Occurrence of contaminants of emerging concern along the California coast (2009-10) using passive sampling devices.

PubMed

Alvarez, David A; Maruya, Keith A; Dodder, Nathan G; Lao, Wenjian; Furlong, Edward T; Smalling, Kelly L

2014-04-30

Three passive sampling devices (PSDs), polar organic chemical integrative samplers (POCIS), polyethylene devices (PEDs), and solid-phase microextraction (SPME) samplers were used to sample a diverse set of chemicals in the coastal waters of San Francisco Bay and the Southern California Bight. Seventy one chemicals (including fragrances, phosphate flame retardants, pharmaceuticals, PAHs, PCBs, PBDEs, and pesticides) were measured in at least 50% of the sites. The chemical profile from the San Francisco Bay sites was distinct from profiles from the sites in the Southern California Bight. This distinction was not due to a single compound or class, but by the relative abundances/concentrations of the chemicals. Comparing the PSDs to mussel (Mytilus spp.) tissues, a positive correlation exists for the 25 and 26 chemicals in common for the PEDs and SPME, respectively. Diphenhydramine was the only common chemical out of 40 analyzed in both POCIS and tissues detected at a common site. Published by Elsevier Ltd.

Occurrence of contaminants of emerging concern along the California coast (2009-10) using passive sampling devices

USGS Publications Warehouse

Alvarez, David A.; Maruya, Keith A.; Dodder, Nathan G.; Lao, Wenjian; Furlong, Edward T.; Smalling, Kelly L.

2014-01-01

Three passive sampling devices (PSDs), polar organic chemical integrative samplers (POCIS), polyethylene devices (PEDs), and solid-phase microextraction (SPME) samplers were used to sample a diverse set of chemicals in the coastal waters of San Francisco Bay and the Southern California Bight. Seventy one chemicals (including fragrances, phosphate flame retardants, pharmaceuticals, PAHs, PCBs, PBDEs, and pesticides) were measured in at least 50% of the sites. The chemical profile from the San Francisco Bay sites was distinct from profiles from the sites in the Southern California Bight. This distinction was not due to a single compound or class, but by the relative abundances/concentrations of the chemicals. Comparing the PSDs to mussel (Mytilus spp.) tissues, a positive correlation exists for the 25 and 26 chemicals in common for the PEDs and SPME, respectively. Diphenhydramine was the only common chemical out of 40 analyzed in both POCIS and tissues detected at a common site.

Integrated field and laboratory tests to evaluate effects of metals-impacted wetlands on amphibians: A case study from Montana

USGS Publications Warehouse

Linder, G.; ,

2003-01-01

Mining activities frequently impact wildlife habitats, and a wide range of habitats may require evaluations of the linkages between wildlife and environmental stressors common to mining activities (e.g., physical alteration of habitat, releases of chemicals such as metals and other inorganic constituents as part of the mining operation). Wetlands, for example, are frequently impacted by mining activities. Within an ecological assessment for a wetland, toxicity evaluations for representative species may be advantageous to the site evaluation, since these species could be exposed to complex chemical mixtures potentially released from the site. Amphibian species common to these transition zones between terrestrial and aquatic habitats are one key biological indicator of exposure, and integrated approaches which involve both field and laboratory methods focused on amphibians are critical to the assessment process. The laboratory and field evaluations of a wetland in western Montana illustrates the integrated approach to risk assessment and causal analysis. Here, amphibians were used to evaluate the potential toxicity associated with heavy metal-laden sediments deposited in a reservoir. Field and laboratory methods were applied to a toxicity assessment for metals characteristic of mine tailings to reduce potential "lab to field" extrapolation errors and provide adaptive management programs with critical site-specific information targeted on remediation.

Common fragile sites (CFS) and extremely large CFS genes are targets for human papillomavirus integrations and chromosome rearrangements in oropharyngeal squamous cell carcinoma.

PubMed

Gao, Ge; Johnson, Sarah H; Vasmatzis, George; Pauley, Christina E; Tombers, Nicole M; Kasperbauer, Jan L; Smith, David I

2017-01-01

Common fragile sites (CFS) are chromosome regions that are prone to form gaps or breaks in response to DNA replication stress. They are often found as hotspots for sister chromatid exchanges, deletions, and amplifications in different cancers. Many of the CFS regions are found to span genes whose genomic sequence is greater than 1 Mb, some of which have been demonstrated to function as important tumor suppressors. CFS regions are also hotspots for human papillomavirus (HPV) integrations in cervical cancer. We used mate-pair sequencing to examine HPV integration events and chromosomal structural variations in 34 oropharyngeal squamous cell carcinoma (OPSCC). We used endpoint PCR and Sanger sequencing to validate each HPV integration event and found HPV integrations preferentially occurred within CFS regions similar to what is observed in cervical cancer. We also found that many of the chromosomal alterations detected also occurred at or near the cytogenetic location of CFSs. Several large genes were also found to be recurrent targets of rearrangements, independent of HPV integrations, including CSMD1 (2.1Mb), LRP1B (1.9Mb), and LARGE1 (0.7Mb). Sanger sequencing revealed that the nucleotide sequences near to identified junction sites contained repetitive and AT-rich sequences that were shown to have the potential to form stem-loop DNA secondary structures that might stall DNA replication fork progression during replication stress. This could then cause increased instability in these regions which could lead to cancer development in human cells. Our findings suggest that CFSs and some specific large genes appear to play important roles in OPSCC. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Multi-site genetic analysis of diffusion images and voxelwise heritability analysis: A pilot project of the ENIGMA–DTI working group

PubMed Central

Jahanshad, Neda; Kochunov, Peter; Sprooten, Emma; Mandl, René C.; Nichols, Thomas E.; Almassy, Laura; Blangero, John; Brouwer, Rachel M.; Curran, Joanne E.; de Zubicaray, Greig I.; Duggirala, Ravi; Fox, Peter T.; Hong, L. Elliot; Landman, Bennett A.; Martin, Nicholas G.; McMahon, Katie L.; Medland, Sarah E.; Mitchell, Braxton D.; Olvera, Rene L.; Peterson, Charles P.; Starr, John M.; Sussmann, Jessika E.; Toga, Arthur W.; Wardlaw, Joanna M.; Wright, Margaret J.; Hulshoff Pol, Hilleke E.; Bastin, Mark E.; McIntosh, Andrew M.; Deary, Ian J.; Thompson, Paul M.; Glahn, David C.

2013-01-01

The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium was set up to analyze brain measures and genotypes from multiple sites across the world to improve the power to detect genetic variants that influence the brain. Diffusion tensor imaging (DTI) yields quantitative measures sensitive to brain development and degeneration, and some common genetic variants may be associated with white matter integrity or connectivity. DTI measures, such as the fractional anisotropy (FA) of water diffusion, may be useful for identifying genetic variants that influence brain microstructure. However, genome-wide association studies (GWAS) require large populations to obtain sufficient power to detect and replicate significant effects, motivating a multi-site consortium effort. As part of an ENIGMA–DTI working group, we analyzed high-resolution FA images from multiple imaging sites across North America, Australia, and Europe, to address the challenge of harmonizing imaging data collected at multiple sites. Four hundred images of healthy adults aged 18–85 from four sites were used to create a template and corresponding skeletonized FA image as a common reference space. Using twin and pedigree samples of different ethnicities, we used our common template to evaluate the heritability of tract-derived FA measures. We show that our template is reliable for integrating multiple datasets by combining results through meta-analysis and unifying the data through exploratory mega-analyses. Our results may help prioritize regions of the FA map that are consistently influenced by additive genetic factors for future genetic discovery studies. Protocols and templates are publicly available at (http://enigma.loni.ucla.edu/ongoing/dti-working-group/). PMID:23629049

Consolidation of trauma programs in the era of large health care delivery networks.

PubMed

Trooskin, S Z; Faucher, M B; Santora, T A; Talucci, R C

1999-03-01

To review the development of an integrated trauma program at two separate campuses brought about by the merger of two medical-affiliated hospitals, each with an integrated program and a common trauma administrator, medical director, and educational coordinator. Each campus has an associate trauma medical director for on-site administrative management, a nurse coordinator, and a registrar. The integration resulted in a reduction of 1.5 full-time equivalents and "cost" savings by consolidated use of the helicopter, outreach, prevention, research, and educational programs. Regular "integration meetings," ad hoc committees, and video-linked conferences were used to institute common quality improvement programs, morbidity and mortality discussions, policies, and clinical management protocols. Reaccreditation by an outside agency, elimination of duplicated services, and maintenance of pre-merger clinical volume results. This integrated trauma program may serve as a model in this era of individual hospitals merging into large health care delivery networks.

RAPTOR: An Enterprise Knowledge Discovery Engine

DOE Office of Scientific and Technical Information (OSTI.GOV)

2010-11-11

SharePoint search capability is commonly criticized by users due to the limited functionality provided. This software takes a world class search capability (Piranha) and integrates it with an Enterprise Level Collaboration Application installed on most major government and commercial sites.

VERSE: a novel approach to detect virus integration in host genomes through reference genome customization.

PubMed

Wang, Qingguo; Jia, Peilin; Zhao, Zhongming

2015-01-01

Fueled by widespread applications of high-throughput next generation sequencing (NGS) technologies and urgent need to counter threats of pathogenic viruses, large-scale studies were conducted recently to investigate virus integration in host genomes (for example, human tumor genomes) that may cause carcinogenesis or other diseases. A limiting factor in these studies, however, is rapid virus evolution and resulting polymorphisms, which prevent reads from aligning readily to commonly used virus reference genomes, and, accordingly, make virus integration sites difficult to detect. Another confounding factor is host genomic instability as a result of virus insertions. To tackle these challenges and improve our capability to identify cryptic virus-host fusions, we present a new approach that detects Virus intEgration sites through iterative Reference SEquence customization (VERSE). To the best of our knowledge, VERSE is the first approach to improve detection through customizing reference genomes. Using 19 human tumors and cancer cell lines as test data, we demonstrated that VERSE substantially enhanced the sensitivity of virus integration site detection. VERSE is implemented in the open source package VirusFinder 2 that is available at http://bioinfo.mc.vanderbilt.edu/VirusFinder/.

Childhood Obesity Research Demonstration (CORD): The Cross-Site Overview and Opportunities for Interventions Addressing Obesity Community-Wide

PubMed Central

Belay, Brook; Dooyema, Carrie A.; Williams, Nancy; Blanck, Heidi M.

2015-01-01

Abstract Background: This is the first of a set of articles in this issue on the Childhood Obesity Research Demonstration (CORD) project and provides an overview of the multisite approach and community-wide interventions. Innovative multisetting, multilevel approaches that integrate primary healthcare and public health interventions to improve outcomes for children with obesity need to be evaluated. The CORD project aims to improve BMI and obesity-related behaviors among underserved 2- to 12-year-old children by utilizing these approaches. Methods: The CORD consortium, structure, model terminology and key components, and common measures were solidified in year 1 of the CORD project. Demonstration sites applied the CORD model across communities in years 2 and 3. Evaluation plans for year 4 include site-specific analyses as well as cross-site impact, process, and sustainability evaluations. Results: The CORD approach resulted in commonalities and differences in participant, intervention, comparison, and outcome elements across sites. Products are to include analytic results as well as cost assessment, lessons learned, tools, and materials. Discussion: Foreseen opportunities and challenges arise from the similarities and unique aspects across sites. Communities adapted interventions to fit their local context and build on strengths, but, in turn, this flexibility makes cross-site evaluation challenging. Conclusion: The CORD project represents an evidence-based approach that integrates primary care and public health strategies and evaluates multisetting multilevel interventions, thus adding to the limited research in this field. CORD products will be disseminated to a variety of stakeholders to aid the understanding, prevention, and management of childhood obesity. PMID:25679059

Using i2b2 to Bootstrap Rural Health Analytics and Learning Networks

PubMed Central

Harris, Daniel R.; Baus, Adam D.; Harper, Tamela J.; Jarrett, Traci D.; Pollard, Cecil R.; Talbert, Jeffery C.

2017-01-01

We demonstrate that the open-source i2b2 (Informatics for Integrating Biology and the Bedside) data model can be used to bootstrap rural health analytics and learning networks. These networks promote communication and research initiatives by providing the infrastructure necessary for sharing data and insights across a group of healthcare and research partners. Data integration remains a crucial challenge in connecting rural healthcare sites with a common data sharing and learning network due to the lack of interoperability and standards within electronic health records. The i2b2 data model acts as a point of convergence for disparate data from multiple healthcare sites. A consistent and natural data model for healthcare data is essential for overcoming integration issues, but challenges such as those caused by weak data standardization must still be addressed. We describe our experience in the context of building the West Virginia/Kentucky Health Analytics and Learning Network, a collaborative, multi-state effort connecting rural healthcare sites. PMID:28261006

Using i2b2 to Bootstrap Rural Health Analytics and Learning Networks.

PubMed

Harris, Daniel R; Baus, Adam D; Harper, Tamela J; Jarrett, Traci D; Pollard, Cecil R; Talbert, Jeffery C

2016-08-01

We demonstrate that the open-source i2b2 (Informatics for Integrating Biology and the Bedside) data model can be used to bootstrap rural health analytics and learning networks. These networks promote communication and research initiatives by providing the infrastructure necessary for sharing data and insights across a group of healthcare and research partners. Data integration remains a crucial challenge in connecting rural healthcare sites with a common data sharing and learning network due to the lack of interoperability and standards within electronic health records. The i2b2 data model acts as a point of convergence for disparate data from multiple healthcare sites. A consistent and natural data model for healthcare data is essential for overcoming integration issues, but challenges such as those caused by weak data standardization must still be addressed. We describe our experience in the context of building the West Virginia/Kentucky Health Analytics and Learning Network, a collaborative, multi-state effort connecting rural healthcare sites.

Integrated geophysical investigations in a fault zone located on southwestern part of İzmir city, Western Anatolia, Turkey

NASA Astrophysics Data System (ADS)

Drahor, Mahmut G.; Berge, Meriç A.

2017-01-01

Integrated geophysical investigations consisting of joint application of various geophysical techniques have become a major tool of active tectonic investigations. The choice of integrated techniques depends on geological features, tectonic and fault characteristics of the study area, required resolution and penetration depth of used techniques and also financial supports. Therefore, fault geometry and offsets, sediment thickness and properties, features of folded strata and tectonic characteristics of near-surface sections of the subsurface could be thoroughly determined using integrated geophysical approaches. Although Ground Penetrating Radar (GPR), Electrical Resistivity Tomography (ERT) and Seismic Refraction Tomography (SRT) methods are commonly used in active tectonic investigations, other geophysical techniques will also contribute in obtaining of different properties in the complex geological environments of tectonically active sites. In this study, six different geophysical methods used to define faulting locations and characterizations around the study area. These are GPR, ERT, SRT, Very Low Frequency electromagnetic (VLF), magnetics and self-potential (SP). Overall integrated geophysical approaches used in this study gave us commonly important results about the near surface geological properties and faulting characteristics in the investigation area. After integrated interpretations of geophysical surveys, we determined an optimal trench location for paleoseismological studies. The main geological properties associated with faulting process obtained after trenching studies. In addition, geophysical results pointed out some indications concerning the active faulting mechanism in the area investigated. Consequently, the trenching studies indicate that the integrated approach of geophysical techniques applied on the fault problem reveals very useful and interpretative results in description of various properties of faulting zone in the investigation site.

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

PubMed

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.

Characterization of the genetic elements required for site-specific integration of plasmid pSE211 in Saccharopolyspora erythraea.

PubMed Central

Brown, D P; Idler, K B; Katz, L

1990-01-01

The 18.1-kilobase plasmid pSE211 integrates into the chromosome of Saccharopolyspora erythraea at a specific attB site. Restriction analysis of the integrated plasmid, pSE211int, and adjacent chromosomal sequences allowed identification of attP, the plasmid attachment site. Nucleotide sequencing of attP, attB, attL, and attR revealed a 57-base-pair sequence common to all sites with no duplications of adjacent plasmid or chromosomal sequences in the integrated state, indicating that integration takes place through conservative, reciprocal strand exchange. An analysis of the sequences indicated the presence of a putative gene for Phe-tRNA at attB which is preserved at attL after integration has occurred. A comparison of the attB site for a number of actinomycete plasmids is presented. Integration at attB was also observed when a 2.4-kilobase segment of pSE211 containing attP and the adjacent plasmid sequence was used to transform a pSE211- host. Nucleotide sequencing of this segment revealed the presence of two complete open reading frames (ORFs) and a segment of a third ORF. The ORF adjacent to attP encodes a putative polypeptide 437 amino acids in length that shows similarity, at its C-terminal domain, to sequences of site-specific recombinases of the integrase family. The adjacent ORF encodes a putative 98-amino-acid basic polypeptide that contains a helix-turn-helix motif at its N terminus which corresponds to domains in the Xis proteins of a number of bacteriophages. A proposal for the function of this polypeptide is presented. The deduced amino acid sequence of the third ORF did not reveal similarities to polypeptide sequences in the current data banks. Images FIG. 2 FIG. 3 PMID:2180909

TECHNIQUES FOR THE FABRICATION OF GEOMEMBRANE FILLED SEAMS

EPA Science Inventory

Geomembranes employed to overlay the excavation for landfills must be seamed together on-site at the landfill. To ensure the integrity of the containment system of the landfill, these sheets or blankets must be carefully seamed. Present methods in common use are: extrusion fil...

Novel pre-mRNA splicing of intronically integrated HBV generates oncogenic chimera in hepatocellular carcinoma.

PubMed

Chiu, Yung-Tuen; Wong, John K L; Choi, Shing-Wan; Sze, Karen M F; Ho, Daniel W H; Chan, Lo-Kong; Lee, Joyce M F; Man, Kwan; Cherny, Stacey; Yang, Wan-Ling; Wong, Chun-Ming; Sham, Pak-Chung; Ng, Irene O L

2016-06-01

Hepatitis B virus (HBV) integration is common in HBV-associated hepatocellular carcinoma (HCC) and may play an important pathogenic role through the production of chimeric HBV-human transcripts. We aimed to screen the transcriptome for HBV integrations in HCCs. Transcriptome sequencing was performed on paired HBV-associated HCCs and corresponding non-tumorous liver tissues to identify viral-human chimeric sites. Validation was further performed in an expanded cohort of human HCCs. Here we report the discovery of a novel pre-mRNA splicing mechanism in generating HBV-human chimeric protein. This mechanism was exemplified by the formation of a recurrent HBV-cyclin A2 (CCNA2) chimeric transcript (A2S), as detected in 12.5% (6 of 48) of HCC patients, but in none of the 22 non-HCC HBV-associated cirrhotic liver samples examined. Upon the integration of HBV into the intron of the CCNA2 gene, the mammalian splicing machinery utilized the foreign splice sites at 282nt. and 458nt. of the HBV genome to generate a pseudo-exon, forming an in-frame chimeric fusion with CCNA2. The A2S chimeric protein gained a non-degradable property and promoted cell cycle progression, demonstrating its potential oncogenic functions. A pre-mRNA splicing mechanism is involved in the formation of HBV-human chimeric proteins. This represents a novel and possibly common mechanism underlying the formation of HBV-human chimeric transcripts from intronically integrated HBV genome with functional impact. HBV is involved in the mammalian pre-mRNA splicing machinery in the generation of potential tumorigenic HBV-human chimeras. This study also provided insight on the impact of intronic HBV integration with the gain of splice sites in the development of HBV-associated HCC. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

A comprehensive analysis of Helicobacter pylori plasticity zones reveals that they are integrating conjugative elements with intermediate integration specificity.

PubMed

Fischer, Wolfgang; Breithaupt, Ute; Kern, Beate; Smith, Stella I; Spicher, Carolin; Haas, Rainer

2014-04-27

The human gastric pathogen Helicobacter pylori is a paradigm for chronic bacterial infections. Its persistence in the stomach mucosa is facilitated by several mechanisms of immune evasion and immune modulation, but also by an unusual genetic variability which might account for the capability to adapt to changing environmental conditions during long-term colonization. This variability is reflected by the fact that almost each infected individual is colonized by a genetically unique strain. Strain-specific genes are dispersed throughout the genome, but clusters of genes organized as genomic islands may also collectively be present or absent. We have comparatively analysed such clusters, which are commonly termed plasticity zones, in a high number of H. pylori strains of varying geographical origin. We show that these regions contain fixed gene sets, rather than being true regions of genome plasticity, but two different types and several subtypes with partly diverging gene content can be distinguished. Their genetic diversity is incongruent with variations in the rest of the genome, suggesting that they are subject to horizontal gene transfer within H. pylori populations. We identified 40 distinct integration sites in 45 genome sequences, with a conserved heptanucleotide motif that seems to be the minimal requirement for integration. The significant number of possible integration sites, together with the requirement for a short conserved integration motif and the high level of gene conservation, indicates that these elements are best described as integrating conjugative elements (ICEs) with an intermediate integration site specificity.

Common coastal foraging areas for loggerheads in the Gulf of Mexico: Opportunities for marine conservation

USGS Publications Warehouse

Hart, Kristen M.; Lamont, Margaret M.; Fujisaki, Ikuko; Tucker, Anton D.; Carthy, Raymond R.

2012-01-01

Designing conservation strategies that protect wide-ranging marine species is a significant challenge, but integrating regional telemetry datasets and synthesizing modeled movements and behavior offer promise for uncovering distinct at-sea areas that are important habitats for imperiled marine species. Movement paths of 10 satellite-tracked female loggerheads (Caretta caretta) from three separate subpopulations in the Gulf of Mexico, USA, revealed migration to discrete foraging sites in two common areas at-sea in 2008, 2009, and 2010. Foraging sites were 102–904 km away from nesting and tagging sites, and located off southwest Florida and the northern Yucatan Peninsula, Mexico. Within 3–35 days, turtles migrated to foraging sites where they all displayed high site fidelity over time. Core-use foraging areas were 13.0–335.2 km2 in size, in water <50 m deep, within a mean distance to nearest coastline of 58.5 km, and in areas of relatively high net primary productivity. The existence of shared regional foraging sites highlights an opportunity for marine conservation strategies to protect important at-sea habitats for these imperiled marine turtles, in both USA and international waters. Until now, knowledge of important at-sea foraging areas for adult loggerheads in the Gulf of Mexico has been limited. To better understand the spatial distribution of marine turtles that have complex life-histories, we propose further integration of disparate tracking data-sets at the oceanic scale along with modeling of movements to identify critical at-sea foraging habitats where individuals may be resident during non-nesting periods.

Cryptocoryne beckettii complex (Araceae) introduced at a Florida spring

USGS Publications Warehouse

Jacono, C.C.

2002-01-01

A vegetative population of Cryptocoryne (Araceae), introduced at a Florida spring, appeared to represent three closely related species in the C. beckettii complex: C. beckettii Thw. ex Trimen, C. wendtii de Wit and C. undulata Wendt. Individuals of C. undulata were true to type and could be delineated at the site. Intergradation of diagnostic features was common in others, upon transplanting and flowering. While some transplants produced spathes characteristic of either C. wendtii or C. beckettii, intermediates between the two species were common. Neither C. beckettii nor C. wendtii could be delineated at the site. The seclusion of the stream and the integrity of native plant communities have likely prevented dispersal downstream.

Developing a data life cycle for carbon and greenhouse gas measurements: challenges, experiences and visions

NASA Astrophysics Data System (ADS)

Kutsch, W. L.

2015-12-01

Environmental research infrastructures and big data integration networks require common data policies, standardized workflows and sophisticated e-infrastructure to optimise the data life cycle. This presentation summarizes the experiences in developing the data life cycle for the Integrated Carbon Observation System (ICOS), a European Research Infrastructure. It will also outline challenges that still exist and visions for future development. As many other environmental research infrastructures ICOS RI built on a large number of distributed observational or experimental sites. Data from these sites are transferred to Thematic Centres and quality checked, processed and integrated there. Dissemination will be managed by the ICOS Carbon Portal. This complex data life cycle has been defined in detail by developing protocols and assigning responsibilities. Since data will be shared under an open access policy there is a strong need for common data citation tracking systems that allow data providers to identify downstream usage of their data so as to prove their importance and show the impact to stakeholders and the public. More challenges arise from interoperating with other infrastructures or providing data for global integration projects as done e.g. in the framework of GEOSS or in global integration approaches such as fluxnet or SOCAt. Here, common metadata systems are the key solutions for data detection and harvesting. The metadata characterises data, services, users and ICT resources (including sensors and detectors). Risks may arise when data of high and low quality are mixed during this process or unexperienced data scientists without detailed knowledge on the data aquisition derive scientific theories through statistical analyses. The vision of fully open data availability is expressed in a recent GEO flagship initiative that will address important issues needed to build a connected and interoperable global network for carbon cycle and greenhouse gas observations and aims to meet the most urgent needs for integration between different information sources and methodologies, between different regional networks and from data providers to users.

INSPECTION TECHNIQUES FOR THE FABRICATION OF GEOMEMBRANE FIELD SEAMS

EPA Science Inventory

Geomembranes employed to overlay the excavation for landfills must be seamed together at the site of the landfill. o ensure the integrity of the containment system of the landfill, these sheets or blankets must be carefully seamed. he methods in present, common use are extrusion ...

Host factors that promote retrotransposon integration are similar in distantly related eukaryotes

PubMed Central

Rai, Sudhir Kumar; Sangesland, Maya; Lee, Michael; Esnault, Caroline; Cui, Yujin; Chatterjee, Atreyi Ghatak

2017-01-01

Retroviruses and Long Terminal Repeat (LTR)-retrotransposons have distinct patterns of integration sites. The oncogenic potential of retrovirus-based vectors used in gene therapy is dependent on the selection of integration sites associated with promoters. The LTR-retrotransposon Tf1 of Schizosaccharomyces pombe is studied as a model for oncogenic retroviruses because it integrates into the promoters of stress response genes. Although integrases (INs) encoded by retroviruses and LTR-retrotransposons are responsible for catalyzing the insertion of cDNA into the host genome, it is thought that distinct host factors are required for the efficiency and specificity of integration. We tested this hypothesis with a genome-wide screen of host factors that promote Tf1 integration. By combining an assay for transposition with a genetic assay that measures cDNA recombination we could identify factors that contribute differentially to integration. We utilized this assay to test a collection of 3,004 S. pombe strains with single gene deletions. Using these screens and immunoblot measures of Tf1 proteins, we identified a total of 61 genes that promote integration. The candidate integration factors participate in a range of processes including nuclear transport, transcription, mRNA processing, vesicle transport, chromatin structure and DNA repair. Two candidates, Rhp18 and the NineTeen complex were tested in two-hybrid assays and were found to interact with Tf1 IN. Surprisingly, a number of pathways we identified were found previously to promote integration of the LTR-retrotransposons Ty1 and Ty3 in Saccharomyces cerevisiae, indicating the contribution of host factors to integration are common in distantly related organisms. The DNA repair factors are of particular interest because they may identify the pathways that repair the single stranded gaps flanking the sites of strand transfer following integration of LTR retroelements. PMID:29232693

Host factors that promote retrotransposon integration are similar in distantly related eukaryotes.

PubMed

Rai, Sudhir Kumar; Sangesland, Maya; Lee, Michael; Esnault, Caroline; Cui, Yujin; Chatterjee, Atreyi Ghatak; Levin, Henry L

2017-12-01

Retroviruses and Long Terminal Repeat (LTR)-retrotransposons have distinct patterns of integration sites. The oncogenic potential of retrovirus-based vectors used in gene therapy is dependent on the selection of integration sites associated with promoters. The LTR-retrotransposon Tf1 of Schizosaccharomyces pombe is studied as a model for oncogenic retroviruses because it integrates into the promoters of stress response genes. Although integrases (INs) encoded by retroviruses and LTR-retrotransposons are responsible for catalyzing the insertion of cDNA into the host genome, it is thought that distinct host factors are required for the efficiency and specificity of integration. We tested this hypothesis with a genome-wide screen of host factors that promote Tf1 integration. By combining an assay for transposition with a genetic assay that measures cDNA recombination we could identify factors that contribute differentially to integration. We utilized this assay to test a collection of 3,004 S. pombe strains with single gene deletions. Using these screens and immunoblot measures of Tf1 proteins, we identified a total of 61 genes that promote integration. The candidate integration factors participate in a range of processes including nuclear transport, transcription, mRNA processing, vesicle transport, chromatin structure and DNA repair. Two candidates, Rhp18 and the NineTeen complex were tested in two-hybrid assays and were found to interact with Tf1 IN. Surprisingly, a number of pathways we identified were found previously to promote integration of the LTR-retrotransposons Ty1 and Ty3 in Saccharomyces cerevisiae, indicating the contribution of host factors to integration are common in distantly related organisms. The DNA repair factors are of particular interest because they may identify the pathways that repair the single stranded gaps flanking the sites of strand transfer following integration of LTR retroelements.

On meta- and mega-analyses for gene–environment interactions

PubMed Central

Huang, Jing; Liu, Yulun; Vitale, Steve; Penning, Trevor M.; Whitehead, Alexander S.; Blair, Ian A.; Vachani, Anil; Clapper, Margie L.; Muscat, Joshua E.; Lazarus, Philip; Scheet, Paul; Moore, Jason H.; Chen, Yong

2017-01-01

Gene-by-environment (G × E) interactions are important in explaining the missing heritability and understanding the causation of complex diseases, but a single, moderately sized study often has limited statistical power to detect such interactions. With the increasing need for integrating data and reporting results from multiple collaborative studies or sites, debate over choice between mega- versus meta-analysis continues. In principle, data from different sites can be integrated at the individual level into a “mega” data set, which can be fit by a joint “mega-analysis.” Alternatively, analyses can be done at each site, and results across sites can be combined through a “meta-analysis” procedure without integrating individual level data across sites. Although mega-analysis has been advocated in several recent initiatives, meta-analysis has the advantages of simplicity and feasibility, and has recently led to several important findings in identifying main genetic effects. In this paper, we conducted empirical and simulation studies, using data from a G × E study of lung cancer, to compare the mega- and meta-analyses in four commonly used G × E analyses under the scenario that the number of studies is small and sample sizes of individual studies are relatively large. We compared the two data integration approaches in the context of fixed effect models and random effects models separately. Our investigations provide valuable insights in understanding the differences between mega- and meta-analyses in practice of combining small number of studies in identifying G × E interactions. PMID:29110346

On meta- and mega-analyses for gene-environment interactions.

PubMed

Huang, Jing; Liu, Yulun; Vitale, Steve; Penning, Trevor M; Whitehead, Alexander S; Blair, Ian A; Vachani, Anil; Clapper, Margie L; Muscat, Joshua E; Lazarus, Philip; Scheet, Paul; Moore, Jason H; Chen, Yong

2017-12-01

Gene-by-environment (G × E) interactions are important in explaining the missing heritability and understanding the causation of complex diseases, but a single, moderately sized study often has limited statistical power to detect such interactions. With the increasing need for integrating data and reporting results from multiple collaborative studies or sites, debate over choice between mega- versus meta-analysis continues. In principle, data from different sites can be integrated at the individual level into a "mega" data set, which can be fit by a joint "mega-analysis." Alternatively, analyses can be done at each site, and results across sites can be combined through a "meta-analysis" procedure without integrating individual level data across sites. Although mega-analysis has been advocated in several recent initiatives, meta-analysis has the advantages of simplicity and feasibility, and has recently led to several important findings in identifying main genetic effects. In this paper, we conducted empirical and simulation studies, using data from a G × E study of lung cancer, to compare the mega- and meta-analyses in four commonly used G × E analyses under the scenario that the number of studies is small and sample sizes of individual studies are relatively large. We compared the two data integration approaches in the context of fixed effect models and random effects models separately. Our investigations provide valuable insights in understanding the differences between mega- and meta-analyses in practice of combining small number of studies in identifying G × E interactions. © 2017 WILEY PERIODICALS, INC.

A Streamlined Molecular Biology Module for Undergraduate Biochemistry Labs

ERIC Educational Resources Information Center

Muth, Gregory W.; Chihade, Joseph W.

2008-01-01

Site-directed mutagenesis and other molecular biology techniques, including plasmid manipulation and restriction analysis, are commonly used tools in the biochemistry research laboratory. In redesigning our biochemistry lab curricula, we sought to integrate these techniques into a term-long, project-based course. In the module presented here,…

We did well but we definitely have to do better: four critical points about fluxnet

NASA Astrophysics Data System (ADS)

Kutsch, W. L.

2014-12-01

Fluxnet is a real success story of data integration. The scientific outcome is overwhelming. Nevertheless: in a time of methodological consolidation and transfer of the networks to technically more integrated infrastructures, a critical view on its weak points may strengthen the future success and our position within biogeochemical science. Four points should be discussed: We have to select our sites more thoroughly. We need better data curation. We should think about 'forgetting' some of the older datasets. We have responsibility for the results of integration studies. ad 1: We had to learn during the past years that the EC is not applicable in all terrains. Slope and footprint problems are widespread and sites have to be critically scrutinized before being sure that we submit valuable ecological information. This is time consuming and may be frustrating since we have to accept that we had sometimes invested lots of work and money for building a flux tower at a site that is not suitable for the method. Nevertheless, a clear site quality policy should be developed among infrastructures and integrating activities. ad 2: In some cases it has turned out that the information about different steps leading from the raw data to a number in integrated scientific papers has been lost. This is a big challenge to research infrastructures that should develop common rules for data curation to increase trust in integration activities. ad 3: In the first approach Fluxnet left the responsibility for site and data quality to the site PI and accepted more or less all data submitted. Further approaches and in particular long-term infrastructures have to develop strategies to reject (or at least flag) data from sites that are prone by terrain problems. This includes that in future integration studies we should stop using some of the datasets from the 'wild old times' when we did not know better. ad4: We need a strategy to communicate with data users that are far away from practical problems at the field sites. The amount of users without experience about possible problems related to terrain or technical limitations of eddy covariance will be dramatically increasing with open data policy, high performance computation and automated processing routines. The question arises how we can avoid misuse or misinterpretation of the data.

BOREAS TE-5 Leaf Carbon Isotope Data

NASA Technical Reports Server (NTRS)

Hall, Forrest G. (Editor); Curd, Shelaine (Editor); Ehleriinger, Jim; Brooks, J. Renee; Flanagan, Larry

2000-01-01

The BOREAS TE-5 team collected measurements in the NSA and SSA on gas exchange, gas composition, and tree growth. This documentation describes leaf carbon isotope data that were collected in 1993 and 1994 at the NSA and SSA OJP sites, the SSA OBS site, and the NSA UBS site. In addition, leaf carbon isotope data were collected in 1994 only at the NSA and SSA OA sites. These data was collected to provide seasonal integrated physiological information for 10 to 15 common species at these 6 BOREAS sites. The data are stored in tabular ASCII files. The data files are available on a CD-ROM (see document number 20010000884), or from the Oak Ridge National Laboratory (ORNL) Distributed Active Archive Center (DAAC).

Implementation of integrated dual disorders treatment: a qualitative analysis of facilitators and barriers.

PubMed

Brunette, Mary F; Asher, Dianne; Whitley, Rob; Lutz, Wilma J; Wieder, Barbara L; Jones, Amanda M; McHugo, Gregory J

2008-09-01

Approximately half of the people who have serious mental illnesses experience a co-occurring substance use disorder at some point in their lifetime. Integrated dual disorders treatment, a program to treat persons with co-occurring disorders, improves outcomes but is not widely available in public mental health settings. This report describes the extent to which this intervention was implemented by 11 community mental health centers participating in a large study of practice implementation. Facilitators and barriers to implementation are described. Trained implementation monitors conducted regular site visits over two years. During visits, monitors interviewed key informants, conducted ethnographic observations of implementation efforts, and assessed fidelity to the practice model. These data were coded and used as a basis for detailed site reports summarizing implementation processes. The authors reviewed the reports and distilled the three top facilitators and barriers for each site. The most prominent cross-site facilitators and barriers were identified. Two sites reached high fidelity, six sites reached moderate fidelity, and three sites remained at low fidelity over the two years. Prominent facilitators and barriers to implementation with moderate to high fidelity were administrative leadership, consultation and training, supervisor mastery and supervision, chronic staff turnover, and finances. Common facilitators and barriers to implementation of integrated dual disorders treatment emerged across sites. The results confirmed the importance of the use of the consultant-trainer in the model of implementation, as well as the need for intensive activities at multiple levels to facilitate implementation. Further research on service implementation is needed, including but not limited to clarifying strategies to overcome barriers.

Comparing the landcapes of common retroviral insertion sites across tumor models

NASA Astrophysics Data System (ADS)

Weishaupt, Holger; Čančer, Matko; Engström, Cristopher; Silvestrov, Sergei; Swartling, Fredrik J.

2017-01-01

Retroviral tagging represents an important technique, which allows researchers to screen for candidate cancer genes. The technique is based on the integration of retroviral sequences into the genome of a host organism, which might then lead to the artificial inhibition or expression of proximal genetic elements. The identification of potential cancer genes in this framework involves the detection of genomic regions (common insertion sites; CIS) which contain a number of such viral integration sites that is greater than expected by chance. During the last two decades, a number of different methods have been discussed for the identification of such loci and the respective techniques have been applied to a variety of different retroviruses and/or tumor models. We have previously established a retrovirus driven brain tumor model and reported the CISs which were found based on a Monte Carlo statistics derived detection paradigm. In this study, we consider a recently proposed alternative graph theory based method for identifying CISs and compare the resulting CIS landscape in our brain tumor dataset to those obtained when using the Monte Carlo approach. Finally, we also employ the graph-based method to compare the CIS landscape in our brain tumor model with those of other published retroviral tumor models.

Emergence of integrated urology-radiation oncology practices in the State of Texas.

PubMed

Jhaveri, Pavan M; Sun, Zhuyi; Ballas, Leslie; Followill, David S; Hoffman, Karen E; Jiang, Jing; Smith, Benjamin D

2012-09-01

Integrated urology-radiation oncology (RO) practices have been advocated as a means to improve community-based prostate cancer care by joining urologic and radiation care in a single-practice environment. However, little is known regarding the scope and actual physical integration of such practices. We sought to characterize the emergence of such practices in Texas, their extent of physical integration, and their potential effect on patient travel times for radiation therapy. A telephone survey identified integrated urology-RO practices, defined as practices owned by urologists that offer RO services. Geographic information software was used to determine the proximity of integrated urology-RO clinic sites with respect to the state's population. We calculated patient travel time and distance from each integrated urology-RO clinic offering urologic services to the RO treatment facility owned by the integrated practice and to the nearest nonintegrated (independent) RO facility. We compared these times and distances using the Wilcoxon-Mann-Whitney test. Of 229 urology practices identified, 12 (5%) offered integrated RO services, and 182 (28%) of 640 Texas urologists worked in such practices. Approximately 53% of the state population resides within 10 miles of an integrated urology-RO clinic site. Patients with a diagnosis of prostate cancer at an integrated urology-RO clinic site travel a mean of 19.7 miles (26.1 min) from the clinic to reach the RO facility owned by the integrated urology-RO practice vs 5.9 miles (9.2 min) to reach the nearest nonintegrated RO facility (P<.001). Integrated urology-RO practices are common in Texas and are generally clustered in urban areas. In most integrated practices, the urology clinics and the integrated RO facilities are not at the same location, and driving times and distances from the clinic to the integrated RO facility exceed those from the clinic to the nearest nonintegrated RO facility. Copyright © 2012 Elsevier Inc. All rights reserved.

Emergence of Integrated Urology-Radiation Oncology Practices in the State of Texas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jhaveri, Pavan M.; Sun Zhuyi; Ballas, Leslie

2012-09-01

Purpose: Integrated urology-radiation oncology (RO) practices have been advocated as a means to improve community-based prostate cancer care by joining urologic and radiation care in a single-practice environment. However, little is known regarding the scope and actual physical integration of such practices. We sought to characterize the emergence of such practices in Texas, their extent of physical integration, and their potential effect on patient travel times for radiation therapy. Methods and Materials: A telephone survey identified integrated urology-RO practices, defined as practices owned by urologists that offer RO services. Geographic information software was used to determine the proximity of integratedmore » urology-RO clinic sites with respect to the state's population. We calculated patient travel time and distance from each integrated urology-RO clinic offering urologic services to the RO treatment facility owned by the integrated practice and to the nearest nonintegrated (independent) RO facility. We compared these times and distances using the Wilcoxon-Mann-Whitney test. Results: Of 229 urology practices identified, 12 (5%) offered integrated RO services, and 182 (28%) of 640 Texas urologists worked in such practices. Approximately 53% of the state population resides within 10 miles of an integrated urology-RO clinic site. Patients with a diagnosis of prostate cancer at an integrated urology-RO clinic site travel a mean of 19.7 miles (26.1 min) from the clinic to reach the RO facility owned by the integrated urology-RO practice vs 5.9 miles (9.2 min) to reach the nearest nonintegrated RO facility (P<.001). Conclusions: Integrated urology-RO practices are common in Texas and are generally clustered in urban areas. In most integrated practices, the urology clinics and the integrated RO facilities are not at the same location, and driving times and distances from the clinic to the integrated RO facility exceed those from the clinic to the nearest nonintegrated RO facility.« less

Interpretations of integration in early accountable care organizations.

PubMed

Kreindler, Sara A; Larson, Bridget K; Wu, Frances M; Carluzzo, Kathleen L; Gbemudu, Josette N; Struthers, Ashley; VAN Citters, Aricca D; Shortell, Stephen M; Nelson, Eugene C; Fisher, Elliott S

2012-09-01

It is widely hoped that accountable care organizations (ACOs) will improve health care quality and reduce costs by fostering integration among diverse provider groups. But how do implementers actually envision integration, and what will integration mean in terms of managing the many social identities that ACOs bring together? Using the lens of the social identity approach, this qualitative study examined how four nascent ACOs engaged with the concept of integration. During multiday site visits, we conducted interviews (114 managers and physicians), observations, and document reviews. In no case was the ACO interpreted as a new, overarching entity uniting disparate groups; rather, each site offered a unique interpretation that flowed from its existing strategies for social-identity management: An independent practice association preserved members' cherished value of autonomy by emphasizing coordination, not "integration"; a medical group promoted integration within its employed core, but not with affiliates; a hospital, engaging community physicians who mistrusted integrated systems, reimagined integration as an equal partnership; an integrated delivery system advanced its careful journey towards intergroup consensus by presenting the ACO as a cultural, not structural, change. The ACO appears to be a model flexible enough to work in synchrony with whatever social strategies are most context appropriate, with the potential to promote alignment and functional integration without demanding common identification with a superordinate group. "Soft integration" may be a promising alternative to the vertically integrated model that, though widely assumed to be ideal, has remained unattainable for most organizations. © 2012 Milbank Memorial Fund.

Treatment of Chemotherapy-Induced Peripheral Neuropathy in Integrative Oncology: A Survey of Acupuncture and Oriental Medicine Practitioners.

PubMed

Lu, Zhaoxue; Moody, Jennifer; Marx, Benjamin L; Hammerstrom, Tracy

2017-12-01

Complementary and alternative medicine is increasingly integrated into cancer care. We sought detail on the treatment of chemotherapy-induced peripheral neuropathy (CIPN) with acupuncture and oriental medicine (AOM) by surveying practitioners at integrative oncology (IO) sites across the United States. Online survey of licensed acupuncturists. IO sites in the United States. Fifteen licensed acupuncturists who completed the survey between February 2014 and June 2014. Demographics, IO setting characteristics, AOM treatment characteristics, and practitioner-reported outcomes. Respondents reported an average of 31.3 ± 17.2 patients per week, and one-third (10.1 mean; 7.2 standard deviation [SD]) were treated for CIPN. Medical doctors (86.7%) were the most common providers with whom respondents worked. Traditional Chinese medicine style acupuncture was utilized by a majority of respondents (86.7%), and the most commonly used points were local, typically in the hands and feet, such as Ba Feng, Ba Xie, LV3, and LI4. In addition to acupuncture, nutritional advice was the most frequent auxiliary modality provided by respondents (85.7%). On average, respondents provided 12.75 ± 4.17 treatments for CIPN patients, and a majority (53%) reported treating patients once per week. Timing of the treatments relative to chemotherapy infusion was evenly distributed between "1-2 days after infusion" (60%), "at time of infusion" (53.3%), and "1-2 days before infusion" (46.7%). Sixty percent of respondents rated outcomes as "moderately successful with moderate improvement seen." This survey provides detail regarding IO sites using acupuncture for CIPN as well as real-world treatment patterns, including common point combinations, visit characteristics, and practitioner-reported outcomes. This information contributes to the emerging evidence on the use of acupuncture to address unmet needs of CIPN patients, and supports the development of best practice guidelines for the treatment of CIPN with acupuncture in the IO setting.

Cooperative activation of cardiac transcription through myocardin bridging of paired MEF2 sites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, Courtney M.; Hu, Jianxin; Thomas, Reuben

2017-03-28

Enhancers frequently contain multiple binding sites for the same transcription factor. These homotypic binding sites often exhibit synergy, whereby the transcriptional output from two or more binding sites is greater than the sum of the contributions of the individual binding sites alone. Although this phenomenon is frequently observed, the mechanistic basis for homotypic binding site synergy is poorly understood. Here in this paper, we identify a bona fide cardiac-specific Prkaa2 enhancer that is synergistically activated by homotypic MEF2 binding sites. We show that two MEF2 sites in the enhancer function cooperatively due to bridging of the MEF2C-bound sites by themore » SAP domain-containing co-activator protein myocardin, and we show that paired sites buffer the enhancer from integration site-dependent effects on transcription in vivo. Paired MEF2 sites are prevalent in cardiac enhancers, suggesting that this might be a common mechanism underlying synergy in the control of cardiac gene expression in vivo.« less

Commercial Biocides Induce Transfer of Prophage Φ13 from Human Strains of Staphylococcus aureus to Livestock CC398.

PubMed

Tang, Yuanyue; Nielsen, Lene N; Hvitved, Annemette; Haaber, Jakob K; Wirtz, Christiane; Andersen, Paal S; Larsen, Jesper; Wolz, Christiane; Ingmer, Hanne

2017-01-01

Human strains of Staphylococcus aureus commonly carry the bacteriophage ΦSa3 that encodes immune evasion factors. Recently, this prophage has been found in livestock-associated, methicillin resistant S. aureus (MRSA) CC398 strains where it may promote human colonization. Here, we have addressed if exposure to biocidal products induces phage transfer, and find that during co-culture, Φ13 from strain 8325, belonging to ΦSa3 group, is induced and transferred from a human strain to LA-MRSA CC398 when exposed to sub-lethal concentrations of commercial biocides containing hydrogen peroxide. Integration of ΦSa3 in LA-MRSA CC398 occurs at multiple positions and the integration site influences the stability of the prophage. We did not observe integration in hlb encoding β-hemolysin that contains the preferred ΦSa3 attachment site in human strains, and we demonstrate that this is due to allelic variation in CC398 strains that disrupts the phage attachment site, but not the expression of β-hemolysin. Our results show that hydrogen peroxide present in biocidal products stimulate transfer of ΦSa3 from human to LA-MRSA CC398 strains and that in these strains prophage stability depends on the integration site. Knowledge of ΦSa3 transfer and stability between human and livestock strains may lead to new intervention measures directed at reducing human infection by LA-MRSA strains.

Commercial Biocides Induce Transfer of Prophage Φ13 from Human Strains of Staphylococcus aureus to Livestock CC398

PubMed Central

Tang, Yuanyue; Nielsen, Lene N.; Hvitved, Annemette; Haaber, Jakob K.; Wirtz, Christiane; Andersen, Paal S.; Larsen, Jesper; Wolz, Christiane; Ingmer, Hanne

2017-01-01

Human strains of Staphylococcus aureus commonly carry the bacteriophage ΦSa3 that encodes immune evasion factors. Recently, this prophage has been found in livestock-associated, methicillin resistant S. aureus (MRSA) CC398 strains where it may promote human colonization. Here, we have addressed if exposure to biocidal products induces phage transfer, and find that during co-culture, Φ13 from strain 8325, belonging to ΦSa3 group, is induced and transferred from a human strain to LA-MRSA CC398 when exposed to sub-lethal concentrations of commercial biocides containing hydrogen peroxide. Integration of ΦSa3 in LA-MRSA CC398 occurs at multiple positions and the integration site influences the stability of the prophage. We did not observe integration in hlb encoding β-hemolysin that contains the preferred ΦSa3 attachment site in human strains, and we demonstrate that this is due to allelic variation in CC398 strains that disrupts the phage attachment site, but not the expression of β-hemolysin. Our results show that hydrogen peroxide present in biocidal products stimulate transfer of ΦSa3 from human to LA-MRSA CC398 strains and that in these strains prophage stability depends on the integration site. Knowledge of ΦSa3 transfer and stability between human and livestock strains may lead to new intervention measures directed at reducing human infection by LA-MRSA strains. PMID:29270158

Combining microsatellite, otolith shape and parasites community analyses as a holistic approach to assess population structure of Dentex dentex

NASA Astrophysics Data System (ADS)

Marengo, M.; Baudouin, M.; Viret, A.; Laporte, M.; Berrebi, P.; Vignon, M.; Marchand, B.; Durieux, E. D. H.

2017-10-01

The common dentex, Dentex dentex, is an iconic marine coastal fish of the Mediterranean Sea. Despite its economic and ecological importance, data on the population structure of this species are still very limited. The aim of this study was to identify the stock structure of the common dentex at relatively fine spatial scale around Corsica Island, using a combination of markers that have different spatial and temporal scales of integration: microsatellite DNA markers, otolith shape analysis and parasites communities. Microsatellite analysis indicated that there was no significant genetic differentiation in D. dentex between the four sampling sites around Corsica. Otolith shape analysis suggests one potential distinct population unit of D. dentex centered in one site (Cap Corse) varying in their degree of differentiation from those in the other zones. Multivariate analysis on parasite abundance data highlights to a lower extent two sites (Bonifacio and Galeria) with some connectivity between adjacent zones. The combination of these three markers together highlights the resulting three sites while giving complementary insights and an opportunity to compare their utility and potential to understand population interactions. A complex population structure around Corsican coasts is then proposed, providing a new perspective on common dentex fishery stock conservation and management strategies.

Interpretations of Integration in Early Accountable Care Organizations

PubMed Central

Kreindler, Sara A; Larson, Bridget K; Wu, Frances M; Carluzzo, Kathleen L; Gbemudu, Josette N; Struthers, Ashley; Van Citters, Aricca D; Shortell, Stephen M; Nelson, Eugene C; Fisher, Elliott S

2012-01-01

Context It is widely hoped that accountable care organizations (ACOs) will improve health care quality and reduce costs by fostering integration among diverse provider groups. But how do implementers actually envision integration, and what will integration mean in terms of managing the many social identities that ACOs bring together? Methods Using the lens of the social identity approach, this qualitative study examined how four nascent ACOs engaged with the concept of integration. During multiday site visits, we conducted interviews (114 managers and physicians), observations, and document reviews. Findings In no case was the ACO interpreted as a new, overarching entity uniting disparate groups; rather, each site offered a unique interpretation that flowed from its existing strategies for social-identity management: An independent practice association preserved members’ cherished value of autonomy by emphasizing coordination, not “integration”; a medical group promoted integration within its employed core, but not with affiliates; a hospital, engaging community physicians who mistrusted integrated systems, reimagined integration as an equal partnership; an integrated delivery system advanced its careful journey towards intergroup consensus by presenting the ACO as a cultural, not structural, change. Conclusions The ACO appears to be a model flexible enough to work in synchrony with whatever social strategies are most context appropriate, with the potential to promote alignment and functional integration without demanding common identification with a superordinate group. “Soft integration” may be a promising alternative to the vertically integrated model that, though widely assumed to be ideal, has remained unattainable for most organizations. PMID:22985278

Exploring a Common Past: Researching and Interpreting the Underground Railroad.

ERIC Educational Resources Information Center

National Park Service (Dept. of Interior), Washington, DC.

Although the Underground Railroad has been an integral part of U.S. history and folklore for well over 150 years, the recent past has seen an increased public interest in the identification of historic sites associated with the experiences of fugitive slaves. This booklet is part of a National Park Service initiative to design research methods…

Integrating Horizontal Gene Transfer and Common Descent to Depict Evolution and Contrast It with “Common Design”1

PubMed Central

GUILLERMO PAZ-Y-MIÑO-C; ESPINOSA, AVELINA

2016-01-01

Horizontal gene transfer (HGT) and common descent interact in space and time. Because events of HGT co-occur with phylogenetic evolution, it is difficult to depict evolutionary patterns graphically. Tree-like representations of life’s diversification are useful, but they ignore the significance of HGT in evolutionary history, particularly of unicellular organisms, ancestors of multicellular life. Here we integrate the reticulated-tree model, ring of life, symbiogenesis whole-organism model, and eliminative pattern pluralism to represent evolution. Using Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2), a bifunctional enzyme in the glycolytic pathway of amoeba, we illustrate how EhADH2 could be the product of both horizontally acquired features from ancestral prokaryotes (i.e. aldehyde dehydrogenase [ALDH] and alcohol dehydrogenase [ADH]), and subsequent functional integration of these enzymes into EhADH2, which is now inherited by amoeba via common descent. Natural selection has driven the evolution of EhADH2 active sites, which require specific amino acids (cysteine 252 in the ALDH domain; histidine 754 in the ADH domain), iron- and NAD+ as cofactors, and the substrates acetyl-CoA for ALDH and acetaldehyde for ADH. Alternative views invoking “common design” (i.e. the non-naturalistic emergence of major taxa independent from ancestry) to explain the interaction between horizontal and vertical evolution are unfounded. PMID:20021546

Long-Term Environmental Research Programs - Evolving Capacity for Discovery

NASA Astrophysics Data System (ADS)

Swanson, F. J.

2008-12-01

Long-term forestry, watershed, and ecological research sites have become critical, productive nodes for environmental science research and in some cases for work in the social sciences and humanities. The Forest Service's century-old Experimental Forests and Ranges and the National Science Foundation's 28- year-old Long-Term Ecological Research program have been remarkably productive in both basic and applied sciences, including characterization of acid rain and old-growth ecosystems and development of forest, watershed, and range management systems for commercial and other land use objectives. A review of recent developments suggests steps to enhance the function of collections of long-term research sites as interactive science networks. The programs at these sites have evolved greatly, especially over the past few decades, as the questions addressed, disciplines engaged, and degree of science integration have grown. This is well displayed by small, experimental watershed studies, which first were used for applied hydrology studies then more fundamental biogeochemical studies and now examination of complex ecosystem processes; all capitalizing on the legacy of intensive studies and environmental monitoring spanning decades. In very modest ways these collections of initially independent sites have functioned increasingly as integrated research networks addressing inter-site questions by using common experimental designs, being part of a single experiment, and examining long-term data in a common analytical framework. The network aspects include data sharing via publicly-accessible data-harvester systems for climate and streamflow data. The layering of one research or environmental monitoring network upon another facilitates synergies. Changing climate and atmospheric chemistry highlight a need to use these networks as continental-scale observatory systems for assessing the impacts of environmental change on ecological services. To better capitalize on long-term research sites and networks, agencies and universities 1) need to encourage collaboration among sites and between science and land manager communities while 2) maintaining long- term studies and monitoring efforts, and staffing the collaboration in each partner organization, including positions specifically designated as liaisons among the participating communities.

Next generation sequencing and its applications in HPVassociated cancers

PubMed Central

Tuna, Musaffe; Amos, Christopher I.

2017-01-01

Approximately 18% of all human cancers have a viral etiology, and human papillomavirus (HPV) has been identified as one of the most prevalent viruses that plays causative role in nearly all cervical cancers and, in addition, in subset of head and neck, anal, penile and vulvar cancers. The recent introduction of next generation sequencing (NGS) and other omics approaches have resulted in comprehensive knowledge on the pathogenesis of HPV-driven tumors. Specifically, these approaches have provided detailed information on genomic HPV integration sites, disrupted genes and pathways, and common and distinct genetic and epigenetic alterations in different human HPV-associated cancers. This review focuses on HPV integration sites, its concomitantly disrupted genes and pathways and its functional consequences in both cervical and head and neck cancers. Integration of NGS data with other omics and clinical data is crucial to better understand the pathophysiology of each individual malignancy and, based on this, to select targets and to design effective personalized treatment options. PMID:27784002

Next generation sequencing and its applications in HPV-associated cancers.

PubMed

Tuna, Musaffe; Amos, Christopher I

2017-01-31

Approximately 18% of all human cancers have a viral etiology, and human papillomavirus (HPV) has been identified as one of the most prevalent viruses that plays causative role in nearly all cervical cancers and, in addition, in subset of head and neck, anal, penile and vulvar cancers. The recent introduction of next generation sequencing (NGS) and other 'omics' approaches have resulted in comprehensive knowledge on the pathogenesis of HPV-driven tumors. Specifically, these approaches have provided detailed information on genomic HPV integration sites, disrupted genes and pathways, and common and distinct genetic and epigenetic alterations in different human HPV-associated cancers. This review focuses on HPV integration sites, its concomitantly disrupted genes and pathways and its functional consequences in both cervical and head and neck cancers. Integration of NGS data with other 'omics' and clinical data is crucial to better understand the pathophysiology of each individual malignancy and, based on this, to select targets and to design effective personalized treatment options.

Overview of DYMCAS, the Y-12 Material Control And Accountability System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alspaugh, D. H.

2001-07-01

This paper gives an overview of DYMCAS, the material control and accountability information system for the Y-12 National Security Complex. A common misconception, even within the DOE community, understates the nature and complexity of material control and accountability (MC and A) systems, likening them to parcel delivery systems tracking packages at various locations or banking systems that account for money, down to the penny. A major point set forth in this paper is that MC and A systems such as DYMCAS can be and often are very complex. Given accountability reporting requirements and the critical and sensitive nature of themore » task, no MC and A system can be simple. The complexity of site-level accountability systems, however, varies dramatically depending on the amounts, kinds, and forms of nuclear materials and the kinds of processing performed at the site. Some accountability systems are tailored to unique and highly complex site-level materials and material processing and, consequently, are highly complex systems. Sites with less complexity require less complex accountability systems, and where processes and practices are the same or similar, sites on the mid-to-low end of the complexity scale can effectively utilize a standard accountability system. In addition to being complex, a unique feature of DYMCAS is its integration with the site production control and manufacturing system. This paper will review the advantages of such integration, as well as related challenges, and make the point that the effectiveness of complex MC and A systems can be significantly enhanced through appropriate systems integration.« less

The LAM-PCR Method to Sequence LV Integration Sites.

PubMed

Wang, Wei; Bartholomae, Cynthia C; Gabriel, Richard; Deichmann, Annette; Schmidt, Manfred

2016-01-01

Integrating viral gene transfer vectors are commonly used gene delivery tools in clinical gene therapy trials providing stable integration and continuous gene expression of the transgene in the treated host cell. However, integration of the reverse-transcribed vector DNA into the host genome is a potentially mutagenic event that may directly contribute to unwanted side effects. A comprehensive and accurate analysis of the integration site (IS) repertoire is indispensable to study clonality in transduced cells obtained from patients undergoing gene therapy and to identify potential in vivo selection of affected cell clones. To date, next-generation sequencing (NGS) of vector-genome junctions allows sophisticated studies on the integration repertoire in vitro and in vivo. We have explored the use of the Illumina MiSeq Personal Sequencer platform to sequence vector ISs amplified by non-restrictive linear amplification-mediated PCR (nrLAM-PCR) and LAM-PCR. MiSeq-based high-quality IS sequence retrieval is accomplished by the introduction of a double-barcode strategy that substantially minimizes the frequency of IS sequence collisions compared to the conventionally used single-barcode protocol. Here, we present an updated protocol of (nr)LAM-PCR for the analysis of lentiviral IS using a double-barcode system and followed by deep sequencing using the MiSeq device.

Chromatin Landscapes of Retroviral and Transposon Integration Profiles

PubMed Central

Badhai, Jitendra; Rust, Alistair G.; Rad, Roland; Hilkens, John; Berns, Anton; van Lohuizen, Maarten; Wessels, Lodewyk F. A.; de Ridder, Jeroen

2014-01-01

The ability of retroviruses and transposons to insert their genetic material into host DNA makes them widely used tools in molecular biology, cancer research and gene therapy. However, these systems have biases that may strongly affect research outcomes. To address this issue, we generated very large datasets consisting of to unselected integrations in the mouse genome for the Sleeping Beauty (SB) and piggyBac (PB) transposons, and the Mouse Mammary Tumor Virus (MMTV). We analyzed (epi)genomic features to generate bias maps at both local and genome-wide scales. MMTV showed a remarkably uniform distribution of integrations across the genome. More distinct preferences were observed for the two transposons, with PB showing remarkable resemblance to bias profiles of the Murine Leukemia Virus. Furthermore, we present a model where target site selection is directed at multiple scales. At a large scale, target site selection is similar across systems, and defined by domain-oriented features, namely expression of proximal genes, proximity to CpG islands and to genic features, chromatin compaction and replication timing. Notable differences between the systems are mainly observed at smaller scales, and are directed by a diverse range of features. To study the effect of these biases on integration sites occupied under selective pressure, we turned to insertional mutagenesis (IM) screens. In IM screens, putative cancer genes are identified by finding frequently targeted genomic regions, or Common Integration Sites (CISs). Within three recently completed IM screens, we identified 7%–33% putative false positive CISs, which are likely not the result of the oncogenic selection process. Moreover, results indicate that PB, compared to SB, is more suited to tag oncogenes. PMID:24721906

Molecular cytogenetic analysis of feline leukemia virus insertions in cat lymphoid tumor cells.

PubMed

Fujino, Yasuhito; Satoh, Hitoshi; Ohno, Koichi; Tsujimoto, Hajime

2010-02-01

This study was conducted to map the acquired proviral insertions in the chromosomal genome of feline lymphoid tumors induced by feline leukemia virus (FeLV). Chromosome specimens of the lymphoid tumor-derived cell lines and normal cat lymphocytes were subjected to fluorescence in situ hybridization and tyramide signal amplification, using an exogenous FeLV-A genome as a probe. Specific hybridization signals were detected only on the metaphase chromosomes of the tumor cells. Poisson's distribution-based statistics indicated that 6 chromosomal loci in each cell line showed FeLV integration. In the examination of metaphase chromosomes of FL-74, FT-1 and KO-1 cells, significant signals were detected on B2p15-p14, B2q11, D1p14, E1p14-p13, E1q12 and F2q16; A2p23-p22, B2p15-p14, B4p15-p14, D4q23-q24, E1p14-p13 and E2p13-p12; and A2p22, A3q22, B1p13, B1q13, D1p13 and D3p15-p14, respectively. Consistently, Southern blot hybridization using an FeLV LTR-U3 probe specific for exogenous FeLV revealed the presence of at least 6 copies of exogenous FeLV proviruses at different integration sites in each cell line. These results indicate that there may be common FeLV integration sites at least in A2p22 and B2p15-p14. The cytogenetic analysis used in this study can promptly screen FeLV insertions and provide tags for identifying the novel common integration site. 2009 Elsevier B.V. All rights reserved.

Development of a QTL-environment-based predictive model for node addition rate in common bean.

PubMed

Zhang, Li; Gezan, Salvador A; Eduardo Vallejos, C; Jones, James W; Boote, Kenneth J; Clavijo-Michelangeli, Jose A; Bhakta, Mehul; Osorno, Juan M; Rao, Idupulapati; Beebe, Stephen; Roman-Paoli, Elvin; Gonzalez, Abiezer; Beaver, James; Ricaurte, Jaumer; Colbert, Raphael; Correll, Melanie J

2017-05-01

This work reports the effects of the genetic makeup, the environment and the genotype by environment interactions for node addition rate in an RIL population of common bean. This information was used to build a predictive model for node addition rate. To select a plant genotype that will thrive in targeted environments it is critical to understand the genotype by environment interaction (GEI). In this study, multi-environment QTL analysis was used to characterize node addition rate (NAR, node day - 1 ) on the main stem of the common bean (Phaseolus vulgaris L). This analysis was carried out with field data of 171 recombinant inbred lines that were grown at five sites (Florida, Puerto Rico, 2 sites in Colombia, and North Dakota). Four QTLs (Nar1, Nar2, Nar3 and Nar4) were identified, one of which had significant QTL by environment interactions (QEI), that is, Nar2 with temperature. Temperature was identified as the main environmental factor affecting NAR while day length and solar radiation played a minor role. Integration of sites as covariates into a QTL mixed site-effect model, and further replacing the site component with explanatory environmental covariates (i.e., temperature, day length and solar radiation) yielded a model that explained 73% of the phenotypic variation for NAR with root mean square error of 16.25% of the mean. The QTL consistency and stability was examined through a tenfold cross validation with different sets of genotypes and these four QTLs were always detected with 50-90% probability. The final model was evaluated using leave-one-site-out method to assess the influence of site on node addition rate. These analyses provided a quantitative measure of the effects on NAR of common beans exerted by the genetic makeup, the environment and their interactions.

From Chaos to Content: An Integrated Approach to Government Web Sites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Demuth, Nora H.; Knudson, Christa K.

2005-01-03

The web development team of the Environmental Technology Directorate (ETD) at the U.S. Department of Energy’s Pacific Northwest National Laboratory (PNNL) redesigned the ETD website as a database-driven system, powered by the newly designed ETD Common Information System (ETD-CIS). The ETD website was redesigned in response to an analysis that showed the previous ETD websites were inefficient, costly, and lacking in a consistent focus. Redesigned and newly created websites based on a new ETD template provide a consistent image, meet or exceed accessibility standards, and are linked through a common database. The protocols used in developing the ETD website supportmore » integration of further organizational sites and facilitate internal use by staff and training on ETD website development and maintenance. Other PNNL organizations have approached the ETD web development team with an interest in applying the methods established by the ETD system. The ETD system protocol could potentially be used by other DOE laboratories to improve their website efficiency and content focus. “The tools by which we share science information must be as extraordinary as the information itself.[ ]” – DOE Science Director Raymond Orbach« less

Practical Steps to Integrate Family Voice in Organization, Policy, Planning, and Decision-Making for Socio-Emotional Trauma-Informed Integrated Pediatric Care.

PubMed

Dayton, Lauren; Buttress, Amelia; Agosti, Jen; Aceves, Javier; Kieschnick, Meredith; Popejoy, Agatha; Robbins, Robyn; Farinholt, Kate

2016-12-01

This article explores barriers and strategies to achieving family-driven integrated child health care. Family involvement in health system design and reform has become a guiding principle in national and local efforts to improve children's mental health services. In practice, primary care clinicians, staff, and families continue to describe common barriers to integrating family voice. Drawing from the collective knowledge of the Pediatric Integrated Care Collaborative (PICC) and the National Alliance on Mental Illness (NAMI), we present strategies to overcome these barriers to successfully recruit, sustain, and expand family influence on health systems. Family advocates and clinical leaders from two clinic sites in Albuquerque, New Mexico and Santa Rosa, California share challenges and strategies for building family involvement in system design. Copyright © 2016. Published by Elsevier Inc.

Exploring the Feasibility of Service Integration in a Low-Income Setting: A Mixed Methods Investigation into Different Models of Reproductive Health and HIV Care in Swaziland

PubMed Central

Church, Kathryn; Wringe, Alison; Lewin, Simon; Ploubidis, George B.; Fakudze, Phelele; Mayhew, Susannah H.

2015-01-01

Integrating reproductive health (RH) with HIV care is a policy priority in high HIV prevalence settings, despite doubts surrounding its feasibility and varying evidence of effects on health outcomes. The process and outcomes of integrated RH-HIV care were investigated in Swaziland, through a comparative case study of four service models, ranging from fully integrated to fully stand-alone HIV services, selected purposively within one town. A client exit survey (n=602) measured integrated care received and unmet family planning (FP) needs. Descriptive statistics were used to assess the degree of integration per clinic and client demand for services. Logistic regression modelling was used to test the hypothesis that clients at more integrated sites had lower unmet FP needs than clients in a stand-alone site. Qualitative methods included in-depth interviews with clients and providers to explore contextual factors influencing the feasibility of integrated RH-HIV care delivery; data were analysed thematically, combining deductive and inductive approaches. Results demonstrated that clinic models were not as integrated in practice as had been claimed. Fragmentation of HIV care was common. Services accessed per provider were no higher at the more integrated clinics compared to stand-alone models (p>0.05), despite reported demand. While women at more integrated sites received more FP and pregnancy counselling than stand-alone models, they received condoms (a method of choice) less often, and there was no statistical evidence of difference in unmet FP needs by model of care. Multiple contextual factors influenced integration practices, including provider de-skilling within sub-specialist roles; norms of task-oriented routinised HIV care; perceptions of heavy client loads; imbalanced client-provider interactions hindering articulation of RH needs; and provider motivation challenges. Thus, despite institutional support, factors related to the social context of care inhibited provision of fully integrated RH-HIV services in these clinics. Programmes should move beyond simplistic training and equipment provision if integrated care interventions are to be sustained. PMID:25978632

Clinical service lines in integrated delivery systems: an initial framework and exploration.

PubMed

Parker, V A; Charns, M P; Young, G J

2001-01-01

The increasing pressures on integrated healthcare delivery systems (IDSs) to provide coordinated and cost-effective care focuses attention on the question of how to best integrate across multiple sites of care. One increasingly common approach to this issue is the development of clinical service lines that integrate specific bundles of services across the operating units of a system. This article presents a conceptual model of service lines and reports results from a descriptive investigation of service line development among members of the Industry Advisory Board--a research consortium comprising IDSs. The experiences of these IDSs (1) provide valuable insights into the range of organizational arrangements and implementation issues that are associated with service line management in healthcare systems and (2) suggest aspects of service line management worthy of further inquiry.

Virtual Manufacturing Techniques Designed and Applied to Manufacturing Activities in the Manufacturing Integration and Technology Branch

NASA Technical Reports Server (NTRS)

Shearrow, Charles A.

1999-01-01

One of the identified goals of EM3 is to implement virtual manufacturing by the time the year 2000 has ended. To realize this goal of a true virtual manufacturing enterprise the initial development of a machinability database and the infrastructure must be completed. This will consist of the containment of the existing EM-NET problems and developing machine, tooling, and common materials databases. To integrate the virtual manufacturing enterprise with normal day to day operations the development of a parallel virtual manufacturing machinability database, virtual manufacturing database, virtual manufacturing paradigm, implementation/integration procedure, and testable verification models must be constructed. Common and virtual machinability databases will include the four distinct areas of machine tools, available tooling, common machine tool loads, and a materials database. The machine tools database will include the machine envelope, special machine attachments, tooling capacity, location within NASA-JSC or with a contractor, and availability/scheduling. The tooling database will include available standard tooling, custom in-house tooling, tool properties, and availability. The common materials database will include materials thickness ranges, strengths, types, and their availability. The virtual manufacturing databases will consist of virtual machines and virtual tooling directly related to the common and machinability databases. The items to be completed are the design and construction of the machinability databases, virtual manufacturing paradigm for NASA-JSC, implementation timeline, VNC model of one bridge mill and troubleshoot existing software and hardware problems with EN4NET. The final step of this virtual manufacturing project will be to integrate other production sites into the databases bringing JSC's EM3 into a position of becoming a clearing house for NASA's digital manufacturing needs creating a true virtual manufacturing enterprise.

Biological relevance of streamflow metrics: Regional and national perspectives

USGS Publications Warehouse

Carlisle, Daren M.; Grantham, Theodore E.; Eng, Kenny; Wolock, David M.

2017-01-01

Protecting the health of streams and rivers requires identifying ecologically significant attributes of the natural flow regime. Streamflow regimes are routinely quantified using a plethora of hydrologic metrics (HMs), most of which have unknown relevance to biological communities. At regional and national scales, we evaluated which of 509 commonly used HMs were associated with biological indicators of fish and invertebrate community integrity. We quantified alteration of each HM by using statistical models to predict site-specific natural baseline values for each of 728 sites across the USA where streamflow monitoring data were available concurrent with assessments of invertebrate or fish community integrity. We then ranked HMs according to their individual association with biological integrity based on random forest models that included HMs and other relevant covariates, such as land cover and stream chemistry. HMs were generally the most important predictors of biological integrity relative to the covariates. At a national scale, the most influential HMs were measures of depleted high flows, homogenization of flows, and erratic flows. Unique combinations of biologically relevant HMs were apparent among regions. We discuss the implications of our findings to the challenge of selecting HMs for streamflow research and management.

ICESpy009, a Conjugative Genetic Element Carrying mef(E) in Streptococcus pyogenes.

PubMed

Del Grosso, Maria; Camilli, Romina; Rizzi, Ermanno; Pietrelli, Alessandro; De Bellis, Gianluca; Pantosti, Annalisa

2016-07-01

Efflux-mediated macrolide resistance due to mef(E) and mel, carried by the mega element, is common in Streptococcus pneumoniae, for which it was originally characterized, but it is rare in Streptococcus pyogenes In S. pyogenes, mega was previously found to be enclosed in Tn2009, a composite genetic element of the Tn916 family containing tet(M) and conferring erythromycin and tetracycline resistance. In this study, S. pyogenes isolates containing mef(E), apparently not associated with other resistance determinants, were examined to characterize the genetic context of mega. By whole-genome sequencing of one isolate, MB56Spyo009, we identified a novel composite integrative and conjugative element (ICE) carrying mega, designated ICESpy009, belonging to the ICESa2603 family. ICESpy009 was 55 kb long, contained 61 putative open reading frames (ORFs), and was found to be integrated into hylA, a novel integration site for the ICESa2603 family. The modular organization of the ICE was similar to that of members of the ICESa2603 family carried by different streptococcal species. In addition, a novel cluster of accessory resistance genes was found inside a region that encloses mega. PCR mapping targeting ICESpy009 revealed the presence of a similar ICE in five other isolates under study. While in three isolates the integration site was the same as that of ICESpy009, in two isolates the ICE was integrated into rplL, the typical integration site of the ICESa2603 family. ICESpy009 was able to transfer macrolide resistance by conjugation to both S. pyogenes and S. pneumoniae, showing the first evidence of the transferability of mega from S. pyogenes. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

ICESpy009, a Conjugative Genetic Element Carrying mef(E) in Streptococcus pyogenes

PubMed Central

Camilli, Romina; Rizzi, Ermanno; Pietrelli, Alessandro; De Bellis, Gianluca; Pantosti, Annalisa

2016-01-01

Efflux-mediated macrolide resistance due to mef(E) and mel, carried by the mega element, is common in Streptococcus pneumoniae, for which it was originally characterized, but it is rare in Streptococcus pyogenes. In S. pyogenes, mega was previously found to be enclosed in Tn2009, a composite genetic element of the Tn916 family containing tet(M) and conferring erythromycin and tetracycline resistance. In this study, S. pyogenes isolates containing mef(E), apparently not associated with other resistance determinants, were examined to characterize the genetic context of mega. By whole-genome sequencing of one isolate, MB56Spyo009, we identified a novel composite integrative and conjugative element (ICE) carrying mega, designated ICESpy009, belonging to the ICESa2603 family. ICESpy009 was 55 kb long, contained 61 putative open reading frames (ORFs), and was found to be integrated into hylA, a novel integration site for the ICESa2603 family. The modular organization of the ICE was similar to that of members of the ICESa2603 family carried by different streptococcal species. In addition, a novel cluster of accessory resistance genes was found inside a region that encloses mega. PCR mapping targeting ICESpy009 revealed the presence of a similar ICE in five other isolates under study. While in three isolates the integration site was the same as that of ICESpy009, in two isolates the ICE was integrated into rplL, the typical integration site of the ICESa2603 family. ICESpy009 was able to transfer macrolide resistance by conjugation to both S. pyogenes and S. pneumoniae, showing the first evidence of the transferability of mega from S. pyogenes. PMID:27067338

The relationship between cancer incidence, stage and poverty in the United States.

PubMed

Boscoe, Francis P; Henry, Kevin A; Sherman, Recinda L; Johnson, Christopher J

2016-08-01

We extend a prior analysis on the relation between poverty and cancer incidence in a sample of 2.90 million cancers diagnosed in 16 US states plus Los Angeles over the 2005-2009 period by additionally considering stage at diagnosis. Recognizing that higher relative disparities are often found among less-common cancer sites, our analysis incorporated both relative and absolute measures of disparities. Fourteen of the 21 cancer sites analyzed were found to have significant variation by stage; in each instance, diagnosis at distant stage was more likely among residents of high-poverty areas. If the incidence rates found in the lowest-poverty areas for these 21 cancer sites were applied to the entire country, 18,000 fewer distant-stage diagnoses per year would be expected, a reduction of 8%. Conversely, 49,000 additional local-stage diagnoses per year would be expected, an increase of 4%. These figures, strongly influenced by the most common sites of prostate and female breast, speak to the trade-offs inherent in cancer screening. Integrating the type of analysis presented here into routine cancer surveillance activities would permit a more complete understanding of the dynamic nature of the relationship between socioeconomic status and cancer incidence. © 2016 UICC.

Multisite formative assessment for the Pathways study to prevent obesity in American Indian schoolchildren123

PubMed Central

Gittelsohn, Joel; Evans, Marguerite; Story, Mary; Davis, Sally M; Metcalfe, Lauve; Helitzer, Deborah L; Clay, Theresa E

2016-01-01

We describe the formative assessment process, using an approach based on social learning theory, for the development of a school-based obesity-prevention intervention into which cultural perspectives are integrated. The feasibility phase of the Pathways study was conducted in multiple settings in 6 American Indian nations. The Pathways formative assessment collected both qualitative and quantitative data. The qualitative data identified key social and environmental issues and enabled local people to express their own needs and views. The quantitative, structured data permitted comparison across sites. Both types of data were integrated by using a conceptual and procedural model. The formative assessment results were used to identify and rank the behavioral risk factors that were to become the focus of the Pathways intervention and to provide guidance on developing common intervention strategies that would be culturally appropriate and acceptable to all sites. PMID:10195601

Beyond grid security

NASA Astrophysics Data System (ADS)

Hoeft, B.; Epting, U.; Koenig, T.

2008-07-01

While many fields relevant to Grid security are already covered by existing working groups, their remit rarely goes beyond the scope of the Grid infrastructure itself. However, security issues pertaining to the internal set-up of compute centres have at least as much impact on Grid security. Thus, this talk will present briefly the EU ISSeG project (Integrated Site Security for Grids). In contrast to groups such as OSCT (Operational Security Coordination Team) and JSPG (Joint Security Policy Group), the purpose of ISSeG is to provide a holistic approach to security for Grid computer centres, from strategic considerations to an implementation plan and its deployment. The generalised methodology of Integrated Site Security (ISS) is based on the knowledge gained during its implementation at several sites as well as through security audits, and this will be briefly discussed. Several examples of ISS implementation tasks at the Forschungszentrum Karlsruhe will be presented, including segregation of the network for administration and maintenance and the implementation of Application Gateways. Furthermore, the web-based ISSeG training material will be introduced. This aims to offer ISS implementation guidance to other Grid installations in order to help avoid common pitfalls.

An index of biological integrity (IBI) for Pacific Northwest rivers

USGS Publications Warehouse

Mebane, C.A.; Maret, T.R.; Hughes, R.M.

2003-01-01

The index of biotic integrity (IBI) is a commonly used measure of relative aquatic ecosystem condition; however, its application to coldwater rivers over large geographic areas has been limited. A seven-step process was used to construct and test an IBI applicable to fish assemblages in coldwater rivers throughout the U.S. portion of the Pacific Northwest. First, fish data from the region were compiled from previous studies and candidate metrics were selected. Second, reference conditions were estimated from historical reports and minimally disturbed reference sites in the region. Third, data from the upper Snake River basin were used to test metrics and develop the initial index. Fourth, candidate metrics were evaluated for their redundancy, variability, precision, and ability to reflect a wide range of conditions while distinguishing reference sites from disturbed sites. Fifth, the selected metrics were standardized by being scored continuously from 0 to 1 and then weighted as necessary to produce an IBI ranging from 0 to 100. The resulting index included 10 metrics: number of native coldwater species, number of age-classes of sculpins Cottus spp., percentage of sensitive native individuals, percentage of coldwater individuals, percentage of tolerant individuals, number of alien species, percentage of common carp Cyprinus carpio individuals, number of selected salmonid age-classes, catch per unit effort of coldwater individuals, and percentage of individuals with selected anomalies. Sixth, the IBI responses were tested with additional data sets from throughout the Pacific Northwest. Last, scores from two minimally disturbed reference rivers were evaluated for longitudinal gradients along the river continuum. The IBI responded to environmental disturbances and was spatially and temporally stable at over 150 sites in the Pacific Northwest. The results support its use across a large geographic area to describe the relative biological condition of coolwater and coldwater rivers with low species richness.

Bioindicator responses and performance of plant species along a vehicular pollution gradient in western Himalaya.

PubMed

Kashyap, Rachit; Sharma, Rohit; Uniyal, Sanjay Kr

2018-04-21

Loss of green cover, and increasing pollution is a prime global concern. The problem calls for screening of pollution-tolerant tree species that can be integrated into plantation drives. Recognizing this, the study analyzed bio-indicator responses and performance of commonly occurring plant species along a pollution gradient in western Himalaya. Based on distance from the road, three sites viz., highly polluted (HP), moderately polluted (MP), and least polluted (LP), were identified. From these sites, leaves of commonly occurring 26 tree species were collected and analyzed for dust accumulation, total chlorophyll, relative water content (RWC), ascorbic acid, and pH using standard protocols. Later, assessment of Air Pollution Tolerance Index (APTI) and Anticipated Performance Indices (API) was carried out. The results revealed variations in biochemical characteristics. The pH, RWC, and total chlorophyll increased with decreasing pollution while ascorbic acid increased with increasing pollution. Dust capturing potential of Ficus carica (1.191 mg/m 2 ) and Toona ciliata (0.820 mg/m 2 ) was relatively higher. Based on the results of APTI, Grevillea robusta was classified as tolerant. It scored significantly higher values (21.06, 21.19, and 19.61 in LP, MP, and HP sites, respectively). Quercus floribunda, G. robusta (68.75% each), Juglans regia (68.7%), and T. ciliata (62.50%) were good performers in HP sites. Acer caesium, Betula utilis, and Morus alba that had low API scores (43.75%) were predicted as poor performers. Thus, G. robusta, Q. floribunda, J. regia, T. ciliata, and F. carica were evaluated as best performers. They could be integrated into plantations drives for environmental management.

Transient Expression of an LEDGF/p75 Chimera Retargets Lentivector Integration and Functionally Rescues in a Model for X-CGD

PubMed Central

Vets, Sofie; De Rijck, Jan; Brendel, Christian; Grez, Manuel; Bushman, Frederic; Debyser, Zeger; Gijsbers, Rik

2013-01-01

Retrovirus-based vectors are commonly used as delivery vehicles to correct genetic diseases because of their ability to integrate new sequences stably. However, adverse events in which vector integration activates proto-oncogenes, leading to clonal expansion and leukemogenesis hamper their application. The host cell-encoded lens epithelium-derived growth factor (LEDGF/p75) binds lentiviral integrase and targets integration to active transcription units. We demonstrated earlier that replacing the LEDGF/p75 chromatin interaction domain with an alternative DNA-binding protein could retarget integration. Here, we show that transient expression of the chimeric protein using mRNA electroporation efficiently redirects lentiviral vector (LV) integration in wild-type (WT) cells. We then employed this technology in a model for X-linked chronic granulomatous disease (X-CGD) using myelomonocytic PLB-985 gp91−/− cells. Following electroporation with mRNA encoding the LEDGF-chimera, the cells were treated with a therapeutic lentivector encoding gp91phox. Integration site analysis revealed retargeted integration away from genes and towards heterochromatin-binding protein 1β (CBX1)-binding sites, in regions enriched in marks associated with gene silencing. Nevertheless, gp91phox expression was stable for at least 6 months after electroporation and NADPH-oxidase activity was restored to normal levels as determined by superoxide production. Together, these data provide proof-of-principle that transient expression of engineered LEDGF-chimera can retarget lentivector integration and rescues the disease phenotype in a cell model, opening perspectives for safer gene therapy. PMID:23462964

Pathways for maintenance of telomeres and common fragile sites during DNA replication stress

PubMed Central

Özer, Özgün

2018-01-01

Oncogene activation during tumour development leads to changes in the DNA replication programme that enhance DNA replication stress. Certain regions of the human genome, such as common fragile sites and telomeres, are particularly sensitive to DNA replication stress due to their inherently ‘difficult-to-replicate’ nature. Indeed, it appears that these regions sometimes fail to complete DNA replication within the period of interphase when cells are exposed to DNA replication stress. Under these conditions, cells use a salvage pathway, termed ‘mitotic DNA repair synthesis (MiDAS)’, to complete DNA synthesis in the early stages of mitosis. If MiDAS fails, the ensuing mitotic errors threaten genome integrity and cell viability. Recent studies have provided an insight into how MiDAS helps cells to counteract DNA replication stress. However, our understanding of the molecular mechanisms and regulation of MiDAS remain poorly defined. Here, we provide an overview of how DNA replication stress triggers MiDAS, with an emphasis on how common fragile sites and telomeres are maintained. Furthermore, we discuss how a better understanding of MiDAS might reveal novel strategies to target cancer cells that maintain viability in the face of chronic oncogene-induced DNA replication stress. PMID:29695617

LIMITED GEOGRAPHIC VARIATION IN THE VOCALIZATIONS OF THE ENDANGERED THICK-BILLED PARROT: IMPLICATIONS FOR CONSERVATION STRATEGIES

PubMed Central

Guerra, Jaime E.; Cruz-Nieto, Javier; Ortiz-Maciel, Sonia Gabriela; Wright, Timothy F.

2012-01-01

The populations of many species are declining worldwide, and conservation efforts struggle to keep pace with extinction rates. Conservation biologists commonly employ strategies such as translocation and reintroduction, which move individuals of endangered species from one part of their range to another. Because individuals from endangered populations are nonexpendable, identifying any potential barriers to the establishment of viable populations prior to release of individuals should be a priority. This study evaluates the potential for learned communication signals to constrain conservation strategies such as reintroduction in an endangered species, the Thick-billed Parrot (Rhynchopsitta pachyrhyncha). We conducted vocal surveys at three geographically distinct breeding populations in the Sierra Madre Occidental of Chihuahua, Mexico. Acoustic analyses utilizing both spectrogram cross-correlations and parameter measurements from spectrograms revealed no significant differences among the three sites in two common call types. Calls did vary among individuals within a site. The apparent lack of significant geographic variation across sampled sites suggests that differences in learned communication signals are unlikely to pose a barrier to the integration of translocated individuals from different populations into newly established populations. PMID:22307993

INVESTIGATING THE EFFICACY OF CLINICAL TRIAL MONITORING STRATEGIES: Design and Implementation of the Cluster Randomized START Monitoring Substudy

PubMed Central

Hullsiek, Katherine Huppler; Kagan, Jonathan M; Engen, Nicole; Grarup, Jesper; Hudson, Fleur; Denning, Eileen T; Carey, Catherine; Courtney-Rodgers, David; Finley, Elizabeth B; Jansson, Per O; Pearson, Mary T; Peavy, Dwight E; Belloso, Waldo H

2014-01-01

Background Trial monitoring protects participant safety and study integrity. While monitors commonly go on-site to verify source data, there is little evidence that this practice is efficient or effective. An ongoing international HIV treatment trial (START) provides an opportunity to explore the usefulness of different monitoring approaches. Methods All START sites are centrally monitored and required to follow a local monitoring plan requiring specific quality assurance activities. Additionally, sites were randomized (1:1) to receive, or not receive, annual on-site monitoring. The study will determine if on-site monitoring increases the identification of major protocol deviations (eligibility or consent violations, improper study drug use, primary or serious event underreporting, data alteration or fraud). Results The START study completed enrollment in December 2013, with planned follow-up through December 2016. The monitoring study is ongoing at 196 sites in 34 countries. Results are expected when the START study concludes in December 2016. PMID:25973346

Using the GlideinWMS System as a Common Resource Provisioning Layer in CMS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balcas, J.; Belforte, S.; Bockelman, B.

2015-12-23

CMS will require access to more than 125k processor cores for the beginning of Run 2 in 2015 to carry out its ambitious physics program with more and higher complexity events. During Run1 these resources were predominantly provided by a mix of grid sites and local batch resources. During the long shut down cloud infrastructures, diverse opportunistic resources and HPC supercomputing centers were made available to CMS, which further complicated the operations of the submission infrastructure. In this presentation we will discuss the CMS effort to adopt and deploy the glideinWMS system as a common resource provisioning layer to grid,more » cloud, local batch, and opportunistic resources and sites. We will address the challenges associated with integrating the various types of resources, the efficiency gains and simplifications associated with using a common resource provisioning layer, and discuss the solutions found. We will finish with an outlook of future plans for how CMS is moving forward on resource provisioning for more heterogenous architectures and services.« less

Integrating repositories with fuel cycles: The airport authority model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Forsberg, C.

2012-07-01

The organization of the fuel cycle is a legacy of World War II and the cold war. Fuel cycle facilities were developed and deployed without consideration of the waste management implications. This led to the fuel cycle model of a geological repository site with a single owner, a single function (disposal), and no other facilities on site. Recent studies indicate large economic, safety, repository performance, nonproliferation, and institutional incentives to collocate and integrate all back-end facilities. Site functions could include geological disposal of spent nuclear fuel (SNF) with the option for future retrievability, disposal of other wastes, reprocessing with fuelmore » fabrication, radioisotope production, other facilities that generate significant radioactive wastes, SNF inspection (navy and commercial), and related services such as SNF safeguards equipment testing and training. This implies a site with multiple facilities with different owners sharing some facilities and using common facilities - the repository and SNF receiving. This requires a different repository site institutional structure. We propose development of repository site authorities modeled after airport authorities. Airport authorities manage airports with government-owned runways, collocated or shared public and private airline terminals, commercial and federal military facilities, aircraft maintenance bases, and related operations - all enabled and benefiting the high-value runway asset and access to it via taxi ways. With a repository site authority the high value asset is the repository. The SNF and HLW receiving and storage facilities (equivalent to the airport terminal) serve the repository, any future reprocessing plants, and others with needs for access to SNF and other wastes. Non-public special-built roadways and on-site rail lines (equivalent to taxi ways) connect facilities. Airport authorities are typically chartered by state governments and managed by commissions with members appointed by the state governor, county governments, and city governments. This structure (1) enables state and local governments to work together to maximize job and tax benefits to local communities and the state, (2) provides a mechanism to address local concerns such as airport noise, and (3) creates an institutional structure with large incentives to maximize the value of the common asset, the runway. A repository site authority would have a similar structure and be the local interface to any national waste management authority. (authors)« less

Interstitial telomeric sequences in human chromosomes cluster with common fragile sites, mutagen sensitive sites, viral integration sites, cancer breakpoints, proto-oncogenes and breakpoints involved in primate evolution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adekunle, S.S.A.; Wyandt, H.; Mark, H.F.L.

1994-09-01

Recently we mapped the telomeric repeat sequences to 111 interstitial sites in the human genome and to sites of gaps and breaks induced by aphidicolin and sister chromatid exchange sites detected by BrdU. Many of these sites correspond to conserved fragile sites in man, gorilla and chimpazee, to sites of conserved sister chromatid exchange in the mammalian X chromosome, to mutagenic sensitive sites, mapped locations of proto-oncogenes, breakpoints implicated in primate evolution and to breakpoints indicated as the sole anomaly in neoplasia. This observation prompted us to investigate if the interstitial telomeric sites cluster with these sites. An extensive literaturemore » search was carried out to find all the available published sites mentioned above. For comparison, we also carried out a statistical analysis of the clustering of the sites of the telomeric repeats with the gene locations where only nucleotide mutations have been observed as the only chromosomal abnormality. Our results indicate that the telomeric repeats cluster most with fragile sites, mutagenic sensitive sites and breakpoints implicated in primate evolution and least with cancer breakpoints, mapped locations of proto-oncogenes and other genes with nucleotide mutations.« less

VISA--Vector Integration Site Analysis server: a web-based server to rapidly identify retroviral integration sites from next-generation sequencing.

PubMed

Hocum, Jonah D; Battrell, Logan R; Maynard, Ryan; Adair, Jennifer E; Beard, Brian C; Rawlings, David J; Kiem, Hans-Peter; Miller, Daniel G; Trobridge, Grant D

2015-07-07

Analyzing the integration profile of retroviral vectors is a vital step in determining their potential genotoxic effects and developing safer vectors for therapeutic use. Identifying retroviral vector integration sites is also important for retroviral mutagenesis screens. We developed VISA, a vector integration site analysis server, to analyze next-generation sequencing data for retroviral vector integration sites. Sequence reads that contain a provirus are mapped to the human genome, sequence reads that cannot be localized to a unique location in the genome are filtered out, and then unique retroviral vector integration sites are determined based on the alignment scores of the remaining sequence reads. VISA offers a simple web interface to upload sequence files and results are returned in a concise tabular format to allow rapid analysis of retroviral vector integration sites.

Vertically Integrated Models for Carbon Storage Modeling in Heterogeneous Domains

NASA Astrophysics Data System (ADS)

Bandilla, K.; Celia, M. A.

2017-12-01

Numerical modeling is an essential tool for studying the impacts of geologic carbon storage (GCS). Injection of carbon dioxide (CO2) into deep saline aquifers leads to multi-phase flow (injected CO2 and resident brine), which can be described by a set of three-dimensional governing equations, including mass-balance equation, volumetric flux equations (modified Darcy), and constitutive equations. This is the modeling approach on which commonly used reservoir simulators such as TOUGH2 are based. Due to the large density difference between CO2 and brine, GCS models can often be simplified by assuming buoyant segregation and integrating the three-dimensional governing equations in the vertical direction. The integration leads to a set of two-dimensional equations coupled with reconstruction operators for vertical profiles of saturation and pressure. Vertically-integrated approaches have been shown to give results of comparable quality as three-dimensional reservoir simulators when applied to realistic CO2 injection sites such as the upper sand wedge at the Sleipner site. However, vertically-integrated approaches usually rely on homogeneous properties over the thickness of a geologic layer. Here, we investigate the impact of general (vertical and horizontal) heterogeneity in intrinsic permeability, relative permeability functions, and capillary pressure functions. We consider formations involving complex fluvial deposition environments and compare the performance of vertically-integrated models to full three-dimensional models for a set of hypothetical test cases consisting of high permeability channels (streams) embedded in a low permeability background (floodplains). The domains are randomly generated assuming that stream channels can be represented by sinusoidal waves in the plan-view and by parabolas for the streams' cross-sections. Stream parameters such as width, thickness and wavelength are based on values found at the Ketzin site in Germany. Results from the vertically-integrated approach are compared to results using TOUGH2, both in terms of depth-averaged saturation and vertical saturation profiles.

Development of concepts for low-cost energy storage assemblies for annual cycle energy system applications

NASA Astrophysics Data System (ADS)

Alexander, G. H.; Cooper, D. L.; Cummings, C. A.; Reiber, E. E.

1981-10-01

Low cost energy storage assemblies were developed. In the search for low overall cost assemblies, many diverse concepts and materials were postulated and briefly evaluated. Cost rankings, descriptions, and discussions of the concepts were presented from which ORNL selected the following three concepts for the Phase 2 development: (1) a site constructed tank with reinforced concrete walls formed with specialized modular blocks which eliminates most concrete form work and provides integral R-20 insulation designated ORNLFF; (2) a site constructed tank with earth supported walls that are formed from elements common to residential, in-ground swimming pools, designated SWPL; (3) and a site assembled tank used in underground utility vaults, designated UTLBX. Detailed designs of free standing versions of the three concepts are presented.

Complete Genome Sequence of Germline Chromosomally Integrated Human Herpesvirus 6A and Analyses Integration Sites Define a New Human Endogenous Virus with Potential to Reactivate as an Emerging Infection.

PubMed

Tweedy, Joshua; Spyrou, Maria Alexandra; Pearson, Max; Lassner, Dirk; Kuhl, Uwe; Gompels, Ursula A

2016-01-15

Human herpesvirus-6A and B (HHV-6A, HHV-6B) have recently defined endogenous genomes, resulting from integration into the germline: chromosomally-integrated "CiHHV-6A/B". These affect approximately 1.0% of human populations, giving potential for virus gene expression in every cell. We previously showed that CiHHV-6A was more divergent than CiHHV-6B by examining four genes in 44 European CiHHV-6A/B cardiac/haematology patients. There was evidence for gene expression/reactivation, implying functional non-defective genomes. To further define the relationship between HHV-6A and CiHHV-6A we used next-generation sequencing to characterize genomes from three CiHHV-6A cardiac patients. Comparisons to known exogenous HHV-6A showed CiHHV-6A genomes formed a separate clade; including all 85 non-interrupted genes and necessary cis-acting signals for reactivation as infectious virus. Greater single nucleotide polymorphism (SNP) density was defined in 16 genes and the direct repeats (DR) terminal regions. Using these SNPs, deep sequencing analyses demonstrated superinfection with exogenous HHV-6A in two of the CiHHV-6A patients with recurrent cardiac disease. Characterisation of the integration sites in twelve patients identified the human chromosome 17p subtelomere as a prevalent site, which had specific repeat structures and phylogenetically related CiHHV-6A coding sequences indicating common ancestral origins. Overall CiHHV-6A genomes were similar, but distinct from known exogenous HHV-6A virus, and have the capacity to reactivate as emerging virus infections.

Complete Genome Sequence of Germline Chromosomally Integrated Human Herpesvirus 6A and Analyses Integration Sites Define a New Human Endogenous Virus with Potential to Reactivate as an Emerging Infection

PubMed Central

Tweedy, Joshua; Spyrou, Maria Alexandra; Pearson, Max; Lassner, Dirk; Kuhl, Uwe; Gompels, Ursula A.

2016-01-01

Human herpesvirus-6A and B (HHV-6A, HHV-6B) have recently defined endogenous genomes, resulting from integration into the germline: chromosomally-integrated “CiHHV-6A/B”. These affect approximately 1.0% of human populations, giving potential for virus gene expression in every cell. We previously showed that CiHHV-6A was more divergent than CiHHV-6B by examining four genes in 44 European CiHHV-6A/B cardiac/haematology patients. There was evidence for gene expression/reactivation, implying functional non-defective genomes. To further define the relationship between HHV-6A and CiHHV-6A we used next-generation sequencing to characterize genomes from three CiHHV-6A cardiac patients. Comparisons to known exogenous HHV-6A showed CiHHV-6A genomes formed a separate clade; including all 85 non-interrupted genes and necessary cis-acting signals for reactivation as infectious virus. Greater single nucleotide polymorphism (SNP) density was defined in 16 genes and the direct repeats (DR) terminal regions. Using these SNPs, deep sequencing analyses demonstrated superinfection with exogenous HHV-6A in two of the CiHHV-6A patients with recurrent cardiac disease. Characterisation of the integration sites in twelve patients identified the human chromosome 17p subtelomere as a prevalent site, which had specific repeat structures and phylogenetically related CiHHV-6A coding sequences indicating common ancestral origins. Overall CiHHV-6A genomes were similar, but distinct from known exogenous HHV-6A virus, and have the capacity to reactivate as emerging virus infections. PMID:26784220

Quality assurance of data collection in the multi-site community randomized trial and prevalence survey of the children's healthy living program.

PubMed

Yamanaka, Ashley; Fialkowski, Marie Kainoa; Wilkens, Lynne; Li, Fenfang; Ettienne, Reynolette; Fleming, Travis; Power, Julianne; Deenik, Jonathan; Coleman, Patricia; Leon Guerrero, Rachael; Novotny, Rachel

2016-09-02

Quality assurance plays an important role in research by assuring data integrity, and thus, valid study results. We aim to describe and share the results of the quality assurance process used to guide the data collection process in a multi-site childhood obesity prevalence study and intervention trial across the US Affiliated Pacific Region. Quality assurance assessments following a standardized protocol were conducted by one assessor in every participating site. Results were summarized to examine and align the implementation of protocol procedures across diverse settings. Data collection protocols focused on food and physical activity were adhered to closely; however, protocols for handling completed forms and ensuring data security showed more variability. Quality assurance protocols are common in the clinical literature but are limited in multi-site community-based studies, especially in underserved populations. The reduction in the number of QA problems found in the second as compared to the first data collection periods for the intervention study attest to the value of this assessment. This paper can serve as a reference for similar studies wishing to implement quality assurance protocols of the data collection process to preserve data integrity and enhance the validity of study findings. NIH clinical trial #NCT01881373.

A Cluster-Randomized Controlled Trial to Reduce Diarrheal Disease and Dengue Entomological Risk Factors in Rural Primary Schools in Colombia

PubMed Central

Overgaard, Hans J.; Alexander, Neal; Matiz, Maria Ines; Jaramillo, Juan Felipe; Olano, Victor Alberto; Vargas, Sandra; Sarmiento, Diana; Lenhart, Audrey; Stenström, Thor Axel

2016-01-01

Background As many neglected tropical diseases are co-endemic and have common risk factors, integrated control can efficiently reduce disease burden and relieve resource-strained public health budgets. Diarrheal diseases and dengue fever are major global health problems sharing common risk factors in water storage containers. Where provision of clean water is inadequate, water storage is crucial. Fecal contamination of stored water is a common source of diarrheal illness, but stored water also provides breeding sites for dengue vector mosquitoes. Integrating improved water management and educational strategies for both diseases in the school environment can potentially improve the health situation for students and the larger community. The objective of this trial was to investigate whether interventions targeting diarrhea and dengue risk factors would significantly reduce absence due to diarrheal disease and dengue entomological risk factors in schools. Methodology/Principal Findings A factorial cluster randomized controlled trial was carried out in 34 rural primary schools (1,301 pupils) in La Mesa and Anapoima municipalities, Cundinamarca, Colombia. Schools were randomized to one of four study arms: diarrhea interventions (DIA), dengue interventions (DEN), combined diarrhea and dengue interventions (DIADEN), and control (CON). Interventions had no apparent effect on pupil school absence due to diarrheal disease (p = 0.45) or on adult female Aedes aegypti density (p = 0.32) (primary outcomes). However, the dengue interventions reduced the Breteau Index on average by 78% (p = 0.029), with Breteau indices of 10.8 and 6.2 in the DEN and DIADEN arms, respectively compared to 37.5 and 46.9 in the DIA and CON arms, respectively. The diarrhea interventions improved water quality as assessed by the amount of Escherichia coli colony forming units (CFU); the ratio of Williams mean E. coli CFU being 0.22, or 78% reduction (p = 0.008). Conclusions/Significance Integrated control of dengue and diarrhea has never been conducted before. This trial presents an example for application of control strategies that may affect both diseases and the first study to apply such an approach in school settings. The interventions were well received and highly appreciated by students and teachers. An apparent absence of effect in primary outcome indicators could be the result of pupils being exposed to risk factors outside the school area and mosquitoes flying in from nearby uncontrolled breeding sites. Integrated interventions targeting these diseases in a school context remain promising because of the reduced mosquito breeding and improved water quality, as well as educational benefits. However, to improve outcomes in future integrated approaches, simultaneous interventions in communities, in addition to schools, should be considered; using appropriate combinations of site-specific, effective, acceptable, and affordable interventions. Trial Registration ClinicalTrials.gov no. ISRCTN40195031 PMID:27820821

Gene therapy using retrovirus vectors: vector development and biosafety at clinical trials.

PubMed

Doi, Knayo; Takeuchi, Yasuhiro

2015-01-01

Retrovirus vectors (gammaretroviral and lentiviral vectors) have been considered as promising tools to transfer therapeutic genes into patient cells because they can permanently integrate into host cellular genome. To treat monogenic, inherited diseases, retroviral vectors have been used to add correct genes into patient cells. Conventional gammaretroviral vectors achieved successful results in clinical trials: treated patients had therapeutic gene expression in target cells and had improved symptoms of diseases. However, serious side-effects of leukemia occurred, caused by retroviral insertional mutagenesis (IM). These incidences stressed the importance of monitoring vector integration sites in patient cells as well as of re-consideration on safer vectors. More recently lentiviral vectors which can deliver genes into non-dividing cells started to be used in clinical trials including neurological disorders, showing their efficacy. Vector integration site analysis revealed that lentiviruses integrate less likely to near promoter regions of oncogenes than gammaretroviruses and no adverse events have been reported in lentiviral vector-mediated gene therapy clinical trials. Therefore lentiviral vectors have promises to be applied to a wide range of common diseases in near future. For example, T cells from cancer patients were transduced to express chimeric T cell receptors recognizing their tumour cells enhancing patients' anti-cancer immunity.

Data management integration for biomedical core facilities

NASA Astrophysics Data System (ADS)

Zhang, Guo-Qiang; Szymanski, Jacek; Wilson, David

2007-03-01

We present the design, development, and pilot-deployment experiences of MIMI, a web-based, Multi-modality Multi-Resource Information Integration environment for biomedical core facilities. This is an easily customizable, web-based software tool that integrates scientific and administrative support for a biomedical core facility involving a common set of entities: researchers; projects; equipments and devices; support staff; services; samples and materials; experimental workflow; large and complex data. With this software, one can: register users; manage projects; schedule resources; bill services; perform site-wide search; archive, back-up, and share data. With its customizable, expandable, and scalable characteristics, MIMI not only provides a cost-effective solution to the overarching data management problem of biomedical core facilities unavailable in the market place, but also lays a foundation for data federation to facilitate and support discovery-driven research.

Comparability of fish-based ecological quality assessments for geographically distinct Iberian regions.

PubMed

Segurado, P; Caiola, N; Pont, D; Oliveira, J M; Delaigue, O; Ferreira, M T

2014-04-01

In this work we compare two Iberian and a pan-European fish-based methods to assess ecological quality in rivers: the Fish-based Index of Biotic Integrity for Portuguese Wadeable Streams (F-IBIP), the Mediterranean Index of Biotic Integrity (IBIMED) and the pan-European Fish Index (EFI+). The results presented herein were developed in the context of the 2nd phase of the Intercalibration Exercise (IC), as required by the Water Frame Directive (WFD). The IC is aimed at ensuring comparability of the quality boundaries among the different WFD assessment methods developed by the Member States for each biological quality element. Although the two national assessment methods were developed for very distinct regions of Iberia (Western and Eastern Iberian Peninsula) they share the same methodological background: both are type-specific and guild-based multimetric indices. EFI+ is a multimetric guild-based model, but it is site-specific and uses a predictive modelling approach. The three indices were computed for all sites included in the Iberian Intercalibration database to allow the direct comparison, by means of linear regressions, of the resulting three quality values per site. The quality boundary harmonization between the two Iberian methods was only possible through an indirect comparison between the two indices, using EFI+ as a common metric. The three indices were also shown to be responsive to a common set of human induced pressures. This study highlights the need to develop general assessment methods adapted to wide geographical ranges with high species turnover to help intercalibrating assessment methods tailored for geographically more restricted regions. © 2013.

Transient Expression of an LEDGF/p75 Chimera Retargets Lentivector Integration and Functionally Rescues in a Model for X-CGD.

PubMed

Vets, Sofie; De Rijck, Jan; Brendel, Christian; Grez, Manuel; Bushman, Frederic; Debyser, Zeger; Gijsbers, Rik

2013-03-05

Retrovirus-based vectors are commonly used as delivery vehicles to correct genetic diseases because of their ability to integrate new sequences stably. However, adverse events in which vector integration activates proto-oncogenes, leading to clonal expansion and leukemogenesis hamper their application. The host cell-encoded lens epithelium-derived growth factor (LEDGF/p75) binds lentiviral integrase and targets integration to active transcription units. We demonstrated earlier that replacing the LEDGF/p75 chromatin interaction domain with an alternative DNA-binding protein could retarget integration. Here, we show that transient expression of the chimeric protein using mRNA electroporation efficiently redirects lentiviral vector (LV) integration in wild-type (WT) cells. We then employed this technology in a model for X-linked chronic granulomatous disease (X-CGD) using myelomonocytic PLB-985 gp91(-/-) cells. Following electroporation with mRNA encoding the LEDGF-chimera, the cells were treated with a therapeutic lentivector encoding gp91(phox). Integration site analysis revealed retargeted integration away from genes and towards heterochromatin-binding protein 1β (CBX1)-binding sites, in regions enriched in marks associated with gene silencing. Nevertheless, gp91(phox) expression was stable for at least 6 months after electroporation and NADPH-oxidase activity was restored to normal levels as determined by superoxide production. Together, these data provide proof-of-principle that transient expression of engineered LEDGF-chimera can retarget lentivector integration and rescues the disease phenotype in a cell model, opening perspectives for safer gene therapy.Molecular Therapy - Nucleic Acids (2013) 2, e77; doi:10.1038/mtna.2013.4; published online 5 March 2013.

Dynamics of bed bug infestations in three low-income housing communities with various bed bug management programs.

PubMed

Wang, Changlu; Eiden, Amanda; Singh, Narinderpal; Zha, Chen; Wang, Desen; Cooper, Richard

2018-06-01

Infestations of the common bed bug, Cimex lectularius L., have become common in low-income communities in the USA over the last 15 years. We evaluated community-based integrated pest management (IPM) programs for reducing bed bug infestations. Two housing authorities (Bayonne and Hackensack) implemented bed bug IPM programs. A third housing authority (Paterson) was used as the control site. Building-wide surveys were conducted in all communities, three times, to evaluate the effectiveness of the IPM programs. From 0 to 24 months, the infestation rate at Bayonne, Hackensack, and Paterson decreased by 49, 64, and 26%, respectively. The two sites that adopted IPM achieved faster bed bug elimination than the control site. The bed bug introduction rate over a 24-month period at Bayonne, Hackensack, and Paterson was 7, 3, and 11%, respectively. The introduction rate was positively associated with the initial infestation rate. Residents from buildings enrolled in IPM programs were more satisfied with the bed bug control services than residents from the control site. IPM programs were more effective in reducing bed bug infestations than traditional pest control services, but many factors contributed to the lower than desired level of reduction in infestation rate. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Characteristics, location and origin of flare activity in a complex active region

NASA Technical Reports Server (NTRS)

Machado, M. E.; Gary, G. A.; Hagyard, M. J.; Hernandez, A. M.; Rovira, M. G.

1986-01-01

The observational characteristics of series of multiple-loop flares from a complex active region are summarized. The location of the highest observed photospheric magnetic shear is found to be the commonly observed site of flare onset, but not, in many cases, the magnetic region where the largest time-integrated energy release is observed. The observations thus reveal a consistent pattern of energy-release processes related to the magnetic-field topology.

CMS users data management service integration and first experiences with its NoSQL data storage

NASA Astrophysics Data System (ADS)

Riahi, H.; Spiga, D.; Boccali, T.; Ciangottini, D.; Cinquilli, M.; Hernàndez, J. M.; Konstantinov, P.; Mascheroni, M.; Santocchia, A.

2014-06-01

The distributed data analysis workflow in CMS assumes that jobs run in a different location to where their results are finally stored. Typically the user outputs must be transferred from one site to another by a dedicated CMS service, AsyncStageOut. This new service is originally developed to address the inefficiency in using the CMS computing resources when transferring the analysis job outputs, synchronously, once they are produced in the job execution node to the remote site. The AsyncStageOut is designed as a thin application relying only on the NoSQL database (CouchDB) as input and data storage. It has progressed from a limited prototype to a highly adaptable service which manages and monitors the whole user files steps, namely file transfer and publication. The AsyncStageOut is integrated with the Common CMS/Atlas Analysis Framework. It foresees the management of nearly nearly 200k users' files per day of close to 1000 individual users per month with minimal delays, and providing a real time monitoring and reports to users and service operators, while being highly available. The associated data volume represents a new set of challenges in the areas of database scalability and service performance and efficiency. In this paper, we present an overview of the AsyncStageOut model and the integration strategy with the Common Analysis Framework. The motivations for using the NoSQL technology are also presented, as well as data design and the techniques used for efficient indexing and monitoring of the data. We describe deployment model for the high availability and scalability of the service. We also discuss the hardware requirements and the results achieved as they were determined by testing with actual data and realistic loads during the commissioning and the initial production phase with the Common Analysis Framework.

Clinical features, proximate causes, and consequences of active convulsive epilepsy in Africa

PubMed Central

Kariuki, Symon M; Matuja, William; Akpalu, Albert; Kakooza-Mwesige, Angelina; Chabi, Martin; Wagner, Ryan G; Connor, Myles; Chengo, Eddie; Ngugi, Anthony K; Odhiambo, Rachael; Bottomley, Christian; White, Steven; Sander, Josemir W; Neville, Brian G R; Newton, Charles R J C

2014-01-01

Purpose Epilepsy is common in sub-Saharan Africa (SSA), but the clinical features and consequences are poorly characterized. Most studies are hospital-based, and few studies have compared different ecological sites in SSA. We described active convulsive epilepsy (ACE) identified in cross-sectional community-based surveys in SSA, to understand the proximate causes, features, and consequences. Methods We performed a detailed clinical and neurophysiologic description of ACE cases identified from a community survey of 584,586 people using medical history, neurologic examination, and electroencephalography (EEG) data from five sites in Africa: South Africa; Tanzania; Uganda; Kenya; and Ghana. The cases were examined by clinicians to discover risk factors, clinical features, and consequences of epilepsy. We used logistic regression to determine the epilepsy factors associated with medical comorbidities. Key Findings Half (51%) of the 2,170 people with ACE were children and 69% of seizures began in childhood. Focal features (EEG, seizure types, and neurologic deficits) were present in 58% of ACE cases, and these varied significantly with site. Status epilepticus occurred in 25% of people with ACE. Only 36% received antiepileptic drugs (phenobarbital was the most common drug [95%]), and the proportion varied significantly with the site. Proximate causes of ACE were adverse perinatal events (11%) for onset of seizures before 18 years; and acute encephalopathy (10%) and head injury prior to seizure onset (3%). Important comorbidities were malnutrition (15%), cognitive impairment (23%), and neurologic deficits (15%). The consequences of ACE were burns (16%), head injuries (postseizure) (1%), lack of education (43%), and being unmarried (67%) or unemployed (57%) in adults, all significantly more common than in those without epilepsy. Significance There were significant differences in the comorbidities across sites. Focal features are common in ACE, suggesting identifiable and preventable causes. Malnutrition and cognitive and neurologic deficits are common in people with ACE and should be integrated into the management of epilepsy in this region. Consequences of epilepsy such as burns, lack of education, poor marriage prospects, and unemployment need to be addressed. PMID:24116877

Clinical features, proximate causes, and consequences of active convulsive epilepsy in Africa.

PubMed

Kariuki, Symon M; Matuja, William; Akpalu, Albert; Kakooza-Mwesige, Angelina; Chabi, Martin; Wagner, Ryan G; Connor, Myles; Chengo, Eddie; Ngugi, Anthony K; Odhiambo, Rachael; Bottomley, Christian; White, Steven; Sander, Josemir W; Neville, Brian G R; Newton, Charles R J C; Twine, Rhian; Gómez Olivé, F Xavier; Collinson, Mark; Kahn, Kathleen; Tollman, Stephen; Masanja, Honratio; Mathew, Alexander; Pariyo, George; Peterson, Stefan; Ndyomughenyi, Donald; Bauni, Evasius; Kamuyu, Gathoni; Odera, Victor Mung'ala; Mageto, James O; Ae-Ngibise, Ken; Akpalu, Bright; Agbokey, Francis; Adjei, Patrick; Owusu-Agyei, Seth; Kleinschmidt, Immo; Doku, Victor C K; Odermatt, Peter; Nutman, Thomas; Wilkins, Patricia; Noh, John

2014-01-01

Epilepsy is common in sub-Saharan Africa (SSA), but the clinical features and consequences are poorly characterized. Most studies are hospital-based, and few studies have compared different ecological sites in SSA. We described active convulsive epilepsy (ACE) identified in cross-sectional community-based surveys in SSA, to understand the proximate causes, features, and consequences. We performed a detailed clinical and neurophysiologic description of ACE cases identified from a community survey of 584,586 people using medical history, neurologic examination, and electroencephalography (EEG) data from five sites in Africa: South Africa; Tanzania; Uganda; Kenya; and Ghana. The cases were examined by clinicians to discover risk factors, clinical features, and consequences of epilepsy. We used logistic regression to determine the epilepsy factors associated with medical comorbidities. Half (51%) of the 2,170 people with ACE were children and 69% of seizures began in childhood. Focal features (EEG, seizure types, and neurologic deficits) were present in 58% of ACE cases, and these varied significantly with site. Status epilepticus occurred in 25% of people with ACE. Only 36% received antiepileptic drugs (phenobarbital was the most common drug [95%]), and the proportion varied significantly with the site. Proximate causes of ACE were adverse perinatal events (11%) for onset of seizures before 18 years; and acute encephalopathy (10%) and head injury prior to seizure onset (3%). Important comorbidities were malnutrition (15%), cognitive impairment (23%), and neurologic deficits (15%). The consequences of ACE were burns (16%), head injuries (postseizure) (1%), lack of education (43%), and being unmarried (67%) or unemployed (57%) in adults, all significantly more common than in those without epilepsy. There were significant differences in the comorbidities across sites. Focal features are common in ACE, suggesting identifiable and preventable causes. Malnutrition and cognitive and neurologic deficits are common in people with ACE and should be integrated into the management of epilepsy in this region. Consequences of epilepsy such as burns, lack of education, poor marriage prospects, and unemployment need to be addressed. Wiley Periodicals, Inc. © 2013 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of the International League Against Epilepsy.

Recommendations From the Common Terminology Panel of the American Council of Academic Physical Therapy.

PubMed

Erickson, Mia; Birkmeier, Marisa; Booth, Melissa; Hack, Laurita M; Hartmann, Julie; Ingram, Debbie A; Jackson-Coty, Janet M; LaFay, Vicki L; Wheeler, Emma; Soper, Shawne

2018-06-19

In 2015, the American Council for Academic Physical Therapy (ACAPT) developed 3 strategic initiative panels to address integrated clinical education, student readiness, and common terminology for physical therapist clinical education. The purpose of this paper is to describe the results of the work from the common terminology panel. This was a descriptive, consensus-based study. Using a consensus process and data that were collected from a review of literature, a document analysis of core and historical professional documents, focus group discussions, and an online open-comment period, panel members developed a glossary for physical therapist clinical education. The final glossary included 34 terms in 4 categories. The categories included clinical education infrastructure, sites, stakeholders, and assessment. The ACAPT Board of Directors approved the glossary in June 2017, and the ACAPT membership approved the glossary in October 2017. The focus of the glossary was on physical therapist clinical education. A future, similar project should be undertaken for physical therapist assistant clinical education. This process resulted in a comprehensive glossary for physical therapist clinical education; changes to several current terms, including "internship" and "full-time clinical education experience"; and the addition of new terms, including "preceptor" and "site coordinator for clinical education." New terminology will provide standard language for consistent communication and a common framework for all stakeholders.

Long-term increase in mVEGF164 in mouse hindlimb muscle mediated by phage phiC31 integrase after nonviral DNA delivery.

PubMed

Portlock, Joylette L; Keravala, Annahita; Bertoni, Carmen; Lee, Solomon; Rando, Thomas A; Calos, Michele P

2006-08-01

Peripheral vascular disease (PVD), characterized by insufficient blood supply to extremities, can be a devastating illness. Although many gene therapy strategies for PVD using vascular endothelial growth factor (VEGF) have resulted in increased blood vessel formation, the vessels are often impermanent and regress after therapy, probably because of the short-lived VEGF expression mediated by gene therapy vectors (14 days or less). phiC31 integrase is a recombinase originally isolated from a bacteriophage of Streptomyces. This integrase performs efficient chromosomal integration of plasmid DNA into mammalian genomes that results in long-term transgene expression. In this study, gene transfer was achieved by intramuscular injection of VEGF and integrase plasmid DNAs into the tibialis anterior muscle in the mouse hindlimb, followed by electroporation of the muscle with needle electrodes. We observed VEGF levels significantly above background 40 days after injection in animals that received phiC31 integrase and the VEGF plasmid. Site-specific integration of plasmid DNA in the chromosomes of muscle tissue was verified by polymerase chain reaction at a common integration site. These results suggest the possible utility of the phiC31 integrase system to treat ischemic disease.

Flight Testing ALHAT Precision Landing Technologies Integrated Onboard the Morpheus Rocket Vehicle

NASA Technical Reports Server (NTRS)

Carson, John M. III; Robertson, Edward A.; Trawny, Nikolas; Amzajerdian, Farzin

2015-01-01

A suite of prototype sensors, software, and avionics developed within the NASA Autonomous precision Landing and Hazard Avoidance Technology (ALHAT) project were terrestrially demonstrated onboard the NASA Morpheus rocket-propelled Vertical Testbed (VTB) in 2014. The sensors included a LIDAR-based Hazard Detection System (HDS), a Navigation Doppler LIDAR (NDL) velocimeter, and a long-range Laser Altimeter (LAlt) that enable autonomous and safe precision landing of robotic or human vehicles on solid solar system bodies under varying terrain lighting conditions. The flight test campaign with the Morpheus vehicle involved a detailed integration and functional verification process, followed by tether testing and six successful free flights, including one night flight. The ALHAT sensor measurements were integrated into a common navigation solution through a specialized ALHAT Navigation filter that was employed in closed-loop flight testing within the Morpheus Guidance, Navigation and Control (GN&C) subsystem. Flight testing on Morpheus utilized ALHAT for safe landing site identification and ranking, followed by precise surface-relative navigation to the selected landing site. The successful autonomous, closed-loop flight demonstrations of the prototype ALHAT system have laid the foundation for the infusion of safe, precision landing capabilities into future planetary exploration missions.

The Structure and Effectiveness of Health Systems: Exploring the Impact of System Integration in Rural China.

PubMed

Wang, Xin; Birch, Stephen; Ma, Huifen; Zhu, Weiming; Meng, Qingyue

2016-08-12

Facing the challenges of aging populations, increasing chronic diseases prevalence and health system fragmentation, there have been several pilots of integrated health systems in China. But little is known about their structure, mechanism and effectiveness. The aim of this paper is to analyze health system integration and develop recommendations for achieving integration. Huangzhong and Hualong counties in Qinghai province were studied as study sites, with only Huangzhong having implemented health system integration. Questionnaires, interviews, and health insurance records were sources of data. Social network analysis was employed to analyze integration, through structure measurement and effectiveness evaluation. Health system integration in Huangzhong is higher than in Hualong, so is system effectiveness. The patient referral network in Hualong has more "leapfrog" referrals. The information sharing networks in both counties are larger than the other types of networks. The average distance in the joint training network of Huangzhong is less than in Hualong. Meanwhile, there are deficiencies common to both systems. Both county health systems have strengths and limitations regarding system integration. The use of medical consortia in Huangzhong has contributed to system effectiveness. Future research might consider alternative more context specific models of health system integration.

NGS-based approach to determine the presence of HPV and their sites of integration in human cancer genome.

PubMed

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.

Restoration of degraded drylands in northern Chile: The need of local stakeholders' participation to prevent and combat desertification

NASA Astrophysics Data System (ADS)

Jorquera-Jaramillo, Carmen; Yáñez-Acevedo, Marcia; Gutiérrez, Julio R.; Cortés-Bugueño, José Luis; Pastén-Marambio, Víctor; Barraza-Cepeda, Claudia

2015-04-01

Desertification is one of the main factors determining poverty, long-term socio-economic problems, natural resources depletion and disturbances in rural communities living at the Coquimbo Region drylands (North-Central Chile). The Chilean State, along with private initiatives, have invested 473.6 Million dollars (1976 to 2008) to recover degraded areas through afforestation and soil management of 1,373,758 hectares. However, there is no information about the impact of the practices and changes experienced by the local stakeholders. Therefore, there is a need for a comprehensive evaluation considering both socioeconomic and biophysical aspects. To this end, a Protocol on Integrated Assessment (IAPro, PRACTICE project) was applied in two rural communities, involving communal afforested sites and their adjacent degraded drylands: El Sauce (ES, Limarí province) and Las Cañas (LC, Choapa province), Coquimbo Region. Participatory afforestation and soil conservation projects were implemented at both sites by the Chilean National Forestry Service (CONAF) in agreement with each local community (Jiménez y Tapia Agricultural Community at ES and Las Cañas de Choapa Peasant's Community at LC). The protocol involved 7 steps: (1) Stakeholder platform identification and engagement; (2) Baseline assessment and selection of site-specific indicators; (3) Integration and weighting of common and site-specific indicators; (4) Data collection; (5) Integrating and perspectives on a MCDA (Multi-Criteria Decision Analysis); (6) Collective Integrated assessment and knowledge sharing; (7) Dissemination. Interviews involved local and institutional stakeholders related to both sites' implementation, administration and/or local impacts. For the ES site, 5 actions were defined and assessed: No action (control); fences; mechanic and biological practices (soil stabilization, runoff control on slopes); runoff control in micro-basins, gullies and ravines; and footpath for educational and demonstration purposes. The same actions plus 'conservation and management of native forests/shrubs at strict exclosure' were identified at LC site. All of the stakeholders interviewed at both sites recognized the actions, but not all of them had specific knowledge about some of the practices. Afforestation was the most selected and valued practice, revealing deep knowledge about the actions and positive valuation of the site experience, but also a need of more support for maintenance. At ES, the main concerns were drought and derived unemployment; at LC, the main concerns were access to the site, prolonged droughts, local conflicts and lack of community commitment. At both sites, many stakeholders highlighted the need for more financial support, better management and assistance in solving local conflicts. External stakeholders value both sites as replicable models and their positive impacts in increasing afforestation and soil conservation experiences; they also identify a need for continuous financial support and the exploration of other models for site implementation and educational activities. The integrated assessment identified a match between the trends in biophysical indicators' results and the perspectives on those indicators expressed by stakeholders. It remained clear that every intervention to combat desertification requires an active involvement of local stakeholders and the implementation of educational modules to ensure the adoption of appropriate practices. Keywords: Land degradation - restoration actions - participatory approach - economic and environmental aspects - recovery of degraded drylands

The need for European professional standards and the challenges facing clinical microbiology.

PubMed

Humphreys, H; Nagy, E; Kahlmeter, G; Ruijs, G J H M

2010-06-01

Microorganisms spread across national boundaries and the professional activities of clinical (medical) microbiologists are critical in minimising their impact. Clinical microbiologists participate in many activities, e.g. diagnosis, antibiotic therapy, and there is a need for a set of professional standards for Europe with a common curriculum, to build upon the current strengths of the specialty and to facilitate the free movement of specialists within the European Union. Such standards will also better highlight the important contribution of clinical microbiologists to healthcare. There is a move to larger centralised microbiology laboratories often located off-site from an acute hospital, driven by the concentration of resources, amalgamation of services, outsourcing of diagnostics, automation, an explosion in the range of staff competencies and accreditation. Large off-site centralised microbiology laboratories are often distant to the patient and may not facilitate the early detection of microbial spread. Ultimately, the needs of patients and the public are paramount in deciding on the future direction of clinical microbiology. Potential conflicts between integration on an acute hospital site and centralisation can be resolved by a common set of professional standards and a team-based approach that puts patients first.

Viability of male gametes in common carp (Cyprinus carpio) along the Lower Colorado River from the Cibola National Wildlife Refuge (NWR), Havasu NWR, and Lake Mohave of Lake Mead National Recreation Area

USGS Publications Warehouse

Jenkins, Jill A.; Goodbred, Steven L.

2005-01-01

To contribute to an investigation on possible endocrine impacts in three sites along the lower Colorado River in Arizona, especially in male fishes, this study addressed the null hypothesis that aquatic species in southern sites did not exhibit evidence of endocrine disruption as compared with those in nonimpacted sites. The results presented are intended to provide managers with science-based information and interpretations about the reproductive condition of biota in their habitat along the lower Colorado River to minimize any potential adverse effects to trust fish and wildlife resources and to identify water resources of acceptable quality. In particular, these data can inform decision making about wastewater discharges into the Colorado River that directly supplies water to Arizona refuges located along the river. These data are integral to the USFWS proposal entitled 'AZ - Endocrine Disruption in Razorback Sucker and Common Carp on National Wildlife Refuges along the Lower Colorado River' that was proposed to assess evidence of endocrine disruption in carp and razorback suckers downstream of Hoover Dam.

The Parallel System for Integrating Impact Models and Sectors (pSIMS)

NASA Technical Reports Server (NTRS)

Elliott, Joshua; Kelly, David; Chryssanthacopoulos, James; Glotter, Michael; Jhunjhnuwala, Kanika; Best, Neil; Wilde, Michael; Foster, Ian

2014-01-01

We present a framework for massively parallel climate impact simulations: the parallel System for Integrating Impact Models and Sectors (pSIMS). This framework comprises a) tools for ingesting and converting large amounts of data to a versatile datatype based on a common geospatial grid; b) tools for translating this datatype into custom formats for site-based models; c) a scalable parallel framework for performing large ensemble simulations, using any one of a number of different impacts models, on clusters, supercomputers, distributed grids, or clouds; d) tools and data standards for reformatting outputs to common datatypes for analysis and visualization; and e) methodologies for aggregating these datatypes to arbitrary spatial scales such as administrative and environmental demarcations. By automating many time-consuming and error-prone aspects of large-scale climate impacts studies, pSIMS accelerates computational research, encourages model intercomparison, and enhances reproducibility of simulation results. We present the pSIMS design and use example assessments to demonstrate its multi-model, multi-scale, and multi-sector versatility.

Computerized engineering logic for nuclear procurement and dedication processes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tulay, M.P.

1996-12-31

In an attempt to better meet the needs of operations and maintenance organizations, many nuclear utility procurement engineering groups have simplified their procedures, developed on-line tools for performing the specification of replacement items, and developed relational databases containing part-level information necessary to automate the procurement process. Although these improvements have helped to reduce the engineering necessary to properly specify and accept/dedicate items for nuclear safety-related applications, a number of utilities have recognized that additional long-term savings can be realized by integrating a computerized logic to assist technical procurement engineering personnel. The most commonly used logic follows the generic processes containedmore » in Electric Power Research Institute (EPRI) published guidelines. The processes are typically customized to some extent to accommodate each utility`s organizational structure, operating procedures, and strategic goals. This paper will discuss a typical logic that integrates the technical evaluation, acceptance, and receipt inspection and testing processes. The logic this paper will describe has been successfully integrated at a growing number of nuclear utilities and has produced numerous positive results. The application of the logic ensures that utility-wide standards or procedures, common among multi-site utilities, are followed.« less

Integrated Genomic and Epigenomic Analysis of Breast Cancer Brain Metastasis

PubMed Central

Salhia, Bodour; Kiefer, Jeff; Ross, Julianna T. D.; Metapally, Raghu; Martinez, Rae Anne; Johnson, Kyle N.; DiPerna, Danielle M.; Paquette, Kimberly M.; Jung, Sungwon; Nasser, Sara; Wallstrom, Garrick; Tembe, Waibhav; Baker, Angela; Carpten, John; Resau, Jim; Ryken, Timothy; Sibenaller, Zita; Petricoin, Emanuel F.; Liotta, Lance A.; Ramanathan, Ramesh K.; Berens, Michael E.; Tran, Nhan L.

2014-01-01

The brain is a common site of metastatic disease in patients with breast cancer, which has few therapeutic options and dismal outcomes. The purpose of our study was to identify common and rare events that underlie breast cancer brain metastasis. We performed deep genomic profiling, which integrated gene copy number, gene expression and DNA methylation datasets on a collection of breast brain metastases. We identified frequent large chromosomal gains in 1q, 5p, 8q, 11q, and 20q and frequent broad-level deletions involving 8p, 17p, 21p and Xq. Frequently amplified and overexpressed genes included ATAD2, BRAF, DERL1, DNMTRB and NEK2A. The ATM, CRYAB and HSPB2 genes were commonly deleted and underexpressed. Knowledge mining revealed enrichment in cell cycle and G2/M transition pathways, which contained AURKA, AURKB and FOXM1. Using the PAM50 breast cancer intrinsic classifier, Luminal B, Her2+/ER negative, and basal-like tumors were identified as the most commonly represented breast cancer subtypes in our brain metastasis cohort. While overall methylation levels were increased in breast cancer brain metastasis, basal-like brain metastases were associated with significantly lower levels of methylation. Integrating DNA methylation data with gene expression revealed defects in cell migration and adhesion due to hypermethylation and downregulation of PENK, EDN3, and ITGAM. Hypomethylation and upregulation of KRT8 likely affects adhesion and permeability. Genomic and epigenomic profiling of breast brain metastasis has provided insight into the somatic events underlying this disease, which have potential in forming the basis of future therapeutic strategies. PMID:24489661

Effect of Plasmid Design and Type of Integration Event on Recombinant Protein Expression in Pichia pastoris.

PubMed

Vogl, Thomas; Gebbie, Leigh; Palfreyman, Robin W; Speight, Robert

2018-03-15

Pichia pastoris (syn. Komagataella phaffii ) is one of the most common eukaryotic expression systems for heterologous protein production. Expression cassettes are typically integrated in the genome to obtain stable expression strains. In contrast to Saccharomyces cerevisiae , where short overhangs are sufficient to target highly specific integration, long overhangs are more efficient in P. pastoris and ectopic integration of foreign DNA can occur. Here, we aimed to elucidate the influence of ectopic integration by high-throughput screening of >700 transformants and whole-genome sequencing of 27 transformants. Different vector designs and linearization approaches were used to mimic the most common integration events targeted in P. pastoris Fluorescence of an enhanced green fluorescent protein (eGFP) reporter protein was highly uniform among transformants when the expression cassettes were correctly integrated in the targeted locus. Surprisingly, most nonspecifically integrated transformants showed highly uniform expression that was comparable to specific integration, suggesting that nonspecific integration does not necessarily influence expression. However, a few clones (<10%) harboring ectopically integrated cassettes showed a greater variation spanning a 25-fold range, surpassing specifically integrated reference strains up to 6-fold. High-expression strains showed a correlation between increased gene copy numbers and high reporter protein fluorescence levels. Our results suggest that for comparing expression levels between strains, the integration locus can be neglected as long as a sufficient numbers of transformed strains are compared. For expression optimization of highly expressible proteins, increasing copy number appears to be the dominant positive influence rather than the integration locus, genomic rearrangements, deletions, or single-nucleotide polymorphisms (SNPs). IMPORTANCE Yeasts are commonly used as biotechnological production hosts for proteins and metabolites. In the yeast Saccharomyces cerevisiae , expression cassettes carrying foreign genes integrate highly specifically at the targeted sites in the genome. In contrast, cassettes often integrate at random genomic positions in nonconventional yeasts, such as Pichia pastoris (syn. Komagataella phaffii ). Hence, cells from the same transformation event often behave differently, with significant clonal variation necessitating the screening of large numbers of strains. The importance of this study is that we systematically investigated the influence of integration events in more than 700 strains. Our findings provide novel insight into clonal variation in P. pastoris and, thus, how to avoid pitfalls and obtain reliable results. The underlying mechanisms may also play a role in other yeasts and hence could be generally relevant for recombinant yeast protein production strains. Copyright © 2018 American Society for Microbiology.

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

PubMed

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.

Ub-ISAP: a streamlined UNIX pipeline for mining unique viral vector integration sites from next generation sequencing data.

PubMed

Kamboj, Atul; Hallwirth, Claus V; Alexander, Ian E; McCowage, Geoffrey B; Kramer, Belinda

2017-06-17

The analysis of viral vector genomic integration sites is an important component in assessing the safety and efficiency of patient treatment using gene therapy. Alongside this clinical application, integration site identification is a key step in the genetic mapping of viral elements in mutagenesis screens that aim to elucidate gene function. We have developed a UNIX-based vector integration site analysis pipeline (Ub-ISAP) that utilises a UNIX-based workflow for automated integration site identification and annotation of both single and paired-end sequencing reads. Reads that contain viral sequences of interest are selected and aligned to the host genome, and unique integration sites are then classified as transcription start site-proximal, intragenic or intergenic. Ub-ISAP provides a reliable and efficient pipeline to generate large datasets for assessing the safety and efficiency of integrating vectors in clinical settings, with broader applications in cancer research. Ub-ISAP is available as an open source software package at https://sourceforge.net/projects/ub-isap/ .

Enhancers Are Major Targets for Murine Leukemia Virus Vector Integration

PubMed Central

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 (<15%) occur in this region. To resolve this apparent discrepancy, we created a high-resolution genome-wide 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

Retrovirus Integration Database (RID): a public database for retroviral insertion sites into host genomes.

PubMed

Shao, Wei; Shan, Jigui; Kearney, Mary F; Wu, Xiaolin; Maldarelli, Frank; Mellors, John W; Luke, Brian; Coffin, John M; Hughes, Stephen H

2016-07-04

The NCI Retrovirus Integration Database is a MySql-based relational database created for storing and retrieving comprehensive information about retroviral integration sites, primarily, but not exclusively, HIV-1. The database is accessible to the public for submission or extraction of data originating from experiments aimed at collecting information related to retroviral integration sites including: the site of integration into the host genome, the virus family and subtype, the origin of the sample, gene exons/introns associated with integration, and proviral orientation. Information about the references from which the data were collected is also stored in the database. Tools are built into the website that can be used to map the integration sites to UCSC genome browser, to plot the integration site patterns on a chromosome, and to display provirus LTRs in their inserted genome sequence. The website is robust, user friendly, and allows users to query the database and analyze the data dynamically. https://rid.ncifcrf.gov ; or http://home.ncifcrf.gov/hivdrp/resources.htm .

Integration of paleoseismic data from multiple sites to develop an objective earthquake chronology: Application to the Weber segment of the Wasatch fault zone, Utah

USGS Publications Warehouse

DuRoss, Christopher B.; Personius, Stephen F.; Crone, Anthony J.; Olig, Susan S.; Lund, William R.

2011-01-01

We present a method to evaluate and integrate paleoseismic data from multiple sites into a single, objective measure of earthquake timing and recurrence on discrete segments of active faults. We apply this method to the Weber segment (WS) of the Wasatch fault zone using data from four fault-trench studies completed between 1981 and 2009. After systematically reevaluating the stratigraphic and chronologic data from each trench site, we constructed time-stratigraphic OxCal models that yield site probability density functions (PDFs) of the times of individual earthquakes. We next qualitatively correlated the site PDFs into a segment-wide earthquake chronology, which is supported by overlapping site PDFs, large per-event displacements, and prominent segment boundaries. For each segment-wide earthquake, we computed the product of the site PDF probabilities in common time bins, which emphasizes the overlap in the site earthquake times, and gives more weight to the narrowest, best-defined PDFs. The product method yields smaller earthquake-timing uncertainties compared to taking the mean of the site PDFs, but is best suited to earthquakes constrained by broad, overlapping site PDFs. We calculated segment-wide earthquake recurrence intervals and uncertainties using a Monte Carlo model. Five surface-faulting earthquakes occurred on the WS at about 5.9, 4.5, 3.1, 1.1, and 0.6 ka. With the exception of the 1.1-ka event, we used the product method to define the earthquake times. The revised WS chronology yields a mean recurrence interval of 1.3 kyr (0.7–1.9-kyr estimated two-sigma [2δ] range based on interevent recurrence). These data help clarify the paleoearthquake history of the WS, including the important question of the timing and rupture extent of the most recent earthquake, and are essential to the improvement of earthquake-probability assessments for the Wasatch Front region.

Integration of paleoseismic data from multiple sites to develop an objective earthquake chronology: Application to the Weber segment of the Wasatch fault zone, Utah

USGS Publications Warehouse

DuRoss, C.B.; Personius, S.F.; Crone, A.J.; Olig, S.S.; Lund, W.R.

2011-01-01

We present a method to evaluate and integrate paleoseismic data from multiple sites into a single, objective measure of earthquake timing and recurrence on discrete segments of active faults. We apply this method to the Weber segment (WS) of the Wasatch fault zone using data from four fault-trench studies completed between 1981 and 2009. After systematically reevaluating the stratigraphic and chronologic data from each trench site, we constructed time-stratigraphic OxCal models that yield site probability density functions (PDFs) of the times of individual earthquakes. We next qualitatively correlated the site PDFs into a segment-wide earthquake chronology, which is supported by overlapping site PDFs, large per-event displacements, and prominent segment boundaries. For each segment-wide earthquake, we computed the product of the site PDF probabilities in common time bins, which emphasizes the overlap in the site earthquake times, and gives more weight to the narrowest, best-defined PDFs. The product method yields smaller earthquake-timing uncertainties compared to taking the mean of the site PDFs, but is best suited to earthquakes constrained by broad, overlapping site PDFs. We calculated segment-wide earthquake recurrence intervals and uncertainties using a Monte Carlo model. Five surface-faulting earthquakes occurred on the WS at about 5.9, 4.5, 3.1, 1.1, and 0.6 ka. With the exception of the 1.1-ka event, we used the product method to define the earthquake times. The revised WS chronology yields a mean recurrence interval of 1.3 kyr (0.7-1.9-kyr estimated two-sigma [2??] range based on interevent recurrence). These data help clarify the paleoearthquake history of the WS, including the important question of the timing and rupture extent of the most recent earthquake, and are essential to the improvement of earthquake-probability assessments for the Wasatch Front region.

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

PubMed

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 integration site analysis, which allows gene therapy integration data to be handled in a cost and time effective fashion. Moreover, the web access of VISPA2 ( http://openserver.itb.cnr.it/vispa/ ) ensures accessibility and ease of usage to researches of a complex analytical tool. We released the source code of VISPA2 in a public repository ( https://bitbucket.org/andreacalabria/vispa2 ).

Integrated Geophysical Analysis at a Legacy Test Site

NASA Astrophysics Data System (ADS)

Yang, X.; Mellors, R. J.; Sweeney, J. J.; Sussman, A. J.

2015-12-01

We integrate magnetic, electromagnetic (EM), gravity, and seismic data to develop a unified and consistent model of the subsurface at the U20ak site on Pahute Mesa at the Nevada National Nuclear Security Site (NNSS). The 1985 test, conducted in tuff at a depth of approximately 600 m did not collapse to the surface or produce a crater. The purpose of the geophysical measurements is to characterize the subsurface above and around the presumed explosion cavity. The magnetic data are used to locate steel borehole casings and pipes and are correlated with surface observations. The EM data show variation in lithology at depth and clear signatures from borehole casings and surface cables. The gravity survey detects a clear gravity low in the area of the explosion. The seismic data indicates shallow low velocity zone and indications of a deeper low velocity zones. In this study, we conduct 2D inversion of EM data for better characterization of site geology and use a common 3D density model to jointly interpret both the seismic and gravity data along with constraints on lithology boundaries from the EM. The integration of disparate geophysical datasets allows improved understanding of the non-prompt physical signatures of an underground nuclear explosion (UNE). LLNL Release Number: LLNL-ABS-675677. The authors express their gratitude to the National Nuclear Security Administration, Defense Nuclear Nonproliferation Research and Development, and the Comprehensive Inspection Technologies and UNESE working group, a multi-institutional and interdisciplinary group of scientists and engineers. This work was performed by Lawrence Livermore National Laboratory and Los Alamos National Laboratory under award number DE-AC52-06NA25946.

HIV integration sites in latently infected cell lines: evidence of ongoing replication.

PubMed

Symons, Jori; Chopra, Abha; Malatinkova, Eva; De Spiegelaere, Ward; Leary, Shay; Cooper, Don; Abana, Chike O; Rhodes, Ajantha; Rezaei, Simin D; Vandekerckhove, Linos; Mallal, Simon; Lewin, Sharon R; Cameron, Paul U

2017-01-13

Assessing the location and frequency of HIV integration sites in latently infected cells can potentially inform our understanding of how HIV persists during combination antiretroviral therapy. We developed a novel high throughput sequencing method to evaluate HIV integration sites in latently infected cell lines to determine whether there was virus replication or clonal expansion in these cell lines observed as multiple integration events at the same position. We modified a previously reported method using random DNA shearing and PCR to allow for high throughput robotic processing to identify the site and frequency of HIV integration in latently infected cell lines. Latently infected cell lines infected with intact virus demonstrated multiple distinct HIV integration sites (28 different sites in U1, 110 in ACH-2 and 117 in J1.1 per 150,000 cells). In contrast, cell lines infected with replication-incompetent viruses (J-Lat cells) demonstrated single integration sites. Following in vitro passaging of the ACH-2 cell line, we observed a significant increase in the frequency of unique HIV integration sites and there were multiple mutations and large deletions in the proviral DNA. When the ACH-2 cell line was cultured with the integrase inhibitor raltegravir, there was a significant decrease in the number of unique HIV integration sites and a transient increase in the frequency of 2-LTR circles consistent with virus replication in these cells. Cell lines latently infected with intact HIV demonstrated multiple unique HIV integration sites indicating that these cell lines are not clonal and in the ACH-2 cell line there was evidence of low level virus replication. These findings have implications for the use of latently infected cell lines as models of HIV latency and for the use of these cells as standards.

Virus-like attachment sites as structural landmarks of plants retrotransposons.

PubMed

Ochoa Cruz, Edgar Andres; Cruz, Guilherme Marcello Queiroga; Vieira, Andréia Prata; Van Sluys, Marie-Anne

2016-01-01

The genomic data available nowadays has enabled the study of repetitive sequences and their relationship to viruses. Among them, long terminal repeat retrotransposons (LTR-RTs) are the largest component of most plant genomes, the Gypsy and Copia superfamilies being the most common. Recently it has been found that Del lineage, an LTR-RT of Gypsy superfamily, has putative virus-like attachment (vl-att) sites. This signature, originally described for retroviruses, is recognized by retroviral integrase conferring specificity to the integration process. Here we retrieved 26,092 putative complete LTR-RTs from 10 lineages found in 10 fully sequenced angiosperm genomes and found putative vl-att sites that are a conserved structural landmark across these genomes. Furthermore, we reveal that each plant genome has a distinguishable LTR-RT lineage amplification pattern that could be related to the vl-att sites diversity. We used these patterns to generate a specific quick-response (QR) code for each genome that could be used as a barcode of identification of plants in the future. The universal distribution of vl-att sites represents a new structural feature common to plant LTR-RTs and retroviruses. This is an important finding that expands the information about the structural similarity between LTR-RT and retroviruses. We speculate that the sequence diversity of vl-att sites could be important for the life cycle of retrotransposons, as it was shown for retroviruses. All the structural vl-att site signatures are strong candidates for further functional studies. Moreover, this is the first identification of specific LTR-RT content and their amplification patterns in a large dataset of LTR-RT lineages and angiosperm genomes. These distribution patterns could be used in the future with biotechnological identification purposes.

Combining Comprehensive Analysis of Off-Site Lambda Phage Integration with a CRISPR-Based Means of Characterizing Downstream Physiology.

PubMed

Tanouchi, Yu; Covert, Markus W

2017-09-19

During its lysogenic life cycle, the phage genome is integrated into the host chromosome by site-specific recombination. In this report, we analyze lambda phage integration into noncanonical sites using next-generation sequencing and show that it generates significant genetic diversity by targeting over 300 unique sites in the host Escherichia coli genome. Moreover, these integration events can have important phenotypic consequences for the host, including changes in cell motility and increased antibiotic resistance. Importantly, the new technologies that we developed to enable this study-sequencing secondary sites using next-generation sequencing and then selecting relevant lysogens using clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-based selection-are broadly applicable to other phage-bacterium systems. IMPORTANCE Bacteriophages play an important role in bacterial evolution through lysogeny, where the phage genome is integrated into the host chromosome. While phage integration generally occurs at a specific site in the host chromosome, it is also known to occur at other, so-called secondary sites. In this study, we developed a new experimental technology to comprehensively study secondary integration sites and discovered that phage can integrate into over 300 unique sites in the host genome, resulting in significant genetic diversity in bacteria. We further developed an assay to examine the phenotypic consequence of such diverse integration events and found that phage integration can cause changes in evolutionarily relevant traits such as bacterial motility and increases in antibiotic resistance. Importantly, our method is readily applicable to other phage-bacterium systems. Copyright © 2017 Tanouchi and Covert.

Integrative Computational Network Analysis Reveals Site-Specific Mediators of Inflammation in Alzheimer's Disease

PubMed Central

Ravichandran, Srikanth; Michelucci, Alessandro; del Sol, Antonio

2018-01-01

Alzheimer's disease (AD) is a major neurodegenerative disease and is one of the most common cause of dementia in older adults. Among several factors, neuroinflammation is known to play a critical role in the pathogenesis of chronic neurodegenerative diseases. In particular, studies of brains affected by AD show a clear involvement of several inflammatory pathways. Furthermore, depending on the brain regions affected by the disease, the nature and the effect of inflammation can vary. Here, in order to shed more light on distinct and common features of inflammation in different brain regions affected by AD, we employed a computational approach to analyze gene expression data of six site-specific neuronal populations from AD patients. Our network based computational approach is driven by the concept that a sustained inflammatory environment could result in neurotoxicity leading to the disease. Thus, our method aims to infer intracellular signaling pathways/networks that are likely to be constantly activated or inhibited due to persistent inflammatory conditions. The computational analysis identified several inflammatory mediators, such as tumor necrosis factor alpha (TNF-a)-associated pathway, as key upstream receptors/ligands that are likely to transmit sustained inflammatory signals. Further, the analysis revealed that several inflammatory mediators were mainly region specific with few commonalities across different brain regions. Taken together, our results show that our integrative approach aids identification of inflammation-related signaling pathways that could be responsible for the onset or the progression of AD and can be applied to study other neurodegenerative diseases. Furthermore, such computational approaches can enable the translation of clinical omics data toward the development of novel therapeutic strategies for neurodegenerative diseases. PMID:29551980

Integrative Computational Network Analysis Reveals Site-Specific Mediators of Inflammation in Alzheimer's Disease.

PubMed

Ravichandran, Srikanth; Michelucci, Alessandro; Del Sol, Antonio

2018-01-01

Alzheimer's disease (AD) is a major neurodegenerative disease and is one of the most common cause of dementia in older adults. Among several factors, neuroinflammation is known to play a critical role in the pathogenesis of chronic neurodegenerative diseases. In particular, studies of brains affected by AD show a clear involvement of several inflammatory pathways. Furthermore, depending on the brain regions affected by the disease, the nature and the effect of inflammation can vary. Here, in order to shed more light on distinct and common features of inflammation in different brain regions affected by AD, we employed a computational approach to analyze gene expression data of six site-specific neuronal populations from AD patients. Our network based computational approach is driven by the concept that a sustained inflammatory environment could result in neurotoxicity leading to the disease. Thus, our method aims to infer intracellular signaling pathways/networks that are likely to be constantly activated or inhibited due to persistent inflammatory conditions. The computational analysis identified several inflammatory mediators, such as tumor necrosis factor alpha (TNF-a)-associated pathway, as key upstream receptors/ligands that are likely to transmit sustained inflammatory signals. Further, the analysis revealed that several inflammatory mediators were mainly region specific with few commonalities across different brain regions. Taken together, our results show that our integrative approach aids identification of inflammation-related signaling pathways that could be responsible for the onset or the progression of AD and can be applied to study other neurodegenerative diseases. Furthermore, such computational approaches can enable the translation of clinical omics data toward the development of novel therapeutic strategies for neurodegenerative diseases.

Integrating the healthcare enterprise in radiation oncology plug and play--the future of radiation oncology?

PubMed

Abdel-Wahab, May; Rengan, Ramesh; Curran, Bruce; Swerdloff, Stuart; Miettinen, Mika; Field, Colin; Ranjitkar, Sunita; Palta, Jatinder; Tripuraneni, Prabhakar

2010-02-01

To describe the processes and benefits of the integrating healthcare enterprises in radiation oncology (IHE-RO). The IHE-RO process includes five basic steps. The first step is to identify common interoperability issues encountered in radiation treatment planning and the delivery process. IHE-RO committees partner with vendors to develop solutions (integration profiles) to interoperability problems. The broad application of these integration profiles across a variety of vender platforms is tested annually at the Connectathon event. Demonstration of the seamless integration and transfer of patient data to the potential users are then presented by vendors at the public demonstration event. Users can then integrate these profiles into requests for proposals and vendor contracts by institutions. Incorporation of completed integration profiles into requests for proposals can be done when purchasing new equipment. Vendors can publish IHE integration statements to document the integration profiles supported by their products. As a result, users can reference integration profiles in requests for proposals, simplifying the systems acquisition process. These IHE-RO solutions are now available in many of the commercial radiation oncology-related treatment planning, delivery, and information systems. They are also implemented at cancer care sites around the world. IHE-RO serves an important purpose for the radiation oncology community at large. Copyright 2010 Elsevier Inc. All rights reserved.

Streamlined Archaeo-geophysical Data Processing and Integration for DoD Field Use

DTIC Science & Technology

2012-04-01

names can now be renamed and are, by default, named B1, B2, etc. It is hard to tell if Band buttons (B1, B2, etc.) are depressed or not. Contrast...consisted of a man-made depression surrounded by low ridges. That aspect of the fort’s layout is discussed further in Chapter 5. 4.1.5 SITE HISTORY...larger rocks, natural depressions representing concentrations of relatively magnetic topsoil, etc., (Bevan 1998). Pits are a common feature type, but

An innovative method for offshore wind farm site selection based on the interval number with probability distribution

NASA Astrophysics Data System (ADS)

Wu, Yunna; Chen, Kaifeng; Xu, Hu; Xu, Chuanbo; Zhang, Haobo; Yang, Meng

2017-12-01

There is insufficient research relating to offshore wind farm site selection in China. The current methods for site selection have some defects. First, information loss is caused by two aspects: the implicit assumption that the probability distribution on the interval number is uniform; and ignoring the value of decision makers' (DMs') common opinion on the criteria information evaluation. Secondly, the difference in DMs' utility function has failed to receive attention. An innovative method is proposed in this article to solve these drawbacks. First, a new form of interval number and its weighted operator are proposed to reflect the uncertainty and reduce information loss. Secondly, a new stochastic dominance degree is proposed to quantify the interval number with a probability distribution. Thirdly, a two-stage method integrating the weighted operator with stochastic dominance degree is proposed to evaluate the alternatives. Finally, a case from China proves the effectiveness of this method.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Urbic, Tomaz, E-mail: tomaz.urbic@fkkt.uni-lj.si; Dias, Cristiano L.

The thermodynamic and structural properties of the planar soft-sites dumbbell fluid are examined by Monte Carlo simulations and integral equation theory. The dimers are built of two Lennard-Jones segments. Site-site integral equation theory in two dimensions is used to calculate the site-site radial distribution functions for a range of elongations and densities and the results are compared with Monte Carlo simulations. The critical parameters for selected types of dimers were also estimated. We analyze the influence of the bond length on critical point as well as tested correctness of site-site integral equation theory with different closures. The integral equations canmore » be used to predict the phase diagram of dimers whose molecular parameters are known.« less

Site occupancy models with heterogeneous detection probabilities

USGS Publications Warehouse

Royle, J. Andrew

2006-01-01

Models for estimating the probability of occurrence of a species in the presence of imperfect detection are important in many ecological disciplines. In these ?site occupancy? models, the possibility of heterogeneity in detection probabilities among sites must be considered because variation in abundance (and other factors) among sampled sites induces variation in detection probability (p). In this article, I develop occurrence probability models that allow for heterogeneous detection probabilities by considering several common classes of mixture distributions for p. For any mixing distribution, the likelihood has the general form of a zero-inflated binomial mixture for which inference based upon integrated likelihood is straightforward. A recent paper by Link (2003, Biometrics 59, 1123?1130) demonstrates that in closed population models used for estimating population size, different classes of mixture distributions are indistinguishable from data, yet can produce very different inferences about population size. I demonstrate that this problem can also arise in models for estimating site occupancy in the presence of heterogeneous detection probabilities. The implications of this are discussed in the context of an application to avian survey data and the development of animal monitoring programs.

Implementation of Tuberculosis Intensive Case Finding, Isoniazid Preventive Therapy, and Infection Control ("Three I's") and HIV-Tuberculosis Service Integration in Lower Income Countries.

PubMed

Charles, M Katherine; Lindegren, Mary Lou; Wester, C William; Blevins, Meridith; Sterling, Timothy R; Dung, Nguyen Thi; Dusingize, Jean Claude; Avit-Edi, Divine; Durier, Nicolas; Castelnuovo, Barbara; Nakigozi, Gertrude; Cortes, Claudia P; Ballif, Marie; Fenner, Lukas

2016-01-01

World Health Organization advocates for integration of HIV-tuberculosis (TB) services and recommends intensive case finding (ICF), isoniazid preventive therapy (IPT), and infection control ("Three I's") for TB prevention and control among persons living with HIV. To assess the implementation of the "Three I's" of TB-control at HIV treatment sites in lower income countries. Survey conducted between March-July, 2012 at 47 sites in 26 countries: 6 (13%) Asia Pacific, 7 (15%), Caribbean, Central and South America, 5 (10%) Central Africa, 8 (17%) East Africa, 14 (30%) Southern Africa, and 7 (15%) West Africa. ICF using symptom-based screening was performed at 38% of sites; 45% of sites used symptom-screening plus additional diagnostics. IPT at enrollment or ART initiation was implemented in only 17% of sites, with 9% of sites providing IPT to tuberculin-skin-test positive patients. Infection control measures varied: 62% of sites separated smear-positive patients, and healthcare workers used masks at 57% of sites. Only 12 (26%) sites integrated HIV-TB services. Integration was not associated with implementation of TB prevention measures except for IPT provision at enrollment (42% integrated vs. 9% non-integrated; p = 0.03). Implementation of TB screening, IPT provision, and infection control measures was low and variable across regional HIV treatment sites, regardless of integration status.

Viral Determinants of Integration Site Preferences of Simian Immunodeficiency Virus-Based Vectors

PubMed Central

Monse, Hella; Laufs, Stephanie; Kuate, Seraphin; Zeller, W. Jens; Fruehauf, Stefan; Überla, Klaus

2006-01-01

Preferential integration into transcriptionally active regions of genomes has been observed for retroviral vectors based on gamma-retroviruses and lentiviruses. However, differences in the integration site preferences were detected, which might be explained by differences in viral components of the preintegration complexes. Viral determinants of integration site preferences have not been defined. Therefore, integration sites of simian immunodeficiency virus (SIV)-based vectors produced in the absence of accessory genes or lacking promoter and enhancer elements were compared. Similar integration patterns for the different SIV vectors indicate that vif, vpr, vpx, nef, env, and promoter or enhancer elements are not required for preferential integration of SIV into transcriptionally active regions of genomes. PMID:16873270

The Swedish Research Infrastructure for Ecosystem Science - SITES

NASA Astrophysics Data System (ADS)

Lindroth, A.; Ahlström, M.; Augner, M.; Erefur, C.; Jansson, G.; Steen Jensen, E.; Klemedtsson, L.; Langenheder, S.; Rosqvist, G. N.; Viklund, J.

2017-12-01

The vision of SITES is to promote long-term field-based ecosystem research at a world class level by offering an infrastructure with excellent technical and scientific support and services attracting both national and international researchers. In addition, SITES will make data freely and easily available through an advanced data portal which will add value to the research. During the first funding period, three innovative joint integrating facilities were established through a researcher-driven procedure: SITES Water, SITES Spectral, and SITES AquaNet. These new facilities make it possible to study terrestrial and limnic ecosystem processes across a range of ecosystem types and climatic gradients, with common protocols and similar equipment. In addition, user-driven development at the nine individual stations has resulted in e.g. design of a long-term agricultural systems experiment, and installation of weather stations, flux systems, etc. at various stations. SITES, with its integrative approach and broad coverage of climate and ecosystem types across Sweden, constitutes an excellent platform for state-of-the-art research projects. SITES' support the development of: A better understanding of the way in which key ecosystems function and interact with each other at the landscape level and with the climate system in terms of mass and energy exchanges. A better understanding of the role of different organisms in controlling different processes and ultimately the functioning of ecosystems. New strategies for forest management to better meet the many and varied requirements from nature conservation, climate and wood, fibre, and energy supply points of view. Agricultural systems that better utilize resources and minimize adverse impacts on the environment. Collaboration with other similar infrastructures and networks is a high priority for SITES. This will enable us to make use of each others' experiences, harmonize metadata for easier exchange of data, and support each other to widen the user community.

Properties of the two-dimensional heterogeneous Lennard-Jones dimers: An integral equation study

PubMed Central

Urbic, Tomaz

2016-01-01

Structural and thermodynamic properties of a planar heterogeneous soft dumbbell fluid are examined using Monte Carlo simulations and integral equation theory. Lennard-Jones particles of different sizes are the building blocks of the dimers. The site-site integral equation theory in two dimensions is used to calculate the site-site radial distribution functions and the thermodynamic properties. Obtained results are compared to Monte Carlo simulation data. The critical parameters for selected types of dimers were also estimated and the influence of the Lennard-Jones parameters was studied. We have also tested the correctness of the site-site integral equation theory using different closures. PMID:27875894

Site-specific integration of Streptomyces PhiC31 integrase-based vectors in the chromosome of Rhodococcus equi.

PubMed

Hong, Yang; Hondalus, Mary K

2008-10-01

Streptomyces PhiC31-based site-specific integration was used to transform the facultative intracellular pathogen Rhodococcus equi. The transformation efficiency of vectors incorporating the PhiC31 integrase and attP sites was comparable to that of replication plasmids using the same electroporation procedure. A single attB integration site was identified within an ORF encoding a pirin-like protein, which deviates slightly from the consensus sequence of Streptomyces attB sites. Vector integration was stably maintained in the R. equi chromosome for as many as 100 generations during unselected passage in vitro. In addition, integration does not appear to affect the replication of bacteria inside macrophages. Finally, this integration system was also used to successfully complement an R. equi mutant.

VISMapper: ultra-fast exhaustive cartography of viral insertion sites for gene therapy.

PubMed

Juanes, José M; Gallego, Asunción; Tárraga, Joaquín; Chaves, Felipe J; Marín-Garcia, Pablo; Medina, Ignacio; Arnau, Vicente; Dopazo, Joaquín

2017-09-20

The possibility of integrating viral vectors to become a persistent part of the host genome makes them a crucial element of clinical gene therapy. However, viral integration has associated risks, such as the unintentional activation of oncogenes that can result in cancer. Therefore, the analysis of integration sites of retroviral vectors is a crucial step in developing safer vectors for therapeutic use. Here we present VISMapper, a vector integration site analysis web server, to analyze next-generation sequencing data for retroviral vector integration sites. VISMapper can be found at: http://vismapper.babelomics.org . Because it uses novel mapping algorithms VISMapper is remarkably faster than previous available programs. It also provides a useful graphical interface to analyze the integration sites found in the genomic context.

Retroviral integration: Site matters

PubMed Central

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

Unaltered repopulation properties of mouse hematopoietic stem cells transduced with lentiviral vectors

PubMed Central

Gonzalez-Murillo, Africa; Lozano, M. Luz; Montini, Eugenio; Bueren, Juan A.

2008-01-01

Recent studies of retroviral-mediated gene transfer have shown that retroviral integrations themselves may trigger nonmalignant clonal expansion of hematopoietic stem cells (HSCs) in transplant recipients. These observations suggested that previous conclusions of HSC dynamics based on gamma-retroviral gene marking should be confirmed with improved vectors having a more limited capacity to transactivate endogenous genes. Because of the low trans-activation activity of self-inactivating lentiviral vectors (LVs), we have investigated whether the LV marking of mouse HSCs induces a competitive repopulation advantage in recipients of serially transplants. As deduced from analyses conducted in primary and secondary recipients, we concluded that lentivirally transduced HSCs have no competitive repopulation advantages over untransduced HSCs. By linear amplification-mediated polymerase chain reaction (LAM-PCR) analysis, we characterized LV-targeted genes in HSC clones that engrafted up to quaternary recipients. Although 9 clones harbored integrations close to defined retroviral insertion sites, none was characterized as a common integration site, and none was present in HSC clones repopulating quaternary recipients. Taken together, our results show unaltered repopulation properties of HSCs transduced with LVs, and confirm early studies suggesting the natural capacity of a few HSC clones to generate a monoclonal or oligoclonal hematopoiesis in transplant recipients. PMID:18684860

A lab-on-a-chip system with integrated sample preparation and loop-mediated isothermal amplification for rapid and quantitative detection of Salmonella spp. in food samples.

PubMed

Sun, Yi; Quyen, Than Linh; Hung, Tran Quang; Chin, Wai Hoe; Wolff, Anders; Bang, Dang Duong

2015-04-21

Foodborne disease is a major public health threat worldwide. Salmonellosis, an infectious disease caused by Salmonella spp., is one of the most common foodborne diseases. Isolation and identification of Salmonella by conventional bacterial culture or molecular-based methods are time consuming and usually take a few hours to days to complete. In response to the demand for rapid on line or on site detection of pathogens, in this study, we describe for the first time an eight-chamber lab-on-a-chip (LOC) system with integrated magnetic bead-based sample preparation and loop-mediated isothermal amplification (LAMP) for rapid and quantitative detection of Salmonella spp. in food samples. The whole diagnostic procedures including DNA isolation, isothermal amplification, and real-time detection were accomplished in a single chamber. Up to eight samples could be handled simultaneously and the system was capable to detect Salmonella at concentration of 50 cells per test within 40 min. The simple design, together with high level of integration, isothermal amplification, and quantitative analysis of multiple samples in short time, will greatly enhance the practical applicability of the LOC system for rapid on-site screening of Salmonella for applications in food safety control, environmental surveillance, and clinical diagnostics.

MiDas: Automatic Extraction of a Common Domain of Discourse in Sleep Medicine for Multi-center Data Integration

PubMed Central

Sahoo, Satya S.; Ogbuji, Chimezie; Luo, Lingyun; Dong, Xiao; Cui, Licong; Redline, Susan S.; Zhang, Guo-Qiang

2011-01-01

Clinical studies often use data dictionaries with controlled sets of terms to facilitate data collection, limited interoperability and sharing at a local site. Multi-center retrospective clinical studies require that these data dictionaries, originating from individual participating centers, be harmonized in preparation for the integration of the corresponding clinical research data. Domain ontologies are often used to facilitate multi-center data integration by modeling terms from data dictionaries in a logic-based language, but interoperability among domain ontologies (using automated techniques) is an unresolved issue. Although many upper-level reference ontologies have been proposed to address this challenge, our experience in integrating multi-center sleep medicine data highlights the need for an upper level ontology that models a common set of terms at multiple-levels of abstraction, which is not covered by the existing upper-level ontologies. We introduce a methodology underpinned by a Minimal Domain of Discourse (MiDas) algorithm to automatically extract a minimal common domain of discourse (upper-domain ontology) from an existing domain ontology. Using the Multi-Modality, Multi-Resource Environment for Physiological and Clinical Research (Physio-MIMI) multi-center project in sleep medicine as a use case, we demonstrate the use of MiDas in extracting a minimal domain of discourse for sleep medicine, from Physio-MIMI’s Sleep Domain Ontology (SDO). We then extend the resulting domain of discourse with terms from the data dictionary of the Sleep Heart and Health Study (SHHS) to validate MiDas. To illustrate the wider applicability of MiDas, we automatically extract the respective domains of discourse from 6 sample domain ontologies from the National Center for Biomedical Ontologies (NCBO) and the OBO Foundry. PMID:22195180

MiDas: automatic extraction of a common domain of discourse in sleep medicine for multi-center data integration.

PubMed

Sahoo, Satya S; Ogbuji, Chimezie; Luo, Lingyun; Dong, Xiao; Cui, Licong; Redline, Susan S; Zhang, Guo-Qiang

2011-01-01

Clinical studies often use data dictionaries with controlled sets of terms to facilitate data collection, limited interoperability and sharing at a local site. Multi-center retrospective clinical studies require that these data dictionaries, originating from individual participating centers, be harmonized in preparation for the integration of the corresponding clinical research data. Domain ontologies are often used to facilitate multi-center data integration by modeling terms from data dictionaries in a logic-based language, but interoperability among domain ontologies (using automated techniques) is an unresolved issue. Although many upper-level reference ontologies have been proposed to address this challenge, our experience in integrating multi-center sleep medicine data highlights the need for an upper level ontology that models a common set of terms at multiple-levels of abstraction, which is not covered by the existing upper-level ontologies. We introduce a methodology underpinned by a Minimal Domain of Discourse (MiDas) algorithm to automatically extract a minimal common domain of discourse (upper-domain ontology) from an existing domain ontology. Using the Multi-Modality, Multi-Resource Environment for Physiological and Clinical Research (Physio-MIMI) multi-center project in sleep medicine as a use case, we demonstrate the use of MiDas in extracting a minimal domain of discourse for sleep medicine, from Physio-MIMI's Sleep Domain Ontology (SDO). We then extend the resulting domain of discourse with terms from the data dictionary of the Sleep Heart and Health Study (SHHS) to validate MiDas. To illustrate the wider applicability of MiDas, we automatically extract the respective domains of discourse from 6 sample domain ontologies from the National Center for Biomedical Ontologies (NCBO) and the OBO Foundry.

HIV integration sites and implications for maintenance of the reservoir.

PubMed

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.

Plasmid integration in a wide range of bacteria mediated by the integrase of Lactobacillus delbrueckii bacteriophage mv4.

PubMed Central

Auvray, F; Coddeville, M; Ritzenthaler, P; Dupont, L

1997-01-01

Bacteriophage mv4 is a temperate phage infecting Lactobacillus delbrueckii subsp. bulgaricus. During lysogenization, the phage integrates its genome into the host chromosome at the 3' end of a tRNA(Ser) gene through a site-specific recombination process (L. Dupont et al., J. Bacteriol., 177:586-595, 1995). A nonreplicative vector (pMC1) based on the mv4 integrative elements (attP site and integrase-coding int gene) is able to integrate into the chromosome of a wide range of bacterial hosts, including Lactobacillus plantarum, Lactobacillus casei (two strains), Lactococcus lactis subsp. cremoris, Enterococcus faecalis, and Streptococcus pneumoniae. Integrative recombination of pMC1 into the chromosomes of all of these species is dependent on the int gene product and occurs specifically at the pMC1 attP site. The isolation and sequencing of pMC1 integration sites from these bacteria showed that in lactobacilli, pMC1 integrated into the conserved tRNA(Ser) gene. In the other bacterial species where this tRNA gene is less or not conserved; secondary integration sites either in potential protein-coding regions or in intergenic DNA were used. A consensus sequence was deduced from the analysis of the different integration sites. The comparison of these sequences demonstrated the flexibility of the integrase for the bacterial integration site and suggested the importance of the trinucleotide CCT at the 5' end of the core in the strand exchange reaction. PMID:9068626

[Prisma France: implementation program of an innovation in health and services system for disabled people. Adaptation of a case-management based integration model].

PubMed

Somme, D; Trouvé, H; Couturier, Y; Carrier, S; Gagnon, D; Lavallart, B; Hébert, R; Cretin, C; Saint-Jean, O

2008-02-01

The French health and services system to maintain at home is characterized by its fragmentation, whereas the need of the people for intervention is generally total. This fragmentation have consequences: delay in services delivery, inadequate transmission of information, redundant evaluation, service conditioned by the entrance point solicited rather than by the need of the person and inappropriate use of expensive resources by ignorance or difficulty of access to the less expensive resources. The purpose of integration is to improve continuity of interventions for people in loss of autonomy. It consists in setting up a whole of organisational, managerial and clinical common tools. Organisational model "Projet et Recherches sur l'Intégration des Services pour le Maintien de l'Autonomie" (Prisma) tested in Quebec showed a strong impact on the prevention of the loss of autonomy in term of public health on a population level. This model rests on six principal elements: partnership, single entry point, case-management, a multidimensional standardized tool for evaluation, an individualized services plan and a system for information transmission. Thus, it was decided to try to implement in France this organisational model. The project is entitled Prisma France and is presented here. The analysis of the context of implementation of the innovation which represents integration in the field of health and services for frail older reveals obstacles (in particular because of diversity of professional concerned and a presentiment of complexity of the implementation of the model) and favourable conditions (in particular the great tension towards change in this field). The current conditions in France appear mainly favourable to the implementation of integration. The establishment of Prisma model in France requires a partnership work of definition of a common language as well on the diagnoses as on the solutions. The strategic and operational dialogue is thus a key element of the construction of integration. This stage currently occurs in parallel in three areas contrasted in France. The results of associated qualitative research should make it possible to define the factors fostering or hindering the realization of integration according to each site (analyzes contrasted) and in all the sites (related to the particular context of care and French services as a whole).

Invasion and Colonisation of a Tropical Stream by an Exotic Loricariid Fish: Indices of Gradual Displacement of the Native Common Pleco (Hypostomus punctatus) by the Red Fin Dwarf Pleco (Parotocinclus maculicauda) over Fifteen Years

PubMed Central

Mazzoni, Rosana; Costa da Silva, Raquel; Pinto, Míriam Plaza

2015-01-01

The introduction of invasive species represents a major threat to the integrity of stream-dwelling fish populations worldwide, and this issue is receiving increasing attention from scientists, in particular because of potential impact on biodiversity. In this study, we analysed the dispersal of an exotic loricariid fish the red fin dwarf pleco (Parotocinclus maculicauda) in a stream of the Atlantic Forest biome in coastal south-eastern Brazil and evaluated the effects of this invasion on the native loricariid common pleco (Hypostomus punctatus). Specimens were collected at eight sites located along the course of the stream over a 15-year period. The distribution and density of the two species were determined by the Successive Removal Method. The introduction of P. maculicauda occurred in the medium sector of the stream, and during the course of the study, the species dispersed to new sites further upstream. By the end of the study, it was found at all points upstream from the original site. Hypostomus punctatus was registered at all sample sites both before and after the introduction of P. maculicauda, but its density decreased at all upstream sites after the arrival of the exotic species. Our analysis shows that colonisation by P. maculicauda seems to have a negative effect on H. punctatus densities. The maintenance of H. punctatus densities at the sites not colonised by P. maculicauda reinforces the conclusion that the colonisation of the stream by the exotic species had deleterious effects on the density of the resident H. punctatus populations, either by direct or indirect action. PMID:26440412

HCLS 2.0/3.0: health care and life sciences data mashup using Web 2.0/3.0.

PubMed

Cheung, Kei-Hoi; Yip, Kevin Y; Townsend, Jeffrey P; Scotch, Matthew

2008-10-01

We describe the potential of current Web 2.0 technologies to achieve data mashup in the health care and life sciences (HCLS) domains, and compare that potential to the nascent trend of performing semantic mashup. After providing an overview of Web 2.0, we demonstrate two scenarios of data mashup, facilitated by the following Web 2.0 tools and sites: Yahoo! Pipes, Dapper, Google Maps and GeoCommons. In the first scenario, we exploited Dapper and Yahoo! Pipes to implement a challenging data integration task in the context of DNA microarray research. In the second scenario, we exploited Yahoo! Pipes, Google Maps, and GeoCommons to create a geographic information system (GIS) interface that allows visualization and integration of diverse categories of public health data, including cancer incidence and pollution prevalence data. Based on these two scenarios, we discuss the strengths and weaknesses of these Web 2.0 mashup technologies. We then describe Semantic Web, the mainstream Web 3.0 technology that enables more powerful data integration over the Web. We discuss the areas of intersection of Web 2.0 and Semantic Web, and describe the potential benefits that can be brought to HCLS research by combining these two sets of technologies.

HCLS 2.0/3.0: Health Care and Life Sciences Data Mashup Using Web 2.0/3.0

PubMed Central

Cheung, Kei-Hoi; Yip, Kevin Y.; Townsend, Jeffrey P.; Scotch, Matthew

2010-01-01

We describe the potential of current Web 2.0 technologies to achieve data mashup in the health care and life sciences (HCLS) domains, and compare that potential to the nascent trend of performing semantic mashup. After providing an overview of Web 2.0, we demonstrate two scenarios of data mashup, facilitated by the following Web 2.0 tools and sites: Yahoo! Pipes, Dapper, Google Maps and GeoCommons. In the first scenario, we exploited Dapper and Yahoo! Pipes to implement a challenging data integration task in the context of DNA microarray research. In the second scenario, we exploited Yahoo! Pipes, Google Maps, and GeoCommons to create a geographic information system (GIS) interface that allows visualization and integration of diverse categories of public health data, including cancer incidence and pollution prevalence data. Based on these two scenarios, we discuss the strengths and weaknesses of these Web 2.0 mashup technologies. We then describe Semantic Web, the mainstream Web 3.0 technology that enables more powerful data integration over the Web. We discuss the areas of intersection of Web 2.0 and Semantic Web, and describe the potential benefits that can be brought to HCLS research by combining these two sets of technologies. PMID:18487092

Finding the Right Candidate for the Right Position: A Fast NMR-Assisted Combinatorial Method for Optimizing Nucleic Acids Binders.

PubMed

Jiménez-Moreno, Ester; Montalvillo-Jiménez, Laura; Santana, Andrés G; Gómez, Ana M; Jiménez-Osés, Gonzalo; Corzana, Francisco; Bastida, Agatha; Jiménez-Barbero, Jesús; Cañada, Francisco Javier; Gómez-Pinto, Irene; González, Carlos; Asensio, Juan Luis

2016-05-25

Development of strong and selective binders from promiscuous lead compounds represents one of the most expensive and time-consuming tasks in drug discovery. We herein present a novel fragment-based combinatorial strategy for the optimization of multivalent polyamine scaffolds as DNA/RNA ligands. Our protocol provides a quick access to a large variety of regioisomer libraries that can be tested for selective recognition by combining microdialysis assays with simple isotope labeling and NMR experiments. To illustrate our approach, 20 small libraries comprising 100 novel kanamycin-B derivatives have been prepared and evaluated for selective binding to the ribosomal decoding A-Site sequence. Contrary to the common view of NMR as a low-throughput technique, we demonstrate that our NMR methodology represents a valuable alternative for the detection and quantification of complex mixtures, even integrated by highly similar or structurally related derivatives, a common situation in the context of a lead optimization process. Furthermore, this study provides valuable clues about the structural requirements for selective A-site recognition.

Sites of Retroviral DNA Integration: From Basic Research to Clinical Applications

PubMed Central

Serrao, Erik; Engelman, Alan N.

2016-01-01

One of the most crucial steps in the life cycle of a retrovirus is the integration of the viral DNA (vDNA) copy of the RNA genome into the genome of an infected host cell. Integration provides for efficient viral gene expression as well as for the segregation of the viral genomes to daughter cells upon cell division. Some integrated viruses are not well expressed, and cells latently infected with HIV-1 can resist the action of potent antiretroviral drugs and remain dormant for decades. Intensive research has been dedicated to understanding the catalytic mechanism of integration, as well as the viral and cellular determinants that influence integration site distribution throughout the host genome. In this review we summarize the evolution of techniques that have been used to recover and map retroviral integration sites, from the early days that first indicated that integration could occur in multiple cellular DNA locations, to current technologies that map upwards of millions of unique integration sites from single in vitro integration reactions or cell culture infections. We further review important insights gained from the use of such mapping techniques, including the monitoring of cell clonal expansion in patients treated with retrovirus-based gene therapy vectors, or AIDS patients on suppressive antiretroviral therapy (ART). These insights span from integrase (IN) enzyme sequence preferences within target DNA (tDNA) at the sites of integration, to the roles of host cellular proteins in mediating global integration distribution, to the potential relationship between genomic location of vDNA integration site and retroviral latency. PMID:26508664

An integrated remote sensing approach for identifying ecological range sites. [parker mountain

NASA Technical Reports Server (NTRS)

Jaynes, R. A.

1983-01-01

A model approach for identifying ecological range sites was applied to high elevation sagebrush-dominated rangelands on Parker Mountain, in south-central Utah. The approach utilizes map information derived from both high altitude color infrared photography and LANDSAT digital data, integrated with soils, geological, and precipitation maps. Identification of the ecological range site for a given area requires an evaluation of all relevant environmental factors which combine to give that site the potential to produce characteristic types and amounts of vegetation. A table is presented which allows the user to determine ecological range site based upon an integrated use of the maps which were prepared. The advantages of identifying ecological range sites through an integrated photo interpretation/LANDSAT analysis are discussed.

Evaluating the adequacy of a reference site pool for ecological assessments in environmentally complex regions

USGS Publications Warehouse

Ode, Peter R.; Rehn, Andrew C.; Mazor, Raphael D.; Schiff, Kenneth C.; Stein, Eric D.; May, Jason; Brown, Larry R.; Herbst, David B.; Gillette, D.D.; Lunde, Kevin; Hawkins, Charles P.

2016-01-01

Many advances in the field of bioassessment have focused on approaches for objectively selecting the pool of reference sites used to establish expectations for healthy waterbodies, but little emphasis has been placed on ways to evaluate the suitability of the reference-site pool for its intended applications (e.g., compliance assessment vs ambient monitoring). These evaluations are critical because an inadequately evaluated reference pool may bias assessments in some settings. We present an approach for evaluating the adequacy of a reference-site pool for supporting biotic-index development in environmentally heterogeneous and pervasively altered regions. We followed common approaches for selecting sites with low levels of anthropogenic stress to screen 1985 candidate stream reaches to create a pool of 590 reference sites for assessing the biological integrity of streams in California, USA. We assessed the resulting pool of reference sites against 2 performance criteria. First, we evaluated how well the reference-site pool represented the range of natural gradients present in the entire population of streams as estimated by sites sampled through probabilistic surveys. Second, we evaluated the degree to which we were successful in rejecting sites influenced by anthropogenic stress by comparing biological metric scores at reference sites with the most vs fewest potential sources of stress. Using this approach, we established a reference-site pool with low levels of human-associated stress and broad coverage of environmental heterogeneity. This approach should be widely applicable and customizable to particular regional or programmatic needs.

Genome-Wide Analysis of Transposon and Retroviral Insertions Reveals Preferential Integrations in Regions of DNA Flexibility.

PubMed

Vrljicak, Pavle; Tao, Shijie; Varshney, Gaurav K; Quach, Helen Ngoc Bao; Joshi, Adita; LaFave, Matthew C; Burgess, Shawn M; Sampath, Karuna

2016-04-07

DNA transposons and retroviruses are important transgenic tools for genome engineering. An important consideration affecting the choice of transgenic vector is their insertion site preferences. Previous large-scale analyses of Ds transposon integration sites in plants were done on the basis of reporter gene expression or germ-line transmission, making it difficult to discern vertebrate integration preferences. Here, we compare over 1300 Ds transposon integration sites in zebrafish with Tol2 transposon and retroviral integration sites. Genome-wide analysis shows that Ds integration sites in the presence or absence of marker selection are remarkably similar and distributed throughout the genome. No strict motif was found, but a preference for structural features in the target DNA associated with DNA flexibility (Twist, Tilt, Rise, Roll, Shift, and Slide) was observed. Remarkably, this feature is also found in transposon and retroviral integrations in maize and mouse cells. Our findings show that structural features influence the integration of heterologous DNA in genomes, and have implications for targeted genome engineering. Copyright © 2016 Vrljicak et al.

Portable integrated capillary-electrophoresis system using disposable polymer chips with capacitively coupled contactless conductivity detection for on-site analysis of foodstuff

NASA Astrophysics Data System (ADS)

Gärtner, Claudia; Hoffmann, Werner; Demattio, Horst; Clemens, Thomas; Klotz, Matthias; Klemm, Richard; Becker, Holger

2009-05-01

We present a compact portable chip-based capillary electrophoresis system that employs capacitively coupled contactless conductivity detection (C4D) operating at 4 MHz as an alternative detection method compared to the commonly used optical detection based on laser-induced fluorescence. Emphasis was put on system integration and industrial manufacturing technologies for the system. Therefore, the disposable chip for this system is fabricated out of PMMA using injection molding; the electrodes are screen-printed or thin-film electrodes. The system is designed for the measurement of small ionic species like Li+, Na+, K+, SO42- or NO3- typically present in foods like milk and mineral water as well as acids e.g. in wine.

Surveying the Commons: Current Implementation of Information Commons Web sites

ERIC Educational Resources Information Center

Leeder, Christopher

2009-01-01

This study assessed the content of 72 academic library Information Commons (IC) Web sites using content analysis, quantitative assessment and qualitative surveys of site administrators to analyze current implementation by the academic library community. Results show that IC Web sites vary widely in content, design and functionality, with few…

Integrating enzyme fermentation in lignocellulosic ethanol production: life-cycle assessment and techno-economic analysis.

PubMed

Olofsson, Johanna; Barta, Zsolt; Börjesson, Pål; Wallberg, Ola

2017-01-01

Cellulase enzymes have been reported to contribute with a significant share of the total costs and greenhouse gas emissions of lignocellulosic ethanol production today. A potential future alternative to purchasing enzymes from an off-site manufacturer is to integrate enzyme and ethanol production, using microorganisms and part of the lignocellulosic material as feedstock for enzymes. This study modelled two such integrated process designs for ethanol from logging residues from spruce production, and compared it to an off-site case based on existing data regarding purchased enzymes. Greenhouse gas emissions and primary energy balances were studied in a life-cycle assessment, and cost performance in a techno-economic analysis. The base case scenario suggests that greenhouse gas emissions per MJ of ethanol could be significantly lower in the integrated cases than in the off-site case. However, the difference between the integrated and off-site cases is reduced with alternative assumptions regarding enzyme dosage and the environmental impact of the purchased enzymes. The comparison of primary energy balances did not show any significant difference between the cases. The minimum ethanol selling price, to reach break-even costs, was from 0.568 to 0.622 EUR L -1 for the integrated cases, as compared to 0.581 EUR L -1 for the off-site case. An integrated process design could reduce greenhouse gas emissions from lignocellulose-based ethanol production, and the cost of an integrated process could be comparable to purchasing enzymes produced off-site. This study focused on the environmental and economic assessment of an integrated process, and in order to strengthen the comparison to the off-site case, more detailed and updated data regarding industrial off-site enzyme production are especially important.

Integrated Care Planning for Cancer Patients: A Scoping Review

PubMed Central

Arthurs, Erin; Gradin, Sharon; MacKinnon, Marnie; Sussman, Jonathan; Kukreti, Vishal

2017-01-01

Introduction: There has been a growing emphasis on the use of integrated care plans to deliver cancer care. However little is known about how integrated care plans for cancer patients are developed including featured core activities, facilitators for uptake and indicators for assessing impact. Methods: Given limited consensus around what constitutes an integrated care plan for cancer patients, a scoping review was conducted to explore the components of integrated care plans and contextual factors that influence design and uptake. Results: Five types of integrated care plans based on the stage of cancer care: surgical, systemic, survivorship, palliative and comprehensive (involving a transition between stages) are described in current literature. Breast, esophageal and colorectal cancers were common disease sites. Multi-disciplinary teams, patient needs assessment and transitional planning emerged as key features. Provider buy-in and training alongside informational technology support served as important facilitators for plan uptake. Provider-level measurement was considerably less robust compared to patient and system-level indicators. Conclusions: Similarities in design features, components and facilitators across the various types of integrated care plans indicates opportunities to leverage shared features and enable a management lens that spans the trajectory of a patient’s journey rather than a phase-specific silo approach to care. PMID:29588638

Allopatric integrations selectively change host transcriptomes, leading to varied expression efficiencies of exotic genes in Myxococcus xanthus.

PubMed

Zhu, Li-Ping; Yue, Xin-Jing; Han, Kui; Li, Zhi-Feng; Zheng, Lian-Shuai; Yi, Xiu-Nan; Wang, Hai-Long; Zhang, You-Ming; Li, Yue-Zhong

2015-07-22

Exotic genes, especially clustered multiple-genes for a complex pathway, are normally integrated into chromosome for heterologous expression. The influences of insertion sites on heterologous expression and allotropic expressions of exotic genes on host remain mostly unclear. We compared the integration and expression efficiencies of single and multiple exotic genes that were inserted into Myxococcus xanthus genome by transposition and attB-site-directed recombination. While the site-directed integration had a rather stable chloramphenicol acetyl transferase (CAT) activity, the transposition produced varied CAT enzyme activities. We attempted to integrate the 56-kb gene cluster for the biosynthesis of antitumor polyketides epothilones into M. xanthus genome by site-direction but failed, which was determined to be due to the insertion size limitation at the attB site. The transposition technique produced many recombinants with varied production capabilities of epothilones, which, however, were not paralleled to the transcriptional characteristics of the local sites where the genes were integrated. Comparative transcriptomics analysis demonstrated that the allopatric integrations caused selective changes of host transcriptomes, leading to varied expressions of epothilone genes in different mutants. With the increase of insertion fragment size, transposition is a more practicable integration method for the expression of exotic genes. Allopatric integrations selectively change host transcriptomes, which lead to varied expression efficiencies of exotic genes.

A novel site-specific recombination system derived from bacteriophage phiMR11.

PubMed

Rashel, Mohammad; Uchiyama, Jumpei; Ujihara, Takako; Takemura, Iyo; Hoshiba, Hiroshi; Matsuzaki, Shigenobu

2008-04-04

We report identification of a novel site-specific DNA recombination system that functions in both in vivo and in vitro, derived from lysogenic Staphylococcus aureus phage phiMR11. In silico analysis of the phiMR11 genome indicated orf1 as a putative integrase gene. Phage and bacterial attachment sites (attP and attB, respectively) and attachment junctions were determined and their nucleotide sequences decoded. Sequences of attP and attB were mostly different to each other except for a two bp common core that was the crossover point. We found several inverted repeats adjacent to the core sequence of attP as potential protein binding sites. The precise and efficient integration properties of phiMR11 integrase were shown on attP and attB in Escherichia coli and the minimum size of attP was found to be 34bp. In in vitro assays using crude or purified integrase, only buffer and substrate DNAs were required for the recombination reaction, indicating that other bacterially encoded factors are not essential for activity.

Landfill site selection by using geographic information systems

NASA Astrophysics Data System (ADS)

Şener, Başak; Süzen, M. Lütfi; Doyuran, Vedat

2006-01-01

One of the serious and growing potential problems in most large urban areas is the shortage of land for waste disposal. Although there are some efforts to reduce and recover the waste, disposal in landfills is still the most common method for waste destination. An inappropriate landfill site may have negative environmental, economic and ecological impacts. Therefore, it should be selected carefully by considering both regulations and constraints on other sources. In this study, candidate sites for an appropriate landfill area in the vicinity of Ankara are determined by using the integration of geographic information systems and multicriteria decision analysis (MCDA). For this purpose, 16 input map layers including topography, settlements (urban centers and villages), roads (Highway E90 and village roads), railways, airport, wetlands, infrastructures (pipelines and power lines), slope, geology, land use, floodplains, aquifers and surface water are prepared and two different MCDA methods (simple additive weighting and analytic hierarchy process) are implemented to a geographical information system. Comparison of the maps produced by these two different methods shows that both methods yield conformable results. Field checks also confirm that the candidate sites agree well with the selected criteria.

Robust estimates of environmental effects on population vital rates: an integrated capture–recapture model of seasonal brook trout growth, survival and movement in a stream network

USGS Publications Warehouse

Letcher, Benjamin H.; Schueller, Paul; Bassar, Ronald D.; Nislow, Keith H.; Coombs, Jason A.; Sakrejda, Krzysztof; Morrissey, Michael; Sigourney, Douglas B.; Whiteley, Andrew R.; O'Donnell, Matthew J.; Dubreuil, Todd L.

2015-01-01

Modelling the effects of environmental change on populations is a key challenge for ecologists, particularly as the pace of change increases. Currently, modelling efforts are limited by difficulties in establishing robust relationships between environmental drivers and population responses.We developed an integrated capture–recapture state-space model to estimate the effects of two key environmental drivers (stream flow and temperature) on demographic rates (body growth, movement and survival) using a long-term (11 years), high-resolution (individually tagged, sampled seasonally) data set of brook trout (Salvelinus fontinalis) from four sites in a stream network. Our integrated model provides an effective context within which to estimate environmental driver effects because it takes full advantage of data by estimating (latent) state values for missing observations, because it propagates uncertainty among model components and because it accounts for the major demographic rates and interactions that contribute to annual survival.We found that stream flow and temperature had strong effects on brook trout demography. Some effects, such as reduction in survival associated with low stream flow and high temperature during the summer season, were consistent across sites and age classes, suggesting that they may serve as robust indicators of vulnerability to environmental change. Other survival effects varied across ages, sites and seasons, indicating that flow and temperature may not be the primary drivers of survival in those cases. Flow and temperature also affected body growth rates; these responses were consistent across sites but differed dramatically between age classes and seasons. Finally, we found that tributary and mainstem sites responded differently to variation in flow and temperature.Annual survival (combination of survival and body growth across seasons) was insensitive to body growth and was most sensitive to flow (positive) and temperature (negative) in the summer and fall.These observations, combined with our ability to estimate the occurrence, magnitude and direction of fish movement between these habitat types, indicated that heterogeneity in response may provide a mechanism providing potential resilience to environmental change. Given that the challenges we faced in our study are likely to be common to many intensive data sets, the integrated modelling approach could be generally applicable and useful.

Robust estimates of environmental effects on population vital rates: an integrated capture-recapture model of seasonal brook trout growth, survival and movement in a stream network.

PubMed

Letcher, Benjamin H; Schueller, Paul; Bassar, Ronald D; Nislow, Keith H; Coombs, Jason A; Sakrejda, Krzysztof; Morrissey, Michael; Sigourney, Douglas B; Whiteley, Andrew R; O'Donnell, Matthew J; Dubreuil, Todd L

2015-03-01

Modelling the effects of environmental change on populations is a key challenge for ecologists, particularly as the pace of change increases. Currently, modelling efforts are limited by difficulties in establishing robust relationships between environmental drivers and population responses. We developed an integrated capture-recapture state-space model to estimate the effects of two key environmental drivers (stream flow and temperature) on demographic rates (body growth, movement and survival) using a long-term (11 years), high-resolution (individually tagged, sampled seasonally) data set of brook trout (Salvelinus fontinalis) from four sites in a stream network. Our integrated model provides an effective context within which to estimate environmental driver effects because it takes full advantage of data by estimating (latent) state values for missing observations, because it propagates uncertainty among model components and because it accounts for the major demographic rates and interactions that contribute to annual survival. We found that stream flow and temperature had strong effects on brook trout demography. Some effects, such as reduction in survival associated with low stream flow and high temperature during the summer season, were consistent across sites and age classes, suggesting that they may serve as robust indicators of vulnerability to environmental change. Other survival effects varied across ages, sites and seasons, indicating that flow and temperature may not be the primary drivers of survival in those cases. Flow and temperature also affected body growth rates; these responses were consistent across sites but differed dramatically between age classes and seasons. Finally, we found that tributary and mainstem sites responded differently to variation in flow and temperature. Annual survival (combination of survival and body growth across seasons) was insensitive to body growth and was most sensitive to flow (positive) and temperature (negative) in the summer and fall. These observations, combined with our ability to estimate the occurrence, magnitude and direction of fish movement between these habitat types, indicated that heterogeneity in response may provide a mechanism providing potential resilience to environmental change. Given that the challenges we faced in our study are likely to be common to many intensive data sets, the integrated modelling approach could be generally applicable and useful. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Population Structure of Montastraea cavernosa on Shallow versus Mesophotic Reefs in Bermuda

PubMed Central

Goodbody-Gringley, Gretchen; Marchini, Chiara; Chequer, Alex D.; Goffredo, Stefano

2015-01-01

Mesophotic coral reef ecosystems remain largely unexplored with only limited information available on taxonomic composition, abundance and distribution. Yet, mesophotic reefs may serve as potential refugia for shallow-water species and thus understanding biodiversity, ecology and connectivity of deep reef communities is integral for resource management and conservation. The Caribbean coral, Montastraea cavernosa, is considered a depth generalist and is commonly found at mesophotic depths. We surveyed abundance and size-frequency of M. cavernosa populations at six shallow (10m) and six upper mesophotic (45m) sites in Bermuda and found population structure was depth dependent. The mean surface area of colonies at mesophotic sites was significantly smaller than at shallow sites, suggesting that growth rates and maximum colony surface area are limited on mesophotic reefs. Colony density was significantly higher at mesophotic sites, however, resulting in equal contributions to overall percent cover. Size-frequency distributions between shallow and mesophotic sites were also significantly different with populations at mesophotic reefs skewed towards smaller individuals. Overall, the results of this study provide valuable baseline data on population structure, which indicate that the mesophotic reefs of Bermuda support an established population of M. cavernosa. PMID:26544963

Short arc orbit determination for altimeter calibration and validation on TOPEX/POSEIDON

NASA Technical Reports Server (NTRS)

Williams, B. G.; Christensen, E. J.; Yuan, D. N.; Mccoll, K. C.; Sunseri, R. F.

1993-01-01

TOPEX/POSEIDON (T/P) is a joint mission of United States' National Aeronautics and Space Administration (NASA) and French Centre National d'Etudes Spatiales (CNES) design launched August 10, 1992. It carries two radar altimeters which alternately share a common antenna. There are two project designated verification sites, a NASA site off the coast at Pt. Conception, CA and a CNES site near Lampedusa Island in the Mediterranean Sea. Altimeter calibration and validation for T/P is performed over these highly instrumented sites by comparing the spacecraft's altimeter radar range to computed range based on in situ measurements which include the estimated orbit position. This paper presents selected results of orbit determination over each of these sites to support altimeter verification. A short arc orbit determination technique is used to estimate a locally accurate position determination of T/P from less than one revolution of satellite laser ranging (SLR) data. This technique is relatively insensitive to gravitational and non-gravitational force modeling errors and is demonstrated by covariance analysis and by comparison to orbits determined from longer arcs of data and other tracking data types, such as Doppler Orbitography and Radiopositioning Integrated by Satellite (DORIS) and Global Positioning System Demonstration Receiver (GPSDR) data.

Population Structure of Montastraea cavernosa on Shallow versus Mesophotic Reefs in Bermuda.

PubMed

Goodbody-Gringley, Gretchen; Marchini, Chiara; Chequer, Alex D; Goffredo, Stefano

2015-01-01

Mesophotic coral reef ecosystems remain largely unexplored with only limited information available on taxonomic composition, abundance and distribution. Yet, mesophotic reefs may serve as potential refugia for shallow-water species and thus understanding biodiversity, ecology and connectivity of deep reef communities is integral for resource management and conservation. The Caribbean coral, Montastraea cavernosa, is considered a depth generalist and is commonly found at mesophotic depths. We surveyed abundance and size-frequency of M. cavernosa populations at six shallow (10m) and six upper mesophotic (45m) sites in Bermuda and found population structure was depth dependent. The mean surface area of colonies at mesophotic sites was significantly smaller than at shallow sites, suggesting that growth rates and maximum colony surface area are limited on mesophotic reefs. Colony density was significantly higher at mesophotic sites, however, resulting in equal contributions to overall percent cover. Size-frequency distributions between shallow and mesophotic sites were also significantly different with populations at mesophotic reefs skewed towards smaller individuals. Overall, the results of this study provide valuable baseline data on population structure, which indicate that the mesophotic reefs of Bermuda support an established population of M. cavernosa.

Some open issues in the analysis of the storage and migration properties of fractured carbonate reservoirs

NASA Astrophysics Data System (ADS)

Agosta, Fabrizio

2017-04-01

Underground CO2 storage in depleted hydrocarbon reservoirs may become a common practice in the future to lower the concentration of greenhouse gases in the atmosphere. Results from the first experiments conducted in carbonate rocks, for instance the Lacq integrated CCS Pilot site, SW France, are quite exciting. All monitored parameters, such as the CO2 concentration at well sites, well pressures, cap rock integrity and environmental indicators show the long-term integrity of this type of geological reservoirs. Other positive news arise from the OXY-CFB-300 Compostilla Project, NW Spain, where most of the injected CO2 dissolved into the formation brines, suggesting the long-term security of this method. However, in both cases, the CO2- rich fluids partially dissolved the carbonate minerals during their migration through the fractured reservoir, modifying the overall pore volume and pressure regimes. These results support the growing need for a better understanding of the mechanical behavior of carbonate rocks over geological time of scales. In fact, it is well known that carbonates exhibit a variety of deformation mechanisms depending upon many intrinsic factors such as composition, texture, connected pore volume, and nature of the primary heterogeneities. Commonly, tight carbonates are prone to opening-mode and/or pressure solution deformation. The interplay between these two mechanisms likely affects the petrophysical properties of the fault damage zones, which form potential sites for CO2 storage due to their high values of both connected porosity and permeability. On the contrary, cataclastic deformation produces fault rocks that often form localized fluid barriers for cross-fault fluid flow. Nowadays, questions on the conditions of sealing/leakage of carbonate fault rocks are still open. In particular, the relative role played by bulk crushing, chipping, cementation, and pressure solution on connected porosity of carbonate fault rocks during structural evolution and diagenesis is not determined yet. Differently, porous rocks are mainly affected by deformation banding. The latter process involves the collapse of primary porosity within narrow bands, which often localize into well-developed clusters. Currently, researchers focus on the assessment of the 3D pore geometry of the shear bands, which may act as possible sites for residual C02 trapping. The fault-bounded rock volumes are mainly crosscut by background fractures. These diffuse fractures are often compartmentalized into discrete mechanical units, which are bounded by primary heterogeneities such as bed interfaces and transgressive erosional surfaces. Moreover, bed-parallel pressure solution seams, structural elements that commonly form in limestone rocks during burial diagenesis, can also act as mechanical interfaces during growth of background fractures. However, early embrittlement of carbonates was also documented, suggesting to further investigate their diagenetic evolution to determine the conditions at which the latter phenomenon takes place. Results could shed new lights into the storage properties and, hence, the amount of CO2 that can be securely stored within significant volumes of fractured carbonates in the underground.

Integration of the Chinese HPC Grid in ATLAS Distributed Computing

NASA Astrophysics Data System (ADS)

Filipčič, A.; ATLAS Collaboration

2017-10-01

Fifteen Chinese High-Performance Computing sites, many of them on the TOP500 list of most powerful supercomputers, are integrated into a common infrastructure providing coherent access to a user through an interface based on a RESTful interface called SCEAPI. These resources have been integrated into the ATLAS Grid production system using a bridge between ATLAS and SCEAPI which translates the authorization and job submission protocols between the two environments. The ARC Computing Element (ARC-CE) forms the bridge using an extended batch system interface to allow job submission to SCEAPI. The ARC-CE was setup at the Institute for High Energy Physics, Beijing, in order to be as close as possible to the SCEAPI front-end interface at the Computing Network Information Center, also in Beijing. This paper describes the technical details of the integration between ARC-CE and SCEAPI and presents results so far with two supercomputer centers, Tianhe-IA and ERA. These two centers have been the pilots for ATLAS Monte Carlo Simulation in SCEAPI and have been providing CPU power since fall 2015.

Using two classification schemes to develop vegetation indices of biological integrity for wetlands in West Virginia, USA.

PubMed

Veselka, Walter; Rentch, James S; Grafton, William N; Kordek, Walter S; Anderson, James T

2010-11-01

Bioassessment methods for wetlands, and other bodies of water, have been developed worldwide to measure and quantify changes in "biological integrity." These assessments are based on a classification system, meant to ensure appropriate comparisons between wetland types. Using a local site-specific disturbance gradient, we built vegetation indices of biological integrity (Veg-IBIs) based on two commonly used wetland classification systems in the USA: One based on vegetative structure and the other based on a wetland's position in a landscape and sources of water. The resulting class-specific Veg-IBIs were comprised of 1-5 metrics that varied in their sensitivity to the disturbance gradient (R2=0.14-0.65). Moreover, the sensitivity to the disturbance gradient increased as metrics from each of the two classification schemes were combined (added). Using this information to monitor natural and created wetlands will help natural resource managers track changes in biological integrity of wetlands in response to anthropogenic disturbance and allows the use of vegetative communities to set ecological performance standards for mitigation banks.

PROFILE: Integrated Management to Create New Breeding Habitat for Dalmatian Pelicans (Pelecanus crispus) in Greece

PubMed

Pyrovetsi

1997-09-01

/ An integrated management plan to create favorable nesting habitat for the world-endangered Dalmatian pelicans, was tested at Kerkini irrigation reservoir, a Ramsar wetland. The lake is the major wintering site of Dalmatian pelicans in Europe, where the species lives year-round without breeding. The rise of water level at the reservoir during spring (exceeding 5 m) has an impact on the whole system, including several birds, which lose their nesting habitat. Although the integrity of the wetland demands ecological restoration with changes in its hydrologic regime, local socioeconomic conditions allow only habitat level interventions. During the planning phase of the management plan, both the ecological and social context of the interventions were considered. Monitoring of all pelican habitats and populations provided the scientific basis, while a socioecological survey on knowledge/attitudes of local fishermen toward wetland identified conflicts with specific resources and planned management. To gain public support, a broad information/education program was implemented. The education program for fishermen was based on the findings of the socioecological survey. The in situ management involved experimental construction of floating rafts, platforms over water, dredged-spoil islands, and platforms at various sites of the wetland. Monitoring of the managed habitats showed that most waterbirds used them for resting and roosting. Common terns nested on the rafts, cormorants on the platforms, and Dalmatian pelicans on the man-made island. Under the prevailing hydrologic and weather conditions, islands seem to be the most suitable habitat for pelican nesting. It is concluded that wildlife habitat management should integrate the ecological component, related to the needs of the species and ecosystem, with the social one, expressed by cooperation and involvement of the local community.KEY WORDS: Integrated management; Pelican; Nesting habitat; Habitat management; Reservoir-wetland; Public participation, Greece

Securing your Site in Development and Beyond

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akopov, Mikhail S.

Why wait until production deployment, or even staging and testing deployment to identify security vulnerabilities? Using tools like Burp Suite, you can find security vulnerabilities before they creep up on you. Prevent cross-site scripting attacks, and establish a firmer trust between your website and your client. Verify that Apache/Nginx have the correct SSL Ciphers set. We explore using these tools and more to validate proper Apache/Nginx configurations, and to be compliant with modern configuration standards as part of the development cycle. Your clients can use tools like https://securityheaders.io and https://ssllabs.com to get a graded report on your level of compliancemore » with OWASP Secure Headers Project and SSLLabs recommendations. Likewise, you should always use the same sites to validate your configurations. Burp Suite will find common misconfigurations and will also perform more thorough security testing of your applications. In this session you will see examples of vulnerabilities that were detected early on, as well has how to integrate these practices into your daily workflow.« less

Integrated proteomic and N-glycoproteomic analyses of doxorubicin sensitive and resistant ovarian cancer cells reveal glycoprotein alteration in protein abundance and glycosylation

PubMed Central

Hou, Junjie; Zhang, Chengqian; Xue, Peng; Wang, Jifeng; Chen, Xiulan; Guo, Xiaojing; Yang, Fuquan

2017-01-01

Ovarian cancer is one of the most common cancer among women in the world, and chemotherapy remains the principal treatment for patients. However, drug resistance is a major obstacle to the effective treatment of ovarian cancers and the underlying mechanism is not clear. An increased understanding of the mechanisms that underline the pathogenesis of drug resistance is therefore needed to develop novel therapeutics and diagnostic. Herein, we report the comparative analysis of the doxorubicin sensitive OVCAR8 cells and its doxorubicin-resistant variant NCI/ADR-RES cells using integrated global proteomics and N-glycoproteomics. A total of 1525 unique N-glycosite-containing peptides from 740 N-glycoproteins were identified and quantified, of which 253 N-glycosite-containing peptides showed significant change in the NCI/ADR-RES cells. Meanwhile, stable isotope labeling by amino acids in cell culture (SILAC) based comparative proteomic analysis of the two ovarian cancer cells led to the quantification of 5509 proteins. As about 50% of the identified N-glycoproteins are low-abundance membrane proteins, only 44% of quantified unique N-glycosite-containing peptides had corresponding protein expression ratios. The comparison and calibration of the N-glycoproteome versus the proteome classified 14 change patterns of N-glycosite-containing peptides, including 8 up-regulated N-glycosite-containing peptides with the increased glycosylation sites occupancy, 35 up-regulated N-glycosite-containing peptides with the unchanged glycosylation sites occupancy, 2 down-regulated N-glycosite-containing peptides with the decreased glycosylation sites occupancy, 46 down-regulated N-glycosite-containing peptides with the unchanged glycosylation sites occupancy. Integrated proteomic and N-glycoproteomic analyses provide new insights, which can help to unravel the relationship of N-glycosylation and multidrug resistance (MDR), understand the mechanism of MDR, and discover the new diagnostic and therapeutic targets. PMID:28077793

[The role of integrons in dissemination of antibiotic resistance].

PubMed

Ploy, M C; Lambert, T; Gassama, A; Denis, F

2000-01-01

Bacteria can transfer genetic information to get protection against most antibiotics. The acquisition of resistance genes involves genetic mobile elements such as plasmids and transposons. Another genetic structures, named integrons, have been described and contain one or more gene cassettes located at a specific site. Integrons contain an intI gene encoding a site-specific recombinase belonging to the integrase family and a recombination site attI. A gene cassette includes an open reading frame and, at the 3'-end, a recombination site attC. Integration or excision of cassettes occurs by a site-specific recombination mechanism catalyzed by the integrase. However, insertion can rarely occur, at non-specific sites leading to a stable situation for the cassette. Cassettes are transcribed from a common promoter located in the 5'-conserved segment and expression of distal genes is reduced by the presence of upstream cassettes. Most gene cassettes encode antibiotic resistant determinants but antiseptic resistant genes have also been described. Integrons seem to have a major role in the spread of multidrug resistance in Gram-negative bacteria but integrons in Gram-positive bacteria have been recently described. Moreover, the finding of super-integrons with gene cassettes coding for other determinants (biochemical functions, virulence factors) in different Gram negative bacteria suggests that integrons are probably implied in bacterial genome evolution.

Molecular Characterization of Transgene Integration by Next-Generation Sequencing in Transgenic Cattle

PubMed Central

Zhang, Ran; Yin, Yinliang; Zhang, Yujun; Li, Kexin; Zhu, Hongxia; Gong, Qin; Wang, Jianwu; Hu, Xiaoxiang; Li, Ning

2012-01-01

As the number of transgenic livestock increases, reliable detection and molecular characterization of transgene integration sites and copy number are crucial not only for interpreting the relationship between the integration site and the specific phenotype but also for commercial and economic demands. However, the ability of conventional PCR techniques to detect incomplete and multiple integration events is limited, making it technically challenging to characterize transgenes. Next-generation sequencing has enabled cost-effective, routine and widespread high-throughput genomic analysis. Here, we demonstrate the use of next-generation sequencing to extensively characterize cattle harboring a 150-kb human lactoferrin transgene that was initially analyzed by chromosome walking without success. Using this approach, the sites upstream and downstream of the target gene integration site in the host genome were identified at the single nucleotide level. The sequencing result was verified by event-specific PCR for the integration sites and FISH for the chromosomal location. Sequencing depth analysis revealed that multiple copies of the incomplete target gene and the vector backbone were present in the host genome. Upon integration, complex recombination was also observed between the target gene and the vector backbone. These findings indicate that next-generation sequencing is a reliable and accurate approach for the molecular characterization of the transgene sequence, integration sites and copy number in transgenic species. PMID:23185606

caCORE: a common infrastructure for cancer informatics.

PubMed

Covitz, Peter A; Hartel, Frank; Schaefer, Carl; De Coronado, Sherri; Fragoso, Gilberto; Sahni, Himanso; Gustafson, Scott; Buetow, Kenneth H

2003-12-12

Sites with substantive bioinformatics operations are challenged to build data processing and delivery infrastructure that provides reliable access and enables data integration. Locally generated data must be processed and stored such that relationships to external data sources can be presented. Consistency and comparability across data sets requires annotation with controlled vocabularies and, further, metadata standards for data representation. Programmatic access to the processed data should be supported to ensure the maximum possible value is extracted. Confronted with these challenges at the National Cancer Institute Center for Bioinformatics, we decided to develop a robust infrastructure for data management and integration that supports advanced biomedical applications. We have developed an interconnected set of software and services called caCORE. Enterprise Vocabulary Services (EVS) provide controlled vocabulary, dictionary and thesaurus services. The Cancer Data Standards Repository (caDSR) provides a metadata registry for common data elements. Cancer Bioinformatics Infrastructure Objects (caBIO) implements an object-oriented model of the biomedical domain and provides Java, Simple Object Access Protocol and HTTP-XML application programming interfaces. caCORE has been used to develop scientific applications that bring together data from distinct genomic and clinical science sources. caCORE downloads and web interfaces can be accessed from links on the caCORE web site (http://ncicb.nci.nih.gov/core). caBIO software is distributed under an open source license that permits unrestricted academic and commercial use. Vocabulary and metadata content in the EVS and caDSR, respectively, is similarly unrestricted, and is available through web applications and FTP downloads. http://ncicb.nci.nih.gov/core/publications contains links to the caBIO 1.0 class diagram and the caCORE 1.0 Technical Guide, which provide detailed information on the present caCORE architecture, data sources and APIs. Updated information appears on a regular basis on the caCORE web site (http://ncicb.nci.nih.gov/core).

Surveying Medieval Archaeology: a New Form for Harris Paradigm Linking Photogrammetry and Temporal Relations

NASA Astrophysics Data System (ADS)

Drap, P.; Papini, O.; Pruno, E.; Nucciotti, M.; Vannini, G.

2017-02-01

The paper presents some reflexions concerning an interdisciplinary project between Medieval Archaeologists from the University of Florence (Italy) and ICT researchers from CNRS LSIS of Marseille (France), aiming towards a connection between 3D spatial representation and archaeological knowledge. It is well known that Laser Scanner, Photogrammetry and Computer Vision are very attractive tools for archaeologists, although the integration of representation of space and representation of archaeological time has not yet found a methodological standard of reference. We try to develop an integrated system for archaeological 3D survey and all other types of archaeological data and knowledge through integrating observable (material) and non-graphic (interpretive) data. Survey plays a central role, since it is both a metric representation of the archaeological site and, to a wider extent, an interpretation of it (being also a common basis for communication between the 2 teams). More specifically 3D survey is crucial, allowing archaeologists to connect actual spatial assets to the stratigraphic formation processes (i.e. to the archaeological time) and to translate spatial observations into historical interpretation of the site. We propose a common formalism for describing photogrammetrical survey and archaeological knowledge stemming from ontologies: Indeed, ontologies are fully used to model and store 3D data and archaeological knowledge. Xe equip this formalism with a qualitative representation of time. Stratigraphic analyses (both of excavated deposits and of upstanding structures) are closely related to E. C. Harris theory of "Stratigraphic Unit" ("US" from now on). Every US is connected to the others by geometric, topological and, eventually, temporal links, and are recorded by the 3D photogrammetric survey. However, the limitations of the Harris Matrix approach lead to use another representation formalism for stratigraphic relationships, namely Qualitative Constraints Networks (QCN) successfully used in the domain of knowledge representation and reasoning in artificial intelligence for representing temporal relations.

One-pot strategy for on-site enzyme production, biomass hydrolysis, and ethanol production using the whole solid-state fermentation medium of mixed filamentous fungi.

PubMed

Maehara, Larissa; Pereira, Sandra C; Silva, Adilson J; Farinas, Cristiane S

2018-02-01

The efficient use of renewable lignocellulosic feedstocks to obtain biofuels and other bioproducts is a key requirement for a sustainable biobased economy. This requires novel and effective strategies to reduce the cost contribution of the cellulolytic enzymatic cocktails needed to convert the carbohydrates into simple sugars, in order to make large-scale commercial processes economically competitive. Here, we propose the use of the whole solid-state fermentation (SSF) medium of mixed filamentous fungi as an integrated one-pot strategy for on-site enzyme production, biomass hydrolysis, and ethanol production. Ten different individual and mixed cultivations of commonly used industrial filamentous fungi (Aspergillus niger, Aspergillus oryzae, Trichoderma harzianum, and Trichoderma reesei) were performed under SSF and the whole media (without the extraction step) were used in the hydrolysis of pretreated sugarcane bagasse. The cocultivation of T. reesei with A. oryzae increased the amount of glucose released by around 50%, compared with individual cultivations. The release of glucose and reducing sugars achieved using the whole SSF medium was around 3-fold higher than obtained with the enzyme extract. The addition of soybean protein (0.5% w/w) during the hydrolysis reaction further significantly improved the saccharification performance by blocking the lignin and avoiding unproductive adsorption of enzymes. The results of the alcoholic fermentation validated the overall integrated process, with a volumetric ethanol productivity of 4.77 g/L.h, representing 83.5% of the theoretical yield. These findings demonstrate the feasibility of the proposed one-pot integrated strategy using the whole SSF medium of mixed filamentous fungi for on-site enzymes production, biomass hydrolysis, and ethanol production. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 2018. © 2018 American Institute of Chemical Engineers.

Comparison of Ultra-Conserved Elements in Drosophilids and Vertebrates

PubMed Central

Makunin, Igor V.; Shloma, Viktor V.; Stephen, Stuart J.; Pheasant, Michael; Belyakin, Stepan N.

2013-01-01

Metazoan genomes contain many ultra-conserved elements (UCEs), long sequences identical between distant species. In this study we identified UCEs in drosophilid and vertebrate species with a similar level of phylogenetic divergence measured at protein-coding regions, and demonstrated that both the length and number of UCEs are larger in vertebrates. The proportion of non-exonic UCEs declines in distant drosophilids whilst an opposite trend was observed in vertebrates. We generated a set of 2,126 Sophophora UCEs by merging elements identified in several drosophila species and compared these to the eutherian UCEs identified in placental mammals. In contrast to vertebrates, the Sophophora UCEs are depleted around transcription start sites. Analysis of 52,954 P-element, piggyBac and Minos insertions in the D. melanogaster genome revealed depletion of the P-element and piggyBac insertions in and around the Sophophora UCEs. We examined eleven fly strains with transposon insertions into the intergenic UCEs and identified associated phenotypes in five strains. Four insertions behave as recessive lethals, and in one case we observed a suppression of the marker gene within the transgene, presumably by silenced chromatin around the integration site. To confirm the lethality is caused by integration of transposons we performed a phenotype rescue experiment for two stocks and demonstrated that the excision of the transposons from the intergenic UCEs restores viability. Sequencing of DNA after the transposon excision in one fly strain with the restored viability revealed a 47 bp insertion at the original transposon integration site suggesting that the nature of the mutation is important for the appearance of the phenotype. Our results suggest that the UCEs in flies and vertebrates have both common and distinct features, and demonstrate that a significant proportion of intergenic drosophila UCEs are sensitive to disruption. PMID:24349264

Stream Invertebrate Communities, Water Quality, and Land-Use Patterns in an Agricultural Drainage Basin of Northeastern Nebraska, USA

NASA Astrophysics Data System (ADS)

Whiles, Matt R.; Brock, Brent L.; Franzen, Annette C.; Dinsmore, Steven C., II

2000-11-01

We used invertebrate bioassessment, habitat analysis, geographic information system analysis of land use, and water chemistry monitoring to evaluate tributaries of a degraded northeast Nebraska, USA, reservoir. Bimonthly invertebrate collections and monthly water chemistry samples were collected for two years on six stream reaches to identify sources contributing to reservoir degradation and test suitability of standard rapid bioassessment methods in this region. A composite biotic index composed of seven commonly used metrics was effective for distinguishing between differentially impacted sites and responded to a variety of disturbances. Individual metrics varied greatly in precision and ability to discriminate between relatively impacted and unimpacted stream reaches. A modified Hilsenhoff index showed the highest precision (reference site CV = 0.08) but was least effective at discriminating among sites. Percent dominance and the EPT (number of Ephemeroptera, Plecoptera, and Trichoptera taxa) metrics were most effective at discriminating between sites and exhibited intermediate precision. A trend of higher biotic integrity during summer was evident, indicating seasonal corrections should differ from other regions. Poor correlations were evident between water chemistry variables and bioassessment results. However, land-use factors, particularly within 18-m riparian zones, were correlated with bioassessment scores. For example, there was a strong negative correlation between percentage of rangeland in 18-m riparian zones and percentage of dominance in streams (r 2 = 0.90, P < 0.01). Results demonstrate that standard rapid bioassessment methods, with some modifications, are effective for use in this agricultural region of the Great Plains and that riparian land use may be the best predictor of stream biotic integrity.

HTLV-1 Integration into Transcriptionally Active Genomic Regions Is Associated with Proviral Expression and with HAM/TSP

PubMed Central

Meekings, Kiran N.; Leipzig, Jeremy; Bushman, Frederic D.; Taylor, Graham P.; Bangham, Charles R. M.

2008-01-01

Human T-lymphotropic virus type 1 (HTLV-1) causes leukaemia or chronic inflammatory disease in ∼5% of infected hosts. The level of proviral expression of HTLV-1 differs significantly among infected people, even at the same proviral load (proportion of infected mononuclear cells in the circulation). A high level of expression of the HTLV-1 provirus is associated with a high proviral load and a high risk of the inflammatory disease of the central nervous system known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). But the factors that control the rate of HTLV-1 proviral expression remain unknown. Here we show that proviral integration sites of HTLV-1 in vivo are not randomly distributed within the human genome but are associated with transcriptionally active regions. Comparison of proviral integration sites between individuals with high and low levels of proviral expression, and between provirus-expressing and provirus non-expressing cells from within an individual, demonstrated that frequent integration into transcription units was associated with an increased rate of proviral expression. An increased frequency of integration sites in transcription units in individuals with high proviral expression was also associated with the inflammatory disease HAM/TSP. By comparing the distribution of integration sites in human lymphocytes infected in short-term cell culture with those from persistent infection in vivo, we infer the action of two selective forces that shape the distribution of integration sites in vivo: positive selection for cells containing proviral integration sites in transcriptionally active regions of the genome, and negative selection against cells with proviral integration sites within transcription units. PMID:18369476

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

PubMed Central

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

49 CFR 40.43 - What steps must operators of collection sites take to protect the security and integrity of urine...

Code of Federal Regulations, 2010 CFR

2010-10-01

... to protect the security and integrity of urine collections? 40.43 Section 40.43 Transportation Office... PROGRAMS Collection Sites, Forms, Equipment and Supplies Used in DOT Urine Collections § 40.43 What steps must operators of collection sites take to protect the security and integrity of urine collections? (a...

49 CFR 40.43 - What steps must operators of collection sites take to protect the security and integrity of urine...

Code of Federal Regulations, 2012 CFR

2012-10-01

... to protect the security and integrity of urine collections? 40.43 Section 40.43 Transportation Office... PROGRAMS Collection Sites, Forms, Equipment and Supplies Used in DOT Urine Collections § 40.43 What steps must operators of collection sites take to protect the security and integrity of urine collections? (a...

49 CFR 40.43 - What steps must operators of collection sites take to protect the security and integrity of urine...

Code of Federal Regulations, 2011 CFR

2011-10-01

... to protect the security and integrity of urine collections? 40.43 Section 40.43 Transportation Office... PROGRAMS Collection Sites, Forms, Equipment and Supplies Used in DOT Urine Collections § 40.43 What steps must operators of collection sites take to protect the security and integrity of urine collections? (a...

49 CFR 40.43 - What steps must operators of collection sites take to protect the security and integrity of urine...

Code of Federal Regulations, 2014 CFR

2014-10-01

... to protect the security and integrity of urine collections? 40.43 Section 40.43 Transportation Office... PROGRAMS Collection Sites, Forms, Equipment and Supplies Used in DOT Urine Collections § 40.43 What steps must operators of collection sites take to protect the security and integrity of urine collections? (a...

49 CFR 40.43 - What steps must operators of collection sites take to protect the security and integrity of urine...

Code of Federal Regulations, 2013 CFR

2013-10-01

... to protect the security and integrity of urine collections? 40.43 Section 40.43 Transportation Office... PROGRAMS Collection Sites, Forms, Equipment and Supplies Used in DOT Urine Collections § 40.43 What steps must operators of collection sites take to protect the security and integrity of urine collections? (a...

The Function of Neuroendocrine Cells in Prostate Cancer

DTIC Science & Technology

2013-04-01

integration site. We then performed deep sequencing and aligned reads to the genome. Our analysis revealed that both histological phenotypes are derived from...lentiviral integration site analysis . (B) Laser capture microdissection was performed on individual glands containing both squamous and...lentiviral integration site analysis . LTR: long terminal repeat (viral DNA), PCR: polymerase chain reaction. (D) Venn diagrams depict shared lentiviral

Qualitative Comparison of IGRA and ESRL Radiosonde Archived Databases

NASA Technical Reports Server (NTRS)

Walker, John R.

2014-01-01

Multiple databases of atmospheric profile information are freely available to individuals and groups such as the Natural Environments group. Two of the primary database archives provided by NOAA that are most frequently used are those from the Earth Science Research Laboratory (ESRL) and the Integrated Global Radiosonde Archive (IGRA). Inquiries have been made as to why one database is used as opposed to the other, yet to the best of knowledge, no formal comparison has been performed. The goal of this study is to provide a qualitative comparison of the ESRL and IGRA radiosonde databases. For part of this analyses, 14 upper air observation sites were selected. These sites all have the common attribute of having been used or are planned for use in the development of Range Reference Atmospheres (RRAs) in support of NASA's and DOD's current and future goals.

Changing needs, opportunities and constraints for the 21st century microbiology laboratory.

PubMed

Van Eldere, J

2005-04-01

Clinical microbiologists and microbiology laboratories are experiencing changes due to evolving views on 'healthcare delivery' as an economic activity, due to changes in the medical environment and the demographics of the workforce, and technical evolution. Cost-effectiveness of laboratory procedures has been achieved through consolidation and integration of laboratories. Consolidation offers economy of scale and reduction in numbers of on-site staff, but also leads to separation of microbiologists from their clinical colleagues. Integration puts different laboratory disciplines under a single management, and leads to reorganisation of laboratories along common work-lines. Cost-savings combined with on-site availability of laboratories are achieved at the expense of a reduction in the influence of microbiologists in the daily running of the laboratory. Medically, there is growing emphasis on evidence-based diagnostics. Because of time-delays inherent in culturing, microbiology through rapid testing is mandatory. There is an increasing shortage in Europe and the USA of trained microbiology laboratory technicians and microbiologists. This reinforces the trend towards more automation and integration. Technological advances, particularly in molecular diagnostics, offer the possibility of rapid reporting and improvement of the impact of clinical microbiology on patient management. Molecular tests, however, fit perfectly the concept of an integrated laboratory and may further loosen the link between microbiologist and microbiology tests. The challenge for clinical microbiology will be to use new techniques to improve its cost-effectiveness and impact on infectious disease management. The future organisation of microbiology laboratories must support this but is itself of secondary importance. The training of future microbiologist must prepare them for this changing environment.

A novel family of integrases associated with prophages and genomic islands integrated within the tRNA-dihydrouridine synthase A (dusA) gene

PubMed Central

Farrugia, Daniel N.; Elbourne, Liam D. H.; Mabbutt, Bridget C.; Paulsen, Ian T.

2015-01-01

Genomic islands play a key role in prokaryotic genome plasticity. Genomic islands integrate into chromosomal loci such as transfer RNA genes and protein coding genes, whilst retaining various cargo genes that potentially bestow novel functions on the host organism. A gene encoding a putative integrase was identified at a single site within the 5′ end of the dusA gene in the genomes of over 200 bacteria. This integrase was discovered to be a component of numerous genomic islands, which appear to share a target site within the dusA gene. dusA encodes the tRNA-dihydrouridine synthase A enzyme, which catalyses the post-transcriptional reduction of uridine to dihydrouridine in tRNA. Genomic islands encoding homologous dusA-associated integrases were found at a much lower frequency within the related dusB and dusC genes, and non-dus genes. Excision of these dusA-associated islands from the chromosome as circularized intermediates was confirmed by polymerase chain reaction. Analysis of the dusA-associated islands indicated that they were highly diverse, with the integrase gene representing the only universal common feature. PMID:25883135

Identification of novel candidate maternal serum protein markers for Down syndrome by integrated proteomic and bioinformatic analysis.

PubMed

Kang, Yuan; Dong, Xinran; Zhou, Qiongjie; Zhang, Ying; Cheng, Yan; Hu, Rong; Su, Cuihong; Jin, Hong; Liu, Xiaohui; Ma, Duan; Tian, Weidong; Li, Xiaotian

2012-03-01

This study aimed to identify candidate protein biomarkers from maternal serum for Down syndrome (DS) by integrated proteomic and bioinformatics analysis. A pregnancy DS group of 18 women and a control group with the same number were prepared, and the maternal serum proteins were analyzed by isobaric tags for relative and absolute quantitation and mass spectrometry, to identify DS differentially expressed maternal serum proteins (DS-DEMSPs). Comprehensive bioinformatics analysis was then employed to analyze DS-DEMSPs both in this paper and seven related publications. Down syndrome differentially expressed maternal serum proteins from different studies are significantly enriched with common Gene Ontology functions, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, transcription factor binding sites, and Pfam protein domains, However, the DS-DEMSPs are less functionally related to known DS-related genes. These evidences suggest that common molecular mechanisms induced by secondary effects may be present upon DS carrying. A simple scoring scheme revealed Alpha-2-macroglobulin, Apolipoprotein A1, Apolipoprotein E, Complement C1s subcomponent, Complement component 5, Complement component 8, alpha polypeptide, Complement component 8, beta polypeptide and Fibronectin as potential DS biomarkers. The integration of proteomics and bioinformatics studies provides a novel approach to develop new prenatal screening methods for noninvasive yet accurate diagnosis of DS. Copyright © 2012 John Wiley & Sons, Ltd.

Ectopic Integration of Transforming DNA Is Rare among Neurospora Transformants Selected for Gene Replacement

PubMed Central

Miao, VPW.; Rountree, M. R.; Selker, E. U.

1995-01-01

In a variety of organisms, DNA-mediated transformation experiments commonly produce transformants with multiple copies of the transforming DNA, including both selected and unselected molecules. Such ``cotransformants'' are much more common than expected from the individual transformation frequencies, suggesting that subpopulations of cells, or nuclei, are particularly competent for transformation. We found that Neurospora crassa transformants selected for gene replacement at the am gene had not efficiently incorporated additional DNA, suggesting that nuclei that undergo transformation by homologous recombination are not highly competent at integration of DNA by illegitimate recombination. Spheroplasts were treated with DNA fragments homologous to am and with an Escherichia coli hph plasmid. Transformants were initially selected for hph (hygromycin(R)), allowed to conidiate to generate homokaryons and then selected for either Am(-) (gene replacements) or hph. Surprisingly, most am replacement strains were hygromycin(S) (124/140) and carried no extraneous DNA (116/140). Most transformants selected for hph also had ectopic copies of am DNA and/or multiple copies of hph sequences (32/35), generally at multiple sites, confirming that efficient cotransformation could occur. To test the implication that cotransformation involving gene replacement and ectopic integration is rare, we compared the yields of am replacement strains with or without prior selection for hph. The initial selection did not appreciably help (or hinder) recovery of strains with replacements. PMID:7789758

Fish assemblages of the upper Little Sioux River basin, Iowa, USA: Relationships with stream size and comparison with historical assemblages

USGS Publications Warehouse

Palic, D.; Helland, L.; Pedersen, B.R.; Pribil, J.R.; Grajeda, R.M.; Loan-Wilsey, Anna; Pierce, C.L.

2007-01-01

We characterized the fish assemblages in second to fifth order streams of the upper Little Sioux River basin in northwest Iowa, USA and compared our results with historical surveys. The fish assemblage consisted of over twenty species, was dominated numerically by creek chub, sand shiner, central stoneroller and other cyprinids, and was dominated in biomass by common carp. Most of the species and the great majority of all individuals present were at least moderately tolerant to environmental degradation, and biotic integrity at most sites was characterized as fair. Biotic integrity declined with increasing stream size, and degraded habitat in larger streams is a possible cause. No significant changes in species richness or the relative distribution of species' tolerance appear to have occurred since the 1930s.

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

NASA Astrophysics Data System (ADS)

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 time via the EuroSITES water column infrastructure. EuroSITES Data management is led by NOCS, UK with CORIOLIS, France as one of the Global Data assembly centre (GDAC) for both EuroSITES and OceanSITES. EuroSITES maintains the OceanSITES and GEO philosophy of open access to data in near real-time. With a common data policy and standardised data formats (OceanSITES NetCDF) EuroSITES is increasing the potential users of in situ ocean datasets and the societal benefit of these data. For instance, CORIOLIS is central to the ever increasing contribution of EuroSITES as an upstream data provider to the GMES project MyOcean (both real-time and delayed-mode data). Outreach and knowledge transfer of EuroSITES activities and results are also a key component to the project with a dedicated outreach website, Fact Sheet, cruise diaries and educational tools being developed in the first 18 months. In 2010 a film will be released to represent the network and this will be distributed to a wide audience through the European network of aquaria and at other outreach events. In addition, the EuroSITES project and it's relevance to global ocean observation initiatives continues to be actively promoted at both scientific and non-specialist meetings and events. By the end of EuroSITES in April 2011, the 9 core ocean observatories will be well integrated. Each observatory will have enhanced infrastructure to include both physical and biogeoechemical sensors. Science missions in the ocean interior and seafloor/subseafloor will have progressed European ocean observational capability significantly. Collaborations will have taken place or will be at an advanced stage of planning with related European and international projects including ESONET FP6 NoE and the NSF funded Ocean Observatories Initiative (OOI) (400M over 5 years). EuroSITES will continue to develop it's contribution to the ocean component of the Group on Earth Observations (GEO) through task AR-09-03c 'Global Ocean Observing Systems' and related societal benefit areas.

Deconstruction of a Metastatic Tumor Microenvironment Reveals a Common Matrix Response in Human Cancers.

PubMed

Pearce, Oliver M T; Delaine-Smith, Robin M; Maniati, Eleni; Nichols, Sam; Wang, Jun; Böhm, Steffen; Rajeeve, Vinothini; Ullah, Dayem; Chakravarty, Probir; Jones, Roanne R; Montfort, Anne; Dowe, Tom; Gribben, John; Jones, J Louise; Kocher, Hemant M; Serody, Jonathan S; Vincent, Benjamin G; Connelly, John; Brenton, James D; Chelala, Claude; Cutillas, Pedro R; Lockley, Michelle; Bessant, Conrad; Knight, Martin M; Balkwill, Frances R

2018-03-01

We have profiled, for the first time, an evolving human metastatic microenvironment by measuring gene expression, matrisome proteomics, cytokine and chemokine levels, cellularity, extracellular matrix organization, and biomechanical properties, all on the same sample. Using biopsies of high-grade serous ovarian cancer metastases that ranged from minimal to extensive disease, we show how nonmalignant cell densities and cytokine networks evolve with disease progression. Multivariate integration of the different components allowed us to define, for the first time, gene and protein profiles that predict extent of disease and tissue stiffness, while also revealing the complexity and dynamic nature of matrisome remodeling during development of metastases. Although we studied a single metastatic site from one human malignancy, a pattern of expression of 22 matrisome genes distinguished patients with a shorter overall survival in ovarian and 12 other primary solid cancers, suggesting that there may be a common matrix response to human cancer. Significance: Conducting multilevel analysis with data integration on biopsies with a range of disease involvement identifies important features of the evolving tumor microenvironment. The data suggest that despite the large spectrum of genomic alterations, some human malignancies may have a common and potentially targetable matrix response that influences the course of disease. Cancer Discov; 8(3); 304-19. ©2017 AACR. This article is highlighted in the In This Issue feature, p. 253 . ©2017 American Association for Cancer Research.

Site directed recombination

DOEpatents

Jurka, Jerzy W.

1997-01-01

Enhanced homologous recombination is obtained by employing a consensus sequence which has been found to be associated with integration of repeat sequences, such as Alu and ID. The consensus sequence or sequence having a single transition mutation determines one site of a double break which allows for high efficiency of integration at the site. By introducing single or double stranded DNA having the consensus sequence flanking region joined to a sequence of interest, one can reproducibly direct integration of the sequence of interest at one or a limited number of sites. In this way, specific sites can be identified and homologous recombination achieved at the site by employing a second flanking sequence associated with a sequence proximal to the 3'-nick.

The opportunities for and challenges of common integrated electronics

NASA Astrophysics Data System (ADS)

Nelson, J. R.; Retterer, Bernard L.; Cloud, Harley A.

1994-02-01

This document summarizes a portion of IDA's work concerning common integrated electronics and the potential cost savings of using common electronic hardware and software. It addresses trends in avionics costs and recent experiences in applying common electronic standards to weapon programs as a way to reduce costs. The following essential elements of a program to acquire common integrated electronics are explored: (1) integrated system architecture; (2) advanced technology programs; (3) open system standards; (4) standard common modules; and (5) associated management and policies. The principal recommendation is that OSD support and coordinate such a-program by taking a strong leadership role and setting standards policy.

Efficient mapping of transgene integration sites and local structural changes in Cre transgenic mice using targeted locus amplification

PubMed Central

Cain-Hom, Carol; Splinter, Erik; van Min, Max; Simonis, Marieke; van de Heijning, Monique; Martinez, Maria; Asghari, Vida

2017-01-01

Abstract Cre/LoxP technology is widely used in the field of mouse genetics for spatial and/or temporal regulation of gene function. For Cre lines generated via pronuclear microinjection of a Cre transgene construct, the integration site is random and in most cases not known. Integration of a transgene can disrupt an endogenous gene, potentially interfering with interpretation of the phenotype. In addition, knowledge of where the transgene is integrated is important for planning of crosses between animals carrying a conditional allele and a given Cre allele in case the alleles are on the same chromosome. We have used targeted locus amplification (TLA) to efficiently map the transgene location in seven previously published Cre and CreERT2 transgenic lines. In all lines, transgene insertion was associated with structural changes of variable complexity, illustrating the importance of testing for rearrangements around the integration site. In all seven lines the exact integration site and breakpoint sequences were identified. Our methods, data and genotyping assays can be used as a resource for the mouse community and our results illustrate the power of the TLA method to not only efficiently map the integration site of any transgene, but also provide additional information regarding the transgene integration events. PMID:28053125

Integrative DNA methylation and gene expression analysis to assess the universality of the CpG island methylator phenotype.

PubMed

Moarii, Matahi; Reyal, Fabien; Vert, Jean-Philippe

2015-10-13

The CpG island methylator phenotype (CIMP) was first characterized in colorectal cancer but since has been extensively studied in several other tumor types such as breast, bladder, lung, and gastric. CIMP is of clinical importance as it has been reported to be associated with prognosis or response to treatment. However, the identification of a universal molecular basis to define CIMP across tumors has remained elusive. We perform a genome-wide methylation analysis of over 2000 tumor samples from 5 cancer sites to assess the existence of a CIMP with common molecular basis across cancers. We then show that the CIMP phenotype is associated with specific gene expression variations. However, we do not find a common genetic signature in all tissues associated with CIMP. Our results suggest the existence of a universal epigenetic and transcriptomic signature that defines the CIMP across several tumor types but does not indicate the existence of a common genetic signature of CIMP.

47 CFR 73.635 - Use of common antenna site.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 4 2012-10-01 2012-10-01 false Use of common antenna site. 73.635 Section 73.635 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Television Broadcast Stations § 73.635 Use of common antenna site. No television license...

47 CFR 73.635 - Use of common antenna site.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 4 2013-10-01 2013-10-01 false Use of common antenna site. 73.635 Section 73.635 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Television Broadcast Stations § 73.635 Use of common antenna site. No television license...

47 CFR 73.239 - Use of common antenna site.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 4 2013-10-01 2013-10-01 false Use of common antenna site. 73.239 Section 73.239 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES FM Broadcast Stations § 73.239 Use of common antenna site. No FM broadcast station...

47 CFR 73.239 - Use of common antenna site.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 4 2011-10-01 2011-10-01 false Use of common antenna site. 73.239 Section 73.239 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES FM Broadcast Stations § 73.239 Use of common antenna site. No FM broadcast station...

47 CFR 73.239 - Use of common antenna site.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 4 2012-10-01 2012-10-01 false Use of common antenna site. 73.239 Section 73.239 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES FM Broadcast Stations § 73.239 Use of common antenna site. No FM broadcast station...

47 CFR 73.635 - Use of common antenna site.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 4 2014-10-01 2014-10-01 false Use of common antenna site. 73.635 Section 73.635 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Television Broadcast Stations § 73.635 Use of common antenna site. No television license...

47 CFR 73.239 - Use of common antenna site.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Use of common antenna site. 73.239 Section 73.239 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES FM Broadcast Stations § 73.239 Use of common antenna site. No FM broadcast station...

47 CFR 73.635 - Use of common antenna site.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Use of common antenna site. 73.635 Section 73.635 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Television Broadcast Stations § 73.635 Use of common antenna site. No television license...

47 CFR 73.239 - Use of common antenna site.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 4 2014-10-01 2014-10-01 false Use of common antenna site. 73.239 Section 73.239 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES FM Broadcast Stations § 73.239 Use of common antenna site. No FM broadcast station...

47 CFR 73.635 - Use of common antenna site.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 4 2011-10-01 2011-10-01 false Use of common antenna site. 73.635 Section 73.635 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Television Broadcast Stations § 73.635 Use of common antenna site. No television license...

Factors influencing integration of TB services in general hospitals in two regions of China: a qualitative study

PubMed Central

2012-01-01

Background In the majority of China, the Centre for Disease Control (CDC) at the county level provides both clinical and public health care for TB cases, with hospitals and other health facilities referring suspected TB cases to the CDC. In recent years, an integrated model has emerged, where the CDC remains the basic management unit for TB control, while a general hospital is designated to provide clinical care for TB patients. This study aims to explore the factors that influence the integration of TB services in general hospitals and generate knowledge to aid the scale-up of integration of TB services in China. Methods This study adopted a qualitative approach using interviews from sites in East and West China. Analysis was conducted using a thematic framework approach. Results The more prosperous site in East China was more coordinated and thus had a better method of resource allocation and more patient-orientated service, compared with the poorer site in the West. The development of public health organizations appeared to influence how effectively integration occurred. An understanding from staff that hospitals had better capacity to treat TB patients than CDCs was a strong rationale for integration. However, the economic and political interests might act as a barrier to effective integration. Both sites shared the same challenges of attracting and retaining a skilled workforce for the TB services. The role of the health bureau was more directive in the Western site, while a more participatory and collaborative approach was adopted in the Eastern site. Conclusion The process of integration identifies similarities and differences between sites in more affluent East China and poorer West China. Integration of TB services in the hospitals needs to address the challenges of stakeholder motivations and resource allocation. Effective inter-organizational collaboration could help to improve the efficiency and quality of TB service. Key words: TB control, service delivery, integration, hospitals, China. PMID:22276746

Real Time Metrics and Analysis of Integrated Arrival, Departure, and Surface Operations

NASA Technical Reports Server (NTRS)

Sharma, Shivanjli; Fergus, John

2017-01-01

To address the Integrated Arrival, Departure, and Surface (IADS) challenge, NASA is developing and demonstrating trajectory-based departure automation under a collaborative effort with the FAA and industry known Airspace Technology Demonstration 2 (ATD-2). ATD-2 builds upon and integrates previous NASA research capabilities that include the Spot and Runway Departure Advisor (SARDA), the Precision Departure Release Capability (PDRC), and the Terminal Sequencing and Spacing (TSAS) capability. As trajectory-based departure scheduling and collaborative decision making tools are introduced in order to reduce delays and uncertainties in taxi and climb operations across the National Airspace System, users of the tools across a number of roles benefit from a real time system that enables common situational awareness. A real time dashboard was developed to inform and present users notifications and integrated information regarding airport surface operations. The dashboard is a supplement to capabilities and tools that incorporate arrival, departure, and surface air-traffic operations concepts in a NextGen environment. In addition to shared situational awareness, the dashboard offers the ability to compute real time metrics and analysis to inform users about capacity, predictability, and efficiency of the system as a whole. This paper describes the architecture of the real time dashboard as well as an initial proposed set of metrics. The potential impact of the real time dashboard is studied at the site identified for initial deployment and demonstration in 2017: Charlotte-Douglas International Airport (CLT). The architecture of implementing such a tool as well as potential uses are presented for operations at CLT. Metrics computed in real time illustrate the opportunity to provide common situational awareness and inform users of system delay, throughput, taxi time, and airport capacity. In addition, common awareness of delays and the impact of takeoff and departure restrictions stemming from traffic flow management initiatives are explored. The potential of the real time tool to inform users of the predictability and efficiency of using a trajectory-based departure scheduling system is also discussed.

From ecological test site to geographic information system: lessons for the 1980's

USGS Publications Warehouse

Alexander, Robert H.

1981-01-01

Geographic information systems were common elements in two kinds of interdisciplinary regional demonstration projects in the 1970's. Ecological test sits attempted to provide for more efficient remote-sensing data delivery for regional environmental management. Regional environmental systems analysis attempted to formally describe and model the interacting regional social and environmental processes, including the resource-use decision making process. Lessons for the 1980's are drawn from recent evaluations and assessments of these programs, focusing on cost, rates of system development and technology transfer, program coordination, integrative analysis capability, and the involvement of system users and decision makers.

The Virtual Learning Commons (VLC): Enabling Co-Innovation Across Disciplines

NASA Astrophysics Data System (ADS)

Pennington, D. D.; Gandara, A.; Del Rio, N.

2014-12-01

A key challenge for scientists addressing grand-challenge problems is identifying, understanding, and integrating potentially relevant methods, models and tools that that are rapidly evolving in the informatics community. Such tools are essential for effectively integrating data and models in complex research projects, yet it is often difficult to know what tools are available and it is not easy to understand or evaluate how they might be used in a given research context. The goal of the National Science Foundation-funded Virtual Learning Commons (VLC) is to improve awareness and understanding of emerging methodologies and technologies, facilitate individual and group evaluation of these, and trace the impact of innovations within and across teams, disciplines, and communities. The VLC is a Web-based social bookmarking site designed specifically to support knowledge exchange in research communities. It is founded on well-developed models of technology adoption, diffusion of innovation, and experiential learning. The VLC makes use of Web 2.0 (Social Web) and Web 3.0 (Semantic Web) approaches. Semantic Web approaches enable discovery of potentially relevant methods, models, and tools, while Social Web approaches enable collaborative learning about their function. The VLC is under development and the first release is expected Fall 2014.

Motion-compensated hand-held common-path Fourier-domain optical coherence tomography probe for image-guided intervention

NASA Astrophysics Data System (ADS)

Huang, Yong; Song, Cheol; Liu, Xuan; Kang, Jin U.

2013-03-01

A motion-compensated hand-held common-path Fourier-domain optical coherence tomography imaging probe has been developed for image guided intervention during microsurgery. A hand-held prototype instrument was designed and fabricated by integrating an imaging fiber probe inside a stainless steel needle which is attached to the ceramic shaft of a piezoelectric motor housed in an aluminum handle. The fiber probe obtains A-scan images. The distance information was extracted from the A-scans to track the sample surface distance and a fixed distance was maintained by a feedback motor control which effectively compensated hand tremor and target movements in the axial direction. Graphical user interface, real-time data processing, and visualization based on a CPU-GPU hybrid programming architecture were developed and used in the implantation of this system. To validate the system, free-hand optical coherence tomography images using various samples were obtained. The system can be easily integrated into microsurgical tools and robotics for a wide range of clinical applications. Such tools could offer physicians the freedom to easily image sites of interest with reduced risk and higher image quality.

An integrated map of genetic variation from 1,092 human genomes

PubMed Central

2012-01-01

Summary Through characterising the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help understand the genetic contribution to disease. We describe the genomes of 1,092 individuals from 14 populations, constructed using a combination of low-coverage whole-genome and exome sequencing. By developing methodologies to integrate information across multiple algorithms and diverse data sources we provide a validated haplotype map of 38 million SNPs, 1.4 million indels and over 14 thousand larger deletions. We show that individuals from different populations carry different profiles of rare and common variants and that low-frequency variants show substantial geographic differentiation, which is further increased by the action of purifying selection. We show that evolutionary conservation and coding consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways and that each individual harbours hundreds of rare non-coding variants at conserved sites, such as transcription-factor-motif disrupting changes. This resource, which captures up to 98% of accessible SNPs at a frequency of 1% in populations of medical genetics focus, enables analysis of common and low-frequency variants in individuals from diverse, including admixed, populations. PMID:23128226

Assessing and Managing Multiple Risks in a Changing World ...

EPA Pesticide Factsheets

Roskilde University hosted a November 2015 workshop on “Environmental Risk – Assessing and Managing Multiple Risks in a Changing World”. Thirty attendees from 9 countries developed consensus recommendations regarding: implementation of a common currency (ecosystem services) for holistic environmental risk assessment and management; improvements to risk assessment and management in a complex, human-modified, and changing world; appropriate development of protection goals in a 2-stage process involving both universal and site-, region-, or problem-specific protection goals; addressing societal issues; risk management information needs; conducting risk assessment of risk management; and development of adaptive and flexible regulatory systems. We encourage both cross- and inter-disciplinary approaches to address 10 recommendations: 1) adopt ecosystem services as a common currency for risk assessment and management; 2) consider cumulative stressors (chemical and non-chemical) and determine which dominate to best manage and restore ecosystem services; 3) fully integrate risk managers and communities of interest into the risk assessment process; 4) fully integrate risk assessors and communities of interest into the risk management process; 5) consider socio-economics and increase transparency in both risk assessment and risk management; 6) recognize the ethical rights of humans and ecosystems to an adequate level of protection; 7) determine relevant reference con

Random integration of SV40 in SV40-transformed, immortalized human fibroblasts.

PubMed

Hara, H; Kaji, H

1987-02-01

We have studied the relationship between immortalization of SV40-transformed human embryonic fibroblasts and their SV40 integration sites. From several independently transformed cell pools, we have isolated clones which do not harbor unintegrated SV40 DNA. We have analysed whole-cell DNA from these clones, using the Southern blot method. Our results suggest that no specific integration sites in the cellular genome exist which are a prerequisite for the immortalization process. Although some integration sites were found to be predominant in pre-crisis clones, they could not be detected in the post-crisis clones. This suggests that none of these predominating sites is selected for during the crisis period.

The effect of undersizing and tapping on bone to implant contact and implant primary stability: A histomorphometric study on bovine ribs.

PubMed

Di Stefano, Danilo Alessio; Perrotti, Vittoria; Greco, Gian Battista; Cappucci, Claudia; Arosio, Paolo; Piattelli, Adriano; Iezzi, Giovanna

2018-06-01

Implant site preparation may be adjusted to achieve the maximum possible primary stability. The aim of this investigation was to study the relation among bone-to-implant contact at insertion, bone density, and implant primary stability intra-operatively measured by a torque-measuring implant motor, when implant sites were undersized or tapped. Undersized (n=14), standard (n=13), and tapped (n=13) implant sites were prepared on 9 segments of bovine ribs. After measuring bone density using the implant motor, 40 implants were placed, and their primary stability assessed by measuring the integral of the torque-depth insertion curve. Bovine ribs were then processed histologically, the bone-to-implant contact measured and statistically correlated to bone density and the integral. Bone-to-implant contact and the integral of the torque-depth curve were significantly greater for undersized sites than tapped sites. Moreover, a correlation between bone to implant contact, the integral and bone density was found under all preparation conditions. The slope of the bone-to-implant/density and integral/density lines was significantly greater for undersized sites, while those corresponding to standard prepared and tapped sites did not differ significantly. The integral of the torque-depth curve provided reliable information about bone-to-implant contact and primary implant stability even in tapped or undersized sites. The linear relations found among the parameters suggests a connection between extent and modality of undersizing and the corresponding increase of the integral and, consequently, of primary stability. These results might help the physician determine the extent of undersizing needed to achieve the proper implant primary stability, according to the planned loading protocol.

LEDGF/p75 interacts with mRNA splicing factors and targets HIV-1 integration to highly spliced genes

PubMed Central

Singh, Parmit Kumar; Plumb, Matthew R.; Ferris, Andrea L.; Iben, James R.; Wu, Xiaolin; Fadel, Hind J.; Luke, Brian T.; Esnault, Caroline; Poeschla, Eric M.; Hughes, Stephen H.; Kvaratskhelia, Mamuka; Levin, Henry L.

2015-01-01

The host chromatin-binding factor LEDGF/p75 interacts with HIV-1 integrase and directs integration to active transcription units. To understand how LEDGF/p75 recognizes transcription units, we sequenced 1 million HIV-1 integration sites isolated from cultured HEK293T cells. Analysis of integration sites showed that cancer genes were preferentially targeted, raising concerns about using lentivirus vectors for gene therapy. Additional analysis led to the discovery that introns and alternative splicing contributed significantly to integration site selection. These correlations were independent of transcription levels, size of transcription units, and length of the introns. Multivariate analysis with five parameters previously found to predict integration sites showed that intron density is the strongest predictor of integration density in transcription units. Analysis of previously published HIV-1 integration site data showed that integration density in transcription units in mouse embryonic fibroblasts also correlated strongly with intron number, and this correlation was absent in cells lacking LEDGF. Affinity purification showed that LEDGF/p75 is associated with a number of splicing factors, and RNA sequencing (RNA-seq) analysis of HEK293T cells lacking LEDGF/p75 or the LEDGF/p75 integrase-binding domain (IBD) showed that LEDGF/p75 contributes to splicing patterns in half of the transcription units that have alternative isoforms. Thus, LEDGF/p75 interacts with splicing factors, contributes to exon choice, and directs HIV-1 integration to transcription units that are highly spliced. PMID:26545813

Audiovisual integration of emotional signals in voice and face: an event-related fMRI study.

PubMed

Kreifelts, Benjamin; Ethofer, Thomas; Grodd, Wolfgang; Erb, Michael; Wildgruber, Dirk

2007-10-01

In a natural environment, non-verbal emotional communication is multimodal (i.e. speech melody, facial expression) and multifaceted concerning the variety of expressed emotions. Understanding these communicative signals and integrating them into a common percept is paramount to successful social behaviour. While many previous studies have focused on the neurobiology of emotional communication in the auditory or visual modality alone, far less is known about multimodal integration of auditory and visual non-verbal emotional information. The present study investigated this process using event-related fMRI. Behavioural data revealed that audiovisual presentation of non-verbal emotional information resulted in a significant increase in correctly classified stimuli when compared with visual and auditory stimulation. This behavioural gain was paralleled by enhanced activation in bilateral posterior superior temporal gyrus (pSTG) and right thalamus, when contrasting audiovisual to auditory and visual conditions. Further, a characteristic of these brain regions, substantiating their role in the emotional integration process, is a linear relationship between the gain in classification accuracy and the strength of the BOLD response during the bimodal condition. Additionally, enhanced effective connectivity between audiovisual integration areas and associative auditory and visual cortices was observed during audiovisual stimulation, offering further insight into the neural process accomplishing multimodal integration. Finally, we were able to document an enhanced sensitivity of the putative integration sites to stimuli with emotional non-verbal content as compared to neutral stimuli.

AAVS1-Targeted Plasmid Integration in AAV Producer Cell Lines.

PubMed

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.

Integrated Remote Sensing Modalities for Classification at a Legacy Test Site

NASA Astrophysics Data System (ADS)

Lee, D. J.; Anderson, D.; Craven, J.

2016-12-01

Detecting, locating, and characterizing suspected underground nuclear test sites is of interest to the worldwide nonproliferation monitoring community. Remote sensing provides both cultural and surface geological information over a large search area in a non-intrusive manner. We have characterized a legacy nuclear test site at the Nevada National Security Site (NNSS) using an aerial system based on RGB imagery, light detection and ranging, and hyperspectral imaging. We integrate these different remote sensing modalities to perform pattern recognition and classification tasks on the test site. These tasks include detecting cultural artifacts and exotic materials. We evaluate if the integration of different remote sensing modalities improves classification performance.

Integrating care for high-risk patients in England using the virtual ward model: lessons in the process of care integration from three case sites

PubMed Central

Lewis, Geraint; Vaithianathan, Rhema; Wright, Lorraine; Brice, Mary R; Lovell, Paul; Rankin, Seth; Bardsley, Martin

2013-01-01

Background Patients at high risk of emergency hospitalisation are particularly likely to experience fragmentation in care. The virtual ward model attempts to integrate health and social care by offering multidisciplinary case management to people at high predicted risk of unplanned hospitalisation. Objective To describe the care practice in three virtual ward sites in England and to explore how well each site had achieved meaningful integration. Method Case studies conducted in Croydon, Devon and Wandsworth during 2011–2012, consisting of semi-structured interviews, workshops, and site visits. Results Different versions of the virtual wards intervention had been implemented in each site. In Croydon, multidisciplinary care had reverted back to one-to-one case management. Conclusions To integrate successfully, virtual ward projects should safeguard the multidisciplinary nature of the intervention, ensure the active involvement of General Practitioners, and establish feedback processes to monitor performance such as the number of professions represented at each team meeting. PMID:24250284

Systematic data ingratiation of clinical trial recruitment locations for geographic-based query and visualization

PubMed Central

Luo, Jake; Chen, Weiheng; Wu, Min; Weng, Chunhua

2018-01-01

Background Prior studies of clinical trial planning indicate that it is crucial to search and screen recruitment sites before starting to enroll participants. However, currently there is no systematic method developed to support clinical investigators to search candidate recruitment sites according to their interested clinical trial factors. Objective In this study, we aim at developing a new approach to integrating the location data of over one million heterogeneous recruitment sites that are stored in clinical trial documents. The integrated recruitment location data can be searched and visualized using a map-based information retrieval method. The method enables systematic search and analysis of recruitment sites across a large amount of clinical trials. Methods The location data of more than 1.4 million recruitment sites of over 183,000 clinical trials was normalized and integrated using a geocoding method. The integrated data can be used to support geographic information retrieval of recruitment sites. Additionally, the information of over 6000 clinical trial target disease conditions and close to 4000 interventions was also integrated into the system and linked to the recruitment locations. Such data integration enabled the construction of a novel map-based query system. The system will allow clinical investigators to search and visualize candidate recruitment sites for clinical trials based on target conditions and interventions. Results The evaluation results showed that the coverage of the geographic location mapping for the 1.4 million recruitment sites was 99.8%. The evaluation of 200 randomly retrieved recruitment sites showed that the correctness of geographic information mapping was 96.5%. The recruitment intensities of the top 30 countries were also retrieved and analyzed. The data analysis results indicated that the recruitment intensity varied significantly across different countries and geographic areas. Conclusion This study contributed a new data processing framework to extract and integrate the location data of heterogeneous recruitment sites from clinical trial documents. The developed system can support effective retrieval and analysis of potential recruitment sites using target clinical trial factors. PMID:29132636

Systematic data ingratiation of clinical trial recruitment locations for geographic-based query and visualization.

PubMed

Luo, Jake; Chen, Weiheng; Wu, Min; Weng, Chunhua

2017-12-01

Prior studies of clinical trial planning indicate that it is crucial to search and screen recruitment sites before starting to enroll participants. However, currently there is no systematic method developed to support clinical investigators to search candidate recruitment sites according to their interested clinical trial factors. In this study, we aim at developing a new approach to integrating the location data of over one million heterogeneous recruitment sites that are stored in clinical trial documents. The integrated recruitment location data can be searched and visualized using a map-based information retrieval method. The method enables systematic search and analysis of recruitment sites across a large amount of clinical trials. The location data of more than 1.4 million recruitment sites of over 183,000 clinical trials was normalized and integrated using a geocoding method. The integrated data can be used to support geographic information retrieval of recruitment sites. Additionally, the information of over 6000 clinical trial target disease conditions and close to 4000 interventions was also integrated into the system and linked to the recruitment locations. Such data integration enabled the construction of a novel map-based query system. The system will allow clinical investigators to search and visualize candidate recruitment sites for clinical trials based on target conditions and interventions. The evaluation results showed that the coverage of the geographic location mapping for the 1.4 million recruitment sites was 99.8%. The evaluation of 200 randomly retrieved recruitment sites showed that the correctness of geographic information mapping was 96.5%. The recruitment intensities of the top 30 countries were also retrieved and analyzed. The data analysis results indicated that the recruitment intensity varied significantly across different countries and geographic areas. This study contributed a new data processing framework to extract and integrate the location data of heterogeneous recruitment sites from clinical trial documents. The developed system can support effective retrieval and analysis of potential recruitment sites using target clinical trial factors. Copyright © 2017 Elsevier B.V. All rights reserved.

MMI: Increasing Community Collaboration

NASA Astrophysics Data System (ADS)

Galbraith, N. R.; Stocks, K.; Neiswender, C.; Maffei, A.; Bermudez, L.

2007-12-01

Building community requires a collaborative environment and guidance to help move members towards a common goal. An effective environment for community collaboration is a workspace that fosters participation and cooperation; effective guidance furthers common understanding and promotes best practices. The Marine Metadata Interoperability (MMI) project has developed a community web site to provide a collaborative environment for scientists, technologists, and data managers from around the world to learn about metadata and exchange ideas. Workshops, demonstration projects, and presentations also provide community-building opportunities for MMI. MMI has developed comprehensive online guides to help users understand and work with metadata standards, ontologies, and other controlled vocabularies. Documents such as "The Importance of Metadata Standards", "Usage vs. Discovery Vocabularies" and "Developing Controlled Vocabularies" guide scientists and data managers through a variety of metadata-related concepts. Members from eight organizations involved in marine science and informatics collaborated on this effort. The MMI web site has moved from Plone to Drupal, two content management systems which provide different opportunities for community-based work. Drupal's "organic groups" feature will be used to provide workspace for future teams tasked with content development, outreach, and other MMI mission-critical work. The new site is designed to enable members to easily create working areas, to build communities dedicated to developing consensus on metadata and other interoperability issues. Controlled-vocabulary-driven menus, integrated mailing-lists, member-based content creation and review tools are facets of the new web site architecture. This move provided the challenge of developing a hierarchical vocabulary to describe the resources presented on the site; consistent and logical tagging of web pages is the basis of Drupal site navigation. The new MMI web site presents enhanced opportunities for electronic discussions, focused collaborative work, and even greater community participation. The MMI project is beginning a new initiative to comprehensively catalog and document tools for marine metadata. The new MMI community-based web site will be used to support this work and to support the work of other ad-hoc teams in the future. We are seeking broad input from the community on this effort.

Cell-type-specific replication initiation programs set fragility of the FRA3B fragile site.

PubMed

Letessier, Anne; Millot, Gaël A; Koundrioukoff, Stéphane; Lachagès, Anne-Marie; Vogt, Nicolas; Hansen, R Scott; Malfoy, Bernard; Brison, Olivier; Debatisse, Michelle

2011-02-03

Common fragile sites have long been identified by cytogeneticists as chromosomal regions prone to breakage upon replication stress. They are increasingly recognized to be preferential targets for oncogene-induced DNA damage in pre-neoplastic lesions and hotspots for chromosomal rearrangements in various cancers. Common fragile site instability was attributed to the fact that they contain sequences prone to form secondary structures that may impair replication fork movement, possibly leading to fork collapse resulting in DNA breaks. Here we show, in contrast to this view, that the fragility of FRA3B--the most active common fragile site in human lymphocytes--does not rely on fork slowing or stalling but on a paucity of initiation events. Indeed, in lymphoblastoid cells, but not in fibroblasts, initiation events are excluded from a FRA3B core extending approximately 700 kilobases, which forces forks coming from flanking regions to cover long distances in order to complete replication. We also show that origins of the flanking regions fire in mid-S phase, leaving the site incompletely replicated upon fork slowing. Notably, FRA3B instability is specific to cells showing this particular initiation pattern. The fact that both origin setting and replication timing are highly plastic in mammalian cells explains the tissue specificity of common fragile site instability we observed. Thus, we propose that common fragile sites correspond to the latest initiation-poor regions to complete replication in a given cell type. For historical reasons, common fragile sites have been essentially mapped in lymphocytes. Therefore, common fragile site contribution to chromosomal rearrangements in tumours should be reassessed after mapping fragile sites in the cell type from which each tumour originates.

Hybrid lentivirus-phiC31-int-NLS vector allows site-specific recombination in murine and human cells but induces DNA damage.

PubMed

Grandchamp, Nicolas; Altémir, Dorothée; Philippe, Stéphanie; Ursulet, Suzanna; Pilet, Héloïse; Serre, Marie-Claude; Lenain, Aude; Serguera, Che; Mallet, Jacques; Sarkis, Chamsy

2014-01-01

Gene transfer allows transient or permanent genetic modifications of cells for experimental or therapeutic purposes. Gene delivery by HIV-derived lentiviral vector (LV) is highly effective but the risk of insertional mutagenesis is important and the random/uncontrollable integration of the DNA vector can deregulate the cell transcriptional activity. Non Integrative Lentiviral Vectors (NILVs) solve this issue in non-dividing cells, but they do not allow long term expression in dividing cells. In this context, obtaining stable expression while avoiding the problems inherent to unpredictable DNA vector integration requires the ability to control the integration site. One possibility is to use the integrase of phage phiC31 (phiC31-int) which catalyzes efficient site-specific recombination between the attP site in the phage genome and the chromosomal attB site of its Streptomyces host. Previous studies showed that phiC31-int is active in many eukaryotic cells, such as murine or human cells, and directs the integration of a DNA substrate into pseudo attP sites (pattP) which are homologous to the native attP site. In this study, we combined the efficiency of NILV for gene delivery and the specificity of phiC31-int for DNA substrate integration to engineer a hybrid tool for gene transfer with the aim of allowing long term expression in dividing and non-dividing cells preventing genotoxicity. We demonstrated the feasibility to target NILV integration in human and murine pattP sites with a dual NILV vectors system: one which delivers phiC31-int, the other which constitute the substrate containing an attB site in its DNA sequence. These promising results are however alleviated by the occurrence of significant DNA damages. Further improvements are thus required to prevent chromosomal rearrangements for a therapeutic use of the system. However, its use as a tool for experimental applications such as transgenesis is already applicable.

Effects and Non-effects of Stream Drying on Stonefly(Plecoptera) Assemblages in two Ouachita Mountains,AR, Catchments

NASA Astrophysics Data System (ADS)

Sheldon, A. L.; Warren, M. L.

2005-05-01

Streams integrate landscape change. To establish baseline conditions and predictive relationships in two experimental catchments, we collected adult stoneflies at 38 sites for a year. We used a stratified random sampling design and regular collections of adults, which are identifiable to species level, to ensure thorough coverage. We collected 43 species (1-27 per site). We characterized sites by two descriptors: stream size as drainage AREA, and DRY, a time-weighted average of absence of surface water in measured sections. Sites ranged from continuous surface flow to partial or total drying for months. Species composition (NMS ordination) was influenced strongly by DRY. Richness of species and genera were well described (R2>85%) by multiple regressions on AREA and DRY. However, species richness was related strongly to AREA (P<0.001) but independent of DRY (P>0.45). Generic richness, in contrast, was related significantly(P<0.001)to both descriptors but the negative effect of DRY was stronger. Seasonal drying is common in the Ouachita region and part of the fauna is resistant to drying. Our results have implications for diversity-stress relationships and taxonomic resolution in community ecology and monitoring.

Are integrated HIV services less stigmatizing than stand-alone models of care? A comparative case study from Swaziland

PubMed Central

Church, Kathryn; Wringe, Alison; Fakudze, Phelele; Kikuvi, Joshua; Simelane, Dudu; Mayhew, Susannah H

2013-01-01

Introduction Integrating HIV with primary health services has the potential to reduce HIV-related stigma through delivering care in settings disassociated with HIV. This study investigated the relationship between integrated care and felt stigma. The study design was a comparative case study of four models of HIV care in Swaziland, ranging from fully integrated to fully stand-alone HIV care. Methods An exit survey (N=602) measured differences in felt stigma across model of care; the primary outcome “perception of HIV status exposure through clinic attendance” was analyzed using multivariable logistic regression. In-depth interviews (N=22) explored whether and how measured differences in stigma experiences were related to service integration. Results There were significant differences in perceived status exposure across models of care. After adjustment for potential confounding between sites, those at a partially integrated site and a partially stand-alone site had greater odds of perceived status exposure than those at the fully stand-alone site (aOR 3.33, 95% CI 1.98–5.60; and aOR 11.84, 95% CI 6.89–20.36, respectively). There was no difference between the fully stand-alone and the fully integrated clinic. Qualitative data suggested that many clients at HIV-only sites felt greater confidentiality knowing that those around them were positive, and support was gained from other HIV care clients. Confidentiality was maintained in various ways, even in stand-alone sites, through separate waiting areas for HIV testing and HIV treatment, and careful clinic and room labelling. Conclusions The relationship between model of care and stigma was complex, and the hypothesis that stigma is higher at stand-alone sites did not hold true in this high prevalence setting. Policy-makers should ensure that service integration does not increase stigma, in particular within partially integrated models of care. PMID:23336726

Efficient mapping of transgene integration sites and local structural changes in Cre transgenic mice using targeted locus amplification.

PubMed

Cain-Hom, Carol; Splinter, Erik; van Min, Max; Simonis, Marieke; van de Heijning, Monique; Martinez, Maria; Asghari, Vida; Cox, J Colin; Warming, Søren

2017-05-05

Cre/LoxP technology is widely used in the field of mouse genetics for spatial and/or temporal regulation of gene function. For Cre lines generated via pronuclear microinjection of a Cre transgene construct, the integration site is random and in most cases not known. Integration of a transgene can disrupt an endogenous gene, potentially interfering with interpretation of the phenotype. In addition, knowledge of where the transgene is integrated is important for planning of crosses between animals carrying a conditional allele and a given Cre allele in case the alleles are on the same chromosome. We have used targeted locus amplification (TLA) to efficiently map the transgene location in seven previously published Cre and CreERT2 transgenic lines. In all lines, transgene insertion was associated with structural changes of variable complexity, illustrating the importance of testing for rearrangements around the integration site. In all seven lines the exact integration site and breakpoint sequences were identified. Our methods, data and genotyping assays can be used as a resource for the mouse community and our results illustrate the power of the TLA method to not only efficiently map the integration site of any transgene, but also provide additional information regarding the transgene integration events. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Genomic and oncogenic preference of HBV integration in hepatocellular carcinoma

PubMed Central

Zhao, Ling-Hao; Liu, Xiao; Yan, He-Xin; Li, Wei-Yang; Zeng, Xi; Yang, Yuan; Zhao, Jie; Liu, Shi-Ping; Zhuang, Xue-Han; Lin, Chuan; Qin, Chen-Jie; Zhao, Yi; Pan, Ze-Ya; Huang, Gang; Liu, Hui; Zhang, Jin; Wang, Ruo-Yu; Yang, Yun; Wen, Wen; Lv, Gui-Shuai; Zhang, Hui-Lu; Wu, Han; Huang, Shuai; Wang, Ming-Da; Tang, Liang; Cao, Hong-Zhi; Wang, Ling; Lee, Tin-Lap; Jiang, Hui; Tan, Ye-Xiong; Yuan, Sheng-Xian; Hou, Guo-Jun; Tao, Qi-Fei; Xu, Qin-Guo; Zhang, Xiu-Qing; Wu, Meng-Chao; Xu, Xun; Wang, Jun; Yang, Huan-Ming; Zhou, Wei-Ping; Wang, Hong-Yang

2016-01-01

Hepatitis B virus (HBV) can integrate into the human genome, contributing to genomic instability and hepatocarcinogenesis. Here by conducting high-throughput viral integration detection and RNA sequencing, we identify 4,225 HBV integration events in tumour and adjacent non-tumour samples from 426 patients with HCC. We show that HBV is prone to integrate into rare fragile sites and functional genomic regions including CpG islands. We observe a distinct pattern in the preferential sites of HBV integration between tumour and non-tumour tissues. HBV insertional sites are significantly enriched in the proximity of telomeres in tumours. Recurrent HBV target genes are identified with few that overlap. The overall HBV integration frequency is much higher in tumour genomes of males than in females, with a significant enrichment of integration into chromosome 17. Furthermore, a cirrhosis-dependent HBV integration pattern is observed, affecting distinct targeted genes. Our data suggest that HBV integration has a high potential to drive oncogenic transformation. PMID:27703150

Efficacy and site-specificity of adenoviral vector integration mediated by the phage φC31 integrase.

PubMed

Robert, Marc-André; Zeng, Yue; Raymond, Benoît; Desfossé, Laurie; Mairey, Emilie; Tremblay, Jacques P; Massie, Bernard; Gilbert, Rénald

2012-12-01

Adenoviral vectors deleted of all their viral genes (helper-dependent [HD]) are efficient gene-transfer vehicles. Because transgene expression is rapidly lost in actively dividing cells, we investigated the feasibility of using phage φC31 integrase (φC31-Int) to integrate an HD carrying an attB site and the puromycin resistance gene into human cells (HeLa) and murine myoblasts (C2C12) by co-infection with a second HD-expressing φC31-Int. Because the HD genome is linear, we also investigated whether its circularization, through expression of Cre using a third HD, affects integration. Efficacy and specificity were determined by scoring the number of puromycin-resistant colonies and by sequencing integration sites. Unexpectedly, circularization of HD was unnecessary and it even reduced the integration efficacy. The maximum integration efficacy achieved was 0.5% in HeLa cells and 0.1% in C2C12 myoblasts. Up to 76% of the integration events occurred at pseudo attP sites and previously characterized hotspots were found. A small (two- to three-fold) increase in the number of γ-H2AX positive foci, accompanied by no noticeable change in γ-H2AX expression, indicated the low genotoxicity of φC31-Int. In conclusion, integration of HD mediated by φC31-Int is an attractive alternative to engineer cells, because it permits site-specific integration of large DNA fragments with low genotoxicity.

Fission yeast retrotransposon Tf1 integration is targeted to 5' ends of open reading frames.

PubMed

Behrens, R; Hayles, J; Nurse, P

2000-12-01

Target site selection of transposable elements is usually not random but involves some specificity for a DNA sequence or a DNA binding host factor. We have investigated the target site selection of the long terminal repeat-containing retrotransposon Tf1 from the fission yeast Schizosaccharomyces pombe. By monitoring induced transposition events we found that Tf1 integration sites were distributed throughout the genome. Mapping these insertions revealed that Tf1 did not integrate into open reading frames, but occurred preferentially in longer intergenic regions with integration biased towards a region 100-420 bp upstream of the translation start site. Northern blot analysis showed that transcription of genes adjacent to Tf1 insertions was not significantly changed.

Fission yeast retrotransposon Tf1 integration is targeted to 5′ ends of open reading frames

PubMed Central

Behrens, Ralf; Hayles, Jacky; Nurse, Paul

2000-01-01

Target site selection of transposable elements is usually not random but involves some specificity for a DNA sequence or a DNA binding host factor. We have investigated the target site selection of the long terminal repeat-containing retrotransposon Tf1 from the fission yeast Schizosaccharomyces pombe. By monitoring induced transposition events we found that Tf1 integration sites were distributed throughout the genome. Mapping these insertions revealed that Tf1 did not integrate into open reading frames, but occurred preferentially in longer intergenic regions with integration biased towards a region 100–420 bp upstream of the translation start site. Northern blot analysis showed that transcription of genes adjacent to Tf1 insertions was not significantly changed. PMID:11095681

"We Are in This Together": Common Group Identity Predicts Majority Members' Active Acculturation Efforts to Integrate Immigrants.

PubMed

Kunst, Jonas R; Thomsen, Lotte; Sam, David L; Berry, John W

2015-10-01

Although integration involves a process of mutual accommodation, the role of majority groups is often downplayed to passive tolerance, leaving immigrants with the sole responsibility for active integration. However, we show that common group identity can actively involve majority members in this process across five studies. Study 1 showed that common identity positively predicted support of integration efforts; Studies 2 and 3 extended these findings, showing that it also predicted real behavior such as monetary donations and volunteering. A decrease in modern racism mediated the relations across these studies, and Studies 4 and 5 further demonstrated that it indeed mediated these effects over and above acculturation expectations and color-blindness, which somewhat compromised integration efforts. Moreover, the last two studies also demonstrated that common, but not dual, groups motivated integration efforts. Common identity appears crucial for securing majorities' altruistic efforts to integrate immigrants and, thus, for achieving functional multiculturalism. © 2015 by the Society for Personality and Social Psychology, Inc.

Cytoreductive conditioning intensity predicts clonal diversity in ADA-SCID retroviral gene therapy patients

PubMed Central

Lill, Georgia R.; Shaw, Kit; Carbonaro-Sarracino, Denise A.; Davila, Alejandra; Sokolic, Robert; Candotti, Fabio; Pellegrini, Matteo

2017-01-01

Retroviral gene therapy has proved efficacious for multiple genetic diseases of the hematopoietic system, but roughly half of clinical gene therapy trial protocols using gammaretroviral vectors have reported leukemias in some of the patients treated. In dramatic contrast, 39 adenosine deaminase–deficient severe combined immunodeficiency (ADA-SCID) patients have been treated with 4 distinct gammaretroviral vectors without oncogenic consequence. We investigated clonal dynamics and diversity in a cohort of 15 ADA-SCID children treated with gammaretroviral vectors and found clear evidence of genotoxicity, indicated by numerous common integration sites near proto-oncogenes and by increased abundance of clones with integrations near MECOM and LMO2. These clones showed stable behavior over multiple years and never expanded to the point of dominance or dysplasia. One patient developed a benign clonal dominance that could not be attributed to insertional mutagenesis and instead likely resulted from expansion of a transduced natural killer clone in response to chronic Epstein-Barr virus viremia. Clonal diversity and T-cell repertoire, measured by vector integration site sequencing and T-cell receptor β-chain rearrangement sequencing, correlated significantly with the amount of busulfan preconditioning delivered to patients and to CD34+ cell dose. These data, in combination with results of other ADA-SCID gene therapy trials, suggest that disease background may be a crucial factor in leukemogenic potential of retroviral gene therapy and underscore the importance of cytoreductive conditioning in this type of gene therapy approach. PMID:28351939

Cytoreductive conditioning intensity predicts clonal diversity in ADA-SCID retroviral gene therapy patients.

PubMed

Cooper, Aaron R; Lill, Georgia R; Shaw, Kit; Carbonaro-Sarracino, Denise A; Davila, Alejandra; Sokolic, Robert; Candotti, Fabio; Pellegrini, Matteo; Kohn, Donald B

2017-05-11

Retroviral gene therapy has proved efficacious for multiple genetic diseases of the hematopoietic system, but roughly half of clinical gene therapy trial protocols using gammaretroviral vectors have reported leukemias in some of the patients treated. In dramatic contrast, 39 adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) patients have been treated with 4 distinct gammaretroviral vectors without oncogenic consequence. We investigated clonal dynamics and diversity in a cohort of 15 ADA-SCID children treated with gammaretroviral vectors and found clear evidence of genotoxicity, indicated by numerous common integration sites near proto-oncogenes and by increased abundance of clones with integrations near MECOM and LMO2 These clones showed stable behavior over multiple years and never expanded to the point of dominance or dysplasia. One patient developed a benign clonal dominance that could not be attributed to insertional mutagenesis and instead likely resulted from expansion of a transduced natural killer clone in response to chronic Epstein-Barr virus viremia. Clonal diversity and T-cell repertoire, measured by vector integration site sequencing and T-cell receptor β-chain rearrangement sequencing, correlated significantly with the amount of busulfan preconditioning delivered to patients and to CD34 + cell dose. These data, in combination with results of other ADA-SCID gene therapy trials, suggest that disease background may be a crucial factor in leukemogenic potential of retroviral gene therapy and underscore the importance of cytoreductive conditioning in this type of gene therapy approach.

Bronze Age pottery from the Aeolian Islands: definition of Temper Compositional Reference Units by an integrated mineralogical and microchemical approach

NASA Astrophysics Data System (ADS)

Brunelli, D.; Levi, S. T.; Fragnoli, P.; Renzulli, A.; Santi, P.; Paganelli, E.; Martinelli, M. C.

2013-12-01

An integrated microchemical-petrographic approach is here proposed to discriminate the provenance of archaeological pottery artefacts from distinct production centres. Our study focuses on a statistically significant sampling ( n=186) of volcanic temper-bearing potteries representative of the manufacturing and dispersion among the islands of the Aeolian Archipelago during the Bronze Age. The widespread establishment of new settlements and the abundant recovery of Aeolian-made ceramic in southern Italy attest for the increased vitality of the Archipelago during the Capo Graziano culture (Early Bronze Age-Middle Bronze Age 2; 2300-1430 BC). Potteries from three of the main known ancient communities (Lipari, Filicudi and Stromboli) have been studied integrating old collections and newly excavated material. Volcanic tempers have been first investigated through multivariate analyses of relative abundances of mineral and rock clasts along with petrographic characters. In addition, we performed in-situ mineral chemistry microanalyses by Electron Microprobe and Laser Ablation—Inductively Coupled Plasma Mass Spectrometry to assess major and trace element composition of the most common mineral phases. Four Temper Compositional Reference Units have been recognised based on compositional trends. Two units (AI and AX) are unequivocally distinct by their peculiar trace element enrichment and petrographic composition; they mostly contain samples from the sites of Lipari and Stromboli, respectively. Units AIV and AVIII, restricted to the sites of Filicudi and Stromboli, show distinct petrographic characters but overlapped geochemical fingerprints.

Psychiatric risk factor ANK3/Ankyrin-G nanodomains regulate the structure and function of glutamatergic synapses

PubMed Central

Smith, Katharine R.; Kopeikina, Katherine J.; Fawcett-Patel, Jessica M.; Leaderbrand, Katherine; Gao, Ruoqi; Schürmann, Britta; Myczek, Kristoffer; Radulovic, Jelena; Swanson, Geoffrey T.; Penzes, Peter

2014-01-01

Summary Recent evidence implicates glutamatergic synapses as key pathogenic sites in psychiatric disorders. Common and rare variants in the ANK3 gene, encoding ankyrin-G, have been associated with bipolar disorder, schizophrenia, and autism. Here we demonstrate that ankyrin-G is integral to AMPAR-mediated synaptic transmission and maintenance of spine morphology. Using super-resolution microscopy we find that ankyrin-G forms distinct nanodomain structures within the spine head and neck. At these sites, it modulates mushroom spine structure and function, likely as a perisynaptic scaffold and barrier within the spine neck. Neuronal activity promotes ankyrin-G accumulation in distinct spine subdomains, where it differentially regulates NMDA receptor-dependent plasticity. These data implicate subsynaptic nanodomains containing a major psychiatric risk molecule, ankyrin-G, as having location-specific functions, and opens directions for basic and translational investigation of psychiatric risk molecules. PMID:25374361

Extreme disorder in an ultrahigh-affinity protein complex

NASA Astrophysics Data System (ADS)

Borgia, Alessandro; Borgia, Madeleine B.; Bugge, Katrine; Kissling, Vera M.; Heidarsson, Pétur O.; Fernandes, Catarina B.; Sottini, Andrea; Soranno, Andrea; Buholzer, Karin J.; Nettels, Daniel; Kragelund, Birthe B.; Best, Robert B.; Schuler, Benjamin

2018-03-01

Molecular communication in biology is mediated by protein interactions. According to the current paradigm, the specificity and affinity required for these interactions are encoded in the precise complementarity of binding interfaces. Even proteins that are disordered under physiological conditions or that contain large unstructured regions commonly interact with well-structured binding sites on other biomolecules. Here we demonstrate the existence of an unexpected interaction mechanism: the two intrinsically disordered human proteins histone H1 and its nuclear chaperone prothymosin-α associate in a complex with picomolar affinity, but fully retain their structural disorder, long-range flexibility and highly dynamic character. On the basis of closely integrated experiments and molecular simulations, we show that the interaction can be explained by the large opposite net charge of the two proteins, without requiring defined binding sites or interactions between specific individual residues. Proteome-wide sequence analysis suggests that this interaction mechanism may be abundant in eukaryotes.

Migration stopover ecology of western avian populations: A southwestern migration workshop

USGS Publications Warehouse

Skagen, Susan K.; Melcher, Cynthia P.; Hazelwood, Rob

2004-01-01

Workshop participants discussed a coordinated approach for addressing immediate research needs regarding migration patterns and crucial stopover sites and types. They envisioned a three­-tiered, coordinated approach: (1) long-term research to address effects of climate change and other large-scale patterns, (2) intensive, short-term survey and monitoring efforts using a stratified random design within habitats of interest to elucidate regional patterns of distribution and habitat use, and (3) research conducted at existing survey and banding sites to address more in-depth questions (e.g., rates of lipid deposition, microhabitat use, isotope analyses). There was considerable interest in developing common research proposals to blend the broad expertise represented at this workshop. A second meeting is recommended to build on the momentum of these discussions, to facilitate collaborations, and further the goals of integrated approaches to broadscale research on migration stopover ecology. 

Application of Multiprotocol Medical Imaging Communications and an Extended DICOM WADO Service in a Teleradiology Architecture

PubMed Central

Koutelakis, George V.; Anastassopoulos, George K.; Lymberopoulos, Dimitrios K.

2012-01-01

Multiprotocol medical imaging communication through the Internet is more flexible than the tight DICOM transfers. This paper introduces a modular multiprotocol teleradiology architecture that integrates DICOM and common Internet services (based on web, FTP, and E-mail) into a unique operational domain. The extended WADO service (a web extension of DICOM) and the other proposed services allow access to all levels of the DICOM information hierarchy as opposed to solely Object level. A lightweight client site is considered adequate, because the server site of the architecture provides clients with service interfaces through the web as well as invulnerable space for temporary storage, called as User Domains, so that users fulfill their applications' tasks. The proposed teleradiology architecture is pilot implemented using mainly Java-based technologies and is evaluated by engineers in collaboration with doctors. The new architecture ensures flexibility in access, user mobility, and enhanced data security. PMID:22489237

Integrative Families and Systems Treatment: A Middle Path toward Integrating Common and Specific Factors in Evidence-Based Family Therapy

ERIC Educational Resources Information Center

Fraser, J. Scott; Solovey, Andrew D.; Grove, David; Lee, Mo Yee; Greene, Gilbert J.

2012-01-01

A moderate common factors approach is proposed as a synthesis or middle path to integrate common and specific factors in evidence-based approaches to high-risk youth and families. The debate in family therapy between common and specific factors camps is reviewed and followed by suggestions from the literature for synthesis and creative flexibility…

Site systems engineering fiscal year 1999 multi-year work plan (MYWP) update for WBS 1.8.2.2

DOE Office of Scientific and Technical Information (OSTI.GOV)

GRYGIEL, M.L.

1998-10-08

Manage the Site Systems Engineering process to provide a traceable integrated requirements-driven, and technically defensible baseline. Through the Site Integration Group(SIG), Systems Engineering ensures integration of technical activities across all site projects. Systems Engineering's primary interfaces are with the RL Project Managers, the Project Direction Office and with the Project Major Subcontractors, as well as with the Site Planning organization. Systems Implementation: (1) Develops, maintains, and controls the site integrated technical baseline, ensures the Systems Engineering interfaces between projects are documented, and maintain the Site Environmental Management Specification. (2) Develops and uses dynamic simulation models for verification of the baselinemore » and analysis of alternatives. (3) Performs and documents fictional and requirements analyses. (4) Works with projects, technology management, and the SIG to identify and resolve technical issues. (5) Supports technical baseline information for the planning and budgeting of the Accelerated Cleanup Plan, Multi-Year Work Plans, Project Baseline Summaries as well as performance measure reporting. (6) Works with projects to ensure the quality of data in the technical baseline. (7) Develops, maintains and implements the site configuration management system.« less

OVERVIEW OF ENHANCED HANFORD SINGLE-SHELL TANK (SST) INTEGRITY PROJECT - 12128

DOE Office of Scientific and Technical Information (OSTI.GOV)

VENETZ TJ; BOOMER KD; WASHENFELDER DJ

2012-01-25

To improve the understanding of the single-shell tanks integrity, Washington River Protection Solutions, LLC, the USDOE Hanford Site tank contractor, developed an enhanced Single-Shell Tank (SST) Integrity Project in 2009. An expert panel on SST integrity, consisting of various subject matters experts in industry and academia, was created to provide recommendations supporting the development of the project. This panel developed 33 recommendations in four main areas of interest: structural integrity, liner degradation, leak integrity and prevention, and mitigation of contamination migration, Seventeen of these recommendations were used to develop the basis for the M-45-10-1 Change Package for the Hanford Federalmore » Agreement and Compliance Order, which is also known as the Tri-Party Agreement. The change package identified two phases of work for SST integrity. The initial phase has been focused on efforts to envelope the integrity of the tanks. The initial phase was divided into two primary areas of investigation: structural integrity and leak integrity. If necessary based on the outcome from the initial work, a second phase would be focused on further definition of the integrity of the concrete and liners. Combined these two phases are designed to support the formal integrity assessment of the Hanford SSTs in 2018 by Independent Qualified Registered Engineer. The work to further define the DOE's understanding of the structural integrity SSTs involves preparing a modern Analysis of Record using a finite element analysis program. Structural analyses of the SSTs have been conducted since 1957, but these analyses used analog calculation, less rigorous models, or focused on individual structures. As such, an integrated understanding of all of the SSTs has not been developed to modern expectations. In support of this effort, other milestones will address the visual inspection of the tank concrete and the collection of concrete core samples from the tanks for analysis of current mechanics properties. The work on the liner leak integrity has examined the leaks from 23 tanks with liner failures. Individual leak assessments are being developed for each tank to identify the leak cause and location. Also a common cause study is being performed to take the data from individual tanks to look for trends in the failure. Supporting this work is an assessment of the leak rate from tanks at both Hanford and the Savannah River Site and a new method to locate leak sites in tank liner using ionic conductivity. A separate activity is being conducted to examine the propensity for corrosion in select single shell tanks with aggressive waste layers. The work for these two main efforts will provide the basis for the phase two planning. If the margins identified aren't sufficient to ensure the integrity through the life of the mission, phase two would focus on activities to further enhance the understanding of tank integrity. Also coincident with any phase-two work would be the integrity analysis for the tanks, which would be complete in 2018. With delays in the completion of waste treatment facilities at Hanford, greater reliance on safe, continued storage of waste in the single shell tanks is increased in importance. The goal of integrity assessment would provide basis to continue SST activities till the end of the treatment mission.« less

Recording, monitoring and managing the conservation of historic sites: a new application for BGS·SIGMA

NASA Astrophysics Data System (ADS)

Tracey, Emily; Smith, Nichola; Lawrie, Ken

2017-04-01

The principles behind, and the methods of, digital data capture can be applied across many scientific, and other, disciplines, as can be demonstrated by the use of a custom modified version of the British Geological Survey's System for Integrated Geoscience Mapping, (BGS·SIGMA), for the capture of data for use in the conservation of Scottish built heritage. Historic Environment Scotland (HES), an executive agency of the Scottish Government charged with safeguarding the nation's historic environment, is directly responsible for 345 sites of national significance, most of which are built from stone. In common with many other heritage organisations, HES needs a system that can capture, store and present conservation, maintenance and condition indicator information for single or multiple historic sites; this system would then be used to better target and plan effective programmes of maintenance and repair. To meet this need, the British Geological Survey (BGS) has worked with HES to develop an integrated digital site assessment system that provides a refined survey process for stone-built (and other) historic sites. Based on BGS·SIGMA—an integrated workflow underpinned by a geo-spatial platform for data capture and interpretation—the new system is built on top of ESRI's ArcGIS software, and underpinned by a relational database. Users can, in the field or in the office, populate custom-built data entry forms to record maintenance issues and repair specifications for architectural elements ranging from individual blocks of stone to entire building elevations. Photographs, sketches, and digital documents can be linked to architectural elements to enhance the usability of the data. Predetermined data fields and supporting dictionaries constrain the input parameters, ensuring a high degree of standardisation in the datasets and, therefore, enabling highly consistent data extraction and querying. The GIS presentation of the data provides a powerful and versatile planning tool for scheduling works, specifying materials, identifying the skills needed for repairs, and allocating resources more effectively and efficiently. Physical alterations and changes in the overall condition of a single site, or a group of sites can be monitored accurately over time by repeating the original survey (e.g. every 5 years). Other datasets can be linked to the database and other geospatially referenced datasets can be superimposed in GIS, adding considerably to the scope and utility of the system. The system can be applied to any geospatially referenced object in a wide range of situations thus providing many potential applications in conservation, archaeology and other related fields.

Enhanced integration of large DNA into E. coli chromosome by CRISPR/Cas9.

PubMed

Chung, Mu-En; Yeh, I-Hsin; Sung, Li-Yu; Wu, Meng-Ying; Chao, Yun-Peng; Ng, I-Son; Hu, Yu-Chen

2017-01-01

Metabolic engineering often necessitates chromosomal integration of multiple genes but integration of large genes into Escherichia coli remains difficult. CRISPR/Cas9 is an RNA-guided system which enables site-specific induction of double strand break (DSB) and programmable genome editing. Here, we hypothesized that CRISPR/Cas9-triggered DSB could enhance homologous recombination and augment integration of large DNA into E. coli chromosome. We demonstrated that CRISPR/Cas9 system was able to trigger DSB in >98% of cells, leading to subsequent cell death, and identified that mutagenic SOS response played roles in the cell survival. By optimizing experimental conditions and combining the λ-Red proteins and linear dsDNA, CRISPR/Cas9-induced DSB enabled homologous recombination of the donor DNA and replacement of lacZ gene in the MG1655 strain at efficiencies up to 99%, and allowed high fidelity, scarless integration of 2.4, 3.9, 5.4, and 7.0 kb DNA at efficiencies approaching 91%, 92%, 71%, and 61%, respectively. The CRISPR/Cas9-assisted gene integration also functioned in different E. coli strains including BL21 (DE3) and W albeit at different efficiencies. Taken together, our methodology facilitated precise integration of dsDNA as large as 7 kb into E. coli with efficiencies exceeding 60%, thus significantly ameliorating the editing efficiency and overcoming the size limit of integration using the commonly adopted recombineering approach. Biotechnol. Bioeng. 2017;114: 172-183. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Packaging of Human Chromosome 19-Specific Adeno-Associated Virus (AAV) Integration Sites in AAV Virions during AAV Wild-Type and Recombinant AAV Vector Production

PubMed Central

Hüser, Daniela; Weger, Stefan; Heilbronn, Regine

2003-01-01

Adeno-associated virus type 2 (AAV-2) establishes latency by site-specific integration into a unique locus on human chromosome 19, called AAVS1. During the development of a sensitive real-time PCR assay for site-specific integration, AAV-AAVS1 junctions were reproducibly detected in highly purified AAV wild-type and recombinant AAV vector stocks. A series of controls documented that the junctions were packaged in AAV capsids and were newly generated during a single round of AAV production. Cloned junctions displayed variable AAV sequences fused to AAVS1. These data suggest that packaged junctions represent footprints of AAV integration during productive infection. Apparently, AAV latency established by site-specific integration and the helper virus-dependent, productive AAV cycle are more closely related than previously thought. PMID:12663794

Physician groups' use of data from patient experience surveys.

PubMed

Friedberg, Mark W; SteelFisher, Gillian K; Karp, Melinda; Schneider, Eric C

2011-05-01

In Massachusetts, physician groups' performance on validated surveys of patient experience has been publicly reported since 2006. Groups also receive detailed reports of their own performance, but little is known about how physician groups have responded to these reports. To examine whether and how physician groups are using patient experience data to improve patient care. During 2008, we conducted semi-structured interviews with the leaders of 72 participating physician groups (out of 117 groups receiving patient experience reports). Based on leaders' responses, we identified three levels of engagement with patient experience reporting: no efforts to improve (level 1), efforts to improve only the performance of low-scoring physicians or practice sites (level 2), and efforts to improve group-wide performance (level 3). Groups' level of engagement and specific efforts to improve patient care. Forty-four group leaders (61%) reported group-wide improvement efforts (level 3), 16 (22%) reported efforts to improve only the performance of low-scoring physicians or practice sites (level 2), and 12 (17%) reported no performance improvement efforts (level 1). Level 3 groups were more likely than others to have an integrated medical group organizational model (84% vs. 31% at level 2 and 33% at level 1; P < 0.005) and to employ the majority of their physicians (69% vs. 25% and 20%; P < 0.05). Among level 3 groups, the most common targets for improvement were access, communication with patients, and customer service. The most commonly reported improvement initiatives were changing office workflow, providing additional training for nonclinical staff, and adopting or enhancing an electronic health record. Despite statewide public reporting, physician groups' use of patient experience data varied widely. Integrated organizational models were associated with greater engagement, and efforts to enhance clinicians' interpersonal skills were uncommon, with groups predominantly focusing on office workflow and support staff.

Childhood Obesity Research Demonstration Project: Cross-Site Evaluation Methods

PubMed Central

Lee, Rebecca E.; Mehta, Paras; Thompson, Debbe; Bhargava, Alok; Carlson, Coleen; Kao, Dennis; Layne, Charles S.; Ledoux, Tracey; O'Connor, Teresia; Rifai, Hanadi; Gulley, Lauren; Hallett, Allen M.; Kudia, Ousswa; Joseph, Sitara; Modelska, Maria; Ortega, Dana; Parker, Nathan; Stevens, Andria

2015-01-01

Abstract Introduction: The Childhood Obesity Research Demonstration (CORD) project links public health and primary care interventions in three projects described in detail in accompanying articles in this issue of Childhood Obesity. This article describes a comprehensive evaluation plan to determine the extent to which the CORD model is associated with changes in behavior, body weight, BMI, quality of life, and healthcare satisfaction in children 2–12 years of age. Design/Methods: The CORD Evaluation Center (EC-CORD) will analyze the pooled data from three independent demonstration projects that each integrate public health and primary care childhood obesity interventions. An extensive set of common measures at the family, facility, and community levels were defined by consensus among the CORD projects and EC-CORD. Process evaluation will assess reach, dose delivered, and fidelity of intervention components. Impact evaluation will use a mixed linear models approach to account for heterogeneity among project-site populations and interventions. Sustainability evaluation will assess the potential for replicability, continuation of benefits beyond the funding period, institutionalization of the intervention activities, and community capacity to support ongoing program delivery. Finally, cost analyses will assess how much benefit can potentially be gained per dollar invested in programs based on the CORD model. Conclusions: The keys to combining and analyzing data across multiple projects include the CORD model framework and common measures for the behavioral and health outcomes along with important covariates at the individual, setting, and community levels. The overall objective of the comprehensive evaluation will develop evidence-based recommendations for replicating and disseminating community-wide, integrated public health and primary care programs based on the CORD model. PMID:25679060

Epidemiology of burns caused by moxibustion in Korea.

PubMed

Yoon, Cheonjae; Cho, Young Soon; Park, Seungchoon; Chung, Sung Phil; Choi, Young Hwan

2016-11-01

Moxibustion, a traditional Chinese treatment that uses dried Artemisia argyi, is a common cause of burns treated in Korean hospitals. We aimed to examine the characteristics of moxibustion-induced burns. This retrospective study examined the records of 59 patients who were treated for moxibustion-induced burns (April 2014-October 2015). All patients completed a questionnaire regarding their general characteristics and moxibustion use. The patients included 16 men and 43 women (average age: 49.1 years, 68 burn sites). Superficial second-degree burns were present at 21 sites, deep second- or third-degree burns at 44 sites, and unknown burns at 3 sites. The most common sites were the lower extremities, abdomen, and upper extremities. The most common practitioners were the patients (27/59, 45.7%) and Oriental medicine practitioners (23/59, 38.9%). The most common locations were the patient's home, Oriental medicine clinic, and moxibustion clinic. The most common reason for moxibustion was pain. Only the burn site was significantly associated with burn depth, and non-abdominal sites were 9.37-fold more likely to involve deep burns (vs. abdominal sites). Korean patients routinely undergo moxibustion, and care must be taken when using moxibustion at non-abdominal sites, due to the risk of deep burns. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Diagnostic accuracy of integrated intravascular ultrasound and optical coherence tomography (IVUS-OCT) system for coronary plaque characterization

NASA Astrophysics Data System (ADS)

Li, Jiawen; Ma, Teng; Mohar, Dilbahar; Correa, Adrian; Minami, Hataka; Jing, Joseph; Zhou, Qifa; Patel, Pranav M.; Chen, Zhongping

2014-03-01

Intravascular ultrasound (IVUS) imaging and optical coherence tomography (OCT), two commonly used intracoronary imaging modalities, play important roles in plaque evaluation. The combined use of IVUS (to visualize the entire plaque volume) and OCT (to quantify the thickness of the plaque cap, if any) is hypothesized to increase plaque diagnostic accuracy. Our group has developed a fully-integrated dual-modality IVUS-OCT imaging system and 3.6F catheter for simultaneous IVUS-OCT imaging with a high resolution and deep penetration depth. However, the diagnostic accuracy of an integrated IVUS-OCT system has not been investigated. In this study, we imaged 175 coronary artery sites (241 regions of interest) from 20 cadavers using our previous reported integrated IVUS-OCT system. IVUS-OCT images were read by two skilled interventional cardiologists. Each region of interest was classified as either calcification, lipid pool or fibrosis. Comparing the diagnosis by cardiologists using IVUSOCT images with the diagnosis by the pathologist, we calculated the sensitivity and specificity for characterization of calcification, lipid pool or fibrosis with this integrated system. In vitro imaging of cadaver coronary specimens demonstrated the complementary nature of these two modalities for plaques classification. A higher accuracy was shown than using a single modality alone.

HPV integration hijacks and multimerizes a cellular enhancer to generate a viral-cellular super-enhancer that drives high viral oncogene expression

PubMed Central

Redmond, Catherine J.; Dooley, Katharine E.; Fu, Haiqing; Gillison, Maura L.; Akagi, Keiko; Symer, David E.; Aladjem, Mirit I.

2018-01-01

Integration of human papillomavirus (HPV) genomes into cellular chromatin is common in HPV-associated cancers. Integration is random, and each site is unique depending on how and where the virus integrates. We recently showed that tandemly integrated HPV16 could result in the formation of a super-enhancer-like element that drives transcription of the viral oncogenes. Here, we characterize the chromatin landscape and genomic architecture of this integration locus to elucidate the mechanisms that promoted de novo super-enhancer formation. Using next-generation sequencing and molecular combing/fiber-FISH, we show that ~26 copies of HPV16 are integrated into an intergenic region of chromosome 2p23.2, interspersed with 25 kb of amplified, flanking cellular DNA. This interspersed, co-amplified viral-host pattern is frequent in HPV-associated cancers and here we designate it as Type III integration. An abundant viral-cellular fusion transcript encoding the viral E6/E7 oncogenes is expressed from the integration locus and the chromatin encompassing both the viral enhancer and a region in the adjacent amplified cellular sequences is strongly enriched in the super-enhancer markers H3K27ac and Brd4. Notably, the peak in the amplified cellular sequence corresponds to an epithelial-cell-type specific enhancer. Thus, HPV16 integration generated a super-enhancer-like element composed of tandem interspersed copies of the viral upstream regulatory region and a cellular enhancer, to drive high levels of oncogene expression. PMID:29364907

WARCProcessor: An Integrative Tool for Building and Management of Web Spam Corpora.

PubMed

Callón, Miguel; Fdez-Glez, Jorge; Ruano-Ordás, David; Laza, Rosalía; Pavón, Reyes; Fdez-Riverola, Florentino; Méndez, Jose Ramón

2017-12-22

In this work we present the design and implementation of WARCProcessor, a novel multiplatform integrative tool aimed to build scientific datasets to facilitate experimentation in web spam research. The developed application allows the user to specify multiple criteria that change the way in which new corpora are generated whilst reducing the number of repetitive and error prone tasks related with existing corpus maintenance. For this goal, WARCProcessor supports up to six commonly used data sources for web spam research, being able to store output corpus in standard WARC format together with complementary metadata files. Additionally, the application facilitates the automatic and concurrent download of web sites from Internet, giving the possibility of configuring the deep of the links to be followed as well as the behaviour when redirected URLs appear. WARCProcessor supports both an interactive GUI interface and a command line utility for being executed in background.

WARCProcessor: An Integrative Tool for Building and Management of Web Spam Corpora

PubMed Central

Callón, Miguel; Fdez-Glez, Jorge; Ruano-Ordás, David; Laza, Rosalía; Pavón, Reyes; Méndez, Jose Ramón

2017-01-01

In this work we present the design and implementation of WARCProcessor, a novel multiplatform integrative tool aimed to build scientific datasets to facilitate experimentation in web spam research. The developed application allows the user to specify multiple criteria that change the way in which new corpora are generated whilst reducing the number of repetitive and error prone tasks related with existing corpus maintenance. For this goal, WARCProcessor supports up to six commonly used data sources for web spam research, being able to store output corpus in standard WARC format together with complementary metadata files. Additionally, the application facilitates the automatic and concurrent download of web sites from Internet, giving the possibility of configuring the deep of the links to be followed as well as the behaviour when redirected URLs appear. WARCProcessor supports both an interactive GUI interface and a command line utility for being executed in background. PMID:29271913

75 FR 76487 - Haldex Brake Corporation, Commercial Vehicle Systems, Including On-Site Leased Workers of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-08

..., Commercial Vehicle Systems, Including On-Site Leased Workers of Johnston Integration Technologies, a... system components. The company reports that workers leased from Johnston Integration Technologies, a... certification to include workers leased from Johnston Integration Technologies, a subsidiary of Johnston...

HIV promoter integration site primarily modulates transcriptional burst size rather than frequency.

PubMed

Skupsky, Ron; Burnett, John C; Foley, Jonathan E; Schaffer, David V; Arkin, Adam P

2010-09-30

Mammalian gene expression patterns, and their variability across populations of cells, are regulated by factors specific to each gene in concert with its surrounding cellular and genomic environment. Lentiviruses such as HIV integrate their genomes into semi-random genomic locations in the cells they infect, and the resulting viral gene expression provides a natural system to dissect the contributions of genomic environment to transcriptional regulation. Previously, we showed that expression heterogeneity and its modulation by specific host factors at HIV integration sites are key determinants of infected-cell fate and a possible source of latent infections. Here, we assess the integration context dependence of expression heterogeneity from diverse single integrations of a HIV-promoter/GFP-reporter cassette in Jurkat T-cells. Systematically fitting a stochastic model of gene expression to our data reveals an underlying transcriptional dynamic, by which multiple transcripts are produced during short, infrequent bursts, that quantitatively accounts for the wide, highly skewed protein expression distributions observed in each of our clonal cell populations. Interestingly, we find that the size of transcriptional bursts is the primary systematic covariate over integration sites, varying from a few to tens of transcripts across integration sites, and correlating well with mean expression. In contrast, burst frequencies are scattered about a typical value of several per cell-division time and demonstrate little correlation with the clonal means. This pattern of modulation generates consistently noisy distributions over the sampled integration positions, with large expression variability relative to the mean maintained even for the most productive integrations, and could contribute to specifying heterogeneous, integration-site-dependent viral production patterns in HIV-infected cells. Genomic environment thus emerges as a significant control parameter for gene expression variation that may contribute to structuring mammalian genomes, as well as be exploited for survival by integrating viruses.

The Integrated Sounding System: Description and Preliminary Observations from TOGA COARE.

NASA Astrophysics Data System (ADS)

Parsons, David; Dabberdt, Walter; Cole, Harold; Hock, Terrence; Martin, Charles; Barrett, Anne-Leslie; Miller, Erik; Spowart, Michael; Howard, Michael; Ecklund, Warner; Carter, David; Gage, Kenneth; Wilson, John

1994-04-01

An Integrated Sounding System (ISS) that combines state-of- the-art remote and in situ sensors into a single transportable facility has been developed jointly by the National Center for Atmospheric Research (NCAR) and the Aeronomy laboratory of the National Oceanic and Atmospheric Administration (NOAA/AL). The instrumentation for each ISS includes a 915-MHz wind profiler, a Radio Acoustic Sounding System (RASS), an Omega-based NAVAID sounding system, and an enhanced surface meteorological station. The general philosophy behind the ISS is that the integration of various measurement systems overcomes each system's respective limitations while taking advantage of its positive attributes. The individual observing systems within the ISS provide high-level data products to a central workstation that manages and integrates these measurements. The ISS software package performs a wide range of functions: real-time data acquisition, database support, and graphical displays; data archival and communications; and operational and post time analysis. The first deployment of the ISS consists of six sites in the western tropical Pacific-four land-based deployments and two ship-based deployments. The sites serve the Coupled Ocean-Atmosphere Response Experiment (COARE) of the Tropical Ocean and Global Atmosphere (TOGA) program and TOGA's enhanced atmospheric monitoring effort. Examples of ISS data taken during this deployment are shown in order to demonstrate the capabilities of this new sounding system and to demonstrate the performance of these in situ and remote sensing instruments in a moist tropical environment. In particular, a strong convective outflow with a pronounced impact of the atmospheric boundary layer and heat fluxes from the ocean surface was examined with a shipboard ISS. If these strong outflows commonly occur, they may prove to be an important component of the surface energy budget of the western tropical Pacific.

Site-Specific Mobilization of Vinyl Chloride Respiration Islands by a Mechanism Common in Dehalococcoides

PubMed Central

2011-01-01

Background Vinyl chloride is a widespread groundwater pollutant and Group 1 carcinogen. A previous comparative genomic analysis revealed that the vinyl chloride reductase operon, vcrABC, of Dehalococcoides sp. strain VS is embedded in a horizontally-acquired genomic island that integrated at the single-copy tmRNA gene, ssrA. Results We targeted conserved positions in available genomic islands to amplify and sequence four additional vcrABC -containing genomic islands from previously-unsequenced vinyl chloride respiring Dehalococcoides enrichments. We identified a total of 31 ssrA-specific genomic islands from Dehalococcoides genomic data, accounting for 47 reductive dehalogenase homologous genes and many other non-core genes. Sixteen of these genomic islands contain a syntenic module of integration-associated genes located adjacent to the predicted site of integration, and among these islands, eight contain vcrABC as genetic 'cargo'. These eight vcrABC -containing genomic islands are syntenic across their ~12 kbp length, but have two phylogenetically discordant segments that unambiguously differentiate the integration module from the vcrABC cargo. Using available Dehalococcoides phylogenomic data we estimate that these ssrA-specific genomic islands are at least as old as the Dehalococcoides group itself, which in turn is much older than human civilization. Conclusions The vcrABC -containing genomic islands are a recently-acquired subset of a diverse collection of ssrA-specific mobile elements that are a major contributor to strain-level diversity in Dehalococcoides, and may have been throughout its evolution. The high similarity between vcrABC sequences is quantitatively consistent with recent horizontal acquisition driven by ~100 years of industrial pollution with chlorinated ethenes. PMID:21635780

Molecular mechanisms of retroviral integration site selection

PubMed Central

Kvaratskhelia, Mamuka; Sharma, Amit; Larue, Ross C.; Serrao, Erik; Engelman, Alan

2014-01-01

Retroviral replication proceeds through an obligate integrated DNA provirus, making retroviral vectors attractive vehicles for human gene-therapy. Though most of the host cell genome is available for integration, the process of integration site selection is not random. Retroviruses differ in their choice of chromatin-associated features and also prefer particular nucleotide sequences at the point of insertion. Lentiviruses including HIV-1 preferentially integrate within the bodies of active genes, whereas the prototypical gammaretrovirus Moloney murine leukemia virus (MoMLV) favors strong enhancers and active gene promoter regions. Integration is catalyzed by the viral integrase protein, and recent research has demonstrated that HIV-1 and MoMLV targeting preferences are in large part guided by integrase-interacting host factors (LEDGF/p75 for HIV-1 and BET proteins for MoMLV) that tether viral intasomes to chromatin. In each case, the selectivity of epigenetic marks on histones recognized by the protein tether helps to determine the integration distribution. In contrast, nucleotide preferences at integration sites seem to be governed by the ability for the integrase protein to locally bend the DNA duplex for pairwise insertion of the viral DNA ends. We discuss approaches to alter integration site selection that could potentially improve the safety of retroviral vectors in the clinic. PMID:25147212

Blueprint for Integration of Academic and Vocational Education.

ERIC Educational Resources Information Center

Clark, Gail

This guide to integrating academic and vocational education is the result of extensive research and experimentation at four pilot sites throughout Texas. The introductory section outlines the project philosophy and activities and describes the pilot sites. Examined in a background section are the origin and nature of integration, important…

Integrated grassland observation sites and integrated cropland observation sites at El Reno, Oklahoma

USDA-ARS?s Scientific Manuscript database

With the financial support from the National Science Foundation and the USDA National Institute of Food and Agriculture, a team of researchers from the University of Oklahoma and the USDA ARS Grazinglands Research Laboratory have worked together and established two Integrated Grassland Observation s...

Cell-mediated remodeling of biomimetic encapsulating hydrogels triggered by adipogenic differentiation of adipose stem cells.

PubMed

Clevenger, Tracy N; Luna, Gabriel; Boctor, Daniel; Fisher, Steven K; Clegg, Dennis O

2016-01-01

One of the most common regenerative therapies is autologous fat grafting, which frequently suffers from unexpected volume loss. One approach is to deliver adipose stem cells encapsulated in the engineered hydrogels supportive of cell survival, differentiation, and integration after transplant. We describe an encapsulating, biomimetic poly(ethylene)-glycol hydrogel, with embedded peptides for attachment and biodegradation. Poly(ethylene)-glycol hydrogels containing an Arg-Gly-Asp attachment sequence and a matrix metalloprotease 3/10 cleavage site supported adipose stem cell survival and showed remodeling initiated by adipogenic differentiation. Arg-Gly-Asp-matrix metalloprotease 3/10 cleavage site hydrogels showed an increased number and area of lacunae or holes after adipose stem cell differentiation. Image analysis of adipose stem cells in Arg-Gly-Asp-matrix metalloprotease 3/10 cleavage site hydrogels showed larger Voronoi domains, while cell density remained unchanged. The differentiated adipocytes residing within these newly remodeled spaces express proteins and messenger RNAs indicative of adipocytic differentiation. These engineered scaffolds may provide niches for stem cell differentiation and could prove useful in soft tissue regeneration.

Cell-mediated remodeling of biomimetic encapsulating hydrogels triggered by adipogenic differentiation of adipose stem cells

PubMed Central

Clevenger, Tracy N; Luna, Gabriel; Boctor, Daniel; Fisher, Steven K; Clegg, Dennis O

2016-01-01

One of the most common regenerative therapies is autologous fat grafting, which frequently suffers from unexpected volume loss. One approach is to deliver adipose stem cells encapsulated in the engineered hydrogels supportive of cell survival, differentiation, and integration after transplant. We describe an encapsulating, biomimetic poly(ethylene)-glycol hydrogel, with embedded peptides for attachment and biodegradation. Poly(ethylene)-glycol hydrogels containing an Arg–Gly–Asp attachment sequence and a matrix metalloprotease 3/10 cleavage site supported adipose stem cell survival and showed remodeling initiated by adipogenic differentiation. Arg–Gly–Asp–matrix metalloprotease 3/10 cleavage site hydrogels showed an increased number and area of lacunae or holes after adipose stem cell differentiation. Image analysis of adipose stem cells in Arg–Gly–Asp–matrix metalloprotease 3/10 cleavage site hydrogels showed larger Voronoi domains, while cell density remained unchanged. The differentiated adipocytes residing within these newly remodeled spaces express proteins and messenger RNAs indicative of adipocytic differentiation. These engineered scaffolds may provide niches for stem cell differentiation and could prove useful in soft tissue regeneration. PMID:27733898

Differential DNA methylation patterns of polycystic ovarian syndrome in whole blood of Chinese women.

PubMed

Li, Shuxia; Zhu, Dongyi; Duan, Hongmei; Ren, Anran; Glintborg, Dorte; Andersen, Marianne; Skov, Vibe; Thomassen, Mads; Kruse, Torben; Tan, Qihua

2017-03-28

As a universally common endocrinopathy in women of reproductive age, the polycystic ovarian syndrome is characterized by composite clinical phenotypes reflecting the contributions of reproductive impact of ovarian dysfunction and metabolic abnormalities with widely varying symptoms resulting from interference of the genome with the environment through integrative biological mechanisms including epigenetics. We have performed a genome-wide DNA methylation analysis on polycystic ovarian syndrome and identified a substantial number of genomic sites differentially methylated in the whole blood of PCOS patients and healthy controls (52 sites, false discovery rate < 0.05 and corresponding p value < 5.68e-06), highly consistently replicating biological pathways extensively implicated in immunity and immunity-related inflammatory disorders (false discovery rate < 0.05) that were reportedly regulated in the DNA methylome from ovarian tissue under PCOS condition. Most importantly, our genome-wide profiling focusing on PCOS patients revealed a large number of DNA methylation sites and their enriched functional pathways significantly associated with diverse clinical features (levels of prolactin, estradiol, progesterone and menstrual cycle) that could serve as novel molecular basis of the clinical heterogeneity observed in PCOS women.

Volcanology curricula development aided by online educational resource

USGS Publications Warehouse

Poland, Michael P.; van der Hoeven Kraft, Katrien J.; Teasdale, Rachel

2011-01-01

Volcanic activity is an excellent hook for engaging college and university students in geoscience classes. An increasing number of Internet-accessible real-time and near–real time volcano monitoring data are now available and constitute an important resource for geoscience education; however, relatively few data sets are comprehensive, and many lack background information to aid in interpretation. In response to the need for organized, accessible, and well-documented volcano education resources, the U.S. Geological Survey's Hawaiian Volcano Observatory (HVO), in collaboration with NASA and the University of Hawai`i at Manoa, established the Volcanoes Exploration Project: Pu`u `Ō`ō (VEPP). The VEPP Web site (http://vepp.wr.usgs.gov) is an educational resource that provides access, in near real time, to geodetic, seismic, and geologic data from the active Pu`u `Ō`ō eruptive vent on Kilauea volcano, Hawaii, along with background and context information. A strength of the VEPP site is the common theme of the Pu`u `Ō`ō eruption, which allows the site to be revisited multiple times to demonstrate different principles and integrate many aspects of volcanology.

Remote carboxylation of halogenated aliphatic hydrocarbons with carbon dioxide

NASA Astrophysics Data System (ADS)

Juliá-Hernández, Francisco; Moragas, Toni; Cornella, Josep; Martin, Ruben

2017-05-01

Catalytic carbon-carbon bond formation has enabled the streamlining of synthetic routes when assembling complex molecules. It is particularly important when incorporating saturated hydrocarbons, which are common motifs in petrochemicals and biologically relevant molecules. However, cross-coupling methods that involve alkyl electrophiles result in catalytic bond formation only at specific and previously functionalized sites. Here we describe a catalytic method that is capable of promoting carboxylation reactions at remote and unfunctionalized aliphatic sites with carbon dioxide at atmospheric pressure. The reaction occurs via selective migration of the catalyst along the hydrocarbon side-chain with excellent regio- and chemoselectivity, representing a remarkable reactivity relay when compared with classical cross-coupling reactions. Our results demonstrate that site-selectivity can be switched and controlled, enabling the functionalization of less-reactive positions in the presence of a priori more reactive ones. Furthermore, we show that raw materials obtained in bulk from petroleum processing, such as alkanes and unrefined mixtures of olefins, can be used as substrates. This offers an opportunity to integrate a catalytic platform en route to valuable fatty acids by transforming petroleum-derived feedstocks directly.

Rural access to clinical pharmacy services.

PubMed

Patterson, Brandon J; Kaboli, Peter J; Tubbs, Traviss; Alexander, Bruce; Lund, Brian C

2014-01-01

To examine the impact of rural residence and primary care site on use of clinical pharmacy services (CPS) and to describe the use of clinical telepharmacy within the Veterans Health Administration (VHA) health care system. Using 2011 national VHA data, the frequency of patients with CPS encounters was compared across patient residence (urban or rural) and principal site of primary care (medical center, urban clinic, or rural clinic). The likelihood of CPS utilization was estimated with random effects logistic regression. Individual service types (e.g., anticoagulation clinics) and delivery modes (e.g., telehealth) were also examined. Of 3,040,635 patients, 711,348 (23.4%) received CPS. Service use varied by patient residence (urban: 24.9%; rural: 19.7%) and principal site of primary care (medical center: 25.9%; urban clinic: 22.5%; rural clinic: 17.6%). However, in adjusted analyses, urban-rural differences were explained primarily by primary care site and less so by patient residence. Similar findings were observed for individual CPS types. Telehealth encounters were common, accounting for nearly one-half of patients receiving CPS. Video telehealth was infrequent (<0.2%), but more common among patients of rural clinics than those receiving CPS at medical centers (odds ratio [OR] = 9.7; 95% CI 9.0-10.5). We identified a potential disparity between rural and urban patients' access to CPS, which was largely explained by greater reliance on community clinics for primary care than on medical centers. Future research is needed to determine if this disparity will be alleviated by emerging organizational changes, including expanding telehealth capacity and integrating pharmacists into primary care teams, and whether lessons learned at VHA translate to other settings.

Synthesizing plant phenological indicators from multispecies datasets

NASA Astrophysics Data System (ADS)

Rutishauser, This; Peñuelas, Josep; Filella, Iolanda; Gehrig, Regula; Scherrer, Simon C.; Röthlisberger, Christian

2014-05-01

Changes in the seasonality of life cycles of plants from phenological observations are traditionally analysed at the species level. Trends and correlations with main environmental driving variables show a coherent picture across the globe. The question arises whether there is an integrated phenological signal across species that describes common interannual variability. Is there a way to express synthetic phenological indicators from multispecies datasets that serve decision makers as usefull tools? Can these indicators be derived in such a robust way that systematic updates yield necessary information for adaptation measures? We address these questions by analysing multi-species phenological data sets with leaf-unfolding and flowering observations from 30 sites across Europe between 40° and 63°N including data from PEP725, the Swiss Plant Phenological Observation Network and one legacy data set. Starting in 1951 the data sets were synthesized by multivariate analysis (Principal Component Analysis). The representativeness of the site specific indicator was tested against subsets including only leaf-unfolding or flowering phases, and by a comparison with a 50% random sample of the available phenophases for 500 time steps. Results show that a synthetic indicators explains up to 79% of the variance at each site - usually 40-50% or more. Robust linear trends over the common period 1971-2000 indicate an overall change of the indicator of -0.32 days/year with lower uncertainty than previous studies. Advances were more pronounced in southern and northern Europe. The indicator-based analysis provides a promising tool for synthesizing site-based plant phenological records and is a companion to, and validating data for, an increasing number of phenological measurements derived from phenological models and satellite sensors.

Assimilating MODIS-based albedo and snow cover fraction into the Common Land Model to improve snow depth simulation with direct insertion and deterministic ensemble Kalman filter methods

NASA Astrophysics Data System (ADS)

Xu, Jianhui; Shu, Hong

2014-09-01

This study assesses the analysis performance of assimilating the Moderate Resolution Imaging Spectroradiometer (MODIS)-based albedo and snow cover fraction (SCF) separately or jointly into the physically based Common Land Model (CoLM). A direct insertion method (DI) is proposed to assimilate the black and white-sky albedos into the CoLM. The MODIS-based albedo is calculated with the MODIS bidirectional reflectance distribution function (BRDF) model parameters product (MCD43B1) and the solar zenith angle as estimated in the CoLM for each time step. Meanwhile, the MODIS SCF (MOD10A1) is assimilated into the CoLM using the deterministic ensemble Kalman filter (DEnKF) method. A new DEnKF-albedo assimilation scheme for integrating the DI and DEnKF assimilation schemes is proposed. Our assimilation results are validated against in situ snow depth observations from November 2008 to March 2009 at five sites in the Altay region of China. The experimental results show that all three data assimilation schemes can improve snow depth simulations. But overall, the DEnKF-albedo assimilation shows the best analysis performance as it significantly reduces the bias and root-mean-square error (RMSE) during the snow accumulation and ablation periods at all sites except for the Fuyun site. The SCF assimilation via DEnKF produces better results than the albedo assimilation via DI, implying that the albedo assimilation that indirectly updates the snow depth state variable is less efficient than the direct SCF assimilation. For the Fuyun site, the DEnKF-albedo scheme tends to overestimate the snow depth accumulation with the maximum bias and RMSE values because of the large positive innovation (observation minus forecast).

Discovery of multiple interacting partners of gankyrin, a proteasomal chaperone and an oncoprotein--evidence for a common hot spot site at the interface and its functional relevance.

PubMed

Nanaware, Padma P; Ramteke, Manoj P; Somavarapu, Arun K; Venkatraman, Prasanna

2014-07-01

Gankyrin, a non-ATPase component of the proteasome and a chaperone of proteasome assembly, is also an oncoprotein. Gankyrin regulates a variety of oncogenic signaling pathways in cancer cells and accelerates degradation of tumor suppressor proteins p53 and Rb. Therefore gankyrin may be a unique hub integrating signaling networks with the degradation pathway. To identify new interactions that may be crucial in consolidating its role as an oncogenic hub, crystal structure of gankyrin-proteasome ATPase complex was used to predict novel interacting partners. EEVD, a four amino acid linear sequence seems a hot spot site at this interface. By searching for EEVD in exposed regions of human proteins in PDB database, we predicted 34 novel interactions. Eight proteins were tested and seven of them were found to interact with gankyrin. Affinity of four interactions is high enough for endogenous detection. Others require gankyrin overexpression in HEK 293 cells or occur endogenously in breast cancer cell line- MDA-MB-435, reflecting lower affinity or presence of a deregulated network. Mutagenesis and peptide inhibition confirm that EEVD is the common hot spot site at these interfaces and therefore a potential polypharmacological drug target. In MDA-MB-231 cells in which the endogenous CLIC1 is silenced, trans-expression of Wt protein (CLIC1_EEVD) and not the hot spot site mutant (CLIC1_AAVA) resulted in significant rescue of the migratory potential. Our approach can be extended to identify novel functionally relevant protein-protein interactions, in expansion of oncogenic networks and in identifying potential therapeutic targets. © 2013 Wiley Periodicals, Inc.

A Simulation Approach to Assessing Sampling Strategies for Insect Pests: An Example with the Balsam Gall Midge

PubMed Central

Carleton, R. Drew; Heard, Stephen B.; Silk, Peter J.

2013-01-01

Estimation of pest density is a basic requirement for integrated pest management in agriculture and forestry, and efficiency in density estimation is a common goal. Sequential sampling techniques promise efficient sampling, but their application can involve cumbersome mathematics and/or intensive warm-up sampling when pests have complex within- or between-site distributions. We provide tools for assessing the efficiency of sequential sampling and of alternative, simpler sampling plans, using computer simulation with “pre-sampling” data. We illustrate our approach using data for balsam gall midge (Paradiplosis tumifex) attack in Christmas tree farms. Paradiplosis tumifex proved recalcitrant to sequential sampling techniques. Midge distributions could not be fit by a common negative binomial distribution across sites. Local parameterization, using warm-up samples to estimate the clumping parameter k for each site, performed poorly: k estimates were unreliable even for samples of n∼100 trees. These methods were further confounded by significant within-site spatial autocorrelation. Much simpler sampling schemes, involving random or belt-transect sampling to preset sample sizes, were effective and efficient for P. tumifex. Sampling via belt transects (through the longest dimension of a stand) was the most efficient, with sample means converging on true mean density for sample sizes of n∼25–40 trees. Pre-sampling and simulation techniques provide a simple method for assessing sampling strategies for estimating insect infestation. We suspect that many pests will resemble P. tumifex in challenging the assumptions of sequential sampling methods. Our software will allow practitioners to optimize sampling strategies before they are brought to real-world applications, while potentially avoiding the need for the cumbersome calculations required for sequential sampling methods. PMID:24376556

Quantifying site-specific physical heterogeneity within an estuarine seascape

USGS Publications Warehouse

Kennedy, Cristina G.; Mather, Martha E.; Smith, Joseph M.

2017-01-01

Quantifying physical heterogeneity is essential for meaningful ecological research and effective resource management. Spatial patterns of multiple, co-occurring physical features are rarely quantified across a seascape because of methodological challenges. Here, we identified approaches that measured total site-specific heterogeneity, an often overlooked aspect of estuarine ecosystems. Specifically, we examined 23 metrics that quantified four types of common physical features: (1) river and creek confluences, (2) bathymetric variation including underwater drop-offs, (3) land features such as islands/sandbars, and (4) major underwater channel networks. Our research at 40 sites throughout Plum Island Estuary (PIE) provided solutions to two problems. The first problem was that individual metrics that measured heterogeneity of a single physical feature showed different regional patterns. We solved this first problem by combining multiple metrics for a single feature using a within-physical feature cluster analysis. With this approach, we identified sites with four different types of confluences and three different types of underwater drop-offs. The second problem was that when multiple physical features co-occurred, new patterns of total site-specific heterogeneity were created across the seascape. This pattern of total heterogeneity has potential ecological relevance to structure-oriented predators. To address this second problem, we identified sites with similar types of total physical heterogeneity using an across-physical feature cluster analysis. Then, we calculated an additive heterogeneity index, which integrated all physical features at a site. Finally, we tested if site-specific additive heterogeneity index values differed for across-physical feature clusters. In PIE, the sites with the highest additive heterogeneity index values were clustered together and corresponded to sites where a fish predator, adult striped bass (Morone saxatilis), aggregated in a related acoustic tracking study. In summary, we have shown general approaches to quantifying site-specific heterogeneity.

Site-Specific Integration of Foreign DNA into Minimal Bacterial and Human Target Sequences Mediated by a Conjugative Relaxase

PubMed Central

Agúndez, Leticia; González-Prieto, Coral; Machón, Cristina; Llosa, Matxalen

2012-01-01

Background Bacterial conjugation is a mechanism for horizontal DNA transfer between bacteria which requires cell to cell contact, usually mediated by self-transmissible plasmids. A protein known as relaxase is responsible for the processing of DNA during bacterial conjugation. TrwC, the relaxase of conjugative plasmid R388, is also able to catalyze site-specific integration of the transferred DNA into a copy of its target, the origin of transfer (oriT), present in a recipient plasmid. This reaction confers TrwC a high biotechnological potential as a tool for genomic engineering. Methodology/Principal Findings We have characterized this reaction by conjugal mobilization of a suicide plasmid to a recipient cell with an oriT-containing plasmid, selecting for the cointegrates. Proteins TrwA and IHF enhanced integration frequency. TrwC could also catalyze integration when it is expressed from the recipient cell. Both Y18 and Y26 catalytic tyrosil residues were essential to perform the reaction, while TrwC DNA helicase activity was dispensable. The target DNA could be reduced to 17 bp encompassing TrwC nicking and binding sites. Two human genomic sequences resembling the 17 bp segment were accepted as targets for TrwC-mediated site-specific integration. TrwC could also integrate the incoming DNA molecule into an oriT copy present in the recipient chromosome. Conclusions/Significance The results support a model for TrwC-mediated site-specific integration. This reaction may allow R388 to integrate into the genome of non-permissive hosts upon conjugative transfer. Also, the ability to act on target sequences present in the human genome underscores the biotechnological potential of conjugative relaxase TrwC as a site-specific integrase for genomic modification of human cells. PMID:22292089

A heterogeneous landscape does not guarantee high crop pollination

PubMed Central

Hambäck, Peter A.; Lemessa, Debissa; Nemomissa, Sileshi; Hylander, Kristoffer

2016-01-01

The expansion of pollinator-dependent crops, especially in the developing world, together with reports of worldwide pollinator declines, raises concern of possible yield gaps. Farmers directly reliant on pollination services for food supply often live in regions where our knowledge of pollination services is poor. In a manipulative experiment replicated at 23 sites across an Ethiopian agricultural landscape, we found poor pollination services and severe pollen limitation in a common oil crop. With supplementary pollination, the yield increased on average by 91%. Despite the heterogeneous agricultural matrix, we found a low bee abundance, which may explain poor pollination services. The variation in pollen limitation was unrelated to surrounding forest cover, local bee richness and bee abundance. While practices that commonly increase pollinators (restricted pesticide use, flower strips) are an integral part of the landscape, these elements are apparently insufficient. Management to increase pollination services is therefore in need of urgent investigation. PMID:27629036

Patellar metastasis from primary tumor

PubMed Central

Li, Gang; Shan, Changxing; Sun, Ran; Liu, Song; Chen, Song; Song, Mingzhi; Lu, Ming

2018-01-01

Although bone tumors are frequently located in the knee area, primary tumors of the patella are rare and patellar metastases are even rarer. Knee pain is the most common complaint of patients with patellar metastases. Owing to the low incidence of patellar metastases, misdiagnosis is not unusual. The present review analyzes ~44 cases of patellar metastases originating from distinct primary sites. Reports of malignant tumors of the lung and kidney metastasizing to the patella were more common than those of other patellar metastases. Relative incidence, symptomatology, imaging features, histopathology and treatment options for these patellar metastatic lesions are described respectively along with a review of the literature. Despite numerous experiments demonstrating the reasons for implantation of tumor in patella, the answer to this question has not yet been revealed. In the light of the increasing attention on the diagnosis and the treatment of these lesions, the availability of the integrated information regarding metastases in the patella becomes more relevant. PMID:29434829

Integrating Monitoring and Genetic Methods To Infer Historical Risks of PCBs and DDE to Common and Roseate Terns Nesting Near the New Bedford Harbor Superfund Site (Massachusetts, USA).

PubMed

Nacci, Diane E; Hahn, Mark E; Karchner, Sibel I; Jayaraman, Saro; Mostello, Carolyn; Miller, Kenneth M; Blackwell, Carma Gilchrist; Nisbet, Ian C T

2016-09-20

Common and roseate terns are migratory piscivorous seabirds with major breeding colonies within feeding range of the polychlorinated biphenyl (PCB)-contaminated New Bedford Harbor (NBH, MA, USA) Superfund site. Our longitudinal study shows that before PCB discharges into NBH ceased (late 1970s), tern eggs had very high but variable PCB concentrations. However, egg concentrations of PCBs as well as DDE (1,1-bis(p-chlorophenyl)-2,2-dichloroethene), the degradation product of the ubiquitous global contaminant DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane), have since declined. Rate constants for temporal decline of PCB congeners in tern eggs varied inversely with log10KOW (n-octanol-water partition coefficient), shifting egg congener patterns away from those characterizing NBH sediment. To estimate the toxic effects on tern eggs of PCB dioxin-like congener (DLC) exposures, we extrapolated published laboratory data on common terns to roseate terns by characterizing genetic and functional similarities in species aryl hydrocarbon receptors (AHRs), which mediate DLC sensitivity. Our assessment of contaminant risks suggests that terns breeding near NBH were exposed historically to toxic levels of PCBs and DDE; however, acute effects on tern egg development have become less likely since the 1970s. Our approach demonstrates how comparative genetics at target loci can effectively increase the range of inference for chemical risk assessments from tested to untested and untestable species.

A causal examination of the effects of confounding factors on multimetric indices

USGS Publications Warehouse

Schoolmaster, Donald R.; Grace, James B.; Schweiger, E. William; Mitchell, Brian R.; Guntenspergen, Glenn R.

2013-01-01

The development of multimetric indices (MMIs) as a means of providing integrative measures of ecosystem condition is becoming widespread. An increasingly recognized problem for the interpretability of MMIs is controlling for the potentially confounding influences of environmental covariates. Most common approaches to handling covariates are based on simple notions of statistical control, leaving the causal implications of covariates and their adjustment unstated. In this paper, we use graphical models to examine some of the potential impacts of environmental covariates on the observed signals between human disturbance and potential response metrics. Using simulations based on various causal networks, we show how environmental covariates can both obscure and exaggerate the effects of human disturbance on individual metrics. We then examine from a causal interpretation standpoint the common practice of adjusting ecological metrics for environmental influences using only the set of sites deemed to be in reference condition. We present and examine the performance of an alternative approach to metric adjustment that uses the whole set of sites and models both environmental and human disturbance effects simultaneously. The findings from our analyses indicate that failing to model and adjust metrics can result in a systematic bias towards those metrics in which environmental covariates function to artificially strengthen the metric–disturbance relationship resulting in MMIs that do not accurately measure impacts of human disturbance. We also find that a “whole-set modeling approach” requires fewer assumptions and is more efficient with the given information than the more commonly applied “reference-set” approach.

Patient experience in a coordinated care model featuring diabetes self-management education integrated into the patient-centered medical home.

PubMed

Janiszewski, Debra; O'Brian, Catherine A; Lipman, Ruth D

2015-08-01

The purpose of this study is to gain insight about patient experience of diabetes self-management education in a patient-centered medical home. Six focus groups consisting of 37 people with diabetes, diverse in race and ethnicity, were conducted at 3 sites. Participants described their experience in the program and their challenges in diabetes self-management; they also suggested services to meet their diabetes care needs. The most common theme was ongoing concerns about care and support. There was much discussion about the value of the support provided by health navigators integrated in the diabetes health care team. Frequent concerns expressed by participants centered on personal challenges in engaging in healthy lifestyle behaviors. Ongoing programmatic support of self-management goals was widely valued. Individuals who received health care in a patient-centered medical home and could participate in diabetes self-management education with integrated support valued both activities. The qualitative results from this study suggest need for more formalized exploration of effective means to meet the ongoing support needs of people with diabetes. © 2015 The Author(s).

Documenting Models for Interoperability and Reusability ...

EPA Pesticide Factsheets

Many modeling frameworks compartmentalize science via individual models that link sets of small components to create larger modeling workflows. Developing integrated watershed models increasingly requires coupling multidisciplinary, independent models, as well as collaboration between scientific communities, since component-based modeling can integrate models from different disciplines. Integrated Environmental Modeling (IEM) systems focus on transferring information between components by capturing a conceptual site model; establishing local metadata standards for input/output of models and databases; managing data flow between models and throughout the system; facilitating quality control of data exchanges (e.g., checking units, unit conversions, transfers between software languages); warning and error handling; and coordinating sensitivity/uncertainty analyses. Although many computational software systems facilitate communication between, and execution of, components, there are no common approaches, protocols, or standards for turn-key linkages between software systems and models, especially if modifying components is not the intent. Using a standard ontology, this paper reviews how models can be described for discovery, understanding, evaluation, access, and implementation to facilitate interoperability and reusability. In the proceedings of the International Environmental Modelling and Software Society (iEMSs), 8th International Congress on Environmental Mod

DNA Physical Properties and Nucleosome Positions Are Major Determinants of HIV-1 Integrase Selectivity

PubMed Central

Naughtin, Monica; Haftek-Terreau, Zofia; Xavier, Johan; Meyer, Sam; Silvain, Maud; Jaszczyszyn, Yan; Levy, Nicolas; Miele, Vincent; Benleulmi, Mohamed Salah; Ruff, Marc; Parissi, Vincent; Vaillant, Cédric; Lavigne, Marc

2015-01-01

Retroviral integrases (INs) catalyse the integration of the reverse transcribed viral DNA into the host cell genome. This process is selective, and chromatin has been proposed to be a major factor regulating this step in the viral life cycle. However, the precise underlying mechanisms are still under investigation. We have developed a new in vitro integration assay using physiologically-relevant, reconstituted genomic acceptor chromatin and high-throughput determination of nucleosome positions and integration sites, in parallel. A quantitative analysis of the resulting data reveals a chromatin-dependent redistribution of the integration sites and establishes a link between integration sites and nucleosome positions. The co-activator LEDGF/p75 enhanced integration but did not modify the integration sites under these conditions. We also conducted an in cellulo genome-wide comparative study of nucleosome positions and human immunodeficiency virus type-1 (HIV-1) integration sites identified experimentally in vivo. These studies confirm a preferential integration in nucleosome-covered regions. Using a DNA mechanical energy model, we show that the physical properties of DNA probed by IN binding are important in determining IN selectivity. These novel in vitro and in vivo approaches confirm that IN has a preference for integration into a nucleosome, and suggest the existence of two levels of IN selectivity. The first depends on the physical properties of the target DNA and notably, the energy required to fit DNA into the IN catalytic pocket. The second depends on the DNA deformation associated with DNA wrapping around a nucleosome. Taken together, these results indicate that HIV-1 IN is a shape-readout DNA binding protein. PMID:26075397

Real Time Metrics and Analysis of Integrated Arrival, Departure, and Surface Operations

NASA Technical Reports Server (NTRS)

Sharma, Shivanjli; Fergus, John

2017-01-01

A real time dashboard was developed in order to inform and present users notifications and integrated information regarding airport surface operations. The dashboard is a supplement to capabilities and tools that incorporate arrival, departure, and surface air-traffic operations concepts in a NextGen environment. As trajectory-based departure scheduling and collaborative decision making tools are introduced in order to reduce delays and uncertainties in taxi and climb operations across the National Airspace System, users across a number of roles benefit from a real time system that enables common situational awareness. In addition to shared situational awareness the dashboard offers the ability to compute real time metrics and analysis to inform users about capacity, predictability, and efficiency of the system as a whole. This paper describes the architecture of the real time dashboard as well as an initial set of metrics computed on operational data. The potential impact of the real time dashboard is studied at the site identified for initial deployment and demonstration in 2017; Charlotte-Douglas International Airport. Analysis and metrics computed in real time illustrate the opportunity to provide common situational awareness and inform users of metrics across delay, throughput, taxi time, and airport capacity. In addition, common awareness of delays and the impact of takeoff and departure restrictions stemming from traffic flow management initiatives are explored. The potential of the real time tool to inform the predictability and efficiency of using a trajectory-based departure scheduling system is also discussed.

Adeno-Associated Virus Type 2 Wild-Type and Vector-Mediated Genomic Integration Profiles of Human Diploid Fibroblasts Analyzed by Third-Generation PacBio DNA Sequencing

PubMed Central

Hüser, Daniela; Gogol-Döring, Andreas; Chen, Wei

2014-01-01

ABSTRACT Genome-wide analysis of adeno-associated virus (AAV) type 2 integration in HeLa cells has shown that wild-type AAV integrates at numerous genomic sites, including AAVS1 on chromosome 19q13.42. Multiple GAGY/C repeats, resembling consensus AAV Rep-binding sites are preferred, whereas rep-deficient AAV vectors (rAAV) regularly show a random integration profile. This study is the first study to analyze wild-type AAV integration in diploid human fibroblasts. Applying high-throughput third-generation PacBio-based DNA sequencing, integration profiles of wild-type AAV and rAAV are compared side by side. Bioinformatic analysis reveals that both wild-type AAV and rAAV prefer open chromatin regions. Although genomic features of AAV integration largely reproduce previous findings, the pattern of integration hot spots differs from that described in HeLa cells before. DNase-Seq data for human fibroblasts and for HeLa cells reveal variant chromatin accessibility at preferred AAV integration hot spots that correlates with variant hot spot preferences. DNase-Seq patterns of these sites in human tissues, including liver, muscle, heart, brain, skin, and embryonic stem cells further underline variant chromatin accessibility. In summary, AAV integration is dependent on cell-type-specific, variant chromatin accessibility leading to random integration profiles for rAAV, whereas wild-type AAV integration sites cluster near GAGY/C repeats. IMPORTANCE Adeno-associated virus type 2 (AAV) is assumed to establish latency by chromosomal integration of its DNA. This is the first genome-wide analysis of wild-type AAV2 integration in diploid human cells and the first to compare wild-type to recombinant AAV vector integration side by side under identical experimental conditions. Major determinants of wild-type AAV integration represent open chromatin regions with accessible consensus AAV Rep-binding sites. The variant chromatin accessibility of different human tissues or cell types will have impact on vector targeting to be considered during gene therapy. PMID:25031342

Data management in clinical research: Synthesizing stakeholder perspectives.

PubMed

Johnson, Stephen B; Farach, Frank J; Pelphrey, Kevin; Rozenblit, Leon

2016-04-01

This study assesses data management needs in clinical research from the perspectives of researchers, software analysts and developers. This is a mixed-methods study that employs sublanguage analysis in an innovative manner to link the assessments. We performed content analysis using sublanguage theory on transcribed interviews conducted with researchers at four universities. A business analyst independently extracted potential software features from the transcriptions, which were translated into the sublanguage. This common sublanguage was then used to create survey questions for researchers, analysts and developers about the desirability and difficulty of features. Results were synthesized using the common sublanguage to compare stakeholder perceptions with the original content analysis. Individual researchers exhibited significant diversity of perspectives that did not correlate by role or site. Researchers had mixed feelings about their technologies, and sought improvements in integration, interoperability and interaction as well as engaging with study participants. Researchers and analysts agreed that data integration has higher desirability and mobile technology has lower desirability but disagreed on the desirability of data validation rules. Developers agreed that data integration and validation are the most difficult to implement. Researchers perceive tasks related to study execution, analysis and quality control as highly strategic, in contrast with tactical tasks related to data manipulation. Researchers have only partial technologic support for analysis and quality control, and poor support for study execution. Software for data integration and validation appears critical to support clinical research, but may be expensive to implement. Features to support study workflow, collaboration and engagement have been underappreciated, but may prove to be easy successes. Software developers should consider the strategic goals of researchers with regard to the overall coordination of research projects and teams, workflow connecting data collection with analysis and processes for improving data quality. Copyright © 2016 Elsevier Inc. All rights reserved.

The Quality of IEP Objectives Associated with Placement on Integrated versus Segregated School Sites.

ERIC Educational Resources Information Center

Hunt, Pam; And Others

1986-01-01

Individualized education programs (IEPs) written for 18 severely disabled students (ages 4-19) who attended integrated school sites scored higher on selected indicators of best practices when compared with IEPs written for students attending segregated sites. IEPs were examined for age-appropriateness, functionality, and potential for…

Location of the unique integration site on an Escherichia coli chromosome by bacteriophage lambda DNA in vivo.

PubMed

Tal, Asaf; Arbel-Goren, Rinat; Costantino, Nina; Court, Donald L; Stavans, Joel

2014-05-20

The search for specific sequences on long genomes is a key process in many biological contexts. How can specific target sequences be located with high efficiency, within physiologically relevant times? We addressed this question for viral integration, a fundamental mechanism of horizontal gene transfer driving prokaryotic evolution, using the infection of Escherichia coli bacteria with bacteriophage λ and following the establishment of a lysogenic state. Following the targeting process in individual live E. coli cells in real time revealed that λ DNA remains confined near the entry point of a cell following infection. The encounter between the 15-bp-long target sequence on the chromosome and the recombination site on the viral genome is facilitated by the directed motion of bacterial DNA generated during chromosome replication, in conjunction with constrained diffusion of phage DNA. Moving the native bacterial integration site to different locations on the genome and measuring the integration frequency in these strains reveals that the frequencies of the native site and a site symmetric to it relative to the origin are similar, whereas both are significantly higher than when the integration site is moved near the terminus, consistent with the replication-driven mechanism we propose. This novel search mechanism is yet another example of the exquisite coevolution of λ with its host.

A multi-landing pad DNA integration platform for mammalian cell engineering

PubMed Central

Gaidukov, Leonid; Wroblewska, Liliana; Teague, Brian; Nelson, Tom; Zhang, Xin; Liu, Yan; Jagtap, Kalpana; Mamo, Selamawit; Tseng, Wen Allen; Lowe, Alexis; Das, Jishnu; Bandara, Kalpanie; Baijuraj, Swetha; Summers, Nevin M; Zhang, Lin; Weiss, Ron

2018-01-01

Abstract Engineering mammalian cell lines that stably express many transgenes requires the precise insertion of large amounts of heterologous DNA into well-characterized genomic loci, but current methods are limited. To facilitate reliable large-scale engineering of CHO cells, we identified 21 novel genomic sites that supported stable long-term expression of transgenes, and then constructed cell lines containing one, two or three ‘landing pad’ recombination sites at selected loci. By using a highly efficient BxB1 recombinase along with different selection markers at each site, we directed recombinase-mediated insertion of heterologous DNA to selected sites, including targeting all three with a single transfection. We used this method to controllably integrate up to nine copies of a monoclonal antibody, representing about 100 kb of heterologous DNA in 21 transcriptional units. Because the integration was targeted to pre-validated loci, recombinant protein expression remained stable for weeks and additional copies of the antibody cassette in the integrated payload resulted in a linear increase in antibody expression. Overall, this multi-copy site-specific integration platform allows for controllable and reproducible insertion of large amounts of DNA into stable genomic sites, which has broad applications for mammalian synthetic biology, recombinant protein production and biomanufacturing. PMID:29617873

Spinal metastases: multimodality imaging in diagnosis and stereotactic body radiation therapy planning.

PubMed

Jabehdar Maralani, Pejman; Lo, Simon S; Redmond, Kristin; Soliman, Hany; Myrehaug, Sten; Husain, Zain A; Heyn, Chinthaka; Kapadia, Anish; Chan, Aimee; Sahgal, Arjun

2017-01-01

Due to increased effectiveness of cancer treatments and increasing survival rates, metastatic disease has become more frequent compared to the past, with the spine being the most common site of bony metastases. Diagnostic imaging is an integral part of screening, diagnosis and follow-up of spinal metastases. In this article, we review the principles of multimodality imaging for tumor detection with respect to their value for diagnosis and stereotactic body radiation therapy planning for spinal metastases. We will also review the current international consensus agreement for stereotactic body radiation therapy planning, and the role of imaging in achieving the best possible treatment plan.

Ancestry of a human endogenous retrovirus family.

PubMed Central

Mariani-Costantini, R; Horn, T M; Callahan, R

1989-01-01

The human endogenous retrovirus type II (HERVII) family of HERV genomes has been found by Southern blot analysis to be characteristic of humans, apes, and Old World monkeys. New World monkeys and prosimians lack HERVII proviral genomes. Cellular DNAs of humans, common chimpanzees, gorillas, and orangutans, but not lesser ape lar gibbons, appear to contain the HERVII-related HLM-2 proviral genome integrated at the same site (HLM-2 maps to human chromosome 1). This suggests that the ancestral HERVII retrovirus(es) entered the genomes of Old World anthropoids by infection after the divergence of New World monkeys (platyrrhines) but before the evolutionary radiation of large hominoids. Images PMID:2507793

Postoperative Aortic Neck Dilation: Myth or Fact?

PubMed

Ribner, A S; Tassiopoulos, A K

2018-06-01

The abdominal aorta is the most common site of an aortic aneurysm. The visceral and most proximal infrarenal segment (aneurysm neck) are usually spared and considered more resistant to aneurysmal degeneration. However, if an abdominal aortic aneurysm (AAA) is left untreated, the natural history of the aortic neck is progressive dilatation and shortening. This may have significant implications for patients undergoing endovascular repair of AAAs (EVAR) as endograft stability and integrity of the repair are dependent on an intact proximal seal zone. Compromised seal zones, caused by progressive diameter enlargement and foreshortening of the aortic neck, may lead to distal endograft migration, type Ia endoleak, aortic sac repressurization, and, ultimately, aortic rupture.

Integrated low noise low power interface for neural bio-potentials recording and conditioning

NASA Astrophysics Data System (ADS)

Bottino, Emanuele; Martinoia, Sergio; Valle, Maurizio

2005-06-01

The recent progress in both neurobiology and microelectronics suggests the creation of new, powerful tools to investigate the basic mechanisms of brain functionality. In particular, a lot of efforts are spent by scientific community to define new frameworks devoted to the analysis of in-vitro cultured neurons. One possible approach is recording their spiking activity to monitor the coordinated cellular behaviour and get insights about neural plasticity. Due to the nature of neurons action-potentials, when considering the design of an integrated microelectronic-based recording system, a number of problems arise. First, one would desire to have a high number of recording sites (i.e. several hundreds): this poses constraints on silicon area and power consumption. In this regard, our aim is to integrate-through on-chip post-processing techniques-hundreds of bio-compatible microsensors together with CMOS standard-process low-power (i.e. some tenths of uW per channel) conditioning electronics. Each recording channel is provided with sampling electronics to insure synchronous recording so that, for example, cross-correlation between signals coming from different sites can be performed. Extra-cellular potentials are in the range of [50-150] uV, so a comparison in terms of noise-efficiency was carried out among different architectures and very low-noise pre-amplification electronics (i.e. less than 5 uVrms) was designed. As spikes measurements are made with respect to the voltage of a reference electrode, we opted for an AC-coupled differential-input preamplifier provided with band-pass filtering capability. To achieve this, we implemented large time-constant (up to seconds) integrated components in the preamp feedback path. Thus, we got rid also of random slow-drifting DC-offsets and common mode signals. The paper will present our achievements in the design and implementation of a fully integrated bio-abio interface to record neural spiking activity. In particular, preliminary results will be reported.

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

PubMed

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.

Simulating dissolved organic carbon dynamics at the swedish integrated monitoring sites with the integrated catchments model for carbon, INCA-C.

PubMed

Futter, M N; Löfgren, S; Köhler, S J; Lundin, L; Moldan, F; Bringmark, L

2011-12-01

Surface water concentrations of dissolved organic carbon ([DOC]) are changing throughout the northern hemisphere due to changes in climate, land use and acid deposition. However, the relative importance of these drivers is unclear. Here, we use the Integrated Catchments model for Carbon (INCA-C) to simulate long-term (1996-2008) streamwater [DOC] at the four Swedish integrated monitoring (IM) sites. These are unmanaged headwater catchments with old-growth forests and no major changes in land use. Daily, seasonal and long-term variations in streamwater [DOC] driven by runoff, seasonal temperature and atmospheric sulfate (SO₄(2-)) deposition were observed at all sites. Using INCA-C, it was possible to reproduce observed patterns of variability in streamwater [DOC] at the four IM sites. Runoff was found to be the main short-term control on [DOC]. Seasonal patterns in [DOC] were controlled primarily by soil temperature. Measured SO₄(2-) deposition explained some of the long-term [DOC] variability at all sites.

Streamlining recombination-mediated genetic engineering by validating three neutral integration sites in Synechococcus sp. PCC 7002.

PubMed

Vogel, Anne Ilse Maria; Lale, Rahmi; Hohmann-Marriott, Martin Frank

2017-01-01

Synechococcus sp. PCC 7002 (henceforth Synechococcus ) is developing into a powerful synthetic biology chassis. In order to streamline the integration of genes into the Synechococcus chromosome, validation of neutral integration sites with optimization of the DNA transformation protocol parameters is necessary. Availability of BioBrick-compatible integration modules is desirable to further simplifying chromosomal integrations. We designed three BioBrick-compatible genetic modules, each targeting a separate neutral integration site, A2842, A0935, and A0159, with varying length of homologous region, spanning from 100 to 800 nt. The performance of the different modules for achieving DNA integration were tested. Our results demonstrate that 100 nt homologous regions are sufficient for inserting a 1 kb DNA fragment into the Synechococcus chromosome. By adapting a transformation protocol from a related cyanobacterium, we shortened the transformation procedure for Synechococcus significantly. The optimized transformation protocol reported in this study provides an efficient way to perform genetic engineering in Synechococcus . We demonstrated that homologous regions of 100 nt are sufficient for inserting a 1 kb DNA fragment into the three tested neutral integration sites. Integration at A2842, A0935 and A0159 results in only a minimal fitness cost for the chassis. This study contributes to developing Synechococcus as the prominent chassis for future synthetic biology applications.

Improved site-specific recombinase-based method to produce selectable marker- and vector-backbone-free transgenic cells

NASA Astrophysics Data System (ADS)

Yu, Yuan; Tong, Qi; Li, Zhongxia; Tian, Jinhai; Wang, Yizhi; Su, Feng; Wang, Yongsheng; Liu, Jun; Zhang, Yong

2014-02-01

PhiC31 integrase-mediated gene delivery has been extensively used in gene therapy and animal transgenesis. However, random integration events are observed in phiC31-mediated integration in different types of mammalian cells; as a result, the efficiencies of pseudo attP site integration and evaluation of site-specific integration are compromised. To improve this system, we used an attB-TK fusion gene as a negative selection marker, thereby eliminating random integration during phiC31-mediated transfection. We also excised the selection system and plasmid bacterial backbone by using two other site-specific recombinases, Cre and Dre. Thus, we generated clean transgenic bovine fetal fibroblast cells free of selectable marker and plasmid bacterial backbone. These clean cells were used as donor nuclei for somatic cell nuclear transfer (SCNT), indicating a similar developmental competence of SCNT embryos to that of non-transgenic cells. Therefore, the present gene delivery system facilitated the development of gene therapy and agricultural biotechnology.

Sequence space and the ongoing expansion of the protein universe.

PubMed

Povolotskaya, Inna S; Kondrashov, Fyodor A

2010-06-17

The need to maintain the structural and functional integrity of an evolving protein severely restricts the repertoire of acceptable amino-acid substitutions. However, it is not known whether these restrictions impose a global limit on how far homologous protein sequences can diverge from each other. Here we explore the limits of protein evolution using sequence divergence data. We formulate a computational approach to study the rate of divergence of distant protein sequences and measure this rate for ancient proteins, those that were present in the last universal common ancestor. We show that ancient proteins are still diverging from each other, indicating an ongoing expansion of the protein sequence universe. The slow rate of this divergence is imposed by the sparseness of functional protein sequences in sequence space and the ruggedness of the protein fitness landscape: approximately 98 per cent of sites cannot accept an amino-acid substitution at any given moment but a vast majority of all sites may eventually be permitted to evolve when other, compensatory, changes occur. Thus, approximately 3.5 x 10(9) yr has not been enough to reach the limit of divergent evolution of proteins, and for most proteins the limit of sequence similarity imposed by common function may not exceed that of random sequences.

The Kaiser Permanente shoulder arthroplasty registry: results from 6,336 primary shoulder arthroplasties.

PubMed

Dillon, Mark T; Ake, Christopher F; Burke, Mary F; Singh, Anshuman; Yian, Edward H; Paxton, Elizabeth W; Navarro, Ronald A

2015-06-01

Shoulder arthroplasty is being performed in the United States with increasing frequency. We describe the medium-term findings from a large integrated healthcare system shoulder arthroplasty registry. Shoulder arthroplasty cases registered between January 2005 and June 2013 were included for analysis. The registry included patient characteristics, surgical information, implant data, attrition, and patient outcomes such as surgical site infections, venous thromboembolism, and revision procedures. During the study period, 6,336 primary cases were registered. Median follow-up time for all primaries was 3.3 years; 461 cases were lost to follow-up by ending of health plan membership. Primary cases were predominantly female (56%) and white (81%), with an average age of 70 years. The most common reason for surgery was osteoarthritis in 60% of cases, followed by acute fracture (17%) and rotator cuff tear arthropathy (15%). In elective shoulder arthroplasty procedures, 200 all-cause revisions (4%) were reported, with glenoid wear being the most common reason. Most arthroplasties were elective procedures: over half performed for osteoarthritis. Glenoid wear was the most common reason for revision of primary shoulder arthroplasty in elective cases.

An Integrated and Collaborative Approach for NASA Earth Science Data

NASA Technical Reports Server (NTRS)

Murphy, K.; Lowe, D.; Behnke, J.; Ramapriyan, H.; Behnke, J.; Sofinowski, E.

2012-01-01

Earth science research requires coordination and collaboration across multiple disparate science domains. Data systems that support this research are often as disparate as the disciplines that they support. These distinctions can create barriers limiting access to measurements, which could otherwise enable cross-discipline Earth science. NASA's Earth Observing System Data and Information System (EOSDIS) is continuing to bridge the gap between discipline-centric data systems with a coherent and transparent system of systems that offers up to date and engaging science related content, creates an active and immersive science user experience, and encourages the use of EOSDIS earth data and services. The new Earthdata Coherent Web (ECW) project encourages cohesiveness by combining existing websites, data and services into a unified website with a common look and feel, common tools and common processes. It includes cross-linking and cross-referencing across the Earthdata site and NASA's Distributed Active Archive Centers (DAAC), and by leveraging existing EOSDIS Cyber-infrastructure and Web Service technologies to foster re-use and to reduce barriers to discovering Earth science data (http://earthdata.nasa.gov).

Use of a Novel Abdominal Aortic and Junctional Tourniquet to Reduce or Eliminate Flow in the Brachial and Popliteal Arteries in Human Subjects.

PubMed

Lyon, Matthew; Johnson, Daniel; Gordon, Richard

2015-01-01

Penetrating injuries of the proximal large arteries are a common cause of death on the battlefield due to rapid exsanguination. Applying an effective tourniquet to stop bleeding at the axillary and proximal femoral arteries (junctional sites) is difficult. Prior studies have shown that the Abdominal Aortic and Junctional Tourniquet (AAJT) effectively reduced blood flow in the common femoral artery with application of the device around the lower abdomen. Our objective was to determine the effectiveness of the AAJT to stop blood flow in the proximal femoral artery (PFA), and the axillary artery (AA). This was a prospective observational trial using human volunteers. The AAJT consists of a wedge-shaped bladder and integrated strap. The bladder has an integrated manometer, which is used to measure the pressure in the bladder. For the AA, the AAJT was placed over the axillary junction at the anterior axillary line with the strap placed across the contralateral shoulder. For the PFA, the AAJT bladder was placed over the right groin with the strap positioned across both femoral trochanters. Spectral Doppler measurements were taken of the PFA and AA at baseline and as the bladder was inflated. Collected data included pressure of the AAJT.

Integrating basic research and long-term management: a case study using avian research at the Savannah River Site

Treesearch

John B. Dunning; John C. Kilgo

2000-01-01

In this introduction to Avian Research at the Savannah River Site: A Model for Integrating Basic Research and Long-term Management, editors Dunning and Kilgo discuss the interrelationship between research and management at the Savannah River Site. They emphasize the increasing need for collaboration between scientists and land managers....

Integrated Approaches On Archaeo-Geophysical Data

NASA Astrophysics Data System (ADS)

Kucukdemirci, M.; Piro, S.; Zamuner, D.; Ozer, E.

2015-12-01

Key words: Ground Penetrating Radar (GPR), Magnetometry, Geophysical Data Integration, Principal Component Analyse (PCA), Aizanoi Archaeological Site An application of geophysical integration methods which often appealed are divided into two classes as qualitative and quantitative approaches. This work focused on the application of quantitative integration approaches, which involve the mathematical and statistical integration techniques, on the archaeo-geophysical data obtained in Aizanoi Archaeological Site,Turkey. Two geophysical methods were applied as Ground Penetrating Radar (GPR) and Magnetometry for archaeological prospection on the selected archaeological site. After basic data processing of each geophysical method, the mathematical approaches of Sums and Products and the statistical approach of Principal Component Analysis (PCA) have been applied for the integration. These integration approches were first tested on synthetic digital images before application to field data. Then the same approaches were applied to 2D magnetic maps and 2D GPR time slices which were obtained on the same unit grids in the archaeological site. Initially, the geophysical data were examined individually by referencing with archeological maps and informations obtained from archaeologists and some important structures as possible walls, roads and relics were determined. The results of all integration approaches provided very important and different details about the anomalies related to archaeological features. By using all those applications, integrated images can provide complementary informations as well about the archaeological relics under the ground. Acknowledgements The authors would like to thanks to Scientific and Technological Research Council of Turkey (TUBITAK), Fellowship for Visiting Scientists Programme for their support, Istanbul University Scientific Research Project Fund, (Project.No:12302) and archaeologist team of Aizanoi Archaeological site for their support during the field work.

A Team-Based Process for Designing Comprehensive, Integrated, Three-Tiered (CI3T) Models of Prevention: How Does My School-Site Leadership Team Design a CI3T Model?

ERIC Educational Resources Information Center

Lane, Kathleen Lynne; Oakes, Wendy Peia; Jenkins, Abbie; Menzies, Holly Mariah; Kalberg, Jemma Robertson

2014-01-01

Comprehensive, integrated, three-tiered models are context specific and developed by school-site teams according to the core values held by the school community. In this article, the authors provide a step-by-step, team-based process for designing comprehensive, integrated, three-tiered models of prevention that integrate academic, behavioral, and…

Integrated control of landscape irrigation and rainwater harvesting for urban water management

NASA Astrophysics Data System (ADS)

Lee, J. H.; Dhakal, B.; Noh, S.; Seo, D. J.

2016-12-01

Demand for freshwater is increasing rapidly in large and fast-growing urban areas such as the Dallas-Fort Worth Metroplex (DFW). With almost complete reliance on surface water, water supply for DFW is limited by the available storage in the reservoir systems which is now subject to larger variability due to climate change. Landscape irrigation is estimated to account for nearly one-third of all residential water use in the US and as much as 60% in dry climate areas. In landscape irrigation, a large portion of freshwater is commonly lost by sub-optimal practices. If practiced over a large area, one may expect optimized smart irrigation to significantly reduce urban freshwater demand. For increasing on-site water supply, rainwater harvesting (RHW) is particularly attractive in that it conserves potable water while reducing stormwater runoff. Traditional static RWH methods, however, have limited success due to the inefficient water usage. If, on the other hand, lawn irrigation and rainwater harvesting can be optimized as an integrated operation and controlled adaptively to the feedback from the environmental sensors, weather conditions and forecast, one may expect the combined benefits for water conservation and stormwater management to be larger. In this work, we develop a prototype system for integrated control of lawn irrigation and RWH for water conservation and stormwater management, and assess and demonstrate the potential impact and value of the system. For in-situ evaluation, we deploy a wireless sensor network consisting of low-cost off-the-shelf sensors and open-sourced components, and collect observations of temperature, humidity, soil moisture, and solar radiation at the test site at the UTA community garden in Arlington, Texas. We assess the health of the lawn grass using normalized vegetation index (NDVI) from the time lapse images at the site. In this poster, we describe the approach and share the initial results.

Challenges and Opportunities for Implementing Integrated Mental Health Care: A District Level Situation Analysis from Five Low- and Middle-Income Countries

PubMed Central

Hanlon, Charlotte; Luitel, Nagendra P.; Kathree, Tasneem; Murhar, Vaibhav; Shrivasta, Sanjay; Medhin, Girmay; Ssebunnya, Joshua; Fekadu, Abebaw; Shidhaye, Rahul; Petersen, Inge; Jordans, Mark; Kigozi, Fred; Thornicroft, Graham; Patel, Vikram; Tomlinson, Mark; Lund, Crick; Breuer, Erica; De Silva, Mary; Prince, Martin

2014-01-01

Background Little is known about how to tailor implementation of mental health services in low- and middle-income countries (LMICs) to the diverse settings encountered within and between countries. In this paper we compare the baseline context, challenges and opportunities in districts in five LMICs (Ethiopia, India, Nepal, South Africa and Uganda) participating in the PRogramme for Improving Mental health carE (PRIME). The purpose was to inform development and implementation of a comprehensive district plan to integrate mental health into primary care. Methods A situation analysis tool was developed for the study, drawing on existing tools and expert consensus. Cross-sectional information obtained was largely in the public domain in all five districts. Results The PRIME study districts face substantial contextual and health system challenges many of which are common across sites. Reliable information on existing treatment coverage for mental disorders was unavailable. Particularly in the low-income countries, many health service organisational requirements for mental health care were absent, including specialist mental health professionals to support the service and reliable supplies of medication. Across all sites, community mental health literacy was low and there were no models of multi-sectoral working or collaborations with traditional or religious healers. Nonetheless health system opportunities were apparent. In each district there was potential to apply existing models of care for tuberculosis and HIV or non-communicable disorders, which have established mechanisms for detection of drop-out from care, outreach and adherence support. The extensive networks of community-based health workers and volunteers in most districts provide further opportunities to expand mental health care. Conclusions The low level of baseline health system preparedness across sites underlines that interventions at the levels of health care organisation, health facility and community will all be essential for sustainable delivery of quality mental health care integrated into primary care. PMID:24558389

Assessing Hydrologic Impacts of Land Configuration Changes Using an Integrated Hydrologic Model at the Rocky Flats Environmental Technology Site, Colorado

NASA Astrophysics Data System (ADS)

Prucha, R. H.; Dayton, C. S.; Hawley, C. M.

2002-12-01

The Rocky Flats Environmental Technology Site (RFETS) in Golden, Colorado, a former Department of Energy nuclear weapons manufacturing facility, is currently undergoing closure. The natural semi-arid interaction between surface and subsurface flow at RFETS is complex and complicated by the industrial modifications to the flow system. Using a substantial site data set, a distributed parameter, fully-integrated hydrologic model was developed to assess the hydrologic impact of different hypothetical site closure configurations on the current flow system and to better understand the integrated hydrologic behavior of the system. An integrated model with this level of detail has not been previously developed in a semi-arid area, and a unique, but comprehensive, approach was required to calibrate and validate the model. Several hypothetical scenarios were developed to simulate hydrologic effects of modifying different aspects of the site. For example, some of the simulated modifications included regrading the current land surface, changing the existing surface channel network, removing subsurface trenches and gravity drain flow systems, installing a slurry wall and geotechnical cover, changing the current vegetative cover, and converting existing buildings and pavement to permeable soil areas. The integrated flow model was developed using a rigorous physically-based code so that realistic design parameters can simulate these changes. This code also permitted evaluation of changes to complex integrated hydrologic system responses that included channelized and overland flow, pond levels, unsaturated zone storage, groundwater heads and flow directions, and integrated water balances for key areas. Results generally show that channel flow offsite decreases substantially for different scenarios, while groundwater heads generally increase within the reconfigured industrial area most of which is then discharged as evapotranspiration. These changes have significant implications to site closure and operation.

Integrating family planning and HIV services in western Kenya: the impact on HIV-infected patients' knowledge of family planning and male attitudes toward family planning.

PubMed

Onono, Maricianah; Guzé, Mary A; Grossman, Daniel; Steinfeld, Rachel; Bukusi, Elizabeth A; Shade, Starley; Cohen, Craig R; Newmann, Sara J

2015-01-01

Little information exists on the impact of integrating family planning (FP) services into HIV care and treatment on patients' familiarity with and attitudes toward FP. We conducted a cluster-randomized trial in 18 public HIV clinics with 12 randomized to integrated FP and HIV services and 6 to the standard referral-based system where patients are referred to an FP clinic. Serial cross-sectional surveys were done before (n = 488 women, 486 men) and after (n = 479 women, 481 men) the intervention to compare changes in familiarity with FP methods and attitudes toward FP between integrated and nonintegrated (NI) sites. We created an FP familiarity score based on the number of more effective FP methods patients could identify (score range: 0-6). Generalized estimating equations were used to control for clustering within sites. An increase in mean familiarity score between baseline (mean = 5.16) and post-intervention (mean = 5.46) occurred with an overall mean change of 0.26 (95% confidence intervals [CI] = 0.09, 0.45; p = 0.003) across all sites. At end line, there was no difference in increase of mean FP familiarity scores at intervention versus control sites (mean = 5.41 vs. 5.49, p = 0.94). We observed a relative decrease in the proportion of males agreeing that FP was "women's business" at integrated sites (baseline 42% to end line 30%; reduction of 12%) compared to males at NI sites (baseline 35% to end line 42%; increase of 7%; adjusted odds ration [aOR] = 0.43; 95% CI = 0.22, 0.85). Following FP-HIV integration, familiarity with FP methods increased but did not differ by study arm. Integration was associated with a decrease in negative attitudes toward FP among men.

Good clinical practice regulatory inspections: Lessons for Indian investigator sites

PubMed Central

Marwah, R.; Van de Voorde, K.; Parchman, J.

2010-01-01

Regulatory inspections are important to evaluate the integrity of the data submitted to health authorities (HAs), protect patient safety, and assess adequacy of site/sponsor quality systems to achieve the same. Inspections generally occur after submission of data for marketing approval of an investigational drug. In recent years, there has been a significant increase in number of inspections by different HAs, including in India. The assessors/inspectors generally do a thorough review of site data before inspections. All aspects of ICH-GCP, site infrastructure, and quality control systems are assessed during the inspection. Findings are discussed during the close out meeting and a detailed inspection report issued afterward, which has to be responded to within 15–30 days with effective Corrective and Preventive Action Plan (CAPA). Protocol noncompliance, inadequate/inaccurate records, inadequate drug accountability, informed consent issues, and adverse event reporting were some of the most common findings observed during recent Food and Drug Administration (FDA) inspections. Drug development is being increasingly globalized and an increased number of patients enrolled in studies submitted as part of applications come from all over the world including India. Because of the steep increase in research activity in the country, inexperienced sites, and more stakeholders, increased efforts will be required to ensure continuous quality and compliance. HAs have also made clear that enforcement will be increased and be swift, aggressive, and effective. PMID:21350732

Core-Shell Processing of Natural Pigment: Upper Palaeolithic Red Ochre from Lovas, Hungary.

PubMed

Sajó, István E; Kovács, János; Fitzsimmons, Kathryn E; Jáger, Viktor; Lengyel, György; Viola, Bence; Talamo, Sahra; Hublin, Jean-Jacques

2015-01-01

Ochre is the common archaeological term for prehistoric pigments. It is applied to a range of uses, from ritual burials to cave art to medications. While a substantial number of Palaeolithic paint mining pits have been identified across Europe, the link between ochre use and provenance, and their antiquity, has never yet been identified. Here we characterise the mineralogical signature of core-shell processed ochre from the Palaeolithic paint mining pits near Lovas in Hungary, using a novel integration of petrographic and mineralogical techniques. We present the first evidence for core-shell processed, natural pigment that was prepared by prehistoric people from hematitic red ochre. This involved combining the darker red outer shell with the less intensely coloured core to efficiently produce an economical, yet still strongly coloured, paint. We demonstrate the antiquity of the site as having operated between 14-13 kcal BP, during the Epigravettian period. This is based on new radiocarbon dating of bone artefacts associated with the quarry site. The dating results indicate the site to be the oldest known evidence for core-shell pigment processing. We show that the ochre mined at Lovas was exported from the site based on its characteristic signature at other archaeological sites in the region. Our discovery not only provides a methodological framework for future characterisation of ochre pigments, but also provides the earliest known evidence for "value-adding" of products for trade.

Comparison of two freshwater turtle species as monitors of radionuclide and chemical contamination: DNA damage and residue analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meyers-Schoene, L.; Shugart, L.R.; Beauchamp, J.J.

1993-08-01

Two species of turtles that occupy different ecological niches were compared for their usefulness as monitors of freshwater ecosystems where both low-level radioactive and nonradioactive contaminants are present. The pond slider (Trachemys scripta) and common snapping turtle (Chelydra serpentina) were analyzed for the presence of [sup 90]Sr, [sup 137]Cs, [sup 60]Co, and Hg, radionuclides and chemicals known to be present at the contaminated site, and single-strand breaks in liver DNA. The integrity of the DNA was examined by the alkaline unwinding assay, a technique that detects strand breaks as a biological marker of possible exposure to genotoxic agents. This measuremore » of DNA damage was significantly increased in both species of turtles at the contaminated site compared with turtles of the same species at a reference site, and shows that contaminant-exposed populations were under more severe genotoxic stress than those at the reference site. The level of strand breaks observed at the contaminated site was high and in the range reported for other aquatic species exposed to deleterious concentrations of genotoxic agents such as chemicals and ionizing radiation. Statistically significantly higher concentrations of radionuclides and Hg were detected in the turtles from the contaminated area. Mercury concentrations were significantly higher in the more carnivorous snapping turtle compared with the slider; however, both species were effective monitors of the contaminants.« less

Complex Structure and Biochemical Characterization of the Staphylococcus aureus Cyclic Diadenylate Monophosphate (c-di-AMP)-binding Protein PstA, the Founding Member of a New Signal Transduction Protein Family*

PubMed Central

Campeotto, Ivan; Zhang, Yong; Mladenov, Miroslav G.; Freemont, Paul S.; Gründling, Angelika

2015-01-01

Signaling nucleotides are integral parts of signal transduction systems allowing bacteria to cope with and rapidly respond to changes in the environment. The Staphylococcus aureus PII-like signal transduction protein PstA was recently identified as a cyclic diadenylate monophosphate (c-di-AMP)-binding protein. Here, we present the crystal structures of the apo- and c-di-AMP-bound PstA protein, which is trimeric in solution as well as in the crystals. The structures combined with detailed bioinformatics analysis revealed that the protein belongs to a new family of proteins with a similar core fold but with distinct features to classical PII proteins, which usually function in nitrogen metabolism pathways in bacteria. The complex structure revealed three identical c-di-AMP-binding sites per trimer with each binding site at a monomer-monomer interface. Although distinctly different from other cyclic-di-nucleotide-binding sites, as the half-binding sites are not symmetrical, the complex structure also highlighted common features for c-di-AMP-binding sites. A comparison between the apo and complex structures revealed a series of conformational changes that result in the ordering of two anti-parallel β-strands that protrude from each monomer and allowed us to propose a mechanism on how the PstA protein functions as a signaling transduction protein. PMID:25505271

Screening and management of mental health and substance use disorders in HIV treatment settings in low- and middle-income countries within the global IeDEA consortium.

PubMed

Parcesepe, Angela M; Mugglin, Catrina; Nalugoda, Fred; Bernard, Charlotte; Yunihastuti, Evy; Althoff, Keri; Jaquet, Antoine; Haas, Andreas D; Duda, Stephany N; Wester, C William; Nash, Denis

2018-03-01

Integration of services to screen and manage mental health and substance use disorders (MSDs) into HIV care settings has been identified as a promising strategy to improve mental health and HIV treatment outcomes among people living with HIV/AIDS (PLWHA) in low- and middle-income countries (LMICs). Data on the extent to which HIV treatment sites in LMICs screen and manage MSDs are limited. The objective of this study was to assess practices for screening and treatment of MSDs at HIV clinics in LMICs participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. We surveyed a stratified random sample of 95 HIV clinics in 29 LMICs in the Caribbean, Central and South America, Asia-Pacific and sub-Saharan Africa. The survey captured information onsite characteristics and screening and treatment practices for depression, post-traumatic stress disorder (PTSD), substance use disorders (SUDs) and other mental health disorders. Most sites (n = 76, 80%) were in urban areas. Mental health screening varied by disorder: 57% of sites surveyed screened for depression, 19% for PTSD, 55% for SUDs and 29% for other mental health disorders. Depression, PTSD, SUDs and other mental health disorders were reported as managed on site (having services provided at the HIV clinic or same health facility) at 70%, 51%, 41% and 47% of sites respectively. Combined availability of screening and on-site management of depression, PTSD, and SUDs, and other mental health disorders was reported by 42%, 14%, 26% and 19% of sites, respectively. On-site management of depression and PTSD was reported significantly less often in rural as compared to urban settings (depression: 33% and 78% respectively; PTSD: 24% and 58% respectively). Screening for depression and SUDs was least commonly reported by HIV programmes that treated only children as compared to HIV programmes that treated only adults or treated both adults and children. Significant gaps exist in the management of MSDs in HIV care settings in LMICs, particularly in rural settings. Identification and evaluation of optimal implementation strategies to scale and sustain integrated MSDs and HIV care is needed. © 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

Hospital site selection using fuzzy AHP and its derivatives.

PubMed

Vahidnia, Mohammad H; Alesheikh, Ali A; Alimohammadi, Abbas

2009-07-01

Environmental managers are commonly faced with sophisticated decisions, such as choosing the location of a new facility subject to multiple conflicting criteria. This paper considers the specific problem of creating a well-distributed network of hospitals that delivers its services to the target population with minimal time, pollution and cost. We develop a Multi-Criteria Decision Analysis process that combines Geographical Information System (GIS) analysis with the Fuzzy Analytical Hierarchy Process (FAHP), and use this process to determine the optimum site for a new hospital in the Tehran urban area. The GIS was used to calculate and classify governing criteria, while FAHP was used to evaluate the decision factors and their impacts on alternative sites. Three methods were used to estimate the total weights and priorities of the candidate sites: fuzzy extent analysis, center-of-area defuzzification, and the alpha-cut method. The three methods yield identical priorities for the five alternatives considered. Fuzzy extent analysis provides less discriminating power, but is simpler to implement and compute than the other two methods. The alpha-cut method is more complicated, but integrates the uncertainty and overall attitude of the decision-maker. The usefulness of the new hospital site is evaluated by computing an accessibility index for each pixel in the GIS, defined as the ratio of population density to travel time. With the addition of a new hospital at the optimum site, this index improved over about 6.5 percent of the geographical area.

Assessing the challenges of multi-scope clinical research sites: an example from NIH HIV/AIDS clinical trials networks.

PubMed

Rosas, Scott R; Cope, Marie T; Villa, Christie; Motevalli, Mahnaz; Utech, Jill; Schouten, Jeffrey T

2014-04-01

Large-scale, multi-network clinical trials are seen as a means for efficient and effective utilization of resources with greater responsiveness to new discoveries. Formal structures instituted within the National Institutes of Health (NIH) HIV/AIDS Clinical Trials facilitate collaboration and coordination across networks and emphasize an integrated approach to HIV/AIDS vaccine, prevention and therapeutics clinical trials. This study examines the joint usage of clinical research sites as means of gaining efficiency, extending capacity, and adding scientific value to the networks. A semi-structured questionnaire covering eight clinical management domains was administered to 74 (62% of sites) clinical site coordinators at single- and multi-network sites to identify challenges and efficiencies related to clinical trials management activities and coordination with multi-network units. Overall, respondents at multi-network sites did not report more challenges than single-network sites, but did report unique challenges to overcome including in the areas of study prioritization, community engagement, staff education and training, and policies and procedures. The majority of multi-network sites reported that such affiliations do allow for the consolidation and cost-sharing of research functions. Suggestions for increasing the efficiency or performance of multi-network sites included streamlining standards and requirements, consolidating protocol activation methods, using a single cross-network coordinating centre, and creating common budget and payment mechanisms. The results of this assessment provide important information to consider in the design and management of multi-network configurations for the NIH HIV/AIDS Clinical Trials Networks, as well as others contemplating and promoting the concept of multi-network settings. © 2013 John Wiley & Sons Ltd.

Evaluation of human amniotic membrane as a wound dressing for split-thickness skin-graft donor sites.

PubMed

Loeffelbein, Denys J; Rohleder, Nils H; Eddicks, Matthias; Baumann, Claudia M; Stoeckelhuber, Mechthild; Wolff, Klaus-D; Drecoll, Enken; Steinstraesser, Lars; Hennerbichler, Simone; Kesting, Marco R

2014-01-01

Human amniotic membrane (HAM) has been used as a biomaterial in various surgical procedures and exceeds some qualities of common materials. We evaluated HAM as wound dressing for split-thickness skin-graft (STSG) donor sites in a swine model (Part A) and a clinical trial (Part B). Part A: STSG donor sites in 4 piglets were treated with HAM or a clinically used conventional polyurethane (PU) foil (n = 8 each). Biopsies were taken on days 5, 7, 10, 20, 40, and 60 and investigated immunohistochemically for alpha-smooth muscle actin (αSMA: wound contraction marker), von Willebrand factor (vWF: angiogenesis), Ki-67 (cell proliferation), and laminin (basement membrane integrity). Part B: STSG donor sites in 45 adult patients (16 female/29 male) were treated with HAM covered by PU foam, solely by PU foam, or PU foil/paraffin gauze (n = 15 each). Part A revealed no difference in the rate of wound closure between groups. HAM showed improved esthetic results and inhibitory effects on cicatrization. Angioneogenesis was reduced, and basement membrane formation was accelerated in HAM group. Part B: no difference in re-epithelialization/infection rate was found. HAM caused less ichor exudation and less pruritus. HAM has no relevant advantage over conventional dressings but might be a cost-effective alternative.

Extreme diagenesis displayed by Pliocene-Pleistocene Calcareous Nannofossils in IODP Hole 1396A, adjacent to Montserrat Island in the Lesser Antilles

NASA Astrophysics Data System (ADS)

Aljahdali, M. H.; Behzad, A.; Missimer, T. M.; Wise, S. W.; Scientists, E.

2013-12-01

Adjacent to Montserrat Island in the Lesser Antilles of the Caribbean Sea, Integrated Ocean Drilling Program (IODP) Site 1396 recovered lower Pliocene to Pleistocene calcareous nannofossil assemblages (CN11 to CN15) that range between common to abundant and display a variety of preservations. High-resolution Scanning Electron Microscopy (SEM) observation of calcareous nannofossil assemblages in selected samples from Hole 1396A, shows severe diagenesis (overgrowth and/or dissolution) even near the top of the sequence. The nannofossil assemblages in this relatively shallow basin (e.g., 800 m) reveal abnormal diagenesis for such young specimens that are quite similar to the heavy overgrowths and dissolution generally seen only in older deposits (e.g., Cretaceous). Our hypothesis is that volcanic activity in the region probably induced this extreme diagenesis. A more detailed examination of these samples should provide a better understanding of the progression of carbonate diagenesis in this basin. The nannofossil biostratigraphy and magnetostratigraphy at Site 1396 also suggest lower sedimentation rates in the Pleistocene than in the Pliocene. A comparison site (ODP Leg 165 Site 1000) in the Caribbean Sea also shows a similar sedimentation-rate pattern. This we interpret as a regional event caused by the closure of the Central American Seaway.

Indoor Air Contamination from Hazardous Waste Sites: Improving the Evidence Base for Decision-Making.

PubMed

Johnston, Jill; MacDonald Gibson, Jacqueline

2015-11-27

At hazardous waste sites, volatile chemicals can migrate through groundwater and soil into buildings, a process known as vapor intrusion. Due to increasing recognition of vapor intrusion as a potential indoor air pollution source, in 2015 the U.S. Environmental Protection Agency (EPA) released a new vapor intrusion guidance document. The guidance specifies two conditions for demonstrating that remediation is needed: (1) proof of a vapor intrusion pathway; and (2) evidence that human health risks exceed established thresholds (for example, one excess cancer among 10,000 exposed people). However, the guidance lacks details on methods for demonstrating these conditions. We review current evidence suggesting that monitoring and modeling approaches commonly employed at vapor intrusion sites do not adequately characterize long-term exposure and in many cases may underestimate risks. On the basis of this evidence, we recommend specific approaches to monitoring and modeling to account for these uncertainties. We propose a value of information approach to integrate the lines of evidence at a site and determine if more information is needed before deciding whether the two conditions specified in the vapor intrusion guidance are satisfied. To facilitate data collection and decision-making, we recommend a multi-directional community engagement strategy and consideration of environment justice concerns.

Indoor Air Contamination from Hazardous Waste Sites: Improving the Evidence Base for Decision-Making

PubMed Central

Johnston, Jill; MacDonald Gibson, Jacqueline

2015-01-01

At hazardous waste sites, volatile chemicals can migrate through groundwater and soil into buildings, a process known as vapor intrusion. Due to increasing recognition of vapor intrusion as a potential indoor air pollution source, in 2015 the U.S. Environmental Protection Agency (EPA) released a new vapor intrusion guidance document. The guidance specifies two conditions for demonstrating that remediation is needed: (1) proof of a vapor intrusion pathway; and (2) evidence that human health risks exceed established thresholds (for example, one excess cancer among 10,000 exposed people). However, the guidance lacks details on methods for demonstrating these conditions. We review current evidence suggesting that monitoring and modeling approaches commonly employed at vapor intrusion sites do not adequately characterize long-term exposure and in many cases may underestimate risks. On the basis of this evidence, we recommend specific approaches to monitoring and modeling to account for these uncertainties. We propose a value of information approach to integrate the lines of evidence at a site and determine if more information is needed before deciding whether the two conditions specified in the vapor intrusion guidance are satisfied. To facilitate data collection and decision-making, we recommend a multi-directional community engagement strategy and consideration of environment justice concerns. PMID:26633433

Potential interoperability problems facing multi-site radiation oncology centers in The Netherlands

NASA Astrophysics Data System (ADS)

Scheurleer, J.; Koken, Ph; Wessel, R.

2014-03-01

Aim: To identify potential interoperability problems facing multi-site Radiation Oncology (RO) departments in the Netherlands and solutions for unambiguous multi-system workflows. Specific challenges confronting the RO department of VUmc (RO-VUmc), which is soon to open a satellite department, were characterized. Methods: A nationwide questionnaire survey was conducted to identify possible interoperability problems and solutions. Further detailed information was obtained by in-depth interviews at 3 Dutch RO institutes that already operate in more than one site. Results: The survey had a 100% response rate (n=21). Altogether 95 interoperability problems were described. Most reported problems were on a strategic and semantic level. The majority were DICOM(-RT) and HL7 related (n=65), primarily between treatment planning and verification systems or between departmental and hospital systems. Seven were identified as being relevant for RO-VUmc. Departments have overcome interoperability problems with their own, or with tailor-made vendor solutions. There was little knowledge about or utilization of solutions developed by Integrating the Healthcare Enterprise Radiation Oncology (IHE-RO). Conclusions: Although interoperability problems are still common, solutions have been identified. Awareness of IHE-RO needs to be raised. No major new interoperability problems are predicted as RO-VUmc develops into a multi-site department.

A homology-based pipeline for global prediction of post-translational modification sites

NASA Astrophysics Data System (ADS)

Chen, Xiang; Shi, Shao-Ping; Xu, Hao-Dong; Suo, Sheng-Bao; Qiu, Jian-Ding

2016-05-01

The pathways of protein post-translational modifications (PTMs) have been shown to play particularly important roles for almost any biological process. Identification of PTM substrates along with information on the exact sites is fundamental for fully understanding or controlling biological processes. Alternative computational strategies would help to annotate PTMs in a high-throughput manner. Traditional algorithms are suited for identifying the common organisms and tissues that have a complete PTM atlas or extensive experimental data. While annotation of rare PTMs in most organisms is a clear challenge. In this work, to this end we have developed a novel homology-based pipeline named PTMProber that allows identification of potential modification sites for most of the proteomes lacking PTMs data. Cross-promotion E-value (CPE) as stringent benchmark has been used in our pipeline to evaluate homology to known modification sites. Independent-validation tests show that PTMProber achieves over 58.8% recall with high precision by CPE benchmark. Comparisons with other machine-learning tools show that PTMProber pipeline performs better on general predictions. In addition, we developed a web-based tool to integrate this pipeline at http://bioinfo.ncu.edu.cn/PTMProber/index.aspx. In addition to pre-constructed prediction models of PTM, the website provides an extensional functionality to allow users to customize models.

Productivity and soil properties 45 years after timber harvest and mechanical site preparation in western Montana

Treesearch

Luke M. Cerise; Deborah S. Page-Dumroese; Paul McDaniel; Cole Mayn; Robert Heinse

2013-01-01

Site preparation following timber harvests is widely used to increase seedling establishment postharvest. Historically, dozer piling and ripping were the most common forms of site preparation in the Intermountain West. Less commonly, terracing of hill slopes was another form of site preparation on the Bitterroot National Forest in western Montana from 1961-1970 on...

Simulating wind energy resources with mesoscale models: Intercomparison of state-of-the-art models over Northern Europe

NASA Astrophysics Data System (ADS)

Hahmann, A. N.

2015-12-01

Mesoscale models are increasingly being used to estimate wind conditions to identify perspective areas and sites where to develop wind farm projects. Mesoscale models are useful because they give information over extensive areas with various terrain complexities where measurements are scarce and measurement campaigns costly. Various mesoscale models and families of mesoscale models are being used, with thousands of setup options. Since long-term integrations are expensive and tedious to carry out, only limited comparisons exist. We have carried out a blind benchmarking study to evaluate the capabilities of mesoscale models used in wind energy to estimate site wind conditions: to highlight common issues on mesoscale modeling of wind conditions on sites with different characteristics, and to identify gaps and strengths of models and understand the root conditions for further evaluating uncertainties. Three experimental sites with tall mast measurements were selected: FINO3 (offshore), Høvsøre (coastal), and Cabauw (land-based). The participants were asked to provide hourly time series of wind speed and direction, temperature, etc., at various heights for 2011. The methods used were left to the choice of the participants, but they were asked for a detailed description of their model and many other parameters (e.g., horizontal and vertical resolution, model parameterizations, surface roughness length) that could be used to group the models and interpret the results of the intercomparison. The analysis of the time series includes comparison to observations, summarized with well-known measures such as biases, RMSE, correlations, and of sector-wise statistics, and the temporal spectra. The statistics were grouped by the models, their spatial resolution, forcing data, various integration methods, etc. The results show high fidelity of the various entries in simulating the wind climate at the offshore and coastal site. Over land and the statistics of other derived fields (e.g. wind shear distributions) show much less similarities among the models and with the observations. Cloud computing now allows the use of mesoscale models by non-experts for site assessment. This tool is very useful and powerful, but users must be aware of the different issues that might be encountered in working with different setups.

Evaluating the Effects of Fire on Semi-Arid Savanna Ecosystem Productivity Using Integrated Spectral and Gas Exchange Measurements

NASA Astrophysics Data System (ADS)

Raub, H. D.; Jimenez, J. R.; Gallery, R. E.; Sutter, L., Jr.; Barron-Gafford, G.; Smith, W. K.

2017-12-01

Drylands account for 40% of the land surface and have been identified as increasingly important in driving interannual variability of the land carbon sink. Yet, understanding of dryland seasonal ecosystem productivity dynamics - termed Gross Primary Productivity (GPP) - is limited due to complex interactions between vegetation health, seasonal drought dynamics, a paucity of long-term measurements across these under-studied regions, and unanticipated disturbances from varying fire regimes. For instance, fire disturbance has been found to either greatly reduce post-fire GPP through vegetation mortality or enhance post-fire GPP though increased resource availability (e.g., water, light, nutrients, etc.). Here, we explore post-fire ecosystem recovery by evaluating seasonal GPP dynamics for two Ameriflux eddy covariance flux tower sites within the Santa Rita Experimental Range of southeastern Arizona: 1) the US-SRG savanna site dominated by a mix of grass and woody mesquite vegetation that was burned in May 2017, and 2) the US-SRM savanna site dominated by similar vegetation but unburned for the full measurement record. For each site, we collected leaf-level spectral and gas exchange measurements, as well as leaf-level chemistry and soil chemistry to characterize differences in nutrient availability and microbial activity throughout the 2017 growing season. From spectral data, we derived and evaluated multiple common vegetation metrics, including normalized difference vegetation index (NDVI), photochemical reflectivity index (PRI), near-infrared reflectance (NIRv), and MERIS terrestrial chlorophyll index (MTCI). Early results suggest rates of photosynthesis were enhanced at the burned site, with productivity increasing immediately following the onset of monsoonal precipitation; whereas initial photosynthesis at the unburned site remained relatively low following first monsoonal rains. MTCI values for burned vegetation appear to track higher levels of leaf-level nitrogen content upon monsoonal onset, but requires further validation by leaf-level chemistry. This work suggests that the integration of spectral, gas exchange, and soil measurements could be a powerful framework toward advancing our understanding of fire-ecosystem productivity feedbacks across spatiotemporal scales.

Implementation green and low cost on landscape design of Manggarai Integrated Station, Jakarta

NASA Astrophysics Data System (ADS)

Suryanti, T.; Meilianti, H.

2018-01-01

The Manggarai Integrated Station is the transit of various transportation modes. The Integrated Station located in Manggarai Jakarta and managed by PT. KAI. The Manggarai station is integrated and have terminal nature of transit areas (switching mode of transportation). There are several problems in the site, such as the problem of the site conditions in the urban area, topography, soil, vegetation, space, visual, users on the site can provide ideas for the concepts. The data was analyzed using the quantitative descriptive methode. The purpose of this research is to design the integrated station atmosphere, not only can support of the activities station users, but can also accommodate the needs of the community. It will “Green, Low cost” at the Manggarai integrated transport transit station in Jakarta. The potential that exists in this area is the lowliest integrated from various areas of the mode of transportation that make the users to facilitate transit transportation to the other. The basic concept of this design refers to the “Green, Low Cost” which unite with theme “user friendly” land use on a more efficient and effective site. The result of this research is landscape design development of Manggarai integrated station. Its consists of landscape design in west and east area, transition area, parking area, solar panel area, and social interaction area.

KDE Bioscience: platform for bioinformatics analysis workflows.

PubMed

Lu, Qiang; Hao, Pei; Curcin, Vasa; He, Weizhong; Li, Yuan-Yuan; Luo, Qing-Ming; Guo, Yi-Ke; Li, Yi-Xue

2006-08-01

Bioinformatics is a dynamic research area in which a large number of algorithms and programs have been developed rapidly and independently without much consideration so far of the need for standardization. The lack of such common standards combined with unfriendly interfaces make it difficult for biologists to learn how to use these tools and to translate the data formats from one to another. Consequently, the construction of an integrative bioinformatics platform to facilitate biologists' research is an urgent and challenging task. KDE Bioscience is a java-based software platform that collects a variety of bioinformatics tools and provides a workflow mechanism to integrate them. Nucleotide and protein sequences from local flat files, web sites, and relational databases can be entered, annotated, and aligned. Several home-made or 3rd-party viewers are built-in to provide visualization of annotations or alignments. KDE Bioscience can also be deployed in client-server mode where simultaneous execution of the same workflow is supported for multiple users. Moreover, workflows can be published as web pages that can be executed from a web browser. The power of KDE Bioscience comes from the integrated algorithms and data sources. With its generic workflow mechanism other novel calculations and simulations can be integrated to augment the current sequence analysis functions. Because of this flexible and extensible architecture, KDE Bioscience makes an ideal integrated informatics environment for future bioinformatics or systems biology research.

The Conjugative Relaxase TrwC Promotes Integration of Foreign DNA in the Human Genome.

PubMed

González-Prieto, Coral; Gabriel, Richard; Dehio, Christoph; Schmidt, Manfred; Llosa, Matxalen

2017-06-15

Bacterial conjugation is a mechanism of horizontal DNA transfer. The relaxase TrwC of the conjugative plasmid R388 cleaves one strand of the transferred DNA at the oriT gene, covalently attaches to it, and leads the single-stranded DNA (ssDNA) into the recipient cell. In addition, TrwC catalyzes site-specific integration of the transferred DNA into its target sequence present in the genome of the recipient bacterium. Here, we report the analysis of the efficiency and specificity of the integrase activity of TrwC in human cells, using the type IV secretion system of the human pathogen Bartonella henselae to introduce relaxase-DNA complexes. Compared to Mob relaxase from plasmid pBGR1, we found that TrwC mediated a 10-fold increase in the rate of plasmid DNA transfer to human cells and a 100-fold increase in the rate of chromosomal integration of the transferred DNA. We used linear amplification-mediated PCR and plasmid rescue to characterize the integration pattern in the human genome. DNA sequence analysis revealed mostly reconstituted oriT sequences, indicating that TrwC is active and recircularizes transferred DNA in human cells. One TrwC-mediated site-specific integration event was detected, proving that TrwC is capable of mediating site-specific integration in the human genome, albeit with very low efficiency compared to the rate of random integration. Our results suggest that TrwC may stabilize the plasmid DNA molecules in the nucleus of the human cell, probably by recircularization of the transferred DNA strand. This stabilization would increase the opportunities for integration of the DNA by the host machinery. IMPORTANCE Different biotechnological applications, including gene therapy strategies, require permanent modification of target cells. Long-term expression is achieved either by extrachromosomal persistence or by integration of the introduced DNA. Here, we studied the utility of conjugative relaxase TrwC, a bacterial protein with site-specific integrase activity in bacteria, as an integrase in human cells. Although it is not efficient as a site-specific integrase, we found that TrwC is active in human cells and promotes random integration of the transferred DNA in the human genome, probably acting as a DNA chaperone until it is integrated by host mechanisms. TrwC-DNA complexes can be delivered to human cells through a type IV secretion system involved in pathogenesis. Thus, TrwC could be used in vivo to transfer the DNA of interest into the appropriate cell and promote its integration. If used in combination with a site-specific nuclease, it could lead to site-specific integration of the incoming DNA by homologous recombination. Copyright © 2017 American Society for Microbiology.

The Conjugative Relaxase TrwC Promotes Integration of Foreign DNA in the Human Genome

PubMed Central

González-Prieto, Coral; Gabriel, Richard; Dehio, Christoph; Schmidt, Manfred

2017-01-01

ABSTRACT Bacterial conjugation is a mechanism of horizontal DNA transfer. The relaxase TrwC of the conjugative plasmid R388 cleaves one strand of the transferred DNA at the oriT gene, covalently attaches to it, and leads the single-stranded DNA (ssDNA) into the recipient cell. In addition, TrwC catalyzes site-specific integration of the transferred DNA into its target sequence present in the genome of the recipient bacterium. Here, we report the analysis of the efficiency and specificity of the integrase activity of TrwC in human cells, using the type IV secretion system of the human pathogen Bartonella henselae to introduce relaxase-DNA complexes. Compared to Mob relaxase from plasmid pBGR1, we found that TrwC mediated a 10-fold increase in the rate of plasmid DNA transfer to human cells and a 100-fold increase in the rate of chromosomal integration of the transferred DNA. We used linear amplification-mediated PCR and plasmid rescue to characterize the integration pattern in the human genome. DNA sequence analysis revealed mostly reconstituted oriT sequences, indicating that TrwC is active and recircularizes transferred DNA in human cells. One TrwC-mediated site-specific integration event was detected, proving that TrwC is capable of mediating site-specific integration in the human genome, albeit with very low efficiency compared to the rate of random integration. Our results suggest that TrwC may stabilize the plasmid DNA molecules in the nucleus of the human cell, probably by recircularization of the transferred DNA strand. This stabilization would increase the opportunities for integration of the DNA by the host machinery. IMPORTANCE Different biotechnological applications, including gene therapy strategies, require permanent modification of target cells. Long-term expression is achieved either by extrachromosomal persistence or by integration of the introduced DNA. Here, we studied the utility of conjugative relaxase TrwC, a bacterial protein with site-specific integrase activity in bacteria, as an integrase in human cells. Although it is not efficient as a site-specific integrase, we found that TrwC is active in human cells and promotes random integration of the transferred DNA in the human genome, probably acting as a DNA chaperone until it is integrated by host mechanisms. TrwC-DNA complexes can be delivered to human cells through a type IV secretion system involved in pathogenesis. Thus, TrwC could be used in vivo to transfer the DNA of interest into the appropriate cell and promote its integration. If used in combination with a site-specific nuclease, it could lead to site-specific integration of the incoming DNA by homologous recombination. PMID:28411218

Integration of High-Risk Human Papillomavirus into Cellular Cancer-Related Genes in Head and Neck Cancer Cell Lines

PubMed Central

Walline, Heather M; Komarck, Christine M; McHugh, Jonathan B; Tang, Alice L; Owen, John H; Teh, Bin T; McKean, Erin; Glover, Thomas; Graham, Martin P; Prince, Mark E; Chepeha, Douglas B; Chinn, Steven B; Ferris, Robert L; Gollin, Susanne M; Hoffmann, Thomas K; Bier, Henning; Brakenhoff, Ruud; Bradford, Carol R; Carey, Thomas E

2017-01-01

Background HPV-positive oropharyngeal cancer is generally associated with excellent response to therapy, but some HPV-positive tumors progress despite aggressive therapy. This study evaluates viral oncogene expression and viral integration sites in HPV16 and HPV18-positive squamous carcinoma cell lines. Methods E6-E7 alternate transcripts were assessed by RT-PCR. Detection of integrated papillomavirus sequences (DIPS-PCR) and sequencing identified viral insertion sites and affected host genes. Cellular gene expression was assessed across viral integration sites. Results All HPV-positive cell lines expressed alternate HPVE6/E7 splicing indicative of active viral oncogenesis. HPV integration occurred within cancer-related genes TP63, DCC, JAK1, TERT, ATR, ETV6, PGR, PTPRN2, and TMEM237 in 8 HNSCC lines but UM-SCC-105 and UM-GCC-1 had only intergenic integration. Conclusions HPV integration into cancer-related genes occurred in 7/9 HPV-positive cell lines and of these six were from tumors that progressed. HPV integration into cancer-related genes may be a secondary carcinogenic driver in HPV-driven tumors. PMID:28236344

Centralized Data Management in a Multicountry, Multisite Population-based Study.

PubMed

Rahman, Qazi Sadeq-ur; Islam, Mohammad Shahidul; Hossain, Belal; Hossain, Tanvir; Connor, Nicholas E; Jaman, Md Jahiduj; Rahman, Md Mahmudur; Ahmed, A S M Nawshad Uddin; Ahmed, Imran; Ali, Murtaza; Moin, Syed Mamun Ibne; Mullany, Luke; Saha, Samir K; El Arifeen, Shams

2016-05-01

A centralized data management system was developed for data collection and processing for the Aetiology of Neonatal Infection in South Asia (ANISA) study. ANISA is a longitudinal cohort study involving neonatal infection surveillance and etiology detection in multiple sites in South Asia. The primary goal of designing such a system was to collect and store data from different sites in a standardized way to pool the data for analysis. We designed the data management system centrally and implemented it to enable data entry at individual sites. This system uses validation rules and audit that reduce errors. The study sites employ a dual data entry method to minimize keystroke errors. They upload collected data weekly to a central server via internet to create a pooled central database. Any inconsistent data identified in the central database are flagged and corrected after discussion with the relevant site. The ANISA Data Coordination Centre in Dhaka provides technical support for operations, maintenance and updating the data management system centrally. Password-protected login identifications and audit trails are maintained for the management system to ensure the integrity and safety of stored data. Centralized management of the ANISA database helps to use common data capture forms (DCFs), adapted to site-specific contextual requirements. DCFs and data entry interfaces allow on-site data entry. This reduces the workload as DCFs do not need to be shipped to a single location for entry. It also improves data quality as all collected data from ANISA goes through the same quality check and cleaning process.

Comparison of Computer-based Clinical Decision Support Systems and Content for Diabetes Mellitus.

PubMed

Kantor, M; Wright, A; Burton, M; Fraser, G; Krall, M; Maviglia, S; Mohammed-Rajput, N; Simonaitis, L; Sonnenberg, F; Middleton, B

2011-01-01

Computer-based clinical decision support (CDS) systems have been shown to improve quality of care and workflow efficiency, and health care reform legislation relies on electronic health records and CDS systems to improve the cost and quality of health care in the United States; however, the heterogeneity of CDS content and infrastructure of CDS systems across sites is not well known. We aimed to determine the scope of CDS content in diabetes care at six sites, assess the capabilities of CDS in use at these sites, characterize the scope of CDS infrastructure at these sites, and determine how the sites use CDS beyond individual patient care in order to identify characteristics of CDS systems and content that have been successfully implemented in diabetes care. We compared CDS systems in six collaborating sites of the Clinical Decision Support Consortium. We gathered CDS content on care for patients with diabetes mellitus and surveyed institutions on characteristics of their site, the infrastructure of CDS at these sites, and the capabilities of CDS at these sites. The approach to CDS and the characteristics of CDS content varied among sites. Some commonalities included providing customizability by role or user, applying sophisticated exclusion criteria, and using CDS automatically at the time of decision-making. Many messages were actionable recommendations. Most sites had monitoring rules (e.g. assessing hemoglobin A1c), but few had rules to diagnose diabetes or suggest specific treatments. All sites had numerous prevention rules including reminders for providing eye examinations, influenza vaccines, lipid screenings, nephropathy screenings, and pneumococcal vaccines. Computer-based CDS systems vary widely across sites in content and scope, but both institution-created and purchased systems had many similar features and functionality, such as integration of alerts and reminders into the decision-making workflow of the provider and providing messages that are actionable recommendations.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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.more » 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.« less

Saturation behavior: a general relationship described by a simple second-order differential equation.

PubMed

Kepner, Gordon R

2010-04-13

The numerous natural phenomena that exhibit saturation behavior, e.g., ligand binding and enzyme kinetics, have been approached, to date, via empirical and particular analyses. This paper presents a mechanism-free, and assumption-free, second-order differential equation, designed only to describe a typical relationship between the variables governing these phenomena. It develops a mathematical model for this relation, based solely on the analysis of the typical experimental data plot and its saturation characteristics. Its utility complements the traditional empirical approaches. For the general saturation curve, described in terms of its independent (x) and dependent (y) variables, a second-order differential equation is obtained that applies to any saturation phenomena. It shows that the driving factor for the basic saturation behavior is the probability of the interactive site being free, which is described quantitatively. Solving the equation relates the variables in terms of the two empirical constants common to all these phenomena, the initial slope of the data plot and the limiting value at saturation. A first-order differential equation for the slope emerged that led to the concept of the effective binding rate at the active site and its dependence on the calculable probability the interactive site is free. These results are illustrated using specific cases, including ligand binding and enzyme kinetics. This leads to a revised understanding of how to interpret the empirical constants, in terms of the variables pertinent to the phenomenon under study. The second-order differential equation revealed the basic underlying relations that describe these saturation phenomena, and the basic mathematical properties of the standard experimental data plot. It was shown how to integrate this differential equation, and define the common basic properties of these phenomena. The results regarding the importance of the slope and the new perspectives on the empirical constants governing the behavior of these phenomena led to an alternative perspective on saturation behavior kinetics. Their essential commonality was revealed by this analysis, based on the second-order differential equation.

A novel, broad-range, CTXΦ-derived stable integrative expression vector for functional studies.

PubMed

Das, Bhabatosh; Kumari, Reena; Pant, Archana; Sen Gupta, Sourav; Saxena, Shruti; Mehta, Ojasvi; Nair, Gopinath Balakrish

2014-12-01

CTXΦ, a filamentous vibriophage encoding cholera toxin, uses a unique strategy for its lysogeny. The single-stranded phage genome forms intramolecular base-pairing interactions between two inversely oriented XerC and XerD binding sites (XBS) and generates a functional phage attachment site, attP(+), for integration. The attP(+) structure is recognized by the host-encoded tyrosine recombinases XerC and XerD (XerCD), which enables irreversible integration of CTXΦ into the chromosome dimer resolution site (dif) of Vibrio cholerae. The dif site and the XerCD recombinases are widely conserved in bacteria. We took advantage of these conserved attributes to develop a broad-host-range integrative expression vector that could irreversibly integrate into the host chromosome using XerCD recombinases without altering the function of any known open reading frame (ORF). In this study, we engineered two different arabinose-inducible expression vectors, pBD62 and pBD66, using XBS of CTXΦ. pBD62 replicates conditionally and integrates efficiently into the dif of the bacterial chromosome by site-specific recombination using host-encoded XerCD recombinases. The expression level of the gene of interest could be controlled through the PBAD promoter by modulating the functions of the vector-encoded transcriptional factor AraC. We validated the irreversible integration of pBD62 into a wide range of pathogenic and nonpathogenic bacteria, such as V. cholerae, Vibrio fluvialis, Vibrio parahaemolyticus, Escherichia coli, Salmonella enterica, and Klebsiella pneumoniae. Gene expression from the PBAD promoter of integrated vectors was confirmed in V. cholerae using the well-studied reporter genes mCherry, eGFP, and lacZ. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Characterization of Equine Infectious Anemia Virus Integration in the Horse Genome.

PubMed

Liu, Qiang; Wang, Xue-Feng; Ma, Jian; He, Xi-Jun; Wang, Xiao-Jun; Zhou, Jian-Hua

2015-06-19

Human immunodeficiency virus (HIV)-1 has a unique integration profile in the human genome relative to murine and avian retroviruses. Equine infectious anemia virus (EIAV) is another well-studied lentivirus that can also be used as a promising retro-transfection vector, but its integration into its native host has not been characterized. In this study, we mapped 477 integration sites of the EIAV strain EIAVFDDV13 in fetal equine dermal (FED) cells during in vitro infection. Published integration sites of EIAV and HIV-1 in the human genome were also analyzed as references. Our results demonstrated that EIAVFDDV13 tended to integrate into genes and AT-rich regions, and it avoided integrating into transcription start sites (TSS), which is consistent with EIAV and HIV-1 integration in the human genome. Notably, the integration of EIAVFDDV13 favored long interspersed elements (LINEs) and DNA transposons in the horse genome, whereas the integration of HIV-1 favored short interspersed elements (SINEs) in the human genome. The chromosomal environment near LINEs or DNA transposons potentially influences viral transcription and may be related to the unique EIAV latency states in equids. The data on EIAV integration in its natural host will facilitate studies on lentiviral infection and lentivirus-based therapeutic vectors.

Characterization of Equine Infectious Anemia Virus Integration in the Horse Genome

PubMed Central

Liu, Qiang; Wang, Xue-Feng; Ma, Jian; He, Xi-Jun; Wang, Xiao-Jun; Zhou, Jian-Hua

2015-01-01

Human immunodeficiency virus (HIV)-1 has a unique integration profile in the human genome relative to murine and avian retroviruses. Equine infectious anemia virus (EIAV) is another well-studied lentivirus that can also be used as a promising retro-transfection vector, but its integration into its native host has not been characterized. In this study, we mapped 477 integration sites of the EIAV strain EIAVFDDV13 in fetal equine dermal (FED) cells during in vitro infection. Published integration sites of EIAV and HIV-1 in the human genome were also analyzed as references. Our results demonstrated that EIAVFDDV13 tended to integrate into genes and AT-rich regions, and it avoided integrating into transcription start sites (TSS), which is consistent with EIAV and HIV-1 integration in the human genome. Notably, the integration of EIAVFDDV13 favored long interspersed elements (LINEs) and DNA transposons in the horse genome, whereas the integration of HIV-1 favored short interspersed elements (SINEs) in the human genome. The chromosomal environment near LINEs or DNA transposons potentially influences viral transcription and may be related to the unique EIAV latency states in equids. The data on EIAV integration in its natural host will facilitate studies on lentiviral infection and lentivirus-based therapeutic vectors. PMID:26102582

Integrated Information Support System (IISS). Volume 5. Common Data Model Subsystem. Part 2. CDMP Test Case Report.

DTIC Science & Technology

1985-11-01

As a o11066v. nlstle VSuSY £6I5PSAY I’ Iu PAS 11. Title Integrated Information Support System (1SS) Vol V - Common Data Model Subsystem Part 2 - CIMP ...AD-Mel1 236 INTEGRATED INFORMATION SUPPORT SYSTEM (IISS) VOLUME 5 1/2 COMMON DATA MODEL S.. (U) GENERAL ELECTRIC CO SCHENECTADY NY PRODUCTION...Volume V - Common Data Model Subsystem Part 2 - CDMP Test Case Report General Electric Company Production Resources Consulting One River Road

Transforming Research and Clinical Knowledge in Traumatic Brain Injury

DTIC Science & Technology

2016-12-01

Szuflita, N., Orman, J., and Schwab, K. (2010). Advancing integrated research in psychological health and traumatic brain injury: common data ele- ments...Szuflita N, Orman J, et al. Advancing Integrated Research in Psychological Health and Traumatic Brain Injury: Common Data Elements. Arch Phys Med Rehabil...R, Gleason T, et al. Advancing integrated research in psychological health and traumatic brain injury: common data elements. Arch Phys Med Rehabil

Better and more efficient care through ICT-enabled integration of social care and healthcare services: experiences from two European projects

PubMed Central

Müller, Sonja; Meyer, Ingo; Kubitschke, Lutz; Delaney, Sarah

2012-01-01

Unsynchronised social and health care service delivery leads to inefficiencies, duplication of resources and reduced levels of quality of care. Older people are particularly affected by this situation. They often need both types of services, such as support with daily living activities and chronic disease management. ICT has the potential to support integrated service delivery to achieve high quality independent living and wellbeing for older people across Europe and elsewhere. Against this background, the presentation will demonstrate experiences and results derived from the development and piloting of ICT-supported integrated care services in eight sites across Europe, namely Dublin, Hull, Milton Keynes, Malaga, Veldhoven, Geldrop, Eindhoven and Bielefeld. Through innovative usage of ICT, current ‘silos’ in service delivery are broken up to allow for cooperation across relevant care sectors and participation of family members. The integrated services are to support the effective management of chronic diseases, and to address issues which affect independence, such as reduced agility, vision or hearing, in order to significantly improve the quality of life for older people and their carers. A dedicated programme of service process innovation complemented by adaptation of technology is being pursued in order to develop an integrated digital support infrastructure and related services: using appropriate existing technology to provide as many older people as possible with digital access to support services they needaugmenting and opening sectoral care platforms to enable coordinated cross-sector support deliveryadopting a clearly demand-driven inclusive approach and avoiding a technology ‘push’. Wider deployment of the services is supported by a dedicated programme of socio-economic service evaluation. The evaluation framework utilises a multi-method and multi-perspective approach, involving end users, family carers, service provider staff and key informants at corporate level. Triangulation is used to cross-reference data from different sources in order to maximize the reliability and robustness of conclusions drawn from the evaluation. Based on an overall framework taking into account themes such as integration, user outcomes, staff impact, organisational impact, technology, implementation and overall satisfaction, the specifics of each site are taken into account in operationally applying the overall framework in each case. The designs to be employed at each site have been developed to be as robust as possible, taking into account the constraints of the realities of the interventions. The evaluation is accompanied by a business case modelling approach that builds largely on a cost-benefit analysis covering the service development and implementation activities as well as the pilots and modelling the further deployment of services in each of the pilot sites. The presentation builds upon experiences gained within the framework of two European projects, CommonWell and INDEPENDENT. They are both co-funded under the EU’s Competitiveness and Innovation Framework Programme (CIP) focus on better joining-up of formal social/healthcare services and strengthening participation of the so-called ‘third sector’.

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

NASA Astrophysics Data System (ADS)

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.

Lectindb: a plant lectin database.

PubMed

Chandra, Nagasuma R; Kumar, Nirmal; Jeyakani, Justin; Singh, Desh Deepak; Gowda, Sharan B; Prathima, M N

2006-10-01

Lectins, a class of carbohydrate-binding proteins, are now widely recognized to play a range of crucial roles in many cell-cell recognition events triggering several important cellular processes. They encompass different members that are diverse in their sequences, structures, binding site architectures, quaternary structures, carbohydrate affinities, and specificities as well as their larger biological roles and potential applications. It is not surprising, therefore, that the vast amount of experimental data on lectins available in the literature is so diverse, that it becomes difficult and time consuming, if not impossible to comprehend the advances in various areas and obtain the maximum benefit. To achieve an effective use of all the data toward understanding the function and their possible applications, an organization of these seemingly independent data into a common framework is essential. An integrated knowledge base ( Lectindb, http://nscdb.bic.physics.iisc.ernet.in ) together with appropriate analytical tools has therefore been developed initially for plant lectins by collating and integrating diverse data. The database has been implemented using MySQL on a Linux platform and web-enabled using PERL-CGI and Java tools. Data for each lectin pertain to taxonomic, biochemical, domain architecture, molecular sequence, and structural details as well as carbohydrate and hence blood group specificities. Extensive links have also been provided for relevant bioinformatics resources and analytical tools. Availability of diverse data integrated into a common framework is expected to be of high value not only for basic studies in lectin biology but also for basic studies in pursuing several applications in biotechnology, immunology, and clinical practice, using these molecules.

Site planning and integration fiscal year 1999 multi-year work plan (MYWP) update for WBS 1.8.2.1

DOE Office of Scientific and Technical Information (OSTI.GOV)

SCHULTZ, E.A.

The primary mission of the Site Planning and Integration (SP and I) project is to assist Fluor Daniel Project Direction to ensure that all work performed under the Project Hanford Management Contract (PHMC) is adequately planned, executed, controlled, and that performance is measured and reported in an integrated fashion. Furthermore, SP and I is responsible for the development, implementation, and management of systems and processes that integrate technical, schedule, and cost baselines for PHMC work.

Diversity/Equity. [SITE 2002 Section].

ERIC Educational Resources Information Center

Justice, Madeline, Ed.

This document contains the following papers on diversity/equity from the SITE (Society for Information Technology & Teacher Education) 2002 conference: (1) "Modeling and Developing Technology Integration with Pre-Service Indigenous Teachers" (Shadow W. J. Armfield and Marilyn Durocher); (2) "Integrating Diversity in Children's…

AGU Launches Web Site for New Scientific Integrity and Professional Ethics Policy

NASA Astrophysics Data System (ADS)

Townsend, Randy

2013-03-01

AGU's Scientific Integrity and Professional Ethics policy, approved by the AGU Board of Directors and Council in December 2012, is now available online on a new Web site, http://ethics.agu.org. As the Web site states, the policy embodies a "set of guidelines for scientific integrity and professional ethics for the actions of the members and the governance of the Union in its internal activities; in its public persona; and most importantly, in the research and peer review processes of its scientific publications, its communications and outreach, and its scientific meetings."

Multi-site study of diffusion metric variability: effects of site, vendor, field strength, and echo time on regions-of-interest and histogram-bin analyses.

PubMed

Helmer, K G; Chou, M-C; Preciado, R I; Gimi, B; Rollins, N K; Song, A; Turner, J; Mori, S

2016-02-27

It is now common for magnetic-resonance-imaging (MRI) based multi-site trials to include diffusion-weighted imaging (DWI) as part of the protocol. It is also common for these sites to possess MR scanners of different manufacturers, different software and hardware, and different software licenses. These differences mean that scanners may not be able to acquire data with the same number of gradient amplitude values and number of available gradient directions. Variability can also occur in achievable b-values and minimum echo times. The challenge of a multi-site study then, is to create a common protocol by understanding and then minimizing the effects of scanner variability and identifying reliable and accurate diffusion metrics. This study describes the effect of site, scanner vendor, field strength, and TE on two diffusion metrics: the first moment of the diffusion tensor field (mean diffusivity, MD), and the fractional anisotropy (FA) using two common analyses (region-of-interest and mean-bin value of whole brain histograms). The goal of the study was to identify sources of variability in diffusion-sensitized imaging and their influence on commonly reported metrics. The results demonstrate that the site, vendor, field strength, and echo time all contribute to variability in FA and MD, though to different extent. We conclude that characterization of the variability of DTI metrics due to site, vendor, field strength, and echo time is a worthwhile step in the construction of multi-center trials.

[Validation of two indices of biological integrity (IBI) for the Angulo River subbasin in Central Mexico].

PubMed

Ramírez-Herrejón, Juan Pablo; Mercado-Silva, Norman; Medina-Nava, Martina; Domínguez-Domínguez, Omar

2012-12-01

Efforts to halt freshwater ecosystem degradation in central Mexico can benefit from using bio-monitoring tools that reflect the condition of their biotic integrity. We analyzed the applicability of two fish-based indices of biotic integrity using data from lotic and lentic systems in the Angulo River subbasin (Lerma-Chapala basin). Both independent data from our own collections during two consecutive years, and existing information detailing the ecological attributes of each species, were used to calculate indices of biological integrity for 16 sites in lotic and lentic habitats. We assessed environmental quality by combining independent evaluations water and habitat quality for each site. We found sites with poor, regular and good biotic integrity. Our study did not find sites with good environmental quality. Fish-based IBI scores were strongly and significantly correlated with scores from independent environmental assessment techniques. IBI scores were adequate at representing environmental conditions in most study sites. These results expand the area where a lotic system fish-based IBI can be used, and constitute an initial validation of a lentic system fish-based IBI. Our results suggest that these bio-monitoring tools can be used in future conservation efforts in freshwater ecosystems in the Middle Lerma Basin.

Converting Maturing Nuclear Sites to Integrated Power Production Islands

DOE PAGES

Solbrig, Charles W.

2011-01-01

Nuclear islands, which are integrated power production sites, could effectively sequester and safeguard the US stockpile of plutonium. A nuclear island, an evolution of the integral fast reactor, utilizes all the Transuranics (Pu plus minor actinides) produced in power production, and it eliminates all spent fuel shipments to and from the site. This latter attribute requires that fuel reprocessing occur on each site and that fast reactors be built on-site to utilize the TRU. All commercial spent fuel shipments could be eliminated by converting all LWR nuclear power sites to nuclear islands. Existing LWR sites have the added advantage ofmore » already possessing a license to produce nuclear power. Each could contribute to an increase in the nuclear power production by adding one or more fast reactors. Both the TRU and the depleted uranium obtained in reprocessing would be used on-site for fast fuel manufacture. Only fission products would be shipped to a repository for storage. The nuclear island concept could be used to alleviate the strain of LWR plant sites currently approaching or exceeding their spent fuel pool storage capacity. Fast reactor breeding ratio could be designed to convert existing sites to all fast reactors, or keep the majority thermal.« less

Physical and Chemical Aerosol Properties At An Urban and A Rural Site During An Episode of Strong Photochemical Activity During Escompte

NASA Astrophysics Data System (ADS)

van Dingenen, R.; Putaud, J. P.; dell'Acqua, A.; Martins-Dos Santos, S.; Viidanoja, J.; Raes, F.

During the ESCOMPTE campaign (10 June to 14 July, 2001), JRC mobile laboratories for aerosol physical and chemical measurements were deployed at two ground-based sites: Vallon Dol, located at the Northern edge of the Marseille agglomeration and Vi- non, a rural site about 80 km North-East of Marseille. Both sites were equipped with on-line instrumentation for number size distributions in the diameter size range 6nm to 10µm (10 minute time resolution), equivalent black carbon (15 minute time reso- lution), major anions and cations (15 minute time resolution). Time-integrated filter sampling at each site with a time resolution of 6-12 hours was performed with 2 sets of virtual impactors, separating the fine and coarse aerosol fraction. One set, loaded with quartz filters, was analyzed off-line using the `evolved gas analysis` technique for organic and elemental carbon. The second set, loaded with paper filters, was analyzed for dust (by ashing) and ionic composition. On top of the common instrumentation, the urban site was additionally performing on-line PM10 measurements (TEOM with sample equilibration system, 10 minute time resolution) and, during intensive obser- vation periods (IOP), size-segregated sampling with a 8 stage low-pressure Berner im- pactor (6-12 hours time resolution). In this presentation we will focus on data obtained during the second IOP (20-6 to 26-6). During this episode, the sea-breeze transported Marseille pollution plume was clearly observed at the Vinon rural site. Comparison of the aerosol properties at both sites will allow to evaluate the processes that contribute to the (trans)formation of particulate matter in the particular conditions of a marine air mass, mixed with local pollution and undergoing strong photochemical processes during in-land transport.

Integration of Student Field-Based Research with Development of Educational Material Utilizing Gigapan Technology

NASA Astrophysics Data System (ADS)

Gonzales, J.; Goodell, P.; Bentley, C.

2013-12-01

Formative field-based research and innovative interactive learning have both shown to dramatically improve student retention and participation in STEM fields. El Paso Community (EPCC), Northern Virginia Community College (NOVA), and the University of Texas at El Paso (UTEP) have formed a collaborative to develop interactive pedagogy regarding local El Paso geology for online learning utilizing Gigapan technology. The pedagogy will be geared for grades 8-12, community and four-year college educational purposes, and as a virtual experience used to elaborate and enhance real field experiences. Field samples for thin-sections and Gigapan material were collected at key geological sites and of key lithologies of the region. The educational material from these site will range from macro-scale (Gigapans) to micro-scale (thin sections) and are expected to be completed by spring 2014. This collaboration between EPCC, NOVA, and UTEP is an example of a successful model of community colleges and universities working together sharing their respective resources to accomplish a common educational goal.

Contamination of water due to major industries and open refuse dumping in the steel city of Orissa--a case study.

PubMed

Mishra, P C; Behera, P C; Patel, R K

2005-04-01

Contamination of ground water is common in the areas surrounded by industrial refuse dumping sites and the probability of contamination is more where dumping is done in low lying areas and the rate of percolation through the soil is high. In order to assess the ground water pollution by leachate around the refuse dumping site, eighteen wells were selected for study. Few wells are nearer to the dumps, few are far away and others are in between. Also an attempt has been made to evaluate the effect of industrial effluents on the ground and surface water due to Integrated Rourkela Steel Plant and other major industries. From the analytical data of physico-chemical parameters, it is indicated that the river water is contaminated mainly due to the industrial and municipal effluents and the ground water of some of the analyzed areas is contaminated due to municipal and industrial solid waste dumping.

Nation Building and Social Signaling in Southern Ontario: A.D. 1350-1650.

PubMed

Hart, John P; Shafie, Termeh; Birch, Jennifer; Dermarkar, Susan; Williamson, Ronald F

2016-01-01

Pottery is a mainstay of archaeological analysis worldwide. Often, high proportions of the pottery recovered from a given site are decorated in some manner. In northern Iroquoia, late pre-contact pottery and early contact decoration commonly occur on collars-thick bands of clay that encircle a pot and extend several centimeters down from the lip. These decorations constitute signals that conveyed information about a pot's user(s). In southern Ontario the period A.D. 1350 to 1650 witnessed substantial changes in socio-political and settlement systems that included population movement, coalescence of formerly separate communities into large villages and towns, waxing and waning of regional strife, the formation of nations, and finally the development of three confederacies that each occupied distinct, constricted areas. Social network analysis demonstrates that signaling practices changed to reflect these regional patterns. Networks become more consolidated through time ultimately resulting in a "small world" network with small degrees of separation between sites reflecting the integration of communities within and between the three confederacies.

Retrotransposon Tf1 is targeted to pol II promoters by transcription activators

PubMed Central

Leem, Young-Eun; Ripmaster, Tracy; Kelly, Felice; Ebina, Hirotaka; Heincelman, Marc; Zhang, Ke; Grewal, Shiv I. S.; Hoffman, Charles S.; Levin, Henry L.

2008-01-01

SUMMARY The LTR-retrotransposon Tf1 preserves the coding capacity of its host Schizosaccharomyces pombe by integrating upstream of open reading frames (ORFs). To determine which features of the target sites were recognized by the transposon, we introduced plasmids containing candidate insertion sites into S. pombe and mapped the positions of integration. We found that Tf1 was targeted specifically to the promoters of pol II transcribed genes. A detailed analysis of integration in plasmids that contained either ade6 or fbp1 revealed insertions occurred in the promoters at positions where transcription factors bound. Further experiments revealed that the activator Atf1p and its binding site were required for directing integration to the promoter of fbp1. An interaction between Tf1 integrase and Atf1p was observed indicating that integration at fbp1 was mediated by the activator bound to its promoter. Surprisingly we found Tf1 contained sequences that activated transcription and these substituted for elements of the ade6 promoter disrupted by integration. PMID:18406330

Retrotransposon Tf1 is targeted to Pol II promoters by transcription activators.

PubMed

Leem, Young-Eun; Ripmaster, Tracy L; Kelly, Felice D; Ebina, Hirotaka; Heincelman, Marc E; Zhang, Ke; Grewal, Shiv I S; Hoffman, Charles S; Levin, Henry L

2008-04-11

The LTR-retrotransposon Tf1 preserves the coding capacity of its host Schizosaccharomyces pombe by integrating upstream of open reading frames (ORFs). To determine which features of the target sites were recognized by the transposon, we introduced plasmids containing candidate insertion sites into S. pombe and mapped the positions of integration. We found that Tf1 was targeted specifically to the promoters of Pol II-transcribed genes. A detailed analysis of integration in plasmids that contained either ade6 or fbp1 revealed insertions occurred in the promoters at positions where transcription factors bound. Further experiments revealed that the activator Atf1p and its binding site were required for directing integration to the promoter of fbp1. An interaction between Tf1 integrase and Atf1p was observed, indicating that integration at fbp1 was mediated by the activator bound to its promoter. Surprisingly, we found Tf1 contained sequences that activated transcription, and these substituted for elements of the ade6 promoter disrupted by integration.

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

PubMed

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.

Terrestrial reference standard sites for postlaunch sensor calibration

USGS Publications Warehouse

Teillet, P.M.; Chander, G.

2010-01-01

In an era when the number of Earth observation satellites is rapidly growing and measurements from satellite sensors are used to address increasingly urgent global issues, often through synergistic and operational combinations of data from multiple sources, it is imperative that scientists and decision-makers are able to rely on the accuracy of Earth observation data products. The characterization and calibration of these sensors, particularly their relative biases, are vital to the success of the developing integrated Global Earth Observation System of Systems (GEOSS) for coordinated and sustained observations of the Earth. This can only reliably be achieved in the postlaunch environment through the careful use of observations by multiple sensor systems over common, well-characterized terrestrial targets (i.e., on or near the Earth's surface). Through greater access to and understanding of these vital reference standard sites and their use, the validity and utility of information gained from Earth remote sensing will continue to improve. This paper provides a brief overview of the use of reference standard sites for postlaunch sensor radiometric calibration from historical, current, and future perspectives. Emphasis is placed on optical sensors operating in the visible, near-infrared, and shortwave infrared spectral regions.

Investigation of frog abnormalities on national wildlife refuges in the Northeast U.S.

USGS Publications Warehouse

Eaton-Poole, L.; Pinkney, A.E.; Green, D.E.; Sutherland, D.R.; Babbitt, K.J.; ,

2003-01-01

To address concerns about frog abnormalities, the U.S. Fish and Wildlife Service examined over 3,643 frogs and toads on National Wildlife Refuges (NWRs) in the Northeast U.S. The objectives were to: 1) determine if certain refuges had sites where abnormalities were frequently observed; 2) evaluate if the prevalence of abnormalities at a site was consistent within a season and among years; and 3) investigate possible causes. Sampling was conducted from 1999 through 2001. A complete sample from a site consisted of ???50 metamorphs of one species. The prevalence of abnormalities ranged from 0 to 15% and fluctuated within season and among years. The most common external abnormalities were truncated limbs, and missing limbs, feet, and digits. Frogs with duplication of limb segments were rare (6). Based on radiographical examinations of 89 abnormal frogs, 55 had abnormalities due to trauma, 22 due to malformations, and 12 could not be classified. Metacercariae of the trematode Ribeiroia were detected in substantial numbers in two species from Iroquois NWR, with one specimen having supernumerary hindlimbs. We recommend continued sampling and integrated, causal evaluations on NWRs where the prevalence of abnormalities exceeds 5% or where the types of abnormalities warrant further study.

Measuring the role of seagrasses in regulating sediment surface elevation

USGS Publications Warehouse

Potouroglou, Maria; Bull, James C.; Krauss, Ken W.; Kennedy, Hilary A.; Fusi, Marco; Daffonchio, Daniele; Mangora, Mwita M.; Githaiga, Michael N.; Diele, Karen; Huxham, Mark

2017-01-01

Seagrass meadows provide numerous ecosystem services and their rapid global loss may reduce human welfare as well as ecological integrity. In common with the other ‘blue carbon’ habitats (mangroves and tidal marshes) seagrasses are thought to provide coastal defence and encourage sediment stabilisation and surface elevation. A sophisticated understanding of sediment elevation dynamics in mangroves and tidal marshes has been gained by monitoring a wide range of different sites, located in varying hydrogeomorphological conditions over long periods. In contrast, similar evidence for seagrasses is sparse; the present study is a contribution towards filling this gap. Surface elevation change pins were deployed in four locations, Scotland, Kenya, Tanzania and Saudi Arabia, in both seagrass and unvegetated control plots in the low intertidal and shallow subtidal zone. The presence of seagrass had a highly significant, positive impact on surface elevation at all sites. Combined data from the current work and the literature show an average difference of 31 mm per year in elevation rates between vegetated and unvegetated areas, which emphasizes the important contribution of seagrass in facilitating sediment surface elevation and reducing erosion. This paper presents the first multi-site study for sediment surface elevation in seagrasses in different settings and species.

Measuring the role of seagrasses in regulating sediment surface elevation.

PubMed

Potouroglou, Maria; Bull, James C; Krauss, Ken W; Kennedy, Hilary A; Fusi, Marco; Daffonchio, Daniele; Mangora, Mwita M; Githaiga, Michael N; Diele, Karen; Huxham, Mark

2017-09-20

Seagrass meadows provide numerous ecosystem services and their rapid global loss may reduce human welfare as well as ecological integrity. In common with the other 'blue carbon' habitats (mangroves and tidal marshes) seagrasses are thought to provide coastal defence and encourage sediment stabilisation and surface elevation. A sophisticated understanding of sediment elevation dynamics in mangroves and tidal marshes has been gained by monitoring a wide range of different sites, located in varying hydrogeomorphological conditions over long periods. In contrast, similar evidence for seagrasses is sparse; the present study is a contribution towards filling this gap. Surface elevation change pins were deployed in four locations, Scotland, Kenya, Tanzania and Saudi Arabia, in both seagrass and unvegetated control plots in the low intertidal and shallow subtidal zone. The presence of seagrass had a highly significant, positive impact on surface elevation at all sites. Combined data from the current work and the literature show an average difference of 31 mm per year in elevation rates between vegetated and unvegetated areas, which emphasizes the important contribution of seagrass in facilitating sediment surface elevation and reducing erosion. This paper presents the first multi-site study for sediment surface elevation in seagrasses in different settings and species.

TECHNOLOGY INTEGRATION FOR CONTAMINATED SITE REMEDIATION: CLEANUP GOALS & PERFORMANCE CRITERIA

EPA Science Inventory

There is a need to develop and field-test integrated remediation technologies that operate in a synergistic manner for cost-effective treatment of contaminated sites to achieve risk-based and rational endpoints. Aggressive technologies designed for rapid source-zone remediation m...

36 CFR 228.64 - Community sites and common-use areas.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 36 Parks, Forests, and Public Property 2 2011-07-01 2011-07-01 false Community sites and common-use areas. 228.64 Section 228.64 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE MINERALS Disposal of Mineral Materials Types and Methods of Disposal § 228.64 Community sites and...

36 CFR 228.64 - Community sites and common-use areas.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 36 Parks, Forests, and Public Property 2 2014-07-01 2014-07-01 false Community sites and common-use areas. 228.64 Section 228.64 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE MINERALS Disposal of Mineral Materials Types and Methods of Disposal § 228.64 Community sites and...

36 CFR 228.64 - Community sites and common-use areas.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 36 Parks, Forests, and Public Property 2 2013-07-01 2013-07-01 false Community sites and common-use areas. 228.64 Section 228.64 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE MINERALS Disposal of Mineral Materials Types and Methods of Disposal § 228.64 Community sites and...

36 CFR 228.64 - Community sites and common-use areas.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Community sites and common-use areas. 228.64 Section 228.64 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE MINERALS Disposal of Mineral Materials Types and Methods of Disposal § 228.64 Community sites and...

36 CFR 228.64 - Community sites and common-use areas.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 2 2012-07-01 2012-07-01 false Community sites and common-use areas. 228.64 Section 228.64 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE MINERALS Disposal of Mineral Materials Types and Methods of Disposal § 228.64 Community sites and...

Sulfometuron methyl: Its use in forestry and potential phytotoxicity

Treesearch

Nathan D. Robertson; Anthony S. Davis

2010-01-01

Planting site preparation is a common practice used to enhance seedling establishment success. Site preparations include herbicide, fire, and mechanical methods. Studies designed to explore the use of herbicides as site preparation and release tools are common, and herbicides have shown their use in forestry to be logistically, economically, and ecologically...

RNAP II Processivity is a Limiting Step for HIV-1 Transcription Independent of Orientation to and Activity of Endogenous Neighboring Promoters

PubMed Central

Michaels, Katarzyna Kaczmarek; Wolschendorf, Frank; Schiralli Lester, Gillian M.; Natarajan, Malini; Kutsch, Olaf; Henderson, Andrew J.

2015-01-01

Since HIV-1 has a propensity to integrate into actively expressed genes, transcriptional interference from neighboring host promoters has been proposed to contribute to the establishment and maintenance HIV-1 latency. To gain insights into how endogenous promoters influence HIV-1 transcription we utilized a set of inducible T cell lines and characterized whether there were correlations between expression of endogenous genes, provirus and long terminal repeat architecture. We show that neighboring promoters are active but have minimal impact on HIV-1 transcription, in particular, expression of the endogenous gene did not prevent expression of HIV-1 following induction of latent provirus. We also demonstrate that releasing paused RNAP II by diminishing negative elongation factor (NELF) is sufficient to reactivate transcriptionally repressed HIV-1 provirus regardless of the integration site and orientation of the provirus suggesting that NELF-mediated RNAP II pausing is a common mechanism of maintaining HIV-1 latency. PMID:26379089

blend4php: a PHP API for galaxy

PubMed Central

Wytko, Connor; Soto, Brian; Ficklin, Stephen P.

2017-01-01

Galaxy is a popular framework for execution of complex analytical pipelines typically for large data sets, and is a commonly used for (but not limited to) genomic, genetic and related biological analysis. It provides a web front-end and integrates with high performance computing resources. Here we report the development of the blend4php library that wraps Galaxy’s RESTful API into a PHP-based library. PHP-based web applications can use blend4php to automate execution, monitoring and management of a remote Galaxy server, including its users, workflows, jobs and more. The blend4php library was specifically developed for the integration of Galaxy with Tripal, the open-source toolkit for the creation of online genomic and genetic web sites. However, it was designed as an independent library for use by any application, and is freely available under version 3 of the GNU Lesser General Public License (LPGL v3.0) at https://github.com/galaxyproject/blend4php. Database URL: https://github.com/galaxyproject/blend4php PMID:28077564

Using fish communities to assess streams in Romania: Initial development of an index of biotic integrity

USGS Publications Warehouse

Angermeier, P.L.; Davideanu, G.

2004-01-01

Multimetric biotic indices increasingly are used to complement physicochemical data in assessments of stream quality. We initiated development of multimetric indices, based on fish communities, to assess biotic integrity of streams in two physiographic regions of central Romania. Unlike previous efforts to develop such indices for European streams, our metrics and scoring criteria were selected largely on the basis of empirical relations in the regions of interest. We categorised 54 fish species with respect to ten natural-history attributes, then used this information to compute 32 candidate metrics of five types (taxonomic, tolerance, abundance, reproductive, and feeding) for each of 35 sites. We assessed the utility of candidate metrics for detecting anthropogenic impact based on three criteria: (a) range of values taken, (b) relation to a site-quality index (SQI), which incorporated information on hydrologic alteration, channel alteration, land-use intensity, and water chemistry, and (c) metric redundancy. We chose seven metrics from each region to include in preliminary multimetric indices (PMIs). Both PMIs included taxonomic, tolerance, and feeding metrics, but only two metrics were common to both PMIs. Although we could not validate our PMIs, their strong association with the SQI in each region suggests that such indices would be valuable tools for assessing stream quality and could provide more comprehensive assessments than the traditional approaches based solely on water chemistry.

Integrating multiple scientific computing needs via a Private Cloud infrastructure

NASA Astrophysics Data System (ADS)

Bagnasco, S.; Berzano, D.; Brunetti, R.; Lusso, S.; Vallero, S.

2014-06-01

In a typical scientific computing centre, diverse applications coexist and share a single physical infrastructure. An underlying Private Cloud facility eases the management and maintenance of heterogeneous use cases such as multipurpose or application-specific batch farms, Grid sites catering to different communities, parallel interactive data analysis facilities and others. It allows to dynamically and efficiently allocate resources to any application and to tailor the virtual machines according to the applications' requirements. Furthermore, the maintenance of large deployments of complex and rapidly evolving middleware and application software is eased by the use of virtual images and contextualization techniques; for example, rolling updates can be performed easily and minimizing the downtime. In this contribution we describe the Private Cloud infrastructure at the INFN-Torino Computer Centre, that hosts a full-fledged WLCG Tier-2 site and a dynamically expandable PROOF-based Interactive Analysis Facility for the ALICE experiment at the CERN LHC and several smaller scientific computing applications. The Private Cloud building blocks include the OpenNebula software stack, the GlusterFS filesystem (used in two different configurations for worker- and service-class hypervisors) and the OpenWRT Linux distribution (used for network virtualization). A future integration into a federated higher-level infrastructure is made possible by exposing commonly used APIs like EC2 and by using mainstream contextualization tools like CloudInit.

Common source cascode amplifiers for integrating IR-FPA applications

NASA Technical Reports Server (NTRS)

Woolaway, James T.; Young, Erick T.

1989-01-01

Space based astronomical infrared measurements present stringent performance requirements on the infrared detector arrays and their associated readout circuitry. To evaluate the usefulness of commercial CMOS technology for astronomical readout applications a theoretical and experimental evaluation was performed on source follower and common-source cascode integrating amplifiers. Theoretical analysis indicates that for conditions where the input amplifier integration capacitance is limited by the detectors capacitance the input referred rms noise electrons of each amplifier should be equivalent. For conditions of input gate limited capacitance the source follower should provide lower noise. Measurements of test circuits containing both source follower and common source cascode circuits showed substantially lower input referred noise for the common-source cascode input circuits. Noise measurements yielded 4.8 input referred rms noise electrons for an 8.5 minute integration. The signal and noise gain of the common-source cascode amplifier appears to offer substantial advantages in acheiving predicted noise levels.

Growth Rate and Relocation Movements of Common Nighthawk (Chordeiles minor) Nestlings in Relation to Age

USGS Publications Warehouse

Kramer, Gunnar R.; Chalfoun, Anna D.

2012-01-01

Relocation by dependent young is a survival strategy that occurs among a wide range of taxa. The Common Nighthawk (Chordeiles minor) lays its eggs on bare substrate and, once hatched, nestlings may relocate to new sites daily. We located and monitored eight Common Nighthawk nests in Grand Teton National Park, Wyoming, quantified inter-use-site distances in relation to nestling age, and calculated a nestling growth rate curve. Common Nighthawk nestlings grow in a nearly linear fashion. Nestlings moved up to 48 m in a single day and larger, older nestlings tended to move greater distances between daily use-sites.

Ames expedited site characterization demonstration at the former manufactured gas plant site, Marshalltown, Iowa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bevolo, A.J.; Kjartanson, B.H.; Wonder, J.D.

1996-03-01

The goal of the Ames Expedited Site Characterization (ESC) project is to evaluate and promote both innovative technologies (IT) and state-of-the-practice technologies (SOPT) for site characterization and monitoring. In April and May 1994, the ESC project conducted site characterization, technology comparison, and stakeholder demonstration activities at a former manufactured gas plant (FMGP) owned by Iowa Electric Services (IES) Utilities, Inc., in Marshalltown, Iowa. Three areas of technology were fielded at the Marshalltown FMGP site: geophysical, analytical and data integration. The geophysical technologies are designed to assess the subsurface geological conditions so that the location, fate and transport of the targetmore » contaminants may be assessed and forecasted. The analytical technologies/methods are designed to detect and quantify the target contaminants. The data integration technology area consists of hardware and software systems designed to integrate all the site information compiled and collected into a conceptual site model on a daily basis at the site; this conceptual model then becomes the decision-support tool. Simultaneous fielding of different methods within each of the three areas of technology provided data for direct comparison of the technologies fielded, both SOPT and IT. This document reports the results of the site characterization, technology comparison, and ESC demonstration activities associated with the Marshalltown FMGP site. 124 figs., 27 tabs.« less

The Planteome database: an integrated resource for reference ontologies, plant genomics and phenomics

PubMed Central

Cooper, Laurel; Meier, Austin; Laporte, Marie-Angélique; Elser, Justin L; Mungall, Chris; Sinn, Brandon T; Cavaliere, Dario; Carbon, Seth; Dunn, Nathan A; Smith, Barry; Qu, Botong; Preece, Justin; Zhang, Eugene; Todorovic, Sinisa; Gkoutos, Georgios; Doonan, John H; Stevenson, Dennis W; Arnaud, Elizabeth

2018-01-01

Abstract The Planteome project (http://www.planteome.org) provides a suite of reference and species-specific ontologies for plants and annotations to genes and phenotypes. Ontologies serve as common standards for semantic integration of a large and growing corpus of plant genomics, phenomics and genetics data. The reference ontologies include the Plant Ontology, Plant Trait Ontology and the Plant Experimental Conditions Ontology developed by the Planteome project, along with the Gene Ontology, Chemical Entities of Biological Interest, Phenotype and Attribute Ontology, and others. The project also provides access to species-specific Crop Ontologies developed by various plant breeding and research communities from around the world. We provide integrated data on plant traits, phenotypes, and gene function and expression from 95 plant taxa, annotated with reference ontology terms. The Planteome project is developing a plant gene annotation platform; Planteome Noctua, to facilitate community engagement. All the Planteome ontologies are publicly available and are maintained at the Planteome GitHub site (https://github.com/Planteome) for sharing, tracking revisions and new requests. The annotated data are freely accessible from the ontology browser (http://browser.planteome.org/amigo) and our data repository. PMID:29186578

T-DNA-genome junctions form early after infection and are influenced by the chromatin state of the host genome

PubMed Central

Tripathi, Pooja; Muth, Theodore R.

2017-01-01

Agrobacterium tumefaciens mediated T-DNA integration is a common tool for plant genome manipulation. However, there is controversy regarding whether T-DNA integration is biased towards genes or randomly distributed throughout the genome. In order to address this question, we performed high-throughput mapping of T-DNA-genome junctions obtained in the absence of selection at several time points after infection. T-DNA-genome junctions were detected as early as 6 hours post-infection. T-DNA distribution was apparently uniform throughout the chromosomes, yet local biases toward AT-rich motifs and T-DNA border sequence micro-homology were detected. Analysis of the epigenetic landscape of previously isolated sites of T-DNA integration in Kanamycin-selected transgenic plants showed an association with extremely low methylation and nucleosome occupancy. Conversely, non-selected junctions from this study showed no correlation with methylation and had chromatin marks, such as high nucleosome occupancy and high H3K27me3, that correspond to three-dimensional-interacting heterochromatin islands embedded within euchromatin. Such structures may play a role in capturing and silencing invading T-DNA. PMID:28742090

TECHNOLOGY INTEGRATION FOR CONTAMINATED SITE REMEDIATION: CLEANUP GOALS AND PERFORMANCE CRITERIA

EPA Science Inventory

There is a need to develop and field-test integrated remediation technologies that operate in a synergistic manner for cost-effective treatment of contaminated sites to achieve risk-based and rational endpoints. Aggressive technologies designed for rapid source-zone remediation m...

Seasonal Liza aurata tissue-specific DNA integrity in a multi-contaminated coastal lagoon (Ria de Aveiro, Portugal).

PubMed

Oliveira, M; Maria, V L; Ahmad, I; Pacheco, M; Santos, M A

2010-10-01

In this study, the DNA integrity of golden grey mullet (Liza aurata) collected in differently contaminated sites of a coastal lagoon, Ria de Aveiro (Portugal), was assessed, over the period of 1 year, using the DNA alkaline unwinding assay, in four different tissues (gill, kidney, liver and blood) and compared to a reference site. The four tissues displayed different DNA integrity basal levels, clearly affected by seasonal factors. Gill and kidney were, respectively, the most and least sensitive tissues. All sites demonstrated the capacity to interfere with DNA integrity. The sites displaying the highest and lowest DNA damage capability were, respectively, Barra (subject to naval traffic) and Vagos (contaminated with polycyclic aromatic hydrocarbons). In terms of seasonal variability, autumn seems to be the more critical season (more DNA damage) unlike summer when no DNA damage was found in any tissue. Data recommend the continued monitoring of this aquatic system. Copyright © 2010 Elsevier Ltd. All rights reserved.

Current Treatments Available for Scleroderma Patients

MedlinePlus

... from infection from bacteria at the site of infusion, the most common include edema (swelling); accumulation of ... irritated skin and/or hardening of skin at infusion site; flushing, faintness, dizziness or lightheadedness. Less common ...

Developing a data infrastructure for a learning health system: the PORTAL network

PubMed Central

McGlynn, Elizabeth A; Lieu, Tracy A; Durham, Mary L; Bauck, Alan; Laws, Reesa; Go, Alan S; Chen, Jersey; Feigelson, Heather Spencer; Corley, Douglas A; Young, Deborah Rohm; Nelson, Andrew F; Davidson, Arthur J; Morales, Leo S; Kahn, Michael G

2014-01-01

The Kaiser Permanente & Strategic Partners Patient Outcomes Research To Advance Learning (PORTAL) network engages four healthcare delivery systems (Kaiser Permanente, Group Health Cooperative, HealthPartners, and Denver Health) and their affiliated research centers to create a new national network infrastructure that builds on existing relationships among these institutions. PORTAL is enhancing its current capabilities by expanding the scope of the common data model, paying particular attention to incorporating patient-reported data more systematically, implementing new multi-site data governance procedures, and integrating the PCORnet PopMedNet platform across our research centers. PORTAL is partnering with clinical research and patient experts to create cohorts of patients with a common diagnosis (colorectal cancer), a rare diagnosis (adolescents and adults with severe congenital heart disease), and adults who are overweight or obese, including those with pre-diabetes or diabetes, to conduct large-scale observational comparative effectiveness research and pragmatic clinical trials across diverse clinical care settings. PMID:24821738

A review of multi-threat medical countermeasures against chemical warfare and terrorism.

PubMed

Cowan, Fred M; Broomfield, Clarence A; Stojiljkovic, Milos P; Smith, William J

2004-11-01

The Multi-Threat Medical Countermeasure (MTMC) hypothesis has been proposed with the aim of developing a single countermeasure drug with efficacy against different pathologies caused by multiple classes of chemical warfare agents. Although sites and mechanisms of action and the pathologies caused by different chemical insults vary, common biochemical signaling pathways, molecular mediators, and cellular processes provide targets for MTMC drugs. This article will review the MTMC hypothesis for blister and nerve agents and will expand the scope of the concept to include other chemicals as well as briefly consider biological agents. The article will also consider how common biochemical signaling pathways, molecular mediators, and cellular processes that contribute to clinical pathologies and syndromes may relate to the toxicity of threat agents. Discovery of MTMC provides the opportunity for the integration of diverse researchers and clinicians, and for the exploitation of cutting-edge technologies and drug discovery. The broad-spectrum nature of MTMC can augment military and civil defense to combat chemical warfare and chemical terrorism.

Anatomical parameterization for volumetric meshing of the liver

NASA Astrophysics Data System (ADS)

Vera, Sergio; González Ballester, Miguel A.; Gil, Debora

2014-03-01

A coordinate system describing the interior of organs is a powerful tool for a systematic localization of injured tissue. If the same coordinate values are assigned to specific anatomical landmarks, the coordinate system allows integration of data across different medical image modalities. Harmonic mappings have been used to produce parametric coordinate systems over the surface of anatomical shapes, given their flexibility to set values at specific locations through boundary conditions. However, most of the existing implementations in medical imaging restrict to either anatomical surfaces, or the depth coordinate with boundary conditions is given at sites of limited geometric diversity. In this paper we present a method for anatomical volumetric parameterization that extends current harmonic parameterizations to the interior anatomy using information provided by the volume medial surface. We have applied the methodology to define a common reference system for the liver shape and functional anatomy. This reference system sets a solid base for creating anatomical models of the patient's liver, and allows comparing livers from several patients in a common framework of reference.

Adeno-associated virus Rep-mediated targeting of integrase-defective retroviral vector DNA circles into human chromosome 19

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Shuohao; Kawabe, Yoshinori; Ito, Akira

2012-01-06

Highlights: Black-Right-Pointing-Pointer Adeno-associated virus (AAV) is capable of targeted integration in human cells. Black-Right-Pointing-Pointer Integrase-defective retroviral vector (IDRV) enables a circular DNA delivery. Black-Right-Pointing-Pointer A targeted integration system of IDRV DNA using the AAV integration mechanism. Black-Right-Pointing-Pointer Targeted IDRV integration ameliorates the safety concerns for retroviral vectors. -- Abstract: Retroviral vectors have been employed in clinical trials for gene therapy owing to their relative large packaging capacity, alterable cell tropism, and chromosomal integration for stable transgene expression. However, uncontrollable integrations of transgenes are likely to cause safety issues, such as insertional mutagenesis. A targeted transgene integration system for retroviral vectors,more » therefore, is a straightforward way to address the insertional mutagenesis issue. Adeno-associated virus (AAV) is the only known virus capable of targeted integration in human cells. In the presence of AAV Rep proteins, plasmids possessing the p5 integration efficiency element (p5IEE) can be integrated into the AAV integration site (AAVS1) in the human genome. In this report, we describe a system that can target the circular DNA derived from non-integrating retroviral vectors to the AAVS1 site by utilizing the Rep/p5IEE integration mechanism. Our results showed that after G418 selection 30% of collected clones had retroviral DNA targeted at the AAVS1 site.« less

Long Term Eddy Covariance Networks - When Collaboration Works: An Example from Ameriflux, ICOS and Fluxnet

NASA Astrophysics Data System (ADS)

Papale, D.; Baldocchi, D. D.; Loescher, H. W.; Torn, M. S.

2014-12-01

Small networks of eddy covariance sites measuring exchanges of CO2, water and energy between ecosystems and atmosphere started to be organized in Europe and USA more than 15 years ago with the AmeriFlux and EuroFlux initiatives. They were composed by less than 20 sites each, mainly over undisturbed forest and without a strong coordination between sites, in particular across the ocean. In the following years the networks grew exponentially both at continental and global level, reaching more than 500 sites few years ago and expanding the eddy covariance measurement to different ecosystem types, climate regions and management/disturbance regimes. At the same time, important steps were done in terms of cooperation and harmonization related to data processing, data description and data sharing policies, leading to inter-continental and global activities under the FLUXNET framework. Today the networks are facing a new evolution step, moving from pure research activities to something that includes also monitoring and research infrastructure characteristics. AmeriFlux and NEON (National Ecological Observatory Network) in USA and ICOS (Integrated Carbon Observation System) in Europe are opening a new phase in the eddy covariance networks: with a long term perspective, increased level of standardization and a completely open access policy, will hopefully stimulate even more global synthesis studies and a wider use of the flux measurements by other scientific communities. AmeriFlux, NEON and ICOS are also strongly involved in cross-networks harmonization activities in terms of data acquisition, data processing and data format, in order to simplify and encourage the joint use of their measurements. A brief history of the development, challenges and solutions in the organization of the different networks and their common activities will be presented, to focus then on selected scientific results that have been possible only thanks to the global integration and international collaboration and finally discuss future developments and current ongoing activities in terms of data harmonization/standardization and sharing.

Research on website construction based on website group platform of Chengdu sport institution

NASA Astrophysics Data System (ADS)

Hu, Zunyu

2018-04-01

This paper describes the necessity of website construction based on the website group of Chengdu sport institute, and discusses the technical features of the website group, Based on the website group platform architecture, the key technologies such as Web Service, AJAX, RSS and other key technologies are used to realize the construction of the website. Based on the website group platform architecture of the site, it effectively solves the information isolated island between the sites, and realizes the information sharing and resource integration. It is also more convenient that site and other sites have composed of site group integrated operation and maintenance.

Common Factors: Where the Soul of Counseling and Psychotherapy Resides

ERIC Educational Resources Information Center

Ottens, Allen J.; Klein, James F.

2005-01-01

The authors show how theoretical and empirical findings from the common factors and psychotherapy integration literatures possess potential for infusing soul into psychotherapy. They describe the term soul, outline how the definition translates into soul-nurturing psychotherapy, examine the common factors and integration literatures, and discuss…

INVESTIGATING UNCERTAINTY AND SENSITIVITY IN INTEGRATED, MULTIMEDIA ENVIRONMENTAL MODELS: TOOLS FOR FRAMES-3MRA

EPA Science Inventory

Elucidating uncertainty and sensitivity structures in environmental models can be a difficult task, even for low-order, single-medium constructs driven by a unique set of site-specific data. Quantitative assessment of integrated, multimedia models that simulate hundreds of sites...

Soil, plant, and structural considerations for surface barriers in arid environments: Application of results from studies in the Mojave Desert near Beatty, Nevada

USGS Publications Warehouse

Andraski, Brian J.; Prudic, David E.; ,

1997-01-01

The suitability of a waste-burial site depends on hydrologic processes that can affect the near-surface water balance. In addition, the loss of burial trench integrity by erosion and subsidence of trench covers may increase the likelihood of infiltration and percolation, thereby reducing the effectiveness of the site in isolating waste. Although the main components of the water balance may be defined, direct measurements can be difficult, and actual data for specific locations are seldom available. A prevalent assumption is that little or no precipitation will percolate to buried wastes at an arid site. Thick unsaturated zones, which are common to arid regions, are thought to slow water movement and minimize the risk of waste migration to the underlying water table. Thus, reliance is commonly placed on the natural system to isolate contaminants at waste-burial sites in the arid West.Few data are available to test assumptions about the natural soil-water flow systems at arid sites, and even less is known about how the natural processes are altered by construction of a waste-burial facility. The lack of data is the result of technical complexity of hydraulic characterization of the dry, stony soils, and insufficient field studies that account for the extreme temporal and spatial variations in precipitation, soils, and plants in arid regions. In 1976, the U.S. Geological Survey (USGS) began a long-term study at a waste site in the Mojave Desert. This paper summarizes the findings of ongoing investigations done under natural-site and waste-burial conditions, and discusses how this information may be applied to the design of surface barriers for waste sites in arid environments.The waste-burial site is in one of the most arid parts of the United States and is about 40 km northeast of Death Valley, near Beatty, Nev. (Figure 1). Precipitation averaged 108 mm/yr during 1981-1992. The water table is 85-115 m below land surface (Fischer, 1992). Sediments are largely alluvial and fluvial deposits (Nichols, 1987). Vegetation is sparse; creosote bush is the dominant species. The waste facility has been used for burial of low-level radioactive waste (1962-1992) and hazardous chemical waste (1970 to present). Burial-trench construction includes excavation of native soil, emplacement of waste, and backfilling with previously stockpiled soil. Only the most recently closed hazardous-waste trench (1991) incorporates a plastic liner in the cover. The surfaces of completed burial trenches and perimeter areas are kept free of vegetation.

Core-Shell Processing of Natural Pigment: Upper Palaeolithic Red Ochre from Lovas, Hungary

PubMed Central

Sajó, István E.; Kovács, János; Fitzsimmons, Kathryn E.; Jáger, Viktor; Lengyel, György; Viola, Bence; Talamo, Sahra; Hublin, Jean-Jacques

2015-01-01

Ochre is the common archaeological term for prehistoric pigments. It is applied to a range of uses, from ritual burials to cave art to medications. While a substantial number of Palaeolithic paint mining pits have been identified across Europe, the link between ochre use and provenance, and their antiquity, has never yet been identified. Here we characterise the mineralogical signature of core-shell processed ochre from the Palaeolithic paint mining pits near Lovas in Hungary, using a novel integration of petrographic and mineralogical techniques. We present the first evidence for core-shell processed, natural pigment that was prepared by prehistoric people from hematitic red ochre. This involved combining the darker red outer shell with the less intensely coloured core to efficiently produce an economical, yet still strongly coloured, paint. We demonstrate the antiquity of the site as having operated between 14–13 kcal BP, during the Epigravettian period. This is based on new radiocarbon dating of bone artefacts associated with the quarry site. The dating results indicate the site to be the oldest known evidence for core-shell pigment processing. We show that the ochre mined at Lovas was exported from the site based on its characteristic signature at other archaeological sites in the region. Our discovery not only provides a methodological framework for future characterisation of ochre pigments, but also provides the earliest known evidence for “value-adding” of products for trade. PMID:26147808

Uranium interaction with soil minerals in the presence of co-contaminants: Case Study- subsurface sediments at or below the water table

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gartman, Brandy N.; Qafoku, Nikolla

2016-03-09

Uranium (U) contaminated subsurface systems are common on a global scale mainly because of its essential role in the production of plutonium for nuclear weapons and other nuclear energy and research activities. Studying the behavior and fate of U in these systems is challenging because of heterogeneities of different types (i.e., physical, chemical and mineralogical) and a complex network of often time-dependent hydrological, biological and chemical reactions and processes that occur sequentially or simultaneously, affecting and/or controlling U mobility. A U contaminated site, i.e., the Integrated Field Research Challenge site in Rifle, CO, USA (a former U mill site) ismore » the focus of this discussion. The overall objectives of this chapter are to 1) provide an overview of the contamination levels (U and other co-contaminants) at this field site; 2) review and discuss different aspects of mineral-U contaminant interactions in reduced and oxidized environments, and in the presence of co-contaminants; 3) present results from a systematic macroscopic, microscopic, and spectroscopic study as an example of the current research efforts and the state-of-knowledge in this important research area; and 4) offer insightful conclusive remarks and future research needs about reactions and processes that control U and other contaminants’ fate and behavior under hydraulically saturated conditions. The implications and applications presented in this chapter are valid for U contaminated sites across the world.« less

Sediment Enzyme Activities and Microbial Community Diversity in an Oligotrophic Drinking Water Reservoir, Eastern China

PubMed Central

Zhang, Haihan; Huang, Tinglin; Liu, Tingting

2013-01-01

Drinking water reservoir plays a vital role in the security of urban water supply, yet little is known about microbial community diversity harbored in the sediment of this oligotrophic freshwater environmental ecosystem. In the present study, integrating community level physiological profiles (CLPPs), nested polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE) and clone sequence technologies, we examined the sediment urease and protease activities, bacterial community functional diversity, genetic diversity of bacterial and fungal communities in sediments from six sampling sites of Zhou cun drinking water reservoir, eastern China. The results showed that sediment urease activity was markedly distinct along the sites, ranged from 2.48 to 11.81 mg NH3-N/(g·24h). The highest average well color development (AWCD) was found in site C, indicating the highest metabolic activity of heterotrophic bacterial community. Principal component analysis (PCA) revealed tremendous differences in the functional (metabolic) diversity patterns of the sediment bacterial communities from different sites. Meanwhile, DGGE fingerprints also indicated spatial changes of genetic diversity of sediment bacterial and fungal communities. The sequence BLAST analysis of all the sediment samples found that Comamonas sp. was the dominant bacterial species harbored in site A. Alternaria alternate, Allomyces macrogynus and Rhizophydium sp. were most commonly detected fungal species in sediments of the Zhou cun drinking water reservoir. The results from this work provide new insights about the heterogeneity of sediment microbial community metabolic activity and genetic diversity in the oligotrophic drinking water reservoir. PMID:24205265

Comparative study of large scale simulation of underground explosions inalluvium and in fractured granite using stochastic characterization

NASA Astrophysics Data System (ADS)

Vorobiev, O.; Ezzedine, S. M.; Antoun, T.; Glenn, L.

2014-12-01

This work describes a methodology used for large scale modeling of wave propagation fromunderground explosions conducted at the Nevada Test Site (NTS) in two different geological settings:fractured granitic rock mass and in alluvium deposition. We show that the discrete nature of rockmasses as well as the spatial variability of the fabric of alluvium is very important to understand groundmotions induced by underground explosions. In order to build a credible conceptual model of thesubsurface we integrated the geological, geomechanical and geophysical characterizations conductedduring recent test at the NTS as well as historical data from the characterization during the undergroundnuclear test conducted at the NTS. Because detailed site characterization is limited, expensive and, insome instances, impossible we have numerically investigated the effects of the characterization gaps onthe overall response of the system. We performed several computational studies to identify the keyimportant geologic features specific to fractured media mainly the joints; and those specific foralluvium porous media mainly the spatial variability of geological alluvium facies characterized bytheir variances and their integral scales. We have also explored common key features to both geologicalenvironments such as saturation and topography and assess which characteristics affect the most theground motion in the near-field and in the far-field. Stochastic representation of these features based onthe field characterizations have been implemented in Geodyn and GeodynL hydrocodes. Both codeswere used to guide site characterization efforts in order to provide the essential data to the modelingcommunity. We validate our computational results by comparing the measured and computed groundmotion at various ranges. This work performed under the auspices of the U.S. Department of Energy by Lawrence LivermoreNational Laboratory under Contract DE-AC52-07NA27344.

Oncoprotein AEG-1 is an endoplasmic reticulum RNA-binding protein whose interactome is enriched in organelle resident protein-encoding mRNAs.

PubMed

Hsu, Jack C-C; Reid, David W; Hoffman, Alyson M; Sarkar, Devanand; Nicchitta, Christopher V

2018-05-01

Astrocyte elevated gene-1 (AEG-1), an oncogene whose overexpression promotes tumor cell proliferation, angiogenesis, invasion, and enhanced chemoresistance, is thought to function primarily as a scaffolding protein, regulating PI3K/Akt and Wnt/β-catenin signaling pathways. Here we report that AEG-1 is an endoplasmic reticulum (ER) resident integral membrane RNA-binding protein (RBP). Examination of the AEG-1 RNA interactome by HITS-CLIP and PAR-CLIP methodologies revealed a high enrichment for endomembrane organelle-encoding transcripts, most prominently those encoding ER resident proteins, and within this cohort, for integral membrane protein-encoding RNAs. Cluster mapping of the AEG-1/RNA interaction sites demonstrated a normalized rank order interaction of coding sequence >5' untranslated region, with 3' untranslated region interactions only weakly represented. Intriguingly, AEG-1/membrane protein mRNA interaction sites clustered downstream from encoded transmembrane domains, suggestive of a role in membrane protein biogenesis. Secretory and cytosolic protein-encoding mRNAs were also represented in the AEG-1 RNA interactome, with the latter category notably enriched in genes functioning in mRNA localization, translational regulation, and RNA quality control. Bioinformatic analyses of RNA-binding motifs and predicted secondary structure characteristics indicate that AEG-1 lacks established RNA-binding sites though shares the property of high intrinsic disorder commonly seen in RBPs. These data implicate AEG-1 in the localization and regulation of secretory and membrane protein-encoding mRNAs and provide a framework for understanding AEG-1 function in health and disease. © 2018 Hsu et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Deriving site-specific clean-up criteria to protect ecological receptors (plants and soil invertebrates) exposed to metal or metalloid soil contaminants via the direct contact exposure pathway

PubMed Central

Checkai, Ron; Van Genderen, Eric; Sousa, José Paulo; Stephenson, Gladys; Smolders, Erik

2014-01-01

Soil contaminant concentration limits for the protection of terrestrial plants and soil invertebrates are commonly based on thresholds derived using data from laboratory ecotoxicity tests. A comprehensive assessment has been made for the derivation of ecological soil screening levels (Eco-SSL) in the United States; however, these limits are conservative because of their focus on high bioavailability scenarios. Here, we explain and evaluate approaches to soil limit derivation taken by 4 jurisdictions, 2 of which allow for correction of data for factors affecting bioavailability among soils, and between spiked and field-contaminated soils (Registration Evaluation Authorisation and Restriction of Chemicals [REACH] Regulation, European Union [EU], and the National Environment Protection Council [NEPC], Australia). Scientifically advanced features from these methods have been integrated into a newly developed method for deriving soil clean-up values (SCVs) within the context of site-specific baseline ecological risk assessment. Resulting site-specific SCVs that account for bioavailability may permit a greater residual concentration in soil when compared to generic screening limit concentrations (e.g., Eco-SSL), while still affording acceptable protection. Two choices for selecting the level of protection are compared (i.e., allowing higher effect levels per species, or allowing a higher percentile of species that are potentially unprotected). Implementation of this new method is presented for the jurisdiction of the United States, with a focus on metal and metalloid contaminants; however, the new method can be used in any jurisdiction. A case study for molybdate shows the large effect of bioavailability corrections and smaller effects of protection level choices when deriving SCVs. Integr Environ Assess Manag 2014;10:346–357. PMID:24470189

The Use of Sahris as a State Sponsored Digital Heritage Repository and Management System in South Africa

NASA Astrophysics Data System (ADS)

Wiltshire, N. G.

2013-07-01

SAHRA has developed versions 1 and 2 of the South African Heritage Resources Information System (SAHRIS - http://www.sahra.org.za) in 2012 and 2013. The system has been rolled out since May 2012 to the national and provincial heritage authorities in South Africa in line with the National Heritage Resources Act (Act 25 of 1999). SAHRIS was developed using Drupal and Geoserver, both of which are free open source software packages. The three core functions of SAHRIS include: an online application system for developments that is integrated with a commenting module for public participation; a national sites archive of heritage sites; and a comprehensive collections management system for objects. With Geoserver, Openlayers and GMAP, users are provided with an online GIS platform that is integrated with most of the content types on SAHRIS. More than 21000 sites have already been migrated into SAHRIS along with over 4300 objects. The media and reports archive has already grown to 500 gigabytes, data storage is offered free of charge and so far 96 Terabytes of replicated storage have been installed. The distribution and dissemination of this content is facilitated by the adoption of The Creative Commons South Africa license. Lessons learnt from previous attempts to develop SAHRIS are covered briefly in light of the opportunities that have been opened up by the relatively recent maturation of FOSS content management systems. The current uptake of SAHRIS and the solutions to the challenges faced thus far are discussed before concluding with the implications for E-governance in South Africa.

An integrated catch-and-hold mechanism activates nicotinic acetylcholine receptors.

PubMed

Jadey, Snehal; Auerbach, Anthony

2012-07-01

In neuromuscular acetylcholine (ACh) receptor channels (AChRs), agonist molecules bind with a low affinity (LA) to two sites that can switch to high affinity (HA) and increase the probability of channel opening. We measured (by using single-channel kinetic analysis) the rate and equilibrium constants for LA binding and channel gating for several different agonists of adult-type mouse AChRs. Almost all of the variation in the equilibrium constants for LA binding was from differences in the association rate constants. These were consistently below the limit set by diffusion and were substantially different even though the agonists had similar sizes and the same charge. This suggests that binding to resting receptors is not by diffusion alone and, hence, that each binding site can undergo two conformational changes ("catch" and "hold") that connect three different structures (apo-, LA-bound, and HA-bound). Analyses of ACh-binding protein structures suggest that this binding site, too, may adopt three discrete structures having different degrees of loop C displacement ("capping"). For the agonists we tested, the logarithms of the equilibrium constants for LA binding and LA↔HA gating were correlated. Although agonist binding and channel gating have long been considered to be separate processes in the activation of ligand-gated ion channels, this correlation implies that the catch-and-hold conformational changes are energetically linked and together comprise an integrated process having a common structural basis. We propose that loop C capping mainly reflects agonist binding, with its two stages corresponding to the formation of the LA and HA complexes. The catch-and-hold reaction coordinate is discussed in terms of preopening states and thermodynamic cycles of activation.

An integrated catch-and-hold mechanism activates nicotinic acetylcholine receptors

PubMed Central

Jadey, Snehal

2012-01-01

In neuromuscular acetylcholine (ACh) receptor channels (AChRs), agonist molecules bind with a low affinity (LA) to two sites that can switch to high affinity (HA) and increase the probability of channel opening. We measured (by using single-channel kinetic analysis) the rate and equilibrium constants for LA binding and channel gating for several different agonists of adult-type mouse AChRs. Almost all of the variation in the equilibrium constants for LA binding was from differences in the association rate constants. These were consistently below the limit set by diffusion and were substantially different even though the agonists had similar sizes and the same charge. This suggests that binding to resting receptors is not by diffusion alone and, hence, that each binding site can undergo two conformational changes (“catch” and “hold”) that connect three different structures (apo-, LA-bound, and HA-bound). Analyses of ACh-binding protein structures suggest that this binding site, too, may adopt three discrete structures having different degrees of loop C displacement (“capping”). For the agonists we tested, the logarithms of the equilibrium constants for LA binding and LA↔HA gating were correlated. Although agonist binding and channel gating have long been considered to be separate processes in the activation of ligand-gated ion channels, this correlation implies that the catch-and-hold conformational changes are energetically linked and together comprise an integrated process having a common structural basis. We propose that loop C capping mainly reflects agonist binding, with its two stages corresponding to the formation of the LA and HA complexes. The catch-and-hold reaction coordinate is discussed in terms of preopening states and thermodynamic cycles of activation. PMID:22732309

Rethinking the Clinically Based Thresholds of TransCelerate BioPharma for Risk-Based Monitoring.

PubMed

Zink, Richard C; Dmitrienko, Anastasia; Dmitrienko, Alex

2018-01-01

The quality of data from clinical trials has received a great deal of attention in recent years. Of central importance is the need to protect the well-being of study participants and maintain the integrity of final analysis results. However, traditional approaches to assess data quality have come under increased scrutiny as providing little benefit for the substantial cost. Numerous regulatory guidance documents and industry position papers have described risk-based approaches to identify quality and safety issues. In particular, the position paper of TransCelerate BioPharma recommends defining risk thresholds to assess safety and quality risks based on past clinical experience. This exercise can be extremely time-consuming, and the resulting thresholds may only be relevant to a particular therapeutic area, patient or clinical site population. In addition, predefined thresholds cannot account for safety or quality issues where the underlying rate of observing a particular problem may change over the course of a clinical trial, and often do not consider varying patient exposure. In this manuscript, we appropriate rules commonly utilized for funnel plots to define a traffic-light system for risk indicators based on statistical criteria that consider the duration of patient follow-up. Further, we describe how these methods can be adapted to assess changing risk over time. Finally, we illustrate numerous graphical approaches to summarize and communicate risk, and discuss hybrid clinical-statistical approaches to allow for the assessment of risk at sites with low patient enrollment. We illustrate the aforementioned methodologies for a clinical trial in patients with schizophrenia. Funnel plots are a flexible graphical technique that can form the basis for a risk-based strategy to assess data integrity, while considering site sample size, patient exposure, and changing risk across time.

Field Validation of POCIS for Monitoring at Underwater Munitions Sites.

PubMed

Rosen, Gunther; Lotufo, Guilherme R; George, Robert D; Wild, Bill; Rabalais, Lauren K; Morrison, Shane; Belden, Jason B

2018-04-24

The present study evaluated Polar Organic Chemical Integrative Samplers (POCIS) for quantification of conventional munitions constituents (MC), including trinitrotoluene (TNT), aminodinitrotoluenes, diaminonitrotoluenes, dinitrotoluene, and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in a field setting. POCIS were deployed at varying distances from the commonly used explosive formulation Composition B (39.5% TNT, 59.5% RDX, 1% wax) in an embayment of Santa Rosa Sound (Florida, USA). Time-weighted averaged (TWA) water concentrations from a 13-day deployment ranged from 9-103 ng/L for TNT and RDX approximately 0.3 to 2 m from the source. Concentrations decreased with increasing distance from the source to below quantitation limits (5-7 ng/L) at stations greater than 2 m away. Moderate biofouling of POCIS membranes after 13-d led to a subsequent effort to quantify potential effects of biofouling on sampling rate for MC. After biofouling was allowed to occur for periods of 0, 7, 14 or 28 days at the field site, POCIS were transferred to aquaria spiked with MC. No significant differences in uptake of TNT or RDX were observed across a gradient of biofouling presence, although mass of fouling organisms on the membranes was statistically greater for the 28-d field exposure. The present study verified the high sensitivity and integrative nature of POCIS for relevant MC potentially present in aquatic environments, indicating that application at underwater military munitions sites may be useful for ecological risk assessment. This article is protected by copyright. All rights reserved This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Viewpoint: Central adjudication of myocardial infarction in outcome-driven clinical trials--common patterns in TRITON, RECORD, and PLATO?

PubMed

Serebruany, Victor L; Atar, Dan

2012-09-01

Central adjudication in randomised controlled outcome-driven trials represents a traditional approach to maintain data integrity by applying uniformed rules for assessment of clinical events. It was the purpose of this investigation to determine the patterns of myocardial infarction (MI) adjudication in the TRITON, RECORD, and PLATO trials. We were matching centrally-adjudicated MI's (CAMI's) from the official trial publication with the site-reported MI (SRMI's) count from the Food and Drug Administration's secondary analyses for the investigational compounds prasugrel (TRITON), rosiglitazone (RECORD), and ticagrelor (PLATO). CAMI numbers showed a remarkable discrepancy to SRMI's by more than a doubling of the difference: from 72 to 145 events in TRITON favoring prasugrel (from a hazard ratio [HR]=0.76, p=0.08; to a HR=0.76, p<0.001), and from 44 to 89 events in favour of ticagrelor in PLATO (from a HR=0.94, p=0.095; to a HR=0.84, p<0.001). In contrast, in the RECORD trial, the CAMI count was less than the SRMI count (from 24 to 8 events, from a HR=1.42, p=0.93; to a HR=1.14, p=0.96), in this case diminishing cardiovascular hazards in favour of rosiglitazone. In conclusion, central adjudication in the TRITON, the RECORD, and the PLATO trial turned out to have a critical impact on study outcomes. Trial publications should in the future include site-reported major efficacy and safety endpoints to preserve data integrity. The regulatory authorities should consider independent audits when there is a major disagreement between centrally adjudicated and site reported events influencing the results of a major clinical trial.

Verification of geomechanical integrity and prediction of long-term mineral trapping for the Ketzin CO2 storage pilot site

NASA Astrophysics Data System (ADS)

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 88.1 %, respectively. We verified the mechanical integrity of the storage system during site operation and predicted the trapping mechanisms for the Ketzin pilot site based on a time-dependent integration of relevant processes for a time period of 16,000 years. Supported by our coupled modelling results, we conclude that CO2 storage at the Ketzin site is safe and reliable on the pilot scale. References [1] Martens, S., Kempka, T., Liebscher, A., Lüth, S., Möller, F., Myrttinen, A., Norden, B., Schmidt-Hattenberger, C., Zimmer, M., Kühn, M. Europe's longest-operating on-shore CO2 storage site at Ketzin, Germany: a progress report after three years of injection. Environmental Earth Sciences 2012 67(2): 323-334. [2] Kempka, T., Kühn, M. Numerical simulations of CO2 arrival times and reservoir pressure coincide with observations from the Ketzin pilot site, Germany. Environmental Earth Sciences 2013 70(8): 3675-3685. [3] Kempka, T., Klein, E., De Lucia, M., Tillner, E., Kühn, M. Assessment of Long-term CO2 Trapping Mechanisms at the Ketzin Pilot Site (Germany) by Coupled Numerical Modelling. Energy Procedia 2013 37: 5419-5426. [4] Klein, E., De Lucia, M., Kempka, T., Kühn, M. Evaluation of long-term mineral trapping at the Ketzin pilot site for CO2 storage: An integrative approach using geochemical modelling and reservoir simulation. International Journal of Greenhouse Gas Control 2013 19: 720-730.

Integration of 3D geological modeling and gravity surveys for geothermal prospection in an Alpine region

NASA Astrophysics Data System (ADS)

Guglielmetti, L.; Comina, C.; Abdelfettah, Y.; Schill, E.; Mandrone, G.

2013-11-01

Thermal sources are common manifestations of geothermal energy resources in Alpine regions. The up-flow of the fluid is well-known to be often linked to cross-cutting fault zones providing a significant volume of fractures. Since conventional exploration methods are challenging in such areas of high topography and complicated logistics, 3D geological modeling based on structural investigation becomes a useful tool for assessing the overall geology of the investigated sites. Geological modeling alone is, however, less effective if not integrated with deep subsurface investigations that could provide a first order information on geological boundaries and an imaging of geological structures. With this aim, in the present paper the combined use of 3D geological modeling and gravity surveys for geothermal prospection of a hydrothermal area in the western Alps was carried out on two sites located in the Argentera Massif (NW Italy). The geothermal activity of the area is revealed by thermal anomalies with surface evidences, such as hot springs, at temperatures up to 70 °C. Integration of gravity measurements and 3D modeling investigates the potential of this approach in the context of geothermal exploration in Alpine regions where a very complex geological and structural setting is expected. The approach used in the present work is based on the comparison between the observed gravity and the gravity effect of the 3D geological models, in order to enhance local effects related to the geothermal system. It is shown that a correct integration of 3D modeling and detailed geophysical survey could allow a better characterization of geological structures involved in geothermal fluids circulation. Particularly, gravity inversions have successfully delineated the continuity in depth of low density structures, such as faults and fractured bands observed at the surface, and have been of great help in improving the overall geological model.

Expression of Hygromycin Phosphotransferase Alters Virulence of Histoplasma capsulatum▿

PubMed Central

Smulian, A. George; Gibbons, Reta S.; Demland, Jeffery A.; Spaulding, Deborah T.; Deepe, George S.

2007-01-01

The Escherichia coli hygromycin phosphotransferase (hph) gene, which confers hygromycin resistance, is commonly used as a dominant selectable marker in genetically modified bacteria, fungi, plants, insects, and mammalian cells. Expression of the hph gene has rarely been reported to induce effects other than those expected. Hygromycin B is the most common dominant selectable marker used in the molecular manipulation of Histoplasma capsulatum in the generation of knockout strains of H. capsulatum or as a marker in mutant strains. hph-expressing organisms appear to have no defect in long-term in vitro growth and survival and have been successfully used to exploit host-parasite interaction in short-term cell culture systems and animal experiments. We introduced the hph gene as a selectable marker together with the gene encoding green fluorescent protein into wild-type strains of H. capsulatum. Infection of mice with hph-expressing H. capsulatum yeast cells at sublethal doses resulted in lethality. The lethality was not attributable to the site of integration of the hph construct into the genomes or to the method of integration and was not H. capsulatum strain related. Death of mice was not caused by altered cytokine profiles or an overwhelming fungal burden. The lethality was dependent on the kinase activity of hygromycin phosphotransferase. These results should raise awareness of the potential detrimental effects of the hph gene. PMID:17873086

Expression of hygromycin phosphotransferase alters virulence of Histoplasma capsulatum.

PubMed

Smulian, A George; Gibbons, Reta S; Demland, Jeffery A; Spaulding, Deborah T; Deepe, George S

2007-11-01

The Escherichia coli hygromycin phosphotransferase (hph) gene, which confers hygromycin resistance, is commonly used as a dominant selectable marker in genetically modified bacteria, fungi, plants, insects, and mammalian cells. Expression of the hph gene has rarely been reported to induce effects other than those expected. Hygromycin B is the most common dominant selectable marker used in the molecular manipulation of Histoplasma capsulatum in the generation of knockout strains of H. capsulatum or as a marker in mutant strains. hph-expressing organisms appear to have no defect in long-term in vitro growth and survival and have been successfully used to exploit host-parasite interaction in short-term cell culture systems and animal experiments. We introduced the hph gene as a selectable marker together with the gene encoding green fluorescent protein into wild-type strains of H. capsulatum. Infection of mice with hph-expressing H. capsulatum yeast cells at sublethal doses resulted in lethality. The lethality was not attributable to the site of integration of the hph construct into the genomes or to the method of integration and was not H. capsulatum strain related. Death of mice was not caused by altered cytokine profiles or an overwhelming fungal burden. The lethality was dependent on the kinase activity of hygromycin phosphotransferase. These results should raise awareness of the potential detrimental effects of the hph gene.

Localized Retroprocessing as a Model of Intron Loss in the Plant Mitochondrial Genome

PubMed Central

Cuenca, Argelia; Ross, T. Gregory; Graham, Sean W.; Barrett, Craig F.; Davis, Jerrold I.; Seberg, Ole; Petersen, Gitte

2016-01-01

Loss of introns in plant mitochondrial genes is commonly explained by retroprocessing. Under this model, an mRNA is reverse transcribed and integrated back into the genome, simultaneously affecting the contents of introns and edited sites. To evaluate the extent to which retroprocessing explains intron loss, we analyzed patterns of intron content and predicted RNA editing for whole mitochondrial genomes of 30 species in the monocot order Alismatales. In this group, we found an unusually high degree of variation in the intron content, even expanding the hitherto known variation among angiosperms. Some species have lost some two-third of the cis-spliced introns. We found a strong correlation between intron content and editing frequency, and detected 27 events in which intron loss is consistent with the presence of nucleotides in an edited state, supporting retroprocessing. However, we also detected seven cases of intron loss not readily being explained by retroprocession. Our analyses are also not consistent with the entire length of a fully processed cDNA copy being integrated into the genome, but instead indicate that retroprocessing usually occurs for only part of the gene. In some cases, several rounds of retroprocessing may explain intron loss in genes completely devoid of introns. A number of taxa retroprocessing seem to be very common and a possibly ongoing process. It affects the entire mitochondrial genome. PMID:27435795

Using in-situ Glider Data to Improve the Interpretation of Time-Series Data in the San Pedro Channel

NASA Astrophysics Data System (ADS)

Teel, E.; Liu, X.; Seegers, B. N.; Ragan, M. A.; Jones, B. H.; Levine, N. M.

2016-02-01

Oceanic time-series have provided insight into biological, physical, and chemical processes and how these processes change over time. However, time-series data collected near coastal zones have not been used as broadly because of regional features that may prevent extrapolation of local results. Though these sites are inherently more affected by local processes, broadening the application of coastal data is crucial for improved modeling of processes such as total carbon drawdown and the development of oxygen minimum zones. Slocum gliders were deployed off the coast of Los Angeles from February to July of 2013 and 2014 providing high temporal and spatial resolution data of the San Pedro Channel (SPC), which includes the San Pedro Ocean Time Series (SPOT). The data were collapsed onto a standardized grid and primary and secondary characteristics of glider profiles were analyzed by principal component analysis to determine the processes impacting SPC and SPOT. The data fell into four categories: active upwelling, offshore intrusion, subsurface bloom, and surface bloom. Waters across the SPC were most similar to offshore water masses, even during the upwelling season when near-shore blooms are commonly observed. The SPOT site was found to be representative of the SPC 86% of the time, suggesting that the findings from SPOT are applicable for the entire SPC. Subsurface blooms were common in both years with co-located chlorophyll and particle maxima, and results suggested that these subsurface blooms contribute significantly to the local primary production. Satellite estimation of integrated chlorophyll was poor, possibly due to the prevalence of subsurface blooms and shallow optical depths during surface blooms. These results indicate that high resolution in-situ glider deployments can be used to determine the spatial domain of coastal time-series data, allowing for broader application of these datasets and greater integration into modeling efforts.

Water quality and the composition of fish and macroinvertebrate communities in the Devils and Pecos Rivers within and upstream from the Amistad National Recreation Area, Texas, 2005-7

USGS Publications Warehouse

Moring, J. Bruce

2012-01-01

The total number of fish species collected was the same in the Devils River and Pecos River, but the species found in the two rivers varied slightly. The number of fish species generally increased from the site farthest upstream to the site farthest downstream in the Devils River, and decreased between the site farthest upstream and site farthest downstream in the Pecos River. The redbreast sunfish was the most abundant species collected in the Devils River, and the blacktail shiner was the most abundant species collected in the Pecos River. Comparing the species from each river, the percentage of omnivorous fish species was larger at the more downstream sites closer to Amistad Reservoir, and the percentage of species tolerant of environmental stressors was larger in the Pecos River. The fish community, assessed on the basis of the number of shared species among the sites sampled, was more similar to the fish community at the other sites on the same river than it was to the fish community from any other site in the other river. More macroinvertebrate taxa were collected in the Devils River than in the Pecos River. The largest number of macroinvertebrate taxa were from the site second farthest downstream on the Devils River, and the smallest numbers of macroinvertebrate taxa were from the farthest downstream site on the Pecos River. Mayflies were more common in the Devils River, and caddisflies were less common than mayflies at most sites. Net-spinning caddisflies were more common at the Devils River sites. The combined percent of mayfly, caddisfly, and stonefly taxa was generally larger at the Pecos River sites. Riffle beetles were the most commonly collected beetle taxon among all sites, and water-penny beetles were only collected at the Pecos River sites. A greater number of true midge taxa were collected more than any other taxa at the genus and species taxonomic level. Non-insect macroinvertebrate taxa were more common at the Devils River sites. Corbicula sp. (presumably the introduced Asian clam) was found at sites in both rivers, and amphipods were more abundant in the Devils River. The Margalef species richness index, based on aquatic insect taxa only, was larger at the Devils River sites than at the Pecos River sites. The Hilsenhoff's biotic index was largest at the site farthest downstream in the Devils River and smallest at the site second farthest downstream in the Pecos River. Overall similarity among sites based on the number of shared macroinvertebrate taxa indicated that each site is more similar to other sites on the same river than to sites on the other river.

Surveying hospital network structure in New York State: how are they structured?

PubMed

Nauenberg, E; Brewer, C S

2000-01-01

We determine the most common network structures in New York state. The taxonomy employed uses three structural dimensions: integration, complexity, and risk-sharing between organizations. Based on a survey conducted in 1996, the most common type of network (26.4 percent) had medium levels of integration, medium or high levels of complexity, and some risk-sharing. Also common were networks with low levels of integration, low levels of complexity, and no risk-sharing (22.1 percent).

Soil conservation through sediment trapping: A review

NASA Astrophysics Data System (ADS)

Mekonnen, Mulatie; Keesstra, Saskia; Baartman, Jantiene; Maroulis, Jerry; Stroosnijder, Leo

2014-05-01

Preventing the off-site effects of soil erosion is an essential part of good catchment management. Most efforts are in the form of on-site soil and water conservation measures. However, sediment trapping (ST) can be an alternative (or additional) measure to prevent the negative off-site effects of soil erosion. Therefore, not all efforts should focus solely on on-site soil conservation, but also on the safe routing of sediment-laden flows and on creating sites and conditions where sediment can be trapped, preferably in a cost effective or even profitable way. ST can be applied on-site (in-field) and off-site and involves both vegetative and structural measures. The main vegetative measures include grass strips, tree or bush buffers, grassed waterways and restoration of the waterways and their riparian zone; while structural measures include terraces, ponds and check dams. This paper provides a review of studies that have assessed the sediment trapping efficacy (STE) of such vegetative and structural measures. Vegetation type and integration of two or more measures (vegetative as well as structural) are important factors influencing STE. In this review, the STE of most measures was evaluated either individually or in such combinations. In real landscape situations, it is not only important to select the most efficient erosion control measures, but also to determine their optimum location in the catchment. Hence, there is a need for research that shows a more integrated determination of STE at the catchment scale. If integrated measures are implemented at the most appropriate spatial locations within a catchment where they can disconnect landscape units from each other, they will decrease runoff velocity and sediment transport and, subsequently, reduce downstream flooding and sedimentation problems. KEY WORDS: Integrated sediment trapping, sediment trapping efficacy, vegetative, structural, on-site and off-site measures.

The “Common Solutions” Strategy of the Experiment Support group at CERN for the LHC Experiments

NASA Astrophysics Data System (ADS)

Girone, M.; Andreeva, J.; Barreiro Megino, F. H.; Campana, S.; Cinquilli, M.; Di Girolamo, A.; Dimou, M.; Giordano, D.; Karavakis, E.; Kenyon, M. J.; Kokozkiewicz, L.; Lanciotti, E.; Litmaath, M.; Magini, N.; Negri, G.; Roiser, S.; Saiz, P.; Saiz Santos, M. D.; Schovancova, J.; Sciabà, A.; Spiga, D.; Trentadue, R.; Tuckett, D.; Valassi, A.; Van der Ster, D. C.; Shiers, J. D.

2012-12-01

After two years of LHC data taking, processing and analysis and with numerous changes in computing technology, a number of aspects of the experiments’ computing, as well as WLCG deployment and operations, need to evolve. As part of the activities of the Experiment Support group in CERN's IT department, and reinforced by effort from the EGI-InSPIRE project, we present work aimed at common solutions across all LHC experiments. Such solutions allow us not only to optimize development manpower but also offer lower long-term maintenance and support costs. The main areas cover Distributed Data Management, Data Analysis, Monitoring and the LCG Persistency Framework. Specific tools have been developed including the HammerCloud framework, automated services for data placement, data cleaning and data integrity (such as the data popularity service for CMS, the common Victor cleaning agent for ATLAS and CMS and tools for catalogue/storage consistency), the Dashboard Monitoring framework (job monitoring, data management monitoring, File Transfer monitoring) and the Site Status Board. This talk focuses primarily on the strategic aspects of providing such common solutions and how this relates to the overall goals of long-term sustainability and the relationship to the various WLCG Technical Evolution Groups. The success of the service components has given us confidence in the process, and has developed the trust of the stakeholders. We are now attempting to expand the development of common solutions into the more critical workflows. The first is a feasibility study of common analysis workflow execution elements between ATLAS and CMS. We look forward to additional common development in the future.

Management of split skin graft donor site in the West African sub region: survey of plastic surgeons' practice.

PubMed

Olawoye, O A; Ademola, S A; Iyun, A O; Michael, A I; Oluwatosin, O M

2017-06-30

Split skin graft (SSG) is one of the most commonly performed operations on any Plastic Surgery service. Rate of donor site healing is affected by various factors including the type of dressing applied. The aim of this study was to survey the practice of plastic surgeons in the sub region with respect to management of SSG donor site and see how it conforms to international standards. Structured questionnaires on various aspects of the harvest and management of SSG donor sites were administered to plastic surgeons during the 53rd annual conference of the West African College of Surgeons (WACS) at Lome, Togo in March 2013. The data were analyzed using descriptive statistics. There were 47 respondents out of 55 plastic surgeons from four West African countries, which represented 85.4% of registered participants at the plastic surgery section of the conference. All the respondents performed SSG regularly, and the thigh was the most commonly used donor site. Different types of paraffin gauze remained the most commonly used primary donor site dressing. Only 17% of the respondents apply a topical local anaesthetic agent on the donor site. The choice of SSG donor site dressing in the sub region was driven mainly by availability. Concerted efforts must be made to access newer wound care products for optimum management of this commonly performed operation.

Low-Impact Development Design—Integrating Suitability Analysis and Site Planning For Reduction Of Post-Development Stormwater Quantity

EPA Science Inventory

A land-suitability analysis (LSA) was integrated with open-space conservation principles, based on watershed physiographic and soil characteristics, to derive a low-impact development (LID) residential plan for a three hectare site in Coshocton OH, USA. The curve number method wa...

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

USDA-ARS?s Scientific Manuscript database

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...

Integrated Decision Support, Sensor Networks and Adaptive Control for Wireless Site-specific Sprinkler Irrigation

USDA-ARS?s Scientific Manuscript database

The development of site-specific sprinkler irrigation water management systems will be a major factor in future efforts to improve the various efficiencies of water-use and to support a sustainable irrigated environment. The challenge is to develop fully integrated management systems with supporting...

Integrated decision support, sensor networks and adaptive control for wireless site-specific sprinkler irrigation

USDA-ARS?s Scientific Manuscript database

The development of site-specific sprinkler irrigation water management systems will be a major factor in future efforts to improve the various efficiencies of water-use and to support a sustainable irrigated environment. The challenge is to develop fully integrated management systems with supporting...

The next step towards making use meaningful: electronic information exchange and care coordination across clinicians and delivery sites.

PubMed

Graetz, Ilana; Reed, Mary; Shortell, Stephen M; Rundall, Thomas G; Bellows, Jim; Hsu, John

2014-12-01

Care for patients with chronic conditions often requires coordination between multiple physicians and delivery sites. Electronic Health Record (EHR) use could improve care quality and efficiency in part by facilitating care coordination. We examined the association between EHR use and clinician perceptions of care coordination for patients transferred across clinicians and delivery sites. Repeated surveys of primary care clinicians during the staggered implementation of an outpatient EHR (2005-2008), followed by an integrated inpatient EHR (2006-2010). We measured the association between EHR use stages (no use, outpatient EHR only, and integrated inpatient-outpatient EHR) and care coordination using logistic regression, adjusting for clinician characteristics, study year, and medical center. Adult primary care clinicians in a large Integrated Delivery System. Three measures of clinician-reported care coordination for patient care transferred across clinicians (eg, from specialist to primary care team) and across delivery sites (eg, from the hospital to outpatient care). Outpatient EHR use was associated with higher reports of access to complete and timely clinical information and higher agreement on clinician roles and responsibilities for patients transferred across clinicians, but not for patients transferred across delivery sites. Use of the integrated outpatient-inpatient EHR was associated with higher reports of access to timely and complete clinical information, clinician agreement on the patient's treatment plan for patients transferred across delivery sites, and with all coordination measures for patients transferred across clinicians. Use of an integrated EHR with health information exchange across delivery settings improved patient care coordination.

The Execution and Evaluation of an Integrated Business Common Core Curriculum.

ERIC Educational Resources Information Center

Pharr, Steven W.; Morris, John S.; Stover, Dana; Byers, C. Randall; Reyes, Mario G.

1998-01-01

Describes the rationale, process, and organization of an integrated, cross-disciplinary undergraduate program known as the Integrated Business Common Core (IBC) at the University of Idaho. Indicates that IBC's goal is to provide students with an understanding of key business issues, with emphasis on processes. (2 tables and 11 references) (JDI)

RNA-protein binding motifs mining with a new hybrid deep learning based cross-domain knowledge integration approach.

PubMed

Pan, Xiaoyong; Shen, Hong-Bin

2017-02-28

RNAs play key roles in cells through the interactions with proteins known as the RNA-binding proteins (RBP) and their binding motifs enable crucial understanding of the post-transcriptional regulation of RNAs. How the RBPs correctly recognize the target RNAs and why they bind specific positions is still far from clear. Machine learning-based algorithms are widely acknowledged to be capable of speeding up this process. Although many automatic tools have been developed to predict the RNA-protein binding sites from the rapidly growing multi-resource data, e.g. sequence, structure, their domain specific features and formats have posed significant computational challenges. One of current difficulties is that the cross-source shared common knowledge is at a higher abstraction level beyond the observed data, resulting in a low efficiency of direct integration of observed data across domains. The other difficulty is how to interpret the prediction results. Existing approaches tend to terminate after outputting the potential discrete binding sites on the sequences, but how to assemble them into the meaningful binding motifs is a topic worth of further investigation. In viewing of these challenges, we propose a deep learning-based framework (iDeep) by using a novel hybrid convolutional neural network and deep belief network to predict the RBP interaction sites and motifs on RNAs. This new protocol is featured by transforming the original observed data into a high-level abstraction feature space using multiple layers of learning blocks, where the shared representations across different domains are integrated. To validate our iDeep method, we performed experiments on 31 large-scale CLIP-seq datasets, and our results show that by integrating multiple sources of data, the average AUC can be improved by 8% compared to the best single-source-based predictor; and through cross-domain knowledge integration at an abstraction level, it outperforms the state-of-the-art predictors by 6%. Besides the overall enhanced prediction performance, the convolutional neural network module embedded in iDeep is also able to automatically capture the interpretable binding motifs for RBPs. Large-scale experiments demonstrate that these mined binding motifs agree well with the experimentally verified results, suggesting iDeep is a promising approach in the real-world applications. The iDeep framework not only can achieve promising performance than the state-of-the-art predictors, but also easily capture interpretable binding motifs. iDeep is available at http://www.csbio.sjtu.edu.cn/bioinf/iDeep.

Integrating sea floor observatory data: the EMSO data infrastructure

NASA Astrophysics Data System (ADS)

Huber, Robert; Azzarone, Adriano; Carval, Thierry; Doumaz, Fawzi; Giovanetti, Gabriele; Marinaro, Giuditta; Rolin, Jean-Francois; Beranzoli, Laura; Waldmann, Christoph

2013-04-01

The European research infrastructure EMSO is a European network of fixed-point, deep-seafloor and water column observatories deployed in key sites of the European Continental margin and Arctic. It aims to provide the technological and scientific framework for the investigation of the environmental processes related to the interaction between the geosphere, biosphere, and hydrosphere and for a sustainable management by long-term monitoring also with real-time data transmission. Since 2006, EMSO is on the ESFRI (European Strategy Forum on Research Infrastructures) roadmap and has entered its construction phase in 2012. Within this framework, EMSO is contributing to large infrastructure integration projects such as ENVRI and COOPEUS. The EMSO infrastructure is geographically distributed in key sites of European waters, spanning from the Arctic, through the Atlantic and Mediterranean Sea to the Black Sea. It is presently consisting of thirteen sites which have been identified by the scientific community according to their importance respect to Marine Ecosystems, Climate Changes and Marine GeoHazards. The data infrastructure for EMSO is being designed as a distributed system. Presently, EMSO data collected during experiments at each EMSO site are locally stored and organized in catalogues or relational databases run by the responsible regional EMSO nodes. Three major institutions and their data centers are currently offering access to EMSO data: PANGAEA, INGV and IFREMER. In continuation of the IT activities which have been performed during EMSOs twin project ESONET, EMSO is now implementing the ESONET data architecture within an operational EMSO data infrastructure. EMSO aims to be compliant with relevant marine initiatives such as MyOceans, EUROSITES, EuroARGO, SEADATANET and EMODNET as well as to meet the requirements of international and interdisciplinary projects such as COOPEUS and ENVRI, EUDAT and iCORDI. A major focus is therefore set on standardization and interoperability of the EMSO data infrastructure. Beneath common standards for metadata exchange such as OpenSearch or OAI-PMH, EMSO has chosen to implement core standards of the Open Geospatial Consortium (OGC) Sensor Web Enablement (SWE) suite of standards, such as Catalogue Service for Web (CS-W), Sensor Observation Service (SOS) and Observations and Measurements (O&M). Further, strong integration efforts are currently undertaken to harmonize data formats e.g NetCDF as well as the used ontologies and terminologies. The presentation will also give information to users about the discovery and visualization procedure for the EMSO data presently available.

Comparison of Multivariate Spatial Dependence Structures of DPIL and Flowmeter Hydraulic Conductivity Data Sets at the MADE Site

NASA Astrophysics Data System (ADS)

Xiao, B.; Haslauer, C. P.; Bohling, G. C.; Bárdossy, A.

2017-12-01

The spatial arrangement of hydraulic conductivity (K) determines water flow and solute transport behaviour in groundwater systems. This presentation demonstrates three advances over commonly used geostatistical methods by integrating measurements from novel measurement techniques and novel multivariate non-Gaussian dependence models: The spatial dependence structure of K was analysed using both data sets of K. Previously encountered similarities were confirmed in low-dimensional dependence. These similarities become less stringent and deviate more from symmetric Gaussian dependence in dimensions larger than two. Measurements of small and large K values are more uncertain than medium K values due to decreased sensitivity of the measurement devices at both ends of the K scale. Nevertheless, these measurements contain useful information that we include in the estimation of the marginal distribution and the spatial dependence structure as ``censored measurements'' that are estimated jointly without the common assumption of independence. The spatial dependence structure of the two data sets and their cross-covariances are used to infer the spatial dependence and the amount of the bias between the two data sets. By doing so, one spatial model for K is constructed that is used for simulation and that reflects the characteristics of both measurement techniques. The concept of the presented methodology is to use all available information for the estimation of a stochastic model of the primary parameter (K) at the highly heterogeneous Macrodispersion Experiment (MADE) site. The primary parameter has been measured by two independent measurement techniques whose sets of locations do not overlap. This site offers the unique opportunity of large quantities of measurements of K (31123 direct push injection logging based measurements and 2611 flowmeter based measurements). This improved dependence structure of K will be included into the estimated non-Gaussian dependence models and is expected to reproduce observed solute concentrations at the site better than existing dependence models of K.

Structural Insights into the Assembly of the Adeno-associated Virus Type 2 Rep68 Protein on the Integration Site AAVS1*

PubMed Central

Musayev, Faik N.; Zarate-Perez, Francisco; Bishop, Clayton; Burgner, John W.; Escalante, Carlos R.

2015-01-01

Adeno-associated virus (AAV) is the only eukaryotic virus with the property of establishing latency by integrating site-specifically into the human genome. The integration site known as AAVS1 is located in chromosome 19 and contains multiple GCTC repeats that are recognized by the AAV non-structural Rep proteins. These proteins are multifunctional, with an N-terminal origin-binding domain (OBD) and a helicase domain joined together by a short linker. As a first step to understand the process of site-specific integration, we proceeded to characterize the recognition and assembly of Rep68 onto the AAVS1 site. We first determined the x-ray structure of AAV-2 Rep68 OBD in complex with the AAVS1 DNA site. Specificity is achieved through the interaction of a glycine-rich loop that binds the major groove and an α-helix that interacts with a downstream minor groove on the same face of the DNA. Although the structure shows a complex with three OBD molecules bound to the AAVS1 site, we show by using analytical centrifugation and electron microscopy that the full-length Rep68 forms a heptameric complex. Moreover, we determined that a minimum of two direct repeats is required to form a stable complex and to melt DNA. Finally, we show that although the individual domains bind DNA poorly, complex assembly requires oligomerization and cooperation between its OBD, helicase, and the linker domains. PMID:26370092

Development of a Global Wetland Sustainability Index for comprehensive land use planning

NASA Astrophysics Data System (ADS)

Schleupner, C.; Schneider, U. A.; Havlik, P.; Stacke, T.

2012-04-01

Allocation of nature reserves for conservation of ecosystem functions and services is a multi-dimensional task. Conservation programs act from local to regional or national scales, and some efforts involve entire continents. Globally, several international environmental agreements have been established which include conservation issues. Examples are the Convention on Biological Diversity, the Convention on Migratory Species of Wild Animals, the UN Framework Convention on Climate Change, and the Ramsar Convention on Wetlands. A common aim of most initiatives is the protection and restoration of valuable natural sites by providing a functional network of sites. The planning of protected habitat networks to safeguard global biodiversity requires substantial knowledge on exposure, services, and functions of ecosystems. Further, the complex spatial relationships between humans and the environment under consideration of costs and land use competition have to be determined. Often such analyses are hindered by lack of data. We developed a global index that ranks sites for wetland protection according to its wetland quantity, wetland quality and pressure upon the wetland sites. Each of the three parts is based on several spatial-ecological datasets that contain important information for the adequate assessment of spatial economic and ecologic interdependencies. Applying cluster analyses and ecological decision trees the data are combined and results are translated to the final index and expressed per simulation unit for integration into the Global Biomass Optimization Model GLOBIOM. This global recursive dynamic partial equilibrium model integrates the agricultural, bio energy and forestry sectors with the aim to provide policy analyses on global issues concerning land use competition between the major land-based production sectors. Results not only show the most vulnerable wetland areas to nature loss and the most valuable wetland areas for biodiversity protection under certain land use scenarios. Moreover, costs of protection are estimated and the results give recommendations for action by illustrating wetland conservation areas in need for conservation. Often wetlands provide numerous ecosystem services to society, such as water retention, flood control, water purification, to name only a few. The sustainable conservation of wetland sites, especially in highly human dominated landscapes, is therefore an important global but still underestimated objective.

Alteration of gene expression in human hepatocellular carcinoma with integrated hepatitis B virus DNA.

PubMed

Tamori, Akihiro; Yamanishi, Yoshihiro; Kawashima, Shuichi; Kanehisa, Minoru; Enomoto, Masaru; Tanaka, Hiromu; Kubo, Shoji; Shiomi, Susumu; Nishiguchi, Shuhei

2005-08-15

Integration of hepatitis B virus (HBV) DNA into the human genome is one of the most important steps in HBV-related carcinogenesis. This study attempted to find the link between HBV DNA, the adjoining cellular sequence, and altered gene expression in hepatocellular carcinoma (HCC) with integrated HBV DNA. We examined 15 cases of HCC infected with HBV by cassette ligation-mediated PCR. The human DNA adjacent to the integrated HBV DNA was sequenced. Protein coding sequences were searched for in the human sequence. In five cases with HBV DNA integration, from which good quality RNA was extracted, gene expression was examined by cDNA microarray analysis. The human DNA sequence successive to integrated HBV DNA was determined in the 15 HCCs. Eight protein-coding regions were involved: ras-responsive element binding protein 1, calmodulin 1, mixed lineage leukemia 2 (MLL2), FLJ333655, LOC220272, LOC255345, LOC220220, and LOC168991. The MLL2 gene was expressed in three cases with HBV DNA integrated into exon 3 of MLL2 and in one case with HBV DNA integrated into intron 3 of MLL2. Gene expression analysis suggested that two HCCs with HBV integrated into MLL2 had similar patterns of gene expression compared with three HCCs with HBV integrated into other loci of human chromosomes. HBV DNA was integrated at random sites of human DNA, and the MLL2 gene was one of the targets for integration. Our results suggest that HBV DNA might modulate human genes near integration sites, followed by integration site-specific expression of such genes during hepatocarcinogenesis.

Chloroplast DNA variation of northern red oak

Treesearch

Jeanne Romero-Severson; Preston Aldrich; Yi Feng; Weilin Sun; Charles Michler

2003-01-01

Chloroplast DNA (cpDNA) variation was examined in 48 northern red oaks at 14 sites representing contrasting glacial histories and age structures within the state of Indiana in the United States. PCR-RFLP of three intergenic regions revealed five haplotypes. Haplotype I was common to seven sites and was the most frequent (17 trees). Haplotype II was common to five sites...

A survey of selected Internet pharmacies in the United States.

PubMed

Peterson, A M

2001-01-01

To determine whether differences in the provision of pharmacy services exist among different types of Internet pharmacies. Survey of selected pharmacies with a presence on the Internet. Data were abstracted onto a data collection form for further analysis. Data collection was limited to 3 weeks. U.S.-based Internet pharmacies that allow patients to purchase prescription medications online. Pharmacies were identified using a metasearch engine with the search terms "Internet pharmacy" and "Internet pharmacist." Survey. Comparisons of availability of 10 commonly used products representing a variety of product categories, prescription verification methods, and privacy issues; and determinations of site navigability, drug information and provider access, and payment methods. Sites were categorized as "chain pharmacy extensions," "mail order pharmacies," "independent pharmacy extensions," and "online pharmacies." Thirty-three sites were reviewed. There was significant variation among the four types of pharmacies selling prescriptions over the Internet. Most pharmacies provided all of the drugs in the survey. Patients were required to provide their own prescription at 88% of the sites, and 75% of sites used mail or fax to verify prescription integrity. More than 50% of sites had privacy policies posted, and 64% used cookies. Chain pharmacy extensions required completion of an average of 10.2 pages to order drugs versus 2.4 to 4 pages for all other site types. Drug information was written at an eighth-grade reading level at 36% of the sites. More than two-thirds of the sites provided a toll-free telephone for a health care professional. Nearly 80% of the sites accepted health insurance, and 95% accepted credit cards; however, only 40% used a secure transmission mechanism for patient or payment information. Internet pharmacies provide varying levels of service. Policies regarding the use of the Internet for obtaining medications should focus on improving the privacy of consumer information and ensuring the secure transmission of financial information.

Deciphering Equatorial Pacific Deep Sea Sediment Transport Regimes by Core-Log-Seismic Integration

NASA Astrophysics Data System (ADS)

Ortiz, E.; Tominaga, M.; Marcantonio, F.

2017-12-01

Investigating deep-sea sediment transportation and deposition regimes is a key to accurately understand implications from geological information recorded by pelagic sediments, e.g. climate signals. However, except for physical oceanographic particle trap experiments, geochemical analyses of in situsediments, and theoretical modeling of the relation between the bottom currents and sediment particle flux, it has remained a challenging task to document the movement of deep sea sediments, that takes place over time. We utilized high-resolution, multichannel reflection seismic data from the eastern equatorial Pacific region with drilling and logging results from two Integrated Ocean Drilling Program (IODP) sites, the Pacific Equatorial Age Transect (PEAT) 7 (Site U1337) and 8 (Site U1338), to characterize sediment transportation regimes on 18-24 Ma oceanic crust. Site U1337, constructed by a series of distinct abyssal hills and abyssal basins; Site U1338, located 570 km SE from Site U1337 site and constructed by a series of ridges, seamounts, and abyssal hills. These sites are of particular interest due to their proximity to the equatorial productivity zone, areas with high sedimentation rates and preservation of carbonate-bearing sediment that provide invaluable insights on equatorial Pacific ecosystems and carbon cycle. We integrate downhole geophysical logging data as well as geochemistry and physical properties measurements on recovered cores from IODP Sites U1337 and U1338 to comprehensively examine the mobility of deep-sea sediments and sediment diagenesis over times in a quasi-3D manner. We also examine 1100 km of high resolution underway seismic surveys from site survey lines in between PEAT 7 and 8 in order to investigate changes in sediment transportation between both sites. Integrating detailed seismic interpretations, high resolution core data, and 230Th flux measurements we aim to create a detailed chronological sedimentation and sediment diagenesis history of this area.

Spawning site selection and contingent behavior in Common Snook, Centropomus undecimalis.

PubMed

Lowerre-Barbieri, Susan; Villegas-Ríos, David; Walters, Sarah; Bickford, Joel; Cooper, Wade; Muller, Robert; Trotter, Alexis

2014-01-01

Reproductive behavior affects spatial population structure and our ability to manage for sustainability in marine and diadromous fishes. In this study, we used fishery independent capture-based sampling to evaluate where Common Snook occurred in Tampa Bay and if it changed with spawning season, and passive acoustic telemetry to assess fine scale behavior at an inlet spawning site (2007-2009). Snook concentrated in three areas during the spawning season only one of which fell within the expected spawning habitat. Although in lower numbers, they remained in these areas throughout the winter months. Acoustically-tagged snook (n = 31) showed two seasonal patterns at the spawning site: Most fish occurred during the spawning season but several fish displayed more extended residency, supporting the capture-based findings that Common Snook exhibit facultative catadromy. Spawning site selection for iteroparous, multiple-batch spawning fishes occurs at the lifetime, annual, or intra-annual temporal scales. In this study we show colonization of a new spawning site, indicating that lifetime spawning site fidelity of Common Snook is not fixed at this fine spatial scale. However, individuals did exhibit annual and intra-seasonal spawning site fidelity to this new site over the three years studied. The number of fish at the spawning site increased in June and July (peak spawning months) and on new and full lunar phases indicating within population variability in spawning and movement patterns. Intra-seasonal patterns of detection also differed significantly with sex. Common Snook exhibited divergent migration tactics and habitat use at the annual and estuarine scales, with contingents using different overwintering habitat. Migration tactics also varied at the spawning site at the intra-seasonal scale and with sex. These results have important implications for understanding how reproductive behavior affects spatio-temporal patterns of fish abundance and their resilience to disturbance events and fishing pressure.

A framework for organizing cancer-related variations from existing databases, publications and NGS data using a High-performance Integrated Virtual Environment (HIVE).

PubMed

Wu, Tsung-Jung; Shamsaddini, Amirhossein; Pan, Yang; Smith, Krista; Crichton, Daniel J; Simonyan, Vahan; Mazumder, Raja

2014-01-01

Years of sequence feature curation by UniProtKB/Swiss-Prot, PIR-PSD, NCBI-CDD, RefSeq and other database biocurators has led to a rich repository of information on functional sites of genes and proteins. This information along with variation-related annotation can be used to scan human short sequence reads from next-generation sequencing (NGS) pipelines for presence of non-synonymous single-nucleotide variations (nsSNVs) that affect functional sites. This and similar workflows are becoming more important because thousands of NGS data sets are being made available through projects such as The Cancer Genome Atlas (TCGA), and researchers want to evaluate their biomarkers in genomic data. BioMuta, an integrated sequence feature database, provides a framework for automated and manual curation and integration of cancer-related sequence features so that they can be used in NGS analysis pipelines. Sequence feature information in BioMuta is collected from the Catalogue of Somatic Mutations in Cancer (COSMIC), ClinVar, UniProtKB and through biocuration of information available from publications. Additionally, nsSNVs identified through automated analysis of NGS data from TCGA are also included in the database. Because of the petabytes of data and information present in NGS primary repositories, a platform HIVE (High-performance Integrated Virtual Environment) for storing, analyzing, computing and curating NGS data and associated metadata has been developed. Using HIVE, 31 979 nsSNVs were identified in TCGA-derived NGS data from breast cancer patients. All variations identified through this process are stored in a Curated Short Read archive, and the nsSNVs from the tumor samples are included in BioMuta. Currently, BioMuta has 26 cancer types with 13 896 small-scale and 308 986 large-scale study-derived variations. Integration of variation data allows identifications of novel or common nsSNVs that can be prioritized in validation studies. Database URL: BioMuta: http://hive.biochemistry.gwu.edu/tools/biomuta/index.php; CSR: http://hive.biochemistry.gwu.edu/dna.cgi?cmd=csr; HIVE: http://hive.biochemistry.gwu.edu.

Treatment of uncommon sites of focal primary hyperhidrosis: experience with pharmacological therapy using oxybutynin

PubMed Central

Teivelis, Marcelo Passos; Wolosker, Nelson; Krutman, Mariana; Kauffman, Paulo; de Campos, José Ribas Milanez; Puech-Leão, Pedro

2014-01-01

OBJECTIVES: Primary hyperhidrosis usually affects the hands, armpits, feet and cranio-facial region. Sweating in other areas is common in secondary hyperhidrosis (after surgery or in specific clinical conditions). Oxybutynin has provided good results and is an alternative for treating hyperhidrosis at common sites. Our aim was to evaluate the efficacy of oxybutynin as a treatment for primary sweating at uncommon sites (e.g., the back and groin). METHODS: This retrospective study analyzed 20 patients (10 females) who received oxybutynin for primary focal hyperhidrosis at uncommon sites. The subjects were evaluated to determine quality of life before beginning oxybutynin and six weeks afterward and they were assigned grades (on a scale from 0 to 10) to measure their improvement at each site of excessive sweating after six weeks and at the last consult. RESULTS: The median follow-up time with oxybutynin was 385 days (133-1526 days). The most common sites were the back (n = 7) and groin (n = 5). After six weeks, the quality of life improved in 85% of the subjects. Dry mouth was very common and was reported by 16 patients, 12 of whom reported moderate/severe dry mouth. Five patients stopped treatment (two: unbearable dry mouth, two: excessive somnolence and one: palpitations). At the last visit, 80% of patients presented with moderate/great improvement at the main sites of sweating. CONCLUSION: After six weeks, more than 80% of the patients presented with improvements in their overall quality of life and at the most important site of sweating. Side effects were common (80% reported at least one side effect) and caused 25% of the patients to discontinue treatment. Oxybutynin is effective for treating bothersome hyperhidrosis, even at atypical locations and most patients cope well with the side effects. PMID:25318092

Telomere formation on macronuclear chromosomes of Oxytricha trifallax and O. fallax: alternatively processed regions have multiple telomere addition sites

PubMed Central

Williams, Kevin R; Doak, Thomas G; Herrick, Glenn

2002-01-01

Background Ciliates employ massive chromatid breakage and de novo telomere formation during generation of the somatic macronucleus. Positions flanking the 81-MAC locus are reproducibly cut. But those flanking the Common Region are proposed to often escape cutting, generating three nested macronuclear chromosomes, two retaining "arms" still appended to the Common Region. Arm-distal positions must differ (in cis) from the Common Region flanks. Results The Common-Region-flanking positions also differ from the arm-distal positions in that they are "multi-TAS" regions: anchored PCR shows heterogeneous patterns of telomere addition sites, but arm-distal sites do not. The multi-TAS patterns are reproducible, but are sensitive to the sequence of the allele being processed. Thus, random degradation following chromatid cutting does not create this heterogeneity; these telomere addition sites also must be dictated by cis-acting sequences. Conclusions Most ciliates show such micro-heterogeneity in the precise positions of telomere addition sites. Telomerase is believed to be tightly associated with, and act in concert with, the chromatid-cutting nuclease: heterogeneity must be the result of intervening erosion activity. Our "weak-sites" hypothesis explains the correlation between alternative chromatid cutting at the Common Region boundaries and their multi-TAS character: when the chromatid-breakage machine encounters either a weak binding site or a weak cut site at these regions, then telomerase dissociates prematurely, leaving the new end subject to erosion by an exonuclease, which pauses at cis-acting sequences; telomerase eventually heals these resected termini. Finally, we observe TAS positioning influenced by trans-allelic interactions, reminiscent of transvection. PMID:12199911

2013 strategic petroleum reserve big hill well integrity grading report.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lord, David L.; Roberts, Barry L.; Lord, Anna C. Snider

2014-02-01

This report summarizes the work performed in developing a framework for the prioritization of cavern access wells for remediation and monitoring at the Big Hill Strategic Petroleum Reserve site. This framework was then applied to all 28 wells at the Big Hill site with each well receiving a grade for remediation and monitoring. Numerous factors affecting well integrity were incorporated into the grading framework including casing survey results, cavern pressure history, results from geomechanical simulations, and site geologic factors. The framework was developed in a way as to be applicable to all four of the Strategic Petroleum Reserve sites.

Assessment of fish assemblages and minimum sampling effort required to determine botic integrity of large rivers in southern Idaho, 2002

USGS Publications Warehouse

Maret, Terry R.; Ott, D.S.

2004-01-01

width was determined to be sufficient for collecting an adequate number of fish to estimate species richness and evaluate biotic integrity. At most sites, about 250 fish were needed to effectively represent 95 percent of the species present. Fifty-three percent of the sites assessed, using an IBI developed specifically for large Idaho rivers, received scores of less than 50, indicating poor biotic integrity.

Air Force is Developing Risk-Mitigation Strategies to Manage Potential Loss of the RD-180 Engine (REDACTED)

DTIC Science & Technology

2015-03-05

launched on its rocket- estimated completion date of May 2015. Air Force will require verification that SpaceX can meet payload integration...design and accelerate integration capability at Space Exploration Technologies Corporation ( SpaceX )1 launch sites. o The Air Force does not intend to...accelerate integration capabilities at SpaceX launch sites because of the studies it directed, but will require verification that SpaceX can meet

Unusual Structure of the attB Site of the Site-Specific Recombination System of Lactobacillus delbrueckii Bacteriophage mv4

PubMed Central

Auvray, Frédéric; Coddeville, Michèle; Ordonez, Romy Catoira; Ritzenthaler, Paul

1999-01-01

The temperate phage mv4 integrates its genome into the chromosome of Lactobacillus delbrueckii subsp. bulgaricus by site-specific recombination within the 3′ end of a tRNASer gene. Recombination is catalyzed by the phage-encoded integrase and occurs between the phage attP site and the bacterial attB site. In this study, we show that the mv4 integrase functions in vivo in Escherichia coli and we characterize the bacterial attB site with a site-specific recombination test involving compatible plasmids carrying the recombination sites. The importance of particular nucleotides within the attB sequence was determined by site-directed mutagenesis. The structure of the attB site was found to be simple but rather unusual. A 16-bp DNA fragment was sufficient for function. Unlike most genetic elements that integrate their DNA into tRNA genes, none of the dyad symmetry elements of the tRNASer gene were present within the minimal attB site. No inverted repeats were detected within this site either, in contrast to the lambda site-specific recombination model. PMID:10572145

Integration of high-risk human papillomavirus into cellular cancer-related genes in head and neck cancer cell lines.

PubMed

Walline, Heather M; Goudsmit, Christine M; McHugh, Jonathan B; Tang, Alice L; Owen, John H; Teh, Bin T; McKean, Erin; Glover, Thomas W; Graham, Martin P; Prince, Mark E; Chepeha, Douglas B; Chinn, Steven B; Ferris, Robert L; Gollin, Susanne M; Hoffmann, Thomas K; Bier, Henning; Brakenhoff, Ruud; Bradford, Carol R; Carey, Thomas E

2017-05-01

Human papillomavirus (HPV)-positive oropharyngeal cancer is generally associated with excellent response to therapy, but some HPV-positive tumors progress despite aggressive therapy. The purpose of this study was to evaluate viral oncogene expression and viral integration sites in HPV16- and HPV18-positive squamous cell carcinoma lines. E6/E7 alternate transcripts were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). Detection of integrated papillomavirus sequences (DIPS-PCR) and sequencing identified viral insertion sites and affected host genes. Cellular gene expression was assessed across viral integration sites. All HPV-positive cell lines expressed alternate HPVE6/E7 splicing indicative of active viral oncogenesis. HPV integration occurred within cancer-related genes TP63, DCC, JAK1, TERT, ATR, ETV6, PGR, PTPRN2, and TMEM237 in 8 head and neck squamous cell carcinoma (HNSCC) lines but UM-SCC-105 and UM-GCC-1 had only intergenic integration. HPV integration into cancer-related genes occurred in 7 of 9 HPV-positive cell lines and of these 6 were from tumors that progressed. HPV integration into cancer-related genes may be a secondary carcinogenic driver in HPV-driven tumors. © 2017 Wiley Periodicals, Inc. Head Neck 39: 840-852, 2017. © 2017 Wiley Periodicals, Inc.

Mapping genetic variations to three-dimensional protein structures to enhance variant interpretation: a proposed framework.

PubMed

Glusman, Gustavo; Rose, Peter W; Prlić, Andreas; Dougherty, Jennifer; Duarte, José M; Hoffman, Andrew S; Barton, Geoffrey J; Bendixen, Emøke; Bergquist, Timothy; Bock, Christian; Brunk, Elizabeth; Buljan, Marija; Burley, Stephen K; Cai, Binghuang; Carter, Hannah; Gao, JianJiong; Godzik, Adam; Heuer, Michael; Hicks, Michael; Hrabe, Thomas; Karchin, Rachel; Leman, Julia Koehler; Lane, Lydie; Masica, David L; Mooney, Sean D; Moult, John; Omenn, Gilbert S; Pearl, Frances; Pejaver, Vikas; Reynolds, Sheila M; Rokem, Ariel; Schwede, Torsten; Song, Sicheng; Tilgner, Hagen; Valasatava, Yana; Zhang, Yang; Deutsch, Eric W

2017-12-18

The translation of personal genomics to precision medicine depends on the accurate interpretation of the multitude of genetic variants observed for each individual. However, even when genetic variants are predicted to modify a protein, their functional implications may be unclear. Many diseases are caused by genetic variants affecting important protein features, such as enzyme active sites or interaction interfaces. The scientific community has catalogued millions of genetic variants in genomic databases and thousands of protein structures in the Protein Data Bank. Mapping mutations onto three-dimensional (3D) structures enables atomic-level analyses of protein positions that may be important for the stability or formation of interactions; these may explain the effect of mutations and in some cases even open a path for targeted drug development. To accelerate progress in the integration of these data types, we held a two-day Gene Variation to 3D (GVto3D) workshop to report on the latest advances and to discuss unmet needs. The overarching goal of the workshop was to address the question: what can be done together as a community to advance the integration of genetic variants and 3D protein structures that could not be done by a single investigator or laboratory? Here we describe the workshop outcomes, review the state of the field, and propose the development of a framework with which to promote progress in this arena. The framework will include a set of standard formats, common ontologies, a common application programming interface to enable interoperation of the resources, and a Tool Registry to make it easy to find and apply the tools to specific analysis problems. Interoperability will enable integration of diverse data sources and tools and collaborative development of variant effect prediction methods.

Lipid Interaction Sites on Channels, Transporters and Receptors: Recent Insights from Molecular Dynamics Simulations

PubMed Central

Hedger, George; Sansom, Mark S. P.

2017-01-01

Lipid molecules are able to selectively interact with specific sites on integral membrane proteins, and modulate their structure and function. Identification and characterisation of these sites is of importance for our understanding of the molecular basis of membrane protein function and stability, and may facilitate the design of lipid-like drug molecules. Molecular dynamics simulations provide a powerful tool for the identification of these sites, complementing advances in membrane protein structural biology and biophysics. We describe recent notable biomolecular simulation studies which have identified lipid interaction sites on a range of different membrane proteins. The sites identified in these simulation studies agree well with those identified by complementary experimental techniques. This demonstrates the power of the molecular dynamics approach in the prediction and characterization of lipid interaction sites on integral membrane proteins. PMID:26946244

Multi-level stressor analysis from the DNA/biochemical level to community levels in an urban stream and integrative health response (IHR) assessments.

PubMed

Lee, Jae Hoon; Kim, Joon Ha; Oh, Hee-Mock; An, Kwang-Guk

2013-01-01

The objectives of this study were to identify multi-level stressors at the DNA/biochemical level to the community level in fish in an urban stream and to develop an integrative health response (IHR) model for ecological health diagnosis. A pristine control site (S (c) ) and an impacted site (S (i) ) were selected from among seven pre-screened sites studied over seven years. Various chemical analyses indicated that nutrient enrichment (Nitrogen, Phosphorus) and organic pollution were significantly greater (t > 8.783, p < 0.01) at the S (i) site compared to the S (c) site. Single-cell gel electrophoresis (comet assays) of DNA-level impairment indicated significantly (t = 5.678, p < 0.01) greater tail intensity, expressed as % tail-DNA, at the S (i) site and genotoxic responses were detected in the downstream reach. Ethoxyresorufin-O-deethylase (EROD) assays, as a physiological bioindicator, were 2.8-fold higher (p < 0.05, NK-test after ANOVA) at the S (i) site. Tissue analysis using a necropsy-based health assessment index (NHAI) showed distinct internal organ disorders in three tissues, i.e., liver, kidney, and gill, at the S (i) site. Population-level analysis using the sentinel species Zacco platypus showed that the regression coefficient (b) was 3.012 for the S (i) site and 2.915 for the S (c) site, indicating population skewness in the downstream reach. Community-level health was impaired at the S (i) site based on an index of biological integrity (IBI), and physical habitat modifications were identified by a qualitative habitat evaluation index (QHEI). Overall, the model values for the integrative health response (IHR), developed using the star plot approach, were 3.22 (80.5%) at the S (c) site and 0.74 (18.5%) at the S (i) site, indicating that, overall, ecological health impairments were evident in the urban reach. Our study was based on multi-level approaches using biological organization and the results suggest that there is a pivotal point of linkage between mechanistic understanding and real ecological consequences of environmental stressors.

LifeWatchGreece Portal development: architecture, implementation and challenges for a biodiversity research e-infrastructure.

PubMed

Gougousis, Alexandros; Bailly, Nicolas

2016-01-01

Biodiversity data is characterized by its cross-disciplinary character, the extremely broad range of data types and structures, and the plethora of different data sources providing resources for the same piece of information in a heterogeneous way. Since the web inception two decades ago, there are multiple initiatives to connect, aggregate, share, and publish biodiversity data, and to establish data and work flows in order to analyze them. The European program LifeWatch aims at establishing a distributed network of nodes implementing virtual research environment in Europe to facilitate the work of biodiversity researchers and managers. LifeWatchGreece is one of these nodes where a portal was developed offering access to a suite of virtual laboratories and e-services. Despite its strict definition in information technology, in practice "portal" is a fairly broad term that embraces many web architectures. In the biodiversity domain, the term "portal" is usually used to indicate either a web site that provides access to a single or an aggregation of data repositories (like: http://indiabiodiversity.org/, http://www.mountainbiodiversity.org/, http://data.freshwaterbiodiversity.eu), a web site that gathers information about various online biodiversity tools (like http://test-eubon.ebd.csic.es/, http://marine.lifewatch.eu/) or a web site that just gathers information and news about the biodiversity domain (like http://chm.moew.government.bg). LifeWatchGreece's portal takes the concept of a portal a step further. In strict IT terms, LifeWatchGreece's portal is partly a portal, partly a platform and partly an aggregator. It includes a number of biodiversity-related web tools integrated into a centrally-controlled software ecosystem. This ecosystem includes subsystems for access control, traffic monitoring, user notifications and web tool management. These subsystems are shared to all the web tools that have been integrated to the portal and thereby are part of this ecosystem. These web tools do not consist in external and completely independent web applications as it happens in most other portals. A quite obvious (to the user) indication of this is the Single-Sign-On (SSO) functionality for all tools and the common user interface wrapper that most of these tools use. Another example of a less obvious functionality is the common user profile that is shared and can be utilized by all tools (e.g user's timezone).

Cross-Cultural Language Learning and Web Design Complexity

ERIC Educational Resources Information Center

Park, Ji Yong

2015-01-01

Accepting the fact that culture and language are interrelated in second language learning (SLL), the web sites should be designed to integrate with the cultural aspects. Yet many SLL web sites fail to integrate with the cultural aspects and/or focus on language acquisition only. This study identified three issues: (1) anthropologists'…

Toward Integrated Family Services in Rural Settings: A Summary of Research and Practice. Program Report.

ERIC Educational Resources Information Center

Stoops, Jack W.; Hull, Janis L.

This report synthesizes research findings with observations of three Pacific Northwest sites attempting service integration in rural settings. At case-study sites in Washington and Oregon, rural schools, communities, and service providers collaborate to deliver services to students and community members suffering from high unemployment, alcohol…

The Portland Harbor Superfund Site Sustainability Project: Introduction.

PubMed

Fitzpatrick, Anne G; Apitz, Sabine E; Harrison, David; Ruffle, Betsy; Edwards, Deborah A

2018-01-01

This article introduces the Portland Harbor Superfund Site Sustainability Project (PHSP) special series in this issue. The Portland Harbor Superfund Site is one of the "mega-sediment sites" in the United States, comprising about 10 miles of the Lower Willamette River, running through the heart of Portland, Oregon. The primary aim of the PHSP was to conduct a comprehensive sustainability assessment, integrating environmental, economic, and social considerations of a selection of the remedial alternatives laid out by the US Environmental Protection Agency. A range of tools were developed for this project to quantitatively address environmental, economic, and social costs and benefits based upon diverse stakeholder values. In parallel, a probabilistic risk assessment was carried out to evaluate the risk assumptions at the core of the remedial investigation and feasibility study process. Integr Environ Assess Manag 2018;14:17-21. © 2017 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC). © 2017 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

The holy grail of soil metal contamination site assessment: reducing risk and increasing confidence of decision making using infield portable X-ray Fluorescence (pXRF) technology

NASA Astrophysics Data System (ADS)

Rouillon, M.; Taylor, M. P.; Dong, C.

2016-12-01

This research assesses the advantages of integrating field portable X-ray Fluorescence (pXRF) technology for reducing the risk and increase confidence of decision making for metal-contaminated site assessments. Metal-contaminated sites are often highly heterogeneous and require a high sampling density to accurately characterize the distribution and concentration of contaminants. The current regulatory assessment approaches rely on a small number of samples processed using standard wet-chemistry methods. In New South Wales (NSW), Australia, the current notification trigger for characterizing metal-contaminated sites require the upper 95% confidence interval of the site mean to equal or exceed the relevant guidelines. The method's low `minimum' sampling requirements can misclassify sites due to the heterogeneous nature of soil contamination, leading to inaccurate decision making. To address this issue, we propose integrating infield pXRF analysis with the established sampling method to overcome sampling limitations. This approach increases the minimum sampling resolution and reduces the 95% CI of the site mean. Infield pXRF analysis at contamination hotspots enhances sample resolution efficiently and without the need to return to the site. In this study, the current and proposed pXRF site assessment methods are compared at five heterogeneous metal-contaminated sites by analysing the spatial distribution of contaminants, 95% confidence intervals of site means, and the sampling and analysis uncertainty associated with each method. Finally, an analysis of costs associated with both the current and proposed methods is presented to demonstrate the advantages of incorporating pXRF into metal-contaminated site assessments. The data shows that pXRF integrated site assessments allows for faster, cost-efficient, characterisation of metal-contaminated sites with greater confidence for decision making.

Recommendations for clinical biomarker specimen preservation and stability assessments.

PubMed

Dakappagari, Naveen; Zhang, Hui; Stephen, Laurie; Amaravadi, Lakshmi; Khan, Masood U

2017-04-01

With the wide use of biomarkers to enable critical drug-development decisions, there is a growing concern from scientific community on the need for a 'standardized process' for ensuring biomarker specimen stability and hence, a strong desire to share best practices on preserving the integrity of biomarker specimens in clinical trials and the design of studies to evaluate analyte stability. By leveraging representative industry experience, we have attempted to provide an overview of critical aspects of biomarker specimen stability commonly encountered during clinical development, including: planning of clinical sample collection procedures, clinical site training, selection of sample preservation buffers, shipping logistics, fit-for-purpose stability assessments in the analytical laboratory and presentation of case studies covering widely utilized biomarker specimen types.

Computer graphics in architecture and engineering

NASA Technical Reports Server (NTRS)

Greenberg, D. P.

1975-01-01

The present status of the application of computer graphics to the building profession or architecture and its relationship to other scientific and technical areas were discussed. It was explained that, due to the fragmented nature of architecture and building activities (in contrast to the aerospace industry), a comprehensive, economic utilization of computer graphics in this area is not practical and its true potential cannot now be realized due to the present inability of architects and structural, mechanical, and site engineers to rely on a common data base. Future emphasis will therefore have to be placed on a vertical integration of the construction process and effective use of a three-dimensional data base, rather than on waiting for any technological breakthrough in interactive computing.

Epidemiology and Molecular Biology of Head and Neck Cancer.

PubMed

Jou, Adriana; Hess, Jochen

2017-01-01

Head and neck cancer is a common and aggressive malignancy with a high morbidity and mortality profile. Although the large majority of cases resemble head and neck squamous cell carcinoma (HNSCC), the current classification based on anatomic site and tumor stage fails to capture the high level of biologic heterogeneity, and appropriate clinical management remains a major challenge. Hence, a better understanding of the molecular biology of HNSCC is urgently needed to support biomarker development and personalized care for patients. This review focuses on recent findings based on integrative genomics analysis and multi-scale modeling approaches and how they are beginning to provide more sophisticated clues as to the biological and clinical diversity of HNSCC. © 2017 S. Karger GmbH, Freiburg.

Selection of suitable NDT methods for building inspection

NASA Astrophysics Data System (ADS)

Pauzi Ismail, Mohamad

2017-11-01

Construction of modern structures requires good quality concrete with adequate strength and durability. Several accidents occurred in the civil constructions and were reported in the media. Such accidents were due to poor workmanship and lack of systematic monitoring during the constructions. In addition, water leaking and cracking in residential houses was commonly reported too. Based on these facts, monitoring the quality of concrete in structures is becoming more and more important subject. This paper describes major Non-destructive Testing (NDT) methods for evaluating structural integrity of concrete building. Some interesting findings during actual NDT inspections on site are presented. The NDT methods used are explained, compared and discussed. The suitable methods are suggested as minimum NDT methods to cover parameters required in the inspection.

Reconstructing Common Era relative sea-level change on the Gulf Coast of Florida

USGS Publications Warehouse

Gerlach, Matthew J.; Engelhart, Simon E.; Kemp, Andrew C.; Moyer, Ryan P.; Smoak, Joseph M.; Bernhardt, Christopher E.; Cahill, Niamh

2017-01-01

To address a paucity of Common Era data in the Gulf of Mexico, we reconstructed ~ 1.1 m of relative sea-level (RSL) rise over the past ~ 2000 years at Little Manatee River (Gulf Coast of Florida, USA). We applied a regional-scale foraminiferal transfer function to fossil assemblages preserved in a core of salt-marsh peat and organic silt that was dated using radiocarbon and recognition of pollution, 137Cs and pollen chronohorizons. Our proxy reconstruction was combined with tide-gauge data from four nearby sites spanning 1913–2014 CE. Application of an Errors-in-Variables Integrated Gaussian Process (EIV-IGP) model to the combined proxy and instrumental dataset demonstrates that RSL fell from ~ 350 to 100 BCE, before rising continuously to present. This initial RSL fall was likely the result of local-scale processes (e.g., silting up of a tidal flat or shallow sub-tidal shoal) as salt-marsh development at the site began. Since ~ 0 CE, we consider the reconstruction to be representative of regional-scale RSL trends. We removed a linear rate of 0.3 mm/yr from the RSL record using the EIV-IGP model to estimate climate-driven sea-level trends and to facilitate comparison among sites. This analysis demonstrates that since ~ 0 CE sea level did not deviate significantly from zero until accelerating continuously from ~ 1500 CE to present. Sea level was rising at 1.33 mm/yr in 1900 CE and accelerated until 2014 CE when a rate of 2.02 mm/yr was attained, which is the fastest, century-scale trend in the ~ 2000-year record. Comparison to existing reconstructions from the Gulf coast of Louisiana and the Atlantic coast of northern Florida reveal similar sea-level histories at all three sites. We explored the influence of compaction and fluvial processes on our reconstruction and concluded that compaction was likely insignificant. Fluvial processes were also likely insignificant, but further proxy evidence is needed to fully test this hypothesis. Our results indicate that no significant Common Era sea-level changes took place on the Gulf and southeastern Atlantic U.S. coasts until the onset of modern sea-level rise in the late 19th century.

Genome-wide Determinants of Proviral Targeting, Clonal Abundance and Expression in Natural HTLV-1 Infection

PubMed Central

Melamed, Anat; Laydon, Daniel J.; Gillet, Nicolas A.; Tanaka, Yuetsu; Taylor, Graham P.; Bangham, Charles R. M.

2013-01-01

The regulation of proviral latency is a central problem in retrovirology. We postulate that the genomic integration site of human T lymphotropic virus type 1 (HTLV-1) determines the pattern of expression of the provirus, which in turn determines the abundance and pathogenic potential of infected T cell clones in vivo. We recently developed a high-throughput method for the genome-wide amplification, identification and quantification of proviral integration sites. Here, we used this protocol to test two hypotheses. First, that binding sites for transcription factors and chromatin remodelling factors in the genome flanking the proviral integration site of HTLV-1 are associated with integration targeting, spontaneous proviral expression, and in vivo clonal abundance. Second, that the transcriptional orientation of the HTLV-1 provirus relative to that of the nearest host gene determines spontaneous proviral expression and in vivo clonal abundance. Integration targeting was strongly associated with the presence of a binding site for specific host transcription factors, especially STAT1 and p53. The presence of the chromatin remodelling factors BRG1 and INI1 and certain host transcription factors either upstream or downstream of the provirus was associated respectively with silencing or spontaneous expression of the provirus. Cells expressing HTLV-1 Tax protein were significantly more frequent in clones of low abundance in vivo. We conclude that transcriptional interference and chromatin remodelling are critical determinants of proviral latency in natural HTLV-1 infection. PMID:23555266

Accuracy and efficiency define Bxb1 integrase as the best of fifteen candidate serine recombinases for the integration of DNA into the human genome

PubMed Central

2013-01-01

Background Phage-encoded serine integrases, such as φC31 integrase, are widely used for genome engineering. Fifteen such integrases have been described but their utility for genome engineering has not been compared in uniform assays. Results We have compared fifteen serine integrases for their utility for DNA manipulations in mammalian cells after first demonstrating that all were functional in E. coli. Chromosomal recombination reporters were used to show that seven integrases were active on chromosomally integrated DNA in human fibroblasts and mouse embryonic stem cells. Five of the remaining eight enzymes were active on extra-chromosomal substrates thereby demonstrating that the ability to mediate extra-chromosomal recombination is no guide to ability to mediate site-specific recombination on integrated DNA. All the integrases that were active on integrated DNA also promoted DNA integration reactions that were not mediated through conservative site-specific recombination or damaged the recombination sites but the extent of these aberrant reactions varied over at least an order of magnitude. Bxb1 integrase yielded approximately two-fold more recombinants and displayed about two fold less damage to the recombination sites than the next best recombinase; φC31 integrase. Conclusions We conclude that the Bxb1 and φC31 integrases are the reagents of choice for genome engineering in vertebrate cells and that DNA damage repair is a major limitation upon the utility of this class of site-specific recombinase. PMID:24139482

HIV Integration at Certain Sites in Host DNA is Linked to the Expansion and Persistence of Infected Cells | Center for Cancer Research

Cancer.gov

When the Human Immunodeficiency Virus (HIV) infects a cell, the virus inserts a copy of its genetic material into the host cell’s DNA. The inserted genetic material, which is also called a provirus, is used to produce new viruses. Because the viral DNA can be inserted at many sites in the host cell DNA, the site of integration marks each infected cell. Patients infected with

Colorectal cancer: Metastases to a single organ

PubMed Central

Vatandoust, Sina; Price, Timothy J; Karapetis, Christos S

2015-01-01

Colorectal cancer (CRC) is a common malignancy worldwide. In CRC patients, metastases are the main cause of cancer-related mortality. In a group of metastatic CRC patients, the metastases are limited to a single site (solitary organ); the liver and lungs are the most commonly involved sites. When metastatic disease is limited to the liver and/or lungs, the resectability of the metastatic lesions will dictate the management approach and the outcome. Less commonly, the site of solitary organ CRC metastasis is the peritoneum. In these patients, cytoreduction followed by hyperthermic intraperitoneal chemotherapy may improve the outcome. Rarely, CRC involves other organs, such as the brain, bone, adrenals and spleen, as the only site of metastatic disease. There are limited data to guide clinical practice in these cases. Here, we have reviewed the disease characteristics, management approaches and prognosis based on the metastatic disease site in patients with CRC with metastases to a single organ. PMID:26557001

An index of biological integrity for northern Mid-Atlantic Slope drainages

USGS Publications Warehouse

Daniels, R.A.; Riva-Murray, K.; Halliwell, D.B.; Vana-Miller, D. L.; Bilger, Michael D.

2002-01-01

An index of biological integrity (IBI) was developed for streams in the Hudson, Delaware, and Susquehanna River drainages in the northeastern United States based on fish assemblage data from the Mohawk River drainage of New York. The original IBI, developed for streams in the U.S. Midwest, was modified to reflect the assemblage composition and structure present in Mid-Atlantic Slope drainages. We replaced several of the Midwestern IBI metrics and criteria scores because fishes common to the Midwest are absent from or poorly represented in the Northeast and because stream fish assemblages in the Northeast are less rich than those in the Midwest. For all replacement metrics we followed the ecology-based rationale used in the development of each of the metrics of the Midwestern IBI so that the basic theoretical underpinnings of the IBI remained unchanged. The validity of this modified IBI is demonstrated by examining the quality of streams in the Hudson, Delaware, and lower Susquehanna River basins. The relationships between the IBI and other indicators of environmental quality are examined using data on assemblages of fish and benthic macroinvertebrates and on chemical and physical stream characteristics obtained during 1993-2000 by the U.S. Geological Survey's National Water Quality Assessment Program in these three river basins. A principal components analysis (PCA) of chemical and physical variables from 27 sites resulted in an environmental quality gradient as the primary PCA axis (eigenvalue, 0.41 ). Principal components analysis site scores were significantly correlated with such benthic macroinvertebrate metrics as the percentage of Ephemeroptera, Plecoptera, and Trichoptera taxa (Spearman R = -0.66, P < 0.001). Index of biological integrity scores for sites in these three river basins were significantly correlated with this environmental quality gradient (Spearman R = -0.78, P = 0.0001). The northern Mid-Atlantic Slope IBI appears to be sensitive to environmental degradation in all three of the river basins addressed in this study. Adjustment of metric scoring criteria may be warranted, depending on composition of fish species in streams in the study area and on the relative effort used in the collection of fish assemblage data.

Effect of integrated infectious disease training and on-site support on the management of childhood illnesses in Uganda: a cluster randomized trial.

PubMed

Imani, Peace; Jakech, Brian; Kirunda, Ibrahim; Mbonye, Martin K; Naikoba, Sarah; Weaver, Marcia R

2015-08-28

The Integrated Infectious Disease Capacity-Building Evaluation (IDCAP) was designed to test the effects of two interventions, Integrated Management of Infectious Disease (IMID) training and on-site support (OSS), on clinical practice of mid-level practitioners. This article reports the effects of these interventions on clinical practice in management of common childhood illnesses. Two trainees from each of 36 health facilities participated in the IMID training. IMID was a three-week core course, two one-week boost courses, and distance learning over nine months. Eighteen of the 36 health facilities were then randomly assigned to arm A, and participated in OSS, while the other 18 health facilities assigned to arm B did not. Clinical faculty assessed trainee practice on clinical practice of six sets of tasks: patient history, physical examination, laboratory tests, diagnosis, treatment, and patient/caregiver education. The effects of IMID were measured by the post/pre adjusted relative risk (aRR) of appropriate practice in arm B. The incremental effects of OSS were measured by the adjusted ratio of relative risks (aRRR) in arm A compared to arm B. All hypotheses were tested at a 5% level of significance. Patient samples were comparable across arms at baseline and endline. The majority of children were aged under five years; 84% at baseline and 97% at endline. The effects of IMID on patient history (aRR = 1.12; 95% CI = 1.04-1.21) and physical examination (aRR = 1.40; 95% CI = 1.16-1.68) tasks were statistically significant. OSS was associated with incremental improvement in patient history (aRRR = 1.18; 95% CI = 1.06-1.31), and physical examination (aRRR = 1.27; 95% CI = 1.02-1.59) tasks. Improvements in laboratory testing, diagnosis, treatment, and patient/caregiver education were not statistically significant. IMID training was associated with improved patient history taking and physical examination, and OSS further improved these clinical practices. On-site training and continuous quality improvement activities support transfer of learning to practice among mid-level practitioners.

Correlates of quality of life among individuals with epilepsy enrolled in self-management research: From the US Centers for Disease Control and Prevention Managing Epilepsy Well Network.

PubMed

Sajatovic, Martha; Tatsuoka, Curtis; Welter, Elisabeth; Friedman, Daniel; Spruill, Tanya M; Stoll, Shelley; Sahoo, Satya S; Bukach, Ashley; Bamps, Yvan A; Valdez, Joshua; Jobst, Barbara C

2017-04-01

Epilepsy is a chronic neurological condition that causes substantial burden on patients and families. Quality of life may be reduced due to the stress of coping with epilepsy. For nearly a decade, the Centers for Disease Control (CDC) Prevention Research Center's Managing Epilepsy Well (MEW) Network has been conducting research on epilepsy self-management to address research and practice gaps. Studies have been conducted by independent centers across the U.S. Recently, the MEW Network sites, collaboratively, began compiling an integrated database to facilitate aggregate secondary analysis of completed and ongoing studies. In this preliminary analysis, correlates of quality of life in people with epilepsy (PWE) were analyzed from pooled baseline data from the MEW Network. For this analysis, data originated from 6 epilepsy studies conducted across 4 research sites and comprised 459 PWE. Descriptive comparisons assessed common data elements that included gender, age, ethnicity, race, education, employment, income, seizure frequency, quality of life, and depression. Standardized rating scales were used for quality of life (QOLIE-10) and for depression (Patient Health Questionnaire, PHQ-9). While not all datasets included all common data elements, baseline descriptive analysis found a mean age of 42 (SD 13.22), 289 women (63.0%), 59 African Americans (13.7%), and 58 Hispanics (18.5%). Most, 422 (92.8%), completed at least high school, while 169 (61.7%) were unmarried, divorced/separated, or widowed. Median 30-day seizure frequency was 0.71 (range 0-308). Depression at baseline was common, with a mean PHQ-9 score of 8.32 (SD 6.04); 69 (29.0%) had depression in the mild range (PHQ-9 score 5-9) and 92 (38.7%) had depression in the moderate to severe range (PHQ-9 score >9). Lower baseline quality of life was associated with greater depressive severity (p<.001), more frequent seizures (p<.04) and lower income (p<.05). The MEW Network Integrated Database offers a unique opportunity for secondary analysis of data from multiple community-based epilepsy research studies. While findings must be tempered by potential sample bias, i.e. a relative under-representation of men and relatively small sample of some racial/ethnic subgroups, results of analyses derived from this first integrated epilepsy self-management database have potential to be useful to the field. Associations between depression severity and lower QOL in PWE are consistent with previous studies derived from clinical samples. Self-management efforts that focus on mental health comorbidity and seizure control may be one way to address modifiable factors that affect quality of life in PWE. Copyright © 2017 Elsevier Inc. All rights reserved.

Integration Testing of Space Flight Systems

NASA Technical Reports Server (NTRS)

Sowards, Stephanie; Honeycutt, Timothy

2008-01-01

This paper discusses the benefits of conducting multi-system integration testing of space flight elements in lieu of merely shipping and shooting to the launch site and launching. "Ship and shoot" is a philosophy that proposes to transport flight elements directly from the factory to the launch site and begin the mission without further testing. Integration testing, relevant to validation testing in this context, is a risk mitigation effort that builds upon the individual element and system levels of qualification and acceptance tests, greatly improving the confidence of operations in space. The International Space Station Program (ISSP) experience is the focus of most discussions from a historical perspective, while proposed integration testing of the Constellation Program is also discussed. The latter will include Multi-Element Integration Testing (MElT) and Flight Element Integration Testing (FElT).

The strength of strategically placed in situ networks: The Critical Zone Observatory Program (Invited)

NASA Astrophysics Data System (ADS)

Bauer, S.; Benisch, K.; Li, D.; Beyer, C.; Mitiku, A. B.; Graupner, B.

2011-12-01

The Critical Zone Observatory (CZO) program, initiated by the U.S. National Science Foundation in 2007 with 3 sites, was expanded to 6 sites in 2009 and is expected to grow to at least 8 sites in FY 2014. The CZO program is now maturing into a coordinated network that enables scientific research around terrestrial fluxes of water, carbon and nutrients and informs societal questions around resource management and adaptation to climate change. Individual CZOs have contributed to understanding of the influences of disturbances and of changes in climate on fluxes and stores in critical ecosystems, and to a better predictive ability. CZOs have enabled the disciplinary integration needed to consider controlling processes together, from bedrock to boundary layer, and over sub-daily to millennial or longer times. Together, the CZO network has shown the role of climate versus disturbance on rain, snowfall and snowmelt reaching the ground surface, and the influences of climate, disturbance and regolith properties on partitioning of infiltrated water into evapotranspiration versus streamflow. The influence of disturbance is manifest both through abiotic factors, e.g. boundary-layer meteorology and turbulence, and through biotic influences, e.g. changes in vegetation density due to fire or disease, and thus interception and evapotranspiration. Climatic influences are overlain on this, including i) changes in rain versus snowfall and thus snowpack and soil-water storage, and ii) growing season and thus evapotranspiration. Carbon and nutrient fluxes are closely linked to those of water. Thus rich data sets and improved models from the CZO sites together provide a better understanding of the bi-directional feedbacks between vegetation structure, regolith properties and climate. Going forward, the CZO network as a whole offers well-instrumented sites with many common measurements and multi-disciplinary data across gradient of climate, parent material, vegetation structure and regolith properties. Measurements are at scales that are sufficiently large for research involving water, carbon or nutrient balances. Results are relevant to help guide decisions around vegetation management, and to understand the water, carbon and nutrient implications of vegetation-management options. The CZO network is a community platform for research, with the common, long-term observations across the multiple sites a resource available to all for multi-disciplinary critical-zone science.

The strength of strategically placed in situ networks: The Critical Zone Observatory Program (Invited)

NASA Astrophysics Data System (ADS)

Bales, R. C.; Brooks, P. D.; Molotch, N. P.

2013-12-01

The Critical Zone Observatory (CZO) program, initiated by the U.S. National Science Foundation in 2007 with 3 sites, was expanded to 6 sites in 2009 and is expected to grow to at least 8 sites in FY 2014. The CZO program is now maturing into a coordinated network that enables scientific research around terrestrial fluxes of water, carbon and nutrients and informs societal questions around resource management and adaptation to climate change. Individual CZOs have contributed to understanding of the influences of disturbances and of changes in climate on fluxes and stores in critical ecosystems, and to a better predictive ability. CZOs have enabled the disciplinary integration needed to consider controlling processes together, from bedrock to boundary layer, and over sub-daily to millennial or longer times. Together, the CZO network has shown the role of climate versus disturbance on rain, snowfall and snowmelt reaching the ground surface, and the influences of climate, disturbance and regolith properties on partitioning of infiltrated water into evapotranspiration versus streamflow. The influence of disturbance is manifest both through abiotic factors, e.g. boundary-layer meteorology and turbulence, and through biotic influences, e.g. changes in vegetation density due to fire or disease, and thus interception and evapotranspiration. Climatic influences are overlain on this, including i) changes in rain versus snowfall and thus snowpack and soil-water storage, and ii) growing season and thus evapotranspiration. Carbon and nutrient fluxes are closely linked to those of water. Thus rich data sets and improved models from the CZO sites together provide a better understanding of the bi-directional feedbacks between vegetation structure, regolith properties and climate. Going forward, the CZO network as a whole offers well-instrumented sites with many common measurements and multi-disciplinary data across gradient of climate, parent material, vegetation structure and regolith properties. Measurements are at scales that are sufficiently large for research involving water, carbon or nutrient balances. Results are relevant to help guide decisions around vegetation management, and to understand the water, carbon and nutrient implications of vegetation-management options. The CZO network is a community platform for research, with the common, long-term observations across the multiple sites a resource available to all for multi-disciplinary critical-zone science.

Towards an integrative soil health assessment strategy: a three tier (integrative biomarker response) approach with Eisenia fetida applied to soils subjected to chronic metal pollution.

PubMed

Asensio, Vega; Rodríguez-Ruiz, Amaia; Garmendia, Larraitz; Andre, Jane; Kille, Peter; Morgan, Andrew John; Soto, Manu; Marigómez, Ionan

2013-01-01

This is a pilot study for assessing soil ecosystem health in chronically polluted sites on the basis of a 3-tier approach (screening+scoring+understanding) designed to be cost-effective and scientifically based, and to provide straightforward advice and support to managers and stakeholders involved in environmental protection. For the initial screening (Tier 1), the use of a highly sensitive, low-cost biomarker such as neutral red uptake (NRU) in earthworm coelomocytes is proposed. In sites where an alteration in NRU has been established, the stress level may be further assessed by utilising a suite of low-cost and rapid biomarkers of effect integrated in an integrative biological response (IBR) index to obtain an objective (scored) assessment of the induced stress syndrome (Tier 2). The IBR/n index is based on the integration of biomarkers at different levels of biological organisation. Acyl-CoA oxidase activity (AOX), catalase activity (CAT), lipofuscin optical density (LOD%), NRU and the mean epithelial thickness (MET) have been used to calculate the IBR/n index. Biomarkers are determined in earthworms, Eisenia fetida, exposed ex situ to real soils (three mining sites and a reference) for 3, 10 and 17d. The 3d NRU (Tier 1) provided signal of stress. After 3d, PCA, based on the suite of biomarkers (Tier 2), discriminated reference and polluted sites according to toxicity profiles and at 17d, the most polluted site is segregated from less polluted and reference sites. Soils were classified as harmful, unhealthy (not apparently toxic) or healthy. Soils were investigated by microarray transcriptomics (Tier 3), to understand the causes (aetiology) and consequences (prognosis) of health impairment. Tier 3 discriminates, according to stress syndrome traits, soils that did not fall into the category of highly stressed and revealed the main agent causing toxicity at each site by identifying the toxicity mechanisms and biological responses. Copyright © 2012 Elsevier B.V. All rights reserved.

Conceptions of Connectivity: How Swiss Teachers, Trainers and Apprentices Perceive Vocational Learning and Teaching across Different Learning Sites

ERIC Educational Resources Information Center

Sappa, Viviana; Aprea, Carmela

2014-01-01

The integration of learning across different learning sites is an important and challenging task for each vocational education and training system. Although various integrative teaching and learning models have been developed and many reforms have been undertaken, their implementation is complicated by several factors. In particular, individual…

Volcanology Curricula Development Aided by Online Educational Resource

NASA Astrophysics Data System (ADS)

Poland, Michael P.; van der Hoeven Kraft, Katrien J.; Teasdale, Rachel

2011-03-01

Using On-Line Volcano Monitoring Data in College and University Courses: The Volcano Exploration Project: Pu`u `Ō`ō (VEPP); Hawaii Volcanoes National Park, Hawaii, 26-30 July 2010; Volcanic activity is an excellent hook for engaging college and university students in geoscience classes. An increasing number of Internet-accessible real-time and near-real time volcano monitoring data are now available and constitute an important resource for geoscience education; however, relatively few data sets are comprehensive, and many lack background information to aid in interpretation. In response to the need for organized, accessible, and well-documented volcano education resources, the U.S. Geological Survey's Hawaiian Volcano Observatory (HVO), in collaboration with NASA and the University of Hawai`i at Manoa, established the Volcanoes Exploration Project: Pu`u `Ō`ō (VEPP). The VEPP Web site (http://vepp.wr.usgs.gov) is an educational resource that provides access, in near real time, to geodetic, seismic, and geologic data from the active Pu`u `Ō`ō eruptive vent on Kilauea volcano, Hawaii, along with background and context information. A strength of the VEPP site is the common theme of the Pu`u `Ō`ō eruption, which allows the site to be revisited multiple times to demonstrate different principles and integrate many aspects of volcanology.

oPOSSUM: identification of over-represented transcription factor binding sites in co-expressed genes

PubMed Central

Ho Sui, Shannan J.; Mortimer, James R.; Arenillas, David J.; Brumm, Jochen; Walsh, Christopher J.; Kennedy, Brian P.; Wasserman, Wyeth W.

2005-01-01

Targeted transcript profiling studies can identify sets of co-expressed genes; however, identification of the underlying functional mechanism(s) is a significant challenge. Established methods for the analysis of gene annotations, particularly those based on the Gene Ontology, can identify functional linkages between genes. Similar methods for the identification of over-represented transcription factor binding sites (TFBSs) have been successful in yeast, but extension to human genomics has largely proved ineffective. Creation of a system for the efficient identification of common regulatory mechanisms in a subset of co-expressed human genes promises to break a roadblock in functional genomics research. We have developed an integrated system that searches for evidence of co-regulation by one or more transcription factors (TFs). oPOSSUM combines a pre-computed database of conserved TFBSs in human and mouse promoters with statistical methods for identification of sites over-represented in a set of co-expressed genes. The algorithm successfully identified mediating TFs in control sets of tissue-specific genes and in sets of co-expressed genes from three transcript profiling studies. Simulation studies indicate that oPOSSUM produces few false positives using empirically defined thresholds and can tolerate up to 50% noise in a set of co-expressed genes. PMID:15933209

Spatial Distribution of an Uranium-Respiring Betaproteobacterium at the Rifle, CO Field Research Site

PubMed Central

Koribanics, Nicole M.; Tuorto, Steven J.; Lopez-Chiaffarelli, Nora; McGuinness, Lora R.; Häggblom, Max M.; Williams, Kenneth H.; Long, Philip E.; Kerkhof, Lee J.

2015-01-01

The Department of Energy’s Integrated Field-Scale Subsurface Research Challenge Site (IFRC) at Rifle, Colorado was created to address the gaps in knowledge on the mechanisms and rates of U(VI) bioreduction in alluvial sediments. Previous studies at the Rifle IFRC have linked microbial processes to uranium immobilization during acetate amendment. Several key bacteria believed to be involved in radionuclide containment have been described; however, most of the evidence implicating uranium reduction with specific microbiota has been indirect. Here, we report on the cultivation of a microorganism from the Rifle IFRC that reduces uranium and appears to utilize it as a terminal electron acceptor for respiration with acetate as electron donor. Furthermore, this bacterium constitutes a significant proportion of the subsurface sediment community prior to biostimulation based on TRFLP profiling of 16S rRNA genes. 16S rRNA gene sequence analysis indicates that the microorganism is a betaproteobacterium with a high similarity to Burkholderia fungorum. This is, to our knowledge, the first report of a betaproteobacterium capable of uranium respiration. Our results indicate that this microorganism occurs commonly in alluvial sediments located between 3-6 m below ground surface at Rifle and may play a role in the initial reduction of uranium at the site. PMID:25874721

Volcanology curricula development aided by online educational resource

USGS Publications Warehouse

Poland, Michael P.; Van Der Hoeven, Kraft; Teasdale, R.

2011-01-01

Using On-Line Volcano Monitoring Data in College and University Courses: The Volcano Exploration Project: Pu`u `Ō`ō (VEPP); Hawaii Volcanoes National Park, Hawaii, 26–30 July 2010; Volcanic activity is an excellent hook for engaging college and university students in geoscience classes. An increasing number of Internet-accessible real-time and near–real time volcano monitoring data are now available and constitute an important resource for geoscience education; however, relatively few data sets are comprehensive, and many lack background information to aid in interpretation. In response to the need for organized, accessible, and well-documented volcano education resources, the U.S. Geological Survey's Hawaiian Volcano Observatory (HVO), in collaboration with NASA and the University of Hawai`i at Manoa, established the Volcanoes Exploration Project: Pu`u `Ō`ō (VEPP). The VEPP Web site (http://vepp.wr.usgs.gov) is an educational resource that provides access, in near real time, to geodetic, seismic, and geologic data from the active Pu`u `Ō`ō eruptive vent on Kilauea volcano, Hawaii, along with background and context information. A strength of the VEPP site is the common theme of the Pu`u `Ō`ō eruption, which allows the site to be revisited multiple times to demonstrate different principles and integrate many aspects of volcanology.

Plant movements and climate warming: intraspecific variation in growth responses to nonlocal soils.

PubMed

De Frenne, Pieter; Coomes, David A; De Schrijver, An; Staelens, Jeroen; Alexander, Jake M; Bernhardt-Römermann, Markus; Brunet, Jörg; Chabrerie, Olivier; Chiarucci, Alessandro; den Ouden, Jan; Eckstein, R Lutz; Graae, Bente J; Gruwez, Robert; Hédl, Radim; Hermy, Martin; Kolb, Annette; Mårell, Anders; Mullender, Samantha M; Olsen, Siri L; Orczewska, Anna; Peterken, George; Petřík, Petr; Plue, Jan; Simonson, William D; Tomescu, Cezar V; Vangansbeke, Pieter; Verstraeten, Gorik; Vesterdal, Lars; Wulf, Monika; Verheyen, Kris

2014-04-01

Most range shift predictions focus on the dispersal phase of the colonization process. Because moving populations experience increasingly dissimilar nonclimatic environmental conditions as they track climate warming, it is also critical to test how individuals originating from contrasting thermal environments can establish in nonlocal sites. We assess the intraspecific variation in growth responses to nonlocal soils by planting a widespread grass of deciduous forests (Milium effusum) into an experimental common garden using combinations of seeds and soil sampled in 22 sites across its distributional range, and reflecting movement scenarios of up to 1600 km. Furthermore, to determine temperature and forest-structural effects, the plants and soils were experimentally warmed and shaded. We found significantly positive effects of the difference between the temperature of the sites of seed and soil collection on growth and seedling emergence rates. Migrant plants might thus encounter increasingly favourable soil conditions while tracking the isotherms towards currently 'colder' soils. These effects persisted under experimental warming. Rising temperatures and light availability generally enhanced plant performance. Our results suggest that abiotic and biotic soil characteristics can shape climate change-driven plant movements by affecting growth of nonlocal migrants, a mechanism which should be integrated into predictions of future range shifts. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

Strategies for more effective monitoring and evaluation systems in HIV programmatic scale-up in resource-limited settings: Implications for health systems strengthening.

PubMed

Nash, Denis; Elul, Batya; Rabkin, Miriam; Tun, May; Saito, Suzue; Becker, Mark; Nuwagaba-Biribonwoha, Harriet

2009-11-01

Program monitoring and evaluation (M&E) has the potential to be a cornerstone of health systems strengthening and of evidence-informed implementation and scale-up of HIV-related services in resource-limited settings. We discuss common challenges to M&E systems used in the rapid scale-up of HIV services as well as innovations that may have relevance to systems used to monitor, evaluate, and inform health systems strengthening. These include (1) Web-based applications with decentralized data entry and real-time access to summary reporting; (2) timely feedback of information to site and district staff; (3) site-level integration of traditionally siloed program area indicators; (4) longitudinal tracking of program and site characteristics; (5) geographic information systems; and (6) use of routinely collected aggregate data for epidemiologic analysis and operations research. Although conventionally used in the context of vertical programs, these approaches can form a foundation on which data relevant to other health services and systems can be layered, including prevention services, primary care, maternal-child health, and chronic disease management. Guiding principles for sustainable national M&E systems include country-led development and ownership, support for national programs and policies, interoperability, and employment of an open-source approach to software development.

Spatial distribution of an uranium-respiring betaproteobacterium at the Rifle, CO field research site

DOE PAGES

Koribanics, Nicole M.; Tuorto, Steven J.; Lopez-Chiaffarelli, Nora; ...

2015-04-13

The Department of Energy’s Integrated Field-Scale Subsurface Research Challenge Site (IFRC) at Rifle, Colorado was created to address the gaps in knowledge on the mechanisms and rates of U(VI) bioreduction in alluvial sediments. Previous studies at the Rifle IFRC have linked microbial processes to uranium immobilization during acetate amendment. Several key bacteria believed to be involved in radionuclide containment have been described; however, most of the evidence implicating uranium reduction with specific microbiota has been indirect. Here, we report on the cultivation of a microorganism from the Rifle IFRC that reduces uranium and appears to utilize it as a terminalmore » electron acceptor for respiration with acetate as electron donor. Furthermore, this bacterium constitutes a significant proportion of the subsurface sediment community prior to biostimulation based on TRFLP profiling of 16S rRNA genes. 16S rRNA gene sequence analysis indicates that the microorganism is a betaproteobacterium with a high similarity to Burkholderia fungorum. This is, to our knowledge, the first report of a betaproteobacterium capable of uranium respiration. Our results indicate that this microorganism occurs commonly in alluvial sediments located between 3-6 m below ground surface at Rifle and may play a role in the initial reduction of uranium at the site.« less

Integrating Indigenous Traditional, Local and Scientific Knowledge for Improved Management, Policy and Decision-Making in Reindeer Husbandry in the Russian Arctic

NASA Technical Reports Server (NTRS)

Maynard, Nancy G.; Yurchak, Boris; Turi, Johan Mathis; Mathiesen, Svein D.; Aissi-Wespi, Rita L.

2004-01-01

As scientists and policy-makers from both indigenous and non-indigenous communities begin to build closer partnerships to address common sustainability issues such as the health impacts of climate change and anthropogenic activities, it becomes increasingly important to create shared information management systems which integrate all relevant factors for optimal information sharing and decision-making. This paper describes a new GIs-based system being designed to bring local and indigenous traditional knowledge together with scientific data and information, remote sensing, and information technologies to address health-related environment, weather, climate, pollution and land use change issues for improved decision/policy-making for reindeer husbandry. The system is building an easily-accessible archive of relevant current and historical, traditional, local and remotely-sensed and other data and observations for shared analysis, measuring, and monitoring parameters of interest. Protection of indigenous culturally sensitive information will be respected through appropriate data protocols. A mechanism which enables easy information sharing among all participants, which is real time and geo-referenced and which allows interconnectivity with remote sites is also being designed into the system for maximum communication among partners. A preliminary version of our system will be described for a Russian reindeer test site, which will include a combination of indigenous knowledge about local conditions and issues, remote sensing and ground-based data on such parameters as the vegetation state and distribution, snow cover, temperature, ice condition, and infrastructure.

Common Utilities in the Energy Systems Integration Facility | Energy

Science.gov Websites

Systems Integration Facility. Common utilities include: Power: Three-phase 480/277 VAC, 208/120 VAC, 240 split-phase VAC, and 120 single-phase VAC Water: Process heating and cooling and research cooling

Common Elements for Success: What Makes the Deal Work at Contaminated Sites

EPA Pesticide Factsheets

This page contains the presentations from the Brown to Green: Make the Connection to Renewable Energy workshop held in Santa Fe, New Mexico, during December 10-11, 2008 regarding Common Elements for Success - What makes the Deal Work at Contaminated Sites.

SITE TECHNOLOGY PROFILES, TENTH EDITION, VOLUME I - DEMONSTRATION PROGRAM

EPA Science Inventory

The Superfund Innovative Technology Evaluation (SITE) Program, now in its thirteenth year, is an integral part of EPA's research into alternative cleanup methods for hazardous waste sites around the nation. The SITE Program was created to encourage the development and routine us...

SITE TECHNOLOGY PROFILES - 11TH EDITION, COMPACT DISC

EPA Science Inventory

The Superfund Innovative Technology Evaluation (SITE) Program, now in its eleventh year is an integral part of EPA's research into alternative cleanup methods for hazardous waste sites around the nation. The SITE Program was created to encourage the development and routine use o...

Assessing the potential for AAV vector genotoxicity in a murine model

PubMed Central

Li, Hojun; Malani, Nirav; Hamilton, Shari R.; Schlachterman, Alexander; Bussadori, Giulio; Edmonson, Shyrie E.; Shah, Rachel; Arruda, Valder R.; Mingozzi, Federico; Fraser Wright, J.; Bushman, Frederic D.

2011-01-01

Gene transfer using adeno-associated virus (AAV) vectors has great potential for treating human disease. Recently, questions have arisen about the safety of AAV vectors, specifically, whether integration of vector DNA in transduced cell genomes promotes tumor formation. This study addresses these questions with high-dose liver-directed AAV-mediated gene transfer in the adult mouse as a model (80 AAV-injected mice and 52 controls). After 18 months of follow-up, AAV-injected mice did not show a significantly higher rate of hepatocellular carcinoma compared with controls. Tumors in mice treated with AAV vectors did not have significantly different amounts of vector DNA compared with adjacent normal tissue. A novel high-throughput method for identifying AAV vector integration sites was developed and used to clone 1029 integrants. Integration patterns in tumor tissue and adjacent normal tissue were similar to each other, showing preferences for active genes, cytosine-phosphate-guanosine islands, and guanosine/cysteine-rich regions. Gene expression data showed that genes near integration sites did not show significant changes in expression patterns compared with genes more distal to integration sites. No integration events were identified as causing increased oncogene expression. Thus, we did not find evidence that AAV vectors cause insertional activation of oncogenes and subsequent tumor formation. PMID:21106988

Health information exchange technology on the front lines of healthcare: workflow factors and patterns of use

PubMed Central

Johnson, Kevin B; Lorenzi, Nancy M

2011-01-01

Objective The goal of this study was to develop an in-depth understanding of how a health information exchange (HIE) fits into clinical workflow at multiple clinical sites. Materials and Methods The ethnographic qualitative study was conducted over a 9-month period in six emergency departments (ED) and eight ambulatory clinics in Memphis, Tennessee, USA. Data were collected using direct observation, informal interviews during observation, and formal semi-structured interviews. The authors observed for over 180 h, during which providers used the exchange 130 times. Results HIE-related workflow was modeled for each ED site and ambulatory clinic group and substantial site-to-site workflow differences were identified. Common patterns in HIE-related workflow were also identified across all sites, leading to the development of two role-based workflow models: nurse based and physician based. The workflow elements framework was applied to the two role-based patterns. An in-depth description was developed of how providers integrated HIE into existing clinical workflow, including prompts for HIE use. Discussion Workflow differed substantially among sites, but two general role-based HIE usage models were identified. Although providers used HIE to improve continuity of patient care, patient–provider trust played a significant role. Types of information retrieved related to roles, with nurses seeking to retrieve recent hospitalization data and more open-ended usage by nurse practitioners and physicians. User and role-specific customization to accommodate differences in workflow and information needs may increase the adoption and use of HIE. Conclusion Understanding end users' perspectives towards HIE technology is crucial to the long-term success of HIE. By applying qualitative methods, an in-depth understanding of HIE usage was developed. PMID:22003156

Public storage for the Open Science Grid

NASA Astrophysics Data System (ADS)

Levshina, T.; Guru, A.

2014-06-01

The Open Science Grid infrastructure doesn't provide efficient means to manage public storage offered by participating sites. A Virtual Organization that relies on opportunistic storage has difficulties finding appropriate storage, verifying its availability, and monitoring its utilization. The involvement of the production manager, site administrators and VO support personnel is required to allocate or rescind storage space. One of the main requirements for Public Storage implementation is that it should use SRM or GridFTP protocols to access the Storage Elements provided by the OSG Sites and not put any additional burden on sites. By policy, no new services related to Public Storage can be installed and run on OSG sites. Opportunistic users also have difficulties in accessing the OSG Storage Elements during the execution of jobs. A typical users' data management workflow includes pre-staging common data on sites before a job's execution, then storing for a subsequent download to a local institution the output data produced by a job on a worker node. When the amount of data is significant, the only means to temporarily store the data is to upload it to one of the Storage Elements. In order to do that, a user's job should be aware of the storage location, availability, and free space. After a successful data upload, users must somehow keep track of the data's location for future access. In this presentation we propose solutions for storage management and data handling issues in the OSG. We are investigating the feasibility of using the integrated Rule-Oriented Data System developed at RENCI as a front-end service to the OSG SEs. The current architecture, state of deployment and performance test results will be discussed. We will also provide examples of current usage of the system by beta-users.

Analysis of illegitimate genomic integration mediated by zinc-finger nucleases: implications for specificity of targeted gene correction

PubMed Central

2010-01-01

Background Formation of site specific genomic double strand breaks (DSBs), induced by the expression of a pair of engineered zinc-finger nucleases (ZFNs), dramatically increases the rates of homologous recombination (HR) between a specific genomic target and a donor plasmid. However, for the safe use of ZFN induced HR in practical applications, possible adverse effects of the technology such as cytotoxicity and genotoxicity need to be well understood. In this work, off-target activity of a pair of ZFNs has been examined by measuring the ratio between HR and illegitimate genomic integration in cells that are growing exponentially, and in cells that have been arrested in the G2/M phase. Results A reporter cell line that contained consensus ZFN binding sites in an enhanced green fluorescent protein (EGFP) reporter gene was used to measure ratios between HR and non-homologous integration of a plasmid template. Both in human cells (HEK 293) containing the consensus ZFN binding sites and in cells lacking the ZFN binding sites, a 3.5 fold increase in the level of illegitimate integration was observed upon ZFN expression. Since the reporter gene containing the consensus ZFN target sites was found to be intact in cells where illegitimate integration had occurred, increased rates of illegitimate integration most likely resulted from the formation of off-target genomic DSBs. Additionally, in a fraction of the ZFN treated cells the co-occurrence of both specific HR and illegitimate integration was observed. As a mean to minimize unspecific effects, cell cycle manipulation of the target cells by induction of a transient G2/M cell cycle arrest was shown to stimulate the activity of HR while having little effect on the levels of illegitimate integration, thus resulting in a nearly eight fold increase in the ratio between the two processes. Conclusions The demonstration that ZFN expression, in addition to stimulating specific gene targeting by HR, leads to increased rates of illegitimate integration emphasizes the importance of careful characterization of ZFN treated cells. In order to reduce off-target events, reversible cell cycle arrest of the target cells in the G2/M phase is an efficient way for increasing the ratio between specific HR and illegitimate integration. PMID:20459736

Improved production of genetically modified fetuses with homogeneous transgene expression after transgene integration site analysis and recloning in cattle.

PubMed

Bressan, Fabiana Fernandes; Dos Santos Miranda, Moyses; Perecin, Felipe; De Bem, Tiago Henrique; Pereira, Flavia Thomaz Verechia; Russo-Carbolante, Elisa Maria; Alves, Daiani; Strauss, Bryan; Bajgelman, Marcio; Krieger, José Eduardo; Binelli, Mario; Meirelles, Flavio Vieira

2011-02-01

Animal cloning by nuclear transfer (NT) has made the production of transgenic animals using genetically modified donor cells possible and ensures the presence of the gene construct in the offspring. The identification of transgene insertion sites in donor cells before cloning may avoid the production of animals that carry undesirable characteristics due to positional effects. This article compares blastocyst development and competence to establish pregnancies of bovine cloned embryos reconstructed with lentivirus-mediated transgenic fibroblasts containing either random integration of a transgene (random integration group) or nuclear transfer derived transgenic fibroblasts with known transgene insertion sites submitted to recloning (recloned group). In the random integration group, eGFP-expressing bovine fetal fibroblasts were selected by fluorescence activated cell sorting (FACS) and used as nuclei donor cells for NT. In the recloned group, a fibroblast cell line derived from a transgenic cloned fetus was characterized regarding transgene insertion and submitted to recloning. The recloned group had higher blastocyst production (25.38 vs. 14.42%) and higher percentage of 30-day pregnancies (14.29 vs. 2.56%) when compared to the random integration group. Relative eGFP expression analysis in fibroblasts derived from each cloned embryo revealed more homogeneous expression in the recloned group. In conclusion, the use of cell lines recovered from transgenic fetuses after identification of the transgene integration site allowed for the production of cells and fetuses with stable transgene expression, and recloning may improve transgenic animal yields.

Ignoring heterozygous sites biases phylogenomic estimates of divergence times: implications for the evolutionary history of microtus voles.

PubMed

Lischer, Heidi E L; Excoffier, Laurent; Heckel, Gerald

2014-04-01

Phylogenetic reconstruction of the evolutionary history of closely related organisms may be difficult because of the presence of unsorted lineages and of a relatively high proportion of heterozygous sites that are usually not handled well by phylogenetic programs. Genomic data may provide enough fixed polymorphisms to resolve phylogenetic trees, but the diploid nature of sequence data remains analytically challenging. Here, we performed a phylogenomic reconstruction of the evolutionary history of the common vole (Microtus arvalis) with a focus on the influence of heterozygosity on the estimation of intraspecific divergence times. We used genome-wide sequence information from 15 voles distributed across the European range. We provide a novel approach to integrate heterozygous information in existing phylogenetic programs by repeated random haplotype sampling from sequences with multiple unphased heterozygous sites. We evaluated the impact of the use of full, partial, or no heterozygous information for tree reconstructions on divergence time estimates. All results consistently showed four deep and strongly supported evolutionary lineages in the vole data. These lineages undergoing divergence processes split only at the end or after the last glacial maximum based on calibration with radiocarbon-dated paleontological material. However, the incorporation of information from heterozygous sites had a significant impact on absolute and relative branch length estimations. Ignoring heterozygous information led to an overestimation of divergence times between the evolutionary lineages of M. arvalis. We conclude that the exclusion of heterozygous sites from evolutionary analyses may cause biased and misleading divergence time estimates in closely related taxa.

Comparison of Bone Grafts From Various Donor Sites in Human Bone Specimens.

PubMed

Kamal, Mohammad; Gremse, Felix; Rosenhain, Stefanie; Bartella, Alexander K; Hölzle, Frank; Kessler, Peter; Lethaus, Bernd

2018-05-14

The objective of the current study was to compare the three-dimensional (3D) morphometric microstructure in human cadaveric bone specimens taken from various commonly utilized donor sites for autogenous bone grafting. Autogenous bone grafts can be harvested from various anatomic sites and express heterogeneous bone quality with a specific 3D microstructure for each site. The long-term structural integrity and susceptibility to resorption of the graft depend on the selected donor bone. Micro-computed tomography generates high-resolution datasets of bone structures and calcifications making this modality versatile for microarchitecture analysis and quantification of the bone. Six bone specimens, 10 mm in length, where anatomically possible, were obtained from various anatomical sites from 10 human dentate cadavers (4 men, 6 women, mean age 69.5 years). Specimens were scanned using a micro-computed tomography device and volumetrically reconstructed. A virtual cylindrical inclusion was reconstructed to analyze the bone mineral density and structural morphometric analysis using bone indices: relative bone volume, surface density, trabecular thicknesses, and trabecular separation. Calvarial bone specimens showed the highest mineral density, followed by the chin, then mandibular ramus then the tibia, whereas iliac crest and maxillary tuberosity had lower bone mineral densities. The pairwise comparison revealed statistically significant differences in the bone mineral density and relative bone volume index in the calvaria, mandibular ramus, mandibular symphysis groups when compared with those in the iliac crest and maxillary tuberosity, suggesting higher bone quality in the former groups than in the latter; tibial specimens expressed variable results.

Interoperable Data Access Services for NOAA IOOS

NASA Astrophysics Data System (ADS)

de La Beaujardiere, J.

2008-12-01

The Integrated Ocean Observing System (IOOS) is intended to enhance our ability to collect, deliver, and use ocean information. The goal is to support research and decision-making by providing data on our open oceans, coastal waters, and Great Lakes in the formats, rates, and scales required by scientists, managers, businesses, governments, and the public. The US National Oceanic and Atmospheric Administration (NOAA) is the lead agency for IOOS. NOAA's IOOS office supports the development of regional coastal observing capability and promotes data management efforts to increase data accessibility. Geospatial web services have been established at NOAA data providers including the National Data Buoy Center (NDBC), the Center for Operational Oceanographic Products and Services (CO-OPS), and CoastWatch, and at regional data provider sites. Services established include Open-source Project for a Network Data Access Protocol (OpenDAP), Open Geospatial Consortium (OGC) Sensor Observation Service (SOS), and OGC Web Coverage Service (WCS). These services provide integrated access to data holdings that have been aggregated at each center from multiple sources. We wish to collaborate with other groups to improve our service offerings to maximize interoperability and enhance cross-provider data integration, and to share common service components such as registries, catalogs, data conversion, and gateways. This paper will discuss the current status of NOAA's IOOS efforts and possible next steps.

Hepatitis B virus and hepatocellular carcinoma

PubMed Central

Arbuthnot, Patrick; Kew, Michael

2001-01-01

Chronic hepatitis B virus (HBV) infection is a major global cause of hepatocellular carcinoma (HCC). Individuals who are chronic carriers have a greater than 100-fold increased relative risk of developing the tumour. Several mechanisms of HBV-induced HCC have been proposed. Integration of HBV DNA into the genome of hepatocytes occurs commonly, although integration at cellular sites that are important for regulation of hepatocyte proliferation appears to be a rare event. Functions of the HBx protein are also potentially oncogenic. These include transcriptional activation of cellular growth regulatory genes, modulation of apoptosis and inhibition of nucleotide excision repair of damaged cellular DNA. The effects of HBx are mediated by interaction with cellular proteins and activation of cell signalling pathways. Variations in HBV genome sequences may be important in hepatocarcinogenesis, although their significance has not yet been completely elucidated. Necroinflammatory hepatic disease, which often accompanies chronic HBV infection, may contribute indirectly to hepatocyte transformation in a number of ways, including by facilitating HBV DNA integration, predisposing to the acquisition of cellular mutations and generating mutagenic oxygen reactive species. Although HCC is a malignancy with a poor prognosis, the availability of an effective vaccine against HBV infection, and its inclusion in the Expanded Programme of Immunization of many countries, augurs well for the eventual elimination of HBV-associated HCC. PMID:11454100

GPS-Lipid: a robust tool for the prediction of multiple lipid modification sites.

PubMed

Xie, Yubin; Zheng, Yueyuan; Li, Hongyu; Luo, Xiaotong; He, Zhihao; Cao, Shuo; Shi, Yi; Zhao, Qi; Xue, Yu; Zuo, Zhixiang; Ren, Jian

2016-06-16

As one of the most common post-translational modifications in eukaryotic cells, lipid modification is an important mechanism for the regulation of variety aspects of protein function. Over the last decades, three classes of lipid modifications have been increasingly studied. The co-regulation of these different lipid modifications is beginning to be noticed. However, due to the lack of integrated bioinformatics resources, the studies of co-regulatory mechanisms are still very limited. In this work, we developed a tool called GPS-Lipid for the prediction of four classes of lipid modifications by integrating the Particle Swarm Optimization with an aging leader and challengers (ALC-PSO) algorithm. GPS-Lipid was proven to be evidently superior to other similar tools. To facilitate the research of lipid modification, we hosted a publicly available web server at http://lipid.biocuckoo.org with not only the implementation of GPS-Lipid, but also an integrative database and visualization tool. We performed a systematic analysis of the co-regulatory mechanism between different lipid modifications with GPS-Lipid. The results demonstrated that the proximal dual-lipid modifications among palmitoylation, myristoylation and prenylation are key mechanism for regulating various protein functions. In conclusion, GPS-lipid is expected to serve as useful resource for the research on lipid modifications, especially on their co-regulation.

The FIFE Project at Fermilab

DOE Office of Scientific and Technical Information (OSTI.GOV)

Box, D.; Boyd, J.; Di Benedetto, V.

2016-01-01

The FabrIc for Frontier Experiments (FIFE) project is an initiative within the Fermilab Scientific Computing Division designed to steer the computing model for non-LHC Fermilab experiments across multiple physics areas. FIFE is a collaborative effort between experimenters and computing professionals to design and develop integrated computing models for experiments of varying size, needs, and infrastructure. The major focus of the FIFE project is the development, deployment, and integration of solutions for high throughput computing, data management, database access and collaboration management within an experiment. To accomplish this goal, FIFE has developed workflows that utilize Open Science Grid compute sites alongmore » with dedicated and commercial cloud resources. The FIFE project has made significant progress integrating into experiment computing operations several services including a common job submission service, software and reference data distribution through CVMFS repositories, flexible and robust data transfer clients, and access to opportunistic resources on the Open Science Grid. The progress with current experiments and plans for expansion with additional projects will be discussed. FIFE has taken the leading role in defining the computing model for Fermilab experiments, aided in the design of experiments beyond those hosted at Fermilab, and will continue to define the future direction of high throughput computing for future physics experiments worldwide.« less

High resolution digital elevation modelling from TLS and UAV campaign reveals structural complexity at the 2014/15 Holuhraun eruption site, Iceland

NASA Astrophysics Data System (ADS)

Müller, Daniel; Walter, Thomas R.; Schöpa, Anne; Witt, Tanja; Steinke, Bastian; Gudmundsson, Magnús T.; Dürig, Tobias

2017-07-01

Fissure eruptions are commonly linked to magma dikes at depth, associated with elastic and anelastic surface deformation. Elastic deformation is well described by subsidence above, uplift and lateral widening perpendicular to the dike plane. The anelastic part is associated with the formation of a graben, bordered by graben parallel faults that might express as sets of fractures at the surface. Additionally secondary structures, like push ups, bends and step overs yield information about the deforming domain. The formation of such structures associated with fissure eruptions, however, is barely preserved in nature because of the rapid erosion or sediment coverage. Therefore, simple normal fault displacements are commonly assumed at dikes. At the 2014/2015 Holuhraun eruption sites (Iceland), evidence is increasing that the developing fractures are showing variations in their displacement modes. In an attempt to investigate these variations, a fieldwork mapping project combining Terrestrial Laser Scanning (TLS) and Unmanned Aerial Vehicle (UAV) based aerophoto analysis was realized. From this data, we generated locally high resolution Digital Elevation Models (DEMs) and a structural map that allows for identification of kinematic indicators and assessing particularities of the observed structures. We identified 315 fracture segments from satellite data. For single segments we measured strike directions including the amount of opening and opening angles, indicating that many of the measured fractures show transtensional dislocations. Out of these, 81 % are showing significant left-lateral slip, only 17% right-lateral slip and 2% pure tensile opening. We show that local complexities in the fracture traces and geometries are closely related to variations in the transtensional opening direction. Moreover, we identified local changes in fracture azimuths and offsets close to eruption sites, which we speculate to be associated with geometrical changes in the magma feeder itself. Results highlight that opening of fractures associated with an erupting fissure commonly show transtensional modes having both, left-lateral and right-lateral slip, with important implications for interpreting the expression of surface structures at rift zones elsewhere. Results further highlight the great value of UAV based high resolution data to contribute to the integrity of observations of structural complexities at local geologic events.

Nip, Tuck and Click: Medical Tourism and the Emergence of Web-Based Health Information

PubMed Central

Lunt, Neil; Hardey, Mariann; Mannion, Russell

2010-01-01

An emerging trend is what has become commonly known as ‘Medical Tourism’ where patients travel to overseas destinations for specialised surgical treatments and other forms of medical care. With the rise of more affordable cross-border travel and rapid technological developments these movements are becoming more commonplace. A key driver is the platform provided by the internet for gaining access to healthcare information and advertising. There has been relatively little attention given to the role and impact of web-based information to inform Medical Tourism decisions. This article provides a brief overview of the most recent development in Medical Tourism and examines how this is linked to the emergence of specialized internet web sites. It produces a summary of the functionality of medical tourist sites, and situates Medical Tourism informatics within the broader literatures relating to information search, information quality and decision-making. This paper is both a call to strengthen the empirical evidence in this area, and also to advocate integrating Medical Tourism research within a broader conceptual framework. PMID:20517465

Familiarity and prevalence of Facebook use for social networking among individuals with traumatic brain injury.

PubMed

Tsaousides, Theodore; Matsuzawa, Yuka; Lebowitz, Matthew

2011-01-01

To examine use of Facebook among individuals with traumatic brain injury (TBI) and to identify barriers preventing Facebook use. An online survey was developed assessing frequency and barriers to use of Facebook. The survey was distributed electronically to individuals with TBI through four state brain injury associations. Ninety-six individuals with TBI completed the survey (60% female, age range: 23-70). The relative majority of respondents (60%) reported using Facebook on a regular basis. Among those who reported not using Facebook, the most commonly reported barriers were security concerns and cognitive deficits. Approximately half of non-users indicated interest in learning to use the site, with 70% reporting that they would use it more if they were more knowledgeable about it. Both users and non-users indicated that they would be interested in receiving training to learn how to use Facebook better. Social networking sites are increasingly important in creating and maintaining social networks. A significant number of survey respondents expressed interest in further training on Facebook use. Increased use of social networking may have important implications for social integration among individuals with TBI.

Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31

PubMed Central

Permuth-Wey, Jennifer; Lawrenson, Kate; Shen, Howard C.; Velkova, Aneliya; Tyrer, Jonathan P.; Chen, Zhihua; Lin, Hui-Yi; Chen, Y. Ann; Tsai, Ya-Yu; Qu, Xiaotao; Ramus, Susan J.; Karevan, Rod; Lee, Janet; Lee, Nathan; Larson, Melissa C.; Aben, Katja K.; Anton-Culver, Hoda; Antonenkova, Natalia; Antoniou, Antonis; Armasu, Sebastian M.; Bacot, François; Baglietto, Laura; Bandera, Elisa V.; Barnholtz-Sloan, Jill; Beckmann, Matthias W.; Birrer, Michael J.; Bloom, Greg; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Brown, Robert; Butzow, Ralf; Cai, Qiuyin; Campbell, Ian; Chang-Claude, Jenny; Chanock, Stephen; Chenevix-Trench, Georgia; Cheng, Jin Q.; Cicek, Mine S.; Coetzee, Gerhard A.; Cook, Linda S.; Couch, Fergus J.; Cramer, Daniel W.; Cunningham, Julie M.; Dansonka-Mieszkowska, Agnieszka; Despierre, Evelyn; Doherty, Jennifer A; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Easton, Douglas F; Eccles, Diana; Edwards, Robert; Ekici, Arif B.; Fasching, Peter A.; Fenstermacher, David A.; Flanagan, James M.; Garcia-Closas, Montserrat; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind M.; Gonzalez-Bosquet, Jesus; Goodman, Marc T.; Gore, Martin; Górski, Bohdan; Gronwald, Jacek; Hall, Per; Halle, Mari K.; Harter, Philipp; Heitz, Florian; Hillemanns, Peter; Hoatlin, Maureen; Høgdall, Claus K.; Høgdall, Estrid; Hosono, Satoyo; Jakubowska, Anna; Jensen, Allan; Jim, Heather; Kalli, Kimberly R.; Karlan, Beth Y.; Kaye, Stanley B.; Kelemen, Linda E.; Kiemeney, Lambertus A.; Kikkawa, Fumitaka; Konecny, Gottfried E.; Krakstad, Camilla; Kjaer, Susanne Krüger; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Lancaster, Johnathan M.; Le, Nhu D.; Leminen, Arto; Levine, Douglas A.; Liang, Dong; Lim, Boon Kiong; Lin, Jie; Lissowska, Jolanta; Lu, Karen H.; Lubiński, Jan; Lurie, Galina; Massuger, Leon F.A.G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B.; Nakanishi, Toru; Narod, Steven A.; Nedergaard, Lotte; Ness, Roberta B.; Nevanlinna, Heli; Nickels, Stefan; Noushmehr, Houtan; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Paul, James; Pearce, Celeste L; Pejovic, Tanja; Pelttari, Liisa M.; Pike, Malcolm C.; Poole, Elizabeth M.; Raska, Paola; Renner, Stefan P.; Risch, Harvey A.; Rodriguez-Rodriguez, Lorna; Rossing, Mary Anne; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schwaab, Ira; Severi, Gianluca; Shridhar, Vijayalakshmi; Shu, Xiao-Ou; Shvetsov, Yurii B.; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Spiewankiewicz, Beata; Stram, Daniel; Sutphen, Rebecca; Teo, Soo-Hwang; Terry, Kathryn L.; Tessier, Daniel C.; Thompson, Pamela J.; Tworoger, Shelley S.; van Altena, Anne M.; Vergote, Ignace; Vierkant, Robert A.; Vincent, Daniel; Vitonis, Allison F.; Wang-Gohrke, Shan; Weber, Rachel Palmieri; Wentzensen, Nicolas; Whittemore, Alice S.; Wik, Elisabeth; Wilkens, Lynne R.; Winterhoff, Boris; Woo, Yin Ling; Wu, Anna H.; Xiang, Yong-Bing; Yang, Hannah P.; Zheng, Wei; Ziogas, Argyrios; Zulkifli, Famida; Phelan, Catherine M.; Iversen, Edwin; Schildkraut, Joellen M.; Berchuck, Andrew; Fridley, Brooke L.; Goode, Ellen L.; Pharoah, Paul D. P.; Monteiro, Alvaro N.A.; Sellers, Thomas A.; Gayther, Simon A.

2013-01-01

Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3′ untranslated region at putative microRNA (miRNA) binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA binding site single nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene-environment Study. We identify several miRSNPs associated with invasive serous EOC risk (OR=1.12, P=10−8) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion (P=10−10). Variation at 17q21.31 associates with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. An integrated molecular analysis in this region provides evidence for ARHGAP27 and PLEKHM1 as candidate EOC susceptibility genes. PMID:23535648

[Disposable nursing applicator-pocket of indwelling central venous catheter].

PubMed

Wei, Congli; Ma, Chunyuan

2017-11-01

Catheter related infection is the most common complication of central venous catheter, which pathogen mainly originate from the pipe joint and the skin around puncture site. How to prevent catheter infection is an important issue in clinical nursing. The utility model disclosed a "disposable nursing applicator-pocket of indwelling central venous catheter", which is mainly used for the fixation and the protection. The main structure consists of two parts, one is medical applicator to protect the skin around puncture site, and the other is gauze pocket to protect the catheter external connector. When in use, the catheter connector is fitted into the pocket, and then the applicator is applied to cover the puncture point of the skin. Integrated design of medical applicator and gauze pocket was designed to realize double functions of fixation and protection. The disposable nursing applicator-pocket is made of medical absorbent gauze (outer layer) and non-woven fabric (inner layer), which has the characteristics of comfortable, breathable, dust filtered, bacteria filtered, waterproof, antiperspirant and anti-pollution. The utility model has the advantages of simple structure, low cost, simple operation, effective protection, easy realization and popularization.

Nip, tuck and click: medical tourism and the emergence of web-based health information.

PubMed

Lunt, Neil; Hardey, Mariann; Mannion, Russell

2010-02-12

An emerging trend is what has become commonly known as 'Medical Tourism' where patients travel to overseas destinations for specialised surgical treatments and other forms of medical care. With the rise of more affordable cross-border travel and rapid technological developments these movements are becoming more commonplace. A key driver is the platform provided by the internet for gaining access to healthcare information and advertising. There has been relatively little attention given to the role and impact of web-based information to inform Medical Tourism decisions.This article provides a brief overview of the most recent development in Medical Tourism and examines how this is linked to the emergence of specialized internet web sites. It produces a summary of the functionality of medical tourist sites, and situates Medical Tourism informatics within the broader literatures relating to information search, information quality and decision-making.This paper is both a call to strengthen the empirical evidence in this area, and also to advocate integrating Medical Tourism research within a broader conceptual framework.

Herbivory Network: An international, collaborative effort to study herbivory in Arctic and alpine ecosystems

NASA Astrophysics Data System (ADS)

Barrio, I. C.; Hik, D. S.; Jónsdóttir, I. S.; Bueno, C. G.; Mörsdorf, M. A.; Ravolainen, V. T.

2016-09-01

Plant-herbivore interactions are central to the functioning of tundra ecosystems, but their outcomes vary over space and time. Accurate forecasting of ecosystem responses to ongoing environmental changes requires a better understanding of the processes responsible for this heterogeneity. To effectively address this complexity at a global scale, coordinated research efforts, including multi-site comparisons within and across disciplines, are needed. The Herbivory Network was established as a forum for researchers from Arctic and alpine regions to collaboratively investigate the multifunctional role of herbivores in these changing ecosystems. One of the priorities is to integrate sites, methodologies, and metrics used in previous work, to develop a set of common protocols and design long-term geographically-balanced, coordinated experiments. The implementation of these collaborative research efforts will also improve our understanding of traditional human-managed systems that encompass significant portions of the sub-Arctic and alpine areas worldwide. A deeper understanding of the role of herbivory in these systems under ongoing environmental changes will guide appropriate adaptive strategies to preserve their natural values and related ecosystem services.

47 CFR 11.56 - Obligation to process CAP-formatted EAS messages.

Code of Federal Regulations, 2013 CFR

2013-10-01

...), and Common Alerting Protocol, v. 1.2 USA Integrated Public Alert and Warning System Profile Version 1...) “Common Alerting Protocol, v. 1.2 USA Integrated Public Alert and Warning System Profile Version 1.0” (Oct...

47 CFR 11.56 - Obligation to process CAP-formatted EAS messages.

Code of Federal Regulations, 2012 CFR

2012-10-01

...), and Common Alerting Protocol, v. 1.2 USA Integrated Public Alert and Warning System Profile Version 1...) “Common Alerting Protocol, v. 1.2 USA Integrated Public Alert and Warning System Profile Version 1.0” (Oct...

47 CFR 11.56 - Obligation to process CAP-formatted EAS messages.

Code of Federal Regulations, 2014 CFR

2014-10-01

...), and Common Alerting Protocol, v. 1.2 USA Integrated Public Alert and Warning System Profile Version 1...) “Common Alerting Protocol, v. 1.2 USA Integrated Public Alert and Warning System Profile Version 1.0” (Oct...

BTEC Integrative Assignments.

ERIC Educational Resources Information Center

Foot, G. E.

1992-01-01

To equip electrical engineering students with common and transferable work skills, a program of integrative assignments was created to develop communication and teamwork skills. Discusses assignment components; the log book, a personal account of each assignment; assessment; conversion of "common skills" to competence statements, and…

Idaho National Laboratory Site Pollution Prevention Plan

DOE Office of Scientific and Technical Information (OSTI.GOV)

E. D. Sellers

2007-03-01

It is the policy of the Department of Energy (DOE) that pollution prevention and sustainable environmental stewardship will be integrated into DOE operations as a good business practice to reduce environmental hazards, protect environmental resources, avoid pollution control costs, and improve operational efficiency and mission sustainability. In furtherance of this policy, DOE established five strategic, performance-based Pollution Prevention (P2) and Sustainable Environmental Stewardship goals and included them as an attachment to DOE O 450.1, Environmental Protection Program. These goals and accompanying strategies are to be implemented by DOE sites through the integration of Pollution Prevention into each site's Environmental Managementmore » System (EMS). This document presents a P2 and Sustainability Program and corresponding plan pursuant to DOE Order 450.1 and DOE O 435.1, Radioactive Waste Management. This plan is also required by the state of Idaho, pursuant to the Resource Conservation and Recovery Act (RCRA) partial permit. The objective of this document is to describe the Idaho National Laboratory (INL) Site P2 and Sustainability Program. The purpose of the program is to decrease the environmental footprint of the INL Site while providing enhanced support of its mission. The success of the program is dependent on financial and management support. The signatures on the previous page indicate INL, ICP, and AMWTP Contractor management support and dedication to the program. P2 requirements have been integrated into working procedures to ensure an effective EMS as part of an Integrated Safety Management System (ISMS). This plan focuses on programmatic functions which include environmentally preferable procurement, sustainable design, P2 and Sustainability awareness, waste generation and reduction, source reduction and recycling, energy management, and pollution prevention opportunity assessments. The INL Site P2 and Sustainability Program is administratively managed by the INL Site P2 Coordinator. Development and maintenance of this overall INL Site plan is ultimately the responsibility of DOE-ID. This plan is applicable to all INL Site contractors except those at the Naval Reactors Facility.« less

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

PubMed Central

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

Not Your Father's Web Site: Corporate Sites Emerge as New Content Innovators.

ERIC Educational Resources Information Center

O'Leary, Mick

2002-01-01

New economy corporate Web sites have pioneered exciting techniques-rich media, interactivity, personalization, community, and integration of much third-party content. Discusses business-to-business (B2B) Web commerce, with examples of several B2B corporate sites; portal and content elements of these sites; and corporate content outlooks. (AEF)

COMPARISON OF THE POPULATIONS OF COMMON WOOD-NYMPH BUTTERFLIES IN BURNED PRAIRIE, UNBURNED PRAIRIE AND OLD FIELD GRASSES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hahn, M.; Walton, R.

2007-01-01

Common wood-nymph butterfl ies are found throughout the United States and Canada. However, not much is known about how they overwinter or their preferences for particular grasses and habitats. In this study, the impact of prairie management plans on the abundance of the wood-nymph population was assessed, as well as the preference of these butterfl ies for areas with native or non-native grasses. The abundance of common wood-nymph butterfl ies was determined using Pollard walks; more common wood-nymph butterfl ies were found in the European grasses than were found in the burned and unburned prairie sites. The majority of themore » vegetation at each of the three sites was identifi ed and documented. Using a 1 X 3 ANOVA analysis, it was determined there were signifi cantly more butterfl ies in the European grasses than in the burned and unburned prairie sites (p < 0.0005). There was no signifi cant difference between the burned and unburned treatments of the prairie on the common wood-nymph population. A multiple variable linear regression model described the effect of temperature and wind speed on the number of observed common wood-nymph butterfl ies per hour (p = 0.026). These preliminary results need to be supplemented with future studies. Quadrat analysis of the vegetation from all three sites should be done to search for a correlation between common wood-nymph butterfl y abundance per hour and the specifi c types or quantity of vegetation at each site. The effect of vegetation height and density on the observer’s visual fi eld should also be assessed.« less

SITE TECHNOLOGY PROFILES, TENTH EDITION, VOLUME 3 - MEASUREMENT AND MONITORING PROGRAM

EPA Science Inventory

The Superfund Innovative Technology Evaluation (SITE) Program, now in its thirteenth year, is an integral part of EPA's research into alternative cleanup methods for hazardous waste sites around the nation. The SITE Program was created to encourage the development and routine us...

SITE TECHNOLOGY PROFILES, TENTH EDITION, VOLUME 2 - EMERGING TECHNOLOGY PROGRAM

EPA Science Inventory

The Superfund Innovative Technology Evaluation (SITE) Program, now in its thirteenth year, is an integral part of EPA's research into alternative cleanup methods for hazardous waste sites around the nation. The SITE Program was created to encourage the development and routine us...