2), bone (1), soft tissue (1) and salivary gland (1)]. The primary physician requesting FNAC of head and neck lesions

  14. Prolonged Integration Site Selection of a Lentiviral Vector in the Genome of Human Keratinocytes.

    Science.gov (United States)

    Qian, Wei; Wang, Yong; Li, Rui-Fu; Zhou, Xin; Liu, Jing; Peng, Dai-Zhi

    2017-03-03

    BACKGROUND Lentiviral vectors have been successfully used for human skin cell gene transfer studies. Defining the selection of integration sites for retroviral vectors in the host genome is crucial in risk assessment analysis of gene therapy. However, genome-wide analyses of lentiviral integration sites in human keratinocytes, especially after prolonged growth, are poorly understood. MATERIAL AND METHODS In this study, 874 unique lentiviral vector integration sites in human HaCaT keratinocytes after long-term culture were identified and analyzed with the online tool GTSG-QuickMap and SPSS software. RESULTS The data indicated that lentiviral vectors showed integration site preferences for genes and gene-rich regions. CONCLUSIONS This study will likely assist in determining the relative risks of the lentiviral vector system and in the design of a safe lentiviral vector system in the gene therapy of skin diseases.

  15. LCA of contaminated site remediation - integration of site-specific impact assessment of local toxic impacts

    DEFF Research Database (Denmark)

    Lemming, Gitte; Hauschild, Michael Zwicky; Chambon, Julie Claire Claudia

    2011-01-01

    impacts have typically been assessed using site-generic characterization models representing a continental scale and excluding the groundwater compartment. Soil contaminants have therefore generally been assigned as emissions to surface soil or surface water compartments. However, such site-generic...... assessments poorly reflect the fate of frequent soil contaminants such as chloroethenes as they exclude the groundwater compartment and assume that the main part escapes to the atmosphere. Another important limitation of the generic impact assessment models is that they do not include the formation......The environmental impacts from remediation can be divided into primary and secondary impacts. Primary impacts cover the local impacts associated with the on-site contamination, whereas the secondary impacts are impacts on the local, regional and global scale generated by the remediation activities...

  16. Taking interim actions: Integrating CERCLA and NEPA to move ahead with site cleanup

    International Nuclear Information System (INIS)

    MacDonell, M.M.; Peterson, J.M.; Valett, G.L.; McCracken, S.H.

    1991-01-01

    The cleanup of contaminated sites can be expedited by using interim response actions in accordance with the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA), as amended, and the National Oil and Hazardous Substances Pollution Contingency Plan (NCP). In fact, a major portion of some Superfund sites can be cleaned up using interim actions. For CERCLA sites being remediated by the US Department of Energy (DOE), such actions must also comply with the National Environmental Policy Act (NEPA) because the DOE has established a policy for integrating CERCLA and NEPA requirements. A strategy for the integrated documentation with implementation of interim actions has been applied successfully at the Weldon Spring site, and major cleanup projects are currently underway. This paper discusses some of the issues associated with integrating CERCLA and NEPA for interim actions and summarizes those actions that have been identified for the Weldon Spring site

  17. Taking interim actions: Integrating CERCLA and NEPA to move ahead with site cleanup

    International Nuclear Information System (INIS)

    MacDonell, M.M.; Peterson, J.M.; Valett, G.L.; McCracken, S.H.

    1991-01-01

    The cleanup of contaminated sites can be expedited by using interim response actions in accordance with the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA), as amended, and the National Oil and Hazardous Substances Pollution Contingency Plan (NCP). In fact, a major portion of some Superfund sites can be cleaned up using interim actions. For CERCLA sites being remediated by the US Department of Energy (DOE), such actions must also comply with the National Environmental Policy Act (NEPA) because the DOE has established a policy for integrating CERCLA and NEPA requirements. A strategy for the integrated documentation and implementation of interim actions has been applied successfully at the Weldon Spring site, and major cleanup projects are currently underway. This paper discusses some of the issues associated with integrating CERCLA and NEPA for interim actions and summarizes those actions that have been identified for the Weldon Spring site

  18. Savannah River Site integrated stabilization management plan. Revision 3

    International Nuclear Information System (INIS)

    Geddes, R.L.; Barone, A.; Shook, H.E.; Varner, C.E.; Rollins, R.

    1996-01-01

    On May 26, 1994, the Defense Nuclear Facilities Safety Board (DNFSB) issued Recommendation 94-1. The concern is that the halt in production of materials to be used in nuclear weapons froze the manufacturing pipeline in a state that, for safety reasons, should not be allowed to persist unremediated. This recommendation had eight specific sub-recommendations that dealt with the potential problems. Specifically, the Board expressed concern about certain liquids and solids containing fissile materials and other radioactive substances located in spent fuel storage pools, reactor basins, reprocessing canyons; and various other facilities once used for processing and weapons manufacture. The WSRC and DOE-SR acknowledges and shares the Board's concerns and has developed this Integrated Stabilization Management Plan (ISMP) to aggressively address these urgent problems in a systems engineering approach

  19. Target molecular weights for red cell band 3 stilbene and mercurial binding sites

    International Nuclear Information System (INIS)

    Verkman, A.S.; Skorecki, K.L.; Jung, C.Y.; Ausiello, D.A.

    1986-01-01

    Radiation inactivation was used to measure the target sizes for binding of disulfonic stilbene anion transport inhibitor 4,4'-dibenzamido-2,2'-disulfonic stilbene (DBDS) and mercurial water transport inhibitor p-chloromercuribenzene sulfonate (pCMBS) to human erythrocytes. The measured target size for erythrocyte ghost acetylcholinesterase was 78 +/- 3 kDa. DBDS binding to ghost membranes was measured by a fluorescence enhancement technique. Radiation (0-26 Mrad) had no effect on total membrane protein and DBDS binding affinity, whereas DBDS binding stoichiometry decreased exponentially with radiation dose, giving a target size of 59 +/- 4 kDa. H2-4,4'-diisothiocyano-2,2'-disulfonic stilbene (H2-DIDS, 5 microM) blocked greater than 95% of DBDS binding at all radiation doses. pCMBS binding was measured from the time course of tryptophan fluorescence quenching in ghosts treated with the sulfhydryl reagent N-ethylmaleimide (NEM). Radiation did not affect the kinetics of tryptophan quenching, whereas the total amplitude of the fluorescence signal inactivated with radiation with a target size of 31 +/- 6 kDa. These results support the notion that DBDS and pCMBS bind to the transmembrane domain of erythrocyte band 3 in NEM-treated ghosts and demonstrate that radiation inactivation may probe a target significantly smaller than a covalently linked protein subunit. The small target size for the band 3 stilbene binding site may correspond to the intramembrane domain of the band 3 monomer (52 kDa), which is physically distinct from the cytoplasmic domain (42 kDa)

  20. Targeting hunter distribution based on host resource selection and kill sites to manage disease risk.

    Science.gov (United States)

    Dugal, Cherie J; van Beest, Floris M; Vander Wal, Eric; Brook, Ryan K

    2013-10-01

    Endemic and emerging diseases are rarely uniform in their spatial distribution or prevalence among cohorts of wildlife. Spatial models that quantify risk-driven differences in resource selection and hunter mortality of animals at fine spatial scales can assist disease management by identifying high-risk areas and individuals. We used resource selection functions (RSFs) and selection ratios (SRs) to quantify sex- and age-specific resource selection patterns of collared (n = 67) and hunter-killed (n = 796) nonmigratory elk (Cervus canadensis manitobensis) during the hunting season between 2002 and 2012, in southwestern Manitoba, Canada. Distance to protected area was the most important covariate influencing resource selection and hunter-kill sites of elk (AICw = 1.00). Collared adult males (which are most likely to be infected with bovine tuberculosis (Mycobacterium bovis) and chronic wasting disease) rarely selected for sites outside of parks during the hunting season in contrast to adult females and juvenile males. The RSFs showed selection by adult females and juvenile males to be negatively associated with landscape-level forest cover, high road density, and water cover, whereas hunter-kill sites of these cohorts were positively associated with landscape-level forest cover and increasing distance to streams and negatively associated with high road density. Local-level forest was positively associated with collared animal locations and hunter-kill sites; however, selection was stronger for collared juvenile males and hunter-killed adult females. In instances where disease infects a metapopulation and eradication is infeasible, a principle goal of management is to limit the spread of disease among infected animals. We map high-risk areas that are regularly used by potentially infectious hosts but currently underrepresented in the distribution of kill sites. We present a novel application of widely available data to target hunter distribution based on host resource

  1. Designing to target cost: one approach to design/construction integration

    DEFF Research Database (Denmark)

    Jørgensen, Bo

    2005-01-01

    One approach to a more integrated construction delivery process is the concept of ‘designing to target cost’ of which the first examples of application within a lean construction framework have recently been seen. This paper introduces the main principles of the design to target cost method...... and discusses the applicability of this approach to construction. The low degree of organizational and technical continuity from one construction project to the next limits the applicability of the design for target cost approach when compared to its origin in product development of mass manufactured artefacts....... It can be argued that design to target cost may also provide a frame for developing the supply chain towards better coordination and collaboration. Thus methods of design to target cost may serve to facilitate the development of a more integrated supply chain....

  2. Evaluation of an integrated treatment system for MGP site groundwaters

    International Nuclear Information System (INIS)

    Scheible, O.K.; Grey, G.M.; Maiello, J.A.

    1995-01-01

    Initially studied at bench scale, process sequences comprising dissolved air flotation (DAF), aerobic biological oxidation, air stripping, filtration, and carbon adsorption were demonstrated at pilot scale at a manufactured gas plant (MGP) site in New Jersey. Benzene, toluene, ethylbenzene, and xylenes (BTEX), and polycyclic aromatic hydrocarbons (PAHs) were the primary organics in the groundwater, ranging from levels of 2 to 8 mg/L and 0.3 to 27 mg/L, respectively; chemical oxygen demand (COD) levels were from 60 to 4,500 mg/L. Significant levels of dense, emulsified, and nonaqueous tars and oils were present in the more highly contaminated waters and were effectively removed by DAF. Carbon-based fluidized-bed biological treatment of the DAF subnatant at COD loadings between 2 and 4 g/L-d yielded effluent-soluble COD levels between 40 and 60 mg/L, with both residual BTEX and PAH concentrations ranging from nondetect levels to 0.1 mg/L. Subsequent polishing by filtration and carbon adsorption resulted in additional COD removal and nondetect levels of volatiles and semivolatiles. Air stripping was effective in lieu of the biological process for both volatile organic compound (VOC) and PAH removal

  3. An integrated in silico approach to design specific inhibitors targeting human poly(a-specific ribonuclease.

    Directory of Open Access Journals (Sweden)

    Dimitrios Vlachakis

    Full Text Available Poly(A-specific ribonuclease (PARN is an exoribonuclease/deadenylase that degrades 3'-end poly(A tails in almost all eukaryotic organisms. Much of the biochemical and structural information on PARN comes from the human enzyme. However, the existence of PARN all along the eukaryotic evolutionary ladder requires further and thorough investigation. Although the complete structure of the full-length human PARN, as well as several aspects of the catalytic mechanism still remain elusive, many previous studies indicate that PARN can be used as potent and promising anti-cancer target. In the present study, we attempt to complement the existing structural information on PARN with in-depth bioinformatics analyses, in order to get a hologram of the molecular evolution of PARNs active site. In an effort to draw an outline, which allows specific drug design targeting PARN, an unequivocally specific platform was designed for the development of selective modulators focusing on the unique structural and catalytic features of the enzyme. Extensive phylogenetic analysis based on all the publicly available genomes indicated a broad distribution for PARN across eukaryotic species and revealed structurally important amino acids which could be assigned as potentially strong contributors to the regulation of the catalytic mechanism of PARN. Based on the above, we propose a comprehensive in silico model for the PARN's catalytic mechanism and moreover, we developed a 3D pharmacophore model, which was subsequently used for the introduction of DNP-poly(A amphipathic substrate analog as a potential inhibitor of PARN. Indeed, biochemical analysis revealed that DNP-poly(A inhibits PARN competitively. Our approach provides an efficient integrated platform for the rational design of pharmacophore models as well as novel modulators of PARN with therapeutic potential.

  4. DNFSB Recommendation 94-1 Hanford site integrated stabilization management plan, volumes 1 and 2

    International Nuclear Information System (INIS)

    Gerber, E.W.

    1996-01-01

    This document comprises the Hanford Site Integrated Stabilization Management Plan (SISMP). This document describes the DOE's plans at the Hanford Site to address concerns identified in Defense Nuclear Facilites Safety Board (DNFSB) Recommendation 94-1. This document also identifies plans for other spent nuclear fuel (SNF) inventories at the Hanford Site which are not within the scope of DNFSB Recommendation 94-1 for reference purposes because of their interrelationship with plans for SNF within the scope of DNFSB Recommendation 94-1. The SISMP was also developed to assist DOE in initial formulation of the Research and Development Plan and the Integrated Facilities Plan

  5. Dual CRISPR-Cas9 Cleavage Mediated Gene Excision and Targeted Integration in Yarrowia lipolytica.

    Science.gov (United States)

    Gao, Difeng; Smith, Spencer; Spagnuolo, Michael; Rodriguez, Gabriel; Blenner, Mark

    2018-05-29

    CRISPR-Cas9 technology has been successfully applied in Yarrowia lipolytica for targeted genomic editing including gene disruption and integration; however, disruptions by existing methods typically result from small frameshift mutations caused by indels within the coding region, which usually resulted in unnatural protein. In this study, a dual cleavage strategy directed by paired sgRNAs is developed for gene knockout. This method allows fast and robust gene excision, demonstrated on six genes of interest. The targeted regions for excision vary in length from 0.3 kb up to 3.5 kb and contain both non-coding and coding regions. The majority of the gene excisions are repaired by perfect nonhomologous end-joining without indel. Based on this dual cleavage system, two targeted markerless integration methods are developed by providing repair templates. While both strategies are effective, homology mediated end joining (HMEJ) based method are twice as efficient as homology recombination (HR) based method. In both cases, dual cleavage leads to similar or improved gene integration efficiencies compared to gene excision without integration. This dual cleavage strategy will be useful for not only generating more predictable and robust gene knockout, but also for efficient targeted markerless integration, and simultaneous knockout and integration in Y. lipolytica. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Targeted Delivery of LXR Agonist Using a Site-Specific Antibody-Drug Conjugate.

    Science.gov (United States)

    Lim, Reyna K V; Yu, Shan; Cheng, Bo; Li, Sijia; Kim, Nam-Jung; Cao, Yu; Chi, Victor; Kim, Ji Young; Chatterjee, Arnab K; Schultz, Peter G; Tremblay, Matthew S; Kazane, Stephanie A

    2015-11-18

    Liver X receptor (LXR) agonists have been explored as potential treatments for atherosclerosis and other diseases based on their ability to induce reverse cholesterol transport and suppress inflammation. However, this therapeutic potential has been hindered by on-target adverse effects in the liver mediated by excessive lipogenesis. Herein, we report a novel site-specific antibody-drug conjugate (ADC) that selectively delivers a LXR agonist to monocytes/macrophages while sparing hepatocytes. The unnatural amino acid para-acetylphenylalanine (pAcF) was site-specifically incorporated into anti-CD11a IgG, which binds the α-chain component of the lymphocyte function-associated antigen 1 (LFA-1) expressed on nearly all monocytes and macrophages. An aminooxy-modified LXR agonist was conjugated to anti-CD11a IgG through a stable, cathepsin B cleavable oxime linkage to afford a chemically defined ADC. The anti-CD11a IgG-LXR agonist ADC induced LXR activation specifically in human THP-1 monocyte/macrophage cells in vitro (EC50-27 nM), but had no significant effect in hepatocytes, indicating that payload delivery is CD11a-mediated. Moreover, the ADC exhibited higher-fold activation compared to a conventional synthetic LXR agonist T0901317 (Tularik) (3-fold). This novel ADC represents a fundamentally different strategy that uses tissue targeting to overcome the limitations of LXR agonists for potential use in treating atherosclerosis.

  7. Contribution of non-target-site resistance in imidazolinone-resistant Imisun sunflower

    Directory of Open Access Journals (Sweden)

    Gabriela Breccia

    2017-08-01

    Full Text Available ABSTRACT The first commercial herbicide-resistant trait in sunflower (Helianthus annuus L. is known as ‘Imisun’. Imidazolinone resistance in Imisun cultivars has been reported to be genetically controlled by a major gene (known as Imr1 or Ahasl1-1 and modifier genes. Imr1 is an allelic variant of the Ahasl1 locus that codes for the acetohydroxyacid synthase, which is the target site of these herbicides. The mechanism of resistance endowed by modifier genes has not been characterized and it could be related to non-target-site resistance. The objective of this study was to evaluate the role of cytochrome P450 monooxygenases (P450s in Imisun resistance. The response to imazapyr herbicide in combination with P450s inhibitor malathion was evaluated in 2 Imisun lines, IMI-1 and RHA426. Malathion reduced herbicide efficacy in both lines, but IMI-1 was affected in a greater extent. A significant reduction in plant growth in response to P450s inhibitors 1-aminobenzotriazole and piperonyl butoxide treatment was detected in the Imisun line HA425. The increased susceptibility to imazapyr after P450s-inhibitor treatment indicates that herbicide metabolism by P450s is a mechanism involved in Imisun resistance. These results also suggest the involvement of different P450s isozymes in endowing resistance to imazapyr in Imisun cultivars.

  8. Epitope-based peptide vaccine design and target site depiction against Ebola viruses: an immunoinformatics study.

    Science.gov (United States)

    Khan, M A; Hossain, M U; Rakib-Uz-Zaman, S M; Morshed, M N

    2015-07-01

    Ebola viruses (EBOVs) have been identified as an emerging threat in recent year as it causes severe haemorrhagic fever in human. Epitope-based vaccine design for EBOVs remains a top priority because a mere progress has been made in this regard. Another reason is the lack of antiviral drug and licensed vaccine although there is a severe outbreak in Central Africa. In this study, we aimed to design an epitope-based vaccine that can trigger a significant immune response as well as to prognosticate inhibitor that can bind with potential drug target sites using various immunoinformatics and docking simulation tools. The capacity to induce both humoral and cell-mediated immunity by T cell and B cell was checked for the selected protein. The peptide region spanning 9 amino acids from 42 to 50 and the sequence TLASIGTAF were found as the most potential B and T cell epitopes, respectively. This peptide could interact with 12 HLAs and showed high population coverage up to 80.99%. Using molecular docking, the epitope was further appraised for binding against HLA molecules to verify the binding cleft interaction. In addition with this, the allergenicity of the epitopes was also evaluated. In the post-therapeutic strategy, docking study of predicted 3D structure identified suitable therapeutic inhibitor against targeted protein. However, this computational epitope-based peptide vaccine designing and target site prediction against EBOVs open up a new horizon which may be the prospective way in Ebola viruses research; the results require validation by in vitro and in vivo experiments. © 2015 John Wiley & Sons Ltd.

  9. Hydrogen peroxide (H2O2) irreversibly inactivates creatine kinase from Pelodiscus sinensis by targeting the active site cysteine.

    Science.gov (United States)

    Wang, Wei; Lee, Jinhyuk; Hao, Hao; Park, Yong-Doo; Qian, Guo-Ying

    2017-12-01

    Creatine kinase (EC 2.7.3.2, CK) plays an important role in cellular energy metabolism and homeostasis by catalysing the transfer of phosphate between ATP and creatine phosphate. In this study, we investigated the effects of H 2 O 2 on PSCKM (muscle type creatine kinase from Pelodiscus sinensis) by the integrating method between enzyme kinetics and docking simulations. We found that H 2 O 2 strongly inactivated PSCKM (IC 50 =0.25mM) in a first-order kinetic process, and targeted the active site cysteine directly. A conformational study showed that H 2 O 2 did not induce the tertiary structural changes in PSCKM with no extensive exposure of hydrophobic surfaces. Sequential docking simulations between PSCKM and H 2 O 2 indicated that H 2 O 2 interacts with the ADP binding region of the active site, consistent with experimental results that demonstrated H 2 O 2 -induced inactivation. Our study demonstrates the effect of H 2 O 2 on PSCKM enzymatic function and unfolding, and provides important insight into the changes undergone by this central metabolic enzyme in ectothermic animals in response to the environment. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Nanoscale Synaptic Membrane Mimetic Allows Unbiased High Throughput Screen That Targets Binding Sites for Alzheimer's-Associated Aβ Oligomers.

    Directory of Open Access Journals (Sweden)

    Kyle C Wilcox

    Full Text Available Despite their value as sources of therapeutic drug targets, membrane proteomes are largely inaccessible to high-throughput screening (HTS tools designed for soluble proteins. An important example comprises the membrane proteins that bind amyloid β oligomers (AβOs. AβOs are neurotoxic ligands thought to instigate the synapse damage that leads to Alzheimer's dementia. At present, the identities of initial AβO binding sites are highly uncertain, largely because of extensive protein-protein interactions that occur following attachment of AβOs to surface membranes. Here, we show that AβO binding sites can be obtained in a state suitable for unbiased HTS by encapsulating the solubilized synaptic membrane proteome into nanoscale lipid bilayers (Nanodiscs. This method gives a soluble membrane protein library (SMPL--a collection of individualized synaptic proteins in a soluble state. Proteins within SMPL Nanodiscs showed enzymatic and ligand binding activity consistent with conformational integrity. AβOs were found to bind SMPL Nanodiscs with high affinity and specificity, with binding dependent on intact synaptic membrane proteins, and selective for the higher molecular weight oligomers known to accumulate at synapses. Combining SMPL Nanodiscs with a mix-incubate-read chemiluminescence assay provided a solution-based HTS platform to discover antagonists of AβO binding. Screening a library of 2700 drug-like compounds and natural products yielded one compound that potently reduced AβO binding to SMPL Nanodiscs, synaptosomes, and synapses in nerve cell cultures. Although not a therapeutic candidate, this small molecule inhibitor of synaptic AβO binding will provide a useful experimental antagonist for future mechanistic studies of AβOs in Alzheimer's model systems. Overall, results provide proof of concept for using SMPLs in high throughput screening for AβO binding antagonists, and illustrate in general how a SMPL Nanodisc system can

  11. Nanoscale Synaptic Membrane Mimetic Allows Unbiased High Throughput Screen That Targets Binding Sites for Alzheimer’s-Associated Aβ Oligomers

    Science.gov (United States)

    Wilcox, Kyle C.; Marunde, Matthew R.; Das, Aditi; Velasco, Pauline T.; Kuhns, Benjamin D.; Marty, Michael T.; Jiang, Haoming; Luan, Chi-Hao; Sligar, Stephen G.; Klein, William L.

    2015-01-01

    Despite their value as sources of therapeutic drug targets, membrane proteomes are largely inaccessible to high-throughput screening (HTS) tools designed for soluble proteins. An important example comprises the membrane proteins that bind amyloid β oligomers (AβOs). AβOs are neurotoxic ligands thought to instigate the synapse damage that leads to Alzheimer’s dementia. At present, the identities of initial AβO binding sites are highly uncertain, largely because of extensive protein-protein interactions that occur following attachment of AβOs to surface membranes. Here, we show that AβO binding sites can be obtained in a state suitable for unbiased HTS by encapsulating the solubilized synaptic membrane proteome into nanoscale lipid bilayers (Nanodiscs). This method gives a soluble membrane protein library (SMPL)—a collection of individualized synaptic proteins in a soluble state. Proteins within SMPL Nanodiscs showed enzymatic and ligand binding activity consistent with conformational integrity. AβOs were found to bind SMPL Nanodiscs with high affinity and specificity, with binding dependent on intact synaptic membrane proteins, and selective for the higher molecular weight oligomers known to accumulate at synapses. Combining SMPL Nanodiscs with a mix-incubate-read chemiluminescence assay provided a solution-based HTS platform to discover antagonists of AβO binding. Screening a library of 2700 drug-like compounds and natural products yielded one compound that potently reduced AβO binding to SMPL Nanodiscs, synaptosomes, and synapses in nerve cell cultures. Although not a therapeutic candidate, this small molecule inhibitor of synaptic AβO binding will provide a useful experimental antagonist for future mechanistic studies of AβOs in Alzheimer’s model systems. Overall, results provide proof of concept for using SMPLs in high throughput screening for AβO binding antagonists, and illustrate in general how a SMPL Nanodisc system can facilitate drug

  12. Nanoscale Synaptic Membrane Mimetic Allows Unbiased High Throughput Screen That Targets Binding Sites for Alzheimer's-Associated Aβ Oligomers.

    Science.gov (United States)

    Wilcox, Kyle C; Marunde, Matthew R; Das, Aditi; Velasco, Pauline T; Kuhns, Benjamin D; Marty, Michael T; Jiang, Haoming; Luan, Chi-Hao; Sligar, Stephen G; Klein, William L

    2015-01-01

    Despite their value as sources of therapeutic drug targets, membrane proteomes are largely inaccessible to high-throughput screening (HTS) tools designed for soluble proteins. An important example comprises the membrane proteins that bind amyloid β oligomers (AβOs). AβOs are neurotoxic ligands thought to instigate the synapse damage that leads to Alzheimer's dementia. At present, the identities of initial AβO binding sites are highly uncertain, largely because of extensive protein-protein interactions that occur following attachment of AβOs to surface membranes. Here, we show that AβO binding sites can be obtained in a state suitable for unbiased HTS by encapsulating the solubilized synaptic membrane proteome into nanoscale lipid bilayers (Nanodiscs). This method gives a soluble membrane protein library (SMPL)--a collection of individualized synaptic proteins in a soluble state. Proteins within SMPL Nanodiscs showed enzymatic and ligand binding activity consistent with conformational integrity. AβOs were found to bind SMPL Nanodiscs with high affinity and specificity, with binding dependent on intact synaptic membrane proteins, and selective for the higher molecular weight oligomers known to accumulate at synapses. Combining SMPL Nanodiscs with a mix-incubate-read chemiluminescence assay provided a solution-based HTS platform to discover antagonists of AβO binding. Screening a library of 2700 drug-like compounds and natural products yielded one compound that potently reduced AβO binding to SMPL Nanodiscs, synaptosomes, and synapses in nerve cell cultures. Although not a therapeutic candidate, this small molecule inhibitor of synaptic AβO binding will provide a useful experimental antagonist for future mechanistic studies of AβOs in Alzheimer's model systems. Overall, results provide proof of concept for using SMPLs in high throughput screening for AβO binding antagonists, and illustrate in general how a SMPL Nanodisc system can facilitate drug discovery

  13. An integrated structure- and system-based framework to identify new targets of metabolites and known drugs

    KAUST Repository

    Naveed, Hammad; Hameed, Umar Farook Shahul; Harrus, Deborah; Bourguet, William; Arold, Stefan T.; Gao, Xin

    2015-01-01

    Results: Here, we present a novel integrated structure- and system-based approach of drug-target prediction (iDTP) to enable the large-scale discovery of new targets for small molecules, such as pharmaceutical drugs, co-factors and metabolites (collectively called ‘drugs’). For a given drug, our method uses sequence order–independent structure alignment, hierarchical clustering, and probabilistic sequence similarity to construct a probabilistic pocket ensemble (PPE) that captures promiscuous structural features of different binding sites on known targets. A drug’s PPE is combined with an approximation of its delivery profile to reduce false positives. In our cross-validation study, we use iDTP to predict the known targets of eleven drugs, with 63% sensitivity and 81% specificity. We then predicted novel targets for these drugs—two that are of high pharmacological interest, the nuclear receptor PPARγ and the oncogene Bcl-2, were successfully validated through in vitro binding experiments. Our method is broadly applicable for the prediction of protein-small molecule interactions with several novel applications to biological research and drug development.

  14. Physicochemical and mineralogical characterization of uranium-contaminated soils from the Fernald Integrated Demonstration Site

    International Nuclear Information System (INIS)

    Elless, M.P.; Lee, S.Y.; Timpson, M.E.

    1994-01-01

    An integrated approach that utilizes various characterization technologies has been developed for the Uranium Soil Integrated Demonstration program. The Fernald Environmental Restoration Management Corporation site near Cincinnati, Ohio, was selected as the host facility for this demonstration. Characterization of background, untreated contaminated, and treated contaminated soils was performed to assess the contamination and the effect of treatment efforts to remove uranium from these soils. Carbonate minerals were present in the contaminated soils (added for erosion control) but were absent in the nearby background soils. Because of the importance of the carbonate anion to uranium solubility, the occurrence of carbonate minerals in these soils will be an important factor in the development of a successful remediation technology. Uranium partitioning data among several particle-size fractions indicate that conventional soil washing will be ineffective for remediation of these soils and that chemical extraction will be necessary to lower the uranium concentration to the target level (52 mg/kg). Carbonate-based (sodium carbonate/bicarbonate) and acid-based (sulfuric and citric acids) lixiviants were employed for the selective removal of uranium from these soils. Characterization results have identified uranium phosphate minerals as the predominant uranium mineral form in both the untreated and treated soils. The low solubility associated with phosphate minerals is primarily responsible for their occurrence in the posttreated soils. Artificial weathering of the treated soils caused by the treatments, particularly acid-based lixiviants, was documented by their detrimental effects on several physicochemical characteristics of these soils (e.g., soil pH, particle-size distribution, and mineralogy)

  15. Integrated Solution of a Back Office System for Serious Games Targeted at Physiotherapy

    Directory of Open Access Journals (Sweden)

    Tiago Martins

    2016-01-01

    Full Text Available Serious games targeted at physiotherapy can be a solution to help the physical therapy professionals. However, the entire game management, in its various aspects, is under the professional’s responsibility. One way to reduce the professional management work will be to integrate a Back Office system in the game. Following this trend, the purpose of this paper is to present a modular Back Office system for centralized management of one or more games targeted at physical therapy.

  16. Virus-Clip: a fast and memory-efficient viral integration site detection tool at single-base resolution with annotation capability.

    Science.gov (United States)

    Ho, Daniel W H; Sze, Karen M F; Ng, Irene O L

    2015-08-28

    Viral integration into the human genome upon infection is an important risk factor for various human malignancies. We developed viral integration site detection tool called Virus-Clip, which makes use of information extracted from soft-clipped sequencing reads to identify exact positions of human and virus breakpoints of integration events. With initial read alignment to virus reference genome and streamlined procedures, Virus-Clip delivers a simple, fast and memory-efficient solution to viral integration site detection. Moreover, it can also automatically annotate the integration events with the corresponding affected human genes. Virus-Clip has been verified using whole-transcriptome sequencing data and its detection was validated to have satisfactory sensitivity and specificity. Marked advancement in performance was detected, compared to existing tools. It is applicable to versatile types of data including whole-genome sequencing, whole-transcriptome sequencing, and targeted sequencing. Virus-Clip is available at http://web.hku.hk/~dwhho/Virus-Clip.zip.

  17. DNFSB Recommendation 94-1 Hanford Site Integrated Stabilization Management Plan. Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    Gerber, E.W.

    1995-10-01

    The US Department of Energy (DOE) has developed an Integrated Program Plan (IPP) to address concerns identified in Defense Nuclear Facilities Safety Board Recommendation 94-1. The IPP describes the actions that DOE plans to implement at its various sites to convert excess fissile materials to forms or conditions suitable for safe interim storage. The baseline IPP was issued as DOE`s Defense Nuclear Facilities Safety Board (DNFSB) Recommendation 94-1 Implementation Plan (IP), which was transmitted to the DNFSB on February 28, 1995. The IPP is being further developed to include complex-wide requirements for research and development and a long-range facility requirements section. The planned additions to the baseline IPP are being developed based on a systems engineering approach that integrates facilities and capabilities at the various DOE sites and focuses on attaining safe interim storage with minimum safety risks and environmental impacts. Each affected DOE site has developed a Site Integrated Stabilization Management Plan (SISMP) to identify individual site plans to implement the DNFSB Recommendation 94-1 and to provide a basis for formulating planned additions to the IPP. The SISMPs were developed based on the objectives, requirements, and commitments identified in the baseline DNFSB Recommendation 94-1 IPP. The SISMPs will be periodically updated to reflect improved integration between DOE sites as identified during the IPP systems engineering evaluations.

  18. DNFSB Recommendation 94-1 Hanford Site Integrated Stabilization Management Plan. Volume 1

    International Nuclear Information System (INIS)

    Gerber, E.W.

    1995-10-01

    The US Department of Energy (DOE) has developed an Integrated Program Plan (IPP) to address concerns identified in Defense Nuclear Facilities Safety Board Recommendation 94-1. The IPP describes the actions that DOE plans to implement at its various sites to convert excess fissile materials to forms or conditions suitable for safe interim storage. The baseline IPP was issued as DOE's Defense Nuclear Facilities Safety Board (DNFSB) Recommendation 94-1 Implementation Plan (IP), which was transmitted to the DNFSB on February 28, 1995. The IPP is being further developed to include complex-wide requirements for research and development and a long-range facility requirements section. The planned additions to the baseline IPP are being developed based on a systems engineering approach that integrates facilities and capabilities at the various DOE sites and focuses on attaining safe interim storage with minimum safety risks and environmental impacts. Each affected DOE site has developed a Site Integrated Stabilization Management Plan (SISMP) to identify individual site plans to implement the DNFSB Recommendation 94-1 and to provide a basis for formulating planned additions to the IPP. The SISMPs were developed based on the objectives, requirements, and commitments identified in the baseline DNFSB Recommendation 94-1 IPP. The SISMPs will be periodically updated to reflect improved integration between DOE sites as identified during the IPP systems engineering evaluations

  19. Formation of target-specific binding sites in enzymes: solid-phase molecular imprinting of HRP

    Science.gov (United States)

    Czulak, J.; Guerreiro, A.; Metran, K.; Canfarotta, F.; Goddard, A.; Cowan, R. H.; Trochimczuk, A. W.; Piletsky, S.

    2016-05-01

    Here we introduce a new concept for synthesising molecularly imprinted nanoparticles by using proteins as macro-functional monomers. For a proof-of-concept, a model enzyme (HRP) was cross-linked using glutaraldehyde in the presence of glass beads (solid-phase) bearing immobilized templates such as vancomycin and ampicillin. The cross-linking process links together proteins and protein chains, which in the presence of templates leads to the formation of permanent target-specific recognition sites without adverse effects on the enzymatic activity. Unlike complex protein engineering approaches commonly employed to generate affinity proteins, the method proposed can be used to produce protein-based ligands in a short time period using native protein molecules. These affinity materials are potentially useful tools especially for assays since they combine the catalytic properties of enzymes (for signaling) and molecular recognition properties of antibodies. We demonstrate this concept in an ELISA-format assay where HRP imprinted with vancomycin and ampicillin replaced traditional enzyme-antibody conjugates for selective detection of templates at micromolar concentrations. This approach can potentially provide a fast alternative to raising antibodies for targets that do not require high assay sensitivities; it can also find uses as a biochemical research tool, as a possible replacement for immunoperoxidase-conjugates.Here we introduce a new concept for synthesising molecularly imprinted nanoparticles by using proteins as macro-functional monomers. For a proof-of-concept, a model enzyme (HRP) was cross-linked using glutaraldehyde in the presence of glass beads (solid-phase) bearing immobilized templates such as vancomycin and ampicillin. The cross-linking process links together proteins and protein chains, which in the presence of templates leads to the formation of permanent target-specific recognition sites without adverse effects on the enzymatic activity. Unlike

  20. Mohawk Tannery Hazardous Waste Site in New Hampshire included on EPA List of Targeted for Immediate Attention

    Science.gov (United States)

    Today, the U.S. Environmental Protection Agency released the list of Superfund sites that Administrator Pruitt has targeted for immediate and intense attention. The former Mohawk Tannery facility (a.k.a. Granite State Leathers) is one of the 21 sites on th

  1. Target-site resistance to pyrethroids in European populations of pollen beetle, Meligethes aeneus F

    DEFF Research Database (Denmark)

    Nauen, Ralf; Zimmer, Christoph T; Andrews, Melanie

    2012-01-01

    by cytochrome P450 monooxygenases was implicated in the resistance of several pollen beetle populations from different European regions. Here, we have also investigated the possible occurrence of a target-site mechanism caused by modification of the pollen beetle para-type voltage-gated sodium channel gene. We...... resulted in high selection pressure and subsequent development of resistance. Resistance to pyrethroid insecticides in this pest is now widespread and the levels of resistance are often sufficient to result in field control failures at recommended application rates. Recently, metabolic resistance mediated...... detected a single nucleotide change that results in an amino acid substitution (L1014F) within the domain IIS6 region of the channel protein. The L1014F mutation, often termed kdr, has been found in several other insect pests and is known to confer moderate levels of resistance to pyrethroids. We developed...

  2. Barriers to Liposomal Gene Delivery: from Application Site to the Target.

    Science.gov (United States)

    Saffari, Mostafa; Moghimi, Hamid Reza; Dass, Crispin R

    2016-01-01

    Gene therapy is a therapeutic approach to deliver genetic material into cells to alter their function in entire organism. One promising form of gene delivery system (DDS) is liposomes. The success of liposome-mediated gene delivery is a multifactorial issue and well-designed liposomal systems might lead to optimized gene transfection particularly in vivo. Liposomal gene delivery systems face different barriers from their site of application to their target, which is inside the cells. These barriers include presystemic obstacles (epithelial barriers), systemic barriers in blood circulation and cellular barriers. Epithelial barriers differ depending on the route of administration. Systemic barriers include enzymatic degradation, binding and opsonisation. Both of these barriers can act as limiting hurdles that genetic material and their vector should overcome before reaching the cells. Finally liposomes should overcome cellular barriers that include cell entrance, endosomal escape and nuclear uptake. These barriers and their impact on liposomal gene delivery will be discussed in this review.

  3. Feasibility of subcutaneously implanted magnetic microarrays for site specific drug and gene targeting

    Directory of Open Access Journals (Sweden)

    M. Babincová

    2010-01-01

    Full Text Available The magnetic nanoparticles play a crucial role as a drug carriers in the human body. The wedge like magnetic arrays creatinga strongly non-homogeneous magnetic field are considered as a useful way to focus magnetic nanoparticles functionalizedwith various drugs or genes to desired sites. The goal of this study is to develop a numerical model of drug targetingusing subcutaneously implanted magnetic microarrays. The Finite Element Method is applied to solve partial differentialequations describing electromagnetic field (Maxwell equations and motion of these particles in a given magnetic field isobtained solving set of ordinary differential equations expressed by Newton law of motion. The results are encouragingshowing the potential to target drug to the tumour cell locally, without unwanted side effects.

  4. Effects of functionalization on the targeting site of carbon nanotubes inside cells

    International Nuclear Information System (INIS)

    Porter, A E; Bendall, J S; Welland, M; Gass, M; Muller, K; Skepper, J; Midgley, P

    2010-01-01

    Functionalized single-walled carbon nanotubes (SWNTs) are currently being investigated for a variety of applications, including contrast agents for medical imaging 1 . However before they can be used commercially it is necessary to assess whether they enter cells, the site they target within the cell and whether they cause any cytotoxicity. Here we characterize uptake of unlabelled, acid-treated, COO - functionalized SWNTs by human monocyte derived macrophage cells using both low-loss and energy loss spectroscopy and compare our findings to previous work on unpurified SWNTs. The acid-treated SWNTs were less aggregated within cells than unpurified SWNTs. Acid treatment was found to affect the distribution of intracellular SWNTs. Bundles, and also individual acid treated SWNTs, were found frequently inside lysosomes, cytoplasm and also inserting into the plasma membrane whereas unpurified non-functionalised SWNTs entered lysosomes and occasionally the nucleus.

  5. Effects of functionalization on the targeting site of carbon nanotubes inside cells

    Energy Technology Data Exchange (ETDEWEB)

    Porter, A E; Bendall, J S; Welland, M [UK SuperSTEM, Daresbury Laboratory, Daresbury, Cheshire WA4 4AD (United Kingdom); Gass, M [The Nanoscience Centre, University of Cambridge, 11 J. J. Thompson Avenue, Cambridge CB3 OFF (United Kingdom); Muller, K; Skepper, J [Multiimaging Centre, Department of PDN, Physiology, Development and Neuroscience, Anatomy Building, University of Cambridge, Downing Street, Cambridge CB2 3DY (United Kingdom); Midgley, P, E-mail: a.porter@imperial.ac.u [Department of Materials Science and Metallurgy, University of Cambridge, Pembroke Street, Cambridge CB2 3QZ (United Kingdom)

    2010-07-01

    Functionalized single-walled carbon nanotubes (SWNTs) are currently being investigated for a variety of applications, including contrast agents for medical imaging{sup 1}. However before they can be used commercially it is necessary to assess whether they enter cells, the site they target within the cell and whether they cause any cytotoxicity. Here we characterize uptake of unlabelled, acid-treated, COO{sup -} functionalized SWNTs by human monocyte derived macrophage cells using both low-loss and energy loss spectroscopy and compare our findings to previous work on unpurified SWNTs. The acid-treated SWNTs were less aggregated within cells than unpurified SWNTs. Acid treatment was found to affect the distribution of intracellular SWNTs. Bundles, and also individual acid treated SWNTs, were found frequently inside lysosomes, cytoplasm and also inserting into the plasma membrane whereas unpurified non-functionalised SWNTs entered lysosomes and occasionally the nucleus.

  6. Integrated ground-water monitoring strategy for NRC-licensed facilities and sites: Case study applications

    Science.gov (United States)

    Price, V.; Temples, T.; Hodges, R.; Dai, Z.; Watkins, D.; Imrich, J.

    2007-01-01

    This document discusses results of applying the Integrated Ground-Water Monitoring Strategy (the Strategy) to actual waste sites using existing field characterization and monitoring data. The Strategy is a systematic approach to dealing with complex sites. Application of such a systematic approach will reduce uncertainty associated with site analysis, and therefore uncertainty associated with management decisions about a site. The Strategy can be used to guide the development of a ground-water monitoring program or to review an existing one. The sites selected for study fall within a wide range of geologic and climatic settings, waste compositions, and site design characteristics and represent realistic cases that might be encountered by the NRC. No one case study illustrates a comprehensive application of the Strategy using all available site data. Rather, within each case study we focus on certain aspects of the Strategy, to illustrate concepts that can be applied generically to all sites. The test sites selected include:Charleston, South Carolina, Naval Weapons Station,Brookhaven National Laboratory on Long Island, New York,The USGS Amargosa Desert Research Site in Nevada,Rocky Flats in Colorado,C-Area at the Savannah River Site in South Carolina, andThe Hanford 300 Area.A Data Analysis section provides examples of detailed data analysis of monitoring data.

  7. Metabolic and Target-Site Mechanisms Combine to Confer Strong DDT Resistance in Anopheles gambiae

    Science.gov (United States)

    Mitchell, Sara N.; Rigden, Daniel J.; Dowd, Andrew J.; Lu, Fang; Wilding, Craig S.; Weetman, David; Dadzie, Samuel; Jenkins, Adam M.; Regna, Kimberly; Boko, Pelagie; Djogbenou, Luc; Muskavitch, Marc A. T.; Ranson, Hilary; Paine, Mark J. I.; Mayans, Olga; Donnelly, Martin J.

    2014-01-01

    The development of resistance to insecticides has become a classic exemplar of evolution occurring within human time scales. In this study we demonstrate how resistance to DDT in the major African malaria vector Anopheles gambiae is a result of both target-site resistance mechanisms that have introgressed between incipient species (the M- and S-molecular forms) and allelic variants in a DDT-detoxifying enzyme. Sequencing of the detoxification enzyme, Gste2, from DDT resistant and susceptible strains of An. gambiae, revealed a non-synonymous polymorphism (I114T), proximal to the DDT binding domain, which segregated with strain phenotype. Recombinant protein expression and DDT metabolism analysis revealed that the proteins from the susceptible strain lost activity at higher DDT concentrations, characteristic of substrate inhibition. The effect of I114T on GSTE2 protein structure was explored through X-ray crystallography. The amino acid exchange in the DDT-resistant strain introduced a hydroxyl group nearby the hydrophobic DDT-binding region. The exchange does not result in structural alterations but is predicted to facilitate local dynamics and enzyme activity. Expression of both wild-type and 114T alleles the allele in Drosophila conferred an increase in DDT tolerance. The 114T mutation was significantly associated with DDT resistance in wild caught M-form populations and acts in concert with target-site mutations in the voltage gated sodium channel (Vgsc-1575Y and Vgsc-1014F) to confer extreme levels of DDT resistance in wild caught An. gambiae. PMID:24675797

  8. Target-site resistance to acetolactate synthase (ALS)-inhibiting herbicides in Amaranthus palmeri from Argentina.

    Science.gov (United States)

    Larran, Alvaro S; Palmieri, Valeria E; Perotti, Valeria E; Lieber, Lucas; Tuesca, Daniel; Permingeat, Hugo R

    2017-12-01

    Herbicide-resistant weeds are a serious problem worldwide. Recently, two populations of Amaranthus palmeri with suspected cross-resistance to acetolactate synthase (ALS)-inhibiting herbicides (R1 and R2) were found by farmers in two locations in Argentina (Vicuña Mackenna and Totoras, respectively). We conducted studies to confirm and elucidate the mechanism of resistance. We performed in vivo dose-response assays, and confirmed that both populations had strong resistance to chlorimuron-ethyl, diclosulam and imazethapyr when compared with a susceptible population (S). In vitro ALS activity inhibition tests only indicated considerable resistance to imazethapyr and chlorimuron-ethyl, indicating that other non-target mechanisms could be involved in diclosulam resistance. Subsequently, molecular analysis of als nucleotide sequences revealed three single base-pair mutations producing substitutions in amino acids previously associated with resistance to ALS inhibitors, A122, W574, and S653. This is the first report of als resistance alleles in A. palmeri in Argentina. The data support the involvement of a target-site mechanism of resistance to ALS-inhibiting herbicides. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  9. In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration

    KAUST Repository

    Suzuki, Keiichiro; Tsunekawa, Yuji; Herná ndez-Bení tez, Reyna; Wu, Jun; Zhu, Jie; Kim, Euiseok J.; Hatanaka, Fumiyuki; Yamamoto, Mako; Araoka, Toshikazu; Li, Zhe; Kurita, Masakazu; Hishida, Tomoaki; Li, Mo; Aizawa, Emi; Guo, Shicheng; Chen, Song; Goebl, April; Soligalla, Rupa Devi; Qu, Jing; Jiang, Tingshuai; Fu, Xin; Jafari, Maryam; Esteban, Concepcion Rodriguez; Berggren, W. Travis; Lajara, Jeronimo; Nuñ ez-Delicado, Estrella; Guillen, Pedro; Campistol, Josep M.; Matsuzaki, Fumio; Liu, Guang-Hui; Magistretti, Pierre J.; Zhang, Kun; Callaway, Edward M.; Zhang, Kang; Belmonte, Juan Carlos Izpisua

    2016-01-01

    regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9)3, 4 technology, here we devise a homology-independent targeted integration (HITI) strategy, which allows for robust DNA knock-in in both dividing and non-dividing cells in vitro and, more

  10. Decaleside: a new class of natural insecticide targeting tarsal gustatory sites

    Science.gov (United States)

    Rajashekar, Yallappa; Rao, Lingamallu J. M.; Shivanandappa, Thimmappa

    2012-10-01

    Natural sources for novel insecticide molecules hold promise in view of their eco-friendly nature, selectivity, and mammalian safety. Recent progress in understanding the biology of insect olfaction and taste offers new strategies for developing selective pest control agents. We have isolated two natural insecticidal molecules from edible roots of Decalepis hamiltonii named Decalesides I and II, which are novel trisaccharides, highly toxic to household insect pests and stored-product insects. We have experimentally shown that insecticidal activity requires contact with tarsi on the legs but is not toxic orally. The insecticidal activity of molecules is lost by hydrolysis, and various sugars modify toxic response, showing that the insecticidal activity is via gustatory sites on the tarsi. Selective toxicity to insects by virtue of their gustatory site of action and the mammalian safety of the new insecticides is inherent in their chemical structure with 1-4 or 1-1 α linkage that is easily hydrolyzed by digestive enzymes of mammals. Decalesides represent a new chemical class of natural insecticides with a unique mode of action targeting tarsal chemosensory/gustatory system of insects.

  11. Demonstration of innovative monitoring technologies at the Savannah River Integrated Demonstration Site

    Energy Technology Data Exchange (ETDEWEB)

    Rossabi, J. [Westinghouse Savannah River Co., Aiken, SC (United States); Jenkins, R.A.; Wise, M.B. [Oak Ridge National Lab., TN (United States)] [and others

    1993-12-31

    The Department of Energy`s Office of Technology Development initiated an Integrated Demonstration Program at the Savannah River Site in 1989. The objective of this program is to develop, demonstrate, and evaluate innovative technologies that can improve present-day environmental restoration methods. The Integrated Demonstration Program at SRS is entitled ``Cleanup of Organics in Soils and Groundwater at Non-Arid Sites.`` New technologies in the areas of drilling, characterization, monitoring, and remediation are being demonstrated and evaluated for their technical performance and cost effectiveness in comparison with baseline technologies. Present site characterization and monitoring methods are costly, time-consuming, overly invasive, and often imprecise. Better technologies are required to accurately describe the subsurface geophysical and geochemical features of a site and the nature and extent of contamination. More efficient, nonintrusive characterization and monitoring techniques are necessary for understanding and predicting subsurface transport. More reliable procedures are also needed for interpreting monitoring and characterization data. Site characterization and monitoring are key elements in preventing, identifying, and restoring contaminated sites. The remediation of a site cannot be determined without characterization data, and monitoring may be required for 30 years after site closure.

  12. Demonstration of innovative monitoring technologies at the Savannah River Integrated Demonstration Site

    International Nuclear Information System (INIS)

    Rossabi, J.; Jenkins, R.A.; Wise, M.B.

    1993-01-01

    The Department of Energy's Office of Technology Development initiated an Integrated Demonstration Program at the Savannah River Site in 1989. The objective of this program is to develop, demonstrate, and evaluate innovative technologies that can improve present-day environmental restoration methods. The Integrated Demonstration Program at SRS is entitled ''Cleanup of Organics in Soils and Groundwater at Non-Arid Sites.'' New technologies in the areas of drilling, characterization, monitoring, and remediation are being demonstrated and evaluated for their technical performance and cost effectiveness in comparison with baseline technologies. Present site characterization and monitoring methods are costly, time-consuming, overly invasive, and often imprecise. Better technologies are required to accurately describe the subsurface geophysical and geochemical features of a site and the nature and extent of contamination. More efficient, nonintrusive characterization and monitoring techniques are necessary for understanding and predicting subsurface transport. More reliable procedures are also needed for interpreting monitoring and characterization data. Site characterization and monitoring are key elements in preventing, identifying, and restoring contaminated sites. The remediation of a site cannot be determined without characterization data, and monitoring may be required for 30 years after site closure

  13. Savannah River Site RCRA/CERCLA/NEPA integrated investigation case study

    International Nuclear Information System (INIS)

    Clark, D.R.; Thomas, R.; Wilson, M.P.

    1992-01-01

    The Savannah River Site (SRS) is a US Department of Energy facility placed on the Superfund National Priority List in 1989. Numerous past disposal facilities and contaminated areas are undergoing the integrated regulatory remediation process detailed in the draft SRS Federal Facility Agreement. This paper will discuss the integration of these requirements by highlighting the investigation of the D-Area Burning/Rubble Pits, a typical waste unit at SRS

  14. Kaiso Directs the Transcriptional Corepressor MTG16 to the Kaiso Binding Site in Target Promoters

    Science.gov (United States)

    Barrett, Caitlyn W.; Smith, J. Joshua; Lu, Lauren C.; Markham, Nicholas; Stengel, Kristy R.; Short, Sarah P.; Zhang, Baolin; Hunt, Aubrey A.; Fingleton, Barbara M.; Carnahan, Robert H.; Engel, Michael E.; Chen, Xi; Beauchamp, R. Daniel; Wilson, Keith T.; Hiebert, Scott W.; Reynolds, Albert B.; Williams, Christopher S.

    2012-01-01

    Myeloid translocation genes (MTGs) are transcriptional corepressors originally identified in acute myelogenous leukemia that have recently been linked to epithelial malignancy with non-synonymous mutations identified in both MTG8 and MTG16 in colon, breast, and lung carcinoma in addition to functioning as negative regulators of WNT and Notch signaling. A yeast two-hybrid approach was used to discover novel MTG binding partners. This screen identified the Zinc fingers, C2H2 and BTB domain containing (ZBTB) family members ZBTB4 and ZBTB38 as MTG16 interacting proteins. ZBTB4 is downregulated in breast cancer and modulates p53 responses. Because ZBTB33 (Kaiso), like MTG16, modulates Wnt signaling at the level of TCF4, and its deletion suppresses intestinal tumorigenesis in the ApcMin mouse, we determined that Kaiso also interacted with MTG16 to modulate transcription. The zinc finger domains of Kaiso as well as ZBTB4 and ZBTB38 bound MTG16 and the association with Kaiso was confirmed using co-immunoprecipitation. MTG family members were required to efficiently repress both a heterologous reporter construct containing Kaiso binding sites (4×KBS) and the known Kaiso target, Matrix metalloproteinase-7 (MMP-7/Matrilysin). Moreover, chromatin immunoprecipitation studies placed MTG16 in a complex occupying the Kaiso binding site on the MMP-7 promoter. The presence of MTG16 in this complex, and its contributions to transcriptional repression both required Kaiso binding to its binding site on DNA, establishing MTG16-Kaiso binding as functionally relevant in Kaiso-dependent transcriptional repression. Examination of a large multi-stage CRC expression array dataset revealed patterns of Kaiso, MTG16, and MMP-7 expression supporting the hypothesis that loss of either Kaiso or MTG16 can de-regulate a target promoter such as that of MMP-7. These findings provide new insights into the mechanisms of transcriptional control by ZBTB family members and broaden the scope of co

  15. Network motif-based identification of transcription factor-target gene relationships by integrating multi-source biological data

    Directory of Open Access Journals (Sweden)

    de los Reyes Benildo G

    2008-04-01

    analysis (GSEA to evaluate the clustering results; (2 Leave-one-out cross-validation (LOOCV to ensure that the SVM classifiers assign TFs to NM categories with high confidence; (3 Binding site enrichment analysis (BSEA to determine enrichment of the gene clusters for the cognate binding sites of their predicted TFs; (4 Comparison with previously reported results in the literatures to confirm the inferred regulations. Conclusion The major contribution of this study is the development of a computational framework to assist the inference of TRN by integrating heterogeneous data from multiple sources and by decomposing a TRN into NM-based modules. The inference capability of the proposed framework is verified statistically (e.g., LOOCV and biologically (e.g., GSEA, BSEA, and literature validation. The proposed framework is useful for inferring small NM-based modules of TF-target gene relationships that can serve as a basis for generating new testable hypotheses.

  16. Integration of multidisciplinary technologies for real time target visualization and verification for radiotherapy.

    Science.gov (United States)

    Chang, Wen-Chung; Chen, Chin-Sheng; Tai, Hung-Chi; Liu, Chia-Yuan; Chen, Yu-Jen

    2014-01-01

    The current practice of radiotherapy examines target coverage solely from digitally reconstructed beam's eye view (BEV) in a way that is indirectly accessible and that is not in real time. We aimed to visualize treatment targets in real time from each BEV. The image data of phantom or patients from ultrasound (US) and computed tomography (CT) scans were captured to perform image registration. We integrated US, CT, US/CT image registration, robotic manipulation of US, a radiation treatment planning system, and a linear accelerator to constitute an innovative target visualization system. The performance of this algorithm segmented the target organ in CT images, transformed and reconstructed US images to match each orientation, and generated image registration in real time mode with acceptable accuracy. This image transformation allowed physicians to visualize the CT image-reconstructed target via a US probe outside the BEV that was non-coplanar to the beam's plane. It allowed the physicians to remotely control the US probe that was equipped on a robotic arm to dynamically trace and real time monitor the coverage of the target within the BEV during a simulated beam-on situation. This target visualization system may provide a direct remotely accessible and real time way to visualize, verify, and ensure tumor targeting during radiotherapy.

  17. Implementation of Treatment Integrity Procedures An Analysis of Outcome Studies of Youth Interventions Targeting Externalizing Behavioral Problems

    NARCIS (Netherlands)

    Goense, Pauline; Boendermaker, Leonieke; van Yperen, Tom; Stams, Geert-Jan; van Laar, Jose

    2014-01-01

    This systematic review evaluates the implementation of treatment integrity procedures in outcome studies of youth interventions targeting behavioral problems. The Implementation of Treatment Integrity Procedures Scale (ITIPS), developed by Perepletchikova, Treat, and Kazdin (2007), was adapted

  18. An evaluation of sensorimotor integration during locomotion toward a target in Parkinson's disease.

    Science.gov (United States)

    Almeida, Q J; Frank, J S; Roy, E A; Jenkins, M E; Spaulding, S; Patla, A E; Jog, M S

    2005-01-01

    Recent research suggests that basal ganglia dysfunction may result in problems integrating concurrent vision and proprioception during movement. We evaluated dopaminergic system involvement in this sensorimotor process during locomotion within a large sample of Parkinson's disease (PD) patients while "On" and "Off" their dopaminergic medications (n=25), in conditions that selectively manipulated the availability of proprioception, vision or both. The present experiment focused on two main objectives: i) to examine the relative influence of visual and proprioceptive inputs on locomotion and target accuracy in patients with PD; and ii) to examine the influence of dopamine replacement therapy on sensorimotor integration while moving toward the target. All participants walked at a self-selected pace on a GAITRite carpet in two baseline conditions (light and dark), as well as four experimental darkness conditions: a) to a remembered target (i.e. proprioception only), b) to a remembered target with light on chest for body position awareness (proprioception plus), c) with vision of a lit target, also with light on chest (vision and proprioception), d) pushed in wheelchair to remembered target (no proprioception or vision). Final position was measured by 2-D radial error, and revealed a group by condition interaction, suggesting that PD patients "Off" their medications move to targets with less accuracy, but approach the accuracy of healthy participants when in the "On" state. Both PD and healthy improved their accuracy with availability of concurrent vision and proprioception (condition c). Interestingly, our results demonstrate that PD "Off" performed the task with greater difficulty than when "On" medication, but only when proprioception was the sole source of feedback. Since PD, whether medicated or unmedicated were even more affected when proprioception was removed (wheelchair), a memory-related explanation can be ruled out. Our results suggest that the basal ganglia

  19. Creation of integrated information model of 'Ukryttya' object premises and industrial site conditions to support works

    International Nuclear Information System (INIS)

    Postil, S.D.; Ermolenko, A.I.; Ivanov, V.V.; Kotlyarov, V.T.

    2004-01-01

    Data integration is made using standard AutoCAD utility and special software developed in Visual Basic for Application language. Mutual transfer is realized between the applications prepared in Access and AutoCAD with displaying the submitted information. The work demonstrates a possibility to apply integrated information model for investigating radiation field's change and analysis regularities in premises and on industrial site area, development and visualization, with the use of computer animation means, of movement routes, displaying of emergency situations being forecast with the help of computer graphics means, integration of raster display of structures and vector computer model of objects

  20. An Integral Model for Target Tracking Based on the Use of a WSN

    Directory of Open Access Journals (Sweden)

    Pietro Manzoni

    2013-06-01

    Full Text Available The use of wireless sensor networks (WSN in tracking applications is growing at a fast pace. In these applications, the sensor nodes discover, monitor and track an event or target object. A significant number of proposals relating the use of WSNs for target tracking have been published to date. However, they either focus on the tracking algorithm or on the communication protocol, and none of them address the problem integrally. In this paper, a comprehensive proposal for target detection and tracking is discussed. We introduce a tracking algorithm to detect and estimate a target location. Moreover, we introduce a low-overhead routing protocol to be used along with our tracking algorithm. The proposed algorithm has low computational complexity and has been designed considering the use of a mobile sink while generating minimal delay and packet loss. We also discuss the results of the evaluation of the proposed algorithms.

  1. Integrated Weed Control for Land Stewardship at Legacy Management's Rocky Flats Site in Colorado - 13086

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, Jody K. [Stoller LMS Team, Contractor to the U.S. Department of Energy Office of Legacy Management, 11025 Dover Street, Suite 1000, Westminster, Colorado 80021 (United States)

    2013-07-01

    species of biocontrol insects have been released to assist with control of different target weed species. Monitoring is conducted to evaluate the effectiveness of control efforts and to provide information for future control efforts. The effective implementation of this integrated approach has reduced the infestation levels of many species and has kept several newly discovered invasive species from spreading and becoming larger problems at the site. (authors)

  2. Integrated test plan for crosswell compressional and shear wave seismic tomography for site characterization at the VOC Arid Site

    International Nuclear Information System (INIS)

    Elbring, G.J.; Narbutovskih, S.M.

    1994-01-01

    This integrated test plan describes the demonstration of the crosswell acoustic tomography technique as part of the Volatile Organic Compounds-Arid Integrated Demonstration (VOC-Arid ID). The purpose of this demonstration is to image the subsurface seismic velocity structure and to relate the resulting velocity model to lithology and saturation. In fiscal year (FY) 1994 an initial fielding will test three different downhole sources at two different sites at the Hanford US Department of Energy facility to identify which sources will provide the energy required to propagate between existing steel-cased wells at these two sites. Once this has been established, a second fielding will perform a full compressional and shear wave tomographic survey at the most favorable site. Data reduction, analysis, and interpretation of this full data set will be completed by the end of this fiscal year. Data collection for a second survey will be completed by the end of the fiscal year, and data reduction for this data set will be completed in FY 1995. The specific need is detailed subsurface characterization with minimum intrusion. This technique also has applications for long term vadose zone monitoring for both Resource Conservation and Recovery Act (RCRA) waste storage facilities and for remediation monitoring. Images produced are continuous between boreholes. This is a significant improvement over the single point data derived solely from core information. Saturation changes, either naturally occurring (e.g., perched water tables) or remediation induced (e.g., water table mounding from injection wells or during inwell air sparging) could be imaged. These crosswell data allow optimal borehole placement for groundwater remediation, associated monitoring wells and possibly evaluation of the effective influence of a particular remediation technique

  3. Integration of aerial imaging and variable-rate technology for site-specific aerial herbicide application

    Science.gov (United States)

    As remote sensing and variable rate technology are becoming more available for aerial applicators, practical methodologies on effective integration of these technologies are needed for site-specific aerial applications of crop production and protection materials. The objectives of this study were to...

  4. Biogeochemical cycling of carbon, nitrogen, and sulfur at the Howland Integrated Forest Study site, Howland, Maine

    Science.gov (United States)

    James W. McLaughlin; Ivan J. Fernandez; Stewart M. Goltz; Lindsey E. Rustad; Larry Zibilske

    1996-01-01

    The biogeochemistry of C, N, and S was studied for six years at the Howland Integrated Forest Study (HIFS) site by measuring those constituents in major above- and below-ground pools and fluxes. Leaching losses of C from the solum were much less than CO2 efflux, with a mean annual leaching rate of 31.2 kg ha-1 yr

  5. What the patient wants: Addressing patients' treatment targets in an integrative group psychotherapy programme.

    Science.gov (United States)

    Kealy, David; Joyce, Anthony S; Weber, Rainer; Ehrenthal, Johannes C; Ogrodniczuk, John S

    2018-02-13

    Limited empirical attention has been devoted to individualized treatment objectives in intensive group therapy for personality dysfunction. This study investigated patients' ratings of distress associated with individual therapy goals - referred to as target object severity - in an intensive Evening Treatment Programme for patients with personality dysfunction. Change in target objective severity was examined in a sample of 81 patients who completed treatment in an intensive, integrative group therapy programme. Correlation and regression analyses were used to examine associations between change in target object severity and patients' pre-treatment diagnosis, symptom distress, and treatment outcome expectancy, and between change in target objective severity and patients' ratings of group therapy process (group climate, therapeutic alliance, group cohesion). The relationship between change in target objective severity and longer-range life satisfaction was also examined in a subsample of patients who rated life satisfaction at follow-up. While change in target objective severity was not significantly related to pre-treatment variables, significant associations were found with several aspects of group therapy process. Patients' experience of a highly engaged group climate was uniquely associated with improvement in target object severity. Such improvement was significantly related to longer-term life satisfaction after controlling for general symptom change. The working atmosphere in group therapy contributes to patients' progress regarding individual treatment targets, and such progress is an important factor in later satisfaction. Attention to individualized treatment targets deserves further clinical and research attention in the context of integrative group therapy for personality dysfunction. This study found that patients attending an integrative group treatment programme for personality dysfunction experienced significant improvement in severity of distress

  6. Glycosylation site-targeted PEGylation of glucose oxidase retains native enzymatic activity.

    Science.gov (United States)

    Ritter, Dustin W; Roberts, Jason R; McShane, Michael J

    2013-04-10

    Targeted PEGylation of glucose oxidase at its glycosylation sites was investigated to determine the effect on enzymatic activity, as well as the bioconjugate's potential in an optical biosensing assay. Methoxy-poly(ethylene glycol)-hydrazide (4.5kDa) was covalently coupled to periodate-oxidized glycosylation sites of glucose oxidase from Aspergillus niger. The bioconjugate was characterized using gel electrophoresis, liquid chromatography, mass spectrometry, and dynamic light scattering. Gel electrophoresis data showed that the PEGylation protocol resulted in a drastic increase (ca. 100kDa) in the apparent molecular mass of the protein subunit, with complete conversion to the bioconjugate; liquid chromatography data corroborated this large increase in molecular size. Mass spectrometry data proved that the extent of PEGylation was six poly(ethylene glycol) chains per glucose oxidase dimer. Dynamic light scattering data indicated the absence of higher-order oligomers in the PEGylated GOx sample. To assess stability, enzymatic activity assays were performed in triplicate at multiple time points over the course of 29 days in the absence of glucose, as well as before and after exposure to 5% w/v glucose for 24h. At a confidence level of 95%, the bioconjugate's performance was statistically equivalent to native glucose oxidase in terms of activity retention over the 29 day time period, as well as following the 24h glucose exposure. Finally, the bioconjugate was entrapped within a poly(2-hydroxyethyl methacrylate) hydrogel containing an oxygen-sensitive phosphor, and the construct was shown to respond approximately linearly with a 220±73% signal change (n=4, 95% confidence interval) over the physiologically-relevant glucose range (i.e., 0-400mg/dL); to our knowledge, this represents the first demonstration of PEGylated glucose oxidase incorporated into an optical biosensing assay. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Low Herbivory among Targeted Reforestation Sites in the Andean Highlands of Southern Ecuador.

    Directory of Open Access Journals (Sweden)

    Marc-Oliver Adams

    Full Text Available Insect herbivory constitutes an important constraint in the viability and management of targeted reforestation sites. Focusing on young experimental stands at about 2000 m elevation in southern Ecuador, we examined foliar damage over one season as a function of tree species and habitat. Native tree species (Successional hardwood: Cedrela montana and Tabebuia chrysantha; fast-growing pioneer: Heliocarpus americanus have been planted among prevailing local landcover types (abandoned pasture, secondary shrub vegetation, and a Pinus patula plantation in 2003/4. Plantation trees were compared to conspecifics in the spontaneous undergrowth of adjacent undisturbed rainforest matched for height and foliar volume. Specifically, we tested the hypotheses that H. americanus as a pioneer species suffers more herbivory compared to the two successional tree species, and that damage is inversely related to habitat complexity. Overall leaf damage caused by folivorous insects (excluding leafcutter ants was low. Average leaf loss was highest among T. chrysantha (7.50% ± 0.19 SE of leaf area, followed by H. americanus (4.67% ± 0.18 SE and C. montana (3.18% ± 0.15 SE. Contrary to expectations, leaf area loss was highest among trees in closed-canopy natural rainforest, followed by pine plantation, pasture, and secondary shrub sites. Harvesting activity of leafcutter ants (Acromyrmex sp. was strongly biased towards T. chrysantha growing in open habitat (mean pasture: 2.5%; shrub: 10.5% where it could result in considerable damage (> 90.0%. Insect folivory is unlikely to pose a barrier for reforestation in the tropical Andean mountain forest zone at present, but leafcutter ants may become problematic if local temperatures increase in the wake of global warming.

  8. Comprehensive mapping of the human papillomavirus (HPV) DNA integration sites in cervical carcinomas by HPV capture technology.

    Science.gov (United States)

    Liu, Ying; Lu, Zheming; Xu, Ruiping; Ke, Yang

    2016-02-02

    Integration of human papillomavirus (HPV) DNA into the host genome can be a driver mutation in cervical carcinoma. Identification of HPV integration at base resolution has been a longstanding technical challenge, largely due to sensitivity masking by HPV in episomes or concatenated forms. The aim was to enhance the understanding of the precise localization of HPV integration sites using an innovative strategy. Using HPV capture technology combined with next generation sequencing, HPV prevalence and the exact integration sites of the HPV DNA in 47 primary cervical cancer samples and 2 cell lines were investigated. A total of 117 unique HPV integration sites were identified, including HPV16 (n = 101), HPV18 (n = 7), and HPV58 (n = 9). We observed that the HPV16 integration sites were broadly located across the whole viral genome. In addition, either single or multiple integration events could occur frequently for HPV16, ranging from 1 to 19 per sample. The viral integration sites were distributed across almost all the chromosomes, except chromosome 22. All the cervical cancer cases harboring more than four HPV16 integration sites showed clinical diagnosis of stage III carcinoma. A significant enrichment of overlapping nucleotides shared between the human genome and HPV genome at integration breakpoints was observed, indicating that it may play an important role in the HPV integration process. The results expand on knowledge from previous findings on HPV16 and HPV18 integration sites and allow a better understanding of the molecular basis of the pathogenesis of cervical carcinoma.

  9. DNFSB Recommendation 94-1 Hanford Site Integrated Stabilization Management Plan. Volume 2

    International Nuclear Information System (INIS)

    Gerber, E.W.

    1995-10-01

    The Hanford Site Integrated Stabilization Management Plan (SISMP) was developed in support of the US Department of Energy's (DOE) Defense Nuclear Facilities Safety Board (DNFSB) Recommendation 94-1 Integrated Program Plan (IPP). Volume 1 of the SISMP identifies the technical scope and costs associated with Hanford Site plans to resolve concerns identified in DNFSB Recommendation 94-1. Volume 2 of the SISMP provides the Resource Loaded Integrated Schedules for Spent Nuclear Fuel Project and Plutonium Finishing Plant activities identified in Volume 1 of the SISMP. Appendix A provides the schedules and progress curves related to spent nuclear fuel management. Appendix B provides the schedules and progress curves related to plutonium-bearing material management. Appendix C provides programmatic logic diagrams that were referenced in Volume 1 of the SISMP

  10. AN/FSY-3 Space Fence System – Sensor Site One/Operations Center Integration Status and Sensor Site Two Planned Capability

    Science.gov (United States)

    Fonder, G. P.; Hack, P. J.; Hughes, M. R.

    This paper covers two topics related to Space Fence System development: Sensor Site One / Operations Center construction and integration status including risk reduction integration and test efforts at the Moorestown, NJ Integrated Test Bed (ITB); and the planned capability of Sensor Site Two. The AN/FSY-3 Space Fence System is a ground-based system of S-band radars integrated with an Operations Center designed to greatly enhance the Air Force Space Surveillance network. The radar architecture is based on Digital Beam-forming. This capability permits tremendous user-defined flexibility to customize volume surveillance and track sectors instantaneously without impacting routine surveillance functions. Space Fence provides unprecedented sensitivity, coverage and tracking accuracy, and contributes to key mission threads with the ability to detect, track and catalog small objects in LEO, MEO and GEO. The system is net-centric and will seamlessly integrate into the existing Space Surveillance Network, providing services to external users—such as JSpOC—and coordinating handoffs to other SSN sites. Sensor Site One construction on the Kwajalein Atoll is in progress and nearing completion. The Operations Center in Huntsville, Alabama has been configured and will be integrated with Sensor Site One in the coming months. System hardware, firmware, and software is undergoing integration testing at the Mooretown, NJ ITB and will be deployed at Sensor Site One and the Operations Center. The preliminary design for Sensor Site Two is complete and will provide critical coverage, timeliness, and operational flexibility to the overall system.

  11. Label-free integrative pharmacology on-target of drugs at the β2-adrenergic receptor

    Science.gov (United States)

    Ferrie, Ann M.; Sun, Haiyan; Fang, Ye

    2011-07-01

    We describe a label-free integrative pharmacology on-target (iPOT) method to assess the pharmacology of drugs at the β2-adrenergic receptor. This method combines dynamic mass redistribution (DMR) assays using an array of probe molecule-hijacked cells with similarity analysis. The whole cell DMR assays track cell system-based, ligand-directed, and kinetics-dependent biased activities of the drugs, and translates their on-target pharmacology into numerical descriptors which are subject to similarity analysis. We demonstrate that the approach establishes an effective link between the label-free pharmacology and in vivo therapeutic indications of drugs.

  12. Heat recovery subsystem and overall system integration of fuel cell on-site integrated energy systems

    Science.gov (United States)

    Mougin, L. J.

    1983-01-01

    The best HVAC (heating, ventilating and air conditioning) subsystem to interface with the Engelhard fuel cell system for application in commercial buildings was determined. To accomplish this objective, the effects of several system and site specific parameters on the economic feasibility of fuel cell/HVAC systems were investigated. An energy flow diagram of a fuel cell/HVAC system is shown. The fuel cell system provides electricity for an electric water chiller and for domestic electric needs. Supplemental electricity is purchased from the utility if needed. An excess of electricity generated by the fuel cell system can be sold to the utility. The fuel cell system also provides thermal energy which can be used for absorption cooling, space heating and domestic hot water. Thermal storage can be incorporated into the system. Thermal energy is also provided by an auxiliary boiler if needed to supplement the fuel cell system output. Fuel cell/HVAC systems were analyzed with the TRACE computer program.

  13. Non-target-site resistance to ALS-inhibiting herbicides in a Sagittaria trifolia L. population.

    Science.gov (United States)

    Zhao, Bochui; Fu, Danni; Yu, Yang; Huang, Chengtian; Yan, Kecheng; Li, Pingsheng; Shafi, Jamil; Zhu, He; Wei, Songhong; Ji, Mingshan

    2017-08-01

    Sagittaria trifolia L. is one of the most competitive weeds in rice fields in northeastern China. The continuous use of acetolactate synthase (ALS)-inhibitors has led to the evolution of herbicide resistant S. trifolia. A subpopulation BC1, which was derived from the L1 population, was analyzed using DNA sequencing and ALS enzyme activity assays and levels of resistance to five ALS-inhibiting herbicides was determined. DNA sequencing and ALS enzyme assays revealed no amino acid substitutions and no significant differences in enzyme sensitivity between susceptible and resistant populations. Whole-plant dose-response experiments showed that the BC1 population exhibited different levels of resistance (resistance ratios ranging from 2.14 to 51.53) to five ALS herbicides, and the addition of malathion (P450 inhibitor) to bensulfuron-methyl, penoxsulam and bispyribac-sodium strongly reduced the dry weight accumulation of the BC1 population compared with the effects of the three herbicides alone. The results of the present study demonstrated that the BC1 population has evolved non-target-site resistance to ALS-inhibiting herbicides. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Integration of multidisciplinary technologies for real time target visualization and verification for radiotherapy

    Directory of Open Access Journals (Sweden)

    Chang WC

    2014-06-01

    Full Text Available Wen-Chung Chang,1,* Chin-Sheng Chen,2,* Hung-Chi Tai,3 Chia-Yuan Liu,4,5 Yu-Jen Chen3 1Department of Electrical Engineering, National Taipei University of Technology, Taipei, Taiwan; 2Graduate Institute of Automation Technology, National Taipei University of Technology, Taipei, Taiwan; 3Department of Radiation Oncology, Mackay Memorial Hospital, Taipei, Taiwan; 4Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan; 5Department of Medicine, Mackay Medical College, New Taipei City, Taiwan  *These authors contributed equally to this work Abstract: The current practice of radiotherapy examines target coverage solely from digitally reconstructed beam's eye view (BEV in a way that is indirectly accessible and that is not in real time. We aimed to visualize treatment targets in real time from each BEV. The image data of phantom or patients from ultrasound (US and computed tomography (CT scans were captured to perform image registration. We integrated US, CT, US/CT image registration, robotic manipulation of US, a radiation treatment planning system, and a linear accelerator to constitute an innovative target visualization system. The performance of this algorithm segmented the target organ in CT images, transformed and reconstructed US images to match each orientation, and generated image registration in real time mode with acceptable accuracy. This image transformation allowed physicians to visualize the CT image-reconstructed target via a US probe outside the BEV that was non-coplanar to the beam's plane. It allowed the physicians to remotely control the US probe that was equipped on a robotic arm to dynamically trace and real time monitor the coverage of the target within the BEV during a simulated beam-on situation. This target visualization system may provide a direct remotely accessible and real time way to visualize, verify, and ensure tumor targeting during radiotherapy. Keywords: ultrasound, computerized tomography

  15. Computational Characterization of Small Molecules Binding to the Human XPF Active Site and Virtual Screening to Identify Potential New DNA Repair Inhibitors Targeting the ERCC1-XPF Endonuclease

    Directory of Open Access Journals (Sweden)

    Francesco Gentile

    2018-04-01

    Full Text Available The DNA excision repair protein ERCC-1-DNA repair endonuclease XPF (ERCC1-XPF is a heterodimeric endonuclease essential for the nucleotide excision repair (NER DNA repair pathway. Although its activity is required to maintain genome integrity in healthy cells, ERCC1-XPF can counteract the effect of DNA-damaging therapies such as platinum-based chemotherapy in cancer cells. Therefore, a promising approach to enhance the effect of these therapies is to combine their use with small molecules, which can inhibit the repair mechanisms in cancer cells. Currently, there are no structures available for the catalytic site of the human ERCC1-XPF, which performs the metal-mediated cleavage of a DNA damaged strand at 5′. We adopted a homology modeling strategy to build a structural model of the human XPF nuclease domain which contained the active site and to extract dominant conformations of the domain using molecular dynamics simulations followed by clustering of the trajectory. We investigated the binding modes of known small molecule inhibitors targeting the active site to build a pharmacophore model. We then performed a virtual screening of the ZINC Is Not Commercial 15 (ZINC15 database to identify new ERCC1-XPF endonuclease inhibitors. Our work provides structural insights regarding the binding mode of small molecules targeting the ERCC1-XPF active site that can be used to rationally optimize such compounds. We also propose a set of new potential DNA repair inhibitors to be considered for combination cancer therapy strategies.

  16. The Site Approach - Lessons Learned from the Integrated Safeguards Approach for JNC-1

    International Nuclear Information System (INIS)

    Kikuchi, M.; Iso, S.; Tomine, K.; Hirato, Y.; Namekawa, M.; Takasugi, N.; Watanabe, M.; Tsutaki, Y.; Asano, T.; Nagatani, T.; Ninagawa, J.; Fujiwara, S.; Takahashi, S.; Kimura, T.; Kodani, Y.; Fukuhara, J.; Miyaji, N.; Kawakami, Y.; Koizumi, A.; Yamazaki, Y.; Nishinosono, S.; Sasaki, K.

    2010-01-01

    Integrated safeguards approaches for specific sites are recognized important elements in the design of a State-level approach under the concept of grouping facilities. Japan and the IAEA agreed further improvement of integrated safeguards implementation in effective and efficient manner, particularly at large complex nuclear sites in Japan. Japan and the IAEA developed the integrated safeguards approach for specific sites defined at Article 18 of Additional Protocol. In 2008, the IAEA started the three-year test implementation of JNC-1 site approach for improving the effectiveness and efficiency of the safeguards implementation of UDU material handling facilities. Japan and IAEA agreed to adopt the sector concept in order to make clear of subjected nuclear material to be verified. The sector is defined as spatial assignment that treats the same material stratum beyond MBAs in the site. The arrangement of MBAs and related material balance calculations as well as statistical analysis is maintained as a fundamental safeguards measure. At the boundaries of each sector, appropriate unattended NDA system and/or C/S system are installed, and material flows across the boundaries are verified by the system or attendance of resident inspectors. For inventory verification of the nuclear material stayed in sectors, an appropriate numbers of randomly scheduled inspections will be implemented. IAEA can access to the randomly selected sectors within 2 hours after notification. NRTA based on frequent operator's declaration will be performed for achievement of timeliness detection goal. The JNC-1 site approach has been implemented under the enhanced co-operation between the IAEA and SSAC through joint use of equipment and arrangements for DA analysis. Especially, national inspectors are working with IAEA together for coordination with operators. Because NMCC lab analyses all DA samples taken from facilities and the analysis results will be shared by the IAEA, certain numbers of DA

  17. Enhancement of high density polyethylene high integrity containers at a low level radioactive waste disposal site

    International Nuclear Information System (INIS)

    Sauer, R.E.; Wong, O.P.

    1989-01-01

    High integrity containers (HIC) made of high density polyethylene (HDPE) have been used for disposal in South Carolina since the late seventies. With the recent definitive position taken by the NRC on the suitability of these containers for disposal, alternative means of assuring the structural integrity of the containers for the long term became necessary. The authors' company has developed an utilized reinforced concrete caissons at the Hanford, Washington site as an additional barrier and structural element to assure the long term high integrity function of the current HDPE HIC's also known as Poly HIC's on the market. This paper outlines the background of the HIC's in question, the NRC positions and ruling, and presents technical bases for the applicability of appropriately designed concrete overpacks to augment the structural integrity of HIC's

  18. An integrated control scheme for space robot after capturing non-cooperative target

    Science.gov (United States)

    Wang, Mingming; Luo, Jianjun; Yuan, Jianping; Walter, Ulrich

    2018-06-01

    How to identify the mass properties and eliminate the unknown angular momentum of space robotic system after capturing a non-cooperative target is of great challenge. This paper focuses on designing an integrated control framework which includes detumbling strategy, coordination control and parameter identification. Firstly, inverted and forward chain approaches are synthesized for space robot to obtain dynamic equation in operational space. Secondly, a detumbling strategy is introduced using elementary functions with normalized time, while the imposed end-effector constraints are considered. Next, a coordination control scheme for stabilizing both base and end-effector based on impedance control is implemented with the target's parameter uncertainty. With the measurements of the forces and torques exerted on the target, its mass properties are estimated during the detumbling process accordingly. Simulation results are presented using a 7 degree-of-freedom kinematically redundant space manipulator, which verifies the performance and effectiveness of the proposed method.

  19. In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration

    KAUST Repository

    Suzuki, Keiichiro

    2016-11-15

    Targeted genome editing via engineered nucleases is an exciting area of biomedical research and holds potential for clinical applications. Despite rapid advances in the field, in vivo targeted transgene integration is still infeasible because current tools are inefficient1, especially for non-dividing cells, which compose most adult tissues. This poses a barrier for uncovering fundamental biological principles and developing treatments for a broad range of genetic disorders2. Based on clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9)3, 4 technology, here we devise a homology-independent targeted integration (HITI) strategy, which allows for robust DNA knock-in in both dividing and non-dividing cells in vitro and, more importantly, in vivo (for example, in neurons of postnatal mammals). As a proof of concept of its therapeutic potential, we demonstrate the efficacy of HITI in improving visual function using a rat model of the retinal degeneration condition retinitis pigmentosa. The HITI method presented here establishes new avenues for basic research and targeted gene therapies.

  20. Integrated fast ignition simulation of cone-guided target with three codes

    Energy Technology Data Exchange (ETDEWEB)

    Sakagami, H. [Hyogo Univ., Computer Engineering, Himeji, Hyogo (Japan); Johzaki, T.; Nagatomo, H.; Mima, K. [Osaka Univ., Institute of Laser Engineering, Suita, Osaka (Japan)

    2004-07-01

    It was reported that the fuel core was heated up to {approx} 0.8 keV in the fast ignition experiments with cone-guided targets, but they could not theoretically explain heating mechanisms and achievement of such high temperature. Thus simulations should play an important role in estimating the scheme performance, and we must simulate each phenomenon with individual codes and integrate them under the Fast Ignition Integrated Interconnecting code project. In the previous integrated simulations, fast electrons generated by the laser-plasma interaction were too hot to efficiently heat the core and we got only a 0.096 keV temperature rise. Including the density gap at the contact surface between the cone tip and the imploded plasma, the period of core heating became longer and the core was heated by 0.162 keV, about 69% higher increment compared with ignoring the density gap effect. (authors)

  1. A dynamic multimedia fuzzy-stochastic integrated environmental risk assessment approach for contaminated sites management

    International Nuclear Information System (INIS)

    Hu, Yan; Wen, Jing-ya; Li, Xiao-li; Wang, Da-zhou; Li, Yu

    2013-01-01

    Highlights: • Using interval mathematics to describe spatial and temporal variability and parameter uncertainty. • Using fuzzy theory to quantify variability of environmental guideline values. • Using probabilistic approach to integrate interval concentrations and fuzzy environmental guideline. • Establishment of dynamic multimedia environmental integrated risk assessment framework. -- Abstract: A dynamic multimedia fuzzy-stochastic integrated environmental risk assessment approach was developed for contaminated sites management. The contaminant concentrations were simulated by a validated interval dynamic multimedia fugacity model, and different guideline values for the same contaminant were represented as a fuzzy environmental guideline. Then, the probability of violating environmental guideline (Pv) can be determined by comparison between the modeled concentrations and the fuzzy environmental guideline, and the constructed relationship between the Pvs and environmental risk levels was used to assess the environmental risk level. The developed approach was applied to assess the integrated environmental risk at a case study site in China, simulated from 1985 to 2020. Four scenarios were analyzed, including “residential land” and “industrial land” environmental guidelines under “strict” and “loose” strictness. It was found that PAH concentrations will increase steadily over time, with soil found to be the dominant sink. Source emission in soil was the leading input and atmospheric sedimentation was the dominant transfer process. The integrated environmental risks primarily resulted from petroleum spills and coke ovens, while the soil environmental risks came from coal combustion. The developed approach offers an effective tool for quantifying variability and uncertainty in the dynamic multimedia integrated environmental risk assessment and the contaminated site management

  2. A dynamic multimedia fuzzy-stochastic integrated environmental risk assessment approach for contaminated sites management

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Yan; Wen, Jing-ya; Li, Xiao-li; Wang, Da-zhou; Li, Yu, E-mail: liyuxx8@hotmail.com

    2013-10-15

    Highlights: • Using interval mathematics to describe spatial and temporal variability and parameter uncertainty. • Using fuzzy theory to quantify variability of environmental guideline values. • Using probabilistic approach to integrate interval concentrations and fuzzy environmental guideline. • Establishment of dynamic multimedia environmental integrated risk assessment framework. -- Abstract: A dynamic multimedia fuzzy-stochastic integrated environmental risk assessment approach was developed for contaminated sites management. The contaminant concentrations were simulated by a validated interval dynamic multimedia fugacity model, and different guideline values for the same contaminant were represented as a fuzzy environmental guideline. Then, the probability of violating environmental guideline (Pv) can be determined by comparison between the modeled concentrations and the fuzzy environmental guideline, and the constructed relationship between the Pvs and environmental risk levels was used to assess the environmental risk level. The developed approach was applied to assess the integrated environmental risk at a case study site in China, simulated from 1985 to 2020. Four scenarios were analyzed, including “residential land” and “industrial land” environmental guidelines under “strict” and “loose” strictness. It was found that PAH concentrations will increase steadily over time, with soil found to be the dominant sink. Source emission in soil was the leading input and atmospheric sedimentation was the dominant transfer process. The integrated environmental risks primarily resulted from petroleum spills and coke ovens, while the soil environmental risks came from coal combustion. The developed approach offers an effective tool for quantifying variability and uncertainty in the dynamic multimedia integrated environmental risk assessment and the contaminated site management.

  3. Integrated Geophysical and Aerial Sensing Methods for Archaeology: A Case History in the Punic Site of Villamar (Sardinia, Italy

    Directory of Open Access Journals (Sweden)

    Carlo Piga

    2014-11-01

    Full Text Available In this paper, the authors present a recent integrated survey carried out on an archaeological urban site, generally free of buildings, except some temporary structures related to excavated areas where multi-chamber tombs were found. The two methods used to investigate this site were thermal infrared and ground penetrating radar (GPR. The thermography was carried out with the sensor mounted under a helium balloon simultaneously with a photographic camera. In order to have a synthetic view of the surface thermal behavior, a simplified version of the existing night thermal gradient algorithm was applied. By this approach, we have a wide extension of thermal maps due to the balloon oscillation, because we are able to compute the maps despite collecting few acquisition samples. By the integration of GPR and the thermal imaging, we can evaluate the depth of the thermal influence of possible archaeological targets, such as buried Punic tombs or walls belonging to the succeeding medieval buildings, which have been subsequently destroyed. The thermal anomalies present correspondences to the radar time slices obtained from 30 to 50 cm. Furthermore, by superimposing historical aerial pictures on the GPR and thermal imaging data, we can identify these anomalies as the foundations of the destroyed buildings.

  4. Background Information for the Nevada National Security Site Integrated Sampling Plan, Revision 0

    Energy Technology Data Exchange (ETDEWEB)

    Farnham, Irene; Marutzky, Sam

    2014-12-01

    This document describes the process followed to develop the Nevada National Security Site (NNSS) Integrated Sampling Plan (referred to herein as the Plan). It provides the Plan’s purpose and objectives, and briefly describes the Underground Test Area (UGTA) Activity, including the conceptual model and regulatory requirements as they pertain to groundwater sampling. Background information on other NNSS groundwater monitoring programs—the Routine Radiological Environmental Monitoring Plan (RREMP) and Community Environmental Monitoring Program (CEMP)—and their integration with the Plan are presented. Descriptions of the evaluations, comments, and responses of two Sampling Plan topical committees are also included.

  5. siRNAs targeted to certain polyadenylation sites promote specific, RISC-independent degradation of messenger RNAs.

    Science.gov (United States)

    Vickers, Timothy A; Crooke, Stanley T

    2012-07-01

    While most siRNAs induce sequence-specific target mRNA cleavage and degradation in a process mediated by Ago2/RNA-induced silencing complex (RISC), certain siRNAs have also been demonstrated to direct target RNA reduction through deadenylation and subsequent degradation of target transcripts in a process which involves Ago1/RISC and P-bodies. In the current study, we present data suggesting that a third class of siRNA exist, which are capable of promoting target RNA reduction that is independent of both Ago and RISC. These siRNAs bind the target messenger RNA at the polyA signal and are capable of redirecting a small amount of polyadenylation to downstream polyA sites when present, however, the majority of the activity appears to be due to inhibition of polyadenylation or deadenylation of the transcript, followed by exosomal degradation of the immature mRNA.

  6. Impact of MicroRNA Levels, Target-Site Complementarity, and Cooperativity on Competing Endogenous RNA-Regulated Gene Expression.

    Science.gov (United States)

    Denzler, Rémy; McGeary, Sean E; Title, Alexandra C; Agarwal, Vikram; Bartel, David P; Stoffel, Markus

    2016-11-03

    Expression changes of competing endogenous RNAs (ceRNAs) have been proposed to influence microRNA (miRNA) activity and thereby regulate other transcripts containing miRNA-binding sites. Here, we find that although miRNA levels define the extent of repression, they have little effect on the magnitude of the ceRNA expression change required to observe derepression. Canonical 6-nt sites, which typically mediate modest repression, can nonetheless compete for miRNA binding, with potency ∼20% of that observed for canonical 8-nt sites. In aggregate, low-affinity/background sites also contribute to competition. Sites with extensive additional complementarity can appear as more potent, but only because they induce miRNA degradation. Cooperative binding of proximal sites for the same or different miRNAs does increase potency. These results provide quantitative insights into the stoichiometric relationship between miRNAs and target abundance, target-site spacing, and affinity requirements for ceRNA-mediated gene regulation, and the unusual circumstances in which ceRNA-mediated gene regulation might be observed. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  7. An integrated stochastic environmental risk assessment method and its application to a petroleum-contaminated site

    International Nuclear Information System (INIS)

    Liu, L.; Fuller, G.A.; Huang, G.H.

    1999-01-01

    Contamination of soil and water and the resulting threat to public health and the environment are the frequent results of oil spills, leaks and other releases of gasoline, diesel fuel, heating oil and other petroleum products. Integrating an analytical groundwater solute transport model within its general framework, this paper proposes an integrated stochastic risk assessment method and ways to apply it to petroleum-contaminated sites. Both the analytical solute transport model and the general risk assessment framework are solved by the Monte Carlo simulation technique for approaching the theoretical output distribution. Results of this study show that the total cancer risk has approximately log-normal distribution, irrespective of the fact that a variety of distributions were used to define the related parameters. It is claimed that the method can improve the effectiveness of the risk assessment for subsurface, and provide useful result for site remediation decisions. 23 refs., 3 tabs., 4 figs

  8. Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release.

    Science.gov (United States)

    Hosoya, Hitomi; Dobroff, Andrey S; Driessen, Wouter H P; Cristini, Vittorio; Brinker, Lina M; Staquicini, Fernanda I; Cardó-Vila, Marina; D'Angelo, Sara; Ferrara, Fortunato; Proneth, Bettina; Lin, Yu-Shen; Dunphy, Darren R; Dogra, Prashant; Melancon, Marites P; Stafford, R Jason; Miyazono, Kohei; Gelovani, Juri G; Kataoka, Kazunori; Brinker, C Jeffrey; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

    2016-02-16

    A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared, thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. These results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications.

  9. Target and identify: triazene linker helps identify azidation sites of labelled proteins via click and cleave strategy.

    Science.gov (United States)

    Lohse, Jonas; Schindl, Alexandra; Danda, Natasha; Williams, Chris P; Kramer, Karl; Kuster, Bernhard; Witte, Martin D; Médard, Guillaume

    2017-10-31

    A method for identifying probe modification of proteins via tandem mass spectrometry was developed. Azide bearing molecules are immobilized on functionalised sepharose beads via copper catalysed Huisgen-type click chemistry and selectively released under acidic conditions by chemical cleavage of the triazene linkage. We applied this method to identify the modification site of targeted-diazotransfer on BirA.

  10. A Generic Multi-Compartmental CNS Distribution Model Structure for 9 Drugs Allows Prediction of Human Brain Target Site Concentrations

    NARCIS (Netherlands)

    Yamamoto, Yumi; Valitalo, Pyry A.; van den Berg, Dirk-Jan; Hartman, Robin; van den Brink, Willem; Wong, Yin Cheong; Huntjens, Dymphy R.; Proost, Johannes H.; Vermeulen, An; Krauwinkel, Walter; Bakshi, Suruchi; Aranzana-Climent, Vincent; Marchand, Sandrine; Dahyot-Fizelier, Claire; Couet, William; Danhof, Meindert; van Hasselt, Johan G. C.; de lange, Elizabeth C. M.

    Purpose Predicting target site drug concentration in the brain is of key importance for the successful development of drugs acting on the central nervous system. We propose a generic mathematical model to describe the pharmacokinetics in brain compartments, and apply this model to predict human

  11. DNFSB recommendation 94-1 Hanford site integrated stabilization management plan

    International Nuclear Information System (INIS)

    McCormack, R.L.

    1997-01-01

    In May 1994, the Defense Nuclear Facilities Safety Board (DNFSB) issued DNFSB Recommendation 94-1 (Conway 1994), which identified concerns related to US Department of Energy (DOE) management of legacy fissile materials remaining from past defense production activities. The DNFSB expressed concern about the existing storage conditions for these materials and the slow pace at which the conditions were being remediated. The DNFSB also expressed its belief that additional delays in stabilizing these fissile materials would be accompanied by further deterioration of safety and unnecessary increased risks to workers and the public. In February 1995, DOE issued the DNFSB Recommendation 94-1 Implementation Plan (O'Leary 1995) to address the concerns identified in DNFSB Recommendation 94-1. The Implementation Plan (IP) identifies several DOE commitments to achieve safe interim storage for the legacy fissile materials, and constitutes DOE's baseline DNFSB Recommendation 94-1 Integrated Program Plan (IPP). The IPP describes the actions DOE plans to implement within the DOE complex to convert its excess fissile materials to forms or conditions suitable for safe interim storage. The IPP was subsequently supplemented with an Integrated Facilities Plan and a Research and Development Plan, which further develop complex-wide research and development and long-range facility requirements and plans. The additions to the baseline IPP were developed based on a systems engineering approach that integrated facilities and capabilities at the various DOE sites and focused on attaining safe interim storage with minimum safety risks and environmental impacts. Each affected DOE site has developed a Site Integrated Stabilization Management Plan (SISMP) to identify individual site plans to implement the DNFSB Recommendation 94-1 IPP. The SISMPs were developed based on the objectives, requirements, and commitments identified in the DNFSB Recommendation 94-1 IP. The SISMPs also supported

  12. DNFSB recommendation 94-1 Hanford site integrated stabilization management plan

    Energy Technology Data Exchange (ETDEWEB)

    McCormack, R.L.

    1997-05-07

    In May 1994, the Defense Nuclear Facilities Safety Board (DNFSB) issued DNFSB Recommendation 94-1 (Conway 1994), which identified concerns related to US Department of Energy (DOE) management of legacy fissile materials remaining from past defense production activities. The DNFSB expressed concern about the existing storage conditions for these materials and the slow pace at which the conditions were being remediated. The DNFSB also expressed its belief that additional delays in stabilizing these fissile materials would be accompanied by further deterioration of safety and unnecessary increased risks to workers and the public. In February 1995, DOE issued the DNFSB Recommendation 94-1 Implementation Plan (O`Leary 1995) to address the concerns identified in DNFSB Recommendation 94-1. The Implementation Plan (IP) identifies several DOE commitments to achieve safe interim storage for the legacy fissile materials, and constitutes DOE`s baseline DNFSB Recommendation 94-1 Integrated Program Plan (IPP). The IPP describes the actions DOE plans to implement within the DOE complex to convert its excess fissile materials to forms or conditions suitable for safe interim storage. The IPP was subsequently supplemented with an Integrated Facilities Plan and a Research and Development Plan, which further develop complex-wide research and development and long-range facility requirements and plans. The additions to the baseline IPP were developed based on a systems engineering approach that integrated facilities and capabilities at the various DOE sites and focused on attaining safe interim storage with minimum safety risks and environmental impacts. Each affected DOE site has developed a Site Integrated Stabilization Management Plan (SISMP) to identify individual site plans to implement the DNFSB Recommendation 94-1 IPP. The SISMPs were developed based on the objectives, requirements, and commitments identified in the DNFSB Recommendation 94-1 IP. The SISMPs also supported

  13. The Integrated Coastal Area Management (ICAM) Initiative in the Nyali-Bamburi-Shanzu Site, Mombasa, Kenya.

    OpenAIRE

    Mwandotto, B.A.J.

    1997-01-01

    A multi-institutional planning team headed by Coast Development Authority (CDA) in Kenya initiated an Integrated Coastal Area Management (ICAM) process in 1994. The pilot study site was Nyali-Bamburi-Shanzu area in Mombasa. The objective was to provide a starting point for addressing urgent coastal issues facing the area and to enrich the dialogue on how to address urgent coastal management problems nationwide. The pertinent coastal issues that were profiled in a participatory and interactive...

  14. Directional R-Loop Formation by the CRISPR-Cas Surveillance Complex Cascade Provides Efficient Off-Target Site Rejection

    Directory of Open Access Journals (Sweden)

    Marius Rutkauskas

    2015-03-01

    Full Text Available CRISPR-Cas systems provide bacteria and archaea with adaptive immunity against foreign nucleic acids. In type I CRISPR-Cas systems, invading DNA is detected by a large ribonucleoprotein surveillance complex called Cascade. The crRNA component of Cascade is used to recognize target sites in foreign DNA (protospacers by formation of an R-loop driven by base-pairing complementarity. Using single-molecule supercoiling experiments with near base-pair resolution, we probe here the mechanism of R-loop formation and detect short-lived R-loop intermediates on off-target sites bearing single mismatches. We show that R-loops propagate directionally starting from the protospacer-adjacent motif (PAM. Upon reaching a mismatch, R-loop propagation stalls and collapses in a length-dependent manner. This unambiguously demonstrates that directional zipping of the R-loop accomplishes efficient target recognition by rapidly rejecting binding to off-target sites with PAM-proximal mutations. R-loops that reach the protospacer end become locked to license DNA degradation by the auxiliary Cas3 nuclease/helicase without further target verification.

  15. The SPOR Domain, a Widely Conserved Peptidoglycan Binding Domain That Targets Proteins to the Site of Cell Division.

    Science.gov (United States)

    Yahashiri, Atsushi; Jorgenson, Matthew A; Weiss, David S

    2017-07-15

    Sporulation-related repeat (SPOR) domains are small peptidoglycan (PG) binding domains found in thousands of bacterial proteins. The name "SPOR domain" stems from the fact that several early examples came from proteins involved in sporulation, but SPOR domain proteins are quite diverse and contribute to a variety of processes that involve remodeling of the PG sacculus, especially with respect to cell division. SPOR domains target proteins to the division site by binding to regions of PG devoid of stem peptides ("denuded" glycans), which in turn are enriched in septal PG by the intense, localized activity of cell wall amidases involved in daughter cell separation. This targeting mechanism sets SPOR domain proteins apart from most other septal ring proteins, which localize via protein-protein interactions. In addition to SPOR domains, bacteria contain several other PG-binding domains that can exploit features of the cell wall to target proteins to specific subcellular sites. Copyright © 2017 American Society for Microbiology.

  16. Integration Site and Clonal Expansion in Human Chronic Retroviral Infection and Gene Therapy

    Science.gov (United States)

    Niederer, Heather A.; Bangham, Charles R. M.

    2014-01-01

    Retroviral vectors have been successfully used therapeutically to restore expression of genes in a range of single-gene diseases, including several primary immunodeficiency disorders. Although clinical trials have shown remarkable results, there have also been a number of severe adverse events involving malignant outgrowth of a transformed clonal population. This clonal expansion is influenced by the integration site profile of the viral integrase, the transgene expressed, and the effect of the viral promoters on the neighbouring host genome. Infection with the pathogenic human retrovirus HTLV-1 also causes clonal expansion of cells containing an integrated HTLV-1 provirus. Although the majority of HTLV-1-infected people remain asymptomatic, up to 5% develop an aggressive T cell malignancy. In this review we discuss recent findings on the role of the genomic integration site in determining the clonality and the potential for malignant transformation of cells carrying integrated HTLV-1 or gene therapy vectors, and how these results have contributed to the understanding of HTLV-1 pathogenesis and to improvements in gene therapy vector safety. PMID:25365582

  17. INTEGRATED REMOTE SENSING AND GIS FOR MODELING ECONOMIC REHABILITATION DEVELOPMENT OF EX-MINE SITES

    Directory of Open Access Journals (Sweden)

    Junaidi Junaidi

    2017-11-01

    economic development of ex-mine sites. The aim of this research is to quantify, model and map the economic potential of the ex-mine sites for built up areas such as housing and other urban infrastructures. Land cover classes were interpreted into maps and the accuracy of the maps were validated to reference data and actual ground scenarios. The study for validation of the proposed modeling tool was carried out using the large prominent mining area in Malaysia namely the Kinta District. Results from the validation study carried out indicate that the correlation of the results obtained from this Integrated Remote Sensing and GIS tool for modeling to field data is in the range of 0.87-0.92 which is acceptable and close to reality.

  18. Adenovirus-Mediated Delivery of Decoy Hyper Binding Sites Targeting Oncogenic HMGA1 Reduces Pancreatic and Liver Cancer Cell Viability.

    Science.gov (United States)

    Hassan, Faizule; Ni, Shuisong; Arnett, Tyler C; McKell, Melanie C; Kennedy, Michael A

    2018-03-30

    High mobility group AT-hook 1 (HMGA1) protein is an oncogenic architectural transcription factor that plays an essential role in early development, but it is also implicated in many human cancers. Elevated levels of HMGA1 in cancer cells cause misregulation of gene expression and are associated with increased cancer cell proliferation and increased chemotherapy resistance. We have devised a strategy of using engineered viruses to deliver decoy hyper binding sites for HMGA1 to the nucleus of cancer cells with the goal of sequestering excess HMGA1 at the decoy hyper binding sites due to binding competition. Sequestration of excess HMGA1 at the decoy binding sites is intended to reduce HMGA1 binding at the naturally occurring genomic HMGA1 binding sites, which should result in normalized gene expression and restored sensitivity to chemotherapy. As proof of principle, we engineered the replication defective adenovirus serotype 5 genome to contain hyper binding sites for HMGA1 composed of six copies of an individual HMGA1 binding site, referred to as HMGA-6. A 70%-80% reduction in cell viability and increased sensitivity to gemcitabine was observed in five different pancreatic and liver cancer cell lines 72 hr after infection with replication defective engineered adenovirus serotype 5 virus containing the HMGA-6 decoy hyper binding sites. The decoy hyper binding site strategy should be general for targeting overexpression of any double-stranded DNA-binding oncogenic transcription factor responsible for cancer cell proliferation.

  19. Human papilloma viruses and cervical tumours: mapping of integration sites and analysis of adjacent cellular sequences

    International Nuclear Information System (INIS)

    Klimov, Eugene; Vinokourova, Svetlana; Moisjak, Elena; Rakhmanaliev, Elian; Kobseva, Vera; Laimins, Laimonis; Kisseljov, Fjodor; Sulimova, Galina

    2002-01-01

    In cervical tumours the integration of human papilloma viruses (HPV) transcripts often results in the generation of transcripts that consist of hybrids of viral and cellular sequences. Mapping data using a variety of techniques has demonstrated that HPV integration occurred without obvious specificity into human genome. However, these techniques could not demonstrate whether integration resulted in the generation of transcripts encoding viral or viral-cellular sequences. The aim of this work was to map the integration sites of HPV DNA and to analyse the adjacent cellular sequences. Amplification of the INTs was done by the APOT technique. The APOT products were sequenced according to standard protocols. The analysis of the sequences was performed using BLASTN program and public databases. To localise the INTs PCR-based screening of GeneBridge4-RH-panel was used. Twelve cellular sequences adjacent to integrated HPV16 (INT markers) expressed in squamous cell cervical carcinomas were isolated. For 11 INT markers homologous human genomic sequences were readily identified and 9 of these showed significant homologies to known genes/ESTs. Using the known locations of homologous cDNAs and the RH-mapping techniques, mapping studies showed that the INTs are distributed among different human chromosomes for each tumour sample and are located in regions with the high levels of expression. Integration of HPV genomes occurs into the different human chromosomes but into regions that contain highly transcribed genes. One interpretation of these studies is that integration of HPV occurs into decondensed regions, which are more accessible for integration of foreign DNA

  20. Non-targeted effects of ionising radiation (note). A new European integrated project, 2006-2010

    International Nuclear Information System (INIS)

    Salomaa, S.; Wright, E.G.; Hildebrandt, G.; Kadhim, M.; Little, M.P.; Prise, K.M.; Belyakov, O.V.

    2007-01-01

    Complete text of publication follows. The general objectives of the NOTE project are: (1) to investigate the mechanisms of nontargeted effects, in particular, bystander effects, genomic instability and adaptive response; (2) to investigate if and how non-targeted effects modulate the cancer risk in the low dose region, and whether they relate to protective or harmful functions; (3) to investigate if ionising radiation can cause non-cancer diseases or beneficial effects at low and intermediate doses; (4) to investigate individual susceptibility and other factors modifying non-targeted responses; (5) to assess the relevance of non-targeted effects for radiation protection and to set the scientific basis for a modern, more realistic, radiation safety system; (6) to contribute to the conceptualisation of a new paradigm in radiation biology that would cover both the classical direct (DNA-targeted) and non-targeted (indirect) effects. The NOTE brings together 19 major European and Canadian groups involved in the discovery, characterisation and mechanistic investigation of non-targeted effects of ionising radiation in cellular, tissue and animal models. The NOTE research activities are organised in six work packages. Four work packages (WPs 2-5) are problem-oriented, focussing on major questions relevant for the scientific basis of the system of radiation protection: WP2 Mechanisms of non-targeted effects, WP3 Non-cancer diseases, WP4 Factors modifying non-targeted responses, WP5 Modelling of non-targeted effects. The integration activities provided by WP6 strengthen the collaboration by supporting the access to infrastructures, mobility and training. WP7 provides dissemination and exploitation activities in the form of workshops and a public website. Managerial activities (WP1) ensure the organisation and structures for decision making, monitoring of progress, knowledge management and efficient flow of information and financing. Coordinator of the NOTE project is Prof

  1. Integration of targeted agents in the neo-adjuvant treatment of gastro-esophageal cancers.

    Science.gov (United States)

    Power, D G; Ilson, D H

    2009-11-01

    Pre- and peri-operative strategies are becoming standard for the management of localized gastro-esophageal cancer. For localized gastric/gastro-esophageal junction (GEJ) cancer there are conflicting data that a peri-operative approach with cisplatin-based chemotherapy improves survival, with the benefits seen in esophageal cancer likely less than a 5-10% incremental improvement. Further trends toward improvement in local control and survival, when combined chemotherapy and radiation therapy are given pre-operatively, are suggested by recent phase III trials. In fit patients, a significant survival benefit with pre-operative chemoradiation is seen in those patients who achieve a pathologic complete response. In esophageal/GEJ cancer, definitive chemoradiation is now considered in medically inoperable patients. In squamous cell carcinoma of the esophagus, surgery after primary chemoradiation is not clearly associated with an improved overall survival, however, local control may be better. In localized gastric/GEJ cancer, the integration of bevacizumab with pre-operative chemotherapy is being explored in large randomized studies, and with chemoradiotherapy in pilot trials. The addition of anti-epidermal growth factor receptor and anti-human epidermal growth factor receptor-2 antibody treatment to pre-operative chemoradiation continues to be explored. Early results show the integration of targeted therapy is feasible. Metabolic imaging can predict early response to pre-operative chemotherapy and biomarkers may further predict response to pre-operative chemo-targeted therapy. A multimodality approach to localized gastro-esophageal cancer has resulted in better outcomes. For T3 or node-positive disease, surgery alone is no longer considered appropriate and neo-adjuvant therapy is recommended. The future of neo-adjuvant strategies in this disease will involve the individualization of therapy with the integration of molecular signatures, targeted therapy, metabolic imaging

  2. ISAR Imaging of Ship Targets Based on an Integrated Cubic Phase Bilinear Autocorrelation Function

    Directory of Open Access Journals (Sweden)

    Jibin Zheng

    2017-03-01

    Full Text Available For inverse synthetic aperture radar (ISAR imaging of a ship target moving with ocean waves, the image constructed with the standard range-Doppler (RD technique is blurred and the range-instantaneous-Doppler (RID technique has to be used to improve the image quality. In this paper, azimuth echoes in a range cell of the ship target are modeled as noisy multicomponent cubic phase signals (CPSs after the motion compensation and a RID ISAR imaging algorithm is proposed based on the integrated cubic phase bilinear autocorrelation function (ICPBAF. The ICPBAF is bilinear and based on the two-dimensionally coherent energy accumulation. Compared to five other estimation algorithms, the ICPBAF can acquire higher cross term suppression and anti-noise performance with a reasonable computational cost. Through simulations and analyses with the synthetic model and real radar data, we verify the effectiveness of the ICPBAF and corresponding RID ISAR imaging algorithm.

  3. Improved prediction of drug-target interactions using regularized least squares integrating with kernel fusion technique

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Ming; Wang, Yanli, E-mail: ywang@ncbi.nlm.nih.gov; Bryant, Stephen H., E-mail: bryant@ncbi.nlm.nih.gov

    2016-02-25

    Identification of drug-target interactions (DTI) is a central task in drug discovery processes. In this work, a simple but effective regularized least squares integrating with nonlinear kernel fusion (RLS-KF) algorithm is proposed to perform DTI predictions. Using benchmark DTI datasets, our proposed algorithm achieves the state-of-the-art results with area under precision–recall curve (AUPR) of 0.915, 0.925, 0.853 and 0.909 for enzymes, ion channels (IC), G protein-coupled receptors (GPCR) and nuclear receptors (NR) based on 10 fold cross-validation. The performance can further be improved by using a recalculated kernel matrix, especially for the small set of nuclear receptors with AUPR of 0.945. Importantly, most of the top ranked interaction predictions can be validated by experimental data reported in the literature, bioassay results in the PubChem BioAssay database, as well as other previous studies. Our analysis suggests that the proposed RLS-KF is helpful for studying DTI, drug repositioning as well as polypharmacology, and may help to accelerate drug discovery by identifying novel drug targets. - Graphical abstract: Flowchart of the proposed RLS-KF algorithm for drug-target interaction predictions. - Highlights: • A nonlinear kernel fusion algorithm is proposed to perform drug-target interaction predictions. • Performance can further be improved by using the recalculated kernel. • Top predictions can be validated by experimental data.

  4. Improved prediction of drug-target interactions using regularized least squares integrating with kernel fusion technique

    International Nuclear Information System (INIS)

    Hao, Ming; Wang, Yanli; Bryant, Stephen H.

    2016-01-01

    Identification of drug-target interactions (DTI) is a central task in drug discovery processes. In this work, a simple but effective regularized least squares integrating with nonlinear kernel fusion (RLS-KF) algorithm is proposed to perform DTI predictions. Using benchmark DTI datasets, our proposed algorithm achieves the state-of-the-art results with area under precision–recall curve (AUPR) of 0.915, 0.925, 0.853 and 0.909 for enzymes, ion channels (IC), G protein-coupled receptors (GPCR) and nuclear receptors (NR) based on 10 fold cross-validation. The performance can further be improved by using a recalculated kernel matrix, especially for the small set of nuclear receptors with AUPR of 0.945. Importantly, most of the top ranked interaction predictions can be validated by experimental data reported in the literature, bioassay results in the PubChem BioAssay database, as well as other previous studies. Our analysis suggests that the proposed RLS-KF is helpful for studying DTI, drug repositioning as well as polypharmacology, and may help to accelerate drug discovery by identifying novel drug targets. - Graphical abstract: Flowchart of the proposed RLS-KF algorithm for drug-target interaction predictions. - Highlights: • A nonlinear kernel fusion algorithm is proposed to perform drug-target interaction predictions. • Performance can further be improved by using the recalculated kernel. • Top predictions can be validated by experimental data.

  5. Predicting 2D target velocity cannot help 2D motion integration for smooth pursuit initiation.

    Science.gov (United States)

    Montagnini, Anna; Spering, Miriam; Masson, Guillaume S

    2006-12-01

    Smooth pursuit eye movements reflect the temporal dynamics of bidimensional (2D) visual motion integration. When tracking a single, tilted line, initial pursuit direction is biased toward unidimensional (1D) edge motion signals, which are orthogonal to the line orientation. Over 200 ms, tracking direction is slowly corrected to finally match the 2D object motion during steady-state pursuit. We now show that repetition of line orientation and/or motion direction does not eliminate the transient tracking direction error nor change the time course of pursuit correction. Nonetheless, multiple successive presentations of a single orientation/direction condition elicit robust anticipatory pursuit eye movements that always go in the 2D object motion direction not the 1D edge motion direction. These results demonstrate that predictive signals about target motion cannot be used for an efficient integration of ambiguous velocity signals at pursuit initiation.

  6. Signatures of RNA binding proteins globally coupled to effective microRNA target sites

    DEFF Research Database (Denmark)

    Jacobsen, Anders; Wen, Jiayu; Marks, Debora S

    2010-01-01

    MicroRNAs (miRNAs) and small interfering RNAs (siRNAs), bound to Argonaute proteins (RISC), destabilize mRNAs through base-pairing with the mRNA. However, the gene expression changes after perturbations of these small RNAs are only partially explained by predicted miRNA/siRNA targeting. Targeting...

  7. Different integrated geophysical approaches to investigate archaeological sites in urban and suburban area.

    Science.gov (United States)

    Piro, Salvatore; Papale, Enrico; Zamuner, Daniela

    2016-04-01

    Geophysical methods are frequently used in archaeological prospection in order to provide detailed information about the presence of structures in the subsurface as well as their position and their geometrical reconstruction, by measuring variations of some physical properties. Often, due to the limited size and depth of an archaeological structure, it may be rather difficult to single out its position and extent because of the generally low signal-to-noise ratio. This problem can be overcome by improving data acquisition, processing techniques and by integrating different geophysical methods. In this work, two sites of archaeological interest, were investigated employing several methods (Ground Penetrating Radar (GPR), Electrical Resistivity Tomography (ERT), Fluxgate Differential Magnetic) to obtain precise and detailed maps of subsurface bodies. The first site, situated in a suburban area between Itri and Fondi, in the Aurunci Natural Regional Park (Central Italy), is characterized by the presence of remains of past human activity dating from the third century B.C. The second site, is instead situated in an urban area in the city of Rome (Basilica di Santa Balbina), where historical evidence is also present. The methods employed, allowed to determine the position and the geometry of some structures in the subsurface related to this past human activity. To have a better understanding of the subsurface, we then performed a qualitative and quantitative integration of this data, which consists in fusing the data from all the methods used, to have a complete visualization of the investigated area. Qualitative integration consists in graphically overlaying the maps obtained by the single methods; this method yields only images, not new data that may be subsequently analyzed. Quantitative integration is instead performed by mathematical and statistical solutions, which allows to have a more accurate reconstruction of the subsurface and generates new data with high

  8. Integrated modelling of material migration and target plate power handling at JET

    International Nuclear Information System (INIS)

    Coster, D.P.; Bonnin, X.; Chankin, A.

    2005-01-01

    The complexity of the tokamak edge and scrape-off layer (SOL) region is such that extrapolation to ITER requires modelling to be pursued through the integration of a number of edge codes, each of which must be thoroughly tested against results from present day machines. This contribution demonstrates how the edge modelling effort at JET is focused on such an approach by considering two examples, target power loading and material erosion and migration, the understanding of which are crucial issues for ITER. (author)

  9. New "persona" concept helps site designers cater to target user segments' needs.

    Science.gov (United States)

    2004-09-01

    Using the relatively new "persona" design concept, Web strategists create a set of archetypical user characters, each one representing one of their site's primary audiences. Then, as their site is constructed or upgraded, they champion the personas, arguing on their behalf and forcing the design team to take each audience's needs and wants into account.

  10. 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.

  11. Examination of CRISPR/Cas9 design tools and the effect of target site accessibility on Cas9 activity.

    Science.gov (United States)

    Lee, Ciaran M; Davis, Timothy H; Bao, Gang

    2018-04-01

    What is the topic of this review? In this review, we analyse the performance of recently described tools for CRISPR/Cas9 guide RNA design, in particular, design tools that predict CRISPR/Cas9 activity. What advances does it highlight? Recently, many tools designed to predict CRISPR/Cas9 activity have been reported. However, the majority of these tools lack experimental validation. Our analyses indicate that these tools have poor predictive power. Our preliminary results suggest that target site accessibility should be considered in order to develop better guide RNA design tools with improved predictive power. The recent adaptation of the clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system for targeted genome engineering has led to its widespread application in many fields worldwide. In order to gain a better understanding of the design rules of CRISPR/Cas9 systems, several groups have carried out large library-based screens leading to some insight into sequence preferences among highly active target sites. To facilitate CRISPR/Cas9 design, these studies have spawned a plethora of guide RNA (gRNA) design tools with algorithms based solely on direct or indirect sequence features. Here, we demonstrate that the predictive power of these tools is poor, suggesting that sequence features alone cannot accurately inform the cutting efficiency of a particular CRISPR/Cas9 gRNA design. Furthermore, we demonstrate that DNA target site accessibility influences the activity of CRISPR/Cas9. With further optimization, we hypothesize that it will be possible to increase the predictive power of gRNA design tools by including both sequence and target site accessibility metrics. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

  12. HPV genotyping and site of viral integration in cervical cancers in Indian women.

    Directory of Open Access Journals (Sweden)

    Poulami Das

    Full Text Available Persistent HPV infection plays a major role in cervical cancer. This study was undertaken to identify HPV types in a cohort of Indian women with locally advanced cervical cancer as well as to determine the physical state and/or site of viral integration in the host genome. Pretreatment biopsies (n = 270 from patients were screened for HPV infection by a high throughput HPV genotyping assay based on luminex xMAP technology as well as MY09/11 PCR and SPF1/2 PCR. Overall HPV positivity was observed to be 95%, with HPV16 being most common (63% followed by infection with HPV18. Integration status of the virus was identified using Amplification of Papillomavirus Oncogene Transcripts (APOT assay in a subset of samples positive for HPV16 and/or HPV18 (n = 86 and with an adequate follow-up. The data was correlated with clinical outcome of the patients. Integration of the viral genome was observed in 79% of the cases and a preference for integration into the chromosomal loci 1p, 3q, 6q, 11q, 13q and 20q was seen. Clinical data revealed that the physical state of the virus (integrated or episomal could be an important prognostic marker for cervical cancer.

  13. Assessment of mycorrhizal colonisation and soil nutrients in unmanaged fire-impacted soils from two target restoration sites

    Energy Technology Data Exchange (ETDEWEB)

    Dias, J. M.; Oliveira, R. S.; Franco, A. R.; Ritz, K.; Nunan, N.; Castro, P. M. L.

    2010-07-01

    The mycorrhizal colonisation of plants grown in unmanaged soils from two restoration sites with a fire history in Northern Portugal was evaluated from the perspective of supporting restoration programmes. To promote restoration of original tree stands, Quercus ilex L. and Pinus pinaster Ait. were used as target species on two sites, denoted Site 1 and 2 respectively. The aim of the study was to assess whether mycorrhizal propagules that survived fire episodes could serve as in situ inoculum sources, and to analyse the spatial distribution of soil nutrients and mycorrhizal parameters. In a laboratory bioassay, P. pinaster and Q. ilex seedlings were grown on soils from the target sites and root colonisation by ectomycorrhizal (ECM) and arbuscular mycorrhizal (AM) fungi was determined. The ECM root colonisation levels found indicated that soil from Site 2 contained sufficient ECM propagules to serve as a primary source of inoculum for P. pinaster. The low levels of ECM and AM colonisation obtained on the roots of plants grown in soil from Site 1 indicated that the existing mycorrhizal propagules might be insufficient for effective root colonisation of Q. ilex. Different ECM morphotypes were found in plants grown in soil from the two sites. At Site 2 mycorrhizal parameters were found to be spatially structured, with significant differences in ECM colonisation and soil P concentrations between regions of either side of an existing watercourse. The spatial distribution of mycorrhizal propagules was related to edaphic parameters (total C and extractable P), and correlations between soil nutrients and mycorrhizal parameters were found. (Author) 31 refs.

  14. An integrated building demolition and waste planning model for the Fernald Site

    International Nuclear Information System (INIS)

    Hampshire, L.H.; Clark, T.R.; Frost, M.L.; Reising, J.W.

    1995-01-01

    The Fernald DOE site will begin full-scale remediation of buildings under the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) during the 1995 fiscal year pursuant to a signed Record of Decision. This effort is currently estimated to cost $350 million and span a minimum duration of 8 years, if funding is not a constraint. The identification of the most viable sequence and schedule for the effort involved the development of an integrated planning model and the commissioning of a sitewide planning team. The resulting work product represents the best combination of assumptions and calculations possible at this time and provides information necessary for compliance with the CERCLA Remedial Design documentation requirements for the over 230 component structures governed by the decision. Sequence and integrated schedule development for the decontamination and dismantlement (D ampersand D) of Fernald structures has involved evaluation of current and future utilization of structures, availability of waste storage and staging space, the needs and impacts of other on-going Fernald projects, Resource Conservation and Recovery Act (RCRA) waste management and remediation projects, the layout of site utilities, site hydrology, and the potential sizing, location, and construction rates for an on-property disposal cell

  15. Brand community integration and customer satisfaction of social media network sites among students

    Directory of Open Access Journals (Sweden)

    Hayford Amegbe

    2017-11-01

    Full Text Available The aim of the study was to examine how consumers integrate into brand communities on social media network sites (SNSs and how it affects overall satisfaction of social media sites users among students. The study depends on the service-dominant logic (SDL to develop the constructs for hypotheses testing. The study used a cross-sectional survey research design. The data were col-lected using a web-based survey of university of Nairobi Students. In all, a total of 608 students participated in the survey. The data was analyzed using structural equation modeling with AMOS software. The results revealed that frequency of usage of SNSs and duration of usage positively affect the self –perceived relevance of SNSs. Also, the self-perceived relevance leads to building brand community which finally leads to customer satisfaction. The research was limited to only students of Nairobi and selecting students in itself, which is a limitation as well as limiting it to uni-versity of Nairobi. The younger or the millennial are not the only users of SNSs. We have older generations as well, who also use SNSs for various activities such as professional development among others. Understanding why consumers of social media network site would integrate brand community is seminal for both local and foreign firms doing business in a developing country. This would enable marketing practitioners to craft marketing strategies best for community brand build-ing.

  16. Hanford Integrated Planning Process: 1993 Hanford Site-specific science and technology plan

    International Nuclear Information System (INIS)

    1993-12-01

    This document is the FY 1993 report on Hanford Site-specific science and technology (S ampersand T) needs for cleanup of the Site as developed via the Hanford Integrated Planning Process (HIPP). It identifies cleanup problems that lack demonstrated technology solutions and technologies that require additional development. Recommendations are provided regarding allocation of funding to address Hanford's highest-priority technology improvement needs, technology development needs, and scientific research needs, all compiled from a Sitewide perspective. In the past, the S ampersand T agenda for Hanford Site cleanup was sometimes driven by scientists and technologists, with minimal input from the ''problem owners'' (i.e., Westinghouse Hanford Company [WHC] staff who are responsible for cleanup activities). At other times, the problem-owners made decisions to proceed with cleanup without adequate scientific and technological inputs. Under both of these scenarios, there was no significant stakeholder involvement in the decision-making process. One of the key objectives of HIPP is to develop an understanding of the integrated S ampersand T requirements to support the cleanup mission, (a) as defined by the needs of the problem owners, the values of the stakeholders, and the technology development expertise that exists at Hanford and elsewhere. This requires a periodic, systematic assessment of these needs and values to appropriately define a comprehensive technology development program and a complementary scientific research program. Basic to our success is a methodology that is defensible from a technical perspective and acceptable to the stakeholders

  17. Regulatory requirements of the integrated technology demonstration program, Savannah River Site (U)

    International Nuclear Information System (INIS)

    Bergren, C.L.

    1992-01-01

    The integrated demonstration program at the Savannah River Site (SRS) involves demonstration, testing and evaluation of new characterization, monitoring, drilling and remediation technologies for soils and groundwater impacted by organic solvent contamination. The regulatory success of the demonstration program has developed as a result of open communications between the regulators and the technical teams involved. This open dialogue is an attempt to allow timely completion of applied environmental restoration demonstrations while meeting all applicable regulatory requirements. Simultaneous processing of multiple regulatory documents (satisfying RCRA, CERCLA, NEPA and various state regulations) has streamlined the overall permitting process. Public involvement is achieved as various regulatory documents are advertised for public comment consistent with the site's community relations plan. The SRS integrated demonstration has been permitted and endorsed by regulatory agencies, including the Environmental Protection Agency (EPA) and the South Carolina Department of Health and Environmental Control. EPA headquarters and regional offices are involved in DOE's integrated Demonstration Program. This relationship allows for rapid regulatory acceptance while reducing federal funding and time requirements. (author)

  18. A novel educational strategy targeting health care workers in underserved communities in Central America to integrate HIV into primary medical care.

    Science.gov (United States)

    Flys, Tamara; González, Rosalba; Sued, Omar; Suarez Conejero, Juana; Kestler, Edgar; Sosa, Nestor; McKenzie-White, Jane; Monzón, Irma Irene; Torres, Carmen-Rosa; Page, Kathleen

    2012-01-01

    Current educational strategies to integrate HIV care into primary medical care in Central America have traditionally targeted managers or higher-level officials, rather than local health care workers (HCWs). We developed a complementary online and on-site interactive training program to reach local HCWs at the primary care level in underserved communities. The training program targeted physicians, nurses, and community HCWs with limited access to traditional onsite training in Panama, Nicaragua, Dominican Republic, and Guatemala. The curriculum focused on principles of HIV care and health systems using a tutor-supported blended educational approach of an 8-week online component, a weeklong on-site problem-solving workshop, and individualized project-based interventions. Of 258 initially active participants, 225 (225/258=87.2%) successfully completed the online component and the top 200 were invited to the on-site workshop. Of those, 170 (170/200=85%) attended the on-site workshop. In total, 142 completed all three components, including the project phase. Quantitative and qualitative evaluation instruments included knowledge assessments, reflexive essays, and acceptability surveys. The mean pre and post-essay scores demonstrating understanding of social determinants, health system organization, and integration of HIV services were 70% and 87.5%, respectively, with an increase in knowledge of 17.2% (pstructure, and effectiveness in improving their HIV-related knowledge and skills. This innovative curriculum utilized technology to target HCWs with limited access to educational resources. Participants benefited from technical skills acquired through the process, and could continue working within their underserved communities while participating in the online component and then implement interventions that successfully converted theoretical knowledge to action to improve integration of HIV care into primary care.

  19. Recent advances in the integrated geophysical exploration of buried archaeological targets

    International Nuclear Information System (INIS)

    Pipan, M.

    2014-01-01

    We propose the integration of magnetic, electromagnetic (groundpenetrating radar, GPR) and seismic methods to study the inner structure of prehistoric funerary mounds. The combination of techniques allows high-resolution imaging and detection of buried targets and characterization of subsurface materials based on magnetic susceptibility, dielectric permittivity, conductivity and seismic velocity/attenuation. The 2012 archaeo-geophysical expedition to Scythian necropoleis in Kazakhstan allowed advancement of the integrated procedure through optimization of the individual techniques. We improve the results of seismic tomography inversion through an ART algorithm with a relaxation parameter which is progressively reduced during the iterative reconstruction process. We use instantaneous attributes and spectral decomposition to improve the interpretation of GPR reflection data. The results obtained from the 2012 dataset allow detailed reconstruction of the inner structure of three kurgans (i.e. funerary mounds) with maximum 7m central elevation. In particular, localized anomalies related to metallic targets smaller than the GPR and seismic resolution limits are identified from magnetic data after high pass filtering; GPR data allow imaging of inner stratigraphy up to a maximum depth of about 250 cm; seismic tomography maps large traveltime anomalies probably related to funerary chambers at the base of the mound.

  20. A Fuzzy Adaptive Tightly-Coupled Integration Method for Mobile Target Localization Using SINS/WSN

    Directory of Open Access Journals (Sweden)

    Wei Li

    2016-11-01

    Full Text Available In recent years, mobile target localization for enclosed environments has been a growing interest. In this paper, we have proposed a fuzzy adaptive tightly-coupled integration (FATCI method for positioning and tracking applications using strapdown inertial navigation system (SINS and wireless sensor network (WSN. The wireless signal outage and severe multipath propagation of WSN often influence the accuracy of measured distance and lead to difficulties with the WSN positioning. Note also that the SINS are known for their drifted error over time. Using as a base the well-known loosely-coupled integration method, we have built a tightly-coupled integrated positioning system for SINS/WSN based on the measured distances between anchor nodes and mobile node. The measured distance value of WSN is corrected with a least squares regression (LSR algorithm, with the aim of decreasing the systematic error for measured distance. Additionally, the statistical covariance of measured distance value is used to adjust the observation covariance matrix of a Kalman filter using a fuzzy inference system (FIS, based on the statistical characteristics. Then the tightly-coupled integration model can adaptively adjust the confidence level for measurement according to the different measured accuracies of distance measurements. Hence the FATCI system is achieved using SINS/WSN. This innovative approach is verified in real scenarios. Experimental results show that the proposed positioning system has better accuracy and stability compared with the loosely-coupled and traditional tightly-coupled integration model for WSN short-term failure or normal conditions.

  1. Active site electrostatics protect genome integrity by blocking abortive hydrolysis during DNA recombination

    Science.gov (United States)

    Ma, Chien-Hui; Rowley, Paul A; Macieszak, Anna; Guga, Piotr; Jayaram, Makkuni

    2009-01-01

    Water, acting as a rogue nucleophile, can disrupt transesterification steps of important phosphoryl transfer reactions in DNA and RNA. We have unveiled this risk, and identified safeguards instituted against it, during strand cleavage and joining by the tyrosine site-specific recombinase Flp. Strand joining is threatened by a latent Flp endonuclease activity (type I) towards the 3′-phosphotyrosyl intermediate resulting from strand cleavage. This risk is not alleviated by phosphate electrostatics; neutralizing the negative charge on the scissile phosphate through methylphosphonate (MeP) substitution does not stimulate type I endonuclease. Rather, protection derives from the architecture of the recombination synapse and conformational dynamics within it. Strand cleavage is protected against water by active site electrostatics. Replacement of the catalytic Arg-308 of Flp by alanine, along with MeP substitution, elicits a second Flp endonuclease activity (type II) that directly targets the scissile phosphodiester bond in DNA. MeP substitution, combined with appropriate active site mutations, will be useful in revealing anti-hydrolytic mechanisms engendered by systems that mediate DNA relaxation, DNA transposition, site-specific recombination, telomere resolution, RNA splicing and retrohoming of mobile introns. PMID:19440204

  2. Integrated Closure and Monitoring Plan for the Area 3 and Area 5 Radioactive Waste Management Sites at the Nevada Test Site

    International Nuclear Information System (INIS)

    Bechtel Nevada

    2005-01-01

    This document is an integrated plan for closing and monitoring two low-level radioactive waste disposal sites at the Nevada Test Site. This document is an integrated plan for closing and monitoring two low-level radioactive waste disposal sites at the Nevada Test Site (NTS). The Area 3 and Area 5 Radioactive Waste Management Sites (RWMSs) are managed and operated by Bechtel Nevada (BN) for the U.S. Department of Energy's (DOE's) National Nuclear Security Administration Nevada Site Office (NNSA/NSO). The Integrated Closure and Monitoring Plan (ICMP) for these sites is based on guidance for developing closure plans issued by the DOE (DOE, 1999a). The plan does not closely follow the format suggested by the DOE guidance to better accommodate differences between the two RWMSs, especially in terms of operations and site characteristics. The modification reduces redundancy and provides a smoother progression of the discussion. Further, much of the information that would be included in the individual plans is the same, and integration provides efficient presentation. A cross-walk between the contents of the ICMP and the DOE guidance is given in Appendix A. Closure and monitoring were integrated because monitoring measures the degree to which the operational and closed disposal facilities are meeting performance objectives specified in the manual to DOE Order O 435.1. Department of Energy Order 435.1 governs management of radioactive waste, and associated with it are Manual DOE M 435.1-1 and Guidance DOE G 435.1-1. The performance objectives are intended to ensure protection of workers, the public, and the environment from radiological exposure associated with the RWMSs now and in the future

  3. Random Tagging Genotyping by Sequencing (rtGBS, an Unbiased Approach to Locate Restriction Enzyme Sites across the Target Genome.

    Directory of Open Access Journals (Sweden)

    Elena Hilario

    Full Text Available Genotyping by sequencing (GBS is a restriction enzyme based targeted approach developed to reduce the genome complexity and discover genetic markers when a priori sequence information is unavailable. Sufficient coverage at each locus is essential to distinguish heterozygous from homozygous sites accurately. The number of GBS samples able to be pooled in one sequencing lane is limited by the number of restriction sites present in the genome and the read depth required at each site per sample for accurate calling of single-nucleotide polymorphisms. Loci bias was observed using a slight modification of the Elshire et al.some restriction enzyme sites were represented in higher proportions while others were poorly represented or absent. This bias could be due to the quality of genomic DNA, the endonuclease and ligase reaction efficiency, the distance between restriction sites, the preferential amplification of small library restriction fragments, or bias towards cluster formation of small amplicons during the sequencing process. To overcome these issues, we have developed a GBS method based on randomly tagging genomic DNA (rtGBS. By randomly landing on the genome, we can, with less bias, find restriction sites that are far apart, and undetected by the standard GBS (stdGBS method. The study comprises two types of biological replicates: six different kiwifruit plants and two independent DNA extractions per plant; and three types of technical replicates: four samples of each DNA extraction, stdGBS vs. rtGBS methods, and two independent library amplifications, each sequenced in separate lanes. A statistically significant unbiased distribution of restriction fragment size by rtGBS showed that this method targeted 49% (39,145 of BamH I sites shared with the reference genome, compared to only 14% (11,513 by stdGBS.

  4. 300 Area Integrated Field-Scale Subsurface Research Challenge (IFRC) Field Site Management Plan

    Energy Technology Data Exchange (ETDEWEB)

    Freshley, Mark D.

    2008-12-31

    Pacific Northwest National Laboratory (PNNL) has established the 300 Area Integrated Field-Scale Subsurface Research Challenge (300 Area IFRC) on the Hanford Site in southeastern Washington State for the U.S. Department of Energy’s (DOE) Office of Biological and Environmental Research (BER) within the Office of Science. The project is funded by the Environmental Remediation Sciences Division (ERSD). The purpose of the project is to conduct research at the 300 IFRC to investigate multi-scale mass transfer processes associated with a subsurface uranium plume impacting both the vadose zone and groundwater. The management approach for the 300 Area IFRC requires that a Field Site Management Plan be developed. This is an update of the plan to reflect the installation of the well network and other changes.

  5. Near-IR Spectral Imaging of Semiconductor Absorption Sites in Integrated Circuits

    Directory of Open Access Journals (Sweden)

    E. C. Samson

    2004-12-01

    Full Text Available We derive spectral maps of absorption sites in integrated circuits (ICs by varying the wavelength of the optical probe within the near-IR range. This method has allowed us to improve the contrast of the acquired images by revealing structures that have a different optical absorption from neighboring sites. A false color composite image from those acquired at different wavelengths is generated from which the response of each semiconductor structure can be deduced. With the aid of the spectral maps, nonuniform absorption was also observed in a semiconductor structure located near an electrical overstress defect. This method may prove important in failure analysis of ICs by uncovering areas exhibiting anomalous absorption, which could improve localization of defective edifices in the semiconductor parts of the microchip

  6. An Integrated Approach to Mitigation Wetland Site Selection: A Case Study in Gwacheon, Korea

    Directory of Open Access Journals (Sweden)

    Junga Lee

    2015-03-01

    Full Text Available This paper presents an integrated approach to mitigation wetland site selection using functional landscape connectivity and landscape structure. This approach enables landscape designers to evaluate the relative priorities of mitigation wetland areas based on functional landscape connectivity and wildlife mobility, as well as landscape structure, composition, and configuration. The least-cost path method is used to evaluate candidate sites for mitigation wetlands with regard to wildlife movement. A set of assessments for landscape indices using FRAGSTATS was applied to identify suitable mitigation wetland areas on the basis of landscape connectivity, composition, and configuration. The study was conducted in Gwacheon, Korea, where there are plans for regional development that will change the landscape. In the first step, a group of 14 candidate sites is identified via analysis of functional landscape connectivity using the least-cost path method. In the second step, candidate mitigation wetland areas are ranked according to landscape connectivity and composition. The five mitigation wetland areas that were found to be suitable were analyzed based on landscape configuration at the class level. This study demonstrates that functional landscape connectivity and landscape structure are important aspects to consider when identifying suitable sites for mitigation wetland planning and restoration.

  7. The basics of integrating environmental and engineering in early wind farm siting

    Energy Technology Data Exchange (ETDEWEB)

    Alberti, A. [Tetra Tech Inc., Oakville, ON (Canada)

    2010-07-01

    This PowerPoint presentation discussed methods of integrating environmental and engineering studies into the early phases of wind farm siting plans. Most renewable energy development projects begin by an assessment of the transmission capability and renewable resources, followed by engineering and environmental screening procedures. Transmission screening is conducted to identify preliminary interconnection corridors between potential development sites and potential interconnecting transmission lines. Critical issues analysis (CIA) studies identify conditions, siting issues, and potential environmental and engineering tasks related to early scheduling and budget procedures. The components of a CIA include desktop and field studies that are conducted to document issues that warrant special consideration. Team members are comprised of qualified experts who are familiar with the geographic region and are able to collaborate at an early stage in the project. However, many CIA studies do not consider engineering constructability issues or develop strategies for ensuring community support for wind power projects. Conceptual layouts for wind power facilities include information related to turbine locations, access roads, and transmission lines and equipment. Engineering studies are used to evaluate conditions and potential hazards. Issues related to agricultural sites must also be considered. The final locations of turbines must be checked to ensure constructability and energy production potential. tabs., figs.

  8. Botanical aspects of the ecological integrity of a radioactive waste disposal site

    International Nuclear Information System (INIS)

    Hall, A.V.

    1986-01-01

    Botanical factors play a key role in maintaining the long term integrity of ecosystems. The results of botanical research at the Vaalputs radioactive waste disposal site in Bushmanland, South Africa, are outlined. Vaalputs is in an arid region and its vegetation is a patchy mosaic of low shrub and grass communities. Soil variation from site to site is the main determinant of community structure and erratic precipitation is a major stochastic forcing factor. Management measures to conserve taxa, ecosystems and local genetic biogeography are discussed in relation to natural and artificial disturbances which may occur over long time-scales. Restoration of vegetation over the burial trenches should as far as possible be to the site's former ecotypes except that deep-rooted species should be excluded. Precautions should be taken against the accidental establishment of exotic plant invaders at Vaalputs especially if they are deep-rooted. More is now known about plant ecology at Vaalputs than any other part of Bushmanland. It would be valuable to develop such studies further and establish Vaalputs as a permanent reserve for arid-zone biological research

  9. Hanford Site's Integrated Risk Assessment Program: No-intervention risk assessment

    International Nuclear Information System (INIS)

    Mahaffey, J.A.; Dukelow, J.S. Jr.; Stenner, R.D.

    1994-08-01

    The long-term goal of the Integrated Risk Assessment program (IRAP) is to estimate risks to workers, the public, organizations, and groups with reserved rights to Site access, the ecosystem, and natural resources to aid in managing environmental restoration and waste management at the Hanford Site. For each of these, information is needed about current risks, risks during cleanup, and endstate risks. The objective is three-fold: to determine if and when to remediate, and to what extent; to identify information unavailable but needed to make better cleanup decisions; to establish technology performance criteria for achieving desired cleanup levels; to understand costs and benefits of activities from a Site-wide perspective. The no-intervention risk, assessment is the initial evaluation of public health risks conducted under IRAP. The objective is to identify types of activities that the US Department of Energy (DOE) must accomplish for closure of the Hanford Site, defined as no further DOE intervention. There are two primary conclusions from the no-intervention risk assessment. First, some maintenance and operations activities at Hanford must be continued to protect the public from grave risks. However, when large Hanford expenditures are compared to cleanup progress, funds expended for maintenance and operations must be put in proper perspective. Second, stakeholder's emphasis on public risks at Hanford, as indicated by remediation priorities, are not in line with those estimated. The focus currently is on compliance with regulations, and on dealing with issues which are visible to stakeholders

  10. The mastermind approach to CNS drug therapy: translational prediction of human brain distribution, target site kinetics, and therapeutic effects

    OpenAIRE

    de Lange, Elizabeth CM

    2013-01-01

    Despite enormous advances in CNS research, CNS disorders remain the world?s leading cause of disability. This accounts for more hospitalizations and prolonged care than almost all other diseases combined, and indicates a high unmet need for good CNS drugs and drug therapies. Following dosing, not only the chemical properties of the drug and blood?brain barrier (BBB) transport, but also many other processes will ultimately determine brain target site kinetics and consequently the CNS effects. ...

  11. Nanoscale Synaptic Membrane Mimetic Allows Unbiased High Throughput Screen That Targets Binding Sites for Alzheimer?s-Associated A? Oligomers

    OpenAIRE

    Wilcox, Kyle C.; Marunde, Matthew R.; Das, Aditi; Velasco, Pauline T.; Kuhns, Benjamin D.; Marty, Michael T.; Jiang, Haoming; Luan, Chi-Hao; Sligar, Stephen G.; Klein, William L.

    2015-01-01

    Despite their value as sources of therapeutic drug targets, membrane proteomes are largely inaccessible to high-throughput screening (HTS) tools designed for soluble proteins. An important example comprises the membrane proteins that bind amyloid β oligomers (AβOs). AβOs are neurotoxic ligands thought to instigate the synapse damage that leads to Alzheimer's dementia. At present, the identities of initial AβO binding sites are highly uncertain, largely because of extensive protein-protein int...

  12. The EuroSITES network: Integrating and enhancing fixed-point open ocean observatories around Europe

    Science.gov (United States)

    Lampitt, Richard S.; Larkin, Kate E.; EuroSITES Consortium

    2010-05-01

    EuroSITES is a 3 year (2008-2011) EU collaborative project (3.5MEuro) with the objective to integrate and enhance the nine existing open ocean fixed point observatories around Europe (www.eurosites.info). These observatories are primarily composed of full depth moorings and make multidisciplinary in situ observations within the water column as the European contribution to the global array OceanSITES (www.oceansites.org). In the first 18 months, all 9 observatories have been active and integration has been significant through the maintenance and enhancement of observatory hardware. Highlights include the enhancement of observatories with sensors to measure O2, pCO2, chlorophyll, and nitrate in near real-time from the upper 1000 m. In addition, some seafloor missions are also actively supported. These include seafloor platforms currently deployed in the Mediterranean, one for tsunami detection and one to monitor fluid flow related to seismic activity and slope stability. Upcoming seafloor science missions in 2010 include monitoring benthic biological communities and associated biogeochemistry as indicators of climate change in both the Northeast Atlantic and Mediterranean. EuroSITES also promotes the development of innovative sensors and samplers in order to progress capability to measure climate-relevant properties of the ocean. These include further developing current technologies for autonomous long-term monitoring of oxygen consumption in the mesopelagic, pH and mesozooplankton abundance. Many of these science missions are directly related to complementary activities in other European projects such as EPOCA, HYPOX and ESONET. In 2010 a direct collaboration including in situ field work will take place between ESONET and EuroSITES. The demonstration mission MODOO (funded by ESONET) will be implemented in 2010 at the EuroSITES PAP observatory. Field work will include deployment of a seafloor lander system with various sensors which will send data to shore in real

  13. Integrated analysis of ischemic stroke datasets revealed sex and age difference in anti-stroke targets

    Directory of Open Access Journals (Sweden)

    Wen-Xing Li

    2016-09-01

    Full Text Available Ischemic stroke is a common neurological disorder and the burden in the world is growing. This study aims to explore the effect of sex and age difference on ischemic stroke using integrated microarray datasets. The results showed a dramatic difference in whole gene expression profiles and influenced pathways between males and females, and also in the old and young individuals. Furthermore, compared with old males, old female patients showed more serious biological function damage. However, females showed less affected pathways than males in young subjects. Functional interaction networks showed these differential expression genes were mostly related to immune and inflammation-related functions. In addition, we found ARG1 and MMP9 were up-regulated in total and all subgroups. Importantly, IL1A, ILAB, IL6 and TNF and other anti-stroke target genes were up-regulated in males. However, these anti-stroke target genes showed low expression in females. This study found huge sex and age differences in ischemic stroke especially the opposite expression of anti-stroke target genes. Future studies are needed to uncover these pathological mechanisms, and to take appropriate pre-prevention, treatment and rehabilitation measures.

  14. D Integrated Methodologies for the Documentation and the Virtual Reconstruction of AN Archaeological Site

    Science.gov (United States)

    Balletti, C.; Guerra, F.; Scocca, V.; Gottardi, C.

    2015-02-01

    Highly accurate documentation and 3D reconstructions are fundamental for analyses and further interpretations in archaeology. In the last years the integrated digital survey (ground-based survey methods and UAV photogrammetry) has confirmed its main role in the documentation and comprehension of excavation contexts, thanks to instrumental and methodological development concerning the on site data acquisition. The specific aim of the project, reported in this paper and realized by the Laboratory of Photogrammetry of the IUAV University of Venice, is to check different acquisition systems and their effectiveness test, considering each methodology individually or integrated. This research focuses on the awareness that the integration of different survey's methodologies can as a matter of fact increase the representative efficacy of the final representations; these are based on a wider and verified set of georeferenced metric data. Particularly the methods' integration allows reducing or neutralizing issues related to composite and complex objects' survey, since the most appropriate tools and techniques can be chosen considering the characteristics of each part of an archaeological site (i.e. urban structures, architectural monuments, small findings). This paper describes the experience in several sites of the municipality of Sepino (Molise, Italy), where the 3d digital acquisition of cities and structure of monuments, sometimes hard to reach, was realized using active and passive techniques (rage-based and image based methods). This acquisition was planned in order to obtain not only the basic support for interpretation analysis, but also to achieve models of the actual state of conservation of the site on which some reconstructive hypotheses can be based on. Laser scanning data were merged with Structure from Motion techniques' clouds into the same reference system, given by a topographical and GPS survey. These 3d models are not only the final results of the metric

  15. Radionuclide disequilibria studies for investigating the integrity of potential nuclear waste disposal sites: subseabed studies

    International Nuclear Information System (INIS)

    Laul, J.C.; Thomas, C.W.; Petersen, M.R.; Perkins, R.W.

    1981-09-01

    This study of subseabed sediments indicates that natural radionuclides can be employed to define past long-term migration rates and thereby evaluate the integrity of potential disposal sites in ocean sediments. The study revealed the following conclusions: (1) the sedimentation rate of both the long and short cores collected in the North Pacific is 2.5 mm/1000 yr or 2.5 m/m.yr in the upper 3 meters; (2) the sedimentation rate has been rather constant over the last one million years; and (3) slow diffusive processes dominate within the sediment. Reworking of the sediment by physical processes or organisms is not observed

  16. mRNA-engineered mesenchymal stem cells for targeted delivery of interleukin-10 to sites of inflammation.

    Science.gov (United States)

    Levy, Oren; Zhao, Weian; Mortensen, Luke J; Leblanc, Sarah; Tsang, Kyle; Fu, Moyu; Phillips, Joseph A; Sagar, Vinay; Anandakumaran, Priya; Ngai, Jessica; Cui, Cheryl H; Eimon, Peter; Angel, Matthew; Lin, Charles P; Yanik, Mehmet Fatih; Karp, Jeffrey M

    2013-10-03

    Mesenchymal stem cells (MSCs) are promising candidates for cell-based therapy to treat several diseases and are compelling to consider as vehicles for delivery of biological agents. However, MSCs appear to act through a seemingly limited "hit-and-run" mode to quickly exert their therapeutic impact, mediated by several mechanisms, including a potent immunomodulatory secretome. Furthermore, MSC immunomodulatory properties are highly variable and the secretome composition following infusion is uncertain. To determine whether a transiently controlled antiinflammatory MSC secretome could be achieved at target sites of inflammation, we harnessed mRNA transfection to generate MSCs that simultaneously express functional rolling machinery (P-selectin glycoprotein ligand-1 [PSGL-1] and Sialyl-Lewis(x) [SLeX]) to rapidly target inflamed tissues and that express the potent immunosuppressive cytokine interleukin-10 (IL-10), which is not inherently produced by MSCs. Indeed, triple-transfected PSGL-1/SLeX/IL-10 MSCs transiently increased levels of IL-10 in the inflamed ear and showed a superior antiinflammatory effect in vivo, significantly reducing local inflammation following systemic administration. This was dependent on rapid localization of MSCs to the inflamed site. Overall, this study demonstrates that despite the rapid clearance of MSCs in vivo, engineered MSCs can be harnessed via a "hit-and-run" action for the targeted delivery of potent immunomodulatory factors to treat distant sites of inflammation.

  17. Using Docker Compose for the Simple Deployment of an Integrated Drug Target Screening Platform

    Directory of Open Access Journals (Sweden)

    List Markus

    2017-06-01

    Full Text Available Docker virtualization allows for software tools to be executed in an isolated and controlled environment referred to as a container. In Docker containers, dependencies are provided exactly as intended by the developer and, consequently, they simplify the distribution of scientific software and foster reproducible research. The Docker paradigm is that each container encapsulates one particular software tool. However, to analyze complex biomedical data sets, it is often necessary to combine several software tools into elaborate workflows. To address this challenge, several Docker containers need to be instantiated and properly integrated, which complicates the software deployment process unnecessarily. Here, we demonstrate how an extension to Docker, Docker compose, can be used to mitigate these problems by providing a unified setup routine that deploys several tools in an integrated fashion. We demonstrate the power of this approach by example of a Docker compose setup for a drug target screening platform consisting of five integrated web applications and shared infrastructure, deployable in just two lines of codes.

  18. Using Docker Compose for the Simple Deployment of an Integrated Drug Target Screening Platform.

    Science.gov (United States)

    List, Markus

    2017-06-10

    Docker virtualization allows for software tools to be executed in an isolated and controlled environment referred to as a container. In Docker containers, dependencies are provided exactly as intended by the developer and, consequently, they simplify the distribution of scientific software and foster reproducible research. The Docker paradigm is that each container encapsulates one particular software tool. However, to analyze complex biomedical data sets, it is often necessary to combine several software tools into elaborate workflows. To address this challenge, several Docker containers need to be instantiated and properly integrated, which complicates the software deployment process unnecessarily. Here, we demonstrate how an extension to Docker, Docker compose, can be used to mitigate these problems by providing a unified setup routine that deploys several tools in an integrated fashion. We demonstrate the power of this approach by example of a Docker compose setup for a drug target screening platform consisting of five integrated web applications and shared infrastructure, deployable in just two lines of codes.

  19. Analysis of Properties of Reflectance Reference Targets for Permanent Radiometric Test Sites of High Resolution Airborne Imaging Systems

    Directory of Open Access Journals (Sweden)

    Eero Ahokas

    2010-08-01

    Full Text Available Reliable and optimal exploitation of rapidly developing airborne imaging methods requires geometric and radiometric quality assurance of production systems in operational conditions. Permanent test sites are the most promising approach for cost-efficient performance assessment. Optimal construction of permanent radiometric test sites for high resolution airborne imaging systems is an unresolved issue. The objective of this study was to assess the performance of commercially available gravels and painted and unpainted concrete targets for permanent, open-air radiometric test sites under sub-optimal climate conditions in Southern Finland. The reflectance spectrum and reflectance anisotropy and their stability were characterized during the summer of 2009. The management of reflectance anisotropy and stability were shown to be the key issues for better than 5% reflectance accuracy.

  20. Plant integration of MITICA and SPIDER experiments with auxiliary plants and buildings on PRIMA site

    Energy Technology Data Exchange (ETDEWEB)

    Fellin, Francesco, E-mail: francesco.fellin@igi.cnr.it; Boldrin, Marco; Zaccaria, Pierluigi; Agostinetti, Piero; Battistella, Manuela; Bigi, Marco; Palma, Samuele Dal Bello Mauro Dalla; Fiorentin, Aldo; Luchetta, Adriano; Maistrello, Alberto; Marcuzzi, Diego; Ocello, Edoardo; Pasqualotto, Roberto; Pavei, Mauro; Pomaro, Nicola; Rizzolo, Andrea; Toigo, Vanni; Valente, Matteo; Zanotto, Loris; Calore, Luca; and others

    2015-10-15

    Highlights: • Focus on plant integration work supporting the realization of SPIDER and MITICA fusion experiments hosted in PRIMA buildings complex in Padova, Italy. • Huge effort of coordination and integration among many stakeholders, taking into account several constrains coming from experiments requirements (on-going) and precise time schedule and budget on buildings construction. • The paper also deals of interfaces management, coordination and integration of many competences, problems solving to find best solution also considering other aspects like safety and maintenance. - Abstract: This paper presents a description of the PRIMA (Padova Research on ITER Megavolt Accelerator) Plant Integration work, aimed at the construction of PRIMA Buildings, which will host two nuclear fusion test facilities named SPIDER and MITICA, finalized to test and optimize the neutral beam injectors for ITER experiment. These activities are very complex: inputs coming from the experiments design are changing time to time, while the buildings construction shall fulfill precise time schedule and budget. Moreover the decision process is often very long due to the high number of stakeholders (RFX, IO, third parties, suppliers, domestic agencies from different countries). The huge effort includes: forecasting what will be necessary for the integration of many experimental plants; collecting requirements and translating into inputs; interfaces management; coordination meetings with hundreds of people with various and different competences in construction and operation of fusion facilities, thermomechanics, electrical and control, buildings design and construction (civil plants plus architectural and structural aspects), safety, maintenance and management. The paper describes these activities and also the tools created to check and to validate the building design, to manage the interfaces and the organization put in place to achieve the required targets.

  1. Plant integration of MITICA and SPIDER experiments with auxiliary plants and buildings on PRIMA site

    International Nuclear Information System (INIS)

    Fellin, Francesco; Boldrin, Marco; Zaccaria, Pierluigi; Agostinetti, Piero; Battistella, Manuela; Bigi, Marco; Palma, Samuele Dal Bello Mauro Dalla; Fiorentin, Aldo; Luchetta, Adriano; Maistrello, Alberto; Marcuzzi, Diego; Ocello, Edoardo; Pasqualotto, Roberto; Pavei, Mauro; Pomaro, Nicola; Rizzolo, Andrea; Toigo, Vanni; Valente, Matteo; Zanotto, Loris; Calore, Luca

    2015-01-01

    Highlights: • Focus on plant integration work supporting the realization of SPIDER and MITICA fusion experiments hosted in PRIMA buildings complex in Padova, Italy. • Huge effort of coordination and integration among many stakeholders, taking into account several constrains coming from experiments requirements (on-going) and precise time schedule and budget on buildings construction. • The paper also deals of interfaces management, coordination and integration of many competences, problems solving to find best solution also considering other aspects like safety and maintenance. - Abstract: This paper presents a description of the PRIMA (Padova Research on ITER Megavolt Accelerator) Plant Integration work, aimed at the construction of PRIMA Buildings, which will host two nuclear fusion test facilities named SPIDER and MITICA, finalized to test and optimize the neutral beam injectors for ITER experiment. These activities are very complex: inputs coming from the experiments design are changing time to time, while the buildings construction shall fulfill precise time schedule and budget. Moreover the decision process is often very long due to the high number of stakeholders (RFX, IO, third parties, suppliers, domestic agencies from different countries). The huge effort includes: forecasting what will be necessary for the integration of many experimental plants; collecting requirements and translating into inputs; interfaces management; coordination meetings with hundreds of people with various and different competences in construction and operation of fusion facilities, thermomechanics, electrical and control, buildings design and construction (civil plants plus architectural and structural aspects), safety, maintenance and management. The paper describes these activities and also the tools created to check and to validate the building design, to manage the interfaces and the organization put in place to achieve the required targets.

  2. IFMIF Li target back-plate design integration and thermo-mechanical analysis

    International Nuclear Information System (INIS)

    Riccardi, B.; Roccella, S.; Micciche, G.

    2006-01-01

    The International Fusion Materials Irradiation Facility (IFMIF) is an accelerator-driven intense neutron source where fusion reactor candidate materials will be tested. The neutron flux is produced by means of a deuteron beam (current 250 mA, energy 40 MeV) that strikes a liquid lithium target circulating in a lithium loop. The support on which the liquid lithium flows, i.e. the back-plate, is the most heavily exposed component to neutron flux. A '' bayonet '' concept solution for the back-plate was proposed by ENEA with the objectives of improving the back-plate reliability and simplifying the remote handling procedures. On the base of this concept, a back-plate mock-up was fabricated and validated. Starting from the findings of the mock up design, a back-plate design integration exercise was carried out in order to check if the back-plate geometrical features are compatible with the target assembly and the Vertical Test Assemblies (VTA). The work carried out has demonstrated that even with the changes operated for the design integration (increase of in-plane dimensions and reduction of thickness) the bayonet concept is able to guarantee a tight connection to the target assembly. A thermo-mechanical analysis of the back-plate has been carried out by means of ABAQUS code. The thermal load used as input for the calculations, i.e. the neutron heat generation, has been estimated by means of Monte Carlo Mc-Delicious code. The two boundary constraint cases (full and minimum contact with target assembly) considered for each back-plate geometry option represent the extreme cases of the real operating condition of the plate. The influence of the contact heat exchange coefficient and the back-plate thickness has been also evaluated. For all these reasons, the results of the analysis can be considered as the domain of variability of the real working conditions. The results show that AISI 316L steel is not suitable as black-plate material: the stress induced in the plate, in

  3. Technology strategy for integrated operations and real time reservoir management; Technology Target Areas; TTA5 - Integrated operations and RTRM

    Energy Technology Data Exchange (ETDEWEB)

    2007-07-01

    In Norway Integrated Operations (IO) is a concept which in the first phase (G1) has been used to describe how to integrate processes and people onshore and offshore using ICT solutions and facilities that improve onshore's ability to support offshore operationally. The second generation (G2) Integrated Operations aims to help operators utilize vendors' core competencies and services more efficiently. Utilizing digital services and vendor products, operators will be able to update reservoir models, drilling targets and well trajectories as wells are drilled, manage well completions remotely, optimize production from reservoir to export lines, and implement condition-based maintenance concepts. The total impact on production, recovery rates, costs and safety will be profound. When the international petroleum business moves to the Arctic region the setting is very different from what is the case on the Norwegian Continental Shelf (NCS) and new challenges will arise. The Norwegian Ministry of Environment has recently issued an Integrated Management Plan for the Barents Sea where one focus is on 'Monitoring of the Marine Environment in the North'. The Government aims to establish a new and more coordinated system for monitoring the marine ecosystems in the north. A representative group consisting of the major Operators, the Service Industry, Academia and the Authorities have developed the enclosed strategy for the OG21 Integrated Operations and Real Time Reservoir Management (IO and RTRM) Technology Target Area (TTA). Major technology and work process research and development gaps have been identified in several areas: Bandwidth down-hole to surface; Sensor development including Nano-technology; Cross discipline use of Visualisation, Simulation and model development particularly in Drilling and Reservoir management areas; Software development in terms of data handling, model updating and calculation speed; Enabling reliable and robust communications particularly for

  4. Technology strategy for integrated operations and real time reservoir management; Technology Target Areas; TTA5 - Integrated operations and RTRM

    Energy Technology Data Exchange (ETDEWEB)

    2007-07-01

    In Norway Integrated Operations (IO) is a concept which in the first phase (G1) has been used to describe how to integrate processes and people onshore and offshore using ICT solutions and facilities that improve onshore's ability to support offshore operationally. The second generation (G2) Integrated Operations aims to help operators utilize vendors' core competencies and services more efficiently. Utilizing digital services and vendor products, operators will be able to update reservoir models, drilling targets and well trajectories as wells are drilled, manage well completions remotely, optimize production from reservoir to export lines, and implement condition-based maintenance concepts. The total impact on production, recovery rates, costs and safety will be profound. When the international petroleum business moves to the Arctic region the setting is very different from what is the case on the Norwegian Continental Shelf (NCS) and new challenges will arise. The Norwegian Ministry of Environment has recently issued an Integrated Management Plan for the Barents Sea where one focus is on 'Monitoring of the Marine Environment in the North'. The Government aims to establish a new and more coordinated system for monitoring the marine ecosystems in the north. A representative group consisting of the major Operators, the Service Industry, Academia and the Authorities have developed the enclosed strategy for the OG21 Integrated Operations and Real Time Reservoir Management (IO and RTRM) Technology Target Area (TTA). Major technology and work process research and development gaps have been identified in several areas: Bandwidth down-hole to surface; Sensor development including Nano-technology; Cross discipline use of Visualisation, Simulation and model development particularly in Drilling and Reservoir management areas; Software development in terms of data handling, model updating and calculation speed; Enabling reliable and robust communications

  5. Integrated Geophysycal Prospecting in Late Antiquity and Early Medieval Sites in Italy

    Science.gov (United States)

    Giannotta, Maria Teresa; Leucci, Giovanni; De Giorgi, Lara; Matera, Loredana; Persico, Raffaele; Muci, Giuseppe

    2016-04-01

    In this contribution, the results of some integrated geophysical prospecting (magnetometric and GPR) are exposed. This work has been performed in collaboration between archaeologists and geophysicists within the research project "History and Global Archaeology of the Rural Landascapes in Italy, between Late Antiquity and Medieval period. Integrated systems of sources, methodologies, and technologies for a sustainable development", financed by the Italian Ministry for Instruction, University and Research MIUR. In particular, the archaeological sites of Badia and San Giovanni in Malcantone, both in the Apulia Region (eastern-southern Italy) have been prospect. The sites have been identified on the basis of available documents, archaeological surveys and testimonies. In particular, we know that in Badia [1] it was probable the presence of an ancient roman villa of the late ancient period (strongly damaged by the subsequent ploughing activities). Whereas in San Giovanni there is still, today, a small chapel (deconsecrated) that was likely to be part of a previous larger church (probably a basilica of the early Christian period) restricted in the subsequent centuries (probably in more phases). The Saracen raids of the XVI centuries made the site ruined and abandoned. In both sites integrated prospecting have been performed [2-6] with a the integration of archaeological, magnetometer and a GPR data have provided some interesting results, allowing to overcome the difficulties relative to an extensive GPR prospecting, that could not be performed because of the intrinsic superficial roughness and/or the intensive ploughing activities. The prospecting activities, in particular, have added elements that seem to confirm the main archaeological hypothesis that motivate their performing, as it will be show at the conference. References [1] M. T, Giannotta, G. Leucci, R. Persico, M. Leo Imperiale, The archaeological site of Badia in terra d'Otranto: contribution of the

  6. Multi-data integration of exploration criteria and selection of prospecting targets

    International Nuclear Information System (INIS)

    Dechang, L.; Jingke, Z.; Maorong, S.; Guojuan, W.

    1991-01-01

    In this paper based on the analysis of the exploration criteria for Shengyuan Basin-a uranium ore field, the multi-data integration and information extraction of exploration criteria are carried out on computer and image processing system so that the areas with best combinations of exploration criteria are directly displayed on the screen. Six prospecting targets are selected through the field examination. Shengyuan basin in Jiangxi province is a uranium-producing, Jurassic Cretaceous volcanic-sedimentary basin with an area of about 400 sq km. Its basement consists of Sinian-Cambrian rocks with Caledonian granites intruded. Several uranium deposits, occurrences and anomalies were discovered over the basin region which, therefore, becomes a very important uranium ore field in China

  7. 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.

  8. Virus Capsids as Targeted Nanoscale Delivery Vessels of Photoactive Compounds for Site-Specific Photodynamic Therapy

    Science.gov (United States)

    Cohen, Brian A.

    The research presented in this work details the use of a viral capsid as an addressable delivery vessel of photoactive compounds for use in photodynamic therapy. Photodynamic therapy is a treatment that involves the interaction of light with a photosensitizing molecule to create singlet oxygen, a reactive oxygen species. Overproduction of singlet oxygen in cells can cause oxidative damage leading to cytotoxicity and eventually cell death. Challenges with the current generation of FDA-approved photosensitizers for photodynamic therapy primarily stem from their lack of tissue specificity. This work describes the packaging of photoactive cationic porphyrins inside the MS2 bacteriophage capsid, followed by external modification of the capsid with cancer cell-targeting G-quadruplex DNA aptamers to generate a tumor-specific photosensitizing agent. First, a cationic porphyrin is loaded into the capsids via nucleotide-driven packaging, a process that involves charge interaction between the porphyrin and the RNA inside the capsid. Results show that over 250 porphyrin molecules associate with the RNA within each MS2 capsid. Removal of RNA from the capsid severely inhibits the packaging of the cationic porphyrins. Porphyrin-virus constructs were then shown to photogenerate singlet oxygen, and cytotoxicity in non-targeted photodynamic treatment experiments. Next, each porphyrin-loaded capsid is externally modified with approximately 60 targeting DNA aptamers by employing a heterobifunctional crosslinking agent. The targeting aptamer is known to bind the protein nucleolin, a ubiquitous protein that is overexpressed on the cell surface by many cancer cell types. MCF-7 human breast carcinoma cells and MCF-10A human mammary epithelial cells were selected as an in vitro model for breast cancer and normal tissue, respectively. Fluorescently tagged virus-aptamer constructs are shown to selectively target MCF-7 cells versus MCF-10A cells. Finally, results are shown in which porphyrin

  9. Research plan for integrated ecosystem and pollutant monitoring at remote wilderness study sites

    International Nuclear Information System (INIS)

    Bruns, D.A.; Wiersma, G.B.

    1988-03-01

    This research plan outlines an approach to the measurement of pollutants and ecosystem parameters at remote, high-elevation, wilderness study sites. A multimedia, systems approach to environmental monitoring is emphasized. The primary purpose of the research is to apply and field test a technical report entitled ''Guidelines for measuring the physical, chemical, and biological condition of wilderness ecosystems.'' This document intended to provide Federal Land Managers with information to establish environmental monitoring programs in wilderness areas. To date, this monitoring document has yet to be evaluated under rigorous field conditions at a remote, high-elevation Rocky Mountain site. For the purpose of field testing approaches to monitoring of pollutants and ecosystems in remote, wilderness areas, evaluation criteria were developed. These include useability, cost-effectiveness, data variability, alternative approaches, ecosystems conceptual approach, and quality assurance. Both the Forest Service and INEL environmental monitoring techniques will be evaluated with these criteria. Another objective of this research plan is to obtain an integrated data base on pollutants and ecosystem structure and function at a remote study site. The methods tested in this project will be used to acquire these data from a systems approach. This includes multimedia monitoring of air and water quality, soils, and forest, stream, and lake ecosystems. 71 refs., 1 fig., 9 tabs

  10. Targeting the breeding sites of malaria mosquitoes: biological and physical control of malaria mosquito larvae

    OpenAIRE

    Bukhari, S.T.

    2011-01-01

    Malaria causes an estimated 225 million cases and 781,000 deaths every year. About 85% of the deaths are in children under five years of age. Malaria is caused by the Plasmodium parasite which is transmitted by the Anopheles mosquito vector. Mainly two methods of intervention are used for vector control, i.e. insecticide-treated bed nets and indoor residual spraying. Both involve the use of insecticides and target Anopheles adults indoors. A rising increase in resistance against these insec...

  11. Analysis of landing site attributes for future missions targeting the rim of the lunar South Pole Aitken basin

    Science.gov (United States)

    Koebel, David; Bonerba, Michele; Behrenwaldt, Daniel; Wieser, Matthias; Borowy, Carsten

    2012-11-01

    For the South polar lunar region between -85 and -90° Latitude an updated analyses of the solar illumination and ground station visibility conditions has been performed in the frame of a feasibility study for an ESA Lunar Lander mission. The analyses are based on the refined lunar digital elevation model provided by the Japanese Kaguya/Selene mission, originating from its LASER altimeter instrument. For the South polar region maps of integral solar illumination are presented for a mission epoch in 2016. The analysis modelling was validated with the help of a Kaguya High Definition video. The solar illumination is driving for the power subsystems of any robotic lander craft or manned lunar outpost, in case they rely on conventional photovoltaic power generation with battery buffering of shadowed periods. In addition the visibility of the terrain from a terrestrial ESA ground station was analysed. The results are presented as an integral ground contact duration map, being crucial for the operations of any lunar outpost. Considering these two quality criteria, several possible landing sites for a future lunar mission have been pre-selected. For these sites a detailed analysis of quasi-continuous illumination conditions is presented. This includes magnified maps of the pre-selected areas, showing any location's longest illumination intervals that are allowed to be interrupted by shadows with limited duration only. As a final quality criterion, the terrain topology has been analysed for its impact on the landing trajectory. From a trade-off between the three quality criteria the connecting ridge between the Shackleton and the de Gerlache was determined to provide the most favourable landing site quality. This site is located at 89°28' South, 136°40' West, and 1947 m altitude, and features and integral illumination of 85.7%. With battery energy to sustain shadows of 120 h, total mission duration of 9.37 sidereal months can be guaranteed.

  12. Targeted Deletion of a Plasmodium Site-2 Protease Impairs Life Cycle Progression in the Mammalian Host

    OpenAIRE

    Koussis, K.; Goulielmaki, E.; Chalari, A.; Withers-Martinez, C.; Siden-Kiamos, I.; Matuschewski, K.; Loukeris, T.

    2017-01-01

    Site-2 proteases (S2P) belong to the M50 family of metalloproteases, which typically perform essential roles by mediating activation of membrane?bound transcription factors through regulated intramembrane proteolysis (RIP). Protease-dependent liberation of dormant transcription factors triggers diverse cellular responses, such as sterol regulation, Notch signalling and the unfolded protein response. Plasmodium parasites rely on regulated proteolysis for controlling essential pathways througho...

  13. Integrated wastewater management planning for DOE's Rocky Flats Environmental Technology Site

    International Nuclear Information System (INIS)

    Hopkins, J.; Barthel, J.; Wheeler, M.; Conroy, K.

    1996-01-01

    Rocky Mountain Remediation Services, L.L.C. (RMRS), jointly formed by Morrison Knudsen Corporation and BNFL Inc., provides international experience in the nuclear, environmental, waste management, decontamination and decommissioning (D ampersand D) , and project management industry. The company is currently the environmental restoration, waste management, and D ampersand D subcontractor for Kaiser-Hill Company at the Rocky Flats Environmental Technology Site (RFETS). RMRS offers unique solutions and state-of-the-art technology to assist in resolving the issues that face industries today. RMRS has been working on methods to improve cost savings recognized at RFETS, through application of unique technologies and process engineering. RMRS prepared and is implementing a strategy that focused on identifying an approach to improve cost savings in current wastewater treatment systems and to define a low-cost, safe and versatile wastewater treatment system for the future. Development of this strategy, was targeted by Department of Energy (DOE) Headquarters, DOE Rocky Flats Field Office and Kaiser-Hill as a ''Project Breakthrough'' where old concepts were thrown out the door and the project goals and objectives were developed from the groundup. The objectives of the strategy developed in a project break through session with DOE included lower lifecycle costs, shutdown of one of two buildings at RFETS, Building 374 or Building 774, reduced government capital investment, and support of site closure program goals, identified as the site's Accelerated Site Action Plan (ASAP). The recommended option allows for removal of water treatment functions from Building 374, the existing process wastewater treatment facility. This option affords the lowest capital cost, lowest unit operating cost, lowest technical management risk, greatest support of ASAP phasing and provides the greatest flexibility for design with unforeseen future needs

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Integrative screening approach identifies regulators of polyploidization and targets for acute megakaryocytic leukemia

    Science.gov (United States)

    Wen, Qiang; Goldenson, Benjamin; Silver, Serena J.; Schenone, Monica; Dancik, Vladimir; Huang, Zan; Wang, Ling-Zhi; Lewis, Timothy; An, W. Frank; Li, Xiaoyu; Bray, Mark-Anthony; Thiollier, Clarisse; Diebold, Lauren; Gilles, Laure; Vokes, Martha S.; Moore, Christopher B.; Bliss-Moreau, Meghan; VerPlank, Lynn; Tolliday, Nicola J.; Mishra, Rama; Vemula, Sasidhar; Shi, Jianjian; Wei, Lei; Kapur, Reuben; Lopez, Cécile K.; Gerby, Bastien; Ballerini, Paola; Pflumio, Francoise; Gilliland, D. Gary; Goldberg, Liat; Birger, Yehudit; Izraeli, Shai; Gamis, Alan S.; Smith, Franklin O.; Woods, William G.; Taub, Jeffrey; Scherer, Christina A.; Bradner, James; Goh, Boon-Cher; Mercher, Thomas; Carpenter, Anne E.; Gould, Robert J.; Clemons, Paul A.; Carr, Steven A.; Root, David E.; Schreiber, Stuart L.; Stern, Andrew M.; Crispino, John D.

    2012-01-01

    Summary The mechanism by which cells decide to skip mitosis to become polyploid is largely undefined. Here we used a high-content image-based screen to identify small-molecule probes that induce polyploidization of megakaryocytic leukemia cells and serve as perturbagens to help understand this process. We found that dimethylfasudil (diMF, H-1152P) selectively increased polyploidization, mature cell-surface marker expression, and apoptosis of malignant megakaryocytes. A broadly applicable, highly integrated target identification approach employing proteomic and shRNA screening revealed that a major target of diMF is Aurora A kinase (AURKA), which has not been studied extensively in megakaryocytes. Moreover, we discovered that MLN8237 (Alisertib), a selective inhibitor of AURKA, induced polyploidization and expression of mature megakaryocyte markers in AMKL blasts and displayed potent anti-AMKL activity in vivo. This research provides the rationale to support clinical trials of MLN8237 and other inducers of polyploidization in AMKL. Finally, we have identified five networks of kinases that regulate the switch to polyploidy. PMID:22863010

  16. A Conserved Target Site in HIV-1 Gag RNA is Accessible to Inhibition by Both an HDV Ribozyme and a Short Hairpin RNA

    Directory of Open Access Journals (Sweden)

    Robert J Scarborough

    2014-01-01

    Full Text Available Antisense-based molecules targeting HIV-1 RNA have the potential to be used as part of gene or drug therapy to treat HIV-1 infection. In this study, HIV-1 RNA was screened to identify more conserved and accessible target sites for ribozymes based on the hepatitis delta virus motif. Using a quantitative screen for effects on HIV-1 production, we identified a ribozyme targeting a highly conserved site in the Gag coding sequence with improved inhibitory potential compared to our previously described candidates targeting the overlapping Tat/Rev coding sequence. We also demonstrate that this target site is highly accessible to short hairpin directed RNA interference, suggesting that it may be available for the binding of antisense RNAs with different modes of action. We provide evidence that this target site is structurally conserved in diverse viral strains and that it is sufficiently different from the human transcriptome to limit off-target effects from antisense therapies. We also show that the modified hepatitis delta virus ribozyme is more sensitive to a mismatch in its target site compared to the short hairpin RNA. Overall, our results validate the potential of a new target site in HIV-1 RNA to be used for the development of antisense therapies.

  17. Integrated Management of Borobudur World Heritage Site: A Conflict Resolution Effort

    Directory of Open Access Journals (Sweden)

    Y Sri Susilo

    2015-09-01

    Full Text Available Management of The Borobudur Cultural Landsape, currently, only focus on the Borobudur Temple Compounds, while its hinterland including the surrounding communities are ignored. The management model is fragmented under three ministries, making it difficult for the coordination and synchronization. Management model like this is regarded as inefficient, ineffective, inharmonious and unfair, giving rise to the conflict. Thus, the purpose of this study is to examine the management model of The Borobudur World Heritage Site appropriate to eliminate conflicts and resolve the problems of benefit redistribution among stakeholders. Data collecting in this study is done by observation and survey, followed by braistorming, expert meetings and focus group discussions. The research results showed that the management of the Borobudur World Heritage Site needs to be done in a single management, unified, integrated, holistic, multi-stakeholders (central and local government, business and local communities by way of a shared-responsibility. The governing body of the Borobudur World Heritage Site, according to the contitution, it should be the government organ that is autonomous or semi-autonomous and its primary purpose is preservation.  Based on various inputs and considerations as well as the prevalence in the management of cultural heritage around the world, then the governing body of the Borobudur World Heritage Site are: (1 work unit with the Financial Application Pattern (FAP of Public Service Agency (PSA has a priority status; (2 a regular working unit, status avoided wherever possible; and (3 the State company (in the form of a limited liability company status is not recommended.

  18. Integrated detection, estimation, and guidance in pursuit of a maneuvering target

    Science.gov (United States)

    Dionne, Dany

    The thesis focuses on efficient solutions of non-cooperative pursuit-evasion games with imperfect information on the state of the system. This problem is important in the context of interception of future maneuverable ballistic missiles. However, the theoretical developments are expected to find application to a broad class of hybrid control and estimation problems in industry. The validity of the results is nevertheless confirmed using a benchmark problem in the area of terminal guidance. A specific interception scenario between an incoming target with no information and a single interceptor missile with noisy measurements is analyzed in the form of a linear hybrid system subject to additive abrupt changes. The general research is aimed to achieve improved homing accuracy by integrating ideas from detection theory, state estimation theory and guidance. The results achieved can be summarized as follows. (i) Two novel maneuver detectors are developed to diagnose abrupt changes in a class of hybrid systems (detection and isolation of evasive maneuvers): a new implementation of the GLR detector and the novel adaptive- H0 GLR detector. (ii) Two novel state estimators for target tracking are derived using the novel maneuver detectors. The state estimators employ parameterized family of functions to described possible evasive maneuvers. (iii) A novel adaptive Bayesian multiple model predictor of the ballistic miss is developed which employs semi-Markov models and ideas from detection theory. (iv) A novel integrated estimation and guidance scheme that significantly improves the homing accuracy is also presented. The integrated scheme employs banks of estimators and guidance laws, a maneuver detector, and an on-line governor; the scheme is adaptive with respect to the uncertainty affecting the probability density function of the filtered state. (v) A novel discretization technique for the family of continuous-time, game theoretic, bang-bang guidance laws is introduced. The

  19. Germline transgenic pigs by Sleeping Beauty transposition in porcine zygotes and targeted integration in the pig genome.

    Directory of Open Access Journals (Sweden)

    Wiebke Garrels

    Full Text Available Genetic engineering can expand the utility of pigs for modeling human diseases, and for developing advanced therapeutic approaches. However, the inefficient production of transgenic pigs represents a technological bottleneck. Here, we assessed the hyperactive Sleeping Beauty (SB100X transposon system for enzyme-catalyzed transgene integration into the embryonic porcine genome. The components of the transposon vector system were microinjected as circular plasmids into the cytoplasm of porcine zygotes, resulting in high frequencies of transgenic fetuses and piglets. The transgenic animals showed normal development and persistent reporter gene expression for >12 months. Molecular hallmarks of transposition were confirmed by analysis of 25 genomic insertion sites. We demonstrate germ-line transmission, segregation of individual transposons, and continued, copy number-dependent transgene expression in F1-offspring. In addition, we demonstrate target-selected gene insertion into transposon-tagged genomic loci by Cre-loxP-based cassette exchange in somatic cells followed by nuclear transfer. Transposase-catalyzed transgenesis in a large mammalian species expands the arsenal of transgenic technologies for use in domestic animals and will facilitate the development of large animal models for human diseases.

  20. How to target inter-regional phase synchronization with dual-site Transcranial Alternating Current Stimulation

    DEFF Research Database (Denmark)

    Saturnino, Guilherme Bicalho; Madsen, Kristoffer Hougaard; Siebner, Hartwig Roman

    2017-01-01

    oscillations in two connected cortical areas. While the frequency of ds-TACS is matched, the phase of stimulation is either identical (in-phase stimulation) or opposite (anti-phase stimulation) in the two cortical target areas. In-phase stimulation is thought to synchronize the endogenous oscillations...... and hereby to improve behavioral performance. Conversely, anti-phase stimulation is thought to desynchronize neural oscillations in the two areas, which is expected to decrease performance. Critically, in- and anti-phase ds-TACS should only differ with respect to temporal phase, while all other stimulation...... unambiguously the causal contribution of phase coupling to specific cognitive processes in the human brain....

  1. Meta-Analysis of DNA Tumor-Viral Integration Site Selection Indicates a Role for Repeats, Gene Expression and Epigenetics

    Directory of Open Access Journals (Sweden)

    Janet M. Doolittle-Hall

    2015-11-01

    Full Text Available Oncoviruses cause tremendous global cancer burden. For several DNA tumor viruses, human genome integration is consistently associated with cancer development. However, genomic features associated with tumor viral integration are poorly understood. We sought to define genomic determinants for 1897 loci prone to hosting human papillomavirus (HPV, hepatitis B virus (HBV or Merkel cell polyomavirus (MCPyV. These were compared to HIV, whose enzyme-mediated integration is well understood. A comprehensive catalog of integration sites was constructed from the literature and experimentally-determined HPV integration sites. Features were scored in eight categories (genes, expression, open chromatin, histone modifications, methylation, protein binding, chromatin segmentation and repeats and compared to random loci. Random forest models determined loci classification and feature selection. HPV and HBV integrants were not fragile site associated. MCPyV preferred integration near sensory perception genes. Unique signatures of integration-associated predictive genomic features were detected. Importantly, repeats, actively-transcribed regions and histone modifications were common tumor viral integration signatures.

  2. The intensity of non-target site mechanisms influences the level of resistance of sourgrass to glyphosate

    Directory of Open Access Journals (Sweden)

    Flávia Regina da Costa

    2014-02-01

    Full Text Available Non-target site mechanisms are involved in the resistance of sourgrass (Digitaria insularis to glyphosate. Studies on the 14C-glyphosate absorption and translocation as well as the detection of glyphosate and its metabolites in sourgrass plants were carried out under controlled conditions to investigate if the differential response of resistant sourgrass biotypes (R1 and R2 is derived from the intensity of non-target site mechanisms involved in the resistance to glyphosate. Different pattern of absorption was observed between S (susceptible and R2 from 12 up to 48 hours after treatment with glyphosate (HAT, and between S and R1 just at 12 HAT. The initial difference in glyphosate absorption among the biotypes did not maintained at 96 HAT and afterwards. Smaller amount of herbicide left the treated leaf into the rest of shoot and roots in R2 (25% than in S (58% and R1 (52%. In addition, slight difference in glyphosate translocation was observed between S and R1. We found high percentage (81% of glyphosate in the S biotype up to 168 HAT, while just 44% and 2% of glyphosate was recovered from R1 and R2 plant tissues. In addition, high percentage of glyphosate metabolites was found in R2 (98% and R1 (56% biotypes, while a very low percentage (11% was found in the S biotype. As previous studies indicated resistant factors of 3.5 and 5.6 for R1 and R2, respectively, we conclude that the differential response of sourgrass biotypes is derived from the intensity of the non-target site mechanisms involved in the resistance to glyphosate.

  3. Genetic variation in IL-16 miRNA target site and time to prostate cancer diagnosis in African American men

    Science.gov (United States)

    Hughes, Lucinda; Ruth, Karen; Rebbeck, Timothy R.; Giri, Veda N.

    2013-01-01

    Background Men with a family history of prostate cancer and African American men are at high risk for prostate cancer and in need of personalized risk estimates to inform screening decisions. This study evaluated genetic variants in genes encoding microRNA (miRNA) binding sites for informing of time to prostate cancer diagnosis among ethnically-diverse, high-risk men undergoing prostate cancer screening. Methods The Prostate Cancer Risk Assessment Program (PRAP) is a longitudinal screening program for high-risk men. Eligibility includes men ages 35-69 with a family history of prostate cancer or African descent. Participants with ≥ 1 follow-up visit were included in the analyses (n=477). Genetic variants in regions encoding miRNA binding sites in four target genes (ALOX15, IL-16, IL-18, and RAF1) previously implicated in prostate cancer development were evaluated. Genotyping methods included Taqman® SNP Genotyping Assay (Applied Biosystems) or pyrosequencing. Cox models were used to assess time to prostate cancer diagnosis by risk genotype. Results Among 256 African Americans with ≥ one follow-up visit, the TT genotype at rs1131445 in IL-16 was significantly associated with earlier time to prostate cancer diagnosis vs. the CC/CT genotypes (p=0.013), with a suggestive association after correction for false-discovery (p=0.065). Hazard ratio after controlling for age and PSA for TT vs. CC/CT among African Americans was 3.0 (95% CI 1.26-7.12). No association to time to diagnosis was detected among Caucasians by IL-16 genotype. No association to time to prostate cancer diagnosis was found for the other miRNA target genotypes. Conclusions Genetic variation in IL-16 encoding miRNA target site may be informative of time to prostate cancer diagnosis among African American men enrolled in prostate cancer risk assessment, which may inform individualized prostate cancer screening strategies in the future. PMID:24061634

  4. EFFECTIVNESS OF TARGET ANTIMICROBIAL THERAPY OF SEVERE CHRONIC PERIODONTITIS PART I: REDUCTION OF GINGIVAL INFLAMATION AND ACTIVE PERIODONTAL DISEASE SITES

    Directory of Open Access Journals (Sweden)

    Kamen Kotsilkov

    2010-10-01

    Full Text Available The correlation between recurrent bleeding on probing and the progression of periodontal destruction is suggested in many studies. One of the main goals of the periodontal treatment is the achievement of good control of the gingival inflammation and the reduction of the active periodontal sites.Aim: Evaluation of the effectiveness of treatment of severe chronic periodontitis with additional target antibiotic administration in comparison with the therapy with adjunctive antimicrobial combination amoxicillin + metronidazole and conventional mechanical periodontal treatment regarding the achieved control of the gingival inflammation and BoP.Results: Significant reduction of the gingival bleeding and the BoP is achieved in all groups. In the group with target antibiotic administration the final mean values of the GB (gingival bleeding and BoP (bleeding on probing are the lowest and could suggest a low risk for progression of the periodontal disease.

  5. Integrated Closure and Monitoring Plan for the Area 3 and Area 5 Radioactive Waste Management Sites at the Nevada Test Site

    Energy Technology Data Exchange (ETDEWEB)

    S. E. Rawlinson

    2001-09-01

    Bechtel Nevada (BN) manages two low-level Radioactive Waste Management Sites (RWMSs) (one site is in Area 3 and the other is in Area 5) at the Nevada Test Site (NTS) for the U.S. Department of Energy's (DOE's) National Nuclear Security Administration Nevada Operations Office (NNSA/NV). The current DOE Order governing management of radioactive waste is 435.1. Associated with DOE Order 435.1 is a Manual (DOE M 435.1-1) and Guidance (DOE G 435.1-1). The Manual and Guidance specify that preliminary closure and monitoring plans for a low-level waste (LLW) management facility be developed and initially submitted with the Performance Assessment (PA) and Composite Analysis (CA) for that facility. The Manual and Guidance, and the Disposal Authorization Statement (DAS) issued for the Area 3 RWMS further specify that the preliminary closure and monitoring plans be updated within one year following issuance of a DAS. This Integrated Closure and Monitoring Plan (ICMP) fulfills both requirements. Additional updates will be conducted every third year hereafter. This document is an integrated plan for closing and monitoring both RWMSs, and is based on guidance issued in 1999 by the DOE for developing closure plans. The plan does not follow the format suggested by the DOE guidance in order to better accommodate differences between the two RWMSs, especially in terms of operations and site characteristics. The modification reduces redundancy and provides a smoother progression of the discussion. The closure and monitoring plans were integrated because much of the information that would be included in individual plans is the same, and integration provides efficient presentation and program management. The ICMP identifies the regulatory requirements, describes the disposal sites and the physical environment where they are located, and defines the approach and schedule for both closing and monitoring the sites.

  6. Isolation of recombinant phage antibodies targeting the hemagglutinin cleavage site of highly pathogenic avian influenza virus.

    Directory of Open Access Journals (Sweden)

    Jinhua Dong

    Full Text Available Highly pathogenic avian influenza (HPAI H5N1 viruses, which have emerged in poultry and other wildlife worldwide, contain a characteristic multi-basic cleavage site (CS in the hemagglutinin protein (HA. Because this arginine-rich CS is unique among influenza virus subtypes, antibodies against this site have the potential to specifically diagnose pathogenic H5N1. By immunizing mice with the CS peptide and screening a phage display library, we isolated four antibody Fab fragment clones that specifically bind the antigen peptide and several HPAI H5N1 HA proteins in different clades. The soluble Fab fragments expressed in Escherichia coli bound the CS peptide and the H5N1 HA protein with nanomolar affinity. In an immunofluorescence assay, these Fab fragments stained cells infected with HPAI H5N1 but not those infected with a less virulent strain. Lastly, all the Fab clones could detect the CS peptide and H5N1 HA protein by open sandwich ELISA. Thus, these recombinant Fab fragments will be useful novel reagents for the rapid and specific detection of HPAI H5N1 virus.

  7. Effect of co-administration of probiotics with polysaccharide based colon targeted delivery systems to optimize site specific drug release.

    Science.gov (United States)

    Prudhviraj, G; Vaidya, Yogyata; Singh, Sachin Kumar; Yadav, Ankit Kumar; Kaur, Puneet; Gulati, Monica; Gowthamarajan, K

    2015-11-01

    Significant clinical success of colon targeted dosage forms has been limited by their inappropriate release profile at the target site. Their failure to release the drug completely in the colon may be attributed to changes in the colonic milieu because of pathological state, drug effect and psychological stress accompanying the diseased state or, a combination of these. Alteration in normal colonic pH and bacterial picture leads to incomplete release of drug from the designed delivery system. We report the effectiveness of a targeted delivery system wherein the constant replenishment of the colonic microbiota is achieved by concomitant administration of probiotics along with the polysaccharide based drug delivery system. Guar gum coated spheroids of sulfasalazine were prepared. In the dissolution studies, these spheroids showed markedly higher release in the simulated colonic fluid. In vivo experiments conducted in rats clearly demonstrated the therapeutic advantage of co-administration of probiotics with guar gum coated spheroids. Our results suggest that concomitant use of probiotics along with the polysaccharide based delivery systems can be a simple strategy to achieve satisfactory colon targeting of drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Integrating Biodiversity and Ecosystem Services in the Post-2015 Development Agenda: Goal Structure, Target Areas and Means of Implementation

    Directory of Open Access Journals (Sweden)

    Paul L. Lucas

    2013-12-01

    Full Text Available The United Nations’ discussions on defining a new set of post-2015 development goals focus on poverty eradication and sustainable development. Biodiversity and ecosystem services are essential for poverty eradication, which is also one of the foundations of the Strategic Plan for Biodiversity of the Convention on Biological Diversity (CBD. Based on an assessment of current proposals of goals and targets, and a quantitative pathway analysis to meet long term biodiversity and food security goals, this paper discusses how biodiversity and ecosystem services can be integrated into a broad set of goals and targets, and concludes with relevant target areas and means of implementation for which specific targets need to be defined. Furthermore, it responds to the call of the CBD to consider the Strategic Plan for Biodiversity and the related Aichi biodiversity targets in the post-2015 development agenda. The paper’s analysis identifies three overlapping but also supplemental ways to integrate biodiversity and ecosystem services in the post-2015 agenda: integrated goals, goals addressing earth system functioning and goals addressing environmental limits. It further concludes seven target areas to be included under the goals to address biodiversity and ecosystem services in the context of food and agriculture: access to food, demand for agricultural products, sustainable intensification, ecosystem fragmentation, protected areas, essential ecosystem services and genetic diversity. The Strategic Plan for Biodiversity provides a good basis for integrating biodiversity and ecosystem services in the post-2015 development agenda. Many Aichi targets address the proposed target areas and the means of implementation discussed, while they need to be complemented with targets that specifically address human well-being, as well as institutions and governance.

  9. CPP-603 Underwater Fuel Storage Facility Site Integrated Stabilization Management Plan (SISMP), Volume I

    International Nuclear Information System (INIS)

    Denney, R.D.

    1995-10-01

    The CPP-603 Underwater Fuel Storage Facility (UFSF) Site Integrated Stabilization Management Plan (SISMP) has been constructed to describe the activities required for the relocation of spent nuclear fuel (SNF) from the CPP-603 facility. These activities are the only Idaho National Engineering Laboratory (INEL) actions identified in the Implementation Plan developed to meet the requirements of the Defense Nuclear Facilities Safety Board (DNFSB) Recommendation 94-1 to the Secretary of Energy regarding an improved schedule for remediation in the Defense Nuclear Facilities Complex. As described in the DNFSB Recommendation 94-1 Implementation Plan, issued February 28, 1995, an INEL Spent Nuclear Fuel Management Plan is currently under development to direct the placement of SNF currently in existing INEL facilities into interim storage, and to address the coordination of intrasite SNF movements with new receipts and intersite transfers that were identified in the DOE SNF Programmatic and INEL Environmental Restoration and Waste Management Environmental Impact Statement Record, of Decision. This SISMP will be a subset of the INEL Spent Nuclear Fuel Management Plan and the activities described are being coordinated with other INEL SNF management activities. The CPP-603 relocation activities have been assigned a high priority so that established milestones will be meet, but there will be some cases where other activities will take precedence in utilization of available resources. The Draft INEL Site Integrated Stabilization Management Plan (SISMP), INEL-94/0279, Draft Rev. 2, dated March 10, 1995, is being superseded by the INEL Spent Nuclear Fuel Management Plan and this CPP-603 specific SISMP

  10. Integrating intrusive and nonintrusive characterization methods to achieve a conceptual site model for the SLDA FUSRAP site

    International Nuclear Information System (INIS)

    Durham, L.A.; Peterson, J.M.; Frothingham, D.G.; Frederick, W.T.; Lenart, W.

    2008-01-01

    The US Army Corps of Engineers (USACE) is addressing radiological contamination following Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) requirements at the Shallow Land Disposal Area (SLDA) site, which is a radiologically contaminated property that is part of the Formerly utilized Sites Remedial Action Program (FUSRAP). The SLDA is an 18-hectare (44-acre) site in Parks township, Armstrong County, Pennsylvania, about 37 kilometers (23 miles) east-northeast of Pittsburgh. According to historical record, radioactive wastes were disposed of at the SLDA in a series of trenches by the Nuclear Materials and Equipment Company (NUMEC) in the 1960s. The wastes originated from the nearby Apollo nuclear fuel fabrication facility, which began operations under NUMEC in the late 1950s and fabricated enriched uranium into naval reactor fuel elements. It is believed that the waste materials were buried in a series of pits constructed adjacent to one another in accordance with an Atomic Energy Commission (AEC) regulation that has since been rescinded. A CERCLA remedial investigation/feasibility study (RI/FS) process was completed for the SLDA site, and the results of the human health risk assessment indicated that the radiologically contaminated wastes could pose a risk to human health in the future. There are no historical records that provide the exact location of these pits. However, based on geophysical survey results conducted in the 1980s, these pits were defined by geophysical anomalies and were depicted on historical site drawings as trenches. At the SLDA site, a combination of investigative methods and tools was used in the RI/FS and site characterization activities. The SLDA site provides an excellent example of how historical documents and data, historical aerial photo analysis, physical sampling, and nonintrusive geophysical and gamma walkover surveys were used in combination to reduce the uncertainty in the location of the trenches. The

  11. Site selection and directional models of deserts used for ERBE validation targets

    Science.gov (United States)

    Staylor, W. F.

    1986-01-01

    Broadband shortwave and longwave radiance measurements obtained from the Nimbus 7 Earth Radiation Budget scanner were used to develop reflectance and emittance models for the Sahara, Gibson, and Saudi Deserts. These deserts will serve as in-flight validation targets for the Earth Radiation Budget Experiment being flown on the Earth Radiation Budget Satellite and two National Oceanic and Atmospheric Administration polar satellites. The directional reflectance model derived for the deserts was a function of the sum and product of the cosines of the solar and viewing zenith angles, and thus reciprocity existed between these zenith angles. The emittance model was related by a power law of the cosine of the viewing zenith angle.

  12. Association of impulsivity and polymorphic microRNA-641 target sites in the SNAP-25 gene.

    Directory of Open Access Journals (Sweden)

    Nóra Németh

    Full Text Available Impulsivity is a personality trait of high impact and is connected with several types of maladaptive behavior and psychiatric diseases, such as attention deficit hyperactivity disorder, alcohol and drug abuse, as well as pathological gambling and mood disorders. Polymorphic variants of the SNAP-25 gene emerged as putative genetic components of impulsivity, as SNAP-25 protein plays an important role in the central nervous system, and its SNPs are associated with several psychiatric disorders. In this study we aimed to investigate if polymorphisms in the regulatory regions of the SNAP-25 gene are in association with normal variability of impulsivity. Genotypes and haplotypes of two polymorphisms in the promoter (rs6077690 and rs6039769 and two SNPs in the 3' UTR (rs3746544 and rs1051312 of the SNAP-25 gene were determined in a healthy Hungarian population (N = 901 using PCR-RFLP or real-time PCR in combination with sequence specific probes. Significant association was found between the T-T 3' UTR haplotype and impulsivity, whereas no association could be detected with genotypes or haplotypes of the promoter loci. According to sequence alignment, the polymorphisms in the 3' UTR of the gene alter the binding site of microRNA-641, which was analyzed by luciferase reporter system. It was observed that haplotypes altering one or two nucleotides in the binding site of the seed region of microRNA-641 significantly increased the amount of generated protein in vitro. These findings support the role of polymorphic SNAP-25 variants both at psychogenetic and molecular biological levels.

  13. Screening of groundwater remedial alternatives for brownfield sites: a comprehensive method integrated MCDA with numerical simulation.

    Science.gov (United States)

    Li, Wei; Zhang, Min; Wang, Mingyu; Han, Zhantao; Liu, Jiankai; Chen, Zhezhou; Liu, Bo; Yan, Yan; Liu, Zhu

    2018-06-01

    Brownfield sites pollution and remediation is an urgent environmental issue worldwide. The screening and assessment of remedial alternatives is especially complex owing to its multiple criteria that involves technique, economy, and policy. To help the decision-makers selecting the remedial alternatives efficiently, the criteria framework conducted by the U.S. EPA is improved and a comprehensive method that integrates multiple criteria decision analysis (MCDA) with numerical simulation is conducted in this paper. The criteria framework is modified and classified into three categories: qualitative, semi-quantitative, and quantitative criteria, MCDA method, AHP-PROMETHEE (analytical hierarchy process-preference ranking organization method for enrichment evaluation) is used to determine the priority ranking of the remedial alternatives and the solute transport simulation is conducted to assess the remedial efficiency. A case study was present to demonstrate the screening method in a brownfield site in Cangzhou, northern China. The results show that the systematic method provides a reliable way to quantify the priority of the remedial alternatives.

  14. Integrated environmental risk assessment for petroleum-contaminated sites - a North American case study

    International Nuclear Information System (INIS)

    Chen, Z.; Huang, G.H.; Chakma, A.

    1998-01-01

    In this study, an integrated risk assessment approach is proposed for evaluating environmental risks derived from petroleum-contaminated sites. The proposed approach is composed of (i) a hydrocarbon spill screening model (HSSM) which is used for simulating immiscible flow of released hydrocarbons in vadose zone, formation of lens in capillary fringe, dissolution of pollutants at water table, and transport of the pollutants to receptors, and (ii) a fuzzy relation analysis (FRA) model which is developed for comprehensively evaluating risks caused by a number of pollutants with different impact characteristics, based on the HSSM results. This hybrid HSSM-FRA approach was applied to a case study for a petroleum-contaminated site in western Canada, where soil and groundwater was contaminated by industrial wastes containing benzene, toluene, ethylbenzene and xylenes (BTEXs). The results suggest that the HSSM-FRA can provide insight into the potential risk to the receptor of concern downward the aquifer and can serve as a basis for further remediation-related decision analysis. (author)

  15. Analysis of a fuel cell on-site integrated energy system for a residential complex

    Science.gov (United States)

    Simons, S. N.; Maag, W. L.

    1979-01-01

    The energy use and costs of the on-site integrated energy system (OS/IES) which provides electric power from an on-site power plant and recovers heat that would normally be rejected to the environment is compared to a conventional system purchasing electricity from a utility and a phosphoric acid fuel cell powered system. The analysis showed that for a 500-unit apartment complex a fuel OS/IES would be about 10% more energy conservative in terms of total coal consumption than a diesel OS/IES system or a conventional system. The fuel cell OS/IES capital costs could be 30 to 55% greater than the diesel OS/IES capital costs for the same life cycle costs. The life cycle cost of a fuel cell OS/IES would be lower than that for a conventional system as long as the cost of electricity is greater than $0.05 to $0.065/kWh. An analysis of several parametric combinations of fuel cell power plant and state-of-art energy recovery systems and annual fuel requirement calculations for four locations were made. It was shown that OS/IES component choices are a major factor in fuel consumption, with the least efficient system using 25% more fuel than the most efficient. Central air conditioning and heat pumps result in minimum fuel consumption while individual air conditioning units increase it, and in general the fuel cell of highest electrical efficiency has the lowest fuel consumption.

  16. Development of Next-generation Technology for Integrated Site Characterization of Deep Geological Repositories

    International Nuclear Information System (INIS)

    Osawa, H.; Umeki, H.; Ota, K.; Hama, K.; Sawada, A.; Takeuchi, S.; Semba, T.; Takase, H.; McKinley, I.G.

    2009-01-01

    As site investigation proceeds and information obtained on geological environments increases, the characterization plan has to be iteratively reviewed and modified to reflect improved understanding. Such modification would also be needed when changes occur in technical or socio-political boundary conditions. JAEA teams involved in implementation of URL projects have used a geo-synthesis data flow diagram to integrate a huge amount of practical experience in order to carry out such management functions. However, much of this experience was gained in the past, when it was possible for staff to learn by taking leading roles in novel, complex and important projects and learn by successes - and mistakes - under boundary conditions that were much more casual than they are at present. It is necessary to transfer such tacit knowledge to implementing and regulatory organizations in a practical manner before it is lost with the retirement of senior staff. An option being examined involves application of advanced technology, termed the Information Synthesis and Interpretation System (ISIS), to capture experience using Knowledge Engineering methods. This is being tested for practical applicability in an exercise involving stepwise 'optimization' of a site characterization plan. (authors)

  17. OC ToGo: bed site image integration into OpenClinica with mobile devices

    Science.gov (United States)

    Haak, Daniel; Gehlen, Johan; Jonas, Stephan; Deserno, Thomas M.

    2014-03-01

    Imaging and image-based measurements nowadays play an essential role in controlled clinical trials, but electronic data capture (EDC) systems insufficiently support integration of captured images by mobile devices (e.g. smartphones and tablets). The web application OpenClinica has established as one of the world's leading EDC systems and is used to collect, manage and store data of clinical trials in electronic case report forms (eCRFs). In this paper, we present a mobile application for instantaneous integration of images into OpenClinica directly during examination on patient's bed site. The communication between the Android application and OpenClinica is based on the simple object access protocol (SOAP) and representational state transfer (REST) web services for metadata, and secure file transfer protocol (SFTP) for image transfer, respectively. OpenClinica's web services are used to query context information (e.g. existing studies, events and subjects) and to import data into the eCRF, as well as export of eCRF metadata and structural information. A stable image transfer is ensured and progress information (e.g. remaining time) visualized to the user. The workflow is demonstrated for a European multi-center registry, where patients with calciphylaxis disease are included. Our approach improves the EDC workflow, saves time, and reduces costs. Furthermore, data privacy is enhanced, since storage of private health data on the imaging devices becomes obsolete.

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

    Science.gov (United States)

    Housh, Mashor; Ohar, Ziv

    2017-03-01

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

  19. Integral Public Activities as a Support to the Site Selection Process for LILW Repository

    International Nuclear Information System (INIS)

    Zeleznik, N.; Kralj, M.

    2008-01-01

    The first site selection process for low and intermediate level radioactive waste (LILW) repository took place between 1990 and 1993 in Slovenia was stopped unsuccessfully with very strong public opposition at local level, followed by political withdrawal on national level. As one of the consequences ARAO started to develop new approach to the site selection based also on the findings from sociology, psychology and other human sciences. The recommendations on public involvement and transparency were so strong that ARAO started with first limited public relation (PR) activities which later grew to the PR process which supports all technical activities in ARAO. Presently the PR process covers communication, information and research activities and assures careful planning, prompt responds and involvement of the highest responsible persons at ARAO. Integral public relation activities are divided in several parts. Majority of activities support the on-going site selection process where activities are presently focused on functioning of local partnerships developed as a basic communication tool to involve as much citizens and public as possible on local level. Presently two local partnerships are working in Krsko and Brezice community with clear role to enhance public involvement according to Aarchus convention. Each of the partnerships is organized in a specific way adjusted to the local needs. Communication activities are organized also for different other projects and are preparing the necessary basis for the work with different groups of stake holders and in different situations. As a foundation very broad information material, such as books, leaflets, reports, magazines, video cassettes, CD and DVD on the radioactive waste management is prepared and used for different purposes. We also try to be proactive with web pages and have a well organized visitors' center. Improvement of public relation process is achieved through constant survey and feed-back information

  20. High-definition mapping of retroviral integration sites defines the fate of allogeneic T cells after donor lymphocyte infusion.

    Directory of Open Access Journals (Sweden)

    Claudia Cattoglio

    2010-12-01

    Full Text Available The infusion of donor lymphocytes transduced with a retroviral vector expressing the HSV-TK suicide gene in patients undergoing hematopoietic stem cell transplantation for leukemia/lymphoma promotes immune reconstitution and prevents infections and graft-versus-host disease. Analysis of the clonal dynamics of genetically modified lymphocytes in vivo is of crucial importance to understand the potential genotoxic risk of this therapeutic approach. We used linear amplification-mediated PCR and pyrosequencing to build a genome-wide, high-definition map of retroviral integration sites in the genome of peripheral blood T cells from two different donors and used gene expression profiling and bioinformatics to associate integration clusters to transcriptional activity and to genetic and epigenetic features of the T cell genome. Comparison with matched random controls and with integrations obtained from CD34(+ hematopoietic stem/progenitor cells showed that integration clusters occur within chromatin regions bearing epigenetic marks associated with active promoters and regulatory elements in a cell-specific fashion. Analysis of integration sites in T cells obtained ex vivo two months after infusion showed no evidence of integration-related clonal expansion or dominance, but rather loss of cells harboring integration events interfering with RNA post-transcriptional processing. The study shows that high-definition maps of retroviral integration sites are a powerful tool to analyze the fate of genetically modified T cells in patients and the biological consequences of retroviral transduction.

  1. Different integration site structures between L1 protein-mediated retrotransposition in cis and retrotransposition in trans

    Directory of Open Access Journals (Sweden)

    Kojima Kenji K

    2010-07-01

    Full Text Available Abstract Background Long interspersed nuclear element-1 (LINE-1 or L1 is a dominant repetitive sequence in the human genome. Besides mediating its own retrotransposition, L1 can mobilize Alu and messenger RNA (mRNA in trans, and probably also SVA and non-coding RNA. The structures of L1 copies and trans-mobilized retrocopies are variable and can be classified into three categories: full-length; 5'-truncated; and 5'-inverted insertions. These structures may be generated by different 5' integration mechanisms. Results In this study, a method to correctly characterize insertions with short target site duplications (TSDs is developed and extranucleotides, TSDs and microhomologies (MHs at junctions were analysed for the three types of insertions. Only 5'-truncated L1 insertions were found to be associated with short TSDs. Both full-length and 5'-truncated retrotransposed sequences in trans, including Alu, SVA and mRNA retrocopies and also full-length and 5'-inverted L1, were not associated with short TSDs, indicating the difference of 5' attachment between retrotransposition in cis and retrotransposition in trans. Target sequence analysis suggested that short TSDs were generated in an L1 endonuclease-dependent manner. The MHs were longer for 5'-inverted L1 than for 5'-truncated L1, indicating less dependence on annealing in 5'-truncated L1 insertions. Conclusions The results suggest that insertions flanked by short TSDs occur more often coupled with the insertion of 5'-truncated L1 than with those of other types of insertions in vivo. The method used in this study can be used to characterize elements without any apparent boundary structures.

  2. Integration of bio-inspired, control-based visual and olfactory data for the detection of an elusive target

    Science.gov (United States)

    Duong, Tuan A.; Duong, Nghi; Le, Duong

    2017-01-01

    In this paper, we present an integration technique using a bio-inspired, control-based visual and olfactory receptor system to search for elusive targets in practical environments where the targets cannot be seen obviously by either sensory data. Bio-inspired Visual System is based on a modeling of extended visual pathway which consists of saccadic eye movements and visual pathway (vertebrate retina, lateral geniculate nucleus and visual cortex) to enable powerful target detections of noisy, partial, incomplete visual data. Olfactory receptor algorithm, namely spatial invariant independent component analysis, that was developed based on data of old factory receptor-electronic nose (enose) of Caltech, is adopted to enable the odorant target detection in an unknown environment. The integration of two systems is a vital approach and sets up a cornerstone for effective and low-cost of miniaturized UAVs or fly robots for future DOD and NASA missions, as well as for security systems in Internet of Things environments.

  3. An integrated study of spatial multicriteria analysis and mathematical modelling for managed aquifer recharge site suitability mapping and site ranking at Northern Gaza coastal aquifer.

    Science.gov (United States)

    Rahman, Mohammad Azizur; Rusteberg, Bernd; Uddin, Mohammad Salah; Lutz, Annegret; Saada, Muath Abu; Sauter, Martin

    2013-07-30

    This paper describes an integrated approach of site suitability mapping and ranking of the most suitable sites, for the implementation of Managed Aquifer Recharge (MAR) projects, using spatial multicriteria decision analysis (SMCDA) techniques and mathematical modelling. The SMCDA procedure contains constraint mapping, site suitability analysis with criteria standardization and weighting, criteria overlay by analytical hierarchy process (AHP) combined with weighted linear combination (WLC) and ordered weighted averaging (OWA), and sensitivity analysis. The hydrogeological impacts of the selected most suitable sites were quantified by using groundwater flow and transport modelling techniques. Finally, ranking of the selected sites was done with the WLC method. The integrated approach is demonstrated by a case study in the coastal aquifer of North Gaza. Constraint mapping shows that 50% of the total study area is suitable for MAR implementation. About 25% of the total area is "very good" and 25% percent is "good" for MAR, according to the site suitability analysis. Six locations were selected and ranked against six representative decision criteria. Long term (year 2003 to year 2040) groundwater flow and transport simulations were performed to quantify the selected criteria under MAR project operation conditions at the selected sites. Finally, the suitability mapping and hydrogeological investigation recommends that the location of the existing infiltration ponds, constructed near the planned North Gaza Wastewater Treatment Plant (NGWWTP) is most suitable for MAR project implementation. This paper concludes that mathematical modelling should be combined with the SMCDA technique in order to select the best location for MAR project implementation. Besides MAR project implementation, the generalised approach can be applicable for any other water resources development project that deals with site selection and implementation. Copyright © 2013 Elsevier Ltd. All rights

  4. Early and late HIV-1 membrane fusion events are impaired by sphinganine lipidated peptides that target the fusion site.

    Science.gov (United States)

    Klug, Yoel A; Ashkenazi, Avraham; Viard, Mathias; Porat, Ziv; Blumenthal, Robert; Shai, Yechiel

    2014-07-15

    Lipid-conjugated peptides have advanced the understanding of membrane protein functions and the roles of lipids in the membrane milieu. These lipopeptides modulate various biological systems such as viral fusion. A single function has been suggested for the lipid, binding to the membrane and thus elevating the local concentration of the peptide at the target site. In the present paper, we challenged this argument by exploring in-depth the antiviral mechanism of lipopeptides, which comprise sphinganine, the lipid backbone of DHSM (dihydrosphingomyelin), and an HIV-1 envelope-derived peptide. Surprisingly, we discovered a partnership between the lipid and the peptide that impaired early membrane fusion events by reducing CD4 receptor lateral diffusion and HIV-1 fusion peptide-mediated lipid mixing. Moreover, only the joint function of sphinganine and its conjugate peptide disrupted HIV-1 fusion protein assembly and folding at the later fusion steps. Via imaging techniques we revealed for the first time the direct localization of these lipopeptides to the virus-cell and cell-cell contact sites. Overall, the findings of the present study may suggest lipid-protein interactions in various biological systems and may help uncover a role for elevated DHSM in HIV-1 and its target cell membranes.

  5. Target-site mutations conferring resistance to glyphosate in feathertop Rhodes grass (Chloris virgata) populations in Australia.

    Science.gov (United States)

    Ngo, The D; Krishnan, Mahima; Boutsalis, Peter; Gill, Gurjeet; Preston, Christopher

    2018-05-01

    Chloris virgata is a warm-season, C 4 , annual grass weed affecting field crops in northern Australia that has become an emerging weed in southern Australia. Four populations with suspected resistance to glyphosate were collected in South Australia, Queensland and New South Wales, Australia, and compared with one susceptible (S) population to confirm glyphosate resistance and elucidate possible mechanisms of resistance. Based on the rate of glyphosate required to kill 50% of treated plants (LD 50 ), glyphosate resistance (GR) was confirmed in four populations of C. virgata (V12, V14.2, V14.16 and V15). GR plants were 2-9.7-fold more resistant and accumulated less shikimate after glyphosate treatment than S plants. GR and S plants did not differ in glyphosate absorption and translocation. Target-site EPSPS mutations corresponding to Pro-106-Leu (V14.2) and Pro-106-Ser (V15, V14.16 and V12) substitutions were found in GR populations. The population with Pro-106-Leu substitution was 2.9-4.9-fold more resistant than the three other populations with Pro-106-Ser substitution. This report confirms glyphosate resistance in C. virgata and shows that target-site EPSPS mutations confer resistance to glyphosate in this species. The evolution of glyphosate resistance in C. virgata highlights the need to identify alternative control tactics. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  6. Targeted Deletion of a Plasmodium Site-2 Protease Impairs Life Cycle Progression in the Mammalian Host.

    Science.gov (United States)

    Koussis, Konstantinos; Goulielmaki, Evi; Chalari, Anna; Withers-Martinez, Chrislaine; Siden-Kiamos, Inga; Matuschewski, Kai; Loukeris, Thanasis G

    2017-01-01

    Site-2 proteases (S2P) belong to the M50 family of metalloproteases, which typically perform essential roles by mediating activation of membrane-bound transcription factors through regulated intramembrane proteolysis (RIP). Protease-dependent liberation of dormant transcription factors triggers diverse cellular responses, such as sterol regulation, Notch signalling and the unfolded protein response. Plasmodium parasites rely on regulated proteolysis for controlling essential pathways throughout the life cycle. In this study we examine the Plasmodium-encoded S2P in a murine malaria model and show that it is expressed in all stages of Plasmodium development. Localisation studies by endogenous gene tagging revealed that in all invasive stages the protein is in close proximity to the nucleus. Ablation of PbS2P by reverse genetics leads to reduced growth rates during liver and blood infection and, hence, virulence attenuation. Strikingly, absence of PbS2P was compatible with parasite life cycle progression in the mosquito and mammalian hosts under physiological conditions, suggesting redundant or dispensable roles in vivo.

  7. Targeted Deletion of a Plasmodium Site-2 Protease Impairs Life Cycle Progression in the Mammalian Host.

    Directory of Open Access Journals (Sweden)

    Konstantinos Koussis

    Full Text Available Site-2 proteases (S2P belong to the M50 family of metalloproteases, which typically perform essential roles by mediating activation of membrane-bound transcription factors through regulated intramembrane proteolysis (RIP. Protease-dependent liberation of dormant transcription factors triggers diverse cellular responses, such as sterol regulation, Notch signalling and the unfolded protein response. Plasmodium parasites rely on regulated proteolysis for controlling essential pathways throughout the life cycle. In this study we examine the Plasmodium-encoded S2P in a murine malaria model and show that it is expressed in all stages of Plasmodium development. Localisation studies by endogenous gene tagging revealed that in all invasive stages the protein is in close proximity to the nucleus. Ablation of PbS2P by reverse genetics leads to reduced growth rates during liver and blood infection and, hence, virulence attenuation. Strikingly, absence of PbS2P was compatible with parasite life cycle progression in the mosquito and mammalian hosts under physiological conditions, suggesting redundant or dispensable roles in vivo.

  8. Optimization of Time Controlled 6-mercaptopurine Delivery for Site- Specific Targeting to Colon Diseases.

    Science.gov (United States)

    Hude, Rahul U; Jagdale, Swati C

    2016-01-01

    6-MP has short elimination time (Mercaptopurine (6-MP) for treatment of colon diseases. Compression coating technique was used. 32 full factorial design was designed for optimization of the outer coat for the core tablet. For outer coat amount of Eudragit RS 100 and hydroxypropyl methylcellulose (HPMC K100) were employed as independent variables each at three levels while responses evaluated were swelling index and bursting time. Direct compression method was used for tablets formulation. 80% w/w of microcrystalline cellulose and 20% w/w of croscarmellose sodium were found to be optimum concentration for the core tablet. The outer coat of optimized batch (ED) contains 21.05% w/w Eudragit RS 100 and 78.95% w/w HPMC K100 of total polymer weight. In-vitro dissolution study indicated that combination of polymer retards the drug release in gastric region and releases ≥95% of drug in colonic region after ≥7 h. Whereas in case of in-vivo placebo x-ray imaging study had shown that the tablet reaches colonic part after 5±0.5 h providing the proof of arrival in the colon. Stability study indicated that the optimized formulation were physically and chemically stable. Present research work concluded that compression coating by Eudragit RS 100 and HPMC K100 to 6-MP core provides potential colon targeted system with advantages of reduced gastric exposure and enhanced bioavailability. Formulation can be considered as potential and promising candidate for the treatment of colon diseases.

  9. Clinically targeted screening for congenital CMV - potential for integration into the National Hearing Screening Programme.

    Science.gov (United States)

    Kadambari, S; Luck, S; Davis, A; Williams, Ej; Berrington, J; Griffiths, Pd; Sharland, M

    2013-10-01

    Screening for a condition should only be undertaken if certain strict criteria are met. Congenital CMV (cCMV) is a leading cause of sensorineuronal hearing loss (SNHL) and meets many of these criteria, but is not currently screened for in the UK. Ganciclovir reduces CMV-induced progressive SNHL if treatment is begun in the first month of life. The Newborn Hearing Screening Programme (NHSP) has been shown to identify SNHL at the earliest possible age. The potential of integrating screening for cCMV into the NHSP is discussed to consolidate the link between screening, early diagnosis and management. The early diagnosis and treatment of cCMV may prevent a small proportion of late SNHL. In the absence of any screening programme, we provide evidence that clinically targeted screening through the NHSP is a potential option in the UK, enhancing the diagnostic pathway and enabling appropriate early treatment to reduce long-term morbidity. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  10. An integrated control and readout circuit for implantable multi-target electrochemical biosensing.

    Science.gov (United States)

    Ghoreishizadeh, Sara S; Baj-Rossi, Camilla; Cavallini, Andrea; Carrara, Sandro; De Micheli, Giovanni

    2014-12-01

    We describe an integrated biosensor capable of sensing multiple molecular targets using both cyclic voltammetry (CV) and chronoamperometry (CA). In particular, we present our custom IC to realize voltage control and current readout of the biosensors. A mixed-signal circuit block generates sub-Hertz triangular waveform for the biosensors by means of a direct-digital-synthesizer to control CV. A current to pulse-width converter is realized to output the data for CA measurement. The IC is fabricated in 0.18 μm technology. It consumes 220 μW from 1.8 V supply voltage, making it suitable for remotely-powered applications. Electrical measurements show excellent linearity in sub- μA current range. Electrochemical measurements including CA measurements of glucose and lactate and CV measurements of the anti-cancer drug Etoposide have been acquired with the fabricated IC and compared with a commercial equipment. The results obtained with the fabricated IC are in good agreement with those of the commercial equipment for both CV and CA measurements.

  11. On the feasibility to perform integral transmission experiments in the GELINA target hall at IRMM

    Science.gov (United States)

    Leconte, Pierre; Jean, Cyrille De Saint; Geslot, Benoit; Plompen, Arjan; Belloni, Francesca; Nyman, Markus

    2017-09-01

    Shielding experiments are relevant to validate elastic and inelastic scattering cross sections in the fast energy range. In this paper, we are focusing on the possibility to use the pulsed white neutron time-of-flight facility GELINA to perform this kind of measurement. Several issues need to be addressed: neutron source intensity, room return effect, distance of the materials to be irradiated from the source, and the sensitivity of various reaction rate distributions through the material to different input cross sections. MCNP6 and TRIPOLI4 calculations of the outgoing neutron spectrum are compared, based on electron/positron/gamma/neutron simulations. A first guess of an integral transmission experiment through a 238U slab is considered. It shows that a 10 cm thickness of uranium is sufficient to reach a high sensitivity to the 238U inelastic scattering cross section in the [2-5 MeV] energy range, with small contributions from elastic and fission cross sections. This experiment would contribute to reduce the uncertainty on this nuclear data, which has a significant impact on the power distribution in large commercial reactors. Other materials that would be relevant for the ASTRID 4th generation prototype reactor are also tested, showing that a sufficient sensitivity to nuclear data would be obtained by using a 50 to 100cm thick slab of side 60x60cm. This study concludes on the feasibility and interest of such experiments in the target hall of the GELINA facility.

  12. The Skogaryd Research Site - Integration of terrestrial and freshwater greenhouse gas sources and sinks

    Science.gov (United States)

    Klemedtsson, L.

    2012-04-01

    atmosphere. The budgets have ignored dissolved carbon (C) and nitrogen (N) transport in water to streams and lakes and the subsequent exchange between the atmosphere and surface waters. Aquatic habitats can be significant net sources of CO2 and methane (CH4) and potential hot spots for N2O release, all important for natural greenhouse gas (GHG) emissions. Inland waters need to be included in the C and GHG balances for terrestrial landscapes. This project aims to quantify GHG balances at the landscape scale in forested regions that include land-atmosphere, land-water, and water-atmosphere exchange of CO2, CH4 and N2O. Different terrestrial and aquatic ecosystems will be linked holistically, using site specific techniques at different scales, from aircraft (km2) to chambers (m2) to develop integrated models that can be used to quantify net GHG flux for management strategies. The LAGGE project involves six Swedish universities and site is open for more cooperations.

  13. Seismic aftershock monitoring for on-site inspection purposes. Experience from Integrated Field Exercise 2008.

    Science.gov (United States)

    Labak, P.; Arndt, R.; Villagran, M.

    2009-04-01

    One of the sub-goals of the Integrated Field Experiment in 2008 (IFE08) in Kazakhstan was testing the prototype elements of the Seismic aftershock monitoring system (SAMS) for on-site inspection purposes. The task of the SAMS is to collect the facts, which should help to clarify nature of the triggering event. Therefore the SAMS has to be capable to detect and identify events as small as magnitude -2 in the inspection area size up to 1000 km2. Equipment for 30 mini-arrays and 10 3-component stations represented the field equipment of the SAMS. Each mini-array consisted of a central 3-component seismometer and 3 vertical seismometers at the distance about 100 m from the central seismometer. The mini-arrays covered approximately 80% of surrogate inspection area (IA) on the territory of former Semipalatinsk test site. Most of the stations were installed during the first four days of field operations by the seismic sub-team, which consisted of 10 seismologists. SAMS data center comprised 2 IBM Blade centers and 8 working places for data archiving, detection list production and event analysis. A prototype of SAMS software was tested. Average daily amount of collected raw data was 15-30 GB and increased according to the amount of stations entering operation. Routine manual data screening and data analyses were performed by 2-6 subteam members. Automatic screening was used for selected time intervals. Screening was performed using the Sonoview program in frequency domain and using the Geotool and Hypolines programs for screening in time domain. The screening results were merged into the master event list. The master event list served as a basis of detailed analysis of unclear events and events identified to be potentially in the IA. Detailed analysis of events to be potentially in the IA was performed by the Hypoline and Geotool programs. In addition, the Hyposimplex and Hypocenter programs were also used for localization of events. The results of analysis were integrated

  14. Geology and MER target site characteristics along the southern rim of Isidis Planitia, Mars

    Science.gov (United States)

    Crumpler, L.S.; Tanaka, K.L.

    2003-01-01

    crustal materials, in the form of rocks within the debris fans, and the weathered condition of the rocky material are potential sources for mineralogical evidence of climatic conditions in earliest Martian geologic history. The absence of alteration within rocks would, on the other hand, support the hypothesis that fluvial runoff during the earliest history of Mars was geologically brief rather than long-term and that long-term saturated groundwater flow was not present. Determination of the presence or absence of alteration would have corresponding implications for hypotheses requiring the long-term presence of aqueous solutions (i.e., complex organic compounds and life). A proposed MER site along the margin addresses realistic field science objectives of the Mars Exploration Rover mission and the current goals of the Mars Exploration Program. In situ measurements may be important in deriving estimates of the longevity and intensity of past wetter climates. Copyright 2003 by the American Geophysical Union.

  15. A novel educational strategy targeting health care workers in underserved communities in Central America to integrate HIV into primary medical care.

    Directory of Open Access Journals (Sweden)

    Tamara Flys

    Full Text Available BACKGROUND: Current educational strategies to integrate HIV care into primary medical care in Central America have traditionally targeted managers or higher-level officials, rather than local health care workers (HCWs. We developed a complementary online and on-site interactive training program to reach local HCWs at the primary care level in underserved communities. METHODS: The training program targeted physicians, nurses, and community HCWs with limited access to traditional onsite training in Panama, Nicaragua, Dominican Republic, and Guatemala. The curriculum focused on principles of HIV care and health systems using a tutor-supported blended educational approach of an 8-week online component, a weeklong on-site problem-solving workshop, and individualized project-based interventions. RESULTS: Of 258 initially active participants, 225 (225/258=87.2% successfully completed the online component and the top 200 were invited to the on-site workshop. Of those, 170 (170/200=85% attended the on-site workshop. In total, 142 completed all three components, including the project phase. Quantitative and qualitative evaluation instruments included knowledge assessments, reflexive essays, and acceptability surveys. The mean pre and post-essay scores demonstrating understanding of social determinants, health system organization, and integration of HIV services were 70% and 87.5%, respectively, with an increase in knowledge of 17.2% (p<0.001. The mean pre- and post-test scores evaluating clinical knowledge were 70.9% and 90.3%, respectively, with an increase in knowledge of 19.4% (p<0.001. A survey of Likert scale and open-ended questions demonstrated overwhelming participant satisfaction with course content, structure, and effectiveness in improving their HIV-related knowledge and skills. CONCLUSION: This innovative curriculum utilized technology to target HCWs with limited access to educational resources. Participants benefited from technical skills

  16. Integration and consistency testing of groundwater flow models with hydro-geochemistry in site investigations in Finland

    International Nuclear Information System (INIS)

    Pitkaenen, P.; Loefman, J.; Korkealaakso, J.; Koskinen, L.; Ruotsalainen, P.; Hautojaervi, A.; Aeikaes, T.

    1999-01-01

    In the assessment of the suitability and safety of a geological repository for radioactive waste the understanding of the fluid flow at a site is essential. In order to build confidence in the assessment of the hydrogeological performance of a site in various conditions, integration of hydrological and hydrogeochemical methods and studies provides the primary method for investigating the evolution that has taken place in the past, and for predicting future conditions at the potential disposal site. A systematic geochemical sampling campaign was started since the beginning of 1990's in the Finnish site investigation programme. This enabled the initiating of integration and evaluation of site scale hydrogeochemical and groundwater flow models. Hydrogeochemical information has been used to screen relevant external processes and variables for definition of the initial and boundary conditions in hydrological simulations. The results obtained from interpretation and modelling hydrogeochemical evolution have been employed in testing the hydrogeochemical consistency of conceptual flow models. Integration and testing of flow models with hydrogeochemical information are considered to improve significantly the hydrogeological understanding of a site and increases confidence in conceptual hydrogeological models. (author)

  17. An Integrated Approach to Change the Outcome Part II: Targeted Neuromuscular Training Techniques to Reduce Identified ACL Injury Risk Factors

    Science.gov (United States)

    Myer, Gregory D.; Ford, Kevin R.; Brent, Jensen L.; Hewett, Timothy E.

    2014-01-01

    Prior reports indicate that female athletes who demonstrate high knee abduction moments (KAMs) during landing are more responsive to neuromuscular training designed to reduce KAM. Identification of female athletes who demonstrate high KAM, which accurately identifies those at risk for noncontact anterior cruciate ligament (ACL) injury, may be ideal for targeted neuromuscular training. Specific neuromuscular training targeted to the underlying biomechanical components that increase KAM may provide the most efficient and effective training strategy to reduce noncontact ACL injury risk. The purpose of the current commentary is to provide an integrative approach to identify and target mechanistic underpinnings to increased ACL injury in female athletes. Specific neuromuscular training techniques will be presented that address individual algorithm components related to high knee load landing patterns. If these integrated techniques are employed on a widespread basis, prevention strategies for noncontact ACL injury among young female athletes may prove both more effective and efficient. PMID:22580980

  18. Integrated account of method, site selection and programme prior to the site investigation phase[Planning for a Swedish repository for spent nuclear fuels

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-12-01

    In order to dispose of the spent nuclear fuel in a safe manner, SKB plans to site a deep repository and an encapsulation plant with associated canister fabrication and transportation system. After an integrated evaluation of feasibility studies and other material, SKB will proceed with investigations of the rock and studies regarding establishment of the deep disposal system in the municipality of Oskarshamn or in Northern Uppland. The plans also include further study of the prospects for a deep repository in the municipality of Nykoeping. In the municipality of Oskarshamn, SKB plans further studies of a siting of the deep repository at Simpevarp. There SKB wants to initiate site investigations with test drilling. For the encapsulation plant, SKB wants to continue studying a siting at CLAB. In Northern Uppland, SKB plans to study two siting alternatives for the deep repository. One is Forsmark in the municipality of Oesthammar, where SKB wants to initiate a site investigation with test drilling. The other is Tierp north of Skutskaer, where SKB intends to start test drilling in an area north of Tierp. First, however, a suitable drilling area with possible transport solutions needs to be defined. This alternative requires the participation of the municipalities of both Tierp and Aelvkarleby. A siting of the encapsulation plant in Northern Uppland will also be studied. For the municipality of Nykoeping, SKB plans to conduct a new safety assessment for the Fjaellveden area, based on data from previous investigations as well as additional studies of how a deep repository could be arranged. SKB will thereby gather data from yet another geographic and geological region beyond those that are prioritized. No test drilling is planned in Nykoeping. The goal of the site investigation phase is to obtain all permits needed to build the planned facilities. It will take an estimated 7 - 8 years to assemble the requisite supporting material, carry out consultations, compile siting

  19. Temporal Target Integration Underlies Performance at Lag 1 in the Attentional Blink

    Science.gov (United States)

    Akyurek, Elkan G.; Eshuis, Sander A. H.; Nieuwenstein, Mark R.; Saija, Jefta D.; Baskent, Deniz; Hommel, Bernhard

    2012-01-01

    When two targets follow each other directly in rapid serial visual presentation (RSVP), they are often identified correctly but reported in the wrong order. These order reversals are commonly explained in terms of the rate at which the two targets are processed, the idea being that the second target can sometimes overtake the first in the race…

  20. Design concepts for an integrated control room used as a site-wide operations facility

    International Nuclear Information System (INIS)

    Simon, B.H.; Raghavan, R.; Ujita, H.; Utena, S.; Sakuma, A.; Itoh, T.; Fukura, M.; Ono, I.

    1995-01-01

    The concept of an Integrated Main Control Room (IMCR) evolved from surveys conducted by Tokyo Electric Power Company (TEPCO) with plant managers and workers as their existing GE-type boiling water reactors (BWRs) on the need for improved operating conditions in a new generation of reactors being developed for the next century (around 2010). These reactors will be a further enhancement of the advanced boiling water reactors (ABWRs) now being constructed at the Kashiwazaki-Kariwa site in Japan (no.6 and no.7). TEPCO also saw a need for new thinking on control room design because of projected social conditions in Japan for the 21st century. These projections forecast a smaller number of skilled engineering graduates and those graduates less willing to work in nuclear power because such work is seen as unappealing, conducted in remote geographical locations, and requiring extensive night duty. As one solution to reducing operator burden and decreasing the night shift staff, while making nuclear plant operation more interesting for the operators and reducing labor and construction costs, the IMCR was conceived. (author)

  1. Integrated GIS-Based Site Selection of Hillside Development for Future Growth of Urban Areas

    Directory of Open Access Journals (Sweden)

    Imtiaz Ahmed Chandio

    2016-04-01

    Full Text Available Urbanization is a challenging issue for developing countries, like Malaysia. Penang Island is one of the states of Malaysia selected as a study area where limited flat land exists. As a result, this would create urban environmental problems, such as unstable slopes and landslides due to uneven topography. The purpose of this study was to develop land suitability model for hillside development. Hence, this research aims land suitability analysis modelling for hillside development by using integrated GIS (Geographic Information System based MCDM (Multi-Criteria Decision Making approach. The hill land portion of Penang Island was selected for hillside site development using GIS and AHP (Analytic Hierarchy Process as a MCDM method for sustainable hillside development. This study found that 15% of land was highly suitable, 27% moderately suitable, 41% less suitable, and 17% not suitable. Therefore, this research can be consistently used by the concerned authorities for sustainable hillside urban planning and development. This approach can be used as a policy tool in decision making of urban planning and development.

  2. An integrated system for conducting radiological surveys of contaminated sites - 16312

    International Nuclear Information System (INIS)

    McCown, Jay P.; Rogers, Donna M.; Waggoner, Charles A.

    2009-01-01

    This paper describes an integrated detection system that has been developed to conduct radiological surveys of sites suspected of contamination of materials such as depleted uranium. This system utilizes cerium activated lanthanum bromide and thallium activated sodium iodide gamma detectors and can be easily adapted to include units for detecting neutrons. The detection system includes software controlling the collection of radiological spectra and GPS data. Two different platforms are described for conducting surveys, a modified zero turn radius (ZTR) mower and a three-wheeled cart that is manually pushed. The detection system software controlling data collection has components that facilitate completing a grid-less survey on user specified spacings. Another package confirms that all data quality activities (calibrations, etc.) are conducted prior to beginning the survey and also reviews data to identify areas that have been missed for which data quality falls below user designated parameters. Advanced digital signal processing algorithms are used to enhance the interpretation of spectra for conducting background subtractions and for mapping. Data from radiation detection instruments and GPS antennae are merged and made compatible with mapping using Geosoft Oasis montaj software. A summary of system performance during field-testing is included in the paper. This includes survey rate, detection limits, duty cycle, supporting ancillary equipment/material, and manpower requirements. The rate of false positives and false negatives is discussed with the benefits of surveys conducted using synergetic detection systems such as electromagnetic induction imaging. (authors)

  3. Management of comments on DOE's Site Characterization Plan (SCP) and integration with the planned geotechnical program

    International Nuclear Information System (INIS)

    Bjerstedt, T.W.; Gil, A.V.; Baird, F.A.

    1991-01-01

    The US DOE has committed to respond to comments on the SCP throughout the site characterization process. As of January 1990 DOE has received 4,574 comments on both the SCP/Consultation Draft and the statutory SCP. Of these, 2,662 responses have been completed and returned to the originators. Many comments are programmatic in nature and express diverse concerns beyond the scope of the SCP. DOE uses a three-tiered process in responding to comments that integrated technical and management responsibilities. The process defines specific roles in developing, reviewing, and concurring on responses. Commitments or open-items can be generated in DOE responses to comments, which are tracked on a relational database. Major changes reflected in the Secretary of Energy's 1989 reassessment of the high-level waste program were advocated in comments on the SCP. Most DOE commitments, however, deal with consideration of recommendations contained in SCP comments relevant to low-levels of technical planning detail (SCP Study Plans). Commitments are discharged when referred to the appropriate quality-affecting or management process whereupon their merits can be evaluated

  4. Integrated report on radionuclide migration at the Savannah River shallow land burial site

    International Nuclear Information System (INIS)

    Towler, O.A. Jr.

    1989-03-01

    The impact of the SRP Solid Radioactive Waste Burial Ground on the environment has been studied since the early 1970s in four subtasks: subsurface monitoring of groundwater, lysimeter tests of waste, soil-water chemistry effects, and radionuclide transport modeling. This document summarizes and integrates the results of the four subtasks. More information has been gathered on the behavior of radionuclides in a solid waste disposal facility located in a humid region than from any other waste disposal site in the world. The design of closure for the SRP Burial Ground has been given a firm technical basis. The limiting pathways for radionuclide migration have been determined to be infiltrating rainwater and root penetration. Closure designs must therefore address both these factors. The designs for new storage/disposal facilities have also been given a firm technical basis. The major conclusions are that tritium will be stored for decay and not allowed to contact the groundwater, waste containing long-lived radionuclides such as iodine-129 must be stored for later geologic disposal, and above and below ground concrete vaults should be used for disposal of other low-level radioactive waste. 61 refs., 18 figs. 8 tabs

  5. Integration of intracellular telomerase monitoring by electrochemiluminescence technology and targeted cancer therapy by reactive oxygen species.

    Science.gov (United States)

    Zhang, Huairong; Li, Binxiao; Sun, Zhaomei; Zhou, Hong; Zhang, Shusheng

    2017-12-01

    Cancer therapies based on reactive oxygen species (ROS) have emerged as promising clinical treatments. Electrochemiluminescence (ECL) technology has also attracted considerable attention in the field of clinical diagnosis. However, studies about the integration of ECL diagnosis and ROS cancer therapy are very rare. Here we introduce a novel strategy that employs ECL technology and ROS to fill the above vacancy. Briefly, an ITO electrode was electrodeposited with polyluminol-Pt NPs composite films and modified with aptamer DNA to capture HL-60 cancer cells with high specificity. After that, mesoporous silica nanoparticles (MSNs) filled with phorbol 12-myristate 13-acetate (PMA) were closed by the telomerase primer DNA (T-primer DNA) and aptamer. After aptamer on MSN@PMA recognized and combined with the HL-60 cancer cells with high specificity, T-primer DNA on MSN@PMA could be moved away from the MSN@PMA surface after extension by telomerase in the HL-60 cancer cells and PMA was released to induce the production of ROS by the HL-60 cancer cells. After that, the polyluminol-Pt NPs composite films could react with hydrogen peroxide (a major ROS) and generate an ECL signal. Thus the intracellular telomerase activity of the HL-60 cancer cells could be detected in situ . Besides, ROS could induce apoptosis in the HL-60 cancer cells with high efficacy by causing oxidative damage to the lipids, protein, and DNA. Above all, the designed platform could not only detect intracellular telomerase activity instead of that of extracted telomerase, but could also kill targeted tumors by ECL technology and ROS.

  6. Dengue vector management using insecticide treated materials and targeted interventions on productive breeding-sites in Guatemala

    Directory of Open Access Journals (Sweden)

    Rizzo Nidia

    2012-10-01

    Full Text Available Abstract Background In view of the epidemiological expansion of dengue worldwide and the availability of new tools and strategies particularly for controlling the primary dengue vector Aedes aegypti, an intervention study was set up to test the efficacy, cost and feasibility of a combined approach of insecticide treated materials (ITMs alone and in combination with appropriate targeted interventions of the most productive vector breeding-sites. Methods The study was conducted as a cluster randomized community trial using “reduction of the vector population” as the main outcome variable. The trial had two arms: 10 intervention clusters (neighborhoods and 10 control clusters in the town of Poptun Guatemala. Activities included entomological assessments (characteristics of breeding-sites, pupal productivity, Stegomyia indices at baseline, 6 weeks after the first intervention (coverage of window and exterior doorways made of PermaNet 2.0 netting, factory treated with deltamethrin at 55 mg/m2, and of 200 L drums with similar treated material and 6 weeks after the second intervention (combination of treated materials and other suitable interventions targeting productive breeding-sites i.e larviciding with Temephos, elimination etc.. The second intervention took place 17 months after the first intervention. The insecticide residual activity and the insecticidal content were also studied at different intervals. Additionally, information about demographic characteristics, cost of the intervention, coverage of houses protected and satisfaction in the population with the interventions was collected. Results At baseline (during the dry season a variety of productive container types for Aedes pupae were identified: various container types holding >20 L, 200 L drums, washbasins and buckets (producing 83.7% of all pupae. After covering 100% of windows and exterior doorways and a small number of drums (where the commercial cover could be fixed in 970 study

  7. Dengue vector management using insecticide treated materials and targeted interventions on productive breeding-sites in Guatemala.

    Science.gov (United States)

    Rizzo, Nidia; Gramajo, Rodrigo; Escobar, Maria Cabrera; Arana, Byron; Kroeger, Axel; Manrique-Saide, Pablo; Petzold, Max

    2012-10-30

    In view of the epidemiological expansion of dengue worldwide and the availability of new tools and strategies particularly for controlling the primary dengue vector Aedes aegypti, an intervention study was set up to test the efficacy, cost and feasibility of a combined approach of insecticide treated materials (ITMs) alone and in combination with appropriate targeted interventions of the most productive vector breeding-sites. The study was conducted as a cluster randomized community trial using "reduction of the vector population" as the main outcome variable. The trial had two arms: 10 intervention clusters (neighborhoods) and 10 control clusters in the town of Poptun Guatemala. Activities included entomological assessments (characteristics of breeding-sites, pupal productivity, Stegomyia indices) at baseline, 6 weeks after the first intervention (coverage of window and exterior doorways made of PermaNet 2.0 netting, factory treated with deltamethrin at 55 mg/m2, and of 200 L drums with similar treated material) and 6 weeks after the second intervention (combination of treated materials and other suitable interventions targeting productive breeding-sites i.e larviciding with Temephos, elimination etc.). The second intervention took place 17 months after the first intervention. The insecticide residual activity and the insecticidal content were also studied at different intervals. Additionally, information about demographic characteristics, cost of the intervention, coverage of houses protected and satisfaction in the population with the interventions was collected. At baseline (during the dry season) a variety of productive container types for Aedes pupae were identified: various container types holding >20 L, 200 L drums, washbasins and buckets (producing 83.7% of all pupae). After covering 100% of windows and exterior doorways and a small number of drums (where the commercial cover could be fixed) in 970 study households, tropical rains occurred in the area and

  8. TALE nickase mediates high efficient targeted transgene integration at the human multi-copy ribosomal DNA locus.

    Science.gov (United States)

    Wu, Yong; Gao, Tieli; Wang, Xiaolin; Hu, Youjin; Hu, Xuyun; Hu, Zhiqing; Pang, Jialun; Li, Zhuo; Xue, Jinfeng; Feng, Mai; Wu, Lingqian; Liang, Desheng

    2014-03-28

    Although targeted gene addition could be stimulated strikingly by a DNA double strand break (DSB) created by either zinc finger nucleases (ZFNs) or TALE nucleases (TALENs), the DSBs are really mutagenic and toxic to human cells. As a compromised solution, DNA single-strand break (SSB) or nick has been reported to mediate high efficient gene addition but with marked reduction of random mutagenesis. We previously demonstrated effective targeted gene addition at the human multicopy ribosomal DNA (rDNA) locus, a genomic safe harbor for the transgene with therapeutic potential. To improve the transgene integration efficiency by using TALENs while lowering the cytotoxicity of DSBs, we created both TALENs and TALE nickases (TALENickases) targeting this multicopy locus. A targeting vector which could integrate a GFP cassette at the rDNA locus was constructed and co-transfected with TALENs or TALENickases. Although the fraction of GFP positive cells using TALENs was greater than that using TALENickases during the first few days after transfection, it reduced to a level less than that using TALENickases after continuous culture. Our findings showed that the TALENickases were more effective than their TALEN counterparts at the multi-copy rDNA locus, though earlier studies using ZFNs and ZFNickases targeting the single-copy loci showed the reverse. Besides, TALENickases mediated the targeted integration of a 5.4 kb fragment at a frequency of up to 0.62% in HT1080 cells after drug selection, suggesting their potential application in targeted gene modification not being limited at the rDNA locus. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Updates on drug-target network; facilitating polypharmacology and data integration by growth of DrugBank database.

    Science.gov (United States)

    Barneh, Farnaz; Jafari, Mohieddin; Mirzaie, Mehdi

    2016-11-01

    Network pharmacology elucidates the relationship between drugs and targets. As the identified targets for each drug increases, the corresponding drug-target network (DTN) evolves from solely reflection of the pharmaceutical industry trend to a portrait of polypharmacology. The aim of this study was to evaluate the potentials of DrugBank database in advancing systems pharmacology. We constructed and analyzed DTN from drugs and targets associations in the DrugBank 4.0 database. Our results showed that in bipartite DTN, increased ratio of identified targets for drugs augmented density and connectivity of drugs and targets and decreased modular structure. To clear up the details in the network structure, the DTNs were projected into two networks namely, drug similarity network (DSN) and target similarity network (TSN). In DSN, various classes of Food and Drug Administration-approved drugs with distinct therapeutic categories were linked together based on shared targets. Projected TSN also showed complexity because of promiscuity of the drugs. By including investigational drugs that are currently being tested in clinical trials, the networks manifested more connectivity and pictured the upcoming pharmacological space in the future years. Diverse biological processes and protein-protein interactions were manipulated by new drugs, which can extend possible target combinations. We conclude that network-based organization of DrugBank 4.0 data not only reveals the potential for repurposing of existing drugs, also allows generating novel predictions about drugs off-targets, drug-drug interactions and their side effects. Our results also encourage further effort for high-throughput identification of targets to build networks that can be integrated into disease networks. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  10. Contamination and UV ageing of diffuser targets used in satellite inflight and ground reference test site calibrations

    Science.gov (United States)

    Vaskuri, Anna; Greenwell, Claire; Hessey, Isabel; Tompkins, Jordan; Woolliams, Emma

    2018-02-01

    Diffuser reflectance targets are key components in in-orbit calibrations and for verifying ground reference test sites. In this work, Spectralon, Diffusil, and Heraeus diffusers were exposed to exhaust gases and ultraviolet (UV) radiation in the ambient air conditions and their degradations were monitored by measuring changes in spectral reflectances. Spectralon is a state-of-the-art diffuser made of polytetrafluoroethylene, and Diffusil and Heraeus diffusers are made of fused silica with gas bubbles inside. Based on the contamination tests, Spectralon degrades faster than fused silica diffusers. For the samples exposed to contamination for 20 minutes, the 250 nm - 400 nm total diffuse spectral reflectance of Spectralon degraded 3-5 times more when exposed to petrol-like emission and 16-23 times more when exposed to diesel-like emission, compared with Diffusil. When the reflectance changes of Spectralon were compared with those of Heraeus, Spectralon degraded 3-4 times more when exposed to petrol-like emission for 20 minutes and 5-7 times more when exposed to diesel-like emission for 7.5 minutes. When the samples contaminated were exposed to UV radiation in the ambient air, their reflectance gradually restored back to the original level. In conclusion, fused silica diffusers are more resistant to hydrocarbon contaminants present in ground reference test sites, and thus more stable under UV radiation in the air.

  11. Using remote sensing data for exploitation of integrated renewable energy at coastal site in South Italy

    Science.gov (United States)

    Calaudi, Rosamaria; Lo Feudo, Teresa; Calidonna, Claudia Roberta; Sempreviva, Anna Maria

    2016-04-01

    Renewable energy sources are major components of the strategy to reduce harmful emissions and to replace depleting fossil energy resources. Data from Remote Sensing can provide detailed information for analysis for sources of renewable energy and to determine the potential energy and socially acceptability of suggested location. Coastal sites of Southern Italy have the advantage of favorable climatic conditions to use renewable energy, such us cloud free days and local breeze phenomena. Many ports are located where they have opportunities for exploitation of renewable energy, by using existing port area and by taking advantage of their coastal locations. Policies of European-Committee and Global-Navigation-PIANC for a better use of energy and an efficient supply from renewable sources are also focused on the construction of port facilities in zero emissions. Using data from Remote Sensing, can reduce the financial resources currently required for finding and assessing suitable areas, we defined an integrated methodology for potential wind and solar energy in harbor areas. In this study we compared the hourly solar power energy using MSG-SEVIRI (Meteosat Second Generation Spinning Enhanced Visible and Infrared) data products DSSF (Down-welling Surface Short-wave-Flux), and PV-Plant measurements with Nominal Power Peak of 19,85 kWp. The PV Plant is situated at a coastal site in Calabrian region, located near Vibo Valentia harbor area. We estimate potential energy by using input solar radiation of Satellite data, with same characteristics of the PV-plant. The RMSE and BIAS for hourly averaged solar electrical reproducibility are estimated including clear and sky conditions. Comparison between energy reproducibility by using DSSF product and PV-plant measurements, made over the period October 2013-June 2014, showed a good agreement in our costal site and generally overestimate (RMSE(35W/m2) and BIAS(4W/m2)) electrical reproducibility from a PV-plant. For wind resource

  12. Cell-laden hydrogel/titanium microhybrids: Site-specific cell delivery to metallic implants for improved integration.

    Science.gov (United States)

    Koenig, Geraldine; Ozcelik, Hayriye; Haesler, Lisa; Cihova, Martina; Ciftci, Sait; Dupret-Bories, Agnes; Debry, Christian; Stelzle, Martin; Lavalle, Philippe; Vrana, Nihal Engin

    2016-03-01

    Porous titanium implants are widely used in dental, orthopaedic and otorhinolaryngology fields to improve implant integration to host tissue. A possible step further to improve the integration with the host is the incorporation of autologous cells in porous titanium structures via cell-laden hydrogels. Fast gelling hydrogels have advantageous properties for in situ applications such as localisation of specific cells and growth factors at a target area without dispersion. The ability to control the cell types in different regions of an implant is important in applications where the target tissue (i) has structural heterogeneity (multiple cell types with a defined spatial configuration with respect to each other); (ii) has physical property gradients essential for its function (such as in the case of osteochondral tissue transition). Due to their near immediate gelation, such gels can also be used for site-specific modification of porous titanium structures, particularly for implants which would face different tissues at different locations. Herein, we describe a step by step design of a model system: the model cell-laden gel-containing porous titanium implants in the form of titanium microbead/hydrogel (maleimide-dextran or maleimide-PVA based) microhybrids. These systems enable the determination of the effect of titanium presence on gel properties and encapsulated cell behaviour as a miniaturized version of full-scale implants, providing a system compatible with conventional analysis methods. We used a fibroblast/vascular endothelial cell co-cultures as our model system and by utilising single microbeads we have quantified the effect of gel microenvironment (degradability, presence of RGD peptides within gel formulation) on cell behaviour and the effect of the titanium presence on cell behaviour and gel formation. Titanium presence slightly changed gel properties without hindering gel formation or affecting cell viability. Cells showed a preference to move towards

  13. The ΦBT1 large serine recombinase catalyzes DNA integration at pseudo-attB sites in the genus Nocardia

    Directory of Open Access Journals (Sweden)

    Marion Herisse

    2018-05-01

    Full Text Available Plasmid vectors based on bacteriophage integrases are important tools in molecular microbiology for the introduction of foreign DNA, especially into bacterial species where other systems for genetic manipulation are limited. Site specific integrases catalyze recombination between phage and bacterial attachment sites (attP and attB, respectively and the best studied integrases in the actinomycetes are the serine integrases from the Streptomyces bacteriophages ΦC31 and ΦBT1. As this reaction is unidirectional and highly stable, vectors containing phage integrase systems have been used in a number of genetic engineering applications. Plasmids bearing the ΦBT1 integrase have been used to introduce DNA into Streptomyces and Amycolatopsis strains; however, they have not been widely studied in other actinobacterial genera. Here, we show that vectors based on ΦBT1 integrase can stably integrate into the chromosomes of a range of Nocardia species, and that this integration occurs despite the absence of canonical attB sites in these genomes. Furthermore, we show that a ΦBT1 integrase-based vector can insert at multiple pseudo-attB sites within a single strain and we determine the sequence of a pseudo-attB motif. These data suggest that ΦBT1 integrase-based vectors can be used to readily and semi-randomly introduce foreign DNA into the genomes of a range of Nocardia species. However, the precise site of insertion will likely require empirical determination in each species to avoid unexpected off-target effects.

  14. Site-specific integration in CHO cells mediated by CRISPR/Cas9 and homology-directed DNA repair pathway

    DEFF Research Database (Denmark)

    Lee, Jae Seong; Beuchert Kallehauge, Thomas; Pedersen, Lasse Ebdrup

    2015-01-01

    gene integration into site-specific loci in CHO cells using CRISPR/Cas9 genome editing system and compatible donor plasmid harboring a gene of interest (GOI) and short homology arms. This strategy has enabled precise insertion of a 3.7-kb gene expression cassette at defined loci in CHO cells following...

  15. A network integration approach for drug-target interaction prediction and computational drug repositioning from heterogeneous information.

    Science.gov (United States)

    Luo, Yunan; Zhao, Xinbin; Zhou, Jingtian; Yang, Jinglin; Zhang, Yanqing; Kuang, Wenhua; Peng, Jian; Chen, Ligong; Zeng, Jianyang

    2017-09-18

    The emergence of large-scale genomic, chemical and pharmacological data provides new opportunities for drug discovery and repositioning. In this work, we develop a computational pipeline, called DTINet, to predict novel drug-target interactions from a constructed heterogeneous network, which integrates diverse drug-related information. DTINet focuses on learning a low-dimensional vector representation of features, which accurately explains the topological properties of individual nodes in the heterogeneous network, and then makes prediction based on these representations via a vector space projection scheme. DTINet achieves substantial performance improvement over other state-of-the-art methods for drug-target interaction prediction. Moreover, we experimentally validate the novel interactions between three drugs and the cyclooxygenase proteins predicted by DTINet, and demonstrate the new potential applications of these identified cyclooxygenase inhibitors in preventing inflammatory diseases. These results indicate that DTINet can provide a practically useful tool for integrating heterogeneous information to predict new drug-target interactions and repurpose existing drugs.Network-based data integration for drug-target prediction is a promising avenue for drug repositioning, but performance is wanting. Here, the authors introduce DTINet, whose performance is enhanced in the face of noisy, incomplete and high-dimensional biological data by learning low-dimensional vector representations.

  16. Verification of geomechanical integrity and prediction of long-term mineral trapping for the Ketzin CO2 storage pilot site

    Science.gov (United States)

    Kempka, Thomas; De Lucia, Marco; Kühn, Michael

    2014-05-01

    Static and dynamic numerical modelling generally accompany the entire CO2 storage site life cycle. Thereto, it is required to match the employed models with field observations on a regular basis in order to predict future site behaviour. We investigated the coupled processes at the Ketzin CO2 storage pilot site [1] using a model coupling concept focusing on the temporal relevance of processes involved (hydraulic, chemical and mechanical) at given time-scales (site operation, abandonment and long-term stabilization). For that purpose, long-term dynamic multi-phase flow simulations [2], [3] established the basis for all simulations discussed in the following. Hereby, pressure changes resulting in geomechanical effects are largest during site operation, whereas geochemical reactions are governed by slow kinetics resulting in a long-term stabilization. To account for mechanical integrity, which may be mainly affected during site operation, we incorporated a regional-scale coupled hydro-mechanical model. Our simulation results show maximum ground surface displacements of about 4 mm, whereas shear and tensile failure are not observed. Consequently, the CO2 storage operation at the Ketzin pilot site does not compromise reservoir, caprock and fault integrity. Chemical processes responsible for mineral trapping are expected to mainly occur during long-term stabilization at the Ketzin pilot site [4]. Hence, our previous assessment [3] was extended by integrating two long-term mineral trapping scenarios. Thereby, mineral trapping contributes to the trapping mechanisms with 11.7 % after 16,000 years of simulation in our conservative and with 30.9 % in our maximum reactivity scenarios. Dynamic flow simulations indicate that only 0.2 % of the CO2 injected (about 67,270 t CO2 in total) is in gaseous state, but structurally trapped after 16,000 years. Depending on the studied long-term scenario, CO2 dissolution is the dominating trapping mechanism with 68.9 % and 88

  17. Methodology and software to detect viral integration site hot-spots

    Science.gov (United States)

    2011-01-01

    Background Modern gene therapy methods have limited control over where a therapeutic viral vector inserts into the host genome. Vector integration can activate local gene expression, which can cause cancer if the vector inserts near an oncogene. Viral integration hot-spots or 'common insertion sites' (CIS) are scrutinized to evaluate and predict patient safety. CIS are typically defined by a minimum density of insertions (such as 2-4 within a 30-100 kb region), which unfortunately depends on the total number of observed VIS. This is problematic for comparing hot-spot distributions across data sets and patients, where the VIS numbers may vary. Results We develop two new methods for defining hot-spots that are relatively independent of data set size. Both methods operate on distributions of VIS across consecutive 1 Mb 'bins' of the genome. The first method 'z-threshold' tallies the number of VIS per bin, converts these counts to z-scores, and applies a threshold to define high density bins. The second method 'BCP' applies a Bayesian change-point model to the z-scores to define hot-spots. The novel hot-spot methods are compared with a conventional CIS method using simulated data sets and data sets from five published human studies, including the X-linked ALD (adrenoleukodystrophy), CGD (chronic granulomatous disease) and SCID-X1 (X-linked severe combined immunodeficiency) trials. The BCP analysis of the human X-linked ALD data for two patients separately (774 and 1627 VIS) and combined (2401 VIS) resulted in 5-6 hot-spots covering 0.17-0.251% of the genome and containing 5.56-7.74% of the total VIS. In comparison, the CIS analysis resulted in 12-110 hot-spots covering 0.018-0.246% of the genome and containing 5.81-22.7% of the VIS, corresponding to a greater number of hot-spots as the data set size increased. Our hot-spot methods enable one to evaluate the extent of VIS clustering, and formally compare data sets in terms of hot-spot overlap. Finally, we show that the

  18. Integration of targeted health interventions into health systems: a conceptual framework for analysis.

    Science.gov (United States)

    Atun, Rifat; de Jongh, Thyra; Secci, Federica; Ohiri, Kelechi; Adeyi, Olusoji

    2010-03-01

    The benefits of integrating programmes that emphasize specific interventions into health systems to improve health outcomes have been widely debated. This debate has been driven by narrow binary considerations of integrated (horizontal) versus non-integrated (vertical) programmes, and characterized by polarization of views with protagonists for and against integration arguing the relative merits of each approach. The presence of both integrated and non-integrated programmes in many countries suggests benefits to each approach. While the terms 'vertical' and 'integrated' are widely used, they each describe a range of phenomena. In practice the dichotomy between vertical and horizontal is not rigid and the extent of verticality or integration varies between programmes. However, systematic analysis of the relative merits of integration in various contexts and for different interventions is complicated as there is no commonly accepted definition of 'integration'-a term loosely used to describe a variety of organizational arrangements for a range of programmes in different settings. We present an analytical framework which enables deconstruction of the term integration into multiple facets, each corresponding to a critical health system function. Our conceptual framework builds on theoretical propositions and empirical research in innovation studies, and in particular adoption and diffusion of innovations within health systems, and builds on our own earlier empirical research. It brings together the critical elements that affect adoption, diffusion and assimilation of a health intervention, and in doing so enables systematic and holistic exploration of the extent to which different interventions are integrated in varied settings and the reasons for the variation. The conceptual framework and the analytical approach we propose are intended to facilitate analysis in evaluative and formative studies of-and policies on-integration, for use in systematically comparing and

  19. Integrated Site Investigation Methods and Modeling: Recent Developments at the BHRS (Invited)

    Science.gov (United States)

    Barrash, W.; Bradford, J. H.; Cardiff, M. A.; Dafflon, B.; Johnson, B. A.; Malama, B.; Thoma, M. J.

    2010-12-01

    The Boise Hydrogeophysical Research Site (BHRS) is a field-scale test facility in an unconfined aquifer with the goals of: developing cost-effective, non-invasive methods for quantitative characterization of heterogeneous aquifers using hydrologic and geophysical techniques; understanding fundamental relations and processes at multiple scales; and testing theories and models for groundwater flow and solute transport. The design of the BHRS supports a wide range of single-well, cross-hole, multiwell and multilevel hydrologic, geophysical, and combined hydrogeophysical experiments. New installations support direct and geophysical monitoring of hydrologic fluxes and states from the aquifer through the vadose zone to the atmosphere, including ET and river boundary behavior. Efforts to date have largely focused on establishing the 1D, 2D, and 3D distributions of geologic, hydrologic, and geophysical parameters which can then be used as the basis for testing methods to integrate direct and indirect data and invert for “known” parameter distributions, material boundaries, and tracer test or other system state behavior. Aquifer structure at the BHRS is hierarchical and includes layers and lenses that are recognized with geologic, hydrologic, radar, electrical, and seismic methods. Recent advances extend findings and method developments, but also highlight the need to examine assumptions and understand secular influences when designing and modeling field tests. Examples of advances and caveats include: New high-resolution 1D K profiles obtained from multi-level slug tests (inversion improves with priors for aquifer K, wellbore skin, and local presence of roots) show variable correlation with porosity and bring into question a Kozeny-Carman-type relation for much of the system. Modeling of 2D conservative tracer transport through a synthetic BHRS-like heterogeneous system shows the importance of including porosity heterogeneity (rather than assuming constant porosity for

  20. Structural integrity of heavy liquid-metal target installed in spallation neutron facility. Part 4: Consideration by fracture mechanics of target container window

    International Nuclear Information System (INIS)

    Ishikura, Syuichi; Kogawa, Hiroyuki; Futakawa, Masatoshi; Kikuchi, Kenji; Haga, Katsuhiro; Kaminaga, Masanori; Hino, Ryutaro

    2004-01-01

    Developments of the neutron scattering facility is carried out under the high-intensity proton accelerator project promoted by JAERI and KEK. To estimate the structural integrity of the heavy liquid-metal (mercury) target used as a spallation neutron source in a MW-class neutron scattering facility, static and dynamic stress (including pressure wave in mercury) behaviors due to the incident of 1MW-pulsed proton beam (Maximum heat density is 461W/cc) were analyzed. In the analyses, two type target containers with semi-cylindrical type and flat-type beam windows were used as analytical models. As a result, it is confirmed that the stress generated by the pressure wave becomes the largest at the center of the beam window, and the flat-type beam window is more advantageous from the structural viewpoint than the semi-cylindrical type beam window. It has been understood that the stress generated in the beam window by the pressure wave can be treated as the secondary stress. Then, it has been understood that the stress and the stress range generated in the target window were bellow the allowable stress level defined by the standard of JIS on the maximum stress and fatigue strength. It has been experimentally confirmed that a cavitation was generated by generating the negative pressure in mercury near the target beam window and a collapse of cavitation damaged to the target container material, as pits. Then, the fracture mechanical analyses were carried out on the pit and a crack on pit tip. Consequently, it was clarified that the crack would not propagate because the inner surface of the beam window was become the compressive stress field due to the steady state thermal stress. Moreover, the evaluation technique of the cavitation which would be needed in the future was summarized. (author)

  1. Monitoring of well integrity by magnetic imaging defectoscopy (MID) at the Ketzin pilot site, Germany

    Science.gov (United States)

    Zemke, Kornelia; Liebscher, Axel; Möller, Fabian

    2017-04-01

    One of the key requirements for safe CO2 storage operation is to ensure wellbore integrity. The CO2 triggered acid in-well environment may lead to pitting and/or surface corrosion and eventually to fatigue of well casings and cementation by this giving raise to wellbore leakage. Corrosion effects are conventionally monitored by measurement of inner casing surface, internal diameter and wall thickness. Caliper logging provides inner surface and internal diameter data while ultrasonic tools measure both the internal diameter and casing thickness as well as the bonding between casing and cement. However, both tools can only monitor and characterize the most inner casing and ultrasonic tools in addition can only be applied in fluid filled wells. At the Ketzin CO2 storage test site, Germany, about 67 kt of CO2 were injected between June 2008 and August 2013 and an interdisciplinary monitoring concept was developed with focus on the storage complex, the overburden, the surface and the wellbores. Four deep wells penetrate the reservoir and their integrity has been monitored by a combination of video inspection, pulsed neutron gamma logging PNG and magnetic imaging defectoscopy MID. MID is an advanced logging method for non-destructive testing and has the great advantages that it can be operated in gas filled boreholes and that it provides information also for outer casings. The MID tool generates electromagnetic pulsed transient eddy currents and records the response of the surrounding media. The distribution and strength of the eddy-currents is then converted into averaged, depth-resolved thicknesses of the individual casings. Run in time-lapse mode, MID provides a measure to detect changes in casing thickness and therefore hints to corrosion. At Ketzin, the four deep wells haven been monitored by repeat MID logging on a roughly annual basis in cooperation with VNG Gasspeicher GmbH (VGS) and GAZPROMENERGODIAGNOSTIKA, applying their in-house MID tool. The MID based depth

  2. Repetitive, Marker-Free, Site-Specific Integration as a Novel Tool for Multiple Chromosomal Integration of DNA

    DEFF Research Database (Denmark)

    Petersen, Kia Vest; Martinussen, Jan; Jensen, Peter Ruhdal

    2013-01-01

    of a minimal bacterial attachment site (attBmin), two mutated loxP sequences (lox66 and lox71) allowing for removal of undesirable vector elements (antibiotic resistance marker), and a counterselection marker (oroP) for selection of loxP recombination on the pKV6 vector. When transformed into L. lactis...

  3. Characterization of the minimum domain required for targeting budding yeast myosin II to the site of cell division

    Directory of Open Access Journals (Sweden)

    Tolliday Nicola J

    2006-06-01

    it to be an oligomer of tentatively 3 monomers. We suggest that this is the minimum oligomeric unit (rather than the traditional myosin II dimer that would allow specific assembly to the site of cytokinesis in a manner similar to the full length molecule. The flexible hinge region also contributes to CR structural integrity and contractility.

  4. General Approach to Identifying Potential Targets for Cancer Imaging by Integrated Bioinformatics Analysis of Publicly Available Genomic Profiles

    Directory of Open Access Journals (Sweden)

    Yongliang Yang

    2011-03-01

    Full Text Available Molecular imaging has moved to the forefront of drug development and biomedical research. The identification of appropriate imaging targets has become the touchstone for the accurate diagnosis and prognosis of human cancer. Particularly, cell surface- or membrane-bound proteins are attractive imaging targets for their aberrant expression, easily accessible location, and unique biochemical functions in tumor cells. Previously, we published a literature mining of potential targets for our in-house enzyme-mediated cancer imaging and therapy technology. Here we present a simple and integrated bioinformatics analysis approach that assembles a public cancer microarray database with a pathway knowledge base for ascertaining and prioritizing upregulated genes encoding cell surface- or membrane-bound proteins, which could serve imaging targets. As examples, we obtained lists of potential hits for six common and lethal human tumors in the prostate, breast, lung, colon, ovary, and pancreas. As control tests, a number of well-known cancer imaging targets were detected and confirmed by our study. Further, by consulting gene-disease and protein-disease databases, we suggest a number of significantly upregulated genes as promising imaging targets, including cell surface-associated mucin-1, prostate-specific membrane antigen, hepsin, urokinase plasminogen activator receptor, and folate receptors. By integrating pathway analysis, we are able to organize and map “focused” interaction networks derived from significantly dysregulated entity pairs to reflect important cellular functions in disease processes. We provide herein an example of identifying a tumor cell growth and proliferation subnetwork for prostate cancer. This systematic mining approach can be broadly applied to identify imaging or therapeutic targets for other human diseases.

  5. Demosite - Demonstration of the integration of photovoltaic elements in buildings; DEMOSITE. Site de demonstration d'elements de construction photovoltaiques integres au batiment

    Energy Technology Data Exchange (ETDEWEB)

    Roecker, C.; Affolter, P.; Muller, A.N.; Ould-Yenia, A.

    2003-07-01

    This final report for the Swiss Federal Office of Energy summarises Phase 4 of the DEMOSITE project and concludes 10 years of DEMOSITE activities. The DEMOSITE project, started in 1992, demonstrates various ways of integrating photovoltaic elements in buildings by providing stands, pavilions and monitoring facilities at its site in Lausanne, Switzerland. Here, at the Swiss Federal Institute of Technology, roof-mounted installations can be found as well as mock-ups of buildings and roofing systems that also serve as covered parking facilities. The DEMOSITE web site and graphical presentations are also reviewed. Furthermore, the six newest pavilions are presented in detail. The report also presents several sets of data from measurements made on the installations and discusses the dissemination of information and results obtained from the project. A comprehensive annex provides illustrations of examples of building-integrated photovoltaics from around the world.

  6. Abundant off-target edits from site-directed RNA editing can be reduced by nuclear localization of the editing enzyme.

    Science.gov (United States)

    Vallecillo-Viejo, Isabel C; Liscovitch-Brauer, Noa; Montiel-Gonzalez, Maria Fernanda; Eisenberg, Eli; Rosenthal, Joshua J C

    2018-01-02

    Site-directed RNA editing (SDRE) is a general strategy for making targeted base changes in RNA molecules. Although the approach is relatively new, several groups, including our own, have been working on its development. The basic strategy has been to couple the catalytic domain of an adenosine (A) to inosine (I) RNA editing enzyme to a guide RNA that is used for targeting. Although highly efficient on-target editing has been reported, off-target events have not been rigorously quantified. In this report we target premature termination codons (PTCs) in messages encoding both a fluorescent reporter protein and the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein transiently transfected into human epithelial cells. We demonstrate that while on-target editing is efficient, off-target editing is extensive, both within the targeted message and across the entire transcriptome of the transfected cells. By redirecting the editing enzymes from the cytoplasm to the nucleus, off-target editing is reduced without compromising the on-target editing efficiency. The addition of the E488Q mutation to the editing enzymes, a common strategy for increasing on-target editing efficiency, causes a tremendous increase in off-target editing. These results underscore the need to reduce promiscuity in current approaches to SDRE.

  7. A Two Million Year Equatorial Paleogeomagnetic and Relative Paleointensity Record from IODP Site U1489 in the West Pacific Warm Pool: Towards an Improved Tuning Target.

    Science.gov (United States)

    Hatfield, R. G.; Stoner, J. S.; Kumagai, Y.

    2017-12-01

    appropriateness of orbital tuning and further constrain the U1489 chronology. Future plans include the measurement of the full 5 Myr sequence and integration of the RPI record with the benthic δ18O chronology over the same period to improve our understanding of the paleogeomagnetic record and provide a robust tuning target extending through the Pliocene.

  8. Contemporary evolution of resistance at the major insecticide target site gene Ace-1 by mutation and copy number variation in the malaria mosquito Anopheles gambiae

    Science.gov (United States)

    Weetman, David; Mitchell, Sara N; Wilding, Craig S; Birks, Daniel P; Yawson, Alexander E; Essandoh, John; Mawejje, Henry D; Djogbenou, Luc S; Steen, Keith; Rippon, Emily J; Clarkson, Christopher S; Field, Stuart G; Rigden, Daniel J; Donnelly, Martin J

    2015-01-01

    Functionally constrained genes are ideal insecticide targets because disruption is often fatal, and resistance mutations are typically costly. Synaptic acetylcholinesterase (AChE) is an essential neurotransmission enzyme targeted by insecticides used increasingly in malaria control. In Anopheles and Culex mosquitoes, a glycine–serine substitution at codon 119 of the Ace-1 gene confers both resistance and fitness costs, especially for 119S/S homozygotes. G119S in Anopheles gambiae from Accra (Ghana) is strongly associated with resistance, and, despite expectations of cost, resistant 119S alleles are increasing significantly in frequency. Sequencing of Accra females detected only a single Ace-1 119S haplotype, whereas 119G diversity was high overall but very low at non-synonymous sites, evidence of strong purifying selection driven by functional constraint. Flanking microsatellites showed reduced diversity, elevated linkage disequilibrium and high differentiation of 119S, relative to 119G homozygotes across up to two megabases of the genome. Yet these signals of selection were inconsistent and sometimes weak tens of kilobases from Ace-1. This unexpected finding is attributable to apparently ubiquitous amplification of 119S alleles as part of a large copy number variant (CNV) far exceeding the size of the Ace-1 gene, whereas 119G alleles were unduplicated. Ace-1 CNV was detectable in archived samples collected when the 119S allele was rare in Ghana. Multicopy amplification of resistant alleles has not been observed previously and is likely to underpin the recent increase in 119S frequency. The large CNV compromised localization of the strong selective sweep around Ace-1, emphasizing the need to integrate CNV analysis into genome scans for selection. PMID:25865270

  9. Contemporary evolution of resistance at the major insecticide target site gene Ace-1 by mutation and copy number variation in the malaria mosquito Anopheles gambiae.

    Science.gov (United States)

    Weetman, David; Mitchell, Sara N; Wilding, Craig S; Birks, Daniel P; Yawson, Alexander E; Essandoh, John; Mawejje, Henry D; Djogbenou, Luc S; Steen, Keith; Rippon, Emily J; Clarkson, Christopher S; Field, Stuart G; Rigden, Daniel J; Donnelly, Martin J

    2015-06-01

    Functionally constrained genes are ideal insecticide targets because disruption is often fatal, and resistance mutations are typically costly. Synaptic acetylcholinesterase (AChE) is an essential neurotransmission enzyme targeted by insecticides used increasingly in malaria control. In Anopheles and Culex mosquitoes, a glycine-serine substitution at codon 119 of the Ace-1 gene confers both resistance and fitness costs, especially for 119S/S homozygotes. G119S in Anopheles gambiae from Accra (Ghana) is strongly associated with resistance, and, despite expectations of cost, resistant 119S alleles are increasing significantly in frequency. Sequencing of Accra females detected only a single Ace-1 119S haplotype, whereas 119G diversity was high overall but very low at non-synonymous sites, evidence of strong purifying selection driven by functional constraint. Flanking microsatellites showed reduced diversity, elevated linkage disequilibrium and high differentiation of 119S, relative to 119G homozygotes across up to two megabases of the genome. Yet these signals of selection were inconsistent and sometimes weak tens of kilobases from Ace-1. This unexpected finding is attributable to apparently ubiquitous amplification of 119S alleles as part of a large copy number variant (CNV) far exceeding the size of the Ace-1 gene, whereas 119G alleles were unduplicated. Ace-1 CNV was detectable in archived samples collected when the 119S allele was rare in Ghana. Multicopy amplification of resistant alleles has not been observed previously and is likely to underpin the recent increase in 119S frequency. The large CNV compromised localization of the strong selective sweep around Ace-1, emphasizing the need to integrate CNV analysis into genome scans for selection. © 2015 The Authors. Molecular Ecology published by John Wiley & Sons Ltd.

  10. Principles and strategies for monitoring data collection integrity in a multi-site randomized clinical trial of a behavioral intervention.

    Science.gov (United States)

    Phillips-Salimi, Celeste R; Donovan Stickler, Molly A; Stegenga, Kristin; Lee, Melissa; Haase, Joan E

    2011-08-01

    Although treatment fidelity strategies for enhancing the integrity of behavioral interventions have been well described, little has been written about monitoring data collection integrity. This article describes the principles and strategies developed to monitor data collection integrity of the "Stories and Music for Adolescent/Young Adult Resilience During Transplant" study (R01NR008583, U10CA098543, and U10CA095861)-a multi-site Children's Oncology Group randomized clinical trial of a music therapy intervention for adolescents and young adults undergoing stem cell transplant. The principles and strategies outlined in this article provide one model for development and evaluation of a data collection integrity monitoring plan for behavioral interventions that may be adapted by investigators and may be useful to funding agencies and grant application reviewers in evaluating proposals. Copyright © 2011 Wiley Periodicals, Inc.

  11. TTP AL921102: An integrated geophysics program for non-intrusive characterization of mixed-waste landfill sites

    International Nuclear Information System (INIS)

    Hasbrouck, J.C.

    1992-11-01

    Chem-Nuclear Geotech, Inc. (Geotech), operating contractor for the US Department of Energy Grand Junction Projects Office, is conducting the Integrated Geophysics Program for Non-Intrusive Characterization of Mixed-Waste Landfill Sites (Technical Task Plan [TTP] AL921102). The TTP is part of the Mixed-Waste Landfill Integrated Demonstration (MWLID). The objective of this task was to demonstrate that an integrated program of surface geophysics can be used to effectively and nonintrusively characterize n-mixed-waste landfill sites. To accomplish this objective, integrated field demonstrations were conducted over two previously identified areas of interest (designated Areas A and B) within the MWLID test site at the Chemical Waste Landfill (CWL), Technical Area 3, at the Sandia National Laboratories, Albuquerque, New Mexico (Figures 1 and 2). Area A was centered roughly around the Chromic Acid and Organics Pits in the southeast-central portion of the landfill and Area B was centered around the ''60's Pits'' area in the northeast-central portion of the landfill. Pit locations were known in Area A and suspected in Area B. This progress report describes the geophysical surveys conducted by Geotech and presents preliminary displays and analyses. Volume 2 of this report contains the raw data for all the surveys conducted by Geotech for this TTP

  12. CRISPR/Cas9 – Mediated Precise Targeted Integration In Vivo Using a Double Cut Donor with Short Homology Arms

    Directory of Open Access Journals (Sweden)

    Xuan Yao

    2017-06-01

    Full Text Available Precisely targeted genome editing is highly desired for clinical applications. However, the widely used homology-directed repair (HDR-based genome editing strategies remain inefficient for certain in vivo applications. We here demonstrate a microhomology-mediated end-joining (MMEJ-based strategy for precisely targeted gene integration in transfected neurons and hepatocytes in vivo with efficiencies up to 20%, much higher (up to 10 fold than HDR-based strategy in adult mouse tissues. As a proof of concept of its therapeutic potential, we demonstrate the efficacy of MMEJ-based strategy in correction of Fah mutation and rescue of Fah−/− liver failure mice, offering an efficient approach for precisely targeted gene therapies.

  13. Two-step interrogation then recognition of DNA binding site by Integration Host Factor: an architectural DNA-bending protein.

    Science.gov (United States)

    Velmurugu, Yogambigai; Vivas, Paula; Connolly, Mitchell; Kuznetsov, Serguei V; Rice, Phoebe A; Ansari, Anjum

    2018-02-28

    The dynamics and mechanism of how site-specific DNA-bending proteins initially interrogate potential binding sites prior to recognition have remained elusive for most systems. Here we present these dynamics for Integration Host factor (IHF), a nucleoid-associated architectural protein, using a μs-resolved T-jump approach. Our studies show two distinct DNA-bending steps during site recognition by IHF. While the faster (∼100 μs) step is unaffected by changes in DNA or protein sequence that alter affinity by >100-fold, the slower (1-10 ms) step is accelerated ∼5-fold when mismatches are introduced at DNA sites that are sharply kinked in the specific complex. The amplitudes of the fast phase increase when the specific complex is destabilized and decrease with increasing [salt], which increases specificity. Taken together, these results indicate that the fast phase is non-specific DNA bending while the slow phase, which responds only to changes in DNA flexibility at the kink sites, is specific DNA kinking during site recognition. Notably, the timescales for the fast phase overlap with one-dimensional diffusion times measured for several proteins on DNA, suggesting that these dynamics reflect partial DNA bending during interrogation of potential binding sites by IHF as it scans DNA.

  14. An integrated approach for estimating oil volume in petroleum-contaminated sites: a North American case study

    International Nuclear Information System (INIS)

    Chen, Z.; Huang, G.H.; Chakma, A.

    1999-01-01

    An integrated approach for estimating the distribution of light nonaqueous phase liquids (LNAPLs) such as oil spill and leakage in a porous media is proposed, based on a study at a site located in western Canada. The site has one original release source that is a flare pit, with on-site soil and groundwater seriously contaminated by petroleum products spilled over the past two decades. Results of the study show that soil properties and site characteristics have significant impact on the spreading of contaminants which affect the estimation of contaminant volume. Although the LNAPLs in the subsurface do not appear as a distinct layer, and the volume and distribution differ from site to site, the proposed method offers insight into the contamination details and is, therefore, considered to be an effective and convenient tool for obtaining a reasonable estimate of residual oil volume in the subsurface. Results could also be used in designing an enhanced recovery scheme for the site under study, as well as in designing multi-component models of the subsurface contamination for the purpose of risk assessment. 13 refs., 2 tabs., 2 figs

  15. A mixed integer linear programming model for integrating thermodynamic cycles for waste heat exploitation in process sites

    International Nuclear Information System (INIS)

    Oluleye, Gbemi; Smith, Robin

    2016-01-01

    Highlights: • MILP model developed for integration of waste heat recovery technologies in process sites. • Five thermodynamic cycles considered for exploitation of industrial waste heat. • Temperature and quantity of multiple waste heat sources considered. • Interactions with the site utility system considered. • Industrial case study presented to illustrate application of the proposed methodology. - Abstract: Thermodynamic cycles such as organic Rankine cycles, absorption chillers, absorption heat pumps, absorption heat transformers, and mechanical heat pumps are able to utilize wasted thermal energy in process sites for the generation of electrical power, chilling and heat at a higher temperature. In this work, a novel systematic framework is presented for optimal integration of these technologies in process sites. The framework is also used to assess the best design approach for integrating waste heat recovery technologies in process sites, i.e. stand-alone integration or a systems-oriented integration. The developed framework allows for: (1) selection of one or more waste heat sources (taking into account the temperatures and thermal energy content), (2) selection of one or more technology options and working fluids, (3) selection of end-uses of recovered energy, (4) exploitation of interactions with the existing site utility system and (5) the potential for heat recovery via heat exchange is also explored. The methodology is applied to an industrial case study. Results indicate a systems-oriented design approach reduces waste heat by 24%; fuel consumption by 54% and CO_2 emissions by 53% with a 2 year payback, and stand-alone design approach reduces waste heat by 12%; fuel consumption by 29% and CO_2 emissions by 20.5% with a 4 year payback. Therefore, benefits from waste heat utilization increase when interactions between the existing site utility system and the waste heat recovery technologies are explored simultaneously. The case study also shows

  16. Simultaneous and Sequential Integration by Cre/loxP Site-Specific Recombination in Saccharomyces cerevisiae.

    Science.gov (United States)

    Choi, Ho-Jung; Kim, Yeon-Hee

    2018-05-28

    A Cre/ loxP -δ-integration system was developed to allow sequential and simultaneous integration of a multiple gene expression cassette in Saccharomyces cerevisiae . To allow repeated integrations, the reusable Candida glabrata MARKER ( CgMARKER ) carrying loxP sequences was used, and the integrated CgMARKER was efficiently removed by inducing Cre recombinase. The XYLP and XYLB genes encoding endoxylanase and β-xylosidase, respectively, were used as model genes for xylan metabolism in this system, and the copy number of these genes was increased to 15.8 and 16.9 copies/cell, respectively, by repeated integration. This integration system is a promising approach for the easy construction of yeast strains with enhanced metabolic pathways through multicopy gene expression.

  17. Prediction of the flooding process at the Ronneburg site - results of an integrated approach

    International Nuclear Information System (INIS)

    Paul, M.; Saenger, H.-J.; Snagowski, S.; Maerten, H.; Eckart, M.

    1998-01-01

    The flooding process of the Ronneburg uranium mine (WISMUT) was initiated at the turn of the year 1997 to 1998. In order to prepare the flooding process and to derive and optimize technological measures an integrated modelling approach was chosen which includes several coupled modules. The most important issues to be answered are: (1) prediction of the flooding time (2) prediction of the groundwater level at the post-flooding stage, assessment of amount, location and quality of flooding waters entering the receiving streams at the final stage (3) water quality prediction within the mine during the flooding process (4) definition of technological measures and assessment of their efficiency A box model which includes the three-dimensional distribution of the cavity volume in the mine represents the model core. The model considers the various types of dewatered cavity volumes for each mine level / mining field and the degree of vertical and horizontal connection between the mining fields. Different types of open mine space as well as the dewatered geological pore and joint volume are considered taking into account the contour of the depression cone prior to flooding and the characteristics of the different rock types. Based on the mine water balance and the flooding technology the model predicts the rise of the water table over time during the flooding process for each mine field separately. In order to predict the mine water quality and the efficiency of in-situ water treatment the box model was linked to a geochemical model (PHREEQC). A three-dimensional flow model is used to evaluate the post-flooding situation at the Ronneburg site. This model is coupled to the box model. The modelling results of various flooding scenarios show that a prediction of the post-flooding geohydraulic situation is possible despite of uncertainties concerning the input parameters which still exist. The post-flooding water table in the central part of the Ronneburg mine will be 270 m

  18. Carbon emission reduction targeting through process integration and fuel switching with mathematical modeling

    International Nuclear Information System (INIS)

    Tiew, B.J.; Shuhaimi, M.; Hashim, H.

    2012-01-01

    Highlights: ► CO 2 emissions reduction targeting for existing plant were categorized into three groups. ► Model for CO 2 emissions reduction targeting via combination approach was developed. ► Effect of combination approach onto HEN area efficiency was discussed. ► Proposed execution strategy can avoid HEN area efficiency deterioration. -- Abstract: Carbon emission reduction targeting is an important and effective effort for industry to contribute in controlling greenhouse gases concentration in atmosphere. Graphical approach has been proposed for CO 2 emissions reduction targeting via HEN retrofit and fuel switching. However, it involves potentially time consuming manual procedures and the quality of solutions produced greatly depends on designer’s experience and judgment. Besides, graphical approach hardly account for the cost factor during the design phase, thus potentially generate complex design. This paper introduces an MINLP model for simultaneous CO 2 emissions reduction targeting via fuel switching and HEN retrofit. A sequential model execution was proposed along with the proposed model. The application of the model on a crude preheat train case study has demonstrated its workability to generate optimal solution for targeted CO 2 emissions reduction at minimum payback period.

  19. The Sensorless Pore Module of Voltage-gated K+ Channel Family 7 Embodies the Target Site for the Anticonvulsant Retigabine.

    Science.gov (United States)

    Syeda, Ruhma; Santos, Jose S; Montal, Mauricio

    2016-02-05

    KCNQ (voltage-gated K(+) channel family 7 (Kv7)) channels control cellular excitability and underlie the K(+) current sensitive to muscarinic receptor signaling (the M current) in sympathetic neurons. Here we show that the novel anti-epileptic drug retigabine (RTG) modulates channel function of pore-only modules (PMs) of the human Kv7.2 and Kv7.3 homomeric channels and of Kv7.2/3 heteromeric channels by prolonging the residence time in the open state. In addition, the Kv7 channel PMs are shown to recapitulate the single-channel permeation and pharmacological specificity characteristics of the corresponding full-length proteins in their native cellular context. A mutation (W265L) in the reconstituted Kv7.3 PM renders the channel insensitive to RTG and favors the conductive conformation of the PM, in agreement to what is observed when the Kv7.3 mutant is heterologously expressed. On the basis of the new findings and homology models of the closed and open conformations of the Kv7.3 PM, we propose a structural mechanism for the gating of the Kv7.3 PM and for the site of action of RTG as a Kv7.2/Kv7.3 K(+) current activator. The results validate the modular design of human Kv channels and highlight the PM as a high-fidelity target for drug screening of Kv channels. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. A systematic review of social networking sites: innovative platforms for health research targeting adolescents and young adults.

    Science.gov (United States)

    Park, Bu Kyung; Calamaro, Christina

    2013-09-01

    To review the evidence to determine if social networking sites (SNS) are effective tools for health research in the adolescent and young adult populations. Systematic review of published research articles focused on use of SNS for youth health research. Seventeen articles were selected that met the following criteria: used SNS at any stage of study, participants between 13 and 25 years of age, English language, and both international and national studies. Reviewers categorized selected studies based on the way SNS were used. Utilization of SNS for effectively implementing research with adolescents and young adults include (a) recruitment, (b) intervention, and (c) measurement. Four findings about advantages of using SNS apparent in this review are (a) ease of access to youth, (b) cost effectiveness in recruitment, (c) ease of intervention, and (d) reliable screening venue of mental status and high-risk behaviors. Although this literature review showed relatively minimal research to date on the use of SNS for research targeting adolescents and young adults, the impact of using SNS for health research is of considerable importance for researchers as well as participants. With careful focus, SNS can become a valuable platform to access, recruit, and deliver health interventions in a cost-effective manner to youth populations as well as hard-to-reach minority or underserved populations. The evidence demonstrates the usefulness of SNS as innovative platforms for health promotion among adolescents and young adults. © 2013 Sigma Theta Tau International.

  1. Systems integration of biodefense omics data for analysis of pathogen-host interactions and identification of potential targets.

    Directory of Open Access Journals (Sweden)

    Peter B McGarvey

    2009-09-01

    Full Text Available The NIAID (National Institute for Allergy and Infectious Diseases Biodefense Proteomics program aims to identify targets for potential vaccines, therapeutics, and diagnostics for agents of concern in bioterrorism, including bacterial, parasitic, and viral pathogens. The program includes seven Proteomics Research Centers, generating diverse types of pathogen-host data, including mass spectrometry, microarray transcriptional profiles, protein interactions, protein structures and biological reagents. The Biodefense Resource Center (www.proteomicsresource.org has developed a bioinformatics framework, employing a protein-centric approach to integrate and support mining and analysis of the large and heterogeneous data. Underlying this approach is a data warehouse with comprehensive protein + gene identifier and name mappings and annotations extracted from over 100 molecular databases. Value-added annotations are provided for key proteins from experimental findings using controlled vocabulary. The availability of pathogen and host omics data in an integrated framework allows global analysis of the data and comparisons across different experiments and organisms, as illustrated in several case studies presented here. (1 The identification of a hypothetical protein with differential gene and protein expressions in two host systems (mouse macrophage and human HeLa cells infected by different bacterial (Bacillus anthracis and Salmonella typhimurium and viral (orthopox pathogens suggesting that this protein can be prioritized for additional analysis and functional characterization. (2 The analysis of a vaccinia-human protein interaction network supplemented with protein accumulation levels led to the identification of human Keratin, type II cytoskeletal 4 protein as a potential therapeutic target. (3 Comparison of complete genomes from pathogenic variants coupled with experimental information on complete proteomes allowed the identification and

  2. A remarkable enhancement of selectivity towards versatile analytes by a strategically integrated H-bonding site containing phase.

    Science.gov (United States)

    Mallik, Abul K; Qiu, Hongdeng; Kuwahara, Yutaka; Takafuji, Makoto; Ihara, Hirotaka

    2015-09-28

    A double β-alanylated L-glutamide-derived organic phase has been newly designed and synthesized in such a way that integrated H-bonding (interaction) sites make it very suitable for the separation of versatile analytes, including shape-constrained isomers, and nonpolar, polar and basic compounds. The β-alanine residues introduced into two long-chain alkyl group moieties provide ordered polar groups through H-bonding among the amide groups.

  3. Signal integration: a framework for understanding the efficacy of therapeutics targeting the human EGFR family

    Science.gov (United States)

    Shepard, H. Michael; Brdlik, Cathleen M.; Schreiber, Hans

    2008-01-01

    The human EGFR (HER) family is essential for communication between many epithelial cancer cell types and the tumor microenvironment. Therapeutics targeting the HER family have demonstrated clinical success in the treatment of diverse epithelial cancers. Here we propose that the success of HER family–targeted monoclonal antibodies in cancer results from their ability to interfere with HER family consolidation of signals initiated by a multitude of other receptor systems. Ligand/receptor systems that initiate these signals include cytokine receptors, chemokine receptors, TLRs, GPCRs, and integrins. We further extrapolate that improvements in cancer therapeutics targeting the HER family are likely to incorporate mechanisms that block or reverse stromal support of malignant progression by isolating the HER family from autocrine and stromal influences. PMID:18982164

  4. Some interactive factors affecting trench-cover integrity on low-level waste sites

    International Nuclear Information System (INIS)

    Hakonson, T.E.; Lane, L.J.; Steger, J.G.; DePoorter, G.L.

    1982-01-01

    This paper describes important mechanisms by which radionuclide can be transported from low-level waste disposal sites into biological pathways, discuss interactions of abiotic and biotic processes, and recommends environmental characteristics that should be measured to design sites that minimize this transport. Past experience at shallow land burial sites for low-level radioactive wastes suggest that occurrences of waste exposure and radionuclide transport are often related to inadequate trench cover designs. Meeting performance standards at low-level waste sites can only be achieved by recognizing that physical, chemical, and biological processes operating on and in a trench cover profile are highly interactive. Failure to do so can lead to improper design criteria and subsequent remedial action procedures that can adversely affect site stability. Based upon field experiments and computer modeling, recommendations are made on site characteristics that require measurement in order to design systems that reduce surface runoff and erosion, manage soil moisture and biota in the cover profile to maximize evapotranspiration and minimize percolation, and place bounds on the intrusion potential of plants and animals into the waste material. Major unresolved problems include developing probabilistic approaches that include climatic variability, improved knowledge of soil-water-plant-erosion relationships, development of practical vegetation establishment and maintenance procedures, prediction and quantification of site potential and plant succession, and understanding the interaction of processes occurring on and in the cover profile with deeper subsurface processes

  5. Digital Reconstruction of AN Archaeological Site Based on the Integration of 3d Data and Historical Sources

    Science.gov (United States)

    Guidi, G.; Russo, M.; Angheleddu, D.

    2013-02-01

    The methodology proposed in this paper in based on an integrated approach for creating a 3D digital reconstruction of an archaeological site, using extensively the 3D documentation of the site in its current state, followed by an iterative interaction between archaeologists and digital modelers, leading to a progressive refinement of the reconstructive hypotheses. The starting point of the method is the reality-based model, which, together with ancient drawings and documents, is used for generating the first reconstructive step. Such rough approximation of a possible architectural structure can be annotated through archaeological considerations that has to be confronted with geometrical constraints, producing a reduction of the reconstructive hypotheses to a limited set, each one to be archaeologically evaluated. This refinement loop on the reconstructive choices is iterated until the result become convincing by both points of view, integrating in the best way all the available sources. The proposed method has been verified on the ruins of five temples in the My Son site, a wide archaeological area located in central Vietnam. The integration of 3D surveyed data and historical documentation has allowed to support a digital reconstruction of not existing architectures, developing their three-dimensional digital models step by step, from rough shapes to highly sophisticate virtual prototypes.

  6. Beyond Information Architecture: A Systems Integration Approach to Web-site Design

    Directory of Open Access Journals (Sweden)

    Krisellen Maloney

    2017-09-01

    Full Text Available Users' needs and expectations regarding access to information have fundamentally changed, creating a disconnect between how users expect to use a library Web site and how the site was designed. At the same time, library technical infrastructures include legacy systems that were not designedf or the Web environment. The authors propose a framework that combines elements of information architecture with approaches to incremental system design and implementation. The framework allows for the development of a Web site that is responsive to changing user needs, while recognizing the need for libraries to adopt a cost-effective approach to implementation and maintenance.

  7. 3-D electromagnetic modeling for very early time sounding of shallow targets using integral equations

    International Nuclear Information System (INIS)

    Xiong, Z.; Tripp, A.C.

    1994-01-01

    This paper presents an integral equation algorithm for 3D EM modeling at high frequencies for applications in engineering an environmental studies. The integral equation method remains the same for low and high frequencies, but the dominant roles of the displacements currents complicate both numerical treatments and interpretations. With singularity extraction technique they successively extended the application of the Hankel filtering technique to the computation of Hankel integrals occurring in high frequency EM modeling. Time domain results are calculated from frequency domain results via Fourier transforms. While frequency domain data are not obvious for interpretations, time domain data show wave-like pictures that resemble seismograms. Both 1D and 3D numerical results show clearly the layer interfaces

  8. Development of an integrated economic decision-support tool for the remediation of contaminated sites. Overview note

    International Nuclear Information System (INIS)

    Samson, R.; Bage, G.

    2004-05-01

    This report concludes the first design phase of an innovative software tool which, when completed, will allow managers of contaminated sites to make optimal decisions with respect to site remediation. The principal objective of the project was to develop the foundations for decision-support software (SITE VII) which will allow a comprehensive and rigorous approach to the comparison of remediation scenarios for sites contaminated with petroleum hydrocarbons. During this first phase of the project, the NSERC Industrial Chair in Site Remediation and Management of the Ecole Polytechnique de Montreal has completed four stages in the design of a decision-support tool that could be applied by any site manager using a simple computer. These four stages are: refinement of a technico-economic evaluation model; development of databases for five soil remediation technologies; design of a structure for integration of the databases with the technico-economic model; and simulation of the remediation of a contaminated site using the technico-economic model and a subset of the databases. In the interim report, the emphasis was placed on the development of the technico-economic model, supported by a very simple, single-technology simulation of remediation. In the present report, the priority is placed on the integration of the different components required for the creation of decision-support software based on the technico-economic model. An entire chapter of this report is devoted to elaborating the decision structure of the software. The treatment of information within the software is shown schematically and explained step-by-step. Five remediation technologies are handled by the software: three in-situ technologies (bio-venting, bio-slurping, bio-sparging) and two ex-situ technologies (thermal desorption, Bio-pile treatment). A technology file has been created for each technology, containing a brief description of the technology, its performance, its criteria of applicability

  9. Cavity quantum electrodynamics studies with site-controlled InGaAs quantum dots integrated into high quality microcavities

    DEFF Research Database (Denmark)

    Reitzenstein, S.; Schneider, C.; Albert, F.

    2011-01-01

    Semiconductor quantum dots (QDs) are fascinating nanoscopic structures for photonics and future quantum information technology. However, the random position of self-organized QDs inhibits a deterministic coupling in devices relying on cavity quantum electrodynamics (cQED) effects which complicates......, e.g., the large scale fabrication of quantum light sources. As a result, large efforts focus on the growth and the device integration of site-controlled QDs. We present the growth of low density arrays of site-controlled In(Ga)As QDs where shallow etched nanoholes act as nucleation sites...... linewidth, the oscillator strength and the quantum efficiency. A stacked growth of strain coupled SCQDs forming on wet chemically etched nanoholes provide the smallest linewidth with an average value of 210 μeV. Using time resolved photoluminescence studies on samples with a varying thickness of the capping...

  10. Integrated test plan ResonantSonic drilling system technology demonstration-1995, at the Hanford Site: Revision 1

    International Nuclear Information System (INIS)

    McLellan, G.W.

    1994-01-01

    This integrated test plan describes the demonstration test of the ResonantSonic drilling system. This demonstration is part of the Office of Technology Development's Volatile Organic Compound Arid Integrated Demonstration (VOC-Arid ID). Two main purposes of this demonstration are (1) to continue testing the ResonantSonic drilling system compatibility with the Hanford Site waste characterization programs, and (2) to transfer this method for use at the Hanford Site, other government sites, and the private sector. The ResonantSonic method is a dry drilling technique. Field testing of this method began in July 1993. During the next four months, nine holes were drilled, and continuous core samples were retrieved. Penetration rates were 2 to 3 times the baseline, and the operational downtime rate was less than 10%. Successfully demonstrated equipment refinements included a prototype 300 series ResonantSonic head, a new drill rod design for 18-centimeter diameter pipe, and an automated pipe handling system. Various configurations of sampling equipment and drill bits were tested, depending on geologic conditions. The principal objective of the VOC-Arid ID is to determine the viability of emerging technologies that can be used to characterize, remediate, and/or monitor arid or semiarid sites containing VOCs (e.g., carbon tetrachloride) with or without associated metal and radionuclide contamination

  11. Development of an Integrated Natural Barrier Database System for Site Evaluation of a Deep Geologic Repository in Korea - 13527

    International Nuclear Information System (INIS)

    Jung, Haeryong; Lee, Eunyong; Jeong, YiYeong; Lee, Jeong-Hwan

    2013-01-01

    Korea Radioactive-waste Management Corporation (KRMC) established in 2009 has started a new project to collect information on long-term stability of deep geological environments on the Korean Peninsula. The information has been built up in the integrated natural barrier database system available on web (www.deepgeodisposal.kr). The database system also includes socially and economically important information, such as land use, mining area, natural conservation area, population density, and industrial complex, because some of this information is used as exclusionary criteria during the site selection process for a deep geological repository for safe and secure containment and isolation of spent nuclear fuel and other long-lived radioactive waste in Korea. Although the official site selection process has not been started yet in Korea, current integrated natural barrier database system and socio-economic database is believed that the database system will be effectively utilized to narrow down the number of sites where future investigation is most promising in the site selection process for a deep geological repository and to enhance public acceptance by providing readily-available relevant scientific information on deep geological environments in Korea. (authors)

  12. Design and integration of components for site specific control of fertilizer application

    NARCIS (Netherlands)

    Bergeijk, van J.

    2001-01-01

    Keywords: Precision Agriculture, Site Specific Agriculture, Global Positioning System, GPS, Fertilizer Application, Information System.

    Spatial and temporal variability in soil, crop and climate characteristics results in non optimal use of fertilizers when the application

  13. Green Remediation Best Management Practices: Integrating Renewable Energy into Site Cleanup

    Science.gov (United States)

    The U.S. Environmental Protection Agency (EPA) Principles for Greener Cleanups outline the Agency's policy for evaluating and minimizing the environmental 'footprint' of activities undertaken when cleaning up a contaminated site.

  14. Argonne's Expedited Site Characterization: An integrated approach to cost- and time-effective remedial investigation

    International Nuclear Information System (INIS)

    Burton, J.C.; Walker, J.L.; Aggarwal, P.K.; Meyer, W.T.

    1995-01-01

    Argonne National Laboratory has developed a methodology for remedial site investigation that has proven to be both technically superior to and more cost- and time-effective than traditional methods. This methodology is referred to as the Argonne Expedited Site Characterization (ESC). Quality is the driving force within the process. The Argonne ESC process is abbreviated only in time and cost and never in terms of quality. More usable data are produced with the Argonne ESC process than with traditional site characterization methods that are based on statistical-grid sampling and multiple monitoring wells. This paper given an overview of the Argonne ESC process and compares it with traditional methods for site characterization. Two examples of implementation of the Argonne ESC process are discussed to illustrate the effectiveness of the process in CERCLA (Comprehensive Environmental Response, Compensation, and Liability Act) and RCRA (Resource Conservation and Recovery Act) programs

  15. Clinical roundtable monograph: unmet needs in the treatment of chronic lymphocytic leukemia: integrating a targeted approach.

    Science.gov (United States)

    O'Brien, Susan M; Furman, Richard R; Byrd, John C; Smith, Ashbel

    2014-01-01

    Chronic lymphocytic leukemia (CLL) is the most frequently diagnosed hematologic malignancy in the United States. Although several features can be useful in the diagnosis of CLL, the most important is the immunophenotype.Two staging systems--the Binet system and the Rai classification--are used to assess risk. After diagnosis, the first major therapeutic decision is when to initiate therapy, as a watchful waiting approach is often appropriate for patients with asymptomatic disease. Once a patient has met the criteria for treatment, the choice of therapy is the next major decision. Younger patients (<65 years) often receive more aggressive treatment that typically consists of cytotoxic chemotherapy. There is a great unmet need concerning treatment of older patients with CLL, who often present with more comorbid conditions that can decrease their ability to tolerate particular regimens. The current standard of care for older patients with CLL is rituximab plus chlorambucil. The concept of targeted agents is currently an area of intense interest in CLL. The Bruton’s tyrosine kinase inhibitor ibrutinib is the targeted agent that is furthest along in clinical development. It is associated with an overall survival rate of 83%. Idelalisib targets the phosphatidyl inositol 3-kinase and is under evaluation in pivotal trials. Targeted agents offer much promise in terms of efficacy, toxicity, and oral availability. They will change the management of patients with CLL.

  16. The fuzzy TOPSIS and generalized Choquet fuzzy integral algorithm for nuclear power plant site selection - a case study from Turkey

    International Nuclear Information System (INIS)

    Kurt, Ünal

    2014-01-01

    The location selection for nuclear power plant (NPP) is a strategic decision, which has significant impact on the economic operation of the plant and sustainable development of the region. This paper proposes fuzzy TOPSIS and generalized Choquet fuzzy integral algorithm for evaluation and selection of optimal locations for NPP in Turkey. Many sub-criteria such as geological, social, touristic, transportation abilities, cooling water capacity and nearest to consumptions markets are taken into account. Among the evaluated locations, according to generalized Choquet fuzzy integral method, Inceburun–Sinop was selected as a study site due to its highest performance and meeting most of the investigated criteria. The Inceburun-Sinop is selected by generalized Choquet fuzzy integral and fuzzy TOPSIS Iğneada–Kırklareli took place in the first turn. The Mersin–Akkuyu is not selected in both methods. (author)

  17. Modelling site-specific N2O emission factors from Austrian agricultural soils for targeted mitigation measures (NitroAustria)

    Science.gov (United States)

    Amon, Barbara; Zechmeister-Boltenstern, Sophie; Kasper, Martina; Foldal, Cecilie; Schiefer, Jasmin; Kitzler, Barbara; Schwarzl, Bettina; Zethner, Gerhard; Anderl, Michael; Sedy, Katrin; Gaugitsch, Helmut; Dersch, Georg; Baumgarten, Andreas; Haas, Edwin; Kiese, Ralf

    2016-04-01

    Results from a previous project "FarmClim" highlight that the IPCC default emission factor is not able to reflect region specific N2O emissions from Austrian arable soils. The methodology is limited in identifying hot spots and hot moments of N2O emissions. When estimations are based on default emission factors no recommendations can be given on optimisation measures that would lead to a reduction of soil N2O emissions. The better the knowledge is about Nitrogen and Carbon budgets in Austrian agricultural managed soils the better the situation can be reflected in the Austrian GHG emission inventory calculations. Therefore national and regionally modelled emission factors should improve the evidence for national deviation from the IPCC default emission factors and reduce the uncertainties. The overall aim of NitroAustria is to identify the drivers for N2O emissions on a regional basis taking different soil types, climate, and agricultural management into account. We use the LandscapeDNDC model to update the N2O emission factors for N fertilizer and animal manure applied to soils. Key regions in Austria were selected and region specific N2O emissions calculated. The model runs at sub-daily time steps and uses data such as maximum and minimum air temperature, precipitation, radiation, and wind speed as meteorological drivers. Further input data are used to reflect agricultural management practices, e.g., planting/harvesting, tillage, fertilizer application, irrigation and information on soil and vegetation properties for site characterization and model initialization. While at site scale, arable management data (crop cultivation, rotations, timings etc.) is obtained by experimental data from field trials or observations, at regional scale such data need to be generated using region specific proxy data such as land use and management statistics, crop cultivations and yields, crop rotations, fertilizer sales, manure resulting from livestock units etc. The farming

  18. The gravity of pollination: integrating at-site features into spatial analysis of contemporary pollen movement.

    Science.gov (United States)

    DiLeo, Michelle F; Siu, Jenna C; Rhodes, Matthew K; López-Villalobos, Adriana; Redwine, Angela; Ksiazek, Kelly; Dyer, Rodney J

    2014-08-01

    Pollen-mediated gene flow is a major driver of spatial genetic structure in plant populations. Both individual plant characteristics and site-specific features of the landscape can modify the perceived attractiveness of plants to their pollinators and thus play an important role in shaping spatial genetic variation. Most studies of landscape-level genetic connectivity in plants have focused on the effects of interindividual distance using spatial and increasingly ecological separation, yet have not incorporated individual plant characteristics or other at-site ecological variables. Using spatially explicit simulations, we first tested the extent to which the inclusion of at-site variables influencing local pollination success improved the statistical characterization of genetic connectivity based upon examination of pollen pool genetic structure. The addition of at-site characteristics provided better models than those that only considered interindividual spatial distance (e.g. IBD). Models parameterized using conditional genetic covariance (e.g. population graphs) also outperformed those assuming panmixia. In a natural population of Cornus florida L. (Cornaceae), we showed that the addition of at-site characteristics (clumping of primary canopy opening above each maternal tree and maternal tree floral output) provided significantly better models describing gene flow than models including only between-site spatial (IBD) and ecological (isolation by resistance) variables. Overall, our results show that including interindividual and local ecological variation greatly aids in characterizing landscape-level measures of contemporary gene flow. © 2014 John Wiley & Sons Ltd.

  19. Design of a novel integration-deficient lentivector technology that incorporates genetic and posttranslational elements to target human dendritic cells.

    Science.gov (United States)

    Tareen, Semih U; Kelley-Clarke, Brenna; Nicolai, Christopher J; Cassiano, Linda A; Nelson, Lisa T; Slough, Megan M; Vin, Chintan D; Odegard, Jared M; Sloan, Derek D; Van Hoeven, Neal; Allen, James M; Dubensky, Thomas W; Robbins, Scott H

    2014-03-01

    As sentinels of the immune system, dendritic cells (DCs) play an essential role in regulating cellular immune responses. One of the main challenges of developing DC-targeted therapies includes the delivery of antigen to DCs in order to promote the activation of antigen-specific effector CD8 T cells. With the goal of creating antigen-directed immunotherapeutics that can be safely administered directly to patients, Immune Design has developed a platform of novel integration-deficient lentiviral vectors that target and deliver antigen-encoding nucleic acids to human DCs. This platform, termed ID-VP02, utilizes a novel genetic variant of a Sindbis virus envelope glycoprotein with posttranslational carbohydrate modifications in combination with Vpx, a SIVmac viral accessory protein, to achieve efficient targeting and transduction of human DCs. In addition, ID-VP02 incorporates safety features in its design that include two redundant mechanisms to render ID-VP02 integration-deficient. Here, we describe the characteristics that allow ID-VP02 to specifically transduce human DCs, and the advances that ID-VP02 brings to conventional third-generation lentiviral vector design as well as demonstrate upstream production yields that will enable manufacturing feasibility studies to be conducted.

  20. TargetM6A: Identifying N6-Methyladenosine Sites From RNA Sequences via Position-Specific Nucleotide Propensities and a Support Vector Machine.

    Science.gov (United States)

    Li, Guang-Qing; Liu, Zi; Shen, Hong-Bin; Yu, Dong-Jun

    2016-10-01

    As one of the most ubiquitous post-transcriptional modifications of RNA, N 6 -methyladenosine ( [Formula: see text]) plays an essential role in many vital biological processes. The identification of [Formula: see text] sites in RNAs is significantly important for both basic biomedical research and practical drug development. In this study, we designed a computational-based method, called TargetM6A, to rapidly and accurately target [Formula: see text] sites solely from the primary RNA sequences. Two new features, i.e., position-specific nucleotide/dinucleotide propensities (PSNP/PSDP), are introduced and combined with the traditional nucleotide composition (NC) feature to formulate RNA sequences. The extracted features are further optimized to obtain a much more compact and discriminative feature subset by applying an incremental feature selection (IFS) procedure. Based on the optimized feature subset, we trained TargetM6A on the training dataset with a support vector machine (SVM) as the prediction engine. We compared the proposed TargetM6A method with existing methods for predicting [Formula: see text] sites by performing stringent jackknife tests and independent validation tests on benchmark datasets. The experimental results show that the proposed TargetM6A method outperformed the existing methods for predicting [Formula: see text] sites and remarkably improved the prediction performances, with MCC = 0.526 and AUC = 0.818. We also provided a user-friendly web server for TargetM6A, which is publicly accessible for academic use at http://csbio.njust.edu.cn/bioinf/TargetM6A.

  1. A nicotinic acetylcholine receptor mutation conferring target-site resistance to imidacloprid in Nilaparvata lugens (brown planthopper).

    Science.gov (United States)

    Liu, Zewen; Williamson, Martin S; Lansdell, Stuart J; Denholm, Ian; Han, Zhaojun; Millar, Neil S

    2005-06-14

    Neonicotinoids, such as imidacloprid, are nicotinic acetylcholine receptor (nAChR) agonists with potent insecticidal activity. Since its introduction in the early 1990s, imidacloprid has become one of the most extensively used insecticides for both crop protection and animal health applications. As with other classes of insecticides, resistance to neonicotinoids is a significant threat and has been identified in several pest species, including the brown planthopper, Nilaparvata lugens, a major rice pest in many parts of Asia. In this study, radioligand binding experiments have been conducted with whole-body membranes prepared from imidacloprid-susceptible and imidacloprid-resistant strains of N. lugens. The results reveal a much higher level of [3H]imidacloprid-specific binding to the susceptible strain than to the resistant strain (16.7 +/- 1.0 and 0.34 +/- 0.21 fmol/mg of protein, respectively). With the aim of understanding the molecular basis of imidacloprid resistance, five nAChR subunits (Nlalpha1-Nlalpha4 and Nlbeta1) have been cloned from N. lugens.A comparison of nAChR subunit genes from imidacloprid-sensitive and imidacloprid-resistant populations has identified a single point mutation at a conserved position (Y151S) in two nAChR subunits, Nlalpha1 and Nlalpha3. A strong correlation between the frequency of the Y151S point mutation and the level of resistance to imidacloprid has been demonstrated by allele-specific PCR. By expression of hybrid nAChRs containing N. lugens alpha and rat beta2 subunits, evidence was obtained that demonstrates that mutation Y151S is responsible for a substantial reduction in specific [3H]imidacloprid binding. This study provides direct evidence for the occurrence of target-site resistance to a neonicotinoid insecticide.

  2. Multiple insecticide resistance mechanisms involving metabolic changes and insensitive target sites selected in anopheline vectors of malaria in Sri Lanka

    Directory of Open Access Journals (Sweden)

    Karunaratne SHP Parakrama

    2008-08-01

    Full Text Available Abstract Background The current status of insecticide resistance and the underlying resistance mechanisms were studied in the major vector of malaria, Anopheles culicifacies, and the secondary vector, Anopheles subpictus in five districts (Anuradhapura, Kurunegala, Moneragala, Puttalam and Trincomalee of Sri Lanka. Eight other anophelines, Anopheles annularis, Anopheles barbirostris, Anopheles jamesii, Anopheles nigerrimus, Anopheles peditaeniatus, Anopheles tessellatus, Anopheles vagus and Anopheles varuna from Anuradhapura district were also tested. Methods Adult females were exposed to the WHO discriminating dosages of DDT, malathion, fenitrothion, propoxur, λ-cyhalothrin, cyfluthrin, cypermethrin, deltamethrin, permethrin and etofenprox. The presence of metabolic resistance by esterase, glutathione S-transferase (GST and monooxygenase-based mechanisms, and the sensitivity of the acetylcholinesterase target site were assessed using synergists, and biochemical, and metabolic techniques. Results All the anopheline species had high DDT resistance. All An. culicifacies and An. subpictus populations were resistant to malathion, except An. culicifacies from Kurunegala, where there was no malathion carboxylesterase activity. Kurunegala and Puttalam populations of An. culicifacies were susceptible to fenitrothion. All the An. culicifacies populations were susceptible to carbamates. Both species were susceptible to the discriminating dosages of cypermethrin and cyfluthrin, but had different levels of resistance to other pyrethroids. Of the 8 other anophelines, only An. nigerrimus and An. peditaeniatus were resistant to all the insecticides tested, probably due to their high exposure to the insecticides used in agriculture. An. vagus showed some resistance to permethrin. Esterases, GSTs and monooxygenases were elevated in both An. culicifacies and An. subpictus. AChE was most sensitive to insecticides in Kurunegala and Trincomalee An. culicifacies

  3. Managing multimorbidity: profiles of integrated care approaches targeting people with multiple chronic conditions in Europe.

    NARCIS (Netherlands)

    Rijken, M.; Hujala, A.; Ginneken, E. van; Melchiorre, M.G.; Groenewegen, P.; Schellevis, F.

    2018-01-01

    In response to the growing populations of people with multiple chronic diseases, new models of care are currently being developed in European countries to better meet the needs of these people. This paper aims to describe the occurrence and characteristics of various types of integrated care

  4. Site-specific quantification of lysine acetylation in the N-terminal tail of histone H4 using a double-labelling, targeted UHPLC MS/MS approach

    NARCIS (Netherlands)

    D'Urzo, Annalisa; Boichenko, Alexander P.; van den Bosch, Thea; Hermans, Jos; Dekker, Frank; Andrisano, Vincenza; Bischoff, Rainer

    We developed a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the site-specific quantification of lysine acetylation in the N-terminal region of histone H4 by combining chemical derivatization at the protein and peptide levels with digestion using chymotrypsin and

  5. Identification of a novel FGFRL1 MicroRNA target site polymorphism for bone mineral density in meta-analyses of genome-wide association studies

    NARCIS (Netherlands)

    T. Niu (Tianhua); N. Liu (Ning); M. Zhao (Ming); G. Xie (Guie); L. Zhang (Lei); J. Li (Jian); Y.-F. Pei (Yu-Fang); H. Shen (Hui); X. Fu (Xiaoying); H. He (Hao); S. Lu (Shan); X. Chen (Xiangding); L. Tan (Lijun); T.-L. Yang (Tie-Lin); Y. Guo (Yan); P.J. Leo (Paul); E.L. Duncan (Emma); J. Shen (Jie); Y.-F. Guo (Yan-fang); G.C. Nicholson (Geoffrey); R.L. Prince (Richard L.); J.A. Eisman (John); G. Jones (Graeme); P.N. Sambrook (Philip); X. Hu (Xiang); P.M. Das (Partha M.); Q. Tian (Qing); X.-Z. Zhu (Xue-Zhen); C.J. Papasian (Christopher J.); M.A. Brown (Matthew); A.G. Uitterlinden (André); Y.-P. Wang (Yu-Ping); S. Xiang (Shuanglin); H.-W. Deng

    2015-01-01

    textabstractMicroRNAs (miRNAs) are critical post-transcriptional regulators. Based on a previous genome-wide association (GWA) scan, we conducted a polymorphism in microRNAs' Target Sites (poly-miRTS)-centric multistage meta-analysis for lumbar spine (LS)-, total hip (HIP)-, and femoral neck

  6. Evaluation of structural integrity of IPNS-I and ZING-P' targets

    International Nuclear Information System (INIS)

    Carpenter, J.; Ahmed, H.; Loomis, B.; Ball, J.; Ewing, T.; Bailey, J.; D'Souza, A.F.

    1982-12-01

    This report discusses the design, production, and evaluation of clad uranium-alloy targets that function as spallation neutron sources in the ZING-P' and IPNS-I facilities with a pulsed (10 to 30 Hz), 500-MeV proton beam. The methodology and results of theoretical nuclear-particle transport, heat transport, and stress analyses that were used in the development of a design for the targets are described. The production of a zirconium-clad uranium-alloy cylinder for ZING-P' and Zircaloy-2-clad uranium-alloy discs for IPNS-I is discussed with particular attention to the procedural details. The theoretical analyses were verified by measuring the thermal and mechanical response of the clad uranium under conditions designed to simulate the operations of the pulsed-neutron sources

  7. An integrated miRNA functional screening and target validation method for organ morphogenesis.

    Science.gov (United States)

    Rebustini, Ivan T; Vlahos, Maryann; Packer, Trevor; Kukuruzinska, Maria A; Maas, Richard L

    2016-03-16

    The relative ease of identifying microRNAs and their increasing recognition as important regulators of organogenesis motivate the development of methods to efficiently assess microRNA function during organ morphogenesis. In this context, embryonic organ explants provide a reliable and reproducible system that recapitulates some of the important early morphogenetic processes during organ development. Here we present a method to target microRNA function in explanted mouse embryonic organs. Our method combines the use of peptide-based nanoparticles to transfect specific microRNA inhibitors or activators into embryonic organ explants, with a microRNA pulldown assay that allows direct identification of microRNA targets. This method provides effective assessment of microRNA function during organ morphogenesis, allows prioritization of multiple microRNAs in parallel for subsequent genetic approaches, and can be applied to a variety of embryonic organs.

  8. Integrated Laser-Target Interaction Experiments on the RAL Petawatt Laser

    International Nuclear Information System (INIS)

    Patel, P. K.; Key, M. H.; Mackinnon, A. J.; Akli, K.; Berry, R.; Borghesi, M.; Brummit, P. A.; Chambers, D.; Clarke, R. J.; Damian, C.; Chen, H.; Eagleton, R.; Freeman, R.; Glenzer, S.; Gregori, G.; Heathcote, R.; Izumi, N.; Kar, S.; King, J. A.; Kock, J.; Kuba, J.; May, M.; Moon, S.; Neely, D.; Neville, D. R.; Nikroo, A.; Niles, A.; Pasley, J.; Patel, N.; Park, H. S.; Romagnani, L.; Shepherd, R.; Snavely, R. A.; Stephens, R.; Stoeckl, C.; Storm, M.; Theobald, W.; Van Maren, R.; Wilks, S. C.; Zhang, B.

    2005-01-01

    We report on two recent experimental campaigns performed on the new Petawatt laser at the Rutherford Appleton Laboratory in the UK.The laser has recently demonstrated performance characteristics of 400 J of laser energy being delivered on target in a sub 400 fs pulse, reaching a peak focal intensity on the order of 10''21 W/cm''2. The experiments covered multiplic areas of investigation including hot electron transport in planar foil and cone focus geometries, relativistic laser-solid interactions proton beam focusing and heating, and high energy K-alpha production and radiography. A somewhat novel approach was taken to the experiments in that all of the diagnostics required for the different areas of study were fielded simultaneously and operated on all shots. Thus, we were able to obtain extensive sets of measurements on a single-shot basis which provides significant benefit to our understanding of the laser-target interaction conditions and plasma properties. (Author)

  9. Evaluation of structural integrity of IPNS-I and ZING-P' targets

    Energy Technology Data Exchange (ETDEWEB)

    Carpenter, J.; Ahmed, H.; Loomis, B.; Ball, J.; Ewing, T.; Bailey, J.; D' Souza, A.F.

    1982-12-01

    This report discusses the design, production, and evaluation of clad uranium-alloy targets that function as spallation neutron sources in the ZING-P' and IPNS-I facilities with a pulsed (10 to 30 Hz), 500-MeV proton beam. The methodology and results of theoretical nuclear-particle transport, heat transport, and stress analyses that were used in the development of a design for the targets are described. The production of a zirconium-clad uranium-alloy cylinder for ZING-P' and Zircaloy-2-clad uranium-alloy discs for IPNS-I is discussed with particular attention to the procedural details. The theoretical analyses were verified by measuring the thermal and mechanical response of the clad uranium under conditions designed to simulate the operations of the pulsed-neutron sources.

  10. Groundwater and vadose Zone Integration Project Nuclear Material Mass Flow and Accountability on the Hanford Site

    International Nuclear Information System (INIS)

    GRASHER, A.A.

    2001-01-01

    The purpose of this report is to provide a discussion of the accountable inventory of Hanford Site nuclear material (NM) over the operating period. This report does not provide judgments on impacts to the Hanford Site environs by the reported waste streams or inventory. The focus of this report is on the processes, facilities, and process streams that constituted the flow primarily of plutonium and uranium through the Hanford Site. The material balance reports (MBRS) are the basis of the NM accountable inventory maintained by each of the various contractors used by the U.S. Department of Energy (DOE) and its predecessors to operate the Hanford Site. The inventory was tracked in terms of a starting inventory, receipts, transfers, and ending inventory. The various components of the inventory are discussed as well as the uncertainty in the measurement values used to establish plant inventory and material transfers. The accountable NM inventory does not report all the NM on the Hanford Site and this difference is discussed relative to some representative nuclides. The composition and location of the current accountable inventory are provided, as well as the latest approved set (2000) of flow diagrams of the proposed disposition of the excess accountable NM inventory listed on the Idaho National Engineering and Environmental Laboratory (INEEL) web page

  11. Integrated laser-target interaction experiments on the RAL petawatt laser

    International Nuclear Information System (INIS)

    Patel, P K; Key, M H; Mackinnon, A J

    2005-01-01

    We review a recent experimental campaign to study the interaction physics of petawatt laser pulses incident at relativistic intensities on solid targets. The campaign was performed on the 500 J sub-picosecond petawatt laser at the Rutherford Appleton Laboratory. An extensive suite of optical, x-ray, and particle diagnostics was employed to characterise the processes of laser absorption, electron generation and transport, thermal and K-alpha x-ray generation, and proton acceleration

  12. An integrative in-silico approach for therapeutic target identification in the human pathogen Corynebacterium diphtheriae.

    Directory of Open Access Journals (Sweden)

    Syed Babar Jamal

    Full Text Available Corynebacterium diphtheriae (Cd is a Gram-positive human pathogen responsible for diphtheria infection and once regarded for high mortalities worldwide. The fatality gradually decreased with improved living standards and further alleviated when many immunization programs were introduced. However, numerous drug-resistant strains emerged recently that consequently decreased the efficacy of current therapeutics and vaccines, thereby obliging the scientific community to start investigating new therapeutic targets in pathogenic microorganisms. In this study, our contributions include the prediction of modelome of 13 C. diphtheriae strains, using the MHOLline workflow. A set of 463 conserved proteins were identified by combining the results of pangenomics based core-genome and core-modelome analyses. Further, using subtractive proteomics and modelomics approaches for target identification, a set of 23 proteins was selected as essential for the bacteria. Considering human as a host, eight of these proteins (glpX, nusB, rpsH, hisE, smpB, bioB, DIP1084, and DIP0983 were considered as essential and non-host homologs, and have been subjected to virtual screening using four different compound libraries (extracted from the ZINC database, plant-derived natural compounds and Di-terpenoid Iso-steviol derivatives. The proposed ligand molecules showed favorable interactions, lowered energy values and high complementarity with the predicted targets. Our proposed approach expedites the selection of C. diphtheriae putative proteins for broad-spectrum development of novel drugs and vaccines, owing to the fact that some of these targets have already been identified and validated in other organisms.

  13. Integrating respiratory-gated PET-based target volume delineation in liver SBRT planning, a pilot study

    International Nuclear Information System (INIS)

    Riou, Olivier; Thariat, Juliette; Serrano, Benjamin; Azria, David; Paulmier, Benoit; Villeneuve, Remy; Fenoglietto, Pascal; Artenie, Antonella; Ortholan, Cécile; Faraggi, Marc

    2014-01-01

    To assess the feasibility and benefit of integrating four-dimensional (4D) Positron Emission Tomography (PET) – computed tomography (CT) for liver stereotactic body radiation therapy (SBRT) planning. 8 patients with 14 metastases were accrued in the study. They all underwent a non-gated PET and a 4D PET centered on the liver. The same CT scan was used for attenuation correction, registration, and considered the planning CT for SBRT planning. Six PET phases were reconstructed for each 4D PET. By applying an individualized threshold to the 4D PET, a Biological Internal Target Volume (BITV) was generated for each lesion. A gated Planning Target Volume (PTVg) was created by adding 3 mm to account for set-up margins. This volume was compared to a manual Planning Target Volume (PTV) delineated with the help of a semi-automatic Biological Target Volume (BTV) obtained from the non-gated exam. A 5 mm radial and a 10 mm craniocaudal margins were applied to account for tumor motion and set-up margins to create the PTV. One undiagnosed liver metastasis was discovered thanks to the 4D PET. The semi-automatic BTV were significantly smaller than the BITV (p = 0.0031). However, after applying adapted margins, 4D PET allowed a statistically significant decrease in the PTVg as compared to the PTV (p = 0.0052). In comparison to non-gated PET, 4D PET may better define the respiratory movements of liver targets and improve SBRT planning for liver metastases. Furthermore, non respiratory-gated PET exams can both misdiagnose liver metastases and underestimate the real internal target volumes

  14. A slingram survey on the Nevada Test Site: part of an integrated geologic geophysical study of site evaluation for nuclear waste disposal

    Science.gov (United States)

    Flanigan, Vincent J.

    1979-01-01

    A slingram geophysical survey was made in early 1978 as part of the integrated geologlcal-geophysical study aimed at evaluating the Eleana Formation as a possible repository for nuclear waste. The slingram data were taken over an alluvial fan and pediments along the eastern flank of Syncline Ridge about 45 km north of Mercury, Nevada, on the Nevada Test Site. The data show that the more conductive argillaceous Eleana Formation varies in depth from 40 to 85 m from west to east along traverse lines. Northeast-trending linear anomalies suggest rather abrupt changes in subsurface geology that may be associated with faults and fractures. The results of the slingram survey will, when interpreted in the light of other geologic and geophysical evidence, assist in understanding the shallow parts of the geologic setting of the Eleana Formation.

  15. Therapeutic Targeting of the Mitochondria Initiates Excessive Superoxide Production and Mitochondrial Depolarization Causing Decreased mtDNA Integrity.

    Science.gov (United States)

    Pokrzywinski, Kaytee L; Biel, Thomas G; Kryndushkin, Dmitry; Rao, V Ashutosh

    2016-01-01

    Mitochondrial dysregulation is closely associated with excessive reactive oxygen species (ROS) production. Altered redox homeostasis has been implicated in the onset of several diseases including cancer. Mitochondrial DNA (mtDNA) and proteins are particularly sensitive to ROS as they are in close proximity to the respiratory chain (RC). Mitoquinone (MitoQ), a mitochondria-targeted redox agent, selectively damages breast cancer cells possibly through damage induced via enhanced ROS production. However, the effects of MitoQ and other triphenylphosphonium (TPP+) conjugated agents on cancer mitochondrial homeostasis remain unknown. The primary objective of this study was to determine the impact of mitochondria-targeted agent [(MTAs) conjugated to TPP+: mitoTEMPOL, mitoquinone and mitochromanol-acetate] on mitochondrial physiology and mtDNA integrity in breast (MDA-MB-231) and lung (H23) cancer cells. The integrity of the mtDNA was assessed by quantifying the degree of mtDNA fragmentation and copy number, as well as by measuring mitochondrial proteins essential to mtDNA stability and maintenance (TFAM, SSBP1, TWINKLE, POLG and POLRMT). Mitochondrial status was evaluated by measuring superoxide production, mitochondrial membrane depolarization, oxygen consumption, extracellular acidification and mRNA or protein levels of the RC complexes along with TCA cycle activity. In this study, we demonstrated that all investigated MTAs impair mitochondrial health and decrease mtDNA integrity in MDA-MB-231 and H23 cells. However, differences in the degree of mitochondrial damage and mtDNA degradation suggest unique properties among each MTA that may be cell line, dose and time dependent. Collectively, our study indicates the potential for TPP+ conjugated molecules to impair breast and lung cancer cells by targeting mitochondrial homeostasis.

  16. Identification of a novel phosphorylation site in c-jun directly targeted in vitro by protein kinase D

    International Nuclear Information System (INIS)

    Waldron, Richard T.; Whitelegge, Julian P.; Faull, Kym F.; Rozengurt, Enrique

    2007-01-01

    Protein kinase D (PKD) phosphorylates the c-jun amino-terminal in vitro at site(s) distinct from JNK [C. Hurd, R.T. Waldron, E. Rozengurt, Protein kinase D complexes with c-jun N-terminal kinase via activation loop phosphorylation and phosphorylates the c-jun N-terminus, Oncogene 21 (2002) 2154-2160], but the sites have not been identified. Here, metabolic 32 P-labeling of c-jun protein in COS-7 cells indicated that PKD phosphorylates c-jun in vivo at a site(s) between aa 43-93, a region containing important functional elements. On this basis, the PKD-mediated phosphorylation site(s) was further characterized in vitro using GST-c-jun fusion proteins. PKD did not incorporate phosphate into Ser63 and Ser73, the JNK sites in GST-c-jun(1-89). Rather, PKD and JNK could sequentially phosphorylate distinct site(s) simultaneously. By mass spectrometry of tryptic phosphopeptides, Ser58 interposed between the JNK-binding portion of the delta domain and the adjacent TAD1 was identified as a prominent site phosphorylated in vitro by PKD. These data were further supported by kinase reactions using truncations or point-mutations of GST-c-jun. Together, these data suggest that PKD-mediated phosphorylation modulates c-jun at the level of its N-terminal functional domains

  17. Integrating knowledge-based multi-criteria evaluation techniques with GIS for landfill site selection: A case study using AHP

    Directory of Open Access Journals (Sweden)

    Fagbohun B.J.

    2016-09-01

    Full Text Available A major challenge in most growing urban areas of developing countries, without a pre-existing land use plan is the sustainable and efficient management of solid wastes. Siting a landfill is a complicated task because of several environmental regulations. This challenge gives birth to the need to develop efficient strategies for the selection of proper waste disposal sites in accordance with all existing environmental regulations. This paper presents a knowledge-based multi-criteria decision analysis using GIS for the selection of suitable landfill site in Ado-Ekiti, Nigeria. In order to identify suitable sites for landfill, seven factors - land use/cover, geology, river, soil, slope, lineament and roads - were taken into consideration. Each factor was classified and ranked based on prior knowledge about the area and existing guidelines. Weights for each factor were determined through pair-wise comparison using Saaty’s 9 point scale and AHP. The integration of factors according to their weights using weighted index overlay analysis revealed that 39.23 km2 within the area was suitable to site a landfill. The resulting suitable area was classified as high suitability covering 6.47 km2 (16.49%, moderate suitability 25.48 km2 (64.95% and low suitability 7.28 km2 (18.56% based on their overall weights.

  18. Peripartum depression and anxiety as an integrative cross domain target for psychiatric preventative measures.

    Science.gov (United States)

    Babb, Jessica A; Deligiannidis, Kristina M; Murgatroyd, Christopher A; Nephew, Benjamin C

    2015-01-01

    Exposure to high levels of early life stress has been identified as a potent risk factor for neurodevelopmental delays in infants, behavioral problems and autism in children, but also for several psychiatric illnesses in adulthood, such as depression, anxiety, autism, and posttraumatic stress disorder. Despite having robust adverse effects on both mother and infant, the pathophysiology of peripartum depression and anxiety are poorly understood. The objective of this review is to highlight the advantages of using an integrated approach addressing several behavioral domains in both animal and clinical studies of peripartum depression and anxiety. It is postulated that a greater focus on integrated cross domain studies will lead to advances in treatments and preventative measures for several disorders associated with peripartum depression and anxiety. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Integrative systems and synthetic biology of cell-matrix adhesion sites.

    Science.gov (United States)

    Zamir, Eli

    2016-09-02

    The complexity of cell-matrix adhesion convolves its roles in the development and functioning of multicellular organisms and their evolutionary tinkering. Cell-matrix adhesion is mediated by sites along the plasma membrane that anchor the actin cytoskeleton to the matrix via a large number of proteins, collectively called the integrin adhesome. Fundamental challenges for understanding how cell-matrix adhesion sites assemble and function arise from their multi-functionality, rapid dynamics, large number of components and molecular diversity. Systems biology faces these challenges in its strive to understand how the integrin adhesome gives rise to functional adhesion sites. Synthetic biology enables engineering intracellular modules and circuits with properties of interest. In this review I discuss some of the fundamental questions in systems biology of cell-matrix adhesion and how synthetic biology can help addressing them.

  20. Business Case Analysis: Continuous Integrated Logistics Support-Targeted Allowance Technique (CILS-TAT)

    Science.gov (United States)

    2013-06-01

    mirrors the civilian equivalent of ERP . The Navy ERP program uses a product from SAP Corporation, the largest provider of ERP solutions in the world...the Navy ERP Enterprise Resource Planning FFG Guided Missile Frigates FY Fiscal Year xiv GAO Government Accountability Office ILS Integrated...suspension of the program since 2009, when the U.S. Navy began its transition to an enterprise resource planning ( ERP ) framework. We expect that by the

  1. Associating Drugs, Targets and Clinical Outcomes into an Integrated Network Affords a New Platform for Computer-Aided Drug Repurposing

    DEFF Research Database (Denmark)

    Oprea, Tudor; Nielsen, Sonny Kim; Ursu, Oleg

    2011-01-01

    benefit from an integrated, semantic-web compliant computer-aided drug repurposing (CADR) effort, one that would enable deep data mining of associations between approved drugs (D), targets (T), clinical outcomes (CO) and SE. We report preliminary results from text mining and multivariate statistics, based...... on 7684 approved drug labels, ADL (Dailymed) via text mining. From the ADL corresponding to 988 unique drugs, the "adverse reactions" section was mapped onto 174 SE, then clustered via principal component analysis into a 5 x 5 self-organizing map that was integrated into a Cytoscape network of SE......Finding new uses for old drugs is a strategy embraced by the pharmaceutical industry, with increasing participation from the academic sector. Drug repurposing efforts focus on identifying novel modes of action, but not in a systematic manner. With intensive data mining and curation, we aim to apply...

  2. MicroRNA-939 governs vascular integrity and angiogenesis through targeting γ-catenin in endothelial cells

    International Nuclear Information System (INIS)

    Hou, Shiqiang; Fang, Ming; Zhu, Qian; Liu, Ying; Liu, Liang; Li, Xinming

    2017-01-01

    Coronary collateral circulation (CCC) functions as a natural bypass in the event of coronary obstruction, which markedly improves prognosis in patients with coronary artery disease (CAD). MicroRNAs (miRNAs) have been implicated in multiple physiological and pathological processes, including angiogenesis involved in CCC growth. The roles that miRNA-939 (miR-939) plays in angiogenesis remain largely unknown. We conducted this study to explore the expression of miR-939 in CAD patients and its role in angiogenesis. For the first time, our results indicated that the expression of circulating miR-939 was down-regulated in patients with sufficient CCC compared with patients with poor CCC. Overexpression of miR-939 in primary human umbilical vein endothelial cells (HUVECs) significantly inhibited the proliferation, adhesion and tube formation, but promoted the migration of cells. In contrast, miR-939 knockdown exerted reverse effects. We further identified that γ-catenin was a novel target of miR-939 by translational repression, which could rescue the effects of miR-939 in HUVECs. In summary, this study revealed that the expression of circulating miR-939 was down-regulated in CAD patients with sufficient CCC. MiR-939 abolished vascular integrity and repressed angiogenesis through directly targeting γ-catenin. It provided a potential biomarker and a therapeutic target for CAD. - Highlights: • Circulating miR-939 is decreased in sufficient coronary collateral circulation. • MiR-939 abolishes vascular integrity in endothelial cells. • MiR-939 represses angiogenesis. • γ-catenin is a novel target of miR-939.

  3. Cell signaling heterogeneity is modulated by both cell-intrinsic and -extrinsic mechanisms: An integrated approach to understanding targeted therapy.

    Science.gov (United States)

    Kim, Eunjung; Kim, Jae-Young; Smith, Matthew A; Haura, Eric B; Anderson, Alexander R A

    2018-03-01

    During the last decade, our understanding of cancer cell signaling networks has significantly improved, leading to the development of various targeted therapies that have elicited profound but, unfortunately, short-lived responses. This is, in part, due to the fact that these targeted therapies ignore context and average out heterogeneity. Here, we present a mathematical framework that addresses the impact of signaling heterogeneity on targeted therapy outcomes. We employ a simplified oncogenic rat sarcoma (RAS)-driven mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase-protein kinase B (PI3K-AKT) signaling pathway in lung cancer as an experimental model system and develop a network model of the pathway. We measure how inhibition of the pathway modulates protein phosphorylation as well as cell viability under different microenvironmental conditions. Training the model on this data using Monte Carlo simulation results in a suite of in silico cells whose relative protein activities and cell viability match experimental observation. The calibrated model predicts distributional responses to kinase inhibitors and suggests drug resistance mechanisms that can be exploited in drug combination strategies. The suggested combination strategies are validated using in vitro experimental data. The validated in silico cells are further interrogated through an unsupervised clustering analysis and then integrated into a mathematical model of tumor growth in a homogeneous and resource-limited microenvironment. We assess posttreatment heterogeneity and predict vast differences across treatments with similar efficacy, further emphasizing that heterogeneity should modulate treatment strategies. The signaling model is also integrated into a hybrid cellular automata (HCA) model of tumor growth in a spatially heterogeneous microenvironment. As a proof of concept, we simulate tumor responses to targeted therapies in a spatially segregated tissue structure containing tumor

  4. Supporting Fernald Site Closure with Integrated Health and Safety Plans as Documented Safety Analyses

    International Nuclear Information System (INIS)

    Kohler, S.; Brown, T.; Fisk, P.; Krach, F.; Klein, B.

    2004-01-01

    At the Fernald Closure Project (FCP) near Cincinnati, Ohio, environmental restoration activities are supported by Documented Safety Analyses (DSAs) that combine the required project-specific Health and Safety Plans, Safety Basis Requirements (SBRs), and Process Requirements (PRs) into single Integrated Health and Safety Plans (I-HASPs). These integrated DSAs employ Integrated Safety Management methodology in support of simplified restoration and remediation activities that, so far, have resulted in the decontamination and demolition (D and D) of over 200 structures, including eight major nuclear production plants. There is one of twelve nuclear facilities still remaining (Silos containing uranium ore residues) with its own safety basis documentation. This paper presents the status of the FCP's safety basis documentation program, illustrating that all of the former nuclear facilities and activities have now replaced. Basis of Interim Operations (BIOs) with I-HASPs as their safety basis during the closure process

  5. Simplifying documentation while approaching site closure: integrated health and safety plans as documented safety analysis

    International Nuclear Information System (INIS)

    Brown, Tulanda

    2003-01-01

    At the Fernald Closure Project (FCP) near Cincinnati, Ohio, environmental restoration activities are supported by Documented Safety Analyses (DSAs) that combine the required project-specific Health and Safety Plans, Safety Basis Requirements (SBRs), and Process Requirements (PRs) into single Integrated Health and Safety Plans (I-HASPs). By isolating any remediation activities that deal with Enriched Restricted Materials, the SBRs and PRs assure that the hazard categories of former nuclear facilities undergoing remediation remain less than Nuclear. These integrated DSAs employ Integrated Safety Management methodology in support of simplified restoration and remediation activities that, so far, have resulted in the decontamination and demolition (D and D) of over 150 structures, including six major nuclear production plants. This paper presents the FCP method for maintaining safety basis documentation, using the D and D I-HASP as an example

  6. Integrated watershed- and farm-scale modeling framework for targeting critical source areas while maintaining farm economic viability.

    Science.gov (United States)

    Ghebremichael, Lula T; Veith, Tamie L; Hamlett, James M

    2013-01-15

    Quantitative risk assessments of pollution and data related to the effectiveness of mitigating best management practices (BMPs) are important aspects of nonpoint source pollution control efforts, particularly those driven by specific water quality objectives and by measurable improvement goals, such as the total maximum daily load (TMDL) requirements. Targeting critical source areas (CSAs) that generate disproportionately high pollutant loads within a watershed is a crucial step in successfully controlling nonpoint source pollution. The importance of watershed simulation models in assisting with the quantitative assessments of CSAs of pollution (relative to their magnitudes and extents) and of the effectiveness of associated BMPs has been well recognized. However, due to the distinct disconnect between the hydrological scale in which these models conduct their evaluation and the farm scale at which feasible BMPs are actually selected and implemented, and due to the difficulty and uncertainty involved in transferring watershed model data to farm fields, there are limited practical applications of these tools in the current nonpoint source pollution control efforts by conservation specialists for delineating CSAs and planning targeting measures. There are also limited approaches developed that can assess impacts of CSA-targeted BMPs on farm productivity and profitability together with the assessment of water quality improvements expected from applying these measures. This study developed a modeling framework that integrates farm economics and environmental aspects (such as identification and mitigation of CSAs) through joint use of watershed- and farm-scale models in a closed feedback loop. The integration of models in a closed feedback loop provides a way for environmental changes to be evaluated with regard to the impact on the practical aspects of farm management and economics, adjusted or reformulated as necessary, and revaluated with respect to effectiveness of

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-05-15

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

  8. Life performance of oil and gas platforms: Site integration and thermodynamic evaluation

    DEFF Research Database (Denmark)

    Nguyen, Tuong-Van; Fülöp, Tamás Gábor; Breuhaus, Peter

    2014-01-01

    requirements are assessed by a process integration study, and the system inefficiencies are pinpointed by performing an exergy accounting. The heating and cooling requirements vary significantly over time, and most inefficiencies take place in processes where chemical exergy is consumed (50-55%), thermal...... exergy is transferred (15-20%), or mechanical exergy is varied (10-15%). These findings are valid for all production periods: this suggests that more attention should be paid on a proper integration of the processing and utility plants, by, for instance, recovering heat from the turbine exhausts and from...

  9. Potential Natural Products for Alzheimer’s Disease: Targeted Search Using the Internal Ribosome Entry Site of Tau and Amyloid-β Precursor Protein

    Directory of Open Access Journals (Sweden)

    Yun-Chieh Tasi

    2015-04-01

    Full Text Available Overexpression of the amyloid precursor protein (APP and the hyperphosphorylation of the tau protein are vital in the understanding of the cause of Alzheimer’s disease (AD. As a consequence, regulation of the expression of both APP and tau proteins is one important approach in combating AD. The APP and tau proteins can be targeted at the levels of transcription, translation and protein structural integrity. This paper reports the utilization of a bi-cistronic vector containing either APP or tau internal ribosome entry site (IRES elements flanked by β-galactosidase gene (cap-dependent and secreted alkaline phosphatase (SEAP (cap-independent to discern the mechanism of action of memantine, an N-methyl-d-aspartate (NMDA receptor antagonist. Results indicate that memantine could reduce the activity of both the APP and tau IRES at a concentration of ~10 μM (monitored by SEAP activity without interfering with the cap-dependent translation as monitored by the β-galactosidase assay. Western blot analysis of the tau protein in neuroblastoma (N2A and rat hippocampal cells confirmed the halting of the expression of the tau proteins. We also employed this approach to identify a preparation named NB34, extracts of Boussingaultia baselloides (madeira-vine fermented with Lactobacillus spp., which can function similarly to memantine in both IRES of APP and Tau. The water maze test demonstrated that NB34 could improve the spatial memory of a high fat diet induced neurodegeneration in apolipoprotein E-knockout (ApoE−/− mice. These results revealed that the bi-cistronic vector provided a simple, and effective platform in screening and establishing the mechanistic action of potential compounds for the treatment and management of AD.

  10. NGS-based approach to determine the presence of HPV and their sites of integration in human cancer genome.

    Science.gov (United States)

    Chandrani, P; Kulkarni, V; Iyer, P; Upadhyay, P; Chaubal, R; Das, P; Mulherkar, R; Singh, R; Dutt, A

    2015-06-09

    Human papilloma virus (HPV) accounts for the most common cause of all virus-associated human cancers. Here, we describe the first graphic user interface (GUI)-based automated tool 'HPVDetector', for non-computational biologists, exclusively for detection and annotation of the HPV genome based on next-generation sequencing data sets. We developed a custom-made reference genome that comprises of human chromosomes along with annotated genome of 143 HPV types as pseudochromosomes. The tool runs on a dual mode as defined by the user: a 'quick mode' to identify presence of HPV types and an 'integration mode' to determine genomic location for the site of integration. The input data can be a paired-end whole-exome, whole-genome or whole-transcriptome data set. The HPVDetector is available in public domain for download: http://www.actrec.gov.in/pi-webpages/AmitDutt/HPVdetector/HPVDetector.html. On the basis of our evaluation of 116 whole-exome, 23 whole-transcriptome and 2 whole-genome data, we were able to identify presence of HPV in 20 exomes and 4 transcriptomes of cervical and head and neck cancer tumour samples. Using the inbuilt annotation module of HPVDetector, we found predominant integration of viral gene E7, a known oncogene, at known 17q21, 3q27, 7q35, Xq28 and novel sites of integration in the human genome. Furthermore, co-infection with high-risk HPVs such as 16 and 31 were found to be mutually exclusive compared with low-risk HPV71. HPVDetector is a simple yet precise and robust tool for detecting HPV from tumour samples using variety of next-generation sequencing platforms including whole genome, whole exome and transcriptome. Two different modes (quick detection and integration mode) along with a GUI widen the usability of HPVDetector for biologists and clinicians with minimal computational knowledge.

  11. Integrating management techniques to restore sites invaded by mile-a-minute weed, Persicaria perfoliata

    Science.gov (United States)

    Ellen C. Lake; Judith Hough-Goldstein; Vincent. D' Amico

    2014-01-01

    Efforts to suppress an invasive weed are often undertaken with the goal of facilitating the recovery of a diverse native plant community. In some cases, however, reduction in the abundance of the target weed results in an increase in other exotic weeds. Mile-a-minute weed (Persicaria perfoliata (L.) H. Gross (Polygonaceae)) is an annual vine from...

  12. An Integrated Decision Model for Evaluating Educational Web Sites from the Fuzzy Subjective and Objective Perspectives

    Science.gov (United States)

    Huang, Tony Cheng-Kui; Huang, Chih-Hong

    2010-01-01

    With advances in information and network technologies, lots of data have been digitized to reveal information for users by the construction of Web sites. Unfortunately, they are both overloading and overlapping in Internet so that users cannot distinguish their quality. To address this issue in education, Hwang, Huang, and Tseng proposed a group…

  13. Integrative invasion science: model systems, multi-site studies, focused meta-analysis, and invasion syndromes

    Czech Academy of Sciences Publication Activity Database

    Kueffer, C.; Pyšek, Petr; Richardson, D. M.

    2013-01-01

    Roč. 200, č. 3 (2013), s. 615-633 ISSN 1469-8137 R&D Projects: GA ČR(CZ) GAP504/11/1028; GA ČR GA206/09/0563 Institutional support: RVO:67985939 Keywords : model systems * invasion syndromes * multi-site studies Subject RIV: EF - Botanics Impact factor: 6.545, year: 2013

  14. GHGT-10 : Assessing the integrity of fault- and top seals at CO2 storage sites

    NARCIS (Netherlands)

    Orlic, B.; Heege J.H. ter; Wassing, B.

    2011-01-01

    Induced stress changes due to CO2 injection into geological reservoirs can mechanically damage bounding fault- and top seals creating preferential pathways for CO2 migration from the containment or trigger existing faults causing seismic activity at storage sites. In this paper we present

  15. UAS Integration in the NAS Project Test Site Kick-off Meeting

    Science.gov (United States)

    Kopardekar, Parimal; Witzberger, Kevin; Hackenberg, Davis L.; Murphy, Jim

    2015-01-01

    This briefing was presented during the Test Site Kick Off Meeting to discuss the contract awards for Task 1 and Task 2. This briefing covered a high level overview for contract deliverables, Task 1 - UAS Traffic Management and Task 2, Live Virtual Constructive Distributed Environment.

  16. Incorporation, integration and irrigation at the ancient Maya site of Baking Pot, Belize

    Directory of Open Access Journals (Sweden)

    James M. Conlon

    1995-11-01

    Full Text Available This paper provides an example of the use of corporate group analysis at the major ceremonial centre of Baking Pot, and uses comparative data from the site core of Baking Pot, other major centres in the upper Belize Valley, and various other sources throughout the Maya lowlands.

  17. Using Remote Sensing Data for Integrating different Renewable Energy Sources at Coastal Site in South Italy

    DEFF Research Database (Denmark)

    Calaudi, Rosamaria; Feudo, Teresa Lo; Calidonna, Claudia Roberta

    2016-01-01

    Italian coastal sites have the advantage of favorable climatic conditions to use mixed renewable energy sources, such as solar and wind. Harbors are safe places to install wind turbines where wind conditions are almost offshore. Space-borne remote sensing can provide information to determine solar...

  18. Integrating geomatics in archaeological research at the site of Thorikos (Greece)

    NARCIS (Netherlands)

    Stal, C.; Docter, R.; van den Eijnde, F.|info:eu-repo/dai/nl/304835188

    2014-01-01

    Archaeological excavation is a destructive process, making accurate, fast and efficient 3D documentation of information essential. With this in mind, our research uses an integrated workflow of topographic measurements and image-based 3D modelling to generate highly accurate reconstructions of

  19. Demethylation of host-cell DNA at the site of avian retrovirus integration

    Czech Academy of Sciences Publication Activity Database

    Hejnar, Jiří; Elleder, Daniel; Hájková, P.; Walter, J.; Blažková, Jana; Svoboda, Jan

    2003-01-01

    Roč. 2003, č. 311 (2003), s. 641-648 ISSN 0006-291X Institutional research plan: CEZ:AV0Z5052915 Keywords : DNA methylation and demethylation * integration of retroviruses * gene silencing Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.836, year: 2003

  20. Implementation of an Integrated, Portable Transformer Condition Monitoring Instrument in the Classroom and On-Site

    Science.gov (United States)

    Chatterjee, B.; Dey, D.; Chakravorti, S.

    2010-01-01

    The development of integrated, portable, transformer condition monitoring (TCM) equipment for classroom demonstrations as well as for student exercises conducted in the field is discussed. Demonstrations include experimentation with real-world transformers to illustrate concepts such as polarization and depolarization current through oil-paper…

  1. The Impact of Online Social Networking Sites on Student Integration into the College Peer Social System

    Science.gov (United States)

    Szura, Jean Mary

    2014-01-01

    Given the value of obtaining a college degree, it is the responsibility of educational administrators and faculty to understand what contributes to or detracts from student success in college. Researchers have shown a strong relationship between students' level of integration with the institutions and persistence to graduation. One factor that…

  2. Application of an Integrated Assessment Model to the Kevin Dome site, Montana

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Minh [Univ. of Wyoming, Laramie, WY (United States); Zhang, Ye [Univ. of Wyoming, Laramie, WY (United States); Carey, James William [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Stauffer, Philip H. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-10-30

    The objectives of the Integrated Assessment Model is to enable the Fault Swarm algorithm in the National Risk Assessment Partnership, ensure faults are working in the NRAP-IAM tool, calculate hypothetical fault leakage in NRAP-IAM, and compare leakage rates to Eclipse simulations.

  3. Savannah River Site FY 2001 Spent Nuclear Fuel Integrated Management Plan

    International Nuclear Information System (INIS)

    Dunsmuir, M.D.

    2000-01-01

    This document presents the SRS integrated near and long-term plans (FY 2001 through 2035) for the safe life cycle management of SNF inventories and other SFSD legacy material programs/projects that impact this mission until final disposition has been implemented

  4. Simultaneous quantification of protein phosphorylation sites using liquid chromatography-tandem mass spectrometry-based targeted proteomics: a linear algebra approach for isobaric phosphopeptides.

    Science.gov (United States)

    Xu, Feifei; Yang, Ting; Sheng, Yuan; Zhong, Ting; Yang, Mi; Chen, Yun

    2014-12-05

    As one of the most studied post-translational modifications (PTM), protein phosphorylation plays an essential role in almost all cellular processes. Current methods are able to predict and determine thousands of phosphorylation sites, whereas stoichiometric quantification of these sites is still challenging. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)-based targeted proteomics is emerging as a promising technique for site-specific quantification of protein phosphorylation using proteolytic peptides as surrogates of proteins. However, several issues may limit its application, one of which relates to the phosphopeptides with different phosphorylation sites and the same mass (i.e., isobaric phosphopeptides). While employment of site-specific product ions allows for these isobaric phosphopeptides to be distinguished and quantified, site-specific product ions are often absent or weak in tandem mass spectra. In this study, linear algebra algorithms were employed as an add-on to targeted proteomics to retrieve information on individual phosphopeptides from their common spectra. To achieve this simultaneous quantification, a LC-MS/MS-based targeted proteomics assay was first developed and validated for each phosphopeptide. Given the slope and intercept of calibration curves of phosphopeptides in each transition, linear algebraic equations were developed. Using a series of mock mixtures prepared with varying concentrations of each phosphopeptide, the reliability of the approach to quantify isobaric phosphopeptides containing multiple phosphorylation sites (≥ 2) was discussed. Finally, we applied this approach to determine the phosphorylation stoichiometry of heat shock protein 27 (HSP27) at Ser78 and Ser82 in breast cancer cells and tissue samples.

  5. Characterization of sulfonylurea-resistant Schoenoplectus juncoides having a target-site Asp(376)Glu mutation in the acetolactate synthase.

    Science.gov (United States)

    Sada, Yoshinao; Ikeda, Hajime; Yamato, Seiji; Kizawa, Satoru

    2013-09-01

    Schoenoplectus juncoides, a noxious weed for paddy rice, is known to become resistant to sulfonylurea (SU) herbicides by a target-site mutation in either of the two acetolactate synthase (ALS) genes (ALS1 and ALS2). SU-resistant S. juncoides plants having an Asp376Glu mutation in ALS2 were found from a paddy rice field in Japan, but their resistance profile has not been quantitatively investigated. In this study, dose-response of the SU-resistant accession was compared with that of a SU-susceptible accession at in vivo whole-plant level as well as at in vitro enzymatic level. In whole-plant tests, resistance factors (RFs) based on 50% growth reduction (GR50) for imazosulfuron (ISF), bensulfuron-methyl (BSM), metsulfuron-methyl (MSM), bispyribac-sodium (BPS), and imazaquin (IMQ) were 176, 40, 14, 5.2 and 1.5, respectively. Thus, the accession having an Asp376Glu mutation in ALS2 was highly resistant to the three SU herbicides and moderately resistant to BPS, but was not substantially resistant to IMQ. This is slightly different from the earlier results reported from other weeds with an Asp376Glu mutation, in which the mutation confers resistance to broadly all the chemical classes of ALS-inhibiting herbicides. In enzymatic tests, ALS2 of S. juncoides was expressed in E. coli; the resultant ALS2 was subjected to an in vitro assay. RFs of the mutated ALS2 based on 50% enzymatic inhibition (I50) for ISF, BSM, MSM, BPS, and IMQ were 3699, 2438, 322, 80, and 4.8, respectively. The RFs of ALS2 were highly correlated with those of the whole-plant; this suggests that the Asp376Glu mutation in ALS2 is a molecular basis for the whole-plant resistance. The presence of two ALS genes in S. juncoides can at least partially explain why the whole-plant RFs were less than those of the expressed ALS2 enzymes. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Agrobacterium tumefaciens T-DNA Integration and Gene Targeting in Arabidopsis thaliana Non-Homologous End-Joining Mutants

    Directory of Open Access Journals (Sweden)

    Qi Jia

    2012-01-01

    Full Text Available In order to study the role of AtKu70 and AtKu80 in Agrobacterium-mediated transformation and gene targeting, plant lines with a T-DNA insertion in AtKu80 or AtKu70 genes were functionally characterized. Such plant lines lacked both subunits, indicating that heterodimer formation between AtKu70 and AtKu80 is needed for the stability of the proteins. Homozygous mutants were phenotypically indistinguishable from wild-type plants and were fertile. However, they were hypersensitive to the genotoxic agent bleomycin, resulting in more DSBs as quantified in comet assays. They had lower end-joining efficiency, suggesting that NHEJ is a critical pathway for DSB repair in plants. Both Atku mutants and a previously isolated Atmre11 mutant were impaired in Agrobacterium T-DNA integration via floral dip transformation, indicating that AtKu70, AtKu80, and AtMre11 play an important role in T-DNA integration in Arabidopsis. The frequency of gene targeting was not significantly increased in the Atku80 and Atku70 mutants, but it was increased at least 10-fold in the Atmre11 mutant compared with the wild type.

  7. A resolvase-like protein is requered for the site-specific integration of the temperate lactococcal bacteriophage TP901-1

    DEFF Research Database (Denmark)

    Christiansen, Bettina; Brøndsted, Lone; Vogensen, Finn K.

    1996-01-01

    upstream of attP. The N-terminal 150 to 1180 amino acids of Orf1 showed 38 to 44% similarity to the resolvase group of site-specific integrases, while no similarity to know proteins was found in the C-terminal end. Bacteriophage 'TP901-1 therefore contains a unique integration system that does not resemble...... the Int class of site-specific integrases usually found in temperate bacteriophages. The constructed integration vector, pBC170, integrates into the chromosomal attachment site very efficiently and forms stable transformants with a frequency corresponding to 20% of the transformation efficiency....

  8. Preoperational test report, cross-site transfer system integrated test (POTR-007)

    Energy Technology Data Exchange (ETDEWEB)

    Pacquet, E.A.

    1998-04-02

    This report documents the results obtained during the performance of Preoperational Test POTP-007, from December 12, 1997 to March 27, 1998. The main objectives were to demonstrate the operation of the following Cross-Site Transfer System components: Booster pumps P-3125A and P-3125B interlocks and controls, both local and remote; Booster pump P-3125A and P-3125B and associated variable speed drives VSD-1 and VSD-2 performance in both manual and automatic modes; and Water filling, circulation, venting and draining of the transfer headers (supernate and slurry line). As described in reference 1, the following components of the Cross-Site Transfer System that would normally be used during an actual waste transfer, are not used in this specific test: Water Flush System; Valving and instrumentation associated with the 241-SY-A valve pit jumpers; and Valving and instrumentation associated with the 244-A lift station.

  9. A DOE multi-site approach to safeguards integration with facility operations

    International Nuclear Information System (INIS)

    Ostenak, C.A.

    1987-01-01

    The Accountability Technology Exchange (ATEX) Working Group was established in October 1986 by the US Department of Energy (DOE) to help identify nuclear materials accountability measurement needs within the DOE plutonium community and recommend potential improvements. ATEX Working Group membership represents nuclear materials production, safeguards, nondestructive assay (NDA), and analytical chemistry at a multitude of DOE plutonium sites. Currently, the ATEX Working Group has identified twenty NDA accountability measurement needs that fall into five major classes: NDA standards representing various nuclear materials and matrix compositions; NDA for impure nuclear materials compounds, residues, and wastes; NDA for product-grade nuclear materials; NDA for nuclear materials process holdup and in-process inventory; and NDA for nuclear materials item control and verification. Specific needs within these classes have been evaluated and ranked for individual sites and for the total DOE plutonium community

  10. Preoperational test report, cross-site transfer system integrated test (POTR-007)

    International Nuclear Information System (INIS)

    Pacquet, E.A.

    1998-01-01

    This report documents the results obtained during the performance of Preoperational Test POTP-007, from December 12, 1997 to March 27, 1998. The main objectives were to demonstrate the operation of the following Cross-Site Transfer System components: Booster pumps P-3125A and P-3125B interlocks and controls, both local and remote; Booster pump P-3125A and P-3125B and associated variable speed drives VSD-1 and VSD-2 performance in both manual and automatic modes; and Water filling, circulation, venting and draining of the transfer headers (supernate and slurry line). As described in reference 1, the following components of the Cross-Site Transfer System that would normally be used during an actual waste transfer, are not used in this specific test: Water Flush System; Valving and instrumentation associated with the 241-SY-A valve pit jumpers; and Valving and instrumentation associated with the 244-A lift station

  11. Assessing the potentialities of integrated modelling during early phases of siting and design of a geological repository: the REGIME exercise

    Energy Technology Data Exchange (ETDEWEB)

    Genty, A.; Certes, C.; Serres, C.; Besnus, F. [Institut de Radioprotection et de Surete Nucleaire IRSN, 92 - Fontenay aux Roses (France); Fischer-Appelt, K.; Baltes, B.; Rohlig, J. [Gesellschaft fuer Anlagen- und Reaktorsicherheit mbH (GRS), Koeln (Germany)

    2003-01-01

    This paper presents the safety assessment exercise 'REGIME' (Repository Evaluation performed by GRS and IRSN through a Modelling Exercise) performed jointly by GRS and IRSN. The main objective of the project is to test the ability of integrated modelling to contribute to site selection and repository conception in the context of high-level radioactive waste disposal. The project is divided in two parts. Phase 1 consisted in studying different flow patterns in a given geological context. The selected hydrogeological contexts and three site locations potentially favourable for hosting a repository are described. Phase 2, under progress, aims at evaluating the rote of limitation of releases played by the different components of the disposal system taking into account possible dysfunctions. The main issues to be addressed in phase 2, the modelling outline and the scenarios to be studied are presented. (authors)

  12. Los Alamos National Laboratory Site Integrated Management plan, uranium 233 storage and disposition. Volume 1: Project scope and description

    International Nuclear Information System (INIS)

    Nielsen, J.B.; Erickson, R.

    1997-01-01

    This Site Integration Management plan provides the Los Alamos Response to the Defense Nuclear Facility Safety Board (DNFSB) Recommendation 97-1. This recommendation addresses the safe storage and management of the Departments uranium 233 ( 233 U) inventory. In the past, Los Alamos has used 233 U for a variety of different weapons related projects. The material was used at a variety of sites in varying quantities. Now, there is a limited need for this material and the emphasis has shifted from use to storage and disposition of the material. The Los Alamos program to address the DNFSB Recommendation 97-1 has two emphases. First, take corrective action to address near term deficiencies required to provide safe interim storage of 233 U. Second, provide a plan to address long term storage and disposition of excess inventory at Los Alamos

  13. Short-range/Long-range Integrated Target (SLIT) for Video Guidance Sensor Rendezvous and Docking

    Science.gov (United States)

    Roe, Fred D. (Inventor); Bryan, Thomas C. (Inventor)

    2009-01-01

    A laser target reflector assembly for mounting upon spacecraft having a long-range reflector array formed from a plurality of unfiltered light reflectors embedded in an array pattern upon a hemispherical reflector disposed upon a mounting plate. The reflector assembly also includes a short-range reflector array positioned upon the mounting body proximate to the long-range reflector array. The short-range reflector array includes three filtered light reflectors positioned upon extensions from the mounting body. The three filtered light reflectors retro-reflect substantially all incident light rays that are transmissive by their monochromatic filters and received by the three filtered light reflectors. In one embodiment the short-range reflector array is embedded within the hemispherical reflector,

  14. Fuzzy adaptive Kalman filter for indoor mobile target positioning with INS/WSN integrated method

    Institute of Scientific and Technical Information of China (English)

    杨海; 李威; 罗成名

    2015-01-01

    Pure inertial navigation system (INS) has divergent localization errors after a long time. In order to compensate the disadvantage, wireless sensor network (WSN) associated with the INS was applied to estimate the mobile target positioning. Taking traditional Kalman filter (KF) as the framework, the system equation of KF was established by the INS and the observation equation of position errors was built by the WSN. Meanwhile, the observation equation of velocity errors was established by the velocity difference between the INS and WSN, then the covariance matrix of Kalman filter measurement noise was adjusted with fuzzy inference system (FIS), and the fuzzy adaptive Kalman filter (FAKF) based on the INS/WSN was proposed. The simulation results show that the FAKF method has better accuracy and robustness than KF and EKF methods and shows good adaptive capacity with time-varying system noise. Finally, experimental results further prove that FAKF has the fast convergence error, in comparison with KF and EKF methods.

  15. Hierarchical mesosilicalite nanoformulation integrated with cisplatin exhibits target-specific efficient anticancer activity

    Science.gov (United States)

    Jermy, B. Rabindran; Acharya, Sadananda; Ravinayagam, Vijaya; Alghamdi, Hajer Saleh; Akhtar, Sultan; Basuwaidan, Rehab S.

    2018-04-01

    Hierarchically structured zeolitic ZSM-5 and meso MCM-41 interlinked domain had an impeccable use as catalysis in many applications. The aim of the study was to develop a new drug delivery nanoformulation, specifically, cisplatin/mesosilicalite using top-down approach for cancer therapy. Hierarchical mesosilicalite with variable porosity was synthesized using alkaline molar solution (0.2 and 0.7 M NaOH) and was loaded with cisplatin through equilibrium adsorption technique. Physico-chemical properties of the nanoformulation (IAUM-56—Imam Abdulrahman Bin Faisal University Mesosilicalite-56) were characterized using X-ray diffraction, surface area analysis (BET), Fourier transformed infrared spectroscopy (FT-IR), diffuse reflectance UV-Vis spectroscopy, and transmission electron microscopy. Drug release study and anticancer activity were assayed on HeLa and MCF7 cancer cells using MTT assay. X-ray diffraction pattern showed interrelated meso- and microphases, while BET analysis revealed considerable mesoporosity formation with a remodulation of isotherm hysteresis indicating the presence of hierarchical pores. FT-IR showed the presence of nanozeolitic subunits into mesostructure with a band at about 550 cm-1. IAUM-56 demonstrated high cytotoxic activity against HeLa cancer cells with an LC50 of 0.02 mg/ml, MCF7 cancer cells with an LC50 of 0.05 mg/ml, and less toxic to normal fibroblast cells with an LC50 of approximately ten times higher at 0.5 mg/ml. Overall, IAUM-56 showed a high rate of sustained release of cisplatin imparting target specific cytotoxic effect against tumor cells with at least tenfold lower toxicity on normal fibroblast cells. Our nanoformulation has the potential use in cancer therapy as a targeted drug delivery system.

  16. Multi-site risk-based project planning, optimization, sequencing, & budgeting process and tool for the integrated facility disposition project

    International Nuclear Information System (INIS)

    Nelson, J.G.; Castillo, C.; Huntsman, J.; Killoy, S.; Lucek, H.; Marks, T.C.

    2011-01-01

    Faced with the Department of Energy (DOE) Complex Transformation, National Nuclear Security Administration (NNSA) was tasked with developing an integrated plan for the decommissioning of over 400 facilities and 300 environmental remediation units, as well as the many reconfiguration and modernization projects at the Oak Ridge National Laboratory (ORNL) and Y-12 Complex. Manual scheduling of remediation activities is time-consuming and inherently introduces bias of the scheduler or organization into the process. Clearly a well-defined process, quantitative risk-based tool was needed to develop an objective, unbiased baseline sequence and schedule with a sound technical foundation for the Integrated Facility Disposition Project (IFDP). Faced with limited available data, innovation was needed to extrapolate intelligent relative data for key risk parameters based on known data elements. The IFDP Supermodel was customized and expanded to provide this capability for conceptual planning of diverse project portfolios and multiple sites. (author)

  17. The role of short-range Cys171-Cys178 disulfide bond in maintaining cutinase active site integrity: A molecular dynamics simulation

    International Nuclear Information System (INIS)

    Matak, Mehdi Youssefi; Moghaddam, Majid Erfani

    2009-01-01

    Understanding structural determinants in enzyme active site integrity can provide a good knowledge to design efficient novel catalytic machineries. Fusarium solani pisi cutinase with classic triad Ser-His-Asp is a promising enzyme to scrutinize these structural determinants. We performed two MD simulations: one, with the native structure, and the other with the broken Cys171-Cys178 disulfide bond. This disulfide bond stabilizes a turn in active site on which catalytic Asp175 is located. Functionally important H-bonds and atomic fluctuations in catalytic pocket have been changed. We proposed that this disulfide bond within active site can be considered as an important determinant of cutinase active site structural integrity.

  18. Insights into Integrated Lead Generation and Target Identification in Malaria and Tuberculosis Drug Discovery.

    Science.gov (United States)

    Okombo, John; Chibale, Kelly

    2017-07-18

    New, safe and effective drugs are urgently needed to treat and control malaria and tuberculosis, which affect millions of people annually. However, financial return on investment in the poor settings where these diseases are mostly prevalent is very minimal to support market-driven drug discovery and development. Moreover, the imminent loss of therapeutic lifespan of existing therapies due to evolution and spread of drug resistance further compounds the urgency to identify novel effective drugs. However, the advent of new public-private partnerships focused on tropical diseases and the recent release of large data sets by pharmaceutical companies on antimalarial and antituberculosis compounds derived from phenotypic whole cell high throughput screening have spurred renewed interest and opened new frontiers in malaria and tuberculosis drug discovery. This Account recaps the existing challenges facing antimalarial and antituberculosis drug discovery, including limitations associated with experimental animal models as well as biological complexities intrinsic to the causative pathogens. We enlist various highlights from a body of work within our research group aimed at identifying and characterizing new chemical leads, and navigating these challenges to contribute toward the global drug discovery and development pipeline in malaria and tuberculosis. We describe a catalogue of in-house efforts toward deriving safe and efficacious preclinical drug development candidates via cell-based medicinal chemistry optimization of phenotypic whole-cell medium and high throughput screening hits sourced from various small molecule chemical libraries. We also provide an appraisal of target-based screening, as invoked in our laboratory for mechanistic evaluation of the hits generated, with particular focus on the enzymes within the de novo pyrimidine biosynthetic and hemoglobin degradation pathways, the latter constituting a heme detoxification process and an associated cysteine

  19. An integrative computational framework based on a two-step random forest algorithm improves prediction of zinc-binding sites in proteins.

    Directory of Open Access Journals (Sweden)

    Cheng Zheng

    Full Text Available Zinc-binding proteins are the most abundant metalloproteins in the Protein Data Bank where the zinc ions usually have catalytic, regulatory or structural roles critical for the function of the protein. Accurate prediction of zinc-binding sites is not only useful for the inference of protein function but also important for the prediction of 3D structure. Here, we present a new integrative framework that combines multiple sequence and structural properties and graph-theoretic network features, followed by an efficient feature selection to improve prediction of zinc-binding sites. We investigate what information can be retrieved from the sequence, structure and network levels that is relevant to zinc-binding site prediction. We perform a two-step feature selection using random forest to remove redundant features and quantify the relative importance of the retrieved features. Benchmarking on a high-quality structural dataset containing 1,103 protein chains and 484 zinc-binding residues, our method achieved >80% recall at a precision of 75% for the zinc-binding residues Cys, His, Glu and Asp on 5-fold cross-validation tests, which is a 10%-28% higher recall at the 75% equal precision compared to SitePredict and zincfinder at residue level using the same dataset. The independent test also indicates that our method has achieved recall of 0.790 and 0.759 at residue and protein levels, respectively, which is a performance better than the other two methods. Moreover, AUC (the Area Under the Curve and AURPC (the Area Under the Recall-Precision Curve by our method are also respectively better than those of the other two methods. Our method can not only be applied to large-scale identification of zinc-binding sites when structural information of the target is available, but also give valuable insights into important features arising from different levels that collectively characterize the zinc-binding sites. The scripts and datasets are available at http://protein.cau.edu.cn/zincidentifier/.

  20. Rhodium(II) Proximity-Labeling Identifies a Novel Target Site on STAT3 for Inhibitors with Potent Anti-Leukemia Activity.

    Science.gov (United States)

    Minus, Matthew B; Liu, Wei; Vohidov, Farrukh; Kasembeli, Moses M; Long, Xin; Krueger, Michael J; Stevens, Alexandra; Kolosov, Mikhail I; Tweardy, David J; Sison, Edward Allan R; Redell, Michele S; Ball, Zachary T

    2015-10-26

    Nearly 40 % of children with acute myeloid leukemia (AML) suffer relapse arising from chemoresistance, often involving upregulation of the oncoprotein STAT3 (signal transducer and activator of transcription 3). Herein, rhodium(II)-catalyzed, proximity-driven modification identifies the STAT3 coiled-coil domain (CCD) as a novel ligand-binding site, and we describe a new naphthalene sulfonamide inhibitor that targets the CCD, blocks STAT3 function, and halts its disease-promoting effects in vitro, in tumor growth models, and in a leukemia mouse model, validating this new therapeutic target for resistant AML. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Drugability of extracellular targets: discovery of small molecule drugs targeting allosteric, functional, and subunit-selective sites on GPCRs and ion channels.

    Science.gov (United States)

    Grigoriadis, Dimitri E; Hoare, Samuel R J; Lechner, Sandra M; Slee, Deborah H; Williams, John A

    2009-01-01

    Beginning with the discovery of the structure of deoxyribose nucleic acid in 1953, by James Watson and Francis Crick, the sequencing of the entire human genome some 50 years later, has begun to quantify the classes and types of proteins that may have relevance to human disease with the promise of rapidly identifying compounds that can modulate these proteins so as to have a beneficial and therapeutic outcome. This so called 'drugable space' involves a variety of membrane-bound proteins including the superfamily of G-protein-coupled receptors (GPCRs), ion channels, and transporters among others. The recent number of novel therapeutics targeting membrane-bound extracellular proteins that have reached the market in the past 20 years however pales in magnitude when compared, during the same timeframe, to the advancements made in the technologies available to aid in the discovery of these novel therapeutics. This review will consider select examples of extracellular drugable targets and focus on the GPCRs and ion channels highlighting the corticotropin releasing factor (CRF) type 1 and gamma-aminobutyric acid receptors, and the Ca(V)2.2 voltage-gated ion channel. These examples will elaborate current technological advancements in drug discovery and provide a prospective framework for future drug development.

  2. DNFSB Recommendation 94-1 Hanford Site Integrated Stabilization Management Plan. Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    McCormack, R.L.

    1995-08-01

    This document describes the plans of the Hanford Site for the safe interim storage of fissile materials. Currently, spent nuclear fuels reside in storage basins that have leaked in the past and are projected to leak in the future. Other problems in the basins include; sludge from decomposition, degraded cladding of fuel elements, and construction defects which make the basins seismically unsafe. This management plan describes the time and cost that it will take to implement a safe interim storage plan for the fissile materials.

  3. An integrated approach to regional waste management and mine site rehabilitation

    Energy Technology Data Exchange (ETDEWEB)

    Reid, A.V.; Nettle, C.

    2000-07-01

    Municipal solid (putrescible) waste is expected to be treated at Woodlawn Mines using 'bioreactor' processes within the existing mine void. This paper briefly outlines legislation and regional waste management planning issues that led to the development of the Woodlawn Waste Management Facility. It also examines the application of 'bioreactor' technology as a rehabilitation strategy at Woodlawn, energy recovery opportunities and greenhouse gas savings, and the integrated manner in which mining and waste management have combined to provide unprecedented environmental outcomes across both industries. 22 refs., 3 figs., 5 tabs.

  4. Operationalisation the Romanian Employment Strategy – Target for European Union Integration

    Directory of Open Access Journals (Sweden)

    Alina Stefania Cretu

    2007-01-01

    Full Text Available In the context of the Romania’s integration into the EU, as resources become more limited and constrains more acute, expectations for government services have become more demanding. Regarding labour market these changes had a significant impact on the Public Employment Services(PES. At the beginning of the new millennium the challenges facing the PES are considerable mostly because of some external problems such as: structural unemployment; social exclusion; the vulnerability of many workers because of shortage of decent work; less stability in employment and careers; an increasing demand for lifelong education and learning; public concern about the escalating costs of social security; a multiplicity of public and private labour markets actors. As it is argued in many recent studies: "there is a general agreement on the need to shift the focus of the labour market policies from the passive provision of income support to more active measures which assist reemployment." Being considered, as well, an objective for the developing countries, as Romania, a country that wants the labour market to be flexible, and also wants a fast economic growth and that is joining to an economy based on knowledge is stimulating the development of the service sector, a key factor of national competitiveness.

  5. Operationalisation the Romanian Employment Strategy – Target for European Union Integration

    Directory of Open Access Journals (Sweden)

    Alina Stefania Cretu

    2007-01-01

    Full Text Available In the context of the Romania's integration into the EU, as resources become more limited and constrains more acute, expectations for government services have become more demanding. Regarding labour market these changes had a significant impact on the Public Employment Services(PES. At the beginning of the new millennium the challenges facing the PES are considerable mostly because of some external problems such as: structural unemployment; social exclusion; the vulnerability of many workers because of shortage of decent work; less stability in employment and careers; an increasing demand for lifelong education and learning; public concern about the escalating costs of social security; a multiplicity of public and private labour markets actors. As it is argued in many recent studies: "there is a general agreement on the need to shift the focus of the labour market policies from the passive provision of income support to more active measures which assist reemployment." Being considered, as well, an objective for the developing countries, as Romania, a country that wants the labour market to be flexible, and also wants a fast economic growth and that is joining to an economy based on knowledge is stimulating the development of the service sector, a key factor of national competitiveness.

  6. Integrating state-of-the-science technology for a cost-effective hazardous waste site characterization

    International Nuclear Information System (INIS)

    Muhr, C.A.; Dickerson, K.S.; Ko