Ecological Condition of Streams in Eastern and Southern NevadaEPA R-EMAP Muddy-Virgin River Project

EPA Science Inventory

The report presents data collected during a one year study period beginning in May of 2000. Sampling sites were selected using a probability-based design (as opposed to subjectively selected sites) using the USEPA River Reach File version 3 (RF3). About 37 sites were sampled. ...

Summary of the US Army Corps of Engineers/US Environmental Protection Agency Field Verification Program

DTIC Science & Technology

1988-10-01

sites tend to be colonized by aquatic organisms adapted to an intertidal existence and by typical wetland plants. These plants may or may not be the...the upland site and within the intertidal range for the wetland site. Site Selection and Design Site selection 15. Acceptable sites for upland and... intertidal range. Along one side of the site, a sandbag dike was constructed that could be removed after filling to provide easy tidal interchange

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.

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

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...

Making the Most of Your School Site. School Buildings Planning, Design, and Construction Series No. 2.

ERIC Educational Resources Information Center

Odell, John H.

A school construction guide offers key personnel in school development projects information on the complex task of master planning and construction of schools in Australia. This chapter of the guide provides advice on site selection covering selection criteria; traffic issues; and site services, such as water, power, and sewer. Additionally…

Discovery of Selective Inhibitors of Imidazoleglycerol-Phosphate Dehydratase from Mycobacterium tuberculosis by Virtual Screening

NASA Astrophysics Data System (ADS)

Podshivalov, D.; Mandzhieva, Yu. B.; Sidorov-Biryukov, D. D.; Timofeev, V. I.; Kuranova, I. P.

2018-01-01

Bacterial imidazoleglycerol-phosphate dehydratase from Mycobacterium tuberculosis (HisB- Mt) is a convenient target for the discovery of selective inhibitors as potential antituberculosis drugs. The virtual screening was performed to find compounds suitable for the design of selective inhibitors of HisB- Mt. The positions of four ligands, which were selected based on the docking scoring function and docked to the activesite region of the enzyme, were refined by molecular dynamics simulation. The nearest environment of the ligands was determined. These compounds selectively bind to functionally essential active-site residues, thus blocking access of substrates to the active site of the enzyme, and can be used as lead compounds for the design of selective inhibitors of HisB- M.

Use of an Improved Matching Algorithm to Select Scaffolds for Enzyme Design Based on a Complex Active Site Model.

PubMed

Huang, Xiaoqiang; Xue, Jing; Lin, Min; Zhu, Yushan

2016-01-01

Active site preorganization helps native enzymes electrostatically stabilize the transition state better than the ground state for their primary substrates and achieve significant rate enhancement. In this report, we hypothesize that a complex active site model for active site preorganization modeling should help to create preorganized active site design and afford higher starting activities towards target reactions. Our matching algorithm ProdaMatch was improved by invoking effective pruning strategies and the native active sites for ten scaffolds in a benchmark test set were reproduced. The root-mean squared deviations between the matched transition states and those in the crystal structures were < 1.0 Å for the ten scaffolds, and the repacking calculation results showed that 91% of the hydrogen bonds within the active sites are recovered, indicating that the active sites can be preorganized based on the predicted positions of transition states. The application of the complex active site model for de novo enzyme design was evaluated by scaffold selection using a classic catalytic triad motif for the hydrolysis of p-nitrophenyl acetate. Eighty scaffolds were identified from a scaffold library with 1,491 proteins and four scaffolds were native esterase. Furthermore, enzyme design for complicated substrates was investigated for the hydrolysis of cephalexin using scaffold selection based on two different catalytic motifs. Only three scaffolds were identified from the scaffold library by virtue of the classic catalytic triad-based motif. In contrast, 40 scaffolds were identified using a more flexible, but still preorganized catalytic motif, where one scaffold corresponded to the α-amino acid ester hydrolase that catalyzes the hydrolysis and synthesis of cephalexin. Thus, the complex active site modeling approach for de novo enzyme design with the aid of the improved ProdaMatch program is a promising approach for the creation of active sites with high catalytic efficiencies towards target reactions.

Use of an Improved Matching Algorithm to Select Scaffolds for Enzyme Design Based on a Complex Active Site Model

PubMed Central

Huang, Xiaoqiang; Xue, Jing; Lin, Min; Zhu, Yushan

2016-01-01

Active site preorganization helps native enzymes electrostatically stabilize the transition state better than the ground state for their primary substrates and achieve significant rate enhancement. In this report, we hypothesize that a complex active site model for active site preorganization modeling should help to create preorganized active site design and afford higher starting activities towards target reactions. Our matching algorithm ProdaMatch was improved by invoking effective pruning strategies and the native active sites for ten scaffolds in a benchmark test set were reproduced. The root-mean squared deviations between the matched transition states and those in the crystal structures were < 1.0 Å for the ten scaffolds, and the repacking calculation results showed that 91% of the hydrogen bonds within the active sites are recovered, indicating that the active sites can be preorganized based on the predicted positions of transition states. The application of the complex active site model for de novo enzyme design was evaluated by scaffold selection using a classic catalytic triad motif for the hydrolysis of p-nitrophenyl acetate. Eighty scaffolds were identified from a scaffold library with 1,491 proteins and four scaffolds were native esterase. Furthermore, enzyme design for complicated substrates was investigated for the hydrolysis of cephalexin using scaffold selection based on two different catalytic motifs. Only three scaffolds were identified from the scaffold library by virtue of the classic catalytic triad-based motif. In contrast, 40 scaffolds were identified using a more flexible, but still preorganized catalytic motif, where one scaffold corresponded to the α-amino acid ester hydrolase that catalyzes the hydrolysis and synthesis of cephalexin. Thus, the complex active site modeling approach for de novo enzyme design with the aid of the improved ProdaMatch program is a promising approach for the creation of active sites with high catalytic efficiencies towards target reactions. PMID:27243223

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.

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

Primer on the Implementation of a Pharmacy Intranet Site to Improve Department Communication

PubMed Central

Hale, Holly J.

2013-01-01

Purpose: The purpose of the article is to describe the experience of selecting, developing, and implementing a pharmacy department intranet site with commentary regarding application to other institutions. Clinical practitioners and supporting staff need an effective, efficient, organized, and user-friendly communication tool to utilize and relay information required to optimize patient care. Summary: To create a functional and user-friendly department intranet site, department leadership and staff should be involved in the process from selection of product through implementation. A product that supports both document storage management and communication delivery and has the capability to be customized to provide varied levels of site access is desirable. The designation of an intranet site owner/developer within the department will facilitate purposeful site design and site maintenance execution. A well-designed and up-to-date site along with formal end-user training are essential for staff adoption and continued utilization. Conclusion: Development of a department intranet site requires a considerable time investment by several members of the department. The implementation of an intranet site can be an important step toward achieving improved communications. Staff utilization of this resource is key to its success. PMID:24421523

Primer on the implementation of a pharmacy intranet site to improve department communication.

PubMed

Hale, Holly J

2013-07-01

The purpose of the article is to describe the experience of selecting, developing, and implementing a pharmacy department intranet site with commentary regarding application to other institutions. Clinical practitioners and supporting staff need an effective, efficient, organized, and user-friendly communication tool to utilize and relay information required to optimize patient care. To create a functional and user-friendly department intranet site, department leadership and staff should be involved in the process from selection of product through implementation. A product that supports both document storage management and communication delivery and has the capability to be customized to provide varied levels of site access is desirable. The designation of an intranet site owner/developer within the department will facilitate purposeful site design and site maintenance execution. A well-designed and up-to-date site along with formal end-user training are essential for staff adoption and continued utilization. Development of a department intranet site requires a considerable time investment by several members of the department. The implementation of an intranet site can be an important step toward achieving improved communications. Staff utilization of this resource is key to its success.

Selection of Stream Insect Larvae for Indicating Anthropogenic Impact

EPA Science Inventory

This study examined the total mercury concentrations, [Hg], and 15N values in macro-invertebrates collected from 35 stream sites in Rhode Island, USA, to determine the organism groups most suitable for use as indicators of anthropogenic impact. Site selection was designed to cov...

15 CFR 922.10 - General.

Code of Federal Regulations, 2011 CFR

2011-01-01

... List (SEL) was established as a comprehensive list of marine sites with high natural resource values... site on the SEL, or selection of a site from the SEL as an active candidate for designation as provided...

15 CFR 922.10 - General.

Code of Federal Regulations, 2010 CFR

2010-01-01

... List (SEL) was established as a comprehensive list of marine sites with high natural resource values... site on the SEL, or selection of a site from the SEL as an active candidate for designation as provided...

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

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.

Systematic optimization model and algorithm for binding sequence selection in computational enzyme design

PubMed Central

Huang, Xiaoqiang; Han, Kehang; Zhu, Yushan

2013-01-01

A systematic optimization model for binding sequence selection in computational enzyme design was developed based on the transition state theory of enzyme catalysis and graph-theoretical modeling. The saddle point on the free energy surface of the reaction system was represented by catalytic geometrical constraints, and the binding energy between the active site and transition state was minimized to reduce the activation energy barrier. The resulting hyperscale combinatorial optimization problem was tackled using a novel heuristic global optimization algorithm, which was inspired and tested by the protein core sequence selection problem. The sequence recapitulation tests on native active sites for two enzyme catalyzed hydrolytic reactions were applied to evaluate the predictive power of the design methodology. The results of the calculation show that most of the native binding sites can be successfully identified if the catalytic geometrical constraints and the structural motifs of the substrate are taken into account. Reliably predicting active site sequences may have significant implications for the creation of novel enzymes that are capable of catalyzing targeted chemical reactions. PMID:23649589

Computational Design of Ligand Binding Proteins with High Affinity and Selectivity

PubMed Central

Dou, Jiayi; Doyle, Lindsey; Nelson, Jorgen W.; Schena, Alberto; Jankowski, Wojciech; Kalodimos, Charalampos G.; Johnsson, Kai; Stoddard, Barry L.; Baker, David

2014-01-01

The ability to design proteins with high affinity and selectivity for any given small molecule would have numerous applications in biosensing, diagnostics, and therapeutics, and is a rigorous test of our understanding of the physiochemical principles that govern molecular recognition phenomena. Attempts to design ligand binding proteins have met with little success, however, and the computational design of precise molecular recognition between proteins and small molecules remains an “unsolved problem”1. We describe a general method for the computational design of small molecule binding sites with pre-organized hydrogen bonding and hydrophobic interfaces and high overall shape complementary to the ligand, and use it to design protein binding sites for the steroid digoxigenin (DIG). Of 17 designs that were experimentally characterized, two bind DIG; the highest affinity design has the lowest predicted interaction energy and the most pre-organized binding site in the set. A comprehensive binding-fitness landscape of this design generated by library selection and deep sequencing was used to guide optimization of binding affinity to a picomolar level, and two X-ray co-crystal structures of optimized complexes show atomic level agreement with the design models. The designed binder has a high selectivity for DIG over the related steroids digitoxigenin, progesterone, and β-estradiol, which can be reprogrammed through the designed hydrogen-bonding interactions. Taken together, the binding fitness landscape, co-crystal structures, and thermodynamic binding parameters illustrate how increases in binding affinity can result from distal sequence changes that limit the protein ensemble to conformers making the most energetically favorable interactions with the ligand. The computational design method presented here should enable the development of a new generation of biosensors, therapeutics, and diagnostics. PMID:24005320

Roads and Airfields I (Programed Instruction). Engineer Subcourse 64-9.

ERIC Educational Resources Information Center

Army Engineer School, Fort Belvoir, VA.

The document is a programed text for a correspondence course in the planning, construction, and maintenance of military roads and airfields. There are seven lessons: construction requirements and design criteria; road reconnaissance and site selection; airfield reconnaissance and site selection; layout procedures, construction staking, and field…

40 CFR 228.5 - General criteria for the selection of sites.

Code of Federal Regulations, 2013 CFR

2013-07-01

... levels or to undetectable contaminant concentrations or effects before reaching any beach, shoreline..., designate ocean dumping sites beyond the edge of the continental shelf and other such sites that have been...

40 CFR 228.5 - General criteria for the selection of sites.

Code of Federal Regulations, 2014 CFR

2014-07-01

... levels or to undetectable contaminant concentrations or effects before reaching any beach, shoreline..., designate ocean dumping sites beyond the edge of the continental shelf and other such sites that have been...

40 CFR 228.5 - General criteria for the selection of sites.

Code of Federal Regulations, 2011 CFR

2011-07-01

... levels or to undetectable contaminant concentrations or effects before reaching any beach, shoreline..., designate ocean dumping sites beyond the edge of the continental shelf and other such sites that have been...

40 CFR 228.5 - General criteria for the selection of sites.

Code of Federal Regulations, 2010 CFR

2010-07-01

... levels or to undetectable contaminant concentrations or effects before reaching any beach, shoreline..., designate ocean dumping sites beyond the edge of the continental shelf and other such sites that have been...

40 CFR 228.5 - General criteria for the selection of sites.

Code of Federal Regulations, 2012 CFR

2012-07-01

... levels or to undetectable contaminant concentrations or effects before reaching any beach, shoreline..., designate ocean dumping sites beyond the edge of the continental shelf and other such sites that have been...

Design of highly selective ethanol dehydration nanocatalysts for ethylene production.

PubMed

Austin, Natalie; Kostetskyy, Pavlo; Mpourmpakis, Giannis

2018-02-22

Rational design of catalysts for selective conversion of alcohols to olefins is key since product selectivity remains an issue due to competing etherification reactions. Using first principles calculations and chemical rules, we designed novel metal-oxide-protected metal nanoclusters (M 13 X 4 O 12 , with M = Cu, Ag, and Au and X = Al, Ga, and In) exhibiting strong Lewis acid sites on their surface, active for the selective formation of olefins from alcohols. These symmetrical nanocatalysts, due to their curvature, show unfavorable etherification chemistries, while favoring the olefin production. Furthermore, we determined that water removal and regeneration of the nanocatalysts is more feasible compared to the equivalent strong acid sites on solid acids used for alcohol dehydration. Our results demonstrate an exceptional stability of these new nanostructures with the most energetically favorable being Cu-based. Thus, the high selectivity and stability of these in-silico-predicted novel nanoclusters (e.g. Cu 13 Al 4 O 12 ) make them attractive catalysts for the selective dehydration of alcohols to olefins.

THE ENVIRONMENTAL MONITORING AND ASSESSMENT PROGRAM (EMAP) SAMPLE DESIGNS AND OVERVIEW

EPA Science Inventory

This presentation will discuss the fundamentals of the EMAP sample design and program elements. Central components of EMAP such as the methodology for site selection and data analysis, indicator selection and interpretation will be discussed. Examples from wadeable surfact water,...

15 CFR 922.10 - General.

Code of Federal Regulations, 2012 CFR

2012-01-01

... site on the SEL, or selection of a site from the SEL as an active candidate for designation as provided... MARINE SANCTUARY PROGRAM REGULATIONS Site Evaluation List (SEL) § 922.10 General. (a) The Site Evaluation List (SEL) was established as a comprehensive list of marine sites with high natural resource values...

15 CFR 922.10 - General.

Code of Federal Regulations, 2013 CFR

2013-01-01

... site on the SEL, or selection of a site from the SEL as an active candidate for designation as provided... MARINE SANCTUARY PROGRAM REGULATIONS Site Evaluation List (SEL) § 922.10 General. (a) The Site Evaluation List (SEL) was established as a comprehensive list of marine sites with high natural resource values...

15 CFR 922.10 - General.

Code of Federal Regulations, 2014 CFR

2014-01-01

... site on the SEL, or selection of a site from the SEL as an active candidate for designation as provided... MARINE SANCTUARY PROGRAM REGULATIONS Site Evaluation List (SEL) § 922.10 General. (a) The Site Evaluation List (SEL) was established as a comprehensive list of marine sites with high natural resource values...

40 CFR 228.4 - Procedures for designation of sites.

Code of Federal Regulations, 2011 CFR

2011-07-01

... environmental studies of each site, regions adjacent to the site, and on historical knowledge of the impact of waste disposal on areas similar to such sites in physical, chemical, and biological characteristics. All studies for the evaluation and potential selection of dumping sites will be conducted in accordance with...

40 CFR 228.4 - Procedures for designation of sites.

Code of Federal Regulations, 2013 CFR

2013-07-01

... environmental studies of each site, regions adjacent to the site, and on historical knowledge of the impact of waste disposal on areas similar to such sites in physical, chemical, and biological characteristics. All studies for the evaluation and potential selection of dumping sites will be conducted in accordance with...

40 CFR 228.4 - Procedures for designation of sites.

Code of Federal Regulations, 2010 CFR

2010-07-01

... environmental studies of each site, regions adjacent to the site, and on historical knowledge of the impact of waste disposal on areas similar to such sites in physical, chemical, and biological characteristics. All studies for the evaluation and potential selection of dumping sites will be conducted in accordance with...

40 CFR 228.4 - Procedures for designation of sites.

Code of Federal Regulations, 2014 CFR

2014-07-01

... environmental studies of each site, regions adjacent to the site, and on historical knowledge of the impact of waste disposal on areas similar to such sites in physical, chemical, and biological characteristics. All studies for the evaluation and potential selection of dumping sites will be conducted in accordance with...

40 CFR 228.4 - Procedures for designation of sites.

Code of Federal Regulations, 2012 CFR

2012-07-01

... environmental studies of each site, regions adjacent to the site, and on historical knowledge of the impact of waste disposal on areas similar to such sites in physical, chemical, and biological characteristics. All studies for the evaluation and potential selection of dumping sites will be conducted in accordance with...

PERFORMANCE MONITORING FOR NATURAL ATTENUATION OF CONTAMINANTS IN AQUIFERS

EPA Science Inventory

Monitoring of hazardous waste sites serves a variety of very distinct purposes. The initial phase of monitoring is designed to determine whether there is a problem at a site (remedial investigation). If a problem exists, the next phase of monitoring is designed to select a reme...

Wait for the Bus: How Lowcountry School Site Selection and Design Deter Walking to School and Contribute to Urban Sprawl.

ERIC Educational Resources Information Center

Kouri, Christopher

This paper presents a study on how the South Carolina school site selection process can affect the quality of the students' experience and access to their schools. Focusing on students options for getting to school, e.g., hazards that prevent students from walking to school and the size of school sites that place schools on the edge of…

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.

Computerized stratified random site-selection approaches for design of a ground-water-quality sampling network

USGS Publications Warehouse

Scott, J.C.

1990-01-01

Computer software was written to randomly select sites for a ground-water-quality sampling network. The software uses digital cartographic techniques and subroutines from a proprietary geographic information system. The report presents the approaches, computer software, and sample applications. It is often desirable to collect ground-water-quality samples from various areas in a study region that have different values of a spatial characteristic, such as land-use or hydrogeologic setting. A stratified network can be used for testing hypotheses about relations between spatial characteristics and water quality, or for calculating statistical descriptions of water-quality data that account for variations that correspond to the spatial characteristic. In the software described, a study region is subdivided into areal subsets that have a common spatial characteristic to stratify the population into several categories from which sampling sites are selected. Different numbers of sites may be selected from each category of areal subsets. A population of potential sampling sites may be defined by either specifying a fixed population of existing sites, or by preparing an equally spaced population of potential sites. In either case, each site is identified with a single category, depending on the value of the spatial characteristic of the areal subset in which the site is located. Sites are selected from one category at a time. One of two approaches may be used to select sites. Sites may be selected randomly, or the areal subsets in the category can be grouped into cells and sites selected randomly from each cell.

Welcome to the Neighborhood.

ERIC Educational Resources Information Center

Schneider, Jay W.

2001-01-01

Discusses how community interest and involvement helps a new school reinvigorate an urban area. Community input into design and site selection, site improvements, interior elements, and construction management are addressed. (GR)

Dihydrofolate reductase: A potential drug target in trypanosomes and leishmania

NASA Astrophysics Data System (ADS)

Zuccotto, Fabio; Martin, Andrew C. R.; Laskowski, Roman A.; Thornton, Janet M.; Gilbert, Ian H.

1998-05-01

Dihydrofolate reductase has successfully been used as a drug target in the area of anti-cancer, anti-bacterial and anti-malarial chemotherapy. Little has been done to evaluate it as a drug target for treatment of the trypanosomiases and leishmaniasis. A crystal structure of Leishmania major dihydrofolate reductase has been published. In this paper, we describe the modelling of Trypanosoma cruzi and Trypanosoma brucei dihydrofolate reductases based on this crystal structure. These structures and models have been used in the comparison of protozoan, bacterial and human enzymes in order to highlight the different features that can be used in the design of selective anti-protozoan agents. Comparison has been made between residues present in the active site, the accessibility of these residues, charge distribution in the active site, and the shape and size of the active sites. Whilst there is a high degree of similarity between protozoan, human and bacterial dihydrofolate reductase active sites, there are differences that provide potential for selective drug design. In particular, we have identified a set of residues which may be important for selective drug design and identified a larger binding pocket in the protozoan than the human and bacterial enzymes.

Candidate locations for SPS rectifying antennas

NASA Technical Reports Server (NTRS)

Eberhardt, A. W.

1977-01-01

The feasibility of placing 120 Satellite Power System (SPS) rectifying antenna (rectenna) sites across the U.S. was studied. An initial attempt is made to put two land sites in each state using several land site selection criteria. When only 69 land sites are located, it is decided to put the remaining sites in the sea and sea site selection criteria are identified. An estimated projection of electrical demand distribution for the year 2000 is then used to determine the distribution of these sites along the Pacific, Atlantic, and Gulf Coasts. A methodology for distributing rectenna sites across the country and for fine-tuning exact locations is developed, and recommendations on rectenna design and operations are made.

Independent Design Review: Grants Chlorinated Solvents Plume, Superfund Site, Grants, Cibola County, New Mexico, EPA Region 6

EPA Pesticide Factsheets

The Grants Chlorinated Solvents Plume Superfund Site in Grants, Cibola County, New Mexico was selected by EPA OSRTI based on a nomination from EPA Region 6. The remedy is in the early design stage and has an estimated cost of $29.5 million.

Propulsive maneuver design for the Mars Exploration Rover mission

NASA Technical Reports Server (NTRS)

Potts, Christopher L.; Kangas, Julie A.; Raofi, Behzad

2006-01-01

Starting from approximately 150 candidate Martian landing sites, two distinct sites have been selected for further investigation by sophisticated rovers. The two rovers, named 'Spirit' and 'Opportunity', begin the surface mission respectively to Gusec Crater and Meridiani Planum in January 2004. the rovers are essentially robotic geologists, sent on a mission to research for evidence in the rocks and soil pertaining to the historical presence of water and the ability to possibly sustain life. Before this scientific search can commence, precise trajectory targeting and control is necessary to achieve the entry requirements for the selected landing sites within the constraints of the flight system. The maneuver design challenge is to meet or exceed these requirements while maintaining the necessary design flexibility to accommodate additional project concerns. Opportunities to improve performance and reduce risk based on trajectory control characteristics are also evaluated.

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.

Design and methods of the Midwest Stream Quality Assessment (MSQA), 2013

USGS Publications Warehouse

Garrett, Jessica D.; Frey, Jeffrey W.; Van Metre, Peter C.; Journey, Celeste A.; Nakagaki, Naomi; Button, Daniel T.; Nowell, Lisa H.

2017-10-18

During 2013, the U.S. Geological Survey (USGS) National Water-Quality Assessment Project (NAWQA), in collaboration with the USGS Columbia Environmental Research Center, the U.S. Environmental Protection Agency (EPA) National Rivers and Streams Assessment (NRSA), and the EPA Office of Pesticide Programs assessed stream quality across the Midwestern United States. This Midwest Stream Quality Assessment (MSQA) simultaneously characterized watershed and stream-reach water-quality stressors along with instream biological conditions, to better understand regional stressor-effects relations. The MSQA design focused on effects from the widespread agriculture in the region and urban development because of their importance as ecological stressors of particular concern to Midwest region resource managers.A combined random stratified selection and a targeted selection based on land-use data were used to identify and select sites representing gradients in agricultural intensity across the region. During a 14-week period from May through August 2013, 100 sites were selected and sampled 12 times for contaminants, nutrients, and sediment. This 14-week water-quality “index” period culminated with an ecological survey of habitat, periphyton, benthic macroinvertebrates, and fish at all sites. Sediment was collected during the ecological survey for analysis of sediment chemistry and toxicity testing. Of the 100 sites, 50 were selected for the MSQA random stratified group from 154 NRSA sites planned for the region, and the other 50 MSQA sites were selected as targeted sites to more evenly cover agricultural and urban stressor gradients in the study area. Of the 50 targeted sites, 12 were in urbanized watersheds and 21 represented “good” biological conditions or “least disturbed” conditions. The remaining 17 targeted sites were selected to improve coverage of the agricultural intensity gradient or because of historical data collection to provide temporal context for the study.This report provides a detailed description of the MSQA study components, including surveys of ecological conditions, routine water sampling, deployment of passive polar organic compound integrative samplers, and stream sediment sampling at all sites. Component studies that were completed to provide finer scale temporal data or more extensive analysis at selected sites, included continuous water-quality monitoring, daily pesticide sampling, laboratory and in-stream water toxicity testing efforts, and deployment of passive suspended-sediment samplers.

The impact of model prediction error in designing geodetic networks for crustal deformation applications

NASA Astrophysics Data System (ADS)

Murray, J. R.

2017-12-01

Earth surface displacements measured at Global Navigation Satellite System (GNSS) sites record crustal deformation due, for example, to slip on faults underground. A primary objective in designing geodetic networks to study crustal deformation is to maximize the ability to recover parameters of interest like fault slip. Given Green's functions (GFs) relating observed displacement to motion on buried dislocations representing a fault, one can use various methods to estimate spatially variable slip. However, assumptions embodied in the GFs, e.g., use of a simplified elastic structure, introduce spatially correlated model prediction errors (MPE) not reflected in measurement uncertainties (Duputel et al., 2014). In theory, selection algorithms should incorporate inter-site correlations to identify measurement locations that give unique information. I assess the impact of MPE on site selection by expanding existing methods (Klein et al., 2017; Reeves and Zhe, 1999) to incorporate this effect. Reeves and Zhe's algorithm sequentially adds or removes a predetermined number of data according to a criterion that minimizes the sum of squared errors (SSE) on parameter estimates. Adapting this method to GNSS network design, Klein et al. select new sites that maximize model resolution, using trade-off curves to determine when additional resolution gain is small. Their analysis uses uncorrelated data errors and GFs for a uniform elastic half space. I compare results using GFs for spatially variable strike slip on a discretized dislocation in a uniform elastic half space, a layered elastic half space, and a layered half space with inclusion of MPE. I define an objective criterion to terminate the algorithm once the next site removal would increase SSE more than the expected incremental SSE increase if all sites had equal impact. Using a grid of candidate sites with 8 km spacing, I find the relative value of the selected sites (defined by the percent increase in SSE that further removal of each site would cause) is more uniform when MPE is included. However, the number and distribution of selected sites depends primarily on site location relative to the fault. For this test case, inclusion of MPE has minimal practical impact; I will investigate whether these findings hold for more densely spaced candidate grids and dipping faults.

Isolation of Cu Atoms in Pd Lattice: Forming Highly Selective Sites for Photocatalytic Conversion of CO2 to CH4.

PubMed

Long, Ran; Li, Yu; Liu, Yan; Chen, Shuangming; Zheng, Xusheng; Gao, Chao; He, Chaohua; Chen, Nanshan; Qi, Zeming; Song, Li; Jiang, Jun; Zhu, Junfa; Xiong, Yujie

2017-03-29

Photocatalytic conversion of CO 2 to CH 4 , a carbon-neutral fuel, represents an appealing approach to remedy the current energy and environmental crisis; however, it suffers from the large production of CO and H 2 by side reactions. The design of catalytic sites for CO 2 adsorption and activation holds the key to address this grand challenge. In this Article, we develop highly selective sites for photocatalytic conversion of CO 2 to CH 4 by isolating Cu atoms in Pd lattice. According to our synchrotron-radiation characterizations and theoretical simulations, the isolation of Cu atoms in Pd lattice can play dual roles in the enhancement of CO 2 -to-CH 4 conversion: (1) providing the paired Cu-Pd sites for the enhanced CO 2 adsorption and the suppressed H 2 evolution; and (2) elevating the d-band center of Cu sites for the improved CO 2 activation. As a result, the Pd 7 Cu 1 -TiO 2 photocatalyst achieves the high selectivity of 96% for CH 4 production with a rate of 19.6 μmol g cat -1 h -1 . This work provides fresh insights into the catalytic site design for selective photocatalytic CO 2 conversion, and highlights the importance of catalyst lattice engineering at atomic precision to catalytic performance.

Structure-Based Design and Synthesis of Potent and Selective Matrix Metalloproteinase 13 Inhibitors.

PubMed

Choi, Jun Yong; Fuerst, Rita; Knapinska, Anna M; Taylor, Alexander B; Smith, Lyndsay; Cao, Xiaohang; Hart, P John; Fields, Gregg B; Roush, William R

2017-07-13

We describe the use of comparative structural analysis and structure-guided molecular design to develop potent and selective inhibitors (10d and (S)-17b) of matrix metalloproteinase 13 (MMP-13). We applied a three-step process, starting with a comparative analysis of the X-ray crystallographic structure of compound 5 in complex with MMP-13 with published structures of known MMP-13·inhibitor complexes followed by molecular design and synthesis of potent but nonselective zinc-chelating MMP inhibitors (e.g., 10a and 10b). After demonstrating that the pharmacophores of the chelating inhibitors (S)-10a, (R)-10a, and 10b were binding within the MMP-13 active site, the Zn 2+ chelating unit was replaced with nonchelating polar residues that bridged over the Zn 2+ binding site and reached into a solvent accessible area. After two rounds of structural optimization, these design approaches led to small molecule MMP-13 inhibitors 10d and (S)-17b, which bind within the substrate-binding site of MMP-13 and surround the catalytically active Zn 2+ ion without chelating to the metal. These compounds exhibit at least 500-fold selectivity versus other MMPs.

Improved design of hammerhead ribozyme for selective digestion of target RNA through recognition of site-specific adenosine-to-inosine RNA editing

PubMed Central

Fukuda, Masatora; Kurihara, Kei; Yamaguchi, Shota; Oyama, Yui; Deshimaru, Masanobu

2014-01-01

Adenosine-to-inosine (A-to-I) RNA editing is an endogenous regulatory mechanism involved in various biological processes. Site-specific, editing-state–dependent degradation of target RNA may be a powerful tool both for analyzing the mechanism of RNA editing and for regulating biological processes. Previously, we designed an artificial hammerhead ribozyme (HHR) for selective, site-specific RNA cleavage dependent on the A-to-I RNA editing state. In the present work, we developed an improved strategy for constructing a trans-acting HHR that specifically cleaves target editing sites in the adenosine but not the inosine state. Specificity for unedited sites was achieved by utilizing a sequence encoding the intrinsic cleavage specificity of a natural HHR. We used in vitro selection methods in an HHR library to select for an extended HHR containing a tertiary stabilization motif that facilitates HHR folding into an active conformation. By using this method, we successfully constructed highly active HHRs with unedited-specific cleavage. Moreover, using HHR cleavage followed by direct sequencing, we demonstrated that this ribozyme could cleave serotonin 2C receptor (HTR2C) mRNA extracted from mouse brain, depending on the site-specific editing state. This unedited-specific cleavage also enabled us to analyze the effect of editing state at the E and C sites on editing at other sites by using direct sequencing for the simultaneous quantification of the editing ratio at multiple sites. Our approach has the potential to elucidate the mechanism underlying the interdependencies of different editing states in substrate RNA with multiple editing sites. PMID:24448449

Principles for selecting earthquake motions in engineering design of large dams

USGS Publications Warehouse

Krinitzsky, E.L.; Marcuson, William F.

1983-01-01

This report gives a synopsis of the various tools and techniques used in selecting earthquake ground motion parameters for large dams. It presents 18 charts giving newly developed relations for acceleration, velocity, and duration versus site earthquake intensity for near- and far-field hard and soft sites and earthquakes having magnitudes above and below 7. The material for this report is based on procedures developed at the Waterways Experiment Station. Although these procedures are suggested primarily for large dams, they may also be applicable for other facilities. Because no standard procedure exists for selecting earthquake motions in engineering design of large dams, a number of precautions are presented to guide users. The selection of earthquake motions is dependent on which one of two types of engineering analyses are performed. A pseudostatic analysis uses a coefficient usually obtained from an appropriate contour map; whereas, a dynamic analysis uses either accelerograms assigned to a site or specified respunse spectra. Each type of analysis requires significantly different input motions. All selections of design motions must allow for the lack of representative strong motion records, especially near-field motions from earthquakes of magnitude 7 and greater, as well as an enormous spread in the available data. Limited data must be projected and its spread bracketed in order to fill in the gaps and to assure that there will be no surprises. Because each site may have differing special characteristics in its geology, seismic history, attenuation, recurrence, interpreted maximum events, etc., as integrated approach gives best results. Each part of the site investigation requires a number of decisions. In some cases, the decision to use a 'least ork' approach may be suitable, simply assuming the worst of several possibilities and testing for it. Because there are no standard procedures to follow, multiple approaches are useful. For example, peak motions at a site may be obtained from several methods that involve magnitude of earthquake, distance from source, and corresponding motions; or, alternately, peak motions may be assigned from other correlations based on earthquake intensity. Various interpretations exist to account for duration, recurrence, effects of site conditions, etc. Comparison of the various interpretations can be very useful. Probabilities can be assigned; however, they can present very serious problems unless appropriate care is taken when data are extrapolated beyond their data base. In making deterministic judgments, probabilistic data can provide useful guidance in estimating the uncertainties of the decision. The selection of a design ground motion for large dams is based in the end on subjective judgments which should depend, to an important extent, on the consequences of failure. Usually, use of a design value of ground motion representing a mean plus one standard deviation of possible variation in the mean of the data puts one in a conservative position. If failure presents no hazard to life, lower values of design ground motion may be justified, providing there are cost benefits and the risk is acceptable to the owner. Where a large hazard to life exists (i.e., a dam above an urbanized area) one may wish to use values of design ground motion that approximate the very worst case. The selection of a design ground motion must be appropriate for its particular set of circumstances.

Achieving full connectivity of sites in the multiperiod reserve network design problem

USGS Publications Warehouse

Jafari, Nahid; Nuse, Bryan L.; Moore, Clinton; Dilkina, Bistra; Hepinstall-Cymerman, Jeffrey

2017-01-01

The conservation reserve design problem is a challenge to solve because of the spatial and temporal nature of the problem, uncertainties in the decision process, and the possibility of alternative conservation actions for any given land parcel. Conservation agencies tasked with reserve design may benefit from a dynamic decision system that provides tactical guidance for short-term decision opportunities while maintaining focus on a long-term objective of assembling the best set of protected areas possible. To plan cost-effective conservation over time under time-varying action costs and budget, we propose a multi-period mixed integer programming model for the budget-constrained selection of fully connected sites. The objective is to maximize a summed conservation value over all network parcels at the end of the planning horizon. The originality of this work is in achieving full spatial connectivity of the selected sites during the schedule of conservation actions.

Quality assurance of road roughness measurement.

DOT National Transportation Integrated Search

2000-01-01

This report describes a study designed to establish the accuracy and repeatability of high-speed, road-profiling equipment. This effort focused on a series of roughness validation sites. The study addresses selecting the appropriate sites, determinin...

The Lawrence Berkeley Laboratory geothermal program in northern Nevada

NASA Technical Reports Server (NTRS)

Mirk, K. F.; Wollenberg, H. A.

1974-01-01

The Lawrence Berkeley Laboratory's geothermal program began with consideration of regions where fluids in the temperature range of 150 to 230 C may be economically accessible. Three valleys, located in an area of high regional heat flow in north central Nevada, were selected for geological, geophysical, and geochemical field studies. The objective of these ongoing field activities is to select a site for a 10-MW demonstration plant. Field activities (which started in September 1973) are described. A parallel effort has been directed toward the conceptual design of a 10-MW isobutane binary plant which is planned for construction at the selected site. Design details of the plant are described. Project schedule with milestones is shown together with a cost summary of the project.

Analogue Study of Actinide Transport at Sites in Russia

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

Novikov, A P; Simmons, A M; Halsey, W G

2003-02-12

The U. S. Department of Energy (DOE) and the Russian Academy of Sciences (RAS) are engaged in a three-year cooperative study to observe the behavior of actinides in the natural environment at selected disposal sites and/or contamination sites in Russia. The purpose is to develop experimental data and models for actinide speciation, mobilization and transport processes in support of geologic repository design, safety and performance analyses. Currently at the mid-point of the study, the accomplishments to date include: evaluation of existing data and data needs, site screening and selection, initial data acquisition, and development of preliminary conceptual models.

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...

Dual-track CCS stakeholder engagement: Lessons learned from FutureGen in Illinois

USGS Publications Warehouse

Hund, G.; Greenberg, S.E.

2011-01-01

FutureGen, as originally planned, was to be the world's first coal-fueled, near-zero emissions power plant with fully integrated, 90% carbon capture and storage (CCS). From conception through siting and design, it enjoyed strong support from multiple stakeholder groups, which benefited the overall project. Understanding the stakeholder engagement process for this project provides valuable insights into the design of stakeholder programs for future CCS projects. FutureGen is one of few projects worldwide that used open competition for siting both the power plant and storage reservoir. Most site proposals were coordinated by State governments. It was unique in this and other respects relative to the site selection method used on other DOE-supported projects. At the time of site selection, FutureGen was the largest proposed facility designed to combine an integrated gasification combined cycle (IGCC) coal-fueled power plant with a CCS system. Stakeholder engagement by states and the industry consortium responsible for siting, designing, building, and operating the facility took place simultaneously and on parallel tracks. On one track were states spearheading state-wide site assessments to identify candidate sites that they wanted to propose for consideration. On the other track was a public-private partnership between an industry consortium of thirteen coal companies and electric utilities that comprised the FutureGen Alliance (Alliance) and the U.S. Department of Energy (DOE). The partnership was based on a cooperative agreement signed by both parties, which assigned the lead for siting to the Alliance. This paper describes the stakeholder engagement strategies used on both of these tracks and provides examples from the engagement process using the Illinois semi-finalist sites. ?? 2011 Published by Elsevier Ltd.

The 21st Century Teachers' Guide to Recommended Internet Sites. Neal-Schuman NetGuide Series [with CD-ROM].

ERIC Educational Resources Information Center

DiGeorgio, Marvin; Lesage, Sylvia

This book is a practical Internet guide designed to help teachers and students at all levels and in all academic disciplines discover a selection of educational sites from around the world. More than 400 sites are described and organized by academic discipline, and these sites offer links to thousands of other educational sites on the Internet.…

15 CFR 922.21 - Selection of active candidates.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 15 Commerce and Foreign Trade 3 2013-01-01 2013-01-01 false Selection of active candidates. 922.21... Selection of active candidates. (a) The Secretary shall, from time to time, select a limited number of sites from the SEL for Active Candidate consideration based on a preliminary assessment of the designation...

15 CFR 922.21 - Selection of active candidates.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Selection of active candidates. 922.21... Selection of active candidates. (a) The Secretary shall, from time to time, select a limited number of sites from the SEL for Active Candidate consideration based on a preliminary assessment of the designation...

15 CFR 922.21 - Selection of active candidates.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 15 Commerce and Foreign Trade 3 2011-01-01 2011-01-01 false Selection of active candidates. 922.21... Selection of active candidates. (a) The Secretary shall, from time to time, select a limited number of sites from the SEL for Active Candidate consideration based on a preliminary assessment of the designation...

15 CFR 922.21 - Selection of active candidates.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 15 Commerce and Foreign Trade 3 2012-01-01 2012-01-01 false Selection of active candidates. 922.21... Selection of active candidates. (a) The Secretary shall, from time to time, select a limited number of sites from the SEL for Active Candidate consideration based on a preliminary assessment of the designation...

15 CFR 922.21 - Selection of active candidates.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 15 Commerce and Foreign Trade 3 2014-01-01 2014-01-01 false Selection of active candidates. 922.21... Selection of active candidates. (a) The Secretary shall, from time to time, select a limited number of sites from the SEL for Active Candidate consideration based on a preliminary assessment of the designation...

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.

77 FR 20590 - Ocean Dumping; Designation of Ocean Dredged Material Disposal Sites Offshore of Yaquina Bay, OR

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-05

... Criteria (40 CFR 228.5) 1. Sites must be selected to minimize interference with other activities in the... conflicts. The proposed Sites spatially overlap with recreational activities such as boating and whale... expected to more heavily use areas that are shoreward of the Sites and to focus their activities on Yaquina...

Site-specific estimation of peak-streamflow frequency using generalized least-squares regression for natural basins in Texas

USGS Publications Warehouse

Asquith, William H.; Slade, R.M.

1999-01-01

The U.S. Geological Survey, in cooperation with the Texas Department of Transportation, has developed a computer program to estimate peak-streamflow frequency for ungaged sites in natural basins in Texas. Peak-streamflow frequency refers to the peak streamflows for recurrence intervals of 2, 5, 10, 25, 50, and 100 years. Peak-streamflow frequency estimates are needed by planners, managers, and design engineers for flood-plain management; for objective assessment of flood risk; for cost-effective design of roads and bridges; and also for the desin of culverts, dams, levees, and other flood-control structures. The program estimates peak-streamflow frequency using a site-specific approach and a multivariate generalized least-squares linear regression. A site-specific approach differs from a traditional regional regression approach by developing unique equations to estimate peak-streamflow frequency specifically for the ungaged site. The stations included in the regression are selected using an informal cluster analysis that compares the basin characteristics of the ungaged site to the basin characteristics of all the stations in the data base. The program provides several choices for selecting the stations. Selecting the stations using cluster analysis ensures that the stations included in the regression will have the most pertinent information about flooding characteristics of the ungaged site and therefore provide the basis for potentially improved peak-streamflow frequency estimation. An evaluation of the site-specific approach in estimating peak-streamflow frequency for gaged sites indicates that the site-specific approach is at least as accurate as a traditional regional regression approach.

Prediction of human disease-associated phosphorylation sites with combined feature selection approach and support vector machine.

PubMed

Xu, Xiaoyi; Li, Ao; Wang, Minghui

2015-08-01

Phosphorylation is a crucial post-translational modification, which regulates almost all cellular processes in life. It has long been recognised that protein phosphorylation has close relationship with diseases, and therefore many researches are undertaken to predict phosphorylation sites for disease treatment and drug design. However, despite the success achieved by these approaches, no method focuses on disease-associated phosphorylation sites prediction. Herein, for the first time the authors propose a novel approach that is specially designed to identify associations between phosphorylation sites and human diseases. To take full advantage of local sequence information, a combined feature selection method-based support vector machine (CFS-SVM) that incorporates minimum-redundancy-maximum-relevance filtering process and forward feature selection process is developed. Performance evaluation shows that CFS-SVM is significantly better than the widely used classifiers including Bayesian decision theory, k nearest neighbour and random forest. With the extremely high specificity of 99%, CFS-SVM can still achieve a high sensitivity. Besides, tests on extra data confirm the effectiveness and general applicability of CFS-SVM approach on a variety of diseases. Finally, the analysis of selected features and corresponding kinases also help the understanding of the potential mechanism of disease-phosphorylation relationships and guide further experimental validations.

Structure based drug design: development of potent and selective factor IXa (FIXa) inhibitors.

PubMed

Wang, Shouming; Beck, Richard; Burd, Andrew; Blench, Toby; Marlin, Frederic; Ayele, Tenagne; Buxton, Stuart; Dagostin, Claudio; Malic, Maja; Joshi, Rina; Barry, John; Sajad, Mohammed; Cheung, Chiming; Shaikh, Shaheda; Chahwala, Suresh; Chander, Chaman; Baumgartner, Christine; Holthoff, Hans-Peter; Murray, Elizabeth; Blackney, Michael; Giddings, Amanda

2010-02-25

On the basis of our understanding on the binding interactions of the benzothiophene template within the FIXa active site by X-ray crystallography and molecular modeling studies, we developed our SAR strategy by targeting the 4-position of the template to access the S1 beta and S2-S4 sites. A number of highly selective and potent factor Xa (FXa) and FIXa inhibitors were identified by simple switch of functional groups with conformational changes toward the S2-S4 sites.

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

Earthquake ground motion: Chapter 3

USGS Publications Warehouse

Luco, Nicolas; Kircher, Charles A.; Crouse, C. B.; Charney, Finley; Haselton, Curt B.; Baker, Jack W.; Zimmerman, Reid; Hooper, John D.; McVitty, William; Taylor, Andy

2016-01-01

Most of the effort in seismic design of buildings and other structures is focused on structural design. This chapter addresses another key aspect of the design process—characterization of earthquake ground motion into parameters for use in design. Section 3.1 describes the basis of the earthquake ground motion maps in the Provisions and in ASCE 7 (the Standard). Section 3.2 has examples for the determination of ground motion parameters and spectra for use in design. Section 3.3 describes site-specific ground motion requirements and provides example site-specific design and MCER response spectra and example values of site-specific ground motion parameters. Section 3.4 discusses and provides an example for the selection and scaling of ground motion records for use in various types of response history analysis permitted in the Standard.

38 CFR 39.26 - Forms.

Code of Federal Regulations, 2010 CFR

2010-07-01

... roads shall be generally 24 feet wide. (4) Pavement design. The pavement section of all roads, service... planning standards. 39.62 Space criteria for support facilities. 39.63 Architectural design standards... this part: (a) Establishment means the process of site selection, land acquisition, design and planning...

23 CFR 1340.13 - Annual reporting requirements.

Code of Federal Regulations, 2013 CFR

2013-04-01

... survey design, alternate observation site selected subsequent to the original survey design), and by... survey design that was approved by NHTSA, in writing, as conforming to the Uniform Criteria for State Observational Surveys of Seat Belt Use, 23 CFR Part 1340; (3) The survey design has remained unchanged since the...

23 CFR 1340.13 - Annual reporting requirements.

Code of Federal Regulations, 2012 CFR

2012-04-01

... survey design, alternate observation site selected subsequent to the original survey design), and by... survey design that was approved by NHTSA, in writing, as conforming to the Uniform Criteria for State Observational Surveys of Seat Belt Use, 23 CFR Part 1340; (3) The survey design has remained unchanged since the...

23 CFR 1340.13 - Annual reporting requirements.

Code of Federal Regulations, 2014 CFR

2014-04-01

... survey design, alternate observation site selected subsequent to the original survey design), and by... survey design that was approved by NHTSA, in writing, as conforming to the Uniform Criteria for State Observational Surveys of Seat Belt Use, 23 CFR Part 1340; (3) The survey design has remained unchanged since the...

Influence of active site location on catalytic activity in de novo-designed zinc metalloenzymes.

PubMed

Zastrow, Melissa L; Pecoraro, Vincent L

2013-04-17

While metalloprotein design has now yielded a number of successful metal-bound and even catalytically active constructs, the question of where to put a metal site along a linear, repetitive sequence has not been thoroughly addressed. Often several possibilities in a given sequence may exist that would appear equivalent but may in fact differ for metal affinity, substrate access, or protein dynamics. We present a systematic variation of active site location for a hydrolytically active ZnHis3O site contained within a de novo-designed three-stranded coiled coil. We find that the maximal rate, substrate access, and metal-binding affinity are dependent on the selected position, while catalytic efficiency for p-nitrophenyl acetate hydrolysis can be retained regardless of the location of the active site. This achievement demonstrates how efficient, tailor-made enzymes which control rate, pKa, substrate and solvent access (and selectivity), and metal-binding affinity may be realized. These findings may be applied to the more advanced de novo design of constructs containing secondary interactions, such as hydrogen-bonding channels. We are now confident that changes to location for accommodating such channels can be achieved without location-dependent loss of catalytic efficiency. These findings bring us closer to our ultimate goal of incorporating the secondary interactions we believe will be necessary in order to improve both active site properties and the catalytic efficiency to be competitive with the native enzyme, carbonic anhydrase.

Virtual screening of selective inhibitors of phosphopantetheine adenylyltransferase from Mycobacterium tuberculosis

NASA Astrophysics Data System (ADS)

Podshivalov, D. D.; Timofeev, V. I.; Sidorov-Biryukov, D. D.; Kuranova, I. P.

2017-05-01

Bacterial phosphopantetheine adenylyltransferase from Mycobacterium tuberculosis (PPAT Mt) is a convenient target protein for the directed search for selective inhibitors as potent antituberculosis drugs. Four compounds suitable for the detailed investigation of their interactions with PPAT Mt were found by virtual screening. The active-site region of the enzyme was chosen as the ligand-binding site. The positions of the ligands found by the docking were refined by molecular dynamics simulation. The nearest environment of the ligands, the positions of which in the active site of the enzyme were found in a computational experiment, was analyzed. The compounds under consideration were shown to directly interact with functionally important active-site amino-acid residues and block access of substrates to the active site. Therefore, these compounds can be used for the design of selective inhibitors of PPAT Mt as potent antituberculosis drugs.

Rationally Designed Sensing Selectivity and Sensitivity of an Aerolysin Nanopore via Site-Directed Mutagenesis.

PubMed

Wang, Ya-Qian; Cao, Chan; Ying, Yi-Lun; Li, Shuang; Wang, Ming-Bo; Huang, Jin; Long, Yi-Tao

2018-04-27

Selectivity and sensitivity are two key parameters utilized to describe the performance of a sensor. In order to investigate selectivity and sensitivity of the aerolysin nanosensor, we manipulated its surface charge at different locations via single site-directed mutagenesis. To study the selectivity, we replaced the positively charged R220 at the entrance of the pore with negatively charged glutamic acid, resulting in barely no current blockages for sensing negatively charged oligonucleotides. For the sensitivity, we substituted the positively charged lumen-exposed amino acid K238 located at trans-ward third of the β-barrel stem with glutamic acid. This leads to a surprisingly longer duration time at +140 mV, which is about 20 times slower in translocation speed for Poly(dA) 4 compared to that of wild-type aerolysin, indicating the stronger pore-analyte interactions and enhanced sensitivity. Therefore, it is both feasible and understandable to rationally design confined biological nanosensors for single molecule detection with high selectivity and sensitivity.

75 FR 22524 - Ocean Dumping; Designation of Ocean Dredged Material Disposal Sites Offshore of the Siuslaw River...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-29

... location to dispose of material dredged from the Siuslaw River navigation channel, and to provide a... sediments from Site A back into the dredged channel resulted in a selection of disposal Sites B and C by the... conflicts. The final Sites are located close to the approach to the Siuslaw River entrance channel but are...

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

[Site selection of nature reserve based on the self-learning tabu search algorithm with space-ecology set covering problem: An example from Daiyun Mountain, Southeast China].

PubMed

Huang, Jia Hang; Liu, Jin Fu; Lin, Zhi Wei; Zheng, Shi Qun; He, Zhong Sheng; Zhang, Hui Guang; Li, Wen Zhou

2017-01-01

Designing the nature reserves is an effective approach to protecting biodiversity. The traditional approaches to designing the nature reserves could only identify the core area for protecting the species without specifying an appropriate land area of the nature reserve. The site selection approaches, which are based on mathematical model, can select part of the land from the planning area to compose the nature reserve and to protect specific species or ecosystem. They are useful approaches to alleviating the contradiction between ecological protection and development. The existing site selection methods do not consider the ecological differences between each unit and has the bottleneck of computational efficiency in optimization algorithm. In this study, we first constructed the ecological value assessment system which was appropriated for forest ecosystem and that was used for calculating ecological value of Daiyun Mountain and for drawing its distribution map. Then, the Ecological Set Covering Problem (ESCP) was established by integrating the ecological values and then the Space-ecology Set Covering Problem (SSCP) was generated based on the spatial compactness of ESCP. Finally, the STS algorithm which possessed good optimizing performance was utilized to search the approximate optimal solution under diverse protection targets, and the optimization solution of the built-up area of Daiyun Mountain was proposed. According to the experimental results, the difference of ecological values in the spatial distribution was obvious. The ecological va-lue of selected sites of ESCP was higher than that of SCP. SSCP could aggregate the sites with high ecological value based on ESCP. From the results, the level of the aggregation increased with the weight of the perimeter. We suggested that the range of the existing reserve could be expanded for about 136 km 2 and the site of Tsuga longibracteata should be included, which was located in the northwest of the study area. Our research aimed at providing an optimization scheme for the sustai-nable development of Daiyun Mountain nature reserve and the optimal allocation of land resource, and a novel idea for designing the nature reserve of forest ecosystem in China.

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

PubMed

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

2007-04-01

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

The problem of site variation within red pine provenance experiments

Treesearch

Mark J. Holst

1966-01-01

In spite of care taken in the selection of site and experimental design of provenance experiments, site heterogenity within the experimental area may be more complex than was anticipated when the experiment was established. The present paper describes a problem of this nature encountered in a red pine (Pinus resinosa Ait.) provenance experiment at...

What is the minimum number of sites needed for precisely assessing the ecological status of mainstem rivers?

EPA Science Inventory

We evaluated the number of sites that would yield relatively precise estimates of physical, chemical, and biological condition for six raftable rivers 100-200 km long and 20-120 m wide. We used a probability design to select 20 sites on each of two rivers in Washington and four ...

A spin transition mechanism for cooperative adsorption in metal-organic frameworks

NASA Astrophysics Data System (ADS)

Reed, Douglas A.; Keitz, Benjamin K.; Oktawiec, Julia; Mason, Jarad A.; Runčevski, Tomče; Xiao, Dianne J.; Darago, Lucy E.; Crocellà, Valentina; Bordiga, Silvia; Long, Jeffrey R.

2017-10-01

Cooperative binding, whereby an initial binding event facilitates the uptake of additional substrate molecules, is common in biological systems such as haemoglobin. It was recently shown that porous solids that exhibit cooperative binding have substantial energetic benefits over traditional adsorbents, but few guidelines currently exist for the design of such materials. In principle, metal-organic frameworks that contain coordinatively unsaturated metal centres could act as both selective and cooperative adsorbents if guest binding at one site were to trigger an electronic transformation that subsequently altered the binding properties at neighbouring metal sites. Here we illustrate this concept through the selective adsorption of carbon monoxide (CO) in a series of metal-organic frameworks featuring coordinatively unsaturated iron(II) sites. Functioning via a mechanism by which neighbouring iron(II) sites undergo a spin-state transition above a threshold CO pressure, these materials exhibit large CO separation capacities with only small changes in temperature. The very low regeneration energies that result may enable more efficient Fischer-Tropsch conversions and extraction of CO from industrial waste feeds, which currently underutilize this versatile carbon synthon. The electronic basis for the cooperative adsorption demonstrated here could provide a general strategy for designing efficient and selective adsorbents suitable for various separations.

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

USGS Publications Warehouse

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

2009-01-01

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

The utility of Geographical Information Systems (GIS) in systems-oriented obesity intervention projects: the selection of comparable study sites for a quasi-experimental intervention design--TX CORD.

PubMed

Oluyomi, Abiodun O; Byars, Allison; Byrd-Williams, Courtney; Sharma, Shreela V; Durand, Casey; Hoelscher, Deanna M; Butte, Nancy F; Kelder, Steven H

2015-02-01

The Texas Childhood Obesity Research Demonstration project (TX CORD) uses a systems-oriented approach to address obesity that includes individual and family interventions, community-level action, as well as environmental and policy initiatives. Given that randomization is seldom possible in community-level intervention studies, TX CORD uses a quasi-experimental design. Comparable intervention and comparison study sites are needed to address internal validity bias. TX CORD was designed to be implemented in low-income, ethnically diverse communities in Austin and Houston, Texas. A three-stage Geographical Information System (GIS) methodology was used to establish and ascertain the comparability of the intervention and comparison study sites. Census tract (stage 1) and school (stage 2) data were used to identify spatially exclusive geographic areas that were comparable. In stage 3, study sites were compared on demographic characteristics, socioeconomic status (SES), food assets, and physical activity (PA) assets. Student's t-test was used to examine significant differences between the selected sites. The methodology that was used resulted in the selection of catchment areas with demographic and socioeconomic characteristics that fit the target population: ethnically diverse population; lower-median household income; and lower home ownership rates. Additionally, the intervention and comparison sites were statistically comparable on demographic and SES variables, as well as food assets and PA assets. This GIS approach can provide researchers, program evaluators, and policy makers with useful tools for both research and practice. Area-level information that allows for robust understanding of communities can enhance analytical procedures in community health research and offer significant contributions in terms of community assessment and engagement.

Binding Pathway of Opiates to μ-Opioid Receptors Revealed by Machine Learning

NASA Astrophysics Data System (ADS)

Barati Farimani, Amir; Feinberg, Evan; Pande, Vijay

2018-02-01

Many important analgesics relieve pain by binding to the $\\mu$-Opioid Receptor ($\\mu$OR), which makes the $\\mu$OR among the most clinically relevant proteins of the G Protein Coupled Receptor (GPCR) family. Despite previous studies on the activation pathways of the GPCRs, the mechanism of opiate binding and the selectivity of $\\mu$OR are largely unknown. We performed extensive molecular dynamics (MD) simulation and analysis to find the selective allosteric binding sites of the $\\mu$OR and the path opiates take to bind to the orthosteric site. In this study, we predicted that the allosteric site is responsible for the attraction and selection of opiates. Using Markov state models and machine learning, we traced the pathway of opiates in binding to the orthosteric site, the main binding pocket. Our results have important implications in designing novel analgesics.

7 CFR 1924.13 - Supplemental requirements for more complex construction.

Code of Federal Regulations, 2013 CFR

2013-01-01

... the site selection and participate in early consultations regarding project scope and design. (3... consecutive phases as follows: (i) Schematic design phase. The architect will: (A) Consult with the applicant... Public Law 103-354 requirements and procedures. (C) Assist in preparing the project design after...

7 CFR 1924.13 - Supplemental requirements for more complex construction.

Code of Federal Regulations, 2011 CFR

2011-01-01

... the site selection and participate in early consultations regarding project scope and design. (3... consecutive phases as follows: (i) Schematic design phase. The architect will: (A) Consult with the applicant... Public Law 103-354 requirements and procedures. (C) Assist in preparing the project design after...

7 CFR 1924.13 - Supplemental requirements for more complex construction.

Code of Federal Regulations, 2012 CFR

2012-01-01

... the site selection and participate in early consultations regarding project scope and design. (3... consecutive phases as follows: (i) Schematic design phase. The architect will: (A) Consult with the applicant... Public Law 103-354 requirements and procedures. (C) Assist in preparing the project design after...

7 CFR 1924.13 - Supplemental requirements for more complex construction.

Code of Federal Regulations, 2014 CFR

2014-01-01

... the site selection and participate in early consultations regarding project scope and design. (3... consecutive phases as follows: (i) Schematic design phase. The architect will: (A) Consult with the applicant... Public Law 103-354 requirements and procedures. (C) Assist in preparing the project design after...

7 CFR 1924.13 - Supplemental requirements for more complex construction.

Code of Federal Regulations, 2010 CFR

2010-01-01

... the site selection and participate in early consultations regarding project scope and design. (3... consecutive phases as follows: (i) Schematic design phase. The architect will: (A) Consult with the applicant... Public Law 103-354 requirements and procedures. (C) Assist in preparing the project design after...

Texas Sustainable School Design Guideline.

ERIC Educational Resources Information Center

Nicklas, Michael; Bailey, Gary; Padia, Harshad D.; Malin, Nadav

This guide offers a detailed listing of the key practices and technologies that can help create a sustainable school. The document includes hundreds of cost-effective recommendations that can improve the energy performance and environmental quality of school designs. Each design and construction phase is addressed, from site selection through…

Assessment of wadeable stream resources in the driftless area ecoregion in Western Wisconsin using a probabilistic sampling design.

PubMed

Miller, Michael A; Colby, Alison C C; Kanehl, Paul D; Blocksom, Karen

2009-03-01

The Wisconsin Department of Natural Resources (WDNR), with support from the U.S. EPA, conducted an assessment of wadeable streams in the Driftless Area ecoregion in western Wisconsin using a probabilistic sampling design. This ecoregion encompasses 20% of Wisconsin's land area and contains 8,800 miles of perennial streams. Randomly-selected stream sites (n = 60) equally distributed among stream orders 1-4 were sampled. Watershed land use, riparian and in-stream habitat, water chemistry, macroinvertebrate, and fish assemblage data were collected at each true random site and an associated "modified-random" site on each stream that was accessed via a road crossing nearest to the true random site. Targeted least-disturbed reference sites (n = 22) were also sampled to develop reference conditions for various physical, chemical, and biological measures. Cumulative distribution function plots of various measures collected at the true random sites evaluated with reference condition thresholds, indicate that high proportions of the random sites (and by inference the entire Driftless Area wadeable stream population) show some level of degradation. Study results show no statistically significant differences between the true random and modified-random sample sites for any of the nine physical habitat, 11 water chemistry, seven macroinvertebrate, or eight fish metrics analyzed. In Wisconsin's Driftless Area, 79% of wadeable stream lengths were accessible via road crossings. While further evaluation of the statistical rigor of using a modified-random sampling design is warranted, sampling randomly-selected stream sites accessed via the nearest road crossing may provide a more economical way to apply probabilistic sampling in stream monitoring programs.

Optimization Under Uncertainty of Site-Specific Turbine Configurations

NASA Astrophysics Data System (ADS)

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

2016-09-01

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 with increasing risk aversion on the part of the designer.

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.

Selecting Patients for Intra-arterial Therapy in the Context of a Clinical Trial for Neuroprotection

PubMed Central

Lyden, Patrick; Weymer, Sara; Coffey, Chris; Cudkowicz, Merit; Berg, Samantha; O’Brien, Sarah; Fisher, Marc; Haley, E. Clarke; Khatri, Pooja; Saver, Jeff; Levine, Steven; Levy, Howard; Rymer, Marilyn; Wechsler, Lawrence; Jadhav, Ashutosh; McNeil, Elizabeth; Waddy, Salina; Pryor, Kent

2016-01-01

Background and Purpose The advent of intra-arterial neurothrombectomy (IAT) for acute ischemic stroke opens a potentially transformative opportunity to improve neuroprotection studies. Combining a putative neuroprotectant with recanalization could produce more powerful trials but could introduce heterogeneity and adverse event possibilities. We sought to demonstrate feasibility of IAT in neuroprotectant trials by defining IAT selection criteria for an ongoing neuroprotectant clinical trial. Methods The study drug, 3K3A-APC, is a pleiotropic cytoprotectant and may reduce thrombolysis associated hemorrhage. The NeuroNEXT trial NN104 (RHAPSODY) is designed to establish a maximally tolerated dose of 3K3A-APC. Each trial site provided their IAT selection criteria. An expert panel reviewed site criteria and published evidence. Finally, the trial leadership designed IAT selection criteria. Results Derived selection criteria reflected consistency among the sites and comparability to published IAT trials. A protocol amendment allowing IAT (and relaxed age, NIHSS, and time limits) in the RHAPSODY trial was implemented on June 15, 2015. Recruitment before and after the amendment improved from 8 enrolled patients (601 screened, 1.3%) to 51 patients (821 screened, 6.2%), OR [95%CL] of 4.9 [2.3,10.4], p<0.001). Gross recruitment was 0.11 patients/site/month vs. 0.43 patients/site/month, respectively, before and after the amendment. Conclusions It is feasible to include IAT in a neuroprotectant trial for acute ischemic stroke. Criteria are presented for including such patients in a manner that is consistent with published evidence for IAT while still preserving the ability to test the role of the putative neuroprotectant. Clinical Trial Registration Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT02222714. PMID:27803392

Selecting Patients for Intra-Arterial Therapy in the Context of a Clinical Trial for Neuroprotection.

PubMed

Lyden, Patrick; Weymer, Sara; Coffey, Chris; Cudkowicz, Merit; Berg, Samantha; O'Brien, Sarah; Fisher, Marc; Haley, E Clarke; Khatri, Pooja; Saver, Jeff; Levine, Steven; Levy, Howard; Rymer, Marilyn; Wechsler, Lawrence; Jadhav, Ashutosh; McNeil, Elizabeth; Waddy, Salina; Pryor, Kent

2016-12-01

The advent of intra-arterial neurothrombectomy (IAT) for acute ischemic stroke opens a potentially transformative opportunity to improve neuroprotection studies. Combining a putative neuroprotectant with recanalization could produce more powerful trials but could introduce heterogeneity and adverse event possibilities. We sought to demonstrate feasibility of IAT in neuroprotectant trials by defining IAT selection criteria for an ongoing neuroprotectant clinical trial. The study drug, 3K3A-APC, is a pleiotropic cytoprotectant and may reduce thrombolysis-associated hemorrhage. The NeuroNEXT trial NN104 (RHAPSODY) is designed to establish a maximally tolerated dose of 3K3A-APC. Each trial site provided their IAT selection criteria. An expert panel reviewed site criteria and published evidence. Finally, the trial leadership designed IAT selection criteria. Derived selection criteria reflected consistency among the sites and comparability to published IAT trials. A protocol amendment allowing IAT (and relaxed age, National Institutes of Health Stroke Scale, and time limits) in the RHAPSODY trial was implemented on June 15, 2015. Recruitment before and after the amendment improved from 8 enrolled patients (601 screened, 1.3%) to 51 patients (821 screened, 6.2%; odds ratio [95% confidence limit] of 4.9 [2.3-10.4]; P<0.001). Gross recruitment was 0.11 patients per site month versus 0.43 patients per site per month, respectively, before and after the amendment. It is feasible to include IAT in a neuroprotectant trial for acute ischemic stroke. Criteria are presented for including such patients in a manner that is consistent with published evidence for IAT while still preserving the ability to test the role of the putative neuroprotectant. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02222714. © 2016 American Heart Association, Inc.

What Teens Want to Know: Sexual Health Questions Submitted to a Teen Web Site

ERIC Educational Resources Information Center

Vickberg, Suzanne M. Johnson; Kohn, Julia E.; Franco, Lydia M.; Criniti, Shannon

2003-01-01

In 1999 Planned Parenthood[R] Federation of America (PPFA[R]) launched teenwire.com[SM], a Web site for young people. This study was designed to determine teens' reproductive health information needs. Selected for analysis were 1,219 submissions to the Ask the Experts section of the Web site. Each submission was independently coded by three of the…

Discovery of a small-molecule HIV-1 integrase inhibitor-binding site | Center for Cancer Research

Cancer.gov

The lowest energy-binding conformation of an inhibitor bound to the dimeric interface of HIV-1 integrase core domain. The yellow region represents a unique allosteric binding site identified by affinity labeling and mass spectrometry and validated through mutagenesis. This site can provide a potential platform for the rational design of inhibitors selective for disruption of

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

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

Not Available

1991-12-01

The uranium mill tailings site near Durango, Colorado, was one of 24 inactive uranium mill sites designated to be remediated by the US Department of Energy (DOE) under the Uranium Mill Tailings Radiation Control Act of 1978 (UMTRCA). Part of the UMTRCA requires that the US Nuclear Regulatory Commission (NRC) concur with the DOE`s Remedial Action Plan (RAP) and certify that the remedial action conducted at the site complies with the standards promulgated by the US Environmental Protection Agency (EPA). Included in the RAP is this Remedial Action Selection Report (RAS), which has been developed to serve a two-fold purpose.more » First, it describes the activities that have been conducted by the DOE to accomplish remediation and long-term stabilization and control of the radioactive materials at the inactive uranium mill processing site near Durango, Colorado. Secondly, this document and the rest of the RAP, upon concurrence and execution by the DOE, the State of Colorado, and the NRC, become Appendix B of the Cooperative Agreement between the DOE and the State of Colorado.« less

Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Durango, Colorado: Remedial action selection report

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

Not Available

1991-12-01

The uranium mill tailings site near Durango, Colorado, was one of 24 inactive uranium mill sites designated to be remediated by the US Department of Energy (DOE) under the Uranium Mill Tailings Radiation Control Act of 1978 (UMTRCA). Part of the UMTRCA requires that the US Nuclear Regulatory Commission (NRC) concur with the DOE's Remedial Action Plan (RAP) and certify that the remedial action conducted at the site complies with the standards promulgated by the US Environmental Protection Agency (EPA). Included in the RAP is this Remedial Action Selection Report (RAS), which has been developed to serve a two-fold purpose.more » First, it describes the activities that have been conducted by the DOE to accomplish remediation and long-term stabilization and control of the radioactive materials at the inactive uranium mill processing site near Durango, Colorado. Secondly, this document and the rest of the RAP, upon concurrence and execution by the DOE, the State of Colorado, and the NRC, become Appendix B of the Cooperative Agreement between the DOE and the State of Colorado.« less

Schools That Sustain: Lessening the Environmental Impact of New Construction.

ERIC Educational Resources Information Center

Peele, Katherine N.; Malone, Sara

2002-01-01

Discusses sustainable school design and its benefits to the environment, offering examples of illustrative schools. Provides suggestions on site selection (such as using smaller sites and recycling existing buildings), sharing facilities with the community, and construction elements that improve environmental impact (such as flexibility,…

Chapter 3: Design of the Saber-Tooth Project.

ERIC Educational Resources Information Center

Ward, Phillip

1999-01-01

Used data from interviews, surveys, and document analysis to describe the methods and reform processes of the Saber Tooth Project, examining selection of sites; demographics (school sites, teachers, data sources, and project assumptions); and project phases (development, planning, implementation, and support). The project's method of reform was…

The complexity of selection at the major primate beta-defensin locus.

PubMed

Semple, Colin A M; Maxwell, Alison; Gautier, Philippe; Kilanowski, Fiona M; Eastwood, Hayden; Barran, Perdita E; Dorin, Julia R

2005-05-18

We have examined the evolution of the genes at the major human beta-defensin locus and the orthologous loci in a range of other primates and mouse. For the first time these data allow us to examine selective episodes in the more recent evolutionary history of this locus as well as the ancient past. We have used a combination of maximum likelihood based tests and a maximum parsimony based sliding window approach to give a detailed view of the varying modes of selection operating at this locus. We provide evidence for strong positive selection soon after the duplication of these genes within an ancestral mammalian genome. Consequently variable selective pressures have acted on beta-defensin genes in different evolutionary lineages, with episodes both of negative, and more rarely positive selection, during the divergence of primates. Positive selection appears to have been more common in the rodent lineage, accompanying the birth of novel, rodent-specific beta-defensin genes. These observations allow a fuller understanding of the evolution of mammalian innate immunity. In both the rodent and primate lineages, sites in the second exon have been subject to positive selection and by implication are important in functional diversity. A small number of sites in the mature human peptides were found to have undergone repeated episodes of selection in different primate lineages. Particular sites were consistently implicated by multiple methods at positions throughout the mature peptides. These sites are clustered at positions predicted to be important for the specificity of the antimicrobial or chemoattractant properties of beta-defensins. Surprisingly, sites within the prepropeptide region were also implicated as being subject to significant positive selection, suggesting previously unappreciated functional significance for this region. Identification of these putatively functional sites has important implications for our understanding of beta-defensin function and for novel antibiotic design.

Landfill Site Selection by AHP Based Multi-criteria Decision Making Tool: A Case Study in Kolkata, India

NASA Astrophysics Data System (ADS)

Majumdar, Ankush; Hazra, Tumpa; Dutta, Amit

2017-09-01

This work presents a Multi-criteria Decision Making (MCDM) tool to select a landfill site from three candidate sites proposed for Kolkata Municipal Corporation (KMC) area that complies with accessibility, receptor, environment, public acceptability, geological and economic criteria. Analytical Hierarchy Process has been used to solve the MCDM problem. Suitability of the three sites (viz. Natagachi, Gangajoara and Kharamba) as landfills as proposed by KMC has been checked by Landfill Site Sensitivity Index (LSSI) as well as Economic Viability Index (EVI). Land area availability for disposing huge quantity of Municipal Solid Waste for the design period has been checked. Analysis of the studied sites show that they are moderately suitable for landfill facility construction as both LSSI and EVI scores lay between 300 and 750. The proposed approach represents an effective MCDM tool for siting sanitary landfill in growing metropolitan cities of developing countries like India.

Mars Exploration Rovers Launch Performance and TCM-1 Maneuver Design

NASA Technical Reports Server (NTRS)

Kangas, Julie A.; Potts, Christopher L.; Raofi, Behzad

2004-01-01

The Mars Exploration Rover (MER) project successfully landed two identical rovers on Mars in order to remotely conduct geologic investigations, including characterization of rocks and soils that may hold clues to past water activity. Two landing sites, Gusev crater and Meridiani Planum, were selected out of nearly 200 candidate sites after balancing science returns and flight system engineering and safety. Precise trajectory targeting and control was necessary to achieve the atmospheric entry requirements for the selected landing sites within the flight system constraints. This paper discusses the expected and achieved launch vehicle performance and the impacts of that performance on the first Trajectory Correction Maneuver (TCM-1) while maintaining targeting flexibility in accommodating additional project concerns about landing site safety and possible in-flight retargeting to alternate landing sites.

Data for the geochemical investigation of UMTRAP designated site at Durango, Colorado

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

Markos, G.; Bush, K.J.

1983-09-01

This report contains the methods of collection and the data used in the geochemical investigation of the former tailings and raffinate pond sites at Durango, Colorado. The methods of data interpretation and results of the investigation are described in the report, ''Geochemical Investigation of UMTRAP Designated Site at Durango, Colorado''. Data are from a one-time sampling of waters and solid material from the background, the area adjacent to the site, and the site. The solid samples are water extracted to remove easily soluble salts and acid extracted to remove carbonates and hydroxides. The waters, extracts, and solid samples were analyzedmore » for selected major and trace elements. A few samples were analyzed for radioisotopes.« less

Artificial Intelligence Support for Landing Site Selection on Mars

NASA Astrophysics Data System (ADS)

Rongier, G.; Pankratius, V.

2017-12-01

Mars is a key target for planetary exploration; a better understanding of its evolution and habitability requires roving in situ. Landing site selection is becoming more challenging for scientists as new instruments generate higher data volumes. The involved engineering and scientific constraints make site selection and the anticipation of possible onsite actions into a complex optimization problem: there may be multiple acceptable solutions depending on various goals and assumptions. Solutions must also account for missing data, errors, and potential biases. To address these problems, we propose an AI-informed decision support system that allows scientists, mission designers, engineers, and committees to explore alternative site selection choices based on data. In particular, we demonstrate first results of an exploratory case study using fuzzy logic and a simulation of a rover's mobility map based on the fast marching algorithm. Our system computes favorability maps of the entire planet to facilitate landing site selection and allows a definition of different configurations for rovers, science target priorities, landing ellipses, and other constraints. For a rover similar to NASA's Mars 2020 rover, we present results in form of a site favorability map as well as four derived exploration scenarios that depend on different prioritized scientific targets, all visualizing inherent tradeoffs. Our method uses the NASA PDS Geosciences Node and the NASA/ICA Integrated Database of Planetary Features. Under common assumptions, the data products reveal Eastern Margaritifer Terra and Meridiani Planum to be the most favorable sites due to a high concentration of scientific targets and a flat, easily navigable surface. Our method also allows mission designers to investigate which constraints have the highest impact on the mission exploration potential and to change parameter ranges. Increasing the elevation limit for landing, for example, provides access to many additional, more interesting sites on the southern terrains of Mars. The speed of current rovers is another limit to exploration capabilities: our system helps quantify how speed increases can improve the number of reachable targets in the search space. We acknowledge support from NASA AISTNNX15AG84G (PI Pankratius) and NSF ACI1442997 (PI Pankratius).

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

NASA Astrophysics Data System (ADS)

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

1981-10-01

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

Rural Housing Site Planning in North Carolina. Agricultural Extension Publication 105.

ERIC Educational Resources Information Center

Hester, Randolph T., Jr.; And Others

Addressing the problems of rural housing site selection and development in North Carolina, this guide is designed for cooperative and coordinated use by: technical assistance personnel employed by the Farmers Home Administration; local lending institutions; Health Departments; the Agricultural Extension Service; the Soil Conservation Service; and…

USING BAYESIAN SPATIAL MODELS TO FACILITATE WATER QUALITY MONITORING

EPA Science Inventory

The Clean Water Act of 1972 requires states to monitor the quality of their surface water. The number of sites sampled on streams and rivers varies widely by state. A few states are now using probability survey designs to select sites, while most continue to rely on other proce...

NASA: Data on the Web.

ERIC Educational Resources Information Center

Galica, Carol

1997-01-01

Provides an annotated bibliography of selected NASA Web sites for K-12 math and science teachers: the NASA Lewis Research Center Learning Technologies K-12 Home Page, Spacelink, NASA Quest, Basic Aircraft Design Page, International Space Station, NASA Shuttle Web Site, LIFTOFF to Space Education, Telescopes in Education, and Space Educator's…

Pipeline bottoming cycle study. Final report

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

Not Available

1980-06-01

The technical and economic feasibility of applying bottoming cycles to the prime movers that drive the compressors of natural gas pipelines was studied. These bottoming cycles convert some of the waste heat from the exhaust gas of the prime movers into shaft power and conserve gas. Three typical compressor station sites were selected, each on a different pipeline. Although the prime movers were different, they were similar enough in exhaust gas flow rate and temperature that a single bottoming cycle system could be designed, with some modifications, for all three sites. Preliminary design included selection of the bottoming cycle workingmore » fluid, optimization of the cycle, and design of the components, such as turbine, vapor generator and condensers. Installation drawings were made and hardware and installation costs were estimated. The results of the economic assessment of retrofitting bottoming cycle systems on the three selected sites indicated that profitability was strongly dependent upon the site-specific installation costs, how the energy was used and the yearly utilization of the apparatus. The study indicated that the bottoming cycles are a competitive investment alternative for certain applications for the pipeline industry. Bottoming cycles are technically feasible. It was concluded that proper design and operating practices would reduce the environmental and safety hazards to acceptable levels. The amount of gas that could be saved through the year 2000 by the adoption of bottoming cycles for two different supply projections was estimated as from 0.296 trillion ft/sup 3/ for a low supply projection to 0.734 trillion ft/sup 3/ for a high supply projection. The potential market for bottoming cycle equipment for the two supply projections varied from 170 to 500 units of varying size. Finally, a demonstration program plan was developed.« less

Case studies of conservation plans that incorporate geodiversity.

PubMed

Anderson, M G; Comer, P J; Beier, P; Lawler, J J; Schloss, C A; Buttrick, S; Albano, C M; Faith, D P

2015-06-01

Geodiversity has been used as a surrogate for biodiversity when species locations are unknown, and this utility can be extended to situations where species locations are in flux. Recently, scientists have designed conservation networks that aim to explicitly represent the range of geophysical environments, identifying a network of physical stages that could sustain biodiversity while allowing for change in species composition in response to climate change. Because there is no standard approach to designing such networks, we compiled 8 case studies illustrating a variety of ways scientists have approached the challenge. These studies show how geodiversity has been partitioned and used to develop site portfolios and connectivity designs; how geodiversity-based portfolios compare with those derived from species and communities; and how the selection and combination of variables influences the results. Collectively, they suggest 4 key steps when using geodiversity to augment traditional biodiversity-based conservation planning: create land units from species-relevant variables combined in an ecologically meaningful way; represent land units in a logical spatial configuration and integrate with species locations when possible; apply selection criteria to individual sites to ensure they are appropriate for conservation; and develop connectivity among sites to maintain movements and processes. With these considerations, conservationists can design more effective site portfolios to ensure the lasting conservation of biodiversity under a changing climate. © 2015 Society for Conservation Biology.

Mars Lander/Rover vehicle development: An advanced space design project for USRA and NASA/OAST

NASA Technical Reports Server (NTRS)

1987-01-01

The results of the studies on one particular part of the Mars Lander/Rover (MLR) system are contained: the Balloon Rover. This component vehicle was selected for further research and design because of the lack of technical literature on this subject, as compared to surface rover technology. Landing site selection; balloon system development and deployment; optics and communications; and the payload power supply are described.

FLARE: The Far Side Lunar Research Expedition. A design of a far side lunar observatory

NASA Technical Reports Server (NTRS)

Bishop, David W.; Chakrabarty, Rudhmala P.; Hannula, Dawn M.; Hargus, William A., Jr.; Melendrez, A. Dean; Niemann, Christopher J.; Neuenschwander, Amy L.; Padgett, Brett D.; Patel, Sanjiv R.; Wiesehuegel, Leland J.

1991-01-01

This document outlines the design completed by members of Lone Star Aerospace, Inc. (L.S.A.) of a lunar observatory on the far side of the Moon. Such a base would not only establish a long term human presence on the Moon, but would also allow more accurate astronomical data to be obtained. A lunar observatory is more desirable than an Earth based observatory for the following reasons: instrument weight is reduced due to the Moon's weaker gravity; near vacuum conditions exist on the Moon; the Moon has slow rotation to reveal the entire sky; and the lunar surface is stable for long baseline instruments. All the conditions listed above are favorable for astronomical data recording. The technical aspects investigated in the completion of this project included site selection, mission scenario, scientific instruments, communication and power systems, habitation and transportation, cargo spacecraft design, thermal systems, robotic systems, and trajectory analysis. The site selection group focused its efforts on finding a suitable location for the observatory. Hertzsprung, a large equatorial crater on the eastern limb, was chosen as the base site.

Optimization Under Uncertainty of Site-Specific Turbine Configurations

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

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

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

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

Tricyclic Covalent Inhibitors Selectively Target Jak3 through an Active Site Thiol*

PubMed Central

Goedken, Eric R.; Argiriadi, Maria A.; Banach, David L.; Fiamengo, Bryan A.; Foley, Sage E.; Frank, Kristine E.; George, Jonathan S.; Harris, Christopher M.; Hobson, Adrian D.; Ihle, David C.; Marcotte, Douglas; Merta, Philip J.; Michalak, Mark E.; Murdock, Sara E.; Tomlinson, Medha J.; Voss, Jeffrey W.

2015-01-01

The action of Janus kinases (JAKs) is required for multiple cytokine signaling pathways, and as such, JAK inhibitors hold promise for treatment of autoimmune disorders, including rheumatoid arthritis, inflammatory bowel disease, and psoriasis. However, due to high similarity in the active sites of the four members (Jak1, Jak2, Jak3, and Tyk2), developing selective inhibitors within this family is challenging. We have designed and characterized substituted, tricyclic Jak3 inhibitors that selectively avoid inhibition of the other JAKs. This is accomplished through a covalent interaction between an inhibitor containing a terminal electrophile and an active site cysteine (Cys-909). We found that these ATP competitive compounds are irreversible inhibitors of Jak3 enzyme activity in vitro. They possess high selectivity against other kinases and can potently (IC50 < 100 nm) inhibit Jak3 activity in cell-based assays. These results suggest irreversible inhibitors of this class may be useful selective agents, both as tools to probe Jak3 biology and potentially as therapies for autoimmune diseases. PMID:25552479

A decision tool for selecting trench cap designs

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

Paige, G.B.; Stone, J.J.; Lane, L.J.

1995-12-31

A computer based prototype decision support system (PDSS) is being developed to assist the risk manager in selecting an appropriate trench cap design for waste disposal sites. The selection of the {open_quote}best{close_quote} design among feasible alternatives requires consideration of multiple and often conflicting objectives. The methodology used in the selection process consists of: selecting and parameterizing decision variables using data, simulation models, or expert opinion; selecting feasible trench cap design alternatives; ordering the decision variables and ranking the design alternatives. The decision model is based on multi-objective decision theory and uses a unique approach to order the decision variables andmore » rank the design alternatives. Trench cap designs are evaluated based on federal regulations, hydrologic performance, cover stability and cost. Four trench cap designs, which were monitored for a four year period at Hill Air Force Base in Utah, are used to demonstrate the application of the PDSS and evaluate the results of the decision model. The results of the PDSS, using both data and simulations, illustrate the relative advantages of each of the cap designs and which cap is the {open_quotes}best{close_quotes} alternative for a given set of criteria and a particular importance order of those decision criteria.« less

CavityPlus: a web server for protein cavity detection with pharmacophore modelling, allosteric site identification and covalent ligand binding ability prediction.

PubMed

Xu, Youjun; Wang, Shiwei; Hu, Qiwan; Gao, Shuaishi; Ma, Xiaomin; Zhang, Weilin; Shen, Yihang; Chen, Fangjin; Lai, Luhua; Pei, Jianfeng

2018-05-10

CavityPlus is a web server that offers protein cavity detection and various functional analyses. Using protein three-dimensional structural information as the input, CavityPlus applies CAVITY to detect potential binding sites on the surface of a given protein structure and rank them based on ligandability and druggability scores. These potential binding sites can be further analysed using three submodules, CavPharmer, CorrSite, and CovCys. CavPharmer uses a receptor-based pharmacophore modelling program, Pocket, to automatically extract pharmacophore features within cavities. CorrSite identifies potential allosteric ligand-binding sites based on motion correlation analyses between cavities. CovCys automatically detects druggable cysteine residues, which is especially useful to identify novel binding sites for designing covalent allosteric ligands. Overall, CavityPlus provides an integrated platform for analysing comprehensive properties of protein binding cavities. Such analyses are useful for many aspects of drug design and discovery, including target selection and identification, virtual screening, de novo drug design, and allosteric and covalent-binding drug design. The CavityPlus web server is freely available at http://repharma.pku.edu.cn/cavityplus or http://www.pkumdl.cn/cavityplus.

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

Rapid Processing of Turner Designs Model 10-Au-005 Internally Logged Fluorescence Data

EPA Science Inventory

Continuous recording of dye fluorescence using field fluorometers at selected sampling sites facilitates acquisition of real-time dye tracing data. The Turner Designs Model 10-AU-005 field fluorometer allows for frequent fluorescence readings, data logging, and easy downloading t...

FORTRAN PROCESSING OF FLUOROMETRIC DATA LOGGED BY A TURNER DESIGNS FIELD FLUOROMETER

EPA Science Inventory

Continuous recording of dye fluorescence using field fluorometers at selected sampling sites facilitate acquisition of real-time dye-tracing data. The Turner Designs Model 10-AU-005 Field Fluorometer allows for frequent fluorescence readings, data logging, and easy downloading t...

Roving Vehicles for Lunar and Planetary Exploration

NASA Technical Reports Server (NTRS)

2004-01-01

This special bibliography includes the design, development, and application of lunar and Mars rovers; vehicle instrumentation and power supplies; navigation and control technologies; and site selection.

Quality evaluation of portal sites in health system, as a tool for education and learning.

PubMed

Hejazi, Sayed Mehdi; Sarmadi, Sima

2013-01-01

The main objective of creating a portal is to make information service available for users who need them for performance of duties and responsibilities regardless of the sources. This article is attempted to consider the parameters that can evaluate these sites since these criteria can be effective in designing and implementing such portals. On the other hand, portal sites in health systems of every country make it possible for leaders, policy makers, and directors to system education as a tool for new learning technologies. One of the main decisions each manager has to make is precise selection of appropriate portal sites. This is a descriptive and qualitative study. The research sample was 53 computer professional working in the area of computer programming and design. In the first part of the study a questionnaire was send to the participants and in the second part of the study based on their response to the questionnaire the participant was interviewed and the main themes of the studies were formulated. The validity and the reliability of the questionnaire were confirmed. The study results were summarized in 10 themes and 50 sub-categories. The main themes included were portal requirements, security, management, and efficiency, user friendliness, built-in applications, portal flexibility, interoperability, and support systems. Portal sites in any education systems make it possible for health system leaders and policy makers to manage their organization information system efficiently and effectively. One of the major decisions each manager has to make is precise selection of an appropriate portal sites design and development. The themes and sub-categories of this study could help health system managers and policy makers and information technology professionals to make appropriate decisions regarding portal design and development.

Experimental Verification of Pneumatic Transport System for the Rapid Excavation of Tunnels: Part 1. Installation of Test Facility

DOT National Transportation Integrated Search

1978-03-01

This report deals with the selection of a test site, the design of a test installation, equipment selection, the installation and start-up of a pneumatic pipeline system for the transportation of tunnel muck. A review of prior pneumatic applications ...

Hydroisomerization of n-hexadecane: remarkable selectivity of mesoporous silica post-synthetically modified with aluminum

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

Sabyrov, Kairat; Musselwhite, Nathan; Melaet, Gérôme

As the impact of acids on catalytically driven chemical transformations is tremendous, fundamental understanding of catalytically relevant factors is essential for the design of more efficient solid acid catalysts. In this work, we employed a post-synthetic doping method to synthesize a highly selective hydroisomerization catalyst and to demonstrate the effect of acid strength and density, catalyst microstructure, and platinum nanoparticle size on the reaction rate and selectivity. Aluminum doped mesoporous silica catalyzed gas-phase n-hexadecane isomerization with remarkably high selectivity to monobranched isomers (~95%), producing a substantially higher amount of isomers than traditional zeolite catalysts. Mildly acidic sites generated by post-syntheticmore » aluminum grafting were found to be the main reason for its high selectivity. The flexibility of the post-synthetic doping method enabled us to systematically explore the effect of the acid site density on the reaction rate and selectivity, which has been extremely difficult to achieve with zeolite catalysts. We found that a higher density of Brønsted acid sites leads to higher cracking of n-hexadecane presumably due to an increased surface residence time. Furthermore, regardless of pore size and microstructure, hydroisomerization turnover frequency linearly increased as a function of Brønsted acid site density. In addition to strength and density of acid sites, platinum nanoparticle size affected catalytic activity and selectivity. The smallest platinum nanoparticles produced the most effective bifunctional catalyst presumably because of higher percolation into aluminum doped mesoporous silica, generating more 'intimate' metallic and acidic sites. Finally, the aluminum doped silica catalyst was shown to retain its remarkable selectivity towards isomers even at increased reaction conversions.« less

Hydroisomerization of n-hexadecane: remarkable selectivity of mesoporous silica post-synthetically modified with aluminum

DOE PAGES

Sabyrov, Kairat; Musselwhite, Nathan; Melaet, Gérôme; ...

2017-01-01

As the impact of acids on catalytically driven chemical transformations is tremendous, fundamental understanding of catalytically relevant factors is essential for the design of more efficient solid acid catalysts. In this work, we employed a post-synthetic doping method to synthesize a highly selective hydroisomerization catalyst and to demonstrate the effect of acid strength and density, catalyst microstructure, and platinum nanoparticle size on the reaction rate and selectivity. Aluminum doped mesoporous silica catalyzed gas-phase n-hexadecane isomerization with remarkably high selectivity to monobranched isomers (~95%), producing a substantially higher amount of isomers than traditional zeolite catalysts. Mildly acidic sites generated by post-syntheticmore » aluminum grafting were found to be the main reason for its high selectivity. The flexibility of the post-synthetic doping method enabled us to systematically explore the effect of the acid site density on the reaction rate and selectivity, which has been extremely difficult to achieve with zeolite catalysts. We found that a higher density of Brønsted acid sites leads to higher cracking of n-hexadecane presumably due to an increased surface residence time. Furthermore, regardless of pore size and microstructure, hydroisomerization turnover frequency linearly increased as a function of Brønsted acid site density. In addition to strength and density of acid sites, platinum nanoparticle size affected catalytic activity and selectivity. The smallest platinum nanoparticles produced the most effective bifunctional catalyst presumably because of higher percolation into aluminum doped mesoporous silica, generating more 'intimate' metallic and acidic sites. Finally, the aluminum doped silica catalyst was shown to retain its remarkable selectivity towards isomers even at increased reaction conversions.« less

Logging utilization in Idaho: Current and past trends

Treesearch

Eric A. Simmons; Todd A. Morgan; Erik C. Berg; Stanley J. Zarnoch; Steven W. Hayes; Mike T. Thompson

2014-01-01

A study of commercial timber-harvesting activities in Idaho was conducted during 2008 and 2011 to characterize current tree utilization, logging operations, and changes from previous Idaho logging utilization studies. A two-stage simple random sampling design was used to select sites and felled trees for measurement within active logging sites. Thirty-three logging...

Recruiter Selection Model

DTIC Science & Technology

2006-05-01

indow s Site ........................................................................................... 31 Figure 17, R-2.2.1 for W indow s Site...current 1O body of knowledge associated with developing and analyzing 1O psychological inventories (Borman and Rosse, 1980) (PDRI, 2005). The physical...a response. The artificial intelligence body of knowledge uses the pairing within a learning algorithm designed to minimize the errors between a

Glacier Lakes Ecosystem Experiment Site: an "Experimental" wilderness

Treesearch

Douglas G. Fox; Anna W. Schoettle; Frank A. Vertucci

1987-01-01

This site, selected to be representative of high-mountain wilderness ecosystems, is being used to study the effects of air pollution and atmospheric deposition In alpine and subalpine, terrestrial and aquatic biotic communities. The research program includes (a) short-term experiments designed to quantify the response of system components hypothesized to be most...

Lunar fiberglass: Properties and process design

NASA Technical Reports Server (NTRS)

Dalton, Robert; Nichols, Todd

1987-01-01

A Clemson University ceramic engineering design for a lunar fiberglass plant is presented. The properties of glass fibers and metal-matrix composites are examined. Lunar geology is also discussed. A raw material and site are selected based on this information. A detailed plant design is presented, and summer experiments to be carried out at Johnson Space Center are reviewed.

The OSIRIS-REx Mission Sample Site Selection Process

NASA Astrophysics Data System (ADS)

Beshore, Edward C.; Lauretta, Dante

2014-11-01

In September of 2016, the OSIRIS-REx (Origins, Spectral Interpretation, Resource Identification, Security, REgolith eXplorer) spacecraft will depart for asteroid (101955) Bennu, and in doing so, will turn an important corner in the exploration of the solar system. After arriving at Bennu in the fall of 2018, OSIRIS-REx will undertake a program of observations designed to select a site suitable for retrieving a sample that will be returned to the Earth in 2023. The third mission in NASA’s New Frontiers program, OSIRIS-REx will return over 60 grams from Bennu’s surface.OSIRIS-REx is unique because the science team will have an operational role to play in preparing data products needed to select a sample site. These include products used to ensure flight system safety — topographic maps and shape models, temperature measurements, maps of hazards — as well as assessments of sampleability and science value. The timing and production of these will be presented, as will the high-level decision-making tools and processes for the interim and final site selection processes.

Ni-Nanocluster Modified Black TiO2 with Dual Active Sites for Selective Photocatalytic CO2 Reduction.

PubMed

Billo, Tadesse; Fu, Fang-Yu; Raghunath, Putikam; Shown, Indrajit; Chen, Wei-Fu; Lien, Hsiang-Ting; Shen, Tzu-Hsien; Lee, Jyh-Fu; Chan, Ting-Shan; Huang, Kuo-You; Wu, Chih-I; Lin, M C; Hwang, Jih-Shang; Lee, Chih-Hao; Chen, Li-Chyong; Chen, Kuei-Hsien

2018-01-01

One of the key challenges in artificial photosynthesis is to design a photocatalyst that can bind and activate the CO 2 molecule with the smallest possible activation energy and produce selective hydrocarbon products. In this contribution, a combined experimental and computational study on Ni-nanocluster loaded black TiO 2 (Ni/TiO 2[Vo] ) with built-in dual active sites for selective photocatalytic CO 2 conversion is reported. The findings reveal that the synergistic effects of deliberately induced Ni nanoclusters and oxygen vacancies provide (1) energetically stable CO 2 binding sites with the lowest activation energy (0.08 eV), (2) highly reactive sites, (3) a fast electron transfer pathway, and (4) enhanced light harvesting by lowering the bandgap. The Ni/TiO 2[Vo] photocatalyst has demonstrated highly selective and enhanced photocatalytic activity of more than 18 times higher solar fuel production than the commercial TiO 2 (P-25). An insight into the mechanisms of interfacial charge transfer and product formation is explored. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Exclusive Ni-N4 Sites Realize Near-Unity CO Selectivity for Electrochemical CO2 Reduction.

PubMed

Li, Xiaogang; Bi, Wentuan; Chen, Minglong; Sun, Yuexiang; Ju, Huanxin; Yan, Wensheng; Zhu, Junfa; Wu, Xiaojun; Chu, Wangsheng; Wu, Changzheng; Xie, Yi

2017-10-25

Electrochemical reduction of carbon dioxide (CO 2 ) to value-added carbon products is a promising approach to reduce CO 2 levels and mitigate the energy crisis. However, poor product selectivity is still a major obstacle to the development of CO 2 reduction. Here we demonstrate exclusive Ni-N 4 sites through a topo-chemical transformation strategy, bringing unprecedentedly high activity and selectivity for CO 2 reduction. Topo-chemical transformation by carbon layer coating successfully ensures preservation of the Ni-N 4 structure to a maximum extent and avoids the agglomeration of Ni atoms to particles, providing abundant active sites for the catalytic reaction. The Ni-N 4 structure exhibits excellent activity for electrochemical reduction of CO 2 with particularly high selectivity, achieving high faradaic efficiency over 90% for CO in the potential range from -0.5 to -0.9 V and gives a maximum faradaic efficiency of 99% at -0.81 V with a current density of 28.6 mA cm -2 . We anticipate exclusive catalytic sites will shed new light on the design of high-efficiency electrocatalysts for CO 2 reduction.

Design study of wind turbines, 50 kW to 3000 kW for electric utility applications: Executive summary

NASA Technical Reports Server (NTRS)

1977-01-01

Preliminary designs of low power (50 to 500 kW) and high power (500 to 3000 kW) wind generator systems (WGS) for electric utility applications were developed. These designs provide the bases for detail design, fabrication, and experimental demonstration testing of these units at selected utility sites. Several feasible WGS configurations were evaluated, and the concept offering the lowest energy cost potential and minimum technical risk for utility applications was selected. The selected concept was optimized utilizing a parametric computer program prepared for this purpose. The utility requirements evaluation task examined the economic, operational and institutional factors affecting the WGS in a utility environment, and provided additional guidance for the preliminary design effort. Results of the conceptual design task indicated that a rotor operating at constant speed, driving an AC generator through a gear transmission is the most cost effective WGS configuration.

76 FR 28925 - Tribal Veterans Cemetery Grants

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-19

... means the process of site selection, land acquisition, design and planning, earth moving, landscaping... space, or functional layout; and it will not enter into a construction contract for the project or... State or Tribal Organization and the design team to provide a standard for preparation of drawings...

ASSESSING THE ECOLOGICAL CONDITION OF A COASTAL PLAIN WATERSHED USING A PROBABILISTIC SURVEY DESIGN

EPA Science Inventory

Using a probabilistic survey design, we assessed the ecological condition of the Florida (USA) portion of the Escambia River watershed using selected environmental and benthic macroinvertebrate data. Macroinvertebrates were sampled at 28 sites during July-August 1996, and 3414 i...

Water-quality assessment of part of the upper Mississippi River basin, Minnesota and Wisconsin: Design and implementation of water-quality studies, 1995-98

USGS Publications Warehouse

Stark, James R.; Fallon, J.D.; Fong, A.L.; Goldstein, R.M.; Hanson, P.E.; Kroening, S.E.; Lee, K.E.

1999-01-01

This report describes the design, site-selection, and implementation of the study. Methods used to collect, process, and analyze samples; characterize sites; and assess habitat are described. A comprehensive list of sample sites is provided. Sample analyses for water-quality studies included chlorophyll a, major inorganic constituents, nutrients, trace elements, tritium, radon, environmental isotopes, organic carbon, pesticides, volatile organic compounds, and other synthetic and naturallyoccurring organic compounds. Aquatic-biological samples included fish, benthic macroinvertebrates, and algal enumeration and identification, as well as synthetic-organic compounds and trace elements in fish tissue.

Superfund record of decision (EPA Region 7): St. Louis Airport/HHS/Futura Coatings Co. , St. Louis County, MO, August 27, 1998

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

Not Available

1999-03-01

This document presents the selected remedial action for the cleanup of wastes related to Manhattan Engineering District/Atomic Energy Commission (MED/AEC) operations in accessible soils and ground water at the St. Louis Downtown Site (SLDS). The main components of the selected remedial action include: Excavation and off-site disposal of approximately 65,000 cubic meters (85,000 cubic yards) (in-situ) contaminated soil; and No remedial action is required for ground water beneath the site. Perimeter monitoring of the ground water in the Mississippi River alluvial aquifer, designated as the hydrostratigraphic B Unit, will be performed and the need for ground water remediation will bemore » evaluated as part of the periodic reviews performed for the site.« less

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

40 CFR 35.4070 - How can my group spend TAG money?

Code of Federal Regulations, 2011 CFR

2011-07-01

... investigation, and feasibility study, record of decision, remedial design, selection and construction of... and maintenance” of a site, including exposure investigation, health study, surveillance program...

The complexity of selection at the major primate β-defensin locus

PubMed Central

Semple, Colin AM; Maxwell, Alison; Gautier, Philippe; Kilanowski, Fiona M; Eastwood, Hayden; Barran, Perdita E; Dorin, Julia R

2005-01-01

Background We have examined the evolution of the genes at the major human β-defensin locus and the orthologous loci in a range of other primates and mouse. For the first time these data allow us to examine selective episodes in the more recent evolutionary history of this locus as well as the ancient past. We have used a combination of maximum likelihood based tests and a maximum parsimony based sliding window approach to give a detailed view of the varying modes of selection operating at this locus. Results We provide evidence for strong positive selection soon after the duplication of these genes within an ancestral mammalian genome. Consequently variable selective pressures have acted on β-defensin genes in different evolutionary lineages, with episodes both of negative, and more rarely positive selection, during the divergence of primates. Positive selection appears to have been more common in the rodent lineage, accompanying the birth of novel, rodent-specific β-defensin genes. These observations allow a fuller understanding of the evolution of mammalian innate immunity. In both the rodent and primate lineages, sites in the second exon have been subject to positive selection and by implication are important in functional diversity. A small number of sites in the mature human peptides were found to have undergone repeated episodes of selection in different primate lineages. Particular sites were consistently implicated by multiple methods at positions throughout the mature peptides. These sites are clustered at positions predicted to be important for the specificity of the antimicrobial or chemoattractant properties of β-defensins. Surprisingly, sites within the prepropeptide region were also implicated as being subject to significant positive selection, suggesting previously unappreciated functional significance for this region. Conclusions Identification of these putatively functional sites has important implications for our understanding of β-defensin function and for novel antibiotic design. PMID:15904491

Estimating Peak-Flow Frequency Statistics for Selected Gaged and Ungaged Sites in Naturally Flowing Streams and Rivers in Idaho

DOT National Transportation Integrated Search

2017-03-01

Reliable estimates of the magnitude and frequency of floods are needed by Federal, regional, State, and local infrastructure designers and water-resource managers for the design of highway, road, and other bridge crossings of rivers, delineation of f...

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...

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...

Chelating effect in short polymers for the design of bidentate binders of increased affinity and selectivity

PubMed Central

Fortuna, Sara; Fogolari, Federico; Scoles, Giacinto

2015-01-01

The design of new strong and selective binders is a key step towards the development of new sensing devices and effective drugs. Both affinity and selectivity can be increased through chelation and here we theoretically explore the possibility of coupling two binders through a flexible linker. We prove the enhanced ability of double binders of keeping their target with a simple model where a polymer composed by hard spheres interacts with a spherical macromolecule, such as a protein, through two sticky spots. By Monte Carlo simulations and thermodynamic integration we show the chelating effect to hold for coupling polymers whose radius of gyration is comparable to size of the chelated particle. We show the binding free energy of flexible double binders to be higher than that of two single binders and to be maximized when the binding sites are at distances comparable to the mean free polymer end-to-end distance. The affinity of two coupled binders is therefore predicted to increase non linearly and in turn, by targeting two non-equivalent binding sites, this will lead to higher selectivity. PMID:26496975

Earthquake design criteria for small hydro projects in the Philippines

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

Martin, P.P.; McCandless, D.H.; Asce, M.

1995-12-31

The definition of the seismic environment and seismic design criteria of more than twenty small hydro projects in the northern part of the island of Luzon in the Philippines took a special urgency on the wake of the Magnitude 7.7 earthquake that shook the island on July 17, 1990. The paper describes the approach followed to determine design shaking level criteria at each hydro site consistent with the seismic environment estimated at that same site. The approach consisted of three steps: (1) Seismicity: understanding the mechanisms and tectonic features susceptible to generate seismicity and estimating the associated seismicity levels, (2)more » Seismic Hazard: in the absence of an accurate historical record, using statistics to determine the expected level of ground shaking at a site during the operational 100-year design life of each Project, and (3) Criteria Selection: finally and most importantly, exercising judgment in estimating the final proposed level of shaking at each site. The resulting characteristics of estimated seismicity and seismic hazard and the proposed final earthquake design criteria are provided.« less

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

Predictive Array Design. A method for sampling combinatorial chemistry library space.

PubMed

Lipkin, M J; Rose, V S; Wood, J

2002-01-01

A method, Predictive Array Design, is presented for sampling combinatorial chemistry space and selecting a subarray for synthesis based on the experimental design method of Latin Squares. The method is appropriate for libraries with three sites of variation. Libraries with four sites of variation can be designed using the Graeco-Latin Square. Simulated annealing is used to optimise the physicochemical property profile of the sub-array. The sub-array can be used to make predictions of the activity of compounds in the all combinations array if we assume each monomer has a relatively constant contribution to activity and that the activity of a compound is composed of the sum of the activities of its constitutive monomers.

MX Siting Investigation. Municipal Water-Supply and Waste-Water Treatment Facilities in Selected Nevada and Utah Communities.

DTIC Science & Technology

1980-06-20

located between the six cells of the lagoon system. Table 23 shows the characteristics of the system. I The detention lagoon was designed to...Wastewater Facilities for Selected Rural Nevada Communities B Municipal Water Resources Analysis for Area Potential- ly Impacted by MX Missile Complex in Utah...order teaet very large grocth up tntiel grond-cater rights In Stepee 0.4e/a , for average demand plus io a designated basin these quentiti Ruth- c~ill

Considering Spatial Scale and Reproductive Consequences of Habitat Selection when Managing Grasslands for a Threatened Species

PubMed Central

Pearson, Scott F.; Knapp, Shannon M.

2016-01-01

Habitat selection that has fitness consequences has important implications for conservation activities. For example, habitat characteristics that influence nest success in birds can be manipulated to improve habitat quality with the goal of ultimately improving reproductive success. We examined habitat selection by the threatened streaked horned lark (Eremophila alpestris strigata) at both the breeding-site (territory) and nest-site scales. Larks were selective at both spatial scales but with contrasting selection. At the territory scale, male larks selected sparsely vegetated grasslands with relatively short vegetation. At the nest-site scale, female larks selected sites within territories with higher vegetation density and more perennial forbs. These nest-site scale choices had reproductive consequences, with greater nest success in areas with higher densities of perennial forbs. We experimentally manipulated lark habitat structure in an attempt to mimic the habitat conditions selected by larks by using late summer prescribed fires. After the burn, changes in vegetation structure were in the direction preferred by larks but habitat effects attenuated by the following year. Our results highlight the importance of evaluating habitat selection at spatial scales appropriate to the species of interest, especially when attempting to improve habitat quality for rare and declining species. They also highlight the importance of conducting restoration activities in a research context. For example, because the sparsely vegetated conditions created by fire attenuate, there may be value in examining more frequent burns or hotter fires as the next management and research action. We hope the design outlined in this study will serve as an integrated research and management example for conserving grassland birds generally. PMID:27322196

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…

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.

Bridging Scales: A Model-Based Assessment of the Technical Tidal-Stream Energy Resource off Massachusetts, USA

NASA Astrophysics Data System (ADS)

Cowles, G. W.; Hakim, A.; Churchill, J. H.

2016-02-01

Tidal in-stream energy conversion (TISEC) facilities provide a highly predictable and dependable source of energy. Given the economic and social incentives to migrate towards renewable energy sources there has been tremendous interest in the technology. Key challenges to the design process stem from the wide range of problem scales extending from device to array. In the present approach we apply a multi-model approach to bridge the scales of interest and select optimal device geometries to estimate the technical resource for several realistic sites in the coastal waters of Massachusetts, USA. The approach links two computational models. To establish flow conditions at site scales ( 10m), a barotropic setup of the unstructured grid ocean model FVCOM is employed. The model is validated using shipboard and fixed ADCP as well as pressure data. For device scale, the structured multiblock flow solver SUmb is selected. A large ensemble of simulations of 2D cross-flow tidal turbines is used to construct a surrogate design model. The surrogate model is then queried using velocity profiles extracted from the tidal model to determine the optimal geometry for the conditions at each site. After device selection, the annual technical yield of the array is evaluated with FVCOM using a linear momentum actuator disk approach to model the turbines. Results for several key Massachusetts sites including comparison with theoretical approaches will be presented.

Direct conversion of bio-ethanol to isobutene on nanosized Zn(x)Zr(y)O(z) mixed oxides with balanced acid-base sites.

PubMed

Sun, Junming; Zhu, Kake; Gao, Feng; Wang, Chongmin; Liu, Jun; Peden, Charles H F; Wang, Yong

2011-07-27

We report the design and synthesis of nanosized Zn(x)Zr(y)O(z) mixed oxides for direct and high-yield conversion of bio-ethanol to isobutene (~83%). ZnO is addded to ZrO(2) to selectively passivate zirconia's strong Lewis acidic sites and weaken Brönsted acidic sites, while simultaneously introducing basicity. As a result, the undesired reactions of bio-ethanol dehydration and acetone polymerization/coking are suppressed. Instead, a surface basic site-catalyzed ethanol dehydrogenation to acetaldehyde, acetaldehyde to acetone conversion via a complex pathway including aldol-condensation/dehydrogenation, and a Brönsted acidic site-catalyzed acetone-to-isobutene reaction pathway dominates on the nanosized Zn(x)Zr(y)O(z) mixed oxide catalyst, leading to a highly selective process for direct conversion of bio-ethanol to isobutene.

Humid site stabilization and closure

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

Cutshall, N.H.

1981-01-01

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

Characterizing the diversity of coral reef habitats and fish communities found in a UNESCO World Heritage Site: the strategy developed for Lagoons of New Caledonia.

PubMed

Andréfouët, S; Wantiez, L

2010-01-01

Since 1972, the UNESCO "World Heritage Convention" offers an international canvas for conservation and management that targets areas of high cultural and environmental significance. To support the designation of areas within the 36.000 km(2) of New Caledonia coral reefs and lagoons as a World Heritage Site, the natural value and diversity of the proposed zones needed to be demonstrated. To exhaustively identify each configuration of shallow habitats, high resolution remote sensing images were used to select the sampling sites. This optimal scheme resulted in the selection of nearly 1300 sampling sites, and was then simplified to render its application realistic. In the final sampling plan, only the most common or the most remarkable coral zones were selected. Following this selection, in situ habitat and fish surveys were conducted in 2006-2008 in five large areas spanning a 600 km-long latitudinal gradient. Habitats were described using line-intercept transects in parallel with underwater visual census of indicator and commercial coral reef fish species. We report here on the results achieved in terms of: (i) the actual diversity of coral habitats captured by the remote sensing based sampling strategy, (ii) the different reef fish communities captured from the different sites, and (iii) how well they represent New Caledonia diversity. We discuss the possible generalization of this scheme to other sites, in the context of World Heritage Site selection and for other large-scale conservation planning activities. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Geoscientific Site Evaluation Approach for Canada's Deep Geological Repository for Used Nuclear Fuel

NASA Astrophysics Data System (ADS)

Sanchez-Rico Castejon, M.; Hirschorn, S.; Ben Belfadhel, M.

2015-12-01

The Nuclear Waste Management Organization (NWMO) is responsible for implementing Adaptive Phased Management, the approach selected by the Government of Canada for long-term management of used nuclear fuel generated by Canadian nuclear reactors. The ultimate objective of APM is the centralized containment and isolation of Canada's used nuclear fuel in a Deep Geological Repository in a suitable crystalline or sedimentary rock formation. In May 2010, the NWMO published and initiated a nine-step site selection process to find an informed and willing community to host a deep geological repository for Canada's used nuclear fuel. The site selection process is designed to address a broad range of technical and social, economic and cultural factors. The site evaluation process includes three main technical evaluation steps: Initial Screenings; Preliminary Assessments; and Detailed Site Characterizations, to assess the suitability of candidate areas in a stepwise manner over a period of many years. By the end of 2012, twenty two communities had expressed interest in learning more about the project. As of July 2015, nine communities remain in the site selection process. To date (July 2015), NWMO has completed Initial Screenings for the 22 communities that expressed interest, and has completed the first phase of Preliminary Assessments (desktop) for 20 of the communities. Phase 2 of the Preliminary Assessments has been initiated in a number of communities, with field activities such as high-resolution airborne geophysical surveys and geological mapping. This paper describes the approach, methods and criteria being used to assess the geoscientific suitability of communities currently involved in the site selection process.

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.

Scanning ARM Cloud Radar Handbook

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

Widener, K; Bharadwaj, N; Johnson, K

2012-06-18

The scanning ARM cloud radar (SACR) is a polarimetric Doppler radar consisting of three different radar designs based on operating frequency. These are designated as follows: (1) X-band SACR (X-SACR); (2) Ka-band SACR (Ka-SACR); and (3) W-band SACR (W-SACR). There are two SACRs on a single pedestal at each site where SACRs are deployed. The selection of the operating frequencies at each deployed site is predominantly determined by atmospheric attenuation at the site. Because RF attenuation increases with atmospheric water vapor content, ARM's Tropical Western Pacific (TWP) sites use the X-/Ka-band frequency pair. The Southern Great Plains (SGP) and Northmore » Slope of Alaska (NSA) sites field the Ka-/W-band frequency pair. One ARM Mobile Facility (AMF1) has a Ka/W-SACR and the other (AMF2) has a X/Ka-SACR.« less

Photovoltaic module encapsulation design and materials selection, volume 1

NASA Technical Reports Server (NTRS)

Cuddihy, E.; Carroll, W.; Coulbert, C.; Gupta, A.; Liang, R. H.

1982-01-01

Encapsulation material system requirements, material selection criteria, and the status and properties of encapsulation materials and processes available are presented. Technical and economic goals established for photovoltaic modules and encapsulation systems and their status are described. Available encapsulation technology and data are presented to facilitate design and material selection for silicon flat plate photovoltaic modules, using the best materials available and processes optimized for specific power applications and geographic sites. The operational and environmental loads that encapsulation system functional requirements and candidate design concepts and materials that are identified to have the best potential to meet the cost and performance goals for the flat plate solar array project are described. Available data on encapsulant material properties, fabrication processing, and module life and durability characteristics are presented.

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…

Tricyclic Covalent Inhibitors Selectively Target Jak3 through an Active Site Thiol

DOE PAGES

Goedken, Eric R.; Argiriadi, Maria A.; Banach, David L.; ...

2014-12-31

The action of Janus kinases (JAKs) is required for multiple cytokine signaling pathways, and as such, JAK inhibitors hold promise for treatment of autoimmune disorders, including rheumatoid arthritis, inflammatory bowel disease, and psoriasis. However, due to high similarity in the active sites of the four members (Jak1, Jak2, Jak3, and Tyk2), developing selective inhibitors within this family is challenging. In this paper, we have designed and characterized substituted, tricyclic Jak3 inhibitors that selectively avoid inhibition of the other JAKs. This is accomplished through a covalent interaction between an inhibitor containing a terminal electrophile and an active site cysteine (Cys-909). Wemore » found that these ATP competitive compounds are irreversible inhibitors of Jak3 enzyme activity in vitro. They possess high selectivity against other kinases and can potently (IC 50 < 100 nM) inhibit Jak3 activity in cell-based assays. Finally, these results suggest irreversible inhibitors of this class may be useful selective agents, both as tools to probe Jak3 biology and potentially as therapies for autoimmune diseases.« less

Tricyclic Covalent Inhibitors Selectively Target Jak3 through an Active Site Thiol

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

Goedken, Eric R.; Argiriadi, Maria A.; Banach, David L.

The action of Janus kinases (JAKs) is required for multiple cytokine signaling pathways, and as such, JAK inhibitors hold promise for treatment of autoimmune disorders, including rheumatoid arthritis, inflammatory bowel disease, and psoriasis. However, due to high similarity in the active sites of the four members (Jak1, Jak2, Jak3, and Tyk2), developing selective inhibitors within this family is challenging. In this paper, we have designed and characterized substituted, tricyclic Jak3 inhibitors that selectively avoid inhibition of the other JAKs. This is accomplished through a covalent interaction between an inhibitor containing a terminal electrophile and an active site cysteine (Cys-909). Wemore » found that these ATP competitive compounds are irreversible inhibitors of Jak3 enzyme activity in vitro. They possess high selectivity against other kinases and can potently (IC 50 < 100 nM) inhibit Jak3 activity in cell-based assays. Finally, these results suggest irreversible inhibitors of this class may be useful selective agents, both as tools to probe Jak3 biology and potentially as therapies for autoimmune diseases.« less

Near-optimal experimental design for model selection in systems biology.

PubMed

Busetto, Alberto Giovanni; Hauser, Alain; Krummenacher, Gabriel; Sunnåker, Mikael; Dimopoulos, Sotiris; Ong, Cheng Soon; Stelling, Jörg; Buhmann, Joachim M

2013-10-15

Biological systems are understood through iterations of modeling and experimentation. Not all experiments, however, are equally valuable for predictive modeling. This study introduces an efficient method for experimental design aimed at selecting dynamical models from data. Motivated by biological applications, the method enables the design of crucial experiments: it determines a highly informative selection of measurement readouts and time points. We demonstrate formal guarantees of design efficiency on the basis of previous results. By reducing our task to the setting of graphical models, we prove that the method finds a near-optimal design selection with a polynomial number of evaluations. Moreover, the method exhibits the best polynomial-complexity constant approximation factor, unless P = NP. We measure the performance of the method in comparison with established alternatives, such as ensemble non-centrality, on example models of different complexity. Efficient design accelerates the loop between modeling and experimentation: it enables the inference of complex mechanisms, such as those controlling central metabolic operation. Toolbox 'NearOED' available with source code under GPL on the Machine Learning Open Source Software Web site (mloss.org).

The method of landing sites selection for Russian lunar lander missions

NASA Astrophysics Data System (ADS)

Mitrofanov, Igor; Djachkova, Maya; Litvak, Maxim; Sanin, Anton

2016-04-01

Russian space agency is planning to launch two lunar landers in the upcoming years - Luna-Glob (2018) and Luna-Resurs (2021). Instruments installed on board the landers are designed to study volatiles and water ice, lunar exosphere, dust particles and regolith composition. As primary scientific interest is concentrated in the south polar region, the landing sites for both landers will be selected there. Since rugged terrain, conditions of solar illumination at high altitudes and necessity of direct radio communication with the Earth, it is essential to select an optimal landing site for each lander. We present the method of landing sites selection, which is based on geographical information systems (GIS) technologies to perform analysis, based on the criteria of surface suitability for landing, such as slopes, illumination conditions and Earth visibility. In addition, the estimations of hydrogen concentration in regolith based on LEND/LRO data were used to evaluate landing site candidates on possible water ice presence. The method gave us 6 canditates to land. Four of them are located in the impact craters: Simpelius D, Simpelius E, Boguslawsky C, Boussingault, and the other two are located to the north of Schomberger crater and to the north-west of Boguslawsky C crater and associated with probable basin-related materials. The main parameters of these sites will be presented with possible prioritization based on both technical requirements and scientific interest.

Artificial genetic selection for an efficient translation initiation site for expression of human RACK1 gene in Escherichia coli

PubMed Central

Zhelyabovskaya, Olga B.; Berlin, Yuri A.; Birikh, Klara R.

2004-01-01

In bacterial expression systems, translation initiation is usually the rate limiting and the least predictable stage of protein synthesis. Efficiency of a translation initiation site can vary dramatically depending on the sequence context. This is why many standard expression vectors provide very poor expression levels of some genes. This notion persuaded us to develop an artificial genetic selection protocol, which allows one to find for a given target gene an individual efficient ribosome binding site from a random pool. In order to create Darwinian pressure necessary for the genetic selection, we designed a system based on translational coupling, in which microorganism survival in the presence of antibiotic depends on expression of the target gene, while putting no special requirements on this gene. Using this system we obtained superproducing constructs for the human protein RACK1 (receptor for activated C kinase). PMID:15034151

Precise small molecule recognition of a toxic CUG RNA repeat expansion

PubMed Central

Rzuczek, Suzanne G; Colgan, Lesley A; Nakai, Yoshio; Cameron, Michael D; Furling, Denis; Yasuda, Ryohei; Disney, Matthew D

2017-01-01

Excluding the ribosome and riboswitches, developing small molecules that selectively target RNA is a longstanding problem in chemical biology. A typical cellular RNA is difficult to target because it has little tertiary, but abundant secondary structure. We designed allele-selective compounds that target such an RNA, the toxic noncoding repeat expansion (r(CUG)exp) that causes myotonic dystrophy type 1 (DM1). We developed several strategies to generate allele-selective small molecules, including non-covalent binding, covalent binding, cleavage and on-site probe synthesis. Covalent binding and cleavage enabled target profiling in cells derived from individuals with DM1, showing precise recognition of r(CUG)exp. In the on-site probe synthesis approach, small molecules bound adjacent sites in r(CUG)exp and reacted to afford picomolar inhibitors via a proximity-based click reaction only in DM1-affected cells. We expanded this approach to image r(CUG)exp in its natural context. PMID:27941760

Precise small-molecule recognition of a toxic CUG RNA repeat expansion.

PubMed

Rzuczek, Suzanne G; Colgan, Lesley A; Nakai, Yoshio; Cameron, Michael D; Furling, Denis; Yasuda, Ryohei; Disney, Matthew D

2017-02-01

Excluding the ribosome and riboswitches, developing small molecules that selectively target RNA is a longstanding problem in chemical biology. A typical cellular RNA is difficult to target because it has little tertiary, but abundant secondary structure. We designed allele-selective compounds that target such an RNA, the toxic noncoding repeat expansion (r(CUG) exp ) that causes myotonic dystrophy type 1 (DM1). We developed several strategies to generate allele-selective small molecules, including non-covalent binding, covalent binding, cleavage and on-site probe synthesis. Covalent binding and cleavage enabled target profiling in cells derived from individuals with DM1, showing precise recognition of r(CUG) exp . In the on-site probe synthesis approach, small molecules bound adjacent sites in r(CUG) exp and reacted to afford picomolar inhibitors via a proximity-based click reaction only in DM1-affected cells. We expanded this approach to image r(CUG) exp in its natural context.

Discovery of novel high potent and cellular active ADC type PTP1B inhibitors with selectivity over TC-PTP via modification interacting with C site.

PubMed

Du, Yongli; Zhang, Yanhui; Ling, Hao; Li, Qunyi; Shen, Jingkang

2018-01-20

PTP1B serving as a key negative regulator of insulin signaling is a novel target for type 2 diabetes and obesity. Modification at ring B of N-{4-[(3-Phenyl-ureido)-methyl]-phenyl}-methane-sulfonamide template to interact with residues Arg47 and Lys41 in the C site of PTP1B by molecular docking aided design resulted in the discovery of a series of novel high potent and selective inhibitors of PTP1B. The structure activity relationship interacting with the C site of PTP1B was well illustrated. Compounds 8 and 18 were shown to be the high potent and most promising PTP1B inhibitors with cellular activity and great selectivity over the highly homologous TCPTP and other PTPs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Flood prevention dams for arid regions at a micro-scale sub-catchment, case study: Tabuk, Saudi Arabia.

PubMed

Abushandi, Eyad

2016-12-01

Unexpected flash flooding is one of the periodic hydrological problems affecting the city of Tabuk in Saudi Arabia. The region has high potential for floods as it suffers high rainfall intensity in a short time and also has high urbanization rates and topographic complexity. Constructing flood prevention dams is one option to solve this problem. A cost-effective design requires a detailed feasibility study and analysis for the selection of suitable sites. The aim of this study was to develop a method for selecting a suitable site for flood protection dams in the Abu Saba'a district, the most affected part of the city of Tabuk during the flash flood in January 2013. Spatial analysis was applied using Landsat Thematic Mapper images and Shuttle Radar Topography Mission digital elevation model to select a site in the Abu Saba'a area. A simple model using ArcGIS was built including all suggested parameters. The results showed the best site for a dam was 2 km distance backfrom the area, where all parameter values matched. The results showed that the dynamic properties of land cover can affect site selection. It is therefore suggested that more field and hydrological data should be gathered for greater accuracy.

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.

The Utility of Geographical Information Systems (GIS) in Systems-Oriented Obesity Intervention Projects: The Selection of Comparable Study Sites for a Quasi-Experimental Intervention Design—TX CORD

PubMed Central

Byars, Allison; Byrd-Williams, Courtney; Sharma, Shreela V.; Durand, Casey; Hoelscher, Deanna M.; Butte, Nancy F.; Kelder, Steven H.

2015-01-01

Abstract Background: The Texas Childhood Obesity Research Demonstration project (TX CORD) uses a systems-oriented approach to address obesity that includes individual and family interventions, community-level action, as well as environmental and policy initiatives. Given that randomization is seldom possible in community-level intervention studies, TX CORD uses a quasi-experimental design. Comparable intervention and comparison study sites are needed to address internal validity bias. Methods: TX CORD was designed to be implemented in low-income, ethnically diverse communities in Austin and Houston, Texas. A three-stage Geographical Information System (GIS) methodology was used to establish and ascertain the comparability of the intervention and comparison study sites. Census tract (stage 1) and school (stage 2) data were used to identify spatially exclusive geographic areas that were comparable. In stage 3, study sites were compared on demographic characteristics, socioeconomic status (SES), food assets, and physical activity (PA) assets. Student's t-test was used to examine significant differences between the selected sites. Results: The methodology that was used resulted in the selection of catchment areas with demographic and socioeconomic characteristics that fit the target population: ethnically diverse population; lower-median household income; and lower home ownership rates. Additionally, the intervention and comparison sites were statistically comparable on demographic and SES variables, as well as food assets and PA assets. Conclusions: This GIS approach can provide researchers, program evaluators, and policy makers with useful tools for both research and practice. Area-level information that allows for robust understanding of communities can enhance analytical procedures in community health research and offer significant contributions in terms of community assessment and engagement. PMID:25587670

Computer-assisted selection of donor sites for autologous grafts

NASA Astrophysics Data System (ADS)

Krol, Zdzislaw; Zeilhofer, Hans-Florian U.; Sader, Robert; Hoffmann, Karl-Heinz; Gerhardt, Paul; Horch, Hans-Henning

1997-05-01

A new method is proposed for a precise planning of autologous bone grafts in cranio- and maxillofacial surgery. In patients with defects of the facial skeleton, autologous bone transplants can be harvested from various donor sites in the body. The preselection of a donor site depends i.a. on the morphological fit of the available bone mass and the shape of the part that is to be transplanted. A thorough planning and simulation of the surgical intervention based on 3D CT studies leads to a geometrical description and the volumetric characterization of the bone part to be resected and transplanted. Both, an optimal fit and a minimal lesion of the donor site are guidelines in this process. We use surface similarity and voxel similarity measures in order to select the optimal donor region for an individually designed transplant.

Design and use of nanostructured single-site heterogeneous catalysts for the selective transformation of fine chemicals.

PubMed

Dal Santo, Vladimiro; Liguori, Francesca; Pirovano, Claudio; Guidotti, Matteo

2010-05-26

Nanostructured single-site heterogeneous catalysts possess the advantages of classical solid catalysts, in terms of easy recovery and recycling, together with a defined tailored chemical and steric environment around the catalytically active metal site. The use of inorganic oxide supports with selected shape and porosity at a nanometric level may have a relevant impact on the regio- and stereochemistry of the catalytic reaction. Analogously, by choosing the optimal preparation techniques to obtain spatially isolated and well-characterised active sites, it is possible to achieve performances that are comparable to (or, in the most favourable cases, better than) those obtained with homogeneous systems. Such catalysts are therefore particularly suitable for the transformation of highly-functionalised fine chemicals and some relevant examples where high chemo-, regio- and stereoselectivity are crucial will be described.

Superfund record of decision amendment (EPA Region 5): Metamora Landfill Site, Metamora, MI, August 28, 1996

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

NONE

The United States Environmental Protection Agency (U.S. EPA) is changing a portion of the remedy selected in the operable unit one (OU1) Record of Decision (ROD) dated September 30, 1986, for the Metamora Landfill Site. Operable Unit 1 ROD (OU1 ROD) addresses the remediation of drummed waste and contaminated soils in Drum Area 1 and Drum Area 4. OU1 ROD selected off-site incineration of the drums and soils in Drum Area 1 and Drum Area 4. State lead remedial action work began in the spring of 1989 and continued until December 1990. During the summer of 1990, off-site incineration capacitymore » became extremely limited and drums awaiting disposal began to accumulate at the site. In addition, many more drums were discovered than originally estimated in the Remedial Design. In April of 1991 a settlement was reached that addressed the completion of all remedial activity remaining at the site, including the completion of OU1.« less

Synthesis of a molecularly defined single-active site heterogeneous catalyst for selective oxidation of N-heterocycles.

PubMed

Zhang, Yujing; Pang, Shaofeng; Wei, Zhihong; Jiao, Haijun; Dai, Xingchao; Wang, Hongli; Shi, Feng

2018-04-13

Generally, a homogeneous catalyst exhibits good activity and defined active sites but it is difficult to recycle. Meanwhile, a heterogeneous catalyst can easily be reused but its active site is difficult to reveal. It is interesting to bridge the gap between homogeneous and heterogeneous catalysis via controllable construction of a heterogeneous catalyst containing defined active sites. Here, we report that a molecularly defined, single-active site heterogeneous catalyst has been designed and prepared via the oxidative polymerization of maleimide derivatives. These polymaleimide derivatives can be active catalysts for the selective oxidation of heterocyclic compounds to quinoline and indole via the recycling of -C=O and -C-OH groups, which was confirmed by tracing the reaction with GC-MS using maleimide as the catalyst and by FT-IR analysis with polymaleimide as the catalyst. These results might promote the development of heterogeneous catalysts with molecularly defined single active sites exhibiting a comparable activity to homogeneous catalysts.

A Programming System for School Location & Facility Utilization.

ERIC Educational Resources Information Center

North Carolina State Dept. of Public Instruction, Raleigh.

A linear program model designed to aid in site selection and the development of pupil assignment plans is illustrated in terms of a hypothetical school system. The model is designed to provide the best possible realization of any single stated objective (for example, "Minimize the distance that pupils must travel") given any number of specified…

Housing for the Physically Impaired; A Guide for Planning and Design.

ERIC Educational Resources Information Center

Department of Housing and Urban Development, Washington, DC.

Problems involved in providing homes for independent living for the physically handicapped, health impaired, or older adults are considered. Basic concepts of low rent housing preface a discussion of neighborhoods and site selection, access, ramps, pedestrian walks, parking, landscaping, and lighting. Guides for building design focus on entrances,…

Facility Issues in Community School Centers. #4 in a Series of 6 Booklets.

ERIC Educational Resources Information Center

Educational Facilities Labs., Inc., New York, NY.

This booklet is the fourth in a series that examines community school centers. The development and substance of the building program, issues related to site selection and development, and overall building design strategies are examined. Also discussed are particularly important design details about which the programming committee and the architect…

A site classification for the mixed-conifer selection forests of the Sierra Nevada

Treesearch

Duncan Dunning

1942-01-01

The site-class curves presented . . . for the irregular pine-fir forests of California, were first prepared in connection with a yield-predicting procedure . . . developed in 1933. The original curves were designed principally for administrative use of the Forest Service in Region 5. Since they have now come to be accepted by other agencies and for general purposes,...

Quantifying and visualizing site performance in clinical trials.

PubMed

Yang, Eric; O'Donovan, Christopher; Phillips, JodiLyn; Atkinson, Leone; Ghosh, Krishnendu; Agrafiotis, Dimitris K

2018-03-01

One of the keys to running a successful clinical trial is the selection of high quality clinical sites, i.e., sites that are able to enroll patients quickly, engage them on an ongoing basis to prevent drop-out, and execute the trial in strict accordance to the clinical protocol. Intuitively, the historical track record of a site is one of the strongest predictors of its future performance; however, issues such as data availability and wide differences in protocol complexity can complicate interpretation. Here, we demonstrate how operational data derived from central laboratory services can provide key insights into the performance of clinical sites and help guide operational planning and site selection for new clinical trials. Our methodology uses the metadata associated with laboratory kit shipments to clinical sites (such as trial and anonymized patient identifiers, investigator names and addresses, sample collection and shipment dates, etc.) to reconstruct the complete schedule of patient visits and derive insights about the operational performance of those sites, including screening, enrollment, and drop-out rates and other quality indicators. This information can be displayed in its raw form or normalized to enable direct comparison of site performance across studies of varied design and complexity. Leveraging Covance's market leadership in central laboratory services, we have assembled a database of operational metrics that spans more than 14,000 protocols, 1400 indications, 230,000 unique investigators, and 23 million patient visits and represents a significant fraction of all clinical trials run globally in the last few years. By analyzing this historical data, we are able to assess and compare the performance of clinical investigators across a wide range of therapeutic areas and study designs. This information can be aggregated across trials and geographies to gain further insights into country and regional trends, sometimes with surprising results. The use of operational data from Covance Central Laboratories provides a unique perspective into the performance of clinical sites with respect to many important metrics such as patient enrollment and retention. These metrics can, in turn, be used to guide operational planning and site selection for new clinical trials, thereby accelerating recruitment, improving quality, and reducing cost.

Wind study for high altitude platform design

NASA Technical Reports Server (NTRS)

Strganac, T. W.

1979-01-01

An analysis of upper air winds was performed to define the wind environment at potential operating altitudes for high-altitude powered platform concepts. Expected wind conditions of the contiguous United States, Pacific area (Alaska to Sea of Japan), and European area (Norwegian and Mediterranean Seas) were obtained using a representative network of sites selected based upon adequate high-altitude sampling, geographic dispersion, and observed upper wind patterns. A data base of twenty plus years of rawinsonde gathered wind information was used in the analysis. Annual variations from surface to 10 mb (approximately 31 km) pressure altitude were investigated to encompass the practical operating range for the platform concepts. Parametric analysis for the United States and foreign areas was performed to provide a basis for vehicle system design tradeoffs. This analysis of wind magnitudes indicates the feasibility of annual operation at a majority of sites and more selective seasonal operation for the extreme conditions between the pressure altitudes of 100 to 25 mb based upon the assumed design speeds.

Possible consequences of severe accidents at the Lubiatowo site, Poland

NASA Astrophysics Data System (ADS)

Seibert, Petra; Philipp, Anne; Hofman, Radek; Gufler, Klaus; Sholly, Steven

2014-05-01

The construction of a nuclear power plant is under consideration in Poland. One of the sites under discussion is near Lubiatowo, located on the cost of the Baltic Sea northwest of Gdansk. An assessment of possible environmental consequences is carried out for 88 real meteorological cases with the Lagrangian particle dispersion model FLEXPART. Based on literature research, three reactor designs (ABWR, EPR, AP 1000) were identified as being under discussion in Poland. For each of the designs, a set of accident scenarios was evaluated and two source terms per reactor design were selected for analysis. One of the selected source terms was a relatively large release while the second one was a severe accident with an intact containment. Considered endpoints of the calculations are ground contamination with Cs-137 and time-integrated concentrations of I-131 in air as well as committed doses. They are evaluated on a grid of ca. 3 km mesh size covering eastern Central Europe.

Wind study for high altitude platform design

NASA Technical Reports Server (NTRS)

Strganac, T. W.

1979-01-01

An analysis of upper air winds was performed to define the wind environment at potential operating altitudes for high altitude powered platform concepts. Wind conditions of the continental United States, Pacific area (Alaska to Sea of Japan), and European area (Norwegian and Mediterranean Sea) were obtained using a representative network of sites selected based upon adequate high altitude sampling, geographic dispersion, and observed upper wind patterns. A data base of twenty plus years of rawinsonde gathered wind information was used in the analysis. Annual variations from surface to 10 mb pressure altitude were investigated to encompass the practical operating range for the platform concepts. Parametric analysis for the United States and foreign areas was performed to provide a basis for vehicle system design tradeoffs. This analysis of wind magnitudes indicates the feasibility of annual operation at a majority of sites and more selective seasonal operation for the extreme conditions between the pressure altitudes of 100 to 25 mb based upon the assumed design speeds.

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

The MedlinePlus public user interface: studies of design challenges and opportunities.

PubMed

Marill, Jennifer L; Miller, Naomi; Kitendaugh, Paula

2006-01-01

What are the challenges involved in designing, modifying, and improving a major health information portal that serves over sixty million page views a month? MedlinePlus, the National Library of Medicine's (NLM's) consumer health Website, is examined. Challenges are presented as six "studies," which describe selected design issues and how NLM staff resolved them. Improving MedlinePlus is an iterative process. Changes in the public user interface are ongoing, reflecting Web design trends, usability testing recommendations, user survey results, new technical requirements, and the need to grow the site in an orderly way. Testing and analysis should accompany Website design modifications. New technologies may enhance a site but also introduce problems. Further modifications to MedlinePlus will be informed by the experiences described here.

Designing a web site for high school geoscience teaching in Iceland

NASA Astrophysics Data System (ADS)

Douglas, George R.

1998-08-01

The need to construct an earth science teaching site on the web prompted a survey of existing sites which, in spite of containing much of value, revealed many weaknesses in basic design, particularly as regards the organisation of links to information resources. Few web sites take into consideration the particular pedagogic needs of the high school science student and there has, as yet, been little serious attempt to exploit and organise the more outstanding advantages offered by the internet to science teaching, such as accessing real-time data. A web site has been constructed which, through basic design, enables students to access relevant information resources over a wide range of subjects and topics easily and rapidly, while at the same time performing an instructional role in how to handle both on-line and off-line resources. Key elements in the design are selection and monitoring by the teacher, task oriented pages and the use of the Dewey decimal classification system. The intention is to increase gradually the extent to which most teaching tasks are carried out via the web pages, in the belief that they can become an efficient central point for all the earth science curriculum.

Advanced on-site power plant development technology program

NASA Technical Reports Server (NTRS)

1984-01-01

A 30-cell, full area short stack containing advanced cell features was tested for 2900 hours. A stack acid addition approach was selected and will be evaluated on the stack at 5000 hours test time. A brassboard inverter was designed and fabrication was initiated. Evaluation of this brassboard inverter will take place in 1984. A Teflon coated commercial heat exchanger was selected as the preferred approach for the acid condenser. A reformer catalyst with significantly less pressure drop and equivalent performance relative to the 40-K baseline catalyst was selected for the development reformer. The early 40-kW field power plant history was reviewed and adjustments were made to the On-Site Technology Development Program to address critical component issues.

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.

Dynamic conversion of solar generated heat to electricity

NASA Technical Reports Server (NTRS)

Powell, J. C.; Fourakis, E.; Hammer, J. M.; Smith, G. A.; Grosskreutz, J. C.; Mcbride, E.

1974-01-01

The effort undertaken during this program led to the selection of the water-superheated steam (850 psig/900 F) crescent central receiver as the preferred concept from among 11 candidate systems across the technological spectrum of the dynamic conversion of solar generated heat to electricity. The solar power plant designs were investigated in the range of plant capacities from 100 to 1000 Mw(e). The investigations considered the impacts of plant size, collector design, feed-water temperature ratio, heat rejection equipment, ground cover, and location on solar power technical and economic feasibility. For the distributed receiver systems, the optimization studies showed that plant capacities less than 100 Mw(e) may be best. Although the size of central receiver concepts was not parametrically investigated, all indications are that the optimal plant capacity for central receiver systems will be in the range from 50 to 200 Mw(e). Solar thermal power plant site selection criteria and methodology were also established and used to evaluate potentially suitable sites. The result of this effort was to identify a site south of Inyokern, California, as typically suitable for a solar thermal power plant. The criteria used in the selection process included insolation and climatological characteristics, topography, and seismic history as well as water availability.

Photovoltaic system criteria documents. Volume 3: Environmental issues and evaluation criteria for photovoltaic applications

NASA Technical Reports Server (NTRS)

Koenig, John C.; Billitti, Joseph W.; Tallon, John M.

1979-01-01

The environmental issues and evaluation criteria relating to the suitability of sites proposed for photovoltaic (PV) system deployment are identified. The important issues are defined, briefly discussed and then developed into evaluation criteria. System designers are provided with information on the environmental sensitivity of PV systems in realistic applications, background material which indicates the applicability of the siting issues identified, and evaluation criteria are defined to facilitate the selection of sites that maximize PV system operation.

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

Strategy for Ranking the Science Value of the Surface of Asteroid 101955 Bennu for Sample Site Selection for Osiris-REx

NASA Technical Reports Server (NTRS)

Nakamura-Messenger, K.; Connolly, H. C., Jr.; Lauretta, D. S.

2014-01-01

OSRIS-REx is NASA's New Frontiers 3 sample return mission that will return at least 60 g of pristine surface material from near-Earth asteroid 101955 Bennu in September 2023. The scientific value of the sample increases enormously with the amount of knowledge captured about the geological context from which the sample is collected. The OSIRIS-REx spacecraft is highly maneuverable and capable of investigating the surface of Bennu at scales down to the sub-cm. The OSIRIS-REx instruments will characterize the overall surface geology including spectral properties, microtexture, and geochemistry of the regolith at the sampling site in exquisite detail for up to 505 days after encountering Bennu in August 2018. The mission requires at the very minimum one acceptable location on the asteroid where a touch-and-go (TAG) sample collection maneuver can be successfully per-formed. Sample site selection requires that the follow-ing maps be produced: Safety, Deliverability, Sampleability, and finally Science Value. If areas on the surface are designated as safe, navigation can fly to them, and they have ingestible regolith, then the scientific value of one site over another will guide site selection.

Sound settlement: noise surpasses land cover in explaining breeding habitat selection of secondary cavity-nesting birds.

PubMed

Kleist, Nathan J; Guralnick, Robert P; Cruz, Alexander; Francis, Clinton D

2017-01-01

Birds breeding in heterogeneous landscapes select nest sites by cueing in on a variety of factors from landscape features and social information to the presence of natural enemies. We focus on determining the relative impact of anthropogenic noise on nest site occupancy, compared to amount of forest cover, which is known to strongly influence the selection process. We examine chronic, industrial noise from natural gas wells directly measured at the nest box as well as site-averaged noise, using a well-established field experimental system in northwestern New Mexico. We hypothesized that high levels of noise, both at the nest site and in the environment, would decrease nest box occupancy. We set up nest boxes using a geospatially paired control and experimental site design and analyzed four years of occupancy data from four secondary cavity-nesting birds common to the Colorado Plateau. We found different effects of noise and landscape features depending on species, with strong effects of noise observed in breeding habitat selection of Myiarchus cinerascens, the Ash-throated Flycatcher, and Sialia currucoides, the Mountain Bluebird. In contrast, the amount of forest cover less frequently explained habitat selection for those species or had a smaller standardized effect than the acoustic environment. Although forest cover characterization and management is commonly employed by natural resource managers, our results show that characterizing and managing the acoustic environment should be an important tool in protected area management. © 2016 by the Ecological Society of America.

Occupancy Modeling Species-Environment Relationships with Non-ignorable Survey Designs.

PubMed

Irvine, Kathryn M; Rodhouse, Thomas J; Wright, Wilson J; Olsen, Anthony R

2018-05-26

Statistical models supporting inferences about species occurrence patterns in relation to environmental gradients are fundamental to ecology and conservation biology. A common implicit assumption is that the sampling design is ignorable and does not need to be formally accounted for in analyses. The analyst assumes data are representative of the desired population and statistical modeling proceeds. However, if datasets from probability and non-probability surveys are combined or unequal selection probabilities are used, the design may be non ignorable. We outline the use of pseudo-maximum likelihood estimation for site-occupancy models to account for such non-ignorable survey designs. This estimation method accounts for the survey design by properly weighting the pseudo-likelihood equation. In our empirical example, legacy and newer randomly selected locations were surveyed for bats to bridge a historic statewide effort with an ongoing nationwide program. We provide a worked example using bat acoustic detection/non-detection data and show how analysts can diagnose whether their design is ignorable. Using simulations we assessed whether our approach is viable for modeling datasets composed of sites contributed outside of a probability design Pseudo-maximum likelihood estimates differed from the usual maximum likelihood occu31 pancy estimates for some bat species. Using simulations we show the maximum likelihood estimator of species-environment relationships with non-ignorable sampling designs was biased, whereas the pseudo-likelihood estimator was design-unbiased. However, in our simulation study the designs composed of a large proportion of legacy or non-probability sites resulted in estimation issues for standard errors. These issues were likely a result of highly variable weights confounded by small sample sizes (5% or 10% sampling intensity and 4 revisits). Aggregating datasets from multiple sources logically supports larger sample sizes and potentially increases spatial extents for statistical inferences. Our results suggest that ignoring the mechanism for how locations were selected for data collection (e.g., the sampling design) could result in erroneous model-based conclusions. Therefore, in order to ensure robust and defensible recommendations for evidence-based conservation decision-making, the survey design information in addition to the data themselves must be available for analysts. Details for constructing the weights used in estimation and code for implementation are provided. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

18 CFR Appendix A to Part 380 - Minimum Filing Requirements for Environmental Reports Under the Natural Gas Act

Code of Federal Regulations, 2010 CFR

2010-04-01

... provide sufficient comparative data to justify the selection of the proposed route. (§ 380.12(l)(2)(ii)) 5... sufficient comparative data to justify the selection of the proposed site. (§ 380.12(l)(2)(ii)) Resource Report 11—Reliability and Safety Describe how the project facilities would be designed, constructed...

18 CFR Appendix A to Part 380 - Minimum Filing Requirements for Environmental Reports Under the Natural Gas Act

Code of Federal Regulations, 2012 CFR

2012-04-01

... provide sufficient comparative data to justify the selection of the proposed route. (§ 380.12(l)(2)(ii)) 5... sufficient comparative data to justify the selection of the proposed site. (§ 380.12(l)(2)(ii)) Resource Report 11—Reliability and Safety Describe how the project facilities would be designed, constructed...

18 CFR Appendix A to Part 380 - Minimum Filing Requirements for Environmental Reports Under the Natural Gas Act

Code of Federal Regulations, 2014 CFR

2014-04-01

... provide sufficient comparative data to justify the selection of the proposed route. (§ 380.12(l)(2)(ii)) 5... sufficient comparative data to justify the selection of the proposed site. (§ 380.12(l)(2)(ii)) Resource Report 11—Reliability and Safety Describe how the project facilities would be designed, constructed...

18 CFR Appendix A to Part 380 - Minimum Filing Requirements for Environmental Reports Under the Natural Gas Act

Code of Federal Regulations, 2013 CFR

2013-04-01

... provide sufficient comparative data to justify the selection of the proposed route. (§ 380.12(l)(2)(ii)) 5... sufficient comparative data to justify the selection of the proposed site. (§ 380.12(l)(2)(ii)) Resource Report 11—Reliability and Safety Describe how the project facilities would be designed, constructed...

18 CFR Appendix A to Part 380 - Minimum Filing Requirements for Environmental Reports Under the Natural Gas Act

Code of Federal Regulations, 2011 CFR

2011-04-01

... provide sufficient comparative data to justify the selection of the proposed route. (§ 380.12(l)(2)(ii)) 5... sufficient comparative data to justify the selection of the proposed site. (§ 380.12(l)(2)(ii)) Resource Report 11—Reliability and Safety Describe how the project facilities would be designed, constructed...

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

DAG telescope site studies and infrastructure for possible international co-operations

NASA Astrophysics Data System (ADS)

Yerli, Sinan K.; Yeşilyaprak, Cahit; Keskin, Onur; Alis, Sinan

2016-07-01

The selected site for the 4 m DAG (Eastern Anatolian Observatory in Turkish) telescope is at "Karakaya Ridge", at 3170 m altitude (3150 m after summit management). The telescope's optical design is performed by the DAG technical team to allow infrared observation at high angular resolution, with its adaptive optics system to be built in Turkey. In this paper; a brief introduction about DAG telescope design; planned instrumentation; the meteorological data collected from 2008, clear night counts, short-term DIMM observations; current infrastructure to hold auxiliary telescopes; auxiliary buildings to assist operations; the observatory design; and coating unit plans will be presented along with possible collaboration possibilities in terms of instrumentation and science programs.

Design and Empirical Evaluation of Search Software for Legal Professionals on the WWW.

ERIC Educational Resources Information Center

Dempsey, Bert J.; Vreeland, Robert C.; Sumner, Robert G., Jr.; Yang, Kiduk

2000-01-01

Discussion of effective search aids for legal researchers on the World Wide Web focuses on the design and evaluation of two software systems developed to explore models for browsing and searching across a user-selected set of Web sites. Describes crawler-enhanced search engines, filters, distributed full-text searching, and natural language…

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

USGS Publications Warehouse

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

2007-01-01

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

Overview of technology modeling in the Remedial Action Assessment System (RAAS)

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

Johnson, C.D.; Bagaasen, L.M.; Chan, T.C.

1994-08-01

There are numerous hazardous waste sites under the jurisdiction of the US Department of Energy (DOE). To assist the cleanup of these sites in a more consistent, timely, and cost-effective manner, the Remedial Action Assessment System (RAAS) is being developed by the Pacific Northwest Laboratory (PNL). RAAS is a software tool designed to automate the initial technology selection within the remedial investigation/feasibility study (RI/FS) process. The software does several things for the user: (1) provides information about available remedial technologies, (2) sorts possible technologies to recommend a list of technologies applicable to a given site, (3) points out technical issuesmore » that may prevent the implementation of a technology, and (4) provides an estimate of the effectiveness of a given technology at a particular site. Information from RAAS can be used to compare remediation options and guide selection of technologies for further study.« less

Use of the Performance Diagnostic Checklist to Select an Intervention Designed to Increase the Offering of Promotional Stamps at Two Sites of a Restaurant Franchise

ERIC Educational Resources Information Center

Rodriguez, Manuel; Wilder, David A.; Therrien, Kelly; Wine, Byron; Miranti, Reylissa; Daratany, Kenneth; Salume, Gloria; Baranovsky, Greg; Rodriquez, Matias

2006-01-01

The performance diagnostic checklist (PDC) was administered to examine the variables influencing the offering of promotional stamps by employees at two sites of a restaurant franchise. PDC results suggested that a lack of appropriate antecedents, equipment and processes, and consequences were responsible for the deficits. Based on these results,…

Guidance for Optimizing Remedy Evaluation, Selection, and Design

DTIC Science & Technology

2004-04-01

attenuation [MNA] and phytovolatilization) and to enhance these processes using low energy techniques (PRB and engineered phytoremediation ) for...technically and commercially viable. This approach promotes the in situ treatment of contaminants through several means such as phytoremediation ... Mercury Burial Sites I and II and Site 11 – Former Waste Oil Tanks 6 and 7) within the boundaries of the Jamaica Island Landfill (JILF). The JILF

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

Harner, E.J.; Gilfillan, E.S.

Two large shoreline assessment studies conducted in 1990 in Prince William Sound, Alaska, after the Exxon Valdez oil spill used different design strategies to determine the impact of oiling on shoreline biota. One of the studies, the Coastal Habitat Injury Assessment (CHIA) conducted for the Exxon Valdez Oil Spill Council, used matched pairs of sites, normal population distributions for biota, and meta-analysis. The power of the CHIA study to detect oiling impacts depends on being able to identify and select appropriate pairs of sites for comparison. The CHIA study also increased the oiling signal by focusing on moderate to heavilymore » oiled sites. The Shoreline Ecology Program (SEP), conducted for Exxon, used a stratified-random-sampling study design, normal and non-normal population distributions and covariates. The SEP study was able to detect oiling impacts by using a sufficient number of sites and widely spaced transects.« less

Investigation of protein selectivity in multimodal chromatography using in silico designed Fab fragment variants.

PubMed

Karkov, Hanne Sophie; Krogh, Berit Olsen; Woo, James; Parimal, Siddharth; Ahmadian, Haleh; Cramer, Steven M

2015-11-01

In this study, a unique set of antibody Fab fragments was designed in silico and produced to examine the relationship between protein surface properties and selectivity in multimodal chromatographic systems. We hypothesized that multimodal ligands containing both hydrophobic and charged moieties would interact strongly with protein surface regions where charged groups and hydrophobic patches were in close spatial proximity. Protein surface property characterization tools were employed to identify the potential multimodal ligand binding regions on the Fab fragment of a humanized antibody and to evaluate the impact of mutations on surface charge and hydrophobicity. Twenty Fab variants were generated by site-directed mutagenesis, recombinant expression, and affinity purification. Column gradient experiments were carried out with the Fab variants in multimodal, cation-exchange, and hydrophobic interaction chromatographic systems. The results clearly indicated that selectivity in the multimodal system was different from the other chromatographic modes examined. Column retention data for the reduced charge Fab variants identified a binding site comprising light chain CDR1 as the main electrostatic interaction site for the multimodal and cation-exchange ligands. Furthermore, the multimodal ligand binding was enhanced by additional hydrophobic contributions as evident from the results obtained with hydrophobic Fab variants. The use of in silico protein surface property analyses combined with molecular biology techniques, protein expression, and chromatographic evaluations represents a previously undescribed and powerful approach for investigating multimodal selectivity with complex biomolecules. © 2015 Wiley Periodicals, Inc.

Molecular design and structure--activity relationships leading to the potent, selective, and orally active thrombin active site inhibitor BMS-189664.

PubMed

Das, Jagabandhu; Kimball, S David; Hall, Steven E; Han, Wen Ching; Iwanowicz, Edwin; Lin, James; Moquin, Robert V; Reid, Joyce A; Sack, John S; Malley, Mary F; Chang, Chiehying Y; Chong, Saeho; Wang-Iverson, David B; Roberts, Daniel G M; Seiler, Steven M; Schumacher, William A; Ogletree, Martin L

2002-01-07

A series of structurally novel small molecule inhibitors of human alpha-thrombin was prepared to elucidate their structure-activity relationships (SARs), selectivity and activity in vivo. BMS-189664 (3) is identified as a potent, selective, and orally active reversible inhibitor of human alpha-thrombin which is efficacious in vivo in a mouse lethality model, and at inhibiting both arterial and venous thrombosis in cynomolgus monkey models.

NASA Parts Selection List (NPSL) WWW Site http://nepp.nasa.gov/npsl

NASA Technical Reports Server (NTRS)

Brusse, Jay

2000-01-01

The NASA Parts Selection List (NPSL) is an on-line resource for electronic parts selection tailored for use by spaceflight projects. The NPSL provides a list of commonly used electronic parts that have a history of satisfactory use in spaceflight applications. The objective of this www site is to provide NASA projects, contractors, university experimenters, et al with an easy to use resource that provides a baseline of electronic parts from which designers are encouraged to select. The NPSL is an ongoing resource produced by Code 562 in support of the NASA HQ funded NASA Electronic Parts and Packaging (NEPP) Program. The NPSL is produced as an electronic format deliverable made available via the referenced www site administered by Code 562. The NPSL does not provide information pertaining to patented or proprietary information. All of the information contained in the NPSL is available through various other public domain resources such as US Military procurement specifications for electronic parts, NASA GSFC's Preferred Parts List (PPL-21), and NASA's Standard Parts List (MIL-STD975).

Defining the Reference Condition for Wadeable Streams in the Sand Hills Subdivision of the Southeastern Plains Ecoregion, USA

NASA Astrophysics Data System (ADS)

Kosnicki, Ely; Sefick, Stephen A.; Paller, Michael H.; Jarrell, Miller S.; Prusha, Blair A.; Sterrett, Sean C.; Tuberville, Tracey D.; Feminella, Jack W.

2014-09-01

The Sand Hills subdivision of the Southeastern Plains ecoregion has been impacted by historical land uses over the past two centuries and, with the additive effects of contemporary land use, determining reference condition for streams in this region is a challenge. We identified reference condition based on the combined use of 3 independent selection methods. Method 1 involved use of a multivariate disturbance gradient derived from several stressors, method 2 was based on variation in channel morphology, and method 3 was based on passing 6 of 7 environmental criteria. Sites selected as reference from all 3 methods were considered primary reference, whereas those selected by 2 or 1 methods were considered secondary or tertiary reference, respectively. Sites not selected by any of the methods were considered non-reference. In addition, best professional judgment (BPJ) was used to exclude some sites from any reference class, and comparisons were made to examine the utility of BPJ. Non-metric multidimensional scaling indicated that use of BPJ may help designate non-reference sites when unidentified stressors are present. The macroinvertebrate community measures Ephemeroptera, Plecoptera, Trichoptera richness and North Carolina Biotic Index showed no differences between primary and secondary reference sites when BPJ was ignored. However, there was no significant difference among primary, secondary, and tertiary reference sites when BPJ was used. We underscore the importance of classifying reference conditions, especially in regions that have endured significant anthropogenic activity. We suggest that the use of secondary reference sites may enable construction of models that target a broader set of management interests.

Lunar Observer Laser Altimeter observations for lunar base site selection

NASA Technical Reports Server (NTRS)

Garvin, James B.; Bufton, Jack L.

1992-01-01

One of the critical datasets for optimal selection of future lunar landing sites is local- to regional-scale topography. Lunar base site selection will require such data for both engineering and scientific operations purposes. The Lunar Geoscience Orbiter or Lunar Observer is the ideal precursory science mission from which to obtain this required information. We suggest that a simple laser altimeter instrument could be employed to measure local-scale slopes, heights, and depths of lunar surface features important to lunar base planning and design. For this reason, we have designed and are currently constructing a breadboard of a Lunar Observer Laser Altimeter (LOLA) instrument capable of acquiring contiguous-footprint topographic profiles with both 30-m and 300-m along-track resolution. This instrument meets all the severe weight, power, size, and data rate limitations imposed by Observer-class spacecraft. In addition, LOLA would be capable of measuring the within-footprint vertical roughness of the lunar surface, and the 1.06-micron relative surface reflectivity at normal incidence. We have used airborne laser altimeter data for a few representative lunar analog landforms to simulate and analyze LOLA performance in a 100-km lunar orbit. We demonstrate that this system in its highest resolution mode (30-m diameter footprints) would quantify the topography of all but the very smallest lunar landforms. At its global mapping resolution (300-m diameter footprints), LOLA would establish the topographic context for lunar landing site selection by providing the basis for constructing a 1-2 km spatial resolution global, geodetic topographic grid that would contain a high density of observations (e.g., approximately 1000 observations per each 1 deg by 1 deg cell at the lunar equator). The high spatial and vertical resolution measurements made with a LOLA-class instrument on a precursory Lunar Observer would be highly synergistic with high-resolution imaging datasets, and will allow for direct quantification of critical slopes, heights, and depths of features visible in images of potential lunar base sites.

Design and synthesis of novel chalcones as potent selective monoamine oxidase-B inhibitors.

PubMed

Hammuda, Arwa; Shalaby, Raed; Rovida, Stefano; Edmondson, Dale E; Binda, Claudia; Khalil, Ashraf

2016-05-23

A novel series of substituted chalcones were designed and synthesized to be evaluated as selective human MAO-B inhibitors. A combination of either methylsulfonyl or trifluoromethyl substituents on the aromatic ketone moiety with a benzodioxol ring on the other end of the chalcone scaffold was investigated. The compounds were tested for their inhibitory activities on both human MAO-A and B. All compounds appeared to be selective MAO-B inhibitors with Ki values in the micromolar to submicromolar range. Molecular modeling studies have been performed to get insight into the binding mode of the synthesized compounds to human MAO-B active site. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Evaluation Plan -- The Minneapolis Ridesharing Commuter Services Demonstration

DOT National Transportation Integrated Search

1978-05-01

In April 1977, the Metropolitan Transit Commission initiated a two-year demonstration project designed to increase work trip-vehicle occupancy at selected employment sites in the Twin Cities region. Key elements of this demonstration which differenti...

Gas Hydrate Research Site Selection and Operational Research Plans

NASA Astrophysics Data System (ADS)

Collett, T. S.; Boswell, R. M.

2009-12-01

In recent years it has become generally accepted that gas hydrates represent a potential important future energy resource, a significant drilling and production hazard, a potential contributor to global climate change, and a controlling factor in seafloor stability and landslides. Research drilling and coring programs carried out by the Ocean Drilling Program (ODP), the Integrated Ocean Drilling Program (IODP), government agencies, and several consortia have contributed greatly to our understanding of the geologic controls on the occurrence of gas hydrates in marine and permafrost environments. For the most part, each of these field projects were built on the lessons learned from the projects that have gone before them. One of the most important factors contributing to the success of some of the more notable gas hydrate field projects has been the close alignment of project goals with the processes used to select the drill sites and to develop the project’s operational research plans. For example, IODP Expedition 311 used a transect approach to successfully constrain the overall occurrence of gas hydrate within the range of geologic environments within a marine accretionary complex. Earlier gas hydrate research drilling, including IODP Leg 164, were designed primarily to assess the occurrence and nature of marine gas hydrate systems, and relied largely on the presence of anomalous seismic features, including bottom-simulating reflectors and “blanking zones”. While these projects were extremely successful, expeditions today are being increasingly mounted with the primary goal of prospecting for potential gas hydrate production targets, and site selection processes designed to specifically seek out anomalously high-concentrations of gas hydrate are needed. This approach was best demonstrated in a recently completed energy resource focused project, the Gulf of Mexico Gas Hydrate Joint Industry Project Leg II (GOM JIP Leg II), which featured the collection of a comprehensive set of logging-while-drilling (LWD) data through expected gas-hydrate-bearing sand reservoirs in seven wells at three sites in the Gulf of Mexico. The discovery of thick hydrate-bearing sands at two of the sites drilled in the Gulf Mexico validated the integrated geological and geophysical approach used in the pre-drill site selection process to identify gas hydrate reservoirs that may be conducive to energy production. The results of the GOM JIP Leg II LWD expedition are also being used to support the selection of sites for a future drilling, logging, and coring program. Operationally, recent drilling programs, such as ODP Leg 204, IODP Expedition 311, the Japanese Toaki-oki to Kumano-nada drilling leg, the Indian NGHP Expedition 01, and the South Korean Gas Hydrate Research and Development Organization Expedition 01 have demonstrated the great benefit of a multi-leg drilling approach, including the initial acquisition of LWD data that was used to then select sites for the drilling of complex core and wireline logging test holes. It is obvious that a fully integrated site selection approach and a “goal based” operational plan, possibly including numerous drill sites and drilling legs, are required considerations for any future gas hydrate research project.

Decision Making on Regional Landfill Site Selection in Hormozgan Province Using Smce

NASA Astrophysics Data System (ADS)

Majedi, A. S.; Kamali, B. M.; Maghsoudi, R.

2015-12-01

Landfill site selection and suitable conditions to bury hazardous wastes are among the most critical issues in modern societies. Taking several factors and limitations into account along with true decision making requires application of different decision techniques. To this end, current paper aims to make decisions about regional landfill site selection in Hormozgan province and utilizes SMCE technique combined with qualitative and quantitative criteria to select the final alternatives. To this respect, we first will describe the existing environmental situation in our study area and set the goals of our study in the framework of SMCE and will analyze the effective factors in regional landfill site selection. Then, methodological procedure of research was conducted using Delphi approach and questionnaires (in order to determine research validity, Chronbach Alpha (0.94) method was used). Spatial multi-criteria analysis model was designed in the form of criteria tree in SMCE using IL WIS software. Prioritization of respective spatial alternatives included: Bandar Abbas city with total 4 spatial alternatives (one zone with 1st priority, one zone with 3rd priority and two zones with 4thpriority) was considered the first priority, Bastak city with total 3 spatial alternatives (one zone with 2nd priority, one zone with 3rdpriorit and one zone with 4th priority) was the second priority and Bandar Abbas, Minab, Jask and Haji Abad cities were considered as the third priority.

Astronomy Village Reaches for New Heights

NASA Astrophysics Data System (ADS)

Croft, S. K.; Pompea, S. M.

2007-12-01

We are developing a set of complex, multimedia-based instructional modules emphasizing technical and scientific issues related to Giant Segmented Mirror Telescope project. The modules" pedagogy will be open-ended and problem-based to promote development of problem-solving skills. Problem- based-learning modules that emphasize work on open-ended complex real world problems are particularly valuable in illustrating and promoting a perspective on the process of science and engineering. Research in this area shows that these kinds of learning experiences are superior to more conventional student training in terms of gains in student learning. The format for the modules will be based on the award-winning multi-media educational Astronomy Village products that present students with a simulated environment: a mountaintop community surrounded by a cluster of telescopes, satellite receivers, and telecommunication towers. A number of "buildings" are found in the Village, such as a library, a laboratory, and an auditorium. Each building contains an array of information sources and computer simulations. Students navigate through their research with a mentor via imbedded video. The first module will be "Observatory Site Selection." Students will use astronomical data, basic weather information, and sky brightness data to select the best site for an observatory. Students will investigate the six GSMT sites considered by the professional site selection teams. Students will explore weather and basic site issues (e.g., roads and topography) using remote sensing images, computational fluid dynamics results, turbulence profiles, and scintillation of the different sites. Comparison of student problem solving with expert problem solving will also be done as part of the module. As part of a site selection team they will have to construct a case and present it on why they chose a particular site. The second module will address aspects of system engineering and optimization for a GSMT-like telescope. Basic system issues will be addressed and studied. These might include various controls issues and optimization issues such as mirror figure, mirror support stability, and wind loading trade-offs. Using system modeling and system optimization results from existing and early GSMT trade studies, we will create a simulation where students are part of an engineering design and optimization team. They will explore the cost/performance/schedule issues associate with the GSMT design.

Nodal failure index approach to groundwater remediation design

USGS Publications Warehouse

Lee, J.; Reeves, H.W.; Dowding, C.H.

2008-01-01

Computer simulations often are used to design and to optimize groundwater remediation systems. We present a new computationally efficient approach that calculates the reliability of remedial design at every location in a model domain with a single simulation. The estimated reliability and other model information are used to select a best remedial option for given site conditions, conceptual model, and available data. To evaluate design performance, we introduce the nodal failure index (NFI) to determine the number of nodal locations at which the probability of success is below the design requirement. The strength of the NFI approach is that selected areas of interest can be specified for analysis and the best remedial design determined for this target region. An example application of the NFI approach using a hypothetical model shows how the spatial distribution of reliability can be used for a decision support system in groundwater remediation design. ?? 2008 ASCE.

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.

Molecular docking studies of selected tricyclic and quinone derivatives on trypanothione reductase of Leishmania infantum.

PubMed

Venkatesan, Santhosh Kannan; Shukla, Anil Kumar; Dubey, Vikash Kumar

2010-10-01

Visceral leishmaniasis, most lethal form of Leishmaniasis, is caused by Leishmania infantum in the Old world. Current therapeutics for the disease is associated with a risk of high toxicity and development of drug resistant strains. Thiol-redox metabolism involving trypanothione and trypanothione reductase, key for survival of Leishmania, is a validated target for rational drug design. Recently published structure of trypanothione reductase (TryR) from L. infantum, in oxidized and reduced form along with Sb(III), provides vital clues on active site of the enzyme. In continuation with our attempts to identify potent inhibitors of TryR, we have modeled binding modes of selected tricyclic compounds and quinone derivatives, using AutoDock4. Here, we report a unique binding mode for quinone derivatives and 9-aminoacridine derivatives, at the FAD binding domain. A conserved hydrogen bonding pattern was observed in all these compounds with residues Thr335, Lys60, His461. With the fact that these residues aid in the orientation of FAD towards the active site forming the core of the FAD binding domain, designing selective and potent compounds that could replace FAD in vivo during the synthesis of Trypanothione reductase can be deployed as an effective strategy in designing new drugs towards Leishmaniasis. We also report the binding of Phenothiazine and 9-aminoacridine derivatives at the Z site of the protein. The biological significance and possible mode of inhibition by quinone derivatives, which binds to FAD binding domain, along with other compounds are discussed. (c) 2010 Wiley Periodicals, Inc.

Directing Reaction Pathways through Controlled Reactant Binding at Pd-TiO2 Interfaces.

PubMed

Zhang, Jing; Wang, Bingwen; Nikolla, Eranda; Medlin, J Will

2017-06-01

Recent efforts to design selective catalysts for multi-step reactions, such as hydrodeoxygenation (HDO), have emphasized the preparation of active sites at the interface between two materials having different properties. However, achieving precise control over interfacial properties, and thus reaction selectivity, has remained a challenge. Here, we encapsulated Pd nanoparticles (NPs) with TiO 2 films of regulated porosity to gain a new level of control over catalyst performance, resulting in essentially 100 % HDO selectivity for two biomass-derived alcohols. This catalyst also showed exceptional reaction specificity in HDO of furfural and m-cresol. In addition to improving HDO activity by maximizing the interfacial contact between the metal and metal oxide sites, encapsulation by the nanoporous oxide film provided a significant selectivity boost by restricting the accessible conformations of aromatics on the surface. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Analysis and Down Select of Flow Passages for Thermal Hydraulic Testing of a SNAP Derived Reactor

NASA Technical Reports Server (NTRS)

Godfroy, T. J.; Sadasivan, P.; Masterson, S.

2007-01-01

As past of the Vision for Space Exploration, man will return to the moon. To enable safe and productive time on the lunar surface will require adequate power resources. To provide the needed power and to give mission planners all landing site possibilities, including a permanently dark crater, a nuclear reactor provides the most options. Designed to be l00kWt providing approx. 25kWe this power plants would be very effective in delivering dependable, site non-specific power to crews or robotic missions on the lunar surface. An affordable reference reactor based upon the successful SNAP program of the 1960's and early 1970's has been designed by Los Alamos National Laboratory that will meet such a requirement. Considering current funding, environmental, and schedule limitations this lunar surface power reactor will be tested using non-nuclear simulators to simulate the heat from fission reactions. Currently a 25kWe surface power SNAP derivative reactor is in the early process of design and testing with collaboration between Los Alamos National Laboratory, Idaho National Laboratory, Glenn Research Center, Marshall Space Flight Center, and Sandia National Laboratory to ensure that this new design is affordable and can be tested using non-nuclear methods as have proven so effective in the past. This paper will discuss the study and down selection of a flow passage concept for a approx. 25kWe lunar surface power reactor. Several different flow passages designs were evaluated using computational fluid dynamics to determine pressure drop and a structural assessment to consider thermal and stress of the passage walls. The reactor design basis conditions are discussed followed by passage problem setup and results for each concept. A recommendation for passage design is made with rationale for selection.

The 50 Constellation Priority Sites

NASA Technical Reports Server (NTRS)

Noble, S.; Joosten, K.; Eppler, D.; Gruener, J.; Mendell, W.; French, R.; Plescia, J.; Spudis, P.; Wargo, M.; Robinson, M.;

Applications of Nonenzymatic Catalysts to the Alteration of Natural Products.

PubMed

Shugrue, Christopher R; Miller, Scott J

2017-09-27

The application of small molecules as catalysts for the diversification of natural product scaffolds is reviewed. Specifically, principles that relate to the selectivity challenges intrinsic to complex molecular scaffolds are summarized. The synthesis of analogues of natural products by this approach is then described as a quintessential "late-stage functionalization" exercise wherein natural products serve as the lead scaffolds. Given the historical application of enzymatic catalysts to the site-selective alteration of complex molecules, the focus of this Review is on the recent studies of nonenzymatic catalysts. Reactions involving hydroxyl group derivatization with a variety of electrophilic reagents are discussed. C-H bond functionalizations that lead to oxidations, aminations, and halogenations are also presented. Several examples of site-selective olefin functionalizations and C-C bond formations are also included. Numerous classes of natural products have been subjected to these studies of site-selective alteration including polyketides, glycopeptides, terpenoids, macrolides, alkaloids, carbohydrates, and others. What emerges is a platform for chemical remodeling of naturally occurring scaffolds that targets virtually all known chemical functionalities and microenvironments. However, challenges for the design of very broad classes of catalysts, with even broader selectivity demands (e.g., stereoselectivity, functional group selectivity, and site-selectivity) persist. Yet, a significant spectrum of powerful, catalytic alterations of complex natural products now exists such that expansion of scope seems inevitable. Several instances of biological activity assays of remodeled natural product derivatives are also presented. These reports may foreshadow further interdisciplinary impacts for catalytic remodeling of natural products, including contributions to SAR development, mode of action studies, and eventually medicinal chemistry.

Water Power in The Wilderness: The History of Bonneville Lock and Dam

DTIC Science & Technology

1997-01-01

to present many complex problems of site selection, proper construction techniques, and equipment design . The project first received serious...Bonneville Dam amply lived up to the hopes and dreams of its promoters and designers . In the short term, Bonneville supplied essential power for the...plan for the Columbia River. It designated Grand Coulee as the key upriver project and Bonneville as the lowermost in the chain . Report data on the

Geophysical investigation, Lake Sherwood dam site, east-central Missouri.

DOT National Transportation Integrated Search

2011-10-01

Electrical resistivity and self potential (SP) data were acquired across selected segment of the Lake Sherwood earth-fill : dam and in designated areas immediately adjacent to the dam. : The 2-D electrical resistivity profile data were acquired with ...

What Are Probability Surveys used by the National Aquatic Resource Surveys?

EPA Pesticide Factsheets

The National Aquatic Resource Surveys (NARS) use probability-survey designs to assess the condition of the nation’s waters. In probability surveys (also known as sample-surveys or statistical surveys), sampling sites are selected randomly.

Evaluation of hot in-place recycle.

DOT National Transportation Integrated Search

2010-06-01

This report documents the construction of hot in-place recycled (HIPR) pavement on SR 542. : HIPR is a process by which rehabilitation of the existing HMA pavement occurs on site in one : operation. HIPR project selection, mix design, construction an...

Engineering issue: Indoor Air Vapor Intrusion Mitigation Approaches

EPA Science Inventory

The US Environmental Protection Agency (EPA) Engineering Issues are a new series of technology transfer documents that summarize the latest available information on selected treatment and site remeediation technologies and related issues. They are designed to help remedial projec...

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.

A Playground for All Children. Book 1: User Groups and Site Selection. Book 2: Design Competition Program.

ERIC Educational Resources Information Center

New York City Dept. of City Planning, NY.

These booklets, parts I and II of a three-part series, describe in detail issues related to the future development of an innovative outdoor public playground especially designed for integrated play between handicapped and able-bodied children. The first booklet describes potential user groups--the types of children who are expected to use the…

Results of hydrologic monitoring on landslide-prone coastal bluffs near Mukilteo, Washington

USGS Publications Warehouse

Smith, Joel B.; Baum, Rex L.; Mirus, Benjamin B.; Michel, Abigail R.; Stark, Ben

2017-08-31

A hydrologic monitoring network was installed to investigate landslide hazards affecting the railway corridor along the eastern shore of Puget Sound between Seattle and Everett, near Mukilteo, Washington. During the summer of 2015, the U.S. Geological Survey installed monitoring equipment at four sites equipped with instrumentation to measure rainfall and air temperature every 15 minutes. Two of the four sites are installed on contrasting coastal bluffs, one landslide scarred and one vegetated. At these two sites, in addition to rainfall and air temperature, volumetric water content, pore pressure, soil suction, soil temperature, and barometric pressure were measured every 15 minutes. The instrumentation was designed to supplement landslide-rainfall thresholds developed by the U.S. Geological Survey with a long-term goal of advancing the understanding of the relationship between landslide potential and hydrologic forcing along the coastal bluffs. Additionally, the system was designed to function as a prototype monitoring system to evaluate criteria for site selection, instrument selection, and placement of instruments. The purpose of this report is to describe the monitoring system, present the data collected since installation, and describe significant events represented within the dataset, which is published as a separate data release. The findings provide insight for building and configuring larger, modular monitoring networks.

Objective sampling design in a highly heterogeneous landscape - characterizing environmental determinants of malaria vector distribution in French Guiana, in the Amazonian region.

PubMed

Roux, Emmanuel; Gaborit, Pascal; Romaña, Christine A; Girod, Romain; Dessay, Nadine; Dusfour, Isabelle

2013-12-01

Sampling design is a key issue when establishing species inventories and characterizing habitats within highly heterogeneous landscapes. Sampling efforts in such environments may be constrained and many field studies only rely on subjective and/or qualitative approaches to design collection strategy. The region of Cacao, in French Guiana, provides an excellent study site to understand the presence and abundance of Anopheles mosquitoes, their species dynamics and the transmission risk of malaria across various environments. We propose an objective methodology to define a stratified sampling design. Following thorough environmental characterization, a factorial analysis of mixed groups allows the data to be reduced and non-collinear principal components to be identified while balancing the influences of the different environmental factors. Such components defined new variables which could then be used in a robust k-means clustering procedure. Then, we identified five clusters that corresponded to our sampling strata and selected sampling sites in each stratum. We validated our method by comparing the species overlap of entomological collections from selected sites and the environmental similarities of the same sites. The Morisita index was significantly correlated (Pearson linear correlation) with environmental similarity based on i) the balanced environmental variable groups considered jointly (p = 0.001) and ii) land cover/use (p-value < 0.001). The Jaccard index was significantly correlated with land cover/use-based environmental similarity (p-value = 0.001). The results validate our sampling approach. Land cover/use maps (based on high spatial resolution satellite images) were shown to be particularly useful when studying the presence, density and diversity of Anopheles mosquitoes at local scales and in very heterogeneous landscapes.

Objective sampling design in a highly heterogeneous landscape - characterizing environmental determinants of malaria vector distribution in French Guiana, in the Amazonian region

PubMed Central

2013-01-01

Background Sampling design is a key issue when establishing species inventories and characterizing habitats within highly heterogeneous landscapes. Sampling efforts in such environments may be constrained and many field studies only rely on subjective and/or qualitative approaches to design collection strategy. The region of Cacao, in French Guiana, provides an excellent study site to understand the presence and abundance of Anopheles mosquitoes, their species dynamics and the transmission risk of malaria across various environments. We propose an objective methodology to define a stratified sampling design. Following thorough environmental characterization, a factorial analysis of mixed groups allows the data to be reduced and non-collinear principal components to be identified while balancing the influences of the different environmental factors. Such components defined new variables which could then be used in a robust k-means clustering procedure. Then, we identified five clusters that corresponded to our sampling strata and selected sampling sites in each stratum. Results We validated our method by comparing the species overlap of entomological collections from selected sites and the environmental similarities of the same sites. The Morisita index was significantly correlated (Pearson linear correlation) with environmental similarity based on i) the balanced environmental variable groups considered jointly (p = 0.001) and ii) land cover/use (p-value << 0.001). The Jaccard index was significantly correlated with land cover/use-based environmental similarity (p-value = 0.001). Conclusions The results validate our sampling approach. Land cover/use maps (based on high spatial resolution satellite images) were shown to be particularly useful when studying the presence, density and diversity of Anopheles mosquitoes at local scales and in very heterogeneous landscapes. PMID:24289184

The Influence of HIV on the Evolution of Mycobacterium tuberculosis

PubMed Central

Brites, Daniela; Stucki, David; Evans, Joanna C.; Seldon, Ronnett; Heekes, Alexa; Mulder, Nicola; Nicol, Mark; Oni, Tolu; Mizrahi, Valerie; Warner, Digby F.; Parkhill, Julian; Gagneux, Sebastien; Martin, Darren P.; Wilkinson, Robert J.

2017-01-01

Abstract HIV significantly affects the immunological environment during tuberculosis coinfection, and therefore may influence the selective landscape upon which M. tuberculosis evolves. To test this hypothesis whole genome sequences were determined for 169 South African M. tuberculosis strains from HIV-1 coinfected and uninfected individuals and analyzed using two Bayesian codon-model based selection analysis approaches: FUBAR which was used to detect persistent positive and negative selection (selection respectively favoring and disfavoring nonsynonymous substitutions); and MEDS which was used to detect episodic directional selection specifically favoring nonsynonymous substitutions within HIV-1 infected individuals. Among the 25,251 polymorphic codon sites analyzed, FUBAR revealed that 189-fold more were detectably evolving under persistent negative selection than were evolving under persistent positive selection. Three specific codon sites within the genes celA2b, katG, and cyp138 were identified by MEDS as displaying significant evidence of evolving under directional selection influenced by HIV-1 coinfection. All three genes encode proteins that may indirectly interact with human proteins that, in turn, interact functionally with HIV proteins. Unexpectedly, epitope encoding regions were enriched for sites displaying weak evidence of directional selection influenced by HIV-1. Although the low degree of genetic diversity observed in our M. tuberculosis data set means that these results should be interpreted carefully, the effects of HIV-1 on epitope evolution in M. tuberculosis may have implications for the design of M. tuberculosis vaccines that are intended for use in populations with high HIV-1 infection rates. PMID:28369607

Thermal power systems, small power systems application project. Volume 1: Executive summary

NASA Technical Reports Server (NTRS)

Marriott, A. T.

1979-01-01

Current small power system technology as applied to power plants up to 10 MWe in size was assessed. Markets for small power systems were characterized and cost goals were established. Candidate power plant system design concepts were selected for evaluation and preliminary performance and cost assessments were made. Economic studies were conducted and breakeven capital costs were determined for leading contenders among the candidate systems. An application study was made of the potential use of small power systems in providing part of the demand for pumping power by the extensive aqueduct system of California, estimated to be 1000 MWe by 1985. Criteria and methodologies were developed for application to the ranking of candidate power plant system design concepts. Experimental power plants concepts of 1 MWe rating were studied leading toward the definition of a power plant configuration for subsequent detail design, construction, testing and evaluation as Engineering Experiment No. 1 (EE No. 1). Site selection criteria and ground rules for the solicitation of EE No. 1 site participation proposals by DOE were developed.

Comparing the effects of infrastructure on bicycling injury at intersections and non-intersections using a case–crossover design

PubMed Central

Harris, M Anne; Reynolds, Conor C O; Winters, Meghan; Cripton, Peter A; Shen, Hui; Chipman, Mary L; Cusimano, Michael D; Babul, Shelina; Brubacher, Jeffrey R; Friedman, Steven M; Hunte, Garth; Monro, Melody; Vernich, Lee; Teschke, Kay

2013-01-01

Background This study examined the impact of transportation infrastructure at intersection and non-intersection locations on bicycling injury risk. Methods In Vancouver and Toronto, we studied adult cyclists who were injured and treated at a hospital emergency department. A case–crossover design compared the infrastructure of injury and control sites within each injured bicyclist's route. Intersection injury sites (N=210) were compared to randomly selected intersection control sites (N=272). Non-intersection injury sites (N=478) were compared to randomly selected non-intersection control sites (N=801). Results At intersections, the types of routes meeting and the intersection design influenced safety. Intersections of two local streets (no demarcated traffic lanes) had approximately one-fifth the risk (adjusted OR 0.19, 95% CI 0.05 to 0.66) of intersections of two major streets (more than two traffic lanes). Motor vehicle speeds less than 30 km/h also reduced risk (adjusted OR 0.52, 95% CI 0.29 to 0.92). Traffic circles (small roundabouts) on local streets increased the risk of these otherwise safe intersections (adjusted OR 7.98, 95% CI 1.79 to 35.6). At non-intersection locations, very low risks were found for cycle tracks (bike lanes physically separated from motor vehicle traffic; adjusted OR 0.05, 95% CI 0.01 to 0.59) and local streets with diverters that reduce motor vehicle traffic (adjusted OR 0.04, 95% CI 0.003 to 0.60). Downhill grades increased risks at both intersections and non-intersections. Conclusions These results provide guidance for transportation planners and engineers: at local street intersections, traditional stops are safer than traffic circles, and at non-intersections, cycle tracks alongside major streets and traffic diversion from local streets are safer than no bicycle infrastructure. PMID:23411678

The human factor in mining reclamation

USGS Publications Warehouse

Arbogast, Belinda F.; Knepper, Daniel H.; Langer, William H.

2000-01-01

Rapid urbanization of the landscape results in less space available for wildlife habitat, agriculture, and recreation. Mineral resources (especially nonmetallic construction materials) become unrecoverable due to inaccessibility caused by development. This report both describes mine sites with serious problems and draws attention to thoughtful reclamation projects for better future management. It presents information from selected sites in terms of their history, landform, design approach, and visual discernment. Examples from Colorado are included to introduce the broader issue of regions soundly developing mining sites, permitting the best utilization of natural resources, and respecting the landscape.

Selection of adequate site location during early stages of construction project management: A multi-criteria decision analysis approach

NASA Astrophysics Data System (ADS)

Marović, Ivan; Hanak, Tomaš

2017-10-01

In the management of construction projects special attention should be given to the planning as the most important phase of decision-making process. Quality decision-making based on adequate and comprehensive collaboration of all involved stakeholders is crucial in project’s early stages. Fundamental reasons for existence of this problem arise from: specific conditions of construction industry (final products are inseparable from the location i.e. location has a strong influence of building design and its structural characteristics as well as technology which will be used during construction), investors’ desires and attitudes, and influence of socioeconomic and environment aspects. Considering all mentioned reasons one can conclude that selection of adequate construction site location for future investment is complex, low structured and multi-criteria problem. To take into account all the dimensions, the proposed model for selection of adequate site location is devised. The model is based on AHP (for designing the decision-making hierarchy) and PROMETHEE (for pairwise comparison of investment locations) methods. As a result of mixing basis feature of both methods, operational synergies can be achieved in multi-criteria decision analysis. Such gives the decision-maker a sense of assurance, knowing that if the procedure proposed by the presented model has been followed, it will lead to a rational decision, carefully and systematically thought out.

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

Women, Co-occurring Disorders, and Violence Study: evaluation design and study population.

PubMed

McHugo, G J; Kammerer, N; Jackson, E W; Markoff, L S; Gatz, M; Larson, M J; Mazelis, R; Hennigan, K

2005-03-01

The Women, Co-occurring Disorders, and Violence Study (WCDVS) was a multi-site cooperative study to evaluate new service models for women with co-occurring mental health and substance use disorders and a history of physical and/or sexual abuse. Despite common features in the service interventions and evaluation procedures, diversity across the nine sites plus differences introduced by non-random assignment led to numerous methodological challenges. This article describes the design, measurement, and analysis decisions behind the WCDVS and lays the foundation for understanding participant-level outcomes and service costs. This article also describes the study population, as recruited and following attrition at the 6-month follow-up, in order to address the threat of selection bias to inferences drawn from this multi-site study.

Discovery of highly potent, selective, covalent inhibitors of JAK3

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

Kempson, James; Ovalle, Damaso; Guo, Junqing

A useful and novel set of tool molecules have been identified which bind irreversibly to the JAK3 active site cysteine residue. The design was based on crystal structure information and a comparative study of several electrophilic warheads.

Electrical Stimulation of the Left and Right Human Fusiform Gyrus Causes Different Effects in Conscious Face Perception

PubMed Central

Rangarajan, Vinitha; Hermes, Dora; Foster, Brett L.; Weiner, Kevin S.; Jacques, Corentin; Grill-Spector, Kalanit

2014-01-01

Neuroimaging and electrophysiological studies across species have confirmed bilateral face-selective responses in the ventral temporal cortex (VTC) and prosopagnosia is reported in patients with lesions in the VTC including the fusiform gyrus (FG). As imaging and electrophysiological studies provide correlative evidence, and brain lesions often comprise both white and gray matter structures beyond the FG, we designed the current study to explore the link between face-related electrophysiological responses in the FG and the causal effects of electrical stimulation of the left or right FG in face perception. We used a combination of electrocorticography (ECoG) and electrical brain stimulation (EBS) in 10 human subjects implanted with intracranial electrodes in either the left (5 participants, 30 FG sites) or right (5 participants, 26 FG sites) hemispheres. We identified FG sites with face-selective ECoG responses, and recorded perceptual reports during EBS of these sites. In line with existing literature, face-selective ECoG responses were present in both left and right FG sites. However, when the same sites were stimulated, we observed a striking difference between hemispheres. Only EBS of the right FG caused changes in the conscious perception of faces, whereas EBS of strongly face-selective regions in the left FG produced non-face-related visual changes, such as phosphenes. This study examines the relationship between correlative versus causal nature of ECoG and EBS, respectively, and provides important insight into the differential roles of the right versus left FG in conscious face perception. PMID:25232118

Prospective analysis of the quality of Spanish health information web sites after 3 years.

PubMed

Conesa-Fuentes, Maria C; Hernandez-Morante, Juan J

2016-12-01

Although the Internet has become an essential source of health information, our study conducted 3 years ago provided evidence of the low quality of Spanish health web sites. The objective of the present study was to evaluate the quality of Spanish health information web sites now, and to compare these results with those obtained 3 years ago. For the original study, the most visited health information web sites were selected through the PageRank® (Google®) system. The present study evaluated the quality of the same web sites from February to May 2013, using the method developed by Bermúdez-Tamayo et al. and HONCode® criteria. The mean quality of the selected web sites was low and has deteriorated since the previous evaluation, especially in regional health services and institutions' web sites. The quality of private web sites remained broadly similar. Compliance with privacy and update criteria also improved in the intervening period. The results indicate that, even in the case of health web sites, design or appearance is more relevant to developers than quality of information. It is recommended that responsible institutions should increase their efforts to eliminate low-quality health information that may further contribute to health problems.

Hummingbird Comet Nucleus Analysis Mission

NASA Technical Reports Server (NTRS)

Kojiro, Daniel; Carle, Glenn C.; Lasher, Larry E.

2000-01-01

Hummingbird is a highly focused scientific mission, proposed to NASA s Discovery Program, designed to address the highest priority questions in cometary science-that of the chemical composition of the cometary nucleus. After rendezvous with the comet, Hummingbird would first methodically image and map the comet, then collect and analyze dust, ice and gases from the cometary atmosphere to enrich characterization of the comet and support landing site selection. Then, like its namesake, Hummingbird would carefully descend to a pre-selected surface site obtaining a high-resolution image, gather a surface material sample, acquire surface temperature and then immediately return to orbit for detailed chemical and elemental analyses followed by a high resolution post-sampling image of the site. Hummingbird s analytical laboratory contains instrumentation for a comprehensive molecular and elemental analysis of the cometary nucleus as well as an innovative surface sample acquisition device.

Camping impact management at Isle Royale National Park: an evaluation of visitor activity containment policies from the perspective of social conditions

USGS Publications Warehouse

Farrell, T.A.; Marion, J.L.

2000-01-01

A survey of backcountry and wilderness campsites at Isle Royale National Park reveals that the park?s policies for managing visitor impacts have been remarkably effective in limiting the areal extent of camping-related disturbance. However, the dense spatial arrangement of designated campsites within backcountry campgrounds has also contributed to problems with visitor crowding and conflict. Only 9% of the sites had no other sites visible, while 22% had three or more other sites visible. Mean intersite distance was only 76 feet, and 34% of the sites are within 50 feet of another site. Visitor education programs and selected relocation of sites could reduce these social problems.

Monitoring-well network and sampling design for ground-water quality, Wind River Indian Reservation, Wyoming

USGS Publications Warehouse

Mason, Jon P.; Sebree, Sonja K.; Quinn, Thomas L.

2005-01-01

The Wind River Indian Reservation, located in parts of Fremont and Hot Springs Counties, Wyoming, has a total land area of more than 3,500 square miles. Ground water on the Wind River Indian Reservation is a valuable resource for Shoshone and Northern Arapahoe tribal members and others who live on the Reservation. There are many types of land uses on the Reservation that have the potential to affect the quality of ground-water resources. Urban areas, rural housing developments, agricultural lands, landfills, oil and natural gas fields, mining, and pipeline utility corridors all have the potential to affect ground-water quality. A cooperative study was developed between the U.S. Geological Survey and the Wind River Environmental Quality Commission to identify areas of the Reservation that have the highest potential for ground-water contamination and develop a comprehensive plan to monitor these areas. An arithmetic overlay model for the Wind River Indian Reservation was created using seven geographic information system data layers representing factors with varying potential to affect ground-water quality. The data layers used were: the National Land Cover Dataset, water well density, aquifer sensitivity, oil and natural gas fields and petroleum pipelines, sites with potential contaminant sources, sites that are known to have ground-water contamination, and National Pollutant Discharge Elimination System sites. A prioritization map for monitoring ground-water quality on the Reservation was created using the model. The prioritization map ranks the priority for monitoring ground-water quality in different areas of the Reservation as low, medium, or high. To help minimize bias in selecting sites for a monitoring well network, an automated stratified random site-selection approach was used to select 30 sites for ground-water quality monitoring within the high priority areas. In addition, the study also provided a sampling design for constituents to be monitored, sampling frequency, and a simple water-table level observation well network.

Installation Restoration Program. Phase II--Confirmation/Quantification. Stage 1.

DTIC Science & Technology

1985-03-01

four phases. Phase I, Initial Assessment/ Records Search, is designed to identify possible hazardous waste contami- nated sites and potential...7 71 -. - - IL’ -, 1% 33 AihlIII Is 33 n~iL t iiC UII! ii CL C LU 1-3, Phase II, Confirmation and Quantification, is designed to confirm the...additional monitoring data upon which design of mitigative actions are based. In Phase III, Technology Base Development, appropriate technology is selected and

A Quantitative Measure of Conformational Changes in Apo, Holo and Ligand-Bound Forms of Enzymes.

PubMed

Singh, Satendra; Singh, Atul Kumar; Wadhwa, Gulshan; Singh, Dev Bukhsh; Dwivedi, Seema; Gautam, Budhayash; Ramteke, Pramod W

2016-06-01

Determination of the native geometry of the enzymes and ligand complexes is a key step in the process of structure-based drug designing. Enzymes and ligands show flexibility in structural behavior as they come in contact with each other. When ligand binds with active site of the enzyme, in the presence of cofactor some structural changes are expected to occur in the active site. Motivation behind this study is to determine the nature of conformational changes as well as regions where such changes are more pronounced. To measure the structural changes due to cofactor and ligand complex, enzyme in apo, holo and ligand-bound forms is selected. Enzyme data set was retrieved from protein data bank. Fifteen triplet groups were selected for the analysis of structural changes based on selection criteria. Structural features for selected enzymes were compared at the global as well as local region. Accessible surface area for the enzymes in entire triplet set was calculated, which describes the change in accessible surface area upon binding of cofactor and ligand with the enzyme. It was observed that some structural changes take place during binding of ligand in the presence of cofactor. This study will helps in understanding the level of flexibility in protein-ligand interaction for computer-aided drug designing.

A model of directional selection applied to the evolution of drug resistance in HIV-1.

PubMed

Seoighe, Cathal; Ketwaroo, Farahnaz; Pillay, Visva; Scheffler, Konrad; Wood, Natasha; Duffet, Rodger; Zvelebil, Marketa; Martinson, Neil; McIntyre, James; Morris, Lynn; Hide, Winston

2007-04-01

Understanding how pathogens acquire resistance to drugs is important for the design of treatment strategies, particularly for rapidly evolving viruses such as HIV-1. Drug treatment can exert strong selective pressures and sites within targeted genes that confer resistance frequently evolve far more rapidly than the neutral rate. Rapid evolution at sites that confer resistance to drugs can be used to help elucidate the mechanisms of evolution of drug resistance and to discover or corroborate novel resistance mutations. We have implemented standard maximum likelihood methods that are used to detect diversifying selection and adapted them for use with serially sampled reverse transcriptase (RT) coding sequences isolated from a group of 300 HIV-1 subtype C-infected women before and after single-dose nevirapine (sdNVP) to prevent mother-to-child transmission. We have also extended the standard models of codon evolution for application to the detection of directional selection. Through simulation, we show that the directional selection model can provide a substantial improvement in sensitivity over models of diversifying selection. Five of the sites within the RT gene that are known to harbor mutations that confer resistance to nevirapine (NVP) strongly supported the directional selection model. There was no evidence that other mutations that are known to confer NVP resistance were selected in this cohort. The directional selection model, applied to serially sampled sequences, also had more power than the diversifying selection model to detect selection resulting from factors other than drug resistance. Because inference of selection from serial samples is unlikely to be adversely affected by recombination, the methods we describe may have general applicability to the analysis of positive selection affecting recombining coding sequences when serially sampled data are available.

Monitoring and mapping selected riparian habitat along the lower Snake River

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

Downs, J. L; Tiller, B. L; Witter, M.

Studies in this document were initiated to establish baseline information on riparian and wetland habitat conditions at the areas studied under the current reservoir operations on the lower Snake River. Two approaches were used to assess habitat at 28 study sites selected on the four pools on the lower Snake River. These areas all contribute significant riparian habitat along the river, and several of these areas are designated habitat management units. At 14 of the 28 sites, we monitored riparian habitat on three dates during the growing season to quantify vegetation abundance and composition along three transects: soil nutrients, moisture,more » and pH and water level and pH. A second approach involved identifying any differences in the extent and amount of riparian/wetland habitat currently found at the study areas from that previously documented. We used both ground and boat surveys to map and classify the changes in vegetative cover along the shoreline at the 14 monitoring sites and at 14 additional sites along the lower Snake selected to represent various riparian/wetland habitat conditions. Results of these mapping efforts are compared with maps of cover types previously generated using aerial photography taken in 1987.« less

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

Pax: A permanent base for human habitation of Mars

NASA Technical Reports Server (NTRS)

Moore, Gary T.; Rebholz, Patrick J.; Fieber, Joseph P.; Huebner-Moths, Janis; Paruleski, Kerry L.

1992-01-01

The Advanced Design Program in Space Architecture at the University of Wisconsin-Milwaukee supported the synthesis report and two of its scenarios - 'Architecture 1' and 'Architecture 4' - and the Weaver ExPO report on near-term extraterrestrial explorations during the spring of 1992. The project investigated the implications of different mission scenarios, the Martian environment, supporting technologies, and especially human factors and environment-behavior considerations for the design of the first permanent Martian base. This paper presents the results of that investigation. The paper summarizes site selection, development of habitability design requirements based on environment-behavior research, construction sequencing, and a full concept design and design development for a first permanent Martian base and habitat. The proposed design is presented in terms of an integrative mission scenario and master plan phased through initial operational configuration, base site plan, and design development details of a complete Martian habitat for 18 crew members including all laboratory, mission control, and crew support spaces.

Potent selective nonpeptidic inhibitors of human lung tryptase

PubMed Central

Burgess, Laurence E.; Newhouse, Bradley J.; Ibrahim, Prabha; Rizzi, James; Kashem, Mohammed A.; Hartman, Ann; Brandhuber, Barbara J.; Wright, Clifford D.; Thomson, David S.; Vigers, Guy P. A.; Koch, Kevin

1999-01-01

Human lung tryptase, a homotetrameric serine protease unique to mast cell secretory granules, has been implicated in the pathogenesis of asthma. A hypothesis that tethered symmetrical inhibitors might bridge two adjacent active sites was explored via a rationally designed series of bisbenzamidines. These compounds demonstrated a remarkable distanced-defined structure–activity relationship against human tryptase with one series possessing subnanomolar potencies. Additional evidence supporting the concept of active-site bridging is also presented. PMID:10411878

Mars Pathfinder Landing Site Workshop

NASA Technical Reports Server (NTRS)

Golombek, Matthew (Editor)

1994-01-01

The Mars Pathfinder Project is an approved Discovery-class mission that will place a lander and rover on the surface of the Red Planet in July 1997. The Mars Pathfinder Landing Site Workshop was designed to allow the Mars scientific community to provide input as to where to land Pathfinder on Mars. The workshop was attended by over 60 people from around the United States and from Europe. Over 20 landing sites were proposed at the workshop, and the scientific questions and problems concerning each were addressed. The workshop and the discussion that occured during and afterward have significantly improved the ability to select a scientifically exciting but safe landing site on Mars.

Environmental impact statement Space Shuttle advanced solid rocket motor program

NASA Technical Reports Server (NTRS)

1989-01-01

The proposed action is design, development, testing, and evaluation of Advanced Solid Rocket Motors (ASRM) to replace the motors currently used to launch the Space Shuttle. The proposed action includes design, construction, and operation of new government-owned, contractor-operated facilities for manufacturing and testing the ASRM's. The proposed action also includes transport of propellant-filled rocket motor segments from the manufacturing facility to the testing and launch sites and the return of used and/or refurbished segments to the manufacturing site. Sites being considered for the new facilities include John C. Stennis Space Center, Hancock County, Mississippi; the Yellow Creek site in Tishomingo County, Mississippi, which is currently in the custody and control of the Tennessee Valley Authority; and John F. Kennedy Space Center, Brevard County, Florida. TVA proposes to transfer its site to the custody and control of NASA if it is the selected site. All facilities need not be located at the same site. Existing facilities which may provide support for the program include Michoud Assembly Facility, New Orleans Parish, Louisiana; and Slidell Computer Center, St. Tammany Parish, Louisiana. NASA's preferred production location is the Yellow Creek site, and the preferred test location is the Stennis Space Center.

Sequence-based design of bioactive small molecules that target precursor microRNAs.

PubMed

Velagapudi, Sai Pradeep; Gallo, Steven M; Disney, Matthew D

2014-04-01

Oligonucleotides are designed to target RNA using base pairing rules, but they can be hampered by poor cellular delivery and nonspecific stimulation of the immune system. Small molecules are preferred as lead drugs or probes but cannot be designed from sequence. Herein, we describe an approach termed Inforna that designs lead small molecules for RNA from solely sequence. Inforna was applied to all human microRNA hairpin precursors, and it identified bioactive small molecules that inhibit biogenesis by binding nuclease-processing sites (44% hit rate). Among 27 lead interactions, the most avid interaction is between a benzimidazole (1) and precursor microRNA-96. Compound 1 selectively inhibits biogenesis of microRNA-96, upregulating a protein target (FOXO1) and inducing apoptosis in cancer cells. Apoptosis is ablated when FOXO1 mRNA expression is knocked down by an siRNA, validating compound selectivity. Markedly, microRNA profiling shows that 1 only affects microRNA-96 biogenesis and is at least as selective as an oligonucleotide.

Sequence-based design of bioactive small molecules that target precursor microRNAs

PubMed Central

Velagapudi, Sai Pradeep; Gallo, Steven M.; Disney, Matthew D.

2014-01-01

Oligonucleotides are designed to target RNA using base pairing rules, however, they are hampered by poor cellular delivery and non-specific stimulation of the immune system. Small molecules are preferred as lead drugs or probes, but cannot be designed from sequence. Herein, we describe an approach termed Inforna that designs lead small molecules for RNA from solely sequence. Inforna was applied to all human microRNA precursors and identified bioactive small molecules that inhibit biogenesis by binding to nuclease processing sites (41% hit rate). Amongst 29 lead interactions, the most avid interaction is between a benzimidazole (1) and precursor microRNA-96. Compound 1 selectively inhibits biogenesis of microRNA-96, upregulating a protein target (FOXO1) and inducing apoptosis in cancer cells. Apoptosis is ablated when FOXO1 mRNA expression is knocked down by an siRNA, validating compound selectivity. Importantly, microRNA profiling shows that 1 only significantly effects microRNA-96 biogenesis and is more selective than an oligonucleotide. PMID:24509821

Ventrogluteal versus dorsogluteal site selection: A cross-sectional study of muscle and subcutaneous fat thicknesses and an algorithm incorporating demographic and anthropometric data to predict injection outcome.

PubMed

Larkin, Theresa A; Ashcroft, Elfriede; Elgellaie, Asmahan; Hickey, Blake A

2017-06-01

The dorsogluteal and ventrogluteal intramuscular injection sites both have their use in clinical practice; however, it has not been established in whom one or the other should be preferentially targeted or avoided. There is a need for an evidence-based approach towards site selection for a successful intramuscular injection outcome and to avoid unwanted injection outcomes of inadvertent subcutaneous injection or bone contact. Injection outcome is dependent on injection site subcutaneous fat thickness and muscle thickness; these are likely influenced by gender and anthropometry. To determine whether subcutaneous fat, muscle, and total tissue thicknesses differ between the dorsogluteal and ventrogluteal sites, and whether theoretical injection outcome (intramuscular, subcutaneous, or bone contact) can be predicted by demographic and anthropometric data and described by an algorithm. Cross-sectional study design. University in Australia. 145 volunteers (57% female) of at least 18 years of age recruited through the university community. Anthropometric data was collected and subcutaneous fat and muscle thicknesses were quantified by ultrasonography. Anthropometric differences between theoretical injection outcome groups (bone contact versus intramuscular versus subcutaneous at the ventrogluteal and dorsogluteal sites) was determined for each gender (ANOVA). Multiple regression analysis was conducted to determine the influence of demographic and anthropometric data on theoretical intramuscular injection outcome. An algorithm to guide site selection was developed for each gender, based on the anthropometric measures that best discriminated between injection outcomes. Subcutaneous fat, muscle and total tissue were significantly thicker at the dorsogluteal site than the ventrogluteal site, and subcutaneous fat was significantly thicker in females than males at both sites (all p<0.001); there was no gender difference for muscle or total tissue thickness at either site. Female gender, and waist and hip circumference were significant predictors of subcutaneous fat thickness at both sites; male gender was a significant predictor of dorsogluteal site muscle thickness (all p<0.05). In the algorithm developed for site selection based on theoretical injection outcome, the best discriminators were: weight, BMI and waist circumference for females, and weight and distance between the iliac tubercle and anterior superior iliac spine for males. The algorithm describes when each of the ventrogluteal and dorsogluteal sites is appropriate or should be avoided, based on easily obtained anthropometric data. This has direct relevance in clinical practice in evidence-based site selection for gluteal intramuscular injections for optimal medication and health outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Strain selection, biomass to biofuel conversion, and resource colocation have strong impacts on the economic performance of algae cultivation sites

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

Venteris, Erik R.; Wigmosta, Mark S.; Coleman, Andre M.

Decisions involving strain selection, biomass to biofuel technology, and the location of cultivation facilities can strongly influence the economic viability of an algae-based biofuel enterprise. In this contribution we summarize our past results in a new analysis to explore the relative economic impact of these design choices. We present strain-specific growth model results from two saline strains (Nannocloropsis salina, Arthrospira sp.), a fresh to brackish strain (Chlorella sp., DOE strain 1412), and a freshwater strain of the order Sphaeropleales. Biomass to biofuel conversion is compared between lipid extraction (LE) and hydrothermal liquefaction (HTL) technologies. National-scale models of water, CO2 (asmore » flue gas), land acquisition, site leveling, construction of connecting roads, and transport of HTL oil to existing refineries are used in conjunction with estimates of fuel value (from HTL) to prioritize and select from 88,692 unit farms (UF, 405 ha in pond area), a number sufficient to produce 136E+9 L yr-1 of renewable diesel (36 billion gallons yr-1, BGY). Strain selection and choice of conversion technology have large economic impacts, with differences between combinations of strains and biomass to biofuel technologies being up to $10 million dollars yr-1 UF-1. Results based on the most productive species, HTL-based fuel conversion, and resource costs show that the economic potential between geographic locations within the selection can differ by up to $4 million yr-1 UF-1, with 2.0 BGY of production possible from the most cost-effective sites. The local spatial variability in site rank is extreme, with very high and low rank sites within 10s of km of each other. Colocation with flue gas sources has a strong influence on site rank, but the most costly resource component varies from site to site. The highest rank sites are located predominantly in Florida and Texas, but most states south of 37°N latitude contain promising locations. Keywords: algae, biofuels, resource assessment, geographic information systems, techno-economics« less

77 FR 11140 - Availability of the Draft Supplementary Risk Assessment for the Boston University (BU) National...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-24

... environments. The urban, suburban, and rural sites that were selected for the purposes of the comparative... construction grant to Boston University Medical Campus to partly fund the design and construction of one of two...

Fact Sheet: Documenting Ground-Water Models Selection at Site Contaminated with Radioactive Substance

EPA Pesticide Factsheets

This fact sheet summarizes the report by a joint Interagency Environmental Pathway Modeling Working Group. It was designed to be used by technical staff responsible for identifying and implementing flow and transport models to support cleanup decisions.

Adsorption-based Treatment Systems for Removing Chemical Vapors from Indoor Air

EPA Science Inventory

The U.S. Environmental Protection Agency (EPA) Engineering Issue Papers (EIPs) are a series of technology transfer documents that summarize the latest information on selected waste treatment and site remediation technologies and related issues. EIPs are designed to help remedial ...

Isoindoline-1,3-dione derivatives targeting cholinesterases: design, synthesis and biological evaluation of potential anti-Alzheimer's agents.

PubMed

Guzior, Natalia; Bajda, Marek; Rakoczy, Jurand; Brus, Boris; Gobec, Stanislav; Malawska, Barbara

2015-04-01

Alzheimer's disease is a fatal neurodegenerative disorder with a complex etiology. Because the available therapy brings limited benefits, the effective treatment for Alzheimer's disease remains the unmet challenge. Our aim was to develop a new series of donepezil-based compounds endowed with inhibitory properties against cholinesterases and β-amyloid aggregation. We designed the target compounds as dual binding site acetylcholinesterase inhibitors with N-benzylamine moiety interacting with the catalytic site of the enzyme and an isoindoline-1,3-dione fragment interacting with the peripheral anionic site of the enzyme. The results of pharmacological evaluation lead us to identify a compound 3b as the most potent and selective human acetylcholinesterase inhibitor (hAChE IC50=0.361μM). Kinetic studies revealed that 3b inhibited acetylcholinesterase in non-competitive mode. The result of the parallel artificial membrane permeability assay for the blood-brain barrier indicated that the compound 3b would be able to cross the blood-brain barrier and reach its biological targets in the central nervous system. The selected compound 3b represents a potential lead structure for further development of anti-Alzheimer's agents. Copyright © 2015 Elsevier Ltd. All rights reserved.

Selective aliphatic carbon-hydrogen bond activation of protected alcohol substrates by cytochrome P450 enzymes.

PubMed

Bell, Stephen G; Spence, Justin T J; Liu, Shenglan; George, Jonathan H; Wong, Luet-Lok

2014-04-21

Protected cyclohexanol and cyclohex-2-enol substrates, containing benzyl ether and benzoate ester moieties, were designed to fit into the active site of the Tyr96Ala mutant of cytochrome P450cam. The protected cyclohexanol substrates were efficiently and selectively hydroxylated by the mutant enzyme at the trans C-H bond of C-4 on the cyclohexyl ring. The selectivity of oxidation of the benzoate ester protected cyclohexanol could be altered by making alternative amino acid substitutions in the P450cam active site. The addition of the double bond in the cyclohexyl ring of the benzoate ester protected cyclohex-2-enol has a debilitative effect on the activity of the Tyr96Ala mutant with this substrate. However, the Phe87Ala/Tyr96Phe double mutant, which introduces space at a different location in the active site than the Tyr96Ala mutant, was able to efficiently hydroxylate the C-H bonds of 1-cyclohex-2-enyl benzoate at the allylic C-4 position. Mutations at Phe87 improved the selectivity of the oxidation of 1-phenyl-1-cyclohexylethylene to trans-4-phenyl-ethenylcyclohexanol (92%) when compared to single mutants at Tyr96 of P450cam.

The effects of publishing emergency department wait time on patient utilization patterns in a community with two emergency department sites: a retrospective, quasi-experiment design.

PubMed

Xie, Bin; Youash, Sabrina

2011-06-14

Providing emergency department (ED) wait time information to the public has been suggested as a mechanism to reduce lengthy ED wait times (by enabling patients to select the ED site with shorter wait time), but the effects of such a program have not been evaluated. We evaluated the effects of such a program in a community with two ED sites. Descriptive statistics for wait times of the two sites before and after the publication of wait time information were used to evaluate the effects of the publication of wait time information on wait times. Multivariate logistical regression was used to test whether or not individual patients used published wait time to decide which site to visit. We found that the rates of wait times exceeding 4 h, and the 95th percentile of wait times in the two sites decreased after the publication of wait time information, even though the average wait times experienced a slight increase. We also found that after controlling for other factors, the site with shorter wait time had a higher likelihood of being selected after the publication of wait time information, but there was no such relationship before the publication. These findings were consistent with the hypothesis that the publication of wait time information leads to patients selecting the site with shorter wait time. While publishing ED wait time information did not improve average wait time, it reduced the rates of lengthy wait times.

Assessing emergency planning zone for new nuclear power plant considering risk of extreme external events

NASA Astrophysics Data System (ADS)

Alzbutas, Robertas

2015-04-01

In general, the Emergency Planning Zones (EPZ) are defined as well as plant site and arrangement structures are designed to minimize the potential for natural and manmade hazards external to the plant from affecting the plant safety related functions, which can affect nearby population and environment. This may include consideration of extreme winds, fires, flooding, aircraft crash, seismic activity, etc. Thus the design basis for plant and site is deeply related to the effects of any postulated external events and the limitation of the plant capability to cope with accidents i.e. perform safety functions. It has been observed that the Probabilistic Safety Assessment (PSA) methodologies to deal with EPZ and extreme external events have not reached the same level of maturity as for severe internal events. The design basis for any plant and site is deeply related to the effects of any postulated external events and the limitation of the plant capability to cope with accidents i.e. perform safety functions. As a prime example of an advanced reactor and new Nuclear Power Plant (NPP) with enhanced safety, the International Reactor Innovative and Secure (IRIS) and Site selection for New NPP in Lithuania had been considered in this work. In the used Safety-by-Design™ approach, the PSA played obviously a key role; therefore a Preliminary IRIS PSA had been developed along with the design. For the design and pre-licensing process of IRIS the external events analysis included both qualitative evaluation and quantitative assessment. As a result of preliminary qualitative analyses, the external events that were chosen for more detailed quantitative scoping evaluation were high winds and tornadoes, aircraft crash, and seismic events. For the site selection in Lithuania a detail site evaluation process was performed and related to the EPZ and risk zoning considerations. In general, applying the quantitative assessment, bounding site characteristics could be used in order to optimize potential redefinition or future restrictions on plant siting and risk zoning. It must be noticed that the use of existing regulations and installations as the basis for this redefinition will not in any way impact the high degree of conservatism inherent in current regulations. Moreover, the remapping process makes this methodology partially independent from the uncertainties still affecting probabilistic techniques. Notwithstanding these considerations, it is still expected that applying this methodology to advanced plant designs with improved safety features will allow significant changes in the emergency planning requirements, and specifically the size of the EPZ. In particular, in the case of IRIS it is expected that taking full credit of the Safety-by-Design™ approach of the IRIS reactor will allow a dramatic changes in the EPZ, while still maintaining a level of protection to the public fully consistent with existing regulations.

Onboard Determination of Vehicle Glide Capability for Shuttle Abort Flight Managment (SAFM)

NASA Technical Reports Server (NTRS)

Straube, Timothy; Jackson, Mark; Fill, Thomas; Nemeth, Scott

2002-01-01

When one or more main engines fail during ascent, the flight crew of the Space Shuttle must make several critical decisions and accurately perform a series of abort procedures. One of the most important decisions for many aborts is the selection ofa landing site. Several factors influence the ability to reach a landing site, including the spacecraft point of atmospheric entry, the energy state at atmospheric entry, the vehicle glide capability from that energy state, and whether one or more suitable landing sites are within the glide capability. Energy assessment is further complicated by the fact that phugoid oscillations in total energy influence glide capability. Once the glide capability is known, the crew must select the "best" site option based upon glide capability and landing site conditions and facilities. Since most of these factors cannot currently be assessed by the crew in flight, extensive planning is required prior to each mission to script a variety of procedures based upon spacecraft velocity at the point of engine failure (or failures). The results of this preflight planning are expressed in tables and diagrams on mission-specific cockpit checklists. Crew checklist procedures involve leafing through several pages of instructions and navigating a decision tree for site selection and flight procedures - all during a time critical abort situation. With the advent of the Cockpit Avionics Upgrade (CAU), the Shuttle will have increased on-board computational power to help alleviate crew workload during aborts and provide valuable situational awareness during nominal operations. One application baselined for the CAU computers is Shuttle Abort Flight Management (SAFM), whose requirements have been designed and prototyped. The SAFM application includes powered and glided flight algorithms. This paper describes the glided flight algorithm which is dispatched by SAFM to determine the vehicle glide capability and make recommendations to the crew for site selection as well as to monitor glide capability while in route to the selected site. Background is provided on Shuttle entry guidance as well as the various types of Shuttle aborts. SAFM entry requirements and cockpit disp lays are discussed briefly to provide background for Glided Flight algorithm design considerations. The central principal of the Glided Flight algorithm is the use of energy-over-weight (EOW) curves to determine range and crossrange boundaries. The major challenges of this technique are exo-atmospheric flight, and phugoid oscillations in energy. During exo-atmospheric flight, energy is constant, so vehicle EOW is not sufficient to determine glide capability. The paper describes how the exo-atmospheric problem is solved by propagating the vehicle state to an "atmospheric pullout" state defined by Shuttle guidance parameters.

A comparative study of surface energies and water adsorption on Ce-bastnäsite, La-bastnäsite, and calcite via density functional theory and water adsorption calorimetry

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

Goverapet Srinivasan, Sriram; Shivaramaiah, Radha; Kent, Paul R. C.

Bastnäsite, a fluoro-carbonate mineral, is the single largest mineral source of light rare earth elements (REE), La, Ce and Nd. Enhancing the efficiency of separation of the mineral from gangue through froth flotation is the first step towards meeting an ever increasing demand for REE. To design and evaluate collector molecules that selectively bind to bastnäsite, a fundamental understanding of the structure and surface properties of bastnäsite is essential. In our earlier work (J Phys Chem C, 2016, 120, 16767), we carried out an extensive study of the structure, surface stability and water adsorption energies of La-bastnäsite. Here in thismore » work, we make a comparative study of the surface properties of Ce-bastnäsite, La-bastnäsite, and calcite using a combination of density functional theory (DFT) and water adsorption calorimetry. Spin polarized DFT+U calculations show that the exchange interaction between the electrons in Ce 4f orbitals is negligible and that these orbitals do not participate in bonding with the oxygen atom of the adsorbed water molecule. In agreement with calorimetry, DFT calculations predict larger surface energies and stronger water adsorption energies on Ce-bastnäsite than on La-bastnäsite. The order of stabilities for stoichiometric surfaces is as follows: [100] > [101] > [102] > [0001] > [112] > [104] and the most favorable adsorption sites for water molecules are the same as for La-bastnäsite. In agreement with water adsorption calorimetry, at low coverage water molecules are strongly stabilized via coordination to the surface Ce3+ ions, whereas at higher coverage they are adsorbed less strongly via hydrogen bonding interaction with the surface anions. Lastly, due to similar water adsorption energies on bastnäsite [101] and calcite [104] surfaces, the design of collector molecules that selectively bind to bastnäsite over calcite must exploit the structural differences in the predominantly exposed facets of these minerals.« less

A comparative study of surface energies and water adsorption on Ce-bastnäsite, La-bastnäsite, and calcite via density functional theory and water adsorption calorimetry

DOE PAGES

Goverapet Srinivasan, Sriram; Shivaramaiah, Radha; Kent, Paul R. C.; ...

2017-02-24

Bastnäsite, a fluoro-carbonate mineral, is the single largest mineral source of light rare earth elements (REE), La, Ce and Nd. Enhancing the efficiency of separation of the mineral from gangue through froth flotation is the first step towards meeting an ever increasing demand for REE. To design and evaluate collector molecules that selectively bind to bastnäsite, a fundamental understanding of the structure and surface properties of bastnäsite is essential. In our earlier work (J Phys Chem C, 2016, 120, 16767), we carried out an extensive study of the structure, surface stability and water adsorption energies of La-bastnäsite. Here in thismore » work, we make a comparative study of the surface properties of Ce-bastnäsite, La-bastnäsite, and calcite using a combination of density functional theory (DFT) and water adsorption calorimetry. Spin polarized DFT+U calculations show that the exchange interaction between the electrons in Ce 4f orbitals is negligible and that these orbitals do not participate in bonding with the oxygen atom of the adsorbed water molecule. In agreement with calorimetry, DFT calculations predict larger surface energies and stronger water adsorption energies on Ce-bastnäsite than on La-bastnäsite. The order of stabilities for stoichiometric surfaces is as follows: [100] > [101] > [102] > [0001] > [112] > [104] and the most favorable adsorption sites for water molecules are the same as for La-bastnäsite. In agreement with water adsorption calorimetry, at low coverage water molecules are strongly stabilized via coordination to the surface Ce3+ ions, whereas at higher coverage they are adsorbed less strongly via hydrogen bonding interaction with the surface anions. Lastly, due to similar water adsorption energies on bastnäsite [101] and calcite [104] surfaces, the design of collector molecules that selectively bind to bastnäsite over calcite must exploit the structural differences in the predominantly exposed facets of these minerals.« less

A comparative study of surface energies and water adsorption on Ce-bastnäsite, La-bastnäsite, and calcite via density functional theory and water adsorption calorimetry.

PubMed

Goverapet Srinivasan, Sriram; Shivaramaiah, Radha; Kent, Paul R C; Stack, Andrew G; Riman, Richard; Anderko, Andre; Navrotsky, Alexandra; Bryantsev, Vyacheslav S

2017-03-15

Bastnäsite, a fluoro-carbonate mineral, is the single largest mineral source of light rare earth elements (REE), La, Ce and Nd. Enhancing the efficiency of separation of the mineral from gangue through froth flotation is the first step towards meeting an ever increasing demand for REE. To design and evaluate collector molecules that selectively bind to bastnäsite, a fundamental understanding of the structure and surface properties of bastnäsite is essential. In our earlier work (J. Phys. Chem. C, 2016, 120, 16767), we carried out an extensive study of the structure, surface stability and water adsorption energies of La-bastnäsite. In this work, we make a comparative study of the surface properties of Ce-bastnäsite, La-bastnäsite, and calcite using a combination of density functional theory (DFT) and water adsorption calorimetry. Spin polarized DFT+U calculations show that the exchange interaction between the electrons in Ce 4f orbitals is negligible and that these orbitals do not participate in bonding with the oxygen atom of the adsorbed water molecule. In agreement with calorimetry, DFT calculations predict larger surface energies and stronger water adsorption energies on Ce-bastnäsite than on La-bastnäsite. The order of stabilities for stoichiometric surfaces is as follows: [101[combining macron]0] > [101[combining macron]1] > [101[combining macron]2] > [0001] > [112[combining macron]2] > [101[combining macron]4] and the most favorable adsorption sites for water molecules are the same as for La-bastnäsite. In agreement with water adsorption calorimetry, at low coverage water molecules are strongly stabilized via coordination to the surface Ce 3+ ions, whereas at higher coverage they are adsorbed less strongly via hydrogen bonding interaction with the surface anions. Due to similar water adsorption energies on bastnäsite [101[combining macron]1] and calcite [101[combining macron]4] surfaces, the design of collector molecules that selectively bind to bastnäsite over calcite must exploit the structural differences in the predominantly exposed facets of these minerals.

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

Not Available

Potomac Electric Power Company (PEPCO) and Acres American Incorporated (AAI) have carried out a preliminary design study of water-compensated Compressed Air Energy Storage (CAES) and Underground Pumped Hydroelectric (UPH) plants for siting in geological conditions suitable for hard rock excavations. The work was carried out over a period of three years and was sponsored by the US Department of Energy (DOE), the Electric Power Research Institute (EPRI) and PEPCO. The study was divided into five primary tasks as follows: establishment of design criteria and analysis of impact on power system; selection of site and establishment of site characteristics; formulation ofmore » design approaches; assessment of environmental and safety aspects; and preparation of preliminary design of plant. The salient aspects considered and the conclusions reached during the consideration of the five primary tasks for both CAES and UPH are presented in this Executive Summary, which forms Volume 1 of the series of reports prepared during the study. The investigations and analyses carried out, together with the results and conclusions reached, are described in detail in Volumes 2 through 13 and ten appendices.« less

Design of Cyclic Peptide Based Glucose Receptors and Their Application in Glucose Sensing.

PubMed

Li, Chao; Chen, Xin; Zhang, Fuyuan; He, Xingxing; Fang, Guozhen; Liu, Jifeng; Wang, Shuo

2017-10-03

Glucose assay is of great scientific significance in clinical diagnostics and bioprocess monitoring, and to design a new glucose receptor is necessary for the development of more sensitive, selective, and robust glucose detection techniques. Herein, a series of cyclic peptide (CP) glucose receptors were designed to mimic the binding sites of glucose binding protein (GBP), and CPs' sequence contained amino acid sites Asp, Asn, His, Asp, and Arg, which constituted the first layer interactions of GBP. The properties of these CPs used as a glucose receptor or substitute for the GBP were studied by using a quartz crystal microbalance (QCM) technique. It was found that CPs can form a self-assembled monolayer at the Au quartz electrode surface, and the monolayer's properties were characterized by using cyclic voltammetry, electrochemical impedance spectroscopy, and atomic force microscopy. The CPs' binding affinity to saccharide (i.e., galactose, fructose, lactose, sucrose, and maltose) was investigated, and the CPs' sensitivity and selectivity toward glucose were found to be dependent upon the configuration,i.e., the amino acids sequence of the CPs. The cyclic unit with a cyclo[-CNDNHCRDNDC-] sequence gave the highest selectivity and sensitivity for glucose sensing. This work suggests that a synthetic peptide bearing a particular functional sequence could be applied for developing a new generation of glucose receptors and would find huge application in biological, life science, and clinical diagnostics fields.

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

Preliminary analysis of Greater Sage-grouse reproduction in the Virginia Mountains of northwestern Nevada

USGS Publications Warehouse

Coates, Peter S.; Lockyer, Zachary B.; Farinha, Melissa A.; Sweeney, Joelle M.; Johnson, Valerie M.; Meshriy, Matthew G.; Espinosa, Shawn P.; Delehanty, David J.; Casazza, Michael L.

2011-01-01

Relationships between habitat selection and population vital rates of greater sage-grouse (Centrocercus urophasianus; hereafter sage-grouse), recently designated as a candidate species under the Endangered Species Act, within the Great Basin are not well-understood. The growing development of renewable energy infrastructure within areas inhabited by sage-grouse is thought to influence predator and vegetation communities. For example, common ravens (Corvus corax), a synanthropic sage-grouse nest predator, are increasing range-wide and select transmission lines and other tall structures for nesting and perching. In the Virginia Mountains of northwestern Nevada, we collected preliminary information of space-use, habitat selection, and population vital rates during the nesting and brood-rearing period over two years on 56 sage-grouse. Additionally, videography at nest sites (n = 22) was used to identify sage-grouse nest predators. The study area is a potential site for renewable energy developments (i.e., wind and solar), and we plan to continue monitoring this population using a before-after-control-impact study design. The results reported here are preliminary and further data are required before conclusions can be drawn from this population of sage-grouse.

Novel tetrahydrocarbazole benzyl pyridine hybrids as potent and selective butryl cholinesterase inhibitors with neuroprotective and β-secretase inhibition activities.

PubMed

Ghobadian, Roshanak; Mahdavi, Mohammad; Nadri, Hamid; Moradi, Alireza; Edraki, Najmeh; Akbarzadeh, Tahmineh; Sharifzadeh, Mohammad; Bukhari, Syed Nasir Abbas; Amini, Mohsen

2018-05-23

Butyrylcholinesterase (BuChE) inhibitors have become interesting target for treatment of Alzheimer's disease (AD). A series of dual binding site BuChE inhibitors were designed and synthesized based on 2,3,4,9-tetrahydro-1H-carbazole attached benzyl pyridine moieties. In-vitro assay revealed that all of the designed compounds were selective and potent BuChE inhibitors. The most potent BuChE inhibitor was compound 6i (IC 50  = 0.088 ± 0.0009 μM) with the mixed-type inhibition. Docking study revealed that 6i is a dual binding site BuChE inhibitor. Also, Pharmacokinetic properties for 6i were accurate to Lipinski's rule. In addition, compound 6i demonstrated neuroprotective and β-secretase (BACE1) inhibition activities. This compound could also inhibit AChE-induced and self-induced Aβ peptide aggregation at concentration of 100 μM and 10 μM respectively. Generally, the results are presented as new potent selective BuChE inhibitors with a therapeutic potential for the treatment of AD. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Zinc binding groups for histone deacetylase inhibitors.

PubMed

Zhang, Lei; Zhang, Jian; Jiang, Qixiao; Zhang, Li; Song, Weiguo

2018-12-01

Zinc binding groups (ZBGs) play a crucial role in targeting histone deacetylase inhibitors (HDACIs) to the active site of histone deacetylases (HDACs), thus determining the potency of HDACIs. Due to the high affinity to the zinc ion, hydroxamic acid is the most commonly used ZBG in the structure of HDACs. An alternative ZBG is benzamide group, which features excellent inhibitory selectivity for class I HDACs. Various ZBGs have been designed and tested to improve the activity and selectivity of HDACIs, and to overcome the pharmacokinetic limitations of current HDACIs. Herein, different kinds of ZBGs are reviewed and their features have been discussed for further design of HDACIs.

Monitoring network-design influence on assessment of ecological condition in wadeable streams

EPA Science Inventory

We investigated outcomes of three monitoring networks for assessing ecological character and condition of wadeable streams in the Waikato region, New Zealand. Sites were selected 1) based on a professional judgment network, 2) within categories of stream and watershed characteris...

MOBILITY AND DEGRADATION OF RESIDUES AT HAZARDOUS WASTE LAND TREATMENT SITES AT CLOSURE

EPA Science Inventory

Soil treatment systems that are designed and managed based on a knowledge of soil-waste interactions may represent a significant technology for simultaneous treatment and ultimate disposal of selected hazardous wastes in an environmentally acceptable manner. hese soil treatment s...

38 CFR 39.60 - General requirements for site selection and construction of veterans cemeteries.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED) AID FOR THE ESTABLISHMENT, EXPANSION, AND IMPROVEMENT, OR OPERATION AND MAINTENANCE, OF VETERANS CEMETERIES Establishment, Expansion, and Improvement... design and construction criteria and shall apply to all Establishment, Expansion, and Improvement...

38 CFR 39.60 - General requirements for site selection and construction of veterans cemeteries.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED) AID FOR THE ESTABLISHMENT, EXPANSION, AND IMPROVEMENT, OR OPERATION AND MAINTENANCE, OF VETERANS CEMETERIES Establishment, Expansion, and Improvement... design and construction criteria and shall apply to all Establishment, Expansion, and Improvement...

38 CFR 39.60 - General requirements for site selection and construction of veterans cemeteries.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED) AID FOR THE ESTABLISHMENT, EXPANSION, AND IMPROVEMENT, OR OPERATION AND MAINTENANCE, OF VETERANS CEMETERIES Establishment, Expansion, and Improvement... design and construction criteria and shall apply to all Establishment, Expansion, and Improvement...

Enhanced, multi criteria based site selection to measure mobile source toxic air pollutants

EPA Science Inventory

Research studies being conducted by the U.S. Environmental Protection Agency in collaboration with the U.S. Federal Highway Administration are designed to establish relationships between concentrations of highway vehicle air pollutants and variations in these concentrations as a ...

Optimal design of stormwater basins with bio-sorption activated media (BAM) in karst environments - phase I : site screening and selection.

DOT National Transportation Integrated Search

2015-12-01

Anthropogenic activities within the Silver Springs springshed over recent decades may have contributed : to elevated nutrient concentrations in stormwater runoff and groundwater, leading to the eutrophication : of Silver Springs. To remove the nutrie...

Guidelines, site selection, and design for implementing truck parking/rest facilities in Chicago's south suburbs.

DOT National Transportation Integrated Search

2012-11-01

This study proposes a network of overnight truck parking facilities in south suburban Chicago intended to : accomplish a wide range of federal, state, and local policy objectives. At the federal and state levels, this : reports policy objectives s...

Instructional Modules: A Paradigm Shift in Teaching.

ERIC Educational Resources Information Center

Darty, Mark; Brophy, James

1999-01-01

Describes the design and development of Internet-based instruction for a physiological psychology class. Discusses reasons for selecting the Internet-based form; tools needed to create the instructional materials; development and implementation of the Psychology Electronic Teaching Source (PETS) site; instructional delivery; feedback; and benefits…

Techniques for estimating magnitude and frequency of floods in Minnesota

USGS Publications Warehouse

Guetzkow, Lowell C.

1977-01-01

 Estimating relations have been developed to provide engineers and designers with improved techniques for defining flow-frequency characteristics to satisfy hydraulic planning and design requirements. The magnitude and frequency of floods up to the 100-year recurrence interval can be determined for most streams in Minnesota by methods presented. By multiple regression analysis, equations have been developed for estimating flood-frequency relations at ungaged sites on natural flow streams. Eight distinct hydrologic regions are delineated within the State with boundaries defined generally by river basin divides. Regression equations are provided for each region which relate selected frequency floods to significant basin parameters. For main-stem streams, graphs are presented showing floods for selected recurrence intervals plotted against contributing drainage area. Flow-frequency estimates for intervening sites along the Minnesota River, Mississippi River, and the Red River of the North can be derived from these graphs. Flood-frequency characteristics are tabulated for 201 paging stations having 10 or more years of record.

A remarkable enhancement of selectivity towards versatile analytes by a strategically integrated H-bonding site containing phase.

PubMed

Mallik, Abul K; Qiu, Hongdeng; Kuwahara, Yutaka; Takafuji, Makoto; Ihara, Hirotaka

2015-09-28

A double β-alanylated L-glutamide-derived organic phase has been newly designed and synthesized in such a way that integrated H-bonding (interaction) sites make it very suitable for the separation of versatile analytes, including shape-constrained isomers, and nonpolar, polar and basic compounds. The β-alanine residues introduced into two long-chain alkyl group moieties provide ordered polar groups through H-bonding among the amide groups.

VS30, site amplifications and some comparisons: The Adapazari (Turkey) case

NASA Astrophysics Data System (ADS)

Ozcep, Tazegul; Ozcep, Ferhat; Ozel, Oguz

The aim of this study was to investigate the role of VS30 in site amplifications in the Adapazari region, Turkey. To fulfil this aim, amplifications from VS30 measurements were compared with earthquake data for different soil types in the seismic design codes. The Adapazari area was selected as the study area, and shear-wave velocity distribution was obtained by the multichannel analysis of surface waves (MASWs) method at 100 sites for the top 50 m of soil. Aftershock data following the Mw 7.4 Izmit earthquake of 17 August 1999 gave magnitudes between 4.0 and 5.6 at six stations installed in and around the Adapazari Basin, at Babalı, Şeker, Genç, Hastane, Toyota and Imar. This data was used to estimate site amplifications by the reference-station method. In addition, the fundamental periods of the station sites were estimated by the single station method. Site classifications based on VS30 in the seismic design codes were compared with the fundamental periods and amplification values. It was found that site amplifications (from earthquake data) and relevant spectra (from VS30) are not in good agreement for soils in Adapazari (Turkey).

Designing of MIP based QCM sensor having thymine recognition sites based on biomimicking DNA approach.

PubMed

Diltemiz, S Emir; Hür, D; Ersöz, A; Denizli, A; Say, R

2009-11-15

Quartz crystal microbalance (QCM) sensors coated with molecular imprinted polymers (MIP) have been developed for the determination of thymine. In this method, methacryloylamidoadenine (MA-Ade) have used as a new monomer and thymine template for inspiration of DNA nucleobases interaction. The thymine can be simultaneously hydrogen binding to MA-Ade and fit into the shape-selective cavities. Thus, the interaction between nucleobases has an effect on the binding ability of the QCM sensors. The binding affinity of the thymine imprinted sensors has investigated by using the Langmuir isotherm. The thymine imprinted QCM electrodes have shown homogeneous binding sites for thymine (K(a): 1.0 x 10(5)M(-1)) while heterogeneous binding sites for uracil. On the other hand, recognition selectivity of the QCM sensor based on thymine imprinted polymer toward to uracil, ssDNA and ssRNA has been reported in this work.

Assessment of radioisotope heaters for remote terrestrial applications

NASA Astrophysics Data System (ADS)

Uherka, Kenneth L.

This paper examines the feasibility of using radioisotope byproducts for special heating applications at remote sites in Alaska and other cold regions. The investigation included assessment of candidate radioisotope materials for heater applications, identification of the most promising cold-region applications, evaluation of key technical issues and implementation constraints, and development of conceptual heater designs for candidate applications. Strontium-90 (Sr-90) was selected as the most viable fuel for radioisotopic heaters used in terrestrial applications. Opportunities for the application of radioisotopic heaters were determined through site visits to representative Alaskan installations. Candidate heater applications included water storage tanks, sludge digesters, sewage lagoons, water piping systems, well-head pumping stations, emergency shelters, and fuel storage tank deicers. Radio-isotopic heaters for freeze-up protection of water storage tanks and for enhancement of biological waste treatment processes at remote sites were selected as the most promising applications.

Afraid to Start Because the Outcome is Uncertain?: Social Site Characterization as a Tool for Informing Public Engagement Efforts

USGS Publications Warehouse

Wade, S.; Greenberg, S.

2009-01-01

This paper introduces the concept of social site characterization as a parallel effort to technical site characterization to be used in evaluating and planning carbon dioxides capture and storage (CCS) projects. Social site characterization, much like technical site characterization, relies on a series of iterative investigations into public attitudes towards a CCS project and the factors that will shape those views. This paper also suggests ways it can be used to design approaches for actively engaging stakeholders and communities in the deployment of CCS projects. This work is informed by observing the site selection process for FutureGen and the implementation of research projects under the Regional Carbon Sequestration Partnership Program. ?? 2009 Elsevier Ltd. All rights reserved.

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.

Northern Great Plains Network water quality monitoring design for tributaries to the Missouri National Recreational River

USGS Publications Warehouse

Rowe, Barbara L.; Wilson, Stephen K.; Yager, Lisa; Wilson, Marcia H.

2013-01-01

The National Park Service (NPS) organized more than 270 parks with important natural resources into 32 ecoregional networks to conduct Inventory and Monitoring (I&M) activities for assessment of natural resources within park units. The Missouri National Recreational River (NRR) is among the 13 parks in the NPS Northern Great Plain Network (NGPN). Park managers and NGPN staff identified surface water resources as a high priority vital sign to monitor in park units. The objectives for the Missouri NRR water quality sampling design are to (1) assess the current status and long-term trends of select water quality parameters; and (2) document trends in streamflow at high-priority stream systems. Due to the large size of the Missouri River main stem, the NGPN water quality design for the Missouri NRR focuses on wadeable tributaries within the park unit. To correlate with the NGPN water quality protocols, monitoring of the Missouri NRR consists of measurement of field core parameters including dissolved oxygen, pH, specific conductance, and temperature; and streamflow. The purpose of this document is to discuss factors examined for selection of water quality monitoring on segments of the Missouri River tributaries within the Missouri NRR.Awareness of the complex history of the Missouri NRR aids in the current understanding and direction for designing a monitoring plan. Historical and current monitoring data from agencies and entities were examined to assess potential NGPN monitoring sites. In addition, the U.S. Environmental Protection Agency 303(d) list was examined for the impaired segments on tributaries to the Missouri River main stem. Because major tributaries integrate water quality effects from complex combinations of land use and environmental settings within contributing areas, a 20-mile buffer of the Missouri NRR was used to establish environmental settings that may impact the water quality of tributaries that feed the Missouri River main stem. For selection of monitoring sites, anthropogenic and natural influences to water quality were assessed for Missouri NRR tributaries. Factors that were examined include the size and contributions of tributaries within watersheds to the main stem; population density; and land use such as urban development and agricultural practices including concentrated animal feeding operations. Based on examination of these data in addition to the park’s legislation and management considerations, two sites were selected for monitoring water quality on Missouri NRR tributaries for the ice-free season (mid-May to mid-October) on a rotational basis every third year. Bow Creek at St. James was selected for water quality monitoring based on lack of long-term water quality monitoring, current recreational use, and proximity of the tributary to intense agricultural practices. In addition, land within the Bow Creek watershed is owned by the NPS. The Niobrara River at Verdel was selected for monitoring due to high use for public recreational activities, adjacent agricultural land use, and documented impairments for designated beneficial uses. Both sites will have access to real-time streamgages that will aid in a greater understanding of water quality.

Lunar lander stage requirements based on the Civil Needs Data Base

NASA Technical Reports Server (NTRS)

Mulqueen, John A.

1992-01-01

This paper examines the lunar lander stages that will be necessary for the future exploration and development of the Moon. Lunar lander stage sizing is discussed based on the projected lunar payloads listed in the Civil Needs Data Base. Factors that will influence the lander stage design are identified and discussed. Some of these factors are (1) lunar orbiting and lunar surface lander bases; (2) implications of direct landing trajectories and landing from a parking orbit; (3) implications of landing site and parking orbit; (4) implications of landing site and parking orbit selection; (5) the use of expendable and reusable lander stages; and (6) the descent/ascent trajectories. Data relating the lunar lander stage design requirements to each of the above factors and others are presented in parametric form. These data will provide useful design data that will be applicable to future mission model modifications and design studies.

Selective Medical Library on Microfiche. An international experiment supported by the Rockefeller Foundation.

PubMed Central

Saracevic, T

1988-01-01

The Selective Medical Library on Microfiche (SMLM) project is designed to improve access to the world's significant biomedical literature in developing countries' medical school libraries through the provision of a first-rate, low-cost core collection of journals. One hundred and five journals representing thirty-six biomedical specialties were selected using a method designed specifically for SMLM. The journals are provided on microfiche because of its relative low cost, durability, easy reproduction, and rapid delivery by air mail. SMLMs have been established at test and demonstration sites in four medical schools in Egypt, Indonesia, Mexico, and Colombia. SMLMs are delivered as turnkey systems consisting of the microfiche collection, a reader-printer, four fiche readers, necessary furniture, and promotional and training materials. The project involves extensive evaluation. PMID:3370375

Geological and technological assessment of artificial reef sites, Louisiana outer continental shelf

USGS Publications Warehouse

Pope, D.L.; Moslow, T.F.; Wagner, J.B.

1993-01-01

This paper describes the general procedures used to select sites for obsolete oil and gas platforms as artificial reefs on the Louisiana outer continental shelf (OCS). The methods employed incorporate six basic steps designed to resolve multiple-use conflicts that might otherwise arise with daily industry and commercial fishery operations, and to identify and assess both geological and technological constraints that could affect placement of the structures. These steps include: (1) exclusion mapping; (2) establishment of artificial reef planning areas; (3) database compilation; (4) assessment and interpretation of database; (5) mapping of geological and man-made features within each proposed reef site; and (6) site selection. Nautical charts, bathymetric maps, and offshore oil and gas maps were used for exclusion mapping, and to select nine regional planning areas. Pipeline maps were acquired from federal agencies and private industry to determine their general locations within each planning area, and to establish exclusion fairways along each pipeline route. Approximately 1600 line kilometers of high-resolution geophysical data collected by federal agencies and private industry was acquired for the nine planning areas. These data were interpreted to determine the nature and extent of near-surface geologic features that could affect placement of the structures. Seismic reflection patterns were also characterized to evaluate near-bottom sedimentation processes in the vicinity of each reef site. Geotechnical borings were used to determine the lithological and physical properties of the sediment, and for correlation with the geophysical data. Since 1987, five sites containing 10 obsolete production platforms have been selected on the Louisiana OCS using these procedures. Industry participants have realized a total savings of approximately US $1 500 000 in salvaging costs by converting these structures into artificial reefs. ?? 1993.

Lipid Interaction Sites on Channels, Transporters and Receptors: Recent Insights from Molecular Dynamics Simulations

PubMed Central

Hedger, George; Sansom, Mark S. P.

2017-01-01

Lipid molecules are able to selectively interact with specific sites on integral membrane proteins, and modulate their structure and function. Identification and characterisation of these sites is of importance for our understanding of the molecular basis of membrane protein function and stability, and may facilitate the design of lipid-like drug molecules. Molecular dynamics simulations provide a powerful tool for the identification of these sites, complementing advances in membrane protein structural biology and biophysics. We describe recent notable biomolecular simulation studies which have identified lipid interaction sites on a range of different membrane proteins. The sites identified in these simulation studies agree well with those identified by complementary experimental techniques. This demonstrates the power of the molecular dynamics approach in the prediction and characterization of lipid interaction sites on integral membrane proteins. PMID:26946244

Site Selection for Hvdc Ground Electrodes

NASA Astrophysics Data System (ADS)

Freire, P. F.; Pereira, S. Y.

2014-12-01

High-Voltage Direct Current (HVDC) transmission systems are composed of a bipole transmission line with a converter substation at each end. Each substation may be equipped with a HVDC ground electrode, which is a wide area (up to 1 km Ø) and deep (from 3 to 100m) electrical grounding. When in normal operation, the ground electrode will dissipate in the soil the unbalance of the bipole (~1.5% of the rated current). When in monopolar operation with ground return, the HVDC electrode will inject in the soil the nominal pole continuous current, of about 2000 to 3000 Amperes, continuously for a period up to a few hours. HVDC ground electrodes site selection is a work based on extensive geophysical and geological surveys, in order to attend the desired design requirements established for the electrodes, considering both its operational conditions (maximum soil temperature, working life, local soil voltage gradients etc.) and the interference effects on the installations located up to 50 km away. This poster presents the geophysical investigations conducted primarily for the electrodes site selection, and subsequently for the development of the crust resistivity model, which will be used for the interference studies. A preliminary site selection is conducted, based on general geographical and geological criteria. Subsequently, the geology of each chosen area is surveyed in detail, by means of electromagnetic/electrical geophysical techniques, such as magnetotelluric (deep), TDEM (near-surface) and electroresistivity (shallow). Other complementary geologic and geotechnical surveys are conducted, such as wells drilling (for geotechnical characterization, measurement of the water table depth and water flow, and electromagnetic profiling), and soil and water sampling (for measurement of thermal parameters and evaluation of electrosmosis risk). The site evaluation is a dynamic process along the surveys, and some sites will be discarded. For the two or three final sites, the inversion of the combined deep, near-surface and shallow apparent resistivity curves, results in the layered crust resistivity models. These models will allow for the preliminary interference studies, that will result on the selection of the final electrode site (one for each converter substation).

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.

Internet marketing 101.

PubMed

Miller, Ryan J

2010-11-01

In an era when social media sites like YouTube, Facebook, and Twitter dominate the popular press, many surgeons overlook the foundational tactics and strategies necessary for long-term practice development and lead generation on the Internet. This article analyzes common errors made by surgeons during the development and implementation of Web site projects, focusing on the areas of strategy development; domain name identification; site plan creation; design considerations; content development; vendor selection; and launch, promotion, and staff training. The article emphasizes that, because the Web site remains the foundation of a surgeon's branding message, minimizing errors during development and construction is critical, particularly in highly competitive or saturated markets, for today's facial plastic surgery practice. Copyright © 2010 Elsevier Inc. All rights reserved.

Abort Options for Human Lunar Missions between Earth Orbit and Lunar Vicinity

NASA Technical Reports Server (NTRS)

Condon, Gerald L.; Senent, Juan S.; Llama, Eduardo Garcia

2005-01-01

Apollo mission design emphasized operational flexibility that supported premature return to Earth. However, that design was tailored to use expendable hardware for short expeditions to low-latitude sites and cannot be applied directly to an evolutionary program requiring long stay times at arbitrary sites. This work establishes abort performanc e requirements for representative onorbit phases of missions involvin g rendezvous in lunar-orbit, lunar-surface and at the Earth-Moon libr ation point. This study submits reference abort delta-V requirements and other Earth return data (e.g., entry speed, flight path angle) and also examines the effect of abort performance requirements on propul sive capability for selected vehicle configurations.

Lysine and the Na+/K+ Selectivity in Mammalian Voltage-Gated Sodium Channels.

PubMed

Li, Yang; Liu, Huihui; Xia, Mengdie; Gong, Haipeng

2016-01-01

Voltage-gated sodium (Nav) channels are critical in the generation and transmission of neuronal signals in mammals. The crystal structures of several prokaryotic Nav channels determined in recent years inspire the mechanistic studies on their selection upon the permeable cations (especially between Na+ and K+ ions), a property that is proposed to be mainly determined by residues in the selectivity filter. However, the mechanism of cation selection in mammalian Nav channels lacks direct explanation at atomic level due to the difference in amino acid sequences between mammalian and prokaryotic Nav homologues, especially at the constriction site where the DEKA motif has been identified to determine the Na+/K+ selectivity in mammalian Nav channels but is completely absent in the prokaryotic counterparts. Among the DEKA residues, Lys is of the most importance since its mutation to Arg abolishes the Na+/K+ selectivity. In this work, we modeled the pore domain of mammalian Nav channels by mutating the four residues at the constriction site of a prokaryotic Nav channel (NavRh) to DEKA, and then mechanistically investigated the contribution of Lys in cation selection using molecular dynamics simulations. The DERA mutant was generated as a comparison to understand the loss of ion selectivity caused by the K-to-R mutation. Simulations and free energy calculations on the mutants indicate that Lys facilitates Na+/K+ selection by electrostatically repelling the cation to a highly Na+-selective location sandwiched by the carboxylate groups of Asp and Glu at the constriction site. In contrast, the electrostatic repulsion is substantially weakened when Lys is mutated to Arg, because of two intrinsic properties of the Arg side chain: the planar geometric design and the sparse charge distribution of the guanidine group.

Representativeness-based sampling network design for the State of Alaska

Treesearch

Forrest M. Hoffman; Jitendra Kumar; Richard T. Mills; William W. Hargrove

2013-01-01

Resource and logistical constraints limit the frequency and extent of environmental observations, particularly in the Arctic, necessitating the development of a systematic sampling strategy to maximize coverage and objectively represent environmental variability at desired scales. A quantitative methodology for stratifying sampling domains, informing site selection,...

Building Earth's Largest Library: Driving into the Future.

ERIC Educational Resources Information Center

Coffman, Steve

1999-01-01

Examines the Amazon.com online bookstore as a blueprint for designing the world's largest library. Topics include selection; accessibility and convenience; quality of Web sites and search tools; personalized service; library collection development, including interlibrary loan; library catalogs and catalog records; a circulation system; costs;…

43 CFR 32.5 - Administrative requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... operation at least 2 years, may apply to the designated State agency for a YACC sub-grant or contract. (b... provide for minimum enrollment numbers. Cost per enrollee limitations imposed on Interior and Forest... furnished through planning advice to Grantees. (c) All grantee camp/project site selections/locations shall...

Economic Evaluation of Townhouse Solar Energy System

NASA Technical Reports Server (NTRS)

1982-01-01

Solar-energy site in Columbia, South Carolina, is comprised of four townhouse apartments. Report summarizes economic evaluation of solar--energy system and projected performance of similar systems in four other selected cities. System is designed to supply 65 percent of heating and 75 percent of hot water.

Aquaculture. Second Edition. Teacher Edition.

ERIC Educational Resources Information Center

Walker, Susan S.; Crummett, Dan

This teacher and student guide for aquaculture contains 15 units of instruction that cover the following topics: (1) introduction to aquaculture; (2) the aquatic environment; (3) fundamental fish biology; (4) marketing; (5) site selection; (6) facility design and layout; (7) water quality management; (8) fish health management; (9) commercial…

X-33 Telemetry Best Source Selection, Processing, Display, and Simulation Model Comparison

NASA Technical Reports Server (NTRS)

Burkes, Darryl A.

1998-01-01

The X-33 program requires the use of multiple telemetry ground stations to cover the launch, ascent, transition, descent, and approach phases for the flights from Edwards AFB to landings at Dugway Proving Grounds, UT and Malmstrom AFB, MT. This paper will discuss the X-33 telemetry requirements and design, including information on fixed and mobile telemetry systems, best source selection, and support for Range Safety Officers. A best source selection system will be utilized to automatically determine the best source based on the frame synchronization status of the incoming telemetry streams. These systems will be used to select the best source at the landing sites and at NASA Dryden Flight Research Center to determine the overall best source between the launch site, intermediate sites, and landing site sources. The best source at the landing sites will be decommutated to display critical flight safety parameters for the Range Safety Officers. The overall best source will be sent to the Lockheed Martin's Operational Control Center at Edwards AFB for performance monitoring by X-33 program personnel and for monitoring of critical flight safety parameters by the primary Range Safety Officer. The real-time telemetry data (received signal strength, etc.) from each of the primary ground stations will also be compared during each nu'ssion with simulation data generated using the Dynamic Ground Station Analysis software program. An overall assessment of the accuracy of the model will occur after each mission. Acknowledgment: The work described in this paper was NASA supported through cooperative agreement NCC8-115 with Lockheed Martin Skunk Works.

Disposing of High-Level Radioactive Waste in Germany - A Note from the Licensing Authority - 12530

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

Pick, Thomas Stefan; Bluth, Joachim; Lauenstein, Christof

Following the national German consensus on the termination of utilisation of nuclear energy in the summer of 2011, the Federal and Laender Governments have declared their intention to work together on a national consensus on the disposal of radioactive waste as well. Projected in the early 1970's the Federal Government had started exploring the possibility to establish a repository for HLW at the Gorleben site in 1977. However, there is still no repository available in Germany today. The delay results mainly from the national conflict over the suitability of the designated Gorleben site, considerably disrupting German society along the crevicemore » that runs between supporters and opponents of nuclear energy. The Gorleben salt dome is situated in Lower Saxony, the German state that also hosts the infamous Asse mine repository for LLW and ILW and the Konrad repository project designated to receive LLW and ILW as well. With the fourth German project, the Morsleben L/ILW repository only 20 km away across the state border, the state of Lower Saxony carries the main load for the disposal of radioactive waste in Germany. After more than 25 years of exploration and a 10 year moratorium the Gorleben project has now reached a cross-road. Current plans for setting up a new site selection procedure in Germany call for the selection and exploration of up to four alternative sites, depending only on suitable geology. In the meantime the discussion is still open on whether the Gorleben project should be terminated in order to pacify the societal conflict or being kept in the selection process on account of its promising geology. The Lower Saxony Ministry for Environment and Climate Protection proposes to follow a twelve-step-program for finding the appropriate site, including the Gorleben site in the process. With its long history of exploration the site is the benchmark that alternative sites will have to compare with. Following the national consensus of 2011 on the termination of nuclear energy utilisation, it is now the time to reach a national consensus on the disposal of radioactive waste as well. This is a task that the country and society, federal and state governments, political parties and the citizens will have to jointly master within the current generation and within German territory. The basis for the consensus will be a reset to the beginning of this process. It has to start with a new site selection procedure that will take into account and compare up to four alternative sites. This procedure will have to follow the principle of highest possible security. It should be based on a stepwise approach, strictly following scientific criteria. Public confidence in the process and trust can only be achieved by a transparent procedure allowing for the participation of the public and the stakeholders. It is therefore mandatory to consult, both on a national and regional level, all involved parties (public authority, scientist and citizen). The national consensus must also include a decision on the future of the Gorleben exploratory site. The site selection procedure must therefore take this site into account as well. Furthermore, the final decision on safe disposal of German radioactive wastes must be made by sovereign rule by Federal Parliament and Federal Council. (authors)« less

Continuous directed evolution of aminoacyl-tRNA synthetases

PubMed Central

Bryson, David I.; Fan, Chenguang; Guo, Li-Tao; Miller, Corwin; Söll, Dieter; Liu, David R.

2017-01-01

Directed evolution of orthogonal aminoacyl-tRNA synthetases (AARSs) enables site-specific installation of non-canonical amino acids (ncAAs) into proteins. Traditional evolution techniques typically produce AARSs with greatly reduced activity and selectivity compared to their wild-type counterparts. We designed phage-assisted continuous evolution (PACE) selections to rapidly produce highly active and selective orthogonal AARSs through hundreds of generations of evolution. PACE of a chimeric Methanosarcina spp. pyrrolysyl-tRNA synthetase (PylRS) improved its enzymatic efficiency (kcat/KMtRNA) 45-fold compared to the parent enzyme. Transplantation of the evolved mutations into other PylRS-derived synthetases improved yields of proteins containing non-canonical residues up to 9.7-fold. Simultaneous positive and negative selection PACE over 48 h greatly improved the selectivity of a promiscuous Methanocaldococcus jannaschii tyrosyl-tRNA synthetase variant for site-specific incorporation of p-iodo-L-phenylalanine. These findings offer new AARSs that increase the utility of orthogonal translation systems and establish the capability of PACE to efficiently evolve orthogonal AARSs with high activity and amino acid specificity. PMID:29035361

Identification of key residues modulating the stereoselectivity of nitrile hydratase toward rac-mandelonitrile by semi-rational engineering.

PubMed

Cheng, Zhongyi; Peplowski, Lukasz; Cui, Wenjing; Xia, Yuanyuan; Liu, Zhongmei; Zhang, Jialei; Kobayashi, Michihiko; Zhou, Zhemin

2018-03-01

Optically pure compounds are important in the synthesis of fine chemicals. Using directed evolution of enzymes to obtain biocatalysts that can selectively produce high-value chiral chemicals is often time-, money-, and resource-intensive; traditional semi-rational designs based on structural data and docking experiments are still limited due to the lack of accurate selection of hot-spot residues. In this study, through ligand-protein collision counts based on steered molecular dynamics simulation, we accurately identified four residues related to improving nitrile hydratase stereoselectivity toward rac-mandelonitrile (MAN). All the four selected residues had numerous collisions with rac-MAN. Five mutants significantly shifting stereoselectivity towards (S)-MAN were obtained from site-saturation mutagenesis, one of them, at position βPhe37, exhibiting efficient production of (S)-MAN with 96.8% ee p , was isolated and further analyzed. The increased pulling force observed during SMD simulation was found to be in good coincidence with the formation of hydrogen bonds between (R)-MAN and residue βHis37. (R)-MAN had to break these barriers to enter the active site of nitrile hydratase and S selectivity was thus improved. The results indicated that combining steered molecular dynamics simulation with a traditional semi-rational design significantly reduced the select range of hot-spot residues for the evolution of NHase stereoselectivity, which could serve as an alternative for the modulation of enzyme stereoselectivity. © 2017 Wiley Periodicals, Inc.

Passive solar water heating: breadbox design for the Fred Young Farm Labor Center in Indio

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

Melzer, B; Maeda, B

1979-10-01

An appropriate passive solar preheater for multifamily housing units in the Fred Young Farm Labor Center in Indio, California, was designed and analyzed. A brief summary of passive preheater systems and the key design features used in current designs is presented. The design features necessary for the site requirements are described. The eight preliminary preheater designs reviewed for the project are presented. The results of thermal performance simulation for the eight prototype systems are discussed. Alternative monitoring systems for the installation are described and evaluated. The consultants' recommendations, working drawings, and performance estimates of the system selected are presented. (MHR)

Diet and density dependent competition affect larval performance and oviposition site selection in the mosquito species Aedes albopictus (Diptera: Culicidae)

PubMed Central

2012-01-01

Background Oviposition-site choice is an essential component of the life history of all mosquito species. According to the oviposition-preference offspring-performance (P-P) hypothesis, if optimizing offspring performance and fitness ensures high overall reproductive fitness for a given species, the female should accurately assess details of the heterogeneous environment and lay her eggs preferentially in sites with conditions more suitable to offspring. Methods We empirically tested the P-P hypothesis using the mosquito species Aedes albopictus by artificially manipulating two habitat conditions: diet (measured as mg of food added to a container) and conspecific density (CD; number of pre-existing larvae of the same species). Immature development (larval mortality, development time to pupation and time to emergence) and fitness (measured as wing length) were monitored from first instar through adult emergence using a factorial experimental design over two ascending gradients of diet (2.0, 3.6, 7.2 and 20 mg food/300 ml water) and CD (0, 20, 40 and 80 larvae/300 ml water). Treatments that exerted the most contrasting values of larval performance were recreated in a second experiment consisting of single-female oviposition site selection assay. Results Development time decreased as food concentration increased, except from 7.2 mg to 20.0 mg (Two-Way CR ANOVA Post-Hoc test, P > 0.1). Development time decreased also as conspecific density increased from zero to 80 larvae (Two-Way CR ANOVA Post-Hoc test, P < 0.5). Combined, these results support the role of density-dependent competition for resources as a limiting factor for mosquito larval performance. Oviposition assays indicated that female mosquitoes select for larval habitats with conspecifics and that larval density was more important than diet in driving selection for oviposition sites. Conclusions This study supports predictions of the P-P hypothesis and provides a mechanistic understanding of the underlying factors driving mosquito oviposition site selection. PMID:23044004

Effect of Methodological and Ecological Approaches on Heterogeneity of Nest-Site Selection of a Long-Lived Vulture

PubMed Central

Moreno-Opo, Rubén; Fernández-Olalla, Mariana; Margalida, Antoni; Arredondo, Ángel; Guil, Francisco

2012-01-01

The application of scientific-based conservation measures requires that sampling methodologies in studies modelling similar ecological aspects produce comparable results making easier their interpretation. We aimed to show how the choice of different methodological and ecological approaches can affect conclusions in nest-site selection studies along different Palearctic meta-populations of an indicator species. First, a multivariate analysis of the variables affecting nest-site selection in a breeding colony of cinereous vulture (Aegypius monachus) in central Spain was performed. Then, a meta-analysis was applied to establish how methodological and habitat-type factors determine differences and similarities in the results obtained by previous studies that have modelled the forest breeding habitat of the species. Our results revealed patterns in nesting-habitat modelling by the cinereous vulture throughout its whole range: steep and south-facing slopes, great cover of large trees and distance to human activities were generally selected. The ratio and situation of the studied plots (nests/random), the use of plots vs. polygons as sampling units and the number of years of data set determined the variability explained by the model. Moreover, a greater size of the breeding colony implied that ecological and geomorphological variables at landscape level were more influential. Additionally, human activities affected in greater proportion to colonies situated in Mediterranean forests. For the first time, a meta-analysis regarding the factors determining nest-site selection heterogeneity for a single species at broad scale was achieved. It is essential to homogenize and coordinate experimental design in modelling the selection of species' ecological requirements in order to avoid that differences in results among studies would be due to methodological heterogeneity. This would optimize best conservation and management practices for habitats and species in a global context. PMID:22413023

A novel allosteric mechanism in the cysteine peptidase cathepsin K discovered by computational methods

NASA Astrophysics Data System (ADS)

Novinec, Marko; Korenč, Matevž; Caflisch, Amedeo; Ranganathan, Rama; Lenarčič, Brigita; Baici, Antonio

2014-02-01

Allosteric modifiers have the potential to fine-tune enzyme activity. Therefore, targeting allosteric sites is gaining increasing recognition as a strategy in drug design. Here we report the use of computational methods for the discovery of the first small-molecule allosteric inhibitor of the collagenolytic cysteine peptidase cathepsin K, a major target for the treatment of osteoporosis. The molecule NSC13345 is identified by high-throughput docking of compound libraries to surface sites on the peptidase that are connected to the active site by an evolutionarily conserved network of residues (protein sector). The crystal structure of the complex shows that NSC13345 binds to a novel allosteric site on cathepsin K. The compound acts as a hyperbolic mixed modifier in the presence of a synthetic substrate, it completely inhibits collagen degradation and has good selectivity for cathepsin K over related enzymes. Altogether, these properties qualify our methodology and NSC13345 as promising candidates for allosteric drug design.

Rationally designed fluorescently labeled sulfate-binding protein mutants: evaluation in the development of a sensing system for sulfate

NASA Technical Reports Server (NTRS)

Shrestha, Suresh; Salins, Lyndon L E.; Mark Ensor, C.; Daunert, Sylvia

2002-01-01

Periplasmic binding proteins from E. coli undergo large conformational changes upon binding their respective ligands. By attaching a fluorescent probe at rationally selected unique sites on the protein, these conformational changes in the protein can be monitored by measuring the changes in fluorescence intensity of the probe which allow the development of reagentless sensing systems for their corresponding ligands. In this work, we evaluated several sites on bacterial periplasmic sulfate-binding protein (SBP) for attachment of a fluorescent probe and rationally designed a reagentless sensing system for sulfate. Eight different mutants of SBP were prepared by employing the polymerase chain reaction (PCR) to introduce a unique cysteine residue at a specific location on the protein. The sites Gly55, Ser90, Ser129, Ala140, Leu145, Ser171, Val181, and Gly186 were chosen for mutagenesis by studying the three-dimensional X-ray crystal structure of SBP. An environment-sensitive fluorescent probe (MDCC) was then attached site-specifically to the protein through the sulfhydryl group of the unique cysteine residue introduced. Each fluorescent probe-conjugated SBP mutant was characterized in terms of its fluorescence properties and Ser171 was determined to be the best site for the attachment of the fluorescent probe that would allow for the development of a reagentless sensing system for sulfate. Three different environment-sensitive fluorescent probes (1,5-IAEDANS, MDCC, and acylodan) were studied with the SBP171 mutant protein. A calibration curve for sulfate was constructed using the labeled protein and relating the change in the fluorescence intensity with the amount of sulfate present in the sample. The detection limit for sulfate was found to be in the submicromolar range using this system. The selectivity of the sensing system was demonstrated by evaluating its response to other anions. A fast and selective sensing system with detection limits for sulfate in the submicromolar range was developed. Copyright 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 78: 517-526, 2002.

Access to Space Interactive Design Web Site

NASA Technical Reports Server (NTRS)

Leon, John; Cutlip, William; Hametz, Mark

2000-01-01

The Access To Space (ATS) Group at NASA's Goddard Space Flight Center (GSFC) supports the science and technology community at GSFC by facilitating frequent and affordable opportunities for access to space. Through partnerships established with access mode suppliers, the ATS Group has developed an interactive Mission Design web site. The ATS web site provides both the information and the tools necessary to assist mission planners in selecting and planning their ride to space. This includes the evaluation of single payloads vs. ride-sharing opportunities to reduce the cost of access to space. Features of this site include the following: (1) Mission Database. Our mission database contains a listing of missions ranging from proposed missions to manifested. Missions can be entered by our user community through data input tools. Data is then accessed by users through various search engines: orbit parameters, ride-share opportunities, spacecraft parameters, other mission notes, launch vehicle, and contact information. (2) Launch Vehicle Toolboxes. The launch vehicle toolboxes provide the user a full range of information on vehicle classes and individual configurations. Topics include: general information, environments, performance, payload interface, available volume, and launch sites.

Variation in anticonvulsant selection and EEG monitoring following severe traumatic brain injury in children – Understanding resource availability in sites participating in a comparative effectiveness study

PubMed Central

Kurz, Jonathan E.; Poloyac, Samuel M.; Abend, Nicholas S.; Fabio, Anthony; Bell, Michael J.; Wainwright, Mark S.

2016-01-01

Objective Early post-traumatic seizures (PTS) may contribute to worsened outcomes after traumatic brain injury (TBI). Evidence to guide the evaluation and management of early PTS in children is limited. We undertook a survey of current practices of continuous electroencephalographic monitoring (cEEG), seizure prophylaxis and the management of early PTS to provide essential information for trial design and the development of PTS management pathways. Design Surveys were sent to site principal investigators at all 43 sites participating in the ADAPT (Approaches and Decisions in Acute Pediatric TBI) trial at the time of the survey. Surveys consisted of 12 questions addressing strategies to (i) implement cEEG monitoring, (ii) PTS prophylaxis, (iii) treat acute PTS, (iv) treat status epilepticus (SE) and refractory status epilepticus (RSE) and (v) monitor anti-seizure drug levels. Setting Institutions comprised a mixture of free-standing children’s hospitals and university medical centers across the United States and Europe. Measurements and Main Results cEEG monitoring was available in the pediatric intensive care unit in the overwhelming majority of clinical sites (98%); however, the plans to operationalize such monitoring for children varied considerably. A similar majority of sites report that administration of prophylactic anti-seizure medications is anticipated in children (93%), yet a minority reports that a specified protocol for treatment of PTS is in place (43%). Reported medication choices varied substantially between sites, but the majority of sites reported pentobarbital for RSE (81%). Presence of an treatment protocols for seizure prophylaxis, early PTS, post-traumatic SE and RSE was associated with decreased reported medications (all p < 0.05). Conclusions This study reports the current management practices for early PTS in select academic centers after pediatric severe TBI. The substantial variation in cEEG implementation, choice of seizure prophylaxis medications, and management of early PTS across institutions was reported, signifying areas of clinical uncertainty that will help provide for focused design of clinical trials. While sites with treatment protocols reported decreased number of medications for the scenarios described, completion of the ADAPT Trial will be able to determine if these protocols lead to decreased variability in medication administration in children at the clinical sites. PMID:27243415

Molecular recognition in protein modification with rhodium metallopeptides

PubMed Central

Ball, Zachary T.

2015-01-01

Chemical manipulation of natural, unengineered proteins is a daunting challenge which tests the limits of reaction design. By combining transition-metal or other catalysts with molecular recognition ideas, it is possible to achieve site-selective protein reactivity without the need for engineered recognition sequences or reactive sites. Some recent examples in this area have used ruthenium photocatalysis, pyridine organocatalysis, and rhodium(II) metallocarbene catalysis, indicating that the fundamental ideas provide opportunities for using diverse reactivity on complex protein substrates and in complex cell-like environments. PMID:25588960

Designing effective drug and device development programs for hospitalized heart failure: A proposal for pretrial registries

PubMed Central

Greene, Stephen J.; Shah, Ami N.; Butler, Javed; Ambrosy, Andrew P.; Anker, Stefan D.; Chioncel, Ovidiu; Collins, Sean P.; Dinh, Wilfried; Dunnmon, Preston M.; Fonarow, Gregg C.; Lam, Carolyn S. P.; Mentz, Robert J.; Pieske, Burkert; Roessig, Lothar; Rosano, Giuseppe M. C.; Sato, Naoki; Vaduganathan, Muthiah; Gheorghiade, Mihai

2014-01-01

Recent international phase III clinical trials of novel therapies for hospitalized heart failure (HHF) have failed to improve the unacceptably high postdischarge event rate. These large studies have demonstrated notable geographic and site-specific variation in patient profiles and enrollment. Possible contributors to the lack of success in HHF outcome trials include challenges in selecting clinical sites capable of (1) providing adequate numbers of appropriately selected patients and (2) properly executing the study protocol. We propose a “pretrial registry” as a novel tool for improving the efficiency and quality of international HHF trials by focusing on the selection and cultivation of high-quality sites. A pretrial registry may help assess a site’s ability to achieve adequate enrollment of the target patient population, integrate protocol requirements into clinical workflow, and accomplish appropriate follow-up. Although such a process would be associated with additional upfront resource investment, this appropriation may be modest in comparison with the downstream costs associated with maintenance of poorly performing sites, failed clinical trials, and the global health and economic burden of HHF. This review is based on discussions between scientists, clinical trialists, and regulatory representatives regarding methods for improving international HHF trials that took place at the United States Food and Drug Administration on January 12th, 2012. PMID:25066552

Selective amyloid β oligomer assay based on abasic site-containing molecular beacon and enzyme-free amplification.

PubMed

Zhu, Linling; Zhang, Junying; Wang, Fengyang; Wang, Ya; Lu, Linlin; Feng, Chongchong; Xu, Zhiai; Zhang, Wen

2016-04-15

Amyloid-beta (Aβ) oligomers are highly toxic species in the process of Aβ aggregation and are regarded as potent therapeutic targets and diagnostic markers for Alzheimer's disease (AD). Herein, a label-free molecular beacon (MB) system integrated with enzyme-free amplification strategy was developed for simple and highly selective assay of Aβ oligomers. The MB system was constructed with abasic site (AP site)-containing stem-loop DNA and a fluorescent ligand 2-amino-5,6,7-trimethyl-1,8-naphyridine (ATMND), of which the fluorescence was quenched upon binding to the AP site in DNA stem. Enzyme-free amplification was realized by target-triggered continuous opening of two delicately designed MBs (MB1 and MB2). Target DNA hybridization with MB1 and then MB2 resulted in the release of two ATMND molecules in one binding event. Subsequent target recycling could greatly amplify the detection sensitivity due to the greatly enhanced turn-on emission of ATMND fluorescence. Combining with Aβ oligomers aptamers, the strategy was applied to analyze Aβ oligomers and the results showed that it could quantify Aβ oligomers with high selectivity and monitor the Aβ aggregation process. This novel method may be conducive to improve the diagnosis and pathogenic study of Alzheimer's disease. Copyright © 2015 Elsevier B.V. All rights reserved.

The ATLAS Public Web Pages: Online Management of HEP External Communication Content

NASA Astrophysics Data System (ADS)

Goldfarb, S.; Marcelloni, C.; Eli Phoboo, A.; Shaw, K.

2015-12-01

The ATLAS Education and Outreach Group is in the process of migrating its public online content to a professionally designed set of web pages built on the Drupal [1] content management system. Development of the front-end design passed through several key stages, including audience surveys, stakeholder interviews, usage analytics, and a series of fast design iterations, called sprints. Implementation of the web site involves application of the html design using Drupal templates, refined development iterations, and the overall population of the site with content. We present the design and development processes and share the lessons learned along the way, including the results of the data-driven discovery studies. We also demonstrate the advantages of selecting a back-end supported by content management, with a focus on workflow. Finally, we discuss usage of the new public web pages to implement outreach strategy through implementation of clearly presented themes, consistent audience targeting and messaging, and the enforcement of a well-defined visual identity.

Chapter 9: 30 Years of Living in a Solar House in Colorado

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

Emery, Keith A; Emery, Pat

2016-12-03

Having met in 1980 while working at the National Renewable Energy Laboratory, we were inspired by the vision of a renewable energy future to raise our family in a passive solar home. A basic, factory-cut, trilevel house design was selected in 1985 and intentionally sited and modified according to passive solar design principles to optimize conservation and solar gain, with a plan to add photovoltaics as soon as feasible.

Payload transportation system study

NASA Technical Reports Server (NTRS)

1976-01-01

A standard size set of shuttle payload transportation equipment was defined that will substantially reduce the cost of payload transportation and accommodate a wide range of payloads with minimum impact on payload design. The system was designed to accommodate payload shipments between the level 4 payload integration sites and the launch site during the calendar years 1979-1982. In addition to defining transportation multi-use mission support equipment (T-MMSE) the mode of travel, prime movers, and ancillary equipment required in the transportation process were also considered. Consistent with the STS goals of low cost and the use of standardized interfaces, the transportation system was designed to commercial grade standards and uses the payload flight mounting interfaces for transportation. The technical, cost, and programmatic data required to permit selection of a baseline system of MMSE for intersite movement of shuttle payloads were developed.

GALLAUDET'S NEW HEARING AND SPEECH CENTER.

ERIC Educational Resources Information Center

FRISINA, D. ROBERT

THIS REPROT DESCRIBES THE DESIGN OF A NEW SPEECH AND HEARING CENTER AND ITS INTEGRATION INTO THE OVERALL ARCHITECTURAL SCHEME OF THE CAMPUS. THE CIRCULAR SHAPE WAS SELECTED TO COMPLEMENT THE SURROUNDING STRUCTURES AND COMPENSATE FOR DIFFERENCES IN SITE, WHILE PROVIDING THE ACOUSTICAL ADVANTAGES OF NON-PARALLEL WALLS, AND FACILITATING TRAFFIC FLOW.…

Bioassessment Tools for Stony Corals: Monitoring Approaches and Proposed Sampling Plan for the U.S. Virgin Islands

EPA Science Inventory

This document describes three general approaches to the design of a sampling plan for biological monitoring of coral reefs. Status assessment, trend detection and targeted monitoring each require a different approach to site selection and statistical analysis. For status assessm...

Preservation Concerns in Construction and Remodeling of Libraries: Planning for Preservation.

ERIC Educational Resources Information Center

Trinkley, Michael

To help libraries and other holdings institutions better incorporate preservation concerns in construction, renovation, and routine maintenance, various techniques are presented that allow preservation concerns to be integrated. The following topics are considered: (1) site selection; (2) design of the building envelope; (3) the library interior;…

Pre-Service and Beginning Teachers Rate the Utility of Virtual Museum Exhibits

ERIC Educational Resources Information Center

Iding, Marie; Nordbotten, Joan

2011-01-01

This study investigated criteria that 91 pre-service teachers used to evaluate award-winning virtual museum exhibits for future use in teaching. Individual differences affected ratings, including teaching experience, age and gender. A categorization of participants' reasons for selection included audience level, site design and information…

Hometown Newspaper Coverage of Developing Countries: Its Effects on Perceived Interdependence of Nations.

ERIC Educational Resources Information Center

Siltanen, Susan A.; And Others

The "Main Street Mississippi Meets the Third World" project was designed to demonstrate that hometown newspapers can provide relevant news stories about developing countries without leaving the local community. Hattiesburg, Mississippi, and the "American" were the selected site and newspaper. The project involved working with…

Swimming Pools.

ERIC Educational Resources Information Center

Ministry of Housing and Local Government, London (England).

Technical and engineering data are set forth on the design and construction of swimming pools. Consideration is given to site selection, pool construction, the comparative merits of combining open air and enclosed pools, and alternative uses of the pool. Guidelines are presented regarding--(1) pool size and use, (2) locker and changing rooms, (3)…

INFORMATION MANAGEMENT AND RELATED QUALITY ASSURANCE FOR A LARGE SCALE, MULTI-SITE RESEARCH PROJECT

EPA Science Inventory

During the summer of 2000, as part of a U.S. Environmental Protection Agency study designed to improve microbial water quality monitoring protocols at public beaches, over 11,000 water samples were collected at five selected beaches across the country. At each beach, samples wer...

Endothelialized ePTFE Graft by Nanobiotechnology

ClinicalTrials.gov

2013-11-29

The Apparatus for Processing the Tubular Graft Modification Will be Designed and Evaluated.; The On-site Capturing of the Endothelial (Progenitor) Cells by Peptide-mediated Selective Adhesion in Vitro and in Vivo Will Also be Elucidated.; The Patency Rate of ITRI-made Artificial Blood Vessels Will be Evaluated by the Porcine Animal Model.

Optimal design of stormwater basins with bio-sorption activated media (BAM) in karst environments - phase I : site screening and selection, [summary].

DOT National Transportation Integrated Search

2015-11-01

Nutrient content is a concern in Floridas aquifers and springs sources of drinking water, : recreation, and the states natural beauty. In recent years, the nitrogen content of Floridas : aquifer springs has risen. This increase in nutrie...

NSAC Recommends a Relativistic Heavy-Ion Collider.

ERIC Educational Resources Information Center

Physics Today, 1984

1984-01-01

Describes the plan submitted by the Nuclear Science Advisory Committee to the Department of Energy and National Science Foundation urging construction of an ultrarelativistic heavy-ion collider designed to accelerate nucleon beams of ions as heavy as uranium. Discusses the process of selecting the type of facility as well as siting. (JM)

Learning Spaces and Collaborative Work: Barriers or Supports?

ERIC Educational Resources Information Center

King, Hayley

2016-01-01

Drawing on 18 months of fieldwork, this article discusses the use of physical, virtual and social space to support collaborative work in translator education programs. The study adopted a contrastive ethnography approach that incorporated single- and multiple-case design rationales for site selection. Extended observation, informal chats and…

Safety Factors in Educational Facilities. An Annotated Reference List.

ERIC Educational Resources Information Center

Wakefield, Howard E.

Abstracts and descriptor terms are presented for 26 selected references with safety orientation. Included in addition to several general planning handbooks are topics related to--(1) stairways, (2) air structures, (3) site planning, (4) lighting, (5) bidding practice, (6) physically handicapped, (7) laboratory design, (8) mobile classrooms, (9)…

[Molecular docking of chlorogenic acid, 3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid with human serum albumin].

PubMed

Zhou, Jing; Ma, Hong-yue; Fan, Xin-sheng; Xiao, Wei; Wang, Tuan-jie

2012-10-01

To investigate the mechanism of binding of human serum albumin (HSA) with potential sensitinogen, including chlorogenic acid and two isochlorogenic acids (3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid). By using the docking algorithm of computer-aided molecular design and the Molegro Virtual Docker, the crystal structures of HSA with warfarin and diazepam (Protein Data Bank ID: 2BXD and 2BXF) were selected as molecular docking receptors of HSA sites I and II. According to docking scores, key residues and H-bond, the molecular docking mode was selected and confirmed. The molecular docking of chlorogenic acid and two isochlorogenic acids on sites I and II was compared based on the above design. The results from molecular docking indicated that chlorogenic acid, 3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid could bind to HSA site I by high affinity scores of -112.3, -155.3 and -153.1, respectively. They could bind to site II on HSA by high affinity scores of -101.7, -138.5 and -133.4, respectively. In site I, two isochlorogenic acids interacted with the key apolar side-chains of Leu238 and Ala291 by higher affinity scores than chlorogenic acid. Furthermore, the H-bonds of isochlorogenic acids with polar residues inside the pocket and at the entrance of the pocket were different from chlorogenic acid. Moreover, the second coffee acyl of isochlorogenic acid occupied the right-hand apolar compartment in the pocket of HSA site I. In site I, the second coffee acyl of isochlorogenic acid formed the H-bonds with polar side-chains, which contributed isochlorogenic acid to binding with site II of HSA. The isochlorogenic acids with two coffee acyls have higher binding abilities with HSA than chlorogenic acid with one coffee acyl, suggesting that isochlorogenic acids binding with HSA may be sensitinogen.

Structural basis for ligand recognition at the benzodiazepine binding site of GABAA alpha 3 receptor, and pharmacophore-based virtual screening approach.

PubMed

Vijayan, R S K; Ghoshal, Nanda

2008-10-01

Given the heterogeneity of GABA(A) receptor, the pharmacological significance of identifying subtype selective modulators is increasingly being recognized. Thus, drugs selective for GABA(A) alpha(3) receptors are expected to display fewer side effects than the drugs presently in clinical use. Hence we carried out 3D QSAR (three-dimensional quantitative structure-activity relationship) studies on a series of novel GABA(A) alpha(3) subtype selective modulators to gain more insight into subtype affinity. To identify the 3D functional attributes required for subtype selectivity, a chemical feature-based pharmacophore, primarily based on selective ligands representing diverse structural classes was generated. The obtained pseudo receptor model of the benzodiazepine binding site revealed a binding mode akin to "Message-Address" concept. Scaffold hopping was carried out across multi-conformational May Bridge database for the identification of novel chemotypes. Further a focused data reduction approach was employed to choose a subset of enriched compounds based on "Drug likeness" and "Similarity-based" methods. These results taken together could provide impetus for rational design and optimization of more selective and high affinity leads with a potential to have decreased adverse effects.

Tolerance design of patient-specific range QA using the DMAIC framework in proton therapy.

PubMed

Rah, Jeong-Eun; Shin, Dongho; Manger, Ryan P; Kim, Tae Hyun; Oh, Do Hoon; Kim, Dae Yong; Kim, Gwe-Ya

2018-02-01

To implement the DMAIC (Define-Measure-Analyze-Improve-Control) can be used for customizing the patient-specific QA by designing site-specific range tolerances. The DMAIC framework (process flow diagram, cause and effect, Pareto chart, control chart, and capability analysis) were utilized to determine the steps that need focus for improving the patient-specific QA. The patient-specific range QA plans were selected according to seven treatment site groups, a total of 1437 cases. The process capability index, C pm was used to guide the tolerance design of patient site-specific range. For prostate field, our results suggested that the patient range measurements were capable at the current tolerance level of ±1 mm in clinical proton plans. For other site-specific ranges, we analyzed that the tolerance tends to be overdesigned to insufficient process capability calculated by the patient-specific QA data. The customized tolerances were calculated for treatment sites. Control charts were constructed to simulate the patient QA time before and after the new tolerances were implemented. It is found that the total simulation QA time was decreased on average of approximately 20% after establishing new site-specific range tolerances. We simulated the financial impact of this project. The QA failure for whole process in proton therapy would lead up to approximately 30% increase in total cost. DMAIC framework can be used to provide an effective QA by setting customized tolerances. When tolerance design is customized, the quality is reasonably balanced with time and cost demands. © 2017 American Association of Physicists in Medicine.

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

Habitat requirements and burrowing depths of rodents in relation to shallow waste burial sites

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

Gano, K.A.; States, J.B.

1982-05-01

The purpose of this paper is to provide a review of the literature and summarize information on factors affecting habitat selection and maximum recorded burrowing depths for representative small mammals that we consider most likely to inhibit waste burial sites in arid and semi-arid regions of the West. The information is intended for waste management designers who need to know what to expect from small mammals that may be present at a particular site. Waste repositories oculd be designed to exclude the deep burrowing rodents of a region by creating an unattractive habitat over the waste. Summaries are given formore » habitat requirements of each group along with generalized modifications that could be employed to deter habitation. Representatives from the major groups considered to be deep burrowers are discussed. Further, detailed information about a particular species can be obtained from the references cited.« less

Expert reasoning within an object-oriented framework

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

Bohn, S.J.; Pennock, K.A.

1991-10-01

A large number of contaminated waste sites across the United States await site remediation efforts. These sites can be physically complex, composed of multiple, possibly interacting, contaminants distributed throughout one or more media. The Remedial Action Assessment System (RAAS) is being designed and developed to support decisions concerning the selection of remediation alternatives. The goal of this system is to broaden the consideration of remediation alternatives, while reducing the time and cost of making these considerations. The Remedial Action Assessment System was designed and constructed using object-oriented techniques. It is a hybrid system which uses a combination of quantitative andmore » qualitative reasoning to consider and suggest remediation alternatives. the reasoning process that drives this application is centered around an object-oriented organization of remediation technology information. This paper briefly describes the waste remediation problem and then discusses the information structure and organization RAAS utilizes to address it. 4 refs., 4 figs.« less

Remote site-selective C–H activation directed by a catalytic bifunctional template

PubMed Central

Zhang, Zhipeng; Tanaka, Keita; Yu, Jin-Quan

2017-01-01

Converting C–H bonds directly into carbon-carbon and carbon-heteroatom bonds can significantly improve step-economy in synthesis by providing alternative disconnections to traditional functional group manipulations. In this context, directed C–H activation reactions have been extensively explored for regioselective functionalization1-5. Though applicability can be severely curtailed by distance from the directing group and the shape of the molecule, a number of approaches have been developed to overcome this limitation6-12. For instance, recognition of the distal and geometric relationship between an existing functional group and multiple C–H bonds has recently been exploited to achieve meta-selective C–H activation by use of a covalently attached U-shaped template13-17. However, stoichiometric installation of the template is not feasible in the absence of an appropriate functional group handle. Here we report the design of a catalytic, bifunctional template that binds heterocyclic substrate via reversible coordination instead of covalent linkage, allowing remote site-selective C–H olefination of heterocycles. The two metal centers coordinated to this template play different roles; anchoring substrates to the proximity of catalyst and cleaving the remote C–H bonds respectively. Using this strategy, we demonstrate remote site-selective C–H olefination of heterocyclic substrates which do not have functional group handles for covalently attaching templates. PMID:28273068

Structural Biology Insight for the Design of Sub-type Selective Aurora Kinase Inhibitors.

PubMed

Sarvagalla, Sailu; Coumar, Mohane Selvaraj

2015-01-01

Aurora kinase A, B and C, are key regulators of mitosis and are over expressed in many of the human cancers, making them an ideal drug target for cancer chemotherapy. Currently, over a dozen of Aurora kinase inhibitors are in various phases of clinical development. The majority of the inhibitors (VX-680/MK-0457, PHA-739358, CYC116, SNS-314, AMG 900, AT-9283, SCH- 1473759, ABT-348, PF-03814735, R-763/AS-703569, KW-2449 and TAK-901) are pan-selective (isoform non-selective) and few are Aurora A (MLN8054, MLN8237, VX-689/MK5108 and ENMD 2076) and Aurora B (AZD1152 and GSK1070916) sub-type selective. Despite the intensive research efforts in the past decade, no Aurora kinase inhibitor has reached the market. Recent evidence suggests that the sub-type selective Aurora kinase A inhibitor could possess advantages over pan-selective Aurora inhibitors, by avoiding Aurora B mediated neutropenia. However, sub-type selective Aurora kinase A inhibitor design is very challenging due to the similarity in the active site among the isoforms. Structural biology and computational aspects pertaining to the design of Aurora kinase inhibitors were analyzed and found that a possible means to develop sub-type selective inhibitor is by targeting Aurora A specific residues (Leu215, Thr217 and Arg220) or Aurora B specific residues (Arg159, Glu161 and Lys164), near the solvent exposed region of the protein. Particularly, a useful strategy for the design of sub-type selective Aurora A inhibitor could be by targeting Thr217 residue as in the case of MLN8054. Further preclinical and clinical studies with the sub-type selective Aurora inhibitors could help bring them to the market for the treatment of cancer.

Analysis Methodology for Optimal Selection of Ground Station Site in Space Missions

NASA Astrophysics Data System (ADS)

Nieves-Chinchilla, J.; Farjas, M.; Martínez, R.

2013-12-01

Optimization of ground station sites is especially important in complex missions that include several small satellites (clusters or constellations) such as the QB50 project, where one ground station would be able to track several spatial vehicles, even simultaneously. In this regard the design of the communication system has to carefully take into account the ground station site and relevant signal phenomena, depending on the frequency band. To propose the optimal location of the ground station, these aspects become even more relevant to establish a trusted communication link due to the ground segment site in urban areas and/or selection of low orbits for the space segment. In addition, updated cartography with high resolution data of the location and its surroundings help to develop recommendations in the design of its location for spatial vehicles tracking and hence to improve effectiveness. The objectives of this analysis methodology are: completion of cartographic information, modelling the obstacles that hinder communication between the ground and space segment and representation in the generated 3D scene of the degree of impairment in the signal/noise of the phenomena that interferes with communication. The integration of new technologies of geographic data capture, such as 3D Laser Scan, determine that increased optimization of the antenna elevation mask, in its AOS and LOS azimuths along the horizon visible, maximizes visibility time with spatial vehicles. Furthermore, from the three-dimensional cloud of points captured, specific information is selected and, using 3D modeling techniques, the 3D scene of the antenna location site and surroundings is generated. The resulting 3D model evidences nearby obstacles related to the cartographic conditions such as mountain formations and buildings, and any additional obstacles that interfere with the operational quality of the antenna (other antennas and electronic devices that emit or receive in the same bandwidth). To check/test the spatial proposal of the ground station site, this analysis methodology uses mission simulation software of spatial vehicles to analyze and quantify how the geographic accuracy of the position of the spatial vehicles along the horizon visible from the antenna, increases communication time with the ground station. Experimental results that have been obtained from a ground station located at ETSIT-UPM in Spain (QBito Nanosatellite, UPM spacecraft mission within the QB50 project) show that selection of the optimal site increases the field of view from the antenna and hence helps to meet mission requirements.

PRO_LIGAND: An approach to de novo molecular design. 4. Application to the design of peptides

NASA Astrophysics Data System (ADS)

Frenkel, David; Clark, David E.; Li, Jin; Murray, Christopher W.; Robson, Barry; Waszkowycz, Bohdan; Westhead, David R.

1995-06-01

In some instances, peptides can play an important role in the discovery of lead compounds. This paper describes the peptide design facility of the de novo drug design package, PRO_LIGAND. The package provides a unified framework for the design of peptides that are similar or complementary to a specified target. The approach uses single amino acid residues, selected from preconstructed libraries of different residues and conformations, and places them on top of predefined target interaction sites. This approach is a well-tested methodology for the design of organics but has not been used for peptides before. Peptides represent a difficulty because of their great conformational flexibility and a study of the advantages and disavantages of this simple approach is an important step in the development of design tools. After a description of our general approach, a more detailed discussion of its adaptation to peptides is given. The method is then applied to the design of peptide-based inhibitors to HIV-1 protease and the design of structural mimics of the surface region of lysozyme. The results are encouraging and point the way towards further development of interaction site-based approaches for peptide design.

Geology of the Apollo 17 site

NASA Technical Reports Server (NTRS)

Muehlberger, W. R.

1992-01-01

The Apollo 17 landing site was unique in several aspects: (1) it was the only site that was not selected from telescopic-based geologic interpretation--interest in the site was generated by the visual observations of Al Worden, Apollo 15 Command Module pilot, who interpreted dark-haloed craters as possible cinder cones; (2) instead of 20-m-resolution photographs, as was the norm for all earlier missions, this site had Apollo 15 panoramic camera photography coverage that had 2-m resolution; and (3) it had a geologist-astronaut aboard who was intimately involved in all stages of planning and mission operation, and was also instrumental in the design of a long-handled sample bag holder that eliminated the need for crew to dismount before collecting a sample, which then permitted sampling between major stations. Details of site geology, sample description, and geologic synthesis of the site as viewed from studies through 1976 are summarized.

Custom-Designed Molecular Scissors for Site-Specific Manipulation of the Plant and Mammalian Genomes

NASA Astrophysics Data System (ADS)

Kandavelou, Karthikeyan; Chandrasegaran, Srinivasan

Zinc finger nucleases (ZFNs) are custom-designed molecular scissors, engineered to cut at specific DNA sequences. ZFNs combine the zinc finger proteins (ZFPs) with the nonspecific cleavage domain of the FokI restriction enzyme. The DNA-binding specificity of ZFNs can be easily altered experimentally. This easy manipulation of the ZFN recognition specificity enables one to deliver a targeted double-strand break (DSB) to a genome. The targeted DSB stimulates local gene targeting by several orders of magnitude at that specific cut site via homologous recombination (HR). Thus, ZFNs have become an important experimental tool to make site-specific and permanent alterations to genomes of not only plants and mammals but also of many other organisms. Engineering of custom ZFNs involves many steps. The first step is to identify a ZFN site at or near the chosen chromosomal target within the genome to which ZFNs will bind and cut. The second step is to design and/or select various ZFP combinations that will bind to the chosen target site with high specificity and affinity. The DNA coding sequence for the designed ZFPs are then assembled by polymerase chain reaction (PCR) using oligonucleotides. The third step is to fuse the ZFP constructs to the FokI cleavage domain. The ZFNs are then expressed as proteins by using the rabbit reticulocyte in vitro transcription/translation system and the protein products assayed for their DNA cleavage specificity.

Fracture stimulation treatment design optimization: What can the NPV vs X{sub f} plot tell us?

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

Huffman, C.H.; Harkrider, J.D.; Thompson, R.S.

1996-12-31

Fracture stimulation production response coupled with the hydrocarbon sales price determines the value of a fracture stimulation treatment. Many factors can significantly effect the production response of a fracture stimulated well. Some examples include stimulation fluid selection, proppant selection, pumping rates, rock properties, reservoir fluid properties, in-situ stresses, stress variations, on-site execution, post-treatment stimulation fluid recovery, and operating practices. The production response in economic terms portrays the net effect of these variables. This paper presents a case study that demonstrates how post-treatment evaluations expressed in economic terms can be used to assess the performance of stimulations and to guide futuremore » design choices.« less

The novel benzopyran class of selective cyclooxygenase-2 inhibitors. Part 2: The second clinical candidate having a shorter and favorable human half-life

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

Wang, Jane L.; Limburg, David; Graneto, Matthew J.

2012-05-29

In this Letter, we provide the structure-activity relationships, optimization of design, testing criteria, and human half-life data for a series of selective COX-2 inhibitors. During the course of our structure-based drug design efforts, we discovered two distinct binding modes within the COX-2 active site for differently substituted members of this class. The challenge of a undesirably long human half-life for the first clinical candidate 1t{sub 1/2} = 360 h was addressed by multiple strategies, leading to the discovery of 29b-(S) (SC-75416) with t{sub 1/2} = 34 h.

Selective Optical Addressing of Nuclear Spins through Superhyperfine Interaction in Rare-Earth Doped Solids.

PubMed

Car, B; Veissier, L; Louchet-Chauvet, A; Le Gouët, J-L; Chanelière, T

2018-05-11

In Er^{3+}:Y_{2}SiO_{5}, we demonstrate the selective optical addressing of the ^{89}Y^{3+} nuclear spins through their superhyperfine coupling with the Er^{3+} electronic spins possessing large Landé g factors. We experimentally probe the electron-nuclear spin mixing with photon echo techniques and validate our model. The site-selective optical addressing of the Y^{3+} nuclear spins is designed by adjusting the magnetic field strength and orientation. This constitutes an important step towards the realization of long-lived solid-state qubits optically addressed by telecom photons.

Selective Optical Addressing of Nuclear Spins through Superhyperfine Interaction in Rare-Earth Doped Solids

NASA Astrophysics Data System (ADS)

Car, B.; Veissier, L.; Louchet-Chauvet, A.; Le Gouët, J.-L.; Chanelière, T.

2018-05-01

In Er3 +:Y2SiO5 , we demonstrate the selective optical addressing of the Y89 3 + nuclear spins through their superhyperfine coupling with the Er3 + electronic spins possessing large Landé g factors. We experimentally probe the electron-nuclear spin mixing with photon echo techniques and validate our model. The site-selective optical addressing of the Y3 + nuclear spins is designed by adjusting the magnetic field strength and orientation. This constitutes an important step towards the realization of long-lived solid-state qubits optically addressed by telecom photons.

Estimation of empirical site amplification factors in Taiwan

NASA Astrophysics Data System (ADS)

Chung, Chi-Hsuan; Wen, Kuo-Liang; Kuo, Chun-Hsiang

2017-04-01

Lots of infrastructures are under construction in metropolises in Taiwan in recent years and thus leads to increasement of population density and urbanization in those area. Taiwan island is located in plate boundaries in which the high seismicity is caused by active tectonic plates. The Chi-Chi earthquake (Mw 7.6) in 1999 caused a fatality of more than 2000, and the Meinong earthquake (Mw 6.5) in 2016 caused a fatality of 117 in Tainan city as well as damages on hundreds of buildings. The cases imply seismic vulnerability of urban area. During the improvements for seismic hazard analysis and seismic design, consideration of seismic site amplifications in different site conditions is one of important issues. This study used selected and processed strong motion records observed by the TSMIP network. The site conditions considered as Vs30 used in this study were investigated at most stations (Kuo et al. 2012; Kuo et al. 2016). Since strong motion records and site conditions are both available, we are able to use the data to analyze site amplifications of seismic waves at different periods. The result may be a reference for future modification of seismic design codes to decrease potential seismic hazards and losses. We adopted the strong motion and site database of the SSHAC (Senior Seismic Hazard Analysis Committee) Level 3 project in Taiwan. The selected significant crustal and subduction events of magnitude larger than six for analysis. The amplification factors of PGA, PGV, PGD, and spectra acceleration at 0.3, 1.0, and 3.0 seconds were evaluated using the processed strong motions. According to the recommendation of SSHAC Level 3 project, the site condition of Vs30 = 760 m/s is considered as the reference rock site in this study. The stations with Vs30 between 600 m/s and 900 m/s and used as the reference rock sites in reality. For each event, we find a reference rock site and other site within a certain distance (region dependent) to calculate site amplifications of ground motions. Relationships of site amplification factors and Vs30 are therefore derived for strong motions by regression analysis. Soil nonlinearity (decrease of amplifications) has to be considered at soft soil sites during a strong shaking. We also discuss amplification factors in terms of different intensities if data is available.

Reclamation of mined organic soils in northern Minnesota to selected conifers

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

Schmitt, M.D.C.

1983-01-01

In a greenhouse experiment designed to evaluate the capacity of residual organic soils from mined peatland sites to support commercially valuable conifers under various fertilization regimes, the six month height growth and dry weight production of Scotch pine, black, white, and Norway spruce was dependent upon the nature and properties of the residual organic soils to be reclaimed, the species selected to revegetate these sites, the type and amount of fertilizer treatments applied, and interactions between these factors. On a highly acid, nutrient poor Fibrist, only Scotch pine seedlings exhibited adequate growth, but their performance appeared to be limited bymore » natural and fertilizer induced soil acidity. On a Ca rich, near neutral Hemist, Scotch pine growth was adequate and unaffected by fertilization. However, spruce growth was vigorous only under a fertilizer treatment containing micronutrients plus a high rate of NPK. Although there is little doubt that residual organic soils from mined peatland sites can be used for forest production, there are important differences between sites requiring that each be considered individually before reclamation procedures are initiated.« less

Natural Environment Corrosion Testing at the Kennedy Space Center Beachside Atmospheric Corrosion Test Site

NASA Technical Reports Server (NTRS)

Calle, Luz M.

2017-01-01

This presentation will provide an overview of how NASA has been conducting corrosion testing in the Natural Marine Environment at the Kennedy Space Center, Florida, U.S. The following questions will be addressed: What factors should be considered when selecting and constructing a test site? What are the attributes of a good test site? Is more severe always better? What environmental parameters should be monitored? How frequently? What factors should be considered when designing test specimens? Are current test standards sufficient? How do diurnal, annual and other fluctuations in corrosivity influence tests? How are test results interpreted? Can they be quantified?

Evolution of Site-Selection Stabilizes Population Dynamics, Promotes Even Distribution of Individuals, and Occasionally Causes Evolutionary Suicide.

PubMed

Parvinen, Kalle; Brännström, Åke

2016-08-01

Species that compete for access to or use of sites, such as parasitic mites attaching to honey bees or apple maggots laying eggs in fruits, can potentially increase their fitness by carefully selecting sites at which they face little or no competition. Here, we systematically investigate the evolution of site-selection strategies among animals competing for discrete sites. By developing and analyzing a mechanistic and population-dynamical model of site selection in which searching individuals encounter sites sequentially and can choose to accept or continue to search based on how many conspecifics are already there, we give a complete characterization of the different site-selection strategies that can evolve. We find that evolution of site-selection stabilizes population dynamics, promotes even distribution of individuals among sites, and occasionally causes evolutionary suicide. We also discuss the broader implications of our findings and propose how they can be reconciled with an earlier study (Nonaka et al. in J Theor Biol 317:96-104, 2013) that reported selection toward ever higher levels of aggregation among sites as a consequence of site-selection.

Bion 11 mission: primate experiments

NASA Technical Reports Server (NTRS)

Ilyin, E. A.; Korolkov, V. I.; Skidmore, M. G.; Viso, M.; Kozlovskaya, I. B.; Grindeland, R. E.; Lapin, B. A.; Gordeev, Y. V.; Krotov, V. P.; Fanton, J. W.;

An assessment of the usability of undergraduate healthcare management program websites.

PubMed

Roggenkamp, Susan D

2005-01-01

Prospective students in higher education programs increasingly use the Internet as a source of information to assist in the selection of both university and major programs of study. Therefore, having an informative and well designed website is now an integral component of a higher education program's marketing mix. This article attempts to inform undergraduate health administration programs about the elements of good website design, namely content that is important and relevant to users, site layout appeal, and ease of navigation. Content analyses of undergraduate health administration program websites in 2002 and 2005 assessed both the extent of content from a standard list of twenty-five information elements and usability features of the sites. Implications for improvements to program websites are discussed.

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.

Yakima/Klickitat Production Preliminary Design Report, Appendix C: Yakima and Klickitat Preliminary Engineering Reports.

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

CH2M Hill; R.W. Beck and Associates.

1990-03-01

This chapter describes the biological and physical fish culture requirements of the hatchery system from which the concepts for the design are formulated. It includes a discussion of the program goals for fish production in the Yakima Basin followed by a brief summary of selected sites. The biological criteria are presented for the water system, adult holding, incubation, rearing, and finally transportation and release. The biological criteria address the water and space requirements, the number and type of vessels, and the related support requirements. To be assured that the components of the system meet all program demands, each life phasemore » from adult capture to the juvenile or smolt transfer into the acclimation sites is analyzed.« less

Concordance with dietary and lifestyle population goals for cancer prevention in Dutch, Scottish, Mexican, and Guatemalan population samples.

PubMed

Vossenaar, Marieke; Solomons, Noel W; Valdés-Ramos, Roxana; Anderson, Annie S

2010-01-01

We assessed concordance with selected population goal components of the 1997 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) diet and lifestyle recommendations to decrease cancer risk across four population samples. This was a prospectively designed survey examining concordance with the population goals of the WCRF/AICR recommendations using target criteria across sites. Population samples were from the Netherlands, Scotland, Mexico, and Guatemala. A total of 3564 men and women aged 18 to 70 y were recruited in equal proportions by site and gender. None of the four pooled samples met the target population average criteria for body mass index or refined sugar intake. The Guatemalan sample had concordance with the largest number of recommended cancer-prevention goals (10 of 12 selected WCRF/AICR components). Successively, Mexican, Scottish, and Dutch samples were concordant with seven, four, and three selected components, respectively. A prospectively designed research instrument and exhaustive prior examination of operative criteria allow for the assessment of group-level concordance with cancer-prevention goals. To the extent that the study samples reflect the respective national situations, geographic variance in concordance exists, with conditions and behaviors in Guatemala bringing that nation into more general compliance with the 1997 WCRF/AICR goals.

Selection of site specific vibration equation by using analytic hierarchy process in a quarry

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

Kalayci, Ulku, E-mail: ukalayci@istanbul.edu.tr; Ozer, Umit, E-mail: uozer@istanbul.edu.tr

This paper presents a new approach for the selection of the most accurate SSVA (Site Specific Vibration Attenuation) equation for blasting processes in a quarry located near settlements in Istanbul, Turkey. In this context, the SSVA equations obtained from the same study area in the literature were considered in terms of distance between the shot points and buildings and the amount of explosive charge. In this purpose, 11 different SSVA equations obtained from the study area in the past 12 years, forecasting capabilities according to designated new conditions, using 102 vibration records as test data obtained from the study areamore » was investigated. In this study, AHP (Analytic Hierarchy Process) was selected as an analysis method in order to determine the most accurate equation among 11 SSAV equations, and the parameters such as year, distance, charge, and r{sup 2} of the equations were used as criteria for AHP. Finally, the most appropriate equation was selected among the existing ones, and the process of selecting according to different target criteria was presented. Furthermore, it was noted that the forecasting results of the selected equation is more accurate than that formed using the test results. - Highlights: • The optimum Site Specific Vibration Attenuation equation for blasting in a quarry located near settlements was determined. • It is indicated that SSVA equations changing over the years don’t give always accurate estimates at changing conditions. • Selection of the blast induced SSVA equation was made using AHP. • Equation selection method was highlighted based on parameters such as charge, distance, and quarry geometry changes (year).« less

Guidelines for Developing Spacecraft Structural Requirements: A Thermal and Environmental Perspective

NASA Technical Reports Server (NTRS)

Holladay, Jon; Day, Greg; Gill, Larry

2004-01-01

Spacecraft are typically designed with a primary focus on weight in order to meet launch vehicle performance parameters. However, for pressurized and/or man-rated spacecraft, it is also necessary to have an understanding of the vehicle operating environments to properly size the pressure vessel. Proper sizing of the pressure vessel requires an understanding of the space vehicle's life cycle and compares the physical design optimization (weight and launch "cost") to downstream operational complexity and total life cycle cost. This paper will provide an overview of some major environmental design drivers and provide examples for calculating the optimal design pressure versus a selected set of design parameters related to thermal and environmental perspectives. In addition, this paper will provide a generic set of cracking pressures for both positive and negative pressure relief valves that encompasses worst case environmental effects for a variety of launch / landing sites. Finally, several examples are included to highlight pressure relief set points and vehicle weight impacts for a selected set of orbital missions.

Canada's Deep Geological Repository For Used Nuclear Fuel -The Geoscientific Site Evaluation Process

NASA Astrophysics Data System (ADS)

Hirschorn, S.; Ben Belfadhel, M.; Blyth, A.; DesRoches, A. J.; McKelvie, J. R. M.; Parmenter, A.; Sanchez-Rico Castejon, M.; Urrutia-Bustos, A.; Vorauer, A.

2014-12-01

The Nuclear Waste Management Organization (NWMO) is responsible for implementing Adaptive Phased Management, the approach selected by the Government of Canada for long-term management of used nuclear fuel generated by Canadian nuclear reactors. In May 2010, the NWMO published and initiated a nine-step site selection process to find an informed and willing community to host a deep geological repository for Canada's used nuclear fuel. The site selection process is designed to address a broad range of technical and social, economic and cultural factors. The suitability of candidate areas will be assessed in a stepwise manner over a period of many years and include three main steps: Initial Screenings; Preliminary Assessments; and Detailed Site Characterizations. The Preliminary Assessment is conducted in two phases. NWMO has completed Phase 1 preliminary assessments for the first eight communities that entered into this step. While the Phase 1 desktop geoscientific assessments showed that each of the eight communities contains general areas that have the potential to satisfy the geoscientific safety requirements for hosting a deep geological repository, the assessment identified varying degrees of geoscientific complexity and uncertainty between communities, reflecting their different geological settings and structural histories. Phase 2 activities will include a sequence of high-resolution airborne geophysical surveys and focused geological field mapping to ground-truth lithology and structural features, followed by limited deep borehole drilling and testing. These activities will further evaluate the site's ability to meet the safety functions that a site would need to ultimately satisfy in order to be considered suitable. This paper provides an update on the site evaluation process and describes the approach, methods and criteria that are being used to conduct the geoscientific Preliminary Assessments.

Lessons Learned from Radioactive Waste Storage and Disposal Facilities

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

Esh, David W.; Bradford, Anna H.

2008-01-15

The safety of radioactive waste disposal facilities and the decommissioning of complex sites may be predicated on the performance of engineered and natural barriers. For assessing the safety of a waste disposal facility or a decommissioned site, a performance assessment or similar analysis is often completed. The analysis is typically based on a site conceptual model that is developed from site characterization information, observations, and, in many cases, expert judgment. Because waste disposal facilities are sited, constructed, monitored, and maintained, a fair amount of data has been generated at a variety of sites in a variety of natural systems. Thismore » paper provides select examples of lessons learned from the observations developed from the monitoring of various radioactive waste facilities (storage and disposal), and discusses the implications for modeling of future waste disposal facilities that are yet to be constructed or for the development of dose assessments for the release of decommissioning sites. Monitoring has been and continues to be performed at a variety of different facilities for the disposal of radioactive waste. These include facilities for the disposal of commercial low-level waste (LLW), reprocessing wastes, and uranium mill tailings. Many of the lessons learned and problems encountered provide a unique opportunity to improve future designs of waste disposal facilities, to improve dose modeling for decommissioning sites, and to be proactive in identifying future problems. Typically, an initial conceptual model was developed and the siting and design of the disposal facility was based on the conceptual model. After facility construction and operation, monitoring data was collected and evaluated. In many cases the monitoring data did not comport with the original site conceptual model, leading to additional investigation and changes to the site conceptual model and modifications to the design of the facility. The following cases are discussed: commercial LLW disposal facilities; uranium mill tailings disposal facilities; and reprocessing waste storage and disposal facilities. The observations developed from the monitoring and maintenance of waste disposal and storage facilities provide valuable lessons learned for the design and modeling of future waste disposal facilities and the decommissioning of complex sites.« less

Rational design of a topical androgen receptor antagonist for the suppression of sebum production with properties suitable for follicular delivery.

PubMed

Mitchell, Lorna H; Johnson, Theodore R; Lu, Guang Wei; Du, Daniel; Datta, Kaushik; Grzemski, Felicity; Shanmugasundaram, Veerabahu; Spence, Julie; Wade, Kim; Wang, Zhi; Sun, Kevin; Lin, Kristin; Hu, Lain-Yen; Sexton, Karen; Raheja, Neil; Kostlan, Catherine; Pocalyko, David

2010-06-10

A novel nonsteroidal androgen receptor antagonist, (R)-4-(1-benzyl-4,4-dimethyl-2-oxopyrrolidin-3-yloxy)-2-(trifluoromethyl)benzonitrile (1), for the topical control of sebum production is reported. This compound, which is potent, selective, and efficacious in the clinically validated golden Syrian hamster ear animal model, was designed to be delivered to the pilosebaceous unit, the site of action, preferentially by the follicular route.

Evaporative oxidation treatability test report

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

NONE

1995-04-01

In 1992, Congress passed the Federal Facilities Compliance Act that requires the U.S. Department of Energy (DOE) to treat and dispose of its mixed waste in accordance with the Resource Conservation and Recovery Act (RCRA) land disposal restrictions (LDRs). In response to the need for mixed-waste treatment capacity where available off-site commercial treatment facilities do not exist or cannot be used, the DOE Albuquerque Operations Office (DOE-AL) organized a Treatment Selection Team to match mixed wastes with treatment options and develop a strategy for treatment of its mixed wastes. DOE-AL manages operations at nine sites with mixed-waste inventories. The Treatmentmore » Selection Team determined a need to develop mobile treatment capacity to treat wastes at the sites where the wastes are generated. Treatment processes used for mixed waste not only must address the hazardous component (i.e., meet LDRs) but also must contain the radioactive component in a form that allows final disposal while protecting workers, the public, and the environment. On the basis of recommendations of the Treatment Selection Team, DOE-AL assigned projects to the sites to bring mixed-waste treatment capacity on-line. The three technologies assigned to the DOE Grand Junction Projects Office (GJPO) are evaporative oxidation, thermal desorption, and treated wastewater evaporation. Rust Geotech, the DOE-GJPO prime contractor, was assigned to design and fabricate mobile treatment units (MTUs) for these three technologies and to deliver the MTUs to selected DOE-AL sites. To conduct treatability tests at the GJPO, Rust leased a pilot-scale evaporative oxidation unit from the Clemson Technical Center (CTC), Anderson, South Carolina. The purpose of this report is to document the findings and results of tests performed using this equipment.« less

Thermal power systems small power systems applications project. Volume 2: Detailed report

NASA Technical Reports Server (NTRS)

Marriott, A. T.

1979-01-01

Small power system technology as applied to power plants up to 10 MW in size was considered. Markets for small power systems were characterized and cost goals were established for the project. Candidate power plant system design concepts were selected for evaluation and preliminary performance and cost assessments were made. Breakeven capital costs were determined for leading contenders among the candidate systems. The potential use of small power systems in providing part of the demand for pumping power by the extensive aqueduct system of California, was studied. Criteria and methodologies were developed for the ranking of candidate power plant system design concepts. Experimental power plant concepts of 1 MW rating were studied to define a power plant configuration for subsequent detail design construction, testing and evaluation. Site selection criteria and ground rules were developed.

The Research Progress of Targeted Drug Delivery Systems

NASA Astrophysics Data System (ADS)

Zhan, Jiayin; Ting, Xizi Liang; Zhu, Junjie

2017-06-01

Targeted drug delivery system (DDS) means to selectively transport drugs to targeted tissues, organs, and cells through a variety of drugs carrier. It is usually designed to improve the pharmacological and therapeutic properties of conventional drugs and to overcome problems such as limited solubility, drug aggregation, poor bio distribution and lack of selectivity, controlling drug release carrier and to reduce normal tissue damage. With the characteristics of nontoxic and biodegradable, it can increase the retention of drug in lesion site and the permeability, improve the concentration of the drug in lesion site. at present, there are some kinds of DDS using at test phase, such as slow controlled release drug delivery system, targeted drug delivery systems, transdermal drug delivery system, adhesion dosing system and so on. This paper makes a review for DDS.

Preparation and evaluation of molecularly imprinted polymer for selective recognition and adsorption of gossypol.

PubMed

Zhi, Keke; Wang, Lulu; Zhang, Yagang; Zhang, Xuemin; Zhang, Letao; Liu, Li; Yao, Jun; Xiang, Wei

2018-03-01

Molecularly imprinted polymers (MIPs) were designed and prepared via bulk thermal polymerization with gossypol as the template molecule and dimethylaminoethyl methacrylate as the functional monomer. The morphology and microstructures of MIPs were characterized by scanning electron microscope and Brunauer-Emmett-Teller surface areas. Static adsorption tests were performed to evaluate adsorption behavior of gossypol by the MIPs. It was found that adsorption kinetics and adsorption isotherms data of MIPs for gossypol were fit well with the pseudo-second-order model and Freundlich model, respectively. Scatchard analysis showed that heterogeneous binding sites were formed in the MIPs, including lower-affinity binding sites with the maximum adsorption of 252 mg/g and higher-affinity binding sites with the maximum adsorption of 632 mg/g. Binding studies also revealed that MIPs had favorable selectivity towards gossypol compared with non-imprinted polymers. Furthermore, adsorption capacity of MIPs maintained above 90% after 5 regeneration cycles, indicating MIPs were recyclable and could be used multiple times. These results demonstrated that prepared MIPs could be a promising functional material for selective adsorption of gossypol. Copyright © 2017 John Wiley & Sons, Ltd.

Treatment of localized gingival recession using the free rotated papilla autograft combined with coronally advanced flap by conventional (macrosurgery) and surgery under magnification (microsurgical) technique: A comparative clinical study

PubMed Central

Pandey, Suraj; Mehta, D. S.

2013-01-01

Background: The aim of the present study was to evaluate and compare the conventional (macro-surgical) and microsurgical approach in performing the free rotated papilla autograft combined with coronally advanced flap surgery in treatment of localized gingival recession. Materials and Methods: A total of 20 sites from 10 systemically healthy patients were selected for the study. The selected sites were randomly divided into experimental site A and experimental site B by using the spilt mouth design. Conventional (macro-surgical) approach for site A and micro-surgery for site B was applied in performing the free rotated papilla autograft combined with coronally advanced flap. Recession depth (RD), recession width (RW) clinical attachment level (CAL.) and width of keratinized tissue (WKT.) were recorded at baseline, 3 months and 6 months post-operatively. Results: Both (macro- and microsurgery) groups showed significant clinical improvement in all the parameters (RD, RW, CAL and WKT). However, on comparing both the groups, these parameters did not reach statistical significance. Conclusion: Both the surgical procedures were equally effective in treatment of localized gingival recession by the free rotated papilla autograft technique combined with coronally advanced flap. However, surgery under magnification (microsurgery) may be clinically better than conventional surgery in terms of less post-operative pain and discomfort experienced by patients at the microsurgical site. PMID:24554888

Multi-locus analysis of genomic time series data from experimental evolution.

PubMed

Terhorst, Jonathan; Schlötterer, Christian; Song, Yun S

2015-04-01

Genomic time series data generated by evolve-and-resequence (E&R) experiments offer a powerful window into the mechanisms that drive evolution. However, standard population genetic inference procedures do not account for sampling serially over time, and new methods are needed to make full use of modern experimental evolution data. To address this problem, we develop a Gaussian process approximation to the multi-locus Wright-Fisher process with selection over a time course of tens of generations. The mean and covariance structure of the Gaussian process are obtained by computing the corresponding moments in discrete-time Wright-Fisher models conditioned on the presence of a linked selected site. This enables our method to account for the effects of linkage and selection, both along the genome and across sampled time points, in an approximate but principled manner. We first use simulated data to demonstrate the power of our method to correctly detect, locate and estimate the fitness of a selected allele from among several linked sites. We study how this power changes for different values of selection strength, initial haplotypic diversity, population size, sampling frequency, experimental duration, number of replicates, and sequencing coverage depth. In addition to providing quantitative estimates of selection parameters from experimental evolution data, our model can be used by practitioners to design E&R experiments with requisite power. We also explore how our likelihood-based approach can be used to infer other model parameters, including effective population size and recombination rate. Then, we apply our method to analyze genome-wide data from a real E&R experiment designed to study the adaptation of D. melanogaster to a new laboratory environment with alternating cold and hot temperatures.

78 FR 17930 - National Rivers and Streams Assessment 2008-009 Draft Report

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-25

... Using a statistical survey design, sites were selected at random to represent the condition of the... describes the results of the nationwide probabilistic survey that was conducted in the summers of 2008 and... conterminous United States. The draft NRSA 2008-2009 report includes information on how the survey was...

Methods for measuring populations of small, diurnal forest birds.

Treesearch

D.A. Manuwal; A.B. Carey

1991-01-01

Before a bird population is measured, the objectives of the study should be clearly defined. Important factors to be considered in designing a study are study site selection, plot size or transect length, distance between sampling points, duration of counts, and frequency and timing of sampling. Qualified field personnel are especially important. Assumptions applying...

Internal hydrological mechanism of permeable pavement and interaction with subsurface water - slides

EPA Science Inventory

A permeable pavement site located at the Seitz Elementary School on Fort Riley, Kansas was selected for this study. An 80-space parking lot was built behind the school as part of an EPA ORD collaboration with the U.S. Army under the Net Zero program. The parking lot design includ...

Inventorying recreation use

Treesearch

George A. James

1971-01-01

Part I is a general discussion about the estimation of recreation use, with descriptions of selected sampling techniques for estimating recreation use on a wide variety of different sites and areas. Part II is a brief discussion of an operational computer oriented information system designed and developed by the USDA Forest Service to fully utilize the inventories of...

34 CFR 491.21 - What selection criteria does the Secretary use?

Code of Federal Regulations, 2010 CFR

2010-07-01

... and group mental health counseling; (iv) Health care; (v) Child care; (vi) Case management; (vii) Job... support services to address the most pressing needs of the target group at, or through, the project site. Support services must be designed to bring members of the target group to a state of readiness for...

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…

The School Site Planner. Land for Learning. Site Selection, Site Planning, Playgrounds, Recreation, and Athletic Fields.

ERIC Educational Resources Information Center

North Carolina State Dept. of Public Instruction, Raleigh. Div. of School Support.

The selection and planning of sites for school facilities can be critical and difficult due to the varied and complex demands schools must satisfy. This publication addresses the many factors that need consideration during the process of site selection, planning, development, and use. The report examines not only the site selection and planning…

Structure-Based Design of Inhibitors Targeting PrfA, the Master Virulence Regulator of Listeria monocytogenes.

PubMed

Kulén, Martina; Lindgren, Marie; Hansen, Sabine; Cairns, Andrew G; Grundström, Christin; Begum, Afshan; van der Lingen, Ingeborg; Brännström, Kristoffer; Hall, Michael; Sauer, Uwe H; Johansson, Jörgen; Sauer-Eriksson, A Elisabeth; Almqvist, Fredrik

2018-05-10

Listeria monocytogenes is a bacterial pathogen that controls much of its virulence through the transcriptional regulator PrfA. In this study, we describe structure-guided design and synthesis of a set of PrfA inhibitors based on ring-fused 2-pyridone heterocycles. Our most effective compound decreased virulence factor expression, reduced bacterial uptake into eukaryotic cells, and improved survival of chicken embryos infected with L. monocytogenes compared to previously identified compounds. Crystal structures identified an intraprotein "tunnel" as the main inhibitor binding site (A I ), where the compounds participate in an extensive hydrophobic network that restricts the protein's ability to form functional DNA-binding helix-turn-helix (HTH) motifs. Our studies also revealed a hitherto unsuspected structural plasticity of the HTH motif. In conclusion, we have designed 2-pyridone analogues that function as site-A I selective PrfA inhibitors with potent antivirulence properties.

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

Effect of seasonal changes in use patterns and cold inlet water temperature on water-heating loads

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

Abrams, D.W.; Shedd, A.C.

This paper presents long-term test data obtained in 20 commercial buildings and 16 residential sites. The information illustrates the effects of variations in hot water load determinants and the effect on energy use. It also is useful as a supplement to the load profiles presented in the ASHRAE Handbooks and other design references. The commercial facilities include supermarkets, fast-food restaurants, full-service restaurants, commercial kitchens, a motel, a nursing home, a hospital, a bakery, and laundry facilities. The residential sites ere selected to provide test sites with higher-than-average hot water use. They include 13 single-family detached residences, one 14-unit apartment building,more » and two apartment laundries. Test data are available at measurement intervals of 1 minute for the residential sites and 15 minutes for the commercial sites. Summary data in tabular and graphical form are presented for average daily volumetric hot water use and cold inlet water temperature. Measured cold inlet water temperature and volumetric hot water use figures are compared to values typically used for design and analysis. Conclusions are offered regarding the effect of cold water inlet temperature and variations in hot water use on water-heating load and energy use. Recommendations for the use of the information presented in water-heating system design, performance optimization, and performance analysis conclude the paper.« less

Characterization of U.S. Wave Energy Converter (WEC) Test Sites: A Catalogue of Met-Ocean Data, 2nd Edition

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

Ann R. Dallman; Neary, Vincent S.

This report presents met-ocean data and wave energy characteristics at eight U.S. wave energy converter (WEC) test and potential deployment sites. Its purpose is to enable the comparison of wave resource characteristics among sites as well as the selection 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 operations and maintenance. For each site, this report catalogues wave statistics recommended in the International Electrotechnical Commission Technical Specimore » cation (IEC 62600-101 TS) on Wave Energy Characterization, as well as the frequency of occurrence 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

Structure and Dynamics of Zr6O8 Metal-Organic Framework Node Surfaces Probed with Ethanol Dehydration as a Catalytic Test Reaction.

PubMed

Yang, Dong; Ortuño, Manuel A; Bernales, Varinia; Cramer, Christopher J; Gagliardi, Laura; Gates, Bruce C

2018-03-14

Some metal-organic frameworks (MOFs) incorporate nodes that are metal oxide clusters such as Zr 6 O 8 . Vacancies on the node surfaces, accidental or by design, act as catalytic sites. Here, we report elucidation of the chemistry of Zr 6 O 8 nodes in the MOFs UiO-66 and UiO-67 having used infrared and nuclear magnetic resonance spectroscopies to determine the ligands on the node surfaces originating from the solvents and modifiers used in the syntheses and having elucidated the catalytic properties of the nodes for ethanol dehydration, which takes place selectively to make diethyl ether but not ethylene at 473-523 K. Density functional theory calculations show that the key to the selective catalysis is the breaking of node-linker bonds (or the accidental adjacency of open/defect sites) that allows catalytically fruitful bonding of the reactant ethanol to neighboring sites on the nodes, facilitating the bimolecular ether formation through an S N 2 mechanism.

Selective binding of choline by a phosphate-coordination-based triple helicate featuring an aromatic box.

PubMed

Jia, Chuandong; Zuo, Wei; Yang, Dong; Chen, Yanming; Cao, Liping; Custelcean, Radu; Hostaš, Jiří; Hobza, Pavel; Glaser, Robert; Wang, Yao-Yu; Yang, Xiao-Juan; Wu, Biao

2017-10-16

In nature, proteins have evolved sophisticated cavities tailored for capturing target guests selectively among competitors of similar size, shape, and charge. The fundamental principles guiding the molecular recognition, such as self-assembly and complementarity, have inspired the development of biomimetic receptors. In the current work, we report a self-assembled triple anion helicate (host 2) featuring a cavity resembling that of the choline-binding protein ChoX, as revealed by crystal and density functional theory (DFT)-optimized structures, which binds choline in a unique dual-site-binding mode. This similarity in structure leads to a similarly high selectivity of host 2 for choline over its derivatives, as demonstrated by the NMR and fluorescence competition experiments. Furthermore, host 2 is able to act as a fluorescence displacement sensor for discriminating choline, acetylcholine, L-carnitine, and glycine betaine effectively.The choline-binding protein ChoX exhibits a synergistic dual-site binding mode that allows it to discriminate choline over structural analogues. Here, the authors design a biomimetic triple anion helicate receptor whose selectivity for choline arises from a similar binding mechanism.

What Can Crystal Structures of Aminergic Receptors Tell Us about Designing Subtype-Selective Ligands?

PubMed Central

Michino, Mayako; Beuming, Thijs; Donthamsetti, Prashant; Newman, Amy Hauck; Javitch, Jonathan A.

2015-01-01

G protein–coupled receptors (GPCRs) are integral membrane proteins that represent an important class of drug targets. In particular, aminergic GPCRs interact with a significant portion of drugs currently on the market. However, most drugs that target these receptors are associated with undesirable side effects, which are due in part to promiscuous interactions with close homologs of the intended target receptors. Here, based on a systematic analysis of all 37 of the currently available high-resolution crystal structures of aminergic GPCRs, we review structural elements that contribute to and can be exploited for designing subtype-selective compounds. We describe the roles of secondary binding pockets (SBPs), as well as differences in ligand entry pathways to the orthosteric binding site, in determining selectivity. In addition, using the available crystal structures, we have identified conformational changes in the SBPs that are associated with receptor activation and explore the implications of these changes for the rational development of selective ligands with tailored efficacy. PMID:25527701

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

Cpf1-Database: web-based genome-wide guide RNA library design for gene knockout screens using CRISPR-Cpf1.

PubMed

Park, Jeongbin; Bae, Sangsu

2018-03-15

Following the type II CRISPR-Cas9 system, type V CRISPR-Cpf1 endonucleases have been found to be applicable for genome editing in various organisms in vivo. However, there are as yet no web-based tools capable of optimally selecting guide RNAs (gRNAs) among all possible genome-wide target sites. Here, we present Cpf1-Database, a genome-wide gRNA library design tool for LbCpf1 and AsCpf1, which have DNA recognition sequences of 5'-TTTN-3' at the 5' ends of target sites. Cpf1-Database provides a sophisticated but simple way to design gRNAs for AsCpf1 nucleases on the genome scale. One can easily access the data using a straightforward web interface, and using the powerful collections feature one can easily design gRNAs for thousands of genes in short time. Free access at http://www.rgenome.net/cpf1-database/. sangsubae@hanyang.ac.kr.

The Euro-Argo education web site: using Argo data to teach data analysis and marine science

NASA Astrophysics Data System (ADS)

Byfield, Valborg; Scheurle, Carolyn; Gould, John; Macama, Emina; King, Brian

2013-04-01

The Euro-Argo education website (www.euroargo-edu.org) aims to make Argo and its data accessible to a non-specialist audience. The site is centred on a selection of floats, which have been chosen because of the insight they provide into key oceanographic processes, the physical and biogeochemical characteristics of different ocean regions around the world, and the role of the ocean in the global climate system. The float selection is a vehicle for teaching data analysis skills, linking these to current topics in the ocean and climate sciences. Each float in the selection has its own page, which provides access to the float data, data plots, background information on the ocean region in which the float can be found, and questions to guide data interpretation. Hidden 'model answers' allow users to check their understanding by comparing their own answers to those provided. The interactive component of the site also includes a series of quizzes, designed to teach data interpretation skills. These start at a basic level and take the students step by step through the most common ways to plot oceanographic data in space and time. More general background information covers the main aspects of the Argo programme, its history and applications, and basic technical information about the floats and sensors. 'World Tour' pages linked to the float selection provide information about the main ocean regions and link information from the Argo programme to oceanographic information from other sources such as satellite observations. The site is primarily aimed at young people between 11 and 18 years of age. However experience from using selected material from the site during science open days shows that children as young as 8-9 and adults of all ages also enjoy the challenge of using and interpreting the Argo data in different contexts.

Long-term lesser prairie-chicken nest ecology in response to grassland management

USGS Publications Warehouse

Fritts, Sarah R.; Grisham, Blake A.; Haukos, David A.; Boal, Clint W.; Patten, Michael; Wolfe, Don H.; Dixon, Charles; Cox, Robert D.; Heck, Willard R.

2016-01-01

Long-term population and range declines from habitat loss and fragmentation caused the lesser prairie-chicken (Tympanuchus pallidicinctus) to be a species of concern throughout its range. Current lesser prairie-chicken range in New Mexico and Texas is partially restricted to sand shinnery oak (Quercus havardii; hereafter shinnery oak) prairies, on which cattle grazing is the main socioeconomic driver for private landowners. Cattle producers within shinnery oak prairies often focus land management on shrub eradication using the herbicide tebuthiuron to promote grass production for forage; however, herbicide application alone, and in combination with grazing, may affect nest site selection and nest survival of lesser prairie-chickens through the reduction of shinnery oak and native grasses. We used a controlled, paired, completely randomized design study to assess the influence of grazing and tebuthiuron application and their combined use on nest site selection and nest survival from 2001 to 2010 in Roosevelt County, New Mexico, USA at 2 spatial scales (i.e., treatment and microhabitat) in 4 treatments: tebuthiuron with grazing, tebuthiuron without grazing, no tebuthiuron with grazing, and a control of no tebuthiuron and no grazing. Grazing treatment was a short-duration system in which plots were grazed once during the dormant season and once during the growing season. Stocking rate was calculated each season based on measured forage production and applied to remove ≤25% of available herbaceous material per season. At the treatment scale, we compared nest site selection among treatments using 1-way χ2 tests and nest survival among treatments using a priori candidate nest survival models in Program MARK. At the microhabitat scale, we identified important habitat predictors of nest site selection and nest survival using logistic regression and a priori candidate nest survival models in Program MARK, respectively. Females typically used treatments as expected and we did not detect trends in selection. Nest survival did not differ among treatments. At the microhabitat scale, nest sites had less bare ground (P = 0.001) and greater angles of obstruction (P ≤ 0.001) compared to random sites. There was a high degree of model selection uncertainty among our candidate models at the microhabitat scale and survival estimates were similar among habitat covariates. Results suggest a tebuthiuron application rate of 0.60 kg/ha, short-duration grazing, and a combination of these management techniques were not detrimental to lesser prairie-chicken nest site selection or nest survival. However, intensified management that increases bare ground or reduces overhead cover may negatively affect lesser prairie-chicken nesting habitat and nest survival.

Transition Metal Ions in Zeolites: Coordination and activation of O2

PubMed Central

Smeets, Pieter J.; Woertink, Julia S.; Sels, Bert F.; Solomon, Edward I.; Schoonheydt, Robert A.

2010-01-01

Zeolites containing transition metal ions (TMI) often show promising activity as heterogeneous catalysts in pollution abatement and selective oxidation reactions. In this paper, two aspects of research on the TMI Cu, Co and Fe in zeolites are discussed: (i) coordination to the lattice and (ii) activated oxygen species. At low loading, TMI preferably occupy exchange sites in six-membered oxygen rings (6MR) where the TMI preferentially coordinate with the oxygen atoms of Al tetrahedra. High TMI loadings result in a variety of TMI species formed at the zeolite surface. Removal of the extra-lattice oxygens during high temperature pretreatments can result in auto-reduction. Oxidation of reduced TMI sites often results in the formation of highly reactive oxygen species. In Cu-ZSM-5, calcination with O2 results in the formation of a species, which was found to be a crucial intermediate in both the direct decomposition of NO and N2O and the selective oxidation of methane into methanol. An activated oxygen species, called α-oxygen, is formed in Fe-ZSM5 and reported to be the active site in the partial oxidation of methane and benzene into methanol and phenol, respectively. However, this reactive α-oxygen can only be formed with N2O, not with O2. O2 activated Co intermediates in Faujasite (FAU) zeolites can selectively oxidize α-pinene and epoxidize styrene. In Co-FAU, CoIII superoxo and peroxo complexes are suggested to be the active cores, whereas in Cu and Fe-ZSM-5 various monomeric and dimeric sites have been proposed, but no consensus has been obtained. Very recently, the active site in Cu-ZSM-5 was identified as a bent [Cu-O-Cu]2+ core (Proc. Natl. Acad. Sci. USA 2009, 106, 18908-18913). Overall, O2 activation depends on the interplay of structural factors such as type of zeolite, size of the channels and cages and chemical factors such as Si/Al ratio and the nature, charge and distribution of the charge balancing cations. The presence of several different TMI sites hinders the direct study of the spectroscopic features of the active site. Spectroscopic techniques capable of selectively probing these sites, even if they only constitute a minor fraction of the total amount of TMI sites, are thus required. Fundamental knowledge of the geometric and electronic structure of the reactive active site can help in the design of novel selective oxidation catalysts. PMID:20380459

Molecular dynamics simulations on the inhibition of cyclin-dependent kinases 2 and 5 in the presence of activators.

PubMed

Zhang, Bing; Tan, Vincent B C; Lim, Kian Meng; Tay, Tong Earn

2006-06-01

Interests in CDK2 and CDK5 have stemmed mainly from their association with cancer and neuronal migration or differentiation related diseases and the need to design selective inhibitors for these kinases. Molecular dynamics (MD) simulations have not only become a viable approach to drug design because of advances in computer technology but are increasingly an integral part of drug discovery processes. It is common in MD simulations of inhibitor/CDK complexes to exclude the activator of the CDKs in the structural models to keep computational time tractable. In this paper, we present simulation results of CDK2 and CDK5 with roscovitine using models with and without their activators (cyclinA and p25). While p25 was found to induce slight changes in CDK5, the calculations support that cyclinA leads to significant conformational changes near the active site of CDK2. This suggests that detailed and structure-based inhibitor design targeted at these CDKs should employ activator-included models of the kinases. Comparisons between P/CDK2/cyclinA/roscovitine and CDK5/p25/roscovitine complexes reveal differences in the conformations of the glutamine around the active sites, which may be exploited to find highly selective inhibitors with respect to CDK2 and CDK5.

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.

Development of an Independent Global Land Cover Validation Dataset

NASA Astrophysics Data System (ADS)

Sulla-Menashe, D. J.; Olofsson, P.; Woodcock, C. E.; Holden, C.; Metcalfe, M.; Friedl, M. A.; Stehman, S. V.; Herold, M.; Giri, C.

2012-12-01

Accurate information related to the global distribution and dynamics in global land cover is critical for a large number of global change science questions. A growing number of land cover products have been produced at regional to global scales, but the uncertainty in these products and the relative strengths and weaknesses among available products are poorly characterized. To address this limitation we are compiling a database of high spatial resolution imagery to support international land cover validation studies. Validation sites were selected based on a probability sample, and may therefore be used to estimate statistically defensible accuracy statistics and associated standard errors. Validation site locations were identified using a stratified random design based on 21 strata derived from an intersection of Koppen climate classes and a population density layer. In this way, the two major sources of global variation in land cover (climate and human activity) are explicitly included in the stratification scheme. At each site we are acquiring high spatial resolution (< 1-m) satellite imagery for 5-km x 5-km blocks. The response design uses an object-oriented hierarchical legend that is compatible with the UN FAO Land Cover Classification System. Using this response design, we are classifying each site using a semi-automated algorithm that blends image segmentation with a supervised RandomForest classification algorithm. In the long run, the validation site database is designed to support international efforts to validate land cover products. To illustrate, we use the site database to validate the MODIS Collection 4 Land Cover product, providing a prototype for validating the VIIRS Surface Type Intermediate Product scheduled to start operational production early in 2013. As part of our analysis we evaluate sources of error in coarse resolution products including semantic issues related to the class definitions, mixed pixels, and poor spectral separation between classes.

Mini-columns for Conducting Breakthrough Experiments. Design and Construction

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

Dittrich, Timothy M.; Reimus, Paul William; Ware, Stuart Douglas

Experiments with moderately and strongly sorbing radionuclides (i.e., U, Cs, Am) have shown that sorption between experimental solutions and traditional column materials must be accounted for to accurately determine stationary phase or porous media sorption properties (i.e., sorption site density, sorption site reaction rate coefficients, and partition coefficients or K d values). This report details the materials and construction of mini-columns for use in breakthrough columns to allow for accurate measurement and modeling of sorption parameters. Material selection, construction techniques, wet packing of columns, tubing connections, and lessons learned are addressed.

Analysis of the binding sites of vitamin D 1α-hydroxylase (CYP27B1) and vitamin D 24-hydroxylase (CYP24A1) for the design of selective CYP24A1 inhibitors: Homology modelling, molecular dynamics simulations and identification of key binding requirements.

PubMed

Taban, Ismail M; Zhu, Jinge; DeLuca, Hector F; Simons, Claire

2017-10-15

A homology model of human CYP27B1 was built using MOE and was further optimised by molecular dynamics simulations of the hCYP27B1 homology model and a hCYP27B1-SDZ-88357 complex. Docking results from the hCYP27B1-SDZ-88357 complex showed amino acids Arg107, Asn387 and Asp320 have an important role in binding interaction, with Asp320 part of the important acid-alcohol pair situated in the I-helix with the conserved sequence (A/G) GX (E/D) (T/S), which assumes an essential role in the binding of an oxygen molecule for catalysis. Additional docking experiments with selective hCYP27B1 or hCYP24A1 inhibitors using both the hCYP27B1 model and a triple mutant hCYP24A1 model provided further support for the importance of H-bonding interactions with the three identified active site amino acids. To confirm the role of Arg107, Asn387 and Asp320 in the active site of hCYP27B1 compounds were designed that would form H-bonding interactions, as determined from docking experiments with the hCYP27B1 model. Subsequent synthesis and CYP24A1 and CYP27B1 enzyme assays of the designed compounds 1a and 1b showed a∼5-fold selectivity for CYP27B1 confirming the importance of Asp320 in particular and also Asn387 and Arg107 as important amino acids for CYP27B1 inhibitory activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Application of ecological criteria in selecting marine reserves and developing reserve networks

USGS Publications Warehouse

Roberts, Callum M.; Branch, George; Bustamante, Rodrigo H.; Castilla, Juan Carlos; Dugan, Jenifer; Halpern, Benjamin S.; Lafferty, Kevin D.; Leslie, Heather; McArdle, Deborah; Ruckelshaus, Mary; Warner, Robert R.

2003-01-01

Marine reserves are being established worldwide in response to a growing recognition of the conservation crisis that is building in the oceans. However, designation of reserves has been largely opportunistic, or protective measures have been implemented (often overlapping and sometimes in conflict) by different entities seeking to achieve different ends. This has created confusion among both users and enforcers, and the proliferation of different measures provides a false sense of protection where little is offered. This paper sets out a procedure grounded in current understanding of ecological processes, that allows the evaluation and selection of reserve sites in order to develop functional, interconnected networks of fully protected reserves that will fulfill multiple objectives. By fully protected we mean permanently closed to fishing and other resource extraction. We provide a framework that unifies the central aims of conservation and fishery management, while also meeting other human needs such as the provision of ecosystem services (e.g., maintenance of coastal water quality, shoreline protection, and recreational opportunities). In our scheme, candidate sites for reserves are evaluated against 12 criteria focused toward sustaining the biological integrity and productivity of marine systems at both local and regional scales. While a limited number of sites will be indispensable in a network, many will be of similar value as reserves, allowing the design of numerous alternative, biologically adequate networks. Devising multiple network designs will help ensure that ecological functionality is preserved throughout the socioeconomic evaluation process. Too often, socioeconomic criteria have dominated the process of reserve selection, potentially undermining their efficacy. We argue that application of biological criteria must precede and inform socioeconomic evaluation, since maintenance of ecosystem functioning is essential for meeting all of the goals for reserves. It is critical that stakeholders are fully involved throughout this process. Application of the proposed criteria will lead to networks whose multifunctionality will help unite the objectives of different management entities, so accelerating progress toward improved stewardship of the oceans.

A survey of whitewater recreation impacts along five West Virginia rivers

USGS Publications Warehouse

Leung, Y.-F.; Marion, J.L.

1998-01-01

Results are reported from an assessment of whitewater river recreation impacts at river accesses and recreation sites along five West Virginia rivers: the New, Gauley, Cheat, Tygart, and Shenandoah. Procedures were developed and applied to assess resource conditions on 24 river access roads, 68 river accesses, and 151 recreation sites. The majority of river accesses and recreation sites are located on the New and Gauley rivers, which account for most of the state?s whitewater recreation use. Site conditions are variable. While some river accesses and sites are situated on resistant rocky substrates, many are poorly designed and/or located on erodible soil and sand substrates. Recreation site sizes and other areal measures of site disturbance are quite large, coincident with the large group sizes associated with commercially outfitted whitewater rafting trips. Recommendations are offered for managing river accesses and sites and whitewater visitation and the selection of indicators and standards as part of a Limits of Acceptable Change management process. Procedures and recommendations for continued visitor impact monitoring are also offered.

Use of tissue-specific microRNA to control pathology of wild-type adenovirus without attenuation of its ability to kill cancer cells.

PubMed

Cawood, Ryan; Chen, Hannah H; Carroll, Fionnadh; Bazan-Peregrino, Miriam; van Rooijen, Nico; Seymour, Leonard W

2009-05-01

Replicating viruses have broad applications in biomedicine, notably in cancer virotherapy and in the design of attenuated vaccines; however, uncontrolled virus replication in vulnerable tissues can give pathology and often restricts the use of potent strains. Increased knowledge of tissue-selective microRNA expression now affords the possibility of engineering replicating viruses that are attenuated at the RNA level in sites of potential pathology, but retain wild-type replication activity at sites not expressing the relevant microRNA. To assess the usefulness of this approach for the DNA virus adenovirus, we have engineered a hepatocyte-safe wild-type adenovirus 5 (Ad5), which normally mediates significant toxicity and is potentially lethal in mice. To do this, we have included binding sites for hepatocyte-selective microRNA mir-122 within the 3' UTR of the E1A transcription cassette. Imaging versions of these viruses, produced by fusing E1A with luciferase, showed that inclusion of mir-122 binding sites caused up to 80-fold decreased hepatic expression of E1A following intravenous delivery to mice. Animals administered a ten-times lethal dose of wild-type Ad5 (5x10(10) viral particles/mouse) showed substantial hepatic genome replication and extensive liver pathology, while inclusion of 4 microRNA binding sites decreased replication 50-fold and virtually abrogated liver toxicity. This modified wild-type virus retained full activity within cancer cells and provided a potent, liver-safe oncolytic virus. In addition to providing many potent new viruses for cancer virotherapy, microRNA control of virus replication should provide a new strategy for designing safe attenuated vaccines applied across a broad range of viral diseases.

40 CFR 761.247 - Sample site selection for pipe segment removal.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Natural Gas Pipeline: Selecting Sample Sites, Collecting Surface Samples, and Analyzing Standard PCB Wipe Samples § 761.247 Sample site selection for pipe segment removal. (a) General. (1) Select the pipe... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Sample site selection for pipe segment...

40 CFR 761.247 - Sample site selection for pipe segment removal.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Sample site selection for pipe segment... Natural Gas Pipeline: Selecting Sample Sites, Collecting Surface Samples, and Analyzing Standard PCB Wipe Samples § 761.247 Sample site selection for pipe segment removal. (a) General. (1) Select the pipe...

Plasmin substrate binding site cooperativity guides the design of potent peptide aldehyde inhibitors.

PubMed

Swedberg, Joakim E; Harris, Jonathan M

2011-10-04

Perioperative bleeding is a cause of major blood loss and is associated with increased rates of postoperative morbidity and mortality. To combat this, antifibrinolytic inhibitors of the serine protease plasmin are commonly used to reduce bleeding during surgery. The most effective and previously widely used of these is the broad range serine protease inhibitor aprotinin. However, adverse clinical outcomes have led to use of alternative serine lysine analogues to inhibit plasmin. These compounds suffer from low selectivity and binding affinity. Consequently, a concerted effort to discover potent and selective plasmin inhibitors has developed. This study used a noncombinatorial peptide library to define plasmin's extended substrate specificity and guide the design of potent transition state analogue inhibitors. The various substrate binding sites of plasmin were found to exhibit a higher degree of cooperativity than had previously been appreciated. Peptide sequences capitalizing on these features produced high-affinity inhibitors of plasmin. The most potent of these, Lys-Met(sulfone)-Tyr-Arg-H [KM(O(2))YR-H], inhibited plasmin with a K(i) of 3.1 nM while maintaining 25-fold selectivity over plasma kallikrein. Furthermore, 125 nM (0.16 μg/mL) KM(O(2))YR-H attenuated fibrinolysis in vitro with an efficacy similar to that of 15 nM (0.20 μg/mL) aprotinin. To date, this is the most potent peptide inhibitor of plasmin that exhibits selectivity against plasma kallikrein, making this compound an attractive candidate for further therapeutic development.

Effects of wind energy development on nesting ecology of greater prairie-chickens in fragmented grasslands.

PubMed

McNew, Lance B; Hunt, Lyla M; Gregory, Andrew J; Wisely, Samantha M; Sandercock, Brett K

2014-08-01

Wind energy is targeted to meet 20% of U.S. energy needs by 2030, but new sites for development of renewable energy may overlap with important habitats of declining populations of grassland birds. Greater Prairie-Chickens (Tympanuchus cupido) are an obligate grassland bird species predicted to respond negatively to energy development. We used a modified before-after control-impact design to test for impacts of a wind energy development on the reproductive ecology of prairie-chickens in a 5-year study. We located 59 and 185 nests before and after development, respectively, of a 201 MW wind energy facility in Greater Prairie-Chicken nesting habitat and assessed nest site selection and nest survival relative to proximity to wind energy infrastructure and habitat conditions. Proximity to turbines did not negatively affect nest site selection (β = 0.03, 95% CI = -1.2-1.3) or nest survival (β = -0.3, 95% CI = -0.6-0.1). Instead, nest site selection and survival were strongly related to vegetative cover and other local conditions determined by management for cattle production. Integration of our project results with previous reports of behavioral avoidance of oil and gas facilities by other species of prairie grouse suggests new avenues for research to mitigate impacts of energy development. © 2014 The Authors. Conservation Biology published by Wiley Periodicals, Inc. on behalf of Society for Conservation Biology.

A comparison of two sampling designs for fish assemblage assessment in a large river

USGS Publications Warehouse

Kiraly, Ian A.; Coghlan, Stephen M.; Zydlewski, Joseph D.; Hayes, Daniel

2014-01-01

We compared the efficiency of stratified random and fixed-station sampling designs to characterize fish assemblages in anticipation of dam removal on the Penobscot River, the largest river in Maine. We used boat electrofishing methods in both sampling designs. Multiple 500-m transects were selected randomly and electrofished in each of nine strata within the stratified random sampling design. Within the fixed-station design, up to 11 transects (1,000 m) were electrofished, all of which had been sampled previously. In total, 88 km of shoreline were electrofished during summer and fall in 2010 and 2011, and 45,874 individuals of 34 fish species were captured. Species-accumulation and dissimilarity curve analyses indicated that all sampling effort, other than fall 2011 under the fixed-station design, provided repeatable estimates of total species richness and proportional abundances. Overall, our sampling designs were similar in precision and efficiency for sampling fish assemblages. The fixed-station design was negatively biased for estimating the abundance of species such as Common Shiner Luxilus cornutus and Fallfish Semotilus corporalis and was positively biased for estimating biomass for species such as White Sucker Catostomus commersonii and Atlantic Salmon Salmo salar. However, we found no significant differences between the designs for proportional catch and biomass per unit effort, except in fall 2011. The difference observed in fall 2011 was due to limitations on the number and location of fixed sites that could be sampled, rather than an inherent bias within the design. Given the results from sampling in the Penobscot River, application of the stratified random design is preferable to the fixed-station design due to less potential for bias caused by varying sampling effort, such as what occurred in the fall 2011 fixed-station sample or due to purposeful site selection.

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

NASA Technical Reports Server (NTRS)

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

1993-01-01

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

Rational Design Synthesis and Evaluation of New Selective Inhibitors of Microbial Class II (Zinc Dependent) Fructose Bis-phosphate Aldolases

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

R Daher; M Coincon; M Fonvielle

2011-12-31

We report the synthesis and biochemical evaluation of several selective inhibitors of class II (zinc dependent) fructose bis-phosphate aldolases (Fba). The products were designed as transition-state analogues of the catalyzed reaction, structurally related to the substrate fructose bis-phosphate (or sedoheptulose bis-phosphate) and based on an N-substituted hydroxamic acid, as a chelator of the zinc ion present in active site. The compounds synthesized were tested on class II Fbas from various pathogenic microorganisms and, by comparison, on a mammalian class I Fba. The best inhibitor shows Ki against class II Fbas from various pathogens in the nM range, with very highmore » selectivity (up to 105). Structural analyses of inhibitors in complex with aldolases rationalize and corroborate the enzymatic kinetics results. These inhibitors represent lead compounds for the preparation of new synthetic antibiotics, notably for tuberculosis prophylaxis.« less

Disentangled Cooperative Orderings in Artificial Rare-Earth Nickelates.

PubMed

Middey, S; Meyers, D; Kareev, M; Cao, Yanwei; Liu, X; Shafer, P; Freeland, J W; Kim, J-W; Ryan, P J; Chakhalian, J

2018-04-13

Coupled transitions between distinct ordered phases are important aspects behind the rich phase complexity of correlated oxides that hinder our understanding of the underlying phenomena. For this reason, fundamental control over complex transitions has become a leading motivation of the designer approach to materials. We have devised a series of new superlattices by combining a Mott insulator and a correlated metal to form ultrashort period superlattices, which allow one to disentangle the simultaneous orderings in RENiO_{3}. Tailoring an incommensurate heterostructure period relative to the bulk charge ordering pattern suppresses the charge order transition while preserving metal-insulator and antiferromagnetic transitions. Such selective decoupling of the entangled phases resolves the long-standing puzzle about the driving force behind the metal-insulator transition and points to the site-selective Mott transition as the operative mechanism. This designer approach emphasizes the potential of heterointerfaces for selective control of simultaneous transitions in complex materials with entwined broken symmetries.

Disentangled Cooperative Orderings in Artificial Rare-Earth Nickelates

NASA Astrophysics Data System (ADS)

Middey, S.; Meyers, D.; Kareev, M.; Cao, Yanwei; Liu, X.; Shafer, P.; Freeland, J. W.; Kim, J.-W.; Ryan, P. J.; Chakhalian, J.

2018-04-01

Coupled transitions between distinct ordered phases are important aspects behind the rich phase complexity of correlated oxides that hinder our understanding of the underlying phenomena. For this reason, fundamental control over complex transitions has become a leading motivation of the designer approach to materials. We have devised a series of new superlattices by combining a Mott insulator and a correlated metal to form ultrashort period superlattices, which allow one to disentangle the simultaneous orderings in RENiO3 . Tailoring an incommensurate heterostructure period relative to the bulk charge ordering pattern suppresses the charge order transition while preserving metal-insulator and antiferromagnetic transitions. Such selective decoupling of the entangled phases resolves the long-standing puzzle about the driving force behind the metal-insulator transition and points to the site-selective Mott transition as the operative mechanism. This designer approach emphasizes the potential of heterointerfaces for selective control of simultaneous transitions in complex materials with entwined broken symmetries.

Biomimetic Artificial Epigenetic Code for Targeted Acetylation of Histones.

PubMed

Taniguchi, Junichi; Feng, Yihong; Pandian, Ganesh N; Hashiya, Fumitaka; Hidaka, Takuya; Hashiya, Kaori; Park, Soyoung; Bando, Toshikazu; Ito, Shinji; Sugiyama, Hiroshi

2018-06-13

While the central role of locus-specific acetylation of histone proteins in eukaryotic gene expression is well established, the availability of designer tools to regulate acetylation at particular nucleosome sites remains limited. Here, we develop a unique strategy to introduce acetylation by constructing a bifunctional molecule designated Bi-PIP. Bi-PIP has a P300/CBP-selective bromodomain inhibitor (Bi) as a P300/CBP recruiter and a pyrrole-imidazole polyamide (PIP) as a sequence-selective DNA binder. Biochemical assays verified that Bi-PIPs recruit P300 to the nucleosomes having their target DNA sequences and extensively accelerate acetylation. Bi-PIPs also activated transcription of genes that have corresponding cognate DNA sequences inside living cells. Our results demonstrate that Bi-PIPs could act as a synthetic programmable histone code of acetylation, which emulates the bromodomain-mediated natural propagation system of histone acetylation to activate gene expression in a sequence-selective manner.

The impact of target site accessibility on the design of effective siRNAs.

PubMed

Tafer, Hakim; Ameres, Stefan L; Obernosterer, Gregor; Gebeshuber, Christoph A; Schroeder, Renée; Martinez, Javier; Hofacker, Ivo L

2008-05-01

Small-interfering RNAs (siRNAs) assemble into RISC, the RNA-induced silencing complex, which cleaves complementary mRNAs. Despite their fluctuating efficacy, siRNAs are widely used to assess gene function. Although this limitation could be ascribed, in part, to variations in the assembly and activation of RISC, downstream events in the RNA interference (RNAi) pathway, such as target site accessibility, have so far not been investigated extensively. In this study we present a comprehensive analysis of target RNA structure effects on RNAi by computing the accessibility of the target site for interaction with the siRNA. Based on our observations, we developed a novel siRNA design tool, RNAxs, by combining known siRNA functionality criteria with target site accessibility. We calibrated our method on two data sets comprising 573 siRNAs for 38 genes, and tested it on an independent set of 360 siRNAs targeting four additional genes. Overall, RNAxs proves to be a robust siRNA selection tool that substantially improves the prediction of highly efficient siRNAs.

Engineering Single-Atom Cobalt Catalysts toward Improved Electrocatalysis.

PubMed

Wan, Gang; Yu, Pengfei; Chen, Hangrong; Wen, Jianguo; Sun, Cheng-Jun; Zhou, Hua; Zhang, Nian; Li, Qianru; Zhao, Wanpeng; Xie, Bing; Li, Tao; Shi, Jianlin

2018-04-01

The development of cost-effective catalysts to replace noble metal is attracting increasing interests in many fields of catalysis and energy, and intensive efforts are focused on the integration of transition-metal sites in carbon as noble-metal-free candidates. Recently, the discovery of single-atom dispersed catalyst (SAC) provides a new frontier in heterogeneous catalysis. However, the electrocatalytic application of SAC is still subject to several theoretical and experimental limitations. Further advances depend on a better design of SAC through optimizing its interaction with adsorbates during catalysis. Here, distinctive from previous studies, favorable 3d electronic occupation and enhanced metal-adsorbates interactions in single-atom centers via the construction of nonplanar coordination is achieved, which is confirmed by advanced X-ray spectroscopic and electrochemical studies. The as-designed atomically dispersed cobalt sites within nonplanar coordination show significantly improved catalytic activity and selectivity toward the oxygen reduction reaction, approaching the benchmark Pt-based catalysts. More importantly, the illustration of the active sites in SAC indicates metal-natured catalytic sites and a media-dependent catalytic pathway. Achieving structural and electronic engineering on SAC that promotes its catalytic performances provides a paradigm to bridge the gap between single-atom catalysts design and electrocatalytic applications. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Site-Selection in Single-Molecule Junction for Highly Reproducible Molecular Electronics.

PubMed

Kaneko, Satoshi; Murai, Daigo; Marqués-González, Santiago; Nakamura, Hisao; Komoto, Yuki; Fujii, Shintaro; Nishino, Tomoaki; Ikeda, Katsuyoshi; Tsukagoshi, Kazuhito; Kiguchi, Manabu

2016-02-03

Adsorption sites of molecules critically determine the electric/photonic properties and the stability of heterogeneous molecule-metal interfaces. Then, selectivity of adsorption site is essential for development of the fields including organic electronics, catalysis, and biology. However, due to current technical limitations, site-selectivity, i.e., precise determination of the molecular adsorption site, remains a major challenge because of difficulty in precise selection of meaningful one among the sites. We have succeeded the single site-selection at a single-molecule junction by performing newly developed hybrid technique: simultaneous characterization of surface enhanced Raman scattering (SERS) and current-voltage (I-V) measurements. The I-V response of 1,4-benzenedithiol junctions reveals the existence of three metastable states arising from different adsorption sites. Notably, correlated SERS measurements show selectivity toward one of the adsorption sites: "bridge sites". This site-selectivity represents an essential step toward the reliable integration of individual molecules on metallic surfaces. Furthermore, the hybrid spectro-electric technique reveals the dependence of the SERS intensity on the strength of the molecule-metal interaction, showing the interdependence between the optical and electronic properties in single-molecule junctions.

A highly selective and sensitive fluorescent chemosensor and its application for rapid on-site detection of Al3 +

NASA Astrophysics Data System (ADS)

Yue, Xiao-li; Wang, Zhao-qing; Li, Chao-rui; Yang, Zheng-yin

2018-03-01

In this paper, a simple naphthalene-based derivative (HL) has been designed and synthesized as a Al3 +-selective fluorescent chemosensor based on the PET mechanism. HL exhibited high selectivity and sensitivity towards Al3 + over other commonly coexisting metal ions in ethanol with a detection limit of 2.72 nM. The 1:1 binding stoichiometry of the complex (HL-Al3 +) was determined from the Job's plot based on fluorescence titrations and the ESI-MS spectrum data. Moreover, the binding site of HL with Al3 + was assured by the 1H NMR titration experiment. The binding constant (Ka) of the complex (HL-Al3 +) was calculated to be 5.06 × 104 M- 1 according to the Benesi-Hildebrand equation. In addition, the recognizing process of HL towards Al3 + was chemically reversible by adding Na2EDTA. Importantly, HL could directly and rapidly detect aluminum ion through the filter paper without resorting to additional instrumental analysis.

Discovery of the 3-Imino-1,2,4-thiadiazinane 1,1-Dioxide Derivative Verubecestat (MK-8931)–A β-Site Amyloid Precursor Protein Cleaving Enzyme 1 Inhibitor for the Treatment of Alzheimer’s Disease

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

Scott, Jack D.; Li, Sarah W.; Brunskill, Andrew P. J.

Verubecestat 3 (MK-8931), a diaryl amide-substituted 3-imino-1,2,4-thiadiazinane 1,1-dioxide derivative, is a high-affinity β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor currently undergoing Phase 3 clinical evaluation for the treatment of mild to moderate and prodromal Alzheimer’s disease. Although not selective over the closely related aspartyl protease BACE2, verubecestat has high selectivity for BACE1 over other key aspartyl proteases, notably cathepsin D, and profoundly lowers CSF and brain Aβ levels in rats and nonhuman primates and CSF Aβ levels in humans. In this annotation, we describe the discovery of 3, including design, validation, and selected SAR around the novel iminothiadiazinanemore » dioxide core as well as aspects of its preclinical and Phase 1 clinical characterization.« less

Halley's comet exploration and the Japanese Usuda large antenna

NASA Technical Reports Server (NTRS)

Nomura, T.

1986-01-01

An overview of the Japanese PLANET-A project to investigate Halley's Comet is given. The objectives and scientific challenges involved in the project are given, and the nature of the contribution made by the large antenna array located at Usuda-Cho, Nagano Prefecture, Japan is discussed. The structural design of the MS-T5 and PLANET-A probes are given, as well as the tracking and control network for the probes. The construction, design, operating system and site selection for the Usuda antenna station are discussed.

Earth resources data systems design: S192 instrument measurements and characteristics

NASA Technical Reports Server (NTRS)

Goldstein, A. S.

1972-01-01

The design, development, and characteristics of the S192 instrument for use with the earth resources data systems are discussed. Subjects presented are: (1) multispectral scanner measurements, (2) measurement characteristics, (3) calibration and aligment, (4) operating modes, and (5) time tagging and references. The S192 will obtain high spatial resolution, quantitative line scan imagery data of the radiation reflected and emitted by selected test sites in up to 13 spectral bands of visible, near infrared, and thermal infrared regions of the electromagnetic spectrum.

Geologic Traverse Planning for Apollo Missions

NASA Technical Reports Server (NTRS)

Lofgren, Gary

2012-01-01

The science on Apollo missions was overseen by the Science Working Panel (SWP), but done by multiple PIs. There were two types of science, packages like the Apollo Lunar Surface Experiment Package (ALSEP) and traverse science. Traverses were designed on Earth for the astronauts to execute. These were under direction of the Lunar Surface PI, but the agreed traverse was a cooperation between the PI and SWP. The landing sites were selected by a different designated committee, not the SWP, and were based on science and safety.

Rational approach to polymer-supported catalysts: synergy between catalytic reaction mechanism and polymer design.

PubMed

Madhavan, Nandita; Jones, Christopher W; Weck, Marcus

2008-09-01

Supported catalysis is emerging as a cornerstone of transition metal catalysis, as environmental awareness necessitates "green" methodologies and transition metal resources become scarcer and more expensive. Although these supported systems are quite useful, especially in their capacity for transition metal catalyst recycling and recovery, higher activity and selectivity have been elusive compared with nonsupported catalysts. This Account describes recent developments in polymer-supported metal-salen complexes, which often surpass nonsupported analogues in catalytic activity and selectivity, demonstrating the effectiveness of a systematic, logical approach to designing supported catalysts from a detailed understanding of the catalytic reaction mechanism. Over the past few decades, a large number of transition metal complex catalysts have been supported on a variety of materials ranging from polymers to mesoporous silica. In particular, soluble polymer supports are advantageous because of the development of controlled and living polymerization methods that are tolerant to a wide variety of functional groups, including controlled radical polymerizations and ring-opening metathesis polymerization. These methods allow for tuning the density and structure of the catalyst sites along the polymer chain, thereby enabling the development of structure-property relationships between a catalyst and its polymer support. The fine-tuning of the catalyst-support interface, in combination with a detailed understanding of catalytic reaction mechanisms, not only permits the generation of reusable and recyclable polymer-supported catalysts but also facilitates the design and realization of supported catalysts that are significantly more active and selective than their nonsupported counterparts. These superior supported catalysts are accessible through the optimization of four basic variables in their design: (i) polymer backbone rigidity, (ii) the nature of the linker, (iii) catalyst site density, and (iv) the nature of the catalyst attachment. Herein, we describe the design of polymer supports tuned to enhance the catalytic activity or decrease, or even eliminate, decomposition pathways of salen-based transition metal catalysts that follow either a monometallic or a bimetallic reaction mechanism. These findings result in the creation of some of the most active and selective salen catalysts in the literature.

A Graphic Overlay Method for Selection of Osteotomy Site in Chronic Radial Head Dislocation: An Evaluation of 3D-printed Bone Models.

PubMed

Kim, Hui Taek; Ahn, Tae Young; Jang, Jae Hoon; Kim, Kang Hee; Lee, Sung Jae; Jung, Duk Young

2017-03-01

Three-dimensional (3D) computed tomography imaging is now being used to generate 3D models for planning orthopaedic surgery, but the process remains time consuming and expensive. For chronic radial head dislocation, we have designed a graphic overlay approach that employs selected 3D computer images and widely available software to simplify the process of osteotomy site selection. We studied 5 patients (2 traumatic and 3 congenital) with unilateral radial head dislocation. These patients were treated with surgery based on traditional radiographs, but they also had full sets of 3D CT imaging done both before and after their surgery: these 3D CT images form the basis for this study. From the 3D CT images, each patient generated 3 sets of 3D-printed bone models: 2 copies of the preoperative condition, and 1 copy of the postoperative condition. One set of the preoperative models was then actually osteotomized and fixed in the manner suggested by our graphic technique. Arcs of rotation of the 3 sets of 3D-printed bone models were then compared. Arcs of rotation of the 3 groups of bone models were significantly different, with the models osteotomized accordingly to our graphic technique having the widest arcs. For chronic radial head dislocation, our graphic overlay approach simplifies the selection of the osteotomy site(s). Three-dimensional-printed bone models suggest that this approach could improve range of motion of the forearm in actual surgical practice. Level IV-therapeutic study.

Archaeological Investigations in the Upper Tombigbee Valley, Mississippi: Phase I. Volume 1.

DTIC Science & Technology

1983-01-01

6.10 Site 221T563: Selected c,ramics; Alexander Incised .............................. 6.90 6.91 6.11 Site 221T563: Selected ceramics: Alexander... Incised .............................. 6.92 6.93 6.12 Site 221T563: Selected ceramics: Alexander Incised .............................. 6.94 6.95 6.13 Site...221T563: Selected ceramics: Alexander Incised .............................. 6.96 6.9i 6.14 Site 221T563: Selected ceramics: Alexander Incised

Purifying Selection on Exonic Splice Enhancers in Intronless Genes

PubMed Central

Savisaar, Rosina; Hurst, Laurence D.

2016-01-01

Exonic splice enhancers (ESEs) are short nucleotide motifs, enriched near exon ends, that enhance the recognition of the splice site and thus promote splicing. Are intronless genes under selection to avoid these motifs so as not to attract the splicing machinery to an mRNA that should not be spliced, thereby preventing the production of an aberrant transcript? Consistent with this possibility, we find that ESEs in putative recent retrocopies are at a higher density and evolving faster than those in other intronless genes, suggesting that they are being lost. Moreover, intronless genes are less dense in putative ESEs than intron-containing ones. However, this latter difference is likely due to the skewed base composition of intronless sequences, a skew that is in line with the general GC richness of few exon genes. Indeed, after controlling for such biases, we find that both intronless and intron-containing genes are denser in ESEs than expected by chance. Importantly, nucleotide-controlled analysis of evolutionary rates at synonymous sites in ESEs indicates that the ESEs in intronless genes are under purifying selection in both human and mouse. We conclude that on the loss of introns, some but not all, ESE motifs are lost, the remainder having functions beyond a role in splice promotion. These results have implications for the design of intronless transgenes and for understanding the causes of selection on synonymous sites. PMID:26802218

Systematic development and implementation of interventions to OPtimise Health Literacy and Access (Ophelia).

PubMed

Beauchamp, Alison; Batterham, Roy W; Dodson, Sarity; Astbury, Brad; Elsworth, Gerald R; McPhee, Crystal; Jacobson, Jeanine; Buchbinder, Rachelle; Osborne, Richard H

2017-03-03

The need for healthcare strengthening to enhance equity is critical, requiring systematic approaches that focus on those experiencing lesser access and outcomes. This project developed and tested the Ophelia (OPtimising HEalth LIteracy and Access) approach for co-design of interventions to improve health literacy and equity of access. Eight principles guided this development: Outcomes focused; Equity driven, Needs diagnosis, Co-design, Driven by local wisdom, Sustainable, Responsive and Systematically applied. We report the application of the Ophelia process where proof-of-concept was defined as successful application of the principles. Nine sites were briefed on the aims of the project around health literacy, co-design and quality improvement. The sites were rural/metropolitan, small/large hospitals, community health centres or municipalities. Each site identified their own priorities for improvement; collected health literacy data using the Health Literacy Questionnaire (HLQ) within the identified priority groups; engaged staff in co-design workshops to generate ideas for improvement; developed program-logic models; and implemented their projects using Plan-Do-Study-Act (PDSA) cycles. Evaluation included assessment of impacts on organisations, practitioners and service users, and whether the principles were applied. Sites undertook co-design workshops involving discussion of service user needs informed by HLQ (n = 813) and interview data. Sites generated between 21 and 78 intervention ideas and then planned their selected interventions through program-logic models. Sites successfully implemented interventions and refined them progressively with PDSA cycles. Interventions generally involved one of four pathways: development of clinician skills and resources for health literacy, engagement of community volunteers to disseminate health promotion messages, direct impact on consumers' health literacy, and redesign of existing services. Evidence of application of the principles was found in all sites. The Ophelia approach guided identification of health literacy issues at each participating site and the development and implementation of locally appropriate solutions. The eight principles provided a framework that allowed flexible application of the Ophelia approach and generation of a diverse set of interventions. Changes were observed at organisational, staff, and community member levels. The Ophelia approach can be used to generate health service improvements that enhance health outcomes and address inequity of access to healthcare.

Rock riprap design for protection of stream channels near highway structures; Volume 2, Evaluation of Riprap design procedures

USGS Publications Warehouse

Blodgett, J.C.; McConaughy, C.E.

1986-01-01

In volume 2, seven procedures now being used for design of rock riprap installations were evaluated using data from 26 field sites. Four basic types of riprap failures were identified: Particle erosion, translational slide, modified slump, and slump. Factors associated with riprap failure include stone size , bank side slope, size gradation, thickness, insufficient toe or endwall, failure of the bank material, overtopping during floods, and geomorphic changes in the channel. A review of field data and the design procedures suggests that estimates of hydraulic forces acting on the boundary based on flow velocity rather than shear stress are more reliable. Several adjustments for local conditions, such as channel curvature, superelevation, or boundary roughness, may be unwarranted in view of the difficulty in estimating critical hydraulic forces for which the riprap is to be designed. Success of the riprap is related not only to the appropriate procedure for selecting stone size, but also to the reliability of estimated hydraulic and channel factors applicable to the site. (See also W89-04910) (Author 's abstract)

Technical and design update in the AUBE French low-level radioactive waste disposal facility

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

Marque, Y.

1989-01-01

Long-term industrial management of radioactive waste in France is carried out by the Agence Nationale pour la Gestion des Dechets Radioactifs (ANDRA). ANDRA is in charge of design, siting, construction, and operation of disposal centers. The solution selected in France for the disposal of low- and medium-level, short-lived radioactive waste is near-surface disposal in the earth using the principle of multiple barriers, in accordance with national safety rules and regulations, and based on operating experience from the Centre de Stockage de la Manche. Since the center's start-up in 1969, 400,000 m{sup 3} of waste have been disposed of. The Frenchmore » national program for waste management is proceeding with the construction of a second near-surface disposal, which is expected to be operational in 1991. It is located in the department of AUBE (from which its name derives), 100 miles southeast of Paris. The paper describes the criteria for siting and design of the AUBE disposal facility, design of the AUBE facility disposal module, and comparison with North Carolina and Pennsylvania disposal facility designs.« less

Progress on the European Extremely Large Telescope

NASA Astrophysics Data System (ADS)

Spyromilio, Jason; Comerón, Fernando; D'Odorico, Sandro; Kissler-Patig, Markus; Gilmozzi, Roberto

2008-09-01

In December 2006 the ESO Council gave the go-ahead for the European Extremely Large Telescope (E-ELT) three-year Phase B study. The Baseline Reference Design (BRD) was presented to the ESO committees in 2006 and to the community at the Marseille meeting in December 2006. Phase B has been running for one and a half years and a progress report is presented covering science activities, telescope design, instrumentation, site selection and operations. The designs are maturing, in close synergy with industrial contracts, and the proposal for E-ELT construction is expected to be presented to the ESO Council in June 2010.

Heterogeneous catalysis: Enigmas, illusions, challenges, realities, and emergent strategies of design

NASA Astrophysics Data System (ADS)

Thomas, John Meurig

2008-05-01

Predominantly this article deals with the question of how to design new solid catalysts for a variety of industrial and laboratory-orientated purposes. A generally applicable strategy, illustrated by numerous examples, is made possible based on the use of nanoporous materials on to the (high-area) inner surfaces of which well-defined (experimentally and computationally) active centers are placed in a spatially separated fashion. Such single-site catalysts, which have much in common with metal-centered homogenous catalysts and enzymes, enable a wide range of new catalysts to be designed for a variety of selective oxidations, hydrogenations, hydrations and hydrodewaxing, and other reactions that the "greening" of industrial processes demand. Examples are given of new shape-selective, regio-selective, and enantioselective catalysts, many of which operate under mild, environmentally benign conditions. Also considered are some of the reasons why detailed studies of adsorption and stoichiometric reactions at single-crystal surfaces have, disappointingly, not hitherto paved the way to the design and production of many new heterogenous catalysts. Recent work of a theoretical and high-throughout nature, allied to some experimental studies of well-chosen model systems, holds promise for the identification of new catalysts for simple, but industrially important reactions.

Assessment of the Unintentional Reuse of Municipal Wastewater

NASA Astrophysics Data System (ADS)

Okasaki, S.; Fono, L.; Sedlak, D. L.; Dracup, J. A.

2002-12-01

Many surface waters that receive wastewater effluent also serve as source waters for drinking water treatment plants. Recent research has shown that a number of previously undiscovered wastewater-derived contaminants are present in these surface waters, including pharmaceuticals and human hormones, several of which are suspected carcinogens or endocrine disrupters and are, as of yet, unregulated through drinking water standards. This research has been designed to determine the extent of contamination of specific wastewater-derived contaminants in surface water bodies that both receive wastewater effluent and serve as a source of drinking water to a sizeable population. We are testing the hypothesis that surface water supplies during low flow are potentially of worse quality than carefully monitored reclaimed water. The first phase of our research involves: (1) the selection of sites for study; (2) a hydrologic analysis of the selected sites to determine average flow of the source water during median- and low-flow conditions; and (3) the development and testing of chemical analyses, including both conservative and reactive tracers that have been studied in microcosms and wetlands for attenuation rates. The second phase involves the development and use of the hydrologic model QUAL2E to simulate each of the selected watersheds in order to estimate potential stream water quality impairments at the drinking water intake at each site. The results of the model are verified with field sampling at designated locations at each site. We expect to identify several critical river basins where surface water at the drinking water intake contains sufficient wastewater-derived contaminants to warrant concern. If wastewater-derived contaminants are detected, we will estimate the average annual exposure of consumers of this water. We will compare these expected and actual concentrations with typical constituent concentrations found in wastewater that has undergone advanced treatment for reclamation. We may demonstrate that the surface water supplies during low flow are actually of worse quality than carefully monitored reclaimed water.

Advanced Envelope Research for Factory Built Housing, Phase 3. Design Development and Prototyping

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

Levy, E.; Kessler, B.; Mullens, M.

2014-01-01

The Advanced Envelope Research effort will provide factory homebuilders with high performance, cost-effective alternative envelope designs. In the near term, these technologies will play a central role in meeting stringent energy code requirements. For manufactured homes, the thermal requirements, last updated by statute in 1994, will move up to the more rigorous IECC 2012 levels in 2013, the requirements of which are consistent with site built and modular housing. This places added urgency on identifying envelope technologies that the industry can implement in the short timeframe. The primary goal of this research is to develop wall designs that meet themore » thermal requirements based on 2012 IECC standards. Given the affordable nature of manufactured homes, impact on first cost is a major consideration in developing the new envelope technologies. This work is part of a four-phase, multi-year effort. Phase 1 identified seven envelope technologies and provided a preliminary assessment of three selected methods for building high performance wall systems. Phase 2 focused on the development of viable product designs, manufacturing strategies, addressing code and structural issues, and cost analysis of the three selected options. An industry advisory committee helped critique and select the most viable solution to move further in the research -- stud walls with continuous exterior insulation. Phase 3, the subject of the current report, focused on the design development of the selected wall concept and explored variations on the use of exterior foam insulation. The scope also included material selection, manufacturing and cost analysis, and prototyping and testing.« less

Advanced Envelope Research for Factory Built Housing, Phase 3 -- Design Development and Prototyping

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

Levy, E.; Kessler, B.; Mullens, M.

2014-01-01

The Advanced Envelope Research effort will provide factory homebuilders with high performance, cost-effective alternative envelope designs. In the near term, these technologies will play a central role in meeting stringent energy code requirements. For manufactured homes, the thermal requirements, last updated by statute in 1994, will move up to the more rigorous IECC 2012 levels in 2013, the requirements of which are consistent with site built and modular housing. This places added urgency on identifying envelope technologies that the industry can implement in the short timeframe. The primary goal of this research is to develop wall designs that meet themore » thermal requirements based on 2012 IECC standards. Given the affordable nature of manufactured homes, impact on first cost is a major consideration in developing the new envelope technologies. This work is part of a four-phase, multi-year effort. Phase 1 identified seven envelope technologies and provided a preliminary assessment of three selected methods for building high performance wall systems. Phase 2 focused on the development of viable product designs, manufacturing strategies, addressing code and structural issues, and cost analysis of the three selected options. An industry advisory committee helped critique and select the most viable solution to move further in the research -- stud walls with continuous exterior insulation. Phase 3, the subject of the current report, focused on the design development of the selected wall concept and explored variations on the use of exterior foam insulation. The scope also included material selection, manufacturing and cost analysis, and prototyping and testing.« less

Superfund record of decision amendment (EPA Region 5): Mid State Disposal Site, Marathon County, WI, August 4, 1995

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

NONE

The United States Environmental Protection Agency (U.S. EPS) is changing the remedy selected in the Original Record of Decision (ROD) dated September 30, 1988 (PB89-189559). The remedial design was completed in 1993, with construction completed in the Spring of 1994. Of the nine remedial components noted above, all except Component 4, the AWS, have been implemented or initiated as part of the Operation and Maintenance. During the course of the Pre-design activities, an initial hydrogeologic evaluation of the area around the site was completed to address the potential of establishing high-capacity water supply wells. The results of the study indicatedmore » that an AWS consisting of two upgradient wells was not a feasible alternative.« less

QUALITY ASSURANCE PROGRAM FOR WET DEPOSITION SAMPLING AND CHEMICAL ANALYSES FOR THE NATIONAL TRENDS NETWORK.

USGS Publications Warehouse

Schroder, LeRoy J.; Malo, Bernard A.; ,

1985-01-01

The purpose of the National Trends Network is to delineate the major inorganic constituents in the wet deposition in the United States. The approach chosen to monitor the Nation's wet deposition is to install approximately 150 automatic sampling devices with at least one collector in each state. Samples are collected at one week intervals, removed from collectors, and transported to an analytical laboratory for chemical analysis. The quality assurance program has divided wet deposition monitoring into 5 parts: (1) Sampling site selection, (2) sampling device, (3) sample container, (4) sample handling, and (5) laboratory analysis. Each of these five components is being examined using existing designs or new designs. Each existing or proposed sampling site is visited and a criteria audit is performed.

Clinical waste incinerators in Cameroon--a case study.

PubMed

Mochungong, Peter Ikome Kuwoh; Gulis, Gabriel; Sodemann, Morten

2012-01-01

Incinerators are widely used to treat clinical waste in Cameroon's Northwest Region. These incinerators cause public apprehension owing to purported risks to operators, communities and the environment. This article aims to summarize findings from an April 2008 case study. Three incinerators were randomly selected and investigated for site, design and operating standards. Empirical field observation was adopted and data collected through inventory and informal interviews. Bottom ash samples collected from the incinerators were prepared according to standard procedures and analyzed for heavy metals using Inductively Coupled Plasma (ICP) Emission Spectroscopy. Shortcomings associated with site selection, design and operation standards were identified. Chemical analysis revealed that Cr, Cu, Fe, Mn, Ni, Pb, Zn, Mg and Ca were present in the bottom ash with mean concentration ranging from 10 mg/kg for Pb to 178080 mg/kg for Ca. For logistic reasons, feedstock quantity and quality into the incinerators were not investigated. Neither were soil samples around and away from the incinerators. Although highly favored, clinical waste incineration methods in this region have to be reconsidered. A thorough health and environmental impact assessment is suggested before subsequent decisions on choice and disposal site is made. This will curb potential negative impacts to the environment and public health. This article adds a different perspective and sheds additional information to the debate on unsatisfactory clinical waste incinerators in resources-poor countries. Alternative methods to incineration are presented that will be helpful to practitioners.

Modernizing sports facilities

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

Dustin, R.

Modernization and renovation of sports facilities challenge the design team to balance a number of requirements: spectator and owner expectations, existing building and site conditions, architectural layouts, code and legislation issues, time constraints and budget issues. System alternatives are evaluated and selected based on the relative priorities of these requirements. These priorities are unique to each project. At Alexander Memorial Coliseum, project schedules, construction funds and facility usage became the priorities. The ACC basketball schedule and arrival of the Centennial Olympics dictated the construction schedule. Initiation and success of the project depended on the commitment of the design team tomore » meet coliseum funding levels established three years ago. Analysis of facility usage and system alternative capabilities drove the design team to select a system that met the project requirements and will maximize the benefits to the owner and spectators for many years to come.« less

Design, synthesis, and evaluation of inhibitors of trypanosomal and leishmanial dihydrofolate reductase.

PubMed

Chowdhury, S F; Villamor, V B; Guerrero, R H; Leal, I; Brun, R; Croft, S L; Goodman, J M; Maes, L; Ruiz-Perez, L M; Pacanowska, D G; Gilbert, I H

1999-10-21

This paper concerns the design, synthesis, and evaluation of inhibitors of leishmanial and trypanosomal dihydrofolate reductase. Initially study was made of the structures of the leishmanial and human enzyme active sites to see if there were significant differences which could be exploited for selective drug design. Then a series of compounds were synthesized based on 5-benzyl-2, 4-diaminopyrimidines. These compounds were assayed against the protozoan and human enzymes and showed selectivity for the protozoan enzymes. The structural data was then used to rationalize the enzyme assay data. Compounds were also tested against the clinically relevant forms of the intact parasite. Activity was seen against the trypanosomes for a number of compounds. The compounds were in general less active against Leishmania. This latter result may be due to uptake problems. Two of the compounds also showed some in vivo activity in a model of African trypanosomiasis.

Testing the efficiency of rover science protocols for robotic sample selection: A GeoHeuristic Operational Strategies Test

NASA Astrophysics Data System (ADS)

Yingst, R. A.; Bartley, J. K.; Chidsey, T. C.; Cohen, B. A.; Gilleaudeau, G. J.; Hynek, B. M.; Kah, L. C.; Minitti, M. E.; Williams, R. M. E.; Black, S.; Gemperline, J.; Schaufler, R.; Thomas, R. J.

2018-05-01

The GHOST field tests are designed to isolate and test science-driven rover operations protocols, to determine best practices. During a recent field test at a potential Mars 2020 landing site analog, we tested two Mars Science Laboratory data-acquisition and decision-making methods to assess resulting science return and sample quality: a linear method, where sites of interest are studied in the order encountered, and a "walkabout-first" method, where sites of interest are examined remotely before down-selecting to a subset of sites that are interrogated with more resource-intensive instruments. The walkabout method cost less time and fewer resources, while increasing confidence in interpretations. Contextual data critical to evaluating site geology was acquired earlier than for the linear method, and given a higher priority, which resulted in development of more mature hypotheses earlier in the analysis process. Combined, this saved time and energy in the collection of data with more limited spatial coverage. Based on these results, we suggest that the walkabout method be used where doing so would provide early context and time for the science team to develop hypotheses-critical tests; and that in gathering context, coverage may be more important than higher resolution.

WWW Motivation Mining: Finding Treasures for Teaching Evaluation Skills, Grades 1-6. Professional Growth Series.

ERIC Educational Resources Information Center

Arnone, Marilyn P.; Small, Ruth V.

Designed for elementary or middle school teachers and library media specialists, this book provides educators with practical, easy-to-use ways of applying motivation assessment techniques when selecting World Wide Web sites for inclusion in their lessons and offers concrete examples of how to use Web evaluation with young learners. WebMAC…

THE RELATIONSHIP BETWEEN TEMPERATURE, PHYSICAL HABITAT AND FISH ASSEMBLAGE DATA IN A STATE WIDE PROBABILITY SURVEY OF OREGON STREAMS

EPA Science Inventory

To assess the ecological condition of streams and rivers in Oregon, we sampled 146 sites
in summer, 1997 as part of the U.S. EPA's Environmental Monitoring and Assessment Program.
Sample reaches were selected using a systematic, randomized sample design from the blue-line n...

A Collaborative Model to Identify and Implement Applications of Research on Effective Teaching to Preservice/Inservice Teacher Education.

ERIC Educational Resources Information Center

Ponzio, Richard

Mills College (California) was one of three sites selected to participate in a project designed to apply and use research in elementary teacher education. The project trained student teachers and cooperating teachers to measure academic learning time and active teacher behaviors with instruments developed by recent research on teacher…

Commercial phosphoric acid fuel cell system technology development

NASA Technical Reports Server (NTRS)

Prokopius, P. R.; Warshay, M.; Simons, S. N.; King, R. B.

1979-01-01

Reducing cost and increasing reliability were the technology drivers in both the electric utility and on-site integrated energy system applications. The longstanding barrier to the attainment of these goals was materials. Differences in approaches and their technological features, including electrodes, matrices, intercell cooling, bipolar/separator plates, electrolyte management, fuel selection, and system design philosophy were discussed.

A relatively nonrestrictive approach to reducing campsite impact: Caney Creek Wilderness, Arkansas

Treesearch

David N. Cole; Thomas E. Ferguson

2009-01-01

An excessive number of highly impacted campsites led managers of the Caney Creek Wilderness to attempt to reduce campsite impacts with a program of trail relocation, education, closure of selected campsites, and site restoration. The strategy involved increasing the concentration of use somewhat, without resorting to the restrictiveness of a designated campsite policy...

40 CFR 761.250 - Sample site selection for pipeline section abandonment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Sample site selection for pipeline... Disposal of Natural Gas Pipeline: Selecting Sample Sites, Collecting Surface Samples, and Analyzing Standard PCB Wipe Samples § 761.250 Sample site selection for pipeline section abandonment. This procedure...

40 CFR 761.250 - Sample site selection for pipeline section abandonment.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Sample site selection for pipeline... Disposal of Natural Gas Pipeline: Selecting Sample Sites, Collecting Surface Samples, and Analyzing Standard PCB Wipe Samples § 761.250 Sample site selection for pipeline section abandonment. This procedure...

Lacie phase 1 Classification and Mensuration Subsystem (CAMS) rework experiment

NASA Technical Reports Server (NTRS)

Chhikara, R. S.; Hsu, E. M.; Liszcz, C. J.

1976-01-01

An experiment was designed to test the ability of the Classification and Mensuration Subsystem rework operations to improve wheat proportion estimates for segments that had been processed previously. Sites selected for the experiment included three in Kansas and three in Texas, with the remaining five distributed in Montana and North and South Dakota. The acquisition dates were selected to be representative of imagery available in actual operations. No more than one acquisition per biophase were used, and biophases were determined by actual crop calendars. All sites were worked by each of four Analyst-Interpreter/Data Processing Analyst Teams who reviewed the initial processing of each segment and accepted or reworked it for an estimate of the proportion of small grains in the segment. Classification results, acquisitions and classification errors and performance results between CAMS regular and ITS rework are tabulated.

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

Northeast Oregon Hatchery Project, Final Siting Report.

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

Watson, Montgomery

1995-03-01

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

Siting a municipal solid waste disposal facility, part II: the effects of external criteria on the final decision.

PubMed

Korucu, M Kemal; Karademir, Aykan

2014-02-01

The procedure of a multi-criteria decision analysis supported by the geographic information systems was applied to the site selection process of a planning municipal solid waste management practice based on twelve different scenarios. The scenarios included two different decision tree modes and two different weighting models for three different area requirements. The suitability rankings of the suitable sites obtained from the application of the decision procedure for the scenarios were assessed by a factorial experimental design concerning the effect of some external criteria on the final decision of the site selection process. The external criteria used in the factorial experimental design were defined as "Risk perception and approval of stakeholders" and "Visibility". The effects of the presence of these criteria in the decision trees were evaluated in detail. For a quantitative expression of the differentiations observed in the suitability rankings, the ranking data were subjected to ANOVA test after a normalization process. Then the results of these tests were evaluated by Tukey test to measure the effects of external criteria on the final decision. The results of Tukey tests indicated that the involvement of the external criteria into the decision trees produced statistically meaningful differentiations in the suitability rankings. Since the external criteria could cause considerable external costs during the operation of the disposal facilities, the presence of these criteria in the decision tree in addition to the other criteria related to environmental and legislative requisites could prevent subsequent external costs in the first place.

Exploration of alternate catalytic mechanisms and optimization strategies for retroaldolase design.

PubMed

Bjelic, Sinisa; Kipnis, Yakov; Wang, Ling; Pianowski, Zbigniew; Vorobiev, Sergey; Su, Min; Seetharaman, Jayaraman; Xiao, Rong; Kornhaber, Gregory; Hunt, John F; Tong, Liang; Hilvert, Donald; Baker, David

2014-01-09

Designed retroaldolases have utilized a nucleophilic lysine to promote carbon-carbon bond cleavage of β-hydroxy-ketones via a covalent Schiff base intermediate. Previous computational designs have incorporated a water molecule to facilitate formation and breakdown of the carbinolamine intermediate to give the Schiff base and to function as a general acid/base. Here we investigate an alternative active-site design in which the catalytic water molecule was replaced by the side chain of a glutamic acid. Five out of seven designs expressed solubly and exhibited catalytic efficiencies similar to previously designed retroaldolases for the conversion of 4-hydroxy-4-(6-methoxy-2-naphthyl)-2-butanone to 6-methoxy-2-naphthaldehyde and acetone. After one round of site-directed saturation mutagenesis, improved variants of the two best designs, RA114 and RA117, exhibited among the highest kcat (>10(-3)s(-1)) and kcat/KM (11-25M(-1)s(-1)) values observed for retroaldolase designs prior to comprehensive directed evolution. In both cases, the >10(5)-fold rate accelerations that were achieved are within 1-3 orders of magnitude of the rate enhancements reported for the best catalysts for related reactions, including catalytic antibodies (kcat/kuncat=10(6) to 10(8)) and an extensively evolved computational design (kcat/kuncat>10(7)). The catalytic sites, revealed by X-ray structures of optimized versions of the two active designs, are in close agreement with the design models except for the catalytic lysine in RA114. We further improved the variants by computational remodeling of the loops and yeast display selection for reactivity of the catalytic lysine with a diketone probe, obtaining an additional order of magnitude enhancement in activity with both approaches. © 2013.

Disaggregated seismic hazard and the elastic input energy spectrum: An approach to design earthquake selection

NASA Astrophysics Data System (ADS)

Chapman, Martin Colby

1998-12-01

The design earthquake selection problem is fundamentally probabilistic. Disaggregation of a probabilistic model of the seismic hazard offers a rational and objective approach that can identify the most likely earthquake scenario(s) contributing to hazard. An ensemble of time series can be selected on the basis of the modal earthquakes derived from the disaggregation. This gives a useful time-domain realization of the seismic hazard, to the extent that a single motion parameter captures the important time-domain characteristics. A possible limitation to this approach arises because most currently available motion prediction models for peak ground motion or oscillator response are essentially independent of duration, and modal events derived using the peak motions for the analysis may not represent the optimal characterization of the hazard. The elastic input energy spectrum is an alternative to the elastic response spectrum for these types of analyses. The input energy combines the elements of amplitude and duration into a single parameter description of the ground motion that can be readily incorporated into standard probabilistic seismic hazard analysis methodology. This use of the elastic input energy spectrum is examined. Regression analysis is performed using strong motion data from Western North America and consistent data processing procedures for both the absolute input energy equivalent velocity, (Vsbea), and the elastic pseudo-relative velocity response (PSV) in the frequency range 0.5 to 10 Hz. The results show that the two parameters can be successfully fit with identical functional forms. The dependence of Vsbea and PSV upon (NEHRP) site classification is virtually identical. The variance of Vsbea is uniformly less than that of PSV, indicating that Vsbea can be predicted with slightly less uncertainty as a function of magnitude, distance and site classification. The effects of site class are important at frequencies less than a few Hertz. The regression modeling does not resolve significant effects due to site class at frequencies greater than approximately 5 Hz. Disaggregation of general seismic hazard models using Vsbea indicates that the modal magnitudes for the higher frequency oscillators tend to be larger, and vary less with oscillator frequency, than those derived using PSV. Insofar as the elastic input energy may be a better parameter for quantifying the damage potential of ground motion, its use in probabilistic seismic hazard analysis could provide an improved means for selecting earthquake scenarios and establishing design earthquakes for many types of engineering analyses.

Designed to dissolve: suppression of colloidal aggregation of Cu(I)-selective fluorescent probes in aqueous buffer and in-gel detection of a metallochaperone.

PubMed

Morgan, M Thomas; Bagchi, Pritha; Fahrni, Christoph J

2011-10-12

Due to the lipophilicity of the metal-ion receptor, previously reported Cu(I)-selective fluorescent probes form colloidal aggregates, as revealed by dynamic light scattering. To address this problem, we have developed a hydrophilic triarylpyrazoline-based fluorescent probe, CTAP-2, that dissolves directly in water and shows a rapid, reversible, and highly selective 65-fold fluorescence turn-on response to Cu(I) in aqueous solution. CTAP-2 proved to be sufficiently sensitive for direct in-gel detection of Cu(I) bound to the metallochaperone Atox1, demonstrating the potential for cation-selective fluorescent probes to serve as tools in metalloproteomics for identifying proteins with readily accessible metal-binding sites.

Material Selection Guidelines to Limit Atomic Oxygen Effects on Spacecraft Surfaces

NASA Technical Reports Server (NTRS)

Dooling, D.; Finckenor, M. M.

1999-01-01

This report provides guidelines in selecting materials for satellites and space platforms, designed to operate within the Low-Earth orbit environment, which limit the effects of atomic oxygen interactions with spacecraft surfaces. This document should be treated as an introduction rather than a comprehensive guide since analytical and flight technologies continue to evolve, flight experiments are conducted as primary or piggyback opportunities arise, and our understanding of materials interactions and protection methods grows. The reader is urged to consult recent literature and current web sites containing information about research and flight results.

Design and Characterization of a Multifunctional pH-Triggered Peptide C8 for Selective Anticancer Activity.

PubMed

Lu, Sheng; Bennett, W F Drew; Ding, Yong; Zhang, Lei; Fan, Helen Y; Zhao, Danyang; Zheng, Tao; Ouyang, Ping-Kai; Li, Jason; Wu, Yan; Xu, Wen; Chu, Dafeng; Yuan, Yongfang; Heerklotz, Heiko; Karttunen, Mikko; Chen, P

2015-12-09

Most drug delivery systems have been developed for efficient delivery to tumor sites via targeting and on-demand strategies, but the carriers rarely execute synergistic therapeutic actions. In this work, C8, a cationic, pH-triggered anticancer peptide, is developed by incorporating histidine-mediated pH-sensitivity, amphipathic helix, and amino acid pairing self-assembly design. We designed C8 to function as a pH-responsive nanostructure whose cytotoxicity can be switched on and off by its self-assembly: Noncytotoxic β-sheet fibers at high pH with neutral histidines, and positively charged monomers with membrane lytic activity at low pH. The selective activity of C8, tested for three different cancer cell lines and two noncancerous cell lines, is shown. Based on liposome leakage assays and multiscale computer simulations, its physical mechanisms of pore-forming action and selectivity are proposed, which originate from differences in the lipid composition of the cellular membrane and changes in hydrogen bonding. C8 is then investigated for its potential as a drug carrier. C8 forms a nanocomplex with ellipticine, a nonselective model anticancer drug. It selectively targets cancer cells in a pH-responsive manner, demonstrating enhanced efficacy and selectivity. This study provides a novel powerful strategy for the design and development of multifunctional self-assembling peptides for therapeutic and drug delivery applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

DESIGNING AN OPPORTUNITY FUEL WITH BIOMASS AND TIRE-DERIVED FUEL FOR COFIRING AT WILLOW ISLAND GENERATING STATION

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

K. Payette; D. Tillman

During the period January 1, 2001-March 31, 2001, Allegheny Energy Supply Co., LLC (Allegheny) finalized the engineering of the Willow Island cofiring project, completed the fuel characterizations for both the Willow Island and Albright Generating Station projects, and initiated construction of both projects. Allegheny and its contractor, Foster Wheeler, selected appropriate fuel blends and issued purchase orders for all processing and mechanical equipment to be installed at both sites. This report summarizes the activities associated with the Designer Opportunity Fuel program, and demonstrations at Willow Island and Albright Generating Stations. The third quarter of the project involved completing the detailedmore » designs for the Willow Island Designer Fuel project. It also included complete characterization of the coal and biomass fuels being burned, focusing upon the following characteristics: proximate and ultimate analysis; higher heating value; carbon 13 nuclear magnetic resonance testing for aromaticity, number of aromatic carbons per cluster, and the structural characteristics of oxygen in the fuel; drop tube reactor testing for high temperature devolatilization kinetics and generation of fuel chars; thermogravimetric analyses (TGA) for char oxidation kinetics; and related testing. The construction at both sites commenced during this quarter, and was largely completed at the Albright Generating Station site.« less

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

Development of cloud-operating platform for detention facility design

NASA Astrophysics Data System (ADS)

Tun Lee, Kwan; Hung, Meng-Chiu; Tseng, Wei-Fan; Chan, Yi-Ping

2017-04-01

In the past 20 years, the population of Taiwan has accumulated in urban areas. The land development has changed the hydrological environment and resulted in the increase of surface runoff and shortened the time to peak discharge. The change of runoff characteristics increases the flood risk and reduces resilient ability of the city during flood. Considering that engineering measures may not be easy to implement in populated cities, detention facilities set on building basements have been proposed to compromise the increase of surface runoff resulting from development activities. In this study, a web-based operational platform has been developed to integrate the GIS technologies, hydrological analyses, as well as relevant regulations for the design of detention facilities. The design procedure embedded in the system includes a prior selection of type and size of the detention facility, integrated hydrological analysis for the developing site, and inspection of relevant regulations. After login the platform, designers can access the system database to retrieve road maps, land use coverages, and storm sewer information. Once the type, size, inlet, and outlet of the detention facility are assigned, the system can acquire the rainfall intensity-duration-frequency information from adjacent rain gauges to perform hydrological analyses for the developing site. The increase of the runoff volume due to the development and the reduction of the outflow peak through the construction of the detention facility can be estimated. The outflow peak at the target site is then checked with relevant regulations to confirm the suitability of the detention facility design. The proposed web-based platform can provide a concise layout of the detention facility and the drainageway of the developing site on a graphical interface. The design information can also be delivered directly through a web link to authorities for inspecting to simplify the complex administrative procedures.

Caseoperoxidase, mixed β-casein-SDS-hemin-imidazole complex: a nano artificial enzyme.

PubMed

Moosavi-Movahedi, Zainab; Gharibi, Hussein; Hadi-Alijanvand, Hamid; Akbarzadeh, Mohammad; Esmaili, Mansoore; Atri, Maliheh S; Sefidbakht, Yahya; Bohlooli, Mousa; Nazari, Khodadad; Javadian, Soheila; Hong, Jun; Saboury, Ali A; Sheibani, Nader; Moosavi-Movahedi, Ali A

2015-01-01

A novel peroxidase-like artificial enzyme, named "caseoperoxidase", was biomimetically designed using a nano artificial amino acid apo-protein hydrophobic pocket. This four-component nano artificial enzyme containing heme-imidazole-β-casein-SDS exhibited high activity growth and k(cat) performance toward the native horseradish peroxidase demonstrated by the steady state kinetics using UV-vis spectrophotometry. The hydrophobicity and secondary structure of the caseoperoxidase were studied by ANS fluorescence and circular dichroism spectroscopy. Camel β-casein (Cβ-casein) was selected as an appropriate apo-protein for the heme active site because of its innate flexibility and exalted hydrophobicity. This selection was confirmed by homology modeling method. Heme docking into the newly obtained Cβ-casein structure indicated one heme was mainly incorporated with Cβ-casein. The presence of a main electrostatic site for the active site in the Cβ-casein was also confirmed by experimental methods through Wyman binding potential and isothermal titration calorimetry. The existence of Cβ-casein protein in this biocatalyst lowered the suicide inactivation and provided a suitable protective role for the heme active-site. Additional experiments confirmed the retention of caseoperoxidase structure and function as an artificial enzyme.

Wet soil cover applicability and design

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

Hunter, F.; Feenstra, S.; Hwang, D.

1996-12-31

As part of a focused feasibility study for the Tyson Superfund site, Daekyoo Hwang, then with ERM, developed a flooding/flushing option. It was not considered a viable option due to concerns over contaminated groundwater control. The concept, however, had several attractive features: control of VOC emissions; the downward movement of water prevents contamination of the overlying clean soil by the upward movement of contaminated soil vapor; and some natural attenuation of the contaminated lagoon area soils. The new concept employs a near saturated soil layer to prevent VOC emission and the downward movement of water to prevent contamination of surfacemore » soil. The wet soil cover became one of five alternatives submitted as part of the focused feasibility study. It was selected as the remedial option for the site by the USEPA. The study was reviewed by the public and they also were positive as to the use of a wet soil cover to control VOC emissions at the site. The wet soil cover is currently being designed by Smith Environmental.« less

Structural insight to mutation effects uncover a common allosteric site in class C GPCRs.

PubMed

Harpsøe, Kasper; Boesgaard, Michael W; Munk, Christian; Bräuner-Osborne, Hans; Gloriam, David E

2017-04-15

Class C G protein-coupled receptors (GPCRs) regulate important physiological functions and allosteric modulators binding to the transmembrane domain constitute an attractive and, due to a lack of structural insight, a virtually unexplored potential for therapeutics and the food industry. Combining pharmacological site-directed mutagenesis data with the recent class C GPCR experimental structures will provide a foundation for rational design of new therapeutics. We uncover one common site for both positive and negative modulators with different amino acid layouts that can be utilized to obtain selectivity. Additionally, we show a large potential for structure-based modulator design, especially for four orphan receptors with high similarity to the crystal structures. All collated mutagenesis data is available in the GPCRdb mutation browser at http://gpcrdb.org/mutations/ and can be analyzed online or downloaded in excel format. david.gloriam@sund.ku.dk. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

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

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).

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

The space station integrated refuse management system

NASA Technical Reports Server (NTRS)

Anderson, Loren A.

1988-01-01

The design and development of an Integrated Refuse Management System for the proposed International Space Station was performed. The primary goal was to make use of any existing potential energy or material properties that refuse may possess. The secondary goal was based on the complete removal or disposal of those products that could not, in any way, benefit astronauts' needs aboard the Space Station. The design of a continuous living and experimental habitat in space has spawned the need for a highly efficient and effective refuse management system capable of managing nearly forty-thousand pounds of refuse annually. To satisfy this need, the following four integrable systems were researched and developed: collection and transfer; recycle and reuse; advance disposal; and propulsion assist in disposal. The design of a Space Station subsystem capable of collecting and transporting refuse from its generation site to its disposal and/or recycling site was accomplished. Several methods of recycling or reusing refuse in the space environment were researched. The optimal solution was determined to be the method of pyrolysis. The objective of removing refuse from the Space Station environment, subsequent to recycling, was fulfilled with the design of a jettison vehicle. A number of jettison vehicle launch scenarios were analyzed. Selection of a proper disposal site and the development of a system to propel the vehicle to that site were completed. Reentry into the earth atmosphere for the purpose of refuse incineration was determined to be the most attractive solution.

Tales from the New Frontier: Pioneers' Experiences with Consumer-Driven Health Care

PubMed Central

Lo Sasso, Anthony T; Rice, Thomas; Gabel, Jon R; Whitmore, Heidi

2004-01-01

Objective To conduct site visits to study the early experiences of firms offering consumer-driven health care (CDHC) plans to their employees and firms that provide CDHC products. Data Sources/Study Setting A convenience sample of three firms offering CDHC products to their employees, one of which is also a large insurer, and one firm offering an early CDHC product to employers. Study Design We conducted onsite interviews of four companies during the spring and summer of 2003. These four cases were not selected randomly. We contacted organizations that already had a consumer-driven plan in place by January 2002 so as to provide a complete year's worth of experience with CDHC. Principal Findings The experience of the companies we visited indicated that favorable selection tends to result when a CDHC plan is introduced alongside traditional preferred provider organization (PPO) and health maintenance organization (HMO) plan offerings. Two sites demonstrated substantial cost-savings. Our case studies also indicate that the more mundane aspects of health care benefits are still crucial under CDHC. The size of the provider network accessible through the CDHC plan was critical, as was the role of premium contributions in the benefit design. Also, companies highlighted the importance of educating employees about new CDHC products: employees who understood the product were more likely to enroll. Conclusions Our site visits suggest the peril (risk selection) and the promise (cost savings) of CDHC. At this point there is still far more that we do not know about CDHC than we do know. Little is known about the extent to which CDHC changes people's behavior, the extent to which quality of care is affected by CDHC, and whether web-based information and tools actually make patients become better consumers. PMID:15230912

Regulatory requirements for nuclear power plant site selection in Malaysia-a review.

PubMed

Basri, N A; Hashim, S; Ramli, A T; Bradley, D A; Hamzah, K

2016-12-01

Malaysia has initiated a range of pre-project activities in preparation for its planned nuclear power programme. Clearly one of the first steps is the selection of sites that are deemed suitable for the construction and operation of a nuclear power plant. Here we outline the Malaysian regulatory requirements for nuclear power plant site selection, emphasizing details of the selection procedures and site characteristics needed, with a clear focus on radiation safety and radiation protection in respect of the site surroundings. The Malaysia Atomic Energy Licensing Board (AELB) site selection guidelines are in accord with those provided in International Atomic Energy Agency (IAEA) and United Stated Nuclear Regulatory Commission (USNRC) documents. To enhance the suitability criteria during selection, as well as to assist in the final decision making process, possible assessments using the site selection characteristics and information are proposed.

In silico designing of hyper-glycosylated analogs for the human coagulation factor IX.

PubMed

Ghasemi, Fahimeh; Zomorodipour, Alireza; Karkhane, Ali Asghar; Khorramizadeh, M Reza

2016-07-01

N-glycosylation is a process during which a glycan moiety attaches to the asparagine residue in the N-glycosylation consensus sequence (Asn-Xxx-Ser/Thr), where Xxx can be any amino acid except proline. Introduction of a new N-glycosylation site into a protein backbone leads to its hyper-glycosylation, and may improve the protein properties such as solubility, folding, stability, and secretion. Glyco-engineering is an approach to facilitate the hyper-glycosylation of recombinant proteins by application of the site-directed mutagenesis methods. In this regard, selection of a suitable location on the surface of a protein for introduction of a new N-glycosylation site is a main concern. In this work, a computational approach was conducted to select suitable location(s) for introducing new N-glycosylation sites into the human coagulation factor IX (hFIX). With this aim, the first 45 residues of mature hFIX were explored to find out suitable positions for introducing either Asn or Ser/Thr residues, to create new N-glycosylation site(s). Our exploration lead to detection of five potential positions, for hyper-glycosylation. For each suggested position, an analog was defined and subjected for N-glycosylation efficiency prediction. After generation of three-dimensional structures, by homology-based modeling, the five designed analogs were examined by molecular dynamic (MD) simulations, to predict their stability levels and probable structural distortions caused by amino acid substitutions, relative to the native counterpart. Three out of five suggested analogs, namely; E15T, K22N, and R37N, reached equilibration state with relatively constant Root Mean Square Deviation values. Additional analysis on the data obtained during MD simulations, lead us to conclude that, R37N is the only qualified analog with the most similar structure and dynamic behavior to that of the native counterpart, to be considered for further experimental investigations. Copyright © 2016 Elsevier Inc. All rights reserved.

40 CFR 228.6 - Specific criteria for site selection.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Specific criteria for site selection... selection. (a) In the selection of disposal sites, in addition to other necessary or appropriate factors...) Existence at or in close proximity to the site of any significant natural or cultural features of historical...

Prevention of EP Migratory Contamination in a Cluster Randomized Trial to Increase tPA Use in Stroke (The INSTINCT Trial)

PubMed Central

Weston, Victoria C.; Meurer, William J.; Frederiksen, Shirley M.; Fox, Allison K.; Scott, Phillip A.

2016-01-01

Objectives Cluster randomized trials (CRTs) are increasingly utilized to evaluate quality improvement interventions aimed at healthcare providers. In trials testing emergency department interventions, migration of emergency physicians (EPs) between hospitals is an important concern, as contamination may affect both internal and external validity. We hypothesized that geographically isolating emergency departments would prevent migratory contamination in a CRT designed to increase ED delivery of tPA in stroke (The INSTINCT Trial). Methods INSTINCT was a prospective, cluster randomized, controlled trial. 24 Michigan community hospitals were randomly selected in matched pairs for study. Contamination was defined at the cluster level, with substantial contamination defined a priori as >10% of EPs affected. Non-adherence, total crossover (contamination + non-adherence), migration distance and characteristics were determined. Results 307 emergency physicians were identified at all sites. Overall, 7 (2.3%) changed study sites. 1 moved between control sites, leaving 6 (2.0%) total crossovers. Of these, 2 (0.7%) moved from intervention to control (contamination) and 4 (1.3%) moved from control to intervention (non-adherence). Contamination was observed in 2 of 12 control sites, with 17% and 9% contamination of the total site EP workforce at follow-up, respectively. Average migration distance was 42 miles for all EPs moving in the study and 35 miles for EPs moving from intervention to control sites. Conclusion The mobile nature of emergency physicians should be considered in the design of quality improvement CRTs. Increased reporting of contamination in CRTs is encouraged to clarify thresholds and facilitate CRT design. PMID:25440230