Using site-selection model to identify suitable sites for seagrass transplantation in the west coast of South Sulawesi

NASA Astrophysics Data System (ADS)

Lanuru, Mahatma; Mashoreng, S.; Amri, K.

2018-03-01

The success of seagrass transplantation is very much depending on the site selection and suitable transplantation methods. The main objective of this study is to develop and use a site-selection model to identify the suitability of sites for seagrass (Enhalus acoroides) transplantation. Model development was based on the physical and biological characteristics of the transplantation site. The site-selection process is divided into 3 phases: Phase I identifies potential seagrass habitat using available knowledge, removes unnecessary sites before the transplantation test is performed. Phase II involves field assessment and transplantation test of the best scoring areas identified in Phase I. Phase III is the final calculation of the TSI (Transplant Suitability Index), based on results from Phases I and II. The model was used to identify the suitability of sites for seagrass transplantation in the West coast of South Sulawesi (3 sites at Labakkang Coast, 3 sites at Awerange Bay, and 3 sites at Lale-Lae Island). Of the 9 sites, two sites were predicted by the site-selection model to be the most suitable sites for seagrass transplantation: Site II at Labakkang Coast and Site III at Lale-Lae Island.

Plant-associated methylobacteria as co-evolved phytosymbionts: a hypothesis.

PubMed

Kutschera, Ulrich

2007-03-01

Due to their wall-associated pectin metabolism, growing plant cells emit significant amounts of the one-carbon alcohol methanol. Pink-pigmented microbes of the genus Methylobacterium that colonize the surfaces of leaves (epiphytes) are capable of growth on this volatile C1-compound as sole source of carbon and energy. In this article the results of experiments with germ-free (gnotobiotic) sporophytes of angiosperms (sunflower, maize) and gametophytes of bryophytes (a moss and two liverwort species) are summarized. The data show that methylobacteria do not stimulate the growth of these angiosperms, but organ development in moss protonemata and in thalli of liverworts is considerably enhanced. Since methylobacteria produce and secrete cytokinins and auxin, a model of plant-microbe-interaction (symbiosis) is proposed in which the methanol-consuming bacteria are viewed as coevolved partners of the gametophyte that determine its growth, survival and reproduction (fitness). This symbiosis is restricted to the haploid cells of moisture-dependent "living fossil" plants; it does not apply to the diploid sporophytes of higher embryophytes, which are fully adapted to life on land and apparently produce sufficient amounts of endogenous phytohormones.

How Life and Rocks Have Co-Evolved

NASA Astrophysics Data System (ADS)

Hazen, R.

2014-04-01

The near-surface environment of terrestrial planets and moons evolves as a consequence of selective physical, chemical, and biological processes - an evolution that is preserved in the mineralogical record. Mineral evolution begins with approximately 12 different refractory minerals that form in the cooling envelopes of exploding stars. Subsequent aqueous and thermal alteration of planetessimals results in the approximately 250 minerals now found in unweathered lunar and meteorite samples. Following Earth's accretion and differentiation, mineral evolution resulted from a sequence of geochemical and petrologic processes, which led to perhaps 1500 mineral species. According to some origin-of-life scenarios, a planet must progress through at least some of these stages of chemical processing as a prerequisite for life. Once life emerged, mineralogy and biology co-evolved and dramatically increased Earth's mineral diversity to >4000 species. Sequential stages of a planet's near-surface evolution arise from three primary mechanisms: (1) the progressive separation and concentration of the elements from their original relatively uniform distribution in the presolar nebula; (2) the increase in range of intensive variables such as pressure, temperature, and volatile activities; and (3) the generation of far-from-equilibrium conditions by living systems. Remote observations of the mineralogy of other terrestrial bodies may thus provide evidence for biological influences beyond Earth. Recent studies of mineral diversification through time reveal striking correlations with major geochemical, tectonic, and biological events, including large-changes in ocean chemistry, the supercontinent cycle, the increase of atmospheric oxygen, and the rise of the terrestrial biosphere.

Identifying Internet Sites to Coordinate with National Science Education Standards

ERIC Educational Resources Information Center

Fehrenbach, Carolyn R.; Morris, Maxine G.

2004-01-01

Identifying Internet sites to coordinate with National Science Education Standards can be challenging for teachers and students. By identifying quality free Internet sites in science, teachers and students can use the extensive resources of the Internet to enhance learning and instruction while meeting National Science Education Content Standards…

A New Scheme to Characterize and Identify Protein Ubiquitination Sites.

PubMed

Nguyen, Van-Nui; Huang, Kai-Yao; Huang, Chien-Hsun; Lai, K Robert; Lee, Tzong-Yi

2017-01-01

Protein ubiquitination, involving the conjugation of ubiquitin on lysine residue, serves as an important modulator of many cellular functions in eukaryotes. Recent advancements in proteomic technology have stimulated increasing interest in identifying ubiquitination sites. However, most computational tools for predicting ubiquitination sites are focused on small-scale data. With an increasing number of experimentally verified ubiquitination sites, we were motivated to design a predictive model for identifying lysine ubiquitination sites for large-scale proteome dataset. This work assessed not only single features, such as amino acid composition (AAC), amino acid pair composition (AAPC) and evolutionary information, but also the effectiveness of incorporating two or more features into a hybrid approach to model construction. The support vector machine (SVM) was applied to generate the prediction models for ubiquitination site identification. Evaluation by five-fold cross-validation showed that the SVM models learned from the combination of hybrid features delivered a better prediction performance. Additionally, a motif discovery tool, MDDLogo, was adopted to characterize the potential substrate motifs of ubiquitination sites. The SVM models integrating the MDDLogo-identified substrate motifs could yield an average accuracy of 68.70 percent. Furthermore, the independent testing result showed that the MDDLogo-clustered SVM models could provide a promising accuracy (78.50 percent) and perform better than other prediction tools. Two cases have demonstrated the effective prediction of ubiquitination sites with corresponding substrate motifs.

Catalytic site identification--a web server to identify catalytic site structural matches throughout PDB.

PubMed

Kirshner, Daniel A; Nilmeier, Jerome P; Lightstone, Felice C

2013-07-01

The catalytic site identification web server provides the innovative capability to find structural matches to a user-specified catalytic site among all Protein Data Bank proteins rapidly (in less than a minute). The server also can examine a user-specified protein structure or model to identify structural matches to a library of catalytic sites. Finally, the server provides a database of pre-calculated matches between all Protein Data Bank proteins and the library of catalytic sites. The database has been used to derive a set of hypothesized novel enzymatic function annotations. In all cases, matches and putative binding sites (protein structure and surfaces) can be visualized interactively online. The website can be accessed at http://catsid.llnl.gov.

Entropic determination of the phase transition in a coevolving opinion-formation model.

PubMed

Burgos, E; Hernández, Laura; Ceva, H; Perazzo, R P J

2015-03-01

We study an opinion formation model by the means of a coevolving complex network where the vertices represent the individuals, characterized by their evolving opinions, and the edges represent the interactions among them. The network adapts to the spreading of opinions in two ways: not only connected agents interact and eventually change their thinking but an agent may also rewire one of its links to a neighborhood holding the same opinion as his. The dynamics, based on a global majority rule, depends on an external parameter that controls the plasticity of the network. We show how the information entropy associated to the distribution of group sizes allows us to locate the phase transition between a phase of full consensus and another, where different opinions coexist. We also determine the minimum size of the most informative sampling. At the transition the distribution of the sizes of groups holding the same opinion is scale free.

Coevolving advances in animal flight and aerial robotics

PubMed Central

Lentink, David

2017-01-01

Our understanding of animal flight has inspired the design of new aerial robots with more effective flight capacities through the process of biomimetics and bioinspiration. The aerodynamic origin of the elevated performance of flying animals remains, however, poorly understood. In this themed issue, animal flight research and aerial robot development coalesce to offer a broader perspective on the current advances and future directions in these coevolving fields of research. Together, four reviews summarize and 14 reports contribute to our understanding of low Reynolds number flight. This area of applied aerodynamics research is challenging to dissect due to the complicated flow phenomena that include laminar–turbulent flow transition, laminar separation bubbles, delayed stall and nonlinear vortex dynamics. Our mechanistic understanding of low Reynolds number flight has perhaps been advanced most by the development of dynamically scaled robot models and new specialized wind tunnel facilities: in particular, the tiltable Lund flight tunnel for animal migration research and the recently developed AFAR hypobaric wind tunnel for high-altitude animal flight studies. These world-class facilities are now complemented with a specialized low Reynolds number wind tunnel for studying the effect of turbulence on animal and robot flight in much greater detail than previously possible. This is particular timely, because the study of flight in extremely laminar versus turbulent flow opens a new frontier in our understanding of animal flight. Advancing this new area will offer inspiration for developing more efficient high-altitude aerial robots and removes roadblocks for aerial robots operating in turbulent urban environments.

Catalytic site identification—a web server to identify catalytic site structural matches throughout PDB

PubMed Central

Kirshner, Daniel A.; Nilmeier, Jerome P.; Lightstone, Felice C.

2013-01-01

The catalytic site identification web server provides the innovative capability to find structural matches to a user-specified catalytic site among all Protein Data Bank proteins rapidly (in less than a minute). The server also can examine a user-specified protein structure or model to identify structural matches to a library of catalytic sites. Finally, the server provides a database of pre-calculated matches between all Protein Data Bank proteins and the library of catalytic sites. The database has been used to derive a set of hypothesized novel enzymatic function annotations. In all cases, matches and putative binding sites (protein structure and surfaces) can be visualized interactively online. The website can be accessed at http://catsid.llnl.gov. PMID:23680785

10 CFR 72.98 - Identifying regions around an ISFSI or MRS site.

Code of Federal Regulations, 2012 CFR

2012-01-01

... WASTE Siting Evaluation Factors § 72.98 Identifying regions around an ISFSI or MRS site. (a) The... ISFSI or MRS must be identified. (b) The potential regional impact due to the construction, operation or decommissioning of the ISFSI or MRS must be identified. The extent of regional impacts must be determined on the...

10 CFR 72.98 - Identifying regions around an ISFSI or MRS site.

Code of Federal Regulations, 2011 CFR

2011-01-01

... WASTE Siting Evaluation Factors § 72.98 Identifying regions around an ISFSI or MRS site. (a) The... ISFSI or MRS must be identified. (b) The potential regional impact due to the construction, operation or decommissioning of the ISFSI or MRS must be identified. The extent of regional impacts must be determined on the...

Central site monitoring: results from a test of accuracy in identifying trials and sites failing Food and Drug Administration inspection.

PubMed

Lindblad, Anne S; Manukyan, Zorayr; Purohit-Sheth, Tejashri; Gensler, Gary; Okwesili, Paul; Meeker-O'Connell, Ann; Ball, Leslie; Marler, John R

2014-04-01

Site monitoring and source document verification account for 15%-30% of clinical trial costs. An alternative is to streamline site monitoring to focus on correcting trial-specific risks identified by central data monitoring. This risk-based approach could preserve or even improve the quality of clinical trial data and human subject protection compared to site monitoring focused primarily on source document verification. To determine whether a central review by statisticians using data submitted to the Food and Drug Administration (FDA) by clinical trial sponsors can identify problem sites and trials that failed FDA site inspections. An independent Analysis Center (AC) analyzed data from four anonymous new drug applications (NDAs) where FDA had performed site inspections overseen by FDA's Office of Scientific Investigations (OSI). FDA team members in the OSI chose the four NDAs from among all NDAs with data in Study Data Tabulation Model (SDTM) format. Two of the NDAs had data that OSI had deemed unreliable in support of the application after FDA site inspections identified serious data integrity problems. The other two NDAs had clinical data that OSI deemed reliable after site inspections. At the outset, the AC knew only that the experimental design specified two NDAs with significant problems. FDA gave the AC no information about which NDAs had problems, how many sites were inspected, or how many were found to have problems until after the AC analysis was complete. The AC evaluated randomization balance, enrollment patterns, study visit scheduling, variability of reported data, and last digit reference. The AC classified sites as 'High Concern', 'Moderate Concern', 'Mild Concern', or 'No Concern'. The AC correctly identified the two NDAs with data deemed unreliable by OSI. In addition, central data analysis correctly identified 5 of 6 (83%) sites for which FDA recommended rejection of data and 13 of 15 sites (87%) for which any regulatory deviations were

SP transcription factor paralogs and DNA-binding sites coevolve and adaptively converge in mammals and birds.

PubMed

Yokoyama, Ken Daigoro; Pollock, David D

2012-01-01

Functional modification of regulatory proteins can affect hundreds of genes throughout the genome, and is therefore thought to be almost universally deleterious. This belief, however, has recently been challenged. A potential example comes from transcription factor SP1, for which statistical evidence indicates that motif preferences were altered in eutherian mammals. Here, we set out to discover possible structural and theoretical explanations, evaluate the role of selection in SP1 evolution, and discover effects on coregulatory proteins. We show that SP1 motif preferences were convergently altered in birds as well as mammals, inducing coevolutionary changes in over 800 regulatory regions. Structural and phylogenic evidence implicates a single causative amino acid replacement at the same SP1 position along both lineages. Furthermore, paralogs SP3 and SP4, which coregulate SP1 target genes through competitive binding to the same sites, have accumulated convergent replacements at the homologous position multiple times during eutherian and bird evolution, presumably to preserve competitive binding. To determine plausibility, we developed and implemented a simple model of transcription factor and binding site coevolution. This model predicts that, in contrast to prevailing beliefs, even small selective benefits per locus can drive concurrent fixation of transcription factor and binding site mutants under a broad range of conditions. Novel binding sites tend to arise de novo, rather than by mutation from ancestral sites, a prediction substantiated by SP1-binding site alignments. Thus, multiple lines of evidence indicate that selection has driven convergent evolution of transcription factors along with their binding sites and coregulatory proteins.

SP Transcription Factor Paralogs and DNA-Binding Sites Coevolve and Adaptively Converge in Mammals and Birds

PubMed Central

Yokoyama, Ken Daigoro; Pollock, David D.

2012-01-01

Functional modification of regulatory proteins can affect hundreds of genes throughout the genome, and is therefore thought to be almost universally deleterious. This belief, however, has recently been challenged. A potential example comes from transcription factor SP1, for which statistical evidence indicates that motif preferences were altered in eutherian mammals. Here, we set out to discover possible structural and theoretical explanations, evaluate the role of selection in SP1 evolution, and discover effects on coregulatory proteins. We show that SP1 motif preferences were convergently altered in birds as well as mammals, inducing coevolutionary changes in over 800 regulatory regions. Structural and phylogenic evidence implicates a single causative amino acid replacement at the same SP1 position along both lineages. Furthermore, paralogs SP3 and SP4, which coregulate SP1 target genes through competitive binding to the same sites, have accumulated convergent replacements at the homologous position multiple times during eutherian and bird evolution, presumably to preserve competitive binding. To determine plausibility, we developed and implemented a simple model of transcription factor and binding site coevolution. This model predicts that, in contrast to prevailing beliefs, even small selective benefits per locus can drive concurrent fixation of transcription factor and binding site mutants under a broad range of conditions. Novel binding sites tend to arise de novo, rather than by mutation from ancestral sites, a prediction substantiated by SP1-binding site alignments. Thus, multiple lines of evidence indicate that selection has driven convergent evolution of transcription factors along with their binding sites and coregulatory proteins. PMID:23019068

SABER: A computational method for identifying active sites for new reactions

PubMed Central

Nosrati, Geoffrey R; Houk, K N

2012-01-01

A software suite, SABER (Selection of Active/Binding sites for Enzyme Redesign), has been developed for the analysis of atomic geometries in protein structures, using a geometric hashing algorithm (Barker and Thornton, Bioinformatics 2003;19:1644–1649). SABER is used to explore the Protein Data Bank (PDB) to locate proteins with a specific 3D arrangement of catalytic groups to identify active sites that might be redesigned to catalyze new reactions. As a proof-of-principle test, SABER was used to identify enzymes that have the same catalytic group arrangement present in o-succinyl benzoate synthase (OSBS). Among the highest-scoring scaffolds identified by the SABER search for enzymes with the same catalytic group arrangement as OSBS were l-Ala d/l-Glu epimerase (AEE) and muconate lactonizing enzyme II (MLE), both of which have been redesigned to become effective OSBS catalysts, demonstrated by experiments. Next, we used SABER to search for naturally existing active sites in the PDB with catalytic groups similar to those present in the designed Kemp elimination enzyme KE07. From over 2000 geometric matches to the KE07 active site, SABER identified 23 matches that corresponded to residues from known active sites. The best of these matches, with a 0.28 Å catalytic atom RMSD to KE07, was then redesigned to be compatible with the Kemp elimination using RosettaDesign. We also used SABER to search for potential Kemp eliminases using a theozyme predicted to provide a greater rate acceleration than the active site of KE07, and used Rosetta to create a design based on the proteins identified. PMID:22492397

SABER: a computational method for identifying active sites for new reactions.

PubMed

Nosrati, Geoffrey R; Houk, K N

2012-05-01

A software suite, SABER (Selection of Active/Binding sites for Enzyme Redesign), has been developed for the analysis of atomic geometries in protein structures, using a geometric hashing algorithm (Barker and Thornton, Bioinformatics 2003;19:1644-1649). SABER is used to explore the Protein Data Bank (PDB) to locate proteins with a specific 3D arrangement of catalytic groups to identify active sites that might be redesigned to catalyze new reactions. As a proof-of-principle test, SABER was used to identify enzymes that have the same catalytic group arrangement present in o-succinyl benzoate synthase (OSBS). Among the highest-scoring scaffolds identified by the SABER search for enzymes with the same catalytic group arrangement as OSBS were L-Ala D/L-Glu epimerase (AEE) and muconate lactonizing enzyme II (MLE), both of which have been redesigned to become effective OSBS catalysts, demonstrated by experiments. Next, we used SABER to search for naturally existing active sites in the PDB with catalytic groups similar to those present in the designed Kemp elimination enzyme KE07. From over 2000 geometric matches to the KE07 active site, SABER identified 23 matches that corresponded to residues from known active sites. The best of these matches, with a 0.28 Å catalytic atom RMSD to KE07, was then redesigned to be compatible with the Kemp elimination using RosettaDesign. We also used SABER to search for potential Kemp eliminases using a theozyme predicted to provide a greater rate acceleration than the active site of KE07, and used Rosetta to create a design based on the proteins identified. Copyright © 2012 The Protein Society.

Carboxylator: incorporating solvent-accessible surface area for identifying protein carboxylation sites

NASA Astrophysics Data System (ADS)

Lu, Cheng-Tsung; Chen, Shu-An; Bretaña, Neil Arvin; Cheng, Tzu-Hsiu; Lee, Tzong-Yi

2011-10-01

In proteins, glutamate (Glu) residues are transformed into γ-carboxyglutamate (Gla) residues in a process called carboxylation. The process of protein carboxylation catalyzed by γ-glutamyl carboxylase is deemed to be important due to its involvement in biological processes such as blood clotting cascade and bone growth. There is an increasing interest within the scientific community to identify protein carboxylation sites. However, experimental identification of carboxylation sites via mass spectrometry-based methods is observed to be expensive, time-consuming, and labor-intensive. Thus, we were motivated to design a computational method for identifying protein carboxylation sites. This work aims to investigate the protein carboxylation by considering the composition of amino acids that surround modification sites. With the implication of a modified residue prefers to be accessible on the surface of a protein, the solvent-accessible surface area (ASA) around carboxylation sites is also investigated. Radial basis function network is then employed to build a predictive model using various features for identifying carboxylation sites. Based on a five-fold cross-validation evaluation, a predictive model trained using the combined features of amino acid sequence (AA20D), amino acid composition, and ASA, yields the highest accuracy at 0.874. Furthermore, an independent test done involving data not included in the cross-validation process indicates that in silico identification is a feasible means of preliminary analysis. Additionally, the predictive method presented in this work is implemented as Carboxylator (http://csb.cse.yzu.edu.tw/Carboxylator/), a web-based tool for identifying carboxylated proteins with modification sites in order to help users in investigating γ-glutamyl carboxylation.

iSS-PseDNC: identifying splicing sites using pseudo dinucleotide composition.

PubMed

Chen, Wei; Feng, Peng-Mian; Lin, Hao; Chou, Kuo-Chen

2014-01-01

In eukaryotic genes, exons are generally interrupted by introns. Accurately removing introns and joining exons together are essential processes in eukaryotic gene expression. With the avalanche of genome sequences generated in the postgenomic age, it is highly desired to develop automated methods for rapid and effective detection of splice sites that play important roles in gene structure annotation and even in RNA splicing. Although a series of computational methods were proposed for splice site identification, most of them neglected the intrinsic local structural properties. In the present study, a predictor called "iSS-PseDNC" was developed for identifying splice sites. In the new predictor, the sequences were formulated by a novel feature-vector called "pseudo dinucleotide composition" (PseDNC) into which six DNA local structural properties were incorporated. It was observed by the rigorous cross-validation tests on two benchmark datasets that the overall success rates achieved by iSS-PseDNC in identifying splice donor site and splice acceptor site were 85.45% and 87.73%, respectively. It is anticipated that iSS-PseDNC may become a useful tool for identifying splice sites and that the six DNA local structural properties described in this paper may provide novel insights for in-depth investigations into the mechanism of RNA splicing.

Identifying protein phosphorylation sites with kinase substrate specificity on human viruses.

PubMed

Bretaña, Neil Arvin; Lu, Cheng-Tsung; Chiang, Chiu-Yun; Su, Min-Gang; Huang, Kai-Yao; Lee, Tzong-Yi; Weng, Shun-Long

2012-01-01

Viruses infect humans and progress inside the body leading to various diseases and complications. The phosphorylation of viral proteins catalyzed by host kinases plays crucial regulatory roles in enhancing replication and inhibition of normal host-cell functions. Due to its biological importance, there is a desire to identify the protein phosphorylation sites on human viruses. However, the use of mass spectrometry-based experiments is proven to be expensive and labor-intensive. Furthermore, previous studies which have identified phosphorylation sites in human viruses do not include the investigation of the responsible kinases. Thus, we are motivated to propose a new method to identify protein phosphorylation sites with its kinase substrate specificity on human viruses. The experimentally verified phosphorylation data were extracted from virPTM--a database containing 301 experimentally verified phosphorylation data on 104 human kinase-phosphorylated virus proteins. In an attempt to investigate kinase substrate specificities in viral protein phosphorylation sites, maximal dependence decomposition (MDD) is employed to cluster a large set of phosphorylation data into subgroups containing significantly conserved motifs. The experimental human phosphorylation sites are collected from Phospho.ELM, grouped according to its kinase annotation, and compared with the virus MDD clusters. This investigation identifies human kinases such as CK2, PKB, CDK, and MAPK as potential kinases for catalyzing virus protein substrates as confirmed by published literature. Profile hidden Markov model is then applied to learn a predictive model for each subgroup. A five-fold cross validation evaluation on the MDD-clustered HMMs yields an average accuracy of 84.93% for Serine, and 78.05% for Threonine. Furthermore, an independent testing data collected from UniProtKB and Phospho.ELM is used to make a comparison of predictive performance on three popular kinase-specific phosphorylation site

Method for Identifying Probable Archaeological Sites from Remotely Sensed Data

NASA Technical Reports Server (NTRS)

Tilton, James C.; Comer, Douglas C.; Priebe, Carey E.; Sussman, Daniel

2011-01-01

Archaeological sites are being compromised or destroyed at a catastrophic rate in most regions of the world. The best solution to this problem is for archaeologists to find and study these sites before they are compromised or destroyed. One way to facilitate the necessary rapid, wide area surveys needed to find these archaeological sites is through the generation of maps of probable archaeological sites from remotely sensed data. We describe an approach for identifying probable locations of archaeological sites over a wide area based on detecting subtle anomalies in vegetative cover through a statistically based analysis of remotely sensed data from multiple sources. We further developed this approach under a recent NASA ROSES Space Archaeology Program project. Under this project we refined and elaborated this statistical analysis to compensate for potential slight miss-registrations between the remote sensing data sources and the archaeological site location data. We also explored data quantization approaches (required by the statistical analysis approach), and we identified a superior data quantization approached based on a unique image segmentation approach. In our presentation we will summarize our refined approach and demonstrate the effectiveness of the overall approach with test data from Santa Catalina Island off the southern California coast. Finally, we discuss our future plans for further improving our approach.

Surface Sites for Engineering Allosteric Control in Proteins

PubMed Central

Lee, Jeeyeon; Natarajan, Madhusudan; Nashine, Vishal C.; Socolich, Michael; Vo, Tina; Russ, William P.; Benkovic, Stephen J.; Ranganathan, Rama

2010-01-01

Statistical analyses of protein families reveal networks of coevolving amino acids that functionally link distantly positioned functional surfaces. Such linkages suggest a concept for engineering allosteric control into proteins: The intramolecular networks of two proteins could be joined across their surface sites such that the activity of one protein might control the activity of the other. We tested this idea by creating PAS-DHFR, a designed chimeric protein that connects a light-sensing signaling domain from a plant member of the Per/Arnt/Sim (PAS) family of proteins with Escherichia coli dihydrofolate reductase (DHFR). With no optimization, PAS-DHFR exhibited light-dependent catalytic activity that depended on the site of connection and on known signaling mechanisms in both proteins. PAS-DHFR serves as a proof of concept for engineering regulatory activities into proteins through interface design at conserved allosteric sites. PMID:18927392

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.

Analysis of evolutionary conservation patterns and their influence on identifying protein functional sites.

PubMed

Fang, Chun; Noguchi, Tamotsu; Yamana, Hayato

2014-10-01

Evolutionary conservation information included in position-specific scoring matrix (PSSM) has been widely adopted by sequence-based methods for identifying protein functional sites, because all functional sites, whether in ordered or disordered proteins, are found to be conserved at some extent. However, different functional sites have different conservation patterns, some of them are linear contextual, some of them are mingled with highly variable residues, and some others seem to be conserved independently. Every value in PSSMs is calculated independently of each other, without carrying the contextual information of residues in the sequence. Therefore, adopting the direct output of PSSM for prediction fails to consider the relationship between conservation patterns of residues and the distribution of conservation scores in PSSMs. In order to demonstrate the importance of combining PSSMs with the specific conservation patterns of functional sites for prediction, three different PSSM-based methods for identifying three kinds of functional sites have been analyzed. Results suggest that, different PSSM-based methods differ in their capability to identify different patterns of functional sites, and better combining PSSMs with the specific conservation patterns of residues would largely facilitate the prediction.

Toward Identifying the Next Generation of Superfund and Hazardous Waste Site Contaminants

PubMed Central

Ela, Wendell P.; Sedlak, David L.; Barlaz, Morton A.; Henry, Heather F.; Muir, Derek C.G.; Swackhamer, Deborah L.; Weber, Eric J.; Arnold, Robert G.; Ferguson, P. Lee; Field, Jennifer A.; Furlong, Edward T.; Giesy, John P.; Halden, Rolf U.; Henry, Tala; Hites, Ronald A.; Hornbuckle, Keri C.; Howard, Philip H.; Luthy, Richard G.; Meyer, Anita K.; Sáez, A. Eduardo; vom Saal, Frederick S.; Vulpe, Chris D.; Wiesner, Mark R.

2011-01-01

Background This commentary evolved from a workshop sponsored by the National Institute of Environmental Health Sciences titled “Superfund Contaminants: The Next Generation” held in Tucson, Arizona, in August 2009. All the authors were workshop participants. Objectives Our aim was to initiate a dynamic, adaptable process for identifying contaminants of emerging concern (CECs) that are likely to be found in future hazardous waste sites, and to identify the gaps in primary research that cause uncertainty in determining future hazardous waste site contaminants. Discussion Superfund-relevant CECs can be characterized by specific attributes: They are persistent, bioaccumulative, toxic, occur in large quantities, and have localized accumulation with a likelihood of exposure. Although still under development and incompletely applied, methods to quantify these attributes can assist in winnowing down the list of candidates from the universe of potential CECs. Unfortunately, significant research gaps exist in detection and quantification, environmental fate and transport, health and risk assessment, and site exploration and remediation for CECs. Addressing these gaps is prerequisite to a preventive approach to generating and managing hazardous waste sites. Conclusions A need exists for a carefully considered and orchestrated expansion of programmatic and research efforts to identify, evaluate, and manage CECs of hazardous waste site relevance, including developing an evolving list of priority CECs, intensifying the identification and monitoring of likely sites of present or future accumulation of CECs, and implementing efforts that focus on a holistic approach to prevention. PMID:21205582

Toward identifying the next generation of superfund and hazardous waste site contaminants.

PubMed

Ela, Wendell P; Sedlak, David L; Barlaz, Morton A; Henry, Heather F; Muir, Derek C G; Swackhamer, Deborah L; Weber, Eric J; Arnold, Robert G; Ferguson, P Lee; Field, Jennifer A; Furlong, Edward T; Giesy, John P; Halden, Rolf U; Henry, Tala; Hites, Ronald A; Hornbuckle, Keri C; Howard, Philip H; Luthy, Richard G; Meyer, Anita K; Sáez, A Eduardo; Vom Saal, Frederick S; Vulpe, Chris D; Wiesner, Mark R

2011-01-01

This commentary evolved from a workshop sponsored by the National Institute of Environmental Health Sciences titled "Superfund Contaminants: The Next Generation" held in Tucson, Arizona, in August 2009. All the authors were workshop participants. Our aim was to initiate a dynamic, adaptable process for identifying contaminants of emerging concern (CECs) that are likely to be found in future hazardous waste sites, and to identify the gaps in primary research that cause uncertainty in determining future hazardous waste site contaminants. Superfund-relevant CECs can be characterized by specific attributes: They are persistent, bioaccumulative, toxic, occur in large quantities, and have localized accumulation with a likelihood of exposure. Although still under development and incompletely applied, methods to quantify these attributes can assist in winnowing down the list of candidates from the universe of potential CECs. Unfortunately, significant research gaps exist in detection and quantification, environmental fate and transport, health and risk assessment, and site exploration and remediation for CECs. Addressing these gaps is prerequisite to a preventive approach to generating and managing hazardous waste sites. A need exists for a carefully considered and orchestrated expansion of programmatic and research efforts to identify, evaluate, and manage CECs of hazardous waste site relevance, including developing an evolving list of priority CECs, intensifying the identification and monitoring of likely sites of present or future accumulation of CECs, and implementing efforts that focus on a holistic approach to prevention.

Coupling of link- and node-ordering in the coevolving voter model.

PubMed

Toruniewska, J; Kułakowski, K; Suchecki, K; Hołyst, J A

2017-10-01

We consider the process of reaching the final state in the coevolving voter model. There is a coevolution of state dynamics, where a node can copy a state from a random neighbor with probabilty 1-p and link dynamics, where a node can rewire its link to another node of the same state with probability p. That exhibits an absorbing transition to a frozen phase above a critical value of rewiring probability. Our analytical and numerical studies show that in the active phase mean values of magnetization of nodes n and links m tend to the same value that depends on initial conditions. In a similar way mean degrees of spins up and spins down become equal. The system obeys a special statistical conservation law since a linear combination of both types magnetizations averaged over many realizations starting from the same initial conditions is a constant of motion: Λ≡(1-p)μm(t)+pn(t)=const., where μ is the mean node degree. The final mean magnetization of nodes and links in the active phase is proportional to Λ while the final density of active links is a square function of Λ. If the rewiring probability is above a critical value and the system separates into disconnected domains, then the values of nodes and links magnetizations are not the same and final mean degrees of spins up and spins down can be different.

Under What Assumptions Do Site-by-Treatment Instruments Identify Average Causal Effects?

ERIC Educational Resources Information Center

Reardon, Sean F.; Raudenbush, Stephen W.

2013-01-01

The increasing availability of data from multi-site randomized trials provides a potential opportunity to use instrumental variables methods to study the effects of multiple hypothesized mediators of the effect of a treatment. We derive nine assumptions needed to identify the effects of multiple mediators when using site-by-treatment interactions…

Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA

PubMed Central

Ashenberg, Orr; Padmakumar, Jai

2017-01-01

The innate-immune restriction factor MxA inhibits influenza replication by targeting the viral nucleoprotein (NP). Human influenza virus is more resistant than avian influenza virus to inhibition by human MxA, and prior work has compared human and avian viral strains to identify amino-acid differences in NP that affect sensitivity to MxA. However, this strategy is limited to identifying sites in NP where mutations that affect MxA sensitivity have fixed during the small number of documented zoonotic transmissions of influenza to humans. Here we use an unbiased deep mutational scanning approach to quantify how all single amino-acid mutations to NP affect MxA sensitivity in the context of replication-competent virus. We both identify new sites in NP where mutations affect MxA resistance and re-identify mutations known to have increased MxA resistance during historical adaptations of influenza to humans. Most of the sites where mutations have the greatest effect are almost completely conserved across all influenza A viruses, and the amino acids at these sites confer relatively high resistance to MxA. These sites cluster in regions of NP that appear to be important for its recognition by MxA. Overall, our work systematically identifies the sites in influenza nucleoprotein where mutations affect sensitivity to MxA. We also demonstrate a powerful new strategy for identifying regions of viral proteins that affect inhibition by host factors. PMID:28346537

Under What Assumptions Do Site-by-Treatment Instruments Identify Average Causal Effects?

ERIC Educational Resources Information Center

Reardon, Sean F.; Raudenbush, Stephen W.

2011-01-01

The purpose of this paper is to clarify the assumptions that must be met if this--multiple site, multiple mediator--strategy, hereafter referred to as "MSMM," is to identify the average causal effects (ATE) in the populations of interest. The authors' investigation of the assumptions of the multiple-mediator, multiple-site IV model demonstrates…

Towards identifying the next generation of superfund and hazardous waste site contaminants

USGS Publications Warehouse

Ela, Wendell P.; Sedlak, David L.; Barlaz, Morton A.; Henry, Heather F.; Muir, Derek C.G.; Swackhamer, Deborah L.; Weber, Eric J.; Arnold, Robert G.; Ferguson, P. Lee; Field, Jennifer A.; Furlong, Edward T.; Giesy, John P.; Halden, Rolf U.; Henry, Tala; Hites, Ronald A.; Hornbuckle, Keri C.; Howard, Philip H.; Luthy, Richard G.; Meyer, Anita K.; Saez, A. Eduardo; vom Saal, Frederick S.; Vulpe, Chris D.; Wiesner, Mark R.

2011-01-01

Conclusions A need exists for a carefully considered and orchestrated expansion of programmatic and research efforts to identify, evaluate, and manage CECs of hazardous waste site relevance, including developing an evolving list of priority CECs, intensifying the identification and monitoring of likely sites of present or future accumulation of CECs, and implementing efforts that focus on a holistic approach to prevention.

Common Viral Integration Sites Identified in Avian Leukosis Virus-Induced B-Cell Lymphomas

PubMed Central

Justice, James F.; Morgan, Robin W.

2015-01-01

ABSTRACT Avian leukosis virus (ALV) induces B-cell lymphoma and other neoplasms in chickens by integrating within or near cancer genes and perturbing their expression. Four genes—MYC, MYB, Mir-155, and TERT—have previously been identified as common integration sites in these virus-induced lymphomas and are thought to play a causal role in tumorigenesis. In this study, we employ high-throughput sequencing to identify additional genes driving tumorigenesis in ALV-induced B-cell lymphomas. In addition to the four genes implicated previously, we identify other genes as common integration sites, including TNFRSF1A, MEF2C, CTDSPL, TAB2, RUNX1, MLL5, CXorf57, and BACH2. We also analyze the genome-wide ALV integration landscape in vivo and find increased frequency of ALV integration near transcriptional start sites and within transcripts. Previous work has shown ALV prefers a weak consensus sequence for integration in cultured human cells. We confirm this consensus sequence for ALV integration in vivo in the chicken genome. PMID:26670384

Identifying potential kidney donors using social networking web sites.

PubMed

Chang, Alexander; Anderson, Emily E; Turner, Hang T; Shoham, David; Hou, Susan H; Grams, Morgan

2013-01-01

Social networking sites like Facebook may be a powerful tool for increasing rates of live kidney donation. They allow for wide dissemination of information and discussion and could lessen anxiety associated with a face-to-face request for donation. However, sparse data exist on the use of social media for this purpose. We searched Facebook, the most popular social networking site, for publicly available English-language pages seeking kidney donors for a specific individual, abstracting information on the potential recipient, characteristics of the page itself, and whether potential donors were tested. In the 91 pages meeting inclusion criteria, the mean age of potential recipients was 37 (range: 2-69); 88% were US residents. Other posted information included the individual's photograph (76%), blood type (64%), cause of kidney disease (43%), and location (71%). Thirty-two percent of pages reported having potential donors tested, and 10% reported receiving a live-donor kidney transplant. Those reporting donor testing shared more potential recipient characteristics, provided more information about transplantation, and had higher page traffic. Facebook is already being used to identify potential kidney donors. Future studies should focus on how to safely, ethically, and effectively use social networking sites to inform potential donors and potentially expand live kidney donation. © 2013 John Wiley & Sons A/S.

Comparative phylogeography of a coevolved community: concerted population expansions in Joshua trees and four yucca moths

USGS Publications Warehouse

Smith, Christopher Irwin; Tank, Shantel; Godsoe, William; Levenick, Jim; Strand, Eva; Esque, Todd C.; Pellmyr, Olle

2011-01-01

Comparative phylogeographic studies have had mixed success in identifying common phylogeographic patterns among co-distributed organisms. Whereas some have found broadly similar patterns across a diverse array of taxa, others have found that the histories of different species are more idiosyncratic than congruent. The variation in the results of comparative phylogeographic studies could indicate that the extent to which sympatrically-distributed organisms share common biogeographic histories varies depending on the strength and specificity of ecological interactions between them. To test this hypothesis, we examined demographic and phylogeographic patterns in a highly specialized, coevolved community – Joshua trees (Yucca brevifolia) and their associated yucca moths. This tightly-integrated, mutually interdependent community is known to have experienced significant range changes at the end of the last glacial period, so there is a strong a priori expectation that these organisms will show common signatures of demographic and distributional changes over time. Using a database of >5000 GPS records for Joshua trees, and multi-locus DNA sequence data from the Joshua tree and four species of yucca moth, we combined paleaodistribution modeling with coalescent-based analyses of demographic and phylgeographic history. We extensively evaluated the power of our methods to infer past population size and distributional changes by evaluating the effect of different inference procedures on our results, comparing our palaeodistribution models to Pleistocene-aged packrat midden records, and simulating DNA sequence data under a variety of alternative demographic histories. Together the results indicate that these organisms have shared a common history of population expansion, and that these expansions were broadly coincident in time. However, contrary to our expectations, none of our analyses indicated significant range or population size reductions at the end of the last glacial

Comparative phylogeography of a coevolved community: Concerted population expansions in Joshua trees and four Yucca moths

USGS Publications Warehouse

Smith, C.I.; Tank, S.; Godsoe, W.; Levenick, J.; Strand, Espen; Esque, T.; Pellmyr, O.

2011-01-01

Comparative phylogeographic studies have had mixed success in identifying common phylogeographic patterns among co-distributed organisms. Whereas some have found broadly similar patterns across a diverse array of taxa, others have found that the histories of different species are more idiosyncratic than congruent. The variation in the results of comparative phylogeographic studies could indicate that the extent to which sympatrically-distributed organisms share common biogeographic histories varies depending on the strength and specificity of ecological interactions between them. To test this hypothesis, we examined demographic and phylogeographic patterns in a highly specialized, coevolved community - Joshua trees (Yucca brevifolia) and their associated yucca moths. This tightly-integrated, mutually interdependent community is known to have experienced significant range changes at the end of the last glacial period, so there is a strong a priori expectation that these organisms will show common signatures of demographic and distributional changes over time. Using a database of >5000 GPS records for Joshua trees, and multi-locus DNA sequence data from the Joshua tree and four species of yucca moth, we combined paleaodistribution modeling with coalescent-based analyses of demographic and phylgeographic history. We extensively evaluated the power of our methods to infer past population size and distributional changes by evaluating the effect of different inference procedures on our results, comparing our palaeodistribution models to Pleistocene-aged packrat midden records, and simulating DNA sequence data under a variety of alternative demographic histories. Together the results indicate that these organisms have shared a common history of population expansion, and that these expansions were broadly coincident in time. However, contrary to our expectations, none of our analyses indicated significant range or population size reductions at the end of the last glacial

Comparative Phylogeography of a Coevolved Community: Concerted Population Expansions in Joshua Trees and Four Yucca Moths

PubMed Central

Smith, Christopher Irwin; Tank, Shantel; Godsoe, William; Levenick, Jim; Strand, Eva; Esque, Todd; Pellmyr, Olle

2011-01-01

Comparative phylogeographic studies have had mixed success in identifying common phylogeographic patterns among co-distributed organisms. Whereas some have found broadly similar patterns across a diverse array of taxa, others have found that the histories of different species are more idiosyncratic than congruent. The variation in the results of comparative phylogeographic studies could indicate that the extent to which sympatrically-distributed organisms share common biogeographic histories varies depending on the strength and specificity of ecological interactions between them. To test this hypothesis, we examined demographic and phylogeographic patterns in a highly specialized, coevolved community – Joshua trees (Yucca brevifolia) and their associated yucca moths. This tightly-integrated, mutually interdependent community is known to have experienced significant range changes at the end of the last glacial period, so there is a strong a priori expectation that these organisms will show common signatures of demographic and distributional changes over time. Using a database of >5000 GPS records for Joshua trees, and multi-locus DNA sequence data from the Joshua tree and four species of yucca moth, we combined paleaodistribution modeling with coalescent-based analyses of demographic and phylgeographic history. We extensively evaluated the power of our methods to infer past population size and distributional changes by evaluating the effect of different inference procedures on our results, comparing our palaeodistribution models to Pleistocene-aged packrat midden records, and simulating DNA sequence data under a variety of alternative demographic histories. Together the results indicate that these organisms have shared a common history of population expansion, and that these expansions were broadly coincident in time. However, contrary to our expectations, none of our analyses indicated significant range or population size reductions at the end of the last glacial

MONKEY: Identifying conserved transcription-factor binding sitesin multiple alignments using a binding site-specific evolutionarymodel

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

Moses, Alan M.; Chiang, Derek Y.; Pollard, Daniel A.

2004-10-28

We introduce a method (MONKEY) to identify conserved transcription-factor binding sites in multispecies alignments. MONKEY employs probabilistic models of factor specificity and binding site evolution, on which basis we compute the likelihood that putative sites are conserved and assign statistical significance to each hit. Using genomes from the genus Saccharomyces, we illustrate how the significance of real sites increases with evolutionary distance and explore the relationship between conservation and function.

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.

A Novel Proteomics Approach to Identify SUMOylated Proteins and Their Modification Sites in Human Cells*

PubMed Central

Galisson, Frederic; Mahrouche, Louiza; Courcelles, Mathieu; Bonneil, Eric; Meloche, Sylvain; Chelbi-Alix, Mounira K.; Thibault, Pierre

2011-01-01

The small ubiquitin-related modifier (SUMO) is a small group of proteins that are reversibly attached to protein substrates to modify their functions. The large scale identification of protein SUMOylation and their modification sites in mammalian cells represents a significant challenge because of the relatively small number of in vivo substrates and the dynamic nature of this modification. We report here a novel proteomics approach to selectively enrich and identify SUMO conjugates from human cells. We stably expressed different SUMO paralogs in HEK293 cells, each containing a His6 tag and a strategically located tryptic cleavage site at the C terminus to facilitate the recovery and identification of SUMOylated peptides by affinity enrichment and mass spectrometry. Tryptic peptides with short SUMO remnants offer significant advantages in large scale SUMOylome experiments including the generation of paralog-specific fragment ions following CID and ETD activation, and the identification of modified peptides using conventional database search engines such as Mascot. We identified 205 unique protein substrates together with 17 precise SUMOylation sites present in 12 SUMO protein conjugates including three new sites (Lys-380, Lys-400, and Lys-497) on the protein promyelocytic leukemia. Label-free quantitative proteomics analyses on purified nuclear extracts from untreated and arsenic trioxide-treated cells revealed that all identified SUMOylated sites of promyelocytic leukemia were differentially SUMOylated upon stimulation. PMID:21098080

Identifying Service Delivery Strategies for Ethnically Diverse Users of a Wildland-Urban Recreation Site

Treesearch

John M. Baas

1992-01-01

Service delivery has become an increasingly important part of managing public lands for recreation. The range of preferences held by ethnically diverse users of recreation sites may warrant the development of more than one service delivery strategy. Two questions were examined: (1) Are there differences in site perceptions that can be identified on the basis on...

Role of social environment and social clustering in spread of opinions in coevolving networks.

PubMed

Malik, Nishant; Mucha, Peter J

2013-12-01

Taking a pragmatic approach to the processes involved in the phenomena of collective opinion formation, we investigate two specific modifications to the coevolving network voter model of opinion formation studied by Holme and Newman [Phys. Rev. E 74, 056108 (2006)]. First, we replace the rewiring probability parameter by a distribution of probability of accepting or rejecting opinions between individuals, accounting for heterogeneity and asymmetric influences in relationships between individuals. Second, we modify the rewiring step by a path-length-based preference for rewiring that reinforces local clustering. We have investigated the influences of these modifications on the outcomes of simulations of this model. We found that varying the shape of the distribution of probability of accepting or rejecting opinions can lead to the emergence of two qualitatively distinct final states, one having several isolated connected components each in internal consensus, allowing for the existence of diverse opinions, and the other having a single dominant connected component with each node within that dominant component having the same opinion. Furthermore, more importantly, we found that the initial clustering in the network can also induce similar transitions. Our investigation also indicates that these transitions are governed by a weak and complex dependence on system size. We found that the networks in the final states of the model have rich structural properties including the small world property for some parameter regimes.

Identifying diabetes knowledge network nodes as sites for a diabetes prevention program.

PubMed

Gesler, Wilbert M; Arcury, Thomas A; Skelly, Anne H; Nash, Sally; Soward, April; Dougherty, Molly

2006-12-01

This paper reports on the methods used and results of a study that identified specific places within a community that have the potential to be sites for a diabetes prevention program. These sites, termed diabetes knowledge network nodes (DKNNs), are based on the concept of socio-spatial knowledge networks (SSKNs), the web of social relationships within which people obtain knowledge about type 2 diabetes. The target population for the study was working poor African Americans, Latinos, and European Americans of both sexes in a small rural southern town who had not been diagnosed with diabetes. Information was collected from a sample of 121 respondents on the places they visited in carrying out their daily activities. Data on number of visits to specific sites, degree of familiarity with these sites, and ratings of sites as places to receive diabetes information were used to develop three categories of DKNNs for six subgroups based on ethnicity and sex. Primary potential sites of importance to one or more subgroups included churches, grocery stores, drugstores, the local library, a beauty salon, laundromats, a community service agency, and a branch of the County Health Department. Secondary potential sites included gas stations, restaurants, banks, and post offices. Latent potential sites included three medical facilities. Most of the DKNNs were located either in the downtown area or in one of two shopping areas along the most used highway that passed through the town. The procedures used in this study can be generalized to other communities and prevention programs for other chronic diseases.

iSS-PC: Identifying Splicing Sites via Physical-Chemical Properties Using Deep Sparse Auto-Encoder.

PubMed

Xu, Zhao-Chun; Wang, Peng; Qiu, Wang-Ren; Xiao, Xuan

2017-08-15

Gene splicing is one of the most significant biological processes in eukaryotic gene expression, such as RNA splicing, which can cause a pre-mRNA to produce one or more mature messenger RNAs containing the coded information with multiple biological functions. Thus, identifying splicing sites in DNA/RNA sequences is significant for both the bio-medical research and the discovery of new drugs. However, it is expensive and time consuming based only on experimental technique, so new computational methods are needed. To identify the splice donor sites and splice acceptor sites accurately and quickly, a deep sparse auto-encoder model with two hidden layers, called iSS-PC, was constructed based on minimum error law, in which we incorporated twelve physical-chemical properties of the dinucleotides within DNA into PseDNC to formulate given sequence samples via a battery of cross-covariance and auto-covariance transformations. In this paper, five-fold cross-validation test results based on the same benchmark data-sets indicated that the new predictor remarkably outperformed the existing prediction methods in this field. Furthermore, it is expected that many other related problems can be also studied by this approach. To implement classification accurately and quickly, an easy-to-use web-server for identifying slicing sites has been established for free access at: http://www.jci-bioinfo.cn/iSS-PC.

Identifying 5-methylcytosine sites in RNA sequence using composite encoding feature into Chou's PseKNC.

PubMed

Sabooh, M Fazli; Iqbal, Nadeem; Khan, Mukhtaj; Khan, Muslim; Maqbool, H F

2018-05-01

This study examines accurate and efficient computational method for identification of 5-methylcytosine sites in RNA modification. The occurrence of 5-methylcytosine (m 5 C) plays a vital role in a number of biological processes. For better comprehension of the biological functions and mechanism it is necessary to recognize m 5 C sites in RNA precisely. The laboratory techniques and procedures are available to identify m 5 C sites in RNA, but these procedures require a lot of time and resources. This study develops a new computational method for extracting the features of RNA sequence. In this method, first the RNA sequence is encoded via composite feature vector, then, for the selection of discriminate features, the minimum-redundancy-maximum-relevance algorithm was used. Secondly, the classification method used has been based on a support vector machine by using jackknife cross validation test. The suggested method efficiently identifies m 5 C sites from non- m 5 C sites and the outcome of the suggested algorithm is 93.33% with sensitivity of 90.0 and specificity of 96.66 on bench mark datasets. The result exhibits that proposed algorithm shown significant identification performance compared to the existing computational techniques. This study extends the knowledge about the occurrence sites of RNA modification which paves the way for better comprehension of the biological uses and mechanism. Copyright © 2018 Elsevier Ltd. All rights reserved.

Coevolution analysis of Hepatitis C virus genome to identify the structural and functional dependency network of viral proteins

NASA Astrophysics Data System (ADS)

Champeimont, Raphaël; Laine, Elodie; Hu, Shuang-Wei; Penin, Francois; Carbone, Alessandra

2016-05-01

A novel computational approach of coevolution analysis allowed us to reconstruct the protein-protein interaction network of the Hepatitis C Virus (HCV) at the residue resolution. For the first time, coevolution analysis of an entire viral genome was realized, based on a limited set of protein sequences with high sequence identity within genotypes. The identified coevolving residues constitute highly relevant predictions of protein-protein interactions for further experimental identification of HCV protein complexes. The method can be used to analyse other viral genomes and to predict the associated protein interaction networks.

Goldilocks and the three inorganic equilibria: how Earth's chemistry and life coevolve to be nearly in tune.

PubMed

Rickaby, R E M

2015-03-13

Life and the chemical environment are united in an inescapable feedback cycle. The periodic table of the elements essential for life has transformed over Earth's history, but, as today, evolved in tune with the elements available in abundance in the environment. The most revolutionary time in life's history was the advent and proliferation of oxygenic photosynthesis which forced the environment towards a greater degree of oxidation. Consideration of three inorganic chemical equilibria throughout this gradual oxygenation prescribes a phased release of trace metals to the environment, which appear to have coevolved with employment of these new chemicals by life. Evolution towards complexity was chemically constrained, and changes in availability of notably Fe, Zn and Cu paced the systematic development of complex organisms. Evolving life repeatedly catalysed its own chemical challenges via the unwitting release of new and initially toxic chemicals. Ultimately, the harnessing of these allowed life to advance to greater complexity, though the mechanism responsible for translating novel chemistry to heritable use remains elusive. Whether a chemical acts as a poison or a nutrient lies both in the dose and in its environmental history. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Host specificity, phenotype matching and the evolution of reproductive isolation in a coevolved plant-pollinator mutualism.

PubMed

Himler, Anna G; Machado, Carlos A

2009-12-01

Coevolutionary interactions between plants and their associated pollinators and seed dispersers are thought to have promoted the diversification of flowering plants (Raven 1977; Regal 1977; Stebbins 1981). The actual mechanisms by which pollinators could drive species diversification in plants are not fully understood. However, it is thought that pollinator host specialization can influence the evolution of reproductive isolation among plant populations because the pollinator's choice of host is what determines patterns of gene flow in its host plant, and host choice may also have important consequences on pollinator and host fitness (Grant 1949; Bawa 1992). In this issue of Molecular Ecology, Smith et al. (2009) present a very interesting study that addresses how host specialization affects pollinator fitness and patterns of gene flow in a plant host. Several aspects of this study match elements of a seminal mathematical model of plant-pollinator codivergence (Kiester et al. 1984) suggesting that reciprocal selection for matched plant and pollinator reproductive traits may lead to speciation in the host and its pollinator when there is strong host specialization and a pattern of geographic subdivision. Smith et al.'s study represents an important step to fill the gap in our understanding of how reciprocal selection may lead to speciation in coevolved plant-pollinator mutualisms.

GASS-WEB: a web server for identifying enzyme active sites based on genetic algorithms.

PubMed

Moraes, João P A; Pappa, Gisele L; Pires, Douglas E V; Izidoro, Sandro C

2017-07-03

Enzyme active sites are important and conserved functional regions of proteins whose identification can be an invaluable step toward protein function prediction. Most of the existing methods for this task are based on active site similarity and present limitations including performing only exact matches on template residues, template size restraints, despite not being capable of finding inter-domain active sites. To fill this gap, we proposed GASS-WEB, a user-friendly web server that uses GASS (Genetic Active Site Search), a method based on an evolutionary algorithm to search for similar active sites in proteins. GASS-WEB can be used under two different scenarios: (i) given a protein of interest, to match a set of specific active site templates; or (ii) given an active site template, looking for it in a database of protein structures. The method has shown to be very effective on a range of experiments and was able to correctly identify >90% of the catalogued active sites from the Catalytic Site Atlas. It also managed to achieve a Matthew correlation coefficient of 0.63 using the Critical Assessment of protein Structure Prediction (CASP 10) dataset. In our analysis, GASS was ranking fourth among 18 methods. GASS-WEB is freely available at http://gass.unifei.edu.br/. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Subcellular metal imaging identifies dynamic sites of Cu accumulation in Chlamydomonas

DOE PAGES

Hong-Hermesdorf, Anne; Miethke, Marcus; Gallaher, Sean D.; ...

2014-10-26

Here we identified a Cu-accumulating structure with a dynamic role in intracellular Cu homeostasis. During Zn limitation, Chlamydomonas reinhardtii hyperaccumulates Cu, a process dependent on the nutritional Cu sensor CRR1, but it is functionally Cu deficient. Visualization of intracellular Cu revealed major Cu accumulation sites coincident with electron-dense structures that stained positive for low pH and polyphosphate, suggesting that they are lysosome-related organelles. Nano-secondary ion MS showed colocalization of Ca and Cu, and X-ray absorption spectroscopy was consistent with Cu + accumulation in an ordered structure. Zn resupply restored Cu homeostasis concomitant with reduced abundance of these structures. Cu isotopemore » labeling demonstrated that sequestered Cu + became bioavailable for the synthesis of plastocyanin, and transcriptome profiling indicated that mobilized Cu became visible to CRR1. Cu trafficking to intracellular accumulation sites may be a strategy for preventing protein mismetallation during Zn deficiency and enabling efficient cuproprotein metallation or remetallation upon Zn resupply.« less

GSHSite: Exploiting an Iteratively Statistical Method to Identify S-Glutathionylation Sites with Substrate Specificity

PubMed Central

Chen, Yi-Ju; Lu, Cheng-Tsung; Huang, Kai-Yao; Wu, Hsin-Yi; Chen, Yu-Ju; Lee, Tzong-Yi

2015-01-01

S-glutathionylation, the covalent attachment of a glutathione (GSH) to the sulfur atom of cysteine, is a selective and reversible protein post-translational modification (PTM) that regulates protein activity, localization, and stability. Despite its implication in the regulation of protein functions and cell signaling, the substrate specificity of cysteine S-glutathionylation remains unknown. Based on a total of 1783 experimentally identified S-glutathionylation sites from mouse macrophages, this work presents an informatics investigation on S-glutathionylation sites including structural factors such as the flanking amino acids composition and the accessible surface area (ASA). TwoSampleLogo presents that positively charged amino acids flanking the S-glutathionylated cysteine may influence the formation of S-glutathionylation in closed three-dimensional environment. A statistical method is further applied to iteratively detect the conserved substrate motifs with statistical significance. Support vector machine (SVM) is then applied to generate predictive model considering the substrate motifs. According to five-fold cross-validation, the SVMs trained with substrate motifs could achieve an enhanced sensitivity, specificity, and accuracy, and provides a promising performance in an independent test set. The effectiveness of the proposed method is demonstrated by the correct identification of previously reported S-glutathionylation sites of mouse thioredoxin (TXN) and human protein tyrosine phosphatase 1b (PTP1B). Finally, the constructed models are adopted to implement an effective web-based tool, named GSHSite (http://csb.cse.yzu.edu.tw/GSHSite/), for identifying uncharacterized GSH substrate sites on the protein sequences. PMID:25849935

Evaluation of methods for identifying spawning sites and habitat selection for alosines

USGS Publications Warehouse

Harris, Julianne E.; Hightower, Joseph E.

2010-01-01

Characterization of riverine spawning habitat is important for the management and restoration of anadromous alosines. We examined the relative effectiveness of oblique plankton tows and spawning pads for collecting the eggs of American shad Alosa sapidissima, hickory shad A. mediocris, and “river herring” (a collective term for alewife A. pseudoharengus and blueback herring A. aestivalis) in the Roanoke River, North Carolina. Relatively nonadhesive American shad eggs were only collected by plankton tows, whereas semiadhesive hickory shad and river herring eggs were collected by both methods. Compared with spawning pads, oblique plankton tows had higher probabilities of collecting eggs and led to the identification of longer spawning periods. In assumed spawning areas, twice-weekly plankton sampling for 15 min throughout the spawning season had a 95% or greater probability of collecting at least one egg for all alosines; however, the probabilities were lower in areas with more limited spawning. Comparisons of plankton tows, spawning pads, and two other methods of identifying spawning habitat (direct observation of spawning and examination of female histology) suggested differences in effectiveness and efficiency. Riverwide information on spawning sites and timing for all alosines is most efficiently obtained by plankton sampling. Spawning pads and direct observations of spawning are the best ways to determine microhabitat selectivity for appropriate species, especially when spawning sites have previously been identified. Histological examination can help determine primary spawning sites but is most useful when information on reproductive biology and spawning periodicity is also desired. The target species, riverine habitat conditions, and research goals should be considered when selecting methods with which to evaluate alosine spawning habitat.

sc-PDB: a database for identifying variations and multiplicity of 'druggable' binding sites in proteins.

PubMed

Meslamani, Jamel; Rognan, Didier; Kellenberger, Esther

2011-05-01

The sc-PDB database is an annotated archive of druggable binding sites extracted from the Protein Data Bank. It contains all-atoms coordinates for 8166 protein-ligand complexes, chosen for their geometrical and physico-chemical properties. The sc-PDB provides a functional annotation for proteins, a chemical description for ligands and the detailed intermolecular interactions for complexes. The sc-PDB now includes a hierarchical classification of all the binding sites within a functional class. The sc-PDB entries were first clustered according to the protein name indifferent of the species. For each cluster, we identified dissimilar sites (e.g. catalytic and allosteric sites of an enzyme). SCOPE AND APPLICATIONS: The classification of sc-PDB targets by binding site diversity was intended to facilitate chemogenomics approaches to drug design. In ligand-based approaches, it avoids comparing ligands that do not share the same binding site. In structure-based approaches, it permits to quantitatively evaluate the diversity of the binding site definition (variations in size, sequence and/or structure). The sc-PDB database is freely available at: http://bioinfo-pharma.u-strasbg.fr/scPDB.

The influenza virus neuraminidase protein transmembrane and head domains have coevolved.

PubMed

da Silva, Diogo V; Nordholm, Johan; Dou, Dan; Wang, Hao; Rossman, Jeremy S; Daniels, Robert

2015-01-15

mutations. These mutations modify the intrinsic TMD assembly to restore the head domain folding compatibility and the resultant budding deficiency. This likely explains why the N1 TMDs have become more polar and suggests the N1 TMD and head domain have coevolved. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Time-saving impact of an algorithm to identify potential surgical site infections.

PubMed

Knepper, B C; Young, H; Jenkins, T C; Price, C S

2013-10-01

To develop and validate a partially automated algorithm to identify surgical site infections (SSIs) using commonly available electronic data to reduce manual chart review. Retrospective cohort study of patients undergoing specific surgical procedures over a 4-year period from 2007 through 2010 (algorithm development cohort) or over a 3-month period from January 2011 through March 2011 (algorithm validation cohort). A single academic safety-net hospital in a major metropolitan area. Patients undergoing at least 1 included surgical procedure during the study period. Procedures were identified in the National Healthcare Safety Network; SSIs were identified by manual chart review. Commonly available electronic data, including microbiologic, laboratory, and administrative data, were identified via a clinical data warehouse. Algorithms using combinations of these electronic variables were constructed and assessed for their ability to identify SSIs and reduce chart review. The most efficient algorithm identified in the development cohort combined microbiologic data with postoperative procedure and diagnosis codes. This algorithm resulted in 100% sensitivity and 85% specificity. Time savings from the algorithm was almost 600 person-hours of chart review. The algorithm demonstrated similar sensitivity on application to the validation cohort. A partially automated algorithm to identify potential SSIs was highly sensitive and dramatically reduced the amount of manual chart review required of infection control personnel during SSI surveillance.

Autonomous Agent-Based Systems and Their Applications in Fluid Dynamics, Particle Separation, and Co-evolving Networks

NASA Astrophysics Data System (ADS)

Graeser, Oliver

This thesis comprises three parts, reporting research results in Fluid Dynamics (Part I), Particle Separation (Part II) and Co-evolving Networks (Part III). Part I deals with the simulation of fluid dynamics using the lattice-Boltzmann method. Microfluidic devices often feature two-dimensional, repetitive arrays. Flows through such devices are pressure-driven and confined by solid walls. We have defined new adaptive generalised periodic boundary conditions to represent the effects of outer solid walls, and are thus able to exploit the periodicity of the array by simulating the flow through one unit cell in lieu of the entire device. The so-calculated fully developed flow describes the flow through the entire array accurately, but with computational requirements that are reduced according to the dimensions of the array. Part II discusses the problem of separating macromolecules like proteins or DNA coils. The reliable separation of such molecules is a crucial task in molecular biology. The use of Brownian ratchets as mechanisms for the separation of such particles has been proposed and discussed during the last decade. Pressure-driven flows have so far been dismissed as possible driving forces for Brownian ratchets, as they do not generate ratchet asymmetry. We propose a microfluidic design that uses pressure-driven flows to create asymmetry and hence allows particle separation. The dependence of the asymmetry on various factors of the microfluidic geometry is discussed. We further exemplify the feasibility of our approach using Brownian dynamics simulations of particles of different sizes in such a device. The results show that ratchet-based particle separation using flows as the driving force is possible. Simulation results and ratchet theory predictions are in excellent agreement. Part III deals with the co-evolution of networks and dynamic models. A group of agents occupies the nodes of a network, which defines the relationship between these agents. The

Identifying N6-methyladenosine sites using multi-interval nucleotide pair position specificity and support vector machine

NASA Astrophysics Data System (ADS)

Xing, Pengwei; Su, Ran; Guo, Fei; Wei, Leyi

2017-04-01

N6-methyladenosine (m6A) refers to methylation of the adenosine nucleotide acid at the nitrogen-6 position. It plays an important role in a series of biological processes, such as splicing events, mRNA exporting, nascent mRNA synthesis, nuclear translocation and translation process. Numerous experiments have been done to successfully characterize m6A sites within sequences since high-resolution mapping of m6A sites was established. However, as the explosive growth of genomic sequences, using experimental methods to identify m6A sites are time-consuming and expensive. Thus, it is highly desirable to develop fast and accurate computational identification methods. In this study, we propose a sequence-based predictor called RAM-NPPS for identifying m6A sites within RNA sequences, in which we present a novel feature representation algorithm based on multi-interval nucleotide pair position specificity, and use support vector machine classifier to construct the prediction model. Comparison results show that our proposed method outperforms the state-of-the-art predictors on three benchmark datasets across the three species, indicating the effectiveness and robustness of our method. Moreover, an online webserver implementing the proposed predictor has been established at http://server.malab.cn/RAM-NPPS/. It is anticipated to be a useful prediction tool to assist biologists to reveal the mechanisms of m6A site functions.

RED: A Java-MySQL Software for Identifying and Visualizing RNA Editing Sites Using Rule-Based and Statistical Filters.

PubMed

Sun, Yongmei; Li, Xing; Wu, Di; Pan, Qi; Ji, Yuefeng; Ren, Hong; Ding, Keyue

2016-01-01

RNA editing is one of the post- or co-transcriptional processes that can lead to amino acid substitutions in protein sequences, alternative pre-mRNA splicing, and changes in gene expression levels. Although several methods have been suggested to identify RNA editing sites, there remains challenges to be addressed in distinguishing true RNA editing sites from its counterparts on genome and technical artifacts. In addition, there lacks a software framework to identify and visualize potential RNA editing sites. Here, we presented a software - 'RED' (RNA Editing sites Detector) - for the identification of RNA editing sites by integrating multiple rule-based and statistical filters. The potential RNA editing sites can be visualized at the genome and the site levels by graphical user interface (GUI). To improve performance, we used MySQL database management system (DBMS) for high-throughput data storage and query. We demonstrated the validity and utility of RED by identifying the presence and absence of C→U RNA-editing sites experimentally validated, in comparison with REDItools, a command line tool to perform high-throughput investigation of RNA editing. In an analysis of a sample data-set with 28 experimentally validated C→U RNA editing sites, RED had sensitivity and specificity of 0.64 and 0.5. In comparison, REDItools had a better sensitivity (0.75) but similar specificity (0.5). RED is an easy-to-use, platform-independent Java-based software, and can be applied to RNA-seq data without or with DNA sequencing data. The package is freely available under the GPLv3 license at http://github.com/REDetector/RED or https://sourceforge.net/projects/redetector.

RED: A Java-MySQL Software for Identifying and Visualizing RNA Editing Sites Using Rule-Based and Statistical Filters

PubMed Central

Sun, Yongmei; Li, Xing; Wu, Di; Pan, Qi; Ji, Yuefeng; Ren, Hong; Ding, Keyue

2016-01-01

RNA editing is one of the post- or co-transcriptional processes that can lead to amino acid substitutions in protein sequences, alternative pre-mRNA splicing, and changes in gene expression levels. Although several methods have been suggested to identify RNA editing sites, there remains challenges to be addressed in distinguishing true RNA editing sites from its counterparts on genome and technical artifacts. In addition, there lacks a software framework to identify and visualize potential RNA editing sites. Here, we presented a software − ‘RED’ (RNA Editing sites Detector) − for the identification of RNA editing sites by integrating multiple rule-based and statistical filters. The potential RNA editing sites can be visualized at the genome and the site levels by graphical user interface (GUI). To improve performance, we used MySQL database management system (DBMS) for high-throughput data storage and query. We demonstrated the validity and utility of RED by identifying the presence and absence of C→U RNA-editing sites experimentally validated, in comparison with REDItools, a command line tool to perform high-throughput investigation of RNA editing. In an analysis of a sample data-set with 28 experimentally validated C→U RNA editing sites, RED had sensitivity and specificity of 0.64 and 0.5. In comparison, REDItools had a better sensitivity (0.75) but similar specificity (0.5). RED is an easy-to-use, platform-independent Java-based software, and can be applied to RNA-seq data without or with DNA sequencing data. The package is freely available under the GPLv3 license at http://github.com/REDetector/RED or https://sourceforge.net/projects/redetector. PMID:26930599

Identifying sites for elk restoration in Arkansas

USGS Publications Warehouse

Telesco, R.L.; Van Manen, F.T.; Clark, J.D.; Cartwright, Michael E.

2007-01-01

We used spatial data to identify potential areas for elk (Cervus elaphus) restoration in Arkansas. To assess habitat, we used locations of 239 elk groups collected from helicopter surveys in the Buffalo National River area of northwestern Arkansas, USA, from 1992 to 2002. We calculated the Mahalanobis distance (D2) statistic based on the relationship between those elk-group locations and a suite of 9 landscape variables to evaluate winter habitat in Arkansas. We tested model performance in the Buffalo National River area by comparing the D2 values of pixels representing areas with and without elk pellets along 19 fixed-width transects surveyed in March 2002. Pixels with elk scat had lower D2 values than pixels in which we found no pellets (logistic regression: Wald χ2 = 24.37, P < 0.001), indicating that habitat characteristics were similar to those selected by the aerially surveyed elk. Our D2 model indicated that the best elk habitat primarily occurred in northern and western Arkansas and was associated with areas of high landscape heterogeneity, heavy forest cover, gently sloping ridge tops and valleys, low human population density, and low road densities. To assess the potential for elk–human conflicts in Arkansas, we used the analytical hierarchy process to rank the importance of 8 criteria based on expert opinion from biologists involved in elk management. The biologists ranked availability of forage on public lands as having the strongest influence on the potential for elk–human conflict (33%), followed by human population growth rate (22%) and the amount of private land in row crops (18%). We then applied those rankings in a weighted linear summation to map the relative potential for elk–human conflict. Finally, we used white-tailed deer (Odocoileus virginianus) densities to identify areas where success of elk restoration may be hampered due to meningeal worm (Parelaphostrongylus tenuis) transmission. By combining results of the 3 spatial data layers

Challenges in identifying sites climatically matched to the native ranges of animal invaders.

PubMed

Rodda, Gordon H; Jarnevich, Catherine S; Reed, Robert N

2011-02-09

Species distribution models are often used to characterize a species' native range climate, so as to identify sites elsewhere in the world that may be climatically similar and therefore at risk of invasion by the species. This endeavor provoked intense public controversy over recent attempts to model areas at risk of invasion by the Indian Python (Python molurus). We evaluated a number of MaxEnt models on this species to assess MaxEnt's utility for vertebrate climate matching. Overall, we found MaxEnt models to be very sensitive to modeling choices and selection of input localities and background regions. As used, MaxEnt invoked minimal protections against data dredging, multi-collinearity of explanatory axes, and overfitting. As used, MaxEnt endeavored to identify a single ideal climate, whereas different climatic considerations may determine range boundaries in different parts of the native range. MaxEnt was extremely sensitive to both the choice of background locations for the python, and to selection of presence points: inclusion of just four erroneous localities was responsible for Pyron et al.'s conclusion that no additional portions of the U.S. mainland were at risk of python invasion. When used with default settings, MaxEnt overfit the realized climate space, identifying models with about 60 parameters, about five times the number of parameters justifiable when optimized on the basis of Akaike's Information Criterion. When used with default settings, MaxEnt may not be an appropriate vehicle for identifying all sites at risk of colonization. Model instability and dearth of protections against overfitting, multi-collinearity, and data dredging may combine with a failure to distinguish fundamental from realized climate envelopes to produce models of limited utility. A priori identification of biologically realistic model structure, combined with computational protections against these statistical problems, may produce more robust models of invasion risk.

Challenges in Identifying Sites Climatically Matched to the Native Ranges of Animal Invaders

PubMed Central

Rodda, Gordon H.; Jarnevich, Catherine S.; Reed, Robert N.

2011-01-01

Background Species distribution models are often used to characterize a species' native range climate, so as to identify sites elsewhere in the world that may be climatically similar and therefore at risk of invasion by the species. This endeavor provoked intense public controversy over recent attempts to model areas at risk of invasion by the Indian Python (Python molurus). We evaluated a number of MaxEnt models on this species to assess MaxEnt's utility for vertebrate climate matching. Methodology/Principal Findings Overall, we found MaxEnt models to be very sensitive to modeling choices and selection of input localities and background regions. As used, MaxEnt invoked minimal protections against data dredging, multi-collinearity of explanatory axes, and overfitting. As used, MaxEnt endeavored to identify a single ideal climate, whereas different climatic considerations may determine range boundaries in different parts of the native range. MaxEnt was extremely sensitive to both the choice of background locations for the python, and to selection of presence points: inclusion of just four erroneous localities was responsible for Pyron et al.'s conclusion that no additional portions of the U.S. mainland were at risk of python invasion. When used with default settings, MaxEnt overfit the realized climate space, identifying models with about 60 parameters, about five times the number of parameters justifiable when optimized on the basis of Akaike's Information Criterion. Conclusions/Significance When used with default settings, MaxEnt may not be an appropriate vehicle for identifying all sites at risk of colonization. Model instability and dearth of protections against overfitting, multi-collinearity, and data dredging may combine with a failure to distinguish fundamental from realized climate envelopes to produce models of limited utility. A priori identification of biologically realistic model structure, combined with computational protections against these

Challenges in identifying sites climatically matched to the native ranges of animal invaders

USGS Publications Warehouse

Rodda, G.H.; Jarnevich, C.S.; Reed, R.N.

2011-01-01

Background: Species distribution models are often used to characterize a species' native range climate, so as to identify sites elsewhere in the world that may be climatically similar and therefore at risk of invasion by the species. This endeavor provoked intense public controversy over recent attempts to model areas at risk of invasion by the Indian Python (Python molurus). We evaluated a number of MaxEnt models on this species to assess MaxEnt's utility for vertebrate climate matching. Methodology/Principal Findings: Overall, we found MaxEnt models to be very sensitive to modeling choices and selection of input localities and background regions. As used, MaxEnt invoked minimal protections against data dredging, multi-collinearity of explanatory axes, and overfitting. As used, MaxEnt endeavored to identify a single ideal climate, whereas different climatic considerations may determine range boundaries in different parts of the native range. MaxEnt was extremely sensitive to both the choice of background locations for the python, and to selection of presence points: inclusion of just four erroneous localities was responsible for Pyron et al.'s conclusion that no additional portions of the U.S. mainland were at risk of python invasion. When used with default settings, MaxEnt overfit the realized climate space, identifying models with about 60 parameters, about five times the number of parameters justifiable when optimized on the basis of Akaike's Information Criterion. Conclusions/Significance: When used with default settings, MaxEnt may not be an appropriate vehicle for identifying all sites at risk of colonization. Model instability and dearth of protections against overfitting, multi-collinearity, and data dredging may combine with a failure to distinguish fundamental from realized climate envelopes to produce models of limited utility. A priori identification of biologically realistic model structure, combined with computational protections against these

Splice-site mutations identified in PDE6A responsible for retinitis pigmentosa in consanguineous Pakistani families

PubMed Central

Khan, Shahid Y.; Ali, Shahbaz; Naeem, Muhammad Asif; Khan, Shaheen N.; Husnain, Tayyab; Butt, Nadeem H.; Qazi, Zaheeruddin A.; Akram, Javed; Riazuddin, Sheikh; Ayyagari, Radha; Hejtmancik, J. Fielding

2015-01-01

Purpose This study was conducted to localize and identify causal mutations associated with autosomal recessive retinitis pigmentosa (RP) in consanguineous familial cases of Pakistani origin. Methods Ophthalmic examinations that included funduscopy and electroretinography (ERG) were performed to confirm the affectation status. Blood samples were collected from all participating individuals, and genomic DNA was extracted. A genome-wide scan was performed, and two-point logarithm of odds (LOD) scores were calculated. Sanger sequencing was performed to identify the causative variants. Subsequently, we performed whole exome sequencing to rule out the possibility of a second causal variant within the linkage interval. Sequence conservation was performed with alignment analyses of PDE6A orthologs, and in silico splicing analysis was completed with Human Splicing Finder version 2.4.1. Results A large multigenerational consanguineous family diagnosed with early-onset RP was ascertained. An ophthalmic clinical examination consisting of fundus photography and electroretinography confirmed the diagnosis of RP. A genome-wide scan was performed, and suggestive two-point LOD scores were observed with markers on chromosome 5q. Haplotype analyses identified the region; however, the region did not segregate with the disease phenotype in the family. Subsequently, we performed a second genome-wide scan that excluded the entire genome except the chromosome 5q region harboring PDE6A. Next-generation whole exome sequencing identified a splice acceptor site mutation in intron 16: c.2028–1G>A, which was completely conserved in PDE6A orthologs and was absent in ethnically matched 350 control chromosomes, the 1000 Genomes database, and the NHLBI Exome Sequencing Project. Subsequently, we investigated our entire cohort of RP familial cases and identified a second family who harbored a splice acceptor site mutation in intron 10: c.1408–2A>G. In silico analysis suggested that these

How the indirect reciprocity with co-evolving norm and strategy for 2 × 2 prisoner's dilemma game works for emerging cooperation

NASA Astrophysics Data System (ADS)

Tanimoto, Jun; Sagara, Hirokji

2015-11-01

We built a new indirect reciprocity model based on binary image scores, where an agent's strategy and norm co-evolve. The norm, meaning what behavior is evaluated as "good" or "bad," stipulates how image scores of two agents playing a game is altered, which has been presumed to be a fixed value in most previous studies. Also, unlike former studies, our model allows an agent to play with an agent who has a different norm. This point of relaxing the freedom of the model pulls down cooperation level vis-à-vis the case where an agent always plays with another one having same norm. However, it is observed that a rather larger dilemma shows robust cooperation establishing compared with a smaller dilemma, since a norm that punishes a so-called second-order free-rider is prompted. To encourage the evolution of norms to be able to punish second-order free-riders, a society needs a small number of defectors. This is elucidated by the fact that cases with action error are more cooperative than those without action error.

Thin-Film Module Reverse-Bias Breakdown Sites Identified by Thermal Imaging

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

Johnston, Steven; Sulas, Dana; Guthrey, Harvey L

Thin-film module sections are stressed under reverse bias to simulate partial shading conditions. Such stresses can cause permanent damage in the form of 'wormlike' defects due to thermal runaway. When large reverse biases with limited current are applied to the cells, dark lock-in thermography (DLIT) can detect where spatially-localized breakdown initiates before thermal runaway leads to permanent damage. Predicted breakdown defect sites have been identified in both CIGS and CdTe modules using DLIT. These defects include small pinholes, craters, or voids in the absorber layer of the film that lead to built-in areas of weakness where high current densities maymore » cause thermal damage in a partial-shading event.« less

A Python Analytical Pipeline to Identify Prohormone Precursors and Predict Prohormone Cleavage Sites

PubMed Central

Southey, Bruce R.; Sweedler, Jonathan V.; Rodriguez-Zas, Sandra L.

2008-01-01

Neuropeptides and hormones are signaling molecules that support cell–cell communication in the central nervous system. Experimentally characterizing neuropeptides requires significant efforts because of the complex and variable processing of prohormone precursor proteins into neuropeptides and hormones. We demonstrate the power and flexibility of the Python language to develop components of an bioinformatic analytical pipeline to identify precursors from genomic data and to predict cleavage as these precursors are en route to the final bioactive peptides. We identified 75 precursors in the rhesus genome, predicted cleavage sites using support vector machines and compared the rhesus predictions to putative assignments based on homology to human sequences. The correct classification rate of cleavage using the support vector machines was over 97% for both human and rhesus data sets. The functionality of Python has been important to develop and maintain NeuroPred (http://neuroproteomics.scs.uiuc.edu/neuropred.html), a user-centered web application for the neuroscience community that provides cleavage site prediction from a wide range of models, precision and accuracy statistics, post-translational modifications, and the molecular mass of potential peptides. The combined results illustrate the suitability of the Python language to implement an all-inclusive bioinformatics approach to predict neuropeptides that encompasses a large number of interdependent steps, from scanning genomes for precursor genes to identification of potential bioactive neuropeptides. PMID:19169350

Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) identifies immune-selected HIV variants

DOE PAGES

Hraber, Peter; Korber, Bette; Wagh, Kshitij; ...

2015-10-21

Within-host genetic sequencing from samples collected over time provides a dynamic view of how viruses evade host immunity. Immune-driven mutations might stimulate neutralization breadth by selecting antibodies adapted to cycles of immune escape that generate within-subject epitope diversity. Comprehensive identification of immune-escape mutations is experimentally and computationally challenging. With current technology, many more viral sequences can readily be obtained than can be tested for binding and neutralization, making down-selection necessary. Typically, this is done manually, by picking variants that represent different time-points and branches on a phylogenetic tree. Such strategies are likely to miss many relevant mutations and combinations ofmore » mutations, and to be redundant for other mutations. Longitudinal Antigenic Sequences and Sites from Intrahost Evolution (LASSIE) uses transmitted founder loss to identify virus “hot-spots” under putative immune selection and chooses sequences that represent recurrent mutations in selected sites. LASSIE favors earliest sequences in which mutations arise. Here, with well-characterized longitudinal Env sequences, we confirmed selected sites were concentrated in antibody contacts and selected sequences represented diverse antigenic phenotypes. Finally, practical applications include rapidly identifying immune targets under selective pressure within a subject, selecting minimal sets of reagents for immunological assays that characterize evolving antibody responses, and for immunogens in polyvalent “cocktail” vaccines.« less

Co-Conserved MAPK Features Couple D-Domain Docking Groove to Distal Allosteric Sites via the C-Terminal Flanking Tail

PubMed Central

Nguyen, Tuan; Ruan, Zheng; Oruganty, Krishnadev; Kannan, Natarajan

2015-01-01

Mitogen activated protein kinases (MAPKs) form a closely related family of kinases that control critical pathways associated with cell growth and survival. Although MAPKs have been extensively characterized at the biochemical, cellular, and structural level, an integrated evolutionary understanding of how MAPKs differ from other closely related protein kinases is currently lacking. Here, we perform statistical sequence comparisons of MAPKs and related protein kinases to identify sequence and structural features associated with MAPK functional divergence. We show, for the first time, that virtually all MAPK-distinguishing sequence features, including an unappreciated short insert segment in the β4-β5 loop, physically couple distal functional sites in the kinase domain to the D-domain peptide docking groove via the C-terminal flanking tail (C-tail). The coupling mediated by MAPK-specific residues confers an allosteric regulatory mechanism unique to MAPKs. In particular, the regulatory αC-helix conformation is controlled by a MAPK-conserved salt bridge interaction between an arginine in the αC-helix and an acidic residue in the C-tail. The salt-bridge interaction is modulated in unique ways in individual sub-families to achieve regulatory specificity. Our study is consistent with a model in which the C-tail co-evolved with the D-domain docking site to allosterically control MAPK activity. Our study provides testable mechanistic hypotheses for biochemical characterization of MAPK-conserved residues and new avenues for the design of allosteric MAPK inhibitors. PMID:25799139

Computerized analysis of the 12-lead electrocardiogram to identify epicardial ventricular tachycardia exit sites.

PubMed

Yokokawa, Miki; Jung, Dae Yon; Joseph, Kim K; Hero, Alfred O; Morady, Fred; Bogun, Frank

2014-11-01

Twelve-lead electrocardiogram (ECG) criteria for epicardial ventricular tachycardia (VT) origins have been described. In patients with structural heart disease, the ability to predict an epicardial origin based on QRS morphology is limited and has been investigated only for limited regions in the heart. The purpose of this study was to determine whether a computerized algorithm is able to accurately differentiate epicardial vs endocardial origins of ventricular arrhythmias. Endocardial and epicardial pace-mapping were performed in 43 patients at 3277 sites. The 12-lead ECGs were digitized and analyzed using a mixture of gaussian model (MoG) to assess whether the algorithm was able to identify an epicardial vs endocardial origin of the paced rhythm. The MoG computerized algorithm was compared to algorithms published in prior reports. The computerized algorithm correctly differentiated epicardial vs endocardial pacing sites for 80% of the sites compared to an accuracy of 42% to 66% of other described criteria. The accuracy was higher in patients without structural heart disease than in those with structural heart disease (94% vs 80%, P = .0004) and for right bundle branch block (82%) compared to left bundle branch block morphologies (79%, P = .001). Validation studies showed the accuracy for VT exit sites to be 84%. A computerized algorithm was able to accurately differentiate the majority of epicardial vs endocardial pace-mapping sites. The algorithm is not region specific and performed best in patients without structural heart disease and with VTs having a right bundle branch block morphology. Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Application of ANS fluorescent probes to identify hydrophobic sites on the surface of DREAM.

PubMed

Gonzalez, Walter G; Miksovska, Jaroslava

2014-09-01

DREAM (calsenilin or KChIP-3) is a calcium sensor involved in regulation of diverse physiological processes by interactions with multiple intracellular partners including DNA, Kv4 channels, and presenilin, however the detailed mechanism of the recognition of the intracellular partners remains unclear. To identify the surface hydrophobic surfaces on apo and Ca(2+)DREAM as a possible interaction sites for target proteins and/or specific regulators of DREAM function the binding interactions of 1,8-ANS and 2,6-ANS with DREAM were characterized by fluorescence and docking studies. Emission intensity of ANS-DREAM complexes increases upon Ca(2+) association which is consistent with an overall decrease in surface polarity. The dissociation constants for ANS binding to apoDREAM and Ca(2+)DREAM were determined to be 195±20μM and 62±4μM, respectively. Fluorescence lifetime measurements indicate that two ANS molecules bind in two independent binding sites on DREAM monomer. One site is near the exiting helix of EF-4 and the second site is located in the hydrophobic crevice between EF-3 and EF-4. 1,8-ANS displacement studies using arachidonic acid demonstrate that the hydrophobic crevice between EF-3 and EF-4 serves as a binding site for fatty acids that modulate functional properties of Kv4 channel:KChIP complexes. Thus, the C-terminal hydrophobic crevice may be involved in DREAM interactions with small hydrophobic ligands as well as other intracellular proteins. Copyright © 2014 Elsevier B.V. All rights reserved.

Creatine kinase: Essential arginine residues at the nucleotide binding site identified by chemical modification and high-resolution tandem mass spectrometry

PubMed Central

Wood, Troy D.; Guan, Ziqiang; Borders, Charles L.; Chen, Lorenzo H.; Kenyon, George L.; McLafferty, Fred W.

1998-01-01

Phenylglyoxal is an arginine-specific reagent that inactivates creatine kinase (CK). Previous results suggest that modification of the dimeric enzyme at a single arginine residue per subunit causes complete inactivation accompanied by the loss of nucleotide binding; the actual site of modification was not identified. Here, high-resolution tandem mass spectrometry (MS/MS) was used to identify three phenylglyoxal-modified Arg residues in monomeric rabbit muscle CK. Electrospray ionizaton Fourier-transform MS of the phenylglyoxal-modified CK that had lost ≈80% activity identified three species: unmodified, once-modified (+116 Da), and twice-modified (+232 Da) enzyme in a ratio of approximately 1:4:1. MS/MS restricts the derivatized sites to P122-P212 and P283-V332, whereas MS of Lys-C digestions revealed two modified peptides, A266-K297 and G116-K137. The only Arg in A266-K297 is Arg-291 (invariant), whereas MS/MS of modified G116-K137 shows that two of the three sites Arg-129, Arg-131, or Arg-134 (all invariant) can contain the modification. The recently reported x-ray crystal structure for the octameric chicken mitochondrial CK indicates that its nucleotide triphosphate-binding site indeed contains the equivalent of R291, R129, and R131 reported here to be at the active site of rabbit muscle CK. PMID:9520370

Epigenetic priors for identifying active transcription factor binding sites.

PubMed

Cuellar-Partida, Gabriel; Buske, Fabian A; McLeay, Robert C; Whitington, Tom; Noble, William Stafford; Bailey, Timothy L

2012-01-01

Accurate knowledge of the genome-wide binding of transcription factors in a particular cell type or under a particular condition is necessary for understanding transcriptional regulation. Using epigenetic data such as histone modification and DNase I, accessibility data has been shown to improve motif-based in silico methods for predicting such binding, but this approach has not yet been fully explored. We describe a probabilistic method for combining one or more tracks of epigenetic data with a standard DNA sequence motif model to improve our ability to identify active transcription factor binding sites (TFBSs). We convert each data type into a position-specific probabilistic prior and combine these priors with a traditional probabilistic motif model to compute a log-posterior odds score. Our experiments, using histone modifications H3K4me1, H3K4me3, H3K9ac and H3K27ac, as well as DNase I sensitivity, show conclusively that the log-posterior odds score consistently outperforms a simple binary filter based on the same data. We also show that our approach performs competitively with a more complex method, CENTIPEDE, and suggest that the relative simplicity of the log-posterior odds scoring method makes it an appealing and very general method for identifying functional TFBSs on the basis of DNA and epigenetic evidence. FIMO, part of the MEME Suite software toolkit, now supports log-posterior odds scoring using position-specific priors for motif search. A web server and source code are available at http://meme.nbcr.net. Utilities for creating priors are at http://research.imb.uq.edu.au/t.bailey/SD/Cuellar2011. t.bailey@uq.edu.au Supplementary data are available at Bioinformatics online.

CORE_TF: a user-friendly interface to identify evolutionary conserved transcription factor binding sites in sets of co-regulated genes

PubMed Central

Hestand, Matthew S; van Galen, Michiel; Villerius, Michel P; van Ommen, Gert-Jan B; den Dunnen, Johan T; 't Hoen, Peter AC

2008-01-01

Background The identification of transcription factor binding sites is difficult since they are only a small number of nucleotides in size, resulting in large numbers of false positives and false negatives in current approaches. Computational methods to reduce false positives are to look for over-representation of transcription factor binding sites in a set of similarly regulated promoters or to look for conservation in orthologous promoter alignments. Results We have developed a novel tool, "CORE_TF" (Conserved and Over-REpresented Transcription Factor binding sites) that identifies common transcription factor binding sites in promoters of co-regulated genes. To improve upon existing binding site predictions, the tool searches for position weight matrices from the TRANSFACR database that are over-represented in an experimental set compared to a random set of promoters and identifies cross-species conservation of the predicted transcription factor binding sites. The algorithm has been evaluated with expression and chromatin-immunoprecipitation on microarray data. We also implement and demonstrate the importance of matching the random set of promoters to the experimental promoters by GC content, which is a unique feature of our tool. Conclusion The program CORE_TF is accessible in a user friendly web interface at . It provides a table of over-represented transcription factor binding sites in the users input genes' promoters and a graphical view of evolutionary conserved transcription factor binding sites. In our test data sets it successfully predicts target transcription factors and their binding sites. PMID:19036135

L-citrulline immunostaining identifies nitric oxide production sites within neurons

NASA Technical Reports Server (NTRS)

Martinelli, G. P. T.; Friedrich, V. L. Jr; Holstein, G. R.

2002-01-01

The cellular and subcellular localization of L-citrulline was analyzed in the adult rat brain and compared with that of traditional markers for the presence of nitric oxide synthase. Light, transmission electron, and confocal laser scanning microscopy were used to study tissue sections processed for immunocytochemistry employing a monoclonal antibody against L-citrulline or polyclonal anti-neuronal nitric oxide synthase sera, and double immunofluorescence to detect neuronal nitric oxide synthase and L-citrulline co-localization. The results demonstrate that the same CNS regions and cell types are labeled by neuronal nitric oxide synthase polyclonal antisera and L-citrulline monoclonal antibodies, using both immunocytochemistry and immunofluorescence. Short-term pretreatment with a nitric oxide synthase inhibitor reduces L-citrulline immunostaining, but does not affect neuronal nitric oxide synthase immunoreactivity. In the vestibular brainstem, double immunofluorescence studies show that many, but not all, neuronal nitric oxide synthase-positive cells co-express L-citrulline, and that local intracellular patches of intense L-citrulline accumulation are present in some neurons. Conversely, all L-citrulline-labeled neurons co-express neuronal nitric oxide synthase. Cells expressing neuronal nitric oxide synthase alone are interpreted as neurons with the potential to produce nitric oxide under other stimulus conditions, and the subcellular foci of enhanced L-citrulline staining are viewed as intracellular sites of nitric oxide production. This interpretation is supported by ultrastructural observations of subcellular foci with enhanced L-citrulline and/or neuronal nitric oxide synthase staining that are located primarily at postsynaptic densities and portions of the endoplasmic reticulum. We conclude that nitric oxide is produced and released at focal sites within neurons that are identifiable using L-citrulline as a marker. Copyright 2002 IBRO.

Dynamic motif occupancy (DynaMO) analysis identifies transcription factors and their binding sites driving dynamic biological processes

PubMed Central

Kuang, Zheng; Ji, Zhicheng

2018-01-01

Abstract Biological processes are usually associated with genome-wide remodeling of transcription driven by transcription factors (TFs). Identifying key TFs and their spatiotemporal binding patterns are indispensable to understanding how dynamic processes are programmed. However, most methods are designed to predict TF binding sites only. We present a computational method, dynamic motif occupancy analysis (DynaMO), to infer important TFs and their spatiotemporal binding activities in dynamic biological processes using chromatin profiling data from multiple biological conditions such as time-course histone modification ChIP-seq data. In the first step, DynaMO predicts TF binding sites with a random forests approach. Next and uniquely, DynaMO infers dynamic TF binding activities at predicted binding sites using their local chromatin profiles from multiple biological conditions. Another landmark of DynaMO is to identify key TFs in a dynamic process using a clustering and enrichment analysis of dynamic TF binding patterns. Application of DynaMO to the yeast ultradian cycle, mouse circadian clock and human neural differentiation exhibits its accuracy and versatility. We anticipate DynaMO will be generally useful for elucidating transcriptional programs in dynamic processes. PMID:29325176

Thin-Film Module Reverse-Bias Breakdown Sites Identified by Thermal Imaging: Preprint

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

Johnston, Steven; Sulas, Dana; Guthrey, Harvey L

Thin-film module sections are stressed under reverse bias to simulate partial shading conditions. Such stresses can cause permanent damage in the form of 'wormlike' defects due to thermal runaway. When large reverse biases with limited current are applied to the cells, dark lock-in thermography (DLIT) can detect where spatially-localized breakdown initiates before thermal runaway leads to permanent damage. Predicted breakdown defect sites have been identified in both CIGS and CdTe modules using DLIT. These defects include small pinholes, craters, or voids in the absorber layer of the film that lead to built-in areas of weakness where high current densities maymore » cause thermal damage in a partial-shading event.« less

Identifying bipolar knapping in the Mesolithic site of Font del Ros (northeast Iberia)

PubMed Central

Roda Gilabert, Xavier; Mora, Rafael; Martínez-Moreno, Jorge

2015-01-01

Despite recent advances in the identification of bipolar knapping, its role in many sites is not well known. We propose to assess the significance of this technique in the context of changes that occur in the Mesolithic. A lithic assemblage was recovered from unit SG at Font del Ros (Catalunya, Spain) in which pitted stones, cores and products arising from bipolar reduction (flakes, fragments and splintered pieces) were identified. This study indicates that the bipolar technique is fundamental in the settlement. These results are key to defining the organization of Holocene hunter-gatherer subsistence in northeast Iberia. PMID:26483532

Biological Characterization of an Improved Pyrrole-Based Colchicine Site Agent Identified through Structure-Based Design

PubMed Central

Rohena, Cristina C.; Telang, Nakul S.; Da, Chenxiao; Risinger, April L.; Sikorski, James A.; Kellogg, Glen E.; Gupton, John T.

2016-01-01

A refined model of the colchicine site on tubulin was used to design an improved analog of the pyrrole parent compound, JG-03-14. The optimized compound, NT-7-16, was evaluated in biological assays that confirm that it has potent activities as a new colchicine site microtubule depolymerizer. NT-7-16 exhibits antiproliferative and cytotoxic activities against multiple cancer cell lines, with IC50 values of 10–16 nM, and it is able to overcome drug resistance mediated by the expression of P-glycoprotein and the βIII isotype of tubulin. NT-7-16 initiated the concentration-dependent loss of cellular microtubules and caused the formation of abnormal mitotic spindles, leading to mitotic accumulation. The direct interaction of NT-7-16 with purified tubulin was confirmed, and it was more potent than combretastatin A-4 in these assays. Binding studies verified that NT-7-16 binds to tubulin within the colchicine site. The antitumor effects of NT-7-16 were evaluated in an MDA-MB-435 xenograft model and it had excellent activity at concentrations that were not toxic. A second compound, NT-9-21, which contains dichloro moieties in place of the 3,5-dibromo substituents of NT-7-16, had a poorer fit within the colchicine site as predicted by modeling and the Hydropathic INTeractions score. Biological evaluations showed that NT-9-21 has 10-fold lower potency than NT-7-16, confirming the modeling predictions. These studies highlight the value of the refined colchicine-site model and identify a new pyrrole-based colchicine-site agent with potent in vitro activities and promising in vivo antitumor actions. PMID:26655304

Dynamic motif occupancy (DynaMO) analysis identifies transcription factors and their binding sites driving dynamic biological processes.

PubMed

Kuang, Zheng; Ji, Zhicheng; Boeke, Jef D; Ji, Hongkai

2018-01-09

Biological processes are usually associated with genome-wide remodeling of transcription driven by transcription factors (TFs). Identifying key TFs and their spatiotemporal binding patterns are indispensable to understanding how dynamic processes are programmed. However, most methods are designed to predict TF binding sites only. We present a computational method, dynamic motif occupancy analysis (DynaMO), to infer important TFs and their spatiotemporal binding activities in dynamic biological processes using chromatin profiling data from multiple biological conditions such as time-course histone modification ChIP-seq data. In the first step, DynaMO predicts TF binding sites with a random forests approach. Next and uniquely, DynaMO infers dynamic TF binding activities at predicted binding sites using their local chromatin profiles from multiple biological conditions. Another landmark of DynaMO is to identify key TFs in a dynamic process using a clustering and enrichment analysis of dynamic TF binding patterns. Application of DynaMO to the yeast ultradian cycle, mouse circadian clock and human neural differentiation exhibits its accuracy and versatility. We anticipate DynaMO will be generally useful for elucidating transcriptional programs in dynamic processes. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Validation of Coevolving Residue Algorithms via Pipeline Sensitivity Analysis: ELSC and OMES and ZNMI, Oh My!

PubMed Central

Brown, Christopher A.; Brown, Kevin S.

2010-01-01

Correlated amino acid substitution algorithms attempt to discover groups of residues that co-fluctuate due to either structural or functional constraints. Although these algorithms could inform both ab initio protein folding calculations and evolutionary studies, their utility for these purposes has been hindered by a lack of confidence in their predictions due to hard to control sources of error. To complicate matters further, naive users are confronted with a multitude of methods to choose from, in addition to the mechanics of assembling and pruning a dataset. We first introduce a new pair scoring method, called ZNMI (Z-scored-product Normalized Mutual Information), which drastically improves the performance of mutual information for co-fluctuating residue prediction. Second and more important, we recast the process of finding coevolving residues in proteins as a data-processing pipeline inspired by the medical imaging literature. We construct an ensemble of alignment partitions that can be used in a cross-validation scheme to assess the effects of choices made during the procedure on the resulting predictions. This pipeline sensitivity study gives a measure of reproducibility (how similar are the predictions given perturbations to the pipeline?) and accuracy (are residue pairs with large couplings on average close in tertiary structure?). We choose a handful of published methods, along with ZNMI, and compare their reproducibility and accuracy on three diverse protein families. We find that (i) of the algorithms tested, while none appear to be both highly reproducible and accurate, ZNMI is one of the most accurate by far and (ii) while users should be wary of predictions drawn from a single alignment, considering an ensemble of sub-alignments can help to determine both highly accurate and reproducible couplings. Our cross-validation approach should be of interest both to developers and end users of algorithms that try to detect correlated amino acid substitutions

Positive Darwinian Selection in the Piston That Powers Proton Pumps in Complex I of the Mitochondria of Pacific Salmon

PubMed Central

Garvin, Michael R.; Bielawski, Joseph P.; Gharrett, Anthony J.

2011-01-01

The mechanism of oxidative phosphorylation is well understood, but evolution of the proteins involved is not. We combined phylogenetic, genomic, and structural biology analyses to examine the evolution of twelve mitochondrial encoded proteins of closely related, yet phenotypically diverse, Pacific salmon. Two separate analyses identified the same seven positively selected sites in ND5. A strong signal was also detected at three sites of ND2. An energetic coupling analysis revealed several structures in the ND5 protein that may have co-evolved with the selected sites. These data implicate Complex I, specifically the piston arm of ND5 where it connects the proton pumps, as important in the evolution of Pacific salmon. Lastly, the lineage to Chinook experienced rapid evolution at the piston arm. PMID:21969854

Positive Darwinian selection in the piston that powers proton pumps in complex I of the mitochondria of Pacific salmon.

PubMed

Garvin, Michael R; Bielawski, Joseph P; Gharrett, Anthony J

2011-01-01

The mechanism of oxidative phosphorylation is well understood, but evolution of the proteins involved is not. We combined phylogenetic, genomic, and structural biology analyses to examine the evolution of twelve mitochondrial encoded proteins of closely related, yet phenotypically diverse, Pacific salmon. Two separate analyses identified the same seven positively selected sites in ND5. A strong signal was also detected at three sites of ND2. An energetic coupling analysis revealed several structures in the ND5 protein that may have co-evolved with the selected sites. These data implicate Complex I, specifically the piston arm of ND5 where it connects the proton pumps, as important in the evolution of Pacific salmon. Lastly, the lineage to Chinook experienced rapid evolution at the piston arm.

Root disease and exotic ecosystems: implications for long-term site productivity

Treesearch

W.J. Otrosina; M. Garbelotto

1998-01-01

Root disease fungi, particularly root-rotting Basidiomycetes, are key drivers of forest ecosystems. These fungi have co?evolved with their hosts in various forest ecosystems and are in various states of equilibrium with them. Management activities and various land uses have taken place in recent times that have dramatically altered edaphic and environmental conditions...

Identifying the Tunneling Site in Strong-Field Ionization of H_{2}^{+}.

PubMed

Liu, Kunlong; Barth, Ingo

2017-12-15

The tunneling site of the electron in a molecule exposed to a strong laser field determines the initial position of the ionizing electron and, as a result, has a large impact on the subsequent ultrafast electron dynamics on the polyatomic Coulomb potential. Here, the tunneling site of the electron of H_{2}^{+} ionized by a strong circularly polarized (CP) laser pulse is studied by numerically solving the time-dependent Schrödinger equation. We show that the electron removed from the down-field site is directly driven away by the CP field and the lateral photoelectron momentum distribution (LPMD) exhibits a Gaussian-like distribution, whereas the corresponding LPMD of the electron removed from the up-field site differs from the Gaussian shape due to the Coulomb focusing and scattering by the down-field core. Our current study presents the direct evidence clarifying a long-standing controversy over the tunneling site in H_{2}^{+} and raises the important role of the tunneling site in strong-field molecular ionization.

Coevolved Mutations Reveal Distinct Architectures for Two Core Proteins in the Bacterial Flagellar Motor

PubMed Central

Pandini, Alessandro; Kleinjung, Jens; Rasool, Shafqat; Khan, Shahid

2015-01-01

Switching of bacterial flagellar rotation is caused by large domain movements of the FliG protein triggered by binding of the signal protein CheY to FliM. FliG and FliM form adjacent multi-subunit arrays within the basal body C-ring. The movements alter the interaction of the FliG C-terminal (FliGC) “torque” helix with the stator complexes. Atomic models based on the Salmonella entrovar C-ring electron microscopy reconstruction have implications for switching, but lack consensus on the relative locations of the FliG armadillo (ARM) domains (amino-terminal (FliGN), middle (FliGM) and FliGC) as well as changes during chemotaxis. The generality of the Salmonella model is challenged by the variation in motor morphology and response between species. We studied coevolved residue mutations to determine the unifying elements of switch architecture. Residue interactions, measured by their coevolution, were formalized as a network, guided by structural data. Our measurements reveal a common design with dedicated switch and motor modules. The FliM middle domain (FliMM) has extensive connectivity most simply explained by conserved intra and inter-subunit contacts. In contrast, FliG has patchy, complex architecture. Conserved structural motifs form interacting nodes in the coevolution network that wire FliMM to the FliGC C-terminal, four-helix motor module (C3-6). FliG C3-6 coevolution is organized around the torque helix, differently from other ARM domains. The nodes form separated, surface-proximal patches that are targeted by deleterious mutations as in other allosteric systems. The dominant node is formed by the EHPQ motif at the FliMMFliGM contact interface and adjacent helix residues at a central location within FliGM. The node interacts with nodes in the N-terminal FliGc α-helix triad (ARM-C) and FliGN. ARM-C, separated from C3-6 by the MFVF motif, has poor intra-network connectivity consistent with its variable orientation revealed by structural data. ARM-C could

Premature extravasation. A bleeding site identified during the dynamic phase of Tc-99m red blood cell bleeding scintigraphy.

PubMed

el-Shirbiny, A; Fernandez, R; Zuckier, L S

1995-08-01

Tc-99m RBC scintigraphy is favored by many investigators because it provides the ability to image the abdomen over a prolonged period of time, thereby allowing identification of delayed bleeding sites that are frequently encountered due to the intermittent nature of gastrointestinal bleeding. The authors describe a case of bleeding scintigraphy with labeled red blood cells in which the bleeding site was identifiable only on the dynamic blood-flow and first static images. On later images, the labeled blood cells had spread throughout the colon, rendering localization of the actual bleeding site impossible. Two previous red blood cell scintigraphies and a subsequent contrast angiogram did not reveal sites of active bleeding. As illustrated by this unusual case, factors governing timing and visualization of abnormal bleeding sites are discussed, as is a differential diagnosis of abnormal foci of activity seen on the dynamic phase of bleeding scintigraphy.

Detecting Coevolution in and among Protein Domains

PubMed Central

Yeang, Chen-Hsiang; Haussler, David

2007-01-01

Correlated changes of nucleic or amino acids have provided strong information about the structures and interactions of molecules. Despite the rich literature in coevolutionary sequence analysis, previous methods often have to trade off between generality, simplicity, phylogenetic information, and specific knowledge about interactions. Furthermore, despite the evidence of coevolution in selected protein families, a comprehensive screening of coevolution among all protein domains is still lacking. We propose an augmented continuous-time Markov process model for sequence coevolution. The model can handle different types of interactions, incorporate phylogenetic information and sequence substitution, has only one extra free parameter, and requires no knowledge about interaction rules. We employ this model to large-scale screenings on the entire protein domain database (Pfam). Strikingly, with 0.1 trillion tests executed, the majority of the inferred coevolving protein domains are functionally related, and the coevolving amino acid residues are spatially coupled. Moreover, many of the coevolving positions are located at functionally important sites of proteins/protein complexes, such as the subunit linkers of superoxide dismutase, the tRNA binding sites of ribosomes, the DNA binding region of RNA polymerase, and the active and ligand binding sites of various enzymes. The results suggest sequence coevolution manifests structural and functional constraints of proteins. The intricate relations between sequence coevolution and various selective constraints are worth pursuing at a deeper level. PMID:17983264

Using the Textpresso Site-Specific Recombinases Web server to identify Cre expressing mouse strains and floxed alleles.

PubMed

Condie, Brian G; Urbanski, William M

2014-01-01

Effective tools for searching the biomedical literature are essential for identifying reagents or mouse strains as well as for effective experimental design and informed interpretation of experimental results. We have built the Textpresso Site Specific Recombinases (Textpresso SSR) Web server to enable researchers who use mice to perform in-depth searches of a rapidly growing and complex part of the mouse literature. Our Textpresso Web server provides an interface for searching the full text of most of the peer-reviewed publications that report the characterization or use of mouse strains that express Cre or Flp recombinase. The database also contains most of the publications that describe the characterization or analysis of strains carrying conditional alleles or transgenes that can be inactivated or activated by site-specific recombinases such as Cre or Flp. Textpresso SSR complements the existing online databases that catalog Cre and Flp expression patterns by providing a unique online interface for the in-depth text mining of the site specific recombinase literature.

Validation of a remote sensing model to identify Simulium damnosum s.l. breeding sites in Sub-Saharan Africa.

PubMed

Jacob, Benjamin G; Novak, Robert J; Toe, Laurent D; Sanfo, Moussa; Griffith, Daniel A; Lakwo, Thomson L; Habomugisha, Peace; Katabarwa, Moses N; Unnasch, Thomas R

2013-01-01

Recently, most onchocerciasis control programs have begun to focus on elimination. Developing an effective elimination strategy relies upon accurately mapping the extent of endemic foci. In areas of Africa that suffer from a lack of infrastructure and/or political instability, developing such accurate maps has been difficult. Onchocerciasis foci are localized near breeding sites for the black fly vectors of the infection. The goal of this study was to conduct ground validation studies to evaluate the sensitivity and specificity of a remote sensing model developed to predict S. damnosum s.l. breeding sites. Remote sensing images from Togo were analyzed to identify areas containing signature characteristics of S. damnosum s.l. breeding habitat. All 30 sites with the spectral signature were found to contain S. damnosum larvae, while 0/52 other sites judged as likely to contain larvae were found to contain larvae. The model was then used to predict breeding sites in Northern Uganda. This area is hyper-endemic for onchocerciasis, but political instability had precluded mass distribution of ivermectin until 2009. Ground validation revealed that 23/25 sites with the signature contained S. damnosum larvae, while 8/10 sites examined lacking the signature were larvae free. Sites predicted to have larvae contained significantly more larvae than those that lacked the signature. This study suggests that a signature extracted from remote sensing images may be used to predict the location of S. damnosum s.l. breeding sites with a high degree of accuracy. This method should be of assistance in predicting communities at risk for onchocerciasis in areas of Africa where ground-based epidemiological surveys are difficult to implement.

Validation of a Remote Sensing Model to Identify Simulium damnosum s.l. Breeding Sites in Sub-Saharan Africa

PubMed Central

Jacob, Benjamin G.; Novak, Robert J.; Toe, Laurent D.; Sanfo, Moussa; Griffith, Daniel A.; Lakwo, Thomson L.; Habomugisha, Peace; Katabarwa, Moses N.; Unnasch, Thomas R.

2013-01-01

Background Recently, most onchocerciasis control programs have begun to focus on elimination. Developing an effective elimination strategy relies upon accurately mapping the extent of endemic foci. In areas of Africa that suffer from a lack of infrastructure and/or political instability, developing such accurate maps has been difficult. Onchocerciasis foci are localized near breeding sites for the black fly vectors of the infection. The goal of this study was to conduct ground validation studies to evaluate the sensitivity and specificity of a remote sensing model developed to predict S. damnosum s.l. breeding sites. Methodology/Principal Findings Remote sensing images from Togo were analyzed to identify areas containing signature characteristics of S. damnosum s.l. breeding habitat. All 30 sites with the spectral signature were found to contain S. damnosum larvae, while 0/52 other sites judged as likely to contain larvae were found to contain larvae. The model was then used to predict breeding sites in Northern Uganda. This area is hyper-endemic for onchocerciasis, but political instability had precluded mass distribution of ivermectin until 2009. Ground validation revealed that 23/25 sites with the signature contained S. damnosum larvae, while 8/10 sites examined lacking the signature were larvae free. Sites predicted to have larvae contained significantly more larvae than those that lacked the signature. Conclusions/Significance This study suggests that a signature extracted from remote sensing images may be used to predict the location of S. damnosum s.l. breeding sites with a high degree of accuracy. This method should be of assistance in predicting communities at risk for onchocerciasis in areas of Africa where ground-based epidemiological surveys are difficult to implement. PMID:23936571

Identifying Martian Hydrothermal Sites: Geological Investigation Utilizing Multiple Datasets

NASA Technical Reports Server (NTRS)

Dohm, J. M.; Baker, V. R.; Anderson, R. C.; Scott, D. H.; Rice, J. W., Jr.; Hare, T. M.

2000-01-01

Comprehensive geological investigations of martian landscapes that may have been modified by magmatic-driven hydrothermal activity, utilizing multiple datasets, will yield prime target sites for future hydrological, mineralogical, and biological investigations.

Pooled Enrichment Sequencing Identifies Diversity and Evolutionary Pressures at NLR Resistance Genes within a Wild Tomato Population

PubMed Central

Stam, Remco; Scheikl, Daniela; Tellier, Aurélien

2016-01-01

Nod-like receptors (NLRs) are nucleotide-binding domain and leucine-rich repeats containing proteins that are important in plant resistance signaling. Many of the known pathogen resistance (R) genes in plants are NLRs and they can recognize pathogen molecules directly or indirectly. As such, divergence and copy number variants at these genes are found to be high between species. Within populations, positive and balancing selection are to be expected if plants coevolve with their pathogens. In order to understand the complexity of R-gene coevolution in wild nonmodel species, it is necessary to identify the full range of NLRs and infer their evolutionary history. Here we investigate and reveal polymorphism occurring at 220 NLR genes within one population of the partially selfing wild tomato species Solanum pennellii. We use a combination of enrichment sequencing and pooling ten individuals, to specifically sequence NLR genes in a resource and cost-effective manner. We focus on the effects which different mapping and single nucleotide polymorphism calling software and settings have on calling polymorphisms in customized pooled samples. Our results are accurately verified using Sanger sequencing of polymorphic gene fragments. Our results indicate that some NLRs, namely 13 out of 220, have maintained polymorphism within our S. pennellii population. These genes show a wide range of πN/πS ratios and differing site frequency spectra. We compare our observed rate of heterozygosity with expectations for this selfing and bottlenecked population. We conclude that our method enables us to pinpoint NLR genes which have experienced natural selection in their habitat. PMID:27189991

Identifying strategic sites for Green-Infrastructures (GI) to manage stormwater in a miscellaneous use urban African watershed

NASA Astrophysics Data System (ADS)

Selker, J. S.; Kahsai, S. K.

2017-12-01

Green Infrastructure (GI) or Low impact development (LID), is a land use planning and design approach with the objective of mitigating land development impacts to the environment, and is ever more looked to as a way to lessen runoff and pollutant loading to receiving water bodies. Broad-scale approaches for siting GI/LID have been developed for agricultural watersheds, but are rare for urban watersheds, largely due to greater land use complexity. And it is even more challenging when it comes to Urban Africa due to the combination of poor data quality, rapid and unplanned development, and civic institutions unable to reliably carry out regular maintenance. We present a spacio-temporal simulation-based approach to identify an optimal prioritization of sites for GI/LID based on DEM, land use and land cover. Optimization used is a multi-objective optimization tool along with an urban storm water management model (SWMM) to identify the most cost-effective combination of LID/GI. This was applied to an urban watershed in NW Kampala, Lubigi Catchment (notorious for being heavily flooded every year), with a miscellaneous use watershed in Uganda, as a case-study to demonstrate the approach.

Evaluation of different approaches for identifying optimal sites to predict mean hillslope soil moisture content

NASA Astrophysics Data System (ADS)

Liao, Kaihua; Zhou, Zhiwen; Lai, Xiaoming; Zhu, Qing; Feng, Huihui

2017-04-01

The identification of representative soil moisture sampling sites is important for the validation of remotely sensed mean soil moisture in a certain area and ground-based soil moisture measurements in catchment or hillslope hydrological studies. Numerous approaches have been developed to identify optimal sites for predicting mean soil moisture. Each method has certain advantages and disadvantages, but they have rarely been evaluated and compared. In our study, surface (0-20 cm) soil moisture data from January 2013 to March 2016 (a total of 43 sampling days) were collected at 77 sampling sites on a mixed land-use (tea and bamboo) hillslope in the hilly area of Taihu Lake Basin, China. A total of 10 methods (temporal stability (TS) analyses based on 2 indices, K-means clustering based on 6 kinds of inputs and 2 random sampling strategies) were evaluated for determining optimal sampling sites for mean soil moisture estimation. They were TS analyses based on the smallest index of temporal stability (ITS, a combination of the mean relative difference and standard deviation of relative difference (SDRD)) and based on the smallest SDRD, K-means clustering based on soil properties and terrain indices (EFs), repeated soil moisture measurements (Theta), EFs plus one-time soil moisture data (EFsTheta), and the principal components derived from EFs (EFs-PCA), Theta (Theta-PCA), and EFsTheta (EFsTheta-PCA), and global and stratified random sampling strategies. Results showed that the TS based on the smallest ITS was better (RMSE = 0.023 m3 m-3) than that based on the smallest SDRD (RMSE = 0.034 m3 m-3). The K-means clustering based on EFsTheta (-PCA) was better (RMSE <0.020 m3 m-3) than these based on EFs (-PCA) and Theta (-PCA). The sampling design stratified by the land use was more efficient than the global random method. Forty and 60 sampling sites are needed for stratified sampling and global sampling respectively to make their performances comparable to the best K

DNA Methylation and BMI: Investigating Identified Methylation Sites at HIF3A in a Causal Framework

PubMed Central

Richmond, Rebecca C.; Ward, Mary E.; Fraser, Abigail; Lyttleton, Oliver; McArdle, Wendy L.; Ring, Susan M.; Gaunt, Tom R.; Lawlor, Debbie A.; Davey Smith, George; Relton, Caroline L.

2016-01-01

Multiple differentially methylated sites and regions associated with adiposity have now been identified in large-scale cross-sectional studies. We tested for replication of associations between previously identified CpG sites at HIF3A and adiposity in ∼1,000 mother-offspring pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC). Availability of methylation and adiposity measures at multiple time points, as well as genetic data, allowed us to assess the temporal associations between adiposity and methylation and to make inferences regarding causality and directionality. Overall, our results were discordant with those expected if HIF3A methylation has a causal effect on BMI and provided more evidence for causality in the reverse direction (i.e., an effect of BMI on HIF3A methylation). These results are based on robust evidence from longitudinal analyses and were also partially supported by Mendelian randomization analysis, although this latter analysis was underpowered to detect a causal effect of BMI on HIF3A methylation. Our results also highlight an apparent long-lasting intergenerational influence of maternal BMI on offspring methylation at this locus, which may confound associations between own adiposity and HIF3A methylation. Further work is required to replicate and uncover the mechanisms underlying the direct and intergenerational effect of adiposity on DNA methylation. PMID:26861784

IDENTIFYING AND PREDICTING DIVING PLUME BEHAVIOR AT GROUNDWATER SITES CONTAINING MTBE: PART 1 SUPPLEMENTAL FUNDING FOR ACTIVITIES IN FY 2002

EPA Science Inventory

This work will complete work began under Identifying and Predicting Plume Diving Behavior at Groundwater Sites Containing MTBE: Part 1. As of September 2001, ORD Staff and ORD Contractors have characterized dividing MTBE plumes at Spring Green, Wisconsin; Milford, Michigan; and ...

Origins of coevolution between residues distant in protein 3D structures

PubMed Central

Ovchinnikov, Sergey; Kamisetty, Hetunandan; Baker, David

2017-01-01

Residue pairs that directly coevolve in protein families are generally close in protein 3D structures. Here we study the exceptions to this general trend—directly coevolving residue pairs that are distant in protein structures—to determine the origins of evolutionary pressure on spatially distant residues and to understand the sources of error in contact-based structure prediction. Over a set of 4,000 protein families, we find that 25% of directly coevolving residue pairs are separated by more than 5 Å in protein structures and 3% by more than 15 Å. The majority (91%) of directly coevolving residue pairs in the 5–15 Å range are found to be in contact in at least one homologous structure—these exceptions arise from structural variation in the family in the region containing the residues. Thirty-five percent of the exceptions greater than 15 Å are at homo-oligomeric interfaces, 19% arise from family structural variation, and 27% are in repeat proteins likely reflecting alignment errors. Of the remaining long-range exceptions (<1% of the total number of coupled pairs), many can be attributed to close interactions in an oligomeric state. Overall, the results suggest that directly coevolving residue pairs not in repeat proteins are spatially proximal in at least one biologically relevant protein conformation within the family; we find little evidence for direct coupling between residues at spatially separated allosteric and functional sites or for increased direct coupling between residue pairs on putative allosteric pathways connecting them. PMID:28784799

Identifying Ca2+-Binding Sites in Proteins by Liquid Chromatography-Mass Spectrometry Using Ca2+-Directed Dissociations

PubMed Central

Jamalian, Azadeh; Sneekes, Evert-Jan; Wienk, Hans; Dekker, Lennard J. M.; Ruttink, Paul J. A.; Ursem, Mario; Luider, Theo M.; Burgers, Peter C.

2014-01-01

Here we describe a new method to identify calcium-binding sites in proteins using high-resolution liquid chromatography-mass spectrometry in concert with calcium-directed collision-induced dissociations. Our method does not require any modifications to the liquid chromatography-mass spectrometry apparatus, uses standard digestion protocols, and can be applied to existing high-resolution MS data files. In contrast to NMR, our method is applicable to very small amounts of complex protein mixtures (femtomole level). Calcium-bound peptides can be identified using three criteria: (1) the calculated exact mass of the calcium containing peptide; (2) specific dissociations of the calcium-containing peptide from threonine and serine residues; and (3) the very similar retention times of the calcium-containing peptide and the free peptide. PMID:25023127

Identifying humanitarian crises in population surveillance field sites: simple procedures and ethical imperatives.

PubMed

Fottrell, E; Byass, P

2009-02-01

Effective early warning systems of humanitarian crises may help to avert substantial increases in mortality and morbidity, and prevent major population movements. The Butajira Rural Health Programme (BRHP) in Ethiopia has maintained a programme of epidemiological surveillance since 1987. Inspection of the BRHP data revealed large peaks of mortality in 1998 and 1999, well in excess of the normally observed year-to-year variation. Further investigation and enquiry revealed that these peaks related to a measles epidemic, and a serious episode of drought and consequent food insecurity that went undetected by the BRHP. This paper applies international humanitarian crisis threshold definitions to the BRHP data in an attempt to identify suitable mortality thresholds that may be used for the prospective detection of humanitarian crises in population surveillance sites in developing countries. Empirical investigation using secondary analysis of longitudinal population-based cohort data. The daily, weekly and monthly thresholds for crises in Butajira were applied to mortality data for the 5-year period incorporating the crisis periods of 1998-1999. Days, weeks and months in which mortality exceeded each threshold level were identified. Each threshold level was assessed in terms of prospectively identifying the true crisis periods in a timely manner whilst avoiding false alarms. The daily threshold definition is too sensitive to accurately detect impending or real crises in the population surveillance setting of the BRHP. However, the weekly threshold level is useful in identifying important increases in mortality in a timely manner without the excessive sensitivity of the daily threshold. The weekly threshold level detects the crisis periods approximately 2 weeks before the monthly threshold level. Mortality measures are highly specific indicators of the health status of populations, and simple procedures can be used to apply international crisis threshold definitions in

Using questions sent to an Ask-A-Scientist site to identify children's interests in science

NASA Astrophysics Data System (ADS)

Baram-Tsabari, Ayelet; Sethi, Ricky J.; Bry, Lynn; Yarden, Anat

2006-11-01

Interest is a powerful motivator; nonetheless, science educators often lack the necessary information to make use of the power of student-specific interests in the reform process of science curricula. This study suggests a novel methodology, which might be helpful in identifying such interests - using children's self-generated questions as an indication of their scientific interests. In this research, children's interests were measured by analyzing 1555 science-related questions submitted to an international Ask-A-Scientist Internet site. The analysis indicated that the popularity of certain topics varies with age and gender. Significant differences were found between children's spontaneous (intrinsically motivated) and school-related (extrinsically motivated) interests. Surprisingly, girls contributed most of the questions to the sample; however, the number of American girls dropped upon entering senior high school. We also found significant differences between girls' and boys' interests, with girls generally preferring biological topics. The two genders kept to their stereotypic fields of interest, in both their school-related and spontaneous questions. Children's science interests, as inferred from questions to Web sites, could ultimately inform classroom science teaching. This methodology extends the context in which children's interests can be investigated.

Application of multiple tracers (SF6 and chloride) to identify the transport by characteristics of contaminant at two separate contaminated sites

NASA Astrophysics Data System (ADS)

Lee, K. K.; Lee, S. S.; Kim, H. H.; Koh, E. H.; Kim, M. O.; Lee, K.; Kim, H. J.

2016-12-01

Multiple tracers were applied for source and pathway detection at two different sites. CO2 gas injected in the subsurface for a shallow-depth CO2 injection and leak test can be regarded as a potential contaminant source. Therefore, it is necessary to identify the migration pattern of CO2 gas. Also, at a DNAPL contaminated site, it is important to figure out the characteristics of plume evolution from the source zone. In this study, multiple tracers (SF6 and chloride) were used to evaluate the applicability of volatile and non-volatile tracers and to identify the characteristics of contaminant transport at each CO2 injection and leak test site and DNAPL contaminated site. Firstly, at the CO2 test site, multiple tracers were used to perform the single well push-drift-pull tracer test at total 3 specific depth zones. As results of tests, volatile and non-volatile tracers showed different mass recovery percentage. Most of chloride mass was recovered but less than half of SF6 mass was recovered due to volatile property. This means that only gaseous SF6 leak out to unsaturated zone. However, breakthrough curves of both tracers indicated similar peak time, effective porosity, and regional groundwater velocity. Also, at both contaminated sites, natural gradient tracer tests were performed with multiple tracers. With the results of natural gradient tracer test, it was possible to confirm the applicability of multiple tracers and to understand the contaminant transport in highly heterogeneous aquifer systems through the long-term monitoring of tracers. Acknowledgement: financial support was provided by the R&D Project on Environmental Management of Geologic CO2 Storage)" from the KEITI (Project Number: 2014001810003) and Korea Ministry of Environment as "The GAIA project (2014000540010)".

Pooled Enrichment Sequencing Identifies Diversity and Evolutionary Pressures at NLR Resistance Genes within a Wild Tomato Population.

PubMed

Stam, Remco; Scheikl, Daniela; Tellier, Aurélien

2016-06-02

Nod-like receptors (NLRs) are nucleotide-binding domain and leucine-rich repeats containing proteins that are important in plant resistance signaling. Many of the known pathogen resistance (R) genes in plants are NLRs and they can recognize pathogen molecules directly or indirectly. As such, divergence and copy number variants at these genes are found to be high between species. Within populations, positive and balancing selection are to be expected if plants coevolve with their pathogens. In order to understand the complexity of R-gene coevolution in wild nonmodel species, it is necessary to identify the full range of NLRs and infer their evolutionary history. Here we investigate and reveal polymorphism occurring at 220 NLR genes within one population of the partially selfing wild tomato species Solanum pennellii. We use a combination of enrichment sequencing and pooling ten individuals, to specifically sequence NLR genes in a resource and cost-effective manner. We focus on the effects which different mapping and single nucleotide polymorphism calling software and settings have on calling polymorphisms in customized pooled samples. Our results are accurately verified using Sanger sequencing of polymorphic gene fragments. Our results indicate that some NLRs, namely 13 out of 220, have maintained polymorphism within our S. pennellii population. These genes show a wide range of πN/πS ratios and differing site frequency spectra. We compare our observed rate of heterozygosity with expectations for this selfing and bottlenecked population. We conclude that our method enables us to pinpoint NLR genes which have experienced natural selection in their habitat. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

DNA Methylation and BMI: Investigating Identified Methylation Sites at HIF3A in a Causal Framework.

PubMed

Richmond, Rebecca C; Sharp, Gemma C; Ward, Mary E; Fraser, Abigail; Lyttleton, Oliver; McArdle, Wendy L; Ring, Susan M; Gaunt, Tom R; Lawlor, Debbie A; Davey Smith, George; Relton, Caroline L

2016-05-01

Multiple differentially methylated sites and regions associated with adiposity have now been identified in large-scale cross-sectional studies. We tested for replication of associations between previously identified CpG sites at HIF3A and adiposity in ∼1,000 mother-offspring pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC). Availability of methylation and adiposity measures at multiple time points, as well as genetic data, allowed us to assess the temporal associations between adiposity and methylation and to make inferences regarding causality and directionality. Overall, our results were discordant with those expected if HIF3A methylation has a causal effect on BMI and provided more evidence for causality in the reverse direction (i.e., an effect of BMI on HIF3A methylation). These results are based on robust evidence from longitudinal analyses and were also partially supported by Mendelian randomization analysis, although this latter analysis was underpowered to detect a causal effect of BMI on HIF3A methylation. Our results also highlight an apparent long-lasting intergenerational influence of maternal BMI on offspring methylation at this locus, which may confound associations between own adiposity and HIF3A methylation. Further work is required to replicate and uncover the mechanisms underlying the direct and intergenerational effect of adiposity on DNA methylation. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Rigorous Screening Technology for Identifying Suitable CO2 Storage Sites II

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

George J. Koperna Jr.; Vello A. Kuuskraa; David E. Riestenberg

2009-06-01

This report serves as the final technical report and users manual for the 'Rigorous Screening Technology for Identifying Suitable CO2 Storage Sites II SBIR project. Advanced Resources International has developed a screening tool by which users can technically screen, assess the storage capacity and quantify the costs of CO2 storage in four types of CO2 storage reservoirs. These include CO2-enhanced oil recovery reservoirs, depleted oil and gas fields (non-enhanced oil recovery candidates), deep coal seems that are amenable to CO2-enhanced methane recovery, and saline reservoirs. The screening function assessed whether the reservoir could likely serve as a safe, long-term CO2more » storage reservoir. The storage capacity assessment uses rigorous reservoir simulation models to determine the timing, ultimate storage capacity, and potential for enhanced hydrocarbon recovery. Finally, the economic assessment function determines both the field-level and pipeline (transportation) costs for CO2 sequestration in a given reservoir. The screening tool has been peer reviewed at an Electrical Power Research Institute (EPRI) technical meeting in March 2009. A number of useful observations and recommendations emerged from the Workshop on the costs of CO2 transport and storage that could be readily incorporated into a commercial version of the Screening Tool in a Phase III SBIR.« less

Genome-Wide Screens for In Vivo Tinman Binding Sites Identify Cardiac Enhancers with Diverse Functional Architectures

PubMed Central

Jin, Hong; Stojnic, Robert; Adryan, Boris; Ozdemir, Anil; Stathopoulos, Angelike; Frasch, Manfred

2013-01-01

The NK homeodomain factor Tinman is a crucial regulator of early mesoderm patterning and, together with the GATA factor Pannier and the Dorsocross T-box factors, serves as one of the key cardiogenic factors during specification and differentiation of heart cells. Although the basic framework of regulatory interactions driving heart development has been worked out, only about a dozen genes involved in heart development have been designated as direct Tinman target genes to date, and detailed information about the functional architectures of their cardiac enhancers is lacking. We have used immunoprecipitation of chromatin (ChIP) from embryos at two different stages of early cardiogenesis to obtain a global overview of the sequences bound by Tinman in vivo and their linked genes. Our data from the analysis of ∼50 sequences with high Tinman occupancy show that the majority of such sequences act as enhancers in various mesodermal tissues in which Tinman is active. All of the dorsal mesodermal and cardiac enhancers, but not some of the others, require tinman function. The cardiac enhancers feature diverse arrangements of binding motifs for Tinman, Pannier, and Dorsocross. By employing these cardiac and non-cardiac enhancers in machine learning approaches, we identify a novel motif, termed CEE, as a classifier for cardiac enhancers. In vivo assays for the requirement of the binding motifs of Tinman, Pannier, and Dorsocross, as well as the CEE motifs in a set of cardiac enhancers, show that the Tinman sites are essential in all but one of the tested enhancers; although on occasion they can be functionally redundant with Dorsocross sites. The enhancers differ widely with respect to their requirement for Pannier, Dorsocross, and CEE sites, which we ascribe to their different position in the regulatory circuitry, their distinct temporal and spatial activities during cardiogenesis, and functional redundancies among different factor binding sites. PMID:23326246

Using transcranial magnetic stimulation of the undamaged brain to identify lesion sites that predict language outcome after stroke

PubMed Central

Lorca-Puls, Diego L.; Gajardo-Vidal, Andrea; Seghier, Mohamed L.; Leff, Alexander P.; Sethi, Varun; Prejawa, Susan; Hope, Thomas M. H.; Devlin, Joseph T.

2017-01-01

Abstract Transcranial magnetic stimulation focused on either the left anterior supramarginal gyrus or opercular part of the left inferior frontal gyrus has been reported to transiently impair the ability to perform phonological more than semantic tasks. Here we tested whether phonological processing abilities were also impaired following lesions to these regions in right-handed, English speaking adults, who were investigated at least 1 year after a left-hemisphere stroke. When our regions of interest were limited to 0.5 cm3 of grey matter centred around sites that had been identified with transcranial magnetic stimulation-based functional localization, phonological impairments were observed in 74% (40/54) of patients with damage to the regions and 21% (21/100) of patients sparing these regions. This classification accuracy was better than that observed when using regions of interest centred on activation sites in previous functional magnetic resonance imaging studies of phonological processing, or transcranial magnetic stimulation sites that did not use functional localization. New regions of interest were generated by redefining the borders of each of the transcranial magnetic stimulation sites to include areas that were consistently damaged in the patients with phonological impairments. This increased the incidence of phonological impairments in the presence of damage to 85% (46/54) and also reduced the incidence of phonological impairments in the absence of damage to 15% (15/100). The difference in phonological processing abilities between those with and without damage to these ‘transcranial magnetic stimulation-guided’ regions remained highly significant even after controlling for the effect of lesion size. The classification accuracy of the transcranial magnetic stimulation-guided regions was validated in a second sample of 108 patients and found to be better than that for (i) functional magnetic resonance imaging-guided regions; (ii) a region identified

Using transcranial magnetic stimulation of the undamaged brain to identify lesion sites that predict language outcome after stroke.

PubMed

Lorca-Puls, Diego L; Gajardo-Vidal, Andrea; Seghier, Mohamed L; Leff, Alexander P; Sethi, Varun; Prejawa, Susan; Hope, Thomas M H; Devlin, Joseph T; Price, Cathy J

2017-06-01

Transcranial magnetic stimulation focused on either the left anterior supramarginal gyrus or opercular part of the left inferior frontal gyrus has been reported to transiently impair the ability to perform phonological more than semantic tasks. Here we tested whether phonological processing abilities were also impaired following lesions to these regions in right-handed, English speaking adults, who were investigated at least 1 year after a left-hemisphere stroke. When our regions of interest were limited to 0.5 cm3 of grey matter centred around sites that had been identified with transcranial magnetic stimulation-based functional localization, phonological impairments were observed in 74% (40/54) of patients with damage to the regions and 21% (21/100) of patients sparing these regions. This classification accuracy was better than that observed when using regions of interest centred on activation sites in previous functional magnetic resonance imaging studies of phonological processing, or transcranial magnetic stimulation sites that did not use functional localization. New regions of interest were generated by redefining the borders of each of the transcranial magnetic stimulation sites to include areas that were consistently damaged in the patients with phonological impairments. This increased the incidence of phonological impairments in the presence of damage to 85% (46/54) and also reduced the incidence of phonological impairments in the absence of damage to 15% (15/100). The difference in phonological processing abilities between those with and without damage to these 'transcranial magnetic stimulation-guided' regions remained highly significant even after controlling for the effect of lesion size. The classification accuracy of the transcranial magnetic stimulation-guided regions was validated in a second sample of 108 patients and found to be better than that for (i) functional magnetic resonance imaging-guided regions; (ii) a region identified from an

Comparing performance of methods used to identify pregnant women, pregnancy outcomes, and child mortality in the Iganga-Mayuge Health and Demographic Surveillance Site, Uganda.

PubMed

Kadobera, Daniel; Waiswa, Peter; Peterson, Stefan; Blencowe, Hannah; Lawn, Joy; Kerber, Kate; Tumwesigye, Nazarius Mbona

2017-01-01

In most low and middle-income countries vital events registration for births and child deaths is poor, with reporting of pregnancy outcomes highly inadequate or non-existent. Health and Demographic Surveillance System (HDSS) sites and periodic population-based household-level surveys can be used to identify pregnancies and retrospectively capture pregnancy outcomes to provide data for decision making. However, little is known about the performance of different methods in identifying pregnancy and pregnancy outcomes, yet this is critical in assessing improvements in reducing maternal and newborn mortality and stillbirths. To explore differences between a population-based household pregnancy survey and prospective health demographic surveillance system in identifying pregnancies and their outcomes in rural eastern Uganda. The study was done within the Iganga-Mayuge HDSS site, a member centre of the INDEPTH Network. Prospective data about pregnancies and their outcomes was collected in the routine biannual census rounds from 2006 to 2010 in the HDSS. In 2011 a cross-sectional survey using the pregnancy history survey (PHS) tool was conducted among women aged 15 to 49 years in the HDSS area. We compared differences between the HDSS biannual census updates and the PHS capture of pregnancies identified as well as neonatal and child deaths, stillbirths and abortions. A total of 10,540 women aged 15 to 49 years were interviewed during the PHS. The PHS captured 12.8% more pregnancies than the HDSS in the most recent year (2010-2011), though between 2006 and 2010 (earlier periods) the PHS captured only 137 (0.8%) more pregnancies overall. The PHS also consistently identified more stillbirths (18.2%), spontaneous abortions (94.5%) and induced abortions (185.8%) than the prospective HDSS update rounds. Surveillance sites are designed to prospectively track population-level outcomes. However, the PHS identified more pregnancy-related outcomes than the HDSS in this study

The repABC plasmids with quorum-regulated transfer systems in members of the Rhizobiales divide into two structurally and separately evolving groups

DOE PAGES

Wetzel, Margaret E.; Olsen, Gary J.; Chakravartty, Vandana; ...

2015-11-19

The large repABC plasmids of the order Rhizobiales with Class I quorum-regulated conjugative transfer systems often define the nature of the bacterium that harbors them. These otherwise diverse plasmids contain a core of highly conserved genes for replication and conjugation raising the question of their evolutionary relationships. In an analysis of 18 such plasmids these elements fall into two organizational classes, Group I and Group II, based on the sites at which cargo DNA is located. Cladograms constructed from proteins of the transfer and quorum-sensing components indicated that those of the Group I plasmids, while coevolving, have diverged from thosemore » coevolving proteins of the Group II plasmids. Moreover, within these groups the phylogenies of the proteins usually occupy similar, if not identical, tree topologies. Remarkably, such relationships were not seen among proteins of the replication system; although RepA and RepB coevolve, RepC does not. Nor do the replication proteins coevolve with the proteins of the transfer and quorum-sensing systems. Functional analysis was mostly consistent with phylogenies. TraR activated promoters from plasmids within its group, but not between groups and dimerized with TraR proteins from within but not between groups. However, oriT sequences, which are highly conserved, were processed by the transfer system of plasmids regardless of group. Here, we conclude that these plasmids diverged into two classes based on the locations at which cargo DNA is inserted, that the quorum-sensing and transfer functions are coevolving within but not between the two groups, and that this divergent evolution extends to function.« less

The repABC plasmids with quorum-regulated transfer systems in members of the Rhizobiales divide into two structurally and separately evolving groups

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

Wetzel, Margaret E.; Olsen, Gary J.; Chakravartty, Vandana

The large repABC plasmids of the order Rhizobiales with Class I quorum-regulated conjugative transfer systems often define the nature of the bacterium that harbors them. These otherwise diverse plasmids contain a core of highly conserved genes for replication and conjugation raising the question of their evolutionary relationships. In an analysis of 18 such plasmids these elements fall into two organizational classes, Group I and Group II, based on the sites at which cargo DNA is located. Cladograms constructed from proteins of the transfer and quorum-sensing components indicated that those of the Group I plasmids, while coevolving, have diverged from thosemore » coevolving proteins of the Group II plasmids. Moreover, within these groups the phylogenies of the proteins usually occupy similar, if not identical, tree topologies. Remarkably, such relationships were not seen among proteins of the replication system; although RepA and RepB coevolve, RepC does not. Nor do the replication proteins coevolve with the proteins of the transfer and quorum-sensing systems. Functional analysis was mostly consistent with phylogenies. TraR activated promoters from plasmids within its group, but not between groups and dimerized with TraR proteins from within but not between groups. However, oriT sequences, which are highly conserved, were processed by the transfer system of plasmids regardless of group. Here, we conclude that these plasmids diverged into two classes based on the locations at which cargo DNA is inserted, that the quorum-sensing and transfer functions are coevolving within but not between the two groups, and that this divergent evolution extends to function.« less

Atomic-scale distortion of optically activated Sm dopants identified with site-selective X-ray absorption spectroscopy

NASA Astrophysics Data System (ADS)

Ishii, Masashi; Crowe, Iain F.; Halsall, Matthew P.; Hamilton, Bruce; Hu, Yongfeng; Sham, Tsun-Kong; Harako, Susumu; Zhao, Xin-Wei; Komuro, Shuji

2013-10-01

The local structure of luminescent Sm dopants was investigated using an X-ray absorption fine-structure technique with X-ray-excited optical luminescence. Because this technique evaluates X-ray absorption from luminescence, only optically active sites are analyzed. The Sm L3 near-edge spectrum contains split 5d states and a shake-up transition that are specific to luminescent Sm. Theoretical calculations using cluster models identified an atomic-scale distortion that can reproduce the split 5d states. The model with C4v local symmetry and compressive bond length of Sm-O of a six-fold oxygen (SmO6) cluster is most consistent with the experimental results.

Refinement of a Method for Identifying Probable Archaeological Sites from Remotely Sensed Data

NASA Technical Reports Server (NTRS)

Tilton, James C.; Comer, Douglas C.; Priebe, Carey E.; Sussman, Daniel; Chen, Li

2012-01-01

To facilitate locating archaeological sites before they are compromised or destroyed, we are developing approaches for generating maps of probable archaeological sites, through detecting subtle anomalies in vegetative cover, soil chemistry, and soil moisture by analyzing remotely sensed data from multiple sources. We previously reported some success in this effort with a statistical analysis of slope, radar, and Ikonos data (including tasseled cap and NDVI transforms) with Student's t-test. We report here on new developments in our work, performing an analysis of 8-band multispectral Worldview-2 data. The Worldview-2 analysis begins by computing medians and median absolute deviations for the pixels in various annuli around each site of interest on the 28 band difference ratios. We then use principle components analysis followed by linear discriminant analysis to train a classifier which assigns a posterior probability that a location is an archaeological site. We tested the procedure using leave-one-out cross validation with a second leave-one-out step to choose parameters on a 9,859x23,000 subset of the WorldView-2 data over the western portion of Ft. Irwin, CA, USA. We used 100 known non-sites and trained one classifier for lithic sites (n=33) and one classifier for habitation sites (n=16). We then analyzed convex combinations of scores from the Archaeological Predictive Model (APM) and our scores. We found that that the combined scores had a higher area under the ROC curve than either individual method, indicating that including WorldView-2 data in analysis improved the predictive power of the provided APM.

Identifying nutrient reference sites in nutrient-enriched regions-Using algal, invertebrate, and fish-community measures to identify stressor-breakpoint thresholds in Indiana rivers and streams, 2005-9

USGS Publications Warehouse

Caskey, Brian J.; Bunch, Aubrey R.; Shoda, Megan E.; Frey, Jeffrey W.; Selvaratnam, Shivi; Miltner, Robert J.

2013-01-01

Excess nutrients in aquatic ecosystems can lead to shifts in species composition, reduced dissolved oxygen concentrations, fish kills, and toxic algal blooms. In this study, nutrients, periphyton chlorophyll a (CHLa), and invertebrate- and fishcommunity data collected during 2005-9 were analyzed from 318 sites on Indiana rivers and streams. The objective of this study was to determine which invertebrate and fish-taxa attributes best reflect the conditions of streams in Indiana along a gradient of nutrient concentrations by (1) determining statistically and ecologically significant relations among the stressor (total nitrogen, total phosphorus, and periphyton CHLa) and response (invertebrate and fish community) variables; and (2) determining the levels at which invertebrate- and fish-community measures change in response to nutrients or periphyton CHLa. For water samples at the headwater sites, total nitrogen (TN) concentrations ranged from 0.343 to 21.6 milligrams per liter (mg/L) (median 2.12 mg/L), total phosphorus (TP) concentrations ranged from 0.050 to 1.44 mg/L (median 0.093 mg/L), and periphyton CHLa ranged from 0.947 to 629 mg/L (median 69.7 mg/L). At the wadable sites, TN concentrations ranged from 0.340 to 10.0 mg/L (median 2.31 mg/L), TP concentrations ranged from 0.050 to 1.24 mg/L (median 0.110 mg/L), and periphyton CHLa ranged from 0.383 to 719 mg/L (median 44.7 mg/L). Recursive partitioning identified statistically significant low and high breakpoint thresholds on invertebrate and fish measures, which demonstrated the ecological response in enriched conditions. The combined community (invertebrate and fish) mean low and high TN breakpoint thresholds were 1.03 and 2.61 mg/L, respectively. The mean low and high breakpoint thresholds for TP were 0.083 and 0.144 mg/L, respectively. The mean low and high breakpoint thresholds for periphyton CHLa were 20.9 and 98.6 milligrams per square meter (mg/m2), respectively. Additive quantile regression analysis

Selection of Inhibitor-Resistant Viral Potassium Channels Identifies a Selectivity Filter Site that Affects Barium and Amantadine Block

PubMed Central

Fujiwara, Yuichiro; Arrigoni, Cristina; Domigan, Courtney; Ferrara, Giuseppina; Pantoja, Carlos; Thiel, Gerhard; Moroni, Anna; Minor, Daniel L.

2009-01-01

Background Understanding the interactions between ion channels and blockers remains an important goal that has implications for delineating the basic mechanisms of ion channel function and for the discovery and development of ion channel directed drugs. Methodology/Principal Findings We used genetic selection methods to probe the interaction of two ion channel blockers, barium and amantadine, with the miniature viral potassium channel Kcv. Selection for Kcv mutants that were resistant to either blocker identified a mutant bearing multiple changes that was resistant to both. Implementation of a PCR shuffling and backcrossing procedure uncovered that the blocker resistance could be attributed to a single change, T63S, at a position that is likely to form the binding site for the inner ion in the selectivity filter (site 4). A combination of electrophysiological and biochemical assays revealed a distinct difference in the ability of the mutant channel to interact with the blockers. Studies of the analogous mutation in the mammalian inward rectifier Kir2.1 show that the T→S mutation affects barium block as well as the stability of the conductive state. Comparison of the effects of similar barium resistant mutations in Kcv and Kir2.1 shows that neighboring amino acids in the Kcv selectivity filter affect blocker binding. Conclusions/Significance The data support the idea that permeant ions have an integral role in stabilizing potassium channel structure, suggest that both barium and amantadine act at a similar site, and demonstrate how genetic selections can be used to map blocker binding sites and reveal mechanistic features. PMID:19834614

Molecular dynamics simulations and statistical coupling analysis of GPI12 in L. major: functional co-evolution and conservedness reveals potential drug-target sites.

PubMed

Singh, Shailza; Mandlik, Vineetha; Shinde, Sonali

2015-03-01

GPI12 represents an important enzyme in the GPI biosynthetic pathway of several parasites like 'Leishmania'. GPI activity is generally regulated through either the hindrance in GPI complex assembly formation or the modulation of the lipophosphoglycan (LPG) flux to either reduce or enhance the pathogenicity in an organism. Of the various GPI molecules known, GPI12 is an important enzyme in the GPI biosynthetic pathway which can be exploited as a target due to the substrate specificity difference in parasites and humans. In the present study, the functional importance of the co-evolving residues of the GPI12 protein of Leishmania has been highlighted using the GPI proteins belonging to the GlcNAC-deacetylase family. Exploring the active site of the GPI12 protein and designing inhibitors against the functional residues provide ways and means to change the efficiency of deacetylation activity of the enzyme. The activity of de-N-acetylase is low in the absence of metal ions like zinc. Hence we designed eight small molecules in order to modulate the activity of GPI12. Compound 8 was found to be an appropriate choice to target the agonist (GPI12) active site thereby targeting the residues which were essential in the Zn binding and chelation activity. Inhibition of these sites offered a strong constraint to block the protein activity and in turn GPI biosynthesis.

A GIS-based approach for identifying potential runoff harvesting sites in the Thukela River basin, South Africa

NASA Astrophysics Data System (ADS)

de Winnaar, G.; Jewitt, G. P. W.; Horan, M.

Water scarce countries such as South Africa are subject to various hydrological constraints which can often be attributed to poor rainfall partitioning, particularly within resource poor farming communities that are reliant on rainfed agriculture. Recent initiatives to address this have shifted focus to explore more efficient alternatives to water supply and the recognition of numerous opportunities to implement runoff harvesting as a means to supplement water availability. However, increasing the implementation of runoff harvesting, without encountering unintended impacts on downstream hydrological and ecological systems, requires better understanding of the hydrologic and environmental impacts at catchment scale. In this paper the representation of spatial variations in landscape characteristics such as soil, land use, rainfall and slope information is shown to be an important step in identifying potential runoff harvesting sites, after which modelling the hydrological response in catchments where extensive runoff harvesting is being considered can be performed and likely impacts assessed. Geographic information systems (GIS) was utilised as an integrating tool to store, analyse and manage spatial information and when linked to hydrological response models, provided a rational means to facilitate decision making by providing catchment level identification, planning and assessment of runoff harvesting sites as illustrated by a case study at the Potshini catchment, a small sub-catchment in the Thukela River basin, South Africa. Through the linked GIS, potential runoff harvesting sites are identified relative to areas that concentrate runoff and where the stored water will be appropriately distributed. Based on GIS analysis it was found that 17% percent of the Potshini catchment area has a high potential for generating surface runoff, whereas an analysis of all factors which influence the location of such systems, shows that 18% is highly suitable for runoff

Criteria for Identifying and Evaluating Candidate Sites for Open-Field Trials of Genetically Engineered Mosquitoes

PubMed Central

Brown, David M.; Alphey, Luke S.; McKemey, Andrew; Beech, Camilla

2014-01-01

Abstract Recent laboratory successes in the development of genetically engineered mosquitoes for controlling pathogen transmission have fostered the need for standardized procedures for advancing the technical achievements to practical tools. It is incumbent in many cases for the same scientists doing the in-laboratory discovery research to also take on the initial challenges of developing the pathway that will move the technologies to the field. One of these challenges is having a set of criteria for selecting collaborators and sites for efficacy and safety field trials that combine rigorous science with good ethical and legal practices. Specific site-selection criteria were developed in four categories—Scientific, Regulatory, Community Engagement, and Resources—in anticipation of open-field releases of a transgenic mosquito strain designed to suppress populations of the dengue vector mosquito, Aedes aegypti. The criteria are derived from previous published material, discussions, and personal experiences with the expectation of providing guidance to laboratory scientists for addressing the conceptual and operational considerations for identifying partner researchers and countries with whom to collaborate. These criteria are not intended to be prescriptive nor can they be applied to every circumstance where genetic approaches are proposed for deployment. However, we encourage those involved in the discovery phase of research to consider each criterion during project planning activities, and where appropriate, incorporate them into a “go/no-go” decision-making process for further development and testing of the technologies. PMID:24689963

[Evaluation of mosquito species (Diptera: Culicidae) identified in Manisa province according to their breeding sites and seasonal differences].

PubMed

Muslu, Hasan; Kurt, Ozgür; Özbilgin, Ahmet

2011-01-01

To identify the mosquito species and the potential mosquito-related infectious diseases in Manisa province, mosquito larvae were collected from aquatic habitats in Manisa between October 2008 and October 2009. Mosquito larvae were collected from the surface water of study sites with a standard larvae collection spoon. The 1st and 2nd stage larvae brought to the laboratory were kept until they become adults, and their species were identified during 3rd or 4th larvae stages. In addition, species identification was made for 3rd or 4th stage larvae as well as pupae in aquatic samples, as well. A total of 8098 larvae samples were collected during the study and Culex (Culex) pipiens and Culex (Neoculex) martini were found to be the predominant species in Manisa. Three Culex [Culex (Culex) pipiens, Culex (Neoculex) martini, Culex (Maillotia) deserticola], two Culiseta [Culiseta (Culiseta) annulata, Culiseta (Allotheobaldia) longiareolata] and one Anopheles [Anopheles (Cellia) superpictus] species were identified. Anopheles superpictus, the vector of malaria; Culex pipiens, Culiseta annulata, Culiseta longiareolata, the vectors of tularemia and arbovirus infections such as West Nile Virus infection, were identified in Manisa province. Conduction of similar larger-scale studies will contribute to the prevention of vector-borne diseases in our region.

10 CFR 960.3-2-1 - Site screening for potentially acceptable sites.

Code of Federal Regulations, 2010 CFR

2010-01-01

... POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Implementation Guidelines § 960.3-2-1 Site screening for... first repository, the process shall begin with site-screening activities that consider large land masses... repositories, the Secretary shall first identify the State within which the site is located in a decision-basis...

THE USE OF SPATIAL ANALYTICAL TECHNIQUES TO IDENTIFY POTENTIAL BROWNFIELDS SITES

EPA Science Inventory

Brownfields are abandoned, idled, or underutilized properties where expansion or redevelopment is complicated by real or perceived environmental contamination. Most Brownfields sites are located in urban, commercial, and industrial areas. Under the Brownfields Program, the United...

Ocean Disposal Site Monitoring

EPA Pesticide Factsheets

EPA is responsible for managing all designated ocean disposal sites. Surveys are conducted to identify appropriate locations for ocean disposal sites and to monitor the impacts of regulated dumping at the disposal sites.

New Measurement for Correlation of Co-evolution Relationship of Subsequences in Protein.

PubMed

Gao, Hongyun; Yu, Xiaoqing; Dou, Yongchao; Wang, Jun

2015-12-01

Many computational tools have been developed to measure the protein residues co-evolution. Most of them only focus on co-evolution for pairwise residues in a protein sequence. However, number of residues participate in co-evolution might be multiple. And some co-evolved residues are clustered in several distinct regions in primary structure. Therefore, the co-evolution among the adjacent residues and the correlation between the distinct regions offer insights into function and evolution of the protein and residues. Subsequence is used to represent the adjacent multiple residues in one distinct region. In the paper, co-evolution relationship in each subsequence is represented by mutual information matrix (MIM). Then, Pearson's correlation coefficient: R value is developed to measure the similarity correlation of two MIMs. MSAs from Catalytic Data Base (Catalytic Site Atlas, CSA) are used for testing. R value characterizes a specific class of residues. In contrast to individual pairwise co-evolved residues, adjacent residues without high individual MI values are found since the co-evolved relationship among them is similar to that among another set of adjacent residues. These subsequences possess some flexibility in the composition of side chains, such as the catalyzed environment.

Identifying malaria hotspots in Keur Soce health and demographic surveillance site in context of low transmission.

PubMed

Ndiath, Mansour; Faye, Babacar; Cisse, Badara; Ndiaye, Jean Louis; Gomis, Jules François; Dia, Anta Tal; Gaye, Oumar

2014-11-24

Malaria is major public health problem in Senegal. In some parts of the country, it occurs almost permanently with a seasonal increase during the rainy season. There is evidence to suggest that the prevalence of malaria in Senegal has decreased considerably during the past few years. Recent data from the Senegalese National Malaria Control Programme (NMCP) indicates that the number of malaria cases decrease from 1,500,000 in 2006 to 174,339 in 2010. With the decline of malaria morbidity in Senegal, the characterization of the new epidemiological profile of this disease is crucial for public health decision makers. SaTScan™ software using the Kulldorf method of retrospective space-time permutation and the Bernoulli purely spatial model was used to identify malaria clusters using confirmed malaria cases in 74 villages. ArcMAp was used to map malaria hotspots. Logistic regression was used to investigate risk factors for malaria hotspots in Keur Soce health and demographic surveillance site. A total of 1,614 individuals in 440 randomly selected households were enrolled. The overall malaria prevalence was 12%. The malaria prevalence during the study period varied from less than 2% to more than 25% from one village to another. The results showed also that rooms located between 50 m to 100 m away from livestock holding place [adjusted O.R = 0.7, P = 0.044, 95% C.I (1.02 - 7.42)], bed net use [adjusted O.R = 1.2, P = 0.024, 95% C.I (1.02 -1.48)], are good predictors for malaria hotspots in the Keur Soce health and demographic surveillance site. The socio economic status of the household also predicted on hotspots patterns. The less poor household are 30% less likely to be classified as malaria hotspots area compared to the poorest household [adjusted O.R = 0.7, P = 0.014, 95% C.I (0.47 - 0.91)]. The study investigated risk factors for malaria hotspots in small communities in the Keur Soce site. The result showed considerable variation of malaria

A screen for immunity genes evolving under positive selection in Drosophila.

PubMed

Jiggins, F M; Kim, K W

2007-05-01

Genes involved in the immune system tend to have higher rates of adaptive evolution than other genes in the genome, probably because they are coevolving with pathogens. We have screened a sample of Drosophila genes to identify those evolving under positive selection. First, we identified rapidly evolving immunity genes by comparing 140 loci in Drosophila erecta and D. yakuba. Secondly, we resequenced 23 of the fastest evolving genes from the independent species pair D. melanogaster and D. simulans, and identified those under positive selection using a McDonald-Kreitman test. There was strong evidence of adaptive evolution in two serine proteases (persephone and spirit) and a homolog of the Anopheles serpin SRPN6, and weaker evidence in another serine protease and the death domain protein dFADD. These results add to mounting evidence that immune signalling pathway molecules often evolve rapidly, possibly because they are sites of host-parasite coevolution.

Promoting Your Web Site.

ERIC Educational Resources Information Center

Raeder, Aggi

1997-01-01

Discussion of ways to promote sites on the World Wide Web focuses on how search engines work and how they retrieve and identify sites. Appropriate Web links for submitting new sites and for Internet marketing are included. (LRW)

A spatial modeling approach to identify potential butternut restoration sites in Mammoth Cave National Park

USGS Publications Warehouse

Thompson, L.M.; Van Manen, F.T.; Schlarbaum, S.E.; DePoy, M.

2006-01-01

Incorporation of disease resistance is nearly complete for several important North American hardwood species threatened by exotic fungal diseases. The next important step toward species restoration would be to develop reliable tools to delineate ideal restoration sites on a landscape scale. We integrated spatial modeling and remote sensing techniques to delineate potential restoration sites for Butternut (Juglans cinerea L.) trees, a hardwood species being decimated by an exotic fungus, in Mammoth Cave National Park (MCNP), Kentucky. We first developed a multivariate habitat model to determine optimum Butternut habitats within MCNP. Habitat characteristics of 54 known Butternut locations were used in combination with eight topographic and land use data layers to calculate an index of habitat suitability based on Mahalanobis distance (D2). We used a bootstrapping technique to test the reliability of model predictions. Based on a threshold value for the D2 statistic, 75.9% of the Butternut locations were correctly classified, indicating that the habitat model performed well. Because Butternut seedlings require extensive amounts of sunlight to become established, we used canopy cover data to refine our delineation of favorable areas for Butternut restoration. Areas with the most favorable conditions to establish Butternut seedlings were limited to 291.6 ha. Our study provides a useful reference on the amount and location of favorable Butternut habitat in MCNP and can be used to identify priority areas for future Butternut restoration. Given the availability of relevant habitat layers and accurate location records, our approach can be applied to other tree species and areas. ?? 2006 Society for Ecological Restoration International.

STD-NMR experiments identify a structural motif with novel second-site activity against West Nile virus NS2B-NS3 protease.

PubMed

Schöne, Tobias; Grimm, Lena Lisbeth; Sakai, Naoki; Zhang, Linlin; Hilgenfeld, Rolf; Peters, Thomas

2017-10-01

West Nile virus (WNV) belongs to the genus Flavivirus of the family Flaviviridae. This mosquito-borne virus that is highly pathogenic to humans has been evolving into a global threat during the past two decades. Despite many efforts, neither antiviral drugs nor vaccines are available. The viral protease NS2B-NS3 pro is essential for viral replication, and therefore it is considered a prime drug target. However, success in the development of specific NS2B-NS3 pro inhibitors had been moderate so far. In the search for new structural motifs with binding affinity for NS2B-NS3 pro , we have screened a fragment library, the Maybridge Ro5 library, employing saturation transfer difference (STD) NMR experiments as readout. About 30% of 429 fragments showed binding to NS2B-NS3 pro . Subsequent STD-NMR competition experiments using the known active site fragment A as reporter ligand yielded 14 competitively binding fragments, and 22 fragments not competing with A. In a fluorophore-based protease assay, all of these fragments showed inhibition in the micromolar range. Interestingly, 10 of these 22 fragments showed a notable increase of STD intensities in the presence of compound A suggesting cooperative binding. The most promising non-competitive inhibitors 1 and 2 (IC 50 ∼ 500 μM) share a structural motif that may guide the development of novel second-site (potentially allosteric) inhibitors of NS2B-NS3 pro . To identify the matching protein binding site, chemical shift perturbation studies employing 1 H, 15 N-TROSY-HSQC experiments with uniformly 2 H, 15 N-labeled protease were performed in the presence of 1, and in the concomitant absence or presence of A. The data suggest that 1 interacts with Met 52* of NS2B, identifying a secondary site adjacent to the binding site of A. Therefore, our study paves the way for the synthesis of novel bidentate NS2B-NS3 pro inhibitors. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization of nicotine binding to the rat brain P/sub 2/ preparation: the identification of multiple binding sites which include specific up-regulatory site(s)

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

Sloan, J.W.

1984-01-01

These studies show that nicotine binds to the rat brain P/sub 2/ preparation by saturable and reversible processes. Multiple binding sites were revealed by the configuration of saturation, kinetic and Scatchard plots. A least squares best fit of Scatchard data using nonlinear curve fitting programs confirmed the presence of a very high affinity site, an up-regulatory site, a high affinity site and one or two low affinity sites. Stereospecificity was demonstrated for the up-regulatory site where (+)-nicotine was more effective and for the high affinity site where (-)-nicotine had a higher affinity. Drugs which selectively up-regulate nicotine binding site(s) havemore » been identified. Further, separate very high and high affinity sites were identified for (-)- and (+)-(/sup 3/H)nicotine, based on evidence that the site density for the (-)-isomer is 10 times greater than that for the (+)-isomer at these sites. Enhanced nicotine binding has been shown to be a statistically significant phenomenon which appears to be a consequence of drugs binding to specific site(s) which up-regulate binding at other site(s). Although Scatchard and Hill plots indicate positive cooperatively, up-regulation more adequately describes the function of these site(s). A separate up-regulatory site is suggested by the following: (1) Drugs vary markedly in their ability to up-regulate binding. (2) Both the affinity and the degree of up-regulation can be altered by structural changes in ligands. (3) Drugs with specificity for up-regulation have been identified. (4) Some drugs enhance binding in a dose-related manner. (5) Competition studies employing cold (-)- and (+)-nicotine against (-)- and (+)-(/sup 3/H)nicotine show that the isomers bind to separate sites which up-regulate binding at the (-)- and (+)-nicotine high affinity sites and in this regard (+)-nicotine is more specific and efficacious than (-)-nicotine.« less

SCS-CN and GIS-based approach for identifying potential water harvesting sites in the Kali Watershed, Mahi River Basin, India

NASA Astrophysics Data System (ADS)

Ramakrishnan, D.; Bandyopadhyay, A.; Kusuma, K. N.

2009-08-01

The Kali sub-watershed is situated in the semi-arid region of Gujarat, India and forms a part of the Mahi River Watershed. This watershed receives an average annual rainfall of 900mm mainly between July and September. Due to high runoff potential, evapo-transpiration and poor infiltration, drought like situation prevails in this area from December to June almost every year. In this paper, augmentation of water resource is proposed by construction of runoff harvesting structures like check dam, percolation pond, farm pond, well and subsurface dyke. The site suitability for different water harvesting structures is determined by considering spatially varying parameters like runoff potential, slope, fracture pattern and micro-watershed area. GIS is utilised as a tool to store, analyse and integrate spatial and attribute information pertaining to runoff, slope, drainage and fracture. The runoff derived by SCS-CN method is a function of runoff potential which can be expressed in terms of runoff coefficient (ratio between the runoff and rainfall) which can be classified into three classes, viz., high (>40%), moderate (20-40%) and low (<20%). In addition to IMSD, FAO specifications for water harvesting/recharging structures, parameters such as effective storage, rock mass permeability are herein considered to augment effective storage. Using the overlay and decision tree concepts in GIS, potential water harvesting sites are identified. The derived sites are field investigated for suitability and implementation. In all, the accuracy of the site selection at implementation level varies from 80-100%.

Exploiting three kinds of interface propensities to identify protein binding sites.

PubMed

Liu, Bin; Wang, Xiaolong; Lin, Lei; Dong, Qiwen; Wang, Xuan

2009-08-01

Predicting the binding sites between two interacting proteins provides important clues to the function of a protein. In this study, we present a building block of proteins called order profiles to use the evolutionary information of the protein sequence frequency profiles and apply this building block to produce a class of propensities called order profile interface propensities. For comparisons, we revisit the usage of residue interface propensities and binary profile interface propensities for protein binding site prediction. Each kind of propensities combined with sequence profiles and accessible surface areas are inputted into SVM. When tested on four types of complexes (hetero-permanent complexes, hetero-transient complexes, homo-permanent complexes and homo-transient complexes), experimental results show that the order profile interface propensities are better than residue interface propensities and binary profile interface propensities. Therefore, order profile is a suitable profile-level building block of the protein sequences and can be widely used in many tasks of computational biology, such as the sequence alignment, the prediction of domain boundary, the designation of knowledge-based potentials and the protein remote homology detection.

HIV-1 protease-substrate coevolution in nelfinavir resistance.

PubMed

Kolli, Madhavi; Ozen, Ayşegül; Kurt-Yilmaz, Nese; Schiffer, Celia A

2014-07-01

Resistance to various human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs) challenges the effectiveness of therapies in treating HIV-1-infected individuals and AIDS patients. The virus accumulates mutations within the protease (PR) that render the PIs less potent. Occasionally, Gag sequences also coevolve with mutations at PR cleavage sites contributing to drug resistance. In this study, we investigated the structural basis of coevolution of the p1-p6 cleavage site with the nelfinavir (NFV) resistance D30N/N88D protease mutations by determining crystal structures of wild-type and NFV-resistant HIV-1 protease in complex with p1-p6 substrate peptide variants with L449F and/or S451N. Alterations of residue 30's interaction with the substrate are compensated by the coevolving L449F and S451N cleavage site mutations. This interdependency in the PR-p1-p6 interactions enhances intermolecular contacts and reinforces the overall fit of the substrate within the substrate envelope, likely enabling coevolution to sustain substrate recognition and cleavage in the presence of PR resistance mutations. Resistance to human immunodeficiency virus type 1 (HIV-1) protease inhibitors challenges the effectiveness of therapies in treating HIV-1-infected individuals and AIDS patients. Mutations in HIV-1 protease selected under the pressure of protease inhibitors render the inhibitors less potent. Occasionally, Gag sequences also mutate and coevolve with protease, contributing to maintenance of viral fitness and to drug resistance. In this study, we investigated the structural basis of coevolution at the Gag p1-p6 cleavage site with the nelfinavir (NFV) resistance D30N/N88D protease mutations. Our structural analysis reveals the interdependency of protease-substrate interactions and how coevolution may restore substrate recognition and cleavage in the presence of protease drug resistance mutations. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

The Lecture as a Transmedial Pedagogical Form: A Historical Analysis

ERIC Educational Resources Information Center

Friesen, Norm

2011-01-01

The lecture has been much maligned as a pedagogical form, yet it persists and even flourishes today in the form of the podcast, the TED talk, and the "smart" lecture hall. This article examines the lecture as a pedagogical genre, as "a site where differences between media are negotiated" (Franzel) as these media coevolve. This examination shows…

Rhodium(II) proximity-labeling identifies a novel target site on STAT3 for inhibitors with potent anti-leukemia activity

PubMed Central

Minus, Matthew B.; Liu, Wei; Vohidov, Farrukh; Kasembeli, Moses M.; Long, Xin; Krueger, Michael; Stevens, Alexandra; Kolosov, Mikhail I.; Sison, Edward Allen R.; Ball, Zachary T.

2015-01-01

Nearly 40% of children with acute myeloid leukemia (AML) suffer relapse due to chemoresistance, often involving upregulation of the oncoprotein STAT3 (signal transducer and activator of transcription 3). In this paper, rhodium(II)-catalyzed, proximity-driven modification identifies the STAT3 coiled-coil domain (CCD) as a novel ligand-binding site, and we describe a new naphthalene sulfonamide inhibitor that targets the CCD, blocks STAT3 function, and halts its disease-promoting effects in vitro, in tumor growth models, and in a leukemia mouse model, validating this new therapeutic target for resistant AML. PMID:26480340

DNAPL SITE EVALUATION - Project Summary

EPA Science Inventory

Dense nonaqueous-phase liquids (DNAPLs), especially chlorinated solvents, are among the most prevalent subsurface contaminants identified in ground-water supplies and at waste disposal sites. There are several site-characterization issues specific to DNAPL sites including (a) the...

Quantitative in vivo Analyses Reveal Calcium-dependent Phosphorylation Sites and Identifies a Novel Component of the Toxoplasma Invasion Motor Complex

PubMed Central

Nebl, Thomas; Prieto, Judith Helena; Kapp, Eugene; Smith, Brian J.; Williams, Melanie J.; Yates, John R.; Cowman, Alan F.; Tonkin, Christopher J.

2011-01-01

Apicomplexan parasites depend on the invasion of host cells for survival and proliferation. Calcium-dependent signaling pathways appear to be essential for micronemal release and gliding motility, yet the target of activated kinases remains largely unknown. We have characterized calcium-dependent phosphorylation events during Toxoplasma host cell invasion. Stimulation of live tachyzoites with Ca2+-mobilizing drugs leads to phosphorylation of numerous parasite proteins, as shown by differential 2-DE display of 32[P]-labeled protein extracts. Multi-dimensional Protein Identification Technology (MudPIT) identified ∼546 phosphorylation sites on over 300 Toxoplasma proteins, including 10 sites on the actomyosin invasion motor. Using a Stable Isotope of Amino Acids in Culture (SILAC)-based quantitative LC-MS/MS analyses we monitored changes in the abundance and phosphorylation of the invasion motor complex and defined Ca2+-dependent phosphorylation patterns on three of its components - GAP45, MLC1 and MyoA. Furthermore, calcium-dependent phosphorylation of six residues across GAP45, MLC1 and MyoA is correlated with invasion motor activity. By analyzing proteins that appear to associate more strongly with the invasion motor upon calcium stimulation we have also identified a novel 15-kDa Calmodulin-like protein that likely represents the MyoA Essential Light Chain of the Toxoplasma invasion motor. This suggests that invasion motor activity could be regulated not only by phosphorylation but also by the direct binding of calcium ions to this new component. PMID:21980283

Pesticide Use Site Index

EPA Pesticide Factsheets

The Pesticide Use Site Index will help a company (or other applicant) identify which data requirements are needed to register a pesticide product. It provides information on pesticide use sites and pesticide major use patterns.

Towards identifying the active sites on RuO 2 (110) in catalyzing oxygen evolution

DOE PAGES

Rao, Reshma R.; Kolb, Manuel J.; Halck, Niels Bendtsen; ...

2017-11-17

While the surface atomic structure of RuO 2 has been well studied in ultra high vacuum, much less is known about the interaction between water and RuO 2 in aqueous solution. In this work, in situ surface X-ray scattering measurements combined with density functional theory (DFT) were used to determine the surface structural changes on single-crystal RuO2(110) as a function of potential in acidic electrolyte. The redox peaks at 0.7, 1.1 and 1.4 V vs. reversible hydrogen electrode (RHE) could be attributed to surface transitions associated with the successive deprotonation of –H 2O on the coordinatively unsaturated Ru sites (CUS)more » and hydrogen adsorbed to the bridging oxygen sites. At potentials relevant to the oxygen evolution reaction (OER), an –OO species on the Ru CUS sites was detected, which was stabilized by a neighboring –OH group on the Ru CUS or bridge site. Combining potential-dependent surface structures with their energetics from DFT led to a new OER pathway, where the deprotonation of the –OH group used to stabilize –OO was found to be rate-limiting.« less

Towards identifying the active sites on RuO 2 (110) in catalyzing oxygen evolution

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

Rao, Reshma R.; Kolb, Manuel J.; Halck, Niels Bendtsen

While the surface atomic structure of RuO 2 has been well studied in ultra high vacuum, much less is known about the interaction between water and RuO 2 in aqueous solution. In this work, in situ surface X-ray scattering measurements combined with density functional theory (DFT) were used to determine the surface structural changes on single-crystal RuO2(110) as a function of potential in acidic electrolyte. The redox peaks at 0.7, 1.1 and 1.4 V vs. reversible hydrogen electrode (RHE) could be attributed to surface transitions associated with the successive deprotonation of –H 2O on the coordinatively unsaturated Ru sites (CUS)more » and hydrogen adsorbed to the bridging oxygen sites. At potentials relevant to the oxygen evolution reaction (OER), an –OO species on the Ru CUS sites was detected, which was stabilized by a neighboring –OH group on the Ru CUS or bridge site. Combining potential-dependent surface structures with their energetics from DFT led to a new OER pathway, where the deprotonation of the –OH group used to stabilize –OO was found to be rate-limiting.« less

Cleaning up contaminated wood-treating sites. Background paper

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

NONE

This report identifies technologies available for organic hazardous waste cleanup at woodtreating sites throughout the country. OTA has identified a range of such technologies that have been selected in the past and could be applied to other sites in the future. The applicability of a technology to a particular Superfund site has to be based on many site-specific factors. Nevertheless, it is clear that a number of the approaches identified by OTA may be appropriate and could prove useful if more detailed site-specific studies and tests were done. Although this study focused on the Texarkana site, decisionmakers and the publicmore » could benefit from this analysis in selecting future cleanup strategies for other sites.« less

Initial direct comparison of 99mTc-TOC and 99mTc-TATE in identifying sites of disease in patients with proven GEP NETs.

PubMed

Cwikla, Jaroslaw B; Mikolajczak, Renata; Pawlak, Dariusz; Buscombe, John R; Nasierowska-Guttmejer, Anna; Bator, Andrzej; Maecke, Helmut R; Walecki, Jerzy

2008-07-01

The imaging of neuroendocrine tumors has become one of the most significant areas in nuclear oncology. In an attempt to provide high-quality imaging and possible sensitivity at a reduced cost, time, and radiation dose, several (99m)Tc agents have been proposed. The aim of this initial study was to compare the tumor uptake and biodistribution of 2 new 6-hydrazinopyridine-3-carboxylic acid (HYNIC)-derivatized Tyr(3)-octreotide analogs, (99m)Tc-[HYNIC,Tyr(3)]octreotide ((99m)Tc-TOC) and (99m)Tc-[HYNIC,Tyr(3),Thr(8)]octreotide ((99m)Tc-TATE), in patients with somatostatin receptor-expressing tumors. Each of 12 patients with proven gastrointestinal pancreatic neuroendocrine tumors received a mean activity of 520 MBq of (99m)Tc-TOC and (99m)Tc-TATE. Scintigraphy with both tracers was performed 3-4 h after their injection using standard whole-body and SPECT imaging. The images were reviewed subjectively by 2 readers, who reported tumor uptake lesion by lesion. Both radiotracers demonstrated concordance between the results in 7 patients (58%). In total, 110 sites of disease were identified with (99m)Tc-TOC, compared with 115 with (99m)Tc-TATE. There was 1 case in which (99m)Tc-TOC identified sites of disease not seen on (99m)Tc-TATE imaging but 4 cases in which some sites of disease were seen with (99m)Tc-TATE and not (99m)Tc-TOC. In this initial study, both tracers seem to show similar sites of tumor, with (99m)Tc-TATE having a slight edge in the total number of lesions seen, especially in lymph node metastases.

Rhodium(II) Proximity-Labeling Identifies a Novel Target Site on STAT3 for Inhibitors with Potent Anti-Leukemia Activity.

PubMed

Minus, Matthew B; Liu, Wei; Vohidov, Farrukh; Kasembeli, Moses M; Long, Xin; Krueger, Michael J; Stevens, Alexandra; Kolosov, Mikhail I; Tweardy, David J; Sison, Edward Allan R; Redell, Michele S; Ball, Zachary T

2015-10-26

Nearly 40 % of children with acute myeloid leukemia (AML) suffer relapse arising from chemoresistance, often involving upregulation of the oncoprotein STAT3 (signal transducer and activator of transcription 3). Herein, rhodium(II)-catalyzed, proximity-driven modification identifies the STAT3 coiled-coil domain (CCD) as a novel ligand-binding site, and we describe a new naphthalene sulfonamide inhibitor that targets the CCD, blocks STAT3 function, and halts its disease-promoting effects in vitro, in tumor growth models, and in a leukemia mouse model, validating this new therapeutic target for resistant AML. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mass spectrometry identifies multiple organophosphorylated sites on tubulin

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

Grigoryan, Hasmik; Schopfer, Lawrence M.; Peeples, Eric S.

2009-10-15

Acute toxicity of organophosphorus poisons (OP) is explained by inhibition of acetylcholinesterase in nerve synapses. Low-dose effects are hypothesized to result from modification of other proteins, whose identity is not yet established. The goal of the present work was to obtain information that would make it possible to identify tubulin as a target of OP exposure. Tubulin was selected for study because live mice injected with a nontoxic dose of a biotinylated organophosphorus agent appeared to have OP-labeled tubulin in brain as determined by binding to avidin beads and mass spectrometry. The experiments with live mice were not conclusive becausemore » binding to avidin beads could be nonspecific. To be convincing, it is necessary to find and characterize the OP-labeled tubulin peptide. The search for OP-labeled tubulin peptides was begun by identifying residues capable of making a covalent bond with OP. Pure bovine tubulin (0.012 mM) was treated with 0.01-0.5 mM chlorpyrifos oxon for 24 h at 37 {sup o}C in pH 8.3 buffer. The identity of labeled amino acids and percent labeling was determined by mass spectrometry. Chlorpyrifos oxon bound covalently to tyrosines 83, 103, 108, 161, 224, 262, 272, 357, and 399 in bovine alpha tubulin, and to tyrosines 50, 51, 59, 106, 159, 281, 310, and 340 in bovine beta tubulin. The most reactive were tyrosine 83 in alpha and tyrosine 281 in beta tubulin. In the presence of 1 mM GTP, percent labeling increased 2-fold. Based on the crystal structure of the tubulin heterodimer (PDB 1jff) tyrosines 83 and 281 are well exposed to solvent. In conclusion seventeen tyrosines in tubulin have the potential to covalently bind chlorpyrifos oxon. These results will be useful when searching for OP-labeled tubulin in live animals.« less

Mass spectrometry identifies multiple organophosphorylated sites on tubulin

PubMed Central

Grigoryan, Hasmik; Schopfer, Lawrence M.; Peeples, Eric S.; Duysen, Ellen G.; Grigoryan, Marine; Thompson, Charles M.; Lockridge, Oksana

2009-01-01

Acute toxicity of organophosphorus poisons (OP) is explained by inhibition of acetylcholinesterase in nerve synapses. Low dose effects are hypothesized to result from modification of other proteins, whose identity is not yet established. The goal of the present work was to obtain information that would make it possible to identify tubulin as a target of OP exposure. Tubulin was selected for study because live mice injected with a nontoxic dose of a biotinylated organophosphorus agent appeared to have OP-labeled tubulin in brain as determined by binding to avidin beads and mass spectrometry. The experiments with live mice were not conclusive because binding to avidin beads could be nonspecific. To be convincing, it is necessary to find and characterize the OP-labeled tubulin peptide. The search for OP-labeled tubulin peptides was begun by identifying residues capable of making a covalent bond with OP. Pure bovine tubulin (0.012 mM) was treated with 0.01–0.5 mM chlorpyrifos oxon for 24 h at 37 °C in pH 8.3 buffer. The identity of labeled amino acids and percent labeling was determined by mass spectrometry. Chlorpyrifos oxon bound covalently to tyrosines 83, 103, 108, 161, 224, 262, 272, 357, and 399 in bovine alpha tubulin, and to tyrosines 50, 51, 59, 106, 159, 281, 310, and 340 in bovine beta tubulin. The most reactive were tyrosine 83 in alpha and tyrosine 281 in beta tubulin. In the presence of 1 mM GTP, percent labeling increased 2-fold. Based on the crystal structure of the tubulin heterodimer (PDB 1jff) tyrosines 83 and 281 are well exposed to solvent. In conclusion seventeen tyrosines in tubulin have the potential to covalently bind chlorpyrifos oxon. These results will be useful when searching for OP-labeled tubulin in live animals. PMID:19632257

Past Project Expo Sites

EPA Pesticide Factsheets

This page provides information for Project Expo sites that were featured at the LMOP Conferences in 2013 and 2014. Project Expo sites were featured as being interested in identifying project partners for the development of an LFG energy project.

Approaches to systematic assessment of environmental exposures posed at hazardous waste sites in the developing world: the Toxic Sites Identification Program.

PubMed

Ericson, Bret; Caravanos, Jack; Chatham-Stephens, Kevin; Landrigan, Philip; Fuller, Richard

2013-02-01

In the developing world, environmental chemical exposures due to hazardous waste sites are poorly documented. We describe the approach taken by the Blacksmith Institute's Toxic Sites Identification Program in documenting environmental chemical exposures due to hazardous waste sites globally, identifying sites of concern and quantifying pathways, populations, and severity of exposure. A network of local environmental investigators was identified and trained to conduct hazardous waste site investigations and assessments. To date, 2,095 contaminated sites have been identified within 47 countries having an estimated population at risk of 71,500,000. Trained researchers and investigators have visited 1,400 of those sites. Heavy metals are the leading primary exposures, with water supply and ambient air being the primary routes of exposure. Even though chemical production has occurred largely in the developed world to date, many hazardous waste sites in the developing world pose significant hazards to the health of large portions of the population. Further research is needed to quantify potential health and economic consequences and identify cost-effective approaches to remediation.

Role of geophysics in identifying and characterizing sites for high-level nuclear waste repositories.

USGS Publications Warehouse

Wynn, J.C.; Roseboom, E.H.

1987-01-01

Evaluation of potential high-level nuclear waste repository sites is an area where geophysical capabilities and limitations may significantly impact a major governmental program. Since there is concern that extensive exploratory drilling might degrade most potential disposal sites, geophysical methods become crucial as the only nondestructive means to examine large volumes of rock in three dimensions. Characterization of potential sites requires geophysicists to alter their usual mode of thinking: no longer are anomalies being sought, as in mineral exploration, but rather their absence. Thus the size of features that might go undetected by a particular method take on new significance. Legal and regulatory considerations that stem from this different outlook, most notably the requirements of quality assurance (necessary for any data used in support of a repository license application), are forcing changes in the manner in which geophysicists collect and document their data. -Authors

Identification of site frequencies from building records

USGS Publications Warehouse

Celebi, M.

2003-01-01

A simple procedure to identify site frequencies using earthquake response records from roofs and basements of buildings is presented. For this purpose, data from five different buildings are analyzed using only spectral analyses techniques. Additional data such as free-field records in close proximity to the buildings and site characterization data are also used to estimate site frequencies and thereby to provide convincing evidence and confirmation of the site frequencies inferred from the building records. Furthermore, simple code-formula is used to calculate site frequencies and compare them with the identified site frequencies from records. Results show that the simple procedure is effective in identification of site frequencies and provides relatively reliable estimates of site frequencies when compared with other methods. Therefore the simple procedure for estimating site frequencies using earthquake records can be useful in adding to the database of site frequencies. Such databases can be used to better estimate site frequencies of those sites with similar geological structures.

AutoSite: an automated approach for pseudo-ligands prediction—from ligand-binding sites identification to predicting key ligand atoms

PubMed Central

Ravindranath, Pradeep Anand; Sanner, Michel F.

2016-01-01

Motivation: The identification of ligand-binding sites from a protein structure facilitates computational drug design and optimization, and protein function assignment. We introduce AutoSite: an efficient software tool for identifying ligand-binding sites and predicting pseudo ligand corresponding to each binding site identified. Binding sites are reported as clusters of 3D points called fills in which every point is labelled as hydrophobic or as hydrogen bond donor or acceptor. From these fills AutoSite derives feature points: a set of putative positions of hydrophobic-, and hydrogen-bond forming ligand atoms. Results: We show that AutoSite identifies ligand-binding sites with higher accuracy than other leading methods, and produces fills that better matches the ligand shape and properties, than the fills obtained with a software program with similar capabilities, AutoLigand. In addition, we demonstrate that for the Astex Diverse Set, the feature points identify 79% of hydrophobic ligand atoms, and 81% and 62% of the hydrogen acceptor and donor hydrogen ligand atoms interacting with the receptor, and predict 81.2% of water molecules mediating interactions between ligand and receptor. Finally, we illustrate potential uses of the predicted feature points in the context of lead optimization in drug discovery projects. Availability and Implementation: http://adfr.scripps.edu/AutoDockFR/autosite.html Contact: sanner@scripps.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27354702

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.

Dipeptide frequency/bias analysis identifies conserved sites of nonrandomness shared by cysteine-rich motifs.

PubMed

Campion, S R; Ameen, A S; Lai, L; King, J M; Munzenmaier, T N

2001-08-15

This report describes the application of a simple computational tool, AAPAIR.TAB, for the systematic analysis of the cysteine-rich EGF, Sushi, and Laminin motif/sequence families at the two-amino acid level. Automated dipeptide frequency/bias analysis detects preferences in the distribution of amino acids in established protein families, by determining which "ordered dipeptides" occur most frequently in comprehensive motif-specific sequence data sets. Graphic display of the dipeptide frequency/bias data revealed family-specific preferences for certain dipeptides, but more importantly detected a shared preference for employment of the ordered dipeptides Gly-Tyr (GY) and Gly-Phe (GF) in all three protein families. The dipeptide Asn-Gly (NG) also exhibited high-frequency and bias in the EGF and Sushi motif families, whereas Asn-Thr (NT) was distinguished in the Laminin family. Evaluation of the distribution of dipeptides identified by frequency/bias analysis subsequently revealed the highly restricted localization of the G(F/Y) and N(G/T) sequence elements at two separate sites of extreme conservation in the consensus sequence of all three sequence families. The similar employment of the high-frequency/bias dipeptides in three distinct protein sequence families was further correlated with the concurrence of these shared molecular determinants at similar positions within the distinctive scaffolds of three structurally divergent, but similarly employed, motif modules.

TSSer: an automated method to identify transcription start sites in prokaryotic genomes from differential RNA sequencing data.

PubMed

Jorjani, Hadi; Zavolan, Mihaela

2014-04-01

Accurate identification of transcription start sites (TSSs) is an essential step in the analysis of transcription regulatory networks. In higher eukaryotes, the capped analysis of gene expression technology enabled comprehensive annotation of TSSs in genomes such as those of mice and humans. In bacteria, an equivalent approach, termed differential RNA sequencing (dRNA-seq), has recently been proposed, but the application of this approach to a large number of genomes is hindered by the paucity of computational analysis methods. With few exceptions, when the method has been used, annotation of TSSs has been largely done manually. In this work, we present a computational method called 'TSSer' that enables the automatic inference of TSSs from dRNA-seq data. The method rests on a probabilistic framework for identifying both genomic positions that are preferentially enriched in the dRNA-seq data as well as preferentially captured relative to neighboring genomic regions. Evaluating our approach for TSS calling on several publicly available datasets, we find that TSSer achieves high consistency with the curated lists of annotated TSSs, but identifies many additional TSSs. Therefore, TSSer can accelerate genome-wide identification of TSSs in bacterial genomes and can aid in further characterization of bacterial transcription regulatory networks. TSSer is freely available under GPL license at http://www.clipz.unibas.ch/TSSer/index.php

An optimized magnetite microparticle-based phosphopeptide enrichment strategy for identifying multiple phosphorylation sites in an immunoprecipitated protein.

PubMed

Huang, Yi; Shi, Qihui; Tsung, Chia-Kuang; Gunawardena, Harsha P; Xie, Ling; Yu, Yanbao; Liang, Hongjun; Yang, Pengyuan; Stucky, Galen D; Chen, Xian

2011-01-01

To further improve the selectivity and throughput of phosphopeptide analysis for the samples from real-time cell lysates, here we demonstrate a highly efficient method for phosphopeptide enrichment via newly synthesized magnetite microparticles and the concurrent mass spectrometric analysis. The magnetite microparticles show excellent magnetic responsivity and redispersibility for a quick enrichment of those phosphopeptides in solution. The selectivity and sensitivity of magnetite microparticles in phosphopeptide enrichment are first evaluated by a known mixture containing both phosphorylated and nonphosphorylated proteins. Compared with the titanium dioxide-coated magnetic beads commercially available, our magnetite microparticles show a better specificity toward phosphopeptides. The selectively-enriched phosphopeptides from tryptic digests of β-casein can be detected down to 0.4 fmol μl⁻¹, whereas the recovery efficiency is approximately 90% for monophosphopeptides. This magnetite microparticle-based affinity technology with optimized enrichment conditions is then immediately applied to identify all possible phosphorylation sites on a signal protein isolated in real time from a stress-stimulated mammalian cell culture. A large fraction of peptides eluted from the magnetic particle enrichment step were identified and characterized as either single- or multiphosphorylated species by tandem mass spectrometry. With their high efficiency and utility for phosphopeptide enrichment, the magnetite microparticles hold great potential in the phosphoproteomic studies on real-time samples from cell lysates. Published by Elsevier Inc.

Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes.

PubMed

Rojas, Daniel; Rager, Julia E; Smeester, Lisa; Bailey, Kathryn A; Drobná, Zuzana; Rubio-Andrade, Marisela; Stýblo, Miroslav; García-Vargas, Gonzalo; Fry, Rebecca C

2015-01-01

Prenatal exposure to inorganic arsenic (iAs) is detrimental to the health of newborns and increases the risk of disease development later in life. Here we examined a subset of newborn cord blood leukocyte samples collected from subjects enrolled in the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez Palacio, Mexico, who were exposed to a range of drinking water arsenic concentrations (0.456-236 µg/l). Changes in iAs-associated DNA 5-methylcytosine methylation were assessed across 424,935 CpG sites representing 18,761 genes and compared with corresponding mRNA expression levels and birth outcomes. In the context of arsenic exposure, a total of 2919 genes were identified with iAs-associated differences in DNA methylation. Site-specific analyses identified DNA methylation changes that were most predictive of gene expression levels where CpG methylation within CpG islands positioned within the first exon, the 5' untranslated region and 200 bp upstream of the transcription start site yielded the most significant association with gene expression levels. A set of 16 genes was identified with correlated iAs-associated changes in DNA methylation and mRNA expression and all were highly enriched for binding sites of the early growth response (EGR) and CCCTC-binding factor (CTCF) transcription factors. Furthermore, DNA methylation levels of 7 of these genes were associated with differences in birth outcomes including gestational age and head circumference.These data highlight the complex interplay between DNA methylation, functional changes in gene expression and health outcomes and underscore the need for functional analyses coupled to epigenetic assessments. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

GSK3β phosphorylates newly identified site in the proline-alanine-rich region of cardiac myosin-binding protein C and alters cross-bridge cycling kinetics in human: short communication.

PubMed

Kuster, Diederik W D; Sequeira, Vasco; Najafi, Aref; Boontje, Nicky M; Wijnker, Paul J M; Witjas-Paalberends, E Rosalie; Marston, Steven B; Dos Remedios, Cristobal G; Carrier, Lucie; Demmers, Jeroen A A; Redwood, Charles; Sadayappan, Sakthivel; van der Velden, Jolanda

2013-02-15

Cardiac myosin-binding protein C (cMyBP-C) regulates cross-bridge cycling kinetics and, thereby, fine-tunes the rate of cardiac muscle contraction and relaxation. Its effects on cardiac kinetics are modified by phosphorylation. Three phosphorylation sites (Ser275, Ser284, and Ser304) have been identified in vivo, all located in the cardiac-specific M-domain of cMyBP-C. However, recent work has shown that up to 4 phosphate groups are present in human cMyBP-C. To identify and characterize additional phosphorylation sites in human cMyBP-C. Cardiac MyBP-C was semipurified from human heart tissue. Tandem mass spectrometry analysis identified a novel phosphorylation site on serine 133 in the proline-alanine-rich linker sequence between the C0 and C1 domains of cMyBP-C. Unlike the known sites, Ser133 was not a target of protein kinase A. In silico kinase prediction revealed glycogen synthase kinase 3β (GSK3β) as the most likely kinase to phosphorylate Ser133. In vitro incubation of the C0C2 fragment of cMyBP-C with GSK3β showed phosphorylation on Ser133. In addition, GSK3β phosphorylated Ser304, although the degree of phosphorylation was less compared with protein kinase A-induced phosphorylation at Ser304. GSK3β treatment of single membrane-permeabilized human cardiomyocytes significantly enhanced the maximal rate of tension redevelopment. GSK3β phosphorylates cMyBP-C on a novel site, which is positioned in the proline-alanine-rich region and increases kinetics of force development, suggesting a noncanonical role for GSK3β at the sarcomere level. Phosphorylation of Ser133 in the linker domain of cMyBP-C may be a novel mechanism to regulate sarcomere kinetics.

Fundamental molecules of life are pigments which arose and co-evolved as a response to the thermodynamic imperative of dissipating the prevailing solar spectrum

NASA Astrophysics Data System (ADS)

Michaelian, K.; Simeonov, A.

2015-08-01

The driving force behind the origin and evolution of life has been the thermodynamic imperative of increasing the entropy production of the biosphere through increasing the global solar photon dissipation rate. In the upper atmosphere of today, oxygen and ozone derived from life processes are performing the short-wavelength UV-C and UV-B dissipation. On Earth's surface, water and organic pigments in water facilitate the near-UV and visible photon dissipation. The first organic pigments probably formed, absorbed, and dissipated at those photochemically active wavelengths in the UV-C and UV-B that could have reached Earth's surface during the Archean. Proliferation of these pigments can be understood as an autocatalytic photochemical process obeying non-equilibrium thermodynamic directives related to increasing solar photon dissipation rate. Under these directives, organic pigments would have evolved over time to increase the global photon dissipation rate by (1) increasing the ratio of their effective photon cross sections to their physical size, (2) decreasing their electronic excited state lifetimes, (3) quenching radiative de-excitation channels (e.g., fluorescence), (4) covering ever more completely the prevailing solar spectrum, and (5) proliferating and dispersing to cover an ever greater surface area of Earth. From knowledge of the evolution of the spectrum of G-type stars, and considering the most probable history of the transparency of Earth's atmosphere, we construct the most probable Earth surface solar spectrum as a function of time and compare this with the history of molecular absorption maxima obtained from the available data in the literature. This comparison supports the conjecture that many fundamental molecules of life are pigments which arose, proliferated, and co-evolved as a response to dissipating the solar spectrum, supports the thermodynamic dissipation theory for the origin of life, constrains models for Earth's early atmosphere, and sheds

Transferring site information for black walnut from native woodlands in southeastern Kansas USA to identify sites for agroforestry practices

Treesearch

Wayne A. Geyer; Felix Ponder

2013-01-01

Black walnut (Juglans nigra) is an important tree species for temperate agroforestry in the United States for timber, nuts, wildlife, and abrasives. Predictions of forestland productivity are needed for proper species selection in tree planting. Potential productivity can be estimated for nonforested areas and agricultural croplands by relating site...

Exploring critical pathways for urban water management to identify robust strategies under deep uncertainties.

PubMed

Urich, Christian; Rauch, Wolfgang

2014-12-01

Long-term projections for key drivers needed in urban water infrastructure planning such as climate change, population growth, and socio-economic changes are deeply uncertain. Traditional planning approaches heavily rely on these projections, which, if a projection stays unfulfilled, can lead to problematic infrastructure decisions causing high operational costs and/or lock-in effects. New approaches based on exploratory modelling take a fundamentally different view. Aim of these is, to identify an adaptation strategy that performs well under many future scenarios, instead of optimising a strategy for a handful. However, a modelling tool to support strategic planning to test the implication of adaptation strategies under deeply uncertain conditions for urban water management does not exist yet. This paper presents a first step towards a new generation of such strategic planning tools, by combing innovative modelling tools, which coevolve the urban environment and urban water infrastructure under many different future scenarios, with robust decision making. The developed approach is applied to the city of Innsbruck, Austria, which is spatially explicitly evolved 20 years into the future under 1000 scenarios to test the robustness of different adaptation strategies. Key findings of this paper show that: (1) Such an approach can be used to successfully identify parameter ranges of key drivers in which a desired performance criterion is not fulfilled, which is an important indicator for the robustness of an adaptation strategy; and (2) Analysis of the rich dataset gives new insights into the adaptive responses of agents to key drivers in the urban system by modifying a strategy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Identifying CpG sites associated with eczema via random forest screening of epigenome-scale DNA methylation.

PubMed

Quraishi, B M; Zhang, H; Everson, T M; Ray, M; Lockett, G A; Holloway, J W; Tetali, S R; Arshad, S H; Kaushal, A; Rezwan, F I; Karmaus, W

2015-01-01

The prevalence of eczema is increasing in industrialized nations. Limited evidence has shown the association of DNA methylation (DNA-M) with eczema. We explored this association at the epigenome-scale to better understand the role of DNA-M. Data from the first generation (F1) of the Isle of Wight (IoW) birth cohort participants and the second generation (F2) were examined in our study. Epigenome-scale DNA methylation of F1 at age 18 years and F2 in cord blood was measured using the Illumina Infinium HumanMethylation450 Beadchip. A total of 307,357 cytosine-phosphate-guanine sites (CpGs) in the F1 generation were screened via recursive random forest (RF) for their potential association with eczema at age 18. Functional enrichment and pathway analysis of resulting genes were carried out using DAVID gene functional classification tool. Log-linear models were performed in F1 to corroborate the identified CpGs. Findings in F1 were further replicated in F2. The recursive RF yielded 140 CpGs, 88 of which showed statistically significant associations with eczema at age 18, corroborated by log-linear models after controlling for false discovery rate (FDR) of 0.05. These CpGs were enriched among many biological pathways, including pathways related to creating transcriptional variety and pathways mechanistically linked to eczema such as cadherins, cell adhesion, gap junctions, tight junctions, melanogenesis, and apoptosis. In the F2 generation, about half of the 83 CpGs identified in F1 showed the same direction of association with eczema risk as in F1, of which two CpGs were significantly associated with eczema risk, cg04850479 of the PROZ gene (risk ratio (RR) = 15.1 in F1, 95 % confidence interval (CI) 1.71, 79.5; RR = 6.82 in F2, 95 % CI 1.52, 30.62) and cg01427769 of the NEU1 gene (RR = 0.13 in F1, 95 % CI 0.03, 0.46; RR = 0.09 in F2, 95 % CI 0.03, 0.36). Via epigenome-scaled analyses using recursive RF followed by log-linear models, we identified 88

Analysis of co-evolving genes in campylobacter jejuni and C. coli

USDA-ARS?s Scientific Manuscript database

Background: The population structure of Campylobacter has been frequently studied by MLST, for which fragments of housekeeping genes are compared. We wished to determine if the used MLST genes are representative of the complete genome. Methods: A set of 1029 core gene families (CGF) was identifie...

Methods for identifying high collision concentration locations (HCCL) for potential safety improvements : phase II, Evaluation of alternative methods for identifying HCCL.

DOT National Transportation Integrated Search

2011-01-01

The objective of network screening should ideally be to not only identify sites for safety : investigation but also to prioritize those sites efficiently. Using roadway, intersection, and : collision data from California, this study compared the perf...

Provocative Endoscopy to Identify Bleeding Site in Upper Gastrointestinal Bleeding: A Novel Approach in Transarterial Embolization.

PubMed

Kamo, Minobu; Fuwa, Sokun; Fukuda, Katsuyuki; Fujita, Yoshiyuki; Kurihara, Yasuyuki

2016-07-01

This report describes a novel approach to endoscopically induce bleeding by removing a clot from the bleeding site during angiography for upper gastrointestinal (UGI) hemorrhage. This procedure enabled accurate identification of the bleeding site, allowing for successful targeted embolization despite a negative initial angiogram. Provocative endoscopy may be a feasible and useful option for angiography of obscure bleeding sites in patients with UGI arterial hemorrhage. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

Guide for Identifying and Converting High-Potential Petroleum Brownfield Sites to Alternative Fuel Stations

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

Johnson, C.; Hettinger, D.; Mosey, G.

Former gasoline stations that are now classified as brownfields can be good sites to sell alternative fuels because they are in locations that are convenient to vehicles and they may be seeking a new source of income. However, their success as alternative fueling stations is highly dependent on location-specific criteria. First, this report outlines what these criteria are, how to prioritize them, and then applies that assessment framework to five of the most popular alternative fuels--electricity, natural gas, hydrogen, ethanol, and biodiesel. The second part of this report delves into the criteria and tools used to assess an alternative fuelmore » retail site at the local level. It does this through two case studies of converting former gasoline stations in the Seattle-Eugene area into electric charge stations. The third part of this report addresses steps to be taken after the specific site has been selected. This includes choosing and installing the recharging equipment, which includes steps to take in the permitting process and key players to include.« less

An evaluation of applicability of seismic refraction method in identifying shallow archaeological features A case study at archaeological site

NASA Astrophysics Data System (ADS)

Jahangardi, Morteza; Hafezi Moghaddas, Naser; Keivan Hosseini, Sayyed; Garazhian, Omran

2015-04-01

We applied the seismic refraction method at archaeological site, Tepe Damghani located in Sabzevar, NE of Iran, in order to determine the structures of archaeological interests. This pre-historical site has special conditions with respect to geographical location and geomorphological setting, so it is an urban archaeological site, and in recent years it has been used as an agricultural field. In spring and summer of 2012, the third season of archaeological excavation was carried out. Test trenches of excavations in this site revealed that cultural layers were often disturbed adversely due to human activities such as farming and road construction in recent years. Conditions of archaeological cultural layers in southern and eastern parts of Tepe are slightly better, for instance, in test trench 3×3 m²1S03, third test trench excavated in the southern part of Tepe, an adobe in situ architectural structure was discovered that likely belongs to cultural features of a complex with 5 graves. After conclusion of the third season of archaeological excavation, all of the test trenches were filled with the same soil of excavated test trenches. Seismic refraction method was applied with12 channels of P geophones in three lines with a geophone interval of 0.5 meter and a 1.5 meter distance between profiles on test trench 1S03. The goal of this operation was evaluation of applicability of seismic method in identification of archaeological features, especially adobe wall structures. Processing of seismic data was done with the seismic software, SiesImager. Results were presented in the form of seismic section for every profile, so that identification of adobe wall structures was achieved hardly. This could be due to that adobe wall had been built with the same materials of the natural surrounding earth. Thus, there is a low contrast and it has an inappropriate effect on seismic processing and identifying of archaeological features. Hence the result could be that application of

Biological data warehousing system for identifying transcriptional regulatory sites from gene expressions of microarray data.

PubMed

Tsou, Ann-Ping; Sun, Yi-Ming; Liu, Chia-Lin; Huang, Hsien-Da; Horng, Jorng-Tzong; Tsai, Meng-Feng; Liu, Baw-Juine

2006-07-01

Identification of transcriptional regulatory sites plays an important role in the investigation of gene regulation. For this propose, we designed and implemented a data warehouse to integrate multiple heterogeneous biological data sources with data types such as text-file, XML, image, MySQL database model, and Oracle database model. The utility of the biological data warehouse in predicting transcriptional regulatory sites of coregulated genes was explored using a synexpression group derived from a microarray study. Both of the binding sites of known transcription factors and predicted over-represented (OR) oligonucleotides were demonstrated for the gene group. The potential biological roles of both known nucleotides and one OR nucleotide were demonstrated using bioassays. Therefore, the results from the wet-lab experiments reinforce the power and utility of the data warehouse as an approach to the genome-wide search for important transcription regulatory elements that are the key to many complex biological systems.

Site Characterization Technologies for DNAPL Investigations

EPA Pesticide Factsheets

This document is intended to help managers at sites with potential or confirmed DNAPL contamination identify suitable characterization technologies, screen the technologies for potential application, learn about applications at similar sites, and...

Identifying the Infection Control Areas Requiring Modifications in Thoracic Surgery Units: Results of a Two-Year Surveillance of Surgical Site Infections in Hospitals in Southern Poland.

PubMed

Dubiel, Grzegorz; Rogoziński, Paweł; Żaloudik, Elżbieta; Bruliński, Krzysztof; Różańska, Anna; Wójkowska-Mach, Jadwiga

2017-10-01

Surgical site infection (SSI) is considered to be a priority in infection control. The objective of this study is the analysis of results of active targeted surveillance conducted over a two-year period in the Department of Thoracic Surgery at the Pulmonology and Thoracic Surgery Center in Bystra, in southern Poland. The retrospective analysis was carried out on the basis of results of active monitoring of SSI in the 45-bed Department of Thoracic Surgery at the Pulmonology and Thoracic Surgery Center in Bystra between April 1, 2014 and April 30, 2016. Surgical site infections were identified based on the definitions of the European Centre for Disease Prevention and Control (ECDC) taking into account the time of symptom onset, specifically, whether the symptoms occurred within 30 d after the surgical procedure. Detection of SSI relied on daily inspection of incisions by a trained nurse, analysis of medical and nursing entries in the computer system, and analysis of all results of microbiologic tests taken in the unit and in the operating room. In the study period, data were collected regarding 1,387 treatment procedures meeting the registration criteria. Forty cases of SSI were detected yielding an incidence rate of 3%. Most cases (55%) were found in the course of hospitalization and 45% were detected after the patient's discharge. The SSIs were classified as follows: superficial, 37.5%; deep infections, 7.5%; and organ/space infection, 55%. Among patients who were diagnosed with SSI, most were male (77.5%). For patients with an American Society of Anesthesiologists (ASA) score I-II the incidence rate was 2%; ASA score III or more, 3.7%. The incidence rate varied from 0.3% in clean surgical site to 6.5% in clean-contaminated site. The study validated the usefulness of targeted surveillance in monitoring SSIs in patients hospitalized in thoracic surgery departments. Surgical site infection surveillance identified areas of care requiring modifications, namely

A Novel Computational Strategy to Identify A-to-I RNA Editing Sites by RNA-Seq Data: De Novo Detection in Human Spinal Cord Tissue

PubMed Central

Picardi, Ernesto; Gallo, Angela; Galeano, Federica; Tomaselli, Sara; Pesole, Graziano

2012-01-01

RNA editing is a post-transcriptional process occurring in a wide range of organisms. In human brain, the A-to-I RNA editing, in which individual adenosine (A) bases in pre-mRNA are modified to yield inosine (I), is the most frequent event. Modulating gene expression, RNA editing is essential for cellular homeostasis. Indeed, its deregulation has been linked to several neurological and neurodegenerative diseases. To date, many RNA editing sites have been identified by next generation sequencing technologies employing massive transcriptome sequencing together with whole genome or exome sequencing. While genome and transcriptome reads are not always available for single individuals, RNA-Seq data are widespread through public databases and represent a relevant source of yet unexplored RNA editing sites. In this context, we propose a simple computational strategy to identify genomic positions enriched in novel hypothetical RNA editing events by means of a new two-steps mapping procedure requiring only RNA-Seq data and no a priori knowledge of RNA editing characteristics and genomic reads. We assessed the suitability of our procedure by confirming A-to-I candidates using conventional Sanger sequencing and performing RNA-Seq as well as whole exome sequencing of human spinal cord tissue from a single individual. PMID:22957051

Application of Geophysical Techniques in Identifying UNE Signatures at Semipalatinsk Test Site (for OSI Purposes)

NASA Astrophysics Data System (ADS)

Belyashov, A.; Shaitorov, V.; Yefremov, M.

2014-03-01

This article describes geological and geophysical studies of an underground nuclear explosion area in one of the boreholes at the Semipalatinsk test site in Kazakhstan. During these studies, the typical elements of mechanical impact of the underground explosion on the host medium—fracturing of rock, spall zones, faults, cracks, etc., were observed. This information supplements to the database of underground nuclear explosion phenomenology and can be applied in fulfilling on-site inspection tasks under the Comprehensive Nuclear-Test-Ban Treaty.

Multi-species comparative analysis of the equine ACE gene identifies a highly conserved potential transcription factor binding site in intron 16.

PubMed

Hamilton, Natasha A; Tammen, Imke; Raadsma, Herman W

2013-01-01

Angiotensin converting enzyme (ACE) is essential for control of blood pressure. The human ACE gene contains an intronic Alu indel (I/D) polymorphism that has been associated with variation in serum enzyme levels, although the functional mechanism has not been identified. The polymorphism has also been associated with cardiovascular disease, type II diabetes, renal disease and elite athleticism. We have characterized the ACE gene in horses of breeds selected for differing physical abilities. The equine gene has a similar structure to that of all known mammalian ACE genes. Nine common single nucleotide polymorphisms (SNPs) discovered in pooled DNA were found to be inherited in nine haplotypes. Three of these SNPs were located in intron 16, homologous to that containing the Alu polymorphism in the human. A highly conserved 18 bp sequence, also within that intron, was identified as being a potential binding site for the transcription factors Oct-1, HFH-1 and HNF-3β, and lies within a larger area of higher than normal homology. This putative regulatory element may contribute to regulation of the documented inter-individual variation in human circulating enzyme levels, for which a functional mechanism is yet to be defined. Two equine SNPs occurred within the conserved area in intron 16, although neither of them disrupted the putative binding site. We propose a possible regulatory mechanism of the ACE gene in mammalian species which was previously unknown. This advance will allow further analysis leading to a better understanding of the mechanisms underpinning the associations seen between the human Alu polymorphism and enzyme levels, cardiovascular disease states and elite athleticism.

Multi-Species Comparative Analysis of the Equine ACE Gene Identifies a Highly Conserved Potential Transcription Factor Binding Site in Intron 16

PubMed Central

Hamilton, Natasha A.; Tammen, Imke; Raadsma, Herman W.

2013-01-01

Angiotensin converting enzyme (ACE) is essential for control of blood pressure. The human ACE gene contains an intronic Alu indel (I/D) polymorphism that has been associated with variation in serum enzyme levels, although the functional mechanism has not been identified. The polymorphism has also been associated with cardiovascular disease, type II diabetes, renal disease and elite athleticism. We have characterized the ACE gene in horses of breeds selected for differing physical abilities. The equine gene has a similar structure to that of all known mammalian ACE genes. Nine common single nucleotide polymorphisms (SNPs) discovered in pooled DNA were found to be inherited in nine haplotypes. Three of these SNPs were located in intron 16, homologous to that containing the Alu polymorphism in the human. A highly conserved 18 bp sequence, also within that intron, was identified as being a potential binding site for the transcription factors Oct-1, HFH-1 and HNF-3β, and lies within a larger area of higher than normal homology. This putative regulatory element may contribute to regulation of the documented inter-individual variation in human circulating enzyme levels, for which a functional mechanism is yet to be defined. Two equine SNPs occurred within the conserved area in intron 16, although neither of them disrupted the putative binding site. We propose a possible regulatory mechanism of the ACE gene in mammalian species which was previously unknown. This advance will allow further analysis leading to a better understanding of the mechanisms underpinning the associations seen between the human Alu polymorphism and enzyme levels, cardiovascular disease states and elite athleticism. PMID:23408978

10 CFR 72.98 - Identifying regions around an ISFSI or MRS site.

Code of Federal Regulations, 2014 CFR

2014-01-01

... regional extent of external phenomena, man-made or natural, that are used as a basis for the design of the ISFSI or MRS must be identified. (b) The potential regional impact due to the construction, operation or decommissioning of the ISFSI or MRS must be identified. The extent of regional impacts must be determined on the...

10 CFR 72.98 - Identifying regions around an ISFSI or MRS site.

Code of Federal Regulations, 2013 CFR

2013-01-01

... regional extent of external phenomena, man-made or natural, that are used as a basis for the design of the ISFSI or MRS must be identified. (b) The potential regional impact due to the construction, operation or decommissioning of the ISFSI or MRS must be identified. The extent of regional impacts must be determined on the...

10 CFR 72.98 - Identifying regions around an ISFSI or MRS site.

Code of Federal Regulations, 2010 CFR

2010-01-01

... regional extent of external phenomena, man-made or natural, that are used as a basis for the design of the ISFSI or MRS must be identified. (b) The potential regional impact due to the construction, operation or decommissioning of the ISFSI or MRS must be identified. The extent of regional impacts must be determined on the...

Analysis of Elementary School Web Sites

ERIC Educational Resources Information Center

Hartshorne, Richard; Friedman, Adam; Algozzine, Bob; Kaur, Daljit

2008-01-01

While researchers have studied the use and value of educational software for many years, study of school Web sites and/or their effectiveness is limited. In this investigation, we identified goals and functions of school Web sites and used the foundations of effective Web site design to develop an evaluation checklist. We then applied these…

SVM-Based Prediction of Propeptide Cleavage Sites in Spider Toxins Identifies Toxin Innovation in an Australian Tarantula

PubMed Central

Wong, Emily S. W.; Hardy, Margaret C.; Wood, David; Bailey, Timothy; King, Glenn F.

2013-01-01

Spider neurotoxins are commonly used as pharmacological tools and are a popular source of novel compounds with therapeutic and agrochemical potential. Since venom peptides are inherently toxic, the host spider must employ strategies to avoid adverse effects prior to venom use. It is partly for this reason that most spider toxins encode a protective proregion that upon enzymatic cleavage is excised from the mature peptide. In order to identify the mature toxin sequence directly from toxin transcripts, without resorting to protein sequencing, the propeptide cleavage site in the toxin precursor must be predicted bioinformatically. We evaluated different machine learning strategies (support vector machines, hidden Markov model and decision tree) and developed an algorithm (SpiderP) for prediction of propeptide cleavage sites in spider toxins. Our strategy uses a support vector machine (SVM) framework that combines both local and global sequence information. Our method is superior or comparable to current tools for prediction of propeptide sequences in spider toxins. Evaluation of the SVM method on an independent test set of known toxin sequences yielded 96% sensitivity and 100% specificity. Furthermore, we sequenced five novel peptides (not used to train the final predictor) from the venom of the Australian tarantula Selenotypus plumipes to test the accuracy of the predictor and found 80% sensitivity and 99.6% 8-mer specificity. Finally, we used the predictor together with homology information to predict and characterize seven groups of novel toxins from the deeply sequenced venom gland transcriptome of S. plumipes, which revealed structural complexity and innovations in the evolution of the toxins. The precursor prediction tool (SpiderP) is freely available on ArachnoServer (http://www.arachnoserver.org/spiderP.html), a web portal to a comprehensive relational database of spider toxins. All training data, test data, and scripts used are available from the Spider

Exome Sequencing Identified a Splice Site Mutation in FHL1 that Causes Uruguay Syndrome, an X-Linked Disorder With Skeletal Muscle Hypertrophy and Premature Cardiac Death.

PubMed

Xue, Yuan; Schoser, Benedikt; Rao, Aliz R; Quadrelli, Roberto; Vaglio, Alicia; Rupp, Verena; Beichler, Christine; Nelson, Stanley F; Schapacher-Tilp, Gudrun; Windpassinger, Christian; Wilcox, William R

2016-04-01

Previously, we reported a rare X-linked disorder, Uruguay syndrome in a single family. The main features are pugilistic facies, skeletal deformities, and muscular hypertrophy despite a lack of exercise and cardiac ventricular hypertrophy leading to premature death. An ≈19 Mb critical region on X chromosome was identified through identity-by-descent analysis of 3 affected males. Exome sequencing was conducted on one affected male to identify the disease-causing gene and variant. A splice site variant (c.502-2A>G) in the FHL1 gene was highly suspicious among other candidate genes and variants. FHL1A is the predominant isoform of FHL1 in cardiac and skeletal muscle. Sequencing cDNA showed the splice site variant led to skipping of exons 6 of the FHL1A isoform, equivalent to the FHL1C isoform. Targeted analysis showed that this splice site variant cosegregated with disease in the family. Western blot and immunohistochemical analysis of muscle from the proband showed a significant decrease in protein expression of FHL1A. Real-time polymerase chain reaction analysis of different isoforms of FHL1 demonstrated that the FHL1C is markedly increased. Mutations in the FHL1 gene have been reported in disorders with skeletal and cardiac myopathy but none has the skeletal or facial phenotype seen in patients with Uruguay syndrome. Our data suggest that a novel FHL1 splice site variant results in the absence of FHL1A and the abundance of FHL1C, which may contribute to the complex and severe phenotype. Mutation screening of the FHL1 gene should be considered for patients with uncharacterized myopathies and cardiomyopathies. © 2016 American Heart Association, Inc.

Diet of pumas (Puma concolor) in Sonora, Mexico, as determined by GPS kill sites and molecular identified scat, with comments on jaguar (Panthera onca) diet

USGS Publications Warehouse

Cassaigne, Ivonne; Medellin, Rodrigo A.; Thompson, Ron W.; Culver, Melanie; Ochoa, Alexander; Vargas, Karla; Childs, Jack L.; Sanderson, Jim; List, Rurik; Torres-Gomez, Armando

2016-01-01

We documented puma (Puma concolor) and jaguar (Panthera onca) prey consumption in northeastern Sonora, Mexico, by investigating global positioning system cluster sites (n = 220), and conducting molecular analyses of scat (n = 116) collected between 2011 and 2013. We used camera trap data (n = 8,976 camera days) to estimate relative abundances of pumas and jaguars. Deer (Odocoileus virginianus) was the most frequent prey for puma found at kill sites (67%) and identified from scat (74%), although based on relative numbers of prey consumed, deer represented 45% and lagomorphs 20% of the proportion of all individuals eaten. A variety of small prey (weighing <15 kg) comprised the majority (52%) of the jaguar kill sites. From prey found at kill sites, jaguars killed calves (Bos taurus) at a lower frequency than previously reported, whereas pumas preyed on calves at a higher frequency than previously reported in the same area. In our study area, jaguars preyed on calves at approximately the same rate as pumas (jaguars 3.7 calves per year, pumas 4.9 calves per year). Calculated predation rates were limited only to collared animals within our study area and therefore should not be considered applicable to all pumas and jaguars in Sonora.

Within-population covariation between sexual reproduction and susceptibility to local parasites.

PubMed

Gibson, Amanda K; Xu, Julie Y; Lively, Curtis M

2016-09-01

Evolutionary biology has yet to reconcile the ubiquity of sex with its costs relative to asexual reproduction. Here, we test the hypothesis that coevolving parasites maintain sex in their hosts. Specifically, we examined the distributions of sexual reproduction and susceptibility to local parasites within a single population of freshwater snails (Potamopyrgus antipodarum). Susceptibility to local trematode parasites (Microphallus sp.) is a relative measure of the strength of coevolutionary selection in this system. Thus, if coevolving parasites maintain sex, sexual snails should be common where susceptibility is high. We tested this prediction in a mixed population of sexual and asexual snails by measuring the susceptibility of snails from multiple sites in a lake. Consistent with the prediction, the frequency of sexual snails was tightly and positively correlated with susceptibility to local parasites. Strikingly, in just two years, asexual females increased in frequency at sites where susceptibility declined. We also found that the frequency of sexual females covaries more strongly with susceptibility than with the prevalence of Microphallus infection in the field. In linking susceptibility to the frequency of sexual hosts, our results directly implicate spatial variation in coevolutionary selection in driving the geographic mosaic of sex. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

St. Louis Airport Site annual site environmental report. Calendar year 1985

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

Not Available

1986-04-01

During 1985, the environmental monitoring program was continued at the St. Louis Airport Site (SLAPS) in St. Louis County, Missouri. The ditches north and south of the site have been designated for cleanup as part of the Formerly Utilized Sites Remedial Action Program (FUSRAP), a United States Department of Energy (DOE) program to identify, decontaminate, or otherwise control sites where low-level radioactive contamination remains from the early years of the nation's atomic energy program. The site is not currently controlled or regulated by DOE or NRC, although radiological monitoring of the site has been authorized by the DOE. The monitoringmore » program at the SLAPS measures radon gas concentrations in air; external gamma radiation dose rates; and uranium, thorium, and radium concentrations in surface water, groundwater, and sediment. Potential radiation doses to the public are also calculated. Because the site is not controlled or regulated by the DOE, the DOE Derived Concentration Guides (DCGs) are not applicable to SLAPS, but are included as a basis for comparison only. The DOE DCGs and the DOE radiation protection standard have been revised.« less

Corrective Action Decision Document for Corrective Action Unit 340: Pesticide Release sites, Nevada Test Site, Nevada

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

DOE /NV

This Corrective Action Decision Document has been prepared for Corrective Action Unit 340, the NTS Pesticide Release Sites, in accordance with the Federal Facility Agreement and Consent Order of 1996 (FFACO, 1996). Corrective Action Unit 340 is located at the Nevada Test Site, Nevada, and is comprised of the following Corrective Action Sites: 23-21-01, Area 23 Quonset Hut 800 Pesticide Release Ditch; 23-18-03, Area 23 Skid Huts Pesticide Storage; and 15-18-02, Area 15 Quonset Hut 15-11 Pesticide Storage. The purpose of this Corrective Action Decision Document is to identify and provide a rationale for the selection of a recommended correctivemore » action alternative for each Corrective Action Site. The scope of this Corrective Action Decision Document consists of the following tasks: Develop corrective action objectives; Identify corrective action alternative screening criteria; Develop corrective action alternatives; Perform detailed and comparative evaluations of the corrective action alternatives in relation to the corrective action objectives and screening criteria; and Recommend and justify a preferred corrective action alternative for each Corrective Action Site.« less

Identifying RNA splicing factors using IFT genes in Chlamydomonas reinhardtii.

PubMed

Lin, Huawen; Zhang, Zhengyan; Iomini, Carlo; Dutcher, Susan K

2018-03-01

Intraflagellar transport moves proteins in and out of flagella/cilia and it is essential for the assembly of these organelles. Using whole-genome sequencing, we identified splice site mutations in two IFT genes, IFT81 ( fla9 ) and IFT121 ( ift121-2 ), which lead to flagellar assembly defects in the unicellular green alga Chlamydomonas reinhardtii The splicing defects in these ift mutants are partially corrected by mutations in two conserved spliceosome proteins, DGR14 and FRA10. We identified a dgr14 deletion mutant, which suppresses the 3' splice site mutation in IFT81 , and a frameshift mutant of FRA10 , which suppresses the 5' splice site mutation in IFT121 Surprisingly, we found dgr14-1 and fra10 mutations suppress both splice site mutations. We suggest these two proteins are involved in facilitating splice site recognition/interaction; in their absence some splice site mutations are tolerated. Nonsense mutations in SMG1 , which is involved in nonsense-mediated decay, lead to accumulation of aberrant transcripts and partial restoration of flagellar assembly in the ift mutants. The high density of introns and the conservation of noncore splicing factors, together with the ease of scoring the ift mutant phenotype, make Chlamydomonas an attractive organism to identify new proteins involved in splicing through suppressor screening. © 2018 The Authors.

Novel colchicine-site binders with a cyclohexanedione scaffold identified through a ligand-based virtual screening approach.

PubMed

Canela, María-Dolores; Pérez-Pérez, María-Jesús; Noppen, Sam; Sáez-Calvo, Gonzalo; Díaz, J Fernando; Camarasa, María-José; Liekens, Sandra; Priego, Eva-María

2014-05-22

Vascular disrupting agents (VDAs) constitute an innovative anticancer therapy that targets the tumor endothelium, leading to tumor necrosis. Our approach for the identification of new VDAs has relied on a ligand 3-D shape similarity virtual screening (VS) approach using the ROCS program as the VS tool and as query colchicine and TN-16, which both bind the α,β-tubulin dimer. One of the hits identified, using TN-16 as query, has been explored by the synthesis of its structural analogues, leading to 2-(1-((2-methoxyphenyl)amino)ethylidene)-5-phenylcyclohexane-1,3-dione (compound 16c) with an IC50 = 0.09 ± 0.01 μM in HMEC-1 and BAEC, being 100-fold more potent than the initial hit. Compound 16c caused cell cycle arrest in the G2/M phase and interacted with the colchicine-binding site in tubulin, as confirmed by a competition assay with N,N'-ethylenebis(iodoacetamide) and by fluorescence spectroscopy. Moreover, 16c destroyed an established endothelial tubular network at 1 μM and inhibited the migration and invasion of human breast carcinoma cells at 0.4 μM. In conclusion, our approach has led to a new chemotype of promising antiproliferative compounds with antimitotic and potential VDA properties.

IDENTIFYING AND PREDICTING DIVING PLUME BEHAVIOR AT GROUNDWATER SITES CONTAMINATED WITH MTBE: PART 2

EPA Science Inventory

As contaminant ground water flows downgradient from a release point, its movement is dictated by site geological conditions and hydraulics that may result in significant perpendicular contamination migration. This vertical migration pattern has been termed 'plume diving'. Under ...

Options for streamlining the site assessment process

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

Myers, R.

The current site assessment process consists of entry into the CERCLA Information System (CERCLIS) database; completion of the Preliminary Assessment (PA), Site Inspection (SI), and Hazard Ranking System (HRS) documents; and placement on the National Priorities List (NPL). The purpose behind site assessment has been to identify sites for the NPL, not identify the most appropriate means for clearup. Several developments have led EPA to consider redesigning the process, including; the need to encourage brownfields redevelopment; the unintended stigma associated with being on CERCLIS; and the increased expertise of State and some Tribal programs. (For purposes of this paper, brownfieldsmore » are considered abandoned, idled, or under-used industrial and commercial facilities where expansion or redevelopment is complicated by real or perceived environmental contamination.) EPA has begun various site assessment pilots to aid in developing a more efficient and effective Superfund site assessment program. Key goals are to give States increased responsibility, encourage early/more efficient cleanups, reduce costs, and promote environmental recovery and economic revitalization. Possible components of a revised site assessment program are presented.« less

40 CFR 300.410 - Removal site evaluation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 27 2010-07-01 2010-07-01 false Removal site evaluation. 300.410... PLAN Hazardous Substance Response § 300.410 Removal site evaluation. (a) A removal site evaluation... evaluation of a release identified for possible CERCLA response pursuant to § 300.415 shall, as appropriate...

Market-Smart Deconstruction and Material Recovery at Brownfield Sites: How to Identify and Reuse Existing Materials Found at Brownfield Sites

DTIC Science & Technology

2011-06-01

efforts to assess , remediate, and sustainably reuse brownfields . This project is based on the premise that communities have finite resources and that the...this work is to develop tools and guidance for brownfields partners to assess the potential of extracting construction material assets from...buildings, structures, and infrastructure on brownfield sites, and to reuse or recycle this material. This assessment will address the physical

The structure of binding curves and practical identifiability of equilibrium ligand-binding parameters

PubMed Central

Middendorf, Thomas R.

2017-01-01

A critical but often overlooked question in the study of ligands binding to proteins is whether the parameters obtained from analyzing binding data are practically identifiable (PI), i.e., whether the estimates obtained from fitting models to noisy data are accurate and unique. Here we report a general approach to assess and understand binding parameter identifiability, which provides a toolkit to assist experimentalists in the design of binding studies and in the analysis of binding data. The partial fraction (PF) expansion technique is used to decompose binding curves for proteins with n ligand-binding sites exactly and uniquely into n components, each of which has the form of a one-site binding curve. The association constants of the PF component curves, being the roots of an n-th order polynomial, may be real or complex. We demonstrate a fundamental connection between binding parameter identifiability and the nature of these one-site association constants: all binding parameters are identifiable if the constants are all real and distinct; otherwise, at least some of the parameters are not identifiable. The theory is used to construct identifiability maps from which the practical identifiability of binding parameters for any two-, three-, or four-site binding curve can be assessed. Instructions for extending the method to generate identifiability maps for proteins with more than four binding sites are also given. Further analysis of the identifiability maps leads to the simple rule that the maximum number of structurally identifiable binding parameters (shown in the previous paper to be equal to n) will also be PI only if the binding curve line shape contains n resolved components. PMID:27993951

Predicting Displaceable Water Sites Using Mixed-Solvent Molecular Dynamics.

PubMed

Graham, Sarah E; Smith, Richard D; Carlson, Heather A

2018-02-26

Water molecules are an important factor in protein-ligand binding. Upon binding of a ligand with a protein's surface, waters can either be displaced by the ligand or may be conserved and possibly bridge interactions between the protein and ligand. Depending on the specific interactions made by the ligand, displacing waters can yield a gain in binding affinity. The extent to which binding affinity may increase is difficult to predict, as the favorable displacement of a water molecule is dependent on the site-specific interactions made by the water and the potential ligand. Several methods have been developed to predict the location of water sites on a protein's surface, but the majority of methods are not able to take into account both protein dynamics and the interactions made by specific functional groups. Mixed-solvent molecular dynamics (MixMD) is a cosolvent simulation technique that explicitly accounts for the interaction of both water and small molecule probes with a protein's surface, allowing for their direct competition. This method has previously been shown to identify both active and allosteric sites on a protein's surface. Using a test set of eight systems, we have developed a method using MixMD to identify conserved and displaceable water sites. Conserved sites can be determined by an occupancy-based metric to identify sites which are consistently occupied by water even in the presence of probe molecules. Conversely, displaceable water sites can be found by considering the sites which preferentially bind probe molecules. Furthermore, the inclusion of six probe types allows the MixMD method to predict which functional groups are capable of displacing which water sites. The MixMD method consistently identifies sites which are likely to be nondisplaceable and predicts the favorable displacement of water sites that are known to be displaced upon ligand binding.

Analyses of Sporocarps, Morphotyped Ectomycorrhizae, Environmental ITS and LSU Sequences Identify Common Genera that Occur at a Periglacial Site

PubMed Central

Jumpponen, Ari; Brown, Shawn P.; Trappe, James M.; Cázares, Efrén; Strömmer, Rauni

2015-01-01

Periglacial substrates exposed by retreating glaciers represent extreme and sensitive environments defined by a variety of abiotic stressors that challenge organismal establishment and survival. The simple communities often residing at these sites enable their analyses in depth. We utilized existing data and mined published sporocarp, morphotyped ectomycorrhizae (ECM), as well as environmental sequence data of internal transcribed spacer (ITS) and large subunit (LSU) regions of the ribosomal RNA gene to identify taxa that occur at a glacier forefront in the North Cascades Mountains in Washington State in the USA. The discrete data types consistently identified several common and widely distributed genera, perhaps best exemplified by Inocybe and Laccaria. Although we expected low diversity and richness, our environmental sequence data included 37 ITS and 26 LSU operational taxonomic units (OTUs) that likely form ECM. While environmental surveys of metabarcode markers detected large numbers of targeted ECM taxa, both the fruiting body and the morphotype datasets included genera that were undetected in either of the metabarcode datasets. These included hypogeous (Hymenogaster) and epigeous (Lactarius) taxa, some of which may produce large sporocarps but may possess small and/or spatially patchy genets. We highlight the importance of combining various data types to provide a comprehensive view of a fungal community, even in an environment assumed to host communities of low species richness and diversity. PMID:29376900

Unravelling and managing fusiform rust disease: a model approach for coevolved forest tree pathosystems.

Treesearch

CD Nelson; TL Kubisiak; HV Amerson

2010-01-01

Fusiform rust disease remains the most destructive disease in pine plantations in the southern United States. Our ongoing research is designed to identify, map, and clone the interacting genes of the host and pathogen. Several resistance (R) genes have been identified and genetically mapped using informative pine families and single-spore isolate inoculations. In...

10 CFR 861.4 - Use of site streets.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OF ENERGY CONTROL OF TRAFFIC AT NEVADA TEST SITE § 861.4 Use of site streets. All persons using the streets of the Nevada Test Site shall do so in a careful and safe manner. (a) The Nevada Test Site Traffic Regulations supplement this section by identifying the specific traffic requirements relating to such matters...

A Bioinformatics Approach to the Structure, Function, and Evolution of the Nucleoprotein of the Order Mononegavirales

PubMed Central

Cleveland, Sean B.; Davies, John; McClure, Marcella A.

2011-01-01

The goal of this Bioinformatic study is to investigate sequence conservation in relation to evolutionary function/structure of the nucleoprotein of the order Mononegavirales. In the combined analysis of 63 representative nucleoprotein (N) sequences from four viral families (Bornaviridae, Filoviridae, Rhabdoviridae, and Paramyxoviridae) we predict the regions of protein disorder, intra-residue contact and co-evolving residues. Correlations between location and conservation of predicted regions illustrate a strong division between families while high- lighting conservation within individual families. These results suggest the conserved regions among the nucleoproteins, specifically within Rhabdoviridae and Paramyxoviradae, but also generally among all members of the order, reflect an evolutionary advantage in maintaining these sites for the viral nucleoprotein as part of the transcription/replication machinery. Results indicate conservation for disorder in the C-terminus region of the representative proteins that is important for interacting with the phosphoprotein and the large subunit polymerase during transcription and replication. Additionally, the C-terminus region of the protein preceding the disordered region, is predicted to be important for interacting with the encapsidated genome. Portions of the N-terminus are responsible for N∶N stability and interactions identified by the presence or lack of co-evolving intra-protein contact predictions. The validation of these prediction results by current structural information illustrates the benefits of the Disorder, Intra-residue contact and Compensatory mutation Correlator (DisICC) pipeline as a method for quickly characterizing proteins and providing the most likely residues and regions necessary to target for disruption in viruses that have little structural information available. PMID:21559282

Report: EPA Could Improve Its Redistribution of Superfund Payments to Specific Sites

EPA Pesticide Factsheets

Report #2006-P-00027, July 31, 2006. EPA did not make timely redistributions of Superfund coop agreement, interagency agreement, and small purchase payments from the general site identifier “WQ” to the specific Superfund sites or other site identifiers.

Site-Mutation of Hydrophobic Core Residues Synchronically Poise Super Interleukin 2 for Signaling: Identifying Distant Structural Effects through Affordable Computations.

PubMed

Mei, Longcan; Zhou, Yanping; Zhu, Lizhe; Liu, Changlin; Wu, Zhuo; Wang, Fangkui; Hao, Gefei; Yu, Di; Yuan, Hong; Cui, Yanfang

2018-03-20

A superkine variant of interleukin-2 with six site mutations away from the binding interface developed from the yeast display technique has been previously characterized as undergoing a distal structure alteration which is responsible for its super-potency and provides an elegant case study with which to get insight about how to utilize allosteric effect to achieve desirable protein functions. By examining the dynamic network and the allosteric pathways related to those mutated residues using various computational approaches, we found that nanosecond time scale all-atom molecular dynamics simulations can identify the dynamic network as efficient as an ensemble algorithm. The differentiated pathways for the six core residues form a dynamic network that outlines the area of structure alteration. The results offer potentials of using affordable computing power to predict allosteric structure of mutants in knowledge-based mutagenesis.

Mirroring co-evolving trees in the light of their topologies.

PubMed

Hajirasouliha, Iman; Schönhuth, Alexander; de Juan, David; Valencia, Alfonso; Sahinalp, S Cenk

2012-05-01

Determining the interaction partners among protein/domain families poses hard computational problems, in particular in the presence of paralogous proteins. Available approaches aim to identify interaction partners among protein/domain families through maximizing the similarity between trimmed versions of their phylogenetic trees. Since maximization of any natural similarity score is computationally difficult, many approaches employ heuristics to evaluate the distance matrices corresponding to the tree topologies in question. In this article, we devise an efficient deterministic algorithm which directly maximizes the similarity between two leaf labeled trees with edge lengths, obtaining a score-optimal alignment of the two trees in question. Our algorithm is significantly faster than those methods based on distance matrix comparison: 1 min on a single processor versus 730 h on a supercomputer. Furthermore, we outperform the current state-of-the-art exhaustive search approach in terms of precision, while incurring acceptable losses in recall. A C implementation of the method demonstrated in this article is available at http://compbio.cs.sfu.ca/mirrort.htm

Identifying key controls on the behavior of an acidic-U(VI) plume in the Savannah River Site using reactive transport modeling.

PubMed

Bea, Sergio A; Wainwright, Haruko; Spycher, Nicolas; Faybishenko, Boris; Hubbard, Susan S; Denham, Miles E

2013-08-01

Acidic low-level waste radioactive waste solutions were discharged to three unlined seepage basins at the F-Area of the Department of Energy (DOE) Savannah River Site (SRS), South Carolina, USA, from 1955 through 1989. Despite many years of active remediation, the groundwater remains acidic and contaminated with significant levels of U(VI) and other radionuclides. Monitored Natural Attenuation (MNA) is a desired closure strategy for the site, based on the premise that regional flow of clean background groundwater will eventually neutralize the groundwater acidity, immobilizing U(VI) through adsorption. An in situ treatment system is currently in place to accelerate this in the downgradient portion of the plume and similar measures could be taken upgradient if necessary. Understanding the long-term pH and U(VI) adsorption behavior at the site is critical to assess feasibility of MNA along with the in-situ remediation treatments. This paper presents a reactive transport (RT) model and uncertainty quantification (UQ) analyses to explore key controls on the U(VI)-plume evolution and long-term mobility at this site. Two-dimensional numerical RT simulations are run including the saturated and unsaturated (vadose) zones, U(VI) and H(+) adsorption (surface complexation) onto sediments, dissolution and precipitation of Al and Fe minerals, and key hydrodynamic processes are considered. UQ techniques are applied using a new open-source tool that is part of the developing ASCEM reactive transport modeling and analysis framework to: (1) identify the complex physical and geochemical processes that control the U(VI) plume migration in the pH range where the plume is highly mobile, (2) evaluate those physical and geochemical parameters that are most controlling, and (3) predict the future plume evolution constrained by historical, chemical and hydrological data. The RT simulation results show a good agreement with the observed historical pH and concentrations of U(VI), nitrates

Identifying transposon insertions and their effects from RNA-sequencing data.

PubMed

de Ruiter, Julian R; Kas, Sjors M; Schut, Eva; Adams, David J; Koudijs, Marco J; Wessels, Lodewyk F A; Jonkers, Jos

2017-07-07

Insertional mutagenesis using engineered transposons is a potent forward genetic screening technique used to identify cancer genes in mouse model systems. In the analysis of these screens, transposon insertion sites are typically identified by targeted DNA-sequencing and subsequently assigned to predicted target genes using heuristics. As such, these approaches provide no direct evidence that insertions actually affect their predicted targets or how transcripts of these genes are affected. To address this, we developed IM-Fusion, an approach that identifies insertion sites from gene-transposon fusions in standard single- and paired-end RNA-sequencing data. We demonstrate IM-Fusion on two separate transposon screens of 123 mammary tumors and 20 B-cell acute lymphoblastic leukemias, respectively. We show that IM-Fusion accurately identifies transposon insertions and their true target genes. Furthermore, by combining the identified insertion sites with expression quantification, we show that we can determine the effect of a transposon insertion on its target gene(s) and prioritize insertions that have a significant effect on expression. We expect that IM-Fusion will significantly enhance the accuracy of cancer gene discovery in forward genetic screens and provide initial insight into the biological effects of insertions on candidate cancer genes. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Truth and probability in evolutionary games

NASA Astrophysics Data System (ADS)

Barrett, Jeffrey A.

2017-01-01

This paper concerns two composite Lewis-Skyrms signalling games. Each consists in a base game that evolves a language descriptive of nature and a metagame that coevolves a language descriptive of the base game and its evolving language. The first composite game shows how a pragmatic notion of truth might coevolve with a simple descriptive language. The second shows how a pragmatic notion of probability might similarly coevolve. Each of these pragmatic notions is characterised by the particular game and role that it comes to play in the game.

Allosteric binding sites in Rab11 for potential drug candidates

PubMed Central

2018-01-01

Rab11 is an important protein subfamily in the RabGTPase family. These proteins physiologically function as key regulators of intracellular membrane trafficking processes. Pathologically, Rab11 proteins are implicated in many diseases including cancers, neurodegenerative diseases and type 2 diabetes. Although they are medically important, no previous study has found Rab11 allosteric binding sites where potential drug candidates can bind to. In this study, by employing multiple clustering approaches integrating principal component analysis, independent component analysis and locally linear embedding, we performed structural analyses of Rab11 and identified eight representative structures. Using these representatives to perform binding site mapping and virtual screening, we identified two novel binding sites in Rab11 and small molecules that can preferentially bind to different conformations of these sites with high affinities. After identifying the binding sites and the residue interaction networks in the representatives, we computationally showed that these binding sites may allosterically regulate Rab11, as these sites communicate with switch 2 region that binds to GTP/GDP. These two allosteric binding sites in Rab11 are also similar to two allosteric pockets in Ras that we discovered previously. PMID:29874286

Discovery of Novel Nonactive Site Inhibitors of the Prothrombinase Enzyme Complex.

PubMed

Kapoor, Karan; McGill, Nicole; Peterson, Cynthia B; Meyers, Harold V; Blackburn, Michael N; Baudry, Jerome

2016-03-28

The risk of serious bleeding is a major liability of anticoagulant drugs that are active-site competitive inhibitors targeting the Factor Xa (FXa) prothrombin (PT) binding site. The present work identifies several new classes of small molecule anticoagulants that can act as nonactive site inhibitors of the prothrombinase (PTase) complex composed of FXa and Factor Va (FVa). These new classes of anticoagulants were identified, using a novel agnostic computational approach to identify previously unrecognized binding pockets at the FXa-FVa interface. From about three million docking calculations of 281,128 compounds in a conformational ensemble of FXa heavy chains identified by molecular dynamics (MD) simulations, 97 compounds and their structural analogues were selected for experimental validation, through a series of inhibition assays. The compound selection was based on their predicted binding affinities to FXa and their ability to successfully bind to multiple protein conformations while showing selectivity for particular binding sites at the FXa/FVa interface. From these, thirty-one (31) compounds were experimentally identified as nonactive site inhibitors. Concentration-based assays further identified 10 compounds represented by four small-molecule families of inhibitors that achieve dose-independent partial inhibition of PTase activity in a nonactive site-dependent and self-limiting mechanism. Several compounds were identified for their ability to bind to protein conformations only seen during MD, highlighting the importance of accounting for protein flexibility in structure-based drug discovery approaches.

5 CFR 2604.202 - Index identifying information for the public.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Index identifying information for the... DISCLOSURE REPORTS FOIA Public Reading Room Facility and Web Site; Index Identifying Information for the Public § 2604.202 Index identifying information for the public. (a) The Office of Government Ethics will...

Small Scale Multisource Site – Hydrogeology Investigation

EPA Science Inventory

A site impacted by brackish water was evaluated using traditional hydrogeologic and geochemical site characterization techniques. No single, specific source of the brine impacted ground water was identified. However, the extent of the brine impacted ground water was found to be...

Strategy for selecting Mars Pathfinder landing sites

NASA Technical Reports Server (NTRS)

Greeley, Ronald; Kuzmin, Ruslin O.

1994-01-01

A strategy for Pathfinder site selection must be developed that is fundamentally different from most previous considerations. At least two approaches can be identified. In one approach, the objective is to select a site representing a key geologic unit on Mars, i.e., a unit that is widespread, easily recognized, and used frequently as a datum in various investigations. The second approach is to select a site that potentially affords access to a wide variety of rock types. Because rover range is limited, rocks from a variety of sources must be assembled in a small area for sampling. Regardless of the approach taken in site selection, the Pathfinder site should include eolian deposits and provisions should be made to obtain measurements on soils. A recommended approach for selecting the Mars Pathfinder landing site is to identify a deltaic deposit, composed of sediments derived from sources of various ages and geologic units that shows evidence of eolian activity. The site should be located as close as possible to the part of the outwash where rapid deposition occurred because the likelihood of 'sorting' by size and composition increases with distance, decreasing the probability of heterogeneity. In addition, it is recommended that field operation tests be conducted to gain experience and insight into conducting science with Pathfinder.

Site and soil characterization of hazardous waste sites using an expert system guide

NASA Astrophysics Data System (ADS)

Cameron, Roy E.

1993-03-01

An expert system guide (knowledge book) has been devised to assist field personnel who must identify, describe, sample, and interpret size and soil characteristics of hazardous waste sites. The guide takes an approach that will be unfamiliar to most soil and environmental scientists and is directed to on-scene coordinators and project managers and others who may have little soil science training. It meets the need of the U.S. Environmental Protection Agency for standard procedures, guidelines, or protocols that address soil and site contamination, particularly heavy metals. The guide is organized to include: (1) general considerations and processes for collecting and using site and soils data, (2) detailed knowledge frames (descriptive profiles) of likely site and soil conditions, (3) a citation of references, (4) an appendix listing common sources of characterization data, and (5) a glossary of more than 900 general definitions.

Site characterization report for the basalt waste isolation project. Volume II

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

None

1982-11-01

The reference location for a repository in basalt for the terminal storage of nuclear wastes on the Hanford Site and the candidate horizons within this reference repository location have been identified and the preliminary characterization work in support of the site screening process has been completed. Fifteen technical questions regarding the qualification of the site were identified to be addressed during the detailed site characterization phase of the US Department of Energy-National Waste Terminal Storage Program site selection process. Resolution of these questions will be provided in the final site characterization progress report, currently planned to be issued in 1987,more » and in the safety analysis report to be submitted with the License Application. The additional information needed to resolve these questions and the plans for obtaining the information have been identified. This Site Characterization Report documents the results of the site screening process, the preliminary site characterization data, the technical issues that need to be addressed, and the plans for resolving these issues. Volume 2 contains chapters 6 through 12: geochemistry; surface hydrology; climatology, meteorology, and air quality; environmental, land-use, and socioeconomic characteristics; repository design; waste package; and performance assessment.« less

Two ancient bacterial endosymbionts have coevolved with the planthoppers (Insecta: Hemiptera: Fulgoroidea).

PubMed

Urban, Julie M; Cryan, Jason R

2012-06-14

Members of the hemipteran suborder Auchenorrhyncha (commonly known as planthoppers, tree- and leafhoppers, spittlebugs, and cicadas) are unusual among insects known to harbor endosymbiotic bacteria in that they are associated with diverse assemblages of bacterial endosymbionts. Early light microscopic surveys of species representing the two major lineages of Auchenorrhyncha (the planthopper superfamily Fulgoroidea; and Cicadomorpha, comprising Membracoidea [tree- and leafhoppers], Cercopoidea [spittlebugs], and Cicadoidea [cicadas]), found that most examined species harbored at least two morphologically distinct bacterial endosymbionts, and some harbored as many as six. Recent investigations using molecular techniques have identified multiple obligate bacterial endosymbionts in Cicadomorpha; however, much less is known about endosymbionts of Fulgoroidea. In this study, we present the initial findings of an ongoing PCR-based survey (sequencing 16S rDNA) of planthopper-associated bacteria to document endosymbionts with a long-term history of codiversification with their fulgoroid hosts. Results of PCR surveys and phylogenetic analyses of 16S rDNA recovered a monophyletic clade of Betaproteobacteria associated with planthoppers; this clade included Vidania fulgoroideae, a recently described bacterium identified in exemplars of the planthopper family Cixiidae. We surveyed 77 planthopper species representing 18 fulgoroid families, and detected Vidania in 40 species (representing 13 families). Further, we detected the Sulcia endosymbiont (identified as an obligate endosymbiont of Auchenorrhyncha in previous studies) in 30 of the 40 species harboring Vidania. Concordance of the Vidania phylogeny with the phylogeny of the planthopper hosts (reconstructed based on sequence data from five genes generated from the same insect specimens from which the bacterial sequences were obtained) was supported by statistical tests of codiversification. Codiversification tests also

Two ancient bacterial endosymbionts have coevolved with the planthoppers (Insecta: Hemiptera: Fulgoroidea)

PubMed Central

2012-01-01

Background Members of the hemipteran suborder Auchenorrhyncha (commonly known as planthoppers, tree- and leafhoppers, spittlebugs, and cicadas) are unusual among insects known to harbor endosymbiotic bacteria in that they are associated with diverse assemblages of bacterial endosymbionts. Early light microscopic surveys of species representing the two major lineages of Auchenorrhyncha (the planthopper superfamily Fulgoroidea; and Cicadomorpha, comprising Membracoidea [tree- and leafhoppers], Cercopoidea [spittlebugs], and Cicadoidea [cicadas]), found that most examined species harbored at least two morphologically distinct bacterial endosymbionts, and some harbored as many as six. Recent investigations using molecular techniques have identified multiple obligate bacterial endosymbionts in Cicadomorpha; however, much less is known about endosymbionts of Fulgoroidea. In this study, we present the initial findings of an ongoing PCR-based survey (sequencing 16S rDNA) of planthopper-associated bacteria to document endosymbionts with a long-term history of codiversification with their fulgoroid hosts. Results Results of PCR surveys and phylogenetic analyses of 16S rDNA recovered a monophyletic clade of Betaproteobacteria associated with planthoppers; this clade included Vidania fulgoroideae, a recently described bacterium identified in exemplars of the planthopper family Cixiidae. We surveyed 77 planthopper species representing 18 fulgoroid families, and detected Vidania in 40 species (representing 13 families). Further, we detected the Sulcia endosymbiont (identified as an obligate endosymbiont of Auchenorrhyncha in previous studies) in 30 of the 40 species harboring Vidania. Concordance of the Vidania phylogeny with the phylogeny of the planthopper hosts (reconstructed based on sequence data from five genes generated from the same insect specimens from which the bacterial sequences were obtained) was supported by statistical tests of codiversification

In Silico Analysis of Gene Expression Network Components Underlying Pigmentation Phenotypes in the Python Identified Evolutionarily Conserved Clusters of Transcription Factor Binding Sites

PubMed Central

2016-01-01

Color variation provides the opportunity to investigate the genetic basis of evolution and selection. Reptiles are less studied than mammals. Comparative genomics approaches allow for knowledge gained in one species to be leveraged for use in another species. We describe a comparative vertebrate analysis of conserved regulatory modules in pythons aimed at assessing bioinformatics evidence that transcription factors important in mammalian pigmentation phenotypes may also be important in python pigmentation phenotypes. We identified 23 python orthologs of mammalian genes associated with variation in coat color phenotypes for which we assessed the extent of pairwise protein sequence identity between pythons and mouse, dog, horse, cow, chicken, anole lizard, and garter snake. We next identified a set of melanocyte/pigment associated transcription factors (CREB, FOXD3, LEF-1, MITF, POU3F2, and USF-1) that exhibit relatively conserved sequence similarity within their DNA binding regions across species based on orthologous alignments across multiple species. Finally, we identified 27 evolutionarily conserved clusters of transcription factor binding sites within ~200-nucleotide intervals of the 1500-nucleotide upstream regions of AIM1, DCT, MC1R, MITF, MLANA, OA1, PMEL, RAB27A, and TYR from Python bivittatus. Our results provide insight into pigment phenotypes in pythons. PMID:27698666

In Silico Analysis of Gene Expression Network Components Underlying Pigmentation Phenotypes in the Python Identified Evolutionarily Conserved Clusters of Transcription Factor Binding Sites.

PubMed

Irizarry, Kristopher J L; Bryden, Randall L

2016-01-01

Color variation provides the opportunity to investigate the genetic basis of evolution and selection. Reptiles are less studied than mammals. Comparative genomics approaches allow for knowledge gained in one species to be leveraged for use in another species. We describe a comparative vertebrate analysis of conserved regulatory modules in pythons aimed at assessing bioinformatics evidence that transcription factors important in mammalian pigmentation phenotypes may also be important in python pigmentation phenotypes. We identified 23 python orthologs of mammalian genes associated with variation in coat color phenotypes for which we assessed the extent of pairwise protein sequence identity between pythons and mouse, dog, horse, cow, chicken, anole lizard, and garter snake. We next identified a set of melanocyte/pigment associated transcription factors (CREB, FOXD3, LEF-1, MITF, POU3F2, and USF-1) that exhibit relatively conserved sequence similarity within their DNA binding regions across species based on orthologous alignments across multiple species. Finally, we identified 27 evolutionarily conserved clusters of transcription factor binding sites within ~200-nucleotide intervals of the 1500-nucleotide upstream regions of AIM1, DCT, MC1R, MITF, MLANA, OA1, PMEL, RAB27A, and TYR from Python bivittatus . Our results provide insight into pigment phenotypes in pythons.

Coupling GIS and multivariate approaches to reference site selection for wadeable stream monitoring.

PubMed

Collier, Kevin J; Haigh, Andy; Kelly, Johlene

2007-04-01

Geographic Information System (GIS) was used to identify potential reference sites for wadeable stream monitoring, and multivariate analyses were applied to test whether invertebrate communities reflected a priori spatial and stream type classifications. We identified potential reference sites in segments with unmodified vegetation cover adjacent to the stream and in >85% of the upstream catchment. We then used various landcover, amenity and environmental impact databases to eliminate sites that had potential anthropogenic influences upstream and that fell into a range of access classes. Each site identified by this process was coded by four dominant stream classes and seven zones, and 119 candidate sites were randomly selected for follow-up assessment. This process yielded 16 sites conforming to reference site criteria using a conditional-probabilistic design, and these were augmented by an additional 14 existing or special interest reference sites. Non-metric multidimensional scaling (NMS) analysis of percent abundance invertebrate data indicated significant differences in community composition among some of the zones and stream classes identified a priori providing qualified support for this framework in reference site selection. NMS analysis of a range standardised condition and diversity metrics derived from the invertebrate data indicated a core set of 26 closely related sites, and four outliers that were considered atypical of reference site conditions and subsequently dropped from the network. Use of GIS linked to stream typology, available spatial databases and aerial photography greatly enhanced the objectivity and efficiency of reference site selection. The multi-metric ordination approach reduced variability among stream types and bias associated with non-random site selection, and provided an effective way to identify representative reference sites.

O-GlcNAcPRED-II: an integrated classification algorithm for identifying O-GlcNAcylation sites based on fuzzy undersampling and a K-means PCA oversampling technique.

PubMed

Jia, Cangzhi; Zuo, Yun; Zou, Quan; Hancock, John

2018-02-06

Protein O-GlcNAcylation (O-GlcNAc) is an important post-translational modification of serine (S)/threonine (T) residues that involves multiple molecular and cellular processes. Recent studies have suggested that abnormal O-G1cNAcylation causes many diseases, such as cancer and various neurodegenerative diseases. With the available protein O-G1cNAcylation sites experimentally verified, it is highly desired to develop automated methods to rapidly and effectively identify O-G1cNAcylation sites. Although some computational methods have been proposed, their performance has been unsatisfactory, particularly in terms of prediction sensitivity. In this study, we developed an ensemble model O-GlcNAcPRED-II to identify potential O-G1cNAcylation sites. A K-means principal component analysis oversampling technique (KPCA) and fuzzy undersampling method (FUS) were first proposed and incorporated to reduce the proportion of the original positive and negative training samples. Then, rotation forest, a type of classifier-integrated system, was adopted to divide the eight types of feature space into several subsets using four sub-classifiers: random forest, k-nearest neighbour, naive Bayesian and support vector machine. We observed that O-GlcNAcPRED-II achieved a sensitivity of 81.05%, specificity of 95.91%, accuracy of 91.43% and Matthew's correlation coefficient of 0.7928 for five-fold cross-validation run 10 times. Additionally, the results obtained by O-GlcNAcPRED-II on two independent datasets also indicated that the proposed predictor outperformed five published prediction tools. http://121.42.167.206/OGlcPred/. cangzhijia@dlmu.edu.cn or zouquan@nclab.net. © The Author (2018). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

The Best Web Sites for Teachers.

ERIC Educational Resources Information Center

Sharp, Vicki F.; Levine, Martin G.; Sharp, Richard M.

This book identifies more than 650 Internet and World Wide Web sites across the K-12 curriculum that can benefit teachers who may not have time to carry out lengthy searches themselves. The Web sites in this book are organized alphabetically by the following K-12 subject areas: art, bilingual education, drama, ESL, foreign language, health…

Characterization of rhizosphere fungi from selenium hyperaccumulator and nonhyperaccumulator plants along the eastern Rocky Mountain Front Range.

PubMed

Wangeline, Ami L; Valdez, J Rodolfo; Lindblom, Stormy Dawn; Bowling, Keri L; Reeves, F Brent; Pilon-Smits, Elizabeth A H

2011-07-01

Selenium-hyperaccumulator plants can store over 1% (dry mass) Se in their tissues, despite the toxicity of this element at high concentrations across eukaryotes. These levels of Se can have widespread effects on the plant's ecological partners, including herbivores and pathogens. Still other partners seem to have coevolved Se tolerance. This is the first known study addressing the rhizosphere mycoflora of Se hyperaccumulators and aims to evaluate the rhizospheric fungal diversity and Se tolerance to further the knowledge of how these organisms interact with their host plants and survive in these extreme habitats. Rhizosphere fungi were isolated from Se-hyperaccumulator and nonaccumulator plant species collected from five sites in Colorado and Wyoming; four seleniferous sites and one nonseleniferous site. 259 isolates were identified to genus or species and evaluated for Se tolerance. Among the 24 represented genera, 11 comprised 86% of the isolates. The majority of isolates from the seleniferous sites were unaffected by 10 mg·L(-1) Se, irrespective of host plant (hyperaccumulator vs. nonaccumulator), while rhizosphere fungi from a control, nonseleniferous site were highly sensitive to Se at 10 mg·L(-1) and as a group were significantly less (α = 0.05) tolerant than the isolates from the seleniferous sites. Even though Se is a commonly used antifungal agent, these results suggest that rhizosphere fungi from seleniferous habitats have widespread Se tolerance, likely an adaptive advantage in their Se-rich habitat.

PolyA_DB 3 catalogs cleavage and polyadenylation sites identified by deep sequencing in multiple genomes

PubMed Central

Wang, Ruijia; Nambiar, Ram; Zheng, Dinghai

2018-01-01

Abstract PolyA_DB is a database cataloging cleavage and polyadenylation sites (PASs) in several genomes. Previous versions were based mainly on expressed sequence tags (ESTs), which had a limited amount and could lead to inaccurate PAS identification due to the presence of internal A-rich sequences in transcripts. Here, we present an updated version of the database based solely on deep sequencing data. First, PASs are mapped by the 3′ region extraction and deep sequencing (3′READS) method, ensuring unequivocal PAS identification. Second, a large volume of data based on diverse biological samples increases PAS coverage by 3.5-fold over the EST-based version and provides PAS usage information. Third, strand-specific RNA-seq data are used to extend annotated 3′ ends of genes to obtain more thorough annotations of alternative polyadenylation (APA) sites. Fourth, conservation information of PAS across mammals sheds light on significance of APA sites. The database (URL: http://www.polya-db.org/v3) currently holds PASs in human, mouse, rat and chicken, and has links to the UCSC genome browser for further visualization and for integration with other genomic data. PMID:29069441

Pathfinder landing sites at candidate SNC impact ejection sites

NASA Technical Reports Server (NTRS)

Golombek, Matthew P.

1994-01-01

If Mars Pathfinder were able to land at a site on Mars from which the SNC meteorites were ejected by impact, the Pathfinder mission would essentially represent a very inexpensive sample return mission. Geologic units that contain four potential impact craters from which SNC meteorites could have been ejected from Mars are accessible to the Mars Pathfinder lander. Determining that SNC meteorites came from a particular spot on Mars raises the intriguing possibility of using Pathfinder as a sample return mission and providing a radiometric age for the considerably uncertain martian crater-age timescale. Pathfinder instruments are capable of determining if the rock type at the landing site is similar to that of one or more of the SNC meteorites, which would strengthen the hypothesis that the SNC meteorites did, in fact, come from Mars. Unfortunately, instrument observations from Pathfinder are probably not capable of determining if the geologic unit sampled by the lander is definitively the unit from which a SNC meteorite came from as opposed to Mars in general or perhaps a particular region on Mars. This abstract evaluates the possibility of landing at potential SNC ejection sites and the ability of Pathfinder to identify the landing site as the place from which an SNC meteorite came.

Antimicrobial Pesticide Use Site Index

EPA Pesticide Factsheets

This Use Site Index provides guidance to assist applicants for antimicrobial pesticide registration by helping them identify the data requirements necessary to register a pesticide or support their product registrations.

Implementation of an original approach on the Mines-Douai Comparative Reactivity Method (MD-CRM) instrument to identify part of the missing OH reactivity at an urban site

NASA Astrophysics Data System (ADS)

Dusanter, S.; Michoud, V.; Leonardis, T.; Riffault, V.; Zhang, S.; Locoge, N.

2015-12-01

Due to the large number of Volatile Organic Compounds (VOCs) expected in the atmosphere (104-105) (Goldstein and Galbally, ES&T, 2007), exhaustive measurements of VOCs appear to be currently unfeasible using common analytical techniques. In this context, measurements of the total sink of OH, referred as total OH reactivity, can provide a critical test to assess the completeness of trace gas measurements during field campaigns. This can be done by comparing the measured total OH reactivity to values calculated from trace gas measurements. Indeed, large discrepancies are usually found between measured and calculated OH reactivity values revealing the presence of important unmeasured reactive species, which have yet to be identified. A Comparative Reactivity Method (CRM) instrument has been setup at Mines Douai to allow sequential measurements of VOCs and OH reactivity using the same Proton Transfer Reaction-Time of Flight Mass Spectrometer. This approach aims at identifying unmeasured reactive VOCs based on a method proposed by Kato et al. (Atmos. Environ., 2011), taking advantage of VOC oxidations occurring in the CRM sampling reactor. MD-CRM has been deployed at an urban site in Dunkirk (France) during July 2014 to test this new approach. During this campaign, a large fraction of the OH reactivity was not explained by collocated measurements of trace gases (67% on average). In this presentation, we will first describe the approach that was implemented in the CRM instrument to identify part of the observed missing OH reactivity and we will then discuss the OH reactivity budget regarding the origin of air masses reaching the measurement site.

Site observational work plan for the UMTRA Project site at Monument Valley, Arizona

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

NONE

1995-09-01

The site observational work plan (SOWP) for the Monument Valley, Arizona, US Department of Energy (DOE) Uranium Mill Tailings Remedial Action (UMTRA) Project site is one of the first site-specific documents developed to achieve ground water compliance at the site. This SOWP applies information about the Monument Valley site to a regulatory compliance framework that identifies strategies that could be used to meet ground water compliance. The compliance framework was developed in the UMTRA Ground Water programmatic environmental impact statement (DOE, 1995). The DOE`s goal is to implement a cost-effective site strategy that complies with the US Environmental Protection Agencymore » (EPA) ground water standards and protects human health and the environment. The compliance strategy that emerges in the final version of the SOWP will assess potential environmental impacts and provide stakeholder a forum for review and comment. When the compliance strategy is acceptable, it will be detailed in a remedial action plan that will be subject to review by the state and/or tribe and concurrence by the US Nuclear Regulatory Commission (NRC). Information available for the preparation of this SOWP indicates active remediation is the most likely compliance strategy for the Monument Valley site. Additional data are needed to determine the most effective remediation technology.« less

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

PubMed

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

2010-01-01

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

Impact of germline and somatic missense variations on drug binding sites.

PubMed

Yan, C; Pattabiraman, N; Goecks, J; Lam, P; Nayak, A; Pan, Y; Torcivia-Rodriguez, J; Voskanian, A; Wan, Q; Mazumder, R

2017-03-01

Advancements in next-generation sequencing (NGS) technologies are generating a vast amount of data. This exacerbates the current challenge of translating NGS data into actionable clinical interpretations. We have comprehensively combined germline and somatic nonsynonymous single-nucleotide variations (nsSNVs) that affect drug binding sites in order to investigate their prevalence. The integrated data thus generated in conjunction with exome or whole-genome sequencing can be used to identify patients who may not respond to a specific drug because of alterations in drug binding efficacy due to nsSNVs in the target protein's gene. To identify the nsSNVs that may affect drug binding, protein-drug complex structures were retrieved from Protein Data Bank (PDB) followed by identification of amino acids in the protein-drug binding sites using an occluded surface method. Then, the germline and somatic mutations were mapped to these amino acids to identify which of these alter protein-drug binding sites. Using this method we identified 12 993 amino acid-drug binding sites across 253 unique proteins bound to 235 unique drugs. The integration of amino acid-drug binding sites data with both germline and somatic nsSNVs data sets revealed 3133 nsSNVs affecting amino acid-drug binding sites. In addition, a comprehensive drug target discovery was conducted based on protein structure similarity and conservation of amino acid-drug binding sites. Using this method, 81 paralogs were identified that could serve as alternative drug targets. In addition, non-human mammalian proteins bound to drugs were used to identify 142 homologs in humans that can potentially bind to drugs. In the current protein-drug pairs that contain somatic mutations within their binding site, we identified 85 proteins with significant differential gene expression changes associated with specific cancer types. Information on protein-drug binding predicted drug target proteins and prevalence of both somatic and

Identifying and Prioritizing Critical Hardwood Resources

Treesearch

Sam C. Doak; Sharon Johnson; Marlyce Myers

1991-01-01

A logical framework is required to provide a focus for the implementation of a variety of landowner incentive techniques in accordance with existing goals to protect and enhance hardwood resources. A system is presented for identifying and prioritizing critical hardwood resources for site specific conservation purposes. Flexibility is built into this system so that...

Use of surveillance data to identify target populations for Staphylococcus aureus vaccines and prevent surgical site infections: A pilot study

PubMed Central

Gustin, Marie-Paule; Giard, Marine; Bénet, Thomas; Vanhems, Philippe

2015-01-01

The development of anti-staphylococcal vaccines is nowadays a priority to prevent surgical site infections (SSI). The objective of the present study was to identify a potential target population by assessing surveillance data on surgery patients for possible anti-staphylococcal vaccine administration. Individuals at high risk of SSI by Staphylococcus aureus (SA) were targeted by the French SSI Surveillance Network in south-eastern France between 2008 and 2011. Among 238,470 patients, those undergoing primary total hip replacement appeared to be an interesting and healthy enough population for anti-staphylococcal vaccine testing. These male patients, subjected to multiple procedures and with American Society of Anesthesiologists score >2, had a probability of SA SSI about 21 times higher than females with no severe systemic disease and no multiple procedures. Our study indicates that surveillance data on SSI might be an interesting epidemiological source for planning vaccine trials to prevent nosocomial infections. PMID:25668663

Isthmus sites identified by Ripple Mapping are usually anatomically stable: A novel method to guide atrial substrate ablation?

PubMed

Luther, Vishal; Qureshi, Norman; Lim, Phang Boon; Koa-Wing, Michael; Jamil-Copley, Shahnaz; Ng, Fu Siong; Whinnett, Zachary; Davies, D Wyn; Peters, Nicholas S; Kanagaratnam, Prapa; Linton, Nick

2018-03-01

Postablation reentrant ATs depend upon conducting isthmuses bordered by scar. Bipolar voltage maps highlight scar as sites of low voltage, but the voltage amplitude of an electrogram depends upon the myocardial activation sequence. Furthermore, a voltage threshold that defines atrial scar is unknown. We used Ripple Mapping (RM) to test whether these isthmuses were anatomically fixed between different activation vectors and atrial rates. We studied post-AF ablation ATs where >1 rhythm was mapped. Multipolar catheters were used with CARTO Confidense for high-density mapping. RM visualized the pattern of activation, and the voltage threshold below which no activation was seen. Isthmuses were characterized at this threshold between maps for each patient. Ten patients were studied (Map 1 was AT1; Map 2: sinus 1/10, LA paced 2/10, AT2 with reverse CS activation 3/10; AT2 CL difference 50 ± 30 ms). Point density was similar between maps (Map 1: 2,589 ± 1,330; Map 2: 2,214 ± 1,384; P  =  0.31). RM activation threshold was 0.16 ± 0.08 mV. Thirty-one isthmuses were identified in Map 1 (median 3 per map; width 27 ± 15 mm; 7 anterior; 6 roof; 8 mitral; 9 septal; 1 posterior). Importantly, 7 of 31 (23%) isthmuses were unexpectedly identified within regions without prior ablation. AT1 was treated following ablation of 11/31 (35%) isthmuses. Of the remaining 20 isthmuses, 14 of 16 isthmuses (88%) were consistent between the two maps (four were inadequately mapped). Wavefront collision caused variation in low voltage distribution in 2 of 16 (12%). The distribution of isthmuses and nonconducting tissue within the ablated left atrium, as defined by RM, appear concordant between rhythms. This could guide a substrate ablative approach. © 2018 Wiley Periodicals, Inc.

Environmental assessment: Richton Dome Site, Mississippi

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

none,

1986-05-01

In February 1983, the US Department of Energy (DOE) identified the Richton Dome site in Mississippi as one of the nine potentially acceptable sites for a mined geologic repository for spent nuclear fuel and high-level radioactive waste. To determine their suitability, the Richton Dome site and the eight other potentially acceptable sites have been evaluated in accordance with the DOE's General Guidelines for the Recommendation of Sites for the Nuclear Waste Repositories. These evaluations were reported in draft environmental assessments (EAs), which were issued for public review and comment. After considering the comments received on the draft EAs, the DOEmore » prepared the final EAs. The site is in the Gulf interior region, which is one of five distinct geohydrologic settings considered for the first repository. This setting contains two other potentially acceptable sites--the Cypress Creek Dome site in Mississippi and the Vacherie Dome site in Louisiana. Although the Cypress Creek Dome and the Vacherie Dome sites are suitable for site characterization, the DOE has concluded that the Richton Dome site is the preferred site in the Gulf interior region. On the basis of the evaluations reported in this EA, the DOE has found that the Richton Dome site is not disqualified under the guidelines.« less

Searching for transcription factor binding sites in vector spaces

PubMed Central

2012-01-01

Background Computational approaches to transcription factor binding site identification have been actively researched in the past decade. Learning from known binding sites, new binding sites of a transcription factor in unannotated sequences can be identified. A number of search methods have been introduced over the years. However, one can rarely find one single method that performs the best on all the transcription factors. Instead, to identify the best method for a particular transcription factor, one usually has to compare a handful of methods. Hence, it is highly desirable for a method to perform automatic optimization for individual transcription factors. Results We proposed to search for transcription factor binding sites in vector spaces. This framework allows us to identify the best method for each individual transcription factor. We further introduced two novel methods, the negative-to-positive vector (NPV) and optimal discriminating vector (ODV) methods, to construct query vectors to search for binding sites in vector spaces. Extensive cross-validation experiments showed that the proposed methods significantly outperformed the ungapped likelihood under positional background method, a state-of-the-art method, and the widely-used position-specific scoring matrix method. We further demonstrated that motif subtypes of a TF can be readily identified in this framework and two variants called the k NPV and k ODV methods benefited significantly from motif subtype identification. Finally, independent validation on ChIP-seq data showed that the ODV and NPV methods significantly outperformed the other compared methods. Conclusions We conclude that the proposed framework is highly flexible. It enables the two novel methods to automatically identify a TF-specific subspace to search for binding sites. Implementations are available as source code at: http://biogrid.engr.uconn.edu/tfbs_search/. PMID:23244338

Identification of potential sites for deep-ocean waste isolation with a geographic site-selection model

NASA Astrophysics Data System (ADS)

Fleischer, Peter; Bowles, Frederick A.; Richardson, Michael D.

1998-05-01

Identification of optimal sites for the isolation of waste on the abyssal seafloor was performed with two approaches: by the traditional method of map overlays of relevant attributes, and by a specially developed, automated Site-Selection Model (SSM). Five initial, Surrogate Sites, identified with the map-overlay approach, were then compared with the more rigorously produced scores from the SSM. The SSM, a process for optimization of site locations, accepts subjective, expert-based judgments and transforms them into a quantitative, reproducible, and documented product. The SSM is adaptable to any siting scenario. Forty-one factors relevant to the isolation scenario, including 21 weightable factors having a total of 123 scorable categories, have been entered into the SSM. Factors are grouped under project definition, unique environments, anthropogenic, geologic, biologic, weather, oceanographic and distance criteria. The factor scores are linked to a georeferenced database array of all factors, corresponding to 1°×1° latitude-longitude squares. The SSM includes a total of 2241 one-degree squares within 1000 n.m. of the U.S. coasts, including the western North Atlantic, the Gulf of Mexico, and the eastern North Pacific. Under a carefully weighted and scored scenario of isolation, the most favorable sites identified with the SSM are on the Hatteras and Nares Abyssal Plains in the Atlantic. High-scoring sites are also located in the Pacific abyssal hills province between the Murray and Molokai Fracture Zones. Acceptable 1° squares in the Gulf of Mexico are few and of lower quality, with the optimum location on the northern Sigsbee Abyssal Plain. Two of the five Surrogate Site locations, on the Hatteras and Sigsbee Abyssal Plains, correspond to the best SSM sites in each ocean area. Two Pacific and a second Atlantic Surrogate Site are located in low-scoring regions or excluded by the SSM. Site-selection results from the SSM, although robust, are an initial attempt

Cleanup Verification Package for the 300-18 Waste Site

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

J. M. Capron

This cleanup verification package documents completion of remedial action for the 300-18 waste site. This site was identified as containing radiologically contaminated soil, metal shavings, nuts, bolts, and concrete.

RNA Sequencing Identifies New RNase III Cleavage Sites in Escherichia coli and Reveals Increased Regulation of mRNA

DOE PAGES

Gordon, Gina C.; Cameron, Jeffrey C.; Pfleger, Brian F.

2017-03-28

Ribonucleases facilitate rapid turnover of RNA, providing cells with another mechanism to adjust transcript and protein levels in response to environmental conditions. While many examples have been documented, a comprehensive list of RNase targets is not available. To address this knowledge gap, we compared levels of RNA sequencing coverage of Escherichia coli and a corresponding RNase III mutant to expand the list of known RNase III targets. RNase III is a widespread endoribonuclease that binds and cleaves double-stranded RNA in many critical transcripts. RNase III cleavage at novel sites found in aceEF, proP, tnaC, dctA, pheM, sdhC, yhhQ, glpT, aceK,more » and gluQ accelerated RNA decay, consistent with previously described targets wherein RNase III cleavage initiates rapid degradation of secondary messages by other RNases. In contrast, cleavage at three novel sites in the ahpF, pflB, and yajQ transcripts led to stabilized secondary transcripts. Two other novel sites in hisL and pheM overlapped with transcriptional attenuators that likely serve to ensure turnover of these highly structured RNAs. Many of the new RNase III target sites are located on transcripts encoding metabolic enzymes. For instance, two novel RNase III sites are located within transcripts encoding enzymes near a key metabolic node connecting glycolysis and the tricarboxylic acid (TCA) cycle. Pyruvate dehydrogenase activity was increased in an rnc deletion mutant compared to the wild-type (WT) strain in early stationary phase, confirming the novel link between RNA turnover and regulation of pathway activity. Identification of these novel sites suggests that mRNA turnover may be an underappreciated mode of regulating metabolism. IMPORTANCE: The concerted action and overlapping functions of endoribonucleases, exoribonucleases, and RNA processing enzymes complicate the study of global RNA turnover and recycling of specific transcripts. More information about RNase specificity and activity is

RNA Sequencing Identifies New RNase III Cleavage Sites in Escherichia coli and Reveals Increased Regulation of mRNA

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

Gordon, Gina C.; Cameron, Jeffrey C.; Pfleger, Brian F.

Ribonucleases facilitate rapid turnover of RNA, providing cells with another mechanism to adjust transcript and protein levels in response to environmental conditions. While many examples have been documented, a comprehensive list of RNase targets is not available. To address this knowledge gap, we compared levels of RNA sequencing coverage of Escherichia coli and a corresponding RNase III mutant to expand the list of known RNase III targets. RNase III is a widespread endoribonuclease that binds and cleaves double-stranded RNA in many critical transcripts. RNase III cleavage at novel sites found in aceEF, proP, tnaC, dctA, pheM, sdhC, yhhQ, glpT, aceK,more » and gluQ accelerated RNA decay, consistent with previously described targets wherein RNase III cleavage initiates rapid degradation of secondary messages by other RNases. In contrast, cleavage at three novel sites in the ahpF, pflB, and yajQ transcripts led to stabilized secondary transcripts. Two other novel sites in hisL and pheM overlapped with transcriptional attenuators that likely serve to ensure turnover of these highly structured RNAs. Many of the new RNase III target sites are located on transcripts encoding metabolic enzymes. For instance, two novel RNase III sites are located within transcripts encoding enzymes near a key metabolic node connecting glycolysis and the tricarboxylic acid (TCA) cycle. Pyruvate dehydrogenase activity was increased in an rnc deletion mutant compared to the wild-type (WT) strain in early stationary phase, confirming the novel link between RNA turnover and regulation of pathway activity. Identification of these novel sites suggests that mRNA turnover may be an underappreciated mode of regulating metabolism. IMPORTANCE: The concerted action and overlapping functions of endoribonucleases, exoribonucleases, and RNA processing enzymes complicate the study of global RNA turnover and recycling of specific transcripts. More information about RNase specificity and activity is

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

Computer-Based Testing: Test Site Security.

ERIC Educational Resources Information Center

Rosen, Gerald A.

Computer-based testing places great burdens on all involved parties to ensure test security. A task analysis of test site security might identify the areas of protecting the test, protecting the data, and protecting the environment as essential issues in test security. Protecting the test involves transmission of the examinations, identifying the…

Site Characterization at a Tidal Energy Site in the East River, NY (usa)

NASA Astrophysics Data System (ADS)

Gunawan, B.; Neary, V. S.; Colby, J.

2012-12-01

A comprehensive tidal energy site characterization is performed using ADV measurements of instantaneous horizontal current magnitude and direction at the planned hub centerline of a tidal turbine over a two month period, and contributes to the growing data base of tidal energy site hydrodynamic conditions. The temporal variation, mean current statistics, and turbulence of the key tidal hydrodynamic parameters are examined in detail, and compared to estimates from two tidal energy sites in Puget Sound. Tidal hydrodynamic conditions, including mean annual current (at hub height), the speed of extreme gusts (instantaneous horizontal currents acting normal to the rotor plane), and turbulence intensity (as proposed here, relative to a mean current of 2 m s-1) can vary greatly among tidal energy sites. Comparison of hydrodynamic conditions measured in the East River tidal straight in New York City with those reported for two tidal energy sites in Puget Sound indicate differences of mean annual current speeds, difference in the instantaneous current speeds of extreme gusts, and differences in turbulence intensities. Significant differences in these parameters among the tidal energy sites, and with the tidal resource assessment map, highlight the importance of conducting site resource characterization with ADV measurements at the machine scale. As with the wind industry, which adopted an International Electrotechnical Commission (IEC) wind class standard to aid in the selection of wind turbines for a particular site, it is recommended that the tidal energy industry adopt an appropriate standard for tidal current classes. Such a standard requires a comprehensive field campaign at multiple tidal energy sites that can identify the key hydrodynamic parameters for tidal current site classification, select a list of tidal energy sites that exhibit the range of hydrodynamic conditions that will be encountered, and adopt consistent measurement practices (standards) for site

Assessing the representativeness of wind data for wind turbine site evaluation

NASA Technical Reports Server (NTRS)

Renne, D. S.; Corotis, R. B.

1982-01-01

Once potential wind turbine sites (either for single installations or clusters) are identified through siting procedures, actual evaluation of the sites must commence. This evaluation is needed to obtain estimates of wind turbine performance and to identify hazards to the machine from the turbulence component of the atmosphere. These estimates allow for more detailed project planning and for preliminary financing arrangements to be secured. The site evaluation process can occur in two stages: (1) utilizing existing nearby data, and (2) establishing and monitoring an onsite measurement program. Since step (2) requires a period of at least 1 yr or more from the time a potential site has been identified, step (1) is often an essential stage in the preliminary evaluation process. Both the methods that have been developed and the unknowns that still exist in assessing the representativeness of available data to a nearby wind turbine site are discussed. How the assessment of the representativeness of available data can be used to develop a more effective onsite meteorological measurement program is also discussed.

Ligation site in proteins recognized in silico

PubMed Central

Brylinski, Michal; Konieczny, Leszek; Roterman, Irena

2006-01-01

Recognition of a ligation site in a protein molecule is important for identifying its biological activity. The model for in silico recognition of ligation sites in proteins is presented. The idealized hydrophobic core stabilizing protein structure is represented by a three-dimensional Gaussian function. The experimentally observed distribution of hydrophobicity compared with the theoretical distribution reveals differences. The area of high differences indicates the ligation site. Availability http://bioinformatics.cm-uj.krakow.pl/activesite PMID:17597871

Human genomic regions with exceptionally high levels of population differentiation identified from 911 whole-genome sequences.

PubMed

Colonna, Vincenza; Ayub, Qasim; Chen, Yuan; Pagani, Luca; Luisi, Pierre; Pybus, Marc; Garrison, Erik; Xue, Yali; Tyler-Smith, Chris; Abecasis, Goncalo R; Auton, Adam; Brooks, Lisa D; DePristo, Mark A; Durbin, Richard M; Handsaker, Robert E; Kang, Hyun Min; Marth, Gabor T; McVean, Gil A

2014-06-30

Population differentiation has proved to be effective for identifying loci under geographically localized positive selection, and has the potential to identify loci subject to balancing selection. We have previously investigated the pattern of genetic differentiation among human populations at 36.8 million genomic variants to identify sites in the genome showing high frequency differences. Here, we extend this dataset to include additional variants, survey sites with low levels of differentiation, and evaluate the extent to which highly differentiated sites are likely to result from selective or other processes. We demonstrate that while sites with low differentiation represent sampling effects rather than balancing selection, sites showing extremely high population differentiation are enriched for positive selection events and that one half may be the result of classic selective sweeps. Among these, we rediscover known examples, where we actually identify the established functional SNP, and discover novel examples including the genes ABCA12, CALD1 and ZNF804, which we speculate may be linked to adaptations in skin, calcium metabolism and defense, respectively. We identify known and many novel candidate regions for geographically restricted positive selection, and suggest several directions for further research.

Identifying Genetic Traces of Historical Expansions: Phoenician Footprints in the Mediterranean

PubMed Central

Zalloua, Pierre A.; Platt, Daniel E.; El Sibai, Mirvat; Khalife, Jade; Makhoul, Nadine; Haber, Marc; Xue, Yali; Izaabel, Hassan; Bosch, Elena; Adams, Susan M.; Arroyo, Eduardo; López-Parra, Ana María; Aler, Mercedes; Picornell, Antònia; Ramon, Misericordia; Jobling, Mark A.; Comas, David; Bertranpetit, Jaume; Wells, R. Spencer; Tyler-Smith, Chris

2008-01-01

The Phoenicians were the dominant traders in the Mediterranean Sea two thousand to three thousand years ago and expanded from their homeland in the Levant to establish colonies and trading posts throughout the Mediterranean, but then they disappeared from history. We wished to identify their male genetic traces in modern populations. Therefore, we chose Phoenician-influenced sites on the basis of well-documented historical records and collected new Y-chromosomal data from 1330 men from six such sites, as well as comparative data from the literature. We then developed an analytical strategy to distinguish between lineages specifically associated with the Phoenicians and those spread by geographically similar but historically distinct events, such as the Neolithic, Greek, and Jewish expansions. This involved comparing historically documented Phoenician sites with neighboring non-Phoenician sites for the identification of weak but systematic signatures shared by the Phoenician sites that could not readily be explained by chance or by other expansions. From these comparisons, we found that haplogroup J2, in general, and six Y-STR haplotypes, in particular, exhibited a Phoenician signature that contributed > 6% to the modern Phoenician-influenced populations examined. Our methodology can be applied to any historically documented expansion in which contact and noncontact sites can be identified. PMID:18976729

Digital Accessible Knowledge and well-inventoried sites for birds in Mexico: baseline sites for measuring faunistic change

PubMed Central

Navarro-Sigüenza, Adolfo G.; Martínez-Meyer, Enrique

2016-01-01

Background Faunal change is a basic and fundamental element in ecology, biogeography, and conservation biology, yet vanishingly few detailed studies have documented such changes rigorously over decadal time scales. This study responds to that gap in knowledge, providing a detailed analysis of Digital Accessible Knowledge of the birds of Mexico, designed to marshal DAK to identify sites that were sampled and inventoried rigorously prior to the beginning of major global climate change (1980). Methods We accumulated DAK records for Mexican birds from all relevant online biodiversity data portals. After extensive cleaning steps, we calculated completeness indices for each 0.05° pixel across the country; we also detected ‘hotspots’ of sampling, and calculated completeness indices for these broader areas as well. Sites were designated as well-sampled if they had completeness indices above 80% and >200 associated DAK records. Results We identified 100 individual pixels and 20 broader ‘hotspots’ of sampling that were demonstrably well-inventoried prior to 1980. These sites are catalogued and documented to promote and enable resurvey efforts that can document events of avifaunal change (and non-change) across the country on decadal time scales. Conclusions Development of repeated surveys for many sites across Mexico, and particularly for sites for which historical surveys document their avifaunas prior to major climate change processes, would pay rich rewards in information about distributional dynamics of Mexican birds. PMID:27651986

Digital Accessible Knowledge and well-inventoried sites for birds in Mexico: baseline sites for measuring faunistic change.

PubMed

Peterson, A Townsend; Navarro-Sigüenza, Adolfo G; Martínez-Meyer, Enrique

2016-01-01

Faunal change is a basic and fundamental element in ecology, biogeography, and conservation biology, yet vanishingly few detailed studies have documented such changes rigorously over decadal time scales. This study responds to that gap in knowledge, providing a detailed analysis of Digital Accessible Knowledge of the birds of Mexico, designed to marshal DAK to identify sites that were sampled and inventoried rigorously prior to the beginning of major global climate change (1980). We accumulated DAK records for Mexican birds from all relevant online biodiversity data portals. After extensive cleaning steps, we calculated completeness indices for each 0.05° pixel across the country; we also detected 'hotspots' of sampling, and calculated completeness indices for these broader areas as well. Sites were designated as well-sampled if they had completeness indices above 80% and >200 associated DAK records. We identified 100 individual pixels and 20 broader 'hotspots' of sampling that were demonstrably well-inventoried prior to 1980. These sites are catalogued and documented to promote and enable resurvey efforts that can document events of avifaunal change (and non-change) across the country on decadal time scales. Development of repeated surveys for many sites across Mexico, and particularly for sites for which historical surveys document their avifaunas prior to major climate change processes, would pay rich rewards in information about distributional dynamics of Mexican birds.

Northeast Oregon Hatchery Project, Final Siting Report.

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

Watson, Montgomery

1995-03-01

This report presents the results of site analysis for the Bonneville Power Administration Northeast Oregon Hatchery Project. The purpose of this project is to provide engineering services for the siting and conceptual design of hatchery facilities for the Bonneville Power Administration. The hatchery project consists of artificial production facilities for salmon and steelhead to enhance production in three adjacent tributaries to the Columbia River in northeast Oregon: the Grande Ronde, Walla Walla, and Imnaha River drainage basins. Facilities identified in the master plan include adult capture and holding facilities; spawning incubation, and early rearing facilities; full-term rearing facilities; and directmore » release or acclimation facilities. The evaluation includes consideration of a main production facility for one or more of the basins or several smaller satellite production facilities to be located within major subbasins. The historic and current distribution of spring and fall chinook salmon and steelhead was summarized for the Columbia River tributaries. Current and future production and release objectives were reviewed. Among the three tributaries, forty seven sites were evaluated and compared to facility requirements for water and space. Site screening was conducted to identify the sites with the most potential for facility development. Alternative sites were selected for conceptual design of each facility type. A proposed program for adult holding facilities, final rearing/acclimation, and direct release facilities was developed.« less

Does your web site draw new patients?

PubMed

Wallin, Wendy S

2009-11-01

The absence of scientific data forces orthodontists to guess at how best to design Internet sites that persuade prospective patients to call for appointments. This study was conducted to identify the Web-site factors that lead prospective patients to make appointments or, conversely, to reject a practice. Ten participants actively looking online for an orthodontist were recruited to participate. They reviewed 64 orthodontic Web sites in their geographic areas and rated their likelihood of calling each practice for an appointment. The sessions were videotaped. Analysis of participant comments, navigation patterns, and ratings suggested 25 distinguishing factors. Statistical analysis showed 10 Web-site characteristics that predict the success of an orthodontic Web site in attracting new patients.

Restrictions on biological adaptation in language evolution.

PubMed

Chater, Nick; Reali, Florencia; Christiansen, Morten H

2009-01-27

Language acquisition and processing are governed by genetic constraints. A crucial unresolved question is how far these genetic constraints have coevolved with language, perhaps resulting in a highly specialized and species-specific language "module," and how much language acquisition and processing redeploy preexisting cognitive machinery. In the present work, we explored the circumstances under which genes encoding language-specific properties could have coevolved with language itself. We present a theoretical model, implemented in computer simulations, of key aspects of the interaction of genes and language. Our results show that genes for language could have coevolved only with highly stable aspects of the linguistic environment; a rapidly changing linguistic environment does not provide a stable target for natural selection. Thus, a biological endowment could not coevolve with properties of language that began as learned cultural conventions, because cultural conventions change much more rapidly than genes. We argue that this rules out the possibility that arbitrary properties of language, including abstract syntactic principles governing phrase structure, case marking, and agreement, have been built into a "language module" by natural selection. The genetic basis of human language acquisition and processing did not coevolve with language, but primarily predates the emergence of language. As suggested by Darwin, the fit between language and its underlying mechanisms arose because language has evolved to fit the human brain, rather than the reverse.

EPA RE-Powering Mapper: Alternative Energy Potential at Cleanup Sites

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management??s (OLEM) Office of Communications, Partnerships and Analysis (OCPA) initiated the RE-Powering America's Land Initiative to demonstrate the enormous potential that contaminated lands, landfills, and mine sites provide for developing renewable energy in the United States. EPA developed national level site screening criteria in partnership with the U.S. Department of Energy (DOE) National Renewable Energy Laboratory (NREL) for wind, solar, biomass, and geothermal facilities. While the screening criteria demonstrate the potential to reuse contaminated land for renewable energy facilities, the criteria and data are neither designed to identify the best sites for developing renewable energy nor all-inclusive. Therefore, more detailed, site-specific analysis is necessary to identify or prioritize the best sites for developing renewable energy facilities based on the technical and economic potential. Please note that these sites were only pre-screened for renewable energy potential. The sites were not evaluated for land use constraints or current on the ground conditions. Additional research and site-specific analysis are needed to verify viability for renewable energy potential at a given site.

The coevolution of recognition and social behavior.

PubMed

Smead, Rory; Forber, Patrick

2016-05-26

Recognition of behavioral types can facilitate the evolution of cooperation by enabling altruistic behavior to be directed at other cooperators and withheld from defectors. While much is known about the tendency for recognition to promote cooperation, relatively little is known about whether such a capacity can coevolve with the social behavior it supports. Here we use evolutionary game theory and multi-population dynamics to model the coevolution of social behavior and recognition. We show that conditional harming behavior enables the evolution and stability of social recognition, whereas conditional helping leads to a deterioration of recognition ability. Expanding the model to include a complex game where both helping and harming interactions are possible, we find that conditional harming behavior can stabilize recognition, and thereby lead to the evolution of conditional helping. Our model identifies a novel hypothesis for the evolution of cooperation: conditional harm may have coevolved with recognition first, thereby helping to establish the mechanisms necessary for the evolution of cooperation.

The coevolution of recognition and social behavior

PubMed Central

Smead, Rory; Forber, Patrick

2016-01-01

Recognition of behavioral types can facilitate the evolution of cooperation by enabling altruistic behavior to be directed at other cooperators and withheld from defectors. While much is known about the tendency for recognition to promote cooperation, relatively little is known about whether such a capacity can coevolve with the social behavior it supports. Here we use evolutionary game theory and multi-population dynamics to model the coevolution of social behavior and recognition. We show that conditional harming behavior enables the evolution and stability of social recognition, whereas conditional helping leads to a deterioration of recognition ability. Expanding the model to include a complex game where both helping and harming interactions are possible, we find that conditional harming behavior can stabilize recognition, and thereby lead to the evolution of conditional helping. Our model identifies a novel hypothesis for the evolution of cooperation: conditional harm may have coevolved with recognition first, thereby helping to establish the mechanisms necessary for the evolution of cooperation. PMID:27225673

An analysis of parameter sensitivities of preference-inspired co-evolutionary algorithms

NASA Astrophysics Data System (ADS)

Wang, Rui; Mansor, Maszatul M.; Purshouse, Robin C.; Fleming, Peter J.

2015-10-01

Many-objective optimisation problems remain challenging for many state-of-the-art multi-objective evolutionary algorithms. Preference-inspired co-evolutionary algorithms (PICEAs) which co-evolve the usual population of candidate solutions with a family of decision-maker preferences during the search have been demonstrated to be effective on such problems. However, it is unknown whether PICEAs are robust with respect to the parameter settings. This study aims to address this question. First, a global sensitivity analysis method - the Sobol' variance decomposition method - is employed to determine the relative importance of the parameters controlling the performance of PICEAs. Experimental results show that the performance of PICEAs is controlled for the most part by the number of function evaluations. Next, we investigate the effect of key parameters identified from the Sobol' test and the genetic operators employed in PICEAs. Experimental results show improved performance of the PICEAs as more preferences are co-evolved. Additionally, some suggestions for genetic operator settings are provided for non-expert users.

Uncovering Global SUMOylation Signaling Networks in a Site-Specific Manner

PubMed Central

Hendriks, Ivo A.; D’Souza, Rochelle C.J.; Yang, Bing; Verlaan-de Vries, Matty; Mann, Matthias; Vertegaal, Alfred C.O.

2014-01-01

SUMOylation is a reversible post-translational modification essential for genome stability. Using high-resolution mass spectrometry, we have studied global SUMOylation in human cells and in a site-specific manner, identifying a total of over 4,300 SUMOylation sites in over 1,600 proteins. Moreover, for the first time in excess of 1,000 SUMOylation sites were identified under standard growth conditions. SUMOylation dynamics were quantitatively studied in response to SUMO protease inhibition, proteasome inhibition and heat shock. A considerable amount of SUMOylated lysines have previously been reported to be ubiquitylated, acetylated or methylated, indicating crosstalk between SUMO and other post-translational modifications. We identified 70 phosphorylation and 4 acetylation events in close proximity to SUMOylation sites, and provide evidence for acetylation-dependent SUMOylation of endogenous histone H3. SUMOylation regulates target proteins involved in all nuclear processes including transcription, DNA repair, chromatin remodeling, pre-mRNA splicing and ribosome assembly. PMID:25218447

Environmental assessment: Davis Canyon site, Utah

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

none,

1986-05-01

In February 1983, the US Department of Energy (DOE) identified the Davis Canyon site in Utah as one of the nine potentially acceptable sites for a mined geologic repository for spent nuclear fuel and high-level radioactive waste. To determine their suitability, the Davis Canyon site and the eight other potentially acceptable sites have been evaluated in accordance with the DOE's General Guidelines for the Recommendation of Sites for the Nuclear Waste Repositories. These evaluations were reported in draft environmental assessments (EAs), which were issued for public review and comment. After considering the comments received on the draft EAs, the DOEmore » prepared the final EA. The Davis Canyon site is in the Paradox Basin, which is one of five distinct geohydrologic settings considered for the first repository. This setting contains one other potentially acceptable site -- the Lavender Canyon site. Although the Lavender Canyon site is suitable for site characterization, the DOE has concluded that the Davis Canyon site is the preferred site in the Paradox Basin. On the basis of the evaluations reported in this EA, the DOE has found that the Davis Canyon site is not disqualified under the guidelines. Furthermore, the DOE has fond that the site is suitable for site characterization because the evidence does not support a conclusion that the site will not be able to meet each of the qualifying conditions specified in the guidelines. On the basis of these findings, the DOE is nominating the Davis Canyon site as one of five sites suitable for characterization. 181 figs., 175 tabs.« less

Environmental assessment: Davis Canyon site, Utah

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

none,

1986-05-01

In February 1983, the US Department of Energy (DOE) identified the Davis Canyon site in Utah as one of the nine potentially acceptable sites for a mined geologic repository for spent nuclear fuel and high- level radioactive waste. To determine their suitability, the Davis Canyon site and the eight other potentially acceptable sites have been evaluated in accordance with the DOE's General Guidelines for the Recommendation of Sites for the Nuclear Waste Repositories. These evaluations were reported in draft environmental assessments (EAs), which were issued for public review and comment. After considering the comments received on the draft EAs, themore » DOE prepared the final EA. The Davis Canyon site is in the Paradox Basin, which is one of five distinct geohydrologic settings considered for the first repository. This setting contains one other potentially acceptable site -- the Lavender Canyon site. Although the Lavender Canyon site is suitable for site characterization, the DOE has concluded that the Davis Canyon site is the preferred site in the Paradox Basin. On the basis of the evaluations reported in this EA, the DOE has found that the Davis Canyon site is not disqualified under the guidelines. Furthermore, the DOE has found that the site is suitable for site characterization because the evidence does not support a conclusion that the site will not be able to meet each of the qualifying conditions specified in the guidelines. On the basis of these findings, the DOE is nominating the Davis Canyon site as one of the five sites suitable for characterization.« less

Environmental assessment: Davis Canyon site, Utah

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

none,

1986-05-01

In February 1983, the US Department of Energy (DOE) identified the Davis Canyon site in Utah as one of the nine potentially acceptable sites for a mined geologic repository for spent nuclear fuel and high-level radioactive waste. To determine their suitability, the Davis Canyon site and the eight other potentially acceptable sites have been evaluated in accordance with the DOE's General Guidelines for the Recommendation of Sites for the Nuclear Waste Repositories. These evaluations were reported in draft environmental assessments (EAs), which were issued for public review and comment. After considering the comments received on the draft EAs, the DOEmore » prepared the final EA. The Davis Canyon site is in the Paradox Basin, which is one of five distinct geohydrologic settings considering for the first repository. This setting contains one other potentially acceptable site -- the Lavender Canyon site. Although the Lavender Canyon site is suitable for site characterization, the DOE has concluded that the Davis Canyon site is the preferred site in the Paradox Basin. On the basis of the evaluations reported in this EA, the DOE has found that the Davis Canyon site is not disqualified under the guidelines. Furthermore, the DOE has found that the site is suitable for site characterization because the evidence does not support a conclusion that the site will not be able to meet each of the qualifying conditions specified in the guidelines. On the basis of these findings, the DOE is nominating the Davis Canyon site as one of five sites suitable for characterization.« less

An integrated approach for identifying priority contaminant in ...

EPA Pesticide Factsheets

Environmental assessment of complex mixtures typically requires integration of chemical and biological measurements. This study demonstrates the use of a combination of instrumental chemical analyses, effects-based monitoring, and bio-effects prediction approaches to help identify potential hazards and priority contaminants in two Great Lakes Areas of Concern (AOCs), the Lower Green Bay/Fox River located near Green Bay, WI, USA and the Milwaukee River Estuary, located near Milwaukee, WI, USA. Fathead minnows were caged at four sites within each AOC (eight sites total). Following 4 d of in situ exposure, tissues and biofluids were sampled and used for targeted biological effects analyses. Additionally, 4 d composite water samples were collected concurrently at each caged fish site and analyzed for 134 analytes as well as evaluated for total estrogenic and androgenic activity using cell-based bioassays. Of the analytes examined, 75 were detected in composite samples from at least one site. Based on multiple analyses, one site in the East River and another site near a paper mill discharge from lower Green Bay/Fox River AOC, were prioritized due to their estrogenic and androgenic acitvity, respectively. The water samples from other sites generally did not exhibit significant estrogenic or androgenic activity, nor was there evidence for endocrine disruption in the fish exposed at these sites as indicated the the lack of alterations in ex vivo steroid production, c

Liquefaction sites, Imperial Valley, California.

USGS Publications Warehouse

Youd, T.L.; Bennett, M.J.

1983-01-01

Sands that did and did not liquefy at two sites during the 1979 Imperial Valley, Calif., earthquake (ML = 6.6) are identified and their properties evaluated. SPT tests were used to evaluate liquefaction susceptibility. Loose fine sands in an abandoned channel liquefied and produced sand boils, ground fissures, and a lateral spread at the Heber Road sites. Evidence of liquefaction was not observed over moderately dense over-bank sand east of the channel nor over dense point-bar sand to the west. -from ASCE Publications Information

Site specific modification of the human plasma proteome by methylglyoxal

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

Kimzey, Michael J.; Kinsky, Owen R.; Yassine, Hussein N.

Increasing evidence identifies dicarbonyl stress from reactive glucose metabolites, such as methylglyoxal (MG), as a major pathogenic link between hyperglycemia and complications of diabetes. MG covalently modifies arginine residues, yet the site specificity of this modification has not been thoroughly investigated. Sites of MG adduction in the plasma proteome were identified using LC–MS/MS analysis in vitro following incubation of plasma proteins with MG. Treatment of plasma proteins with MG yielded 14 putative MG hotspots from five plasma proteins (albumin [nine hotspots], serotransferrin, haptoglobin [2 hotspots], hemopexin, and Ig lambda-2 chain C regions). The search results revealed two versions of MG-argininemore » modification, dihydroxyimidazolidine (R + 72) and hydroimidazolone (R + 54) adducts. One of the sites identified was R257 in human serum albumin, which is a critical residue located in drug binding site I. This site was validated as a target for MG modification by a fluorescent probe displacement assay, which revealed significant drug dissociation at 300 μM MG from a prodan–HSA complex (75 μM). Moreover, twelve human plasma samples (six male, six female, with two type 2 diabetic subjects from both genders) were analyzed using multiple reaction monitoring (MRM) tandem mass spectrometry and revealed the presence of the MG-modified albumin R257 peptide. These data provide insights into the nature of the site-specificity of MG modification of arginine, which may be useful for therapeutic treatments that aim to prevent MG-mediated adverse responses in patients. - Highlights: • Methylglyoxal (MG) selectively modifies arginine sites in human plasma proteome. • Dihydroxyimidazolidine and hydroimidazolone adducts on serum albumin identified • MG modification on albumin R257 associated with loss of drug site I binding capacity • MRM-tandem mass spectrometry enables sensitive detection of albumin MG-R257. • Site-specific MG modification may

System-wide identification of wild-type SUMO-2 conjugation sites

PubMed Central

Hendriks, Ivo A.; D'Souza, Rochelle C.; Chang, Jer-Gung; Mann, Matthias; Vertegaal, Alfred C. O.

2015-01-01

SUMOylation is a reversible post-translational modification (PTM) regulating all nuclear processes. Identification of SUMOylation sites by mass spectrometry (MS) has been hampered by bulky tryptic fragments, which thus far necessitated the use of mutated SUMO. Here we present a SUMO-specific protease-based methodology which circumvents this problem, dubbed Protease-Reliant Identification of SUMO Modification (PRISM). PRISM allows for detection of SUMOylated proteins as well as identification of specific sites of SUMOylation while using wild-type SUMO. The method is generic and could be widely applied to study lysine PTMs. We employ PRISM in combination with high-resolution MS to identify SUMOylation sites from HeLa cells under standard growth conditions and in response to heat shock. We identified 751 wild-type SUMOylation sites on endogenous proteins, including 200 dynamic SUMO sites in response to heat shock. Thus, we have developed a method capable of quantitatively studying wild-type mammalian SUMO at the site-specific and system-wide level. PMID:26073453

Identifying personal microbiomes using metagenomic codes

PubMed Central

Franzosa, Eric A.; Huang, Katherine; Meadow, James F.; Gevers, Dirk; Lemon, Katherine P.; Bohannan, Brendan J. M.; Huttenhower, Curtis

2015-01-01

Community composition within the human microbiome varies across individuals, but it remains unknown if this variation is sufficient to uniquely identify individuals within large populations or stable enough to identify them over time. We investigated this by developing a hitting set-based coding algorithm and applying it to the Human Microbiome Project population. Our approach defined body site-specific metagenomic codes: sets of microbial taxa or genes prioritized to uniquely and stably identify individuals. Codes capturing strain variation in clade-specific marker genes were able to distinguish among 100s of individuals at an initial sampling time point. In comparisons with follow-up samples collected 30–300 d later, ∼30% of individuals could still be uniquely pinpointed using metagenomic codes from a typical body site; coincidental (false positive) matches were rare. Codes based on the gut microbiome were exceptionally stable and pinpointed >80% of individuals. The failure of a code to match its owner at a later time point was largely explained by the loss of specific microbial strains (at current limits of detection) and was only weakly associated with the length of the sampling interval. In addition to highlighting patterns of temporal variation in the ecology of the human microbiome, this work demonstrates the feasibility of microbiome-based identifiability—a result with important ethical implications for microbiome study design. The datasets and code used in this work are available for download from huttenhower.sph.harvard.edu/idability. PMID:25964341

Humid site stabilization and closure

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

Cutshall, N.H.

1981-01-01

The purpose of the work described here is to identify and evaluate the importance of factors that are expected to dictate the nature of site stabilization and closure requirements. Subsequent efforts will plan for implementation of such requirements. Two principal areas of site stabilization and closure effort will be pursued initially - geological management and vegetation management. The geological effort will focus on chemical weathering and surficial erosion. Such catastrophic geologic events as landslides, flooding, earthquakes, volcanos, etc. are already considered in site selection and operation and these factors will not be emphasized initially. Vegetation management will be designed tomore » control erosion, to minimize nuclide mobilization by roots and to be compatible with natural successional pressures. It is anticipated that the results of this work will be important both to site selection and operation as well as the actual stabilization and closure procedure.« less

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

Site Reconnaissance for the EarthScope/USArray Transportable Seismic Array

NASA Astrophysics Data System (ADS)

Anderson, B.; Anderson, P.; Bauer, J.; Bernard, M.; Meyers, M.; Moore, M.; Potter, S.; Rios, C.; Trehu, A.; Zennaro, B.; Busby, R.; Helbock, S.; Lippert, D.; Mecurio, M.; Ruckdeschel, M.

2005-12-01

Identification and permitting of sites for seismic stations of EarthScope's USArray Transportable Seismic Array is a very ambitious undertaking. Initial site reconnaissance requires skills to integrate information from a variety of geographic databases as well as an understanding of the regional geology and tectonics and of the objectives of the EarthScope and USArray programs. It thus provides rich opportunities for students in earth sciences and geography to apply and enhance their knowledge. During summer, 2005, Oregon State University participated in site reconnaissance for USArray in Oregon and southern Washington as part of a USArray-sponsored internship program. The program began with a 3-day workshop attended by authors of this presentation. The workshop included lectures about the scientific objectives of EarthScope, training on procedures to identify sites that meet the requirements of USArray, and a field trip to find a few local sites. Prior to going into the field, GIS tools using databases assembled by OSU, IAGT and IRIS were used to identify locations that met as many requirements as possible: 1) appropriate topography and geology, 2) adequate distance from cultural noise sources, 3) private ownership, and 4) digital cell phone coverage. Lab work was followed by field visits to make contact with landowners and identify specific sites. In rural areas, University extension agents provided a valuable introduction to the local community. The "products" of this project were formal "Reconnaissance Reports" that included contact information, special site considerations and detailed instructions for finding the sites. Site locations were finalized by professional USArray staff. This has proven to be an efficient and cost-effective way to locate a large number of sites while simultaneously providing an exciting practical training opportunity for students, involving a variety of units throughout the university system, and transmitting the excitement of USArray

Technology for Waste Treatment at Remote Army Sites

DTIC Science & Technology

1986-09-01

Management "AD-A.17 6 801 i echnology for Waste Treatment at Remote Army Sites by * Richard J. Scholze James E. Alleinan Steve R. Struss EdD. Smith This...62720 IA896 A 1039 IT TITLE (include Security Classification) Technology for Waste Treatment at Remote Army Sites (Unclassified) 12 PERSONAL...management human wastes 13 02 waste treatment remote sites I I wastes (sanitary engineering)~ 19 ABSTRACT (Continue on reverse if necessary and identify by

Whooping crane stopover site use intensity within the Great Plains

USGS Publications Warehouse

Pearse, Aaron T.; Brandt, David A.; Harrell, Wade C.; Metzger, Kristine L.; Baasch, David M.; Hefley, Trevor J.

2015-09-23

Whooping cranes (Grus americana) of the Aransas-Wood Buffalo population migrate twice each year through the Great Plains in North America. Recovery activities for this endangered species include providing adequate places to stop and rest during migration, which are generally referred to as stopover sites. To assist in recovery efforts, initial estimates of stopover site use intensity are presented, which provide opportunity to identify areas across the migration range used more intensively by whooping cranes. We used location data acquired from 58 unique individuals fitted with platform transmitting terminals that collected global position system locations. Radio-tagged birds provided 2,158 stopover sites over 10 migrations and 5 years (2010–14). Using a grid-based approach, we identified 1,095 20-square-kilometer grid cells that contained stopover sites. We categorized occupied grid cells based on density of stopover sites and the amount of time cranes spent in the area. This assessment resulted in four categories of stopover site use: unoccupied, low intensity, core intensity, and extended-use core intensity. Although provisional, this evaluation of stopover site use intensity offers the U.S. Fish and Wildlife Service and partners a tool to identify landscapes that may be of greater conservation significance to migrating whooping cranes. Initially, the tool will be used by the U.S. Fish and Wildlife Service and other interested parties in evaluating the Great Plains Wind Energy Habitat Conservation Plan.

A cross-site comparison of methods used for hydrogeologic characterization of the Galena-Platteville aquifer in Illinois and Wisconsin, with examples from selected Superfund sites

USGS Publications Warehouse

Kay, Robert T.; Mills, Patrick C.; Dunning, Charles P.; Yeskis, Douglas J.; Ursic, James R.; Vendl, Mark

2004-01-01

The effectiveness of 28 methods used to characterize the fractured Galena-Platteville aquifer at eight sites in northern Illinois and Wisconsin is evaluated. Analysis of government databases, previous investigations, topographic maps, aerial photographs, and outcrops was essential to understanding the hydrogeology in the area to be investigated. The effectiveness of surface-geophysical methods depended on site geology. Lithologic logging provided essential information for site characterization. Cores were used for stratigraphy and geotechnical analysis. Natural-gamma logging helped identify the effect of lithology on the location of secondary- permeability features. Caliper logging identified large secondary-permeability features. Neutron logs identified trends in matrix porosity. Acoustic-televiewer logs identified numerous secondary-permeability features and their orientation. Borehole-camera logs also identified a number of secondary-permeability features. Borehole ground-penetrating radar identified lithologic and secondary-permeability features. However, the accuracy and completeness of this method is uncertain. Single-point-resistance, density, and normal resistivity logs were of limited use. Water-level and water-quality data identified flow directions and indicated the horizontal and vertical distribution of aquifer permeability and the depth of the permeable features. Temperature, spontaneous potential, and fluid-resistivity logging identified few secondary-permeability features at some sites and several features at others. Flowmeter logging was the most effective geophysical method for characterizing secondary-permeability features. Aquifer tests provided insight into the permeability distribution, identified hydraulically interconnected features, the presence of heterogeneity and anisotropy, and determined effective porosity. Aquifer heterogeneity prevented calculation of accurate hydraulic properties from some tests. Different methods, such as flowmeter

Teacher Preferences for Alternative School Site Administrative Models

ERIC Educational Resources Information Center

Hewitt, Paul M.; Denny, George S.; Pijanowski, John C.

2012-01-01

Public school teachers with high leadership potential who stated that they had no interest in being school principals were surveyed on their attitudes about six alternative school site administrative organizational models. Of the 391 teachers surveyed, 53% identified the Co-Principal model as the preferred school site administrative structure. In…

2002 Hyperspectral Analysis of Hazardous Waste Sites on the Savannah River Site

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

Gladden, J.B.

2003-08-28

Hazardous waste site inspection is a labor intensive, time consuming job, performed primarily on the ground using visual inspection and instrumentation. It is an expensive process to continually monitor hazardous waste and/or landfill sites to determine if they are maintaining their integrity. In certain instances, it may be possible to monitor aspects of the hazardous waste sites and landfills remotely. The utilization of multispectral data was suggested for the mapping of clays and iron oxides associated with contaminated groundwater, vegetation stress, and methane gas emissions (which require longer wavelength detectors). The Savannah River Site (SRS) near Aiken, S.C. is amore » United States Department of Energy facility operated by the Westinghouse Savannah River Company. For decades the SRS was responsible for developing weapons grade plutonium and other materials for the nation's nuclear defense. Hazardous waste was generated during this process. Waste storage site inspection is a particularly important issue at the SRS because there are over 100 hazardous waste sites scattered throughout the 300 mile complex making it difficult to continually monitor all of the facilities. The goal is to use remote sensing technology to identify surface anomalies on the hazardous waste sites as early as possible so that remedial work can take place rapidly to maintain the integrity of the storage sites. The anomalous areas are then targeted for intensive in situ human examination and measurement. During the 1990s, many of the hazardous waste sites were capped with protective layers of polyethelene sheeting and soil, and planted with bahia grass and/or centipede grass. This research investigated hyperspectral remote sensing technology to determine if it can be used to measure accurately and monitor possible indicators of change on vegetated hazardous waste sites. Specifically, it evaluated the usefulness of hyperspectral remote sensing to assess the condition of vegetation

Identifiability, reducibility, and adaptability in allosteric macromolecules.

PubMed

Bohner, Gergő; Venkataraman, Gaurav

2017-05-01

The ability of macromolecules to transduce stimulus information at one site into conformational changes at a distant site, termed "allostery," is vital for cellular signaling. Here, we propose a link between the sensitivity of allosteric macromolecules to their underlying biophysical parameters, the interrelationships between these parameters, and macromolecular adaptability. We demonstrate that the parameters of a canonical model of the mSlo large-conductance Ca 2+ -activated K + (BK) ion channel are non-identifiable with respect to the equilibrium open probability-voltage relationship, a common functional assay. We construct a reduced model with emergent parameters that are identifiable and expressed as combinations of the original mechanistic parameters. These emergent parameters indicate which coordinated changes in mechanistic parameters can leave assay output unchanged. We predict that these coordinated changes are used by allosteric macromolecules to adapt, and we demonstrate how this prediction can be tested experimentally. We show that these predicted parameter compensations are used in the first reported allosteric phenomena: the Bohr effect, by which hemoglobin adapts to varying pH. © 2017 Bohner and Venkataraman.

Identifiability, reducibility, and adaptability in allosteric macromolecules

PubMed Central

Bohner, Gergő

2017-01-01

The ability of macromolecules to transduce stimulus information at one site into conformational changes at a distant site, termed “allostery,” is vital for cellular signaling. Here, we propose a link between the sensitivity of allosteric macromolecules to their underlying biophysical parameters, the interrelationships between these parameters, and macromolecular adaptability. We demonstrate that the parameters of a canonical model of the mSlo large-conductance Ca2+-activated K+ (BK) ion channel are non-identifiable with respect to the equilibrium open probability-voltage relationship, a common functional assay. We construct a reduced model with emergent parameters that are identifiable and expressed as combinations of the original mechanistic parameters. These emergent parameters indicate which coordinated changes in mechanistic parameters can leave assay output unchanged. We predict that these coordinated changes are used by allosteric macromolecules to adapt, and we demonstrate how this prediction can be tested experimentally. We show that these predicted parameter compensations are used in the first reported allosteric phenomena: the Bohr effect, by which hemoglobin adapts to varying pH. PMID:28416647

Conservation analysis and decomposition of residue correlation networks in the phospholipase A2 superfamily (PLA2s): Insights into the structure-function relationships of snake venom toxins.

PubMed

Oliveira, Alberto; Bleicher, Lucas; Schrago, Carlos G; Silva Junior, Floriano Paes

2018-05-01

Phospholipases A2 (PLA 2 s) comprise a superfamily of glycerophospholipids hydrolyzing enzymes present in many organisms in nature, whose catalytic activity was majorly unveiled by analysis of snake venoms. The latter have pharmaceutical and biotechnological interests and can be divided into different functional sub-classes. Our goal was to identify important residues and their relation to the functional and class-specific characteristics in the PLA 2 s family with special emphasis on snake venom PLA 2 s (svPLA 2 s). We identified such residues by conservation analysis and decomposition of residue coevolution networks (DRCN), annotated the results based on the available literature on PLA 2 s, structural analysis and molecular dynamics simulations, and related the results to the phylogenetic distribution of these proteins. A filtered alignment of PLA 2 s revealed 14 highly conserved positions and 3 sets of coevolved residues, which were annotated according to their structural or functional role. These residues are mostly involved in ligand binding and catalysis, calcium-binding, the formation of disulfide bridges and a hydrophobic cluster close to the binding site. An independent validation of the inference of structure-function relationships from our co-evolution analysis on the svPLA2s family was obtained by the analysis of the pattern of selection acting on the Viperidae and Elapidae lineages. Additionally, a molecular dynamics simulation on the Lys49 PLA 2 from Agkistrodon contortrix laticinctus was carried out to further investigate the correlation of the Lys49-Glu69 pair. Our results suggest this configuration can result in a novel conformation where the binding cavity collapses due to the approximation of two loops caused by a strong salt bridge between Glu69 and Arg34. Finally, phylogenetic analysis indicated a correlation between the presence of residues in the coevolved sets found in this analysis and the clade localization. The results provide a guide for

Social networking sites and older users - a systematic review.

PubMed

Nef, Tobias; Ganea, Raluca L; Müri, René M; Mosimann, Urs P

2013-07-01

Social networking sites can be beneficial for senior citizens to promote social participation and to enhance intergenerational communication. Particularly for older adults with impaired mobility, social networking sites can help them to connect with family members and other active social networking users. The aim of this systematic review is to give an overview of existing scientific literature on social networking in older users. Computerized databases were searched and 105 articles were identified and screened using exclusion criteria. After exclusion of 87 articles, 18 articles were included, reviewed, classified, and the key findings were extracted. Common findings are identified and critically discussed and possible future research directions are outlined. The main benefit of using social networking sites for older adults is to enter in an intergenerational communication with younger family members (children and grandchildren) that is appreciated by both sides. Identified barriers are privacy concerns, technical difficulties and the fact that current Web design does not take the needs of older users into account. Under the conditions that these problems are carefully addressed, social networking sites have the potential to support today's and tomorrow's communication between older and younger family members.

Modification site localization scoring integrated into a search engine.

PubMed

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

2011-07-01

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

REGULATORY PERSPECTIVE ON MANAGING RISKS AT WOOD TREATING SITES

EPA Science Inventory

Over 700 sites in the United States have been identified where wood preserving operations have been conducted. The most common types of wood preservatives found at these sites are creosote, pentachlorophenol (PCP), and copper chromated arsenate (CCA). When properly used and dis...

Towards a comprehensive picture of C-to-U RNA editing sites in angiosperm mitochondria.

PubMed

Edera, Alejandro A; Gandini, Carolina L; Sanchez-Puerta, M Virginia

2018-05-14

Our understanding of the dynamic and evolution of RNA editing in angiosperms is in part limited by the few editing sites identified to date. This study identified 10,217 editing sites from 17 diverse angiosperms. Our analyses confirmed the universality of certain features of RNA editing, and offer new evidence behind the loss of editing sites in angiosperms. RNA editing is a post-transcriptional process that substitutes cytidines (C) for uridines (U) in organellar transcripts of angiosperms. These substitutions mostly take place in mitochondrial messenger RNAs at specific positions called editing sites. By means of publicly available RNA-seq data, this study identified 10,217 editing sites in mitochondrial protein-coding genes of 17 diverse angiosperms. Even though other types of mismatches were also identified, we did not find evidence of non-canonical editing processes. The results showed an uneven distribution of editing sites among species, genes, and codon positions. The analyses revealed that editing sites were conserved across angiosperms but there were some species-specific sites. Non-synonymous editing sites were particularly highly conserved (~ 80%) across the plant species and were efficiently edited (80% editing extent). In contrast, editing sites at third codon positions were poorly conserved (~ 30%) and only partially edited (~ 40% editing extent). We found that the loss of editing sites along angiosperm evolution is mainly occurring by replacing editing sites with thymidines, instead of a degradation of the editing recognition motif around editing sites. Consecutive and highly conserved editing sites had been replaced by thymidines as result of retroprocessing, by which edited transcripts are reverse transcribed to cDNA and then integrated into the genome by homologous recombination. This phenomenon was more pronounced in eudicots, and in the gene cox1. These results suggest that retroprocessing is a widespread driving force underlying the loss

Identify, Organize, and Retrieve Items Using Zotero

ERIC Educational Resources Information Center

Clark, Brian; Stierman, John

2009-01-01

Librarians build collections. To do this they use tools that help them identify, organize, and retrieve items for the collection. Zotero (zoh-TAIR-oh) is such a tool that helps the user build a library of useful books, articles, web sites, blogs, etc., discovered while surfing online. A visit to Zotero's homepage, www.zotero.org, shows a number of…

India: From SITE to INSAT.

ERIC Educational Resources Information Center

Chaudhri, M. M.

1986-01-01

Identifies core of India's illiteracy problem and describes use of educational technology to educate rural children. Highlights include descriptions of the Satellite Instructional Television Experiment (SITE) project; motivation behind low-cost educational aids development in rural areas; an educational radio pilot project; and development and…

Deriving amplification factors from simple site parameters using generalized regression neural networks: implications for relevant site proxies

NASA Astrophysics Data System (ADS)

Boudghene Stambouli, Ahmed; Zendagui, Djawad; Bard, Pierre-Yves; Derras, Boumédiène

2017-07-01

Most modern seismic codes account for site effects using an amplification factor (AF) that modifies the rock acceleration response spectra in relation to a "site condition proxy," i.e., a parameter related to the velocity profile at the site under consideration. Therefore, for practical purposes, it is interesting to identify the site parameters that best control the frequency-dependent shape of the AF. The goal of the present study is to provide a quantitative assessment of the performance of various site condition proxies to predict the main AF features, including the often used short- and mid-period amplification factors, Fa and Fv, proposed by Borcherdt (in Earthq Spectra 10:617-653, 1994). In this context, the linear, viscoelastic responses of a set of 858 actual soil columns from Japan, the USA, and Europe are computed for a set of 14 real accelerograms with varying frequency contents. The correlation between the corresponding site-specific average amplification factors and several site proxies (considered alone or as multiple combinations) is analyzed using the generalized regression neural network (GRNN). The performance of each site proxy combination is assessed through the variance reduction with respect to the initial amplification factor variability of the 858 profiles. Both the whole period range and specific short- and mid-period ranges associated with the Borcherdt factors Fa and Fv are considered. The actual amplification factor of an arbitrary soil profile is found to be satisfactorily approximated with a limited number of site proxies (4-6). As the usual code practice implies a lower number of site proxies (generally one, sometimes two), a sensitivity analysis is conducted to identify the "best performing" site parameters. The best one is the overall velocity contrast between underlying bedrock and minimum velocity in the soil column. Because these are the most difficult and expensive parameters to measure, especially for thick deposits, other

Short-time windowed covariance: A metric for identifying non-stationary, event-related covariant cortical sites

PubMed Central

Blakely, Timothy; Ojemann, Jeffrey G.; Rao, Rajesh P.N.

2014-01-01

Background Electrocorticography (ECoG) signals can provide high spatio-temporal resolution and high signal to noise ratio recordings of local neural activity from the surface of the brain. Previous studies have shown that broad-band, spatially focal, high-frequency increases in ECoG signals are highly correlated with movement and other cognitive tasks and can be volitionally modulated. However, significant additional information may be present in inter-electrode interactions, but adding additional higher order inter-electrode interactions can be impractical from a computational aspect, if not impossible. New method In this paper we present a new method of calculating high frequency interactions between electrodes called Short-Time Windowed Covariance (STWC) that builds on mathematical techniques currently used in neural signal analysis, along with an implementation that accelerates the algorithm by orders of magnitude by leveraging commodity, off-the-shelf graphics processing unit (GPU) hardware. Results Using the hardware-accelerated implementation of STWC, we identify many types of event-related inter-electrode interactions from human ECoG recordings on global and local scales that have not been identified by previous methods. Unique temporal patterns are observed for digit flexion in both low- (10 mm spacing) and high-resolution (3 mm spacing) electrode arrays. Comparison with existing methods Covariance is a commonly used metric for identifying correlated signals, but the standard covariance calculations do not allow for temporally varying covariance. In contrast STWC allows and identifies event-driven changes in covariance without identifying spurious noise correlations. Conclusions: STWC can be used to identify event-related neural interactions whose high computational load is well suited to GPU capabilities. PMID:24211499

Evaluation of breastfeeding Web sites for patient education.

PubMed

Dornan, Barbara A; Oermann, Marilyn H

2006-01-01

To evaluate the quality of Web sites on breastfeeding for patient education. Descriptive study of 30 Web sites on breastfeeding for patient education, evaluated based on the Health Information Technology Institute (HITI) criteria, readability, and eight content criteria from the American Academy of Pediatrics (AAP) policy statement on breastfeeding. The mean Flesch-Kincaid Grade Level for readability of the 30 sites was 9.2. Seven of the sites included all eight of the content criteria from the AAP, and three sites did not include any of the information recommended by the AAP content criteria. Nurses should be able to recommend best patient education materials for their patients. The five best Web sites for breastfeeding education are identified for patient teaching, and the HITI criteria are explained for nurses to learn how to evaluate Web sites for themselves and their patients.

Improving Outcomes for Students with Disabilities: Identifying Characteristics of Successful Districts

ERIC Educational Resources Information Center

DeVries, Melissa; Tkatchov, Oran

2017-01-01

The common characteristics among Arizona districts and charters with high academic outcomes for student disabilities were identified in a qualitative study involving site visits and interviews. In 2014, the Arizona Department of Education examined over three years of state testing data to identify districts and charter schools that closed the…

Identifying Inefficient Single-Family Homes With Utility Bill Analysis: Preprint

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

Casey, S.; Krarti, M.; Bianchi, M.

2010-08-01

Differentiating between energy-efficient and inefficient single-family homes on a community scale helps identify and prioritize candidates for energy-efficiency upgrades. Prescreening diagnostic procedures can further retrofit efforts by providing efficiency information before a site-visit is conducted. We applied the prescreening diagnostic to a simulated community of homes in Boulder, Colorado and analyzed energy consumption data to identify energy-inefficient homes.

2016 Inspection and Annual Site Status Report for the Site A/Plot M, Illinois, Decommissioned Reactor Site July 2016

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

Murl, Jeffrey; Miller, Michele

The Site A/Plot M, Illinois, Decommissioned Reactor Site was inspected on May 17, 2016. The site, located within Cook County forest preserve that is open to the public, was found to be in good condition with one exception. Erosion on top of the grass-covered mound at Plot M continues to be a concern as presented in previous inspections. Ruts form in the soil on top of Plot M as a result of bike traffic using the open field as a pass thru between established bike trails within the forest preserve. Argonne National Laboratory (ANL) who is contracted directly from U.S.more » Department of Energy (DOE) has filled in the ruts with top soil and reseeding remains an ongoing process. Reseeded areas from 2015 are progressing nicely. No cause for a follow-up inspection was identified. In 2015, ANL plugged and abandoned 8 of 25 monitoring wells (BH41, BH51, BH52, BH54, DH9, DH10, DH13, and DH17). The 17 groundwater monitoring wells remaining at the site were inspected to confirm that they were locked and in good condition. Preliminary environmental monitoring results for 2015 are provided in a draft report titled Surveillance of Site A and Plot M, Report for 2015, prepared by ANL. The report also contains results of an independent analysis conducted by the Illinois Emergency Management Agency on some of the samples collected by ANL in 2015. The draft report states that the results of the surveillance program continue to indicate that the impact of radioactivity at Site A/Plot M is very low and does not endanger the health of those living in the area or visiting the site. The ANL monitoring report will be made available to the public on the DOE Office of Legacy Management public website when it is issued as final. A new county forest preserve campsite opened in 2015 at Bull Frog Lake, which is east of Plot M. Hiking trails connect Bull Frog Lake with Site A/Plot M. The site might receive more traffic from forest preserve visitors now that this new campsite is opened.« less

Assembly constraints drive co-evolution among ribosomal constituents.

PubMed

Mallik, Saurav; Akashi, Hiroshi; Kundu, Sudip

2015-06-23

Ribosome biogenesis, a central and essential cellular process, occurs through sequential association and mutual co-folding of protein-RNA constituents in a well-defined assembly pathway. Here, we construct a network of co-evolving nucleotide/amino acid residues within the ribosome and demonstrate that assembly constraints are strong predictors of co-evolutionary patterns. Predictors of co-evolution include a wide spectrum of structural reconstitution events, such as cooperativity phenomenon, protein-induced rRNA reconstitutions, molecular packing of different rRNA domains, protein-rRNA recognition, etc. A correlation between folding rate of small globular proteins and their topological features is known. We have introduced an analogous topological characteristic for co-evolutionary network of ribosome, which allows us to differentiate between rRNA regions subjected to rapid reconstitutions from those hindered by kinetic traps. Furthermore, co-evolutionary patterns provide a biological basis for deleterious mutation sites and further allow prediction of potential antibiotic targeting sites. Understanding assembly pathways of multicomponent macromolecules remains a key challenge in biophysics. Our study provides a 'proof of concept' that directly relates co-evolution to biophysical interactions during multicomponent assembly and suggests predictive power to identify candidates for critical functional interactions as well as for assembly-blocking antibiotic target sites. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Vegetation of the Glacier Lakes Ecosystem Experiments Site

Treesearch

Claudia M. Regan; Robert C. Musselman; June D. Haines

1997-01-01

Vegetation at the Glacier Lakes Ecosystem Experiment Site, a 600 ha research site at 3200 to 3500 m elevation in the Snowy Range of southeastern Wyoming, was categorized and described from an intensive sampling of species abundances. A total of 304 vascular plant taxa were identified through collection and herbarium documentation. Plots with tree species were separated...

Who Was that Masked Man? Biographical Sites on the Web.

ERIC Educational Resources Information Center

Byerly, Greg; Brodie, Carolyn S.

1999-01-01

Identifies some of the best general biographical sites on the Web and offers examples of some categorized biographical sites. Highlights include Web encyclopedias; presidents; women; scientists; children's literature authors and illustrators; popular culture; and classroom applications. (LRW)

Analysis of ILRS Site Ties

NASA Astrophysics Data System (ADS)

Husson, V. S.; Long, J. L.; Pearlman, M.

2001-12-01

By the end of 2000, 94% of ILRS stations had completed station and site information forms (i.e. site logs). These forms contain six types of information. These six categories include site identifiers, contact information, approximate coordinates, system configuration history, system ranging capabilities, and local survey ties. The ILRS Central Bureau, in conjunction with the ILRS Networks and Engineering Working Group, has developed procedures to quality control site log contents. Part of this verification entails data integrity checks of local site ties and is the primary focus of this paper. Local survey ties are critical to the combination of space geodetic network coordinate solutions (i.e. GPS, SLR, VLBI, DORIS) of the International Terrestrial Reference Frame (ITRF). Approximately 90% of active SLR sites are collocated with at least one other space geodetic technique. The process used to verify these SLR ties, at collocated sites, is identical to the approach used in ITRF2000. Local vectors (X, Y, Z) from each ILRS site log are differenced from its corresponding ITRF2000 position vectors (i.e. no transformations). These X, Y, and Z deltas are converted into North, East, and Up. Any deltas, in any component, larger than 5 millimeter is flagged for investigation. In the absence of ITRF2000 SLR positions, CSR positions were used. To further enhance this comparison and to fill gaps in information, local ties contained in site logs from the other space geodetic services (i.e. IGS, IVS, IDS) were used in addition to ITRF2000 ties. Case studies of two collocated sites (McDonald/Ft. Davis and Hartebeeshtoek) will be explored in-depth. Recommendations on how local site surveys should be conducted and how this information should be managed will also be presented.

Secondary plant succession on disturbed sites at Yucca Mountain, Nevada

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

Angerer, J.P.; Ostler, W.K.; Gabbert, W.D.

1994-12-01

This report presents the results of a study of secondary plant succession on disturbed sites created during initial site investigations in the late 1970s and early 1980s at Yucca Mountain, NV. Specific study objectives were to determine the rate and success of secondary plant succession, identify plant species found in disturbances that may be suitable for site-specific reclamation, and to identify environmental variables that influence succession on disturbed sites. During 1991 and 1992, fifty seven disturbed sites were located. Vegetation parameters, disturbance characteristics and environmental variables were measured at each site. Disturbed site vegetation parameters were compared to that ofmore » undisturbed sites to determine the status of disturbed site plant succession. Vegetation on disturbed sites, after an average of ten years, was different from undisturbed areas. Ambrosia dumosa, Chrysothamnus teretifolius, Hymenoclea salsola, Gutierrezia sarothrae, Atriplex confertifolia, Atriplex canescens, and Stephanomeria pauciflora were the most dominant species across all disturbed sites. With the exception of A. dumosa, these species were generally minor components of the undisturbed vegetation. Elevation, soil compaction, soil potassium, and amounts of sand and gravel in the soil were found to be significant environmental variables influencing the species composition and abundance of perennial plants on disturbed sites. The recovery rate for disturbed site secondary succession was estimated. Using a linear function (which would represent optimal conditions), the recovery rate for perennial plant cover, regardless of which species comprised the cover, was estimated to be 20 years. However, when a logarithmic function (which would represent probable conditions) was used, the recovery rate was estimated to be 845 years. Recommendations for future studies and site-specific reclamation of disturbances are presented.« less

Safety Oversight of Decommissioning Activities at DOE Nuclear Sites

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

Zull, Lawrence M.; Yeniscavich, William

2008-01-15

The Defense Nuclear Facilities Safety Board (Board) is an independent federal agency established by Congress in 1988 to provide nuclear safety oversight of activities at U.S. Department of Energy (DOE) defense nuclear facilities. The activities under the Board's jurisdiction include the design, construction, startup, operation, and decommissioning of defense nuclear facilities at DOE sites. This paper reviews the Board's safety oversight of decommissioning activities at DOE sites, identifies the safety problems observed, and discusses Board initiatives to improve the safety of decommissioning activities at DOE sites. The decommissioning of former defense nuclear facilities has reduced the risk of radioactive materialmore » contamination and exposure to the public and site workers. In general, efforts to perform decommissioning work at DOE defense nuclear sites have been successful, and contractors performing decommissioning work have a good safety record. Decommissioning activities have recently been completed at sites identified for closure, including the Rocky Flats Environmental Technology Site, the Fernald Closure Project, and the Miamisburg Closure Project (the Mound site). The Rocky Flats and Fernald sites, which produced plutonium parts and uranium materials for defense needs (respectively), have been turned into wildlife refuges. The Mound site, which performed R and D activities on nuclear materials, has been converted into an industrial and technology park called the Mound Advanced Technology Center. The DOE Office of Legacy Management is responsible for the long term stewardship of these former EM sites. The Board has reviewed many decommissioning activities, and noted that there are valuable lessons learned that can benefit both DOE and the contractor. As part of its ongoing safety oversight responsibilities, the Board and its staff will continue to review the safety of DOE and contractor decommissioning activities at DOE defense nuclear sites.« less

A Sleeping Beauty forward genetic screen identifies new genes and pathways driving osteosarcoma development and metastasis

PubMed Central

Moriarity, Branden S; Otto, George M; Rahrmann, Eric P; Rathe, Susan K; Wolf, Natalie K; Weg, Madison T; Manlove, Luke A; LaRue, Rebecca S; Temiz, Nuri A; Molyneux, Sam D; Choi, Kwangmin; Holly, Kevin J; Sarver, Aaron L; Scott, Milcah C; Forster, Colleen L; Modiano, Jaime F; Khanna, Chand; Hewitt, Stephen M; Khokha, Rama; Yang, Yi; Gorlick, Richard; Dyer, Michael A; Largaespada, David A

2016-01-01

Osteosarcomas are sarcomas of the bone, derived from osteoblasts or their precursors, with a high propensity to metastasize. Osteosarcoma is associated with massive genomic instability, making it problematic to identify driver genes using human tumors or prototypical mouse models, many of which involve loss of Trp53 function. To identify the genes driving osteosarcoma development and metastasis, we performed a Sleeping Beauty (SB) transposon-based forward genetic screen in mice with and without somatic loss of Trp53. Common insertion site (CIS) analysis of 119 primary tumors and 134 metastatic nodules identified 232 sites associated with osteosarcoma development and 43 sites associated with metastasis, respectively. Analysis of CIS-associated genes identified numerous known and new osteosarcoma-associated genes enriched in the ErbB, PI3K-AKT-mTOR and MAPK signaling pathways. Lastly, we identified several oncogenes involved in axon guidance, including Sema4d and Sema6d, which we functionally validated as oncogenes in human osteosarcoma. PMID:25961939

Reliable Refuge: Two Sky Island Scorpion Species Select Larger, Thermally Stable Retreat Sites.

PubMed

Becker, Jamie E; Brown, Christopher A

2016-01-01

Sky island scorpions shelter under rocks and other surface debris, but, as with other scorpions, it is unclear whether these species select retreat sites randomly. Furthermore, little is known about the thermal preferences of scorpions, and no research has been done to identify whether reproductive condition might influence retreat site selection. The objectives were to (1) identify physical or thermal characteristics for retreat sites occupied by two sky island scorpions (Vaejovis cashi Graham 2007 and V. electrum Hughes 2011) and those not occupied; (2) determine whether retreat site selection differs between the two study species; and (3) identify whether thermal selection differs between species and between gravid and non-gravid females of the same species. Within each scorpion's habitat, maximum dimensions of rocks along a transect line were measured and compared to occupied rocks to determine whether retreat site selection occurred randomly. Temperature loggers were placed under a subset of occupied and unoccupied rocks for 48 hours to compare the thermal characteristics of these rocks. Thermal gradient trials were conducted before parturition and after dispersal of young in order to identify whether gravidity influences thermal preference. Vaejovis cashi and V. electrum both selected larger retreat sites that had more stable thermal profiles. Neither species appeared to have thermal preferences influenced by reproductive condition. However, while thermal selection did not differ among non-gravid individuals, gravid V. electrum selected warmer temperatures than its gravid congener. Sky island scorpions appear to select large retreat sites to maintain thermal stability, although biotic factors (e.g., competition) could also be involved in this choice. Future studies should focus on identifying the various biotic or abiotic factors that could influence retreat site selection in scorpions, as well as determining whether reproductive condition affects thermal

Geothermal energy in Washington: site data base and development status

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

Bloomquist, R.G.

1979-04-01

This is an attempt to identify the factors which have affected and will continue to affect geothermal assessment and development in the state. The eight potential sites chosen for detailed analysis include: Indian Heaven KGRA, Mount St. Helens KGRA, Kennedy Hot Springs KGRA, Mount Adams PGRA (Potential Geothermal Resource Area), Mount Rainier PGRA, Mount Baker PGRA, Olympic-Sol Duc Hot Springs, and Yakima. The following information is included for each site: site data, site location and physical description, geological/geophysical description, reservoir characteristics, land ownership and leasing, geothermal development status, institutional characteristics, environmental factors, transportation and utilities, and population. A number ofmore » serious impediments to geothermal development were identified which can be solved only by legislative action at the state or federal level and/or changes in attitudes by regulatory agencies. (MHR)« less

Hotspots for allosteric regulation on protein surfaces

PubMed Central

Reynolds, Kimberly A.; McLaughlin, Richard N.; Ranganathan, Rama

2012-01-01

Recent work indicates a general architecture for proteins in which sparse networks of physically contiguous and co-evolving amino acids underlie basic aspects of structure and function. These networks, termed sectors, are spatially organized such that active sites are linked to many surface sites distributed throughout the structure. Using the metabolic enzyme dihydrofolate reductase as a model system, we show that (1) the sector is strongly correlated to a network of residues undergoing millisecond conformational fluctuations associated with enzyme catalysis and (2) sector-connected surface sites are statistically preferred locations for the emergence of allosteric control in vivo. Thus, sectors represent an evolutionarily conserved “wiring” mechanism that can enable perturbations at specific surface positions to rapidly initiate conformational control over protein function. These findings suggest that sectors enable the evolution of intermolecular communication and regulation. PMID:22196731

5 CFR 2604.201 - Public reading room facility and Web site.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Public reading room facility and Web site... DISCLOSURE REPORTS FOIA Public Reading Room Facility and Web Site; Index Identifying Information for the Public § 2604.201 Public reading room facility and Web site. (a)(1) Location of public reading room...

5 CFR 2604.201 - Public reading room facility and Web site.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Public reading room facility and Web site... DISCLOSURE REPORTS FOIA Public Reading Room Facility and Web Site; Index Identifying Information for the Public § 2604.201 Public reading room facility and Web site. (a)(1) Location of public reading room...

2013 Annual Site Inspection and Monitoring Report for Uranium Mill Tailings Radiation Control Act Title II Disposal Sites

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

None

This report, in fulfillment of a license requirement, presents the results of long-term surveillance and maintenance activities conducted by the U.S. Department of Energy (DOE) Office of Legacy Management in 2013 at six uranium mill tailings disposal sites reclaimed under Title II of the Uranium Mill Tailings Radiation Control Act (UMTRCA) of 1978. These activities verified that the UMTRCA Title II disposal sites remain in compliance with license requirements. DOE manages six UMTRCA Title II disposal sites under a general license granted by the U.S. Nuclear Regulatory Commission (NRC) established at Title 10 Code of Federal Regulations Part 40.28. Reclamationmore » and site transition activities continue at other sites, and DOE ultimately expects to manage approximately 27 Title II disposal sites. Long-term surveillance and maintenance activities and services for these disposal sites include inspecting and maintaining the sites; monitoring environmental media and institutional controls; conducting any necessary corrective action; and performing administrative, records, stakeholder services, and other regulatory functions. Annual site inspections and monitoring are conducted in accordance with site-specific long-term surveillance plans (LTSPs) and procedures established by DOE to comply with license requirements. Each site inspection is performed to verify the integrity of visible features at the site; to identify changes or new conditions that may affect the long-term performance of the site; and to determine the need, if any, for maintenance, follow-up inspections, or corrective action. LTSPs and site compliance reports are available online at http://www.lm.doe.gov« less

SigniSite: Identification of residue-level genotype-phenotype correlations in protein multiple sequence alignments.

PubMed

Jessen, Leon Eyrich; Hoof, Ilka; Lund, Ole; Nielsen, Morten

2013-07-01

Identifying which mutation(s) within a given genotype is responsible for an observable phenotype is important in many aspects of molecular biology. Here, we present SigniSite, an online application for subgroup-free residue-level genotype-phenotype correlation. In contrast to similar methods, SigniSite does not require any pre-definition of subgroups or binary classification. Input is a set of protein sequences where each sequence has an associated real number, quantifying a given phenotype. SigniSite will then identify which amino acid residues are significantly associated with the data set phenotype. As output, SigniSite displays a sequence logo, depicting the strength of the phenotype association of each residue and a heat-map identifying 'hot' or 'cold' regions. SigniSite was benchmarked against SPEER, a state-of-the-art method for the prediction of specificity determining positions (SDP) using a set of human immunodeficiency virus protease-inhibitor genotype-phenotype data and corresponding resistance mutation scores from the Stanford University HIV Drug Resistance Database, and a data set of protein families with experimentally annotated SDPs. For both data sets, SigniSite was found to outperform SPEER. SigniSite is available at: http://www.cbs.dtu.dk/services/SigniSite/.

Identifying and Further Understanding the Role of Bacteria and Archaea in a Basic Mine Drainage Remediation Site in Tanoma, PA

NASA Astrophysics Data System (ADS)

Sharp, G.; Mount, G.

2017-12-01

Acid mine drainage pollutes over 3000 miles of streams and ground water in Pennsylvania alone, and in response many solutions have been developed to counteract the effects of acidic mine drainage. It is estimated by USGS that restoring these watersheds would cost 5 billion-15 billion in total. As economic conditions place limits on expenditures, cost effective means of remediation will be of critical importance. One such method is passive bioremediation, and in the case of metal contamination, self-sustaining oxygenation. Our location of interest is the Tanoma Acid Mine Drainage engineered wetland near Tanoma, Pennsylvania. It is estimated that up to 5,000 gallons per minute is currently being discharged into the site. While most local remediation sites are acidic (pH <4), the Tanoma wetland allows for the study of bioremediation in more neutral pH setting (pH of 5.5-7.5). In this study, we look to further understand biologic, chemical, and hydrologic controls that contribute to the efficiency of the wetland. Our research will focus on the spatial and temporal distribution of biomass through the wetland system as well as changes in water and soil chemistry. Local biofilm (Leptothrix discophora ) are an important part of the remediation process, using iron from the water as an energy source. The bacteria reduce the iron content of the water, precipitating it onto the pond bed as Terraced Iron Formations (TIF). Terraces iron formations (TIF's) are correlated with localized biofilm-archaea densities where archaea thrive in iron rich sediments. By determining bacteria densities in the wetland through gram stain analysis, we can further understand their role in terraced iron formation creation, find localized TIF's that occur, and correlate methane production due to archaea in that location. Mapping TIF locations and identifying bacteria densities will help determine the bioremediation effects on the overall efficiency of iron reduction throughout the Tanoma AMD passive

ENVIRONMENTAL METHODS TESTING SITE PROJECT: DATA MANAGEMENT PROCEDURES PLAN

EPA Science Inventory

The Environmental Methods Testing Site (EMTS) Data Management Procedures Plan identifies the computer hardware and software resources used in the EMTS project. It identifies the major software packages that are available for use by principal investigators for the analysis of data...

Pediatric injury prevention programs: Identifying markers for success and sustainability.

PubMed

Chaudhary, Sofia; Pomerantz, Wendy J; Miller, Beverly; Pan, Anqi; Agarwal, Maneesha

2017-11-01

Injury is the leading cause of death in children. Although many pediatric hospitals and trauma centers provide injury prevention (IP) programming, there is no national standard. This study aims to identify characteristics of a sustainable and successful IP program by querying programs affiliated with the Injury Free Coalition for Kids (IFCK). The IFCK sites were sent a 30-question survey via e-mail. Questions focused on demographics, scope of IP activities, self-efficacy, and outcome measures including finances, academic productivity, and legislative advocacy. Counts and frequencies were calculated and compared using χ tests. The survey was completed by 38 (90.4%) of 42 sites. The majority were associated with a freestanding children's hospital (57.9%) and Level I pediatric trauma center (86.8%). Most programs (79%) had at least one dedicated full-time equivalent (FTE) staff. Research was most common on child passenger safety and teen driving. Nearly 30% of programs offered educational curricula to health care providers; these sites were more likely to have FTE support (p = 0.036). Steady sources of funding were identified for 60.5% of programs, with 47.8% citing their hospital as the primary source; 73% of respondents were confident in their program's capacity to sustain activities; these were more likely to be larger programs (p = 0.001) with steady sources of funding (p < 0.001). Despite 73.7% of sites having academic affiliations, 60.5% had 5 or fewer publications over the previous 5 years. In the prior 2 years, 55.3% of programs impacted legislative or policy changes. Funding, size of program, and FTE had no statistical correlation with research productivity or number of legislative/policy contributions. This study characterizes the variation among pediatric IP programs within IFCK sites, while highlighting the association between financial and FTE support from programs' institutions with sustainable IP programming. These results can assist programs in

SITEHOUND-web: a server for ligand binding site identification in protein structures.

PubMed

Hernandez, Marylens; Ghersi, Dario; Sanchez, Roberto

2009-07-01

SITEHOUND-web (http://sitehound.sanchezlab.org) is a binding-site identification server powered by the SITEHOUND program. Given a protein structure in PDB format SITEHOUND-web will identify regions of the protein characterized by favorable interactions with a probe molecule. These regions correspond to putative ligand binding sites. Depending on the probe used in the calculation, sites with preference for different ligands will be identified. Currently, a carbon probe for identification of binding sites for drug-like molecules, and a phosphate probe for phosphorylated ligands (ATP, phoshopeptides, etc.) have been implemented. SITEHOUND-web will display the results in HTML pages including an interactive 3D representation of the protein structure and the putative sites using the Jmol java applet. Various downloadable data files are also provided for offline data analysis.

Anaerobic carboxydotrophic bacteria in geothermal springs identified using stable isotope probing.

PubMed

Brady, Allyson L; Sharp, Christine E; Grasby, Stephen E; Dunfield, Peter F

2015-01-01

Carbon monoxide (CO) is a potential energy and carbon source for thermophilic bacteria in geothermal environments. Geothermal sites ranging in temperature from 45 to 65°C were investigated for the presence and activity of anaerobic CO-oxidizing bacteria. Anaerobic CO oxidation potentials were measured at up to 48.9 μmoles CO g(-1) (wet weight) day(-1) within five selected sites. Active anaerobic carboxydotrophic bacteria were identified using (13)CO DNA stable isotope probing (SIP) combined with pyrosequencing of 16S rRNA genes amplified from labeled DNA. Bacterial communities identified in heavy DNA fractions were predominated by Firmicutes, which comprised up to 95% of all sequences in (13)CO incubations. The predominant bacteria that assimilated (13)C derived from CO were closely related (>98% 16S rRNA gene sequence identity) to genera of known carboxydotrophs including Thermincola, Desulfotomaculum, Thermolithobacter, and Carboxydocella, although a few species with lower similarity to known bacteria were also found that may represent previously unconfirmed CO-oxidizers. While the distribution was variable, many of the same OTUs were identified across sample sites from different temperature regimes. These results show that bacteria capable of using CO as a carbon source are common in geothermal springs, and that thermophilic carboxydotrophs are probably already quite well known from cultivation studies.

Electrical studies at the proposed Wahmonie and Calico Hills nuclear waste sites, Nevada Test Site, Nye County, Nevada

USGS Publications Warehouse

Hoover, D.B.; Chornack, Michael P.; Nervick, K.H.; Broker, M.M.

1982-01-01

Two sites in the southwest quadrant of the Nevada Test Site (NTS) were investigated as potential repositories for high-level nuclear waste. These are designated the Wahmonie and Calico Hills sites. The emplacement medium at both sites was to be an inferred intrusive body at shallow depth; the inference of the presence of the body was based on aeromagnetic and regional gravity data. This report summarizes results of Schlumberger VES, induced polarization dipole-dipole traverses and magnetotelluric soundings made in the vicinity of the sites in order to characterize the geoelectric section. At the Wahmonie site VES work identified a low resistivity unit at depth surrounding the inferred intrusive body. The low resistivity unit is believed to be either the argillite (Mississippian Eleana Formation) or a thick unit of altered volcanic rock (Tertiary). Good electrical contrast is provided between the low resistivity unit and a large volume of intermediate resistivity rock correlative with the aeromagnetic and gravity data. The intermediate resistivity unit (100-200 ohm-m) is believed to be the intrusive body. The resistivity values are very low for a fresh, tight intrusive and suggest significant fracturing, alteration and possible mineralization have occurred within the upper kilometer of rock. Induced polarization data supports the VES work, identifies a major fault on the northwest side of the inferred intrusive and significant potential for disseminated mineralization within the body. The mineralization potential is particularly significant because as late as 1928, a strike of high grade silver-gold ore was made at the site. The shallow electrical data at Calico Hills revealed no large volume high resistivity body that could be associated with a tight intrusive mass in the upper kilometer of section. A drill hole UE 25A-3 sunk to 762 m (2500 ft) at the site revealed only units of the Eleana argillite thermally metamorphosed below 396 m (1300 ft) and in part highly

iDHS-EL: identifying DNase I hypersensitive sites by fusing three different modes of pseudo nucleotide composition into an ensemble learning framework.

PubMed

Liu, Bin; Long, Ren; Chou, Kuo-Chen

2016-08-15

Regulatory DNA elements are associated with DNase I hypersensitive sites (DHSs). Accordingly, identification of DHSs will provide useful insights for in-depth investigation into the function of noncoding genomic regions. In this study, using the strategy of ensemble learning framework, we proposed a new predictor called iDHS-EL for identifying the location of DHS in human genome. It was formed by fusing three individual Random Forest (RF) classifiers into an ensemble predictor. The three RF operators were respectively based on the three special modes of the general pseudo nucleotide composition (PseKNC): (i) kmer, (ii) reverse complement kmer and (iii) pseudo dinucleotide composition. It has been demonstrated that the new predictor remarkably outperforms the relevant state-of-the-art methods in both accuracy and stability. For the convenience of most experimental scientists, a web server for iDHS-EL is established at http://bioinformatics.hitsz.edu.cn/iDHS-EL, which is the first web-server predictor ever established for identifying DHSs, and by which users can easily get their desired results without the need to go through the mathematical details. We anticipate that IDHS-EL: will become a very useful high throughput tool for genome analysis. bliu@gordonlifescience.org or bliu@insun.hit.edu.cn Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

PhosphoSitePlus, 2014: mutations, PTMs and recalibrations

PubMed Central

Hornbeck, Peter V.; Zhang, Bin; Murray, Beth; Kornhauser, Jon M.; Latham, Vaughan; Skrzypek, Elzbieta

2015-01-01

PhosphoSitePlus® (PSP, http://www.phosphosite.org/), a knowledgebase dedicated to mammalian post-translational modifications (PTMs), contains over 330 000 non-redundant PTMs, including phospho, acetyl, ubiquityl and methyl groups. Over 95% of the sites are from mass spectrometry (MS) experiments. In order to improve data reliability, early MS data have been reanalyzed, applying a common standard of analysis across over 1 000 000 spectra. Site assignments with P > 0.05 were filtered out. Two new downloads are available from PSP. The ‘Regulatory sites’ dataset includes curated information about modification sites that regulate downstream cellular processes, molecular functions and protein-protein interactions. The ‘PTMVar’ dataset, an intersect of missense mutations and PTMs from PSP, identifies over 25 000 PTMVars (PTMs Impacted by Variants) that can rewire signaling pathways. The PTMVar data include missense mutations from UniPROTKB, TCGA and other sources that cause over 2000 diseases or syndromes (MIM) and polymorphisms, or are associated with hundreds of cancers. PTMVars include 18 548 phosphorlyation sites, 3412 ubiquitylation sites, 2316 acetylation sites, 685 methylation sites and 245 succinylation sites. PMID:25514926

APAtrap: identification and quantification of alternative polyadenylation sites from RNA-seq data.

PubMed

Ye, Congting; Long, Yuqi; Ji, Guoli; Li, Qingshun Quinn; Wu, Xiaohui

2018-06-01

Alternative polyadenylation (APA) has been increasingly recognized as a crucial mechanism that contributes to transcriptome diversity and gene expression regulation. As RNA-seq has become a routine protocol for transcriptome analysis, it is of great interest to leverage such unprecedented collection of RNA-seq data by new computational methods to extract and quantify APA dynamics in these transcriptomes. However, research progress in this area has been relatively limited. Conventional methods rely on either transcript assembly to determine transcript 3' ends or annotated poly(A) sites. Moreover, they can neither identify more than two poly(A) sites in a gene nor detect dynamic APA site usage considering more than two poly(A) sites. We developed an approach called APAtrap based on the mean squared error model to identify and quantify APA sites from RNA-seq data. APAtrap is capable of identifying novel 3' UTRs and 3' UTR extensions, which contributes to locating potential poly(A) sites in previously overlooked regions and improving genome annotations. APAtrap also aims to tally all potential poly(A) sites and detect genes with differential APA site usages between conditions. Extensive comparisons of APAtrap with two other latest methods, ChangePoint and DaPars, using various RNA-seq datasets from simulation studies, human and Arabidopsis demonstrate the efficacy and flexibility of APAtrap for any organisms with an annotated genome. Freely available for download at https://apatrap.sourceforge.io. liqq@xmu.edu.cn or xhuister@xmu.edu.cn. Supplementary data are available at Bioinformatics online.

An elm EST database for identifying leaf beetle egg-induced defense genes

PubMed Central

2012-01-01

primary metabolism. Conclusion Here we present a dataset for a large-scale study of the mechanisms of plant defense against insect eggs in a co-evolved, natural ecological plant–insect system. The EST database analysis provided here is a first step in elucidating the transcriptional responses of elm to elm leaf beetle infestation, and adds further to our knowledge on insect egg-induced transcriptomic changes in plants. The sequences identified in our comparative analysis give many hints about novel defense mechanisms directed towards eggs. PMID:22702658

An elm EST database for identifying leaf beetle egg-induced defense genes.

PubMed

Büchel, Kerstin; McDowell, Eric; Nelson, Will; Descour, Anne; Gershenzon, Jonathan; Hilker, Monika; Soderlund, Carol; Gang, David R; Fenning, Trevor; Meiners, Torsten

2012-06-15

. Here we present a dataset for a large-scale study of the mechanisms of plant defense against insect eggs in a co-evolved, natural ecological plant-insect system. The EST database analysis provided here is a first step in elucidating the transcriptional responses of elm to elm leaf beetle infestation, and adds further to our knowledge on insect egg-induced transcriptomic changes in plants. The sequences identified in our comparative analysis give many hints about novel defense mechanisms directed towards eggs.

SOLIDIFICATION/STABILIZATION: A LOW COST TREATMENT FOR WOOD PRESERVING SITES

EPA Science Inventory

Over 600 curent and former wood preserving sites have been identified across the U.S. Many of these have been placed on the EPA Superfund NPL (National Priorities List). Most of these sites contain soils contaminated with pentachlorophenol, dioxins, and/or creosote. Treatability...

A Bayesian belief network approach for assessing uncertainty in conceptual site models at contaminated sites

NASA Astrophysics Data System (ADS)

Thomsen, Nanna I.; Binning, Philip J.; McKnight, Ursula S.; Tuxen, Nina; Bjerg, Poul L.; Troldborg, Mads

2016-05-01

A key component in risk assessment of contaminated sites is in the formulation of a conceptual site model (CSM). A CSM is a simplified representation of reality and forms the basis for the mathematical modeling of contaminant fate and transport at the site. The CSM should therefore identify the most important site-specific features and processes that may affect the contaminant transport behavior at the site. However, the development of a CSM will always be associated with uncertainties due to limited data and lack of understanding of the site conditions. CSM uncertainty is often found to be a major source of model error and it should therefore be accounted for when evaluating uncertainties in risk assessments. We present a Bayesian belief network (BBN) approach for constructing CSMs and assessing their uncertainty at contaminated sites. BBNs are graphical probabilistic models that are effective for integrating quantitative and qualitative information, and thus can strengthen decisions when empirical data are lacking. The proposed BBN approach facilitates a systematic construction of multiple CSMs, and then determines the belief in each CSM using a variety of data types and/or expert opinion at different knowledge levels. The developed BBNs combine data from desktop studies and initial site investigations with expert opinion to assess which of the CSMs are more likely to reflect the actual site conditions. The method is demonstrated on a Danish field site, contaminated with chlorinated ethenes. Four different CSMs are developed by combining two contaminant source zone interpretations (presence or absence of a separate phase contamination) and two geological interpretations (fractured or unfractured clay till). The beliefs in each of the CSMs are assessed sequentially based on data from three investigation stages (a screening investigation, a more detailed investigation, and an expert consultation) to demonstrate that the belief can be updated as more information

Installation restoration program. Site investigation report, IRP sites No. 1, No. 2, and No. 3. 106th Civil Engineering Flight, New York Air National Guard, Roslyn Air National Guard Station, Roslyn, New York. Volume 1. Site Investigation report

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

NONE

1996-11-01

This report presents the results of the Site Investigation (SI) conducted at IRP Sites No. 1, No. 2, and No. 3 at the 106th Civil Engineering Flight (CEF) located at Roslyn Air National Guard Station (ANGS), Roslyn, Long Island, New York. A Preliminary Assessment (PA) (AD-A238 847) of the 106th CEF resulted in the identification of two potentially contaminated waste holding areas and a waste sludge application site. These sites were identified as IRP Site No. 1 (Access Road to Aerospace Ground Equipment `AGE` Shop), IRP Site No. 2 (Old Waste Holding Area No. 1), and IRP Site No. 3more » (Old Waste Holding Area No. 2) and recommended for further investigation under the Installation Restoration Program (IRP).« less

FF Site Information

EPA Pesticide Factsheets

This asset includes the EPA Federal Agency Hazardous Waste Compliance Docket (Docket), which is required by Section 120(c) of the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA). The Docket contains information reported to EPA by federal facilities that manage hazardous waste or from which hazardous substances, pollutants or contaminants have been or may be released. The Docket serves three major purposes:1. To identify all federal facilities that must be evaluated through the site assessment process to determine whether they pose a risk to human health and the environment sufficient to warrant inclusion on the National Priorities List (NPL); 2. To compile and maintain the information submitted to EPA on such facilities under the provisions listed in section 120(c) of CERCLA; and3. To provide a mechanism to make the information available to the public.The docket includes facilities which have provided information to EPA through documents such as reports under a Federal agency environmental restoration program, regardless of the absence of section 103 reporting. E-Docket is an internal business management tool that will improve the tracking and record keeping of information about facilities that have been identified as potential Docket sites. The functionality of the system is basic record tracking, and it will contain a list of draft proposed facilities which can be sorted based on Agency ownership, region, or status (Draft Propose

Site Selection Appraisal for Tidal Turbine Development in the River Mersey

NASA Astrophysics Data System (ADS)

Kelly, C. L.; Blanco-Davis, E.; Michailides, C.; Davies, P. A.; Wang, J.

2018-03-01

This paper used a specialist software package to produce a detailed model of the River Mersey estuary, which can be subjected to a range of simulated tidal conditions. The aim of this research was to use the validated model to identify the optimal location for the positioning of a tidal turbine. Progress was made identifying a new optimal site for power generation using velocity data produced from simulations conducted using the MIKE 3 software. This process resulted in the identification of site 8, which sits mid-river between the Morpeth Dock and the Albert Dock, being identified as the favoured location for tidal power generation in the River Mersey. Further analysis of the site found that a 17.2-m diameter single rota multidirectional turbine with a 428-kW-rated capacity could produce 1.12 GWh annually.

7 CFR 12.31 - On-site wetland identification criteria.

Code of Federal Regulations, 2011 CFR

2011-01-01

... CONSERVATION Wetland Conservation § 12.31 On-site wetland identification criteria. (a) Hydric soils. (1) NRCS shall identify hydric soils through the use of published soil maps which reflect soil surveys completed by NRCS or through the use of on-site reviews. If a published soil map is unavailable for a given...

7 CFR 12.31 - On-site wetland identification criteria.

Code of Federal Regulations, 2014 CFR

2014-01-01

... CONSERVATION Wetland Conservation § 12.31 On-site wetland identification criteria. (a) Hydric soils. (1) NRCS shall identify hydric soils through the use of published soil maps which reflect soil surveys completed by NRCS or through the use of on-site reviews. If a published soil map is unavailable for a given...

7 CFR 12.31 - On-site wetland identification criteria.

Code of Federal Regulations, 2010 CFR

2010-01-01

... CONSERVATION Wetland Conservation § 12.31 On-site wetland identification criteria. (a) Hydric soils. (1) NRCS shall identify hydric soils through the use of published soil maps which reflect soil surveys completed by NRCS or through the use of on-site reviews. If a published soil map is unavailable for a given...

7 CFR 12.31 - On-site wetland identification criteria.

Code of Federal Regulations, 2013 CFR

2013-01-01

... CONSERVATION Wetland Conservation § 12.31 On-site wetland identification criteria. (a) Hydric soils. (1) NRCS shall identify hydric soils through the use of published soil maps which reflect soil surveys completed by NRCS or through the use of on-site reviews. If a published soil map is unavailable for a given...

7 CFR 12.31 - On-site wetland identification criteria.

Code of Federal Regulations, 2012 CFR

2012-01-01

... CONSERVATION Wetland Conservation § 12.31 On-site wetland identification criteria. (a) Hydric soils. (1) NRCS shall identify hydric soils through the use of published soil maps which reflect soil surveys completed by NRCS or through the use of on-site reviews. If a published soil map is unavailable for a given...

Future management strategies for state maintained wetlands and stream mitigation sites.

DOT National Transportation Integrated Search

2008-06-01

This study was to identify existing wetland/stream mitigation sites owned by the Kentucky Transportation Cabinet (KYTC) and assess performance of those sites including problems encountered and maintenance costs. Initial work determined that KYTC Dist...

A framework for implementing biodiversity offsets: selecting sites and determining scale

USGS Publications Warehouse

Kiesecker, Joseph M.; Copeland, Holly; Pocewicz, Amy; Nibbelink, Nate; McKenney, Bruce; Dahlke, John; Holloran, Matthew J.; Stroud, Dan

2009-01-01

Biodiversity offsets provide a mechanism for maintaining or enhancing environmental values in situations where development is sought despite detrimental environmental impacts. They seek to ensure that unavoidable negative environmental impacts of development are balanced by environmental gains, with the overall aim of achieving a net neutral or positive outcome. Once the decision has been made to offset, multiple issues arise regarding how to do so in practice. A key concern is site selection. In light of the general aim to locate offsets close to the affected sites to ensure that benefits accrue in the same area, what is the appropriate spatial scale for identifying potential offset sites (e.g., local, ecoregional)? We use the Marxan site-selection algorithm to address conceptual and methodological challenges associated with identifying a set of potential offset sites and determining an appropriate spatial scale for them. To demonstrate this process, we examined the design of offsets for impacts from development on the Jonah natural gas field in Wyoming.

Screening of a library of T7 phage-displayed peptides identifies alphaC helix in 14-3-3 protein as a CBP501-binding site.

PubMed

Matsumoto, Yuki; Shindo, Yosuke; Takakusagi, Yoichi; Takakusagi, Kaori; Tsukuda, Senko; Kusayanagi, Tomoe; Sato, Hitoshi; Kawabe, Takumi; Sugawara, Fumio; Sakaguchi, Kengo

2011-12-01

CBP501 is a chemically modified peptide composed of twelve unnatural d-amino acids, which inhibits Chk kinase and abrogates G2 arrest induced by DNA-damaging agents. Here we identified an alphaC helix in 14-3-3 protein as a CBP501-binding site using T7 phage display technology. An affinity selection of T7 phage-displayed peptide using biotinylated CBP501 identified a 14-mer peptide NSDCIISRKIEQKE. This peptide sequence showed similarity to a portion of the alphaC helix of human 14-3-3ε, suggesting that CBP501 may bind to this region. Surface plasmon resonance (SPR) and ELISA demonstrated that CBP501 interacts with 14-3-3ε specifically at the screen-guided region. An avidin-agarose bead pull-down assay showed that CBP501 also binds to other 14-3-3 isoforms in Jurkat cells. Among the other known Chk kinase inhibitors tested, CBP501 showed the strongest affinity for 14-3-3ε. Thus, we conclude that in addition to the direct inhibition of Chk kinase activity, CBP501 directly binds to cellular 14-3-3 proteins through alphaC helix. Copyright © 2011 Elsevier Ltd. All rights reserved.

Wilderness on the internet: identifying wilderness information domains

Treesearch

Chuck Burgess

2000-01-01

Data collected from an online needs assessment revealed that Web site visitors with an interest in wilderness seek several different types of information. In order to gain further insight into the process of Web use for wilderness information, a follow-up analysis was conducted. This analysis was exploratory in nature, with the goal of identifying information domains...

The placenta harbors a unique microbiome.

PubMed

Aagaard, Kjersti; Ma, Jun; Antony, Kathleen M; Ganu, Radhika; Petrosino, Joseph; Versalovic, James

2014-05-21

Humans and their microbiomes have coevolved as a physiologic community composed of distinct body site niches with metabolic and antigenic diversity. The placental microbiome has not been robustly interrogated, despite recent demonstrations of intracellular bacteria with diverse metabolic and immune regulatory functions. A population-based cohort of placental specimens collected under sterile conditions from 320 subjects with extensive clinical data was established for comparative 16S ribosomal DNA-based and whole-genome shotgun (WGS) metagenomic studies. Identified taxa and their gene carriage patterns were compared to other human body site niches, including the oral, skin, airway (nasal), vaginal, and gut microbiomes from nonpregnant controls. We characterized a unique placental microbiome niche, composed of nonpathogenic commensal microbiota from the Firmicutes, Tenericutes, Proteobacteria, Bacteroidetes, and Fusobacteria phyla. In aggregate, the placental microbiome profiles were most akin (Bray-Curtis dissimilarity <0.3) to the human oral microbiome. 16S-based operational taxonomic unit analyses revealed associations of the placental microbiome with a remote history of antenatal infection (permutational multivariate analysis of variance, P = 0.006), such as urinary tract infection in the first trimester, as well as with preterm birth <37 weeks (P = 0.001). Copyright © 2014, American Association for the Advancement of Science.

Epibenthic assessment of a renewable tidal energy site.

PubMed

Sheehan, Emma V; Gall, Sarah C; Cousens, Sophie L; Attrill, Martin J

2013-01-01

Concern over global climate change as a result of fossil fuel use has resulted in energy production from renewable sources. Marine renewable energy devices provide clean electricity but can also cause physical disturbance to the local environment. There is a considerable paucity of ecological data at potential marine renewable energy sites that is needed to assess potential future impacts and allow optimal siting of devices. Here, we provide a baseline benthic survey for the Big Russel in Guernsey, UK, a potential site for tidal energy development. To assess the suitability of proposed sites for marine renewable energy in the Big Russel and to identify potential control sites, we compared species assemblages and habitat types. This baseline survey can be used to select control habitats to compare and monitor the benthic communities after installation of the device and contribute towards the optimal siting of any future installation.

Prioritizing ecological restoration among sites in multi-stressor landscapes.

PubMed

Neeson, Thomas M; Smith, Sigrid D P; Allan, J David; McIntyre, Peter B

2016-09-01

Most ecosystems are impacted by multiple local and long-distance stressors, many of which interact in complex ways. We present a framework for prioritizing ecological restoration efforts among sites in multi-stressor landscapes. Using a simple model, we show that both the economic and sociopolitical costs of restoration will typically be lower at sites with a relatively small number of severe problems than at sites with numerous lesser problems. Based on these results, we propose using cumulative stress and evenness of stressor impact as complementary indices that together reflect key challenges of restoring a site to improved condition. To illustrate this approach, we analyze stressor evenness across the world's rivers and the Laurentian Great Lakes. This exploration reveals that evenness and cumulative stress are decoupled, enabling selection of sites where remediating a modest number of high-intensity stressors could substantially reduce cumulative stress. Just as species richness and species evenness are fundamental axes of biological diversity, we argue that cumulative stress and stressor evenness constitute fundamental axes for identifying restoration opportunities in multi-stressor landscapes. Our results highlight opportunities to boost restoration efficiency through strategic use of multi-stressor datasets to identify sites that maximize ecological response per stressor remediated. This prioritization framework can also be expanded to account for the feasibility of remediation and the expected societal benefits of restoration projects. © 2016 by the Ecological Society of America.

Pharmacophore screening of the protein data bank for specific binding site chemistry.

PubMed

Campagna-Slater, Valérie; Arrowsmith, Andrew G; Zhao, Yong; Schapira, Matthieu

2010-03-22

A simple computational approach was developed to screen the Protein Data Bank (PDB) for putative pockets possessing a specific binding site chemistry and geometry. The method employs two commonly used 3D screening technologies, namely identification of cavities in protein structures and pharmacophore screening of chemical libraries. For each protein structure, a pocket finding algorithm is used to extract potential binding sites containing the correct types of residues, which are then stored in a large SDF-formatted virtual library; pharmacophore filters describing the desired binding site chemistry and geometry are then applied to screen this virtual library and identify pockets matching the specified structural chemistry. As an example, this approach was used to screen all human protein structures in the PDB and identify sites having chemistry similar to that of known methyl-lysine binding domains that recognize chromatin methylation marks. The selected genes include known readers of the histone code as well as novel binding pockets that may be involved in epigenetic signaling. Putative allosteric sites were identified on the structures of TP53BP1, L3MBTL3, CHEK1, KDM4A, and CREBBP.

Genome-wide identification and characterisation of human DNA replication origins by initiation site sequencing (ini-seq)

PubMed Central

Langley, Alexander R.; Gräf, Stefan; Smith, James C.; Krude, Torsten

2016-01-01

Next-generation sequencing has enabled the genome-wide identification of human DNA replication origins. However, different approaches to mapping replication origins, namely (i) sequencing isolated small nascent DNA strands (SNS-seq); (ii) sequencing replication bubbles (bubble-seq) and (iii) sequencing Okazaki fragments (OK-seq), show only limited concordance. To address this controversy, we describe here an independent high-resolution origin mapping technique that we call initiation site sequencing (ini-seq). In this approach, newly replicated DNA is directly labelled with digoxigenin-dUTP near the sites of its initiation in a cell-free system. The labelled DNA is then immunoprecipitated and genomic locations are determined by DNA sequencing. Using this technique we identify >25,000 discrete origin sites at sub-kilobase resolution on the human genome, with high concordance between biological replicates. Most activated origins identified by ini-seq are found at transcriptional start sites and contain G-quadruplex (G4) motifs. They tend to cluster in early-replicating domains, providing a correlation between early replication timing and local density of activated origins. Origins identified by ini-seq show highest concordance with sites identified by SNS-seq, followed by OK-seq and bubble-seq. Furthermore, germline origins identified by positive nucleotide distribution skew jumps overlap with origins identified by ini-seq and OK-seq more frequently and more specifically than do sites identified by either SNS-seq or bubble-seq. PMID:27587586

Genome-wide identification and characterisation of human DNA replication origins by initiation site sequencing (ini-seq).

PubMed

Langley, Alexander R; Gräf, Stefan; Smith, James C; Krude, Torsten

2016-12-01

Next-generation sequencing has enabled the genome-wide identification of human DNA replication origins. However, different approaches to mapping replication origins, namely (i) sequencing isolated small nascent DNA strands (SNS-seq); (ii) sequencing replication bubbles (bubble-seq) and (iii) sequencing Okazaki fragments (OK-seq), show only limited concordance. To address this controversy, we describe here an independent high-resolution origin mapping technique that we call initiation site sequencing (ini-seq). In this approach, newly replicated DNA is directly labelled with digoxigenin-dUTP near the sites of its initiation in a cell-free system. The labelled DNA is then immunoprecipitated and genomic locations are determined by DNA sequencing. Using this technique we identify >25,000 discrete origin sites at sub-kilobase resolution on the human genome, with high concordance between biological replicates. Most activated origins identified by ini-seq are found at transcriptional start sites and contain G-quadruplex (G4) motifs. They tend to cluster in early-replicating domains, providing a correlation between early replication timing and local density of activated origins. Origins identified by ini-seq show highest concordance with sites identified by SNS-seq, followed by OK-seq and bubble-seq. Furthermore, germline origins identified by positive nucleotide distribution skew jumps overlap with origins identified by ini-seq and OK-seq more frequently and more specifically than do sites identified by either SNS-seq or bubble-seq. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

A genome-wide map of hyper-edited RNA reveals numerous new sites.

PubMed

Porath, Hagit T; Carmi, Shai; Levanon, Erez Y

2014-08-27

Adenosine-to-inosine editing is one of the most frequent post-transcriptional modifications, manifested as A-to-G mismatches when comparing RNA sequences with their source DNA. Recently, a number of RNA-seq data sets have been screened for the presence of A-to-G editing, and hundreds of thousands of editing sites identified. Here we show that existing screens missed the majority of sites by ignoring reads with excessive ('hyper') editing that do not easily align to the genome. We show that careful alignment and examination of the unmapped reads in RNA-seq studies reveal numerous new sites, usually many more than originally discovered, and in precisely those regions that are most heavily edited. Specifically, we discover 327,096 new editing sites in the heavily studied Illumina Human BodyMap data and more than double the number of detected sites in several published screens. We also identify thousands of new sites in mouse, rat, opossum and fly. Our results establish that hyper-editing events account for the majority of editing sites.

Regional risk assessment for contaminated sites part 2: ranking of potentially contaminated sites.

PubMed

Pizzol, Lisa; Critto, Andrea; Agostini, Paola; Marcomini, Antonio

2011-11-01

Environmental risks are traditionally assessed and presented in non spatial ways although the heterogeneity of the contaminants spatial distributions, the spatial positions and relations between receptors and stressors, as well as the spatial distribution of the variables involved in the risk assessment, strongly influence exposure estimations and hence risks. Taking into account spatial variability is increasingly being recognized as a further and essential step in sound exposure and risk assessment. To address this issue an innovative methodology which integrates spatial analysis and a relative risk approach was developed. The purpose of this methodology is to prioritize sites at regional scale where a preliminary site investigation may be required. The methodology aimed at supporting the inventory of contaminated sites was implemented within the spatial decision support sYstem for Regional rIsk Assessment of DEgraded land, SYRIADE, and was applied to the case-study of the Upper Silesia region (Poland). The developed methodology and tool are both flexible and easy to adapt to different regional contexts, allowing the user to introduce the regional relevant parameters identified on the basis of user expertise and regional data availability. Moreover, the used GIS functionalities, integrated with mathematical approaches, allow to take into consideration, all at once, the multiplicity of sources and impacted receptors within the region of concern, to assess the risks posed by all contaminated sites in the region and, finally, to provide a risk-based ranking of the potentially contaminated sites. Copyright © 2011. Published by Elsevier Ltd.

[Current status of illegal trade in pharmaceutical products on Internet auction sites in Japan and responses of site administrators to such transactions].

PubMed

Ohtani, Hisakazu; Imaoka, Ayuko; Akiyoshi, Takeshi

2015-01-01

In Japan, it is illegal to sell pharmaceuticals on Internet auction sites, although a considerable number of pharmaceuticals are listed on such sites. We investigated the current situation regarding the illegal trade in pharmaceuticals on Japanese Internet auction sites and the responses of site administrators to such transactions. We searched for pharmaceuticals and "gray" items that were suspected of being pharmaceuticals on Yahoo-oku! (Yahoo! Auctions, Japan) over a 37-day period and then submitted violation reports indicating that selling pharmaceuticals is illegal or that the description of an item was insufficient. The reports were directed to the site administrators and forwarded to the sellers. One hundred and six pharmaceutical products and 34 gray items were identified during the study period. After the submission of the violation reports, only 28 of the pharmaceutical products and one of the gray items were deleted by the administrator, while 18 of the pharmaceutical products and 7 of the gray items were withdrawn by their sellers. However, 41 pharmaceuticals and 20 gray items were sold. Most of the gray items were listed using characteristic terms or abbreviations without photographic images. More than 70% of the identified pharmaceuticals had a contraindication(s) other than hypersensitivity. In conclusion, the illegal trade in pharmaceuticals on Internet auction sites remains a serious problem in Japan, and the responses of site administrators to such transactions are inadequate. The government and pharmaceutical industry may have to take measures such as providing public and administrative guidance to stop the illegal trade in pharmaceuticals on the Internet.

A Weighting Method for Assessing Between-Site Heterogeneity in Causal Mediation Mechanism

ERIC Educational Resources Information Center

Qin, Xu; Hong, Guanglei

2017-01-01

When a multisite randomized trial reveals between-site variation in program impact, methods are needed for further investigating heterogeneous mediation mechanisms across the sites. We conceptualize and identify a joint distribution of site-specific direct and indirect effects under the potential outcomes framework. A method-of-moments procedure…

Cleanup Verification Package for the 600-47 Waste Site

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

M. J. Cutlip

This cleanup verification package documents completion of interim remedial action for the 600-47 waste site. This site consisted of several areas of surface debris and contamination near the banks of the Columbia River across from Johnson Island. Contaminated material identified in field surveys included four areas of soil, wood, nuts, bolts, and other metal debris.

Living memorials project: year 1 social and site assessment

Treesearch

Erika S. Svendsen; Lindsay K. Campbell

2005-01-01

The Living Memorials Project (LMP) social and site assessment identified more than 200 public open spaces created, used, or enhanced in memory of the tragic events of September 11, 2001 (9-11). A national registry of these sites is available for viewing and updating online. Researchers interviewed 100 community groups using social ecology methods of observation,...

Level 2 Therapeutic Model Site

ERIC Educational Resources Information Center

Spears, Brad; Sanchez, David; Bishop, Jane; Rogers, Sharon; DeJong, Judith A.

2006-01-01

L2, one of the original sites first funded under the Therapeutic Residential Model Initiative in 2001-2002, is operated as a peripheral dormitory This dormitory cares for 185 boys and girls in grades 1-12 who attend local public schools. L2 presented an outstanding proposal which identified gaps in services and presented a reasonable budget to…

Lunar resource evaluation and mine site selection

NASA Technical Reports Server (NTRS)

Bence, A. Edward

1992-01-01

Two scenarios in this evaluation of lunar mineral resources and the selection of possible mining and processing sites are considered. The first scenario assumes that no new surface or near-surface data will be available before site selection (presumably one of the Apollo sites). The second scenario assumes that additional surface geology data will have been obtained by a lunar orbiter mission, an unmanned sample return mission (or missions), and followup manned missions. Regardless of the scenario, once a potentially favorable mine site has been identified, a minimum amount of fundamental data is needed to assess the resources at that site and to evaluate its suitability for mining and downstream processing. Since much of the required data depends on the target mineral(s), information on the resource, its beneficiation, and the refining, smelting, and fabricating processes must be factored into the evaluation. The annual capacity and producing lifetime of the mine and its associated processing plant must be estimated before the resource reserves can be assessed. The available market for the product largely determines the capacity and lifetime of the mine. The Apollo 17 site is described as a possible mining site. The use of new sites is briefly addressed.

US EPA record of decision review for landfills: Sanitary landfill (740-G), Savannah River Site

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

Not Available

1993-06-01

This report presents the results of a review of the US Environmental Protection Agency (EPA) Record of Decision System (RODS) database search conducted to identify Superfund landfill sites where a Record of Decision (ROD) has been prepared by EPA, the States or the US Army Corps of Engineers describing the selected remedy at the site. ROD abstracts from the database were reviewed to identify site information including site type, contaminants of concern, components of the selected remedy, and cleanup goals. Only RODs from landfill sites were evaluated so that the results of the analysis can be used to support themore » remedy selection process for the Sanitary Landfill at the Savannah River Site (SRS).« less

CNS sites cooperate to detect duplicate subjects with a clinical trial subject registry.

PubMed

Shiovitz, Thomas M; Wilcox, Charles S; Gevorgyan, Lilit; Shawkat, Adnan

2013-02-01

To report the results of the first 1,132 subjects in a pilot project where local central nervous system trial sites collaborated in the use of a subject database to identify potential duplicate subjects. Central nervous system sites in Los Angeles and Orange County, California, were contacted by the lead author to seek participation in the project. CTSdatabase, a central nervous system-focused trial subject registry, was utilized to track potential subjects at pre-screen. Subjects signed an institutional review board-approved authorization prior to participation, and site staff entered their identifiers by accessing a website. Sites were prompted to communicate with each other or with the database administrator when a match occurred between a newly entered subject and a subject already in the database. Between October 30, 2011, and August 31, 2012, 1,132 subjects were entered at nine central nervous system sites. Subjects continue to be entered, and more sites are anticipated to begin participation by the time of publication. Initially, there were concerns at a few sites over patient acceptance, financial implications, and/or legal and privacy issues, but these were eventually overcome. Patient acceptance was estimated to be above 95 percent. Duplicate Subjects (those that matched several key identifiers with subjects at different sites) made up 7.78 percent of the sample and Certain Duplicates (matching identifiers with a greater than 1 in 10 million likelihood of occurring by chance in the general population) accounted for 3.45 percent of pre-screens entered into the database. Many of these certain duplicates were not consented for studies because of the information provided by the registry. The use of a clinical trial subject registry and cooperation between central nervous system trial sites can reduce the number of duplicate and professional subjects entering clinical trials. To be fully effective, a trial subject database could be integrated into protocols

Genome-Wide Profiling of p63 DNA–Binding Sites Identifies an Element that Regulates Gene Expression during Limb Development in the 7q21 SHFM1 Locus

PubMed Central

Oti, Martin; Dutilh, Bas E.; Alonso, M. Eva; de la Calle-Mustienes, Elisa; Smeenk, Leonie; Rinne, Tuula; Parsaulian, Lilian; Bolat, Emine; Jurgelenaite, Rasa; Huynen, Martijn A.; Hoischen, Alexander; Veltman, Joris A.; Brunner, Han G.; Roscioli, Tony; Oates, Emily; Wilson, Meredith; Manzanares, Miguel; Gómez-Skarmeta, José Luis; Stunnenberg, Hendrik G.; Lohrum, Marion; van Bokhoven, Hans; Zhou, Huiqing

2010-01-01

Heterozygous mutations in p63 are associated with split hand/foot malformations (SHFM), orofacial clefting, and ectodermal abnormalities. Elucidation of the p63 gene network that includes target genes and regulatory elements may reveal new genes for other malformation disorders. We performed genome-wide DNA–binding profiling by chromatin immunoprecipitation (ChIP), followed by deep sequencing (ChIP–seq) in primary human keratinocytes, and identified potential target genes and regulatory elements controlled by p63. We show that p63 binds to an enhancer element in the SHFM1 locus on chromosome 7q and that this element controls expression of DLX6 and possibly DLX5, both of which are important for limb development. A unique micro-deletion including this enhancer element, but not the DLX5/DLX6 genes, was identified in a patient with SHFM. Our study strongly indicates disruption of a non-coding cis-regulatory element located more than 250 kb from the DLX5/DLX6 genes as a novel disease mechanism in SHFM1. These data provide a proof-of-concept that the catalogue of p63 binding sites identified in this study may be of relevance to the studies of SHFM and other congenital malformations that resemble the p63-associated phenotypes. PMID:20808887

Anaerobic carboxydotrophic bacteria in geothermal springs identified using stable isotope probing

PubMed Central

Brady, Allyson L.; Sharp, Christine E.; Grasby, Stephen E.; Dunfield, Peter F.

2015-01-01

Carbon monoxide (CO) is a potential energy and carbon source for thermophilic bacteria in geothermal environments. Geothermal sites ranging in temperature from 45 to 65°C were investigated for the presence and activity of anaerobic CO-oxidizing bacteria. Anaerobic CO oxidation potentials were measured at up to 48.9 μmoles CO g−1 (wet weight) day−1 within five selected sites. Active anaerobic carboxydotrophic bacteria were identified using 13CO DNA stable isotope probing (SIP) combined with pyrosequencing of 16S rRNA genes amplified from labeled DNA. Bacterial communities identified in heavy DNA fractions were predominated by Firmicutes, which comprised up to 95% of all sequences in 13CO incubations. The predominant bacteria that assimilated 13C derived from CO were closely related (>98% 16S rRNA gene sequence identity) to genera of known carboxydotrophs including Thermincola, Desulfotomaculum, Thermolithobacter, and Carboxydocella, although a few species with lower similarity to known bacteria were also found that may represent previously unconfirmed CO-oxidizers. While the distribution was variable, many of the same OTUs were identified across sample sites from different temperature regimes. These results show that bacteria capable of using CO as a carbon source are common in geothermal springs, and that thermophilic carboxydotrophs are probably already quite well known from cultivation studies. PMID:26388850

Commercial fishery data from three proposed OTEC sites

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

Ryan, C.J.; Jones, A.T.

1981-06-01

The operation of Ocean Thermal Energy Conversion (OTEC) power plants may affect fish populations in the regions surrounding the plants. As an initial step in estimating the possible impacts of OTEC power plants on local fishery resources at three proposed sites, commercial fishery records were used to identify common commercially-important species and to obtain a general impression of the abundance of those species at the sites. The sites examind are in the waters adjacent to Punta Tuna, Puerto Rico (PROTEC), and in the Islands of Hawaii offshore from Kahe Point, Oahu (O'OTEC) and Keahole Point, Hawaii (HOTEC).

Identifying and overcoming the constraints that prevent the full implementation of decommissioning and remediation programs in uranium mining sites.

PubMed

Franklin, Mariza Ramalho; Fernandes, Horst Monken

2013-05-01

Environmental remediation of radioactive contamination is about achieving appropriate reduction of exposures to ionizing radiation. This goal can be achieved by means of isolation or removal of the contamination source(s) or by breaking the exposure pathways. Ideally, environmental remediation is part of the planning phase of any industrial operation with the potential to cause environmental contamination. This concept is even more important in mining operations due to the significant impacts produced. This approach has not been considered in several operations developed in the past. Therefore many legacy sites face the challenge to implement appropriate remediation plans. One of the first barriers to remediation works is the lack of financial resources as environmental issues used to be taken in the past as marginal costs and were not included in the overall budget of the company. This paper analyses the situation of the former uranium production site of Poços de Caldas in Brazil. It is demonstrated that in addition to the lack of resources, other barriers such as the lack of information on site characteristics, appropriate regulatory framework, funding mechanisms, stakeholder involvement, policy and strategy, technical experience and mechanism for the appropriation of adequate technical expertise will play key roles in preventing the implementation of remediation programs. All these barriers are discussed and some solutions are suggested. It is expected that lessons learned from the Poços de Caldas legacy site may stimulate advancement of more sustainable options in the development of future uranium production centers. Copyright © 2011 Elsevier Ltd. All rights reserved.

Homeless Veterans: Management Improvements Could Help VA Better Identify Supportive Housing Projects

DTIC Science & Technology

2016-12-01

HOMELESS VETERANS Management Improvements Could Help VA Better Identify Supportive-Housing Projects Report to...VETERANS Management Improvements Could Help VA Better Identify Supportive-Housing Projects What GAO Found As of September 2016, for veterans who...disabled veterans. These supportive-housing EULs receive project -based HUD-VASH vouchers, which provide housing subsidies, on-site case management

Applying quantile regression for modeling equivalent property damage only crashes to identify accident blackspots.

PubMed

Washington, Simon; Haque, Md Mazharul; Oh, Jutaek; Lee, Dongmin

2014-05-01

Hot spot identification (HSID) aims to identify potential sites-roadway segments, intersections, crosswalks, interchanges, ramps, etc.-with disproportionately high crash risk relative to similar sites. An inefficient HSID methodology might result in either identifying a safe site as high risk (false positive) or a high risk site as safe (false negative), and consequently lead to the misuse the available public funds, to poor investment decisions, and to inefficient risk management practice. Current HSID methods suffer from issues like underreporting of minor injury and property damage only (PDO) crashes, challenges of accounting for crash severity into the methodology, and selection of a proper safety performance function to model crash data that is often heavily skewed by a preponderance of zeros. Addressing these challenges, this paper proposes a combination of a PDO equivalency calculation and quantile regression technique to identify hot spots in a transportation network. In particular, issues related to underreporting and crash severity are tackled by incorporating equivalent PDO crashes, whilst the concerns related to the non-count nature of equivalent PDO crashes and the skewness of crash data are addressed by the non-parametric quantile regression technique. The proposed method identifies covariate effects on various quantiles of a population, rather than the population mean like most methods in practice, which more closely corresponds with how black spots are identified in practice. The proposed methodology is illustrated using rural road segment data from Korea and compared against the traditional EB method with negative binomial regression. Application of a quantile regression model on equivalent PDO crashes enables identification of a set of high-risk sites that reflect the true safety costs to the society, simultaneously reduces the influence of under-reported PDO and minor injury crashes, and overcomes the limitation of traditional NB model in dealing

Identifying criteria and establishing parameters for forest-based ecotourism in Northern Ontario, Canada

Treesearch

Stephen W. Boyd; Richard W. Butler; Wolfgang Haider

1995-01-01

This paper identifies the following criteria as indicators for ecotourism suitability within a Northern Ontario context: naturalness, wildlife, cultural heritage, landscape and community. A methodology is proposed which uses Geographical Information Systems (GIS) to identify ecotourism sites by linking criteria deemed important with actual landscape characteristics of...

Site comparison for optical visibility statistics in southern Arizona

NASA Technical Reports Server (NTRS)

Cowles, K. A.

1990-01-01

One of the best locations in the continental United States for astronomical telescopes is southern Arizona. The mountains surrounding Tucson have clear skies 80 percent of the year, with image quality generally better than 2 seconds on peaks. Two of the existing observatory sites in this area are being considered as locations for one of the three Atmospheric Visibility Monitoring (AVM) observatories. These sites are Mount Lemmon and Mount Hopkins. A comparison of the characteristics of each of the sites is made here to identify the more desirable of the two locations. It is recommended that Mount Lemmon be selected as the Arizona site for this project.

Usefulness and pitfalls of MAA SPECT/CT in identifying digestive extrahepatic uptake when planning liver radioembolization.

PubMed

Lenoir, Laurence; Edeline, Julien; Rolland, Yann; Pracht, Marc; Raoul, Jean-Luc; Ardisson, Valérie; Bourguet, Patrick; Clément, Bruno; Boucher, Eveline; Garin, Etienne

2012-05-01

Identifying gastroduodenal uptake of (99m)Tc-macroaggregated albumin (MAA), which is associated with an increased risk of ulcer disease, is a crucial part of the therapeutic management of patients undergoing radioembolization for liver tumours. Given this context, the use of MAA single photon emission computed tomography (SPECT)/CT may be essential, but the procedure has still not been thoroughly evaluated. The aim of this retrospective study was to determine the effectiveness of MAA SPECT/CT in identifying digestive extrahepatic uptake, while determining potential diagnostic pitfalls. Overall, 139 MAA SPECT/CT scans were performed on 103 patients with different hepatic tumour types. Patients were followed up for at least 6 months according to standard requirements. Digestive, or digestive-like, uptake other than free pertechnetate was identified in 5.7% of cases using planar imaging and in 36.6% of cases using SPECT/CT. Uptake sites identified by SPECT/CT included the gastroduodenal region (3.6%), gall bladder (12.2%), portal vein thrombosis (6.5%), hepatic artery (6.5%), coil embolization site (2.1%) as well as falciform artery (5.0%). For 2.1% of explorations, a coregistration error between SPECT and CT imaging could have led to a false diagnosis by erroneously attributing an uptake site to the stomach or gall bladder, when the uptake actually occurred in the liver. SPECT/CT is more efficacious than planar imaging in identifying digestive extrahepatic uptake sites, with extrahepatic uptake observed in one third of scans using the former procedure. However, more than half of the uptake sites in our study were vascular in nature, without therapeutic implications. The risk of coregistration errors must also be kept in mind.

Open chromatin defined by DNaseI and FAIRE identifies regulatory elements that shape cell-type identity

PubMed Central

Song, Lingyun; Zhang, Zhancheng; Grasfeder, Linda L.; Boyle, Alan P.; Giresi, Paul G.; Lee, Bum-Kyu; Sheffield, Nathan C.; Gräf, Stefan; Huss, Mikael; Keefe, Damian; Liu, Zheng; London, Darin; McDaniell, Ryan M.; Shibata, Yoichiro; Showers, Kimberly A.; Simon, Jeremy M.; Vales, Teresa; Wang, Tianyuan; Winter, Deborah; Zhang, Zhuzhu; Clarke, Neil D.; Birney, Ewan; Iyer, Vishwanath R.; Crawford, Gregory E.; Lieb, Jason D.; Furey, Terrence S.

2011-01-01

The human body contains thousands of unique cell types, each with specialized functions. Cell identity is governed in large part by gene transcription programs, which are determined by regulatory elements encoded in DNA. To identify regulatory elements active in seven cell lines representative of diverse human cell types, we used DNase-seq and FAIRE-seq (Formaldehyde Assisted Isolation of Regulatory Elements) to map “open chromatin.” Over 870,000 DNaseI or FAIRE sites, which correspond tightly to nucleosome-depleted regions, were identified across the seven cell lines, covering nearly 9% of the genome. The combination of DNaseI and FAIRE is more effective than either assay alone in identifying likely regulatory elements, as judged by coincidence with transcription factor binding locations determined in the same cells. Open chromatin common to all seven cell types tended to be at or near transcription start sites and to be coincident with CTCF binding sites, while open chromatin sites found in only one cell type were typically located away from transcription start sites and contained DNA motifs recognized by regulators of cell-type identity. We show that open chromatin regions bound by CTCF are potent insulators. We identified clusters of open regulatory elements (COREs) that were physically near each other and whose appearance was coordinated among one or more cell types. Gene expression and RNA Pol II binding data support the hypothesis that COREs control gene activity required for the maintenance of cell-type identity. This publicly available atlas of regulatory elements may prove valuable in identifying noncoding DNA sequence variants that are causally linked to human disease. PMID:21750106

Heat- and light-induced transformations of Yb trapping sites in an Ar matrix

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

Tao, L.-G.; Lambo, R., E-mail: lambo@mail.ustc.edu.cn; Zhou, X.-G.

2015-11-07

The low-lying electronic states of Yb isolated in a solid Ar matrix grown at 4.2 K are characterized through absorption and emission spectroscopy. Yb atoms are found to occupy three distinct thermally stable trapping sites labeled “red,” “blue,” and “violet” according to the relative positions of the absorption features they produce. Classical simulations of the site structure and relative stability broadly reproduced the experimentally observed matrix-induced frequency shifts and thus identified the red, blue, and violet sites as due to respective single substitutional (SS), tetravacancy (TV), and hexavacancy (HV) occupation. Prolonged excitation of the {sup 1}S → {sup 1}P transitionmore » was found to transfer the Yb population from HV sites into TV and SS sites. The process showed reversibility in that annealing to 24 K predominantly transferred the TV population back into HV sites. Population kinetics were used to deduce the effective rate parameters for the site transformation processes. Experimental observations indicate that the blue and violet sites lie close in energy, whereas the red one is much less stable. Classical simulations identify the blue site as the most stable one.« less

Early LROC Views of Lunar 'Heritage' Sites

NASA Astrophysics Data System (ADS)

Stooke, P. J.

2010-03-01

Early LROC images show some old hardware locations including Apollo and Surveyor sites. The images are used to improve EVA traverse maps and to identify the discarded Surveyor 3 retro-rocket. Future opportunities to observe other items are discussed.

Success of cuckoo catfish brood parasitism reflects coevolutionary history and individual experience of their cichlid hosts

PubMed Central

Polačik, Matej; Smith, Carl; Honza, Marcel; Reichard, Martin

2018-01-01

Obligate brood parasites manipulate other species into raising their offspring. Avian and insect brood parasitic systems demonstrate how interacting species engage in reciprocal coevolutionary arms races through behavioral and morphological adaptations and counteradaptations. Mouthbrooding cichlid fishes are renowned for their remarkable evolutionary radiations and complex behaviors. In Lake Tanganyika, mouthbrooding cichlids are exploited by the only obligate nonavian vertebrate brood parasite, the cuckoo catfish Synodontis multipunctatus. We show that coevolutionary history and individual learning both have a major impact on the success of cuckoo catfish parasitism between coevolved sympatric and evolutionarily naïve allopatric cichlid species. The rate of cuckoo catfish parasitism in coevolved Tanganyikan hosts was 3 to 11 times lower than in evolutionarily naïve cichlids. Moreover, using experimental infections, we demonstrate that parasite egg rejection in sympatric hosts was much higher, leading to seven times greater parasite survival in evolutionarily naïve than sympatric hosts. However, a high rejection frequency of parasitic catfish eggs by coevolved sympatric hosts came at a cost of increased rejection of their own eggs. A significant cost of catfish parasitism was universal, except for coevolved sympatric cichlid species with previous experience of catfish parasitism, demonstrating that learning and individual experience both contribute to a successful host response. PMID:29732407

Concealed Accessory Pathways with a Single Ventricular and Two Discrete Atrial Insertion Sites.

PubMed

Kipp, Ryan T; Abu Sham'a, Raed; Hiroyuki, Ito; Han, Frederick T; Refaat, Marwan; Hsu, Jonathan C; Field, Michael E; Kopp, Douglas E; Marcus, Gregory M; Scheinman, Melvin M; Hoffmayer, Kurt S

2017-03-01

Atrioventricular reciprocating tachycardia (AVRT) utilizing a concealed accessory pathway is common. It is well appreciated that some patients may have multiple accessory pathways with separate atrial and ventricular insertion sites. We present three cases of AVRT utilizing concealed pathways with evidence that each utilizing a single ventricular insertion and two discrete atrial insertion sites. In case one, two discrete atrial insertion sites were mapped in two separate procedures, and only during the second ablation was the Kent potential identified. Ablation of the Kent potential at this site remote from the two atrial insertion sites resulted in the termination of the retrograde conduction in both pathways. Case two presented with supraventricular tachycardia (SVT) with alternating eccentric atrial activation patterns without alteration in the tachycardia cycle length. The two distinct atrial insertion sites during orthodromic AVRT and ventricular pacing were targeted and each of the two atrial insertion sites were successfully mapped and ablated. In case three, retrograde decremental conduction utilizing both atrial insertion sites was identified prior to ablation. After mapping and ablation of the first discrete atrial insertion site, tachycardia persisted utilizing the second atrial insertion site. Only after ablation of the second atrial insertion site was SVT noninducible, and VA conduction was no longer present. Concealed retrograde accessory pathways with discrete atrial insertion sites may have a common ventricular insertion site. Identification and ablation of the ventricular insertion site or the separate discrete atrial insertion sites result in successful treatment. © 2017 Wiley Periodicals, Inc.

Report of the Peer Review Panel on the early site suitability evaluation of the Potential Repository Site at Yucca Mountain, Nevada; Yucca Mountain Site Characterization Project

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

NONE

1992-01-01

The US Department of Energy (DOE) Yucca mountain Site Characterization Project Office (YMPO) assigned Science Applications International Corporation (SAIC), the Technical and Management Support Services (T&MSS) contractor to the YmPo, the task of conducting an Early Site Suitability Evaluation (ESSE) of the Yucca mountain site as a potential site for a high-level radioactive waste repository. First, the assignment called for the development of a method to evaluate a single site against the DOE General Guidelines for Recommendation of Sites for Nuclear Waste Repositories, 10 CFR Part 960. Then, using this method, an evaluation team, the ESSE Core Team, of seniormore » YMP scientists, engineers, and technical experts, evaluated new information obtained about the site since publication of the final Environmental Assessment (DOE, 1986) to determine if new suitability/unsuitability findings could be recommended. Finally, the Core Team identified further information and analyses needed to make final determinations for each of the guidelines. As part of the task, an independent peer review of the ESSE report has been conducted. Expertise was solicited that covered the entire spectrum of siting guidelines in 10 CFR Part 960 in order to provide a complete, in-depth critical review of the data evaluated and cited in the ESSE report, the methods used to evaluate the data, and the conclusions and recommendations offered by the report. Fourteen nationally recognized technical experts (Table 2) served on the Peer Review Panel. The comments from the Panel and the responses prepared by the ESSE Core Team, documented on formal Comment Response Forms, constitute the body of this document.« less

Feral swine disturbance at important archaeological sites.

PubMed

Engeman, Richard M; Couturier, Kathy J; Felix, Rodney K; Avery, Michael L

2013-06-01

Feral swine are well known as environmentally destructive invasive animals in many areas around the world, where they degrade native habitats, harm rare plant and animal species, damage agricultural interests, and spread disease. We provide the first quantification of their potential as agents of disturbance at archaeological sites. Our study was conducted in south-central Florida at Avon Park Air Force Range, a base comprising over 40,000 ha and containing many archaeological sites. To determine the identifiable prevalence of feral swine disturbance, we examined 36 sites registered with the Florida State Historic Preservation Office and also eligible for inclusion in the National Register of Historic Places (NRHP). Moreover, we evaluated the extent of swine disturbance at a prehistoric site of extraordinary significance to Florida's prehistory, "Dead Cow." Fifteen of the 36 NRHP-eligible sites (42 %) had some level of swine disturbance, including 14 of 30 (47 %) sites known to have artifacts within 20 cm of the surface (well within swine rooting depths). At the Dead Cow site, we documented disturbance at 74 % of shovel test points. Sites with shallow artifact depositions appeared highly vulnerable to disturbance by feral swine, threatening destruction of artifact stratigraphy and provenience. Our observations likely are a minimal representation of accumulated damage. These irreplaceable sites tell the area's land use story across the millennia. That they are under threat from feral swine should serve broad notice of potential threats that feral swine may pose to archaeological sites globally, making effective swine management imperative for site protection.

Analytic hierarchy process helps select site for limestone quarry expansion in Barbados.

PubMed

Dey, Prasanta Kumar; Ramcharan, Eugene K

2008-09-01

Site selection is a key activity for quarry expansion to support cement production, and is governed by factors such as resource availability, logistics, costs, and socio-economic-environmental factors. Adequate consideration of all the factors facilitates both industrial productivity and sustainable economic growth. This study illustrates the site selection process that was undertaken for the expansion of limestone quarry operations to support cement production in Barbados. First, alternate sites with adequate resources to support a 25-year development horizon were identified. Second, technical and socio-economic-environmental factors were then identified. Third, a database was developed for each site with respect to each factor. Fourth, a hierarchical model in analytic hierarchy process (AHP) framework was then developed. Fifth, the relative ranking of the alternate sites was then derived through pair wise comparison in all the levels and through subsequent synthesizing of the results across the hierarchy through computer software (Expert Choice). The study reveals that an integrated framework using the AHP can help select a site for the quarry expansion project in Barbados.

Report: Nationwide Identification of Hardrock Mining Sites

EPA Pesticide Factsheets

Report #2004-P-00005, March 31, 2004. We identified 156 hardrock mining sites nationwide that have the potential to cost between $7 billion and $24 billion total to clean up (at a maximum total cost to EPA of approximately $15 billion).

Closure Report for Corrective Action Unit 139: Waste Disposal Sites, Nevada Test Site, Nevada

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

NSTec Environmental Restoration

2009-07-31

Corrective Action Unit (CAU) 139 is identified in the Federal Facility Agreement and Consent Order (FFACO) as 'Waste Disposal Sites' and consists of the following seven Corrective Action Sites (CASs), located in Areas 3, 4, 6, and 9 of the Nevada Test Site: CAS 03-35-01, Burn Pit; CAS 04-08-02, Waste Disposal Site; CAS 04-99-01, Contaminated Surface Debris; CAS 06-19-02, Waste Disposal Site/Burn Pit; CAS 06-19-03, Waste Disposal Trenches; CAS 09-23-01, Area 9 Gravel Gertie; and CAS 09-34-01, Underground Detection Station. Closure activities were conducted from December 2008 to April 2009 according to the FFACO (1996, as amended February 2008) andmore » the Corrective Action Plan for CAU 139 (U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office, 2007b). The corrective action alternatives included No Further Action, Clean Closure, and Closure in Place with Administrative Controls. Closure activities are summarized. CAU 139, 'Waste Disposal Sites,' consists of seven CASs in Areas 3, 4, 6, and 9 of the NTS. The closure alternatives included No Further Action, Clean Closure, and Closure in Place with Administrative Controls. This CR provides a summary of completed closure activities, documentation of waste disposal, and confirmation that remediation goals were met. The following site closure activities were performed at CAU 139 as documented in this CR: (1) At CAS 03-35-01, Burn Pit, soil and debris were removed and disposed as LLW, and debris was removed and disposed as sanitary waste. (2) At CAS 04-08-02, Waste Disposal Site, an administrative UR was implemented. No postings or post-closure monitoring are required. (3) At CAS 04-99-01, Contaminated Surface Debris, soil and debris were removed and disposed as LLW, and debris was removed and disposed as sanitary waste. (4) At CAS 06-19-02, Waste Disposal Site/Burn Pit, no work was performed. (5) At CAS 06-19-03, Waste Disposal Trenches, a native soil cover was installed, and a UR was

Environmental assessment: Reference repository location, Hanford site, Washington

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

none,

1986-05-01

In February 1983, the US Department of Energy (DOE) identified a reference repository location at the Hanford Site in Washington as one of the nine potentially acceptable sites for a mined geologic repository for spent nuclear fuel and high-level radioactive waste. The site is in the Columbia Plateau, which is one of five distinct geohydrologic settings considered for the first repository. To determine their suitability, the Hanford Site and the eight other potentially acceptable sites have been evaluated in accordance with the DOE's General Guidelines for the Recommendation of Sites for the Nuclear Waste Repositories. These evaluations were reported inmore » draft environmental assessments (EAs), which were issued for public review and comment. After considering the comments received on the draft EAs, the DOE prepared the final EAs. On the basis of the evaluations reported in this EA, the DOE has found that the Hanford site is not disqualified under the guidelines. The DOE has also found that it is suitable for site characterization because the evidence does not support a conclusion that the site will not be able to meet each of the qualifying conditions specified in the guidelines. On the basis of these findings, the DOE is nominating the Hanford site as one of five sites suitable for characterization.« less

Assessing Non-Technical Site Suitability Criteria for Stormwater Capture, Treatment and Recharge

NASA Astrophysics Data System (ADS)

Eisenstein, W.

2016-12-01

This presentation will describe a new method for assessing non-technical site suitability criteria for the siting of stormwater capture, treatment and recharge (or stormwater CTR) facilities in Sonoma County, California, USA. "Non-technical site suitability criteria" include issues such as community acceptance, aesthetics, nuisances and hazards, and compatibility with neighboring land uses, and are distinguished from "technical criteria" such as hydrology and soil characteristics that are the traditional subject of suitability analyses. Non-technical criteria are rarely, if ever, considered in formal siting suitability studies conducted by agencies and municipalities, yet can be fatal to the prospects of a given project's construction if not identified and mitigated. The researchers developed a new method for identifying and spatially characterizing relevant non-technical criteria through interviews and questionnaires with community stakeholders, and introducing those criteria into a spatial multi-criteria decision analysis framework that assesses site suitabilty across a study watershed (the Upper Petaluma River watershed in Sonoma County).

Prediction of allosteric sites on protein surfaces with an elastic-network-model-based thermodynamic method.

PubMed

Su, Ji Guo; Qi, Li Sheng; Li, Chun Hua; Zhu, Yan Ying; Du, Hui Jing; Hou, Yan Xue; Hao, Rui; Wang, Ji Hua

2014-08-01

Allostery is a rapid and efficient way in many biological processes to regulate protein functions, where binding of an effector at the allosteric site alters the activity and function at a distant active site. Allosteric regulation of protein biological functions provides a promising strategy for novel drug design. However, how to effectively identify the allosteric sites remains one of the major challenges for allosteric drug design. In the present work, a thermodynamic method based on the elastic network model was proposed to predict the allosteric sites on the protein surface. In our method, the thermodynamic coupling between the allosteric and active sites was considered, and then the allosteric sites were identified as those where the binding of an effector molecule induces a large change in the binding free energy of the protein with its ligand. Using the proposed method, two proteins, i.e., the 70 kD heat shock protein (Hsp70) and GluA2 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor, were studied and the allosteric sites on the protein surface were successfully identified. The predicted results are consistent with the available experimental data, which indicates that our method is a simple yet effective approach for the identification of allosteric sites on proteins.

Prediction of allosteric sites on protein surfaces with an elastic-network-model-based thermodynamic method

NASA Astrophysics Data System (ADS)

Su, Ji Guo; Qi, Li Sheng; Li, Chun Hua; Zhu, Yan Ying; Du, Hui Jing; Hou, Yan Xue; Hao, Rui; Wang, Ji Hua

2014-08-01

Allostery is a rapid and efficient way in many biological processes to regulate protein functions, where binding of an effector at the allosteric site alters the activity and function at a distant active site. Allosteric regulation of protein biological functions provides a promising strategy for novel drug design. However, how to effectively identify the allosteric sites remains one of the major challenges for allosteric drug design. In the present work, a thermodynamic method based on the elastic network model was proposed to predict the allosteric sites on the protein surface. In our method, the thermodynamic coupling between the allosteric and active sites was considered, and then the allosteric sites were identified as those where the binding of an effector molecule induces a large change in the binding free energy of the protein with its ligand. Using the proposed method, two proteins, i.e., the 70 kD heat shock protein (Hsp70) and GluA2 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor, were studied and the allosteric sites on the protein surface were successfully identified. The predicted results are consistent with the available experimental data, which indicates that our method is a simple yet effective approach for the identification of allosteric sites on proteins.

Genome wide approaches to identify protein-DNA interactions.

PubMed

Ma, Tao; Ye, Zhenqing; Wang, Liguo

2018-05-29

Transcription factors are DNA-binding proteins that play key roles in many fundamental biological processes. Unraveling their interactions with DNA is essential to identify their target genes and understand the regulatory network. Genome-wide identification of their binding sites became feasible thanks to recent progress in experimental and computational approaches. ChIP-chip, ChIP-seq, and ChIP-exo are three widely used techniques to demarcate genome-wide transcription factor binding sites. This review aims to provide an overview of these three techniques including their experiment procedures, computational approaches, and popular analytic tools. ChIP-chip, ChIP-seq, and ChIP-exo have been the major techniques to study genome-wide in vivo protein-DNA interaction. Due to the rapid development of next-generation sequencing technology, array-based ChIP-chip is deprecated and ChIP-seq has become the most widely used technique to identify transcription factor binding sites in genome-wide. The newly developed ChIP-exo further improves the spatial resolution to single nucleotide. Numerous tools have been developed to analyze ChIP-chip, ChIP-seq and ChIP-exo data. However, different programs may employ different mechanisms or underlying algorithms thus each will inherently include its own set of statistical assumption and bias. So choosing the most appropriate analytic program for a given experiment needs careful considerations. Moreover, most programs only have command line interface so their installation and usage will require basic computation expertise in Unix/Linux. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Human Mars Landing Site and Impacts on Mars Surface Operations

NASA Technical Reports Server (NTRS)

Bussey, Ben; Hoffman, Stephen J.

2016-01-01

NASA has begun a process to identify and discuss candidate locations where humans could land, live and work on the Martian surface. These locations are referred to as Exploration Zones (EZs). Given current mission concepts, an EZ is a collection of Regions of Interest (ROIs) that are located within approximately 100 kilometers of a centralized landing site. ROIs are areas that are relevant for scientific investigation and/or development/maturation of capabilities and resources necessary for a sustainable human presence. The EZ also contains a landing site and a habitation site that will be used by multiple human crews during missions to explore and utilize the ROIs within the EZ. These candidate EZs will be used by NASA as part of a multi-year process of determining where and how humans could explore Mars. In the near term this process includes: (a) identifying locations that would maximize the potential science return from future human exploration missions, (b) identifying locations with the potential for resources required to support humans, (c) developing concepts and engineering systems needed by future human crews to conduct operations within an EZ, and (d) identifying key characteristics of the proposed candidate EZs that cannot be evaluated using existing data sets, thus helping to define precursor measurements needed in advance of human missions. Existing and future robotic spacecraft will be tasked to gather data from specific Mars surface sites within the representative EZs to support these NASA activities. The proposed paper will describe NASA's initial steps for identifying and evaluating candidate EZs and ROIs. This includes plans for the "First Landing Site/Exploration Zone Workshop for Human Missions to the Surface of Mars" to be held in October 2015 at which proposals for EZs and ROIs will be presented and discussed. It will also include a discussion of how these considerations are (or will be) taken into account as future robotic Mars missions are

Identifying unstable sites on logging roads

Treesearch

R. M. Rice; J. Lewis

1986-01-01

Logging roads are an important source of forestry-related erosion. The amount of erosion on a forest road is determined by the interaction between how the road is constructed and maintained and the environment in which it is built. The roads in this study were constructed with large bulldozers, and most excavated material was sidecast. The roads studied were...

Identifying Hardwoods Growing on Pine Sites

Treesearch

Clair A. Brown; Harold E. Grelen

1977-01-01

This publication illustrates and describes 26 hardwood species or varieties, including 16 oaks and hickories with photographs of leaves, bark, buds, flowers, and fruits. Line drawings feature the winter silhouette of each species and a key is included to assist in identification.

Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites.

PubMed

Betel, Doron; Koppal, Anjali; Agius, Phaedra; Sander, Chris; Leslie, Christina

2010-01-01

mirSVR is a new machine learning method for ranking microRNA target sites by a down-regulation score. The algorithm trains a regression model on sequence and contextual features extracted from miRanda-predicted target sites. In a large-scale evaluation, miRanda-mirSVR is competitive with other target prediction methods in identifying target genes and predicting the extent of their downregulation at the mRNA or protein levels. Importantly, the method identifies a significant number of experimentally determined non-canonical and non-conserved sites.

Identification and characterization of a novel high affinity metal-binding site in the hammerhead ribozyme.

PubMed Central

Hansen, M R; Simorre, J P; Hanson, P; Mokler, V; Bellon, L; Beigelman, L; Pardi, A

1999-01-01

A novel metal-binding site has been identified in the hammerhead ribozyme by 31P NMR. The metal-binding site is associated with the A13 phosphate in the catalytic core of the hammerhead ribozyme and is distinct from any previously identified metal-binding sites. 31P NMR spectroscopy was used to measure the metal-binding affinity for this site and leads to an apparent dissociation constant of 250-570 microM at 25 degrees C for binding of a single Mg2+ ion. The NMR data also show evidence of a structural change at this site upon metal binding and these results are compared with previous data on metal-induced structural changes in the core of the hammerhead ribozyme. These NMR data were combined with the X-ray structure of the hammerhead ribozyme (Pley HW, Flaherty KM, McKay DB. 1994. Nature 372:68-74) to model RNA ligands involved in binding the metal at this A13 site. In this model, the A13 metal-binding site is structurally similar to the previously identified A(g) metal-binding site and illustrates the symmetrical nature of the tandem G x A base pairs in domain 2 of the hammerhead ribozyme. These results demonstrate that 31P NMR represents an important method for both identification and characterization of metal-binding sites in nucleic acids. PMID:10445883

Thermodynamic Modeling of Donor Splice Site Recognition in pre-mRNA

NASA Astrophysics Data System (ADS)

Aalberts, Daniel P.; Garland, Jeffrey A.

2004-03-01

When eukaryotic genes are edited by the spliceosome, the first step in intron recognition is the binding of a U1 snRNA with the donor (5') splice site. We model this interaction thermodynamically to identify splice sites. Applied to a set of 65 annotated genes, our Finding with Binding method achieves a significant separation between real and false sites. Analyzing binding patterns allows us to discard a large number of decoy sites. Our results improve statistics-based methods for donor site recognition, demonstrating the promise of physical modeling to find functional elements in the genome.

Thermodynamic modeling of donor splice site recognition in pre-mRNA

NASA Astrophysics Data System (ADS)

Garland, Jeffrey A.; Aalberts, Daniel P.

2004-04-01

When eukaryotic genes are edited by the spliceosome, the first step in intron recognition is the binding of a U1 small nuclear RNA with the donor ( 5' ) splice site. We model this interaction thermodynamically to identify splice sites. Applied to a set of 65 annotated genes, our “finding with binding” method achieves a significant separation between real and false sites. Analyzing binding patterns allows us to discard a large number of decoy sites. Our results improve statistics-based methods for donor site recognition, demonstrating the promise of physical modeling to find functional elements in the genome.

Mars Pathfinder Landing Site and Surroundings

NASA Technical Reports Server (NTRS)

2007-01-01

of 3:35 p.m., and the scene is illuminated from the west with a solar incidence angle of 52 degrees, thus the sun was about 38 degrees above the horizon. At a solar longitude of 154.0 degrees, the season on Mars is northern summer.

[figure removed for brevity, see original site] Landing Site Region This is a close-up of the area in the vicinity of the Pathfinder landing site. Major features are named. The white box outlines the area of the image, discussed next, where hardware is seen.

[figure removed for brevity, see original site] Hardware on the Surface This image shows the Pathfinder lander on the surface. Zooming in, one can discern the ramps, science deck, and portions of the airbags on the Pathfinder lander. (See next image for closer view.) The back shell and parachute are to the south, and four features that may be portions of the heat shield are identified. Two of these were visible from Pathfinder. At the time of that mission, the nearest object was provisionally identified as the back shell. However, analysis of the HiRISE image and reinterpretation of Pathfinder images, plus an improved understanding of how hardware looks on the Martian surface based on ground-level and orbital images of the Mars Exploration Rover landing sites, indicate that the glint is bright enough that it may be insulating material from inside the heat shield. The back shell and parachute were out of sight behind a ridge from Pathfinder's ground view. One of the three bright features, identified as heat shield debris, was also identified during the Pathfinder mission.

[figure removed for brevity, see original site] [figure removed for brevity, see original site] Annotated Version Unannotated Version Topographic Map of Landing Site Region Portions of the HiRISE image are overlaid onto color-coded topographic maps constructed by the U.S. Geological Survey from stereo images acquired by the Imager for Mars Pathfinder on the lander. The white feature

Preferential Allele Expression Analysis Identifies Shared Germline and Somatic Driver Genes in Advanced Ovarian Cancer

PubMed Central

Halabi, Najeeb M.; Martinez, Alejandra; Al-Farsi, Halema; Mery, Eliane; Puydenus, Laurence; Pujol, Pascal; Khalak, Hanif G.; McLurcan, Cameron; Ferron, Gwenael; Querleu, Denis; Al-Azwani, Iman; Al-Dous, Eman; Mohamoud, Yasmin A.; Malek, Joel A.; Rafii, Arash

2016-01-01

Identifying genes where a variant allele is preferentially expressed in tumors could lead to a better understanding of cancer biology and optimization of targeted therapy. However, tumor sample heterogeneity complicates standard approaches for detecting preferential allele expression. We therefore developed a novel approach combining genome and transcriptome sequencing data from the same sample that corrects for sample heterogeneity and identifies significant preferentially expressed alleles. We applied this analysis to epithelial ovarian cancer samples consisting of matched primary ovary and peritoneum and lymph node metastasis. We find that preferentially expressed variant alleles include germline and somatic variants, are shared at a relatively high frequency between patients, and are in gene networks known to be involved in cancer processes. Analysis at a patient level identifies patient-specific preferentially expressed alleles in genes that are targets for known drugs. Analysis at a site level identifies patterns of site specific preferential allele expression with similar pathways being impacted in the primary and metastasis sites. We conclude that genes with preferentially expressed variant alleles can act as cancer drivers and that targeting those genes could lead to new therapeutic strategies. PMID:26735499

Use of ultrasonography to identify late-stage maturity in rainbow trout Oncorhynchus mykiss

USDA-ARS?s Scientific Manuscript database

Morphometric measurements by ultrasonography has been used to determine gonad and follicle size in many species of fish for purposes of identifying sex and estimating stage of maturation. We have been using a portable ultrasound system (SonoSite MicroMaxx, L25e/13-6 MHz transducer) to identify fem...

Bioterrorism web site resources for infectious disease clinicians and epidemiologists.

PubMed

Ferguson, Natalie E; Steele, Lynn; Crawford, Carol Y; Huebner, Nathan L; Fonseka, Jamila C; Bonander, Jason C; Kuehnert, Matthew J

2003-06-01

Finding bioterrorism-related information on the World Wide Web can be laborious. We hope to help readers find such information more easily by summarizing essential information in a consistent framework. A panel of 7 Centers for Disease Control and Prevention reviewers identified Web sites and evaluated them for sponsorship, mission, content usefulness, online ease of use, and adherence to commonly accepted quality criteria. Of >100 potential sites identified, 81 were chosen for target content of interest, and 43 were selected for inclusion. The results were classified into general purpose/portal sites; biological agent information; laboratory, infection control, epidemiology, and mental health information; and emergency contact sources, news and updates, event preparedness resources, information for first-responder settings, clinical and public education materials, and research resources. Agents covered included anthrax, smallpox, plague, botulism, tularemia, and viral hemorrhagic fever.

2013 Annual Site Inspection and Monitoring Report for Uranium Mill Tailings Radiation Control Act Title I Disposal Sites

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

None, None

This report, in fulfillment of a license requirement, presents the results of long-term surveillance and maintenance activities conducted by the U.S. Department of Energy (DOE) Office of Legacy Management (LM) in 2013 at 19 uranium mill tailings disposal sites established under Title I of the Uranium Mill Tailings Radiation Control Act (UMTRCA) of 1978.1 These activities verified that the UMTRCA Title I disposal sites remain in compliance with license requirements. DOE operates 18 UMTRCA Title I sites under a general license granted by the U.S. Nuclear Regulatory Commission (NRC) in accordance with Title 10 Code of Federal Regulations Part 40.27more » (10 CFR 40.27). As required under the general license, a long-term surveillance plan (LTSP) for each site was prepared by DOE and accepted by NRC. The Grand Junction, Colorado, Disposal Site, one of the 19 Title I sites, will not be included under the general license until the open, operating portion of the cell is closed. The open portion will be closed either when it is filled or in 2023. This site is inspected in accordance with an interim LTSP. Long-term surveillance and maintenance services for these disposal sites include inspecting and maintaining the sites; monitoring environmental media and institutional controls; conducting any necessary corrective actions; and performing administrative, records, stakeholder relations, and other regulatory stewardship functions. Annual site inspections and monitoring are conducted in accordance with site-specific LTSPs and procedures established by DOE to comply with license requirements. Each site inspection is performed to verify the integrity of visible features at the site; to identify changes or new conditions that may affect the long-term performance of the site; and to determine the need, if any, for maintenance, follow-up or contingency inspections, or corrective action in accordance with the LTSP. LTSPs and site compliance reports are available on the Internet at

Resolving protein structure-function-binding site relationships from a binding site similarity network perspective.

PubMed

Mudgal, Richa; Srinivasan, Narayanaswamy; Chandra, Nagasuma

2017-07-01

Functional annotation is seldom straightforward with complexities arising due to functional divergence in protein families or functional convergence between non-homologous protein families, leading to mis-annotations. An enzyme may contain multiple domains and not all domains may be involved in a given function, adding to the complexity in function annotation. To address this, we use binding site information from bound cognate ligands and catalytic residues, since it can help in resolving fold-function relationships at a finer level and with higher confidence. A comprehensive database of 2,020 fold-function-binding site relationships has been systematically generated. A network-based approach is employed to capture the complexity in these relationships, from which different types of associations are deciphered, that identify versatile protein folds performing diverse functions, same function associated with multiple folds and one-to-one relationships. Binding site similarity networks integrated with fold, function, and ligand similarity information are generated to understand the depth of these relationships. Apart from the observed continuity in the functional site space, network properties of these revealed versatile families with topologically different or dissimilar binding sites and structural families that perform very similar functions. As a case study, subtle changes in the active site of a set of evolutionarily related superfamilies are studied using these networks. Tracing of such similarities in evolutionarily related proteins provide clues into the transition and evolution of protein functions. Insights from this study will be helpful in accurate and reliable functional annotations of uncharacterized proteins, poly-pharmacology, and designing enzymes with new functional capabilities. Proteins 2017; 85:1319-1335. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

An Unbiased Approach to Identifying Tau Kinases That Phosphorylate Tau at Sites Associated with Alzheimer Disease

PubMed Central

Cavallini, Annalisa; Brewerton, Suzanne; Bell, Amanda; Sargent, Samantha; Glover, Sarah; Hardy, Clare; Moore, Roger; Calley, John; Ramachandran, Devaki; Poidinger, Michael; Karran, Eric; Davies, Peter; Hutton, Michael; Szekeres, Philip; Bose, Suchira

2013-01-01

Neurofibrillary tangles, one of the hallmarks of Alzheimer disease (AD), are composed of paired helical filaments of abnormally hyperphosphorylated tau. The accumulation of these proteinaceous aggregates in AD correlates with synaptic loss and severity of dementia. Identifying the kinases involved in the pathological phosphorylation of tau may identify novel targets for AD. We used an unbiased approach to study the effect of 352 human kinases on their ability to phosphorylate tau at epitopes associated with AD. The kinases were overexpressed together with the longest form of human tau in human neuroblastoma cells. Levels of total and phosphorylated tau (epitopes Ser(P)-202, Thr(P)-231, Ser(P)-235, and Ser(P)-396/404) were measured in cell lysates using AlphaScreen assays. GSK3α, GSK3β, and MAPK13 were found to be the most active tau kinases, phosphorylating tau at all four epitopes. We further dissected the effects of GSK3α and GSK3β using pharmacological and genetic tools in hTau primary cortical neurons. Pathway analysis of the kinases identified in the screen suggested mechanisms for regulation of total tau levels and tau phosphorylation; for example, kinases that affect total tau levels do so by inhibition or activation of translation. A network fishing approach with the kinase hits identified other key molecules putatively involved in tau phosphorylation pathways, including the G-protein signaling through the Ras family of GTPases (MAPK family) pathway. The findings identify novel tau kinases and novel pathways that may be relevant for AD and other tauopathies. PMID:23798682

Dominant Mutations in S. cerevisiae PMS1 Identify the Mlh1-Pms1 Endonuclease Active Site and an Exonuclease 1-Independent Mismatch Repair Pathway

PubMed Central

Smith, Catherine E.; Mendillo, Marc L.; Bowen, Nikki; Hombauer, Hans; Campbell, Christopher S.; Desai, Arshad; Putnam, Christopher D.; Kolodner, Richard D.

2013-01-01

Lynch syndrome (hereditary nonpolypsis colorectal cancer or HNPCC) is a common cancer predisposition syndrome. Predisposition to cancer in this syndrome results from increased accumulation of mutations due to defective mismatch repair (MMR) caused by a mutation in one of the mismatch repair genes MLH1, MSH2, MSH6 or PMS2/scPMS1. To better understand the function of Mlh1-Pms1 in MMR, we used Saccharomyces cerevisiae to identify six pms1 mutations (pms1-G683E, pms1-C817R, pms1-C848S, pms1-H850R, pms1-H703A and pms1-E707A) that were weakly dominant in wild-type cells, which surprisingly caused a strong MMR defect when present on low copy plasmids in an exo1Δ mutant. Molecular modeling showed these mutations caused amino acid substitutions in the metal coordination pocket of the Pms1 endonuclease active site and biochemical studies showed that they inactivated the endonuclease activity. This model of Mlh1-Pms1 suggested that the Mlh1-FERC motif contributes to the endonuclease active site. Consistent with this, the mlh1-E767stp mutation caused both MMR and endonuclease defects similar to those caused by the dominant pms1 mutations whereas mutations affecting the predicted metal coordinating residue Mlh1-C769 had no effect. These studies establish that the Mlh1-Pms1 endonuclease is required for MMR in a previously uncharacterized Exo1-independent MMR pathway. PMID:24204293

Dominant mutations in S. cerevisiae PMS1 identify the Mlh1-Pms1 endonuclease active site and an exonuclease 1-independent mismatch repair pathway.

PubMed

Smith, Catherine E; Mendillo, Marc L; Bowen, Nikki; Hombauer, Hans; Campbell, Christopher S; Desai, Arshad; Putnam, Christopher D; Kolodner, Richard D

2013-10-01

Lynch syndrome (hereditary nonpolypsis colorectal cancer or HNPCC) is a common cancer predisposition syndrome. Predisposition to cancer in this syndrome results from increased accumulation of mutations due to defective mismatch repair (MMR) caused by a mutation in one of the mismatch repair genes MLH1, MSH2, MSH6 or PMS2/scPMS1. To better understand the function of Mlh1-Pms1 in MMR, we used Saccharomyces cerevisiae to identify six pms1 mutations (pms1-G683E, pms1-C817R, pms1-C848S, pms1-H850R, pms1-H703A and pms1-E707A) that were weakly dominant in wild-type cells, which surprisingly caused a strong MMR defect when present on low copy plasmids in an exo1Δ mutant. Molecular modeling showed these mutations caused amino acid substitutions in the metal coordination pocket of the Pms1 endonuclease active site and biochemical studies showed that they inactivated the endonuclease activity. This model of Mlh1-Pms1 suggested that the Mlh1-FERC motif contributes to the endonuclease active site. Consistent with this, the mlh1-E767stp mutation caused both MMR and endonuclease defects similar to those caused by the dominant pms1 mutations whereas mutations affecting the predicted metal coordinating residue Mlh1-C769 had no effect. These studies establish that the Mlh1-Pms1 endonuclease is required for MMR in a previously uncharacterized Exo1-independent MMR pathway.

Identification of adsorption sites in Cu-BTC by experimentation and molecular simulation.

PubMed

García-Pérez, Elena; Gascón, Jorge; Morales-Flórez, Víctor; Castillo, Juan Manuel; Kapteijn, Freek; Calero, Sofía

2009-02-03

The adsorption of several quadrupolar and nonpolar gases on the Metal Organic Framework Cu-BTC has been studied by combining experimental measurements and Monte Carlo simulations. Four main adsorption sites for this structure have been identified: site I close to the copper atoms, site I' in the bigger cavities, site II located in the small octahedral cages, and site III at the windows of the four open faces of the octahedral cage. Our simulations identify the octahedral cages (sites II and III) and the big cages (site I') as the preferred positions for adsorption, while site I, near the copper atoms, remains empty over the entire range of pressures analyzed due to its reduced accessibility. The occupation of the different sites for ethane and propane in Cu-BTC proceeds similarly as for methane, and shows small differences for O2 and N2 that can be attributed to the quadrupole moment of these molecules. Site II is filled predominantly for methane (the nonpolar molecule), whereas for N2, the occupation of II and I' can be considered almost equivalent. The molecular sitting for O2 shows an intermediate behavior between those observed for methane and for N2. The differences between simulated and experimental data at elevated temperatures for propane are tentatively attributed to a reversible change in the lattice parameters of Cu-BTC by dehydration and by temperature, blocking the accessibility to site III and reducing that to site I'. Adsorption parameters of the investigated molecules have been determined from the simulations.

Quantitative Analysis of Localized Sources Identified by Focal Impulse and Rotor Modulation Mapping in Atrial Fibrillation

PubMed Central

Benharash, Peyman; Buch, Eric; Frank, Paul; Share, Michael; Tung, Roderick; Shivkumar, Kalyanam; Mandapati, Ravi

2015-01-01

Background New approaches to ablation of atrial fibrillation (AF) include focal impulse and rotor modulation (FIRM) mapping, and initial results reported with this technique have been favorable. We sought to independently evaluate the approach by analyzing quantitative characteristics of atrial electrograms used to identify rotors and describe acute procedural outcomes of FIRM-guided ablation. Methods and Results All FIRM-guided ablation procedures (n=24; 50% paroxysmal) at University of California, Los Angeles Medical Center were included for analysis. During AF, unipolar atrial electrograms collected from a 64-pole basket catheter were used to construct phase maps and identify putative AF sources. These sites were targeted for ablation, in conjunction with pulmonary vein isolation in most patients (n=19; 79%). All patients had rotors identified (mean, 2.3±0.9 per patient; 72% in left atrium). Prespecified acute procedural end point was achieved in 12 of 24 (50%) patients: AF termination (n=1), organization (n=3), or >10% slowing of AF cycle length (n=8). Basket electrodes were within 1 cm of 54% of left atrial surface area, and a mean of 31 electrodes per patient showed interpretable atrial electrograms. Offline analysis revealed no differences between rotor and distant sites in dominant frequency or Shannon entropy. Electroanatomic mapping showed no rotational activation at FIRM-identified rotor sites in 23 of 24 patients (96%). Conclusions FIRM-identified rotor sites did not exhibit quantitative atrial electrogram characteristics expected from rotors and did not differ quantitatively from surrounding tissue. Catheter ablation at these sites, in conjunction with pulmonary vein isolation, resulted in AF termination or organization in a minority of patients (4/24; 17%). Further validation of this approach is necessary. PMID:25873718

Wildflowers of the Savannah River Site

Treesearch

T. Segar

2015-01-01

This guidebook is a resource to help field personnel (nonbotanists) identify plants on the Savannah River Site (SRS) premises. Although not a complete flora guide, this publication contains information about 123 plant species found on the SRS. Plants are listed by their common names and arranged by the color of the flower.

Using Carbohydrate Interaction Assays to Reveal Novel Binding Sites in Carbohydrate Active Enzymes.

PubMed

Cockburn, Darrell; Wilkens, Casper; Dilokpimol, Adiphol; Nakai, Hiroyuki; Lewińska, Anna; Abou Hachem, Maher; Svensson, Birte

2016-01-01

Carbohydrate active enzymes often contain auxiliary binding sites located either on independent domains termed carbohydrate binding modules (CBMs) or as so-called surface binding sites (SBSs) on the catalytic module at a certain distance from the active site. The SBSs are usually critical for the activity of their cognate enzyme, though they are not readily detected in the sequence of a protein, but normally require a crystal structure of a complex for their identification. A variety of methods, including affinity electrophoresis (AE), insoluble polysaccharide pulldown (IPP) and surface plasmon resonance (SPR) have been used to study auxiliary binding sites. These techniques are complementary as AE allows monitoring of binding to soluble polysaccharides, IPP to insoluble polysaccharides and SPR to oligosaccharides. Here we show that these methods are useful not only for analyzing known binding sites, but also for identifying new ones, even without structural data available. We further verify the chosen assays discriminate between known SBS/CBM containing enzymes and negative controls. Altogether 35 enzymes are screened for the presence of SBSs or CBMs and several novel binding sites are identified, including the first SBS ever reported in a cellulase. This work demonstrates that combinations of these methods can be used as a part of routine enzyme characterization to identify new binding sites and advance the study of SBSs and CBMs, allowing them to be detected in the absence of structural data.

Using Carbohydrate Interaction Assays to Reveal Novel Binding Sites in Carbohydrate Active Enzymes

PubMed Central

Wilkens, Casper; Dilokpimol, Adiphol; Nakai, Hiroyuki; Lewińska, Anna; Abou Hachem, Maher; Svensson, Birte

2016-01-01

Carbohydrate active enzymes often contain auxiliary binding sites located either on independent domains termed carbohydrate binding modules (CBMs) or as so-called surface binding sites (SBSs) on the catalytic module at a certain distance from the active site. The SBSs are usually critical for the activity of their cognate enzyme, though they are not readily detected in the sequence of a protein, but normally require a crystal structure of a complex for their identification. A variety of methods, including affinity electrophoresis (AE), insoluble polysaccharide pulldown (IPP) and surface plasmon resonance (SPR) have been used to study auxiliary binding sites. These techniques are complementary as AE allows monitoring of binding to soluble polysaccharides, IPP to insoluble polysaccharides and SPR to oligosaccharides. Here we show that these methods are useful not only for analyzing known binding sites, but also for identifying new ones, even without structural data available. We further verify the chosen assays discriminate between known SBS/CBM containing enzymes and negative controls. Altogether 35 enzymes are screened for the presence of SBSs or CBMs and several novel binding sites are identified, including the first SBS ever reported in a cellulase. This work demonstrates that combinations of these methods can be used as a part of routine enzyme characterization to identify new binding sites and advance the study of SBSs and CBMs, allowing them to be detected in the absence of structural data. PMID:27504624

Identifying riparian sinks for watershed nitrate using soil surveys.

PubMed

Rosenblatt, A E; Gold, A J; Stolt, M H; Groffman, P M; Kellogg, D Q

2001-01-01

The capacity of riparian zones to serve as critical control locations for watershed nitrogen flux varies with site characteristics. Without a means to stratify riparian zones into different levels of ground water nitrate removal capacity, this variability will confound spatially explicit source-sink models of watershed nitrate flux and limit efforts to target riparian restoration and management. We examined the capability of SSURGO (1:15 840 Soil Survey Geographic database) map classifications (slope class, geomorphology, and/or hydric soil designation) to identify riparian sites with high capacity for ground water nitrate removal. The study focused on 100 randomly selected riparian locations in a variety of forested and glaciated settings within Rhode Island. Geomorphic settings included till, outwash, and organic/alluvial deposits. We defined riparian zones with "high ground water nitrate removal capacity" as field sites possessing both >10 m of hydric soil width and an absence of ground water surface seeps. SSURGO classification based on a combination of geomorphology and hydric soil status created two functionally distinct sets of riparian sites. More than 75% of riparian sites classified by SSURGO as organic/alluviumhydric or as outwash-hydric had field attributes that suggest a high capacity for ground water nitrate removal. In contrast, >85% of all till sites and nonhydric outwash sites had field characteristics that minimize the capacity for ground water nitrate removal. Comparing the STATSGO and SSURGO databases for a 64000-ha watershed, STATSGO grossly under-represented critical riparian features. We conclude that the SSURGO database can provide modelers and managers with important insights into riparian zone nitrogen removal potential.

Adding Value to the Health Care System: Identifying Value-Added Systems Roles for Medical Students.

PubMed

Gonzalo, Jed D; Graaf, Deanna; Johannes, Bobbie; Blatt, Barbara; Wolpaw, Daniel R

To catalyze learning in Health Systems Science and add value to health systems, education programs are seeking to incorporate students into systems roles, which are not well described. The authors sought to identify authentic roles for students within a range of clinical sites and explore site leaders' perceptions of the value of students performing these roles. From 2013 to 2015, site visits and interviews with leadership from an array of clinical sites (n = 30) were conducted. Thematic analysis was used to identify tasks and benefits of integrating students into interprofessional care teams. Types of systems roles included direct patient benefit activities, including monitoring patient progress with care plans and facilitating access to resources, and clinic benefit activities, including facilitating coordination and improving clinical processes. Perceived benefits included improved value of the clinical mission and enhanced student education. These results elucidate a framework for student roles that enhance learning and add value to health systems.

Nevada Test Site Wetlands Assessment

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

D. J. Hansen

1997-05-01

This report identifies 16 Nevada Test Site (NTS) natural water sources that may be classified by the U.S. Army Corps of Engineers (USACE) as jurisdictional wetlands and identifies eight water sources that may be classified as waters of the United States. These water sources are rare, localized habitats on the NTS that are important to regional wildlife and to isolated populations of water tolerant plants and aquatic organisms. No field investigations on the NTS have been conducted in the past to identify those natural water sources which would be protected as rare habitats and which may fall under regulatory authoritymore » of the Clean Water Act (CWA) of 1997. This report identifies and summarizes previous studies of NTS natural water sources, and identifies the current DOE management practices related to the protection of NTS wetlands. This report also presents management goals specific for NTS wetlands that incorporate the intent of existing wetlands legislation, the principles of ecosystem management, and the interests of regional land managers and other stakeholders.« less

Recognition of functional sites in protein structures.

PubMed

Shulman-Peleg, Alexandra; Nussinov, Ruth; Wolfson, Haim J

2004-06-04

Recognition of regions on the surface of one protein, that are similar to a binding site of another is crucial for the prediction of molecular interactions and for functional classifications. We first describe a novel method, SiteEngine, that assumes no sequence or fold similarities and is able to recognize proteins that have similar binding sites and may perform similar functions. We achieve high efficiency and speed by introducing a low-resolution surface representation via chemically important surface points, by hashing triangles of physico-chemical properties and by application of hierarchical scoring schemes for a thorough exploration of global and local similarities. We proceed to rigorously apply this method to functional site recognition in three possible ways: first, we search a given functional site on a large set of complete protein structures. Second, a potential functional site on a protein of interest is compared with known binding sites, to recognize similar features. Third, a complete protein structure is searched for the presence of an a priori unknown functional site, similar to known sites. Our method is robust and efficient enough to allow computationally demanding applications such as the first and the third. From the biological standpoint, the first application may identify secondary binding sites of drugs that may lead to side-effects. The third application finds new potential sites on the protein that may provide targets for drug design. Each of the three applications may aid in assigning a function and in classification of binding patterns. We highlight the advantages and disadvantages of each type of search, provide examples of large-scale searches of the entire Protein Data Base and make functional predictions.

Rac1 GTPase activates the WAVE regulatory complex through two distinct binding sites.

PubMed

Chen, Baoyu; Chou, Hui-Ting; Brautigam, Chad A; Xing, Wenmin; Yang, Sheng; Henry, Lisa; Doolittle, Lynda K; Walz, Thomas; Rosen, Michael K

2017-09-26

The Rho GTPase Rac1 activates the WAVE regulatory complex (WRC) to drive Arp2/3 complex-mediated actin polymerization, which underpins diverse cellular processes. Here we report the structure of a WRC-Rac1 complex determined by cryo-electron microscopy. Surprisingly, Rac1 is not located at the binding site on the Sra1 subunit of the WRC previously identified by mutagenesis and biochemical data. Rather, it binds to a distinct, conserved site on the opposite end of Sra1. Biophysical and biochemical data on WRC mutants confirm that Rac1 binds to both sites, with the newly identified site having higher affinity and both sites required for WRC activation. Our data reveal that the WRC is activated by simultaneous engagement of two Rac1 molecules, suggesting a mechanism by which cells may sense the density of active Rac1 at membranes to precisely control actin assembly.

Identifying the site of spin trapping in proteins by a combination of liquid chromatography, ELISA, and off-line tandem mass spectrometry.

PubMed

Lardinois, Olivier M; Detweiler, Charles D; Tomer, Kenneth B; Mason, Ronald P; Deterding, Leesa J

2008-03-01

An off-line mass spectrometry method that combines immuno-spin trapping and chromatographic procedures has been developed for selective detection of the nitrone spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) covalently attached to proteins, an attachment which occurs only subsequent to DMPO trapping of free radicals. In this technique, the protein-DMPO nitrone adducts are digested to peptides with proteolytic agents, peptides from the enzymatic digest are separated by HPLC, and enzyme-linked immunosorbent assays (ELISA) using polyclonal anti-DMPO nitrone antiserum are used to detect the eluted HPLC fractions that contain DMPO nitrone adducts. The fractions showing positive ELISA signals are then concentrated and characterized by tandem mass spectrometry (MS/MS). This method, which constitutes the first liquid chromatography-ELISA-mass spectrometry (LC-ELISA-MS)-based strategy for selective identification of DMPO-trapped protein residues in complex peptide mixtures, facilitates location and preparative fractionation of DMPO nitrone adducts for further structural characterization. The strategy is demonstrated for human hemoglobin, horse heart myoglobin, and sperm whale myoglobin, three globin proteins known to form DMPO-trappable protein radicals on treatment with H(2)O(2). The results demonstrate the power of the new experimental strategy to select DMPO-labeled peptides and identify sites of DMPO covalent attachments.

The frequency of company-sponsored alcohol brand-related sites on Facebook™-2012.

PubMed

Nhean, Siphannay; Nyborn, Justin; Hinchey, Danielle; Valerio, Heather; Kinzel, Kathryn; Siegel, Michael; Jernigan, David H

2014-06-01

This research provides an estimate of the frequency of company-sponsored alcohol brand-related sites on Facebook™. We conducted a systematic overview of the extent of alcohol brand-related sites on Facebook™ in 2012. We conducted a 2012 Facebook™ search for sites specifically related to 898 alcohol brands across 16 different alcoholic beverage types. Descriptive statistics were produced using Microsoft SQL Server. We identified 1,017 company-sponsored alcohol-brand related sites on Facebook™. Our study advances previous literature by providing a systematic overview of the extent of alcohol brand sites on Facebook™.

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.

PS2-06: Best Practices for Advancing Multi-site Chart Abstraction Research

PubMed Central

Blick, Noelle; Cole, Deanna; King, Colleen; Riordan, Rick; Von Worley, Ann; Yarbro, Patty

2012-01-01

Background/Aims Multi-site chart abstraction studies are becoming increasingly common within the HMORN. Differences in systems among HMORN sites can pose significant obstacles to the success of these studies. It is therefore crucial to standardize abstraction activities by following best practices for multi-site chart abstraction, as consistency of processes across sites will increase efficiencies and enhance data quality. Methods Over the past few months the authors have been meeting to identify obstacles to multi-site chart abstraction and to address ways in which multi-site chart abstraction processes can be systemized and standardized. The aim of this workgroup is to create a best practice guide for multi-site chart abstraction studies. Focus areas include: abstractor training, format for chart abstraction (database, paper, etc), data quality, redaction, mechanism for transferring data, site specific access to medical records, IRB/HIPAA concerns, and budgetary issues. Results The results of the workgroup’s efforts (the best practice guide) will be presented by a panel of experts at the 2012 HMORN conference. The presentation format will also focus on discussion among attendees to elicit further input and to identify areas that need to be further addressed. Subsequently, the best practice guide will be posted on the HMORN website. Discussion The best practice guide for multi-site chart abstraction studies will establish sound guidelines and serve as an aid to researchers embarking on multi-site chart abstraction studies. Efficiencies and data quality will be further enhanced with standardized multi-site chart abstraction practices.

SiteDB: Marshalling people and resources available to CMS

NASA Astrophysics Data System (ADS)

Metson, S.; Bonacorsi, D.; Dias Ferreira, M.; Egeland, R.

2010-04-01

In a collaboration the size of CMS (approx. 3000 users, and almost 100 computing centres of varying size) communication and accurate information about the sites it has access to is vital in co-ordinating the multitude of computing tasks required for smooth running. SiteDB is a tool developed by CMS to track sites available to the collaboration, the allocation to CMS of resources available at those sites and the associations between CMS members and the sites (as either a manager/operator of the site or a member of a group associated to the site). It is used to track the roles a person has for an associated site or group. SiteDB eases the coordination load for the operations teams by providing a consistent interface to manage communication with the people working at a site, by identifying who is responsible for a given task or service at a site and by offering a uniform interface to information on CMS contacts and sites. SiteDB provides api's and reports for other CMS tools to use to access the information it contains, for instance enabling CRAB to use "user friendly" names when black/white listing CE's, providing role based authentication and authorisation for other web based services and populating various troubleshooting squads in external ticketing systems in use daily by CMS Computing operations.

The effects of para-chloromercuribenzoic acid and different oxidative and sulfhydryl agents on a novel, non-AT1, non-AT2 angiotensin binding site identified as neurolysin

PubMed Central

Santos, Kira L.; Vento, Megan A; Wright, John W.; Speth, Robert C.

2013-01-01

A novel, non-AT1, non-AT2 brain binding site for angiotensin peptides that is unmasked by p-chloromercuribenzoate (PCMB) has been identified as a membrane associated variant of neurolysin. The ability of different organic and inorganic oxidative and sulfhydryl reactive agents to unmask or inhibit 125I-Sar1Ile8 angiotensin II (SI-Ang II) binding to this site was presently examined. In tissue membranes from homogenates of rat brain and testis incubated in assay buffer containing losartan (10 μM) and PD123319 (10 μM) plus 100 μM PCMB, 5 of the 39 compounds tested inhibited 125I-SI Ang II binding in brain and testis. Mersalyl acid, mercuric chloride (HgCl2) and silver nitrate (AgNO3) most potently inhibited 125I-SI Ang II binding with IC50’s ~1–20 μM This HgCl2 inhibition was independent of any interaction of HgCl2 with angiotensin II (Ang II) based on the lack of effect of HgCl2 on the dipsogenic effects of intracerebroventricularly administered Ang II and 125I-SI Ang II binding to AT1 receptors in the liver. Among sulfhydryl reagents, cysteamine and reduced glutathione (GSH), but not oxidized glutathione (GSSG) up to 1 mM, inhibited PCMB-unmasked 125I-SI Ang II binding in brain and testis. Thimerosal and 4-hydroxymercuribenzoate moderately inhibited PCMB-unmasked 125I-SI Ang II binding in brain and testis at 100 μM; however, they also unmasked non-AT1, non-AT2 binding independent of PCMB. 4-hydroxybenzoic acid did not promote 125 I-SI Ang II binding to this binding site indicating that only specific organomercurial compounds can unmask the binding site. The common denominator for all of these interacting substances is the ability to bind to protein cysteine sulfur. Comparison of cysteines between neurolysin and the closely related enzyme thimet oligopeptidase revealed an unconserved cysteine (cys650, based on the full length variant) in the proposed ligand binding channel (Brown et al., 2001) [1] near the active site of neurolysin. It is proposed that the

Binding Sites Analyser (BiSA): Software for Genomic Binding Sites Archiving and Overlap Analysis

PubMed Central

Khushi, Matloob; Liddle, Christopher; Clarke, Christine L.; Graham, J. Dinny

2014-01-01

Genome-wide mapping of transcription factor binding and histone modification reveals complex patterns of interactions. Identifying overlaps in binding patterns by different factors is a major objective of genomic studies, but existing methods to archive large numbers of datasets in a personalised database lack sophistication and utility. Therefore we have developed transcription factor DNA binding site analyser software (BiSA), for archiving of binding regions and easy identification of overlap with or proximity to other regions of interest. Analysis results can be restricted by chromosome or base pair overlap between regions or maximum distance between binding peaks. BiSA is capable of reporting overlapping regions that share common base pairs; regions that are nearby; regions that are not overlapping; and average region sizes. BiSA can identify genes located near binding regions of interest, genomic features near a gene or locus of interest and statistical significance of overlapping regions can also be reported. Overlapping results can be visualized as Venn diagrams. A major strength of BiSA is that it is supported by a comprehensive database of publicly available transcription factor binding sites and histone modifications, which can be directly compared to user data. The documentation and source code are available on http://bisa.sourceforge.net PMID:24533055

2011 Annual Ecological Survey: Pacific Northwest National Laboratory Site

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

Becker, James M.; Chamness, Michele A.

The U.S. Department of Energy (DOE) Pacific Northwest Site Office (PNSO) oversees and manages the DOE contract for the Pacific Northwest National Laboratory (PNNL), a DOE Office of Science multi-program laboratory located in Richland, Washington. PNSO is responsible for ensuring that all activities conducted on the PNNL site comply with applicable laws, policies, and DOE Orders. The DOE Pacific Northwest Site Office Cultural and Biological Resources Management Plan (DOE/PNSO 2008) addresses the requirement for annual surveys and monitoring for species of concern and to identify and map invasive species. In addition to the requirement for an annual survey, proposed projectmore » activities must be reviewed to assess any potential environmental consequences of conducting the project. The assessment process requires a thorough understanding of the resources present, the potential impacts of a proposed action to those resources, and the ultimate consequences of those actions. The PNNL site is situated on the southeastern corner of the DOE Hanford Site, located at the north end of the city of Richland in south-central Washington. The site is bordered on the east by the Columbia River, on the west by Stevens Drive, and on the north by the Hanford Site 300 Area (Figure 1). The environmental setting of the PNNL site is described in Larson and Downs (2009). There are currently two facilities on the PNNL site: the William R. Wiley Environmental Molecular Sciences Laboratory and the Physical Sciences Facility. This report describes the annual survey of biological resources found on the undeveloped upland portions of the PNNL site. The annual survey is comprised of a series of individual field surveys conducted on various days in late May and throughout June 2011. A brief description of the methods PNNL ecologists used to conduct the baseline surveys and a summary of the results of the surveys are presented. Appendix A provides a list of plant and animal species identified

GPS-PAIL: prediction of lysine acetyltransferase-specific modification sites from protein sequences.

PubMed

Deng, Wankun; Wang, Chenwei; Zhang, Ying; Xu, Yang; Zhang, Shuang; Liu, Zexian; Xue, Yu

2016-12-22

Protein acetylation catalyzed by specific histone acetyltransferases (HATs) is an essential post-translational modification (PTM) and involved in the regulation a broad spectrum of biological processes in eukaryotes. Although several ten thousands of acetylation sites have been experimentally identified, the upstream HATs for most of the sites are unclear. Thus, the identification of HAT-specific acetylation sites is fundamental for understanding the regulatory mechanisms of protein acetylation. In this work, we first collected 702 known HAT-specific acetylation sites of 205 proteins from the literature and public data resources, and a motif-based analysis demonstrated that different types of HATs exhibit similar but considerably distinct sequence preferences for substrate recognition. Using 544 human HAT-specific sites for training, we constructed a highly useful tool of GPS-PAIL for the prediction of HAT-specific sites for up to seven HATs, including CREBBP, EP300, HAT1, KAT2A, KAT2B, KAT5 and KAT8. The prediction accuracy of GPS-PAIL was critically evaluated, with a satisfying performance. Using GPS-PAIL, we also performed a large-scale prediction of potential HATs for known acetylation sites identified from high-throughput experiments in nine eukaryotes. Both online service and local packages were implemented, and GPS-PAIL is freely available at: http://pail.biocuckoo.org.

GPS-PAIL: prediction of lysine acetyltransferase-specific modification sites from protein sequences

PubMed Central

Deng, Wankun; Wang, Chenwei; Zhang, Ying; Xu, Yang; Zhang, Shuang; Liu, Zexian; Xue, Yu

2016-01-01

Protein acetylation catalyzed by specific histone acetyltransferases (HATs) is an essential post-translational modification (PTM) and involved in the regulation a broad spectrum of biological processes in eukaryotes. Although several ten thousands of acetylation sites have been experimentally identified, the upstream HATs for most of the sites are unclear. Thus, the identification of HAT-specific acetylation sites is fundamental for understanding the regulatory mechanisms of protein acetylation. In this work, we first collected 702 known HAT-specific acetylation sites of 205 proteins from the literature and public data resources, and a motif-based analysis demonstrated that different types of HATs exhibit similar but considerably distinct sequence preferences for substrate recognition. Using 544 human HAT-specific sites for training, we constructed a highly useful tool of GPS-PAIL for the prediction of HAT-specific sites for up to seven HATs, including CREBBP, EP300, HAT1, KAT2A, KAT2B, KAT5 and KAT8. The prediction accuracy of GPS-PAIL was critically evaluated, with a satisfying performance. Using GPS-PAIL, we also performed a large-scale prediction of potential HATs for known acetylation sites identified from high-throughput experiments in nine eukaryotes. Both online service and local packages were implemented, and GPS-PAIL is freely available at: http://pail.biocuckoo.org. PMID:28004786

Genome-wide transcription start site profiling in biofilm-grown Burkholderia cenocepacia J2315.

PubMed

Sass, Andrea M; Van Acker, Heleen; Förstner, Konrad U; Van Nieuwerburgh, Filip; Deforce, Dieter; Vogel, Jörg; Coenye, Tom

2015-10-13

Burkholderia cenocepacia is a soil-dwelling Gram-negative Betaproteobacterium with an important role as opportunistic pathogen in humans. Infections with B. cenocepacia are very difficult to treat due to their high intrinsic resistance to most antibiotics. Biofilm formation further adds to their antibiotic resistance. B. cenocepacia harbours a large, multi-replicon genome with a high GC-content, the reference genome of strain J2315 includes 7374 annotated genes. This study aims to annotate transcription start sites and identify novel transcripts on a whole genome scale. RNA extracted from B. cenocepacia J2315 biofilms was analysed by differential RNA-sequencing and the resulting dataset compared to data derived from conventional, global RNA-sequencing. Transcription start sites were annotated and further analysed according to their position relative to annotated genes. Four thousand ten transcription start sites were mapped over the whole B. cenocepacia genome and the primary transcription start site of 2089 genes expressed in B. cenocepacia biofilms were defined. For 64 genes a start codon alternative to the annotated one was proposed. Substantial antisense transcription for 105 genes and two novel protein coding sequences were identified. The distribution of internal transcription start sites can be used to identify genomic islands in B. cenocepacia. A potassium pump strongly induced only under biofilm conditions was found and 15 non-coding small RNAs highly expressed in biofilms were discovered. Mapping transcription start sites across the B. cenocepacia genome added relevant information to the J2315 annotation. Genes and novel regulatory RNAs putatively involved in B. cenocepacia biofilm formation were identified. These findings will help in understanding regulation of B. cenocepacia biofilm formation.

Sensory coding of nest-site value in honeybee swarms.

PubMed

Seeley, Thomas D; Visscher, P Kirk

2008-12-01

This study investigates the first stage of the decision-making process of a honeybee swarm as it chooses a nest site: how a scout bee codes the value of a potential nest site in the waggle dances she produces to represent this site. We presented honeybee swarms with a two-alternative choice between a high-value site and a medium-value site and recorded the behavior of individually identifiable scout bees as they reported on these two alternatives. We found that bees performed equally lengthy inspections at the two sites, but that, on the swarm cluster, they performed more dance circuits per bee for the high-value site. We also found that there was much individual-level noise in the coding of site value, but that there were clear population-level differences in total dance circuits produced for the two sites. The first bee to find a site had a high probability of reporting the site with a waggle dance, regardless of its value. This discoverer-should-dance phenomenon may help ensure that a swarm gives attention to all discovered sites. There was rapid decay in the dance response; the number of dance circuits produced by a bee after visiting a site decreased linearly over sequential visits, and eventually each bee ceased visiting her site. This decay, or ;leakage', in the accumulation of bees at a site improves a swarm's decision-making ability by helping a swarm avoid making fast-decision errors.

Framework for Identifying Key Environmental Concerns in Marine Renewable Energy Projects- Appendices

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

Kramer, Sharon; Previsic, Mirko; Nelson, Peter

2010-06-17

Marine wave and tidal energy technology could interact with marine resources in ways that are not well understood. As wave and tidal energy conversion projects are planned, tested, and deployed, a wide range of stakeholders will be engaged; these include developers, state and federal regulatory agencies, environmental groups, tribal governments, recreational and commercial fishermen, and local communities. Identifying stakeholders’ environmental concerns in the early stages of the industry’s development will help developers address and minimize potential environmental effects. Identifying important concerns will also assist with streamlining siting and associated permitting processes, which are considered key hurdles by the industry inmore » the U.S. today. In September 2008, RE Vision consulting, LLC was selected by the Department of Energy (DoE) to conduct a scenario-based evaluation of emerging hydrokinetic technologies. The purpose of this evaluation is to identify and characterize environmental impacts that are likely to occur, demonstrate a process for analyzing these impacts, identify the “key” environmental concerns for each scenario, identify areas of uncertainty, and describe studies that could address that uncertainty. This process is intended to provide an objective and transparent tool to assist in decision-making for siting and selection of technology for wave and tidal energy development. RE Vision worked with H. T. Harvey & Associates, to develop a framework for identifying key environmental concerns with marine renewable technology. This report describes the results of this study. This framework was applied to varying wave and tidal power conversion technologies, scales, and locations. The following wave and tidal energy scenarios were considered: 4 wave energy generation technologies 3 tidal energy generation technologies 3 sites: Humboldt coast, California (wave); Makapu’u Point, Oahu, Hawaii (wave); and the Tacoma Narrows, Washington

2010 Ecological Survey of the Pacific Northwest National Laboratory Site

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

Chamness, Michele A.; Perry, Christopher; Downs, Janelle L.

The U.S. Department of Energy (DOE) Pacific Northwest Site Office (PNSO) oversees and manages the DOE contract for the Pacific Northwest National Laboratory (PNNL), a DOE Office of Science multi-program laboratory located in Richland, Washington. PNSO is responsible for ensuring that all activities conducted on the PNNL Site comply with applicable laws, policies, and DOE orders. The DOE Pacific Northwest Site Office Cultural and Biological Resources Management Plan (DOE/PNSO 2008) addresses the requirement for annual surveys and monitoring for species of concern and to identify and map invasive species. In addition to the requirement for an annual survey, proposed projectmore » activities must be reviewed to assess any potential environmental consequences of conducting the project. The assessment process requires a thorough understanding of the resources present, the potential impacts of a proposed action to those resources, and the ultimate consequences of those actions. The PNNL Site is situated on the southeastern corner of the DOE Hanford Site, located at the north end of the city of Richland in south-central Washington. The site is bordered on the east by the Columbia River, on the west by Stevens Drive, and on the north by the Hanford Site 300 Area (Figure 1). The environmental setting of the PNNL Site is described in Larson and Downs (2009). There are currently two facilities on the PNNL Site: the William R. Wiley Environmental Molecular Sciences Laboratory (EMSL), and the recently completed Physical Sciences Facility (PSF). This report describes the results of the annual survey of the biological resources found on the undeveloped portions of the PNNL Site in 2010. A brief description of the methods PNNL ecologists used to conduct the surveys and the results of the surveys are presented. Actions taken to fully delineate noxious weed populations discovered in 2009 and efforts in 2010 to control those weeds also are described. Appendix A provides a list of

Fall hazard control observed on residential construction sites.

PubMed

Kaskutas, Vicki; Dale, Ann Marie; Nolan, James; Patterson, Dennis; Lipscomb, Hester J; Evanoff, Bradley

2009-06-01

Falls are a leading cause of mortality and morbidity in the construction industry. This study measured fall hazards at residential construction sites. Trained carpenters administered the St. Louis Audit of Fall Risks and interviewed carpenters. The prevalence of fall prevention practices meeting safety criteria was counted and correlations explored. We identified a high prevalence of fall hazards at the 197 residential sites audited. Roof sheathing met safety criteria most consistently (81%) and truss setting least consistently (28%). Use of personal fall arrest and monitoring of unguarded floor openings were rare. Safer performance on several scales was correlated. Construction sites of large-sized contractors were generally safer than smaller contractors. Apprentice carpenters were less familiar with their employers' fall prevention plan than experienced workers. Safety could be improved with consistent use of recognized fall prevention practices at residential construction sites.

Likelihood of Bone Recurrence in Prior Sites of Metastasis in Patients With High-Risk Neuroblastoma

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

Polishchuk, Alexei L.; Li, Richard; Hill-Kayser, Christine

2014-07-15

Purpose/Objectives: Despite recent improvements in outcomes, 40% of children with high-risk neuroblastoma will experience relapse, facing a guarded prognosis for long-term cure. Whether recurrences are at new sites or sites of original disease may guide decision making during initial therapy. Methods and Materials: Eligible patients were retrospectively identified from institutional databases at first metastatic relapse of high-risk neuroblastoma. Included patients had disease involving metaiodobenzylguanidine (MIBG)-avid metastatic sites at diagnosis and first relapse, achieved a complete or partial response with no more than one residual MIBG-avid site before first relapse, and received no total body irradiation or therapy with {sup 131}I-MIBGmore » before first relapse. Anatomically defined metastatic sites were tracked from diagnosis through first relapse to determine tendency of disease to recur at previously involved versus uninvolved sites and to assess whether this pattern was influenced by site irradiation. Results: Of 159 MIBG-avid metastatic sites identified among 43 patients at first relapse, 131 (82.4%) overlapped anatomically with the set of 525 sites present at diagnosis. This distribution was similar for bone sites, but patterns of relapse were more varied for the smaller subset of soft tissue metastases. Among all metastatic sites at diagnosis in our subsequently relapsed patient cohort, only 3 of 19 irradiated sites (15.8%) recurred as compared with 128 of 506 (25.3%) unirradiated sites. Conclusions: Metastatic bone relapse in neuroblastoma usually occurs at anatomic sites of previous disease. Metastatic sites identified at diagnosis that did not receive radiation during frontline therapy appeared to have a higher risk of involvement at first relapse relative to previously irradiated metastatic sites. These observations support the current paradigm of irradiating metastases that persist after induction chemotherapy in high-risk patients

Vegetative characteristics of swift fox denning and foraging sites in southwestern South Dakota

Treesearch

Daniel W. Uresk; Kieth E. Severson; Jody Javersak

2003-01-01

Vegetative characteristics of swift fox (Vulpes velox) denning and foraging habitats were studied in southwestern South Dakota. We followed 14 radio-collared foxes over a two-year period and identified 17 den sites and 82 foraging sites. Height-density of vegetation (visual obstruction reading, VOR) was determined on each den and foraging site and on...

TarPmiR: a new approach for microRNA target site prediction.

PubMed

Ding, Jun; Li, Xiaoman; Hu, Haiyan

2016-09-15

The identification of microRNA (miRNA) target sites is fundamentally important for studying gene regulation. There are dozens of computational methods available for miRNA target site prediction. Despite their existence, we still cannot reliably identify miRNA target sites, partially due to our limited understanding of the characteristics of miRNA target sites. The recently published CLASH (crosslinking ligation and sequencing of hybrids) data provide an unprecedented opportunity to study the characteristics of miRNA target sites and improve miRNA target site prediction methods. Applying four different machine learning approaches to the CLASH data, we identified seven new features of miRNA target sites. Combining these new features with those commonly used by existing miRNA target prediction algorithms, we developed an approach called TarPmiR for miRNA target site prediction. Testing on two human and one mouse non-CLASH datasets, we showed that TarPmiR predicted more than 74.2% of true miRNA target sites in each dataset. Compared with three existing approaches, we demonstrated that TarPmiR is superior to these existing approaches in terms of better recall and better precision. The TarPmiR software is freely available at http://hulab.ucf.edu/research/projects/miRNA/TarPmiR/ CONTACTS: haihu@cs.ucf.edu or xiaoman@mail.ucf.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

Identifying protein kinase target preferences using mass spectrometry

PubMed Central

Douglass, Jacqueline; Gunaratne, Ruwan; Bradford, Davis; Saeed, Fahad; Hoffert, Jason D.; Steinbach, Peter J.; Pisitkun, Trairak

2012-01-01

A general question in molecular physiology is how to identify candidate protein kinases corresponding to a known or hypothetical phosphorylation site in a protein of interest. It is generally recognized that the amino acid sequence surrounding the phosphorylation site provides information that is relevant to identification of the cognate protein kinase. Here, we present a mass spectrometry-based method for profiling the target specificity of a given protein kinase as well as a computational tool for the calculation and visualization of the target preferences. The mass spectrometry-based method identifies sites phosphorylated in response to in vitro incubation of protein mixtures with active recombinant protein kinases followed by standard phosphoproteomic methodologies. The computational tool, called “PhosphoLogo,” uses an information-theoretic algorithm to calculate position-specific amino acid preferences and anti-preferences from the mass-spectrometry data (http://helixweb.nih.gov/PhosphoLogo/). The method was tested using protein kinase A (catalytic subunit α), revealing the well-known preference for basic amino acids in positions −2 and −3 relative to the phosphorylated amino acid. It also provides evidence for a preference for amino acids with a branched aliphatic side chain in position +1, a finding compatible with known crystal structures of protein kinase A. The method was also employed to profile target preferences and anti-preferences for 15 additional protein kinases with potential roles in regulation of epithelial transport: CK2, p38, AKT1, SGK1, PKCδ, CaMK2δ, DAPK1, MAPKAPK2, PKD3, PIM1, OSR1, STK39/SPAK, GSK3β, Wnk1, and Wnk4. PMID:22723110

Draft Site Treatment Plan (DSTP), Volumes I and II

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

D`Amelio, J.

1994-08-30

Site Treatment Plans (STP) are required for facilities at which the DOE generates or stores mixed waste. This Draft Site Treatment Plan (DSTP) the second step in a three-phase process, identifies the currently preferred options for treating mixed waste at the Savannah River Site (SRS) or for developing treatment technologies where technologies do not exist or need modification. The DSTP reflects site-specific preferred options, developed with the state`s input and based on existing available information. To the extent possible, the DSTP identifies specific treatment facilities for treating the mixed waste and proposes schedules. Where the selection of specific treatment facilitiesmore » is not possible, schedules for alternative activities such as waste characterization and technology assessment are provided. All schedule and cost information presented is preliminary and is subject to change. The DSTP is comprised of two volumes: this Compliance Plan Volume and the Background Volume. This Compliance Plan Volume proposes overall schedules with target dates for achieving compliance with the land disposal restrictions (LDR) of RCRA and procedures for converting the target dates into milestones to be enforced under the Order. The more detailed discussion of the options contained in the Background Volume is provided for informational purposes only.« less

Regional Seismic Methods of Identifying Explosions

NASA Astrophysics Data System (ADS)

Walter, W. R.; Ford, S. R.; Pasyanos, M.; Pyle, M. L.; Hauk, T. F.

2013-12-01

A lesson from the 2006, 2009 and 2013 DPRK declared nuclear explosion Ms:mb observations is that our historic collection of data may not be representative of future nuclear test signatures (e.g. Selby et al., 2012). To have confidence in identifying future explosions amongst the background of other seismic signals, we need to put our empirical methods on a firmer physical footing. Here we review the two of the main identification methods: 1) P/S ratios and 2) Moment Tensor techniques, which can be applied at the regional distance (200-1600 km) to very small events, improving nuclear explosion monitoring and confidence in verifying compliance with the Comprehensive Nuclear-Test-Ban Treaty (CTBT). Amplitude ratios of seismic P-to-S waves at sufficiently high frequencies (~>2 Hz) can identify explosions among a background of natural earthquakes (e.g. Walter et al., 1995). However the physical basis for the generation of explosion S-waves, and therefore the predictability of this P/S technique as a function of event properties such as size, depth, geology and path, remains incompletely understood. Calculated intermediate period (10-100s) waveforms from regional 1-D models can match data and provide moment tensor results that separate explosions from earthquakes and cavity collapses (e.g. Ford et al. 2009). However it has long been observed that some nuclear tests produce large Love waves and reversed Rayleigh waves that complicate moment tensor modeling. Again the physical basis for the generation of these effects from explosions remains incompletely understood. We are re-examining regional seismic data from a variety of nuclear test sites including the DPRK and the former Nevada Test Site (now the Nevada National Security Site (NNSS)). Newer relative amplitude techniques can be employed to better quantify differences between explosions and used to understand those differences in term of depth, media and other properties. We are also making use of the Source Physics

Structure-function discrepancy in Clostridium botulinum C3 toxin for its rational prioritization as a subunit vaccine.

PubMed

Prathiviraj, R; Prisilla, A; Chellapandi, P

2016-06-01

Clostridium botulinum is anaerobic pathogenic bacterium causing food-born botulism in human and animals by producing botulinum neurotoxins A-H, C2, and C3 cytotoxins. Physiological group III strains (type C and D) of this bacterium are capable of producing C2 and C3 toxins in cattle and avian. Herein, we have revealed the structure-function disparity of C3 toxins from two different C. botulinum type C phage (CboC) and type D phage (CboD) to design avirulent toxins rationally. Structure-function discrepancy of the both toxins was computationally evaluated from their homology models based on the conservation in sequence-structure-function relationships upon covariation and point mutations. It has shown that 8 avirulent mutants were generated from CboC of 34 mutants while 27 avirulent mutants resulted from CboD mutants. No major changes were found in tertiary structure of these toxins; however, some structural variations appeared in the coiled and loop regions. Correlated mutation on the first residue would disorder or revolutionize the hydrogen bonding pattern of the coevolved pairs. It suggested that the residues coupling in the local structural environments were compensated with coevolved pairs so as to preserve a pseudocatalytic function in the avirulent mutants. Avirulent mutants of C3 toxins have shown a stable structure with a common blue print of folding process and also attained a near-native backrub ensemble. Thus, we concluded that selecting the site-directed mutagenesis sites are very important criteria for designing avirulent toxins, in development of rational subunit vaccines, to cattle and avian, but the vaccine specificity can be determined by the C3 toxins of C. botulinum harboring phages.

Draft environmental assessment: Lavender Canyon site, Utah. Nuclear Waste Policy Act (Section 112). [Contains glossary

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

Not Available

1984-12-01

In February 1983, the US Department of Energy (DOE) identified the Lavender Canyon site in Utah, as one of nine potentially acceptable sites for a mined geologic repository for spent nuclear fuel and high-level radioactive waste. To determine their suitability, the Lavender Canyon site and the eight other potentially acceptable sites h

Fibrosarcomas at presumed sites of injection in dogs: characteristics and comparison with non-vaccination site fibrosarcomas and feline post-vaccinal fibrosarcomas.

PubMed

Vascellari, M; Melchiotti, E; Bozza, M A; Mutinelli, F

2003-08-01

Fifteen fibrosarcomas, surgically excised from presumed sites of injection in dogs, and 10 canine fibrosarcomas excised from sites not used for injection were histologically and immunohistochemically compared with 20 feline post-vaccinal fibrosarcomas. Canine fibrosarcomas from presumed injection sites were of grade I (3), of grade II (4) and grade III (8). Two fibrosarcomas from non-injection sites were of grade I, four of grade II and four of grade III. Feline samples were classified as grade I (2), grade II (4) and grade III (14). All fibrosarcomas from presumed injection sites of both species showed lymphocytic inflammatory infiltration located at the tumour periphery, while two canine fibrosarcomas from non-injection sites showed perivascular inflammatory infiltration within the neoplasm. All samples were immunohistochemically examined for vimentin, smooth muscle actin, muscle specific actin and desmin expression. All tumours were positive for vimentin. Ten canine fibrosarcomas from presumed injection sites and all feline samples contained cells consistent with a myofibroblastic immunophenotype. Aluminium deposits were detected in eight canine fibrosarcomas from presumed injection sites and 11 feline post-vaccinal fibrosarcomas by the aurintricarboxylic acid method. The present study identifies distinct similarities between canine fibrosarcomas from presumed injection sites and feline post-vaccinal fibrosarcomas, suggesting the possibility of the development of post-injection sarcomas not only in cats, but also in dogs.

Prioritizing Sites for Protection and Restoration for Grizzly Bears (Ursus arctos) in Southwestern Alberta, Canada.

PubMed

Braid, Andrew C R; Nielsen, Scott E

2015-01-01

As the influence of human activities on natural systems continues to expand, there is a growing need to prioritize not only pristine sites for protection, but also degraded sites for restoration. We present an approach for simultaneously prioritizing sites for protection and restoration that considers landscape patterns for a threatened population of grizzly bears (Ursus arctos) in southwestern Alberta, Canada. We considered tradeoffs between bottom-up (food resource supply) and top-down (mortality risk from roads) factors affecting seasonal habitat quality for bears. Simulated annealing was used to prioritize source-like sites (high habitat productivity, low mortality risk) for protection, as well as sink-like sites (high habitat productivity, high mortality risk) for restoration. Priority source-like habitats identified key conservation areas where future developments should be limited, whereas priority sink-like habitats identified key areas for mitigating road-related mortality risk with access management. Systematic conservation planning methods can be used to complement traditional habitat-based methods for individual focal species by identifying habitats where conservation actions (both protection and restoration) have the highest potential utility.

Microdensitometry to identify saline rangelands on 70-mm color-infrared aerial film

NASA Technical Reports Server (NTRS)

Everitt, J. H.; Gerbermann, A. H.; Alaniz, M. A.

1981-01-01

Many of the world's rangelands are affected by salinity. The detection of these areas is important to range and resource managers who are concerned with productivity, condition, and animal carrying capacity. The reported study was conducted along a north-to-south flight line 24 km long and 1.6 wide in Starr County, TX. Everitt et al. (1977) described seven different native range sites (four nonsaline and three saline) along this flight line. The study showed that photointerpretation by microdensitometry could be used to identify saline range sites quantitatively on CIR (0.50 to 0.90 micrometers) aerial film (scales 1:19,000, 1:42,000, and 1:80,000) exposed in May 1976, June 1976, and June 1979. Microdensitometer readings made on CIR film using white or blue light generally gave the best separation between saline and nonsaline range sites. The differences in microdensitometry readings among saline and nonsaline range sites were caused by less plant cover on the saline sites.

The Researcher's Journey: Scholarly Navigation of an Academic Library Web Site

ERIC Educational Resources Information Center

McCann, Steve; Ravas, Tammy; Zoellner, Kate

2010-01-01

A qualitative study of the Maureen and Mike Mansfield Library's Web site identified the ways in which students and faculty of the University of Montana used the site for research purposes. This study employed open-ended interview questions and observations to spontaneously capture a user's experience in researching topics in which they…

Maywood Interim Storage Site annual environmental report for calendar year 1991, Maywood, New Jersey. [Maywood Interim Storage Site

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

None

1992-09-01

This document describes the environmental monitoring program at the Maywood Interim Storage Site (MISS) and surrounding area, implementation of the program, and monitoring results for 1991. Environmental monitoring of MISS began in 1984 when congress added the site to the US Department of Energy's (DOE) Formerly Utilized Sites Remedial Action Program (FUSRAP). FUSRAP is a DOE program to identify and decontaminate or otherwise control sites where residual radioactive materials remain from the early years of the nation's atomic energy program or from commercial operations causing conditions that Congress has authorized DOE to remedy. The environmental monitoring program at MISS includesmore » sampling networks for radon and thoron concentrations in air; external gamma radiation-exposure; and total uranium, radium-226, radium-228, thorium-232, and thorium-230 concentrations in surface water, sediment, and groundwater. Additionally, several nonradiological parameters are measured in surface water, sediment, and groundwater. Monitoring results are compared with applicable Environmental Protection Agency standards, DOE derived concentration guides (DCGs), dose limits, and other requirements in DOE orders. Environmental standards are established to protect public health and the environment.« less

Web vulnerability study of online pharmacy sites.

PubMed

Kuzma, Joanne

2011-01-01

Consumers are increasingly using online pharmacies, but these sites may not provide an adequate level of security with the consumers' personal data. There is a gap in this research addressing the problems of security vulnerabilities in this industry. The objective is to identify the level of web application security vulnerabilities in online pharmacies and the common types of flaws, thus expanding on prior studies. Technical, managerial and legal recommendations on how to mitigate security issues are presented. The proposed four-step method first consists of choosing an online testing tool. The next steps involve choosing a list of 60 online pharmacy sites to test, and then running the software analysis to compile a list of flaws. Finally, an in-depth analysis is performed on the types of web application vulnerabilities. The majority of sites had serious vulnerabilities, with the majority of flaws being cross-site scripting or old versions of software that have not been updated. A method is proposed for the securing of web pharmacy sites, using a multi-phased approach of technical and managerial techniques together with a thorough understanding of national legal requirements for securing systems.

Non-competitive inhibition by active site binders.

PubMed

Blat, Yuval

2010-06-01

Classical enzymology has been used for generations to understand the interactions of inhibitors with their enzyme targets. Enzymology tools enabled prediction of the biological impact of inhibitors as well as the development of novel, more potent, ones. Experiments designed to examine the competition between the tested inhibitor and the enzyme substrate(s) are the tool of choice to identify inhibitors that bind in the active site. Competition between an inhibitor and a substrate is considered a strong evidence for binding of the inhibitor in the active site, while the lack of competition suggests binding to an alternative site. Nevertheless, exceptions to this notion do exist. Active site-binding inhibitors can display non-competitive inhibition patterns. This unusual behavior has been observed with enzymes utilizing an exosite for substrate binding, isomechanism enzymes, enzymes with multiple substrates and/or products and two-step binding inhibitors. In many of these cases, the mechanisms underlying the lack of competition between the substrate and the inhibitor are well understood. Tools like alternative substrates, testing the enzyme reaction in the reverse direction and monitoring inhibition time dependence can be applied to enable distinction between 'badly behaving' active site binders and true exosite inhibitors.

A 1.4-Billion Pixel Map of the Seafloor: BOEM's Mission to Visualize Dynamic Geology and Identify Natural Seep Sites in the Gulf of Mexico

NASA Astrophysics Data System (ADS)

Kramer, K.; Shedd, W. W.

2017-12-01

In May, 2017, the U.S. Department of the Interior's Bureau of Ocean Energy Management (BOEM) published a high-resolution seafloor map of the northern Gulf of Mexico region. The new map, derived from 3-D seismic surveys, provides the scientific community with enhanced resolution and reveals previously undiscovered and poorly resolved geologic features of the continental slope, salt minibasin province, abyssal plain, Mississippi Fan, and the Florida Shelf and Escarpment. It becomes an even more powerful scientific tool when paired with BOEM's public database of 35,000 seafloor features, identifying natural hydrocarbon seeps, hard grounds, mud volcanoes, sediment flows, pockmarks, slumps, and many others. BOEM has mapped the Gulf of Mexico seafloor since 1998 in a regulatory mission to identify natural oil and gas seeps and protect the coral and chemosynthetic communities growing at those sites. The nineteen-year mapping effort, still ongoing, resulted in the creation of the 1.4-billion pixel map and the seafloor features database. With these tools and continual collaboration with academia, professional scientific institutions, and the offshore energy industry, BOEM will continue to incorporate new data to update and expand these two resources on a regular basis. They can be downloaded for free from BOEM's website at https://www.boem.gov/Gulf-of-Mexico-Deepwater-Bathymetry/ and https://www.boem.gov/Seismic-Water-Bottom-Anomalies-Map-Gallery/.

Subcortical electrostimulation to identify network subserving motor control.

PubMed

Schucht, Philippe; Moritz-Gasser, Sylvie; Herbet, Guillaume; Raabe, Andreas; Duffau, Hugues

2013-11-01

Recent anatomical-functional studies have transformed our understanding of cerebral motor control away from a hierarchical structure and toward parallel and interconnected specialized circuits. Subcortical electrical stimulation during awake surgery provides a unique opportunity to identify white matter tracts involved in motor control. For the first time, this study reports the findings on motor modulatory responses evoked by subcortical stimulation and investigates the cortico-subcortical connectivity of cerebral motor control. Twenty-one selected patients were operated while awake for frontal, insular, and parietal diffuse low-grade gliomas. Subcortical electrostimulation mapping was used to search for interference with voluntary movements. The corresponding stimulation sites were localized on brain schemas using the anterior and posterior commissures method. Subcortical negative motor responses were evoked in 20/21 patients, whereas acceleration of voluntary movements and positive motor responses were observed in three and five patients, respectively. The majority of the stimulation sites were detected rostral of the corticospinal tract near the vertical anterior-commissural line, and additional sites were seen in the frontal and parietal white matter. The diverse interferences with motor function resulting in inhibition and acceleration imply a modulatory influence of the detected fiber network. The subcortical stimulation sites were distributed veil-like, anterior to the primary motor fibers, suggesting descending pathways originating from premotor areas known for negative motor response characteristics. Further stimulation sites in the parietal white matter as well as in the anterior arm of the internal capsule indicate a large-scale fronto-parietal motor control network. Copyright © 2012 Wiley Periodicals, Inc.

Selective Self-Presentation and Social Comparison Through Photographs on Social Networking Sites.

PubMed

Fox, Jesse; Vendemia, Megan A

2016-10-01

Through social media and camera phones, users enact selective self-presentation as they choose, edit, and post photographs of themselves (such as selfies) to social networking sites for an imagined audience. Photos typically focus on users' physical appearance, which may compound existing sociocultural pressures about body image. We identified users of social networking sites among a nationally representative U.S. sample (N = 1,686) and examined women's and men's photo-related behavior, including posting photos, editing photos, and feelings after engaging in upward and downward social comparison with others' photos on social networking sites. We identified some sex differences: women edited photos more frequently and felt worse after upward social comparison than men. Body image and body comparison tendency mediated these effects.

Development of a Site Comparison Index: Southeast Upland Forests

DTIC Science & Technology

2007-05-01

was recorded to 0.1 cm, and only individual trees with a DBH =/> 5 cm were tallied. Pine snags and deciduous snags were also measured. Forty-three... tree species (plus Pine Snags and Deciduous Snags) represent- ing 7031 individuals were identified at the 40 sites, ranging from 1433 Loblolly Pines...of 40 sites. Based on basal areas of 24 tree species (N=6903), pine and deciduous snags. Table 1. Ten forest communities independently

Statistical tests and identifiability conditions for pooling and analyzing multisite datasets