Optimization under Uncertainty of Site-Specific Turbine Configurations: Preprint

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

Quick, Julian; Dykes, Katherine; Graf, Peter

Uncertainty affects many aspects of wind energy plant performance and cost. In this study, we explore opportunities for site-specific turbine configuration optimization that accounts for uncertainty in the wind resource. As a demonstration, a simple empirical model for wind plant cost of energy is used in an optimization under uncertainty to examine how different risk appetites affect the optimal selection of a turbine configuration for sites of different wind resource profiles. If there is unusually high uncertainty in the site wind resource, the optimal turbine configuration diverges from the deterministic case and a generally more conservative design is obtained withmore » increasing risk aversion on the part of the designer.« less

Optimization Under Uncertainty of Site-Specific Turbine Configurations

DOE PAGES

Quick, J.; Dykes, K.; Graf, P.; ...

2016-10-03

Uncertainty affects many aspects of wind energy plant performance and cost. In this study, we explore opportunities for site-specific turbine configuration optimization that accounts for uncertainty in the wind resource. As a demonstration, a simple empirical model for wind plant cost of energy is used in an optimization under uncertainty to examine how different risk appetites affect the optimal selection of a turbine configuration for sites of different wind resource profiles. Lastly, if there is unusually high uncertainty in the site wind resource, the optimal turbine configuration diverges from the deterministic case and a generally more conservative design is obtainedmore » with increasing risk aversion on the part of the designer.« less

A Modular Vaccine Development Platform Based on Sortase-Mediated Site-Specific Tagging of Antigens onto Virus-Like Particles

PubMed Central

Tang, Shubing; Xuan, Baoqin; Ye, Xiaohua; Huang, Zhong; Qian, Zhikang

2016-01-01

Virus-like particles (VLPs) can be used as powerful nanoscale weapons to fight against virus infection. In addition to direct use as vaccines, VLPs have been extensively exploited as platforms on which to display foreign antigens for prophylactic vaccination and immunotherapeutic treatment. Unfortunately, fabrication of new chimeric VLP vaccines in a versatile, site-specific and highly efficient manner is beyond the capability of traditional VLP vaccine design approaches, genetic insertion and chemical conjugation. In this study, we described a greatly improved VLP display strategy by chemoenzymatic site-specific tailoring antigens on VLPs surface with high efficiency. Through the transpeptidation mediated by sortase A, one protein and two epitopes containing N-terminal oligoglycine were conjugated to the LPET motif on the surface of hepatitis B virus core protein (HBc) VLPs with high density. All of the new chimeric VLPs induced strong specific IgG responses. Furthermore, the chimeric VLPs with sortase A tagged enterovirus 71 (EV71) SP70 epitope could elicit effective antibodies against EV71 lethal challenging as well as the genetic insertion chimeric VLPs. The sortase A mediated chemoenzymatic site-specific tailoring of the HBc VLP approach shows great potential in new VLP vaccine design for its simplicity, site specificity, high efficiency, and versatility. PMID:27170066

Discovery of Nigri/nox and Panto/pox site-specific recombinase systems facilitates advanced genome engineering.

PubMed

Karimova, Madina; Splith, Victoria; Karpinski, Janet; Pisabarro, M Teresa; Buchholz, Frank

2016-07-22

Precise genome engineering is instrumental for biomedical research and holds great promise for future therapeutic applications. Site-specific recombinases (SSRs) are valuable tools for genome engineering due to their exceptional ability to mediate precise excision, integration and inversion of genomic DNA in living systems. The ever-increasing complexity of genome manipulations and the desire to understand the DNA-binding specificity of these enzymes are driving efforts to identify novel SSR systems with unique properties. Here, we describe two novel tyrosine site-specific recombination systems designated Nigri/nox and Panto/pox. Nigri originates from Vibrio nigripulchritudo (plasmid VIBNI_pA) and recombines its target site nox with high efficiency and high target-site selectivity, without recombining target sites of the well established SSRs Cre, Dre, Vika and VCre. Panto, derived from Pantoea sp. aB, is less specific and in addition to its native target site, pox also recombines the target site for Dre recombinase, called rox. This relaxed specificity allowed the identification of residues that are involved in target site selectivity, thereby advancing our understanding of how SSRs recognize their respective DNA targets.

Computational design of a red fluorophore ligase for site-specific protein labeling in living cells

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

Liu, Daniel S.; Nivon, Lucas G.; Richter, Florian

In this study, chemical fluorophores offer tremendous size and photophysical advantages over fluorescent proteins but are much more challenging to target to specific cellular proteins. Here, we used Rosetta-based computation to design a fluorophore ligase that accepts the red dye resorufin, starting from Escherichia coli lipoic acid ligase. X-ray crystallography showed that the design closely matched the experimental structure. Resorufin ligase catalyzed the site-specific and covalent attachment of resorufin to various cellular proteins genetically fused to a 13-aa recognition peptide in multiple mammalian cell lines and in primary cultured neurons. We used resorufin ligase to perform superresolution imaging of themore » intermediate filament protein vimentin by stimulated emission depletion and electron microscopies. This work illustrates the power of Rosetta for major redesign of enzyme specificity and introduces a tool for minimally invasive, highly specific imaging of cellular proteins by both conventional and superresolution microscopies.« less

Computational design of a red fluorophore ligase for site-specific protein labeling in living cells

DOE PAGES

Liu, Daniel S.; Nivon, Lucas G.; Richter, Florian; ...

2014-10-13

In this study, chemical fluorophores offer tremendous size and photophysical advantages over fluorescent proteins but are much more challenging to target to specific cellular proteins. Here, we used Rosetta-based computation to design a fluorophore ligase that accepts the red dye resorufin, starting from Escherichia coli lipoic acid ligase. X-ray crystallography showed that the design closely matched the experimental structure. Resorufin ligase catalyzed the site-specific and covalent attachment of resorufin to various cellular proteins genetically fused to a 13-aa recognition peptide in multiple mammalian cell lines and in primary cultured neurons. We used resorufin ligase to perform superresolution imaging of themore » intermediate filament protein vimentin by stimulated emission depletion and electron microscopies. This work illustrates the power of Rosetta for major redesign of enzyme specificity and introduces a tool for minimally invasive, highly specific imaging of cellular proteins by both conventional and superresolution microscopies.« less

77 FR 74421 - Approval and Promulgation of Air Quality Implementation Plans for PM2.5

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-14

... calculation of future year PM 2.5 design values using the SMAT assumptions contained in the modeled guidance\\4... components. Future PM 2.5 design values at specified monitoring sites were estimated by adding the future... nonattainment area, all future site-specific PM 2.5 design values were below the concentration specified in the...

Dancing in Place: Site-Specific Work

ERIC Educational Resources Information Center

Metal-Corbin, Josie

2012-01-01

In her lecture the 2012 NDA Scholar/Artist, Josie Metal-Corbin, chronicles four decades of working with artists, educators, librarians, and scientists. The kinetic language of dance and the visual impact of specific environments provide provocative opportunities for collaboration, wherein the site becomes the framework or map for the dance design.…

Site-Specific Research Conducted in Support of the Salton Sea Solar Pond Project - FY 1982 Report

NASA Technical Reports Server (NTRS)

French, R. L.; Marsh, H. E.; Roschke, E. J.; Wu, Y. C.

1984-01-01

The design and operation of a salt-gradient solar pond power plant at the Salton Sea presents problems not encountered at small research ponds that were built in the United States. The specific characteristics of the Salton Sea site and the desire to construct the pond using the local clay as a sealant represent major deviations from previous solar pond experience. The site-specific research in support of the plant design is described. The research activity included validation of the spectrophotometric light transmission measurement technique, a search for options for clarifying the turbid and colored water of the Salton Sea, development of water clarification specifications in terms common to industry practice, quantification of gas production from microbiological reactions in the ground, a determination of the combined effects of temperature and salinity on the permeation of the local clays, and a preliminary evaluation of material corrosion.

The Way of the Web: Answers to Your Questions about Web Site Marketing.

ERIC Educational Resources Information Center

Wassom, Julie

2002-01-01

Provides suggestions for effective web site marketing for child care and early education programs. Includes key considerations in designing a web site, specific elements that cause visitors to stay on and return to the site, use of interactive sites, web-site updating and revision, and use of traditional marketing activities to direct prospective…

AFB/open cycle gas turbine conceptual design study

NASA Technical Reports Server (NTRS)

Dickinson, T. W.; Tashjian, R.

1983-01-01

Applications of coal fired atmospheric fluidized bed gas turbine systems in industrial cogeneration are identified. Based on site-specific conceptual designs, the potential benefits of the AFB/gas turbine system were compared with an atmospheric fluidized design steam boiler/steam turbine system. The application of these cogeneration systems at four industrial plant sites is reviewed. A performance and benefit analysis was made along with a study of the representativeness of the sites both in regard to their own industry and compared to industry as a whole. A site was selected for the conceptual design, which included detailed site definition, AFB/gas turbine and AFB/steam turbine cogeneration system designs, detailed cost estimates, and comparative performance and benefit analysis. Market and benefit analyses identified the potential market penetration for the cogeneration technologies and quantified the potential benefits.

AFB/open cycle gas turbine conceptual design study

NASA Astrophysics Data System (ADS)

Dickinson, T. W.; Tashjian, R.

1983-09-01

Applications of coal fired atmospheric fluidized bed gas turbine systems in industrial cogeneration are identified. Based on site-specific conceptual designs, the potential benefits of the AFB/gas turbine system were compared with an atmospheric fluidized design steam boiler/steam turbine system. The application of these cogeneration systems at four industrial plant sites is reviewed. A performance and benefit analysis was made along with a study of the representativeness of the sites both in regard to their own industry and compared to industry as a whole. A site was selected for the conceptual design, which included detailed site definition, AFB/gas turbine and AFB/steam turbine cogeneration system designs, detailed cost estimates, and comparative performance and benefit analysis. Market and benefit analyses identified the potential market penetration for the cogeneration technologies and quantified the potential benefits.

Musite, a tool for global prediction of general and kinase-specific phosphorylation sites.

PubMed

Gao, Jianjiong; Thelen, Jay J; Dunker, A Keith; Xu, Dong

2010-12-01

Reversible protein phosphorylation is one of the most pervasive post-translational modifications, regulating diverse cellular processes in various organisms. High throughput experimental studies using mass spectrometry have identified many phosphorylation sites, primarily from eukaryotes. However, the vast majority of phosphorylation sites remain undiscovered, even in well studied systems. Because mass spectrometry-based experimental approaches for identifying phosphorylation events are costly, time-consuming, and biased toward abundant proteins and proteotypic peptides, in silico prediction of phosphorylation sites is potentially a useful alternative strategy for whole proteome annotation. Because of various limitations, current phosphorylation site prediction tools were not well designed for comprehensive assessment of proteomes. Here, we present a novel software tool, Musite, specifically designed for large scale predictions of both general and kinase-specific phosphorylation sites. We collected phosphoproteomics data in multiple organisms from several reliable sources and used them to train prediction models by a comprehensive machine-learning approach that integrates local sequence similarities to known phosphorylation sites, protein disorder scores, and amino acid frequencies. Application of Musite on several proteomes yielded tens of thousands of phosphorylation site predictions at a high stringency level. Cross-validation tests show that Musite achieves some improvement over existing tools in predicting general phosphorylation sites, and it is at least comparable with those for predicting kinase-specific phosphorylation sites. In Musite V1.0, we have trained general prediction models for six organisms and kinase-specific prediction models for 13 kinases or kinase families. Although the current pretrained models were not correlated with any particular cellular conditions, Musite provides a unique functionality for training customized prediction models (including condition-specific models) from users' own data. In addition, with its easily extensible open source application programming interface, Musite is aimed at being an open platform for community-based development of machine learning-based phosphorylation site prediction applications. Musite is available at http://musite.sourceforge.net/.

Air/Superfund national technical guidance study series, Volume 2. Estimation of baseline air emission at Superfund sites. Interim report(Final)

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

Not Available

1989-01-01

This volume is one in a series of manuals prepared for EPA to assist its Remedial Project Managers in the assessment of the air contaminant pathway and developing input data for risk assessment. The manual provides guidance on developing baseline-emission estimates from hazardous waste sites. Baseline-emission estimates (BEEs) are defined as emission rates estimated for a site in its undisturbed state. Specifically, the manual is intended to: Present a protocol for selecting the appropriate level of effort to characterize baseline air emissions; Assist site managers in designing an approach for BEEs; Describe useful technologies for developing site-specific baseline emission estimatesmore » (BEEs); Help site managers select the appropriate technologies for generating site-specific BEEs.« less

Discovery of Nigri/nox and Panto/pox site-specific recombinase systems facilitates advanced genome engineering

PubMed Central

Karimova, Madina; Splith, Victoria; Karpinski, Janet; Pisabarro, M. Teresa; Buchholz, Frank

2016-01-01

Precise genome engineering is instrumental for biomedical research and holds great promise for future therapeutic applications. Site-specific recombinases (SSRs) are valuable tools for genome engineering due to their exceptional ability to mediate precise excision, integration and inversion of genomic DNA in living systems. The ever-increasing complexity of genome manipulations and the desire to understand the DNA-binding specificity of these enzymes are driving efforts to identify novel SSR systems with unique properties. Here, we describe two novel tyrosine site-specific recombination systems designated Nigri/nox and Panto/pox. Nigri originates from Vibrio nigripulchritudo (plasmid VIBNI_pA) and recombines its target site nox with high efficiency and high target-site selectivity, without recombining target sites of the well established SSRs Cre, Dre, Vika and VCre. Panto, derived from Pantoea sp. aB, is less specific and in addition to its native target site, pox also recombines the target site for Dre recombinase, called rox. This relaxed specificity allowed the identification of residues that are involved in target site selectivity, thereby advancing our understanding of how SSRs recognize their respective DNA targets. PMID:27444945

Sensing Site-Specific Variability in Soil and Plant Phosphorus and Other Mineral Nutrients by X-Ray Fluorescence Spectrometry

USDA-ARS?s Scientific Manuscript database

Detection and rapid response to in-season changes of soil nutrient availability and plant needs with weather conditions and site-specific characteristics are essential to the optimal performance of an agronomic crop production system. With recent advances in material science, detector design and se...

Design, development and evaluation of a tree planting-site-specific fumigant applicator

USDA-ARS?s Scientific Manuscript database

The goal of this research was to use recent advances in the global positioning system (GPS) and computer technology to apply just the right amount of fumigant where it is most needed (i.e., tree-planting-site-specific application) to decrease the incidence of replant disease, and achieve the environ...

29 CFR 1926.752 - Site layout, site-specific erection plan and construction sequence.

Code of Federal Regulations, 2011 CFR

2011-07-01

... standard test method of field-cured samples, either 75 percent of the intended minimum compressive design... the basis of an appropriate ASTM standard test method of field-cured samples, either 75 percent of the intended minimum compressive design strength or sufficient strength to support the loads imposed during...

29 CFR 1926.752 - Site layout, site-specific erection plan and construction sequence.

Code of Federal Regulations, 2013 CFR

2013-07-01

... standard test method of field-cured samples, either 75 percent of the intended minimum compressive design... the basis of an appropriate ASTM standard test method of field-cured samples, either 75 percent of the intended minimum compressive design strength or sufficient strength to support the loads imposed during...

29 CFR 1926.752 - Site layout, site-specific erection plan and construction sequence.

Code of Federal Regulations, 2012 CFR

2012-07-01

... standard test method of field-cured samples, either 75 percent of the intended minimum compressive design... the basis of an appropriate ASTM standard test method of field-cured samples, either 75 percent of the intended minimum compressive design strength or sufficient strength to support the loads imposed during...

29 CFR 1926.752 - Site layout, site-specific erection plan and construction sequence.

Code of Federal Regulations, 2010 CFR

2010-07-01

... standard test method of field-cured samples, either 75 percent of the intended minimum compressive design... the basis of an appropriate ASTM standard test method of field-cured samples, either 75 percent of the intended minimum compressive design strength or sufficient strength to support the loads imposed during...

29 CFR 1926.752 - Site layout, site-specific erection plan and construction sequence.

Code of Federal Regulations, 2014 CFR

2014-07-01

... standard test method of field-cured samples, either 75 percent of the intended minimum compressive design... the basis of an appropriate ASTM standard test method of field-cured samples, either 75 percent of the intended minimum compressive design strength or sufficient strength to support the loads imposed during...

Anchored plasticity opens doors for selective inhibitor design in nitric oxide synthase

PubMed Central

Garcin, Elsa D.; Arvai, Andrew S.; Rosenfeld, Robin J.; Kroeger, Matt D.; Crane, Brian R.; Andersson, Gunilla; Andrews, Glen; Hamley, Peter J.; Mallinder, Philip R.; Nicholls, David J.; St-Gallay, Stephen A.; Tinker, Alan C.; Gensmantel, Nigel P.; Mete, Antonio; Cheshire, David R.; Connolly, Stephen; Stuehr, Dennis J.; Åberg, Anders; Wallace, Alan V.; Tainer, John A.; Getzoff, Elizabeth D.

2008-01-01

Nitric oxide synthase (NOS) enzymes synthesize nitric oxide, a signal for vasodilatation and neurotransmission at low levels, and a defensive cytotoxin at higher levels. The high active-site conservation among all three NOS isozymes hinders the design of selective NOS inhibitors to treat inflammation, arthritis, stroke, septic shock, and cancer. Our structural and mutagenesis results identified an isozyme-specific induced-fit binding mode linking a cascade of conformational changes to a novel specificity pocket. Plasticity of an isozyme-specific triad of distant second- and third-shell residues modulates conformational changes of invariant first-shell residues to determine inhibitor selectivity. To design potent and selective NOS inhibitors, we developed the anchored plasticity approach: anchor an inhibitor core in a conserved binding pocket, then extend rigid bulky substituents towards remote specificity pockets, accessible upon conformational changes of flexible residues. This approach exemplifies general principles for the design of selective enzyme inhibitors that overcome strong active-site conservation. PMID:18849972

NGA-West 2 GMPE average site coefficients for use in earthquake-resistant design

USGS Publications Warehouse

Borcherdt, Roger D.

2015-01-01

Site coefficients corresponding to those in tables 11.4–1 and 11.4–2 of Minimum Design Loads for Buildings and Other Structures published by the American Society of Civil Engineers (Standard ASCE/SEI 7-10) are derived from four of the Next Generation Attenuation West2 (NGA-W2) Ground-Motion Prediction Equations (GMPEs). The resulting coefficients are compared with those derived by other researchers and those derived from the NGA-West1 database. The derivation of the NGA-W2 average site coefficients provides a simple procedure to update site coefficients with each update in the Maximum Considered Earthquake Response MCER maps. The simple procedure yields average site coefficients consistent with those derived for site-specific design purposes. The NGA-W2 GMPEs provide simple scale factors to reduce conservatism in current simplified design procedures.

Geohydrology of the Antelope Valley Area, California and design for a ground-water-quality monitoring network

USGS Publications Warehouse

Duell, L.F.

1987-01-01

A basinwide ideal network and an actual network were designed to identify ambient groundwater quality, trends in groundwater quality, and degree of threat from potential pollution sources in Antelope Valley, California. In general, throughout the valley groundwater quality has remained unchanged, and no specific trends are apparent. The main source of groundwater for the valley is generally suitable for domestic, irrigation, and most industrial uses. Water quality data for selected constituents of some network wells and surface-water sites are presented. The ideal network of 77 sites was selected on the basis of site-specific criteria, geohydrology, and current land use (agricultural, residential, and industrial). These sites were used as a guide in the design of the actual network consisting of 44 existing wells. Wells are currently being monitored and were selected whenever possible because of budgetary constraints. Of the remaining ideal sites, 20 have existing wells not part of a current water quality network, and 13 are locations where no wells exist. The methodology used for the selection of sites, constituents monitored, and frequency of analysis will enable network users to make appropriate future changes to the monitoring network. (USGS)

Dengue Virus NS2B/NS3 Protease Inhibitors Exploiting the Prime Side.

PubMed

Lin, Kuan-Hung; Ali, Akbar; Rusere, Linah; Soumana, Djade I; Kurt Yilmaz, Nese; Schiffer, Celia A

2017-05-15

The mosquito-transmitted dengue virus (DENV) infects millions of people in tropical and subtropical regions. Maturation of DENV particles requires proper cleavage of the viral polyprotein, including processing of 8 of the 13 substrate cleavage sites by dengue virus NS2B/NS3 protease. With no available direct-acting antiviral targeting DENV, NS2/NS3 protease is a promising target for inhibitor design. Current design efforts focus on the nonprime side of the DENV protease active site, resulting in highly hydrophilic and nonspecific scaffolds. However, the prime side also significantly modulates DENV protease binding affinity, as revealed by engineering the binding loop of aprotinin, a small protein with high affinity for DENV protease. In this study, we designed a series of cyclic peptides interacting with both sides of the active site as inhibitors of dengue virus protease. The design was based on two aprotinin loops and aimed to leverage both key specific interactions of substrate sequences and the entropic advantage driving aprotinin's high affinity. By optimizing the cyclization linker, length, and amino acid sequence, the tightest cyclic peptide achieved a K i value of 2.9 μM against DENV3 wild-type (WT) protease. These inhibitors provide proof of concept that both sides of DENV protease active site can be exploited to potentially achieve specificity and lower hydrophilicity in the design of inhibitors targeting DENV. IMPORTANCE Viruses of the flaviviral family, including DENV and Zika virus transmitted by Aedes aegypti , continue to be a threat to global health by causing major outbreaks in tropical and subtropical regions, with no available direct-acting antivirals for treatment. A better understanding of the molecular requirements for the design of potent and specific inhibitors against flaviviral proteins will contribute to the development of targeted therapies for infections by these viruses. The cyclic peptides reported here as DENV protease inhibitors provide novel scaffolds that enable exploiting the prime side of the protease active site, with the aim of achieving better specificity and lower hydrophilicity than those of current scaffolds in the design of antiflaviviral inhibitors. Copyright © 2017 American Society for Microbiology.

Low-cost modular array-field designs for flat-panel and concentrator photovoltaic systems

NASA Astrophysics Data System (ADS)

Post, H. N.; Carmichael, D. C.; Alexander, G.; Castle, J. A.

1982-09-01

Described are the design and development of low-cost, modular array fields for flat-panel and concentrator photovoltaic (PV) systems. The objective of the work was to reduce substantially the cost of the array-field Balance-of-System (BOS) subsystems and site-specific design costs as compared to previous PV installations. These subsystems include site preparation, foundations, support structures, electrical writing, grounding, lightning protection, electromagnetic interference considerations, and controls. To reduce these BOS and design costs, standardized modular (building-block) designs for flat-panel and concentrator array fields have been developed that are fully integrated and optimized for lowest life-cycle costs. Using drawings and specifications now available, these building-block designs can be used in multiples to install various size array fields. The developed designs are immediately applicable (1982) and reduce the array-field BOS costs to a fraction of previous costs.

MOBILE ON-SITE RECYCLING OF METALWORKING FLUIDS

EPA Science Inventory

Product quality, waste reduction, and economic issues were evaluated for a technology designed to recycle metalworking fluids. mulsion-type fluids were tested at two sites and a synthetic fluid was tested at a third site. he specific recycling unit evaluated is based on the techn...

Implications of NGA for NEHRP site coefficients

USGS Publications Warehouse

Borcherdt, Roger D.

2012-01-01

Three proposals are provided to update tables 11.4-1 and 11.4-2 of Minimum Design Loads for Buildings and Other Structures (7-10), by the American Society of Civil Engineers (2010) (ASCE/SEI 7-10), with site coefficients implied directly by NGA (Next Generation Attenuation) ground motion prediction equations (GMPEs). Proposals include a recommendation to use straight-line interpolation to infer site coefficients at intermediate values of ̅vs (average shear velocity). Site coefficients are recommended to ensure consistency with ASCE/SEI 7-10 MCER (Maximum Considered Earthquake) seismic-design maps and simplified site-specific design spectra procedures requiring site classes with associated tabulated site coefficients and a reference site class with unity site coefficients. Recommended site coefficients are confirmed by independent observations of average site amplification coefficients inferred with respect to an average ground condition consistent with that used for the MCER maps. The NGA coefficients recommended for consideration are implied directly by the NGA GMPEs and do not require introduction of additional models.

SU-E-T-760: Tolerance Design for Site-Specific Range in Proton Patient QA Process Using the Six Sigma Model

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

Lah, J; Shin, D; Kim, G

Purpose: To show how tolerance design and tolerancing approaches can be used to predict and improve the site-specific range in patient QA process in implementing the Six Sigma. Methods: In this study, patient QA plans were selected according to 6 site-treatment groups: head &neck (94 cases), spine (76 cases), lung (89 cases), liver (53 cases), pancreas (55 cases), and prostate (121 cases), treated between 2007 and 2013. We evaluated a model of the Six Sigma that determines allowable deviations in design parameters and process variables in patient-specific QA, where possible, tolerance may be loosened, then customized if it necessary tomore » meet the functional requirements. A Six Sigma problem-solving methodology is known as DMAIC phases, which are used stand for: Define a problem or improvement opportunity, Measure process performance, Analyze the process to determine the root causes of poor performance, Improve the process by fixing root causes, Control the improved process to hold the gains. Results: The process capability for patient-specific range QA is 0.65 with only ±1 mm of tolerance criteria. Our results suggested the tolerance level of ±2–3 mm for prostate and liver cases and ±5 mm for lung cases. We found that customized tolerance between calculated and measured range reduce that patient QA plan failure and almost all sites had failure rates less than 1%. The average QA time also improved from 2 hr to less than 1 hr for all including planning and converting process, depth-dose measurement and evaluation. Conclusion: The objective of tolerance design is to achieve optimization beyond that obtained through QA process improvement and statistical analysis function detailing to implement a Six Sigma capable design.« less

The Impact of a Simulation and Problem-Based Learning Design Project on Student Learning and Teamwork Skills. CSE Technical Report.

ERIC Educational Resources Information Center

Chung, Gregory K. W. K.

This study examined a civil engineering capstone course that embedded a sophisticated simulation-based task within instruction. Students (n=28) were required to conduct a hazardous waste site investigation using simulation software designed specifically for the course (Interactive Site Investigation Software) (ISIS). The software simulated…

A rhodium(III) complex for high-affinity DNA base-pair mismatch recognition

PubMed Central

Junicke, Henrik; Hart, Jonathan R.; Kisko, Jennifer; Glebov, Oleg; Kirsch, Ilan R.; Barton, Jacqueline K.

2003-01-01

A rhodium(III) complex, rac-[Rh(bpy)2phzi]3+ (bpy, 2,2′-bipyridine; phzi, benzo[a]phenazine-5,6-quinone diimine) has been designed as a sterically demanding intercalator targeted to destabilized mismatched sites in double-helical DNA. The complex is readily synthesized by condensation of the phenazine quinone with the corresponding diammine complex. Upon photoactivation, the complex promotes direct strand scission at single-base mismatch sites within the DNA duplex. As with the parent mismatch-specific reagent, [Rh(bpy)2(chrysi)]3+ [chrysene-5,6-quinone diimine (chrysi)], mismatch selectivity depends on the helix destabilization associated with mispairing. Unlike the parent chrysi complex, the phzi analogue binds and cleaves with high affinity and efficiency. The specific binding constants for CA, CC, and CT mismatches within a 31-mer oligonucleotide duplex are 0.3, 1, and 6 × 107 M−1, respectively; site-specific photocleavage is evident at nanomolar concentrations. Moreover, the specificity, defined as the ratio in binding affinities for mispaired vs. well paired sites, is maintained. The increase in affinity is attributed to greater stability in the mismatched site associated with stacking by the heterocyclic aromatic ligand. The high-affinity complex is also applied in the differential cleavage of DNA obtained from cell lines deficient in mismatch repair vs. those proficient in mismatch repair. Agreement is found between photocleavage by the mismatch-specific probes and deficiency in mismatch repair. This mismatch-specific targeting, therefore, offers a potential strategy for new chemotherapeutic design. PMID:12610209

Preliminary design of a solar central receiver for a site-specific repowering application (Saguaro Power Plant). Volume III. Specifications. Final report, October 1982-September 1983

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

Weber, E.R.

1983-09-01

This volume on specifications for the Saguaro Power Plant includes the following: subsystem interface definition document; solar collector subsystem specification; receiver specification; thermal energy storage specification; solar steam generator specification; and master control system specification.

Computational Tools for Allosteric Drug Discovery: Site Identification and Focus Library Design.

PubMed

Huang, Wenkang; Nussinov, Ruth; Zhang, Jian

2017-01-01

Allostery is an intrinsic phenomenon of biological macromolecules involving regulation and/or signal transduction induced by a ligand binding to an allosteric site distinct from a molecule's active site. Allosteric drugs are currently receiving increased attention in drug discovery because drugs that target allosteric sites can provide important advantages over the corresponding orthosteric drugs including specific subtype selectivity within receptor families. Consequently, targeting allosteric sites, instead of orthosteric sites, can reduce drug-related side effects and toxicity. On the down side, allosteric drug discovery can be more challenging than traditional orthosteric drug discovery due to difficulties associated with determining the locations of allosteric sites and designing drugs based on these sites and the need for the allosteric effects to propagate through the structure, reach the ligand binding site and elicit a conformational change. In this study, we present computational tools ranging from the identification of potential allosteric sites to the design of "allosteric-like" modulator libraries. These tools may be particularly useful for allosteric drug discovery.

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

ERIC Educational Resources Information Center

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

2014-01-01

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

Targeted Nanotechnology for Cancer Imaging

PubMed Central

Toy, Randall; Bauer, Lisa; Hoimes, Christopher; Ghaghada, Ketan B.; Karathanasis, Efstathios

2014-01-01

Targeted nanoparticle imaging agents provide many benefits and new opportunities to facilitate accurate diagnosis of cancer and significantly impact patient outcome. Due to the highly engineerable nature of nanotechnology, targeted nanoparticles exhibit significant advantages including increased contrast sensitivity, binding avidity and targeting specificity. Considering the various nanoparticle designs and their adjustable ability to target a specific site and generate detectable signals, nanoparticles can be optimally designed in terms of biophysical interactions (i.e., intravascular and interstitial transport) and biochemical interactions (i.e., targeting avidity towards cancer-related biomarkers) for site-specific detection of very distinct microenvironments. This review seeks to illustrate that the design of a nanoparticle dictates its in vivo journey and targeting of hard-to-reach cancer sites, facilitating early and accurate diagnosis and interrogation of the most aggressive forms of cancer. We will report various targeted nanoparticles for cancer imaging using X-ray computed tomography, ultrasound, magnetic resonance imaging, nuclear imaging and optical imaging. Finally, to realize the full potential of targeted nanotechnology for cancer imaging, we will describe the challenges and opportunities for the clinical translation and widespread adaptation of targeted nanoparticles imaging agents. PMID:25116445

THE OHIO RIVER BASIN ENERGY FACILITY SITING MODEL. VOLUME II: SITES AND ON-LINE DATES

EPA Science Inventory

The report was prepared as part of the Ohio River Basin Energy Study (ORBES), a multidisciplinary policy research program. The siting model developed for ORBES is specifically designed for regional policy analysis. The region includes 423 counties in an area that consists of all ...

Investigation of seismicity and related effects at NASA Ames-Dryden Flight Research Facility, Computer Center, Edwards, California

NASA Technical Reports Server (NTRS)

Cousineau, R. D.; Crook, R., Jr.; Leeds, D. J.

1985-01-01

This report discusses a geological and seismological investigation of the NASA Ames-Dryden Flight Research Facility site at Edwards, California. Results are presented as seismic design criteria, with design values of the pertinent ground motion parameters, probability of recurrence, and recommended analogous time-history accelerograms with their corresponding spectra. The recommendations apply specifically to the Dryden site and should not be extrapolated to other sites with varying foundation and geologic conditions or different seismic environments.

A divide-and-conquer approach to determine the Pareto frontier for optimization of protein engineering experiments.

PubMed

He, Lu; Friedman, Alan M; Bailey-Kellogg, Chris

2012-03-01

In developing improved protein variants by site-directed mutagenesis or recombination, there are often competing objectives that must be considered in designing an experiment (selecting mutations or breakpoints): stability versus novelty, affinity versus specificity, activity versus immunogenicity, and so forth. Pareto optimal experimental designs make the best trade-offs between competing objectives. Such designs are not "dominated"; that is, no other design is better than a Pareto optimal design for one objective without being worse for another objective. Our goal is to produce all the Pareto optimal designs (the Pareto frontier), to characterize the trade-offs and suggest designs most worth considering, but to avoid explicitly considering the large number of dominated designs. To do so, we develop a divide-and-conquer algorithm, Protein Engineering Pareto FRontier (PEPFR), that hierarchically subdivides the objective space, using appropriate dynamic programming or integer programming methods to optimize designs in different regions. This divide-and-conquer approach is efficient in that the number of divisions (and thus calls to the optimizer) is directly proportional to the number of Pareto optimal designs. We demonstrate PEPFR with three protein engineering case studies: site-directed recombination for stability and diversity via dynamic programming, site-directed mutagenesis of interacting proteins for affinity and specificity via integer programming, and site-directed mutagenesis of a therapeutic protein for activity and immunogenicity via integer programming. We show that PEPFR is able to effectively produce all the Pareto optimal designs, discovering many more designs than previous methods. The characterization of the Pareto frontier provides additional insights into the local stability of design choices as well as global trends leading to trade-offs between competing criteria. Copyright © 2011 Wiley Periodicals, Inc.

MODEST: a web-based design tool for oligonucleotide-mediated genome engineering and recombineering

PubMed Central

Bonde, Mads T.; Klausen, Michael S.; Anderson, Mads V.; Wallin, Annika I.N.; Wang, Harris H.; Sommer, Morten O.A.

2014-01-01

Recombineering and multiplex automated genome engineering (MAGE) offer the possibility to rapidly modify multiple genomic or plasmid sites at high efficiencies. This enables efficient creation of genetic variants including both single mutants with specifically targeted modifications as well as combinatorial cell libraries. Manual design of oligonucleotides for these approaches can be tedious, time-consuming, and may not be practical for larger projects targeting many genomic sites. At present, the change from a desired phenotype (e.g. altered expression of a specific protein) to a designed MAGE oligo, which confers the corresponding genetic change, is performed manually. To address these challenges, we have developed the MAGE Oligo Design Tool (MODEST). This web-based tool allows designing of MAGE oligos for (i) tuning translation rates by modifying the ribosomal binding site, (ii) generating translational gene knockouts and (iii) introducing other coding or non-coding mutations, including amino acid substitutions, insertions, deletions and point mutations. The tool automatically designs oligos based on desired genotypic or phenotypic changes defined by the user, which can be used for high efficiency recombineering and MAGE. MODEST is available for free and is open to all users at http://modest.biosustain.dtu.dk. PMID:24838561

Innovative vitrification for soil remediation

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

Jetta, N.W.; Patten, J.S.; Hart, J.G.

1995-12-01

The objective of this DOE demonstration program is to validate the performance and operation of the Vortec Cyclone Melting System (CMS{trademark}) for the processing of LLW contaminated soils found at DOE sites. This DOE vitrification demonstration project has successfully progressed through the first two phases. Phase 1 consisted of pilot scale testing with surrogate wastes and the conceptual design of a process plant operating at a generic DOE site. The objective of Phase 2, which is scheduled to be completed the end of FY 95, is to develop a definitive process plant design for the treatment of wastes at amore » specific DOE facility. During Phase 2, a site specific design was developed for the processing of LLW soils and muds containing TSCA organics and RCRA metal contaminants. Phase 3 will consist of a full scale demonstration at the DOE gaseous diffusion plant located in Paducah, KY. Several DOE sites were evaluated for potential application of the technology. Paducah was selected for the demonstration program because of their urgent waste remediation needs as well as their strong management and cost sharing financial support for the project. During Phase 2, the basic nitrification process design was modified to meet the specific needs of the new waste streams available at Paducah. The system design developed for Paducah has significantly enhanced the processing capabilities of the Vortec vitrification process. The overall system design now includes the capability to shred entire drums and drum packs containing mud, concrete, plastics and PCB`s as well as bulk waste materials. This enhanced processing capability will substantially expand the total DOE waste remediation applications of the technology.« less

Rational approaches for engineering novel functionalities in carbon-carbon bond forming enzymes

PubMed Central

Baker, Perrin; Seah, Stephen Y. K.

2012-01-01

Enzymes that catalyze carbon-carbon bond formation can be exploited as biocatalyst for synthetic organic chemistry. However, natural enzymes frequently do not possess the required properties or specificities to catalyze industrially useful transformations. This mini-review describes recent work using knowledge-guided site-specific mutagenesis of key active site residues to alter substrate specificity, stereospecificity and reaction specificity of these enzymes. In addition, examples of de novo designed enzymes that catalyze C-C bond reactions not found in nature will be discussed. PMID:24688644

Conservation planning for offsetting the impacts of development: a case study of biodiversity and renewable energy in the Mojave Desert

USGS Publications Warehouse

Kreitler, Jason R.; Schloss, Carrie A.; Soong, Oliver; Lee Hannah,; Davis, Frank W.

2015-01-01

Balancing society’s competing needs of development and conservation requires careful consideration of tradeoffs. Renewable energy development and biodiversity conservation are often considered beneficial environmental goals. The direct footprint and disturbance of renewable energy, however, can displace species’ habitat and negatively impact populations and natural communities if sited without ecological consideration. Offsets have emerged as a potentially useful tool to mitigate residual impacts after trying to avoid, minimize, or restore affected sites. Yet the problem of efficiently designing a set of offset sites becomes increasingly complex where many species or many sites are involved. Spatial conservation prioritization tools are designed to handle this problem, but have seen little application to offset siting and analysis. To address this need we designed an offset siting support tool for the Desert Renewable Energy Conservation Plan (DRECP) of California, and present a case study of hypothetical impacts from solar development in the Western Mojave subsection. We compare two offset scenarios designed to mitigate a hypothetical 15,331 ha derived from proposed utility-scale solar energy development (USSED) projects. The first scenario prioritizes offsets based precisely on impacted features, while the second scenario offsets impacts to maximize biodiversity conservation gains in the region. The two methods only agree on 28% of their prioritized sites and differ in meeting species-specific offset goals. Differences between the two scenarios highlight the importance of clearly specifying choices and priorities for offset siting and mitigation in general. Similarly, the effects of background climate and land use change may lessen the durability or effectiveness of offsets if not considered. Our offset siting support tool was designed specifically for the DRECP area, but with minor code modification could work well in other offset analyses, and could provide continuing support for a potentially innovative mitigation solution to environmental impacts.

Conservation Planning for Offsetting the Impacts of Development: A Case Study of Biodiversity and Renewable Energy in the Mojave Desert.

PubMed

Kreitler, Jason; Schloss, Carrie A; Soong, Oliver; Hannah, Lee; Davis, Frank W

2015-01-01

Balancing society's competing needs of development and conservation requires careful consideration of tradeoffs. Renewable energy development and biodiversity conservation are often considered beneficial environmental goals. The direct footprint and disturbance of renewable energy, however, can displace species' habitat and negatively impact populations and natural communities if sited without ecological consideration. Offsets have emerged as a potentially useful tool to mitigate residual impacts after trying to avoid, minimize, or restore affected sites. Yet the problem of efficiently designing a set of offset sites becomes increasingly complex where many species or many sites are involved. Spatial conservation prioritization tools are designed to handle this problem, but have seen little application to offset siting and analysis. To address this need we designed an offset siting support tool for the Desert Renewable Energy Conservation Plan (DRECP) of California, and present a case study of hypothetical impacts from solar development in the Western Mojave subsection. We compare two offset scenarios designed to mitigate a hypothetical 15,331 ha derived from proposed utility-scale solar energy development (USSED) projects. The first scenario prioritizes offsets based precisely on impacted features, while the second scenario offsets impacts to maximize biodiversity conservation gains in the region. The two methods only agree on 28% of their prioritized sites and differ in meeting species-specific offset goals. Differences between the two scenarios highlight the importance of clearly specifying choices and priorities for offset siting and mitigation in general. Similarly, the effects of background climate and land use change may lessen the durability or effectiveness of offsets if not considered. Our offset siting support tool was designed specifically for the DRECP area, but with minor code modification could work well in other offset analyses, and could provide continuing support for a potentially innovative mitigation solution to environmental impacts.

Conservation Planning for Offsetting the Impacts of Development: A Case Study of Biodiversity and Renewable Energy in the Mojave Desert

PubMed Central

Kreitler, Jason; Schloss, Carrie A.; Soong, Oliver; Hannah, Lee; Davis, Frank W.

2015-01-01

Balancing society’s competing needs of development and conservation requires careful consideration of tradeoffs. Renewable energy development and biodiversity conservation are often considered beneficial environmental goals. The direct footprint and disturbance of renewable energy, however, can displace species’ habitat and negatively impact populations and natural communities if sited without ecological consideration. Offsets have emerged as a potentially useful tool to mitigate residual impacts after trying to avoid, minimize, or restore affected sites. Yet the problem of efficiently designing a set of offset sites becomes increasingly complex where many species or many sites are involved. Spatial conservation prioritization tools are designed to handle this problem, but have seen little application to offset siting and analysis. To address this need we designed an offset siting support tool for the Desert Renewable Energy Conservation Plan (DRECP) of California, and present a case study of hypothetical impacts from solar development in the Western Mojave subsection. We compare two offset scenarios designed to mitigate a hypothetical 15,331 ha derived from proposed utility-scale solar energy development (USSED) projects. The first scenario prioritizes offsets based precisely on impacted features, while the second scenario offsets impacts to maximize biodiversity conservation gains in the region. The two methods only agree on 28% of their prioritized sites and differ in meeting species-specific offset goals. Differences between the two scenarios highlight the importance of clearly specifying choices and priorities for offset siting and mitigation in general. Similarly, the effects of background climate and land use change may lessen the durability or effectiveness of offsets if not considered. Our offset siting support tool was designed specifically for the DRECP area, but with minor code modification could work well in other offset analyses, and could provide continuing support for a potentially innovative mitigation solution to environmental impacts. PMID:26529595

A terrain-based paired-site sampling design to assess biodiversity losses from eastern hemlock decline

USGS Publications Warehouse

Young, J.A.; Smith, D.R.; Snyder, C.D.; Lemarie, D.P.

2002-01-01

Biodiversity surveys are often hampered by the inability to control extraneous sources of variability introduced into comparisons of populations across a heterogenous landscape. If not specifically accounted for a priori, this noise can weaken comparisons between sites, and can make it difficult to draw inferences about specific ecological processes. We developed a terrain-based, paired-site sampling design to analyze differences in aquatic biodiversity between streams draining eastern hemlock (Tsuga canadensis) forests, and those draining mixed hardwood forests in Delaware Water Gap National Recreation Area (USA). The goal of this design was to minimize variance due to terrain influences on stream communities, while representing the range of hemlock dominated stream environments present in the park. We used geographic information systems (GIS) and cluster analysis to define and partition hemlock dominated streams into terrain types based on topographic variables and stream order. We computed similarity of forest stands within terrain types and used this information to pair hemlock-dominated streams with hardwood counterparts prior to sampling. We evaluated the effectiveness of the design through power analysis and found that power to detect differences in aquatic invertebrate taxa richness was highest when sites were paired and terrain type was included as a factor in the analysis. Precision of the estimated difference in mean richness was nearly doubled using the terrain-based, paired site design in comparison to other evaluated designs. Use of this method allowed us to sample stream communities representative of park-wide forest conditions while effectively controlling for landscape variability.

Preliminary design of a solar central receiver for site-specific repowering application (Saguaro Power Plant). Volume II. Preliminary design. Final report, October 1982-September 1983

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

Weber, E.R.

1983-09-01

The solar central receiver technology, site, and specific unit for repowering were selected in prior analyses and studies. The objectives of this preliminary design study were to: develop a solar central receiver repowering design for Saguaro that (1) has potential to be economically competitive with fossil fueled plants in near and long term applications, (2) has the greatest chance for completion without further government funding, (3) will further define technical and economic feasibility of a 66 MWe gross size plant that is adequate to meet the requirements for utility and industrial process heat applications, (4) can potentially be constructed andmore » operated within the next five years, and (5) incorporates solar central receiver technology and represents state-of-the-art development. This volume on the preliminary design includes the following sections: executive summary; introduction; changes from advanced conceptual design; preliminary design; system characteristics; economic analysis; and development plan.« less

Part 2: Conserving and Planting Trees at Development Sites

Treesearch

Karen Cappiella; Tom Schueler; Tiffany Wright

2006-01-01

This manual presents specific ways to enable developers, engineers or landscape architects to incorporate more trees into a development site. The proposed approach focuses on protecting existing trees, planting trees in storm water treatment practices, and planting trees in other open spaces at the development site. This manual introduces conceptual designs for storm...

Employer-Sponsored Child Care Models and Related Issues.

ERIC Educational Resources Information Center

Renfroe, Martha Lou

This study was designed to describe the different models of Employer-Sponsored Child Care (ESCC) available to employers and child care professionals. Examples of specific child care programs sponsored by employers are described, and five ESCC models are identified: on-site and off-site centers for a single employer, off-site centers for multiple…

Steric and thermodynamic limits of design for the incorporation of large unnatural amino acids in aminoacyl-tRNA synthetase enzymes.

PubMed

Armen, Roger S; Schiller, Stefan M; Brooks, Charles L

2010-06-01

Orthogonal aminoacyl-tRNA synthetase/tRNA pairs from archaea have been evolved to facilitate site specific in vivo incorporation of unnatural amino acids into proteins in Escherichia coli. Using this approach, unnatural amino acids have been successfully incorporated with high translational efficiency and fidelity. In this study, CHARMM-based molecular docking and free energy calculations were used to evaluate rational design of specific protein-ligand interactions for aminoacyl-tRNA synthetases. A series of novel unnatural amino acid ligands were docked into the p-benzoyl-L-phenylalanine tRNA synthetase, which revealed that the binding pocket of the enzyme does not provide sufficient space for significantly larger ligands. Specific binding site residues were mutated to alanine to create additional space to accommodate larger target ligands, and then mutations were introduced to improve binding free energy. This approach was used to redesign binding sites for several different target ligands, which were then tested against the standard 20 amino acids to verify target specificity. Only the synthetase designed to bind Man-alpha-O-Tyr was predicted to be sufficiently selective for the target ligand and also thermodynamically stable. Our study suggests that extensive redesign of the tRNA synthatase binding pocket for large bulky ligands may be quite thermodynamically unfavorable.

Estimating occupancy rates with imperfect detection under complex survey designs

EPA Science Inventory

Monitoring the occurrence of specific amphibian species is of interest. Typically, the monitoring design is a complex design that involves stratification and unequal probability of selection. When conducting field visits to selected sites, a common problem is that during a singl...

An industrialized construction approach to concrete superstructures for bridges.

DOT National Transportation Integrated Search

1974-01-01

The objective of this study was to develop drawings for a specific site or sites that incorporated the best concepts of industrialized bridge superstructure construction, that is, great emphasis was placed upon the use of modular design and assembly ...

The Ohio River Basin energy facility siting model. Volume 1: Methodology

NASA Astrophysics Data System (ADS)

Fowler, G. L.; Bailey, R. E.; Gordon, S. I.; Jansen, S. D.; Randolph, J. C.; Jones, W. W.

1981-04-01

The siting model developed for ORBES is specifically designed for regional policy analysis. The region includes 423 counties in an area that consists of all of Kentucky and substantial portions of Illinois, Indiana, Ohio, Pennsylvania, and West Virginia.

10 CFR 963.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... the sealing of shafts and ramps, except those openings that may be designed for ventilation or... repository, as defined by this section, at the Yucca Mountain site. Design means a description of the... includes the engineered barrier system. Design bases means that information that identifies the specific...

10 CFR 963.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... the sealing of shafts and ramps, except those openings that may be designed for ventilation or... repository, as defined by this section, at the Yucca Mountain site. Design means a description of the... includes the engineered barrier system. Design bases means that information that identifies the specific...

10 CFR 963.2 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... the sealing of shafts and ramps, except those openings that may be designed for ventilation or... repository, as defined by this section, at the Yucca Mountain site. Design means a description of the... includes the engineered barrier system. Design bases means that information that identifies the specific...

10 CFR 963.2 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... the sealing of shafts and ramps, except those openings that may be designed for ventilation or... repository, as defined by this section, at the Yucca Mountain site. Design means a description of the... includes the engineered barrier system. Design bases means that information that identifies the specific...

10 CFR 963.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... the sealing of shafts and ramps, except those openings that may be designed for ventilation or... repository, as defined by this section, at the Yucca Mountain site. Design means a description of the... includes the engineered barrier system. Design bases means that information that identifies the specific...

NASA/MSFC Large Stretch Press Study

NASA Technical Reports Server (NTRS)

Choate, M. W.; Nealson, W. P.; Jay, G. C.; Buss, W. D.

1985-01-01

The purpose of this study was to: A. assess and document the advantages/disadvantages of a government agency investment in a large stretch form press on the order of 5000 tons capacity (per jaw); B. develop a procurement specification for the press; and C. provide trade study data that will permit an optimum site location. Tasks were separated into four major elements: cost study, user survey, site selection, and press design/procurement specification.

Maritime Spatial Planning supported by systematic site selection: Applying Marxan for offshore wind power in the western Baltic Sea

PubMed Central

Dahl, Karsten; Mohn, Christian

2018-01-01

The development of offshore wind energy and other competing interests in sea space are a major incentive for designating marine and coastal areas for specific human activities. Maritime Spatial Planning (MSP) considers human activities at sea in a more integrated way by analysing and designating spatial and temporal distributions of human activities based on ecological, economic and social targets. However, specific tools supporting spatial decisions at sea incorporating all relevant sectors are rarely adopted. The decision support tool Marxan is traditionally used for systematic selection and designation of nature protection and conservation areas. In this study, Marxan was applied as a support tool to identify suitable sites for offshore wind power in the pilot area Pomeranian Bight / Arkona Basin in the western Baltic Sea. The software was successfully tested and scenarios were developed that support the sites indicated in existing national plans, but also show options for alternative developments of offshore wind power in the Pomeranian Bight / Arkona Basin area. PMID:29543878

Wind/Tornado Guidelines Study

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

Ng, D.S.; Holman, G.S.

1991-10-01

This report documents the strategy employed to develop recommended wind/tornado hazard design guidelines for a New Production Reactor (NRP) currently planned for either the Idaho National Engineering Laboratory (INEL) or the Savannah River (SR) site. The Wind/Tornado Working Group (WTWG), comprising six nationally recognized experts in structural engineering, wind engineering, and meteorology, formulated an independent set of guidelines based on site-specific wind/tornado hazard curves and state-of-the-art tornado missile technology. The basic philosophy was to select realistic wind and missile load specifications, and to meet performance goals by applying conservative structural response evaluation and acceptance criteria. Simplified probabilistic risk analyses (PRAs)more » for wind speeds and missile impact were performed to estimate annual damage risk frequencies for both the INEL and SR sites. These PRAs indicate that the guidelines will lead to facilities that meet the US Department of Energy (DOE) design requirements and that the Nuclear Regulatory Commission guidelines adopted by the DOE for design are adequate to meet the NPR safety goals.« less

Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Durango, Colorado: Attachment 2, Geology report. Revised final report

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

Not Available

1991-12-01

Detailed investigations of geologic, geomorphic, and seismic conditions at the Bodo Canyon disposal site were conducted. The purpose of these investigations was basic site characterization and identification of potential geologic hazards that could affect long-term site stability. Subsequent engineering studies, such as analyses of hydrologic and liquefaction hazards, used the data developed in these studies. The geomorphic analysis was employed in the design of effective erosion protection. Studies of the regional and local seismotectonic setting, which included a detailed search for possible capable faults within a 65 kilometer radius of the site, provided the basis for seismic design parameters. Themore » scope of work performed included the following: Compilation and analysis of previous published and unpublished geologic literature and maps; Review of historical and instrumental earthquake data; Review of site-specific subsurface geologic data, including lithologic and geophysical logs of exploratory boreholes advanced in the site area; Photogeologic interpretations of existing conventional aerial photographs; and, Ground reconnaissance and mapping of the site region.« less

Bifunctional chelating agent for the design and development of site specific radiopharmaceuticals and biomolecule conjugation strategy

DOEpatents

Katti, Kattesh V.; Prabhu, Kandikere R.; Gali, Hariprasad; Pillarsetty, Nagavara Kishore; Volkert, Wynn A.

2003-10-21

There is provided a method of labeling a biomolecule with a transition metal or radiometal in a site specific manner to produce a diagnostic or therapeutic pharmaceutical compound by synthesizing a P.sub.2 N.sub.2 -bifunctional chelating agent intermediate, complexing the intermediate with a radio metal or a transition metal, and covalently linking the resulting metal-complexed bifunctional chelating agent with a biomolecule in a site specific manner. Also provided is a method of synthesizing the --PR.sub.2 containing biomolecules by synthesizing a P.sub.2 N.sub.2 -bifunctional chelating agent intermediate, complexing the intermediate with a radiometal or a transition metal, and covalently linking the resulting radio metal-complexed bifunctional chelating agent with a biomolecule in a site specific manner. There is provided a therapeutic or diagnostic agent comprising a --PR.sub.2 containing biomolecule.

Critical design elements of e-health applications for users with severe mental illness: singular focus, simple architecture, prominent contents, explicit navigation, and inclusive hyperlinks.

PubMed

Rotondi, Armando J; Eack, Shaun M; Hanusa, Barbara H; Spring, Michael B; Haas, Gretchen L

2015-03-01

E-health applications are becoming integral components of general medical care delivery models and emerging for mental health care. Few exist for treatment of those with severe mental illness (SMI). In part, this is due to a lack of models to design such technologies for persons with cognitive impairments and lower technology experience. This study evaluated the effectiveness of an e-health design model for persons with SMI termed the Flat Explicit Design Model (FEDM). Persons with schizophrenia (n = 38) performed tasks to evaluate the effectiveness of 5 Web site designs: 4 were prominent public Web sites, and 1 was designed according to the FEDM. Linear mixed-effects regression models were used to examine differences in usability between the Web sites. Omnibus tests of between-site differences were conducted, followed by post hoc pairwise comparisons of means to examine specific Web site differences when omnibus tests reached statistical significance. The Web site designed using the FEDM required less time to find information, had a higher success rate, and was rated easier to use and less frustrating than the other Web sites. The home page design of one of the other Web sites provided the best indication to users about a Web site's contents. The results are consistent with and were used to expand the FEDM. The FEDM provides evidence-based guidelines to design e-health applications for person with SMI, including: minimize an application's layers or hierarchy, use explicit text, employ navigational memory aids, group hyperlinks in 1 area, and minimize the number of disparate subjects an application addresses. © The Author 2013. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Are Biophilic-Designed Site Office Buildings Linked to Health Benefits and High Performing Occupants?

PubMed Central

Gray, Tonia; Birrell, Carol

2014-01-01

This paper discusses the first phase of a longitudinal study underway in Australia to ascertain the broad health benefits of specific types of biophilic design for workers in a building site office. A bespoke site design was formulated to include open plan workspace, natural lighting, ventilation, significant plants, prospect and views, recycled materials and use of non-synthetic materials. Initial data in the first three months was gathered from a series of demographic questions and from interviews and observations of site workers. Preliminary data indicates a strong positive effect from incorporating aspects of biophilic design to boost productivity, ameliorate stress, enhance well-being, foster a collaborative work environment and promote workplace satisfaction, thus contributing towards a high performance workspace. The longitudinal study spanning over two years will track human-plant interactions in a biophilic influenced space, whilst also assessing the concomitant cognitive, social, psychological and physical health benefits for workers. PMID:25431874

Building a Playground: General Guidelines for Creating Educational Web Sites for Children

PubMed Central

Meloncon, Lisa; Haynes, Erin; Varelmann, Megan; Groh, Lisa

2015-01-01

Purpose Since 2004, the number of children online has increased 18%, compared with a 10% increase in total users. Not only do children represent a growing segment of Internet users, much of what they do online has a specific purpose: education. To help technical communicators create educational Web sites for children, we offer a set of guidelines to direct the design process. Method Nine children participated in a usability test of the CARES Playground, an educational Web site geared toward 7- to 9-year-olds. The site was designed by a group of graduate students in professional writing based on a review of the (admittedly limited) literature dealing with designing Web sites for children. This paper matches common themes from existing literature to the results of the usability tests. Results Since all the information on designing Web sites for children emerged from the literature of designing Web sites for adults, the themes of navigation, appearance, and content are not unfamiliar. However, the interpretation of those common issues for children—as well as the children’s reaction to them—may be surprising. Conclusion Technical communicators need to be conscious and deliberate when designing Web sites for children. To ensure that educational Web sites are able to meet their learning goals, careful consideration of children’s developmental abilities and Web preferences must be considered. We present several guidelines as a starting point, though further research is needed to confirm and expand upon them. PMID:26633909

Deep Borehole Disposal Safety Analysis.

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

Freeze, Geoffrey A.; Stein, Emily; Price, Laura L.

This report presents a preliminary safety analysis for the deep borehole disposal (DBD) concept, using a safety case framework. A safety case is an integrated collection of qualitative and quantitative arguments, evidence, and analyses that substantiate the safety, and the level of confidence in the safety, of a geologic repository. This safety case framework for DBD follows the outline of the elements of a safety case, and identifies the types of information that will be required to satisfy these elements. At this very preliminary phase of development, the DBD safety case focuses on the generic feasibility of the DBD concept.more » It is based on potential system designs, waste forms, engineering, and geologic conditions; however, no specific site or regulatory framework exists. It will progress to a site-specific safety case as the DBD concept advances into a site-specific phase, progressing through consent-based site selection and site investigation and characterization.« less

10 CFR 60.133 - Additional design criteria for the underground facility.

Code of Federal Regulations, 2012 CFR

2012-01-01

... specific site conditions identified through in situ monitoring, testing, or excavation. (c) Retrieval of waste. The underground facility shall be designed to permit retrieval of waste in accordance with the... RADIOACTIVE WASTES IN GEOLOGIC REPOSITORIES Technical Criteria Design Criteria for the Geologic Repository...

10 CFR 60.133 - Additional design criteria for the underground facility.

Code of Federal Regulations, 2013 CFR

2013-01-01

... specific site conditions identified through in situ monitoring, testing, or excavation. (c) Retrieval of waste. The underground facility shall be designed to permit retrieval of waste in accordance with the... RADIOACTIVE WASTES IN GEOLOGIC REPOSITORIES Technical Criteria Design Criteria for the Geologic Repository...

10 CFR 60.133 - Additional design criteria for the underground facility.

Code of Federal Regulations, 2011 CFR

2011-01-01

... specific site conditions identified through in situ monitoring, testing, or excavation. (c) Retrieval of waste. The underground facility shall be designed to permit retrieval of waste in accordance with the... RADIOACTIVE WASTES IN GEOLOGIC REPOSITORIES Technical Criteria Design Criteria for the Geologic Repository...

10 CFR 60.133 - Additional design criteria for the underground facility.

Code of Federal Regulations, 2014 CFR

2014-01-01

... specific site conditions identified through in situ monitoring, testing, or excavation. (c) Retrieval of waste. The underground facility shall be designed to permit retrieval of waste in accordance with the... RADIOACTIVE WASTES IN GEOLOGIC REPOSITORIES Technical Criteria Design Criteria for the Geologic Repository...

A PROTOCOL FOR DETERMINING WWF SETTLING VELOCITIES FOR TREATMENT PROCESS DESIGN ENHANCEMENT

EPA Science Inventory

Urban wet weather flows (WWF) contain a high proportion of suspended solids (SS) which must be rapidly reduced before release to receiving waters. Site specific, storm-event data evaluations for designing WWF-treatment facilities differs from dry-weather flow design. WWF-sett...

The sequence specificity of UV-induced DNA damage in a systematically altered DNA sequence.

PubMed

Khoe, Clairine V; Chung, Long H; Murray, Vincent

2018-06-01

The sequence specificity of UV-induced DNA damage was investigated in a specifically designed DNA plasmid using two procedures: end-labelling and linear amplification. Absorption of UV photons by DNA leads to dimerisation of pyrimidine bases and produces two major photoproducts, cyclobutane pyrimidine dimers (CPDs) and pyrimidine(6-4)pyrimidone photoproducts (6-4PPs). A previous study had determined that two hexanucleotide sequences, 5'-GCTC*AC and 5'-TATT*AA, were high intensity UV-induced DNA damage sites. The UV clone plasmid was constructed by systematically altering each nucleotide of these two hexanucleotide sequences. One of the main goals of this study was to determine the influence of single nucleotide alterations on the intensity of UV-induced DNA damage. The sequence 5'-GCTC*AC was designed to examine the sequence specificity of 6-4PPs and the highest intensity 6-4PP damage sites were found at 5'-GTTC*CC nucleotides. The sequence 5'-TATT*AA was devised to investigate the sequence specificity of CPDs and the highest intensity CPD damage sites were found at 5'-TTTT*CG nucleotides. It was proposed that the tetranucleotide DNA sequence, 5'-YTC*Y (where Y is T or C), was the consensus sequence for the highest intensity UV-induced 6-4PP adduct sites; while it was 5'-YTT*C for the highest intensity UV-induced CPD damage sites. These consensus tetranucleotides are composed entirely of consecutive pyrimidines and must have a DNA conformation that is highly productive for the absorption of UV photons. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

Protein Arginine Methyltransferase Product Specificity Is Mediated by Distinct Active-site Architectures*

PubMed Central

Jain, Kanishk; Warmack, Rebeccah A.; Stavropoulos, Peter

2016-01-01

In the family of protein arginine methyltransferases (PRMTs) that predominantly generate either asymmetric or symmetric dimethylarginine (SDMA), PRMT7 is unique in producing solely monomethylarginine (MMA) products. The type of methylation on histones and other proteins dictates changes in gene expression, and numerous studies have linked altered profiles of methyl marks with disease phenotypes. Given the importance of specific inhibitor development, it is crucial to understand the mechanisms by which PRMT product specificity is conferred. We have focused our attention on active-site residues of PRMT7 from the protozoan Trypanosoma brucei. We have designed 26 single and double mutations in the active site, including residues in the Glu-Xaa8-Glu (double E) loop and the Met-Gln-Trp sequence of the canonical Thr-His-Trp (THW) loop known to interact with the methyl-accepting substrate arginine. Analysis of the reaction products by high resolution cation exchange chromatography combined with the knowledge of PRMT crystal structures suggests a model where the size of two distinct subregions in the active site determines PRMT7 product specificity. A dual mutation of Glu-181 to Asp in the double E loop and Gln-329 to Ala in the canonical THW loop enables the enzyme to produce SDMA. Consistent with our model, the mutation of Cys-431 to His in the THW loop of human PRMT9 shifts its product specificity from SDMA toward MMA. Together with previous results, these findings provide a structural basis and a general model for product specificity in PRMTs, which will be useful for the rational design of specific PRMT inhibitors. PMID:27387499

Hercules Single-Stage Reusable Vehicle (HSRV) Operating Base

NASA Technical Reports Server (NTRS)

Moon, Michael J.; McCleskey, Carey M.

2017-01-01

Conceptual design for the layout of lunar-planetary surface support systems remains an important area needing further master planning. This paper explores a structured approach to organize the layout of a Mars-based site equipped for routinely flying a human-scale reusable taxi system. The proposed Hercules Transportation System requires a surface support capability to sustain its routine, affordable, and dependable operation. The approach organizes a conceptual Hercules operating base through functional station sets. The station set approach will allow follow-on work to trade design approaches and consider technologies for more efficient flow of material, energy, and information at future Mars bases and settlements. The station set requirements at a Mars site point to specific capabilities needed. By drawing from specific Hercules design characteristics, the technology requirements for surface-based systems will come into greater focus. This paper begins a comprehensive process for documenting functional needs, architectural design methods, and analysis techniques necessary for follow-on concept studies.

Principles of nanoparticle design for overcoming biological barriers to drug delivery

PubMed Central

Blanco, Elvin; Shen, Haifa; Ferrari, Mauro

2016-01-01

Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery. PMID:26348965

Binding site size limit of the 2:1 pyrrole-imidazole polyamide-DNA motif.

PubMed Central

Kelly, J J; Baird, E E; Dervan, P B

1996-01-01

Polyamides containing N-methylimidazole (Im) and N-methylpyrrole (Py) amino acids can be combined in antiparallel side-by-side dimeric complexes for sequence-specific recognition in the minor groove of DNA. Six polyamides containing three to eight rings bind DNA sites 5-10 bp in length, respectively. Quantitative DNase I footprint titration experiments demonstrate that affinity maximizes and is similar at ring sizes of five, six, and seven. Sequence specificity decreases as the length of the polyamides increases beyond five rings. These results provide useful guidelines for the design of new polyamides that bind longer DNA sites with enhanced affinity and specificity. Images Fig. 4 PMID:8692930

Orion Entry, Descent, and Landing Performance and Mission Design

NASA Technical Reports Server (NTRS)

Broome, Joel M.; Johnson, Wyatt

2007-01-01

The Orion Vehicle is the next spacecraft to take humans into space and will include missions to ISS as well as missions to the Moon. As part of that challenge, the vehicle will have to accommodate multiple mission design concepts, since return from Low Earth Orbit and return from the Moon can be quite different. Commonality between the different missions as it relates to vehicle systems, guidance capability, and operations concepts is the goal. Several unique mission design concepts include the specification of multiple land-based landing sites for a vehicle with closed-loop direct and skip entry guidance, followed by a parachute descent and landing attenuation system. This includes the ability of the vehicle to accurately target and land at a designated landing site, including site location aspects, landing site size, and landing opportunities assessments. Analyses associated with these mission design and flight performance challenges and constraints will be discussed as well as potential operational concepts to provide feasibility and/or mission commonality.

The potential of magneto-electric nanocarriers for drug delivery

PubMed Central

Kaushik, Ajeet; Jayant, Rahul Dev; Sagar, Vidya; Nair, Madhavan

2015-01-01

Introduction The development and design of personalized nanomedicine for better health quality is receiving great attention. In order to deliver and release a therapeutic concentration at the target site, novel nanocarriers (NCs) were designed, for example, magneto-electric (ME) which possess ideal properties of high drug loading, site-specificity and precise on-demand controlled drug delivery. Areas covered This review explores the potential of ME-NCs for on-demand and site-specific drug delivery and release for personalized therapeutics. The main features including effect of magnetism, improvement in drug loading, drug transport across blood-brain barriers and on-demand controlled release are also discussed. The future directions and possible impacts on upcoming nanomedicine are highlighted. Expert opinion Numerous reports suggest that there is an urgent need to explore novel NC formulations for safe and targeted drug delivery and release at specific disease sites. The challenges of formulation lie in the development of NCs that improve biocompatibility and surface modifications for optimum drug loading/preservation/transmigration and tailoring of electrical–magnetic properties for on-demand drug release. Thus, the development of novel NCs is anticipated to overcome the problems of targeted delivery of therapeutic agents with desired precision that may lead to better patient compliance. PMID:24986772

The potential of magneto-electric nanocarriers for drug delivery.

PubMed

Kaushik, Ajeet; Jayant, Rahul Dev; Sagar, Vidya; Nair, Madhavan

2014-10-01

The development and design of personalized nanomedicine for better health quality is receiving great attention. In order to deliver and release a therapeutic concentration at the target site, novel nanocarriers (NCs) were designed, for example, magneto-electric (ME) which possess ideal properties of high drug loading, site-specificity and precise on-demand controlled drug delivery. This review explores the potential of ME-NCs for on-demand and site-specific drug delivery and release for personalized therapeutics. The main features including effect of magnetism, improvement in drug loading, drug transport across blood-brain barriers and on-demand controlled release are also discussed. The future directions and possible impacts on upcoming nanomedicine are highlighted. Numerous reports suggest that there is an urgent need to explore novel NC formulations for safe and targeted drug delivery and release at specific disease sites. The challenges of formulation lie in the development of NCs that improve biocompatibility and surface modifications for optimum drug loading/preservation/transmigration and tailoring of electrical-magnetic properties for on-demand drug release. Thus, the development of novel NCs is anticipated to overcome the problems of targeted delivery of therapeutic agents with desired precision that may lead to better patient compliance.

Integrated medical and behavioral laboratory measurement system engineering analysis and laboratory specification

NASA Technical Reports Server (NTRS)

Grave, C.; Margold, D. W.

1973-01-01

Site selection, program planning, cost and design studies for support of the IMBLMS program were investigated. Accomplishments are reported for the following areas: analysis of responses to site selection criteria, space-oriented biotechnology, life sciences payload definition, and program information transfer.

24 CFR 3286.505 - Minimum elements to be inspected.

Code of Federal Regulations, 2010 CFR

2010-04-01

... with respect to home design and construction; (b) Consideration of site-specific conditions; (c) Site... HOUSING AND URBAN DEVELOPMENT MANUFACTURED HOME INSTALLATION PROGRAM Inspection of Installations in HUD-Administered States § 3286.505 Minimum elements to be inspected. The installation of every manufactured home...

Steric and Thermodynamic Limits of Design for the Incorporation of Large UnNatural Amino Acids in Aminoacyl-tRNA Synthetase Enzymes

PubMed Central

Armen, Roger S.; Schiller, Stefan M.; Brooks, Charles L.

2015-01-01

Orthogonal aminoacyl-tRNA synthetase/tRNA pairs from archaea have been evolved to facilitate site specific in vivo incorporation of unnatural amino acids into proteins in Escherichia coli. Using this approach, unnatural amino acids have been successfully incorporated with high translational efficiency and fidelity. In this study, CHARMM-based molecular docking and free energy calculations were used to evaluate rational design of specific protein-ligand interactions for aminoacyl-tRNA synthetases. A series of novel unnatural amino acid ligands were docked into the p-benzoyl-L-phenylalanine tRNA synthetase, which revealed that the binding pocket of the enzyme does not provide sufficient space for significantly larger ligands. Specific binding site residues were mutated to alanine to create additional space to accommodate larger target ligands, and then mutations were introduced to improve binding free energy. This approach was used to redesign binding sites for several different target ligands, which were then tested against the standard 20 amino acids to verify target specificity. Only the synthetase designed to bind Man-α-O-Tyr was predicted to be sufficiently selective for the target ligand and also thermodynamically stable. Our study suggests that extensive redesign of the tRNA synthatase binding pocket for large bulky ligands may be quite thermodynamically unfavorable. PMID:20310065

An Investigation into Web Content Accessibility Guideline Conformance for an Aging Population

ERIC Educational Resources Information Center

Curran, Kevin; Robinson, David

2007-01-01

Poor web site design can cause difficulties for specific groups of users. By applying the Web Content Accessibility Guidelines to a web site, the amount of possible users who can successfully view the content of that site will increase, especially for those who are in the disabled and older adult categories of online users. Older adults are coming…

76 FR 5365 - Environmental Management Site-Specific Advisory Board, Nevada

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-31

... related activities. Tentative Agenda: 1. Recommendation Development--Industrial Sites, CAU 566 Rail Cars 2... presentations pertaining to agenda items should contact Denise Rupp at the telephone number listed above. The... the presentation in the agenda. The Deputy Designated Federal Officer is empowered to conduct the...

Cape Blanco wind farm feasibility study

NASA Astrophysics Data System (ADS)

1987-11-01

The Cape Blanco Wind Farm (CBWF) Feasibility Study was undertaken as a prototype for determining the feasibility of proposals for wind energy projects at Northwest sites. It was intended to test for conditions under which wind generation of electricity could be commercially feasible, not by another abstract survey of alternative technologies, but rather through a site-specific, machine-specific analysis of one proposal. Some of the study findings would be most pertinent to the Cape Blanco site - local problems require local solutions. Other findings would be readily applicable to other sites and other machines, and study methodologies would be designed to be modified for appraisal of other proposals. This volume discusses environmental, economic, and technical issues of the Wind Farm.

Development of traffic data input resources for the mechanistic empirical pavement design process.

DOT National Transportation Integrated Search

2011-12-12

The Mechanistic-Empirical Pavement Design Guide (MEPDG) for New and Rehabilitated Pavement Structures uses : nationally based data traffic inputs and recommends that state DOTs develop their own site-specific and regional : values. To support the MEP...

Embedded data collector (EDC) phase II load and resistance factor design (LRFD) : [summary].

DOT National Transportation Integrated Search

2015-07-01

Piles that support bridge structures are designed for the specific site characteristics and loads : that the piles are expected to bear. In Florida, driven piles are monitored during installation : (dynamically tested) to assess resistance, com...

A Task-oriented Approach for Hydrogeological Site Characterization

NASA Astrophysics Data System (ADS)

Rubin, Y.; Nowak, W.; de Barros, F.

2010-12-01

Hydrogeological site characterization is a challenging task from several reasons: (1) the large spatial variability and scarcity of prior information render the outcome of any planned sampling campaign uncertain; (2) there are no simple tools for comparing between the many alternative measurement techniques and data acquisition strategies, and (3) physical and budgetary constraints associated with data acquisition. This paper presents several ideas on how to plan sampling campaigns in a rational manner while addressing these challenges. The first idea is to recognize that different sites and different problems require different characterization strategies. Hence the idea is to plan data acquisition according to its capability for meeting site-specific goals. For example, the characterization needs at a “research problem” site (e.g., a site intended to investigate the transport of uranium in the subsurface such as in Hanford) are different from those of a “problem” site (e.g., contaminated site associated with a health risk to human such as Camp Lejeune, or determining the safe yield of an aquifer). This distinction requires planners to define the characterization goal(s) in a quantitative manner. The second idea is to define metrics that could link specific data types and data acquisition strategies with the site-specific goals in a way that would allow planners to compare between strongly different, alternatives strategies at the design stage (even prior to data acquisition) and to modify the strategies as more data become available. To meet this goal, we developed the concept of the (comparative) information yield curve. Finally, we propose to look at site characterization from the perspective of statistical hypothesis testing, whereby data acquisition strategies could be evaluated in terms of their ability to support or refute various hypotheses made with regard to the characterization goals, and the strategies could be modified once the test is completed. Accept/reject regions for hypothesis testing can be determined based on goals determined by regulations or by agreement between the stakeholders. Hypothesis-driven design could help in minimizing the chances of making wrong decision (false positives or false negatives) with regard to the site-specific goals.

High precision and high yield fabrication of dense nanoparticle arrays onto DNA origami at statistically independent binding sites

NASA Astrophysics Data System (ADS)

Takabayashi, Sadao; Klein, William P.; Onodera, Craig; Rapp, Blake; Flores-Estrada, Juan; Lindau, Elias; Snowball, Lejmarc; Sam, Joseph T.; Padilla, Jennifer E.; Lee, Jeunghoon; Knowlton, William B.; Graugnard, Elton; Yurke, Bernard; Kuang, Wan; Hughes, William L.

2014-10-01

High precision, high yield, and high density self-assembly of nanoparticles into arrays is essential for nanophotonics. Spatial deviations as small as a few nanometers can alter the properties of near-field coupled optical nanostructures. Several studies have reported assemblies of few nanoparticle structures with controlled spacing using DNA nanostructures with variable yield. Here, we report multi-tether design strategies and attachment yields for homo- and hetero-nanoparticle arrays templated by DNA origami nanotubes. Nanoparticle attachment yield via DNA hybridization is comparable with streptavidin-biotin binding. Independent of the number of binding sites, >97% site-occupation was achieved with four tethers and 99.2% site-occupation is theoretically possible with five tethers. The interparticle distance was within 2 nm of all design specifications and the nanoparticle spatial deviations decreased with interparticle spacing. Modified geometric, binomial, and trinomial distributions indicate that site-bridging, steric hindrance, and electrostatic repulsion were not dominant barriers to self-assembly and both tethers and binding sites were statistically independent at high particle densities.High precision, high yield, and high density self-assembly of nanoparticles into arrays is essential for nanophotonics. Spatial deviations as small as a few nanometers can alter the properties of near-field coupled optical nanostructures. Several studies have reported assemblies of few nanoparticle structures with controlled spacing using DNA nanostructures with variable yield. Here, we report multi-tether design strategies and attachment yields for homo- and hetero-nanoparticle arrays templated by DNA origami nanotubes. Nanoparticle attachment yield via DNA hybridization is comparable with streptavidin-biotin binding. Independent of the number of binding sites, >97% site-occupation was achieved with four tethers and 99.2% site-occupation is theoretically possible with five tethers. The interparticle distance was within 2 nm of all design specifications and the nanoparticle spatial deviations decreased with interparticle spacing. Modified geometric, binomial, and trinomial distributions indicate that site-bridging, steric hindrance, and electrostatic repulsion were not dominant barriers to self-assembly and both tethers and binding sites were statistically independent at high particle densities. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr03069a

Protein Arginine Methyltransferase Product Specificity Is Mediated by Distinct Active-site Architectures.

PubMed

Jain, Kanishk; Warmack, Rebeccah A; Debler, Erik W; Hadjikyriacou, Andrea; Stavropoulos, Peter; Clarke, Steven G

2016-08-26

In the family of protein arginine methyltransferases (PRMTs) that predominantly generate either asymmetric or symmetric dimethylarginine (SDMA), PRMT7 is unique in producing solely monomethylarginine (MMA) products. The type of methylation on histones and other proteins dictates changes in gene expression, and numerous studies have linked altered profiles of methyl marks with disease phenotypes. Given the importance of specific inhibitor development, it is crucial to understand the mechanisms by which PRMT product specificity is conferred. We have focused our attention on active-site residues of PRMT7 from the protozoan Trypanosoma brucei We have designed 26 single and double mutations in the active site, including residues in the Glu-Xaa8-Glu (double E) loop and the Met-Gln-Trp sequence of the canonical Thr-His-Trp (THW) loop known to interact with the methyl-accepting substrate arginine. Analysis of the reaction products by high resolution cation exchange chromatography combined with the knowledge of PRMT crystal structures suggests a model where the size of two distinct subregions in the active site determines PRMT7 product specificity. A dual mutation of Glu-181 to Asp in the double E loop and Gln-329 to Ala in the canonical THW loop enables the enzyme to produce SDMA. Consistent with our model, the mutation of Cys-431 to His in the THW loop of human PRMT9 shifts its product specificity from SDMA toward MMA. Together with previous results, these findings provide a structural basis and a general model for product specificity in PRMTs, which will be useful for the rational design of specific PRMT inhibitors. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Design package for solar domestic hot water system

NASA Technical Reports Server (NTRS)

1980-01-01

The initial design of a solar domestic hot water system is considered. The system performance specification and detailed design drawings are included. The hot water systems consist of the following subsystems: collector, storage, control, transport, auxiliary energy, and government-furnished site data acquisition. The two systems are installed at Tempe, Arizona, and San Diego, California.

Design of an allosterically modulated doxycycline and doxorubicin drug-binding protein.

PubMed

Schmidt, Karin; Gardill, Bernd R; Kern, Alina; Kirchweger, Peter; Börsch, Michael; Muller, Yves A

2018-05-14

The allosteric interplay between distant functional sites present in a single protein provides for one of the most important regulatory mechanisms in biological systems. While the design of ligand-binding sites into proteins remains challenging, this holds even truer for the coupling of a newly engineered binding site to an allosteric mechanism that regulates the ligand affinity. Here it is shown how computational design algorithms enabled the introduction of doxycycline- and doxorubicin-binding sites into the serine proteinase inhibitor (serpin) family member α1-antichymotrypsin. Further engineering allowed exploitation of the proteinase-triggered serpin-typical S-to-R transition to modulate the ligand affinities. These design variants follow strategies observed in naturally occurring plasma globulins that allow for the targeted delivery of hormones in the blood. By analogy, we propose that the variants described in the present study could be further developed to allow for the delivery of the antibiotic doxycycline and the anticancer compound doxorubicin to tissues/locations that express specific proteinases, such as bacterial infection sites or tumor cells secreting matrix metalloproteinases.

Engineering Nucleotide Specificity of Succinyl-CoA Synthetase in Blastocystis: The Emerging Role of Gatekeeper Residues.

PubMed

Vashisht, Kapil; Verma, Sonia; Gupta, Sunita; Lynn, Andrew M; Dixit, Rajnikant; Mishra, Neelima; Valecha, Neena; Hamblin, Karleigh A; Maytum, Robin; Pandey, Kailash C; van der Giezen, Mark

2017-01-24

Charged, solvent-exposed residues at the entrance to the substrate binding site (gatekeeper residues) produce electrostatic dipole interactions with approaching substrates, and control their access by a novel mechanism called "electrostatic gatekeeper effect". This proof-of-concept study demonstrates that the nucleotide specificity can be engineered by altering the electrostatic properties of the gatekeeper residues outside the binding site. Using Blastocystis succinyl-CoA synthetase (SCS, EC 6.2.1.5), we demonstrated that the gatekeeper mutant (ED) resulted in ATP-specific SCS to show high GTP specificity. Moreover, nucleotide binding site mutant (LF) had no effect on GTP specificity and remained ATP-specific. However, via combination of the gatekeeper mutant with the nucleotide binding site mutant (ED+LF), a complete reversal of nucleotide specificity was obtained with GTP, but no detectable activity was obtained with ATP. This striking result of the combined mutant (ED+LF) was due to two changes; negatively charged gatekeeper residues (ED) favored GTP access, and nucleotide binding site residues (LF) altered ATP binding, which was consistent with the hypothesis of the "electrostatic gatekeeper effect". These results were further supported by molecular modeling and simulation studies. Hence, it is imperative to extend the strategy of the gatekeeper effect in a different range of crucial enzymes (synthetases, kinases, and transferases) to engineer substrate specificity for various industrial applications and substrate-based drug design.

Designing HIV Testing Algorithms Based on 2015 WHO Guidelines Using Data from Six Sites in Sub-Saharan Africa

PubMed Central

Kosack, Cara S.; Shanks, Leslie; Beelaert, Greet; Benson, Tumwesigye; Savane, Aboubacar; Ng'ang'a, Anne; Bita, André; Zahinda, Jean-Paul B. N.; Fransen, Katrien

2017-01-01

ABSTRACT Our objective was to evaluate the performance of HIV testing algorithms based on WHO recommendations, using data from specimens collected at six HIV testing and counseling sites in sub-Saharan Africa (Conakry, Guinea; Kitgum and Arua, Uganda; Homa Bay, Kenya; Douala, Cameroon; Baraka, Democratic Republic of Congo). A total of 2,780 samples, including 1,306 HIV-positive samples, were included in the analysis. HIV testing algorithms were designed using Determine as a first test. Second and third rapid diagnostic tests (RDTs) were selected based on site-specific performance, adhering where possible to the WHO-recommended minimum requirements of ≥99% sensitivity and specificity. The threshold for specificity was reduced to 98% or 96% if necessary. We also simulated algorithms consisting of one RDT followed by a simple confirmatory assay. The positive predictive values (PPV) of the simulated algorithms ranged from 75.8% to 100% using strategies recommended for high-prevalence settings, 98.7% to 100% using strategies recommended for low-prevalence settings, and 98.1% to 100% using a rapid test followed by a simple confirmatory assay. Although we were able to design algorithms that met the recommended PPV of ≥99% in five of six sites using the applicable high-prevalence strategy, options were often very limited due to suboptimal performance of individual RDTs and to shared falsely reactive results. These results underscore the impact of the sequence of HIV tests and of shared false-reactivity data on algorithm performance. Where it is not possible to identify tests that meet WHO-recommended specifications, the low-prevalence strategy may be more suitable. PMID:28747371

Active site specificity profiling datasets of matrix metalloproteinases (MMPs) 1, 2, 3, 7, 8, 9, 12, 13 and 14.

PubMed

Eckhard, Ulrich; Huesgen, Pitter F; Schilling, Oliver; Bellac, Caroline L; Butler, Georgina S; Cox, Jennifer H; Dufour, Antoine; Goebeler, Verena; Kappelhoff, Reinhild; Auf dem Keller, Ulrich; Klein, Theo; Lange, Philipp F; Marino, Giada; Morrison, Charlotte J; Prudova, Anna; Rodriguez, David; Starr, Amanda E; Wang, Yili; Overall, Christopher M

2016-06-01

The data described provide a comprehensive resource for the family-wide active site specificity portrayal of the human matrix metalloproteinase family. We used the high-throughput proteomic technique PICS (Proteomic Identification of protease Cleavage Sites) to comprehensively assay 9 different MMPs. We identified more than 4300 peptide cleavage sites, spanning both the prime and non-prime sides of the scissile peptide bond allowing detailed subsite cooperativity analysis. The proteomic cleavage data were expanded by kinetic analysis using a set of 6 quenched-fluorescent peptide substrates designed using these results. These datasets represent one of the largest specificity profiling efforts with subsequent structural follow up for any protease family and put the spotlight on the specificity similarities and differences of the MMP family. A detailed analysis of this data may be found in Eckhard et al. (2015) [1]. The raw mass spectrometry data and the corresponding metadata have been deposited in PRIDE/ProteomeXchange with the accession number PXD002265.

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.

Design package for instrumentation of the Decade 80 house in Tucson, Arizona

NASA Technical Reports Server (NTRS)

1978-01-01

A design package covering instrumentation and system design for the Decade 80 House in Tucson, Arizona is presented. The solar house is instrumented for the purpose of gathering data to determine the solar heating and cooling system performance. The use of copper in the construction of the house is a first choice construction material because it conducts heat and resists corrosion better than other materials and therefore provides a more efficient and economical system. Equipment and site specifications are reported, along with floor plans showing the location of the site instrumentation hardware.

megaTALs: a rare-cleaving nuclease architecture for therapeutic genome engineering.

PubMed

Boissel, Sandrine; Jarjour, Jordan; Astrakhan, Alexander; Adey, Andrew; Gouble, Agnès; Duchateau, Philippe; Shendure, Jay; Stoddard, Barry L; Certo, Michael T; Baker, David; Scharenberg, Andrew M

2014-02-01

Rare-cleaving endonucleases have emerged as important tools for making targeted genome modifications. While multiple platforms are now available to generate reagents for research applications, each existing platform has significant limitations in one or more of three key properties necessary for therapeutic application: efficiency of cleavage at the desired target site, specificity of cleavage (i.e. rate of cleavage at 'off-target' sites), and efficient/facile means for delivery to desired target cells. Here, we describe the development of a single-chain rare-cleaving nuclease architecture, which we designate 'megaTAL', in which the DNA binding region of a transcription activator-like (TAL) effector is used to 'address' a site-specific meganuclease adjacent to a single desired genomic target site. This architecture allows the generation of extremely active and hyper-specific compact nucleases that are compatible with all current viral and nonviral cell delivery methods.

Effects of organizational scheme and labeling on task performance in product-centered and user-centered retail Web sites.

PubMed

Resnick, Marc L; Sanchez, Julian

2004-01-01

As companies increase the quantity of information they provide through their Web sites, it is critical that content is structured with an appropriate architecture. However, resource constraints often limit the ability of companies to apply all Web design principles completely. This study quantifies the effects of two major information architecture principles in a controlled study that isolates the incremental effects of organizational scheme and labeling on user performance and satisfaction. Sixty participants with a wide range of Internet and on-line shopping experience were recruited to complete a series of shopping tasks on a prototype retail shopping Web site. User-centered labels provided a significant benefit in performance and satisfaction over labels obtained through company-centered methods. User-centered organization did not result in improved performance except when the label quality was poor. Significant interactions suggest specific guidelines for allocating resources in Web site design. Applications of this research include the design of Web sites for any commercial application, particularly E-commerce.

Dredging Operations Technical Support Program. Guidelines for Physical and Biological Monitoring of Aquatic Dredged Material Disposal Sites

DTIC Science & Technology

1990-09-01

I C4 -44 0 i r Uo IP Stop I Designation of Site-Specific Managerial Needs and Objectives Step 2 Identification of Physical and Chemical Parameters...improved as experience dictates. Emphasis is placed on the establishment of concise objectives and hypotheses, the use of multidisciplinary approaches to...resulting monitoring can thus focus on the detection of changes in specific conditions rather than identifying any or all detectable changes. A monitoring

Studying the Education of Educators: Methodology.

ERIC Educational Resources Information Center

Sirotnik, Kenneth A.

1988-01-01

Describes the methodology and research design of SEE, the study of the Education of Educators. The approach is multimethodological, exploratory, descriptive, and evaluative. The research design permits examination of working assumptions and concentration on the individual site--the college, the education departments, and specific programs within…

Analysis of Virginia-specific traffic data inputs for use with the mechanistic-empirical pavement design guide.

DOT National Transportation Integrated Search

2010-02-01

This study developed traffic inputs for use with the Guide for the Mechanistic-Empirical Design of New & Rehabilitated Pavement Structures (MEPDG) in Virginia and sought to determine if the predicted distresses showed differences between site-specifi...

Interconversion of the Specificities of Human Lysosomal Enzymes Associated with Fabry and Schindler Diseases

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

Tomasic, Ivan B.; Metcalf, Matthew C.; Guce, Abigail I.

2010-09-03

The human lysosomal enzymes {alpha}-galactosidase ({alpha}-GAL, EC 3.2.1.22) and {alpha}-N-acetylgalactosaminidase ({alpha}-NAGAL, EC 3.2.1.49) share 46% amino acid sequence identity and have similar folds. The active sites of the two enzymes share 11 of 13 amino acids, differing only where they interact with the 2-position of the substrates. Using a rational protein engineering approach, we interconverted the enzymatic specificity of {alpha}-GAL and {alpha}-NAGAL. The engineered {alpha}-GAL (which we call {alpha}-GALSA) retains the antigenicity of {alpha}-GAL but has acquired the enzymatic specificity of {alpha}-NAGAL. Conversely, the engineered {alpha}-NAGAL (which we call {alpha}-NAGAL{sup EL}) retains the antigenicity of {alpha}-NAGAL but has acquired themore » enzymatic specificity of the {alpha}-GAL enzyme. Comparison of the crystal structures of the designed enzyme {alpha}-GAL{sup SA} to the wild-type enzymes shows that active sites of {alpha}-GAL{sup SA} and {alpha}-NAGAL superimpose well, indicating success of the rational design. The designed enzymes might be useful as non-immunogenic alternatives in enzyme replacement therapy for treatment of lysosomal storage disorders such as Fabry disease.« less

50 CFR 32.49 - New Jersey.

Code of Federal Regulations, 2010 CFR

2010-10-01

... through the end of the State common snipe season. 5. You may only possess approved nontoxic shot while in... Division, we restrict hunting to designated sites, with each site limited to one party of hunters. 5. In.... We require persons hunting on the refuge for the first time to attend one of the four refuge-specific...

Redesigning the specificity of protein-DNA interactions with Rosetta.

PubMed

Thyme, Summer; Baker, David

2014-01-01

Building protein tools that can selectively bind or cleave specific DNA sequences requires efficient technologies for modifying protein-DNA interactions. Computational design is one method for accomplishing this goal. In this chapter, we present the current state of protein-DNA interface design with the Rosetta macromolecular modeling program. The LAGLIDADG endonuclease family of DNA-cleaving enzymes, under study as potential gene therapy reagents, has been the main testing ground for these in silico protocols. At this time, the computational methods are most useful for designing endonuclease variants that can accommodate small numbers of target site substitutions. Attempts to engineer for more extensive interface changes will likely benefit from an approach that uses the computational design results in conjunction with a high-throughput directed evolution or screening procedure. The family of enzymes presents an engineering challenge because their interfaces are highly integrated and there is significant coordination between the binding and catalysis events. Future developments in the computational algorithms depend on experimental feedback to improve understanding and modeling of these complex enzymatic features. This chapter presents both the basic method of design that has been successfully used to modulate specificity and more advanced procedures that incorporate DNA flexibility and other properties that are likely necessary for reliable modeling of more extensive target site changes.

TU-A-201-02: Treatment Site-Specific Considerations for Clinical IGRT

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

Wijesooriya, K.

2016-06-15

Recent years have seen a widespread proliferation of available in-room image guidance systems for radiation therapy target localization with many centers having multiple in-room options. In this session, available imaging systems for in-room IGRT will be reviewed highlighting the main differences in workflow efficiency, targeting accuracy and image quality as it relates to target visualization. Decision-making strategies for integrating these tools into clinical image guidance protocols that are tailored to specific disease sites like H&N, lung, pelvis, and spine SBRT will be discussed. Learning Objectives: Major system characteristics of a wide range of available in-room imaging systems for IGRT. Advantagesmore » / disadvantages of different systems for site-specific IGRT considerations. Concepts of targeting accuracy and time efficiency in designing clinical imaging protocols.« less

Designing Playgrounds for Multifamily Dwellings

ERIC Educational Resources Information Center

Corrado, Paul

1978-01-01

Substantive, cost-sensitive guidelines are offered for determining basic playground needs, performance specifications, and site location, as well as construction techniques, for playgrounds servicing multi-family dwellings. (MJB)

Design, Synthesis, and Evaluation of N- and C-Terminal Protein Bioconjugates as G Protein-Coupled Receptor Agonists.

PubMed

Healey, Robert D; Wojciechowski, Jonathan P; Monserrat-Martinez, Ana; Tan, Susan L; Marquis, Christopher P; Sierecki, Emma; Gambin, Yann; Finch, Angela M; Thordarson, Pall

2018-02-21

A G protein-coupled receptor (GPCR) agonist protein, thaumatin, was site-specifically conjugated at the N- or C-terminus with a fluorophore for visualization of GPCR:agonist interactions. The N-terminus was specifically conjugated using a synthetic 2-pyridinecarboxyaldehyde reagent. The interaction profiles observed for N- and C-terminal conjugates were varied; N-terminal conjugates interacted very weakly with the GPCR of interest, whereas C-terminal conjugates bound to the receptor. These chemical biology tools allow interactions of therapeutic proteins:GPCR to be monitored and visualized. The methodology used for site-specific bioconjugation represents an advance in application of 2-pyridinecarboxyaldehydes for N-terminal specific bioconjugations.

Facility Systems, Ground Support Systems, and Ground Support Equipment General Design Requirements

NASA Technical Reports Server (NTRS)

Thaxton, Eric A.

2014-01-01

KSC-DE-512-SM establishes overall requirements and best design practices to be used at the John F. Kennedy Space Center (KSC) for the development of ground systems (GS) in support of operations at launch, landing, and retrieval sites. These requirements apply to the design and development of hardware and software for ground support equipment (GSE), ground support systems (GSS), and facility ground support systems (F-GSS) used to support the KSC mission for transportation, receiving, handling, assembly, test, checkout, servicing, and launch of space vehicles and payloads and selected flight hardware items for retrieval. This standards manual supplements NASA-STD-5005 by including KSC-site-specific and local environment requirements. These requirements and practices are optional for equipment used at manufacturing, development, and test sites.

An Extreme Meteorological Events Analysis For Nuclear Power Plant (NPP) Siting Project at Bangka Island, Indonesia

NASA Astrophysics Data System (ADS)

Septiadi, Deni; S, Yarianto Sugeng B.; Sriyana; Anzhar, Kurnia; Suntoko, Hadi

2018-03-01

The potential sources of meteorological phenomena in Nuclear Power Plant (NPP) area of interest are identified and the extreme values of the possible resulting hazards associated which such phenomena are evaluated to derive the appropriate design bases for the NPP. The appropriate design bases shall be determined according to the Nuclear Energy Regulatory Agency (Bapeten) applicable regulations, which presently do not indicate quantitative criteria for purposes of determining the design bases for meteorological hazards. These meteorological investigations are also carried out to evaluate the regional and site specific meteorological parameters which affect the transport and dispersion of radioactive effluents on the environment of the region around the NPP site. The meteorological hazards are to be monitored and assessed periodically over the lifetime of the plant to ensure that consistency with the design assumptions is maintained throughout the full lifetime of the facility.

Site-specific Seismic Hazard Assessment to Establish Elastic Design Properties for Oman Museum-Across Ages, Manah, Sultante of Oman

NASA Astrophysics Data System (ADS)

El Hussain, I. W.

2017-12-01

The current study provides a site specific deterministic seismic hazard assessment (DSHA) at the selected site for establishing the Oman Museum-Across Ages at Manah area, as a part of a comprehensive geotechnical and seismological plan to design the facilities accordingly. The DSHA first defines the seismic sources that might influence the site and assesses the maximum possible earthquake magnitude for each of them. By assuming each of these maximum earthquakes to occur at a location placing them at the closest distances to the site, the ground motion is predicted utilizing empirical ground motion prediction equations. The local site effects are performed by determining the fundamental frequency of the soft soil using HVSR technique and by estimating amplification spectra using the soil characteristics (mainly shear-wave velocity). Shear-wave velocity has been evaluated using the MASW technique. The maximum amplification value of 2.1 at spectral period 0.06 sec is observed at the ground surface, while the largest amplification value at the top of the conglomerate layer (at 5m depth) is 1.6 for a spectral period of 0.04 Sec. The maximum median 5% damped peak ground acceleration is found to be 0.263g at a spectral period of 0.1 sec. Keywords: DSHA; Site Effects; HVSR; MASW; PGA; Spectral Period

Multiple nucleotide preferences determine cleavage-site recognition by the HIV-1 and M-MuLV RNases H.

PubMed

Schultz, Sharon J; Zhang, Miaohua; Champoux, James J

2010-03-19

The RNase H activity of reverse transcriptase is required during retroviral replication and represents a potential target in antiviral drug therapies. Sequence features flanking a cleavage site influence the three types of retroviral RNase H activity: internal, DNA 3'-end-directed, and RNA 5'-end-directed. Using the reverse transcriptases of HIV-1 (human immunodeficiency virus type 1) and Moloney murine leukemia virus (M-MuLV), we evaluated how individual base preferences at a cleavage site direct retroviral RNase H specificity. Strong test cleavage sites (designated as between nucleotide positions -1 and +1) for the HIV-1 and M-MuLV enzymes were introduced into model hybrid substrates designed to assay internal or DNA 3'-end-directed cleavage, and base substitutions were tested at specific nucleotide positions. For internal cleavage, positions +1, -2, -4, -5, -10, and -14 for HIV-1 and positions +1, -2, -6, and -7 for M-MuLV significantly affected RNase H cleavage efficiency, while positions -7 and -12 for HIV-1 and positions -4, -9, and -11 for M-MuLV had more modest effects. DNA 3'-end-directed cleavage was influenced substantially by positions +1, -2, -4, and -5 for HIV-1 and positions +1, -2, -6, and -7 for M-MuLV. Cleavage-site distance from the recessed end did not affect sequence preferences for M-MuLV reverse transcriptase. Based on the identified sequence preferences, a cleavage site recognized by both HIV-1 and M-MuLV enzymes was introduced into a sequence that was otherwise resistant to RNase H. The isolated RNase H domain of M-MuLV reverse transcriptase retained sequence preferences at positions +1 and -2 despite prolific cleavage in the absence of the polymerase domain. The sequence preferences of retroviral RNase H likely reflect structural features in the substrate that favor cleavage and represent a novel specificity determinant to consider in drug design. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Solar Water-Heater Design Package

NASA Technical Reports Server (NTRS)

1982-01-01

Information on a solar domestic-hot water heater is contained in 146 page design package. System consists of solar collector, storage tanks, automatic control circuitry and auxiliary heater. Data-acquisition equipment at sites monitors day-by-day performance. Includes performance specifications, schematics, solar-collector drawings and drawings of control parts.

Mechanics of Multifunctional Materials & Microsystems

DTIC Science & Technology

2012-03-09

Mechanics of Materials; Life Prediction (Materials & Micro-devices); Sensing, Precognition & Diagnosis; Multifunctional Design of Autonomic...Life Prediction (Materials & Micro-devices); Sensing, Precognition & Diagnosis; Multifunctional Design of Autonomic Systems; Multifunctional...release; distribution is unlimited. 7 VISION: EXPANDED • site specific • autonomic AUTONOMIC AEROSPACE STRUCTURES • Sensing & Precognition • Self

Biomimicry enhances sequential reactions of tethered glycolytic enzymes, TPI and GAPDHS.

PubMed

Mukai, Chinatsu; Gao, Lizeng; Bergkvist, Magnus; Nelson, Jacquelyn L; Hinchman, Meleana M; Travis, Alexander J

2013-01-01

Maintaining activity of enzymes tethered to solid interfaces remains a major challenge in developing hybrid organic-inorganic devices. In nature, mammalian spermatozoa have overcome this design challenge by having glycolytic enzymes with specialized targeting domains that enable them to function while tethered to a cytoskeletal element. As a step toward designing a hybrid organic-inorganic ATP-generating system, we implemented a biomimetic site-specific immobilization strategy to tether two glycolytic enzymes representing different functional enzyme families: triose phosphoisomerase (TPI; an isomerase) and glyceraldehyde 3-phosphate dehydrogenase (GAPDHS; an oxidoreductase). We then evaluated the activities of these enzymes in comparison to when they were tethered via classical carboxyl-amine crosslinking. Both enzymes show similar surface binding regardless of immobilization method. Remarkably, specific activities for both enzymes were significantly higher when tethered using the biomimetic, site-specific immobilization approach. Using this biomimetic approach, we tethered both enzymes to a single surface and demonstrated their function in series in both forward and reverse directions. Again, the activities in series were significantly higher in both directions when the enzymes were coupled using this biomimetic approach versus carboxyl-amine binding. Our results suggest that biomimetic, site-specific immobilization can provide important functional advantages over chemically specific, but non-oriented attachment, an important strategic insight given the growing interest in recapitulating entire biological pathways on hybrid organic-inorganic devices.

Biomimicry Enhances Sequential Reactions of Tethered Glycolytic Enzymes, TPI and GAPDHS

PubMed Central

Mukai, Chinatsu; Gao, Lizeng; Bergkvist, Magnus; Nelson, Jacquelyn L.; Hinchman, Meleana M.; Travis, Alexander J.

2013-01-01

Maintaining activity of enzymes tethered to solid interfaces remains a major challenge in developing hybrid organic-inorganic devices. In nature, mammalian spermatozoa have overcome this design challenge by having glycolytic enzymes with specialized targeting domains that enable them to function while tethered to a cytoskeletal element. As a step toward designing a hybrid organic-inorganic ATP-generating system, we implemented a biomimetic site-specific immobilization strategy to tether two glycolytic enzymes representing different functional enzyme families: triose phosphoisomerase (TPI; an isomerase) and glyceraldehyde 3-phosphate dehydrogenase (GAPDHS; an oxidoreductase). We then evaluated the activities of these enzymes in comparison to when they were tethered via classical carboxyl-amine crosslinking. Both enzymes show similar surface binding regardless of immobilization method. Remarkably, specific activities for both enzymes were significantly higher when tethered using the biomimetic, site-specific immobilization approach. Using this biomimetic approach, we tethered both enzymes to a single surface and demonstrated their function in series in both forward and reverse directions. Again, the activities in series were significantly higher in both directions when the enzymes were coupled using this biomimetic approach versus carboxyl-amine binding. Our results suggest that biomimetic, site-specific immobilization can provide important functional advantages over chemically specific, but non-oriented attachment, an important strategic insight given the growing interest in recapitulating entire biological pathways on hybrid organic-inorganic devices. PMID:23626684

Toward the Design of Personalized Continuum Surgical Robots.

PubMed

Morimoto, Tania K; Greer, Joseph D; Hawkes, Elliot W; Hsieh, Michael H; Okamura, Allison M

2018-05-31

Robot-assisted minimally invasive surgical systems enable procedures with reduced pain, recovery time, and scarring compared to traditional surgery. While these improvements benefit a large number of patients, safe access to diseased sites is not always possible for specialized patient groups, including pediatric patients, due to their anatomical differences. We propose a patient-specific design paradigm that leverages the surgeon's expertise to design and fabricate robots based on preoperative medical images. The components of the patient-specific robot design process are a virtual reality design interface enabling the surgeon to design patient-specific tools, 3-D printing of these tools with a biodegradable polyester, and an actuation and control system for deployment. The designed robot is a concentric tube robot, a type of continuum robot constructed from precurved, elastic, nesting tubes. We demonstrate the overall patient-specific design workflow, from preoperative images to physical implementation, for an example clinical scenario: nonlinear renal access to a pediatric kidney. We also measure the system's behavior as it is deployed through real and artificial tissue. System integration and successful benchtop experiments in ex vivo liver and in a phantom patient model demonstrate the feasibility of using a patient-specific design workflow to plan, fabricate, and deploy personalized, flexible continuum robots.

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.

Eucalyptus Energy Farm: feasibility study and demonstration. Phase 1: site and species selection

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

Mariani, E.O.; Wood, W.A.; Kouchoukos, P.C.

1978-06-01

The results of investigations to determine the feasibility for establishing ''Eucalyptus Energy Farms'' as a potential source of biomass derived energy are presented. Included in this report are: the results of an extensive literature search and numerous field interviews (both domestically and internationally) to identify those Eucalyptus species most suitable for use within the United States; a description of the site selection criteria, site selection process, and identification of potential sites for use in testing the Eucalyptus Energy Farm concept; a description of the Eucalyptus species selection criteria, species selection process, and an identification of the specific species recommended formore » testing at specific sites; preliminary engineering designs for each of the proposed plantation sites; and environmental impact considerations related to Eucalyptus growing. It is concluded that although the Eucalyptus are extremely temperature sensitive and the geographic areas which appear suitable for their planting (within the United States) are principally confined to western and central California and the warmest regions of the southeastern United States, each of the areas contain large amounts of marginal land which could be converted into Eucalyptus based biomass plantations. Suitable sites, which are representative of the larger marginal land areas, are immediately available for use in establishing Eucalyptus screening test sites. Furthermore, there are not significant environmental conditions which would preclude the establishment of these initial test sites. It is therefore recommended that efforts be initiated to obtain selected provenances of Eucalyptus seeds (of the designated species) for further field testing and data collection within the United States, and that actual site selection be initiated.« less

Groundwater contamination from waste management sites: The interaction between risk-based engineering design and regulatory policy: 2. Results

NASA Astrophysics Data System (ADS)

Massmann, Joel; Freeze, R. Allan

1987-02-01

The risk-cost-benefit analysis developed in the companion paper (J. Massmann and R. A. Freeze, this issue) is here applied to (1) an assessment of the relative worth of containment-construction activities, site-exploration activities, and monitoring activities as components of a design strategy for the owner/operator of a waste management facility; (2) an assessment of alternative policy options available to a regulatory agency; and (3) a case history. Sensitivity analyses designed to address the first issue show that the allocation of resources by the owner/operator is sensitive to the stochastic parameters used to describe the hydraulic conductivity field at a site. For the cases analyzed, the installation of a dense monitoring network is of less value to the owner/operator than a more conservative containment design. Sensitivity analyses designed to address the second issue suggest that from a regulatory perspective, design standards should be more effective than performance standards in reducing risk, and design specifications on the containment structure should be more effective than those on the monitoring network. Performance bonds posted before construction have a greater potential to influence design than prospective penalties to be imposed at the time of failure. Siting on low-conductivity deposits is a more effective method of risk reduction than any form of regulatory influence. Results of the case history indicate that the methodology can be successfully applied at field sites.

Vegetation study in support of the design and optimization of vegetative soil covers, Sandia National Laboratories, Albuquerque, New Mexico.

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

Peace, Gerald; Goering, Timothy James; Knight, Paul J.

A vegetation study was conducted in Technical Area 3 at Sandia National Laboratories, Albuquerque, New Mexico in 2003 to assist in the design and optimization of vegetative soil covers for hazardous, radioactive, and mixed waste landfills at Sandia National Laboratories/New Mexico and Kirtland Air Force Base. The objective of the study was to obtain site-specific, vegetative input parameters for the one-dimensional code UNSAT-H and to identify suitable, diverse native plant species for use on vegetative soil covers that will persist indefinitely as a climax ecological community with little or no maintenance. The identification and selection of appropriate native plant speciesmore » is critical to the proper design and long-term performance of vegetative soil covers. Major emphasis was placed on the acquisition of representative, site-specific vegetation data. Vegetative input parameters measured in the field during this study include root depth, root length density, and percent bare area. Site-specific leaf area index was not obtained in the area because there was no suitable platform to measure leaf area during the 2003 growing season due to severe drought that has persisted in New Mexico since 1999. Regional LAI data was obtained from two unique desert biomes in New Mexico, Sevilletta Wildlife Refuge and Jornada Research Station.« less

Precipitation Depth-Duration-Frequency Analysis for the Nevada National Security Site and Surrounding Areas

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

Chen, Li; Miller, Julianne J.

Accurate precipitation frequency data are important for Environmental Management Soils Activities on the Nevada National Security Site (NNSS). These data are important for environmental assessments performed for regulatory closure of Soils Corrective Action Unit (CAU) Sites, as well as engineering mitigation designs and post-closure monitoring strategies to assess and minimize potential contaminant migration from Soils CAU Sites. Although the National Oceanic and Atmospheric Administration (NOAA) Atlas 14 (Bonnin et al., 2011) provides precipitation frequency data for the NNSS area, the NNSS-specific observed precipitation data were not consistent with the NOAA Atlas 14 predicted data. This is primarily due to themore » NOAA Atlas 14 products being produced from analyses without including the approximately 30 NNSS precipitation gage records, several of which approach or exceed 50 year of record. Therefore, a study of precipitation frequency that incorporated the NNSS precipitation gage records into the NOAA Atlas 14 dataset, was performed specifically for the NNSS to derive more accurate site-specific precipitation data products. Precipitation frequency information, such as the depth-duration-frequency (DDF) relationships, are required to generate synthetic standard design storm hydrographs and assess actual precipitation events. In this study, the actual long-term NNSS precipitation gage records, some of which are the longest gage records in southern and central Nevada, were analyzed to allow for more accurate precipitation DDF estimates to be developed for the NNSS. Gridded maps of precipitation frequency for the NNSS and surrounding areas were then produced.« less

DESIGNS FOR THE FUTURE: BRIDGING THE GAP BETWEEN ASSESSMENT OF CONDITION AND DIAGNOSIS OF IMPAIRMENT

EPA Science Inventory

As the EPA, states, and tribes move towards a consolidated assessment and listing process to satisfy requirements of the Clean Water Act, multi-purpose monitoring designs will be needed to assess regional condition as well as predict site-specific probabilities of impairment. Th...

Marker development

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

Adams, M.R.

This report is to discuss the marker development for radioactive waste disposal sites. The markers must be designed to last 10,000 years, and place no undue burdens on the future generations. Barriers cannot be constructed that preclude human intrusion. Design specifications for surface markers will be discussed, also marker pictograms will also be covered.

Coupling Protein Side-Chain and Backbone Flexibility Improves the Re-design of Protein-Ligand Specificity.

PubMed

Ollikainen, Noah; de Jong, René M; Kortemme, Tanja

2015-01-01

Interactions between small molecules and proteins play critical roles in regulating and facilitating diverse biological functions, yet our ability to accurately re-engineer the specificity of these interactions using computational approaches has been limited. One main difficulty, in addition to inaccuracies in energy functions, is the exquisite sensitivity of protein-ligand interactions to subtle conformational changes, coupled with the computational problem of sampling the large conformational search space of degrees of freedom of ligands, amino acid side chains, and the protein backbone. Here, we describe two benchmarks for evaluating the accuracy of computational approaches for re-engineering protein-ligand interactions: (i) prediction of enzyme specificity altering mutations and (ii) prediction of sequence tolerance in ligand binding sites. After finding that current state-of-the-art "fixed backbone" design methods perform poorly on these tests, we develop a new "coupled moves" design method in the program Rosetta that couples changes to protein sequence with alterations in both protein side-chain and protein backbone conformations, and allows for changes in ligand rigid-body and torsion degrees of freedom. We show significantly increased accuracy in both predicting ligand specificity altering mutations and binding site sequences. These methodological improvements should be useful for many applications of protein-ligand design. The approach also provides insights into the role of subtle conformational adjustments that enable functional changes not only in engineering applications but also in natural protein evolution.

Coyote Creek (Santa Clara County) Pilot Revegetation Project

Treesearch

John T. Stanley; L. R. Silva; H. C. Appleton; M. S. Marangio; W. J. Lapaz; B. H. Goldner

1989-01-01

The Santa Clara Valley Water District, located in Northern California, is currently evaluating a pilot riparian revegetation project on a 1.6 ha (4 ac) site adjacent to Coyote Creek in the south San Francisco Bay Area. Specific techniques used during the design, site preparation and installation of 3640 plants (including seed planting locations) are described. This...

Designing Websites for ESL Learners: A Usability Testing Study

ERIC Educational Resources Information Center

Liu, Min; Traphagan, Tomoko; Huh, Jin; Koh, Young Ihn; Choi, Gilok; McGregor, Allison

2008-01-01

The purpose of this paper is to report on a usability study for ESL websites conducted to gain insights from learners of English as a second language (ESL) as they interacted with specific sites. Five carefully selected ESL sites were tested by 10 different users generating a total of fifty testing sessions. Two major research questions guided the…

Student Evaluation Web Sites as Potential Sources of Consumer Information in the United Arab Emirates

ERIC Educational Resources Information Center

Wilkins, Stephen; Epps, Alun

2011-01-01

Purpose: The purpose of this paper is to investigate the attitudes of students in the United Arab Emirates (UAE) towards non-institutionally sanctioned student evaluation web sites, and to consider how educational institutions might respond to the demands of students for specific information. Design/methodology/approach: The study involved a…

Infants Infected with Respiratory Syncytial Virus Generate Potent Neutralizing Antibodies that Lack Somatic Hypermutation

PubMed Central

Goodwin, Eileen; Gilman, Morgan S. A.; Wrapp, Daniel; Chen, Man; Ngwuta, Joan O.; Moin, Syed M.; Bai, Patricia; Sivasubramanian, Arvind; Connor, Ruth I.; Wright, Peter F.; Graham, Barney S.; McLellan, Jason S.; Walker, Laura M.

2018-01-01

SUMMARY Respiratory syncytial virus (RSV) is a leading cause of infant mortality, and there are currently no licensed vaccines to protect this vulnerable population. A comprehensive understanding of infant antibody responses to natural RSV infection would facilitate vaccine development. Here, we isolated over 450 RSV fusion glycoprotein (F)-specific antibodies from seven RSV-infected infants and found that half of the antibodies recognized only two antigenic sites. Antibodies targeting both sites showed convergent sequence features, and structural studies revealed the molecular basis for their recognition of RSV F. A subset of antibodies targeting one of these sites displayed potent neutralizing activity despite lacking somatic mutations, and similar antibodies were detected in RSV-naïve B cell repertoires, suggesting that expansion of these B cells in infants may be possible with suitably designed vaccine antigens. Collectively, our results provide fundamental insights into infant antibody responses and a framework for the rational design of age-specific RSV vaccines. PMID:29396163

Computational design of an enzyme catalyst for a stereoselective bimolecular Diels-Alder reaction

PubMed Central

Siegel, Justin B.; Zanghellini, Alexandre; Lovick, Helena M.; Kiss, Gert; Lambert, Abigail R.; St.Clair, Jennifer L.; Gallaher, Jasmine L.; Hilvert, Donald; Gelb, Michael H.; Stoddard, Barry L.; Houk, Kendall N.; Michael, Forrest E.; Baker, David

2011-01-01

The Diels-Alder reaction is a cornerstone in organic synthesis, forming two carbon-carbon bonds and up to four new stereogenic centers in one step. No naturally occurring enzymes have been shown to catalyze bimolecular Diels-Alder reactions. We describe the de novo computational design and experimental characterization of enzymes catalyzing a bimolecular Diels-Alder reaction with high stereoselectivity and substrate specificity. X-ray crystallography confirms that the structure matches the design for the most active of the enzymes, and binding site substitutions reprogram the substrate specificity. Designed stereoselective catalysts for carbon-carbon bond forming reactions should be broadly useful in synthetic chemistry. PMID:20647463

Computational design of an enzyme catalyst for a stereoselective bimolecular Diels-Alder reaction.

PubMed

Siegel, Justin B; Zanghellini, Alexandre; Lovick, Helena M; Kiss, Gert; Lambert, Abigail R; St Clair, Jennifer L; Gallaher, Jasmine L; Hilvert, Donald; Gelb, Michael H; Stoddard, Barry L; Houk, Kendall N; Michael, Forrest E; Baker, David

2010-07-16

The Diels-Alder reaction is a cornerstone in organic synthesis, forming two carbon-carbon bonds and up to four new stereogenic centers in one step. No naturally occurring enzymes have been shown to catalyze bimolecular Diels-Alder reactions. We describe the de novo computational design and experimental characterization of enzymes catalyzing a bimolecular Diels-Alder reaction with high stereoselectivity and substrate specificity. X-ray crystallography confirms that the structure matches the design for the most active of the enzymes, and binding site substitutions reprogram the substrate specificity. Designed stereoselective catalysts for carbon-carbon bond-forming reactions should be broadly useful in synthetic chemistry.

Rural Schools Prototype Analysis. Volume II: Methodology. An Example Process of Identifying Determinants, Selecting Options, & Developing Schematic Designs.

ERIC Educational Resources Information Center

Construction Systems Management, Inc., Anchorage, AK.

Volume II of a 3-volume report demonstrates the use of Design Determinants and Options (presented in Volume I) in the planning and design of small rural Alaskan secondary schools. Section I, a checklist for gathering site-specific information to be used as a data base for facility design, is organized in the same format as Volume I, which can be…

EPA RE-Powering Mapper Region 10

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (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.

EPA RE-Powering Mapper Region 4

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (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.

EPA RE-Powering Mapper Large Scale

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (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.

EPA RE-Powering Mapper Region 2

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (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.

EPA RE-Powering Mapper Region 6

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (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.

EPA RE-Powering Mapper Region 8

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (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.

EPA RE-Powering Mapper Region 7

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (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.

EPA RE-Powering Mapper Region 5

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (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.

EPA RE-Powering Mapper Region 3

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (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.

EPA RE-Powering Mapper Solar on Landfills

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (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.

EPA RE-Powering Mapper Region 9

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (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.

EPA RE-Powering Mapper Utility Scale

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (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.

EPA RE-Powering Screening Shapefile

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (OLEM) Center for Program Analysis (CPA) 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.

EPA RE-Powering Mapper Region 1

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (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.

Toward rules relating zinc finger protein sequences and DNA binding site preferences.

PubMed

Desjarlais, J R; Berg, J M

1992-08-15

Zinc finger proteins of the Cys2-His2 type consist of tandem arrays of domains, where each domain appears to contact three adjacent base pairs of DNA through three key residues. We have designed and prepared a series of variants of the central zinc finger within the DNA binding domain of Sp1 by using information from an analysis of a large data base of zinc finger protein sequences. Through systematic variations at two of the three contact positions (underlined), relatively specific recognition of sequences of the form 5'-GGGGN(G or T)GGG-3' has been achieved. These results provide the basis for rules that may develop into a code that will allow the design of zinc finger proteins with preselected DNA site specificity.

Integrated platform for optimized solar PV system design and engineering plan set generation

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

Adeyemo, Samuel

2015-12-30

The Aurora team has developed software that allows users to quickly generate a three-dimensional model for a building, with a corresponding irradiance map, from any two-dimensional image with associated geo-coordinates. The purpose of this project is to build upon that technology by developing and distributing to solar installers a software platform that automatically retrieves engineering, financial and geographic data for a specific site, and quickly generates an optimal customer proposal and corresponding engineering plans for that site. At the end of the project, Aurora’s optimization platform would have been used to make at least one thousand proposals from at leastmore » ten unique solar installation companies, two of whom would sign economically viable contracts to use the software. Furthermore, Aurora’s algorithms would be tested to show that in at least seventy percent of cases, Aurora automatically generated a design equivalent to or better than what a human could have done manually. A ‘better’ design is one that generates more energy for the same cost, or that generates a higher return on investment, while complying with all site-specific aesthetic, electrical and spatial requirements.« less

Characterizing site specific considerations for protecting aircraft during LGS operations at W. M. Keck Observatory

NASA Astrophysics Data System (ADS)

Stomski, Paul J., Jr.; Campbell, Randy; McCann, Kevin; Shimko, Steve

2010-07-01

W. M. Keck Observatory (WMKO) routinely operates laser guide star (LGS) Adaptive Optics (AO) systems at the telescope facility on the Big Island of Hawaii. One of the operational requirements for the LGS system is that a safety system to prevent nearby aircraft from being adversely affected by the laser must be provided. We will support operations in the near term with human aircraft spotters until we can successfully develop and get the appropriate approvals needed for an Automated, Integrated and Reliable System for an Aircraft Friendly Environment (AIRSAFE). This report describes some of the preliminary requirements development work at WMKO in support of the future development of AIRSAFE. We discuss the results of recent work to characterize site specific considerations that impact requirements development. The site specific considerations include the proximity of WMKO laser operations to nearby commercial airports, the implications of military operations in the area and the character of the air traffic volume and flight patterns over the telescope facility. Finally, we discuss how the design and implementation of AIRSAFE will be impacted by these site specific considerations.

Chemical Insights into the Design and Development of Face-Centered Cubic Ruthenium Catalysts for Fischer-Tropsch Synthesis.

PubMed

Li, Wei-Zhen; Liu, Jin-Xun; Gu, Jun; Zhou, Wu; Yao, Si-Yu; Si, Rui; Guo, Yu; Su, Hai-Yan; Yan, Chun-Hua; Li, Wei-Xue; Zhang, Ya-Wen; Ma, Ding

2017-02-15

Ruthenium is a promising low-temperature catalyst for Fischer-Tropsch synthesis (FTS). However, its scarcity and modest specific activity limit its widespread industrialization. We demonstrate here a strategy for tuning the crystal phase of catalysts to expose denser and active sites for a higher mass-specific activity. Density functional theory calculations show that upon CO dissociation there are a number of open facets with modest barrier available on the face-centered cubic (fcc) Ru but only a few step edges with a lower barrier on conventional hexagonal-closest packed (hcp) Ru. Guided by theoretical calculations, water-dispersible fcc Ru catalysts containing abundant open facets were synthesized and showed an unprecedented mass-specific activity in the aqueous-phase FTS, 37.8 mol CO ·mol Ru -1 ·h -1 at 433 K. The mass-specific activity of the fcc Ru catalysts with an average size of 6.8 nm is about three times larger than the previous best hcp catalyst with a smaller size of 1.9 nm and a higher specific surface area. The origin of the higher mass-specific activity of the fcc Ru catalysts is identified experimentally from the 2 orders of magnitude higher density of the active sites, despite its slightly higher apparent barrier. Experimental results are in excellent agreement with prediction of theory. The great influence of the crystal phases on site distribution and their intrinsic activities revealed here provides a rationale design of catalysts for higher mass-specific activity without decrease of the particle size.

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

Keller, M.R.

A pneumatically deployed membrane system was used to conduct radiological surveys of the pipes and drains at a Department of Energy (DOE) Formerly Utilized Sites Remedial Action Program (FUSRAP) site in Adrian, Michigan. Remedial action consisted of the removal of residual radioactive sludge and oil. The innovative technology was used to transport a high-sensitivity probe specifically designed for this application, through designated pipes and drains. Use of this system made it possible to survey over 1,000 linear ft of underground drain line in one week, with no significant safety hazards. This was the first time this technology had been fieldmore » tested at a site, resulting in cost savings of more than $1.5 million.« less

Conserved epitope on influenza-virus hemagglutinin head defined by a vaccine-induced antibody

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

Raymond, Donald D.; Bajic, Goran; Ferdman, Jack

Antigenic variation requires frequent revision of annual influenza vaccines. Next-generation vaccine design strategies aim to elicit a broader immunity by directing the human immune response toward conserved sites on the principal viral surface protein, the hemagglutinin (HA). We describe a group of antibodies that recognize a hitherto unappreciated, conserved site on the HA of H1 subtype influenza viruses. Mutations in that site, which required a change in the H1 component of the 2017 vaccine, had not previously “taken over” among circulating H1 viruses. Our results encourage vaccine design strategies that resurface a protein to focus the immune response on amore » specific region.« less

PepComposer: computational design of peptides binding to a given protein surface

PubMed Central

Obarska-Kosinska, Agnieszka; Iacoangeli, Alfredo; Lepore, Rosalba; Tramontano, Anna

2016-01-01

There is a wide interest in designing peptides able to bind to a specific region of a protein with the aim of interfering with a known interaction or as starting point for the design of inhibitors. Here we describe PepComposer, a new pipeline for the computational design of peptides binding to a given protein surface. PepComposer only requires the target protein structure and an approximate definition of the binding site as input. We first retrieve a set of peptide backbone scaffolds from monomeric proteins that harbor the same backbone arrangement as the binding site of the protein of interest. Next, we design optimal sequences for the identified peptide scaffolds. The method is fully automatic and available as a web server at http://biocomputing.it/pepcomposer/webserver. PMID:27131789

Development of a domain-specific genetic language to design Chlamydomonas reinhardtii expression vectors.

PubMed

Wilson, Mandy L; Okumoto, Sakiko; Adam, Laura; Peccoud, Jean

2014-01-15

Expression vectors used in different biotechnology applications are designed with domain-specific rules. For instance, promoters, origins of replication or homologous recombination sites are host-specific. Similarly, chromosomal integration or viral delivery of an expression cassette imposes specific structural constraints. As de novo gene synthesis and synthetic biology methods permeate many biotechnology specialties, the design of application-specific expression vectors becomes the new norm. In this context, it is desirable to formalize vector design strategies applicable in different domains. Using the design of constructs to express genes in the chloroplast of Chlamydomonas reinhardtii as an example, we show that a vector design strategy can be formalized as a domain-specific language. We have developed a graphical editor of context-free grammars usable by biologists without prior exposure to language theory. This environment makes it possible for biologists to iteratively improve their design strategies throughout the course of a project. It is also possible to ensure that vectors designed with early iterations of the language are consistent with the latest iteration of the language. The context-free grammar editor is part of the GenoCAD application. A public instance of GenoCAD is available at http://www.genocad.org. GenoCAD source code is available from SourceForge and licensed under the Apache v2.0 open source license.

Cancer Clusters

MedlinePlus

... sites, performs health consultations on specific hazardous substances, designs and conducts health surveillance programs, and provides education ... the National Cancer Institute.” Please note that blog posts that are written by individuals from outside the ...

Principles for designing proteins with cavities formed by curved β sheets

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

Marcos, Enrique; Basanta, Benjamin; Chidyausiku, Tamuka M.

Active sites and ligand-binding cavities in native proteins are often formed by curved β sheets, and the ability to control β-sheet curvature would allow design of binding proteins with cavities customized to specific ligands. Toward this end, we investigated the mechanisms controlling β-sheet curvature by studying the geometry of β sheets in naturally occurring protein structures and folding simulations. The principles emerging from this analysis were used to design, de novo, a series of proteins with curved β sheets topped with α helices. Nuclear magnetic resonance and crystal structures of the designs closely match the computational models, showing that β-sheetmore » curvature can be controlled with atomic-level accuracy. Our approach enables the design of proteins with cavities and provides a route to custom design ligand-binding and catalytic sites.« less

An integrated assessment of location-dependent scaling for microalgae biofuel production facilities

DOE PAGES

Coleman, André M.; Abodeely, Jared M.; Skaggs, Richard L.; ...

2014-06-19

Successful development of a large-scale microalgae-based biofuels industry requires comprehensive analysis and understanding of the feedstock supply chain—from facility siting and design through processing and upgrading of the feedstock to a fuel product. The evolution from pilot-scale production facilities to energy-scale operations presents many multi-disciplinary challenges, including a sustainable supply of water and nutrients, operational and infrastructure logistics, and economic competitiveness with petroleum-based fuels. These challenges are partially addressed by applying the Integrated Assessment Framework (IAF) – an integrated multi-scale modeling, analysis, and data management suite – to address key issues in developing and operating an open-pond microalgae production facility.more » This is done by analyzing how variability and uncertainty over space and through time affect feedstock production rates, and determining the site-specific “optimum” facility scale to minimize capital and operational expenses. This approach explicitly and systematically assesses the interdependence of biofuel production potential, associated resource requirements, and production system design trade-offs. To provide a baseline analysis, the IAF was applied in this paper to a set of sites in the southeastern U.S. with the potential to cumulatively produce 5 billion gallons per year. Finally, the results indicate costs can be reduced by scaling downstream processing capabilities to fit site-specific growing conditions, available and economically viable resources, and specific microalgal strains.« less

Oak Ridge Environmental Information System (ORIES) site workstation information packet for OREIS V1.2. Environmental Restoration Program

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

Voorhees, L.D.; McCord, R.A.; Durfee, R.C.

1993-02-01

The OREIS site workstation information packet was developed to accompany the OREIS site workstations, which are being delivered to the Environmental Restoration programs at the five DOE-OR sites. The packet is written specifically for the Site ER program staff at each of the five Sites who have been designated the OREIS contact by their ER program manager, and is not intended for general distribution. The packet provides an overview of the components of OREIS, points to more detailed information provided in the accompanying vendor and OREIS developed manuals, and includes information on training opportunities and user support.

Oak Ridge Environmental Information System (ORIES) site workstation information packet for OREIS V1. 2

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

Voorhees, L.D.; McCord, R.A.; Durfee, R.C.

1993-02-01

The OREIS site workstation information packet was developed to accompany the OREIS site workstations, which are being delivered to the Environmental Restoration programs at the five DOE-OR sites. The packet is written specifically for the Site ER program staff at each of the five Sites who have been designated the OREIS contact by their ER program manager, and is not intended for general distribution. The packet provides an overview of the components of OREIS, points to more detailed information provided in the accompanying vendor and OREIS developed manuals, and includes information on training opportunities and user support.

Metal stabilization of collagen and de novo designed mimetic peptides

PubMed Central

Parmar, Avanish S.; Xu, Fei; Pike, Douglas H.; Belure, Sandeep V.; Hasan, Nida F.; Drzewiecki, Kathryn E.; Shreiber, David I.; Nanda, Vikas

2017-01-01

We explore the design of metal binding sites to modulate triple-helix stability of collagen and collagen-mimetic peptides. Globular proteins commonly utilize metals to connect tertiary structural elements that are well separated in sequence, constraining structure and enhancing stability. It is more challenging to engineer structural metals into fibrous protein scaffolds, which lack the extensive tertiary contacts seen in globular proteins. In the collagen triple helix, the structural adjacency of the carboxy-termini of the three chains makes this region an attractive target for introducing metal binding sites. We engineered His3 sites based on structural modeling constraints into a series of designed homotrimeric and heterotrimeric peptides, assessing the capacity of metal binding to improve stability and in the case of heterotrimers, affect specificity of assembly. Notable enhancements in stability for both homo and heteromeric systems were observed upon addition of zinc(II) and several other metal ions only when all three histidine ligands were present. Metal binding affinities were consistent with the expected Irving-Williams series for imidazole. Unlike other metals tested, copper(II) also bound to peptides lacking histidine ligands. Acetylation of the peptide N-termini prevented copper binding, indicating proline backbone amide metal-coordination at this site. Copper similarly stabilized animal extracted Type I collagen in a metal specific fashion, highlighting the potential importance of metal homeostasis within the extracellular matrix. PMID:26225466

Metal Stabilization of Collagen and de Novo Designed Mimetic Peptides.

PubMed

Parmar, Avanish S; Xu, Fei; Pike, Douglas H; Belure, Sandeep V; Hasan, Nida F; Drzewiecki, Kathryn E; Shreiber, David I; Nanda, Vikas

2015-08-18

We explore the design of metal binding sites to modulate triple-helix stability of collagen and collagen-mimetic peptides. Globular proteins commonly utilize metals to connect tertiary structural elements that are well separated in sequence, constraining structure and enhancing stability. It is more challenging to engineer structural metals into fibrous protein scaffolds, which lack the extensive tertiary contacts seen in globular proteins. In the collagen triple helix, the structural adjacency of the carboxy-termini of the three chains makes this region an attractive target for introducing metal binding sites. We engineered His3 sites based on structural modeling constraints into a series of designed homotrimeric and heterotrimeric peptides, assessing the capacity of metal binding to improve stability and in the case of heterotrimers, affect specificity of assembly. Notable enhancements in stability for both homo- and heteromeric systems were observed upon addition of zinc(II) and several other metal ions only when all three histidine ligands were present. Metal binding affinities were consistent with the expected Irving-Williams series for imidazole. Unlike other metals tested, copper(II) also bound to peptides lacking histidine ligands. Acetylation of the peptide N-termini prevented copper binding, indicating proline backbone amide metal-coordination at this site. Copper similarly stabilized animal extracted Type I collagen in a metal-specific fashion, highlighting the potential importance of metal homeostasis within the extracellular matrix.

[Substrate specificities of bile salt hydrolase 1 and its mutants from Lactobacillus salivarius].

PubMed

Bi, Jie; Fang, Fang; Qiu, Yuying; Yang, Qingli; Chen, Jian

2014-03-01

In order to analyze the correlation between critical residues in the catalytic centre of BSH and the enzyme substrate specificity, seven mutants of Lactobacillus salivarius bile salt hydrolase (BSH1) were constructed by using the Escherichia coli pET-20b(+) gene expression system, rational design and site-directed mutagenesis. These BSH1 mutants exhibited different hydrolytic activities against various conjugated bile salts through substrate specificities comparison. Among the residues being tested, Cys2 and Thr264 were deduced as key sites for BSH1 to catalyze taurocholic acid and glycocholic acid, respectively. Moreover, Cys2 and Thr264 were important for keeping the catalytic activity of BSH1. The high conservative Cys2 was not the only active site, other mutant amino acid sites were possibly involved in substrate binding. These mutant residues might influence the space and shape of the substrate-binding pockets or the channel size for substrate passing through and entering active site of BSH1, thus, the hydrolytic activity of BSH1 was changed to different conjugated bile salt.

Achieving appropriate design for developing world heath care: the case of a low-cost autoclave for primary health clinics.

PubMed

Cho, Hallie S; Tao, Gregory D; Winter, Amos

2012-01-01

In developing world health clinics, incidence of surgical site infection is 2 to 10 times higher than in developed world hospitals. This paper identifies lack of availability of appropriately designed, low-cost autoclaves in developing world health clinics as a major contributing factor to the dramatic gap in surgical site infection rates. The paper describes the process of developing a low-cost autoclave that addresses the unique challenges faced by developing world primary health clinics and discusses how appropriateness of design was determined. The resulting pressure cooker-based autoclave design was fabricated and tested against the CDC specifications. Twelve partnering clinics in Nepal trialed these autoclaves from July until December 2012.

Health and safety impacts of nuclear, geothermal, and fossil-fuel electric generation in California. Volume 9. Methodologies for review of the health and safety aspects of proposed nuclear, geothermal, and fossil-fuel sites and facilities

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

Nero, A.V.; Quinby-Hunt, M.S.

1977-01-01

This report sets forth methodologies for review of the health and safety aspects of proposed nuclear, geothermal, and fossil-fuel sites and facilities for electric power generation. The review is divided into a Notice of Intention process and an Application for Certification process, in accordance with the structure to be used by the California Energy Resources Conservation and Development Commission, the first emphasizing site-specific considerations, the second examining the detailed facility design as well. The Notice of Intention review is divided into three possible stages: an examination of emissions and site characteristics, a basic impact analysis, and an assessment of publicmore » impacts. The Application for Certification review is divided into five possible stages: a review of the Notice of Intention treatment, review of the emission control equipment, review of the safety design, review of the general facility design, and an overall assessment of site and facility acceptability.« less

Identification and correction of systematic error in high-throughput sequence data

PubMed Central

2011-01-01

Background A feature common to all DNA sequencing technologies is the presence of base-call errors in the sequenced reads. The implications of such errors are application specific, ranging from minor informatics nuisances to major problems affecting biological inferences. Recently developed "next-gen" sequencing technologies have greatly reduced the cost of sequencing, but have been shown to be more error prone than previous technologies. Both position specific (depending on the location in the read) and sequence specific (depending on the sequence in the read) errors have been identified in Illumina and Life Technology sequencing platforms. We describe a new type of systematic error that manifests as statistically unlikely accumulations of errors at specific genome (or transcriptome) locations. Results We characterize and describe systematic errors using overlapping paired reads from high-coverage data. We show that such errors occur in approximately 1 in 1000 base pairs, and that they are highly replicable across experiments. We identify motifs that are frequent at systematic error sites, and describe a classifier that distinguishes heterozygous sites from systematic error. Our classifier is designed to accommodate data from experiments in which the allele frequencies at heterozygous sites are not necessarily 0.5 (such as in the case of RNA-Seq), and can be used with single-end datasets. Conclusions Systematic errors can easily be mistaken for heterozygous sites in individuals, or for SNPs in population analyses. Systematic errors are particularly problematic in low coverage experiments, or in estimates of allele-specific expression from RNA-Seq data. Our characterization of systematic error has allowed us to develop a program, called SysCall, for identifying and correcting such errors. We conclude that correction of systematic errors is important to consider in the design and interpretation of high-throughput sequencing experiments. PMID:22099972

Design tradeoffs for trend assessment in aquatic biological monitoring programs

USGS Publications Warehouse

Gurtz, Martin E.; Van Sickle, John; Carlisle, Daren M.; Paulsen, Steven G.

2013-01-01

Assessments of long-term (multiyear) temporal trends in biological monitoring programs are generally undertaken without an adequate understanding of the temporal variability of biological communities. When the sources and levels of variability are unknown, managers cannot make informed choices in sampling design to achieve monitoring goals in a cost-effective manner. We evaluated different trend sampling designs by estimating components of both short- and long-term variability in biological indicators of water quality in streams. Invertebrate samples were collected from 32 sites—9 urban, 6 agricultural, and 17 relatively undisturbed (reference) streams—distributed throughout the United States. Between 5 and 12 yearly samples were collected at each site during the period 1993–2008, plus 2 samples within a 10-week index period during either 2007 or 2008. These data allowed calculation of four sources of variance for invertebrate indicators: among sites, among years within sites, interaction among sites and years (site-specific annual variation), and among samples collected within an index period at a site (residual). When estimates of these variance components are known, changes to sampling design can be made to improve trend detection. Design modifications that result in the ability to detect the smallest trend with the fewest samples are, from most to least effective: (1) increasing the number of years in the sampling period (duration of the monitoring program), (2) decreasing the interval between samples, and (3) increasing the number of repeat-visit samples per year (within an index period). This order of improvement in trend detection, which achieves the greatest gain for the fewest samples, is the same whether trends are assessed at an individual site or an average trend of multiple sites. In multiple-site surveys, increasing the number of sites has an effect similar to that of decreasing the sampling interval; the benefit of adding sites is greater when a new set of different sites is selected for each sampling effort than when the same sites are sampled each time. Understanding variance components of the ecological attributes of interest can lead to more cost-effective monitoring designs to detect trends.

Design of RCSS

PubMed Central

Strum, David P.; Vargas, Luis G.; May, Jerrold H.

1997-01-01

Abstract The plans for Resource Coordination for Surgical Services system (RCSS) incorporate a distributed objectbase with a coordinating server. User-centered information screens are customized for each geographic location in surgical services. User interfaces are designed to mimic paper lists and worksheets used by health care providers. Patient-specific and site-specific data will be entered and maintained by providers at each geographic location, but also rebroadcast and displayed for all providers. Although RCSS is primarily a communications system, it will also support review of surgical utilization and operative scheduling. PMID:9067878

In vitro optimization of antisense oligodeoxynucleotide design: an example using the connexin gene family.

PubMed

Law, Lee Yong; Zhang, Wei V; Stott, N Susan; Becker, David L; Green, Colin R

2006-09-01

The completion of the human and mouse genomes has identified at least 20 connexin isomers in this family of intercellular channel proteins. However, there are no specific gap junction blockers or channel-blocking mimetic peptides available for the study of specific connexins. We designed antisense oligodeoxynucleotides that functionally reduce targeted connexin protein expression and can be used to reveal the biological function of individual connexins in vivo. Connexin mRNA was firstly exposed in vitro to deoxyribozymes complementing the sense coding sequence. Those that cleaved the target connexin mRNA in defined regions were used as the basis to design oligodeoxynucleotides to the accessible sites, thus taking into account tertiary mRNA configurations rather than relying on computed predictions. Antisense oligodeoxynucleotides designed to bind to accessible mRNA sites selectively reduced connexin26 and -43 mRNA expression in a corneal epithelium ex vivo model. Connexin43 protein levels were reduced correlating with the knockdown in mRNA and the protein's rapid turnover; protein levels of connexin26 did not alter, supporting lower turnover rates reported for that protein. We show, for the first time, an inexpensive and empirical approach to the preparation of specific and functional antisense oligodeoxynucleotides against known gene targets in the post-genomic era.

SP-100 ground engineering system test site description and progress update

NASA Astrophysics Data System (ADS)

Baxter, William F.; Burchell, Gail P.; Fitzgibbon, Davis G.; Swita, Walter R.

1991-01-01

The SP-100 Ground Engineering System Test Site will provide the facilities for the testing of an SP-100 reactor, which is technically prototypic of the generic design for producing 100 kilowatts of electricity. This effort is part of the program to develop a compact, space-based power system capable of producing several hundred kilowatts of electrical power. The test site is located on the U.S. Department of Energy's Hanford Site near Richland, Washington. The site is minimizing capital equipment costs by utilizing existing facilities and equipment to the maximum extent possible. The test cell is located in a decommissioned reactor containment building, and the secondary sodium cooling loop will use equipment from the Fast Flux Test Facility plant which has never been put into service. Modifications to the facility and special equipment are needed to accommodate the testing of the SP-100 reactor. Definitive design of the Ground Engineering System Test Site facility modifications and systems is in progress. The design of the test facility and the testing equipment will comply with the regulations and specifications of the U.S. Department of Energy and the State of Washington.

Tissue-specific tumorigenesis – Context matters

PubMed Central

Schneider, Günter; Schmidt-Supprian, Marc; Rad, Roland; Saur, Dieter

2018-01-01

Preface How can we treat cancer more effectively? Traditionally, tumours from the same anatomical site are treated as one tumour entity. This concept has been challenged by recent breakthroughs in cancer genomics and translational research enabling molecular tumour profiling. The identification and validation of cancer drivers, which are shared between different tumour types, spurred the new paradigm to target driver pathways across anatomical sites by off-label drug use, or within so called “basket or umbrella trials”, which are designed to test whether molecular alterations in one tumour entity can be extrapolated to all others. However, recent clinical and preclinical studies suggest that there are tissue- and cell type-specific differences in tumourigenesis and the organization of oncogenic signalling pathways. In this Opinion article, we focus on the molecular, cellular, systemic and environmental determinants of organ-specific tumourigenesis and mechanisms of context-specific oncogenic signalling outputs. Investigation, recognition and in-depth biological understanding of these differences will be vital for the design of next-generation clinical trials and the implementation of molecularly-guided cancer therapies in the future. PMID:28256574

Developing Educational Materials about Risks on Social Network Sites: A Design Based Research Approach

ERIC Educational Resources Information Center

Vanderhoven, Ellen; Schellens, Tammy; Vanderlinde, Ruben; Valcke, Martin

2016-01-01

Nearly all of today's Western teenagers have a profile on a social network site (SNS). As many risks have been reported, researchers and governments have emphasized the role of school education to teach teenagers how to deal safely with SNSs. However, little is known about the specific characteristics which would make interventions effective.…

Changes in DNA Methylation of Oocytes and Granulosa Cells Assessed by HELMET during Folliculogenesis in Mouse Ovary

PubMed Central

Liu, Jin; Zhang, Wenchang; Wu, Zhiren; Dai, Lei; Koji, Takehiko

2018-01-01

For a better understanding of epigenetic regulation of cell differentiation, it is important to analyze DNA methylation at a specific site. In this study, we examined changes in the methylation level of CCGG and GATCG sites during mouse folliculogenesis in paraffin-embedded sections of mouse ovaries. For the purpose, we used a new method, histo endonuclease-linked detection of methylation sites of DNA (HELMET), designed to detect methylation sites of DNA with a specific sequence in a tissue section. Unlike the global level of DNA methylation, which was no change in immunohistochemical staining of 5-methylcytosine throughout folliculogenesis, we found that there were hypermethylation of CCGG and GATCG sites in most of the granulosa cells of tertiary follicles compared to that of primary and secondary follicles. Interestingly, TUNEL-positive granulosa cells, which were frequent in mammalian folliculogenesis, became markedly Hpa II-reactive and Sau3A I-reactive, indicating that the CCGG and GATCG sites may be preferentially demethylated during apoptosis. PMID:29867282

Changes in DNA Methylation of Oocytes and Granulosa Cells Assessed by HELMET during Folliculogenesis in Mouse Ovary.

PubMed

Liu, Jin; Zhang, Wenchang; Wu, Zhiren; Dai, Lei; Koji, Takehiko

2018-04-27

For a better understanding of epigenetic regulation of cell differentiation, it is important to analyze DNA methylation at a specific site. In this study, we examined changes in the methylation level of CCGG and GATCG sites during mouse folliculogenesis in paraffin-embedded sections of mouse ovaries. For the purpose, we used a new method, histo endonuclease-linked detection of methylation sites of DNA (HELMET), designed to detect methylation sites of DNA with a specific sequence in a tissue section. Unlike the global level of DNA methylation, which was no change in immunohistochemical staining of 5-methylcytosine throughout folliculogenesis, we found that there were hypermethylation of CCGG and GATCG sites in most of the granulosa cells of tertiary follicles compared to that of primary and secondary follicles. Interestingly, TUNEL-positive granulosa cells, which were frequent in mammalian folliculogenesis, became markedly Hpa II-reactive and Sau 3A I-reactive, indicating that the CCGG and GATCG sites may be preferentially demethylated during apoptosis.

Data Integration Tool: Permafrost Data Debugging

NASA Astrophysics Data System (ADS)

Wilcox, H.; Schaefer, K. M.; Jafarov, E. E.; Pulsifer, P. L.; Strawhacker, C.; Yarmey, L.; Basak, R.

2017-12-01

We developed a Data Integration Tool (DIT) to significantly speed up the time of manual processing needed to translate inconsistent, scattered historical permafrost data into files ready to ingest directly into the Global Terrestrial Network-Permafrost (GTN-P). The United States National Science Foundation funded this project through the National Snow and Ice Data Center (NSIDC) with the GTN-P to improve permafrost data access and discovery. We leverage this data to support science research and policy decisions. DIT is a workflow manager that divides data preparation and analysis into a series of steps or operations called widgets (https://github.com/PermaData/DIT). Each widget does a specific operation, such as read, multiply by a constant, sort, plot, and write data. DIT allows the user to select and order the widgets as desired to meet their specific needs, incrementally interact with and evolve the widget workflows, and save those workflows for reproducibility. Taking ideas from visual programming found in the art and design domain, debugging and iterative design principles from software engineering, and the scientific data processing and analysis power of Fortran and Python it was written for interactive, iterative data manipulation, quality control, processing, and analysis of inconsistent data in an easily installable application. DIT was used to completely translate one dataset (133 sites) that was successfully added to GTN-P, nearly translate three datasets (270 sites), and is scheduled to translate 10 more datasets ( 1000 sites) from the legacy inactive site data holdings of the Frozen Ground Data Center (FGDC). Iterative development has provided the permafrost and wider scientific community with an extendable tool designed specifically for the iterative process of translating unruly data.

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

Oney, Stephen K.; Hogan, Timothy; Steinbeck, John

Ocean thermal energy conversion (OTEC) is a marine renewable energy technology with the potential to contribute significantly to the baseload power needs of tropical island communities and remote U.S. military installations. As with other renewable energy technologies, however, there are potential challenges to its commercialization: technological, financial, social, and environmental. Given the large volumes of seawater required to drive the electricity-producing cycle, there is potential for the intakes to negatively impact the marine resources of the source waterbody through the impingement and entrainment of marine organisms. The goal of this project was to identify feasible warm water intake designs formore » a land-based OTEC facility proposed for development in Port Allen, Kauai and to characterize the populations of ichthyoplankton near the proposed warm water intake location that could be at risk of entrainment. The specific objectives of this project were to: • Complete a site-specific assessment of available and feasible warm water intake technologies to determine the best intake designs for minimizing impacts to aquatic organisms at the proposed land-based OTEC site in Port Allen, Kauai. • Complete a field sampling program to collect biological data to characterize the baseline populations of ichthyoplankton near the sites being considered for the warm water intake at the proposed land-based OTEC site in Port Allen, Kauai. Various intake design options are presented with the focus on providing adequate environmental protection to the local ichthyoplankton population while providing an economically viable intake option to the OTEC developer. Further definition by NOAA and other environmental regulators is required to further refine the designs presented to meet all US regulations for future OTEC development.« less

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay.

PubMed

Cui, Heying; Loftus, Kyle M; Noell, Crystal R; Solmaz, Sozanne R

2018-05-03

Cyclin-dependent kinase 1 (Cdk1) is a master controller for the cell cycle in all eukaryotes and phosphorylates an estimated 8 - 13% of the proteome; however, the number of identified targets for Cdk1, particularly in human cells is still low. The identification of Cdk1-specific phosphorylation sites is important, as they provide mechanistic insights into how Cdk1 controls the cell cycle. Cell cycle regulation is critical for faithful chromosome segregation, and defects in this complicated process lead to chromosomal aberrations and cancer. Here, we describe an in vitro kinase assay that is used to identify Cdk1-specific phosphorylation sites. In this assay, a purified protein is phosphorylated in vitro by commercially available human Cdk1/cyclin B. Successful phosphorylation is confirmed by SDS-PAGE, and phosphorylation sites are subsequently identified by mass spectrometry. We also describe purification protocols that yield highly pure and homogeneous protein preparations suitable for the kinase assay, and a binding assay for the functional verification of the identified phosphorylation sites, which probes the interaction between a classical nuclear localization signal (cNLS) and its nuclear transport receptor karyopherin α. To aid with experimental design, we review approaches for the prediction of Cdk1-specific phosphorylation sites from protein sequences. Together these protocols present a very powerful approach that yields Cdk1-specific phosphorylation sites and enables mechanistic studies into how Cdk1 controls the cell cycle. Since this method relies on purified proteins, it can be applied to any model organism and yields reliable results, especially when combined with cell functional studies.

76 FR 61350 - Environmental Management Site-Specific Advisory Board, Paducah

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-04

... Water Model. [cir] Presentation by Swift & Staley: Environmental Information Center. Subcommittee Chairs... in the agenda. The Deputy Designated Federal Officer is empowered to conduct the meeting in a fashion...

Offshore fatigue design turbulence

NASA Astrophysics Data System (ADS)

Larsen, Gunner C.

2001-07-01

Fatigue damage on wind turbines is mainly caused by stochastic loading originating from turbulence. While onshore sites display large differences in terrain topology, and thereby also in turbulence conditions, offshore sites are far more homogeneous, as the majority of them are likely to be associated with shallow water areas. However, despite this fact, specific recommendations on offshore turbulence intensities, applicable for fatigue design purposes, are lacking in the present IEC code. This article presents specific guidelines for such loading. These guidelines are based on the statistical analysis of a large number of wind data originating from two Danish shallow water offshore sites. The turbulence standard deviation depends on the mean wind speed, upstream conditions, measuring height and thermal convection. Defining a population of turbulence standard deviations, at a given measuring position, uniquely by the mean wind speed, variations in upstream conditions and atmospheric stability will appear as variability of the turbulence standard deviation. Distributions of such turbulence standard deviations, conditioned on the mean wind speed, are quantified by fitting the measured data to logarithmic Gaussian distributions. By combining a simple heuristic load model with the parametrized conditional probability density functions of the turbulence standard deviations, an empirical offshore design turbulence intensity is determined. For pure stochastic loading (as associated with standstill situations), the design turbulence intensity yields a fatigue damage equal to the average fatigue damage caused by the distributed turbulence intensity. If the stochastic loading is combined with a periodic deterministic loading (as in the normal operating situation), the proposed design turbulence intensity is shown to be conservative.

Procurement Specifications Templates for On-Site Solar Photovoltaic: For Use in Developing Federal Solicitations

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

Robinson, G.

With the increasing adaption of on-site renewable energy systems designed to feed site loads, there is a critical need to develop tools that allow the federal sector to become a mature and sophisticated consumer. This document is intended to reduce project development and operational risks while increasing the speed at which projects are completed; two necessary components to reach the scale required to meet mandates and achieve cost savings for taxpayers. This guide is intended to act as a living document where lessons learned from the increasing number of projects can be incorporated and provide guidance for efforts. While additionalmore » guides will be developed to cover other renewable technologies, this guide covers on-site solar photovoltaic systems with an emphasis on third-party designed, financed, owned, and operated systems.« less

75 FR 7576 - Environmental Management Site-Specific Advisory Board, Oak Ridge Reservation

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-22

... environmental restoration, waste management, and related activities. Tentative Agenda: The main meeting... agenda. The Deputy Designated Federal Officer is empowered to conduct the meeting in a fashion that will...

76 FR 59393 - Environmental Management Site-Specific Advisory Board, Oak Ridge Reservation

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-26

... environmental restoration, waste management, and related activities. Tentative Agenda: The main meeting... agenda. The Deputy Designated Federal Officer is empowered to conduct the meeting in a fashion that will...

76 FR 65190 - Environmental Management Site-Specific Advisory Board, Oak Ridge Reservation

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-20

... environmental restoration, waste management, and related activities. Tentative Agenda: The main meeting... in the agenda. The Deputy Designated Federal Officer is empowered to conduct the meeting in a fashion...

75 FR 51027 - Environmental Management Site-Specific Advisory Board, Oak Ridge Reservation

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-18

... environmental restoration, waste management, and related activities. Tentative Agenda: The main meeting... agenda. The Deputy Designated Federal Officer is empowered to conduct the meeting in a fashion that will...

75 FR 6370 - Environmental Management Site-Specific Advisory Board, Nevada

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-09

..., waste management, and related activities. Tentative Agenda 1. Presentation--History of the Nevada Test... agenda. The Deputy Designated Federal Officer is empowered to conduct the meeting in a fashion that will...

PAM multiplicity marks genomic target sites as inhibitory to CRISPR-Cas9 editing.

PubMed

Malina, Abba; Cameron, Christopher J F; Robert, Francis; Blanchette, Mathieu; Dostie, Josée; Pelletier, Jerry

2015-12-08

In CRISPR-Cas9 genome editing, the underlying principles for selecting guide RNA (gRNA) sequences that would ensure for efficient target site modification remain poorly understood. Here we show that target sites harbouring multiple protospacer adjacent motifs (PAMs) are refractory to Cas9-mediated repair in situ. Thus we refine which substrates should be avoided in gRNA design, implicating PAM density as a novel sequence-specific feature that inhibits in vivo Cas9-driven DNA modification.

PAM multiplicity marks genomic target sites as inhibitory to CRISPR-Cas9 editing

PubMed Central

Malina, Abba; Cameron, Christopher J. F.; Robert, Francis; Blanchette, Mathieu; Dostie, Josée; Pelletier, Jerry

2015-01-01

In CRISPR-Cas9 genome editing, the underlying principles for selecting guide RNA (gRNA) sequences that would ensure for efficient target site modification remain poorly understood. Here we show that target sites harbouring multiple protospacer adjacent motifs (PAMs) are refractory to Cas9-mediated repair in situ. Thus we refine which substrates should be avoided in gRNA design, implicating PAM density as a novel sequence-specific feature that inhibits in vivo Cas9-driven DNA modification. PMID:26644285

Event-based total suspended sediment particle size distribution model

NASA Astrophysics Data System (ADS)

Thompson, Jennifer; Sattar, Ahmed M. A.; Gharabaghi, Bahram; Warner, Richard C.

2016-05-01

One of the most challenging modelling tasks in hydrology is prediction of the total suspended sediment particle size distribution (TSS-PSD) in stormwater runoff generated from exposed soil surfaces at active construction sites and surface mining operations. The main objective of this study is to employ gene expression programming (GEP) and artificial neural networks (ANN) to develop a new model with the ability to more accurately predict the TSS-PSD by taking advantage of both event-specific and site-specific factors in the model. To compile the data for this study, laboratory scale experiments using rainfall simulators were conducted on fourteen different soils to obtain TSS-PSD. This data is supplemented with field data from three construction sites in Ontario over a period of two years to capture the effect of transport and deposition within the site. The combined data sets provide a wide range of key overlooked site-specific and storm event-specific factors. Both parent soil and TSS-PSD in runoff are quantified by fitting each to a lognormal distribution. Compared to existing regression models, the developed model more accurately predicted the TSS-PSD using a more comprehensive list of key model input parameters. Employment of the new model will increase the efficiency of deployment of required best management practices, designed based on TSS-PSD, to minimize potential adverse effects of construction site runoff on aquatic life in the receiving watercourses.

Cleavage-site specificity of prolyl endopeptidase FAP investigated with a full-length protein substrate.

PubMed

Huang, Chih-Hsiang; Suen, Ching-Shu; Lin, Ching-Ting; Chien, Chia-Hui; Lee, Hsin-Ying; Chung, Kuei-Min; Tsai, Ting-Yueh; Jiaang, Weir-Tong; Hwang, Ming-Jing; Chen, Xin

2011-06-01

Fibroblast activation protein (FAP) is a prolyl-cleaving endopeptidase proposed as an anti-cancer drug target. It is necessary to define its cleavage-site specificity to facilitate the identification of its in vivo substrates and to understand its biological functions. We found that the previously identified substrate of FAP, α(2)-anti-plasmin, is not a robust substrate in vitro. Instead, an intracellular protein, SPRY2, is cleavable by FAP and more suitable for investigation of its substrate specificity in the context of the full-length globular protein. FAP prefers uncharged residues, including small or bulky hydrophobic amino acids, but not charged amino acids, especially acidic residue at P1', P3 and P4 sites. Molecular modelling analysis shows that the substrate-binding site of FAP is surrounded by multiple tyrosine residues and some negatively charged residues, which may exert least preference for substrates with acidic residues. This provides an explanation why FAP cannot cleave interleukins, which have a glutamate at either P4 or P2', despite their P3-P2-P1 sites being identical to SPRY2 or α-AP. Our study provided new information on FAP cleavage-site specificity, which differs from the data obtained by profiling with a peptide library or with the denatured protein, gelatin, as the substrate. Furthermore, our study suggests that negatively charged residues should be avoided when designing FAP inhibitors.

Structure of an N276-Dependent HIV-1 Neutralizing Antibody Targeting a Rare V5 Glycan Hole Adjacent to the CD4 Binding Site.

PubMed

Wibmer, Constantinos Kurt; Gorman, Jason; Anthony, Colin S; Mkhize, Nonhlanhla N; Druz, Aliaksandr; York, Talita; Schmidt, Stephen D; Labuschagne, Phillip; Louder, Mark K; Bailer, Robert T; Abdool Karim, Salim S; Mascola, John R; Williamson, Carolyn; Moore, Penny L; Kwong, Peter D; Morris, Lynn

2016-11-15

All HIV-1-infected individuals develop strain-specific neutralizing antibodies to their infecting virus, which in some cases mature into broadly neutralizing antibodies. Defining the epitopes of strain-specific antibodies that overlap conserved sites of vulnerability might provide mechanistic insights into how broadly neutralizing antibodies arise. We previously described an HIV-1 clade C-infected donor, CAP257, who developed broadly neutralizing plasma antibodies targeting an N276 glycan-dependent epitope in the CD4 binding site. The initial CD4 binding site response potently neutralized the heterologous tier 2 clade B viral strain RHPA, which was used to design resurfaced gp120 antigens for single-B-cell sorting. Here we report the isolation and structural characterization of CAP257-RH1, an N276 glycan-dependent CD4 binding site antibody representative of the early CD4 binding site plasma response in donor CAP257. The cocrystal structure of CAP257-RH1 bound to RHPA gp120 revealed critical interactions with the N276 glycan, loop D, and V5, but not with aspartic acid 368, similarly to HJ16 and 179NC75. The CAP257-RH1 monoclonal antibody was derived from the immunoglobulin-variable IGHV3-33 and IGLV3-10 genes and neutralized RHPA but not the transmitted/founder virus from donor CAP257. Its narrow neutralization breadth was attributed to a binding angle that was incompatible with glycosylated V5 loops present in almost all HIV-1 strains, including the CAP257 transmitted/founder virus. Deep sequencing of autologous CAP257 viruses, however, revealed minority variants early in infection that lacked V5 glycans. These glycan-free V5 loops are unusual holes in the glycan shield that may have been necessary for initiating this N276 glycan-dependent CD4 binding site B-cell lineage. The conserved CD4 binding site on gp120 is a major target for HIV-1 vaccine design, but key events in the elicitation and maturation of different antibody lineages to this site remain elusive. Studies have shown that strain-specific antibodies can evolve into broadly neutralizing antibodies or in some cases act as helper lineages. Therefore, characterizing the epitopes of strain-specific antibodies may help to inform the design of HIV-1 immunogens to elicit broadly neutralizing antibodies. In this study, we isolate a narrowly neutralizing N276 glycan-dependent antibody and use X-ray crystallography and viral deep sequencing to describe how gp120 lacking glycans in V5 might have elicited these early glycan-dependent CD4 binding site antibodies. These data highlight how glycan holes can play a role in the elicitation of B-cell lineages targeting the CD4 binding site. Copyright © 2016 Wibmer et al.

Structure of an N276-Dependent HIV-1 Neutralizing Antibody Targeting a Rare V5 Glycan Hole Adjacent to the CD4 Binding Site

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

Wibmer, Constantinos Kurt; Gorman, Jason; Anthony, Colin S.

ABSTRACT All HIV-1-infected individuals develop strain-specific neutralizing antibodies to their infecting virus, which in some cases mature into broadly neutralizing antibodies. Defining the epitopes of strain-specific antibodies that overlap conserved sites of vulnerability might provide mechanistic insights into how broadly neutralizing antibodies arise. We previously described an HIV-1 clade C-infected donor, CAP257, who developed broadly neutralizing plasma antibodies targeting an N276 glycan-dependent epitope in the CD4 binding site. The initial CD4 binding site response potently neutralized the heterologous tier 2 clade B viral strain RHPA, which was used to design resurfaced gp120 antigens for single-B-cell sorting. Here we report themore » isolation and structural characterization of CAP257-RH1, an N276 glycan-dependent CD4 binding site antibody representative of the early CD4 binding site plasma response in donor CAP257. The cocrystal structure of CAP257-RH1 bound to RHPA gp120 revealed critical interactions with the N276 glycan, loop D, and V5, but not with aspartic acid 368, similarly to HJ16 and 179NC75. The CAP257-RH1 monoclonal antibody was derived from the immunoglobulin-variable IGHV3-33 and IGLV3-10 genes and neutralized RHPA but not the transmitted/founder virus from donor CAP257. Its narrow neutralization breadth was attributed to a binding angle that was incompatible with glycosylated V5 loops present in almost all HIV-1 strains, including the CAP257 transmitted/founder virus. Deep sequencing of autologous CAP257 viruses, however, revealed minority variants early in infection that lacked V5 glycans. These glycan-free V5 loops are unusual holes in the glycan shield that may have been necessary for initiating this N276 glycan-dependent CD4 binding site B-cell lineage. IMPORTANCEThe conserved CD4 binding site on gp120 is a major target for HIV-1 vaccine design, but key events in the elicitation and maturation of different antibody lineages to this site remain elusive. Studies have shown that strain-specific antibodies can evolve into broadly neutralizing antibodies or in some cases act as helper lineages. Therefore, characterizing the epitopes of strain-specific antibodies may help to inform the design of HIV-1 immunogens to elicit broadly neutralizing antibodies. In this study, we isolate a narrowly neutralizing N276 glycan-dependent antibody and use X-ray crystallography and viral deep sequencing to describe how gp120 lacking glycans in V5 might have elicited these early glycan-dependent CD4 binding site antibodies. These data highlight how glycan holes can play a role in the elicitation of B-cell lineages targeting the CD4 binding site.« less

Structure of an N276-Dependent HIV-1 Neutralizing Antibody Targeting a Rare V5 Glycan Hole Adjacent to the CD4 Binding Site

PubMed Central

Wibmer, Constantinos Kurt; Gorman, Jason; Anthony, Colin S.; Mkhize, Nonhlanhla N.; Druz, Aliaksandr; York, Talita; Schmidt, Stephen D.; Labuschagne, Phillip; Louder, Mark K.; Bailer, Robert T.; Abdool Karim, Salim S.; Mascola, John R.; Williamson, Carolyn; Moore, Penny L.

2016-01-01

ABSTRACT All HIV-1-infected individuals develop strain-specific neutralizing antibodies to their infecting virus, which in some cases mature into broadly neutralizing antibodies. Defining the epitopes of strain-specific antibodies that overlap conserved sites of vulnerability might provide mechanistic insights into how broadly neutralizing antibodies arise. We previously described an HIV-1 clade C-infected donor, CAP257, who developed broadly neutralizing plasma antibodies targeting an N276 glycan-dependent epitope in the CD4 binding site. The initial CD4 binding site response potently neutralized the heterologous tier 2 clade B viral strain RHPA, which was used to design resurfaced gp120 antigens for single-B-cell sorting. Here we report the isolation and structural characterization of CAP257-RH1, an N276 glycan-dependent CD4 binding site antibody representative of the early CD4 binding site plasma response in donor CAP257. The cocrystal structure of CAP257-RH1 bound to RHPA gp120 revealed critical interactions with the N276 glycan, loop D, and V5, but not with aspartic acid 368, similarly to HJ16 and 179NC75. The CAP257-RH1 monoclonal antibody was derived from the immunoglobulin-variable IGHV3-33 and IGLV3-10 genes and neutralized RHPA but not the transmitted/founder virus from donor CAP257. Its narrow neutralization breadth was attributed to a binding angle that was incompatible with glycosylated V5 loops present in almost all HIV-1 strains, including the CAP257 transmitted/founder virus. Deep sequencing of autologous CAP257 viruses, however, revealed minority variants early in infection that lacked V5 glycans. These glycan-free V5 loops are unusual holes in the glycan shield that may have been necessary for initiating this N276 glycan-dependent CD4 binding site B-cell lineage. IMPORTANCE The conserved CD4 binding site on gp120 is a major target for HIV-1 vaccine design, but key events in the elicitation and maturation of different antibody lineages to this site remain elusive. Studies have shown that strain-specific antibodies can evolve into broadly neutralizing antibodies or in some cases act as helper lineages. Therefore, characterizing the epitopes of strain-specific antibodies may help to inform the design of HIV-1 immunogens to elicit broadly neutralizing antibodies. In this study, we isolate a narrowly neutralizing N276 glycan-dependent antibody and use X-ray crystallography and viral deep sequencing to describe how gp120 lacking glycans in V5 might have elicited these early glycan-dependent CD4 binding site antibodies. These data highlight how glycan holes can play a role in the elicitation of B-cell lineages targeting the CD4 binding site. PMID:27581986

Independent Verification Final Summary Report for the David Witherspoon, Inc. 1630 Site Knoxville, Tennessee

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

P.C. Weaver

2009-04-29

The primary objective of the independent verification was to determine if BJC performed the appropriate actions to meet the specified “hot spot” cleanup criteria of 500 picocuries per gram (pCi/g) uranium-238 (U-238) in surface soil. Specific tasks performed by the independent verification team (IVT) to satisfy this objective included: 1) performing radiological walkover surveys, and 2) collecting soil samples for independent analyses. The independent verification (IV) efforts were designed to evaluate radioactive contaminants (specifically U-238) in the exposed surfaces below one foot of the original site grade, given that the top one foot layer of soil on the site wasmore » removed in its entirety.« less

Superfund record of decision (EPA Region 9): Mather Air Force Base, Soil and Groundwater operable units, Sacramento, CA, June 21, 1996

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

NONE

The decision document presents the selected remedial actions for the Soil Operable Unit (OU) Sites and Groundwater OU Plumes, at the formerly active Mather Air Force Base (AFB), Sacramento County, California. The purpose of the Record of Decision (ROD) is to decide the appropriate level of remediation necessary to protect human health and the environment, and determine what requirements are applicable or relevant and appropriate requirements (ARARs) based on the groundwater beneficial use designation and site-specific conditions. The ROD has been divided into seven sections which specifically address the range of selected remedial actions for the Soil OU sites andmore » Groundwater OU plumes.« less

Evolution of a designed retro-aldolase leads to complete active site remodeling

PubMed Central

Giger, Lars; Caner, Sami; Obexer, Richard; Kast, Peter; Baker, David; Ban, Nenad; Hilvert, Donald

2013-01-01

Evolutionary advances are often fueled by unanticipated innovation. Directed evolution of a computationally designed enzyme suggests that dramatic molecular changes can also drive the optimization of primitive protein active sites. The specific activity of an artificial retro-aldolase was boosted >4,400 fold by random mutagenesis and screening, affording catalytic efficiencies approaching those of natural enzymes. However, structural and mechanistic studies reveal that the engineered catalytic apparatus, consisting of a reactive lysine and an ordered water molecule, was unexpectedly abandoned in favor of a new lysine residue in a substrate binding pocket created during the optimization process. Structures of the initial in silico design, a mechanistically promiscuous intermediate, and one of the most evolved variants highlight the importance of loop mobility and supporting functional groups in the emergence of the new catalytic center. Such internal competition between alternative reactive sites may have characterized the early evolution of many natural enzymes. PMID:23748672

Theory on the mechanism of site-specific DNA-protein interactions in the presence of traps

NASA Astrophysics Data System (ADS)

Niranjani, G.; Murugan, R.

2016-08-01

The speed of site-specific binding of transcription factor (TFs) proteins with genomic DNA seems to be strongly retarded by the randomly occurring sequence traps. Traps are those DNA sequences sharing significant similarity with the original specific binding sites (SBSs). It is an intriguing question how the naturally occurring TFs and their SBSs are designed to manage the retarding effects of such randomly occurring traps. We develop a simple random walk model on the site-specific binding of TFs with genomic DNA in the presence of sequence traps. Our dynamical model predicts that (a) the retarding effects of traps will be minimum when the traps are arranged around the SBS such that there is a negative correlation between the binding strength of TFs with traps and the distance of traps from the SBS and (b) the retarding effects of sequence traps can be appeased by the condensed conformational state of DNA. Our computational analysis results on the distribution of sequence traps around the putative binding sites of various TFs in mouse and human genome clearly agree well the theoretical predictions. We propose that the distribution of traps can be used as an additional metric to efficiently identify the SBSs of TFs on genomic DNA.

Review of Natural Phenomena Hazard (NPH) Assessments for the Hanford 200 Areas (Non-Seismic)

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

Snow, Robert L.; Ross, Steven B.; Sullivan, Robin S.

2010-09-24

The purpose of this review is to assess the need for updating Natural Phenomena Hazard (NPH) assessments for the Hanford 200 Areas, as required by DOE Order 420.1B Chapter IV, Natural Phenomena Hazards Mitigation, based on significant changes in state-of-the-art NPH assessment methodology or site-specific information. The review includes all natural phenomena hazards with the exception of seismic/earthquake hazards, which are being addressed under a separate effort. It was determined that existing non-seismic NPH assessments are consistent with current design methodology and site specific data.

Preliminary design package for prototype solar heating system

NASA Technical Reports Server (NTRS)

1978-01-01

A summary is given of the preliminary analysis and design activity on solar heating systems. The analysis was made without site specific data other than weather; therefore, the results indicate performance expected under these special conditions. Major items include system candidates, design approaches, trade studies and other special data required to evaluate the preliminary analysis and design. The program calls for the development and delivery of eight prototype solar heating and cooling systems for installation and operational test.

Structure of Insoluble Rat Sperm Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH) via Heterotetramer Formation with Escherichia coli GAPDH Reveals Target for Contraceptive Design*

PubMed Central

Frayne, Jan; Taylor, Abby; Cameron, Gus; Hadfield, Andrea T.

2009-01-01

Sperm glyceraldehyde-3-phosphate dehydrogenase has been shown to be a successful target for a non-hormonal contraceptive approach, but the agents tested to date have had unacceptable side effects. Obtaining the structure of the sperm-specific isoform to allow rational inhibitor design has therefore been a goal for a number of years but has proved intractable because of the insoluble nature of both native and recombinant protein. We have obtained soluble recombinant sperm glyceraldehyde-3-phosphate dehydrogenase as a heterotetramer with the Escherichia coli glyceraldehyde-3-phosphate dehydrogenase in a ratio of 1:3 and have solved the structure of the heterotetramer which we believe represents a novel strategy for structure determination of an insoluble protein. A structure was also obtained where glyceraldehyde 3-phosphate binds in the Ps pocket in the active site of the sperm enzyme subunit in the presence of NAD. Modeling and comparison of the structures of human somatic and sperm-specific glyceraldehyde-3-phosphate dehydrogenase revealed few differences at the active site and hence rebut the long presumed structural specificity of 3-chlorolactaldehyde for the sperm isoform. The contraceptive activity of α-chlorohydrin and its apparent specificity for the sperm isoform in vivo are likely to be due to differences in metabolism to 3-chlorolactaldehyde in spermatozoa and somatic cells. However, further detailed analysis of the sperm glyceraldehyde-3-phosphate dehydrogenase structure revealed sites in the enzyme that do show significant difference compared with published somatic glyceraldehyde-3-phosphate dehydrogenase structures that could be exploited by structure-based drug design to identify leads for novel male contraceptives. PMID:19542219

Administrative goals and safety standards for hazard control on forested recreation sites

Treesearch

Lee A. Paine

1973-01-01

For efficient control of tree hazard on recreation sites, a specific administrative goal must be selected. A safety standard designed to achieve the selected goal and a uniform hazard-rating procedure will then promote a consistent level of safety at an acceptable cost. Safety standards can be established with the aid of data for past years, and dollar evaluations are...

SIMS prototype system 1: Design data brochure. [solar heating system

NASA Technical Reports Server (NTRS)

1978-01-01

A prototype solar heating and hot water system using air as the collector fluid and a pebble bed for heat storage was designed for installation into a single family dwelling. The system, subsystem, and installation requirements are described. System operation and performance are discussed, and procedures for sizing the system to a specific site are presented.

75 FR 57462 - Environmental Management Site-Specific Advisory Board, Oak Ridge Reservation

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-21

... areas of environmental restoration, waste management, and related activities. Tentative Agenda: The main... agenda. The Deputy Designated Federal Officer is empowered to conduct the meeting in a fashion that will...

76 FR 9572 - Environmental Management Site-Specific Advisory Board, Oak Ridge Reservation

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-18

... areas of environmental restoration, waste management, and related activities. Tentative Agenda: The main... agenda. The Deputy Designated Federal Officer is empowered to conduct the meeting in a fashion that will...

75 FR 71424 - Environmental Management Site-Specific Advisory Board, Oak Ridge Reservation

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-23

... areas of environmental restoration, waste management, and related activities. Tentative Agenda: The main... Designated Federal Officer is empowered to conduct the meeting in a fashion that will facilitate the orderly...

76 FR 10018 - Environmental Management Site-Specific Advisory Board, Idaho National Laboratory

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-23

... Idaho's 2015 Cleanup Vision Government Budget Cycle American Recovery and Reinvestment Act Idaho Cleanup.... The Deputy Designated Federal Officer is empowered to conduct the meeting in a fashion that will...

Targeted modulation of reactive oxygen species in the vascular endothelium.

PubMed

Shuvaev, Vladimir V; Muzykantov, Vladimir R

2011-07-15

'Endothelial cells lining vascular luminal surface represent an important site of signaling and injurious effects of reactive oxygen species (ROS) produced by other cells and endothelium itself in ischemia, inflammation and other pathological conditions. Targeted delivery of ROS modulating enzymes conjugated with antibodies to endothelial surface molecules (vascular immunotargeting) provides site-specific interventions in the endothelial ROS, unattainable by other formulations including PEG-modified enzymes. Targeting of ROS generating enzymes (e.g., glucose oxidase) provides ROS- and site-specific models of endothelial oxidative stress, whereas targeting of antioxidant enzymes SOD and catalase offers site-specific quenching of superoxide anion and H(2)O(2). These targeted antioxidant interventions help to clarify specific role of endothelial ROS in vascular and pulmonary pathologies and provide basis for design of targeted therapeutics for treatment of these pathologies. In particular, antibody/catalase conjugates alleviate acute lung ischemia/reperfusion injury, whereas antibody/SOD conjugates inhibit ROS-mediated vasoconstriction and inflammatory endothelial signaling. Encapsulation in protease-resistant, ROS-permeable carriers targeted to endothelium prolongs protective effects of antioxidant enzymes, further diversifying the means for targeted modulation of endothelial ROS. Copyright © 2011 Elsevier B.V. All rights reserved.

Derivation of site-specific relationships between hydraulic parameters and p-wave velocities based on hydraulic and seismic tomography

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

Brauchler, R.; Doetsch, J.; Dietrich, P.

2012-01-10

In this study, hydraulic and seismic tomographic measurements were used to derive a site-specific relationship between the geophysical parameter p-wave velocity and the hydraulic parameters, diffusivity and specific storage. Our field study includes diffusivity tomograms derived from hydraulic travel time tomography, specific storage tomograms, derived from hydraulic attenuation tomography, and p-wave velocity tomograms, derived from seismic tomography. The tomographic inversion was performed in all three cases with the SIRT (Simultaneous Iterative Reconstruction Technique) algorithm, using a ray tracing technique with curved trajectories. The experimental set-up was designed such that the p-wave velocity tomogram overlaps the hydraulic tomograms by half. Themore » experiments were performed at a wellcharacterized sand and gravel aquifer, located in the Leine River valley near Göttingen, Germany. Access to the shallow subsurface was provided by direct-push technology. The high spatial resolution of hydraulic and seismic tomography was exploited to derive representative site-specific relationships between the hydraulic and geophysical parameters, based on the area where geophysical and hydraulic tests were performed. The transformation of the p-wave velocities into hydraulic properties was undertaken using a k-means cluster analysis. Results demonstrate that the combination of hydraulic and geophysical tomographic data is a promising approach to improve hydrogeophysical site characterization.« less

Combined Shuttle-Box Training with Electrophysiological Cortex Recording and Stimulation as a Tool to Study Perception and Learning.

PubMed

Happel, Max F K; Deliano, Matthias; Ohl, Frank W

2015-10-22

Shuttle-box avoidance learning is a well-established method in behavioral neuroscience and experimental setups were traditionally custom-made; the necessary equipment is now available by several commercial companies. This protocol provides a detailed description of a two-way shuttle-box avoidance learning paradigm in rodents (here Mongolian gerbils; Meriones unguiculatus) in combination with site-specific electrical intracortical microstimulation (ICMS) and simultaneous chronical electrophysiological in vivo recordings. The detailed protocol is applicable to study multiple aspects of learning behavior and perception in different rodent species. Site-specific ICMS of auditory cortical circuits as conditioned stimuli here is used as a tool to test the perceptual relevance of specific afferent, efferent and intracortical connections. Distinct activation patterns can be evoked by using different stimulation electrode arrays for local, layer-dependent ICMS or distant ICMS sites. Utilizing behavioral signal detection analysis it can be determined which stimulation strategy is most effective for eliciting a behaviorally detectable and salient signal. Further, parallel multichannel-recordings using different electrode designs (surface electrodes, depth electrodes, etc.) allow for investigating neuronal observables over the time course of such learning processes. It will be discussed how changes of the behavioral design can increase the cognitive complexity (e.g. detection, discrimination, reversal learning).

Combined Shuttle-Box Training with Electrophysiological Cortex Recording and Stimulation as a Tool to Study Perception and Learning

PubMed Central

Happel, Max F.K.

2015-01-01

Shuttle-box avoidance learning is a well-established method in behavioral neuroscience and experimental setups were traditionally custom-made; the necessary equipment is now available by several commercial companies. This protocol provides a detailed description of a two-way shuttle-box avoidance learning paradigm in rodents (here Mongolian gerbils; Meriones unguiculatus) in combination with site-specific electrical intracortical microstimulation (ICMS) and simultaneous chronical electrophysiological in vivo recordings. The detailed protocol is applicable to study multiple aspects of learning behavior and perception in different rodent species. Site-specific ICMS of auditory cortical circuits as conditioned stimuli here is used as a tool to test the perceptual relevance of specific afferent, efferent and intracortical connections. Distinct activation patterns can be evoked by using different stimulation electrode arrays for local, layer-dependent ICMS or distant ICMS sites. Utilizing behavioral signal detection analysis it can be determined which stimulation strategy is most effective for eliciting a behaviorally detectable and salient signal. Further, parallel multichannel-recordings using different electrode designs (surface electrodes, depth electrodes, etc.) allow for investigating neuronal observables over the time course of such learning processes. It will be discussed how changes of the behavioral design can increase the cognitive complexity (e.g. detection, discrimination, reversal learning). PMID:26556300

Improving website accessibility for people with early-stage dementia: a preliminary investigation.

PubMed

Freeman, E D; Clare, Linda; Savitch, Nada; Royan, Lindsay; Litherland, Rachael; Lindsay, Margot

2005-09-01

This study, conducted collaboratively with five men who have a diagnosis of early-stage Alzheimer's disease (AD), is the first stage of a formative research project aimed at developing a new website for people with dementia. Recommendations derived from a literature review of the implications of dementia-related cognitive changes for website design were combined with general web accessibility guidelines to provide a basis for the initial design of a new website. This website was compared with an equivalent site, containing the same information but based on an existing design, in terms of accessibility, ease of use, and user satisfaction. Participants were very satisfied with both sites, but responses did indicate some specific areas where one site was preferred over another. Observational data highlighted significant strengths of the new site as well as some limitations, and resulted in clear recommendations for enhancing the design. In particular, the study suggested that limiting the size of web pages to the amount of information that can be displayed on a computer screen at any one time could reduce the level of difficulty encountered by the participants. The results also suggested the importance of reducing cognitive load through limiting the number of choices required at any one time, the very opposite of the ethos of much website design.

Elements of museum mobile augmented reality for engaging hearing impaired visitors

NASA Astrophysics Data System (ADS)

Baker, Esraa Jaffar; Bakar, Juliana Aida Abu; Zulkifli, Abdul Nasir

2017-10-01

Nowadays, designers are more concern with the issue of engagement and informal learning at museum and gallery sites. This has made studies to focus more on the use of Mobile Augmented Reality (MAR) at museum and gallery sites. However, most of the MAR applications for museum visitors are largely tailored to normal hearing visitors while the hearing-impaired (HI) visitors are not supported. The hearing impaired (HI) community account for over 5% of the world's populace which is about 360 million people. Thus, this paper explores the design elements of mobile augmented reality for engaging hearing impaired visitors at the museum site. The findings of this paper argues that there are eleven major elements of engagement of MAR needed for the design of an efficient museum MAR app for hearing impaired visitors. These eleven elements include Aesthetics, Curiosity, Usability, Interaction, Motivation, Satisfaction, Self-Efficacy, Perceived Control, Enjoyment, Focused Attention and Interest. This study pointed out that for an efficient and engaged MAR app for the HI community especially HI visitors to museum sites, these eleven elements are critical. This finding will help MAR designers and developers on how to design an efficient and engaged MAR app for the HI community at large and museum HI visitors specifically.

Plasma 25-hydroxyvitamin D concentration and subsequent risk of total and site specific cancers in Japanese population: large case-cohort study within Japan Public Health Center-based Prospective Study cohort

PubMed Central

Budhathoki, Sanjeev; Hidaka, Akihisa; Sawada, Norie; Tanaka-Mizuno, Sachiko; Kuchiba, Aya; Charvat, Hadrien; Goto, Atsushi; Kojima, Satoshi; Sudo, Natsuki; Shimazu, Taichi; Sasazuki, Shizuka; Inoue, Manami; Tsugane, Shoichiro; Iwasaki, Motoki

2018-01-01

Abstract Objective To evaluate the association between pre-diagnostic circulating vitamin D concentration and the subsequent risk of overall and site specific cancer in a large cohort study. Design Nested case-cohort study within the Japan Public Health Center-based Prospective Study cohort. Setting Nine public health centre areas across Japan. Participants 3301 incident cases of cancer and 4044 randomly selected subcohort participants. Exposure Plasma concentration of 25-hydroxyvitamin D measured by enzyme immunoassay. Participants were divided into quarters based on the sex and season specific distribution of 25-hydroxyvitamin D among subcohorts. Weighted Cox proportional hazard models were used to calculate the multivariable adjusted hazard ratios for overall and site specific cancer across categories of 25-hydroxyvitamin D concentration, with the lowest quarter as the reference. Main outcome measure Incidence of overall or site specific cancer. Results Plasma 25-hydroxyvitamin D concentration was inversely associated with the risk of total cancer, with multivariable adjusted hazard ratios for the second to fourth quarters compared with the lowest quarter of 0.81 (95% confidence interval 0.70 to 0.94), 0.75 (0.65 to 0.87), and 0.78 (0.67 to 0.91), respectively (P for trend=0.001). Among the findings for cancers at specific sites, an inverse association was found for liver cancer, with corresponding hazard ratios of 0.70 (0.44 to 1.13), 0.65 (0.40 to 1.06), and 0.45 (0.26 to 0.79) (P for trend=0.006). A sensitivity analysis showed that alternately removing cases of cancer at one specific site from total cancer cases did not substantially change the overall hazard ratios. Conclusions In this large prospective study, higher vitamin D concentration was associated with lower risk of total cancer. These findings support the hypothesis that vitamin D has protective effects against cancers at many sites. PMID:29514781

An Energy Overview of the Kingdom of Thailand

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

anon.

The DOE Office of Fossil Energy is maintaining a web site that is meant to provide useful business- and energy-related information about countries and regions of the world for exporters, project developers, and researchers. The site consists of more than 130 country pages (organized into seven different world regions), with each country page having its own set of links to information sources about that country. There are also more than 30 Country Energy Overviews at the web site -- each of these is a comprehensive review of a specific country's entire energy situation, including sections on Energy Policy, Oil, Naturalmore » Gas, Coal, Hydroelectric/Renewables, Nuclear Power, Energy Transmission Infrastructure, Electricity, Electric Industry Overview, Environmental Activities, Privatization, Trade, and Economic Situation. The specific country highlighted in this Country Energy Overview is Thailand. The site is designed to be dynamic. Updates to the overviews will be made as need and resource s permit.« less

An Energy Overview of the Republic of Egypt

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

anon.

2003-10-17

The DOE Office of Fossil Energy is maintaining a web site that is meant to provide useful business- and energy-related information about countries and regions of the world for exporters, project developers, and researchers. The site consists of more than 130 country pages (organized into seven different world regions), with each country page having its own set of links to information sources about that country. There are also more than 30 Country Energy Overviews at the web site -- each of these is a comprehensive review of a specific country's entire energy situation, including sections on Energy Policy, Oil, Naturalmore » Gas, Coal, Hydroelectric/Renewables, Nuclear Power, Energy Transmission Infrastructure, Electricity, Electric Industry Overview, Environmental Activities, Privatization, Trade, and Economic Situation. The specific country highlighted in this Country Energy Overview is Egypt. The site is designed to be dynamic. Updates to the overviews will be made as need and resources permit.« less

An Energy Overview of Romania

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

anon.

2003-10-20

The DOE Office of Fossil Energy is maintaining a web site that is meant to provide useful business- and energy-related information about countries and regions of the world for exporters, project developers, and researchers. The site consists of more than 130 country pages (organized into seven different world regions), with each country page having its own set of links to information sources about that country. There are also more than 30 Country Energy Overviews at the web site -- each of these is a comprehensive review of a specific country's entire energy situation, including sections on Energy Policy, Oil, Naturalmore » Gas, Coal, Hydroelectric/Renewables, Nuclear Power, Energy Transmission Infrastructure, Electricity, Electric Industry Overview, Environmental Activities, Privatization, Trade, and Economic Situation. The specific country highlighted in this Country Energy Overview is Romania. The site is designed to be dynamic. Updates to the overviews will be made as need and resources permit.« less

An Energy Overview of Venezuela

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

anon.

2003-10-20

The DOE Office of Fossil Energy is maintaining a web site that is meant to provide useful business- and energy-related information about countries and regions of the world for exporters, project developers, and researchers. The site consists of more than 130 country pages (organized into seven different world regions), with each country page having its own set of links to information sources about that country. There are also more than 30 Country Energy Overviews at the web site -- each of these is a comprehensive review of a specific country's entire energy situation, including sections on Energy Policy, Oil, Naturalmore » Gas, Coal, Hydroelectric/Renewables, Nuclear Power, Energy Transmission Infrastructure, Electricity, Electric Industry Overview, Environmental Activities, Privatization, Trade, and Economic Situation. The specific country highlighted in this Country Energy Overview is Venezuela. The site is designed to be dynamic. Updates to the overviews will be made as need and resources permit.« less

Variable context Markov chains for HIV protease cleavage site prediction.

PubMed

Oğul, Hasan

2009-06-01

Deciphering the knowledge of HIV protease specificity and developing computational tools for detecting its cleavage sites in protein polypeptide chain are very desirable for designing efficient and specific chemical inhibitors to prevent acquired immunodeficiency syndrome. In this study, we developed a generative model based on a generalization of variable order Markov chains (VOMC) for peptide sequences and adapted the model for prediction of their cleavability by certain proteases. The new method, called variable context Markov chains (VCMC), attempts to identify the context equivalence based on the evolutionary similarities between individual amino acids. It was applied for HIV-1 protease cleavage site prediction problem and shown to outperform existing methods in terms of prediction accuracy on a common dataset. In general, the method is a promising tool for prediction of cleavage sites of all proteases and encouraged to be used for any kind of peptide classification problem as well.

An Energy Overview of the Czech Republic

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

anon.

2003-10-17

The DOE Office of Fossil Energy is maintaining a web site that is meant to provide useful business- and energy-related information about countries and regions of the world for exporters, project developers, and researchers. The site consists of more than 130 country pages (organized into seven different world regions), with each country page having its own set of links to information sources about that country. There are also more than 30 Country Energy Overviews at the web site -- each of these is a comprehensive review of a specific country's entire energy situation, including sections on Energy Policy, Oil, Naturalmore » Gas, Coal, Hydroelectric/Renewables, Nuclear Power, Energy Transmission Infrastructure, Electricity, Electric Industry Overview, Environmental Activities, Privatization, Trade, and Economic Situation. The specific country highlighted in this Country Energy Overview is the Czech Republic. The site is designed to be dynamic. Updates to the overviews will be made as need an d resources permit.« less

An Energy Overview of Argentina

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

anon.

2003-10-20

The DOE Office of Fossil Energy is maintaining a web site that is meant to provide useful business- and energy-related information about countries and regions of the world for exporters, project developers, and researchers. The site consists of more than 130 country pages (organized into seven different world regions), with each country page having its own set of links to information sources about that country. There are also more than 30 Country Energy Overviews at the web site -- each of these is a comprehensive review of a specific country's entire energy situation, including sections on Energy Policy, Oil, Naturalmore » Gas, Coal, Hydroelectric/Renewables, Nuclear Power, Energy Transmission Infrastructure, Electricity, Electric Industry Overview, Environmental Activities, Privatization, Trade, and Economic Situation. The specific country highlighted in this Country Energy Overview is Argentina. The site is designed to be dynamic. Updates to the overviews will be made as need and resources permit.« less

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

anon.

The DOE Office of Fossil Energy is maintaining a web site that is meant to provide useful business- and energy-related information about countries and regions of the world for exporters, project developers, and researchers. The site consists of more than 130 country pages (organized into seven different world regions), with each country page having its own set of links to information sources about that country. There are also more than 30 Country Energy Overviews at the web site--each of these is a comprehensive review of a specific country's entire energy situation, including sections on Energy Policy, Oil, Natural Gas, Coal,more » Hydroelectric/Renewables, Nuclear Power, Energy Transmission Infrastructure, Electricity, Electric Industry Overview, Environmental Activities, Privatization, Trade, and Economic Situation. The specific country highlighted in this Country Energy Overview is Colombia. The site is designed to be dynamic. Updates to the overviews will be made as need and resources permit.« less

An Energy Overview of the Republic of Poland

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

anon.

The DOE Office of Fossil Energy is maintaining a web site that is meant to provide useful business- and energy-related information about countries and regions of the world for exporters, project developers, and researchers. The site consists of more than 130 country pages (organized into seven different world regions), with each country page having its own set of links to information sources about that country. There are also more than 30 Country Energy Overviews at the web site -- each of these is a comprehensive review of a specific country's entire energy situation, including sections on Energy Policy, Oil, Naturalmore » Gas, Coal, Hydroelectric/Renewables, Nuclear Power, Energy Transmission Infrastructure, Electricity, Electric Industry Overview, Environmental Activities, Privatization, Trade, and Economic Situation. The specific country highlighted in this Country Energy Overview is Poland. The site is designed to be dynamic. Updates to the overviews will be made as need and resources permit.« less

MusiteDeep: a deep-learning framework for general and kinase-specific phosphorylation site prediction.

PubMed

Wang, Duolin; Zeng, Shuai; Xu, Chunhui; Qiu, Wangren; Liang, Yanchun; Joshi, Trupti; Xu, Dong

2017-12-15

Computational methods for phosphorylation site prediction play important roles in protein function studies and experimental design. Most existing methods are based on feature extraction, which may result in incomplete or biased features. Deep learning as the cutting-edge machine learning method has the ability to automatically discover complex representations of phosphorylation patterns from the raw sequences, and hence it provides a powerful tool for improvement of phosphorylation site prediction. We present MusiteDeep, the first deep-learning framework for predicting general and kinase-specific phosphorylation sites. MusiteDeep takes raw sequence data as input and uses convolutional neural networks with a novel two-dimensional attention mechanism. It achieves over a 50% relative improvement in the area under the precision-recall curve in general phosphorylation site prediction and obtains competitive results in kinase-specific prediction compared to other well-known tools on the benchmark data. MusiteDeep is provided as an open-source tool available at https://github.com/duolinwang/MusiteDeep. xudong@missouri.edu. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Decreased Surgical Site Infection Rate in Hysterectomy: Effect of a Gynecology-Specific Bundle.

PubMed

Andiman, Sarah E; Xu, Xiao; Boyce, John M; Ludwig, Elizabeth M; Rillstone, Heidi R W; Desai, Vrunda B; Fan, Linda L

2018-06-01

We implemented a hysterectomy-specific surgical site infection prevention bundle after a higher-than-expected surgical site infection rate was identified at our institution. We evaluate how this bundle affected the surgical site infection rate, length of hospital stay, and 30-day postoperative readmission rate. This is a quality improvement study featuring retrospective analysis of a prospectively implemented, multidisciplinary team-designed surgical site infection prevention bundle that consisted of chlorhexidine-impregnated preoperative wipes, standardized aseptic surgical preparation, standardized antibiotic dosing, perioperative normothermia, surgical dressing maintenance, and direct feedback to clinicians when the protocol was breached. There were 2,099 hysterectomies completed during the 33-month study period. There were 61 surgical site infections (4.51%) in the pre-full bundle implementation period and 14 (1.87%) in the post-full bundle implementation period; we found a sustained reduction in the proportion of patients experiencing surgical site infection during the last 8 months of the study period. After adjusting for clinical characteristics, patients who underwent surgery after full implementation were less likely to develop a surgical site infection (adjusted odds ratio [OR] 0.46, P=.01) than those undergoing surgery before full implementation. Multivariable regression analysis showed no statistically significant difference in postoperative days of hospital stay (adjusted mean ratio 0.95, P=.09) or rate of readmission for surgical site infection-specific indication (adjusted OR 2.65, P=.08) between the before and after full-bundle implementation periods. The multidisciplinary implementation of a gynecologic perioperative surgical site infection prevention bundle was associated with a significant reduction in surgical site infection rate in patients undergoing hysterectomy.

E-KIT: An Electronic-Knowledge Information Tool for Organizing Site Information and Improving Technical Communication with Stakeholders - 13082

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

Kautsky, Mark; Findlay, Richard C.; Hodges, Rex A.

2013-07-01

Managing technical references for projects that have long histories is hampered by the large collection of documents, each of which might contain discrete pieces of information relevant to the site conceptual model. A database application has been designed to improve the efficiency of retrieving technical information for a project. Although many databases are currently used for accessing analytical and geo-referenced data, applications designed specifically to manage technical reference material for projects are scarce. Retrieving site data from the array of available references becomes an increasingly inefficient use of labor. The electronic-Knowledge Information Tool (e-KIT) is designed as a project-level resourcemore » to access and communicate technical information. The e-KIT is a living tool that grows as new information becomes available, and its value to the project increases as the volume of site information increases. Having all references assembled in one location with complete reference citations and links to elements of the site conceptual model offers a way to enhance communication with outside groups. The published and unpublished references are incorporated into the e-KIT, while the compendium of references serves as a complete bibliography for the project. (authors)« less

Design and evaluation guidelines for Department of Energy facilities subjected to natural phenomena hazards

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

Kennedy, R.P.; Short, S.A.; McDonald, J.R.

1990-06-01

The Department of Energy (DOE) and the DOE Natural Phenomena Hazards Panel have developed uniform design and evaluation guidelines for protection against natural phenomena hazards at DOE sites throughout the United States. The goal of the guidelines is to assure that DOE facilities can withstand the effects of natural phenomena such as earthquakes, extreme winds, tornadoes, and flooding. The guidelines apply to both new facilities (design) and existing facilities (evaluation, modification, and upgrading). The intended audience is primarily the civil/structural or mechanical engineers conducting the design or evaluation of DOE facilities. The likelihood of occurrence of natural phenomena hazards atmore » each DOE site has been evaluated by the DOE Natural Phenomena Hazard Program. Probabilistic hazard models are available for earthquake, extreme wind/tornado, and flood. Alternatively, site organizations are encouraged to develop site-specific hazard models utilizing the most recent information and techniques available. In this document, performance goals and natural hazard levels are expressed in probabilistic terms, and design and evaluation procedures are presented in deterministic terms. Design/evaluation procedures conform closely to common standard practices so that the procedures will be easily understood by most engineers. Performance goals are expressed in terms of structure or equipment damage to the extent that: (1) the facility cannot function; (2) the facility would need to be replaced; or (3) personnel are endangered. 82 refs., 12 figs., 18 tabs.« less

Context influences on TALE–DNA binding revealed by quantitative profiling

PubMed Central

Rogers, Julia M.; Barrera, Luis A.; Reyon, Deepak; Sander, Jeffry D.; Kellis, Manolis; Joung, J Keith; Bulyk, Martha L.

2015-01-01

Transcription activator-like effector (TALE) proteins recognize DNA using a seemingly simple DNA-binding code, which makes them attractive for use in genome engineering technologies that require precise targeting. Although this code is used successfully to design TALEs to target specific sequences, off-target binding has been observed and is difficult to predict. Here we explore TALE–DNA interactions comprehensively by quantitatively assaying the DNA-binding specificities of 21 representative TALEs to ∼5,000–20,000 unique DNA sequences per protein using custom-designed protein-binding microarrays (PBMs). We find that protein context features exert significant influences on binding. Thus, the canonical recognition code does not fully capture the complexity of TALE–DNA binding. We used the PBM data to develop a computational model, Specificity Inference For TAL-Effector Design (SIFTED), to predict the DNA-binding specificity of any TALE. We provide SIFTED as a publicly available web tool that predicts potential genomic off-target sites for improved TALE design. PMID:26067805

Context influences on TALE-DNA binding revealed by quantitative profiling.

PubMed

Rogers, Julia M; Barrera, Luis A; Reyon, Deepak; Sander, Jeffry D; Kellis, Manolis; Joung, J Keith; Bulyk, Martha L

2015-06-11

Transcription activator-like effector (TALE) proteins recognize DNA using a seemingly simple DNA-binding code, which makes them attractive for use in genome engineering technologies that require precise targeting. Although this code is used successfully to design TALEs to target specific sequences, off-target binding has been observed and is difficult to predict. Here we explore TALE-DNA interactions comprehensively by quantitatively assaying the DNA-binding specificities of 21 representative TALEs to ∼5,000-20,000 unique DNA sequences per protein using custom-designed protein-binding microarrays (PBMs). We find that protein context features exert significant influences on binding. Thus, the canonical recognition code does not fully capture the complexity of TALE-DNA binding. We used the PBM data to develop a computational model, Specificity Inference For TAL-Effector Design (SIFTED), to predict the DNA-binding specificity of any TALE. We provide SIFTED as a publicly available web tool that predicts potential genomic off-target sites for improved TALE design.

Bridge scour countermeasure assessments at select bridges in the United States, 2014–16

USGS Publications Warehouse

Dudunake, Taylor J.; Huizinga, Richard J.; Fosness, Ryan L.

2017-05-23

In 2009, the Federal Highway Administration published Hydraulic Engineering Circular No. 23 (HEC-23) to provide specific design and implementation guidelines for bridge scour and stream instability countermeasures. However, the effectiveness of countermeasures implemented over the past decade following those guidelines has not been evaluated. Therefore, in 2013, the U.S. Geological Survey, in cooperation with the Federal Highway Administration, began a study to assess the current condition of bridge-scour countermeasures at selected sites to evaluate their effectiveness. Bridge-scour countermeasures were assessed during 2014-2016. Site assessments included reviewing countermeasure design plans, summarizing the peak and daily streamflow history, and assessments at each site. Each site survey included a photo log summary, field form, and topographic and bathymetric geospatial data and metadata. This report documents the study area and site-selection criteria, explains the survey methods used to evaluate the condition of countermeasures, and presents the complete documentation for each countermeasure assessment.

Structure-based design of bacterial nitric oxide synthase inhibitors

DOE PAGES

Holden, Jeffrey K.; Kang, Soosung; Hollingsworth, Scott A.; ...

2014-12-18

Inhibition of bacterial nitric oxide synthase (bNOS) has the potential to improve the efficacy of antimicrobials used to treat infections by Gram-positive pathogens Staphylococcus aureus and Bacillus anthracis. However, inhibitor specificity toward bNOS over the mammalian NOS (mNOS) isoforms remains a challenge because of the near identical NOS active sites. One key structural difference between the NOS isoforms is the amino acid composition of the pterin cofactor binding site that is adjacent to the NOS active site. Previously, we demonstrated that a NOS inhibitor targeting both the active and pterin sites was potent and functioned as an antimicrobial. Here wemore » present additional crystal structures, binding analyses, and bacterial killing studies of inhibitors that target both the active and pterin sites of a bNOS and function as antimicrobials. Lastly, these data provide a framework for continued development of bNOS inhibitors, as each molecule represents an excellent chemical scaffold for the design of isoform selective bNOS inhibitors.« less

Challenges in forest reclamation of marginal lands: a balance between site conditions and seedling quality

NASA Astrophysics Data System (ADS)

Landhäusser, Simon

2017-04-01

Forest loss and degradation is occurring worldwide, but at the same time efforts in forest restoration are ever increasing. While approaches to restoration often follow specific stakeholder objectives, regional climates and the degree of site degradation also play an important role in the prioritization of restoration efforts. Often the restoration of degraded lands can satisfy only few measurable objectives; however, to design and restore resistant and resilient ecosystems that can adapt to changing conditions, there is a need for new and adaptive management approaches. Mining and other resource extraction industries are affecting more and more forested areas worldwide. A priority in the reclamation and certification of forest lands disturbed by industrial activity is their expeditious redevelopment to functioning forests. To rehabilitate these heavily disturbed areas back to forest ecosystems, planting of trees remains one of the most effective strategies for the redevelopment of a continuous tree canopy on a site. It is well understood that access to good quality seedling stock is essential to achieve establishment success and early growth of seedlings. However, most reclamation areas have challenging initial site conditions and these conditions are often not a single factor but a combination of factors that can be additive or synergistic. Therefore successful forest restoration on degraded lands needs to consider multiple objectives and approaches to minimize trade-offs in achieving these objectives. To meet these demands, new methods for the production and evaluation of seedling stock types are needed to ensure that that seedlings are fit to grow on a wide range of site conditions or are particularly designed to grow in very specific conditions. Generally, defining seedling quality is difficult as it is species specific and results have been mixed; likely influenced by site conditions, further reiterating the need to carefully evaluate sites allowing appropriate seedling qualities to be identified. In this presentation, I will show results from a range of studies that explored the role of seedling characteristics in response to challenging site conditions and explore the need for a balance between the recognition and improvement of limiting site conditions and the availability of quality seedling stock in forest restoration.

Development studies for a novel wet oxidation process. Phase 2

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

NONE

1994-07-01

DETOX{sup SM} is a catalyzed wet oxidation process which destroys organic materials in an acidic water solution of iron at 373 to 473 K. The solution can be used repeatedly to destroy great amounts of organic materials. Since the process is conducted in a contained vessel, air emissions from the process can be well controlled. The solution is also capable of dissolving and concentrating many heavy and radioactive metals for eventual stabilization and disposal. The Phase 2 effort for this project is site selection and engineering design for a DETOX demonstration unit. Site selection was made using a set ofmore » site selection criteria and evaluation factors. A survey of mixed wastes at DOE sites was conducted using the Interim Mixed Waste Inventory Report. Sites with likely suitable waste types were identified. Potential demonstration sites were ranked based on waste types, interest, regulatory needs, scheduling, ability to provide support, and available facilities. Engineering design for the demonstration unit is in progress and is being performed by Jacobs Applied Technology. The engineering design proceeded through preliminary process flow diagrams (PFDs), calculation of mass and energy balances for representative waste types, process and instrumentation diagrams (P and IDs), preparation of component specifications, and a firm cost estimate for fabrication of the demonstration unit.« less

Approach to the E-ELT dome and main structure challenges

NASA Astrophysics Data System (ADS)

Bilbao, Armando; Murga, Gaizka; Gómez, Celia; Llarena, Javier

2014-07-01

The E-ELT as a whole could be classified as an extremely challenging project. More precisely, it should be defined as an array of many different sub-challenges, which comprise technical, logistical and managerial matters. This paper reviews some of these critical challenges, in particular those related to the Dome and the Main Structure, suggesting ways to face them in the most pragmatic way possible. Technical challenges for the Dome and the Main Structure are mainly related to the need to upscale current design standards to an order of magnitude larger design. Trying a direct design escalation is not feasible; it would not work. A design effort is needed to cross hybridize current design standards with technologies coming from other different applications. Innovative design is therefore not a wish but a must. And innovative design comes along with design risk. Design risk needs to be tackled from two angles: on the one hand through thorough design validation analysis and on the other hand through extensive pre-assembly and testing. And, once again, full scale integrated pre-assembly and testing of extremely large subsystems is not always possible. Therefore, defining a comprehensive test plan for critical components, critical subsystems and critical subassemblies becomes essential. Logistical challenges are linked to the erection site. Cerro Armazones is a remote site and this needs to be considered when evaluating transport and erection requirements. But it is not only the remoteness of the site that needs to be considered. The size of both Dome and Main Structure require large construction cranes and a well defined erection plan taking into account pre-assembly strategies, limited plan area utilization, erection sequence, erection stability during intermediate stages and, very specifically, efficient coordination between the Dome and the Main Structure erection processes. Managerial issues pose another set of challenges in this project. Both the size of the project and its special technical characteristics require specific managerial skills. Due to the size of the project it becomes essential to effectively manage and integrate a large number of suppliers and fabricators, of very different nature and geographically distributed. Project management plans need to cope with this situation. Also, extensive on site activities require intensive on site organization in line with large construction management strategies. Finally, the technical edge of the project requires deep technical understanding at management level in order to be able to take sound strategic decisions throughout the project in terms of the overall project quality, cost and schedule.

Accurate in silico prediction of species-specific methylation sites based on information gain feature optimization.

PubMed

Wen, Ping-Ping; Shi, Shao-Ping; Xu, Hao-Dong; Wang, Li-Na; Qiu, Jian-Ding

2016-10-15

As one of the most important reversible types of post-translational modification, protein methylation catalyzed by methyltransferases carries many pivotal biological functions as well as many essential biological processes. Identification of methylation sites is prerequisite for decoding methylation regulatory networks in living cells and understanding their physiological roles. Experimental methods are limitations of labor-intensive and time-consuming. While in silicon approaches are cost-effective and high-throughput manner to predict potential methylation sites, but those previous predictors only have a mixed model and their prediction performances are not fully satisfactory now. Recently, with increasing availability of quantitative methylation datasets in diverse species (especially in eukaryotes), there is a growing need to develop a species-specific predictor. Here, we designed a tool named PSSMe based on information gain (IG) feature optimization method for species-specific methylation site prediction. The IG method was adopted to analyze the importance and contribution of each feature, then select the valuable dimension feature vectors to reconstitute a new orderly feature, which was applied to build the finally prediction model. Finally, our method improves prediction performance of accuracy about 15% comparing with single features. Furthermore, our species-specific model significantly improves the predictive performance compare with other general methylation prediction tools. Hence, our prediction results serve as useful resources to elucidate the mechanism of arginine or lysine methylation and facilitate hypothesis-driven experimental design and validation. The tool online service is implemented by C# language and freely available at http://bioinfo.ncu.edu.cn/PSSMe.aspx CONTACT: jdqiu@ncu.edu.cnSupplementary information: 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.

Accounting for substitution and spatial heterogeneity in a labelled choice experiment.

PubMed

Lizin, S; Brouwer, R; Liekens, I; Broeckx, S

2016-10-01

Many environmental valuation studies using stated preferences techniques are single-site studies that ignore essential spatial aspects, including possible substitution effects. In this paper substitution effects are captured explicitly in the design of a labelled choice experiment and the inclusion of different distance variables in the choice model specification. We test the effect of spatial heterogeneity on welfare estimates and transfer errors for minor and major river restoration works, and the transferability of river specific utility functions, accounting for key variables such as site visitation, spatial clustering and income. River specific utility functions appear to be transferable, resulting in low transfer errors. However, ignoring spatial heterogeneity increases transfer errors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Crystal structures of mammalian glutamine synthetases illustrate substrate-induced conformational changes and provide opportunities for drug and herbicide design.

PubMed

Krajewski, Wojciech W; Collins, Ruairi; Holmberg-Schiavone, Lovisa; Jones, T Alwyn; Karlberg, Tobias; Mowbray, Sherry L

2008-01-04

Glutamine synthetase (GS) catalyzes the ligation of glutamate and ammonia to form glutamine, with concomitant hydrolysis of ATP. In mammals, the activity eliminates cytotoxic ammonia, at the same time converting neurotoxic glutamate to harmless glutamine; there are a number of links between changes in GS activity and neurodegenerative disorders, such as Alzheimer's disease. In plants, because of its importance in the assimilation and re-assimilation of ammonia, the enzyme is a target of some herbicides. GS is also a central component of bacterial nitrogen metabolism and a potential drug target. Previous studies had investigated the structures of bacterial and plant GSs. In the present publication, we report the first structures of mammalian GSs. The apo form of the canine enzyme was solved by molecular replacement and refined at a resolution of 3 A. Two structures of human glutamine synthetase represent complexes with: a) phosphate, ADP, and manganese, and b) a phosphorylated form of the inhibitor methionine sulfoximine, ADP and manganese; these structures were refined to resolutions of 2.05 A and 2.6 A, respectively. Loop movements near the active site generate more closed forms of the eukaryotic enzymes when substrates are bound; the largest changes are associated with the binding of the nucleotide. Comparisons with earlier structures provide a basis for the design of drugs that are specifically directed at either human or bacterial enzymes. The site of binding the amino acid substrate is highly conserved in bacterial and eukaryotic GSs, whereas the nucleotide binding site varies to a much larger degree. Thus, the latter site offers the best target for specific drug design. Differences between mammalian and plant enzymes are much more subtle, suggesting that herbicides targeting GS must be designed with caution.

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

PubMed Central

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

2016-01-01

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

Butterfly Gardens.

ERIC Educational Resources Information Center

Denman, Kim

1996-01-01

Describes designing and planting a garden to attract butterflies specifically as a project for school grounds. Site and soil requirements are covered as well as types of plants. Includes a list of educational opportunities a garden provides in various subject areas. (AIM)

Migrant Education Administrative Guide.

ERIC Educational Resources Information Center

North Carolina State Dept. of Public Instruction, Raleigh. Div. of Compensatory Education.

Relating specifically to the North Carolina migrant education program's administrative responsibilities, this guide is designed to aid administrators in program management, monitoring project activities, project evaluation, self-assessment, determining needs for training and staff development, site-visit preparation, policy development, and…

A general way for quantitative magnetic measurement by transmitted electrons

NASA Astrophysics Data System (ADS)

Song, Dongsheng; Li, Gen; Cai, Jianwang; Zhu, Jing

2016-01-01

EMCD (electron magnetic circular dichroism) technique opens a new door to explore magnetic properties by transmitted electrons. The recently developed site-specific EMCD technique makes it possible to obtain rich magnetic information from the Fe atoms sited at nonequivalent crystallographic planes in NiFe2O4, however it is based on a critical demand for the crystallographic structure of the testing sample. Here, we have further improved and tested the method for quantitative site-specific magnetic measurement applicable for more complex crystallographic structure by using the effective dynamical diffraction effects (general routine for selecting proper diffraction conditions, making use of the asymmetry of dynamical diffraction for design of experimental geometry and quantitative measurement, etc), and taken yttrium iron garnet (Y3Fe5O12, YIG) with more complex crystallographic structure as an example to demonstrate its applicability. As a result, the intrinsic magnetic circular dichroism signals, spin and orbital magnetic moment of iron with site-specific are quantitatively determined. The method will further promote the development of quantitative magnetic measurement with high spatial resolution by transmitted electrons.

Merlin: Computer-Aided Oligonucleotide Design for Large Scale Genome Engineering with MAGE.

PubMed

Quintin, Michael; Ma, Natalie J; Ahmed, Samir; Bhatia, Swapnil; Lewis, Aaron; Isaacs, Farren J; Densmore, Douglas

2016-06-17

Genome engineering technologies now enable precise manipulation of organism genotype, but can be limited in scalability by their design requirements. Here we describe Merlin ( http://merlincad.org ), an open-source web-based tool to assist biologists in designing experiments using multiplex automated genome engineering (MAGE). Merlin provides methods to generate pools of single-stranded DNA oligonucleotides (oligos) for MAGE experiments by performing free energy calculation and BLAST scoring on a sliding window spanning the targeted site. These oligos are designed not only to improve recombination efficiency, but also to minimize off-target interactions. The application further assists experiment planning by reporting predicted allelic replacement rates after multiple MAGE cycles, and enables rapid result validation by generating primer sequences for multiplexed allele-specific colony PCR. Here we describe the Merlin oligo and primer design procedures and validate their functionality compared to OptMAGE by eliminating seven AvrII restriction sites from the Escherichia coli genome.

An i2b2-based, generalizable, open source, self-scaling chronic disease registry

PubMed Central

Quan, Justin; Ortiz, David M; Bousvaros, Athos; Ilowite, Norman T; Inman, Christi J; Marsolo, Keith; McMurry, Andrew J; Sandborg, Christy I; Schanberg, Laura E; Wallace, Carol A; Warren, Robert W; Weber, Griffin M; Mandl, Kenneth D

2013-01-01

Objective Registries are a well-established mechanism for obtaining high quality, disease-specific data, but are often highly project-specific in their design, implementation, and policies for data use. In contrast to the conventional model of centralized data contribution, warehousing, and control, we design a self-scaling registry technology for collaborative data sharing, based upon the widely adopted Integrating Biology & the Bedside (i2b2) data warehousing framework and the Shared Health Research Information Network (SHRINE) peer-to-peer networking software. Materials and methods Focusing our design around creation of a scalable solution for collaboration within multi-site disease registries, we leverage the i2b2 and SHRINE open source software to create a modular, ontology-based, federated infrastructure that provides research investigators full ownership and access to their contributed data while supporting permissioned yet robust data sharing. We accomplish these objectives via web services supporting peer-group overlays, group-aware data aggregation, and administrative functions. Results The 56-site Childhood Arthritis & Rheumatology Research Alliance (CARRA) Registry and 3-site Harvard Inflammatory Bowel Diseases Longitudinal Data Repository now utilize i2b2 self-scaling registry technology (i2b2-SSR). This platform, extensible to federation of multiple projects within and between research networks, encompasses >6000 subjects at sites throughout the USA. Discussion We utilize the i2b2-SSR platform to minimize technical barriers to collaboration while enabling fine-grained control over data sharing. Conclusions The implementation of i2b2-SSR for the multi-site, multi-stakeholder CARRA Registry has established a digital infrastructure for community-driven research data sharing in pediatric rheumatology in the USA. We envision i2b2-SSR as a scalable, reusable solution facilitating interdisciplinary research across diseases. PMID:22733975

An i2b2-based, generalizable, open source, self-scaling chronic disease registry.

PubMed

Natter, Marc D; Quan, Justin; Ortiz, David M; Bousvaros, Athos; Ilowite, Norman T; Inman, Christi J; Marsolo, Keith; McMurry, Andrew J; Sandborg, Christy I; Schanberg, Laura E; Wallace, Carol A; Warren, Robert W; Weber, Griffin M; Mandl, Kenneth D

2013-01-01

Registries are a well-established mechanism for obtaining high quality, disease-specific data, but are often highly project-specific in their design, implementation, and policies for data use. In contrast to the conventional model of centralized data contribution, warehousing, and control, we design a self-scaling registry technology for collaborative data sharing, based upon the widely adopted Integrating Biology & the Bedside (i2b2) data warehousing framework and the Shared Health Research Information Network (SHRINE) peer-to-peer networking software. Focusing our design around creation of a scalable solution for collaboration within multi-site disease registries, we leverage the i2b2 and SHRINE open source software to create a modular, ontology-based, federated infrastructure that provides research investigators full ownership and access to their contributed data while supporting permissioned yet robust data sharing. We accomplish these objectives via web services supporting peer-group overlays, group-aware data aggregation, and administrative functions. The 56-site Childhood Arthritis & Rheumatology Research Alliance (CARRA) Registry and 3-site Harvard Inflammatory Bowel Diseases Longitudinal Data Repository now utilize i2b2 self-scaling registry technology (i2b2-SSR). This platform, extensible to federation of multiple projects within and between research networks, encompasses >6000 subjects at sites throughout the USA. We utilize the i2b2-SSR platform to minimize technical barriers to collaboration while enabling fine-grained control over data sharing. The implementation of i2b2-SSR for the multi-site, multi-stakeholder CARRA Registry has established a digital infrastructure for community-driven research data sharing in pediatric rheumatology in the USA. We envision i2b2-SSR as a scalable, reusable solution facilitating interdisciplinary research across diseases.

Riparian buffer design guidelines for water quality and wildlife habitat functions on agricultural landscapes in the Intermountain West: Case Study

Treesearch

Craig W. Johnson; Susan Buffler

2008-01-01

This hypothetical case study illustrates how the riparian buffer planning protocol described in the RB handbook is used to plan a buffer for both water quality and wildlife conservation on a specific project site. The case study site includes riparian buffer characteristics typical of the study area-variable topography and soils, flood plain wetlands, seeps, springs,...

An Integrated Assessment of Location-Dependent Scaling for Microalgae Biofuel Production Facilities

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

Coleman, Andre M.; Abodeely, Jared; Skaggs, Richard

Successful development of a large-scale microalgae-based biofuels industry requires comprehensive analysis and understanding of the feedstock supply chain—from facility siting/design through processing/upgrading of the feedstock to a fuel product. The evolution from pilot-scale production facilities to energy-scale operations presents many multi-disciplinary challenges, including a sustainable supply of water and nutrients, operational and infrastructure logistics, and economic competitiveness with petroleum-based fuels. These challenges are addressed in part by applying the Integrated Assessment Framework (IAF)—an integrated multi-scale modeling, analysis, and data management suite—to address key issues in developing and operating an open-pond facility by analyzing how variability and uncertainty in space andmore » time affect algal feedstock production rates, and determining the site-specific “optimum” facility scale to minimize capital and operational expenses. This approach explicitly and systematically assesses the interdependence of biofuel production potential, associated resource requirements, and production system design trade-offs. The IAF was applied to a set of sites previously identified as having the potential to cumulatively produce 5 billion-gallons/year in the southeastern U.S. and results indicate costs can be reduced by selecting the most effective processing technology pathway and scaling downstream processing capabilities to fit site-specific growing conditions, available resources, and algal strains.« less

Meteorology Assessment of Historic Rainfall for Los Alamos During September 2013

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

Bruggeman, David Alan; Dewart, Jean Marie

2016-02-12

DOE Order 420.1, Facility Safety, requires that site natural phenomena hazards be evaluated every 10 years to support the design of nuclear facilities. The evaluation requires calculating return period rainfall to determine roof loading requirements and flooding potential based on our on-site rainfall measurements. The return period rainfall calculations are done based on statistical techniques and not site-specific meteorology. This and future studies analyze the meteorological factors that produce the significant rainfall events. These studies provide the meteorology context of the return period rainfall events.

Enhanced sensitivity of CpG island search and primer design based on predicted CpG island position.

PubMed

Park, Hyun-Chul; Ahn, Eu-Ree; Jung, Ju Yeon; Park, Ji-Hye; Lee, Jee Won; Lim, Si-Keun; Kim, Won

2018-05-01

DNA methylation has important biological roles, such as gene expression regulation, as well as practical applications in forensics, such as in body fluid identification and age estimation. DNA methylation often occurs in the CpG site, and methylation within the CpG islands affects various cellular functions and is related to tissue-specific identification. Several programs have been developed to identify CpG islands; however, the size, location, and number of predicted CpG islands are not identical due to different search algorithms. In addition, they only provide structural information for predicted CpG islands without experimental information, such as primer design. We developed an analysis pipeline package, CpGPNP, to integrate CpG island prediction and primer design. CpGPNP predicts CpG islands more accurately and sensitively than other programs, and designs primers easily based on the predicted CpG island locations. The primer design function included standard, bisulfite, and methylation-specific PCR to identify the methylation of particular CpG sites. In this study, we performed CpG island prediction on all chromosomes and compared CpG island search performance of CpGPNP with other CpG island prediction programs. In addition, we compared the position of primers designed for a specific region within the predicted CpG island using other bisulfite PCR primer programs. The primers designed by CpGPNP were used to experimentally verify the amplification of the target region of markers for body fluid identification and age estimation. CpGPNP is freely available at http://forensicdna.kr/cpgpnp/. Copyright © 2018 Elsevier B.V. All rights reserved.

Activity-Based Probes for Isoenzyme- and Site-Specific Functional Characterization of Glutathione S -Transferases

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

Stoddard, Ethan G.; Killinger, Bryan J.; Nair, Reji N.

Glutathione S-transferases (GSTs) comprise a highly diverse family of phase II drug metabolizing enzymes whose shared function is the conjugation of reduced glutathione to various endo- and xenobiotics. Although the conglomerate activity of these enzymes can be measured by colorimetric assays, measurement of the individual contribution from specific isoforms and their contribution to the detoxification of xenobiotics in complex biological samples has not been possible. For this reason, we have developed two activity-based probes that characterize active glutathione transferases in mammalian tissues. The GST active site is comprised of a glutathione binding “G site” and a distinct substrate binding “Hmore » site”. Therefore, we developed (1) a glutathione-based photoaffinity probe (GSH-ABP) to target the “G site”, and (2) a probe designed to mimic a substrate molecule and show “H site” activity (GST-ABP). The GSH-ABP features a photoreactive moiety for UV-induced covalent binding to GSTs and glutathione-binding enzymes. The GST-ABP is a derivative of a known mechanism-based GST inhibitor that binds within the active site and inhibits GST activity. Validation of probe targets and “G” and “H” site specificity was carried out using a series of competitors in liver homogenates. Herein, we present robust tools for the novel characterization of enzyme- and active site-specific GST activity in mammalian model systems.« less

Design approaches in quarrying and pit-mining reclamation

USGS Publications Warehouse

Arbogast, Belinda F.

1999-01-01

Reclaimed mine sites have been evaluated so that the public, industry, and land planners may recognize there are innovative designs available for consideration and use. People tend to see cropland, range, and road cuts as a necessary part of their everyday life, not as disturbed areas despite their high visibility. Mining also generates a disturbed landscape, unfortunately one that many consider waste until reclaimed by human beings. The development of mining provides an economic base and use of a natural resource to improve the quality of human life. Equally important is a sensitivity to the geologic origin and natural pattern of the land. Wisely shaping out environment requires a design plan and product that responds to a site's physiography, ecology, function, artistic form, and publication perception. An examination of selected sites for their landscape design suggested nine approaches for mining reclamation. The oldest design approach around is nature itself. Humans may sometimes do more damage going to an area in the attempt to repair it. Given enough geologic time, a small-site area, and stable adjacent ecosystems, disturbed areas recover without mankind's input. Visual screens and buffer zones conceal the facility in a camouflage approach. Typically, earth berms, fences, and plantings are used to disguise the mining facility. Restoration targets social or economic benefits by reusing the site for public amenities, most often in urban centers with large populations. A mitigation approach attempts to protect the environment and return mined areas to use with scientific input. The reuse of cement, building rubble, macadam meets only about 10% of the demand from aggregate. Recognizing the limited supply of mineral resources and encouraging recycling efforts are steps are steps in a renewable resource approach. An educative design approach effectively communicates mining information through outreach, land stewardship, and community service. Mine sites used for art show a celebration of beauty and experience -- abstract geology. The last design approach combines art and science in a human-nature ecosystem termed integration. With environmental concerns, an operating or reclaimed mine site can no longer be considered isolated from its surroundings. Site analysis of mine works needs to go beyond site-specific information and relate to the regional context of the greater landscape. Understanding design approach can turn undesirable features (mines and pits) into something perceived as desirable by the public.

Virtual Beach 3: User's Guide

EPA Science Inventory

Virtual Beach version 3 (VB3) is a decision support tool that constructs site-specific statistical models to predict fecal indicator bacteria (FIB) concentrations at recreational beaches. VB3 is primarily designed for beach managers responsible for making decisions regarding beac...

Strategies for Prospecting and Extracting Water on Mars for Long-Term Human Exploration

NASA Astrophysics Data System (ADS)

Rolley, R. J.; Saikia, S. J.

2017-02-01

We aim to develop a specific set of criteria to classify water reserves on Mars, and to design water prospecting and extraction systems for various human landing sites using a requirements-driven framework.

Anatomy-Based Algorithms for Detecting Oral Cancer Using Reflectance and Fluorescence Spectroscopy

PubMed Central

McGee, Sasha; Mardirossian, Vartan; Elackattu, Alphi; Mirkovic, Jelena; Pistey, Robert; Gallagher, George; Kabani, Sadru; Yu, Chung-Chieh; Wang, Zimmern; Badizadegan, Kamran; Grillone, Gregory; Feld, Michael S.

2010-01-01

Objectives We used reflectance and fluorescence spectroscopy to noninvasively and quantitatively distinguish benign from dysplastic/malignant oral lesions. We designed diagnostic algorithms to account for differences in the spectral properties among anatomic sites (gingiva, buccal mucosa, etc). Methods In vivo reflectance and fluorescence spectra were collected from 71 patients with oral lesions. The tissue was then biopsied and the specimen evaluated by histopathology. Quantitative parameters related to tissue morphology and biochemistry were extracted from the spectra. Diagnostic algorithms specific for combinations of sites with similar spectral properties were developed. Results Discrimination of benign from dysplastic/malignant lesions was most successful when algorithms were designed for individual sites (area under the receiver operator characteristic curve [ROC-AUC], 0.75 for the lateral surface of the tongue) and was least accurate when all sites were combined (ROC-AUC, 0.60). The combination of sites with similar spectral properties (floor of mouth and lateral surface of the tongue) yielded an ROC-AUC of 0.71. Conclusions Accurate spectroscopic detection of oral disease must account for spectral variations among anatomic sites. Anatomy-based algorithms for single sites or combinations of sites demonstrated good diagnostic performance in distinguishing benign lesions from dysplastic/malignant lesions and consistently performed better than algorithms developed for all sites combined. PMID:19999369

Recharge at the Hanford Site: Status report

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

Gee, G.W.

A variety of field programs designed to evaluate recharge and other water balance components including precipitation, infiltration, evaporation, and water storage changes, have been carried out at the Hanford Site since 1970. Data from these programs have indicated that a wide range of recharge rates can occur depending upon specific site conditions. Present evidence suggests that minimum recharge occurs where soils are fine-textured and surfaces are vegetated with deep-rooted plants. Maximum recharge occurs where coarse soils or gravels exist at the surface and soils are kept bare. Recharge can occur in areas where shallow-rooted plants dominate the surface, particularly wheremore » soils are coarse-textured. Recharge estimates have been made for the site using simulation models. A US Geological Survey model that attempts to account for climate variability, soil storage parameters, and plant factors has calculated recharge values ranging from near zero to an average of about 1 cm/yr for the Hanford Site. UNSAT-H, a deterministic model developed for the site, appears to be the best code available for estimating recharge on a site-specific basis. Appendix I contains precipitation data from January 1979 to June 1987. 42 refs., 11 figs., 11 tabs.« less

Stereoscopically Observing Manipulative Actions

PubMed Central

Ferri, S.; Pauwels, K.; Rizzolatti, G.; Orban, G. A.

2016-01-01

The purpose of this study was to investigate the contribution of stereopsis to the processing of observed manipulative actions. To this end, we first combined the factors “stimulus type” (action, static control, and dynamic control), “stereopsis” (present, absent) and “viewpoint” (frontal, lateral) into a single design. Four sites in premotor, retro-insular (2) and parietal cortex operated specifically when actions were viewed stereoscopically and frontally. A second experiment clarified that the stereo-action-specific regions were driven by actions moving out of the frontoparallel plane, an effect amplified by frontal viewing in premotor cortex. Analysis of single voxels and their discriminatory power showed that the representation of action in the stereo-action-specific areas was more accurate when stereopsis was active. Further analyses showed that the 4 stereo-action-specific sites form a closed network converging onto the premotor node, which connects to parietal and occipitotemporal regions outside the network. Several of the specific sites are known to process vestibular signals, suggesting that the network combines observed actions in peripersonal space with gravitational signals. These findings have wider implications for the function of premotor cortex and the role of stereopsis in human behavior. PMID:27252350

Stereoscopically Observing Manipulative Actions.

PubMed

Ferri, S; Pauwels, K; Rizzolatti, G; Orban, G A

2016-08-01

The purpose of this study was to investigate the contribution of stereopsis to the processing of observed manipulative actions. To this end, we first combined the factors "stimulus type" (action, static control, and dynamic control), "stereopsis" (present, absent) and "viewpoint" (frontal, lateral) into a single design. Four sites in premotor, retro-insular (2) and parietal cortex operated specifically when actions were viewed stereoscopically and frontally. A second experiment clarified that the stereo-action-specific regions were driven by actions moving out of the frontoparallel plane, an effect amplified by frontal viewing in premotor cortex. Analysis of single voxels and their discriminatory power showed that the representation of action in the stereo-action-specific areas was more accurate when stereopsis was active. Further analyses showed that the 4 stereo-action-specific sites form a closed network converging onto the premotor node, which connects to parietal and occipitotemporal regions outside the network. Several of the specific sites are known to process vestibular signals, suggesting that the network combines observed actions in peripersonal space with gravitational signals. These findings have wider implications for the function of premotor cortex and the role of stereopsis in human behavior. © The Author 2016. Published by Oxford University Press.

Preliminary design package for solar heating and hot water system

NASA Technical Reports Server (NTRS)

1977-01-01

The preliminary design review on the development of two prototype solar heating and hot water systems is presented. The information contained in this report includes system certification, system functional description, system configuration, system specification, system performance and other documents pertaining to the progress and the design of the system. This system, which is intended for use in the normal single-family residence, consists of the following subsystems: collector, storage, control, transport, and Government-furnished Site Data Acquisition.

In Vitro and In Vivo Evaluation of Cysteine and Site Specific Conjugated Herceptin Antibody-Drug Conjugates

PubMed Central

Jackson, Dowdy; Atkinson, John; Guevara, Claudia I.; Zhang, Chunying; Kery, Vladimir; Moon, Sung-Ju; Virata, Cyrus; Yang, Peng; Lowe, Christine; Pinkstaff, Jason; Cho, Ho; Knudsen, Nick; Manibusan, Anthony; Tian, Feng; Sun, Ying; Lu, Yingchun; Sellers, Aaron; Jia, Xiao-Chi; Joseph, Ingrid; Anand, Banmeet; Morrison, Kendall; Pereira, Daniel S.; Stover, David

2014-01-01

Antibody drug conjugates (ADCs) are monoclonal antibodies designed to deliver a cytotoxic drug selectively to antigen expressing cells. Several components of an ADC including the selection of the antibody, the linker, the cytotoxic drug payload and the site of attachment used to attach the drug to the antibody are critical to the activity and development of the ADC. The cytotoxic drugs or payloads used to make ADCs are typically conjugated to the antibody through cysteine or lysine residues. This results in ADCs that have a heterogeneous number of drugs per antibody. The number of drugs per antibody commonly referred to as the drug to antibody ratio (DAR), can vary between 0 and 8 drugs for a IgG1 antibody. Antibodies with 0 drugs are ineffective and compete with the ADC for binding to the antigen expressing cells. Antibodies with 8 drugs per antibody have reduced in vivo stability, which may contribute to non target related toxicities. In these studies we incorporated a non-natural amino acid, para acetyl phenylalanine, at two unique sites within an antibody against Her2/neu. We covalently attached a cytotoxic drug to these sites to form an ADC which contains two drugs per antibody. We report the results from the first direct preclinical comparison of a site specific non-natural amino acid anti-Her2 ADC and a cysteine conjugated anti-Her2 ADC. We report that the site specific non-natural amino acid anti-Her2 ADCs have superior in vitro serum stability and preclinical toxicology profile in rats as compared to the cysteine conjugated anti-Her2 ADCs. We also demonstrate that the site specific non-natural amino acid anti-Her2 ADCs maintain their in vitro potency and in vivo efficacy against Her2 expressing human tumor cell lines. Our data suggests that site specific non-natural amino acid ADCs may have a superior therapeutic window than cysteine conjugated ADCs. PMID:24454709

Bromide, Chloride, and Sulfate Concentrations, and Specific Conductance, Lake Texoma, Texas and Oklahoma, 2007-08

USGS Publications Warehouse

Baldys, Stanley

2009-01-01

The U.S. Geological Survey, in cooperation with the City of Dallas Water Utilities Division, collected water-quality data from 11 sites on Lake Texoma, a reservoir on the Texas-Oklahoma border, during April 2007-September 2008. At 10 of the sites, physical properties (depth, specific conductance, pH, temperature, dissolved oxygen, and alkalinity) were measured and samples were collected for analysis of selected dissolved constituents (bromide, calcium, magnesium, potassium, sodium, carbonate, bicarbonate, chloride, and sulfate); at one site, only physical properties were measured. The primary constituent of interest was bromide. Bromate can form when ozone is used to disinfect raw water containing bromide, and bromate is a suspected human carcinogen. Chloride and sulfate were of secondary interest. Only the analytical results for bromide, chloride, sulfate, and measured specific conductance are discussed in this report. Median dissolved bromide concentrations ranged from 0.28 to 0.60 milligrams per liter. The largest median dissolved bromide concentration (0.60 milligram per liter at site 11) was from the Red River arm of Lake Texoma. Dissolved bromide concentrations generally were larger in the Red River arm of Lake Texoma than in the Washita arm of the lake. Median dissolved chloride concentrations were largest in the Red River arm of Lake Texoma at site 11 (431 milligrams per liter) and smallest at site 8 (122 milligrams per liter) in the Washita arm. At site 11 in the Red River arm, the mean and median chloride concentrations exceeded the secondary maximum contaminant level of 300 milligrams per liter for chloride established by the 'Texas Surface Water Quality Standards' for surface-water bodies designated for the public water supply use. Median dissolved sulfate concentrations ranged from 182 milligrams per liter at site 4 in the Big Mineral arm to 246 milligrams per liter at site 11 in the Red River arm. None of the mean or median sulfate concentrations exceeded the secondary maximum contaminant level of 300 milligrams per liter. Median specific conductance measurements at sites ranged from 1,120 microsiemens per centimeter at site 8 in the Washita arm to 2,100 microsiemens per centimeter in the Red River arm. The spatial distribution of specific conductance in Lake Texoma was similar to that of bromide and chloride, with larger specific conductance values in the Red River arm compared to those in the Washita arm.

Eco-Design of River Fishways for Upstream Passage: Application for Hanfeng Dam, Pengxi River, China

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

Johnson, Gary E.; Rainey, William S.

2012-05-20

This paper provides a scientific approach to eco-design of river fishways to allow upstream movement of fish past new and existing dams in China. This eco-design approach integrates principles of fish ecology/behavior and engineering, a scientific field also known as bio-engineering or eco-hydraulics. We define a fishway as a structure or mechanism to convey fish upstream past a dam. Man-made or natural stream beds can be part of the fishway mechanism. Fish include bony and non-bony fishes, and upstream passage is the concern here, not downstream passage. The problem is dams block access to upstream habitat used for spawning, rearing,more » and refuge, i.e., dams decrease habitat connectivity. A solution to alleviate this problem is to design fishways, preferably while the dam is being designed, but if necessary, as retrofits afterward to provide a route that fish can and will use to pass safely upstream without undue delay. Our eco-design approach for fishways involves eight steps: 1) identify the primary species of importance; 2) understand basic ecology and behavior of these fish; 3) characterize the environmental conditions where passage is or will be blocked; 4 identify fishway alternatives and select a preferred alternative; 5) establish eco-design criteria for the fishway, either from management agencies or, if necessary, developed specifically for the given site; 6) where needed, identify and perform research required to resolve critical uncertainties and finalize the eco-design criteria; 7) apply the eco-design criteria and site-specific considerations to design the fishway, involving peer-review by local stakeholders in the process; 8) build the fishway, monitor its effectiveness, and apply the lessons learned. Example fishways are described showing a range of eco-designs depending on the dam site and fish species of concern. We apply the eco-design principles to recommend an approach and next steps for a fishway to pass fish upstream at Hanfeng Dam, an existing regulating dam forming Hanfeng Lake on the Pengxi River near Kaixian, China.« less

Temporal trends in algae, benthic invertebrate, and fish assemblages in streams and rivers draining basins of varying land use in the south-central United States, 1993-2007

USGS Publications Warehouse

Miller, Matthew P.; Kennen, Jonathan G.; Mabe, Jeffrey A.; Mize, Scott V.

2012-01-01

Site-specific temporal trends in algae, benthic invertebrate, and fish assemblages were investigated in 15 streams and rivers draining basins of varying land use in the south-central United States from 1993–2007. A multivariate approach was used to identify sites with statistically significant trends in aquatic assemblages which were then tested for correlations with assemblage metrics and abiotic environmental variables (climate, water quality, streamflow, and physical habitat). Significant temporal trends in one or more of the aquatic assemblages were identified at more than half (eight of 15) of the streams in the study. Assemblage metrics and abiotic environmental variables found to be significantly correlated with aquatic assemblages differed between land use categories. For example, algal assemblages at undeveloped sites were associated with physical habitat, while algal assemblages at more anthropogenically altered sites (agricultural and urban) were associated with nutrient and streamflow metrics. In urban stream sites results indicate that streamflow metrics may act as important controls on water quality conditions, as represented by aquatic assemblage metrics. The site-specific identification of biotic trends and abiotic–biotic relations presented here will provide valuable information that can inform interpretation of continued monitoring data and the design of future studies. In addition, the subsets of abiotic variables identified as potentially important drivers of change in aquatic assemblages provide policy makers and resource managers with information that will assist in the design and implementation of monitoring programs aimed at the protection of aquatic resources.

XX/XY Sex Chromosomes in the South American Dwarf Gecko (Gonatodes humeralis).

PubMed

Gamble, Tony; McKenna, Erin; Meyer, Wyatt; Nielsen, Stuart V; Pinto, Brendan J; Scantlebury, Daniel P; Higham, Timothy E

2018-05-11

Sex-specific genetic markers identified using restriction site-associated DNA sequencing, or RADseq, permits the recognition of a species' sex chromosome system in cases where standard cytogenetic methods fail. Thus, species with male-specific RAD markers have an XX/XY sex chromosome system (male heterogamety) while species with female-specific RAD markers have a ZZ/ZW sex chromosome (female heterogamety). Here, we use RADseq data from 5 male and 5 female South American dwarf geckos (Gonatodes humeralis) to identify an XX/XY sex chromosome system. This is the first confidently known sex chromosome system in a Gonatodes species. We used a low-coverage de novo G. humeralis genome assembly to design PCR primers to validate the male-specificity of a subset of the sex-specific RADseq markers and describe how even modest genome assemblies can facilitate the design of sex-specific PCR primers in species with diverse sex chromosome systems.

Numerical Modelling of Rayleigh Wave Propagation in Course of Rapid Impulse Compaction

NASA Astrophysics Data System (ADS)

Herbut, Aneta; Rybak, Jarosław

2017-10-01

As the soil improvement technologies are the area of a rapid development, they require designing and implementing novel methods of control and calibration in order to ensure the safety of geotechnical works. At Wroclaw University of Science and Technology (Poland), these new methods are continually developed with the aim to provide the appropriate tools for the preliminary design of work process, as well as for the further ongoing on-site control of geotechnical works (steel sheet piling, pile driving or soil improvement technologies). The studies include preliminary numerical simulations and field tests concerning measurements and continuous histogram recording of shocks and vibrations and its ground-born dynamic impact on engineering structures. The impact of vibrations on reinforced concrete and masonry structures in the close proximity of the construction site may be destroying in both architectural and structural meaning. Those limits are juxtaposed in codes of practice, but always need an individual judgment. The results and observations make it possible to delineate specific modifications to the parameters of technology applied (e.g. hammer drop height). On the basis of numerous case studies of practical applications, already summarized and published, we were able to formulate the guidelines for work on the aforementioned sites. This work presents specific aspects of the active design (calibration of building site numerical model) by means of technology calibration, using the investigation of the impact of vibrations that occur during the Impulse Compaction on adjacent structures. A case study entails the impact of construction works on Rayleigh wave propagation in the zone of 100 m (radius) around the Compactor.

Cofactor specificity switch in Shikimate dehydrogenase by rational design and consensus engineering.

PubMed

García-Guevara, Fernando; Bravo, Iris; Martínez-Anaya, Claudia; Segovia, Lorenzo

2017-08-01

Consensus engineering has been used to design more stable variants using the most frequent amino acid at each site of a multiple sequence alignment; sometimes consensus engineering modifies function, but efforts have mainly been focused on studying stability. Here we constructed a consensus Rossmann domain for the Shikimate dehydrogenase enzyme; separately we decided to switch the cofactor specificity through rational design in the Escherichia coli Shikimate dehydrogenase enzyme and then analyzed the effect of consensus mutations on top of our design. We found that consensus mutations closest to the 2' adenine moiety increased the activity in our design. Consensus engineering has been shown to result in more stable proteins and our findings suggest it could also be used as a complementary tool for increasing or modifying enzyme activity during design. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

78 FR 64208 - Environmental Management Site-Specific Advisory Board Chairs

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-28

... Designated Federal Officer is empowered to conduct the meeting in a fashion that will facilitate the orderly... meetings of this federal advisory board. The EM SSAB Chairs have not had a face-to-face meeting in over a...

SITE DEMONSTRATION CAPSULE --MATCON MODIFIED ASPHALT FOR WASTE CONTAINMENT

EPA Science Inventory

MatCon is a polymer modified asphalt material designed specifically for waste contaminment applications. The modifications to the material differentiate it from conventional paving asphalt by minimizing the damaging effects of environmental exposure that could detract from the d...

40 CFR Table 4 to Subpart Ggg of... - [Reserved

Code of Federal Regulations, 2011 CFR

2011-07-01

... Part 62-Site-Specific Compliance Schedules and Increments of Progress Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF STATE PLANS FOR DESIGNATED FACILITIES AND POLLUTANTS Federal Plan Requirements for Municipal Solid Waste Landfills...

40 CFR Table 4 to Subpart Ggg of... - [Reserved

Code of Federal Regulations, 2010 CFR

2010-07-01

... Part 62-Site-Specific Compliance Schedules and Increments of Progress Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF STATE PLANS FOR DESIGNATED FACILITIES AND POLLUTANTS Federal Plan Requirements for Municipal Solid Waste Landfills...

Structural basis for modulation of a G-protein-coupled receptor by allosteric drugs

NASA Astrophysics Data System (ADS)

Dror, Ron O.; Green, Hillary F.; Valant, Celine; Borhani, David W.; Valcourt, James R.; Pan, Albert C.; Arlow, Daniel H.; Canals, Meritxell; Lane, J. Robert; Rahmani, Raphaël; Baell, Jonathan B.; Sexton, Patrick M.; Christopoulos, Arthur; Shaw, David E.

2013-11-01

The design of G-protein-coupled receptor (GPCR) allosteric modulators, an active area of modern pharmaceutical research, has proved challenging because neither the binding modes nor the molecular mechanisms of such drugs are known. Here we determine binding sites, bound conformations and specific drug-receptor interactions for several allosteric modulators of the M2 muscarinic acetylcholine receptor (M2 receptor), a prototypical family A GPCR, using atomic-level simulations in which the modulators spontaneously associate with the receptor. Despite substantial structural diversity, all modulators form cation-π interactions with clusters of aromatic residues in the receptor extracellular vestibule, approximately 15Å from the classical, `orthosteric' ligand-binding site. We validate the observed modulator binding modes through radioligand binding experiments on receptor mutants designed, on the basis of our simulations, either to increase or to decrease modulator affinity. Simulations also revealed mechanisms that contribute to positive and negative allosteric modulation of classical ligand binding, including coupled conformational changes of the two binding sites and electrostatic interactions between ligands in these sites. These observations enabled the design of chemical modifications that substantially alter a modulator's allosteric effects. Our findings thus provide a structural basis for the rational design of allosteric modulators targeting muscarinic and possibly other GPCRs.

Changes to Idaho's statewide surface-water quality monitoring program since 1995

USGS Publications Warehouse

O'Dell, Ivalou; Maret, Terry R.; Moore, Susan E.

1998-01-01

The program design included chemical analyses of water samples collected at 56 sites on the Bear, Clearwater, Kootenai, Pend Oreille, Salmon, Snake, and Spokane Rivers and their tributaries (fig. 1). Samples were collected every year (1990 through 1995) at 5 sites (annual sites), every other year at 19 sites (biennial sites), and every third year at 32 sites (triennial sites). Each year, 25 of the 56 sites were sampled. During water years 1990–95 (October 1, 1989, to September 30, 1995), samples were collected bimonthly. Onsite analyses consisted of discharge, specific conductance, pH, temperature, dissolved oxygen, bacteria (fecal coliform and fecal streptococci), and alkalinity. Laboratory analyses consisted of major ions, nutrients, trace elements, turbidity, and suspended sediment. Analytical results from the five annual sites sampled during water years 1990–93 are presented in a report by O’Dell and Berenbrock (1994).

Modeled structure of trypanothione reductase of Leishmania infantum.

PubMed

Singh, Bishal K; Sarkar, Nandini; Jagannadham, M V; Dubey, Vikash K

2008-06-30

Trypanothione reductase is an important target enzyme for structure-based drug design against Leishmania. We used homology modeling to construct a three-dimensional structure of the trypanothione reductase (TR) of Leishmania infantum. The structure shows acceptable Ramachandran statistics and a remarkably different active site from glutathione reductase(GR). Thus, a specific inhibitor against TR can be designed without interfering with host (human) GR activity.

Drilling and completion specifications for CA series multilevel piezometers

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

Clawson, T.S.

1986-08-01

CX Series multilevel piezometer boreholes will provide information on hydraulic heads in the Rosalia, Sentinel Gap, Ginkgo, Rocky Coulee, Cohassett, Birkett, and Umtanum flow tops. The borehole sites will be located adjacent to the reference repository location. In addition, information from the boreholes will provide input data used to determine horizontal and vertical flow rates, and identify possible geologic structures. This specification includes details for drilling, piezometer design, hydrologic testing, and hydrochemical sampling of the boreholes. It includes drilling requirements, design, and installation procedures for the series piezometer nests, intervals selected for head monitoring and schedules for drilling and piezometermore » installation. Specific drilling and piezometer installation specifications for boreholes DC-24CX and DC-25CX are also included. 27 refs., 5 figs., 3 tabs.« less

A sucrose-binding site provides a lead towards an isoform-specific inhibitor of the cancer-associated enzyme carbonic anhydrase IX

DOE PAGES

Pinard, Melissa A.; Aggarwal, Mayank; Mahon, Brian P.; ...

2015-09-23

Human carbonic anhydrase (CA; EC 4.2.1.1) isoform IX (CA IX) is an extracellular zinc metalloenzyme that catalyzes the reversible hydration of CO 2to HCO 3 $-$, thereby playing a role in pH regulation. The majority of normal functioning cells exhibit low-level expression of CA IX. However, in cancer cells CA IX is upregulated as a consequence of a metabolic transition known as the Warburg effect. The upregulation of CA IX for cancer progression has drawn interest in it being a potential therapeutic target. CA IX is a transmembrane protein, and its purification, yield and crystallization have proven challenging to structure-basedmore » drug design, whereas the closely related cytosolic soluble isoform CA II can be expressed and crystallized with ease. Therefore, we have utilized structural alignments and site-directed mutagenesis to engineer a CA II that mimics the active site of CA IX. In this paper, the X-ray crystal structure of this CA IX mimic in complex with sucrose is presented and has been refined to a resolution of 1.5 Å, anR cryst of 18.0% and anR free of 21.2%. Finally, the binding of sucrose at the entrance to the active site of the CA IX mimic, and not CA II, in a non-inhibitory mechanism provides a novel carbohydrate moiety binding site that could be further exploited to design isoform-specific inhibitors of CA IX.« less

Conceptual design studies of the 5 m terahertz antenna for Dome A, Antarctica

NASA Astrophysics Data System (ADS)

Yang, Ji; Zuo, Ying-Xi; Lou, Zheng; Cheng, Jing-Quan; Zhang, Qi-Zhou; Shi, Sheng-Cai; Huang, Jia-Sheng; Yao, Qi-Jun; Wang, Zhong

2013-12-01

As the highest, coldest and driest place in Antarctica, Dome A provides exceptionally good observing conditions for ground-based observations over terahertz wavebands. The 5 m Dome A Terahertz Explorer (DATE5) has been proposed to explore new terahertz windows, primarily over wavelengths between 350 and 200 μm. DATE5 will be an open-air, fully-steerable telescope that can function by unmanned operation with remote control. The telescope will be able to endure the harsh polar environment, including high altitude, very low temperature and very low air pressure. The unique specifications, including high accuracies for surface shape and pointing and fully automatic year-around remote operation, along with a stringent limit on the periods of on-site assembly, testing and maintenance, bring a number of challenges to the design, construction, assembly and operation of this telescope. This paper introduces general concepts related to the design of the DATE5 antenna. Beginning from an overview of the environmental and operational limitations, the design specifications and requirements of the DATE5 antenna are listed. From these, major aspects on the conceptual design studies, including the antenna optics, the backup structure, the panels, the subreflector, the mounting and the antenna base structure, are explained. Some critical issues of performance are justified through analyses that use computational fluid dynamics, thermal analysis and de-icing studies, and the proposed approaches for test operation and on-site assembly. Based on these studies, we conclude that the specifications of the DATE5 antenna can generally be met by using enhanced technological approaches.

Rational design of aminoacyl-tRNA synthetase specific for p-acetyl-L-phenylalanine.

PubMed

Sun, Renhua; Zheng, Heng; Fang, Zhengzhi; Yao, Wenbing

2010-01-01

The Methanococcus jannaschii tRNA(Tyr)/tyrosyl-tRNA synthetase pair has been engineered to incorporate unnatural amino acids into proteins in Escherichia coli site-specifically. In order to add other unnatural amino acids into proteins by this approach, the amino acid binding site of M. jannaschii tyrosyl-tRNA synthetase need to be mutated. The crystal structures of M. jannaschii tyrosyl-tRNA synthetase and its mutations were determined, which provided an opportunity to design aminoacyl-tRNA synthetases specific for other unnatural amino acids. In our study, we attempted to design aminoacyl-tRNA synthetases being able to deliver p-acetyl-L-phenylalanine into proteins. p-Acetyl-L-phenylalanine was superimposed on tyrosyl in M. jannaschii tyrosyl-tRNA synthetase-tyrosine complex. Tyr32 needed to be changed to non-polar amino acid with shorter side chain, Val, Leu, Ile, Gly or Ala, in order to reduce steric clash and provide hydrophobic environment to acetyl on p-acetyl-L-phenylalanine. Asp158 and Ile159 would be changed to specific amino acids for the same reason. So we designed 60 aminoacyl-tRNA synthetases. Binding of these aminoacyl-tRNA synthetases with p-acetyl-L-phenylalanine indicated that only 15 of them turned out to be able to bind p-acetyl-L-phenylalanine with reasonable poses. Binding affinity computation proved that the mutation of Tyr32Leu and Asp158Gly benefited p-acetyl-L-phenylalanine binding. And two of the designed aminoacyl-tRNA synthetases had considerable binding affinities. They seemed to be very promising to be able to incorporate p-acetyl-L-phenylalanine into proteins in E. coli. The results show that the combination of homology modeling and molecular docking is a feasible method to filter inappropriate mutations in molecular design and point out beneficial mutations. Copyright 2009 Elsevier Inc. All rights reserved.

Guidance for implementing the long-term surveillance program for UMTRA Project Title I Disposal Sites

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

NONE

1996-02-01

This guidance document has two purposes: it provides guidance for writing site-specific long-term surveillance plans (LTSP) and it describes site surveillance, monitoring, and long-term care techniques for Title I disposal sites of the Uranium Mill Tailings Radiation Control Act (UMTRCA) (42 USC Section 7901 et seq.). Long-term care includes monitoring, maintenance, and emergency measures needed to protect public health and safety and the environment after remedial action is completed. This document applies to the UMTRCA-designated Title I disposal sites. The requirements for long-term care of the Title I sites and the contents of the LTSPs are provided in U.S. Nuclearmore » Regulatory Commission (NRC) regulations (10 CFR Section 40.27) provided in Attachment 1.« less

Recognizing critical mine spoil health characteristics to design ...

EPA Pesticide Factsheets

Biochar can be used as an amendment to remediate metal-contaminated mine spoils for improved site phytostabilization. For successful phytostabilization to occur, biochar amendments must improve mine spoil health with respect to plant rooting plus uptake of water and nutrients. An inappropriate biochar may negatively impact plant growth conditions resulting in poor plant establishment and growth. Matching the appropriate biochar for each mine site requires reconnaissance of spoil chemical and physical conditions and then identifying which properties need rectified to promote plant growth. A rectification hierarchy needs to be established with the primary limiting factor being addressed first, then successive limitations addressed simultaneously or thereafter. We posit that spoils at each site will have a unique chemical, physical, and biological signature that will affect plant growth. For example, some spoils may be extremely acidic, possess phytotoxic concentrations of heavy metals, or have physical conditions that limits water storage and root penetration. Quantifying these and other conditions beforehand allows for the production of designer biochar with specific characteristics tailored for specific plant growth deficiencies within each spoil. Additionally, we recommend the use of proximally located, undisturbed soils to establish spoil remediation targets. In our work, we have developed a decision-tree flow-chart that identifies salient chemical,

MRP4/ABCC4 as a new therapeutic target: meta-analysis to determine cAMP binding sites as a tool for drug design.

PubMed

Yaneff, Agustín; Sahores, Ana; Gomez, Natalia; Carozzo, Alejandro; Shayo, Carina; Davio, Carlos

2017-12-29

MRP4 transports multiple endogenous and exogenous substances and is critical not only for detoxification but also in the homeostasis of several signaling molecules. Its dysregulation has been reported in numerous pathological disorders, thus MRP4 appears as an attractive therapeutic target. However, the efficacy of MRP4 inhibitors is still controversial. The design of specific pharmacological agents with the ability to selectively modulate the activity of this transporter or modify its affinity to certain substrates represents a challenge in current medicine and chemical biology. The first step in the long process of drug rational design is to identify the therapeutic target and characterize the mechanism by which it affects the given pathology. In order to develop a pharmacological agent with high specific activity, the second step is to systematically study the structure of the target and identify all the possible binding sites. Using available homology models and mutagenesis assays, in this review we recapitulate the up-to-date knowledge about MRP structure and aligned amino acid sequences to identify the candidate MRP4 residues where cyclic nucleotides bind. We have also listed the most relevant MRP inhibitors studied to date, considering drug safety and specificity for MRP4 in particular. This metaanalysis platform may serve as a basis for the future development of inhibitors of MRP4 cAMP specific transport. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Monitoring Ras Interactions with the Nucleotide Exchange Factor Son of Sevenless (Sos) Using Site-specific NMR Reporter Signals and Intrinsic Fluorescence*

PubMed Central

Vo, Uybach; Vajpai, Navratna; Flavell, Liz; Bobby, Romel; Breeze, Alexander L.; Embrey, Kevin J.; Golovanov, Alexander P.

2016-01-01

The activity of Ras is controlled by the interconversion between GTP- and GDP-bound forms partly regulated by the binding of the guanine nucleotide exchange factor Son of Sevenless (Sos). The details of Sos binding, leading to nucleotide exchange and subsequent dissociation of the complex, are not completely understood. Here, we used uniformly 15N-labeled Ras as well as [13C]methyl-Met,Ile-labeled Sos for observing site-specific details of Ras-Sos interactions in solution. Binding of various forms of Ras (loaded with GDP and mimics of GTP or nucleotide-free) at the allosteric and catalytic sites of Sos was comprehensively characterized by monitoring signal perturbations in the NMR spectra. The overall affinity of binding between these protein variants as well as their selected functional mutants was also investigated using intrinsic fluorescence. The data support a positive feedback activation of Sos by Ras·GTP with Ras·GTP binding as a substrate for the catalytic site of activated Sos more weakly than Ras·GDP, suggesting that Sos should actively promote unidirectional GDP → GTP exchange on Ras in preference of passive homonucleotide exchange. Ras·GDP weakly binds to the catalytic but not to the allosteric site of Sos. This confirms that Ras·GDP cannot properly activate Sos at the allosteric site. The novel site-specific assay described may be useful for design of drugs aimed at perturbing Ras-Sos interactions. PMID:26565026

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

Polymeric drug delivery systems for intraoral site-specific chemoprevention of oral cancer.

PubMed

Desai, Kashappa Goud H

2018-04-01

Oral cancer is among the most prevalent cancers in the world. Moreover, it is one of the major health problems and causes of death in many regions of the world. The traditional treatment modalities include surgical removal, radiation therapy, systemic chemotherapy, or a combination of these methods. In recent decades, there has been significant interest in intraoral site-specific chemoprevention via local drug delivery using polymeric systems. Because of its easy accessibility and clear visibility, the oral mucosa is amenable for local drug delivery. A variety of polymeric systems-such as gels, tablets, films, patches, injectable systems (e.g., millicylindrical implants, microparticles, and in situ-forming depots), and nanosized carriers (e.g., polymeric nanoparticles, nanofibers, polymer-drug conjugates, polymeric micelles, nanoliposomes, nanoemulsions, and polymersomes)-have been developed and evaluated for the local delivery of natural and synthetic chemopreventive agents. The findings of in vitro, ex vivo, and in vivo studies and the positive outcome of clinical trials demonstrate that intraoral site-specific drug delivery is an attractive, highly effective and patient-friendly strategy for the management of oral cancer. Intraoral site-specific drug delivery provides unique therapeutic advantages when compared to systemic chemotherapy. Moreover, intraoral drug delivery systems are self-administrable and can be removed when needed, increasing patient compliance. This article covers important aspects and advances related to the design, development, and efficacy of polymeric systems for intraoral site-specific drug delivery. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1383-1413, 2018. © 2017 Wiley Periodicals, Inc.

Cyclosporine a inhibits apoptosis of rat gingival epithelium.

PubMed

Ma, Su; Liu, Peihong; Li, Yanwu; Hou, Lin; Chen, Li; Qin, Chunlin

2014-08-01

The use of cyclosporine A (CsA) induces hyperplasia of the gingival epithelium in a site-specific response manner, but the molecular mechanism via which the lesion occurs is unclear. The present research aims to investigate the site-specific effect of CsA on the apoptosis of gingival epithelium associated with gingival hyperplasia. Forty Wistar rats were divided into CsA-treated and non-treated groups. Paraffin-embedded sections of mandibular first molars were selected for hematoxylin and eosin staining, immunohistochemistry analyses of bcl-2 and caspase-3, and the staining of terminal deoxynucleotidyl transfer-mediated dUTP nick-end labeling (TUNEL). The area of the whole gingival epithelium and the length of rete pegs were measured, and the number of bcl-2- and caspase-3-positive cells in the longest rete peg were counted. The analysis of variance for factorial designs and Fisher least significant difference test for post hoc analysis were used to determine the significance levels. In CsA-treated rats, bcl-2 expression was significantly upregulated, whereas caspase-3 expression was downregulated, along with a reduced number of TUNEL-positive cells. The site-specific distribution of bcl-2 was consistent with the site-specific hyperplasia of the gingival epithelium in CsA-treated rats. CsA inhibited gingival epithelial apoptosis via the mitochondrial pathway and common pathway. The antiapoptotic protein bcl-2 might play a critical role in the pathogenesis of the site-specific hyperplasia of gingival epithelium induced by CsA. There were mechanistic differences in the regulation of apoptosis for cells in the attached gingival epithelium, free gingival epithelium, and junctional epithelium.

Sugar-binding sites of the HA1 subcomponent of Clostridium botulinum type C progenitor toxin.

PubMed

Nakamura, Toshio; Tonozuka, Takashi; Ide, Azusa; Yuzawa, Takayuki; Oguma, Keiji; Nishikawa, Atsushi

2008-02-22

Clostridium botulinum type C 16S progenitor toxin contains a hemagglutinin (HA) subcomponent, designated HA1, which appears to play an important role in the effective internalization of the toxin in gastrointestinal epithelial cells and in creating a broad specificity for the oligosaccharide structure that corresponds to various targets. In this study, using the recombinant protein fused to glutathione S-transferase, we investigated the binding specificity of the HA1 subcomponent to sugars and estimated the binding sites of HA1 based on X-ray crystallography and soaking experiments using various sugars. N-Acetylneuraminic acid, N-acetylgalactosamine, and galactose effectively inhibited the binding that occurs between glutathione S-transferase-HA1 and mucins, whereas N-acetylglucosamine and glucose did not inhibit it. The crystal structures of HA1 complex with N-acetylneuraminic acid, N-acetylgalactosamine, and galactose were also determined. There are two sugar-binding sites, sites I and II. Site I corresponds to the electron densities noted for all sugars and is located at the C-terminal beta-trefoil domain, while site II corresponds to the electron densities noted only for galactose. An aromatic amino acid residue, Trp176, at site I has a stacking interaction with the hexose ring of the sugars. On the other hand, there is no aromatic residue at site II; thus, the interaction with galactose seems to be poor. The double mutant W176A at site I and D271F at site II has no avidity for N-acetylneuraminic acid but has avidity for galactose. In this report, the binding specificity of botulinum C16S toxin HA1 to various sugars is demonstrated based on its structural features.

Improving Student Safety.

ERIC Educational Resources Information Center

Dorn, Michael; Trump, Kenneth S.; Nichols, R. Leslie

2001-01-01

Presents the latest information on how schools can keep their students safe. Safety oriented actions discussed cover incident reporting and tracking, tactical site surveys, school safety and emergency operations planning, staff development efforts, and facility design. Explains the need to review and test specific prevention concepts and emergency…

19 CFR 12.104g - Specific items or categories designated by agreements or emergency actions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 15th century A.D CBP Dec. 07-52. El Salvador Archaeological material representing Prehispanic cultures of El Salvador T.D. 95-20 extended by CBP Dec. 10-01 Guatemala Archaeological material from sites in...

Imprinting of confining sites for cell cultures on thermoplastic substrates

NASA Technical Reports Server (NTRS)

Cone, C. D.; Fleenor, E. N.

1969-01-01

Prevention of test cell migration beyond the field of observation involves confining cells or cultures in microlagoons made in either a layer of grease or a thermoplastic substrate. Thermoplastic films or dishes are easily imprinted with specifically designed patterns of microlagoons.

76 FR 52944 - Environmental Management Site-Specific Advisory Board, Oak Ridge Reservation

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-24

... Agenda: The main meeting presentation will be an overview of URS/CH2M Oak Ridge LLC (UCOR), the new prime... agenda. The Deputy Designated Federal Officer is empowered to conduct the meeting in a fashion that will...

Virtual Beach v2.2 User Guide

EPA Science Inventory

Virtual Beach version 2.2 (VB 2.2) is a decision support tool. It is designed to construct site-specific Multi-Linear Regression (MLR) models to predict pathogen indicator levels (or fecal indicator bacteria, FIB) at recreational beaches. MLR analysis has outperformed persisten...

Site-specific seismic ground motion analyses for transportation infrastructure in the New Madrid seismic zone.

DOT National Transportation Integrated Search

2012-11-01

Generic, code-based design procedures cannot account for the anticipated short-period attenuation and long-period amplification of earthquake ground motions in the deep, soft sediments of the Mississippi Embayment within the New Madrid Seismic Zone (...

Preparing Florida for deployment of SafetyAnalyst for all roads.

DOT National Transportation Integrated Search

2012-05-01

SafetyAnalyst is an advanced software system designed to provide the state and local highway agencies with a comprehensive set of tools to enhance their programming of site-specific highway safety improvements. As one of the 27 states that sponsored ...

Conventional Weapons Effects on Reinforced Soil Walls.

DTIC Science & Technology

1995-03-01

parametric study of the influence of specific design variables on wall panel response. D. METHODOLOGY A single degree of freedom model was modified to...t. dAev AVoF design methodologies for reinforced soil subjected o bl...at lad, LM, r..s.o.s. of these systems to such loading must be established...for many years and then on short notice be shipped to a location for use. The design for this shelter would be done as needed, although some non -site

Prostate Specific Expression of Maspin in a Transgenic Mouse Model: Implications in Prostate Carcinogenesis

DTIC Science & Technology

2004-05-01

should not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation. 20050603 257 r...such material. Where material from documents designated for limited distribution is quoted, permission has been obtained to use the material...amino acid peptide located in the reactive site loop of maspin, a region designated as AbS4A. The antibody was purified using an AbS4A sulfo-linked

Single-Stranded γPNAs for In Vivo Site-Specific Genome Editing via Watson-Crick Recognition

PubMed Central

Bahal, Raman; Quijano, Elias; McNeer, Nicole Ali; Liu, Yanfeng; Bhunia, Dinesh C.; López-Giráldez, Francesco; Fields, Rachel J.; Saltzman, W. Mark; Ly, Danith H.; Glazer, Peter M.

2014-01-01

Triplex-forming peptide nucleic acids (PNAs) facilitate gene editing by stimulating recombination of donor DNAs within genomic DNA via site-specific formation of altered helical structures that further stimulate DNA repair. However, PNAs designed for triplex formation are sequence restricted to homopurine sites. Herein we describe a novel strategy where next generation single-stranded gamma PNAs (γPNAs) containing miniPEG substitutions at the gamma position can target genomic DNA in mouse bone marrow at mixed-sequence sites to induce targeted gene editing. In addition to enhanced binding, γPNAs confer increased solubility and improved formulation into poly(lactic-co-glycolic acid) (PLGA) nanoparticles for efficient intracellular delivery. Single-stranded γPNAs induce targeted gene editing at frequencies of 0.8% in mouse bone marrow cells treated ex vivo and 0.1% in vivo via IV injection, without detectable toxicity. These results suggest that γPNAs may provide a new tool for induced gene editing based on Watson-Crick recognition without sequence restriction. PMID:25174576

Single-stranded γPNAs for in vivo site-specific genome editing via Watson-Crick recognition.

PubMed

Bahal, Raman; Quijano, Elias; McNeer, Nicole A; Liu, Yanfeng; Bhunia, Dinesh C; Lopez-Giraldez, Francesco; Fields, Rachel J; Saltzman, William M; Ly, Danith H; Glazer, Peter M

2014-01-01

Triplex-forming peptide nucleic acids (PNAs) facilitate gene editing by stimulating recombination of donor DNAs within genomic DNA via site-specific formation of altered helical structures that further stimulate DNA repair. However, PNAs designed for triplex formation are sequence restricted to homopurine sites. Herein we describe a novel strategy where next generation single-stranded gamma PNAs (γPNAs) containing miniPEG substitutions at the gamma position can target genomic DNA in mouse bone marrow at mixed-sequence sites to induce targeted gene editing. In addition to enhanced binding, γPNAs confer increased solubility and improved formulation into poly(lactic-co-glycolic acid) (PLGA) nanoparticles for efficient intracellular delivery. Single-stranded γPNAs induce targeted gene editing at frequencies of 0.8% in mouse bone marrow cells treated ex vivo and 0.1% in vivo via IV injection, without detectable toxicity. These results suggest that γPNAs may provide a new tool for induced gene editing based on Watson-Crick recognition without sequence restriction.

Substrate tunnels in enzymes: structure-function relationships and computational methodology.

PubMed

Kingsley, Laura J; Lill, Markus A

2015-04-01

In enzymes, the active site is the location where incoming substrates are chemically converted to products. In some enzymes, this site is deeply buried within the core of the protein, and, in order to access the active site, substrates must pass through the body of the protein via a tunnel. In many systems, these tunnels act as filters and have been found to influence both substrate specificity and catalytic mechanism. Identifying and understanding how these tunnels exert such control has been of growing interest over the past several years because of implications in fields such as protein engineering and drug design. This growing interest has spurred the development of several computational methods to identify and analyze tunnels and how ligands migrate through these tunnels. The goal of this review is to outline how tunnels influence substrate specificity and catalytic efficiency in enzymes with buried active sites and to provide a brief summary of the computational tools used to identify and evaluate these tunnels. © 2015 Wiley Periodicals, Inc.

Human HDAC7 Harbors a Class IIa Histone Deacetylase-specific Zinc Binding Motif and Cryptic Deacetylase Activity*S⃞

PubMed Central

Schuetz, Anja; Min, Jinrong; Allali-Hassani, Abdellah; Schapira, Matthieu; Shuen, Michael; Loppnau, Peter; Mazitschek, Ralph; Kwiatkowski, Nick P.; Lewis, Timothy A.; Maglathin, Rebecca L.; McLean, Thomas H.; Bochkarev, Alexey; Plotnikov, Alexander N.; Vedadi, Masoud; Arrowsmith, Cheryl H.

2008-01-01

Histone deacetylases (HDACs) are protein deacetylases that play a role in repression of gene transcription and are emerging targets in cancer therapy. Here, we characterize the structure and enzymatic activity of the catalytic domain of human HDAC7 (cdHDAC7). Although HDAC7 normally exists as part of a multiprotein complex, we show that cdHDAC7 has a low level of deacetylase activity which can be inhibited by known HDAC inhibitors. The crystal structures of human cdHDAC7 and its complexes with two hydroxamate inhibitors are the first structures of the catalytic domain of class IIa HDACs and demonstrate significant differences with previously reported class I and class IIb-like HDAC structures. We show that cdHDAC7 has an additional class IIa HDAC-specific zinc binding motif adjacent to the active site which is likely to participate in substrate recognition and protein-protein interaction and may provide a site for modulation of activity. Furthermore, a different active site topology results in modified catalytic properties and in an enlarged active site pocket. Our studies provide mechanistic insights into class IIa HDACs and facilitate the design of specific modulators. PMID:18285338

Human HDAC7 harbors a class IIa histone deacetylase-specific zinc binding motif and cryptic deacetylase activity.

PubMed

Schuetz, Anja; Min, Jinrong; Allali-Hassani, Abdellah; Schapira, Matthieu; Shuen, Michael; Loppnau, Peter; Mazitschek, Ralph; Kwiatkowski, Nick P; Lewis, Timothy A; Maglathin, Rebecca L; McLean, Thomas H; Bochkarev, Alexey; Plotnikov, Alexander N; Vedadi, Masoud; Arrowsmith, Cheryl H

2008-04-25

Histone deacetylases (HDACs) are protein deacetylases that play a role in repression of gene transcription and are emerging targets in cancer therapy. Here, we characterize the structure and enzymatic activity of the catalytic domain of human HDAC7 (cdHDAC7). Although HDAC7 normally exists as part of a multiprotein complex, we show that cdHDAC7 has a low level of deacetylase activity which can be inhibited by known HDAC inhibitors. The crystal structures of human cdHDAC7 and its complexes with two hydroxamate inhibitors are the first structures of the catalytic domain of class IIa HDACs and demonstrate significant differences with previously reported class I and class IIb-like HDAC structures. We show that cdHDAC7 has an additional class IIa HDAC-specific zinc binding motif adjacent to the active site which is likely to participate in substrate recognition and protein-protein interaction and may provide a site for modulation of activity. Furthermore, a different active site topology results in modified catalytic properties and in an enlarged active site pocket. Our studies provide mechanistic insights into class IIa HDACs and facilitate the design of specific modulators.

Conformational diversity and computational enzyme design

PubMed Central

Lassila, Jonathan K.

2010-01-01

The application of computational protein design methods to the design of enzyme active sites offers potential routes to new catalysts and new reaction specificities. Computational design methods have typically treated the protein backbone as a rigid structure for the sake of computational tractability. However, this fixed-backbone approximation introduces its own special challenges for enzyme design and it contrasts with an emerging picture of natural enzymes as dynamic ensembles with multiple conformations and motions throughout a reaction cycle. This review considers the impact of conformational variation and dynamics on computational enzyme design and it highlights new approaches to addressing protein conformational diversity in enzyme design including recent advances in multistate design, backbone flexibility, and computational library design. PMID:20829099

Final Environmental Assessment of the 801 Housing Program at Whiteman Air Force Base, Missouri

DTIC Science & Technology

1988-11-01

elatior), yellow foxtail (Setaria glauca (L.) Beauv.), red-top (Ag ostis alba L.), goose grass ( Eleusine indica (L.) Gaertn.), and others such as Panicum...steepness, and perched water table/wetness properties of soils at each proposed site require specif’: treatment in project design to reduce potential...Cultural Resources. A total of four archaeological sites presently are known to exist on the properties proposed for 801 housing: one at Knob Noster

Design criteria for a high energy Compton Camera and possible application to targeted cancer therapy

NASA Astrophysics Data System (ADS)

Conka Nurdan, T.; Nurdan, K.; Brill, A. B.; Walenta, A. H.

2015-07-01

The proposed research focuses on the design criteria for a Compton Camera with high spatial resolution and sensitivity, operating at high gamma energies and its possible application for molecular imaging. This application is mainly on the detection and visualization of the pharmacokinetics of tumor targeting substances specific for particular cancer sites. Expected high resolution (< 0.5 mm) permits monitoring the pharmacokinetics of labeled gene constructs in vivo in small animals with a human tumor xenograft which is one of the first steps in evaluating the potential utility of a candidate gene. The additional benefit of high sensitivity detection will be improved cancer treatment strategies in patients based on the use of specific molecules binding to cancer sites for early detection of tumors and identifying metastasis, monitoring drug delivery and radionuclide therapy for optimum cell killing at the tumor site. This new technology can provide high resolution, high sensitivity imaging of a wide range of gamma energies and will significantly extend the range of radiotracers that can be investigated and used clinically. The small and compact construction of the proposed camera system allows flexible application which will be particularly useful for monitoring residual tumor around the resection site during surgery. It is also envisaged as able to test the performance of new drug/gene-based therapies in vitro and in vivo for tumor targeting efficacy using automatic large scale screening methods.

Generation of TALE-Based Designer Epigenome Modifiers.

PubMed

Nitsch, Sandra; Mussolino, Claudio

2018-01-01

Manipulation of gene expression can be facilitated by editing the genome or the epigenome. Precise genome editing is traditionally achieved by using designer nucleases which are generally exploited to eliminate a specific gene product. Upon the introduction of a site-specific DNA double-strand break (DSB) by the nuclease, endogenous DSB repair mechanisms are in turn harnessed to induce DNA sequence changes that can result in target gene inactivation. Minimal off-target effects can be obtained by endowing designer nucleases with the highly specific DNA-binding domain (DBD) derived from transcription activator-like effectors (TALEs). In contrast, epigenome editing allows gene expression control without inducing changes in the DNA sequence by specifically altering epigenetic marks, as histone tails modifications or DNA methylation patterns within promoter or enhancer regions. Importantly, this approach allows both up- and downregulation of the target gene expression, and the effect is generally reversible. TALE-based designer epigenome modifiers combine the high specificity of TALE-derived DBDs with the power of epigenetic modifier domains to induce fast and long-lasting changes in the epigenetic landscape of a target gene and control its expression. Here we provide a detailed description for the generation of TALE-based designer epigenome modifiers and of a suitable reporter cell line to easily monitor their activity.

Universal light-switchable gene promoter system

DOEpatents

Quail, Peter H.; Huq, Enamul; Tepperman, James; Sato, Sae

2005-02-22

An artificial promoter system that can be fused upstream of any desired gene enabling reversible induction or repression of the expression of the gene at will in any suitable host cell or organisms by light is described. The design of the system is such that a molecule of the plant photoreceptor phytochrome is targeted to the specific DNA binding site in the promoter by a protein domain that is fused to the phytochrome and that specifically recognizes this binding site. This bound phytochrome, upon activation by light, recruits a second fusion protein consisting of a protein that binds to phytochrome only upon light activation and a transcriptional activation domain that activates expression of the gene downstream of the promoter.

Bauhinia proteinase inhibitor-based synthetic fluorogenic substrates for enzymes isolated from insect midgut and caterpillar bristles.

PubMed

Andrade, Sonia A; Santomauro-Vaz, Eugênio M; Lopes, Adriana R; Chudzinski-Tavassi, Ana M; Juliano, Maria A; Terra, Walter R; Sampaio, Misako U; Sampaio, Claudio A M; Oliva, Maria Luiza V

2003-03-01

Bauhinia ungulata factor Xa inhibitor (BuXI) inactivates factor Xa and LOPAP, a prothrombin activator proteinase isolated from the venom of Lonomia obliqua caterpillar bristles. The reactive site of the enzyme-inhibitor interaction was explored to design specific substrates for both enzymes. Methionine is crucial for LOPAP and factor Xa substrate interaction, since the change of both Met residues in the substrates abolished the hydrolysis. Synthetic substrates containing the sequence around the reactive site of BbKI, a plasma kallikrein inhibitor, were shown to be specific for trypsin hydrolysis. Therefore, these substrates may be an alternative in studies aiming at a characterization of trypsin-like enzyme activities, especially non-mammalian enzymes.

Engineering the Pseudomonas aeruginosa II lectin: designing mutants with changed affinity and specificity

NASA Astrophysics Data System (ADS)

Kříž, Zdeněk; Adam, Jan; Mrázková, Jana; Zotos, Petros; Chatzipavlou, Thomais; Wimmerová, Michaela; Koča, Jaroslav

2014-09-01

This article focuses on designing mutations of the PA-IIL lectin from Pseudomonas aeruginosa that lead to change in specificity. Following the previous results revealing the importance of the amino acid triad 22-23-24 (so-called specificity-binding loop), saturation in silico mutagenesis was performed, with the intent of finding mutations that increase the lectin's affinity and modify its specificity. For that purpose, a combination of docking, molecular dynamics and binding free energy calculation was used. The combination of methods revealed mutations that changed the performance of the wild-type lectin and its mutants to their preferred partners. The mutation at position 22 resulted in 85 % in inactivation of the binding site, and the mutation at 23 did not have strong effects thanks to the side chain being pointed away from the binding site. Molecular dynamics simulations followed by binding free energy calculation were performed on mutants with promising results from docking, and also at those where the amino acid at position 24 was replaced for bulkier or longer polar chain. The key mutants were also prepared in vitro and their binding properties determined by isothermal titration calorimetry. Combination of the used methods proved to be able to predict changes in the lectin performance and helped in explaining the data observed experimentally.

Molecular design of sequence specific DNA alkylating agents.

PubMed

Minoshima, Masafumi; Bando, Toshikazu; Shinohara, Ken-ichi; Sugiyama, Hiroshi

2009-01-01

Sequence-specific DNA alkylating agents have great interest for novel approach to cancer chemotherapy. We designed the conjugates between pyrrole (Py)-imidazole (Im) polyamides and DNA alkylating chlorambucil moiety possessing at different positions. The sequence-specific DNA alkylation by conjugates was investigated by using high-resolution denaturing polyacrylamide gel electrophoresis (PAGE). The results showed that polyamide chlorambucil conjugates alkylate DNA at flanking adenines in recognition sequences of Py-Im polyamides, however, the reactivities and alkylation sites were influenced by the positions of conjugation. In addition, we synthesized conjugate between Py-Im polyamide and another alkylating agent, 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI). DNA alkylation reactivies by both alkylating polyamides were almost comparable. In contrast, cytotoxicities against cell lines differed greatly. These comparative studies would promote development of appropriate sequence-specific DNA alkylating polyamides against specific cancer cells.

Airborne remote sensors applied to engineering geology and civil works design investigations

NASA Technical Reports Server (NTRS)

Gelnett, R. H.

1975-01-01

The usefulness of various airborne remote sensing systems in the detection and identification of regional and specific geologic structural features that may affect the design and location of engineering structures on major civil works projects is evaluated. The Butler Valley Dam and Blue Lake Project in northern California was selected as a demonstration site. Findings derived from the interpretation of various kinds of imagery used are given.

A Novel Photoelectrochemical Biosensor for Tyrosinase and Thrombin Detection

PubMed Central

Chen, Jiexia; Liu, Yifan; Zhao, Guang-Chao

2016-01-01

A novel photoelectrochemical biosensor for step-by-step assay of tyrosinase and thrombin was fabricated based on the specific interactions between the designed peptide and the target enzymes. A peptide chain with a special sequence which contains a positively charged lysine-labeled terminal, tyrosine at the other end and a cleavage site recognized by thrombin between them was designed. The designed peptide can be fixed on surface of the CdTe quantum dots (QDs)-modified indium-tin oxide (ITO) electrode through electrostatic attraction to construct the photoelectrochemical biosensor. The tyrosinase target can catalyze the oxidization of tyrosine by oxygen into ortho-benzoquinone residues, which results in a decrease in the sensor photocurrent. Subsequently, the cleavage site could be recognized and cut off by another thrombin target, restoring the sensor photocurrent. The decrease or increase of photocurrent in the sensor enables us to assay tyrosinase and thrombin. Thus, the detection of tyrosinase and thrombin can be achieved in the linear range from 2.6 to 32 μg/mL and from 4.5 to 100 μg/mL with detection limits of 1.5 μg/mL and 1.9 μg/mL, respectively. Most importantly, this strategy shall allow us to detect different classes of enzymes simultaneously by designing various enzyme-specific peptide substrates. PMID:26805846

Design and performance evaluation of a 1000-year evapotranspiration-capillary surface barrier.

PubMed

Zhang, Zhuanfang Fred; Strickland, Christopher E; Link, Steven O

2017-02-01

Surface barrier technology is used to isolate radioactive waste and to reduce or eliminate recharge water to the waste zone for 1000 years or longer. However, the design and evaluation of such a barrier is challenging because of the extremely long design life. After establishing a set of design and performance objectives, a package of design solutions was developed for 1000-year surface barriers over nuclear waste sites. The Prototype Hanford Barrier (PHB) was then constructed in 1994 in the field over an existing waste site as a demonstration. The barrier was tested to evaluate surface-barrier design and performance at the field scale under conditions of enhanced and natural precipitation and of no vegetation. The monitoring data demonstrate that the barrier satisfied nearly all objectives in the past two decades. The PHB far exceeded the Resource Conservation and Recovery Act criteria, functioned in Hanford's semiarid climate, limited drainage to well below the 0.5 mm yr -1 performance criterion, limited runoff, and minimized erosion and bio-intrusion. Given the two-decade record of successful performance and consideration of the processes and mechanisms that could affect barrier stability and hydrology in the future, the results suggest the PHB is very likely to perform for its 1000-year design life. This conclusion is based on two assumptions: (1) the exposed subgrade receives protection against erosion and (2) institutional controls prevent inadvertent human activity at the barrier. The PHB design can serve as the basis for site-specific barriers over waste sites containing underground nuclear waste, uranium mine tailings, and hazardous mine waste. Copyright © 2016 Elsevier Ltd. All rights reserved.

30 CFR 250.216 - What biological, physical, and socioeconomic information must accompany the EP?

Code of Federal Regulations, 2011 CFR

2011-07-01

.... Site-specific information on chemosynthetic communities, federally listed threatened or endangered species, marine mammals protected under the Marine Mammal Protection Act (MMPA), sensitive underwater features, marine sanctuaries, critical habitat designated under the Endangered Species Act (ESA), or other...

40 CFR 172.1 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... grants permission to a permittee or a permittee's designated participant for the use of an experimental use pesticide at an application site owned or controlled by the cooperator. Experimental animals means... supervising the use or evaluation of, an experimental use pesticide to be applied at a specific application...

10 CFR 850.3 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

.... Beryllium article means a manufactured item that is formed to a specific shape or design during manufacture... particles. Immune response refers to the series of cellular events by which the immune system reacts to... medical removal from beryllium areas following a recommendation by the Site Occupational Medicine Director...

Advanced Decision-Support for Coastal Beach Health: Virtual Beach 3.0

EPA Science Inventory

Virtual Beach is a free decision-support system designed to help beach managers and researchers construct, evaluate, and operate site-specific statistical models that can predict levels of fecal indicator bacteria (FIB) based on environmental conditions that are more readily mea...

In vivo covalent cross-linking of photon-converted rare-earth nanostructures for tumour localization and theranostics

NASA Astrophysics Data System (ADS)

Ai, Xiangzhao; Ho, Chris Jun Hui; Aw, Junxin; Attia, Amalina Binte Ebrahim; Mu, Jing; Wang, Yu; Wang, Xiaoyong; Wang, Yong; Liu, Xiaogang; Chen, Huabing; Gao, Mingyuan; Chen, Xiaoyuan; Yeow, Edwin K. L.; Liu, Gang; Olivo, Malini; Xing, Bengang

2016-01-01

The development of precision nanomedicines to direct nanostructure-based reagents into tumour-targeted areas remains a critical challenge in clinics. Chemical reaction-mediated localization in response to tumour environmental perturbations offers promising opportunities for rational design of effective nano-theranostics. Here, we present a unique microenvironment-sensitive strategy for localization of peptide-premodified upconversion nanocrystals (UCNs) within tumour areas. Upon tumour-specific cathepsin protease reactions, the cleavage of peptides induces covalent cross-linking between the exposed cysteine and 2-cyanobenzothiazole on neighbouring particles, thus triggering the accumulation of UCNs into tumour site. Such enzyme-triggered cross-linking of UCNs leads to enhanced upconversion emission upon 808 nm laser irradiation, and in turn amplifies the singlet oxygen generation from the photosensitizers attached on UCNs. Importantly, this design enables remarkable tumour inhibition through either intratumoral UCNs injection or intravenous injection of nanoparticles modified with the targeting ligand. Our strategy may provide a multimodality solution for effective molecular sensing and site-specific tumour treatment.

On the design of paleoenvironmental data networks for estimating large-scale patterns of climate

NASA Astrophysics Data System (ADS)

Kutzbach, J. E.; Guetter, P. J.

1980-09-01

Guidelines are determined for the spatial density and location of climatic variables (temperature and precipitation) that are appropriate for estimating the continental- to hemispheric-scale pattern of atmospheric circulation (sea-level pressure). Because instrumental records of temperature and precipitation simulate the climatic information that is contained in certain paleoenvironmental records (tree-ring, pollen, and written-documentary records, for example), these guidelines provide useful sampling strategies for reconstructing the pattern of atmospheric circulation from paleoenvironmental records. The statistical analysis uses a multiple linear regression model. The sampling strategies consist of changes in site density (from 0.5 to 2.5 sites per million square kilometers) and site location (from western North American sites only to sites in Japan, North America, and western Europe) of the climatic data. The results showed that the accuracy of specification of the pattern of sea-level pressure: (1) is improved if sites with climatic records are spread as uniformly as possible over the area of interest; (2) increases with increasing site density-at least up to the maximum site density used in this study; (3) is improved if sites cover an area that extends considerably beyond the limits of the area of interest. The accuracy of specification was lower for independent data than for the data that were used to develop the regression model; some skill was found for almost all sampling strategies.

Statistical Algorithms Accounting for Background Density in the Detection of UXO Target Areas at DoD Munitions Sites

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

Matzke, Brett D.; Wilson, John E.; Hathaway, J.

2008-02-12

Statistically defensible methods are presented for developing geophysical detector sampling plans and analyzing data for munitions response sites where unexploded ordnance (UXO) may exist. Detection methods for identifying areas of elevated anomaly density from background density are shown. Additionally, methods are described which aid in the choice of transect pattern and spacing to assure with degree of confidence that a target area (TA) of specific size, shape, and anomaly density will be identified using the detection methods. Methods for evaluating the sensitivity of designs to variation in certain parameters are also discussed. Methods presented have been incorporated into the Visualmore » Sample Plan (VSP) software (free at http://dqo.pnl.gov/vsp) and demonstrated at multiple sites in the United States. Application examples from actual transect designs and surveys from the previous two years are demonstrated.« less

Towards soft robotic devices for site-specific drug delivery.

PubMed

Alici, Gursel

2015-01-01

Considerable research efforts have recently been dedicated to the establishment of various drug delivery systems (DDS) that are mechanical/physical, chemical and biological/molecular DDS. In this paper, we report on the recent advances in site-specific drug delivery (site-specific, controlled, targeted or smart drug delivery are terms used interchangeably in the literature, to mean to transport a drug or a therapeutic agent to a desired location within the body and release it as desired with negligibly small toxicity and side effect compared to classical drug administration means such as peroral, parenteral, transmucosal, topical and inhalation) based on mechanical/physical systems consisting of implantable and robotic drug delivery systems. While we specifically focus on the robotic or autonomous DDS, which can be reprogrammable and provide multiple doses of a drug at a required time and rate, we briefly cover the implanted DDS, which are well-developed relative to the robotic DDS, to highlight the design and performance requirements, and investigate issues associated with the robotic DDS. Critical research issues associated with both DDSs are presented to describe the research challenges ahead of us in order to establish soft robotic devices for clinical and biomedical applications.

Hydrogeological controls on spatial patterns of groundwater discharge in peatlands

NASA Astrophysics Data System (ADS)

Hare, Danielle K.; Boutt, David F.; Clement, William P.; Hatch, Christine E.; Davenport, Glorianna; Hackman, Alex

2017-11-01

Peatland environments provide important ecosystem services including water and carbon storage, nutrient processing and retention, and wildlife habitat. However, these systems and the services they provide have been degraded through historical anthropogenic agricultural conversion and dewatering practices. Effective wetland restoration requires incorporating site hydrology and understanding groundwater discharge spatial patterns. Groundwater discharge maintains wetland ecosystems by providing relatively stable hydrologic conditions, nutrient inputs, and thermal buffering important for ecological structure and function; however, a comprehensive site-specific evaluation is rarely feasible for such resource-constrained projects. An improved process-based understanding of groundwater discharge in peatlands may help guide ecological restoration design without the need for invasive methodologies and detailed site-specific investigation. Here we examine a kettle-hole peatland in southeast Massachusetts historically modified for commercial cranberry farming. During the time of our investigation, a large process-based ecological restoration project was in the assessment and design phases. To gain insight into the drivers of site hydrology, we evaluated the spatial patterning of groundwater discharge and the subsurface structure of the peatland complex using heat-tracing methods and ground-penetrating radar. Our results illustrate that two groundwater discharge processes contribute to the peatland hydrologic system: diffuse lower-flux marginal matrix seepage and discrete higher-flux preferential-flow-path seepage. Both types of groundwater discharge develop through interactions with subsurface peatland basin structure, often where the basin slope is at a high angle to the regional groundwater gradient. These field observations indicate strong correlation between subsurface structures and surficial groundwater discharge. Understanding these general patterns may allow resource managers to more efficiently predict and locate groundwater seepage, confirm these using remote sensing technologies, and incorporate this information into restoration design for these critical ecosystems.

Progressive engineering of a homing endonuclease genome editing reagent for the murine X-linked immunodeficiency locus

PubMed Central

Wang, Yupeng; Khan, Iram F.; Boissel, Sandrine; Jarjour, Jordan; Pangallo, Joseph; Thyme, Summer; Baker, David; Scharenberg, Andrew M.; Rawlings, David J.

2014-01-01

LAGLIDADG homing endonucleases (LHEs) are compact endonucleases with 20–22 bp recognition sites, and thus are ideal scaffolds for engineering site-specific DNA cleavage enzymes for genome editing applications. Here, we describe a general approach to LHE engineering that combines rational design with directed evolution, using a yeast surface display high-throughput cleavage selection. This approach was employed to alter the binding and cleavage specificity of the I-Anil LHE to recognize a mutation in the mouse Bruton tyrosine kinase (Btk) gene causative for mouse X-linked immunodeficiency (XID)—a model of human X-linked agammaglobulinemia (XLA). The required re-targeting of I-AniI involved progressive resculpting of the DNA contact interface to accommodate nine base differences from the native cleavage sequence. The enzyme emerging from the progressive engineering process was specific for the XID mutant allele versus the wild-type (WT) allele, and exhibited activity equivalent to WT I-AniI in vitro and in cellulo reporter assays. Fusion of the enzyme to a site-specific DNA binding domain of transcription activator-like effector (TALE) resulted in a further enhancement of gene editing efficiency. These results illustrate the potential of LHE enzymes as specific and efficient tools for therapeutic genome engineering. PMID:24682825

Conoco's new approach to drill site construction in difficult, remote, swamp and jungle terrain Irian Jaya, Indonesia

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

Roodriguez, F.H.

1984-02-01

In October 1982, Conoco Irian Jaya as operator: and partners: Pertamina, Inpex Bintuni Limited, and Moeco Irian Jaya Company, mobilized construction equipment from Singapore to the KBS ''A'' contract area in Irian Jaya, Indonesia for the purpose of constructing a base camp and drill three exploratory sites. What made this construction effort different from others previously used in Irian Jaya; was that it incorporated several new and unique features, namely: a turnkey approach to construction; that is Conoco providing complete set of specifications and conditions with contractor assuming risks for a lump sum payment; special equipment designed by contractor formore » Irian Jaya operations; an incentive to co pensate or penalize contractor for helicopter hours flown below or above a predetermined number; structural steel pile platform designs for two swamp locations (Ayot and Aum), as opposed to the more conventional corduroy timber log-plank arrangement; and drilling rig pads designed for specific heli-rig with limited extra space. All work was successfully completed within the time frame stipulated in the contract, that is five months from the time the contractor was notified to begin mobilization of equipment, materials and personnel.« less

Mod-5A wind turbine generator program design report. Volume 4: Drawings and specifications, book 2

NASA Technical Reports Server (NTRS)

1984-01-01

The design, development and analysis of the 7.3 MW MOD-5A wind turbine generator is documented. There are four volumes. This volume contains the drawings and specifications that were developed in preparation for building the MOD-5A wind turbine generator. This is the second book of volume four. Some of the items it contains are specs for the emergency shutdown panel, specs for the simulator software, simulator hardware specs, site operator terminal requirements, control data system requirements, software project management plan, elastomeric teeter bearing requirement specs, specs for the controls electronic cabinet, and specs for bolt pretensioning.

Results of external quality-assurance program for the National Atmospheric Deposition Program and National Trends Network during 1985

USGS Publications Warehouse

Brooks, M.H.; Schroder, L.J.; Willoughby, T.C.

1988-01-01

External quality assurance monitoring of the National Atmospheric Deposition Program (NADP) and National Trends Network (NTN) was performed by the U.S. Geological Survey during 1985. The monitoring consisted of three primary programs: (1) an intersite comparison program designed to assess the precision and accuracy of onsite pH and specific conductance measurements made by NADP and NTN site operators; (2) a blind audit sample program designed to assess the effect of routine field handling on the precision and bias of NADP and NTN wet deposition data; and (3) an interlaboratory comparison program designed to compare analytical data from the laboratory processing NADP and NTN samples with data produced by other laboratories routinely analyzing wet deposition samples and to provide estimates of individual laboratory precision. An average of 94% of the site operators participated in the four voluntary intersite comparisons during 1985. A larger percentage of participating site operators met the accuracy goal for specific conductance measurements (average, 87%) than for pH measurements (average, 67%). Overall precision was dependent on the actual specific conductance of the test solution and independent of the pH of the test solution. Data for the blind audit sample program indicated slight positive biases resulting from routine field handling for all analytes except specific conductance. These biases were not large enough to be significant for most data users. Data for the blind audit sample program also indicated that decreases in hydrogen ion concentration were accompanied by decreases in specific conductance. Precision estimates derived from the blind audit sample program indicate that the major source of uncertainty in wet deposition data is the routine field handling that each wet deposition sample receives. Results of the interlaboratory comparison program were similar to results of previous years ' evaluations, indicating that the participating laboratories produced comparable data when they analyzed identical wet deposition samples, and that the laboratory processing NADP and NTN samples achieved the best analyte precision of the participating laboratories. (Author 's abstract)

"Phylogenetic and evolutionary analysis of functional divergence among Gamma glutamyl transpeptidase (GGT) subfamilies".

PubMed

Verma, Ved Vrat; Gupta, Rani; Goel, Manisha

2015-09-14

γ-glutamyltranspeptidase (GGT) is a bi-substrate enzyme conserved in all three domains of life. It catalyzes the cleavage and transfer of γ-glutamyl moiety of glutathione to either water (hydrolysis) or substrates like peptides (transpeptidation). GGTs exhibit great variability in their enzyme kinetics although the mechanism of catalysis is conserved. Recently, GGT has been shown to be a virulence factor in microbes like Helicobacter pylori and Bacillus anthracis. In mammalian cells also, GGT inhibition prior to chemotherapy has been shown to sensitize tumors to the therapy. Therefore, lately both bacterial and eukaryotic GGTs have emerged as potential drug targets, but the efforts directed towards finding suitable inhibitors have not yielded any significant results yet. We propose that delineating the residues responsible for the functional diversity associated with these proteins could help in design of species/clade specific inhibitors. In the present study, we have carried out phylogenetic analysis on a set of 47 GGT-like proteins to address the functional diversity. These proteins segregate into various subfamilies, forming separate clades on the tree. Sequence conservation and motif prediction studies show that even though most of the highly conserved residues have been characterized biochemically in previous studies, a significant number of novel putative sites and motifs are discovered that vary in a clade specific manner. Many of the putative sites predicted during the functional divergence type I and type II analysis, lie close to the known catalytic residues and line the walls of the substrate binding cavity, reinforcing their role in modulating the substrate specificity, catalytic rates and stability of this protein. The study offers interesting insights into the evolution of GGT-like proteins in pathogenic vs. non-pathogenic bacteria, archaea and eukaryotes. Our analysis delineates residues that are highly specific to each GGT subfamily. We propose that these sites not only explain the differences in stability and catalytic variability of various GGTs but can also aid in design of specific inhibitors against particular GGTs. Thus, apart from the commonly used in-silico inhibitor screening approaches, evolutionary analysis identifying the functional divergence hotspots in GGT proteins could augment the structure based drug design approaches.

Two-color SERS microscopy for protein co-localization in prostate tissue with primary antibody-protein A/G-gold nanocluster conjugates

NASA Astrophysics Data System (ADS)

Salehi, Mohammad; Schneider, Lilli; Ströbel, Philipp; Marx, Alexander; Packeisen, Jens; Schlücker, Sebastian

2014-01-01

SERS microscopy is a novel staining technique in immunohistochemistry, which is based on antibodies labeled with functionalized noble metal colloids called SERS labels or nanotags for optical detection. Conventional covalent bioconjugation of these SERS labels cannot prevent blocking of the antigen recognition sites of the antibody. We present a rational chemical design for SERS label-antibody conjugates which addresses this issue. Highly sensitive, silica-coated gold nanoparticle clusters as SERS labels are non-covalently conjugated to primary antibodies by using the chimeric protein A/G, which selectively recognizes the Fc part of antibodies and therefore prevents blocking of the antigen recognition sites. In proof-of-concept two-color imaging experiments for the co-localization of p63 and PSA on non-neoplastic prostate tissue FFPE specimens, we demonstrate the specificity and signal brightness of these rationally designed primary antibody-protein A/G-gold nanocluster conjugates.SERS microscopy is a novel staining technique in immunohistochemistry, which is based on antibodies labeled with functionalized noble metal colloids called SERS labels or nanotags for optical detection. Conventional covalent bioconjugation of these SERS labels cannot prevent blocking of the antigen recognition sites of the antibody. We present a rational chemical design for SERS label-antibody conjugates which addresses this issue. Highly sensitive, silica-coated gold nanoparticle clusters as SERS labels are non-covalently conjugated to primary antibodies by using the chimeric protein A/G, which selectively recognizes the Fc part of antibodies and therefore prevents blocking of the antigen recognition sites. In proof-of-concept two-color imaging experiments for the co-localization of p63 and PSA on non-neoplastic prostate tissue FFPE specimens, we demonstrate the specificity and signal brightness of these rationally designed primary antibody-protein A/G-gold nanocluster conjugates. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr05890e

Associations between provider designation and female-specific cancer screening in women Veterans.

PubMed

Bean-Mayberry, Bevanne; Bastian, Lori; Trentalange, Mark; Murphy, Terrence E; Skanderson, Melissa; Allore, Heather; Reyes-Harvey, Evelyn; Maisel, Natalya C; Gaetano, Vera; Wright, Steven; Haskell, Sally; Brandt, Cynthia

2015-04-01

In 2010, the Department of Veterans Affairs Healthcare System (VA) implemented policy to provide Comprehensive Primary Care (for acute, chronic, and female-specific care) from designated Women's Health providers (DWHPs) at all VA sites. However, since that time no comparisons of quality measures have been available to assess the level of care for women Veterans assigned to these providers. To evaluate the associations between cervical and breast cancer screening rates among age-appropriate women Veterans and designation of primary-care provider (DWHP vs. non-DWHP). Cross-sectional analyses using the fiscal year 2012 data on VA women's health providers, administrative files, and patient-specific quality measures. The sample included 37,128 women Veterans aged 21 through 69 years. Variables included patient demographic and clinical factors (ie, age, race, ethnicity, mental health diagnoses, obesity, and site), and provider factors (ie, DWHP status, sex, and panel size). Screening measures were defined by age-appropriate subgroups using VA national guidelines. Female-specific cancer screening rates were higher among patients assigned to DWHPs (cervical cytology 94.4% vs. 91.9%, P<0.0001; mammography 86.3% vs. 83.3%, P<0.0001). In multivariable models with adjustment for patient and provider characteristics, patients assigned to DWHPs had higher odds of cervical cancer screening (odds ratio, 1.26; 95% confidence interval, 1.07-1.47; P<0.0001) and breast cancer screening (odds ratio, 1.24; 95% CI, 1.10-1.39; P<0.0001). As the proportion of women Veterans increases, assignment to DWHPs may raise rate of female-specific cancer screening within VA. Separate evaluation of sex neutral measures is needed to determine whether other measures accrue benefits for patients with DWHPs.

Designing and Testing of Novel Taxanes to Probe the Highly Complex Mechanisms by Which Taxanes Bind to Microtubules and Cause Cytotoxicity to Cancer Cells

PubMed Central

St. George, Marc; Ayoub, Ahmed T.; Banerjee, Asok; Churchill, Cassandra D. M.; Winter, Philip; Klobukowski, Mariusz; Cass, Carol E.; Ludueña, Richard F.; Tuszynski, Jack A.; Damaraju, Sambasivarao

2015-01-01

Our previous work identified an intermediate binding site for taxanes in the microtubule nanopore. The goal of this study was to test derivatives of paclitaxel designed to bind to this intermediate site differentially depending on the isotype of β-tubulin. Since β-tubulin isotypes have tissue-dependent expression—specifically, the βIII isotype is very abundant in aggressive tumors and much less common in normal tissues—this is expected to lead to tubulin targeted drugs that are more efficacious and have less side effects. Seven derivatives of paclitaxel were designed and four of these were amenable for synthesis in sufficient purity and yield for further testing in breast cancer model cell lines. None of the derivatives studied were superior to currently used taxanes, however computer simulations provided insights into the activity of the derivatives. Our results suggest that neither binding to the intermediate binding site nor the final binding site is sufficient to explain the activities of the derivative taxanes studied. These findings highlight the need to iteratively improve on the design of taxanes based on their activity in model systems. Knowledge gained on the ability of the engineered drugs to bind to targets and bring about activity in a predictable manner is a step towards personalizing therapies. PMID:26052950

Identifying agro-ecoregions for the Long Term Agroecosystem Research (LTAR) network

USDA-ARS?s Scientific Manuscript database

The LTAR network exists to examine questions of agricultural sustainability in working lands across the continental US. To effectively address agricultural sustainability at this scale, experimental designs must be placed into the context of a regional framework that can extrapolate site-specific re...

Managing Mission-Critical Infrastructure

ERIC Educational Resources Information Center

Breeding, Marshall

2012-01-01

In the library context, they depend on sophisticated business applications specifically designed to support their work. This infrastructure consists of such components as integrated library systems, their associated online catalogs or discovery services, and self-check equipment, as well as a Web site and the various online tools and services…

Live load monitoring for the I-10 twin span bridge : research project capsule.

DOT National Transportation Integrated Search

2014-10-01

To establish a site-specific database for bridge evaluation and future bridge design, : DOTD established a long-term health monitoring system at the I-10 Twin Span Bridge. : The bridge is instrumented from deck to piles to capture bridge response (bo...

Predicting Fecal Indicator Bacteria Concentrations in the South Fork Broad River Watershed Using Virtual Beach

EPA Science Inventory

Virtual Beach (VB) is a decision support tool that constructs site-specific statistical models to predict fecal indicator bacteria (FIB) at recreational beaches. Although primarily designed for making decisions regarding beach closures or issuance of swimming advisories based on...

Site-specific variable rate irrigation a means to enhance water use efficiency

USDA-ARS?s Scientific Manuscript database

The majority of irrigated cropland in the US is watered with sprinkler irrigation systems. These systems are inherently more efficient in distributing water than furrow or flood irrigation. Appropriate system design of sprinkler irrigation equipment, application methods, and farming practices (e.g. ...

Site-specific variable rate irrigation as a means to enhance water use efficiency

USDA-ARS?s Scientific Manuscript database

The majority of irrigated cropland in the US is watered with sprinkler irrigation systems. These systems are inherently more efficient in distributing water than furrow or flood irrigation. Appropriate system design of sprinkler irrigation equipment, application methods, and farming practices (e.g. ...

Construction of transformed, cultured silkworm cells and transgenic silkworm using the site-specific integrase system from phage φC31.

PubMed

Yin, Yajuan; Cao, Guangli; Xue, Renyu; Gong, Chengliang

2014-10-01

The Streptomyces bacteriophage, φC31, uses a site-specific integrase enzyme to perform efficient recombination. The recombination system uses specific sequences to integrate exogenous DNA from the phage into a host. The sequences are known as the attP site in the phage and the attB site in the host. The system can be used as a genetic manipulation tool. In this study it has been applied to the transformation of cultured BmN cells and the construction of transgenic Bombyx mori individuals. A plasmid, pSK-attB/Pie1-EGFP/Zeo-PASV40, containing a cassette designed to express a egfp-zeocin fusion gene, was co-transfected into cultured BmN cells with a helper plasmid, pSK-Pie1/NLS-Int/NSL. Expression of the egfp-zeocin fusion gene was driven by an ie-1 promoter, downstream of a φC31 attB site. The helper plasmid encoded the φC31 integrase enzyme, which was flanked by two nuclear localization signals. Expression of the egfp-zeocin fusion gene could be observed in transformed cells. The two plasmids were also transferred into silkworm eggs to obtain transgenic silkworms. Successful integration of the fusion gene was indicated by the detection of green fluorescence, which was emitted by the silkworms. Nucleotide sequence analysis demonstrated that the attB site had been cut, to allow recombination between the attB and endogenous pseudo attP sites in the cultured silkworm cells and silkworm individuals.

Monitoring Ras Interactions with the Nucleotide Exchange Factor Son of Sevenless (Sos) Using Site-specific NMR Reporter Signals and Intrinsic Fluorescence.

PubMed

Vo, Uybach; Vajpai, Navratna; Flavell, Liz; Bobby, Romel; Breeze, Alexander L; Embrey, Kevin J; Golovanov, Alexander P

2016-01-22

The activity of Ras is controlled by the interconversion between GTP- and GDP-bound forms partly regulated by the binding of the guanine nucleotide exchange factor Son of Sevenless (Sos). The details of Sos binding, leading to nucleotide exchange and subsequent dissociation of the complex, are not completely understood. Here, we used uniformly (15)N-labeled Ras as well as [(13)C]methyl-Met,Ile-labeled Sos for observing site-specific details of Ras-Sos interactions in solution. Binding of various forms of Ras (loaded with GDP and mimics of GTP or nucleotide-free) at the allosteric and catalytic sites of Sos was comprehensively characterized by monitoring signal perturbations in the NMR spectra. The overall affinity of binding between these protein variants as well as their selected functional mutants was also investigated using intrinsic fluorescence. The data support a positive feedback activation of Sos by Ras·GTP with Ras·GTP binding as a substrate for the catalytic site of activated Sos more weakly than Ras·GDP, suggesting that Sos should actively promote unidirectional GDP → GTP exchange on Ras in preference of passive homonucleotide exchange. Ras·GDP weakly binds to the catalytic but not to the allosteric site of Sos. This confirms that Ras·GDP cannot properly activate Sos at the allosteric site. The novel site-specific assay described may be useful for design of drugs aimed at perturbing Ras-Sos interactions. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

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

Simultaneous non-contiguous deletions using large synthetic DNA and site-specific recombinases

PubMed Central

Krishnakumar, Radha; Grose, Carissa; Haft, Daniel H.; Zaveri, Jayshree; Alperovich, Nina; Gibson, Daniel G.; Merryman, Chuck; Glass, John I.

2014-01-01

Toward achieving rapid and large scale genome modification directly in a target organism, we have developed a new genome engineering strategy that uses a combination of bioinformatics aided design, large synthetic DNA and site-specific recombinases. Using Cre recombinase we swapped a target 126-kb segment of the Escherichia coli genome with a 72-kb synthetic DNA cassette, thereby effectively eliminating over 54 kb of genomic DNA from three non-contiguous regions in a single recombination event. We observed complete replacement of the native sequence with the modified synthetic sequence through the action of the Cre recombinase and no competition from homologous recombination. Because of the versatility and high-efficiency of the Cre-lox system, this method can be used in any organism where this system is functional as well as adapted to use with other highly precise genome engineering systems. Compared to present-day iterative approaches in genome engineering, we anticipate this method will greatly speed up the creation of reduced, modularized and optimized genomes through the integration of deletion analyses data, transcriptomics, synthetic biology and site-specific recombination. PMID:24914053

Performance of species occurrence estimators when basic assumptions are not met: a test using field data where true occupancy status is known

USGS Publications Warehouse

Miller, David A. W.; Bailey, Larissa L.; Grant, Evan H. Campbell; McClintock, Brett T.; Weir, Linda A.; Simons, Theodore R.

2015-01-01

Our results demonstrate that even small probabilities of misidentification and among-site detection heterogeneity can have severe effects on estimator reliability if ignored. We challenge researchers to place greater attention on both heterogeneity and false positives when designing and analysing occupancy studies. We provide 9 specific recommendations for the design, implementation and analysis of occupancy studies to better meet this challenge.

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

None

Information used to evaluate the initial design of the Elcam, Inc., Solar Domestic Hot Water System is presented. Included are such items as the system performance specification, detailed design drawings and other information. Elcam, Inc., has developed two solar heated prototype hot water systems and two heat exchangers. The hot water systems consist of the following subsystems: collector, storage, control, transport, auxiliary energy, and government-furnished Site Data Acquisition. The two systems are installed at Tempe, Arizona, and San Diego, California.

Long-period amplification in deep alluvial basins and consequences for site-specific probabilistic seismic-hazard: the case of Castelleone in the Po Plain (Northern Italy)

NASA Astrophysics Data System (ADS)

Barani, S.; Mascandola, C.; Massa, M.; Spallarossa, D.

2017-12-01

The recent Emilia seismic sequence (Northern Italy) occurred at the end of the first half of 2012 with main shock of Mw6.1 highlighted the importance of studying site effects in the Po Plain, the larger and deeper sedimentary basin in Italy. As has long been known, long-period amplification related to deep sedimentary basins can significantly affect the characteristics of the ground-motion induced by strong earthquakes. It follows that the effects of deep sedimentary deposits on ground shaking require special attention during the definition of the design seismic action. The work presented here analyzes the impact of deep-soil discontinuities on ground-motion amplification, with particular focus on long-period probabilistic seismic-hazard assessment. The study focuses on the site of Castelleone, where a seismic station of the Italian National Seismic Network has been recording since 2009. Our study includes both experimental and numerical site response analyses. Specifically, extensive active and passive geophysical measurements were carried out in order to define a detailed shear-wave velocity (VS) model to be used in the numerical analyses. These latter are needed to assess the site-specific ground-motion hazard. Besides classical seismic refraction profiles and multichannel analysis of surface waves, we analyzed ambient vibration measurements in both single and array configurations. The VS profile was determined via joint inversion of the experimental phase-velocity dispersion curve with the ellipticity curve derived from horizontal-to-vertical spectral ratios. The profile shows two main discontinuities at depths of around 160 and 1350 m, respectively. The probabilistic site-specific hazard was assessed in terms of both spectral acceleration and displacement. A partially non-ergodic approach was adopted. We have found that the spectral acceleration hazard is barely sensitive to long-period (up to 10 s) amplification related to the deeper discontinuity whereas the displacement hazard is strongly affected. Our results show that neglecting the effects of the deeper discontinuity implies an underestimation of the hazard of up to about 49% for a mean return period (MRP) of 475 years and 57% for an MRP of 2475 years, with possible consequences on the design of very tall buildings and large bridges.

Characterization and design of the FutureGen 2.0 carbon storage site

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

Gilmore, Tyler; Bonneville, Alain; Sullivan, Charlotte

2016-10-01

The objective of the FutureGen 2.0 Project was to demonstrate, at the commercial scale, the technical feasibility of implementing carbon capture and storage (CCS) in a deep saline formation in Illinois, USA. Over approximately 5 years, the FutureGen Alliance conducted a detailed site-selection process and identified a site for carbon sequestration storage in Morgan County, Illinois. The storage site was fully characterized, including the collection of seismic data and the drilling and characterization of a stratigraphic borehole. The characterization data provided critical input for developing a site-specific conceptual model and subsequent numerical modeling simulations. The modeling simulations, coupled with themore » upstream designs of the pipeline and power plant supported the development of a detailed 90 percent design that included the injection wells and associated control and monitoring infrastructure. Collectively, all these data were used by the FutureGen Alliance to develop the required documentation to support the applications for four underground injection control (UIC) permits (one for each proposed well). In August 2014, the U.S. Environmental Protection Agency issued four, first-of-their-kind, Class VI UIC permits for carbon sequestration in the United States to the FutureGen Alliance. The information and data generated under this project have been made publically available through reports and publications, including this journal and others.« less

Theoretical study of native point defects in strained-layer superlattice systems

NASA Astrophysics Data System (ADS)

Krishnamurthy, S.; Yu, Zhi Gang

2018-04-01

We developed a theoretical approach that employs first-principles Hamiltonians, tight-binding Hamiltonians, and Green's function techniques to obtain energy levels arising from native point defects (NPDs) in InAs-GaSb and InAs-InAs1-xSbx strained layer superlattice (SLS) systems. In InAs and GaSb regions, we considered four types of NPDs—anion vacancy, cation vacancy, anion anti-site, and cation anti-site—as well as isoelectronic substitution at anion sites (Sb at the As site and As at the Sb site). Additionally, we considered three types of defects—the cation at the second anion site, the second anion at the cation site, and second anion vacancy—in the InAs1-xSbx alloy region of the SLS. For a selected few designs, we studied NPDs both in the bulk region and near the interfaces of the SLS. We have considered 12 designs of InAs-GaSb systems and two designs of InAs-InAs0.7Sb0.3 systems lattice-matched to the GaSb substrate. The calculated defect levels not only agreed well with available measurements, but also revealed the connection between mid-gap levels and specific NPDs. We further calculated defect formation energies both in compounds and in all superlattices considered above. Since the absolute value of defect formation energy depends considerably on growth conditions, we evaluated the formation energies in SLS with respect to their value in the corresponding bulk or alloy. The calculated defect formation energies, together with defect energy level results, allow us to identify a few promising SLS designs for high-performing photodetectors.

Loads specification and embedded plate definition for the ITER cryoline system

NASA Astrophysics Data System (ADS)

Badgujar, S.; Benkheira, L.; Chalifour, M.; Forgeas, A.; Shah, N.; Vaghela, H.; Sarkar, B.

2015-12-01

ITER cryolines (CLs) are complex network of vacuum-insulated multi and single process pipe lines, distributed in three different areas at ITER site. The CLs will support different operating loads during the machine life-time; either considered as nominal, occasional or exceptional. The major loads, which form the design basis are inertial, pressure, temperature, assembly, magnetic, snow, wind, enforced relative displacement and are put together in loads specification. Based on the defined load combinations, conceptual estimation of reaction loads have been carried out for the lines located inside the Tokamak building. Adequate numbers of embedded plates (EPs) per line have been defined and integrated in the building design. The finalization of building EPs to support the lines, before the detailed design, is one of the major design challenges as the usual logic of the design may alter. At the ITER project level, it was important to finalize EPs to allow adequate design and timely availability of the Tokamak building. The paper describes the single loads, load combinations considered in load specification and the approach for conceptual load estimation and selection of EPs for Toroidal Field (TF) Cryoline as an example by converting the load combinations in two main load categories; pressure and seismic.

Site Selection for Mars Surveyor Landing Sites: Some Key Factors for 2001 and Relation to Long-Term Exploration of Mars

NASA Astrophysics Data System (ADS)

Head, James W.

1999-01-01

The Site Selection Process: Site selection as a process can be subdivided into several main elements and these can be represented as the corners of a tetrahedron. Successful site selection outcome requires the interactions between these elements or corners, and should also take into account several other external factors or considerations. In principle, elements should be defined in approximately the following order: (1) major scientific and programmatic goals and objectives: What are the major questions that are being asked, goals that should be achieved, and objectives that must be accomplished. Do programmatic goals (e.g., sample return) differ from mission goals (e.g., precursor to sample return)? It is most helpful if these questions can be placed in the context of site characterization and hypothesis testing (e.g., Was Mars warm and wet in the Noachian? Land at a Noachian-aged site that shows evidence of surface water and characterize it specifically to address this question). Goals and objectives, then, help define important engineering factors such as type of payload, landing regions of interest (highlands, lowlands, smooth, rough, etc.), mobility, mission duration, etc. Goals and objectives then lead to: (2) spacecraft design and engineering landing site constraints: the spacecraft is designed to optimize the areas that will meet the goals and objectives, but this in turn introduces constraints that must be met in the selection of a landing site. Scientific and programmatic goals and objectives also help to define (3), the specific lander scientific payload requirements and capabilities. For example, what observations and experiments are required to address the major questions? How do we characterize the site in reference to the specific questions? Is mobility required and if so, how much? Which experiments are on the spacecraft, which on the rover? The results of these deliberations should lead to a surface exploration strategy, in which the goals and objectives can in principle be achieved through the exploration of a site meeting the basic engineering constraints. Armed with all of this important background information, one can then proceed to (4) the selection of optimum sites to address major scientific and programmatic objectives. Following the successful completion of this process and the selection of a site or region, there is a further step of mission optimization, in which a detailed mission profile and surface exploration plan is developed. In practice, the process never works in a linear fashion. Scientific goals are influenced by ongoing discoveries and developments and simple crystallization of thinking. Programmatic goals are influenced by evolving fiscal constraints, perspectives on program duration, and roles of specific missions in the context of the larger program. Engineering constraints are influenced by evolving fiscal constraints, decisions on hardware design that may have little to do with scientific goals (e.g., lander clearance; size of landing ellipse), and evolving understanding (e.g., assessment of engineering constraint space reveals further the degree to which mission duration is severely influenced by available solar energy and thus latitude). Lander scientific payload is influenced by fiscal constraints, total mass, evolving complexity, technological developments, and a payload selection process that may involve very long-term goals (e.g., human exploration) as well as shorter term scientific and programmatic goals. Site selection activities commonly involve scientists who are actively trying to decipher the complex geology of the crust of Mars and to unravel its geologic history through geological mapping. By the nature of the process, they are thinking in terms of broad morphostratigraphic units which may have multiple possible origins, defined using images with resolutions of many tens to hundreds of meters, and whose surfaces at the scale of the lander and rover are virtually unknown; this approach and effort is crucially important but does not necessarily readily lend itself to integration with the other elements.

Collection, processing and dissemination of data for the national solar demonstration program

NASA Technical Reports Server (NTRS)

Day, R. E.; Murphy, L. J.; Smok, J. T.

1978-01-01

A national solar data system developed for the DOE by IBM provides for automatic gathering, conversion, transfer, and analysis of demonstration site data. NASA requirements for this system include providing solar site hardware, engineering, data collection, and analysis. The specific tasks include: (1) solar energy system design/integration; (2) developing a site data acquisition subsystem; (3) developing a central data processing system; (4) operating the test facility at Marshall Space Flight Center; (5) collecting and analyzing data. The systematic analysis and evaluation of the data from the National Solar Data System is reflected in a monthly performance report and a solar energy system performance evaluation report.

Design and structure of stapled peptides binding to estrogen receptors.

PubMed

Phillips, Chris; Roberts, Lee R; Schade, Markus; Bazin, Richard; Bent, Andrew; Davies, Nichola L; Moore, Rob; Pannifer, Andrew D; Pickford, Andrew R; Prior, Stephen H; Read, Christopher M; Scott, Andrew; Brown, David G; Xu, Bin; Irving, Stephen L

2011-06-29

Synthetic peptides that specifically bind nuclear hormone receptors offer an alternative approach to small molecules for the modulation of receptor signaling and subsequent gene expression. Here we describe the design of a series of novel stapled peptides that bind the coactivator peptide site of estrogen receptors. Using a number of biophysical techniques, including crystal structure analysis of receptor-stapled peptide complexes, we describe in detail the molecular interactions and demonstrate that all-hydrocarbon staples modulate molecular recognition events. The findings have implications for the design of stapled peptides in general.

Waveform generation in the EETS

NASA Astrophysics Data System (ADS)

Wilshire, J. P.

1985-05-01

Design decisions and analysis for the waveform generation portion of an electrical equipment test set are discussed. This test set is unlike conventional ATE in that it is portable and designed to operate in forward area sites for the USMC. It is also unique in that it provides for functional testing for 32 electronic units from the AV-88 Harrier II aircraft. Specific requirements for the waveform generator are discussed, including a wide frequency range, high resolution and accuracy, and low total harmonic distortion. Several approaches to meet these requirements are considered and a specific concept is presented in detail, which consists of a digitally produced waveform that feeds a deglitched analog conversion circuit. Rigorous mathematical analysis is presented to prove that this concept meets the requirements. Finally, design alternatives and enhancements are considered.

Controlled experiments for dense gas diffusion: Experimental design and execution, model comparison

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

Egami, R.; Bowen, J.; Coulombe, W.

1995-07-01

An experimental baseline CO2 release experiment at the DOE Spill Test Facility on the Nevada Test Site in Southern Nevada is described. This experiment was unique in its use of CO2 as a surrogate gas representative of a variety of specific chemicals. Introductory discussion places the experiment in historical perspective. CO2 was selected as a surrogate gas to provide a data base suitable for evaluation of model scenarios involving a variety of specific dense gases. The experiment design and setup are described, including design rationale and quality assurance methods employed. Resulting experimental data are summarized. Data usefulness is examined throughmore » a preliminary comparison of experimental results with simulations performed using the SLAV and DEGADIS dense gas models.« less

The prospect of gene therapy for prostate cancer: update on theory and status.

PubMed

Koeneman, K S; Hsieh, J T

2001-09-01

Molecularly based novel therapeutic agents are needed to address the problem of locally recurrent, or metastatic, advanced hormone-refractory prostate cancer. Recent basic science advances in mechanisms of gene expression, vector delivery, and targeting have rendered clinically relevant gene therapy to the prostatic fossa and distant sites feasible in the near future. Current research and clinical investigative efforts involving methods for more effective vector delivery and targeting, with enhanced gene expression to selected (specific) sites, are reviewed. These areas of research involve tissue-specific promoters, transgene exploration, vector design and delivery, and selective vector targeting. The 'vectorology' involved mainly addresses selective tissue homing with ligands, mechanisms of innate immune system evasion for durable transgene expression, and the possibility of repeat administration.

NEW APPROACHES TO ESTIMATION OF SOLID-WASTE QUANTITY AND COMPOSITION

EPA Science Inventory

Efficient and statistically sound sampling protocols for estimating the quantity and composition of solid waste over a stated period of time in a given location, such as a landfill site or at a specific point in an industrial or commercial process, are essential to the design ...

Differences between Perceived Usefulness of Social Media and Institutional Channels by Undergraduate Students

ERIC Educational Resources Information Center

Garcia, Leandro Sumida; Silva, Camila Mariane Costa

2016-01-01

Social media technologies were introduced among the modern society and are part of its routine in many ways--knowledge acquisition and sharing, interpersonal relationships, media diffusion--sometimes complementing and even substituting tools that were specifically designed for similar activities. This research compares social media sites and…

77 FR 33729 - Disability and Rehabilitation Research Projects and Centers Program-National Data and Statistical...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-07

... statistical and other methodological consultation to this collaborative project. Discussion: Grantees under... and technical assistance must be designed to contribute to the following outcomes: (a) Maintenance of... methodological consultation available for research projects that use the BMS Database, as well as site- specific...

Developing a Watershed Challenge

ERIC Educational Resources Information Center

Roman, Harry T.

2010-01-01

This article presents a watershed challenge that gives students an opportunity to investigate the challenge of using a watershed area as a site for development, examining the many aspects of this multifaceted problem. This design challenge could work well in a team-based format, with students taking on specific aspects of the challenges and…

78 FR 35072 - Proposed Revisions to Reliability Assurance Program

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-11

... current staff review methods and practices based on lessons learned from NRC reviews of design... following methods (unless this document describes a different method for submitting comments on a specific... possesses and is publicly-available, by the following methods: Federal Rulemaking Web site: Go to http://www...

An Analytical Index to the Internet: Dreams of Utopia.

ERIC Educational Resources Information Center

Casey, Carol

1999-01-01

Explores the need for analytical indexes to access Internet resources. Considers bibliographic control, Web site design, keyword search engines, hierarchical subject indexes, and special indexes and compilations of links, and concludes that the creation of small, focused indexes may be the best solution for accessing specific types of digital…

General Chemistry for Waste Handlers.

ERIC Educational Resources Information Center

Sixtus, Michael E.

This manual is intended for use in presenting a course which provides the content-specific general chemistry education required for the safety awareness and job enhancement of persons employed as waste handlers. The course, which was designed to be delivered to technicians at job sites in a lecture/demonstration format with several hands-on…

DESIGN OF AQUIFER REMEDIATION SYSTEMS: (2) Estimating site-specific performance and benefits of partial source removal

EPA Science Inventory

A Lagrangian stochastic model is proposed as a tool that can be utilized in forecasting remedial performance and estimating the benefits (in terms of flux and mass reduction) derived from a source zone remedial effort. The stochastic functional relationships that describe the hyd...

Plotting landscape perspectives of clearcut units.

Treesearch

Roger H. Twito

1978-01-01

The aesthetics of clearcut units potentially visible from a distance can be improved by judicious design. Screening clearcuts from view or shaping them to characterize natural openings are current methods used for this purpose. Perspective plots illustrating how proposed clearcut units will look from specific off-site viewing points provide an...

15 CFR 923.21 - Areas of particular concern.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Areas of particular concern. 923.21... concern. (a) The management program must include an inventory and designation of areas of particular concern within the coastal zone, on a generic and/or site-specific basis, and broad guidelines on...

Project PARTnership: Instructional Kit. A Model Program for Encouraging Self-Determination through Access to the Arts.

ERIC Educational Resources Information Center

Harris, Carolyn DeMeyer, Ed.; McKinney, David D., Ed.

This instructional kit outlines procedures for implementing Project PARTnership, a program for teaching students with disabilities greater self-determination skills through specifically designed arts experiences. An introductory section describes key project activities, including establishing a site steering committee comprised of teachers,…

10 CFR 52.47 - Contents of applications; technical information.

Code of Federal Regulations, 2013 CFR

2013-01-01

... accidents, e.g., challenges to containment integrity caused by core-concrete interaction, steam explosion... such as the service water intake structure and the ultimate heat sink; (2) An application for... design except for site-specific elements such as the service water intake structure and the ultimate heat...

10 CFR 52.47 - Contents of applications; technical information.

Code of Federal Regulations, 2010 CFR

2010-01-01

... accidents, e.g., challenges to containment integrity caused by core-concrete interaction, steam explosion... such as the service water intake structure and the ultimate heat sink; (2) An application for... design except for site-specific elements such as the service water intake structure and the ultimate heat...

10 CFR 52.47 - Contents of applications; technical information.

Code of Federal Regulations, 2011 CFR

2011-01-01

... accidents, e.g., challenges to containment integrity caused by core-concrete interaction, steam explosion... such as the service water intake structure and the ultimate heat sink; (2) An application for... design except for site-specific elements such as the service water intake structure and the ultimate heat...

10 CFR 52.47 - Contents of applications; technical information.

Code of Federal Regulations, 2014 CFR

2014-01-01

... accidents, e.g., challenges to containment integrity caused by core-concrete interaction, steam explosion... such as the service water intake structure and the ultimate heat sink; (2) An application for... design except for site-specific elements such as the service water intake structure and the ultimate heat...

10 CFR 52.47 - Contents of applications; technical information.

Code of Federal Regulations, 2012 CFR

2012-01-01

... accidents, e.g., challenges to containment integrity caused by core-concrete interaction, steam explosion... such as the service water intake structure and the ultimate heat sink; (2) An application for... design except for site-specific elements such as the service water intake structure and the ultimate heat...

A Recombinant Platform for Prioritizing Aerolysin Molecular Grenades for Metastatic Prostate Cancer

DTIC Science & Technology

2016-12-01

the extracellular microenvironment at cancer sites. The objective for this proposal is to use a bio -engineering approach to produce recombinant pro...ominous diagnosis. The objective for this project is to use a bio -engineering approach to produce recombinant pro-toxins designed for specific cleavage

Predicting E. Coli and Enterococci Concentrations in the South Fork Broad River Watershed Using Virtual Beach

EPA Science Inventory

Virtual Beach (VB) is a decision support tool that constructs site-specific statistical models to predict fecal indicator bacteria (FIB) at locations of exposure. Although primarily designed for making decisions regarding beach closures or issuance of swimming advisories based on...

24 CFR 3285.312 - Footings.

Code of Federal Regulations, 2014 CFR

2014-04-01

... section. Footings must be placed on undisturbed soil or fill compacted to 90 percent of maximum relative... (psi). Site-specific soil conditions or design load requirements may also require the use of... footings must consist of a minimum of two layers of nominal 2-inch thick pressure-treated wood, a single...

24 CFR 3285.312 - Footings.

Code of Federal Regulations, 2012 CFR

2012-04-01

... section. Footings must be placed on undisturbed soil or fill compacted to 90 percent of maximum relative... (psi). Site-specific soil conditions or design load requirements may also require the use of... footings must consist of a minimum of two layers of nominal 2-inch thick pressure-treated wood, a single...

24 CFR 3285.312 - Footings.

Code of Federal Regulations, 2011 CFR

2011-04-01

... section. Footings must be placed on undisturbed soil or fill compacted to 90 percent of maximum relative... (psi). Site-specific soil conditions or design load requirements may also require the use of... footings must consist of a minimum of two layers of nominal 2-inch thick pressure-treated wood, a single...

24 CFR 3285.312 - Footings.

Code of Federal Regulations, 2010 CFR

2010-04-01

... section. Footings must be placed on undisturbed soil or fill compacted to 90 percent of maximum relative... (psi). Site-specific soil conditions or design load requirements may also require the use of... footings must consist of a minimum of two layers of nominal 2-inch thick pressure-treated wood, a single...

24 CFR 3285.312 - Footings.

Code of Federal Regulations, 2013 CFR

2013-04-01

... section. Footings must be placed on undisturbed soil or fill compacted to 90 percent of maximum relative... (psi). Site-specific soil conditions or design load requirements may also require the use of... footings must consist of a minimum of two layers of nominal 2-inch thick pressure-treated wood, a single...

Adenosine and inflammation: what's new on the horizon?

PubMed

Antonioli, Luca; Csóka, Balázs; Fornai, Matteo; Colucci, Rocchina; Kókai, Endre; Blandizzi, Corrado; Haskó, György

2014-08-01

Adenosine contributes to the maintenance of tissue integrity by modulating the immune system. Encouraging results have emerged with adenosine receptor ligands for the management of several inflammatory conditions in preclinical and clinical settings. However, therapeutic applications of these drugs are sometimes complicated by the occurrence of serious adverse effects. The scientific community is making intensive efforts to design novel adenosine receptor ligands endowed with greater selectivity or to develop innovative compounds acting as allosteric receptor modulators. In parallel, research is focusing on novel pharmacological entities (designated as adenosine-regulating agents) that can increase, in a site- and event-specific manner, adenosine concentrations at the inflammatory site, thereby minimizing the adverse systemic effects of adenosine. Copyright © 2014 Elsevier Ltd. All rights reserved.

On-Site Pilot Study - Removal of Uranium, Radium-226 and Arsenic from Impacted Leachate by Reverse Osmosis - 13155

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

McMurray, Allan; Everest, Chris; Rilling, Ken

Conestoga-Rovers and Associates (CRA-LTD) performed an on-site pilot study at the Welcome Waste Management Facility in Port Hope, Ontario, Canada, to evaluate the effectiveness of a unique leachate treatment process for the removal of radioactive contaminants from leachate impacted by low-level radioactive waste. Results from the study also provided the parameters needed for the design of the CRA-LTD full scale leachate treatment process design. The final effluent water quality discharged from the process to meet the local surface water discharge criteria. A statistical software package was utilized to obtain the analysis of variance (ANOVA) for the results from design ofmore » experiment applied to determine the effect of the evaluated factors on the measured responses. The factors considered in the study were: percent of reverse osmosis permeate water recovery, influent coagulant dosage, and influent total dissolved solids (TDS) dosage. The measured responses evaluated were: operating time, average specific flux, and rejection of radioactive contaminants along with other elements. The ANOVA for the design of experiment results revealed that the operating time is affected by the percent water recovery to be achieved and the flocculant dosage over the range studied. The average specific flux and rejection for the radioactive contaminants were not affected by the factors evaluated over the range studied. The 3 month long on-site pilot testing on the impacted leachate revealed that the CRA-LTD leachate treatment process was robust and produced an effluent water quality that met the surface water discharge criteria mandated by the Canadian Nuclear Safety Commission and the local municipality. (authors)« less

Colonization of UK coastal realignment sites by mosquitoes: implications for design, management, and public health.

PubMed

Medlock, J M; Vaux, A G C

2013-06-01

Coastal realignment is now widely instituted in the UK as part of local flood risk management plans to compensate for the loss of European protected habitat and to mitigate the effects of sea-level rise and coastal squeeze. Coastal aquatic habitats have long been known to provide suitable habitats for brackish-water mosquitoes and historically, coastal marshes were considered to support anopheline mosquito populations that were responsible for local malaria transmission. This study surveyed the eight largest managed realignment (MRA) sites in England (Essex and the Humber) for mosquito habitats. The apparent absence of anopheline mosquitoes exploiting aquatic habitats at all of these sites suggests that the risk of malaria associated with MRA sites is currently negligible. However, three of the eight sites supported populations of two nuisance and potential arboviral vector species, Aedes detritus and Aedes caspius. The aquatic habitats that supported mosquitoes resulted from a) specific design aspects of the new sea wall (ballast to mitigate wave action and constructed saline borrow ditches) that could be designed out or managed or b) isolated pools created through silt accretion or expansion of flooded zones to neighbouring pasture. The public health risks and recommendations for management are discussed in this report. This report highlights the need for pro-active public health impact assessments prior to MRA development in consultation with the Health Protection Agency, as well as the need for a case-by-case approach to design and management to mitigate mosquito or mosquito-borne disease issues now and in the future. © 2013 The Society for Vector Ecology.

Atrium building study

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

Not Available

1990-01-01

The CIGNA design team was faced with creating a new 500,000 square foot office building on a pastoral 610 acre corporate campus in Bloomfield, Connecticut, just outside of Hartford. Challenges abounded during the design process, from the selection of a specific building site on the sprawling campus to the evolution of a building form incorporating an atrium, to the selection of building systems and materials, to the design to the office interiors and atrium landscape. This document summarizes the original design problem, focusing on design criteria and performance standards that led to the decision to design an atrium building asmore » well as decision concerning its function, its form, its building systems and materials, and its passive energy strategies.« less

An electrostatic potassium channel opener targeting the final voltage sensor transition

PubMed Central

Börjesson, Sara I.

2011-01-01

Free polyunsaturated fatty acids (PUFAs) modulate the voltage dependence of voltage-gated ion channels. As an important consequence thereof, PUFAs can suppress epileptic seizures and cardiac arrhythmia. However, molecular details for the interaction between PUFA and ion channels are not well understood. In this study, we have localized the site of action for PUFAs on the voltage-gated Shaker K channel by introducing positive charges on the channel surface, which potentiated the PUFA effect. Furthermore, we found that PUFA mainly affects the final voltage sensor movement, which is closely linked to channel opening, and that specific charges at the extracellular end of the voltage sensor are critical for the PUFA effect. Because different voltage-gated K channels have different charge profiles, this implies channel-specific PUFA effects. The identified site and the pharmacological mechanism will potentially be very useful in future drug design of small-molecule compounds specifically targeting neuronal and cardiac excitability. PMID:21624947

HIV-1 protease cleavage site prediction based on two-stage feature selection method.

PubMed

Niu, Bing; Yuan, Xiao-Cheng; Roeper, Preston; Su, Qiang; Peng, Chun-Rong; Yin, Jing-Yuan; Ding, Juan; Li, HaiPeng; Lu, Wen-Cong

2013-03-01

Knowledge of the mechanism of HIV protease cleavage specificity is critical to the design of specific and effective HIV inhibitors. Searching for an accurate, robust, and rapid method to correctly predict the cleavage sites in proteins is crucial when searching for possible HIV inhibitors. In this article, HIV-1 protease specificity was studied using the correlation-based feature subset (CfsSubset) selection method combined with Genetic Algorithms method. Thirty important biochemical features were found based on a jackknife test from the original data set containing 4,248 features. By using the AdaBoost method with the thirty selected features the prediction model yields an accuracy of 96.7% for the jackknife test and 92.1% for an independent set test, with increased accuracy over the original dataset by 6.7% and 77.4%, respectively. Our feature selection scheme could be a useful technique for finding effective competitive inhibitors of HIV protease.

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

PubMed Central

Herbert, Martha

2017-01-01

Many hypothyroid and autoimmune thyroid patients experience reactions with specific foods. Additionally, food interactions may play a role in a subset of individuals who have difficulty finding a suitable thyroid hormone dosage. Our study was designed to investigate the potential role of dietary protein immune reactivity with thyroid hormones and thyroid axis target sites. We identified immune reactivity between dietary proteins and target sites on the thyroid axis that includes thyroid hormones, thyroid receptors, enzymes, and transport proteins. We also measured immune reactivity of either target specific monoclonal or polyclonal antibodies for thyroid-stimulating hormone (TSH) receptor, 5′deiodinase, thyroid peroxidase, thyroglobulin, thyroxine-binding globulin, thyroxine, and triiodothyronine against 204 purified dietary proteins commonly consumed in cooked and raw forms. Dietary protein determinants included unmodified (raw) and modified (cooked and roasted) foods, herbs, spices, food gums, brewed beverages, and additives. There were no dietary protein immune reactions with TSH receptor, thyroid peroxidase, and thyroxine-binding globulin. However, specific antigen-antibody immune reactivity was identified with several purified food proteins with triiodothyronine, thyroxine, thyroglobulin, and 5′deiodinase. Laboratory analysis of immunological cross-reactivity between thyroid target sites and dietary proteins is the initial step necessary in determining whether dietary proteins may play a potential immunoreactive role in autoimmune thyroid disease. PMID:28894619

A neural network based methodology to predict site-specific spectral acceleration values

NASA Astrophysics Data System (ADS)

Kamatchi, P.; Rajasankar, J.; Ramana, G. V.; Nagpal, A. K.

2010-12-01

A general neural network based methodology that has the potential to replace the computationally-intensive site-specific seismic analysis of structures is proposed in this paper. The basic framework of the methodology consists of a feed forward back propagation neural network algorithm with one hidden layer to represent the seismic potential of a region and soil amplification effects. The methodology is implemented and verified with parameters corresponding to Delhi city in India. For this purpose, strong ground motions are generated at bedrock level for a chosen site in Delhi due to earthquakes considered to originate from the central seismic gap of the Himalayan belt using necessary geological as well as geotechnical data. Surface level ground motions and corresponding site-specific response spectra are obtained by using a one-dimensional equivalent linear wave propagation model. Spectral acceleration values are considered as a target parameter to verify the performance of the methodology. Numerical studies carried out to validate the proposed methodology show that the errors in predicted spectral acceleration values are within acceptable limits for design purposes. The methodology is general in the sense that it can be applied to other seismically vulnerable regions and also can be updated by including more parameters depending on the state-of-the-art in the subject.

Novel approaches for an enhanced geothermal development of residential sites

NASA Astrophysics Data System (ADS)

Schelenz, Sophie; Firmbach, Linda; Shao, Haibing; Dietrich, Peter; Vienken, Thomas

2015-04-01

An ongoing technological enhancement drives an increasing use of shallow geothermal systems for heating and cooling applications. However, even in areas with intensive shallow geothermal use, planning of geothermal systems is in many cases solely based on geological maps, drilling databases, and literature references. Thus, relevant heat transport parameters are rather approximated than measured for the specific site. To increase the planning safety and promote the use of renewable energies in the domestic sector, this study investigates a novel concept for an enhanced geothermal development of residential neighbourhoods. This concept is based on a site-specific characterization of subsurface conditions and the implementation of demand-oriented geothermal usage options. Therefore, an investigation approach has been tested that combines non-invasive with minimum-invasive exploration methods. While electrical resistivity tomography has been applied to characterize the geological subsurface structure, Direct Push soundings enable a detailed, vertical high-resolution characterization of the subsurface surrounding the borehole heat exchangers. The benefit of this site-specific subsurface investigation is highlighted for 1) a more precise design of shallow geothermal systems and 2) a reliable prediction of induced long-term changes in groundwater temperatures. To guarantee the financial feasibility and practicability of the novel geothermal development, three different options for its implementation in residential neighbourhoods were consequently deduced.

Quantum mechanical calculation of electric fields and vibrational Stark shifts at active site of human aldose reductase

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

Wang, Xianwei; State Key Laboratory of Precision Spectroscopy, Institute of Theoretical and Computational Science, East China Normal University, Shanghai 200062; Zhang, John Z. H.

2015-11-14

Recent advance in biophysics has made it possible to directly measure site-specific electric field at internal sites of proteins using molecular probes with C = O or C≡N groups in the context of vibrational Stark effect. These measurements directly probe changes of electric field at specific protein sites due to, e.g., mutation and are very useful in protein design. Computational simulation of the Stark effect based on force fields such as AMBER and OPLS, while providing good insight, shows large errors in comparison to experimental measurement due to inherent difficulties associated with point charge based representation of force fields. Inmore » this study, quantum mechanical calculation of protein’s internal electrostatic properties and vibrational Stark shifts was carried out by using electrostatically embedded generalized molecular fractionation with conjugate caps method. Quantum calculated change of mutation-induced electric field and vibrational Stark shift is reported at the internal probing site of enzyme human aldose reductase. The quantum result is in much better agreement with experimental data than those predicted by force fields, underscoring the deficiency of traditional point charge models describing intra-protein electrostatic properties.« less

Interim pressure garment therapy (4-6 mmHg) and its effect on donor site healing in burn patients: study protocol for a randomised controlled trial.

PubMed

Donovan, Michelle L; Muller, Michael J; Simpson, Claire; Rudd, Michael; Paratz, Jennifer

2016-04-26

Pressure garment therapy (PGT) is well accepted and commonly used by clinicians in the treatment of burns scars and grafts. The medium to high pressures (24-40 mmHg) in these garments can support scar minimisation, and evidence is well documented for this particular application. However, PGT specifically for burn donor sites, of which a sequela is also scarring, is not well documented. This study protocol investigates the impact of a low pressure (4-6 mmHg) interim garment on donor site healing and scarring. With a primary purpose of holding donor dressings in place, the application of the interim pressure garment (IPG) appears to have been twofold. IPGs for donor sites have involved inconsistent application with a focus on securing wound dressing rather than scar management. However, anecdotal and observational evidence suggests that IPGs also make a difference to some patient's scar outcomes for donor sites. This study protocol outlines a randomised controlled trial designed to test the effectiveness of this treatment on reducing scarring to burn donor sites. This study is a single-centre, single (assessor)-blinded, randomised control trial in patients with burns donor sites to their thighs. Patients will be randomly allocated to a control group (with no compression to donor sites) or to an experimental group (with compression to donor sites) as the comparative treatment. Groups will be compared at baseline regarding the important prognostic indicators: donor site location, depth, size, age, and time since graft (5 days). The IPG treatment will be administered post-operatively (on day 5). Follow-up assessments and garment replacement will be undertaken fortnightly for a period of 2 months. This study focuses on a unique area of burns scar management using a low-pressure tubular support garment for the reduction of donor site scars. Such therapy specifically for donor scar management is poorly represented in the literature. This study was designed to test a potentially cost-effective scar prevention for patients with donor sites to the thigh. No known studies of this nature have been carried out to date, and there is a need for rigorous clinical evidence for low-pressure support garments for donor site scar minimisation. Australian New Zealand Clinical Trials Registry identifier ACTRN12610000127000 . Registered 8 Mar 2010.

Project MEDSAT: The design of a remote sensing platform for malaria research and control

NASA Astrophysics Data System (ADS)

1991-04-01

Project MEDSAT was proposed with the specific goal of designing a satellite to remotely sense pertinent information useful in establishing strategies to control malaria. The 340 kg MEDSAT satellite is to be inserted into circular earth orbit aboard the Pegasus Air-Launched Space Booster at an inclination of 21 degrees and an altitude of 473 km. It is equipped with a synthetic aperture radar and a visible thermal/infrared sensor to remotely sense conditions at the target area of Chiapas, Mexico. The orbit is designed so that MEDSAT will pass over the target site twice each day. The data from each scan will be downlinked to Hawaii for processing, resulting in maps indicating areas of high malaria risk. These will be distributed to health officials at the target site. A relatively inexpensive launch by Pegasus and a design using mainly proven, off-the-shelf technology permit a low mission cost, while innovations in the satellite controls and the scientific instruments allow a fairly complex mission.

Project MEDSAT: The design of a remote sensing platform for malaria research and control

NASA Technical Reports Server (NTRS)

1991-01-01

Project MEDSAT was proposed with the specific goal of designing a satellite to remotely sense pertinent information useful in establishing strategies to control malaria. The 340 kg MEDSAT satellite is to be inserted into circular earth orbit aboard the Pegasus Air-Launched Space Booster at an inclination of 21 degrees and an altitude of 473 km. It is equipped with a synthetic aperture radar and a visible thermal/infrared sensor to remotely sense conditions at the target area of Chiapas, Mexico. The orbit is designed so that MEDSAT will pass over the target site twice each day. The data from each scan will be downlinked to Hawaii for processing, resulting in maps indicating areas of high malaria risk. These will be distributed to health officials at the target site. A relatively inexpensive launch by Pegasus and a design using mainly proven, off-the-shelf technology permit a low mission cost, while innovations in the satellite controls and the scientific instruments allow a fairly complex mission.

Design and Evaluation of a Web-Based Symptom Monitoring Tool for Heart Failure.

PubMed

Wakefield, Bonnie J; Alexander, Gregory; Dohrmann, Mary; Richardson, James

2017-05-01

Heart failure is a chronic condition where symptom recognition and between-visit communication with providers are critical. Patients are encouraged to track disease-specific data, such as weight and shortness of breath. Use of a Web-based tool that facilitates data display in graph form may help patients recognize exacerbations and more easily communicate out-of-range data to clinicians. The purposes of this study were to (1) design a Web-based tool to facilitate symptom monitoring and symptom recognition in patients with chronic heart failure and (2) conduct a usability evaluation of the Web site. Patient participants generally had a positive view of the Web site and indicated it would support recording their health status and communicating with their doctors. Clinician participants generally had a positive view of the Web site and indicated it would be a potentially useful adjunct to electronic health delivery systems. Participants expressed a need to incorporate decision support within the site and wanted to add other data, for example, blood pressure, and have the ability to adjust font size. A few expressed concerns about data privacy and security. Technologies require careful design and testing to ensure they are useful, usable, and safe for patients and do not add to the burden of busy providers.

Evapotranspiration (ET) covers.

PubMed

Rock, Steve; Myers, Bill; Fiedler, Linda

2012-01-01

Evapotranspiration (ET) cover systems are increasingly being used at municipal solid waste (MSW) landfills, hazardous waste landfills, at industrial monofills, and at mine sites. Conventional cover systems use materials with low hydraulic permeability (barrier layers) to minimize the downward migration of water from the surface to the waste (percolation), ET cover systems use water balance components to minimize percolation. These cover systems rely on soil to capture and store precipitation until it is either transpired through vegetation or evaporated from the soil surface. Compared to conventional membrane or compacted clay cover systems, ET cover systems are expected to cost less to construct. They are often aesthetic because they employ naturalized vegetation, require less maintenance once the vegetative system is established, including eliminating mowing, and may require fewer repairs than a barrier system. All cover systems should consider the goals of the cover in terms of protectiveness, including the pathways of risk from contained material, the lifecycle of the containment system. The containment system needs to be protective of direct contact of people and animals with the waste, prevent surface and groundwater water pollution, and minimize release of airborne contaminants. While most containment strategies have been based on the dry tomb strategy of keeping waste dry, there are some sites where adding or allowing moisture to help decompose organic waste is the current plan. ET covers may work well in places where complete exclusion of precipitation is not needed. The U.S. EPA Alternative Cover Assessment Program (ACAP), USDOE, the Nuclear Regulatory Commission, and others have researched ET cover design and efficacy, including the history of their use, general considerations in their design, performance, monitoring, cost, current status, limitations on their use, and project specific examples. An on-line database has been developed with information about specific projects using ET covers. There are three general approaches for non-conventional cover systems to achieve approval for installation; the first is when equivalent performance to conventional final cover systems can be demonstrated directly on site. This is the approach used by the Sandia study, by most ACAP sites, and the Rocky Mountain Arsenal. A second approach is used when there are data from a site specific study such as an ACAP installation at a site that has analogous soil and climate conditions. Several sites in Colorado and Southern California have achieved approval based on data from similar sites. The third most common approach for regulatory approval is by installation of data collection systems with the agreement that the permanence of the ET cover installation is contingent on success of the cover in meeting certain performance goals. This article is intended as an introduction to the topic and is not intended to serve as guidance for design or construction, nor indicate the appropriateness of using an ET cover systems at a particular site.

Nanoparticles for Site Specific Genome Editing

NASA Astrophysics Data System (ADS)

McNeer, Nicole Ali

Triplex-forming peptide nucleic acids (PNAs) can be used to coordinate the recombination of short 50-60 by "donor DNA" fragments into genomic DNA, resulting in site-specific correction of genetic mutations or the introduction of advantageous genetic modifications. Site-specific gene editing in hematopoietic stem and progenitor cells (HSPCs) could result in treatment or cure of inherited disorders of the blood such as beta-thalassemia. Gene editing in HSPCs and differentiated T cells could help combat HIV/AIDs by modifying receptors, such as CCR5, necessary for R5-tropic HIV entry. However, translation of genome modification technologies to clinical practice is limited by challenges in intracellular delivery, especially in difficult-to-transfect hematolymphoid cells. In vivo gene editing could also provide novel treatment for systemic monogenic disorders such as cystic fibrosis, an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane receptor. Here, we have engineered biodegradable nanoparticles to deliver oligonucleotides for site-specific genome editing of disease-relevant genes in human cells, with high efficiency, low toxicity, and editing of clinically relevant cell types. We designed nanoparticles to edit the human beta-globin and CCR5 genes in hematopoietic cells. We show that poly(lactic-co-glycolic acid) (PLGA) nanoparticles can delivery PNA and donor DNA for site-specific gene modification in human hematopoietic cells in vitro and in vivo in NOD-scid IL2rgammanull mice. Nanoparticles delivered by tail vein localized to hematopoietic compartments in the spleen and bone marrow of humanized mice, resulting in modification of the beta-globin and CCR5 genes. Modification frequencies ranged from 0.005 to 20% of cells depending on the organ and cell type, without detectable toxicity. This project developed highly versatile methods for delivery of therapeutics to hematolymphoid cells and hematopoietic stem cells, and will help to translate gene therapies for diseases of the blood and immune system to clinical practice. In addition, we have expanded the use of this technology to an additional nonhematopoietic model system: correction of the human cystic fibrosis transmembrane receptor gene in human bronchial epithelial cells. The work presented here represents (1) the first use of biodegradable nanoparticles for PNA delivery, (2) the first direct in vivo site-specific genome modification in human cells, and (3) the first use of triplex-PNA technology for site-specific genome editing in cystic fibrosis.

Using maximum entropy modeling for optimal selection of sampling sites for monitoring networks

USGS Publications Warehouse

Stohlgren, Thomas J.; Kumar, Sunil; Barnett, David T.; Evangelista, Paul H.

2011-01-01

Environmental monitoring programs must efficiently describe state shifts. We propose using maximum entropy modeling to select dissimilar sampling sites to capture environmental variability at low cost, and demonstrate a specific application: sample site selection for the Central Plains domain (453,490 km2) of the National Ecological Observatory Network (NEON). We relied on four environmental factors: mean annual temperature and precipitation, elevation, and vegetation type. A “sample site” was defined as a 20 km × 20 km area (equal to NEON’s airborne observation platform [AOP] footprint), within which each 1 km2 cell was evaluated for each environmental factor. After each model run, the most environmentally dissimilar site was selected from all potential sample sites. The iterative selection of eight sites captured approximately 80% of the environmental envelope of the domain, an improvement over stratified random sampling and simple random designs for sample site selection. This approach can be widely used for cost-efficient selection of survey and monitoring sites.

Simulations in site error estimation for direction finders

NASA Astrophysics Data System (ADS)

López, Raúl E.; Passi, Ranjit M.

1991-08-01

The performance of an algorithm for the recovery of site-specific errors of direction finder (DF) networks is tested under controlled simulated conditions. The simulations show that the algorithm has some inherent shortcomings for the recovery of site errors from the measured azimuth data. These limitations are fundamental to the problem of site error estimation using azimuth information. Several ways for resolving or ameliorating these basic complications are tested by means of simulations. From these it appears that for the effective implementation of the site error determination algorithm, one should design the networks with at least four DFs, improve the alignment of the antennas, and increase the gain of the DFs as much as it is compatible with other operational requirements. The use of a nonzero initial estimate of the site errors when working with data from networks of four or more DFs also improves the accuracy of the site error recovery. Even for networks of three DFs, reasonable site error corrections could be obtained if the antennas could be well aligned.

A Web-based approach to blood donor preparation.

PubMed

France, Christopher R; France, Janis L; Kowalsky, Jennifer M; Copley, Diane M; Lewis, Kristin N; Ellis, Gary D; McGlone, Sarah T; Sinclair, Kadian S

2013-02-01

Written and video approaches to donor education have been shown to enhance donation attitudes and intentions to give blood, particularly when the information provides specific coping suggestions for donation-related concerns. This study extends this work by comparing Web-based approaches to donor preparation among donors and nondonors. Young adults (62% female; mean [±SD] age, 19.3 [±1.5] years; mean [range] number of prior blood donations, 1.1 [0-26]; 60% nondonors) were randomly assigned to view 1) a study Web site designed to address common blood donor concerns and suggest specific coping strategies (n = 238), 2) a standard blood center Web site (n = 233), or 3) a control Web site where participants viewed videos of their choice (n = 202). Measures of donation attitude, anxiety, confidence, intention, anticipated regret, and moral norm were completed before and after the intervention. Among nondonors, the study Web site produced greater changes in donation attitude, confidence, intention, and anticipated regret relative to both the standard and the control Web sites, but only differed significantly from the control Web site for moral norm and anxiety. Among donors, the study Web site produced greater changes in donation confidence and anticipated regret relative to both the standard and the control Web sites, but only differed significantly from the control Web site for donation attitude, anxiety, intention, and moral norm. Web-based donor preparation materials may provide a cost-effective way to enhance donation intentions and encourage donation behavior. © 2012 American Association of Blood Banks.

Hydrologic data for Leviathan Mine and vicinity, Alpine County, California, 1981-83

USGS Publications Warehouse

Hammermeister, D.P.; Walmsley, S.J.

1985-01-01

The U.S. Geological Survey collected basic hydrologic and water-quality data during 1981-83 to facilitate the geohydrologic evaluation of the Leviathan Mine area and the design of a pollution-abatement project. Surface-water field data included one or more measurements of pH, water temperature, and specific conductance at 45 sites in and adjacent to the mine area. At nine of these sites, daily data on discharge, specific conductance, and water temperature were collected during parts of 1981-82 by using electronic monitor-recorder systems. Ground-water field data included one or more of the water-quality measurements listed above at 71 piezometers in the mine area. Borehole geophysical data included neutron-moisture, neutron-porosity, gamma-gamma density, natural gamma, and temperature logs at three sites. Mineralogic and hydrologic data were obtained for cores taken from nine test holes. One or more surface-water samples from 26 sites were analyzed for major cations, major anions, and a wide range of minor inorganic constituents. Single ground-water samples from 36 piezometers were analyzed for the same array of major and minor constituents. (USGS)

NIF optical materials and fabrication technologies: an overview

NASA Astrophysics Data System (ADS)

Campbell, John H.; Hawley-Fedder, Ruth A.; Stolz, Christopher J.; Menapace, Joseph A.; Borden, Michael R.; Whitman, Pamela K.; Yu, June; Runkel, Michael J.; Riley, Michael O.; Feit, Michael D.; Hackel, Richard P.

2004-05-01

The high-energy/high-power section of the NIF laser system contains 7360 meter-scale optics. Advanced optical materials and fabrication technologies needed to manufacture the NIF optics have been developed and put into production at key vendor sites. Production rates are up to 20 times faster and per-optic costs 5 times lower than could be achieved prior to the NIF. In addition, the optics manufactured for NIF are better than specification giving laser performance better than the design. A suite of custom metrology tools have been designed, built and installed at the vendor sites to verify compliance with NIF optical specifications. A brief description of the NIF optical wavefront specifications for the glass and crystal optics is presented. The wavefront specifications span a continuous range of spatial scale-lengths from 10 μm to 0.5 m (full aperture). We have continued our multi-year research effort to improve the lifetime (i.e. damage resistance) of bulk optical materials, finished optical surfaces and multi-layer dielectric coatings. New methods for post-processing the completed optic to improve the damage resistance have been developed and made operational. This includes laser conditioning of coatings, glass surfaces and bulk KDP and DKDP and well as raster and full aperture defect mapping systems. Research on damage mechanisms continues to drive the development of even better optical materials.

Masked Chimeric Antigen Receptor for Tumor-Specific Activation.

PubMed

Han, Xiaolu; Bryson, Paul D; Zhao, Yifan; Cinay, Gunce E; Li, Si; Guo, Yunfei; Siriwon, Natnaree; Wang, Pin

2017-01-04

Adoptive cellular therapy based on chimeric antigen receptor (CAR)-engineered T (CAR-T) cells is a powerful form of cancer immunotherapy. CAR-T cells can be redirected to specifically recognize tumor-associated antigens (TAAs) and induce high levels of antitumor activity. However, they may also display "on-target off-tumor" toxicities, resulting from low-level expression of TAAs in healthy tissues. These adverse effects have raised considerable safety concerns and limited the clinical application of this otherwise promising therapeutic modality. To minimize such side effects, we have designed an epidermal growth factor receptor (EGFR)-specific masked CAR (mCAR), which consists of a masking peptide that blocks the antigen-binding site and a protease-sensitive linker. Proteases commonly active in the tumor microenvironment can cleave the linker and disengage the masking peptide, thereby enabling CAR-T cells to recognize target antigens only at the tumor site. In vitro mCAR showed dramatically reduced antigen binding and antigen-specific activation in the absence of proteases, but normal levels of binding and activity upon treatment with certain proteases. Masked CAR-T cells also showed antitumor efficacy in vivo comparable to that of unmasked CAR. Our study demonstrates the feasibility of improving the safety profile of conventional CARs and may also inspire future design of CAR molecules targeting broadly expressed TAAs. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Missile Defense Information Technology Small Business Conference

DTIC Science & Technology

2009-09-01

NetOps Survivability 4 • Supported User Base • Number of Workstations • Number of Servers • Number of Special Circuits • Number of Sites • Number...Contracts, MDIOC • Ground Test (DTC) • MDSEC (SS) • Infrastructure (IC) • BMDS Support (BCT) • JTAAS – SETA • Mod & Sim ( DES ) • Analysis (GML) • Tenants...AUG 09) 4 MDA DOCE Engineering Functions • Design Engineers – Develop detailed design artifacts based on architectural specifications – Coordinate

External Device to Incrementally Skid the Habitat (E-DISH)

NASA Technical Reports Server (NTRS)

Brazell, J. W.; Introne, Steve; Bedell, Lisa; Credle, Ben; Holp, Graham; Ly, Siao; Tait, Terry

1994-01-01

A Mars habitat transport system was designed as part of the NASA Mars exploration program. The transport system, the External Device to Incrementally Skid the Habitat (E - DISH), will be used to transport Mars habitats from their landing sites to the colony base and will be detached after unloading. The system requirements for Mars were calculated and scaled for model purposes. Specific model materials are commonly found and recommendations for materials for the Mars design are included.

Human Mars Ascent Vehicle Performance Sensitivities

NASA Technical Reports Server (NTRS)

Polsgrove, Tara P.; Thomas, Herbert D.

2016-01-01

Human Mars mission architecture studies have shown that the ascent vehicle mass drives performance requirements for the descent and in-space transportation elements. Understanding the sensitivity of Mars ascent vehicle (MAV) mass to various mission and vehicle design choices enables overall transportation system optimization. This paper presents the results of a variety of sensitivity trades affecting MAV performance including: landing site latitude, target orbit, initial thrust to weight ratio, staging options, specific impulse, propellant type and engine design.

Ocean thermal energy conversion cold water pipe preliminary design project. Appendices to final report

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

Not Available

1979-11-20

NOAA/DOE has selected three concepts for a baseline design of the cold water pipe (CWP) for OTEC plants: (1) a FRP CWP of sandwich wall construction suspended from the Applied Physical Laboratory/John Hopkins University (APL/JHU) barge at a site 200 miles east of the coast of Brazil using a horizontal deployment scheme; (2) an elastomer CWP suspended from the APL/JHU barge off the southeast coast of Puerto Rico using either a horizontal or vertical deployment scheme; and (3) a polyethylene CWP (single or multiple pipe) suspended from the Gibbs and Cox spar at the Puerto Rico site using a horizontalmore » deployment scheme. TRW has developed a baseline design for each of these configurations. This volume of the report includes the following appendices: (A) fiberglass reinforced plastic cold water pipe (specification and drawingss); (B) specification for polyethylene CWP; (C) elastomer pipe drawings; (D) drawings for OTEC 10/40 hull/CWP transitions; (E) structural design of OTEC 10/40 CWP support and CWP transitions; (F) universal transition joint for CWP; (G) dynamic spherical seal of CWP; (H) at-sea deployment loads - surface towing loads; (I) OTEC 10/40 CWP deployment up-ending loads; (J) cost estimates for OTEC 10/40 hull/CWP transitions; and (K) OTEC 10/40 CWP deployment scenario and cost estimate. (WHK)« less

Evaluating a complex, multi-site, community-based program to improve healthcare quality: the summative research design for the Aligning Forces for Quality initiative.

PubMed

Scanlon, Dennis P; Wolf, Laura J; Alexander, Jeffrey A; Christianson, Jon B; Greene, Jessica; Jean-Jacques, Muriel; McHugh, Megan; Shi, Yunfeng; Leitzell, Brigitt; Vanderbrink, Jocelyn M

2016-08-01

The Aligning Forces for Quality (AF4Q) initiative was the Robert Wood Johnson Foundation's (RWJF's) signature effort to increase the overall quality of healthcare in targeted communities throughout the country. In addition to sponsoring this 16-site complex program, RWJF funded an independent scientific evaluation to support objective research on the initiative's effectiveness and contributions to basic knowledge in 5 core programmatic areas. The research design, data, and challenges faced during the summative evaluation phase of this near decade-long program are discussed. A descriptive overview of the summative research design and its development for a multi-site, community-based, healthcare quality improvement initiative is provided. The summative research design employed by the evaluation team is discussed. The evaluation team's summative research design involved a data-driven assessment of the effectiveness of the AF4Q program at large, assessments of the impact of AF4Q in the specific programmatic areas, and an assessment of how the AF4Q alliances were positioned for the future at the end of the program. The AF4Q initiative was the largest privately funded community-based healthcare improvement initiative in the United States to date and was implemented at a time of rapid change in national healthcare policy. The implementation of large-scale, multi-site initiatives is becoming an increasingly common approach for addressing problems in healthcare. The summative evaluation research design for the AF4Q initiative, and the lessons learned from its approach, may be valuable to others tasked with evaluating similarly complex community-based initiatives.

DNA Origami Patterned Colloids for Programmed Design and Chirality

NASA Astrophysics Data System (ADS)

Ben Zion, Matan Yah; He, Xiaojin; Maass, Corinna; Sha, Ruojie; Seeman, Ned; Chaikin, Paul

Micron size colloidal particles are scientifically important as model systems for equilibrium and active systems in physics, chemistry and biology and for technologies ranging from catalysis to photonics. The past decade has seen development of new particles with directional patches, lock and key reactions and specific recognition that guide assembly of structures such as complex crystalline arrays. What remains lacking is the ability to self-assemble structures of arbitrary shape with specific chirality, placement and orientation of neighbors. Here we demonstrate the adaptation of DNA origami nanotechnology to the micron colloidal scale with designed control of neighbor type, placement and dihedral angle. We use DNA origami belts with programmed flexibility, and functionality to pattern colloidal surfaces and bind particles to specific sites at specific angles and make uniquely right handed or left handed structures. The hybrid DNA origami colloid technology should allow the synthesis of designed functional structural and active materials. This work was supported as part of the Center for Bio-Inspired Energy Science, an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Basic Energy Sciences under Award # DE-SC0000989.

The Semantic Environment: Heuristics for a Cross-Context Human-Information Interaction Model

NASA Astrophysics Data System (ADS)

Resmini, Andrea; Rosati, Luca

This chapter introduces a multidisciplinary holistic approach for the general design of successful bridge experiences as a cross-context human-information interaction model. Nowadays it is common to interact through a number of different domains in order to communicate successfully, complete a task, or elicit a desired response: Users visit a reseller’s web site to find a specific item, book it, then drive to the closest store to complete their purchase. As such, one of the crucial challenges user experience design will face in the near future is how to structure and provide bridge experiences seamlessly spanning multiple communication channels or media formats for a specific purpose.

Site-selective and stereoselective functionalization of non-activated tertiary C-H bonds

NASA Astrophysics Data System (ADS)

Liao, Kuangbiao; Pickel, Thomas C.; Boyarskikh, Vyacheslav; Bacsa, John; Musaev, Djamaladdin G.; Davies, Huw M. L.

2017-11-01

The synthesis of complex organic compounds usually relies on controlling the reactions of the functional groups. In recent years, it has become possible to carry out reactions directly on the C-H bonds, previously considered to be unreactive. One of the major challenges is to control the site-selectivity because most organic compounds have many similar C-H bonds. The most well developed procedures so far rely on the use of substrate control, in which the substrate has one inherently more reactive C-H bond or contains a directing group or the reaction is conducted intramolecularly so that a specific C-H bond is favoured. A more versatile but more challenging approach is to use catalysts to control which site in the substrate is functionalized. p450 enzymes exhibit C-H oxidation site-selectivity, in which the enzyme scaffold causes a specific C-H bond to be functionalized by placing it close to the iron-oxo haem complex. Several studies have aimed to emulate this enzymatic site-selectivity with designed transition-metal catalysts but it is difficult to achieve exceptionally high levels of site-selectivity. Recently, we reported a dirhodium catalyst for the site-selective functionalization of the most accessible non-activated (that is, not next to a functional group) secondary C-H bonds by means of rhodium-carbene-induced C-H insertion. Here we describe another dirhodium catalyst that has a very different reactivity profile. Instead of the secondary C-H bond, the new catalyst is capable of precise site-selectivity at the most accessible tertiary C-H bonds. Using this catalyst, we modify several natural products, including steroids and a vitamin E derivative, indicating the applicability of this method of synthesis to the late-stage functionalization of complex molecules. These studies show it is possible to achieve site-selectivity at different positions within a substrate simply by selecting the appropriate catalyst. We hope that this work will inspire the design of even more sophisticated catalysts, such that catalyst-controlled C-H functionalization becomes a broadly applied strategy for the synthesis of complex molecules.

Tracking Hazard Analysis Data in a Jungle of Changing Design

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

Sullivan, Robin S.; Young, Jonathan

2006-05-14

The biggest fear of the hazard analyst is the loss of data in the middle of the design jungle. When project schedules are demanding and design is changing rapidly it is essential that the hazard analysis data be tracked and kept current in order to provide the required project design, development, and regulatory support. Being able to identify the current information, as well as the past archived information, as the design progresses and to be able to show how the project is designing in safety through modifications based on hazard analysis results is imperative. At the DOE Hanford site inmore » Washington State, Flour Hanford Inc is in the process of the removal and disposition of sludge from the 100 Area K Basins. The K Basins were used to store spent fuel from the operating reactors at the Hanford Site. The sludge is a by-product from the corrosion of the fuel and fuel storage canisters. The sludge removal project has been very dynamic involving the design, procurement and, more recently, the operation of processes at two basins, K East and K West. The project has an ambitious schedule with a large number of changes to design concepts. In order to support the complex K Basins project a technique to track the status of the hazard analysis data was developed. This paper will identify the most important elements of the tracking system and how it was used to assist the project in ensuring that current design data was reflected in a specific version of the hazard analysis and to show how the project was keeping up with the design and ensuring compliance with the requirements to design in safety. While the specifics of the data tracking strategy for the K Basins sludge removal project will be described in the paper, the general concepts of the strategy are applicable to similar projects requiring iteration of hazard analysis and design.« less

Computational Design of DNA-Binding Proteins.

PubMed

Thyme, Summer; Song, Yifan

2016-01-01

Predicting the outcome of engineered and naturally occurring sequence perturbations to protein-DNA interfaces requires accurate computational modeling technologies. It has been well established that computational design to accommodate small numbers of DNA target site substitutions is possible. This chapter details the basic method of design used in the Rosetta macromolecular modeling program that has been successfully used to modulate the specificity of DNA-binding proteins. More recently, combining computational design and directed evolution has become a common approach for increasing the success rate of protein engineering projects. The power of such high-throughput screening depends on computational methods producing multiple potential solutions. Therefore, this chapter describes several protocols for increasing the diversity of designed output. Lastly, we describe an approach for building comparative models of protein-DNA complexes in order to utilize information from homologous sequences. These models can be used to explore how nature modulates specificity of protein-DNA interfaces and potentially can even be used as starting templates for further engineering.

Measles Virus Hemagglutinin epitopes immunogenic in natural infection and vaccination are targeted by broad or genotype-specific neutralizing monoclonal antibodies.

PubMed

Muñoz-Alía, Miguel Angel; Casasnovas, José M; Celma, María Luisa; Carabaña, Juan; Liton, Paloma B; Fernandez-Muñoz, Rafael

2017-05-15

Measles virus (MV) remains a leading cause of vaccine-preventable deaths in children. Protection against MV is associated with neutralizing antibodies that preferentially recognize the viral hemagglutinin (MV-H), and to a lesser extent, the fusion protein (MV-F). Although MV is serologically monotypic, 24 genotypes have been identified. Here we report three neutralization epitopes conserved in the more prevalent circulating MV genotypes, two located in the MV-H receptor binding site (RBS) (antigenic site III) and a third in MV-H/MV-F interphase (antigenic site Ia) which are essential for MV multiplication. In contrast, two MV-H neutralization epitopes, showed a genotype-specific neutralization escape due to a single amino acid change, that we mapped in the "noose" antigenic site, or an enhanced neutralization epitope (antigenic site IIa). The monoclonal antibody (mAb) neutralization potency correlated with its binding affinity and was mainly driven by kinetic dissociation rate (k off ). We developed an immunoassay for mAb binding to MV-H in its native hetero-oligomeric structure with MV-F on the surface of a MV productive steady-state persistently infected (p.i.) human cell lines, and a competitive-binding assay with serum from individuals with past infection by different MV genotypes. Binding assays revealed that a broad neutralization epitope, in RBS antigenic site, a genotype specific neutralization epitopes, in noose and IIa sites, were immunogenic in natural infection and vaccination and may elicit long-lasting humoral immunity that might contribute to explain MV immunogenic stability. These results support the design of improved measles vaccines, broad-spectrum prophylactic or therapeutic antibodies and MV-used in oncolytic therapies. Copyright © 2017 Elsevier B.V. All rights reserved.

Young adults with mental health conditions and social networking websites: seeking tools to build community.

PubMed

Gowen, Kris; Deschaine, Matthew; Gruttadara, Darcy; Markey, Dana

2012-01-01

This study examined ways that young adults with mental illnesses (1) currently use social networking; and (2) how they would like to use a social networking site tailored for them. The authors examined differences between those with mental health conditions and those without. An online survey was administered by the National Alliance on Mental Illness (NAMI) to 274 participants; of those, 207 reported being between 18 and 24 years old. The survey included questions about current social networking use, the key resources respondents believed young adults living with mental illness need, and the essential components that should be included in a social networking site specifically tailored to young adults living with mental illness. Pearson Chi-square analyses examined the differences between those who reported having a mental illness and those who did not. Results indicate that almost all (94%) participants with mental illnesses currently use social networking sites. Individuals living with a mental illness are more likely than those not living with a mental illness to report engaging in various social networking activities that promote connectivity and making online friends. Individuals living with mental illnesses are also more likely to report wanting resources on independent living skills and overcoming social isolation available on a social networking site. Young adults living with mental illnesses are currently using social networking sites and express high interest in a social networking site specifically tailored to their population with specific tools designed to decrease social isolation and help them live more independently. These results indicate that practitioners should themselves be aware of the different social networking sites frequented by their young adult clients, ask clients about their use of social networking, and encourage safe and responsible online behaviors.

Structure And Specificity of a Quorum-Quenching Lactonase (AiiB) From Agrobacterium Tumefaciens

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

Liu, D.; Thomas, P.W.; Momb, J.

2009-06-03

N-Acyl-l-homoserine lactone (AHL) mediated quorum-sensing regulates virulence factor production in a variety of Gram-negative bacteria. Proteins capable of degrading these autoinducers have been called 'quorum-quenching' enzymes, can block many quorum-sensing dependent phenotypes, and represent potentially useful reagents for clinical, agricultural, and industrial applications. The most characterized quorum-quenching enzymes to date are the AHL lactonases, which are metalloproteins that belong to the metallo-beta-lactamase superfamily. Here, we report the cloning, heterologous expression, purification, metal content, substrate specificity, and three-dimensional structure of AiiB, an AHL lactonase from Agrobacterium tumefaciens. Much like a homologous AHL lactonase from Bacillus thuringiensis, AiiB appears to be amore » metal-dependent AHL lactonase with broad specificity. A phosphate dianion is bound to the dinuclear zinc site and the active-site structure suggests specific mechanistic roles for an active site tyrosine and aspartate. To our knowledge, this is the second representative structure of an AHL lactonase and the first of an AHL lactonase from a microorganism that also produces AHL autoinducers. This work should help elucidate the hydrolytic ring-opening mechanism of this family of enzymes and also facilitate the design of more effective quorum-quenching catalysts.« less

On-site detection of stacked genetically modified soybean based on event-specific TM-LAMP and a DNAzyme-lateral flow biosensor.

PubMed

Cheng, Nan; Shang, Ying; Xu, Yuancong; Zhang, Li; Luo, Yunbo; Huang, Kunlun; Xu, Wentao

2017-05-15

Stacked genetically modified organisms (GMO) are becoming popular for their enhanced production efficiency and improved functional properties, and on-site detection of stacked GMO is an urgent challenge to be solved. In this study, we developed a cascade system combining event-specific tag-labeled multiplex LAMP with a DNAzyme-lateral flow biosensor for reliable detection of stacked events (DP305423× GTS 40-3-2). Three primer sets, both event-specific and soybean species-specific, were newly designed for the tag-labeled multiplex LAMP system. A trident-like lateral flow biosensor displayed amplified products simultaneously without cross contamination, and DNAzyme enhancement improved the sensitivity effectively. After optimization, the limit of detection was approximately 0.1% (w/w) for stacked GM soybean, which is sensitive enough to detect genetically modified content up to a threshold value established by several countries for regulatory compliance. The entire detection process could be shortened to 120min without any large-scale instrumentation. This method may be useful for the in-field detection of DP305423× GTS 40-3-2 soybean on a single kernel basis and on-site screening tests of stacked GM soybean lines and individual parent GM soybean lines in highly processed foods. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of medical students' expectations for multimedia teaching materials: Illustration by an original method using the evaluation of a web site on cardiovascular rehabilitation.

PubMed

Casillas, J-M; Gremeaux, V

2012-02-01

Different multimedia tools have been developed to help medical students prepare for the National Ranking Examination (NRE), rendering their choice quite difficult. No study has specifically evaluated students' expectations regarding these materials. To learn how medical students in Dijon assessed a website dedicated to cardiovascular rehabilitation, and collecting their suggestions in order to meet their expectations and the goals of second cycle medical studies. Eighteen second-cyle students were evaluated in a semi-directed manner and in ecological situation, a website specifically designed for the national curricula on cardiovascular rehabilitation for obtaining the Diploma of Specialty Studies (DES) for physical medicine and rehabilitation (PM&R) residents. Students also had to fill out a pretest and a posttest (5 MCQs). The overall quality of the site was deemed satisfactory (65.6 ± 7.7 points/100). Medical information was considered better than non-medical data and site's design (respectively 84.8 ± 8.1, 61.1 ± 20 and 64.4 ± 14.9/100). Students found the site useful in terms of understanding the items related to cardiovascular rehabilitation, although they judged it not completely in line with the NRE goals. The average score increased significantly between the pre-and post-test (6.8 ± 0.8 vs. 5 ± 1.5/8, p<0.05). This site appears to be significantly useful for short-term knowledge improvement, but only partially meeting the expectations of second-cycle students. It seems relevant to study further possibilities for customizing and providing summarized learning for the NRE. These elements could serve as building grounds for the future version of this website. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Homology modeling and molecular dynamics simulation of N-myristoyltransferase from protozoan parasites: active site characterization and insights into rational inhibitor design

NASA Astrophysics Data System (ADS)

Sheng, Chunquan; Ji, Haitao; Miao, Zhenyuan; Che, Xiaoyin; Yao, Jianzhong; Wang, Wenya; Dong, Guoqiang; Guo, Wei; Lü, Jiaguo; Zhang, Wannian

2009-06-01

Myristoyl-CoA:protein N-myristoyltransferase (NMT) is a cytosolic monomeric enzyme that catalyzes the transfer of the myristoyl group from myristoyl-CoA to the N-terminal glycine of a number of eukaryotic cellular and viral proteins. Recent experimental data suggest NMT from parasites could be a promising new target for the design of novel antiparasitic agents with new mode of action. However, the active site topology and inhibitor specificity of these enzymes remain unclear. In this study, three-dimensional models of NMT from Plasmodium falciparum (PfNMT), Leishmania major (LmNMT) and Trypanosoma brucei (TbNMT) were constructed on the basis of the crystal structures of fungal NMTs using homology modeling method. The models were further refined by energy minimization and molecular dynamics simulations. The active sites of PfNMT, LmNMT and TbNMT were characterized by multiple copy simultaneous search (MCSS). MCSS functional maps reveal that PfNMT, LmNMT and TbNMT share a similar active site topology, which is defined by two hydrophobic pockets, a hydrogen-bonding (HB) pocket, a negatively-charged HB pocket and a positively-charged HB pocket. Flexible docking approaches were then employed to dock known inhibitors into the active site of PfNMT. The binding mode, structure-activity relationships and selectivity of inhibitors were investigated in detail. From the results of molecular modeling, the active site architecture and certain key residues responsible for inhibitor binding were identified, which provided insights for the design of novel inhibitors of parasitic NMTs.

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.

Insights into the structural biology of G-protein coupled receptors impacts drug design for central nervous system neurodegenerative processes

PubMed Central

Dalet, Farfán-García Eunice; Guadalupe, Trujillo-Ferrara José; María del Carmen, Castillo-Hernández; Humberto, Guerra-Araiza Christian; Antonio, Soriano-Ursúa Marvin

2013-01-01

In the last few years, there have been important new insights into the structural biology of G-protein coupled receptors. It is now known that allosteric binding sites are involved in the affinity and selectivity of ligands for G-protein coupled receptors, and that signaling by these receptors involves both G-protein dependent and independent pathways. The present review outlines the physiological and pharmacological implications of this perspective for the design of new drugs to treat disorders of the central nervous system. Specifically, new possibilities are explored in relation to allosteric and orthosteric binding sites on dopamine receptors for the treatment of Parkinson's disease, and on muscarinic receptors for Alzheimer's disease. Future research can seek to identify ligands that can bind to more than one site on the same receptor, or simultaneously bind to two receptors and form a dimer. For example, the design of bivalent drugs that can reach homo/hetero-dimers of D2 dopamine receptor holds promise as a relevant therapeutic strategy for Parkinson's disease. Regarding the treatment of Alzheimer's disease, the design of dualsteric ligands for mono-oligomeric rinic receptors could increase therapeutic effectiveness by generating potent compounds that could activate more than one signaling pathway. PMID:25206539

Crysalis: an integrated server for computational analysis and design of protein crystallization.

PubMed

Wang, Huilin; Feng, Liubin; Zhang, Ziding; Webb, Geoffrey I; Lin, Donghai; Song, Jiangning

2016-02-24

The failure of multi-step experimental procedures to yield diffraction-quality crystals is a major bottleneck in protein structure determination. Accordingly, several bioinformatics methods have been successfully developed and employed to select crystallizable proteins. Unfortunately, the majority of existing in silico methods only allow the prediction of crystallization propensity, seldom enabling computational design of protein mutants that can be targeted for enhancing protein crystallizability. Here, we present Crysalis, an integrated crystallization analysis tool that builds on support-vector regression (SVR) models to facilitate computational protein crystallization prediction, analysis, and design. More specifically, the functionality of this new tool includes: (1) rapid selection of target crystallizable proteins at the proteome level, (2) identification of site non-optimality for protein crystallization and systematic analysis of all potential single-point mutations that might enhance protein crystallization propensity, and (3) annotation of target protein based on predicted structural properties. We applied the design mode of Crysalis to identify site non-optimality for protein crystallization on a proteome-scale, focusing on proteins currently classified as non-crystallizable. Our results revealed that site non-optimality is based on biases related to residues, predicted structures, physicochemical properties, and sequence loci, which provides in-depth understanding of the features influencing protein crystallization. Crysalis is freely available at http://nmrcen.xmu.edu.cn/crysalis/.

Crysalis: an integrated server for computational analysis and design of protein crystallization

PubMed Central

Wang, Huilin; Feng, Liubin; Zhang, Ziding; Webb, Geoffrey I.; Lin, Donghai; Song, Jiangning

2016-01-01

The failure of multi-step experimental procedures to yield diffraction-quality crystals is a major bottleneck in protein structure determination. Accordingly, several bioinformatics methods have been successfully developed and employed to select crystallizable proteins. Unfortunately, the majority of existing in silico methods only allow the prediction of crystallization propensity, seldom enabling computational design of protein mutants that can be targeted for enhancing protein crystallizability. Here, we present Crysalis, an integrated crystallization analysis tool that builds on support-vector regression (SVR) models to facilitate computational protein crystallization prediction, analysis, and design. More specifically, the functionality of this new tool includes: (1) rapid selection of target crystallizable proteins at the proteome level, (2) identification of site non-optimality for protein crystallization and systematic analysis of all potential single-point mutations that might enhance protein crystallization propensity, and (3) annotation of target protein based on predicted structural properties. We applied the design mode of Crysalis to identify site non-optimality for protein crystallization on a proteome-scale, focusing on proteins currently classified as non-crystallizable. Our results revealed that site non-optimality is based on biases related to residues, predicted structures, physicochemical properties, and sequence loci, which provides in-depth understanding of the features influencing protein crystallization. Crysalis is freely available at http://nmrcen.xmu.edu.cn/crysalis/. PMID:26906024

Determining Optimal Location and Numbers of Sample Transects for Characterization of UXO Sites

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

BILISOLY, ROGER L.; MCKENNA, SEAN A.

2003-01-01

Previous work on sample design has been focused on constructing designs for samples taken at point locations. Significantly less work has been done on sample design for data collected along transects. A review of approaches to point and transect sampling design shows that transects can be considered as a sequential set of point samples. Any two sampling designs can be compared through using each one to predict the value of the quantity being measured on a fixed reference grid. The quality of a design is quantified in two ways: computing either the sum or the product of the eigenvalues ofmore » the variance matrix of the prediction error. An important aspect of this analysis is that the reduction of the mean prediction error variance (MPEV) can be calculated for any proposed sample design, including one with straight and/or meandering transects, prior to taking those samples. This reduction in variance can be used as a ''stopping rule'' to determine when enough transect sampling has been completed on the site. Two approaches for the optimization of the transect locations are presented. The first minimizes the sum of the eigenvalues of the predictive error, and the second minimizes the product of these eigenvalues. Simulated annealing is used to identify transect locations that meet either of these objectives. This algorithm is applied to a hypothetical site to determine the optimal locations of two iterations of meandering transects given a previously existing straight transect. The MPEV calculation is also used on both a hypothetical site and on data collected at the Isleta Pueblo to evaluate its potential as a stopping rule. Results show that three or four rounds of systematic sampling with straight parallel transects covering 30 percent or less of the site, can reduce the initial MPEV by as much as 90 percent. The amount of reduction in MPEV can be used as a stopping rule, but the relationship between MPEV and the results of excavation versus no-further-action decisions is site specific and cannot be calculated prior to the sampling. It may be advantageous to use the reduction in MPEV as a stopping rule for systematic sampling across the site that can then be followed by focused sampling in areas identified has having UXO during the systematic sampling. The techniques presented here provide answers to the questions of ''Where to sample?'' and ''When to stop?'' and are capable of running in near real time to support iterative site characterization campaigns.« less

Preliminary design package for prototype solar heating and cooling systems

NASA Technical Reports Server (NTRS)

1978-01-01

A summary is given of the preliminary analysis and design activity on solar heating and cooling systems. The analysis was made without site specific data other than weather; therefore, the results indicate performance expected under these special conditions. Major items include a market analysis, design approaches, trade studies and other special data required to evaluate the preliminary analysis and design. The program calls for the development and delivery of eight prototype solar heating and cooling systems for installation and operational test. Two heating and six heating and cooling units will be delivered for Single Family Residences, Multiple-family Residences and commercial applications.

Dynamics Govern Specificity of a Protein-Protein Interface: Substrate Recognition by Thrombin.

PubMed

Fuchs, Julian E; Huber, Roland G; Waldner, Birgit J; Kahler, Ursula; von Grafenstein, Susanne; Kramer, Christian; Liedl, Klaus R

2015-01-01

Biomolecular recognition is crucial in cellular signal transduction. Signaling is mediated through molecular interactions at protein-protein interfaces. Still, specificity and promiscuity of protein-protein interfaces cannot be explained using simplistic static binding models. Our study rationalizes specificity of the prototypic protein-protein interface between thrombin and its peptide substrates relying solely on binding site dynamics derived from molecular dynamics simulations. We find conformational selection and thus dynamic contributions to be a key player in biomolecular recognition. Arising entropic contributions complement chemical intuition primarily reflecting enthalpic interaction patterns. The paradigm "dynamics govern specificity" might provide direct guidance for the identification of specific anchor points in biomolecular recognition processes and structure-based drug design.

A DNAzyme-mediated logic gate for programming molecular capture and release on DNA origami.

PubMed

Li, Feiran; Chen, Haorong; Pan, Jing; Cha, Tae-Gon; Medintz, Igor L; Choi, Jong Hyun

2016-06-28

Here we design a DNA origami-based site-specific molecular capture and release platform operated by a DNAzyme-mediated logic gate process. We show the programmability and versatility of this platform with small molecules, proteins, and nanoparticles, which may also be controlled by external light signals.

Environmental Asbestos Assessment Manual Superfund Method for the Determination of Asbestos in Ambient Air Part 2: Technical Background Document

EPA Science Inventory

A sampling and analysis method for the determination of asbestos in air is presented in Part 1 of this report, under separate cover. This method is designed specifically to provide results suitable for supporting risk assessments at Superfund sites, although it is applicable t...

40 CFR 412.46 - New source performance standards (NSPS).

Code of Federal Regulations, 2014 CFR

2014-07-01

... designed open manure storage structure. For those CAFOs where 100 years of local weather data for the CAFO... based upon a site-specific evaluation of the CAFO's open surface manure storage structure. The NPDES... the case of any CAFO using an open surface manure storage structure for which the Director establishes...

40 CFR 412.46 - New source performance standards (NSPS).

Code of Federal Regulations, 2013 CFR

2013-07-01

... designed open manure storage structure. For those CAFOs where 100 years of local weather data for the CAFO... based upon a site-specific evaluation of the CAFO's open surface manure storage structure. The NPDES... the case of any CAFO using an open surface manure storage structure for which the Director establishes...

40 CFR 412.46 - New source performance standards (NSPS).

Code of Federal Regulations, 2012 CFR

2012-07-01

... designed open manure storage structure. For those CAFOs where 100 years of local weather data for the CAFO... based upon a site-specific evaluation of the CAFO's open surface manure storage structure. The NPDES... the case of any CAFO using an open surface manure storage structure for which the Director establishes...

Developing and Validating a Rapid Small-Scale Column Test Procedure for GAC Selection using Reconstituted Lyophilized NOM

EPA Science Inventory

Cost effective design and operation of Granular Activated Carbon (GAC) facilities requires the selection of GAC that is optimal for a specific site. Rapid small-scale column tests (RSSCTs) are widely used for GAC assessment due to several advantages, including the ability to simu...

Hypercontextualized Learning Games: Fantasy, Motivation, and Engagement in Reality

ERIC Educational Resources Information Center

Islas Sedano, Carolina; Leendertz, Verona; Vinni, Mikko; Sutinen, Erkki; Ellis, Suria

2013-01-01

A Hypercontextualized Game (HCG) is a locally designed game that supports its players in gathering context-specific information and in-depth understanding and knowledge regarding the context of a site. LIEKSAMYST, an exciting mobile application, with which visitors can play various games based on stories, was originally developed for the open-air…

CONTRIBUTIONS OF QUALITY ASSURANCE/QUALITY CONTROL TO EMERGING TECHNIQUES IN ECOLOGY: NOT JUST FOR CHEMISTS ANYMORE

EPA Science Inventory

The structure of biological monitoring designs has become critical as support not only for assessments of condition under Section 305(b) of the Clean Water Act but also as the starting point for site-specific determinations of impairment, diagnosis of causes of impairment, alloca...

Solar heating for a restaurant--North Little Rock, Arkansas

NASA Technical Reports Server (NTRS)

1981-01-01

Hot water consumption of large building affects solar-energy system design. Continual demand for hot water at restaurant makes storage less important than at other sites. Storage capacity of system installed in December 1979 equals estimated daily hot-water requirement. Report describes equipment specifications and modifications to existing building heating and hot water systems.

40 CFR 258.42 - Approval of site-specific flexibility requests in Indian country.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (CONTINUED) SOLID WASTES CRITERIA FOR MUNICIPAL SOLID WASTE LANDFILLS Design Criteria § 258.42 Approval of...) of this section applies to the Salt River Landfill, a municipal solid waste landfill owned and operated by the SPRMIC on the SRPMIC's reservation in Arizona, which includes waste disposal areas...

40 CFR 258.42 - Approval of site-specific flexibility requests in Indian country.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (CONTINUED) SOLID WASTES CRITERIA FOR MUNICIPAL SOLID WASTE LANDFILLS Design Criteria § 258.42 Approval of...) of this section applies to the Salt River Landfill, a municipal solid waste landfill owned and operated by the SPRMIC on the SRPMIC's reservation in Arizona, which includes waste disposal areas...

75 FR 346 - Environmental Management Site-Specific Advisory Board, Idaho National Laboratory

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-05

... current agenda): Progress to Cleanup. InSitu Grouting--Draft Remedial Design and Remedial Action Work Plan... this meeting be announced in the Federal Register. DATES: Wednesday, January 20, 2010, 8 a.m.-5 p.m... in the areas of environmental restoration, waste management, and related activities. Tentative Topics...

Where and Why There? Spatial Thinking with Geographic Information Systems

ERIC Educational Resources Information Center

Milson, Andrew J.; Curtis, Mary D.

2009-01-01

The authors developed and implemented a project for high school geography students that modeled the processes in a site selection analysis using Geographic Information Systems (GIS). They sought to explore how spatial thinking could be fostered by using the MyWorld GIS software that was designed specifically for educational uses. The task posed…

Developing and Validating a Rapid Small-Scale Column Test Procedure for GAC Selection using Reconstituted Lyophilized NOM - Portland, OR

EPA Science Inventory

Cost effective design and operation of Granular Activated Carbon (GAC) facilities requires the selection of GAC that is optimal for a specific site. Rapid small-scale column tests (RSSCTs) are widely used for GAC assessment due to several advantages, including the ability to simu...

Detection of possible restriction sites for type II restriction enzymes in DNA sequences.

PubMed

Gagniuc, P; Cimponeriu, D; Ionescu-Tîrgovişte, C; Mihai, Andrada; Stavarachi, Monica; Mihai, T; Gavrilă, L

2011-01-01

In order to make a step forward in the knowledge of the mechanism operating in complex polygenic disorders such as diabetes and obesity, this paper proposes a new algorithm (PRSD -possible restriction site detection) and its implementation in Applied Genetics software. This software can be used for in silico detection of potential (hidden) recognition sites for endonucleases and for nucleotide repeats identification. The recognition sites for endonucleases may result from hidden sequences through deletion or insertion of a specific number of nucleotides. Tests were conducted on DNA sequences downloaded from NCBI servers using specific recognition sites for common type II restriction enzymes introduced in the software database (n = 126). Each possible recognition site indicated by the PRSD algorithm implemented in Applied Genetics was checked and confirmed by NEBcutter V2.0 and Webcutter 2.0 software. In the sequence NG_008724.1 (which includes 63632 nucleotides) we found a high number of potential restriction sites for ECO R1 that may be produced by deletion (n = 43 sites) or insertion (n = 591 sites) of one nucleotide. The second module of Applied Genetics has been designed to find simple repeats sizes with a real future in understanding the role of SNPs (Single Nucleotide Polymorphisms) in the pathogenesis of the complex metabolic disorders. We have tested the presence of simple repetitive sequences in five DNA sequence. The software indicated exact position of each repeats detected in the tested sequences. Future development of Applied Genetics can provide an alternative for powerful tools used to search for restriction sites or repetitive sequences or to improve genotyping methods.

Periodically microstructured composite films made by electric- and magnetic-directed colloidal assembly

PubMed Central

Demirörs, Ahmet Faik; Courty, Diana; Libanori, Rafael; Studart, André R.

2016-01-01

Living organisms often combine soft and hard anisotropic building blocks to fabricate composite materials with complex microstructures and outstanding mechanical properties. An optimum design and assembly of the anisotropic components reinforces the material in specific directions and sites to best accommodate multidirectional external loads. Here, we fabricate composite films with periodic modulation of the soft–hard microstructure by simultaneously using electric and magnetic fields. We exploit forefront directed-assembly approaches to realize highly demanded material microstructural designs and showcase a unique example of how one can bridge colloidal sciences and composite technology to fabricate next-generation advanced structural materials. In the proof-of-concept experiments, electric fields are used to dictate the position of the anisotropic particles through dielectrophoresis, whereas a rotating magnetic field is used to control the orientation of the particles. By using such unprecedented control over the colloidal assembly process, we managed to fabricate ordered composite microstructures with up to 2.3-fold enhancement in wear resistance and unusual site-specific hardness that can be locally modulated by a factor of up to 2.5. PMID:27071113

Osmotically regulated floating asymmetric membrane capsule for controlled site-specific delivery of ranitidine hydrochloride: optimization by central composite design.

PubMed

Chauhan, Manvendra S; Kumar, Anil; Pathak, Kamla

2012-12-01

A nondisintegrating, floating asymmetric membrane capsule (FAMC) was developed to achieve site-specific osmotic flow of a highly water-soluble drug, ranitidine hydrochloride (RHCl), in a controlled manner. Solubility suppression of RHCl was achieved by the common ion effect, using optimized coated sodium chloride as a formulation component. The capsular wall of FAMC was prepared by the phase inversion process wherein the polymeric membrane was precipitated on glass pins by dipping them in a solution of cellulose acetate followed by quenching. Central composite design was utilized to investigate the influence of independent variables, namely, level(s) of membrane former, pore former, and osmogen, on percent cumulative drug release (response). The release mechanism of RHCl through FAMC was confirmed as osmotic pumping. The asymmetry of the membrane was characterized by scanning electron microscopy that revealed a dense nonporous outer region of membrane supported by an inner porous region. Differential scanning calorimetry indicated no incompatibility between the drug and excipients. In vitro drug release in three biorelevant media, pH 2.5 (low fed), pH 4.5 (intermediate fed), and pH 6.5 (high fed), demonstrated pH-independent release of RHCl (P > 0.05). Floating ability for 12 h of the optimized FAMC9 was visually examined during the in vitro release studies that showed maximal drug release with zero-order kinetics (r (2) = 0.9991). Thus, a novel osmotically regulated floating capsular system was developed for site-specific delivery of RHCl.

Preliminary economic analysis of aquifer winter-chill storage at the John F. Kennedy airport

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

Fox, E.C.; Thomas, J.F.

A conceptual design was formulated in conjuction with a cost analysis to determine the feasibility of retrofitting the present John F. Kennedy (JFK) airport air-conditioning system with an aquifer cold water storage system. It appears technically feasible to chill and store aquifer water at the airport site during the winter months for later air-conditioning use. However, the economic analysis shows that although a significant energy savings is realized, the money saved from reduced energy costs would not be enough to recover the necessary capital investment over a 20-year period. JFK airport may be a poor economic choice for an aquifermore » cold water storage demonstration site due to site specific problems, and other sites may provide economic incentive.« less

Onco-Regulon: an integrated database and software suite for site specific targeting of transcription factors of cancer genes

PubMed Central

Tomar, Navneet; Mishra, Akhilesh; Mrinal, Nirotpal; Jayaram, B.

2016-01-01

Transcription factors (TFs) bind at multiple sites in the genome and regulate expression of many genes. Regulating TF binding in a gene specific manner remains a formidable challenge in drug discovery because the same binding motif may be present at multiple locations in the genome. Here, we present Onco-Regulon (http://www.scfbio-iitd.res.in/software/onco/NavSite/index.htm), an integrated database of regulatory motifs of cancer genes clubbed with Unique Sequence-Predictor (USP) a software suite that identifies unique sequences for each of these regulatory DNA motifs at the specified position in the genome. USP works by extending a given DNA motif, in 5′→3′, 3′ →5′ or both directions by adding one nucleotide at each step, and calculates the frequency of each extended motif in the genome by Frequency Counter programme. This step is iterated till the frequency of the extended motif becomes unity in the genome. Thus, for each given motif, we get three possible unique sequences. Closest Sequence Finder program predicts off-target drug binding in the genome. Inclusion of DNA-Protein structural information further makes Onco-Regulon a highly informative repository for gene specific drug development. We believe that Onco-Regulon will help researchers to design drugs which will bind to an exclusive site in the genome with no off-target effects, theoretically. Database URL: http://www.scfbio-iitd.res.in/software/onco/NavSite/index.htm PMID:27515825

Long-term energy capture and the effects of optimizing wind turbine operating strategies

NASA Technical Reports Server (NTRS)

Miller, A. H.; Formica, W. J.

1982-01-01

Methods of increasing energy capture without affecting the turbine design were investigated. The emphasis was on optimizing the wind turbine operating strategy. The operating strategy embodies the startup and shutdown algorithm as well as the algorithm for determining when to yaw (rotate) the axis of the turbine more directly into the wind. Using data collected at a number of sites, the time-dependent simulation of a MOD-2 wind turbine using various, site-dependent operating strategies provided evidence that site-specific fine tuning can produce significant increases in long-term energy capture as well as reduce the number of start-stop cycles and yawing maneuvers, which may result in reduced fatigue and subsequent maintenance.

Size Matters: Developing Design Rules to Engineer Nanoparticles for Solid Tumour Targeting

NASA Astrophysics Data System (ADS)

Sykes, Edward Alexander

Nanotechnology enables the design of highly customizable platforms for producing minimally invasive and programmable strategies for cancer diagnosis and treatment. Advances in this field have demonstrated that nanoparticles can enhance specificity of anti-cancer agents, respond to tumour-specific cues, and direct the visualization of biological targets in vivo. . Nanoparticles can be synthesized within the 1 to 100 nm range to achieve different electromagnetic properties and specifically interact with biological tissues by tuning their size, shape, and surface chemistry. However, it remains unclear which physicochemical parameters are critical for delivering nanomaterials to the tumour site. With less than 5% of administered nanoparticles reaching the tumour, engineering of nanoparticles for effective delivery to solid tumours remains a critical challenge to cancer nanomedicine. A more comprehensive understanding of the interplay between the nanomaterial physicochemical properties and biological systems is necessary to enhance the efficacy of nanoparticle tumour targeting. This thesis explores how nanoparticle size and functionalization with cancer cell specific agents impact nanoparticle delivery to tumours. Furthermore, this doctoral work (i) discusses how tumour structure evolves with growth, (ii) elucidates how such changes modulate nanoparticle accumulation, and (iii) identifies how the skin serves as a significant off-target site for nanoparticle uptake. This thesis also demonstrates the utility of empirically-derived parametric models, Monte Carlo simulations, and decision matrices for mechanistically understanding and predicting the impact of nanomaterial features and tumour biology on nanoparticle fate in vivo. These topics establish key design considerations to tailor nanoparticles for enhanced tumour targeting. Collectively, the concepts presented herein form a fundamental framework for the development of personalized nanomedicine and nano-diagnostic agents in the future.

TU-A-201-01: Introduction to In-Room Imaging System Characteristics

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

Chang, J.

2016-06-15

Recent years have seen a widespread proliferation of available in-room image guidance systems for radiation therapy target localization with many centers having multiple in-room options. In this session, available imaging systems for in-room IGRT will be reviewed highlighting the main differences in workflow efficiency, targeting accuracy and image quality as it relates to target visualization. Decision-making strategies for integrating these tools into clinical image guidance protocols that are tailored to specific disease sites like H&N, lung, pelvis, and spine SBRT will be discussed. Learning Objectives: Major system characteristics of a wide range of available in-room imaging systems for IGRT. Advantagesmore » / disadvantages of different systems for site-specific IGRT considerations. Concepts of targeting accuracy and time efficiency in designing clinical imaging protocols.« less

TU-A-201-00: Image Guidance Technologies and Management Strategies

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

NONE

2016-06-15

Recent years have seen a widespread proliferation of available in-room image guidance systems for radiation therapy target localization with many centers having multiple in-room options. In this session, available imaging systems for in-room IGRT will be reviewed highlighting the main differences in workflow efficiency, targeting accuracy and image quality as it relates to target visualization. Decision-making strategies for integrating these tools into clinical image guidance protocols that are tailored to specific disease sites like H&N, lung, pelvis, and spine SBRT will be discussed. Learning Objectives: Major system characteristics of a wide range of available in-room imaging systems for IGRT. Advantagesmore » / disadvantages of different systems for site-specific IGRT considerations. Concepts of targeting accuracy and time efficiency in designing clinical imaging protocols.« less

2'-modified nucleosides for site-specific labeling of oligonucleotides

NASA Technical Reports Server (NTRS)

Krider, Elizabeth S.; Miller, Jeremiah E.; Meade, Thomas J.

2002-01-01

We report the synthesis of 2'-modified nucleosides designed specifically for incorporating labels into oligonucleotides. Conversion of these nucleosides to phosphoramidite and solid support-bound derivatives proceeds in good yield. Large-scale synthesis of 11-mer oligonucleotides possessing the 2'-modified nucleosides is achieved using these derivatives. Thermal denaturation studies indicate that the presence of 2'-modified nucleosides in 11-mer duplexes has minimal destabilizing effects on the duplex structure when the nucleosides are placed at the duplex termini. The powerful combination of phosphoramidite and support-bound derivatives of 2'-modified nucleosides affords the large-scale preparation of an entirely new class of oligonucleotides. The ability to synthesize oligonucleotides containing label attachment sites at 3', intervening, and 5' locations of a duplex is a significant advance in the development of oligonucleotide conjugates.

Advancements in nano-enabled therapeutics for neuroHIV management.

PubMed

Kaushik, Ajeet; Jayant, Rahul Dev; Nair, Madhavan

This viewpoint is a global call to promote fundamental and applied research aiming toward designing smart nanocarriers of desired properties, novel noninvasive strategies to open the blood-brain barrier (BBB), delivery/release of single/multiple therapeutic agents across the BBB to eradicate neurohuman immunodeficiency virus (HIV), strategies for on-demand site-specific release of antiretroviral therapy, developing novel nanoformulations capable to recognize and eradicate latently infected HIV reservoirs, and developing novel smart analytical diagnostic tools to detect and monitor HIV infection. Thus, investigation of novel nanoformulations, methodologies for site-specific delivery/release, analytical methods, and diagnostic tools would be of high significance to eradicate and monitor neuroacquired immunodeficiency syndrome. Overall, these developments will certainly help to develop personalized nanomedicines to cure HIV and to develop smart HIV-monitoring analytical systems for disease management.

Environment of Mars, 1988

NASA Technical Reports Server (NTRS)

Kaplan, David I. (Compiler)

1988-01-01

A compilation of scientific knowledge about the planet Mars is provided. Information is divided into three categories: atmospheric data, surface data, and astrodynamic data. The discussion of atmospheric data includes the presentation of nine different models of the Mars atmosphere. Also discussed are Martian atmospheric constituents, winds, clouds, and solar irradiance. The great dust storms of Mars are presented. The section on Mars surface data provides an in-depth examination of the physical and chemical properties observed at the two Viking landing sites. Bulk densities, dielectric constants, and thermal inertias across the planet are then described and related back to those specific features found at the Viking landing sites. The astrodynamic materials provide the astronomical constants, time scales, and reference coordinate frames necessary to perform flightpath analysis, navigation design, and science observation design.

Canadian Health Measures Survey pre-test: design, methods, results.

PubMed

Tremblay, Mark; Langlois, Renée; Bryan, Shirley; Esliger, Dale; Patterson, Julienne

2007-01-01

The Canadian Health Measures Survey (CHMS) pre-test was conducted to provide information about the challenges and costs associated with administering a physical health measures survey in Canada. To achieve the specific objectives of the pre-test, protocols were developed and tested, and methods for household interviewing and clinic testing were designed and revised. The cost, logistics and suitability of using fixed sites for the CHMS were assessed. Although data collection, transfer and storage procedures are complex, the pre-test experience confirmed Statistics Canada's ability to conduct a direct health measures survey and the willingness of Canadians to participate in such a health survey. Many operational and logistical procedures worked well and, with minor modifications, are being employed in the main survey. Fixed sites were problematic, and survey costs were higher than expected.

Architecture of the 99 bp DNA-six-protein regulatory complex of the lambda att site.

PubMed

Sun, Xingmin; Mierke, Dale F; Biswas, Tapan; Lee, Sang Yeol; Landy, Arthur; Radman-Livaja, Marta

2006-11-17

The highly directional and tightly regulated recombination reaction used to site-specifically excise the bacteriophage lambda chromosome out of its E. coli host chromosome requires the binding of six sequence-specific proteins to a 99 bp segment of the phage att site. To gain structural insights into this recombination pathway, we measured 27 FRET distances between eight points on the 99 bp regulatory DNA bound with all six proteins. Triangulation of these distances using a metric matrix distance-geometry algorithm provided coordinates for these eight points. The resulting path for the protein-bound regulatory DNA, which fits well with the genetics, biochemistry, and X-ray crystal structures describing the individual proteins and their interactions with DNA, provides a new structural perspective into the molecular mechanism and regulation of the recombination reaction and illustrates a design by which different families of higher-order complexes can be assembled from different numbers and combinations of the same few proteins.

Substrate Tunnels in Enzymes: Structure-Function Relationships and Computational Methodology

PubMed Central

Kingsley, Laura J.; Lill, Markus A.

2015-01-01

In enzymes, the active site is the location where incoming substrates are chemically converted to products. In some enzymes, this site is deeply buried within the core of the protein and in order to access the active site, substrates must pass through the body of the protein via a tunnel. In many systems, these tunnels act as filters and have been found to influence both substrate specificity and catalytic mechanism. Identifying and understanding how these tunnels exert such control has been of growing interest over the past several years due to implications in fields such as protein engineering and drug design. This growing interest has spurred the development of several computational methods to identify and analyze tunnels and how ligands migrate through these tunnels. The goal of this review is to outline how tunnels influence substrate specificity and catalytic efficiency in enzymes with tunnels and to provide a brief summary of the computational tools used to identify and evaluate these tunnels. PMID:25663659

Rapid Prototyping of Hydrologic Model Interfaces with IPython

NASA Astrophysics Data System (ADS)

Farthing, M. W.; Winters, K. D.; Ahmadia, A. J.; Hesser, T.; Howington, S. E.; Johnson, B. D.; Tate, J.; Kees, C. E.

2014-12-01

A significant gulf still exists between the state of practice and state of the art in hydrologic modeling. Part of this gulf is due to the lack of adequate pre- and post-processing tools for newly developed computational models. The development of user interfaces has traditionally lagged several years behind the development of a particular computational model or suite of models. As a result, models with mature interfaces often lack key advancements in model formulation, solution methods, and/or software design and technology. Part of the problem has been a focus on developing monolithic tools to provide comprehensive interfaces for the entire suite of model capabilities. Such efforts require expertise in software libraries and frameworks for creating user interfaces (e.g., Tcl/Tk, Qt, and MFC). These tools are complex and require significant investment in project resources (time and/or money) to use. Moreover, providing the required features for the entire range of possible applications and analyses creates a cumbersome interface. For a particular site or application, the modeling requirements may be simplified or at least narrowed, which can greatly reduce the number and complexity of options that need to be accessible to the user. However, monolithic tools usually are not adept at dynamically exposing specific workflows. Our approach is to deliver highly tailored interfaces to users. These interfaces may be site and/or process specific. As a result, we end up with many, customized interfaces rather than a single, general-use tool. For this approach to be successful, it must be efficient to create these tailored interfaces. We need technology for creating quality user interfaces that is accessible and has a low barrier for integration into model development efforts. Here, we present efforts to leverage IPython notebooks as tools for rapid prototyping of site and application-specific user interfaces. We provide specific examples from applications in near-shore environments as well as levee analysis. We discuss our design decisions and methodology for developing customized interfaces, strategies for delivery of the interfaces to users in various computing environments, as well as implications for the design/implementation of simulation models.

IMAGESEER - IMAGEs for Education and Research

NASA Technical Reports Server (NTRS)

Le Moigne, Jacqueline; Grubb, Thomas; Milner, Barbara

2012-01-01

IMAGESEER is a new Web portal that brings easy access to NASA image data for non-NASA researchers, educators, and students. The IMAGESEER Web site and database are specifically designed to be utilized by the university community, to enable teaching image processing (IP) techniques on NASA data, as well as to provide reference benchmark data to validate new IP algorithms. Along with the data and a Web user interface front-end, basic knowledge of the application domains, benchmark information, and specific NASA IP challenges (or case studies) are provided.

Lunar surface mine feasibility study

NASA Astrophysics Data System (ADS)

Blair, Brad R.

This paper describes a lunar surface mine, and demonstrates the economic feasibility of mining oxygen from the moon. The mine will be at the Apollo 16 landing site. Mine design issues include pit size and shape, excavation equipment, muck transport, and processing requirements. The final mine design will be driven by production requirements, and constrained by the lunar environment. This mining scenario assumes the presence of an operating lunar base. Lunar base personnel will set-up a and run the mine. The goal of producing lunar oxygen is to reduce dependence on fuel shipped from Earth. Thus, the lunar base is the customer for the finished product. The perspective of this paper is that of a mining contractor who must produce a specific product at a remote location, pay local labor, and sell the product to an onsite captive market. To make a profit, it must be less costly to build and ship specialized equipment to the site, and pay high labor and operating costs, than to export the product directly to the site.

Design of potent and selective human cathepsin K inhibitors that span the active site

PubMed Central

Thompson, Scott K.; Halbert, Stacie M.; Bossard, Mary J.; Tomaszek, Thaddeus A.; Levy, Mark A.; Zhao, Baoguang; Smith, Ward W.; Abdel-Meguid, Sherin S.; Janson, Cheryl A.; D’Alessio, Karla J.; McQueney, Michael S.; Amegadzie, Bernard Y.; Hanning, Charles R.; DesJarlais, Renee L.; Briand, Jacques; Sarkar, Susanta K.; Huddleston, Michael J.; Ijames, Carl F.; Carr, Steven A.; Garnes, Keith T.; Shu, Art; Heys, J. Richard; Bradbeer, Jeremy; Zembryki, Denise; Lee-Rykaczewski, Liz; James, Ian E.; Lark, Michael W.; Drake, Fred H.; Gowen, Maxine; Gleason, John G.; Veber, Daniel F.

1997-01-01

Potent and selective active-site-spanning inhibitors have been designed for cathepsin K, a cysteine protease unique to osteoclasts. They act by mechanisms that involve tight binding intermediates, potentially on a hydrolytic pathway. X-ray crystallographic, MS, NMR spectroscopic, and kinetic studies of the mechanisms of inhibition indicate that different intermediates or transition states are being represented that are dependent on the conditions of measurement and the specific groups flanking the carbonyl in the inhibitor. The species observed crystallographically are most consistent with tetrahedral intermediates that may be close approximations of those that occur during substrate hydrolysis. Initial kinetic studies suggest the possibility of irreversible and reversible active-site modification. Representative inhibitors have demonstrated antiresorptive activity both in vitro and in vivo and therefore are promising leads for therapeutic agents for the treatment of osteoporosis. Expansion of these inhibitor concepts can be envisioned for the many other cysteine proteases implicated for therapeutic intervention. PMID:9405598

In Situ Corrosion and Heat Loss Assessment of Two Nonstandard Underground Heat Distribution System Piping Designs

DTIC Science & Technology

2011-06-01

of this specific design consists of a carrier pipe, carrier pipe insulation ( mineral wool ), an annular air space, steel casing, a layer of exterior...excavation site agree with Perma-Pipe “Multi-Therm 500” nominal specs for 10” carrier with 2” mineral wool insulation. 3. Conduit Temperature: Supply...the ASHRAE calculation method or by manufacturer performance claims. MEC is reasonably certain that the mineral wool insulation used by the

Definition of design criteria of mechanical transfer: an interaction between engineering and health areas.

PubMed

Luz, Taciana Ramos; Echternacht, Eliza Helena de Oliveira

2012-01-01

This study aims to analyze the factors that justify the low use of a mechanical transfer in the context of a long-term institution. It is a device intended for internal transportation of individuals who have mobility problems. The analysis involves researchers from the fields of health and engineering in order to generate design criteria that consider the needs of caregivers and patients of this institution. To understand the reality of this site and their specificities, was used Ergonomic Work Analysis.

Quantifying Construction Site Sediment Discharge Risk and Treatment Potential

NASA Astrophysics Data System (ADS)

Ferrell, L.; Beighley, R. E.

2006-12-01

Dealing with soil erosion and sediment transport can be a significant challenge during the construction process due to the potentially large spatial and temporal extent and conditions of bare soils. Best Management Practices (BMP) are commonly used to eliminate or reduce offsite discharge of sediment. However, few efforts have investigated the time varying risk of sediment discharge from construction sites, which often have dynamic soil conditions and the potential for less than optimal BMP installations. The goal of this research is to improve the design, implementation and effectiveness of sediment and erosion control at construction sites using site specific, temporal distributions of sediment discharge risk. Sediment risk is determined from individual factors leading to sediment expert, such as rainfall frequency, the adequacy of BMP installations, and the extent and duration of bare soil conditions. This research specifically focuses on quantifying: (a) the effectiveness of temporary sediment and control erosion control BMPs in preventing, containing, and/or treating construction site sediment discharge at varying levels of "proper" installation, and (b) sediment discharge potential from construction sites during different phases of construction, (ex., disturbed earth operations). BMPs are evaluated at selected construction sites in southern California and at the Soil Erosion Research Laboratory (SERL) in the Civil and Environmental Engineering department at San Diego State University. SERL experiments are performed on a 3-m by 10-m tilting soil bed with soil depths up to 1 meter, slopes ranging from 0 to 50 percent, and rainfall rates up to 150 mm/hr (6 in/hr). BMP performance is assessed based on experiments where BMPs are installed per manufacture specifications, potential less than optimal installations, and no treatment conditions. Soil conditions are also varied to represent site conditions during different phases of construction (i.e., loose lifts, stock piles, temporary roads, finished grade, others). Preliminary site monitoring, experimental results, and a conceptual model for estimating the time depend risk of sediment discharge over the duration of a construction project are presented.

Heat pump centered integrated community energy systems: system development. Georgia Institute of Technology final report

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

Wade, D.W.; Trammell, B.C.; Dixit, B.S.

1979-12-01

Heat Pump Centered-Integrated Community Energy Systems (HP-ICES) show the promise of utilizing low-grade thermal energy for low-quality energy requirements such as space heating and cooling. The Heat Pump - Wastewater Heat Recovery (HP-WHR) scheme is one approach to an HP-ICES that proposes to reclaim low-grade thermal energy from a community's wastewater effluent. This report develops the concept of an HP-WHR system, evaluates the potential performance and economics of such a system, and examines the potential for application. A thermodynamic performance analysis of a hypothetical system projects an overall system Coefficient of Performance (C.O.P.) of from 2.181 to 2.264 for waste-watermore » temperatures varying from 50/sup 0/F to 80/sup 0/F. Primary energy source savings from the nationwide implementation of this system is projected to be 6.0 QUADS-fuel oil, or 8.5 QUADS - natural gas, or 29.7 QUADS - coal for the period 1980 to 2000, depending upon the type and mix of conventional space conditioning systems which could be displaced with the HP-WHR system. Site-specific HP-WHR system designs are presented for two application communities in Georgia. Performance analyses for these systems project annual cycle system C.O.P.'s of 2.049 and 2.519. Economic analysis on the basis of a life cycle cost comparison shows one site-specific system design to be cost competitive in the immediate market with conventional residential and light commercial HVAC systems. The second site-specific system design is shown through a similar economic analysis to be more costly than conventional systems due mainly to the current low energy costs for natural gas. It is anticipated that, as energy costs escalate, this HP-WHR system will also approach the threshold of economic viability.« less

Content and Design Features of Academic Health Sciences Libraries' Home Pages.

PubMed

McConnaughy, Rozalynd P; Wilson, Steven P

2018-01-01

The goal of this content analysis was to identify commonly used content and design features of academic health sciences library home pages. After developing a checklist, data were collected from 135 academic health sciences library home pages. The core components of these library home pages included a contact phone number, a contact email address, an Ask-a-Librarian feature, the physical address listed, a feedback/suggestions link, subject guides, a discovery tool or database-specific search box, multimedia, social media, a site search option, a responsive web design, and a copyright year or update date.

The ARCO 1 megawatt Photovoltaic Power Plant

NASA Astrophysics Data System (ADS)

Rhodes, G. W.; Reilly, M. R.

The world's largest Photovoltaic Power Plant is in operation and meeting performance specifications on the Southern California Edison (SCE) grid near Hesperia, California. The 1 MW plant designed and constructed by The BDM Corporation, for ARCO Solar Inc., occupies a 20 acre site adjacent to the SCE Lugo substation. The entire design and construction process took 7 1/2 months and was not only on schedule but below budget. Because of its vast photovoltaic experience, BDM was chosen over several engineering firms to perform this complex job. We were provided a conceptual design from ARCO which we quickly refined and immediately initiated construction.

Upscaling the pollutant emission from mixed recycled aggregates under compaction for civil applications.

PubMed

Galvín, Adela P; Ayuso, Jesús; Barbudo, Auxi; Cabrera, Manuel; López-Uceda, Antonio; Rosales, Julia

2017-12-27

In general terms, plant managers of sites producing construction wastes assess materials according to concise, legally recommended leaching tests that do not consider the compaction stage of the materials when they are applied on-site. Thus, the tests do not account for the real on-site physical conditions of the recycled aggregates used in civil works (e.g., roads or embankments). This leads to errors in estimating the pollutant potential of these materials. For that reason, in the present research, an experimental procedure is designed as a leaching test for construction materials under compaction. The aim of this laboratory test (designed specifically for the granular materials used in civil engineering infrastructures) is to evaluate the release of pollutant elements when the recycled aggregate is tested at its commercial grain-size distribution and when the material is compacted under on-site conditions. Two recycled aggregates with different gypsum contents (0.95 and 2.57%) were used in this study. In addition to the designed leaching laboratory test, the conventional compliance leaching test and the Dutch percolation test were performed. The results of the new leaching method were compared with the conventional leaching test results. After analysis, the chromium and sulphate levels obtained from the newly designed test were lower than those obtained from the conventional leaching test, and these were considered more seriously pollutant elements. This result confirms that when the leaching behaviour is evaluated for construction aggregates without density alteration, crushing the aggregate and using only the finest fraction, as is done in the conventional test (which is an unrealistic situation for aggregates that are applied under on-site conditions), the leaching behaviour is not accurately assessed.

Confronting Challenges in Intervention Research with Ethnically Diverse Older Adults: The USC Well Elderly II Trial

PubMed Central

Jackson, Jeanne; Mandel, Deborah; Blanchard, Jeanine; Carlson, Mike; Cherry, Barbara; Azen, Stanley; Chou, Chih-Ping; Jordan-Marsh, Maryalice; Forman, Todd; White, Brett; Granger, Douglas; Knight, Bob; Clark, Florence

2011-01-01

Background Community-dwelling older adults are at risk for declines in physical health, cognition, and psychosocial well-being. However, their enactment of active and health-promoting lifestyles can reduce such declines. Purpose The purpose of this article is to describe the USC Well Elderly II study, a randomized clinical trial designed to test the effectiveness of a healthy lifestyle program for elders, and document how various methodological challenges were addressed during the course of the trial. Methods In the study, 460 ethnically diverse elders recruited from a variety of sites in the urban Los Angeles area were enrolled in a randomized experiment involving a crossover design component. Within either the first or second six month phase of their study involvement, each elder received a lifestyle intervention designed to improve a variety of aging outcomes. At 4–5 time points over an 18–24 month interval, the research participants were assessed on measures of healthy activity, coping, social support, perceived control, stress-related biomarkers, perceived physical health, psychosocial well-being, and cognitive functioning to test the effectiveness of the intervention and document the process mechanisms responsible for its effects. Results The study protocol was successfully implemented, including the enrollment of study sites, the recruitment of 460 older adults, administration of the intervention, adherence to the plan for assessment, and establishment of a large computerized data base. Limitations Methodological challenges were encountered in the areas of site recruitment, participant recruitment, testing, and intervention delivery. Conclusions The completion of clinical trials involving elders from numerous local sites requires careful oversight and anticipation of threats to the study design that stem from: (a) social situations that are particular to specific study sites; and (b) physical, functional, and social challenges pertaining to the elder population. PMID:19254939

Confronting challenges in intervention research with ethnically diverse older adults: the USC Well Elderly II Trial.

PubMed

Jackson, Jeanne; Mandel, Deborah; Blanchard, Jeanine; Carlson, Mike; Cherry, Barbara; Azen, Stanley; Chou, Chih-Ping; Jordan-Marsh, Maryalice; Forman, Todd; White, Brett; Granger, Douglas; Knight, Bob; Clark, Florence

2009-02-01

Community-dwelling older adults are at risk for declines in physical health, cognition, and psychosocial well-being. However, their enactment of active and health-promoting lifestyles can reduce such declines. The purpose of this article is to describe the USC Well Elderly II study, a randomized clinical trial designed to test the effectiveness of a healthy lifestyle program for elders, and document how various methodological challenges were addressed during the course of the trial. In the study, 460 ethnically diverse elders recruited from a variety of sites in the urban Los Angeles area were enrolled in a randomized experiment involving a crossover design component. Within either the first or second 6-month phase of their study involvement, each elder received a lifestyle intervention designed to improve a variety of aging outcomes. At 4-5 time points over an 18-24 month interval, the research participants were assessed on measures of healthy activity, coping, social support, perceived control, stress-related biomarkers, perceived physical health, psychosocial well-being, and cognitive functioning to test the effectiveness of the intervention and document the process mechanisms responsible for its effects. The study protocol was successfully implemented, including the enrollment of study sites, the recruitment of 460 older adults, administration of the intervention, adherence to the plan for assessment, and establishment of a large computerized data base. Methodological challenges were encountered in the areas of site recruitment, participant recruitment, testing, and intervention delivery. The completion of clinical trials involving elders from numerous local sites requires careful oversight and anticipation of threats to the study design that stem from: (a) social situations that are particular to specific study sites; and (b) physical, functional, and social challenges pertaining to the elder population.

The energy trilogy: An integrated sustainability model to bridge wastewater treatment plant energy and emissions gaps

NASA Astrophysics Data System (ADS)

Al-Talibi, A. Adhim

An estimated 4% of national energy consumption is used for drinking water and wastewater services. Despite the awareness and optimization initiatives for energy conservation, energy consumption is on the rise owing to population and urbanization expansion and to commercial and industrial business advancement. The principal concern is since energy consumption grows, the higher will be the energy production demand, leading to an increase in CO2 footprints and the contribution to global warming potential. This research is in the area of energy-water nexus, focusing on wastewater treatment plant (WWTP) energy trilogy -- the group of three related entities, which includes processes: (1) consuming energy, (2) producing energy, and (3) the resulting -- CO2 equivalents. Detailed and measurable energy information is not readily obtained for wastewater facilities, specifically during facility preliminary design phases. These limitations call for data-intensive research approach on GHG emissions quantification, plant efficiencies and source reduction techniques. To achieve these goals, this research introduced a model integrating all plant processes and their pertinent energy sources. In a comprehensive and "Energy Source-to-Effluent Discharge" pattern, this model is capable of bridging the gaps of WWTP energy, facilitating plant designers' decision-making for meeting energy assessment, sustainability and the environmental regulatory compliance. Protocols for estimating common emissions sources are available such as for fuels, whereas, site-specific emissions for other sources have to be developed and are captured in this research. The dissertation objectives were met through an extensive study of the relevant literature, models and tools, originating comprehensive lists of processes and energy sources for WWTPs, locating estimation formulas for each source, identifying site specific emissions factors, and linking the sources in a mathematical model for site specific CO2 e determination. The model was verified and showed a good agreement with billed and measured data from a base case study. In a next phase, a supplemental computational tool can be created for conducting plant energy design comparisons and plant energy and emissions parameters assessments. The main conclusions drawn from this research is that current approaches are severely limited, not covering plant's design phase and not fully considering the balance of energy consumed (EC), energy produced (EP) and the resulting CO2 e emission integration. Finally their results are not representative. This makes reported governmental and institutional national energy consumption figures incomplete and/or misleading, since they are mainly considering energy consumptions from electricity and some fuels or certain processes only. The distinction of the energy trilogy model over existing approaches is based on the following: (1) the ET energy model is unprecedented, prepared to fit WWTP energy assessment during the design and rehabilitation phases, (2) links the energy trilogy eliminating the need for using several models or tools, (3) removes the need for on-site expensive energy measurements or audits, (4) offers alternatives for energy optimization during plant's life-cycle, and (5) ensures reliable GHG emissions inventory reporting for permitting and regulatory compliance.

Development of a molecular approach to describe the composition of Trichoderma communities.

PubMed

Meincke, Remo; Weinert, Nicole; Radl, Viviane; Schloter, Michael; Smalla, Kornelia; Berg, Gabriele

2010-01-01

Trichoderma and its teleomorphic stage Hypocrea play a key role for ecosystem functioning in terrestrial habitats. However, little is known about the ecology of the fungus. In this study we developed a novel Trichoderma-specific primer pair for diversity analysis. Based on a broad range master alignment, specific Trichoderma primers (ITSTrF/ITSTrR) were designed that comprise an approximate 650bp fragment of the internal transcribed spacer region from all taxonomic clades of the genus Trichoderma. This amplicon is suitable for identification with TrichoKey and TrichoBLAST. Moreover, this primer system was successfully applied to study the Trichoderma communities in the rhizosphere of different potato genotypes grown at two field sites in Germany. Cloning and sequencing confirmed the specificity of the primer and revealed a site-dependent Trichoderma composition. Based on the new primer system a semi-nested approach was used to generate amplicons suitable for denaturing gradient gel electrophoresis (DGGE) analysis and applied to analyse Trichoderma communities in the rhizosphere of potatoes. High field heterogeneity of Trichoderma communities was revealed by both DGGE. Furthermore, qPCR showed significantly different Trichoderma copy numbers between the sites. Copyright 2009 Elsevier B.V. All rights reserved.

Natural attenuation software (NAS): Assessing remedial strategies and estimating timeframes

USGS Publications Warehouse

Mendez, E.; Widdowson, M.; Chapelle, F.; Casey, C.

2005-01-01

Natural Attenuation Software (NAS) is a screening tool to estimate remediation timeframes for monitored natural attenuation (MNA) and to assist in decision-making on the level of source zone treatment in conjunction with MNA using site-specific remediation objectives. Natural attenuation processes that NAS models include are advection, dispersion, sorption, non-aqueous phase liquid (NAPL) dissolution, and biodegradation of either petroleum hydrocarbons or chlorinated ethylenes. Newly-implemented enhancements to NAS designed to maximize the utility of NAS for site managers were observed. NAS has expanded source contaminant specification options to include chlorinated ethanes and chlorinated methanes, and to allow for the analysis of any other user-defined contaminants that may be subject to microbially-mediated transformations (heavy metals, radioisotopes, etc.). Included is the capability to model co-mingled plumes, with constituents from multiple contaminant categories. To enable comparison of remediation timeframe estimates between MNA and specific engineered remedial actions , NAS was modified to incorporate an estimation technique for timeframes associated with pump-and-treat remediation technology for comparison to MNA. This is an abstract of a paper presented at the 8th International In Situ and On-Site Bioremediation Symposium (Baltimore, MD 6/6-9/2005).

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

Dallman, Ann Renee; Neary, Vincent Sinclair

This report presents met - ocean data and wave energy characteristics at three U.S. wave energy converter (WEC) test and potential deployment sites . Its purpose is to enable the compari son of wave resource characteristics among sites as well as the select io n of test sites that are most suitable for a developer's device and that best meet their testing needs and objectives . It also provides essential inputs for the design of WEC test devices and planning WEC tests, including the planning of deployment and op eration s and maintenance. For each site, this report catalogues wavemore » statistics recommended in the (draft) International Electrotechnical Commission Technical Specification (IEC 62600 - 101 TS) on Wave Energy Characterization, as well as the frequency of oc currence of weather windows and extreme sea states, and statistics on wind and ocean currents. It also provides useful information on test site infrastructure and services .« less

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

Haney, Thomas Jay

This report documents the Data Quality Objectives (DQOs) developed for the Idaho National Laboratory (INL) Site ambient air surveillance program. The development of the DQOs was based on the seven-step process recommended “for systematic planning to generate performance and acceptance criteria for collecting environmental data” (EPA 2006). The process helped to determine the type, quantity, and quality of data needed to meet current regulatory requirements and to follow U.S. Department of Energy guidance for environmental surveillance air monitoring design. It also considered the current air monitoring program that has existed at INL Site since the 1950s. The development of themore » DQOs involved the application of the atmospheric dispersion model CALPUFF to identify likely contamination dispersion patterns at and around the INL Site using site-specific meteorological data. Model simulations were used to quantitatively assess the probable frequency of detection of airborne radionuclides released by INL Site facilities using existing and proposed air monitors.« less

The use of tetragnathid spiders as bioindicators of metal exposure at a coal ash spill site.

PubMed

Otter, Ryan R; Hayden, Mary; Mathews, Teresa; Fortner, Allison; Bailey, Frank C

2013-09-01

On 22 December 2008, a dike containing coal fly ash from the Tennessee Valley Authority Kingston Fossil Fuel Plant (TN, USA) failed, resulting in the largest coal ash spill in US history. The present study was designed to determine sediment metal concentrations at multiple site locations and to determine whether site-specific bioaccumulation of metals existed in tetragnathid spiders. Selenium and nickel were the only 2 metals to exceed the US Environmental Protection Agency sediment screening levels. Selenium concentrations in spiders were significantly higher at ash-affected sites than in those from reference sites. The ratio of methylmercury to total mercury in spiders was found to be similar to that in other organisms (65-75%), which highlights the potential use of tetragnathid spiders as an indicator species for tracing contaminant transfer between the aquatic and terrestrial ecosystems. Copyright © 2013 SETAC.

Kirschenmann Road multi-well monitoring site, Cuyama Valley, Santa Barbara County, California

USGS Publications Warehouse

Everett, R.R.; Hanson, R.T.; Sweetkind, D.S.

2011-01-01

The U.S. Geological Survey (USGS), in cooperation with the Water Agency Division of the Santa Barbara County Department of Public Works, is evaluating the geohydrology and water availability of the Cuyama Valley, California (fig. 1). As part of this evaluation, the USGS installed the Cuyama Valley Kirschenmann Road multiple-well monitoring site (CVKR) in the South-Main subregion of the Cuyama Valley (fig. 1). The CVKR well site is designed to allow for the collection of depth-specific water-level and water-quality data. Data collected at this site provides information about the geology, hydrology, geophysics, and geochemistry of the local aquifer system, thus, enhancing the understanding of the geohydrologic framework of the Cuyama Valley. This report presents the construction information and initial geohydrologic data collected from the CVKR monitoring site, along with a brief comparison to selected supply and irrigation wells from the major subregions of the Cuyama Valley (fig. 1).

A procedure to select ground-motion time histories for deterministic seismic hazard analysis from the Next Generation Attenuation (NGA) database

NASA Astrophysics Data System (ADS)

Huang, Duruo; Du, Wenqi; Zhu, Hong

2017-10-01

In performance-based seismic design, ground-motion time histories are needed for analyzing dynamic responses of nonlinear structural systems. However, the number of ground-motion data at design level is often limited. In order to analyze seismic performance of structures, ground-motion time histories need to be either selected from recorded strong-motion database or numerically simulated using stochastic approaches. In this paper, a detailed procedure to select proper acceleration time histories from the Next Generation Attenuation (NGA) database for several cities in Taiwan is presented. Target response spectra are initially determined based on a local ground-motion prediction equation under representative deterministic seismic hazard analyses. Then several suites of ground motions are selected for these cities using the Design Ground Motion Library (DGML), a recently proposed interactive ground-motion selection tool. The selected time histories are representatives of the regional seismic hazard and should be beneficial to earthquake studies when comprehensive seismic hazard assessments and site investigations are unavailable. Note that this method is also applicable to site-specific motion selections with the target spectra near the ground surface considering the site effect.

Preliminary Thermal Modeling of HI-STORM 100 Storage Modules at Diablo Canyon Power Plant ISFSI

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

Cuta, Judith M.; Adkins, Harold E.

Thermal analysis is being undertaken at Pacific Northwest National Laboratory (PNNL) in support of inspections of selected storage modules at various locations around the United States, as part of the Used Fuel Disposition Campaign of the U.S. Department of Energy, Office of Nuclear Energy (DOE-NE) Fuel Cycle Research and Development. This report documents pre-inspection predictions of temperatures for two modules at the Diablo Canyon Power Plant ISFSI identified as candidates for inspection. These are HI-STORM 100 modules of a site-specific design for storing PWR 17x17 fuel in MPC-32 canisters. The temperature predictions reported in this document were obtained with detailedmore » COBRA-SFS models of these storage systems, with the following boundary conditions and assumptions. • storage module overpack configuration based on FSAR documentation of HI-STORM100S-218, Version B; due to unavailability of site-specific design data for Diablo Canyon ISFSI modules • Individual assembly and total decay heat loadings for each canister, based on at-loading values provided by PG&E, “aged” to time of inspection using ORIGEN modeling o Special Note: there is an inherent conservatism of unquantified magnitude – informally estimated as up to approximately 20% -- in the utility-supplied values for at-loading assembly decay heat values • Axial decay heat distributions based on a bounding generic profile for PWR fuel. • Axial location of beginning of fuel assumed same as WE 17x17 OFA fuel, due to unavailability of specific data for WE17x17 STD and WE 17x17 Vantage 5 fuel designs • Ambient conditions of still air at 50°F (10°C) assumed for base-case evaluations o Wind conditions at the Diablo Canyon site are unquantified, due to unavailability of site meteorological data o additional still-air evaluations performed at 70°F (21°C), 60°F (16°C), and 40°F (4°C), to cover a range of possible conditions at the time of the inspection. (Calculations were also performed at 80°F (27°C), for comparison with design basis assumptions.) All calculations are for steady-state conditions, on the assumption that the surfaces of the module that are accessible for temperature measurements during the inspection will tend to follow ambient temperature changes relatively closely. Comparisons to the results of the inspections, and post-inspection evaluations of temperature measurements obtained in the specific modules, will be documented in a separate follow-on report, to be issued in a timely manner after the inspection has been performed.« less

LSST summit facility construction progress report: reacting to design refinements and field conditions

NASA Astrophysics Data System (ADS)

Barr, Jeffrey D.; Gressler, William; Sebag, Jacques; Seriche, Jaime; Serrano, Eduardo

2016-07-01

The civil work, site infrastructure and buildings for the summit facility of the Large Synoptic Survey Telescope (LSST) are among the first major elements that need to be designed, bid and constructed to support the subsequent integration of the dome, telescope, optics, camera and supporting systems. As the contracts for those other major subsystems now move forward under the management of the LSST Telescope and Site (T and S) team, there has been inevitable and beneficial evolution in their designs, which has resulted in significant modifications to the facility and infrastructure. The earliest design requirements for the LSST summit facility were first documented in 2005, its contracted full design was initiated in 2010, and construction began in January, 2015. During that entire development period, and extending now roughly halfway through construction, there continue to be necessary modifications to the facility design resulting from the refinement of interfaces to other major elements of the LSST project and now, during construction, due to unanticipated field conditions. Changes from evolving interfaces have principally involved the telescope mount, the dome and mirror handling/coating facilities which have included significant variations in mass, dimensions, heat loads and anchorage conditions. Modifications related to field conditions have included specifying and testing alternative methods of excavation and contending with the lack of competent rock substrate where it was predicted to be. While these and other necessary changes are somewhat specific to the LSST project and site, they also exemplify inherent challenges related to the typical timeline for the design and construction of astronomical observatory support facilities relative to the overall development of the project.

Role of particle size, shape, and stiffness in design of intravascular drug delivery systems: insights from computations, experiments, and nature.

PubMed

Sen Gupta, Anirban

2016-01-01

Packaging of drug molecules within microparticles and nanoparticles has become an important strategy in intravascular drug delivery, where the particles are designed to protect the drugs from plasma effects, increase drug residence time in circulation, and often facilitate drug delivery specifically at disease sites. To this end, over the past few decades, interdisciplinary research has focused on developing biocompatible materials for particle fabrication, technologies for particle manufacture, drug formulation within the particles for efficient loading, and controlled release and refinement of particle surface chemistries to render selectivity toward disease site for site-selective action. Majority of the particle systems developed for such purposes are spherical nano and microparticles and they have had low-to-moderate success in clinical translation. To refine the design of delivery systems for enhanced performance, in recent years, researchers have started focusing on the physicomechanical aspects of carrier particles, especially their shape, size, and stiffness, as new design parameters. Recent computational modeling studies, as well as, experimental studies using microfluidic devices are indicating that these design parameters greatly influence the particles' behavior in hemodynamic circulation, as well as cell-particle interactions for targeted payload delivery. Certain cellular components of circulation are also providing interesting natural cues for refining the design of drug carrier systems. Based on such findings, new benefits and challenges are being realized for the next generation of drug carriers. The current article will provide a comprehensive review of these findings and discuss the emerging design paradigm of incorporating physicomechanical components in fabrication of particulate drug delivery systems. © 2015 Wiley Periodicals, Inc.

An unconventional origin of metal-ion rescue and inhibition in the Tetrahymena group I ribozyme reaction.

PubMed Central

Shan, S O; Herschlag, D

2000-01-01

The presence of catalytic metal ions in RNA active sites has often been inferred from metal-ion rescue of modified substrates and sometimes from inhibitory effects of alternative metal ions. Herein we report that, in the Tetrahymena group I ribozyme reaction, the deleterious effect of a thio substitution at the pro-Sp position of the reactive phosphoryl group is rescued by Mn2+. However, analysis of the reaction of this thio substrate and of substrates with other modifications strongly suggest that this rescue does not stem from a direct Mn2+ interaction with the Sp sulfur. Instead, the apparent rescue arises from a Mn2+ ion interacting with the residue immediately 3' of the cleavage site, A(+1), that stabilizes the tertiary interactions between the oligonucleotide substrate (S) and the active site. This metal site is referred to as site D herein. We also present evidence that a previously observed Ca2+ ion that inhibits the chemical step binds to metal site D. These and other observations suggest that, whereas the interactions of Mn2+ at site D are favorable for the chemical reaction, the Ca2+ at site D exerts its inhibitory effect by disrupting the alignment of the substrates within the active site. These results emphasize the vigilance necessary in the design and interpretation of metal-ion rescue and inhibition experiments. Conversely, in-depth mechanistic analysis of the effects of site-specific substrate modifications can allow the effects of specific metal ion-RNA interactions to be revealed and the properties of individual metal-ion sites to be probed, even within the sea of metal ions bound to RNA. PMID:10864040

Statistical and Economic Techniques for Site-specific Nematode Management.

PubMed

Liu, Zheng; Griffin, Terry; Kirkpatrick, Terrence L

2014-03-01

Recent advances in precision agriculture technologies and spatial statistics allow realistic, site-specific estimation of nematode damage to field crops and provide a platform for the site-specific delivery of nematicides within individual fields. This paper reviews the spatial statistical techniques that model correlations among neighboring observations and develop a spatial economic analysis to determine the potential of site-specific nematicide application. The spatial econometric methodology applied in the context of site-specific crop yield response contributes to closing the gap between data analysis and realistic site-specific nematicide recommendations and helps to provide a practical method of site-specifically controlling nematodes.

Widespread evidence of cooperative DNA binding by transcription factors in Drosophila development

PubMed Central

Kazemian, Majid; Pham, Hannah; Wolfe, Scot A.; Brodsky, Michael H.; Sinha, Saurabh

2013-01-01

Regulation of eukaryotic gene transcription is often combinatorial in nature, with multiple transcription factors (TFs) regulating common target genes, often through direct or indirect mutual interactions. Many individual examples of cooperative binding by directly interacting TFs have been identified, but it remains unclear how pervasive this mechanism is during animal development. Cooperative TF binding should be manifest in genomic sequences as biased arrangements of TF-binding sites. Here, we explore the extent and diversity of such arrangements related to gene regulation during Drosophila embryogenesis. We used the DNA-binding specificities of 322 TFs along with chromatin accessibility information to identify enriched spacing and orientation patterns of TF-binding site pairs. We developed a new statistical approach for this task, specifically designed to accurately assess inter-site spacing biases while accounting for the phenomenon of homotypic site clustering commonly observed in developmental regulatory regions. We observed a large number of short-range distance preferences between TF-binding site pairs, including examples where the preference depends on the relative orientation of the binding sites. To test whether these binding site patterns reflect physical interactions between the corresponding TFs, we analyzed 27 TF pairs whose binding sites exhibited short distance preferences. In vitro protein–protein binding experiments revealed that >65% of these TF pairs can directly interact with each other. For five pairs, we further demonstrate that they bind cooperatively to DNA if both sites are present with the preferred spacing. This study demonstrates how DNA-binding motifs can be used to produce a comprehensive map of sequence signatures for different mechanisms of combinatorial TF action. PMID:23847101

Widespread evidence of cooperative DNA binding by transcription factors in Drosophila development.

PubMed

Kazemian, Majid; Pham, Hannah; Wolfe, Scot A; Brodsky, Michael H; Sinha, Saurabh

2013-09-01

Regulation of eukaryotic gene transcription is often combinatorial in nature, with multiple transcription factors (TFs) regulating common target genes, often through direct or indirect mutual interactions. Many individual examples of cooperative binding by directly interacting TFs have been identified, but it remains unclear how pervasive this mechanism is during animal development. Cooperative TF binding should be manifest in genomic sequences as biased arrangements of TF-binding sites. Here, we explore the extent and diversity of such arrangements related to gene regulation during Drosophila embryogenesis. We used the DNA-binding specificities of 322 TFs along with chromatin accessibility information to identify enriched spacing and orientation patterns of TF-binding site pairs. We developed a new statistical approach for this task, specifically designed to accurately assess inter-site spacing biases while accounting for the phenomenon of homotypic site clustering commonly observed in developmental regulatory regions. We observed a large number of short-range distance preferences between TF-binding site pairs, including examples where the preference depends on the relative orientation of the binding sites. To test whether these binding site patterns reflect physical interactions between the corresponding TFs, we analyzed 27 TF pairs whose binding sites exhibited short distance preferences. In vitro protein-protein binding experiments revealed that >65% of these TF pairs can directly interact with each other. For five pairs, we further demonstrate that they bind cooperatively to DNA if both sites are present with the preferred spacing. This study demonstrates how DNA-binding motifs can be used to produce a comprehensive map of sequence signatures for different mechanisms of combinatorial TF action.

Wind energy development: methods for assessing risks to birds and bats pre-construction

USGS Publications Warehouse

Katzner, Todd E.; Bennett, Victoria; Miller, Tricia A.; Duerr, Adam E.; Braham, Melissa A.; Hale, Amanda

2016-01-01

Wind power generation is rapidly expanding. Although wind power is a low-carbon source of energy, it can impact negatively birds and bats, either directly through fatality or indirectly by displacement or habitat loss. Pre-construction risk assessment at wind facilities within the United States is usually required only on public lands. When conducted, it generally involves a 3-tier process, with each step leading to more detailed and rigorous surveys. Preliminary site assessment (U.S. Fish and Wildlife Service, Tier 1) is usually conducted remotely and involves evaluation of existing databases and published materials. If potentially at-risk wildlife are present and the developer wishes to continue the development process, then on-site surveys are conducted (Tier 2) to verify the presence of those species and to assess site-specific features (e.g., topography, land cover) that may influence risk from turbines. The next step in the process (Tier 3) involves quantitative or scientific studies to assess the potential risk of the proposed project to wildlife. Typical Tier-3 research may involve acoustic, aural, observational, radar, capture, tracking, or modeling studies, all designed to understand details of risk to specific species or groups of species at the given site. Our review highlights several features lacking from many risk assessments, particularly the paucity of before-and-after-control- impact (BACI) studies involving modeling and a lack of understanding of cumulative effects of wind facilities on wildlife. Both are essential to understand effective designs for pre-construction monitoring and both would help expand risk assessment beyond eagles.

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

Jacob, Reed B.; Ding, Feng; Ye, Dongmei

Organophosphates are widely used for peaceful (agriculture) and military purposes (chemical warfare agents). The extraordinary toxicity of organophosphates and the risk of deployment, make it critical to develop means for their rapid and efficient deactivation. Organophosphate hydrolase (OPH) already plays an important role in organophosphate remediation, but is insufficient for therapeutic or prophylactic purposes primarily due to low substrate affinity. Current efforts focus on directly modifying the active site to differentiate substrate specificity and increase catalytic activity. Here, we present a novel strategy for enhancing the general catalytic efficiency of OPH through computational redesign of the residues that are allostericallymore » coupled to the active site and validated our design by mutagenesis. Specifically, we identify five such hot-spot residues for allosteric regulation and assay these mutants for hydrolysis activity against paraoxon, a chemical-weapons simulant. A high percentage of the predicted mutants exhibit enhanced activity over wild-type (k cat =16.63 s -1), such as T199I/T54I (899.5 s -1) and C227V/T199I/T54I (848 s -1), while the Km remains relatively unchanged in our high-throughput cell-free expression system. Further computational studies of protein dynamics reveal four distinct distal regions coupled to the active site that display significant changes in conformation dynamics upon these identified mutations. These results validate a computational design method that is both efficient and easily adapted as a general procedure for enzymatic enhancement.« less

3D simulation as a tool for improving the safety culture during remediation work at Andreeva Bay.

PubMed

Chizhov, K; Sneve, M K; Szőke, I; Mazur, I; Mark, N K; Kudrin, I; Shandala, N; Simakov, A; Smith, G M; Krasnoschekov, A; Kosnikov, A; Kemsky, I; Kryuchkov, V

2014-12-01

Andreeva Bay in northwest Russia hosts one of the former coastal technical bases of the Northern Fleet. Currently, this base is designated as the Andreeva Bay branch of Northwest Center for Radioactive Waste Management (SevRAO) and is a site of temporary storage (STS) for spent nuclear fuel (SNF) and other radiological waste generated during the operation and decommissioning of nuclear submarines and ships. According to an integrated expert evaluation, this site is the most dangerous nuclear facility in northwest Russia. Environmental rehabilitation of the site is currently in progress and is supported by strong international collaboration. This paper describes how the optimization principle (ALARA) has been adopted during the planning of remediation work at the Andreeva Bay STS and how Russian-Norwegian collaboration greatly contributed to ensuring the development and maintenance of a high level safety culture during this process. More specifically, this paper describes how integration of a system, specifically designed for improving the radiological safety of workers during the remediation work at Andreeva Bay, was developed in Russia. It also outlines the 3D radiological simulation and virtual reality based systems developed in Norway that have greatly facilitated effective implementation of the ALARA principle, through supporting radiological characterisation, work planning and optimization, decision making, communication between teams and with the authorities and training of field operators.

Site specificity of adrenalectomy-induced brain growth.

PubMed

Thomas, T L; Devenport, L D

1988-12-01

Infant, juvenile, and adult brain growth is modulated by corticosterone. This study was designed to determine whether such modulation is confined to certain specific brain areas, and if the pattern of growth revealed is consistent across strains of rats. Young female Sprague-Dawley-derived rats were either adrenalectomized (ADX) or sham-operated (Sham) and allowed to mature 45 days before they were sacrificed for histological analysis. Fore brain sections were taken at several planes for display by projection microscope. Of the 21 sites examined, ADX exerted its greatest effect upon neocortical tissue and myelinated fiber tracts. The only other brain region affected was thalamus, which exhibited a significant widening as a result of ADX. In contrast, archicortical structures were notably unaffected by ADX. Neither the hippocampus, measured from a variety of planes, nor nuclei in the septal area were subject to increased growth by ADX. This general portrayal of ADX's site specificity held across strains of rats. However, there were local differences. Within the neopallium, the frontal region underwent the greatest thickening in one strain, while the occipital area was most strongly affected in the other. Parietal cortex was equally responsive in both strains. The pattern of sensitive vs insensitive sites bore a resemblance to the pattern of increased growth brought about by environmental enrichment as well as the fore brain distribution of Type 2 corticosterone receptors.

Investigation of the Binding Profiles of AZD2184 and Thioflavin T with Amyloid-β(1-42) Fibril by Molecular Docking and Molecular Dynamics Methods.

PubMed

Kuang, Guanglin; Murugan, N Arul; Tu, Yaoquan; Nordberg, Agneta; Ågren, Hans

2015-09-03

Detecting deposits of amyloid β fibrils in the brain is of paramount importance for an early diagnosis of Alzheimer's disease. A number of PET tracers have been developed for amyloid imaging, but many suffer from poor specificity and large signal to background ratio. Design of tracers with specificity and improved binding affinity requires knowledge about various potential binding sites in the amyloid β fibril available for the tracers and the nature of the local microenvironment of these sites. In this study we investigate the local structure of fibrils using two important probes, namely, thioflavin T (a fluorescent probe) and AZD2184 (a PET tracer). The target structures for amyloid-β(1-42) fibril are based on reported NMR solution models. By explicitly considering the effect of fibril flexibility on the available binding sites for all these models, the binding affinity of these probes has been investigated. The binding profiles of AZD2184 and thioflavin T were studied by molecular docking and molecular dynamics simulation methods. The two compounds were found to bind at the same sites of the fibril: three of which are within the fibril, and one is on the two sides of the Met35 residue on the surface. The binding affinity of AZD2184 and thioflavin T is found to be higher at the core sites than on the surface due to more contact residues. The binding affinity of AZD2184 is much higher than that of thioflavin T at every site due to electrostatic interaction and spatial restriction, which is in good agreement with experimental observation. However, the structural change of thioflavin T is much more significant than that of AZD2184, which is the chemical basis for its usage as a fluorescent probe. The ramifications of these results for the design and optimization of PET radioligands and fluorescent probes are briefly discussed.

Design and implementation of a fault-tolerant and dynamic metadata database for clinical trials

NASA Astrophysics Data System (ADS)

Lee, J.; Zhou, Z.; Talini, E.; Documet, J.; Liu, B.

2007-03-01

In recent imaging-based clinical trials, quantitative image analysis (QIA) and computer-aided diagnosis (CAD) methods are increasing in productivity due to higher resolution imaging capabilities. A radiology core doing clinical trials have been analyzing more treatment methods and there is a growing quantity of metadata that need to be stored and managed. These radiology centers are also collaborating with many off-site imaging field sites and need a way to communicate metadata between one another in a secure infrastructure. Our solution is to implement a data storage grid with a fault-tolerant and dynamic metadata database design to unify metadata from different clinical trial experiments and field sites. Although metadata from images follow the DICOM standard, clinical trials also produce metadata specific to regions-of-interest and quantitative image analysis. We have implemented a data access and integration (DAI) server layer where multiple field sites can access multiple metadata databases in the data grid through a single web-based grid service. The centralization of metadata database management simplifies the task of adding new databases into the grid and also decreases the risk of configuration errors seen in peer-to-peer grids. In this paper, we address the design and implementation of a data grid metadata storage that has fault-tolerance and dynamic integration for imaging-based clinical trials.

Building clinical trial capacity to develop a new treatment for multidrug-resistant tuberculosis.

PubMed

Tupasi, Thelma; Gupta, Rajesh; Danilovits, Manfred; Cirule, Andra; Sanchez-Garavito, Epifanio; Xiao, Heping; Cabrera-Rivero, Jose L; Vargas-Vasquez, Dante E; Gao, Mengqiu; Awad, Mohamed; Gentry, Leesa M; Geiter, Lawrence J; Wells, Charles D

2016-02-01

New drugs for infectious diseases often need to be evaluated in low-resource settings. While people working in such settings often provide high-quality care and perform operational research activities, they generally have less experience in conducting clinical trials designed for drug approval by stringent regulatory authorities. We carried out a capacity-building programme during a multi-centre randomized controlled trial of delamanid, a new drug for the treatment of multidrug-resistant tuberculosis. The programme included: (i) site identification and needs assessment; (ii) achieving International Conference on Harmonization - Good Clinical Practice (ICH-GCP) standards; (iii) establishing trial management; and (iv) increasing knowledge of global and local regulatory issues. Trials were conducted at 17 sites in nine countries (China, Egypt, Estonia, Japan, Latvia, Peru, the Philippines, the Republic of Korea and the United States of America). Eight of the 10 sites in low-resource settings had no experience in conducting the requisite clinical trials. Extensive capacity-building was done in all 10 sites. The programme resulted in improved local capacity in key areas such as trial design, data safety and monitoring, trial conduct and laboratory services. Clinical trials designed to generate data for regulatory approval require additional efforts beyond traditional research-capacity strengthening. Such capacity-building approaches provide an opportunity for product development partnerships to improve health systems beyond the direct conduct of the specific trial.

Efficient Hepatic Delivery of Drugs: Novel Strategies and Their Significance

PubMed Central

Yadav, Narayan Prasad; Jain, Sanyog; Arora, Sumit

2013-01-01

Liver is a vital organ responsible for plethora of functions including detoxification, protein synthesis, and the production of biochemicals necessary for the sustenance of life. Therefore, patients with chronic liver diseases such as viral hepatitis, liver cirrhosis, and hepatocellular carcinoma need immediate attention to sustain life and as a result are often exposed to the prolonged treatment with drugs/herbal medications. Lack of site-specific delivery of these medications to the hepatocytes/nonparenchymal cells and adverse effects associated with their off-target interactions limit their continuous use. This calls for the development and fabrication of targeted delivery systems which can deliver the drug payload at the desired site of action for defined period of time. The primary aim of drug targeting is to manipulate the whole body distribution of drugs, that is, to prevent distribution to non-target cells and concomitantly increase the drug concentration at the targeted site. Carrier molecules are designed for their selective cellular uptake, taking advantage of specific receptors or binding sites present on the surface membrane of the target cell. In this review, various aspects of liver targeting of drug molecules and herbal medications have been discussed which elucidate the importance of delivering the drugs/herbal medications at their desired site of action. PMID:24286077

Adaptive Sampling approach to environmental site characterization at Joliet Army Ammunition Plant: Phase 2 demonstration

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

Bujewski, G.E.; Johnson, R.L.

1996-04-01

Adaptive sampling programs provide real opportunities to save considerable time and money when characterizing hazardous waste sites. This Strategic Environmental Research and Development Program (SERDP) project demonstrated two decision-support technologies, SitePlanner{trademark} and Plume{trademark}, that can facilitate the design and deployment of an adaptive sampling program. A demonstration took place at Joliet Army Ammunition Plant (JAAP), and was unique in that it was tightly coupled with ongoing Army characterization work at the facility, with close scrutiny by both state and federal regulators. The demonstration was conducted in partnership with the Army Environmental Center`s (AEC) Installation Restoration Program and AEC`s Technology Developmentmore » Program. AEC supported researchers from Tufts University who demonstrated innovative field analytical techniques for the analysis of TNT and DNT. SitePlanner{trademark} is an object-oriented database specifically designed for site characterization that provides an effective way to compile, integrate, manage and display site characterization data as it is being generated. Plume{trademark} uses a combination of Bayesian analysis and geostatistics to provide technical staff with the ability to quantitatively merge soft and hard information for an estimate of the extent of contamination. Plume{trademark} provides an estimate of contamination extent, measures the uncertainty associated with the estimate, determines the value of additional sampling, and locates additional samples so that their value is maximized.« less

A global optimization algorithm for protein surface alignment

PubMed Central

2010-01-01

Background A relevant problem in drug design is the comparison and recognition of protein binding sites. Binding sites recognition is generally based on geometry often combined with physico-chemical properties of the site since the conformation, size and chemical composition of the protein surface are all relevant for the interaction with a specific ligand. Several matching strategies have been designed for the recognition of protein-ligand binding sites and of protein-protein interfaces but the problem cannot be considered solved. Results In this paper we propose a new method for local structural alignment of protein surfaces based on continuous global optimization techniques. Given the three-dimensional structures of two proteins, the method finds the isometric transformation (rotation plus translation) that best superimposes active regions of two structures. We draw our inspiration from the well-known Iterative Closest Point (ICP) method for three-dimensional (3D) shapes registration. Our main contribution is in the adoption of a controlled random search as a more efficient global optimization approach along with a new dissimilarity measure. The reported computational experience and comparison show viability of the proposed approach. Conclusions Our method performs well to detect similarity in binding sites when this in fact exists. In the future we plan to do a more comprehensive evaluation of the method by considering large datasets of non-redundant proteins and applying a clustering technique to the results of all comparisons to classify binding sites. PMID:20920230