Retirement investment theory explains patterns in songbird nest-site choice

USGS Publications Warehouse

Streby, Henry M.; Refsnider, Jeanine M.; Peterson, Sean M.; Andersen, David E.

2014-01-01

When opposing evolutionary selection pressures act on a behavioural trait, the result is often stabilizing selection for an intermediate optimal phenotype, with deviations from the predicted optimum attributed to tracking a moving target, development of behavioural syndromes or shifts in riskiness over an individual's lifetime. We investigated nest-site choice by female golden-winged warblers, and the selection pressures acting on that choice by two fitness components, nest success and fledgling survival. We observed strong and consistent opposing selection pressures on nest-site choice for maximizing these two fitness components, and an abrupt, within-season switch in the fitness component birds prioritize via nest-site choice, dependent on the time remaining for additional nesting attempts. We found that females consistently deviated from the predicted optimal behaviour when choosing nest sites because they can make multiple attempts at one fitness component, nest success, but only one attempt at the subsequent component, fledgling survival. Our results demonstrate a unique natural strategy for balancing opposing selection pressures to maximize total fitness. This time-dependent switch from high to low risk tolerance in nest-site choice maximizes songbird fitness in the same way a well-timed switch in human investor risk tolerance can maximize one's nest egg at retirement. Our results also provide strong evidence for the adaptive nature of songbird nest-site choice, which we suggest has been elusive primarily due to a lack of consideration for fledgling survival.

Using maximum entropy modeling for optimal selection of sampling sites for monitoring networks

USGS Publications Warehouse

Stohlgren, Thomas J.; Kumar, Sunil; Barnett, David T.; Evangelista, Paul H.

2011-01-01

Environmental monitoring programs must efficiently describe state shifts. We propose using maximum entropy modeling to select dissimilar sampling sites to capture environmental variability at low cost, and demonstrate a specific application: sample site selection for the Central Plains domain (453,490 km2) of the National Ecological Observatory Network (NEON). We relied on four environmental factors: mean annual temperature and precipitation, elevation, and vegetation type. A “sample site” was defined as a 20 km × 20 km area (equal to NEON’s airborne observation platform [AOP] footprint), within which each 1 km2 cell was evaluated for each environmental factor. After each model run, the most environmentally dissimilar site was selected from all potential sample sites. The iterative selection of eight sites captured approximately 80% of the environmental envelope of the domain, an improvement over stratified random sampling and simple random designs for sample site selection. This approach can be widely used for cost-efficient selection of survey and monitoring sites.

Assessment of Distributed Generation Potential in JapaneseBuildings

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

Zhou, Nan; Marnay, Chris; Firestone, Ryan

2005-05-25

To meet growing energy demands, energy efficiency, renewable energy, and on-site generation coupled with effective utilization of exhaust heat will all be required. Additional benefit can be achieved by integrating these distributed technologies into distributed energy resource (DER) systems (or microgrids). This research investigates a method of choosing economically optimal DER, expanding on prior studies at the Berkeley Lab using the DER design optimization program, the Distributed Energy Resources Customer Adoption Model (DER-CAM). DER-CAM finds the optimal combination of installed equipment from available DER technologies, given prevailing utility tariffs, site electrical and thermal loads, and a menu of available equipment.more » It provides a global optimization, albeit idealized, that shows how the site energy loads can be served at minimum cost by selection and operation of on-site generation, heat recovery, and cooling. Five prototype Japanese commercial buildings are examined and DER-CAM applied to select the economically optimal DER system for each. The five building types are office, hospital, hotel, retail, and sports facility. Based on the optimization results, energy and emission reductions are evaluated. Furthermore, a Japan-U.S. comparison study of policy, technology, and utility tariffs relevant to DER installation is presented. Significant decreases in fuel consumption, carbon emissions, and energy costs were seen in the DER-CAM results. Savings were most noticeable in the sports facility (a very favourable CHP site), followed by the hospital, hotel, and office building.« less

Selecting at-risk populations for sexually transmitted disease/HIV intervention studies.

PubMed

Wu, Zunyou; Rotheram-Borus, Mary Jane; Detels, Roger; Li, Li; Guan, Jihui; Liang, Guojun; Yap, Lorraine

2007-12-01

This paper describes one option to select populations for randomized, controlled trials (RCT). We used a popular opinion leader intervention in Fuzhou, China, to: (1) identify population selection criteria; (2) systematically examine the suitability of potential target populations and settings; (3) briefly evaluate risk and stability in the population; and (4) evaluate regional and organizational support among administrators and government officials. After comparing migrant villagers, truck drivers, factory workers, construction workers, and market employees in five regions of China, market employees in Fuzhou were identified as the optimal target population. Markets were the optimal sites for several reasons: (1) the population demonstrated a sufficient base rate of sexually transmitted diseases; (2) the population was stable over time; (3) a sufficient number of sites of manageable sizes were available; (4) stable networks existed; (5) local gatekeepers/stakeholders supported the intervention; (6) there was organizational capacity in the local health department to mount the intervention; (7) the demographic profile was similar across potential sites; and (8) the sites were sufficiently distanced to minimize contamination. Evaluating intervention efficacy in an RCT requires a time-consuming and rigorous process that systematically and routinely documents selection criteria, evaluates multiple populations, sites, and organizations for their appropriateness.

Optimal location selection for the installation of urban green roofs considering honeybee habitats along with socio-economic and environmental effects.

PubMed

Gwak, Jae Ha; Lee, Bo Kyeong; Lee, Won Kyung; Sohn, So Young

2017-03-15

This study proposes a new framework for the selection of optimal locations for green roofs to achieve a sustainable urban ecosystem. The proposed framework selects building sites that can maximize the benefits of green roofs, based not only on the socio-economic and environmental benefits to urban residents, but also on the provision of urban foraging sites for honeybees. The framework comprises three steps. First, building candidates for green roofs are selected considering the building type. Second, the selected building candidates are ranked in terms of their expected socio-economic and environmental effects. The benefits of green roofs are improved energy efficiency and air quality, reduction of urban flood risk and infrastructure improvement costs, reuse of storm water, and creation of space for education and leisure. Furthermore, the estimated cost of installing green roofs is also considered. We employ spatial data to determine the expected effects of green roofs on each building unit, because the benefits and costs may vary depending on the location of the building. This is due to the heterogeneous spatial conditions. In the third step, the final building sites are proposed by solving the maximal covering location problem (MCLP) to determine the optimal locations for green roofs as urban honeybee foraging sites. As an illustrative example, we apply the proposed framework in Seoul, Korea. This new framework is expected to contribute to sustainable urban ecosystems. Copyright © 2016 Elsevier Ltd. All rights reserved.

Retirement investment theory explains patterns in songbird nest-site choice

PubMed Central

Streby, Henry M.; Refsnider, Jeanine M.; Peterson, Sean M.; Andersen, David E.

2014-01-01

When opposing evolutionary selection pressures act on a behavioural trait, the result is often stabilizing selection for an intermediate optimal phenotype, with deviations from the predicted optimum attributed to tracking a moving target, development of behavioural syndromes or shifts in riskiness over an individual's lifetime. We investigated nest-site choice by female golden-winged warblers, and the selection pressures acting on that choice by two fitness components, nest success and fledgling survival. We observed strong and consistent opposing selection pressures on nest-site choice for maximizing these two fitness components, and an abrupt, within-season switch in the fitness component birds prioritize via nest-site choice, dependent on the time remaining for additional nesting attempts. We found that females consistently deviated from the predicted optimal behaviour when choosing nest sites because they can make multiple attempts at one fitness component, nest success, but only one attempt at the subsequent component, fledgling survival. Our results demonstrate a unique natural strategy for balancing opposing selection pressures to maximize total fitness. This time-dependent switch from high to low risk tolerance in nest-site choice maximizes songbird fitness in the same way a well-timed switch in human investor risk tolerance can maximize one's nest egg at retirement. Our results also provide strong evidence for the adaptive nature of songbird nest-site choice, which we suggest has been elusive primarily due to a lack of consideration for fledgling survival. PMID:24403320

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.

Switches in Genomic GC Content Drive Shifts of Optimal Codons under Sustained Selection on Synonymous Sites

PubMed Central

Sun, Yu; Tamarit, Daniel

2017-01-01

Abstract The major codon preference model suggests that codons read by tRNAs in high concentrations are preferentially utilized in highly expressed genes. However, the identity of the optimal codons differs between species although the forces driving such changes are poorly understood. We suggest that these questions can be tackled by placing codon usage studies in a phylogenetic framework and that bacterial genomes with extreme nucleotide composition biases provide informative model systems. Switches in the background substitution biases from GC to AT have occurred in Gardnerella vaginalis (GC = 32%), and from AT to GC in Lactobacillus delbrueckii (GC = 62%) and Lactobacillus fermentum (GC = 63%). We show that despite the large effects on codon usage patterns by these switches, all three species evolve under selection on synonymous sites. In G. vaginalis, the dramatic codon frequency changes coincide with shifts of optimal codons. In contrast, the optimal codons have not shifted in the two Lactobacillus genomes despite an increased fraction of GC-ending codons. We suggest that all three species are in different phases of an on-going shift of optimal codons, and attribute the difference to a stronger background substitution bias and/or longer time since the switch in G. vaginalis. We show that comparative and correlative methods for optimal codon identification yield conflicting results for genomes in flux and discuss possible reasons for the mispredictions. We conclude that switches in the direction of the background substitution biases can drive major shifts in codon preference patterns even under sustained selection on synonymous codon sites. PMID:27540085

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

PubMed

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

2016-05-25

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

Analysis and Prediction of Myristoylation Sites Using the mRMR Method, the IFS Method and an Extreme Learning Machine Algorithm.

PubMed

Wang, ShaoPeng; Zhang, Yu-Hang; Huang, GuoHua; Chen, Lei; Cai, Yu-Dong

2017-01-01

Myristoylation is an important hydrophobic post-translational modification that is covalently bound to the amino group of Gly residues on the N-terminus of proteins. The many diverse functions of myristoylation on proteins, such as membrane targeting, signal pathway regulation and apoptosis, are largely due to the lipid modification, whereas abnormal or irregular myristoylation on proteins can lead to several pathological changes in the cell. To better understand the function of myristoylated sites and to correctly identify them in protein sequences, this study conducted a novel computational investigation on identifying myristoylation sites in protein sequences. A training dataset with 196 positive and 84 negative peptide segments were obtained. Four types of features derived from the peptide segments following the myristoylation sites were used to specify myristoylatedand non-myristoylated sites. Then, feature selection methods including maximum relevance and minimum redundancy (mRMR), incremental feature selection (IFS), and a machine learning algorithm (extreme learning machine method) were adopted to extract optimal features for the algorithm to identify myristoylation sites in protein sequences, thereby building an optimal prediction model. As a result, 41 key features were extracted and used to build an optimal prediction model. The effectiveness of the optimal prediction model was further validated by its performance on a test dataset. Furthermore, detailed analyses were also performed on the extracted 41 features to gain insight into the mechanism of myristoylation modification. This study provided a new computational method for identifying myristoylation sites in protein sequences. We believe that it can be a useful tool to predict myristoylation sites from protein sequences. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Getting to the top of Google: search engine optimization.

PubMed

Maley, Catherine; Baum, Neil

2010-01-01

Search engine optimization is the process of making your Web site appear at or near the top of popular search engines such as Google, Yahoo, and MSN. This is not done by luck or knowing someone working for the search engines but by understanding the process of how search engines select Web sites for placement on top or on the first page. This article will review the process and provide methods and techniques to use to have your site rated at the top or very near the top.

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.

Biomolecular structure manipulation using tailored electromagnetic radiation: a proof of concept on a simplified model of the active site of bacterial DNA topoisomerase.

PubMed

Jarukanont, Daungruthai; Coimbra, João T S; Bauerhenne, Bernd; Fernandes, Pedro A; Patel, Shekhar; Ramos, Maria J; Garcia, Martin E

2014-10-21

We report on the viability of breaking selected bonds in biological systems using tailored electromagnetic radiation. We first demonstrate, by performing large-scale simulations, that pulsed electric fields cannot produce selective bond breaking. Then, we present a theoretical framework for describing selective energy concentration on particular bonds of biomolecules upon application of tailored electromagnetic radiation. The theory is based on the mapping of biomolecules to a set of coupled harmonic oscillators and on optimal control schemes to describe optimization of temporal shape, the phase and polarization of the external radiation. We have applied this theory to demonstrate the possibility of selective bond breaking in the active site of bacterial DNA topoisomerase. For this purpose, we have focused on a model that was built based on a case study. Results are given as a proof of concept.

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.

Effects of spatial disturbance on common loon nest site selection and territory success

USGS Publications Warehouse

McCarthy, K.P.; DeStefano, S.

2011-01-01

The common loon (Gavia immer) breeds during the summer on northern lakes and water bodies that are also often desirable areas for aquatic recreation and human habitation. In northern New England, we assessed how the spatial nature of disturbance affects common loon nest site selection and territory success. We found through classification and regression analysis that distance to and density of disturbance factors can be used to classify observed nest site locations versus random points, suggesting that these factors affect loon nest site selection (model 1: Correct classification = 75%, null = 50%, K = 0.507, P < 0.001; model 2: Correct classification = 78%, null = 50%, K = 0.551, P < 0.001). However, in an exploratory analysis, we were unable to show a relation between spatial disturbance variables and breeding success (P = 0.595, R 2 = 0.436), possibly because breeding success was so low during the breeding seasons of 2007-2008. We suggest that by selecting nest site locations that avoid disturbance factors, loons thereby limit the effect that disturbance will have on their breeding success. Still, disturbance may force loons to use sub-optimal nesting habitat, limiting the available number of territories, and overall productivity. We advise that management efforts focus on limiting disturbance factors to allow breeding pairs access to the best nesting territories, relieving disturbance pressures that may force sub-optimal nest placement. ?? 2011 The Wildlife Society.

An ArcGIS decision support tool for artificial reefs site selection (ArcGIS ARSS)

NASA Astrophysics Data System (ADS)

Stylianou, Stavros; Zodiatis, George

2017-04-01

Although the use and benefits of artificial reefs, both socio-economic and environmental, have been recognized with research and national development programmes worldwide their development is rarely subjected to a rigorous site selection process and the majority of the projects use the traditional (non-GIS) approach, based on trial and error mode. Recent studies have shown that the use of Geographic Information Systems, unlike to traditional methods, for the identification of suitable areas for artificial reefs siting seems to offer a number of distinct advantages minimizing possible errors, time and cost. A decision support tool (DSS) has been developed based on the existing knowledge, the multi-criteria decision analysis techniques and the GIS approach used in previous studies in order to help the stakeholders to identify the optimal locations for artificial reefs deployment on the basis of the physical, biological, oceanographic and socio-economic features of the sites. The tool provides to the users the ability to produce a final report with the results and suitability maps. The ArcGIS ARSS support tool runs within the existing ArcMap 10.2.x environment and for the development the VB .NET high level programming language has been used along with ArcObjects 10.2.x. Two local-scale case studies were conducted in order to test the application of the tool focusing on artificial reef siting. The results obtained from the case studies have shown that the tool can be successfully integrated within the site selection process in order to select objectively the optimal site for artificial reefs deployment.

Visibility Analysis of Domestic Satellites on Proposed Ground Sites for Optical Surveillance

NASA Astrophysics Data System (ADS)

Kim, Jae-Hyuk; Jo, Jung Hyun; Choi, Jin; Moon, Hong-Kyu; Choi, Young-Jun; Yim, Hong-Suh; Park, Jang-Hyun; Park, Eun-Seo; Park, Jong-Uk

2011-12-01

The objectives of this study are to analyze the satellite visibility at the randomly established ground sites, to determine the five optimal ground sites to perform the optical surveillance and tracking of domestic satellites, and to verify the acquisition of the optical observation time sufficient to maintain the precise ephemeris at optimal ground sites that have been already determined. In order to accomplish these objectives, we analyzed the visibility for sun-synchronous orbit satellites, low earth orbit satellites, middle earth orbit satellites and domestic satellites as well as the continuous visibility along with the fictitious satellite ground track, and calculate the effective visibility. For the analysis, we carried out a series of repetitive process using the satellite tool kit simulation software developed by Analytical Graphics Incorporated. The lighting states of the penumbra and direct sun were set as the key constraints of the optical observation. The minimum of the observation satellite elevation angle was set to be 20 degree, whereas the maximum of the sun elevation angle was set to be -10 degree which is within the range of the nautical twilight. To select the candidates for the optimal optical observation, the entire globe was divided into 84 sectors in a constant interval, the visibility characteristics of the individual sectors were analyzed, and 17 ground sites were arbitrarily selected and analyzed further. Finally, five optimal ground sites (Khurel Togoot Observatory, Assy-Turgen Observatory, Tubitak National Observatory, Bisdee Tier Optical Astronomy Observatory, and South Africa Astronomical Observatory) were determined. The total observation period was decided as one year. To examine the seasonal variation, the simulation was performed for the period of three days or less with respect to spring, summer, fall and winter. In conclusion, we decided the optimal ground sites to perform the optical surveillance and tracking of domestic satellites and verified that optical observ! ation ti me sufficient to maintain the precise ephemeris could be acquired at the determined observatories.

GIS-based approach for optimized siting of municipal solid waste landfill.

PubMed

Sumathi, V R; Natesan, Usha; Sarkar, Chinmoy

2008-11-01

The exponential rise in the urban population of the developing countries in the past few decades and the resulting accelerated urbanization phenomenon has brought to the fore the necessity to develop environmentally sustainable and efficient waste management systems. Sanitary landfill constitutes one of the primary methods of municipal solid waste disposal. Optimized siting decisions have gained considerable importance in order to ensure minimum damage to the various environmental sub-components as well as reduce the stigma associated with the residents living in its vicinity, thereby enhancing the overall sustainability associated with the life cycle of a landfill. This paper addresses the siting of a new landfill using a multi-criteria decision analysis (MCDA) and overlay analysis using a geographic information system (GIS). The proposed system can accommodate new information on the landfill site selection by updating its knowledge base. Several factors are considered in the siting process including geology, water supply resources, land use, sensitive sites, air quality and groundwater quality. Weightings were assigned to each criterion depending upon their relative importance and ratings in accordance with the relative magnitude of impact. The results from testing the system using different sites show the effectiveness of the system in the selection process.

Optimal design of compact and connected nature reserves for multiple species.

PubMed

Wang, Yicheng; Önal, Hayri

2016-04-01

When designing a conservation reserve system for multiple species, spatial attributes of the reserves must be taken into account at species level. The existing optimal reserve design literature considers either one spatial attribute or when multiple attributes are considered the analysis is restricted only to one species. We built a linear integer programing model that incorporates compactness and connectivity of the landscape reserved for multiple species. The model identifies multiple reserves that each serve a subset of target species with a specified coverage probability threshold to ensure the species' long-term survival in the reserve, and each target species is covered (protected) with another probability threshold at the reserve system level. We modeled compactness by minimizing the total distance between selected sites and central sites, and we modeled connectivity of a selected site to its designated central site by selecting at least one of its adjacent sites that has a nearer distance to the central site. We considered structural distance and functional distances that incorporated site quality between sites. We tested the model using randomly generated data on 2 species, one ground species that required structural connectivity and the other an avian species that required functional connectivity. We applied the model to 10 bird species listed as endangered by the state of Illinois (U.S.A.). Spatial coherence and selection cost of the reserves differed substantially depending on the weights assigned to these 2 criteria. The model can be used to design a reserve system for multiple species, especially species whose habitats are far apart in which case multiple disjunct but compact and connected reserves are advantageous. The model can be modified to increase or decrease the distance between reserves to reduce or promote population connectivity. © 2015 Society for Conservation Biology.

DHSpred: support-vector-machine-based human DNase I hypersensitive sites prediction using the optimal features selected by random forest.

PubMed

Manavalan, Balachandran; Shin, Tae Hwan; Lee, Gwang

2018-01-05

DNase I hypersensitive sites (DHSs) are genomic regions that provide important information regarding the presence of transcriptional regulatory elements and the state of chromatin. Therefore, identifying DHSs in uncharacterized DNA sequences is crucial for understanding their biological functions and mechanisms. Although many experimental methods have been proposed to identify DHSs, they have proven to be expensive for genome-wide application. Therefore, it is necessary to develop computational methods for DHS prediction. In this study, we proposed a support vector machine (SVM)-based method for predicting DHSs, called DHSpred (DNase I Hypersensitive Site predictor in human DNA sequences), which was trained with 174 optimal features. The optimal combination of features was identified from a large set that included nucleotide composition and di- and trinucleotide physicochemical properties, using a random forest algorithm. DHSpred achieved a Matthews correlation coefficient and accuracy of 0.660 and 0.871, respectively, which were 3% higher than those of control SVM predictors trained with non-optimized features, indicating the efficiency of the feature selection method. Furthermore, the performance of DHSpred was superior to that of state-of-the-art predictors. An online prediction server has been developed to assist the scientific community, and is freely available at: http://www.thegleelab.org/DHSpred.html.

DHSpred: support-vector-machine-based human DNase I hypersensitive sites prediction using the optimal features selected by random forest

PubMed Central

Manavalan, Balachandran; Shin, Tae Hwan; Lee, Gwang

2018-01-01

DNase I hypersensitive sites (DHSs) are genomic regions that provide important information regarding the presence of transcriptional regulatory elements and the state of chromatin. Therefore, identifying DHSs in uncharacterized DNA sequences is crucial for understanding their biological functions and mechanisms. Although many experimental methods have been proposed to identify DHSs, they have proven to be expensive for genome-wide application. Therefore, it is necessary to develop computational methods for DHS prediction. In this study, we proposed a support vector machine (SVM)-based method for predicting DHSs, called DHSpred (DNase I Hypersensitive Site predictor in human DNA sequences), which was trained with 174 optimal features. The optimal combination of features was identified from a large set that included nucleotide composition and di- and trinucleotide physicochemical properties, using a random forest algorithm. DHSpred achieved a Matthews correlation coefficient and accuracy of 0.660 and 0.871, respectively, which were 3% higher than those of control SVM predictors trained with non-optimized features, indicating the efficiency of the feature selection method. Furthermore, the performance of DHSpred was superior to that of state-of-the-art predictors. An online prediction server has been developed to assist the scientific community, and is freely available at: http://www.thegleelab.org/DHSpred.html PMID:29416743

Effects of spatial disturbance on common loon nest site selection and territory success

USGS Publications Warehouse

McCarthy, Kyle P.; DeStefano, Stephen

2011-01-01

The common loon (Gavia immer) breeds during the summer on northern lakes and water bodies that are also often desirable areas for aquatic recreation and human habitation. In northern New England, we assessed how the spatial nature of disturbance affects common loon nest site selection and territory success. We found through classification and regression analysis that distance to and density of disturbance factors can be used to classify observed nest site locations versus random points, suggesting that these factors affect loon nest site selection (model 1: Correct classification = 75%, null = 50%, K = 0.507, P < 0.001; model 2: Correct classification = 78%, null = 50%, K = 0.551, P < 0.001). However, in an exploratory analysis, we were unable to show a relation between spatial disturbance variables and breeding success (P = 0.595, R2 = 0.436), possibly because breeding success was so low during the breeding seasons of 2007–2008. We suggest that by selecting nest site locations that avoid disturbance factors, loons thereby limit the effect that disturbance will have on their breeding success. Still, disturbance may force loons to use sub-optimal nesting habitat, limiting the available number of territories, and overall productivity. We advise that management efforts focus on limiting disturbance factors to allow breeding pairs access to the best nesting territories, relieving disturbance pressures that may force sub-optimal nest placement.

HIV Drug Resistance Early Warning Indicators in Namibia for Public Health Action

PubMed Central

Jonas, Anna; Gweshe, Justice; Siboleka, Milner; DeKlerk, Michael; Gawanab, Michael; Badi, Alfons; Sumbi, Victor; Pereko, Dawn; Blom, Abraham; Mwinga, Samson; Jordan, Michael R.; Jerger, Logan; Lau, Kiger; Hong, Steven Y.

2013-01-01

Background HIV drug resistance (HIVDR) testing is not routinely available in many resource-limited settings, therefore antiretroviral therapy (ART) program and site factors known to be associated with emergence of HIVDR should be monitored to optimize the quality of patient care and minimize the emergence of preventable HIVDR. Methods In 2010, Namibia selected five World Health Organization Early Warning Indicators (EWIs) and scaled-up monitoring from 9 to 33 ART sites: ART prescribing practices, Patients lost to follow-up (LTFU) at 12 months, Patients switched to a second-line regimen at 12 months, On-time antiretroviral (ARV) drug pick-up, and ARV drug-supply continuity. Results Records allowed reporting on three of the five selected EWIs. 22 of 33 (67%) sites met the target of 100% initiated on appropriate first-line regimens. 17 of 33 (52%) sites met the target of ≤20% LTFU. 15 of 33 (45%) sites met the target of 0% switched to a second-line regimen. Conclusions EWI monitoring directly resulted in public health action which will optimize the quality of care, specifically the strengthening of ART record systems, engagement of ART sites, and operational research for improved adherence assessment and ART patient defaulter tracing. PMID:23762406

RESULTS OF A METHOD VERIFICATION STUDY FOR ANALYSES OF PCP IN SOIL

EPA Science Inventory

As a prelude to a field demonstration of the fungal treatment technology by the SITE Program, a field treatability study was performed to select optimal fungal species and loading rates.using the site-specific soil matrix contaminated with Wood preserving wastes: PCP and PAHS. ur...

An Optimization and Assessment on DG adoption in JapanesePrototype Buildings

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

Zhou, Nan; Marnay, Chris; Firestone, Ryan

2005-11-30

This research investigates a method of choosing economicallyoptimal DER, expanding on prior studies at the Berkeley Lab using the DERdesign optimization program, the Distributed Energy Resources CustomerAdoption Model (DER-CAM). DER-CAM finds the optimal combination ofinstalled equipment from available DER technologies, given prevailingutility tariffs, site electrical and thermal loads, and a menu ofavailable equipment. It provides a global optimization, albeit idealized,that shows how the site energy load scan be served at minimum cost byselection and operation of on-site generation, heat recovery, andcooling. Five prototype Japanese commercial buildings are examined andDER-CAM applied to select thee conomically optimal DER system for each.The fivemore » building types are office, hospital, hotel, retail, and sportsfacility. Based on the optimization results, energy and emissionreductions are evaluated. Furthermore, a Japan-U.S. comparison study ofpolicy, technology, and utility tariffs relevant to DER installation ispresented. Significant decreases in fuel consumption, carbon emissions,and energy costs were seen in the DER-CAM results. Savings were mostnoticeable in the sports facility, followed by the hospital, hotel, andoffice building.« less

Skin impedance is not a factor in transcutaneous electrical nerve stimulation effectiveness

PubMed Central

Vance, Carol GT; Rakel, Barbara A; Dailey, Dana L; Sluka, Kathleen A

2015-01-01

Objective Transcutaneous electrical nerve stimulation (TENS) is a nonpharmacological intervention used to manage pain using skin surface electrodes. Optimal electrode placement is unclear. We hypothesized that better analgesia would occur if electrodes were placed over sites with lower skin impedance. Optimal site selection (OSS) and sham site selection (SSS) electrode sites on the forearm were identified using a standard clinical technique. Methods Experiment 1 measured skin impedance in the forearm at OSS and SSS. Experiment 2 was a crossover design double-blind randomized controlled trial comparing OSS-TENS, SSS-TENS, and placebo TENS (P-TENS) to confirm differences in skin impedance between OSS and SSS, and measure change in pressure pain threshold (PPT) following a 30-minute TENS treatment. Healthy volunteers were recruited (ten for Experiment 1 [five male, five female] and 24 for Experiment 2 [12 male, 12 female]). TENS was applied for 30 minutes at 100 Hz frequency, 100 µs pulse duration, and “strong but nonpainful” amplitude. Results Experiment 1 results demonstrate significantly higher impedance at SSS (17.69±1.24 Ω) compared to OSS (13.53±0.57 Ω) (P=0.007). For Experiment 2, electrode site impedance was significantly higher over SSS, with both the impedance meter (P=0.001) and the TENS unit (P=0.012) compared to OSS. PPT change was significantly greater for both OSS-TENS (P=0.024) and SSS-TENS (P=0.025) when compared to P-TENS. PPT did not differ between the two active TENS treatments (P=0.81). Conclusion Skin impedance is lower at sites characterized as optimal using the described technique of electrode site selection. When TENS is applied at adequate intensities, skin impedance is not a factor in attainment of hypoalgesia of the forearm in healthy subjects. Further investigation should include testing in patients presenting with painful conditions. PMID:26316808

Strong Purifying Selection at Synonymous Sites in D. melanogaster

PubMed Central

Lawrie, David S.; Messer, Philipp W.; Hershberg, Ruth; Petrov, Dmitri A.

2013-01-01

Synonymous sites are generally assumed to be subject to weak selective constraint. For this reason, they are often neglected as a possible source of important functional variation. We use site frequency spectra from deep population sequencing data to show that, contrary to this expectation, 22% of four-fold synonymous (4D) sites in Drosophila melanogaster evolve under very strong selective constraint while few, if any, appear to be under weak constraint. Linking polymorphism with divergence data, we further find that the fraction of synonymous sites exposed to strong purifying selection is higher for those positions that show slower evolution on the Drosophila phylogeny. The function underlying the inferred strong constraint appears to be separate from splicing enhancers, nucleosome positioning, and the translational optimization generating canonical codon bias. The fraction of synonymous sites under strong constraint within a gene correlates well with gene expression, particularly in the mid-late embryo, pupae, and adult developmental stages. Genes enriched in strongly constrained synonymous sites tend to be particularly functionally important and are often involved in key developmental pathways. Given that the observed widespread constraint acting on synonymous sites is likely not limited to Drosophila, the role of synonymous sites in genetic disease and adaptation should be reevaluated. PMID:23737754

Epibenthic assessment of a renewable tidal energy site.

PubMed

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

2013-01-01

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

Study for the selection of optimal site in northeastern, Mexico for wind power generation using genetic algorithms.

NASA Astrophysics Data System (ADS)

Gonzalez, T.; Ruvalcaba, A.; Oliver, L.

2016-12-01

The electricity generation from renewable resources has acquired a leading role. Mexico particularrly it has great interest in renewable natural resources for power generation, especially wind energy. Therefore, the country is rapidly entering in the development of wind power generators sites. The development of a wind places as an energy project, does not have a standardized methodology. Techniques vary according to the developer to select the best place to install a wind turbine system. Generally to install the system the developers consider three key factors: 1) the characteristics of the wind, 2) the potential distribution of electricity and 3) transport access to the site. This paper presents a study with a different methodology which is carried out in two stages: the first at regional scale uses "space" and "natural" criteria in order to select a region based on its cartographic features such as politics and physiographic division, location of conservation natural areas, water bodies, urban criteria; and natural criteria such as the amount and direction of the wind, the type and land use, vegetation, topography and biodiversity of the site. The result of the application of these criteria, gives a first optimal selection area. The second part of the methodology includes criteria and variables on detail scale. The analysis of all data information collected will provide new parameters (decision variables) for the site. The overall analysis of the information, based in these criteria, indicates that the best location that the best location of the field would be the southern Coahuila and the central part of Nuevo Leon. The wind power site will contribute to the economy grow of important cities including Monterrey. Finally, computational model of genetic algorithm will be used as a tool to determine the best site selection depending on the parameters considered.

Space-planning and structural solutions of low-rise buildings: Optimal selection methods

NASA Astrophysics Data System (ADS)

Gusakova, Natalya; Minaev, Nikolay; Filushina, Kristina; Dobrynina, Olga; Gusakov, Alexander

2017-11-01

The present study is devoted to elaboration of methodology used to select appropriately the space-planning and structural solutions in low-rise buildings. Objective of the study is working out the system of criteria influencing the selection of space-planning and structural solutions which are most suitable for low-rise buildings and structures. Application of the defined criteria in practice aim to enhance the efficiency of capital investments, energy and resource saving, create comfortable conditions for the population considering climatic zoning of the construction site. Developments of the project can be applied while implementing investment-construction projects of low-rise housing at different kinds of territories based on the local building materials. The system of criteria influencing the optimal selection of space-planning and structural solutions of low-rise buildings has been developed. Methodological basis has been also elaborated to assess optimal selection of space-planning and structural solutions of low-rise buildings satisfying the requirements of energy-efficiency, comfort and safety, and economical efficiency. Elaborated methodology enables to intensify the processes of low-rise construction development for different types of territories taking into account climatic zoning of the construction site. Stimulation of low-rise construction processes should be based on the system of approaches which are scientifically justified; thus it allows enhancing energy efficiency, comfort, safety and economical effectiveness of low-rise buildings.

ROLE OF LABORATORY SAMPLING DEVICES AND LABORATORY SUBSAMPLING METHODS IN OPTIMIZING REPRESENTATIVENESS STRATEGIES

EPA Science Inventory

Sampling is the act of selecting items from a specified population in order to estimate the parameters of that population (e.g., selecting soil samples to characterize the properties at an environmental site). Sampling occurs at various levels and times throughout an environmenta...

Optimizing Travel Time to Outpatient Interventional Radiology Procedures in a Multi-Site Hospital System Using a Google Maps Application.

PubMed

Mandel, Jacob E; Morel-Ovalle, Louis; Boas, Franz E; Ziv, Etay; Yarmohammadi, Hooman; Deipolyi, Amy; Mohabir, Heeralall R; Erinjeri, Joseph P

2018-02-20

The purpose of this study is to determine whether a custom Google Maps application can optimize site selection when scheduling outpatient interventional radiology (IR) procedures within a multi-site hospital system. The Google Maps for Business Application Programming Interface (API) was used to develop an internal web application that uses real-time traffic data to determine estimated travel time (ETT; minutes) and estimated travel distance (ETD; miles) from a patient's home to each a nearby IR facility in our hospital system. Hypothetical patient home addresses based on the 33 cities comprising our institution's catchment area were used to determine the optimal IR site for hypothetical patients traveling from each city based on real-time traffic conditions. For 10/33 (30%) cities, there was discordance between the optimal IR site based on ETT and the optimal IR site based on ETD at non-rush hour time or rush hour time. By choosing to travel to an IR site based on ETT rather than ETD, patients from discordant cities were predicted to save an average of 7.29 min during non-rush hour (p = 0.03), and 28.80 min during rush hour (p < 0.001). Using a custom Google Maps application to schedule outpatients for IR procedures can effectively reduce patient travel time when more than one location providing IR procedures is available within the same hospital system.

An Optimal Centralized Carbon Dioxide Repository for Florida, USA

PubMed Central

Poiencot, Brandon; Brown, Christopher

2011-01-01

For over a decade, the United States Department of Energy, and engineers, geologists, and scientists from all over the world have investigated the potential for reducing atmospheric carbon emissions through carbon sequestration. Numerous reports exist analyzing the potential for sequestering carbon dioxide at various sites around the globe, but none have identified the potential for a statewide system in Florida, USA. In 2005, 83% of Florida’s electrical energy was produced by natural gas, coal, or oil (e.g., fossil fuels), from power plants spread across the state. In addition, only limited research has been completed on evaluating optimal pipeline transportation networks to centralized carbon dioxide repositories. This paper describes the feasibility and preliminary locations for an optimal centralized Florida-wide carbon sequestration repository. Linear programming optimization modeling is used to plan and route an idealized pipeline network to existing Florida power plants. Further analysis of the subsurface geology in these general locations will provide insight into the suitability of the subsurface conditions and the available capacity for carbon sequestration at selected possible repository sites. The identification of the most favorable site(s) is also presented. PMID:21695024

An optimal centralized carbon dioxide repository for Florida, USA.

PubMed

Poiencot, Brandon; Brown, Christopher

2011-04-01

For over a decade, the United States Department of Energy, and engineers, geologists, and scientists from all over the world have investigated the potential for reducing atmospheric carbon emissions through carbon sequestration. Numerous reports exist analyzing the potential for sequestering carbon dioxide at various sites around the globe, but none have identified the potential for a statewide system in Florida, USA. In 2005, 83% of Florida's electrical energy was produced by natural gas, coal, or oil (e.g., fossil fuels), from power plants spread across the state. In addition, only limited research has been completed on evaluating optimal pipeline transportation networks to centralized carbon dioxide repositories. This paper describes the feasibility and preliminary locations for an optimal centralized Florida-wide carbon sequestration repository. Linear programming optimization modeling is used to plan and route an idealized pipeline network to existing Florida power plants. Further analysis of the subsurface geology in these general locations will provide insight into the suitability of the subsurface conditions and the available capacity for carbon sequestration at selected possible repository sites. The identification of the most favorable site(s) is also presented.

Multidimensional Programming Methods for Energy Facility Siting: Alternative Approaches

NASA Technical Reports Server (NTRS)

Solomon, B. D.; Haynes, K. E.

1982-01-01

The use of multidimensional optimization methods in solving power plant siting problems, which are characterized by several conflicting, noncommensurable objectives is addressed. After a discussion of data requirements and exclusionary site screening methods for bounding the decision space, classes of multiobjective and goal programming models are discussed in the context of finite site selection. Advantages and limitations of these approaches are highlighted and the linkage of multidimensional methods with the subjective, behavioral components of the power plant siting process is emphasized.

EGU2013 SM1.4/GI1.6 session: "Improving seismic networks performances: from site selection to data integration"

NASA Astrophysics Data System (ADS)

Pesaresi, D.; Busby, R.

2013-08-01

The number and quality of seismic stations and networks in Europe continually improves, nevertheless there is always scope to optimize their performance. In this session we welcomed contributions from all aspects of seismic network installation, operation and management. This includes site selection; equipment testing and installation; planning and implementing communication paths; policies for redundancy in data acquisition, processing and archiving; and integration of different datasets including GPS and OBS.

Environmental concern-based site screening of carbon dioxide geological storage in China.

PubMed

Cai, Bofeng; Li, Qi; Liu, Guizhen; Liu, Lancui; Jin, Taotao; Shi, Hui

2017-08-08

Environmental impacts and risks related to carbon dioxide (CO 2 ) capture and storage (CCS) projects may have direct effects on the decision-making process during CCS site selection. This paper proposes a novel method of environmental optimization for CCS site selection using China's ecological red line approach. Moreover, this paper established a GIS based spatial analysis model of environmental optimization during CCS site selection by a large database. The comprehensive data coverage of environmental elements and fine 1 km spatial resolution were used in the database. The quartile method was used for value assignment for specific indicators including the prohibited index and restricted index. The screening results show that areas classified as having high environmental suitability (classes III and IV) in China account for 620,800 km 2 and 156,600 km 2 , respectively, and are mainly distributed in Inner Mongolia, Qinghai and Xinjiang. The environmental suitability class IV areas of Bayingol Mongolian Autonomous Prefecture, Hotan Prefecture, Aksu Prefecture, Hulunbuir, Xilingol League and other prefecture-level regions not only cover large land areas, but also form a continuous area in the three provincial-level administrative units. This study may benefit the national macro-strategic deployment and implementation of CCS spatial layout and environmental management in China.

Optimization of protease-inhibitor interactions by randomizing adventitious contacts

PubMed Central

Komiyama, Tomoko; VanderLugt, Bryan; Fugère, Martin; Day, Robert; Kaufman, Randal J.; Fuller, Robert S.

2003-01-01

Polypeptide protease inhibitors are often found to inhibit targets with which they did not coevolve, as in the case of high-affinity inhibition of bacterial subtilisin by the leech inhibitor eglin c. Two kinds of contacts exist in such complexes: (i) reactive site loop-active site contacts and (ii) interactions outside of these that form the broader enzyme-inhibitor interface. We hypothesized that the second class of “adventitious” contacts could be optimized to generate significant increases in affinity for a target enzyme or discrimination of an inhibitor for closely related target proteases. We began with a modified eglin c, Arg-42–Arg-45–eglin, in which the reactive site loop had been optimized for subtilisin-related processing proteases of the Kex2/furin family. We randomized 10 potential adventitious contact residues and screened for inhibition of soluble human furin. Substitutions at one of these sites, Y49, were also screened against yeast Kex2 and human PC7. These screens identified not only variants that exhibited increased affinity (up to 20-fold), but also species that exhibited enhanced selectivity, that is, increased discrimination between the target enzymes (up to 41-fold for furin versus PC7 and 20-fold for PC7 versus furin). One variant, Asp-49–Arg-42–Arg-45–eglin, exhibited a Ki of 310 pM for furin and blocked furin-dependent processing of von Willebrand factor in COS-1 cells when added to the culture medium of the cells. The exploitation of adventitious contact sites may provide a versatile technique for developing potent, selective inhibitors for newly discovered proteases and could in principle be applied to optimize numerous protein–protein interactions. PMID:12832612

Epicardial left ventricular lead placement for cardiac resynchronization therapy: optimal pace site selection with pressure-volume loops.

PubMed

Dekker, A L A J; Phelps, B; Dijkman, B; van der Nagel, T; van der Veen, F H; Geskes, G G; Maessen, J G

2004-06-01

Patients in heart failure with left bundle branch block benefit from cardiac resynchronization therapy. Usually the left ventricular pacing lead is placed by coronary sinus catheterization; however, this procedure is not always successful, and patients may be referred for surgical epicardial lead placement. The objective of this study was to develop a method to guide epicardial lead placement in cardiac resynchronization therapy. Eleven patients in heart failure who were eligible for cardiac resynchronization therapy were referred for surgery because of failed coronary sinus left ventricular lead implantation. Minithoracotomy or thoracoscopy was performed, and a temporary epicardial electrode was used for biventricular pacing at various sites on the left ventricle. Pressure-volume loops with the conductance catheter were used to select the best site for each individual patient. Relative to the baseline situation, biventricular pacing with an optimal left ventricular lead position significantly increased stroke volume (+39%, P =.01), maximal left ventricular pressure derivative (+20%, P =.02), ejection fraction (+30%, P =.007), and stroke work (+66%, P =.006) and reduced end-systolic volume (-6%, P =.04). In contrast, biventricular pacing at a suboptimal site did not significantly change left ventricular function and even worsened it in some cases. To optimize cardiac resynchronization therapy with epicardial leads, mapping to determine the best pace site is a prerequisite. Pressure-volume loops offer real-time guidance for targeting epicardial lead placement during minimal invasive surgery.

Big maggots dig deeper: size-dependent larval dispersal in flies.

PubMed

Davis, Jeremy M; Coogan, Laura E; Papaj, Daniel R

2015-09-01

The ability of individual animals to select habitats optimal for development and survival can be constrained by the costs of moving through the environment. Animals that seek overwintering sites underground, for example, may be constrained by the energy required to burrow into the soil. We conducted field and laboratory studies to determine the relationship between individual size and overwintering site selection in the tephritid flies, Rhagoletis juglandis and Rhagoletis suavis. We also explored the effect of site selection on pupal mortality, parasitism, and the ability to emerge from overwintering sites after eclosion. In both species, and in both lab and field tests, larger pupae were found at deeper soil depths. In addition, marginally non-significant trends indicated pupae in deeper sites were 48% more likely to survive the overwintering period. Finally, larger individuals were more likely to eclose and emerge from the soil at a given depth, but flies in deep overwintering sites were less likely to emerge from those sites than flies in shallow sites. Our data indicate that overwintering site selection represents a trade-off between avoiding predators and parasites that occur at shallow sites, and the energetic and mortality costs of burrowing to, overwintering in, and emerging from, deeper sites. The size-dependent overwintering site selection demonstrated here has implications for population dynamics and pest control strategies. Some fly control measures, such as the introduction of parasites or predators, will be mitigated when the deepest and least accessible overwintering pupae represent a disproportionately large amount of the population's reproductive capacity.

Computer-based planning of optimal donor sites for autologous osseous grafts

NASA Astrophysics Data System (ADS)

Krol, Zdzislaw; Chlebiej, Michal; Zerfass, Peter; Zeilhofer, Hans-Florian U.; Sader, Robert; Mikolajczak, Pawel; Keeve, Erwin

2002-05-01

Bone graft surgery is often necessary for reconstruction of craniofacial defects after trauma, tumor, infection or congenital malformation. In this operative technique the removed or missing bone segment is filled with a bone graft. The mainstay of the craniofacial reconstruction rests with the replacement of the defected bone by autogeneous bone grafts. To achieve sufficient incorporation of the autograft into the host bone, precise planning and simulation of the surgical intervention is required. The major problem is to determine as accurately as possible the donor site where the graft should be dissected from and to define the shape of the desired transplant. A computer-aided method for semi-automatic selection of optimal donor sites for autografts in craniofacial reconstructive surgery has been developed. The non-automatic step of graft design and constraint setting is followed by a fully automatic procedure to find the best fitting position. In extension to preceding work, a new optimization approach based on the Levenberg-Marquardt method has been implemented and embedded into our computer-based surgical planning system. This new technique enables, once the pre-processing step has been performed, selection of the optimal donor site in time less than one minute. The method has been applied during surgery planning step in more than 20 cases. The postoperative observations have shown that functional results, such as speech and chewing ability as well as restoration of bony continuity were clearly better compared to conventionally planned operations. Moreover, in most cases the duration of the surgical interventions has been distinctly reduced.

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...

Spatially-Correlated Risk in Nature Reserve Site Selection

PubMed Central

Albers, Heidi J.; Busby, Gwenlyn M.; Hamaide, Bertrand; Ando, Amy W.; Polasky, Stephen

2016-01-01

Establishing nature reserves protects species from land cover conversion and the resulting loss of habitat. Even within a reserve, however, many factors such as fires and defoliating insects still threaten habitat and the survival of species. To address the risk to species survival after reserve establishment, reserve networks can be created that allow some redundancy of species coverage to maximize the expected number of species that survive in the presence of threats. In some regions, however, the threats to species within a reserve may be spatially correlated. As examples, fires, diseases, and pest infestations can spread from a starting point and threaten neighboring parcels’ habitats, in addition to damage caused at the initial location. This paper develops a reserve site selection optimization framework that compares the optimal reserve networks in cases where risks do and do not reflect spatial correlation. By exploring the impact of spatially-correlated risk on reserve networks on a stylized landscape and on an Oregon landscape, this analysis demonstrates an appropriate and feasible method for incorporating such post-reserve establishment risks in the reserve site selection literature as an additional tool to be further developed for future conservation planning. PMID:26789127

Selecting optimal monitoring site locations for peak ambient particulate material concentrations using the MM5-CAMx4 numerical modelling system.

PubMed

Sturman, Andrew; Titov, Mikhail; Zawar-Reza, Peyman

2011-01-15

Installation of temporary or long term monitoring sites is expensive, so it is important to rationally identify potential locations that will achieve the requirements of regional air quality management strategies. A simple, but effective, numerical approach to selecting ambient particulate matter (PM) monitoring site locations has therefore been developed using the MM5-CAMx4 air pollution dispersion modelling system. A new method, 'site efficiency,' was developed to assess the ability of any monitoring site to provide peak ambient air pollution concentrations that are representative of the urban area. 'Site efficiency' varies from 0 to 100%, with the latter representing the most representative site location for monitoring peak PM concentrations. Four heavy pollution episodes in Christchurch (New Zealand) during winter 2005, representing 4 different aerosol dispersion patterns, were used to develop and test this site assessment technique. Evaluation of the efficiency of monitoring sites was undertaken for night and morning aerosol peaks for 4 different particulate material (PM) spatial patterns. The results demonstrate that the existing long term monitoring site at Coles Place is quite well located, with a site efficiency value of 57.8%. A temporary ambient PM monitoring site (operating during winter 2006) showed a lower ability to capture night and morning peak aerosol concentrations. Evaluation of multiple site locations used during an extensive field campaign in Christchurch (New Zealand) in 2000 indicated that the maximum efficiency achieved by any site in the city would be 60-65%, while the efficiency of a virtual background site is calculated to be about 7%. This method of assessing the appropriateness of any potential monitoring site can be used to optimize monitoring site locations for any air pollution measurement programme. Copyright © 2010 Elsevier B.V. All rights reserved.

Bispecific small molecule-antibody conjugate targeting prostate cancer.

PubMed

Kim, Chan Hyuk; Axup, Jun Y; Lawson, Brian R; Yun, Hwayoung; Tardif, Virginie; Choi, Sei Hyun; Zhou, Quan; Dubrovska, Anna; Biroc, Sandra L; Marsden, Robin; Pinstaff, Jason; Smider, Vaughn V; Schultz, Peter G

2013-10-29

Bispecific antibodies, which simultaneously target CD3 on T cells and tumor-associated antigens to recruit cytotoxic T cells to cancer cells, are a promising new approach to the treatment of hormone-refractory prostate cancer. Here we report a site-specific, semisynthetic method for the production of bispecific antibody-like therapeutics in which a derivative of the prostate-specific membrane antigen-binding small molecule DUPA was selectively conjugated to a mutant αCD3 Fab containing the unnatural amino acid, p-acetylphenylalanine, at a defined site. Homogeneous conjugates were generated in excellent yields and had good solubility. The efficacy of the conjugate was optimized by modifying the linker structure, relative binding orientation, and stoichiometry of the ligand. The optimized conjugate showed potent and selective in vitro activity (EC50 ~ 100 pM), good serum half-life, and potent in vivo activity in prophylactic and treatment xenograft mouse models. This semisynthetic approach is likely to be applicable to the generation of additional bispecific agents using drug-like ligands selective for other cell-surface receptors.

Implications of high-spatial-resolution thermal infrared (Termoskan) data for Mars landing site selection

NASA Technical Reports Server (NTRS)

Betts, Bruce H.

1994-01-01

Thermal infrared observations of Mars from spacecraft provide physical information about the upper thermal skin depth of the surface, which is on the order of a few centimeters in depth and thus very significant for lander site selection. The Termoskan instrument onboard the Soviet Phobos '88 spacecraft acquired the highest spatial-resolution thermal infrared data obtained for Mars, ranging in resolution from 300 m to 3 km per pixel. It simultaneously obtained broadband reflected solar flux data. Although the 6 deg N - 30 deg S Termoskan coverage only slightly overlaps the nominal Mars Pathfinder target range, the implications of Termoskan data for that overlap region and the extrapolations that can be made to other regions give important clues for optimal landing site selection.

Development of the hard and soft constraints based optimisation model for unit sizing of the hybrid renewable energy system designed for microgrid applications

NASA Astrophysics Data System (ADS)

Sundaramoorthy, Kumaravel

2017-02-01

The hybrid energy systems (HESs) based electricity generation system has become a more attractive solution for rural electrification nowadays. Economically feasible and technically reliable HESs are solidly based on an optimisation stage. This article discusses about the optimal unit sizing model with the objective function to minimise the total cost of the HES. Three typical rural sites from southern part of India have been selected for the application of the developed optimisation methodology. Feasibility studies and sensitivity analysis on the optimal HES are discussed elaborately in this article. A comparison has been carried out with the Hybrid Optimization Model for Electric Renewable optimisation model for three sites. The optimal HES is found with less total net present rate and rate of energy compared with the existing method

Ensemble of surrogates-based optimization for identifying an optimal surfactant-enhanced aquifer remediation strategy at heterogeneous DNAPL-contaminated sites

NASA Astrophysics Data System (ADS)

Jiang, Xue; Lu, Wenxi; Hou, Zeyu; Zhao, Haiqing; Na, Jin

2015-11-01

The purpose of this study was to identify an optimal surfactant-enhanced aquifer remediation (SEAR) strategy for aquifers contaminated by dense non-aqueous phase liquid (DNAPL) based on an ensemble of surrogates-based optimization technique. A saturated heterogeneous medium contaminated by nitrobenzene was selected as case study. A new kind of surrogate-based SEAR optimization employing an ensemble surrogate (ES) model together with a genetic algorithm (GA) is presented. Four methods, namely radial basis function artificial neural network (RBFANN), kriging (KRG), support vector regression (SVR), and kernel extreme learning machines (KELM), were used to create four individual surrogate models, which were then compared. The comparison enabled us to select the two most accurate models (KELM and KRG) to establish an ES model of the SEAR simulation model, and the developed ES model as well as these four stand-alone surrogate models was compared. The results showed that the average relative error of the average nitrobenzene removal rates between the ES model and the simulation model for 20 test samples was 0.8%, which is a high approximation accuracy, and which indicates that the ES model provides more accurate predictions than the stand-alone surrogate models. Then, a nonlinear optimization model was formulated for the minimum cost, and the developed ES model was embedded into this optimization model as a constrained condition. Besides, GA was used to solve the optimization model to provide the optimal SEAR strategy. The developed ensemble surrogate-optimization approach was effective in seeking a cost-effective SEAR strategy for heterogeneous DNAPL-contaminated sites. This research is expected to enrich and develop the theoretical and technical implications for the analysis of remediation strategy optimization of DNAPL-contaminated aquifers.

Ensemble of Surrogates-based Optimization for Identifying an Optimal Surfactant-enhanced Aquifer Remediation Strategy at Heterogeneous DNAPL-contaminated Sites

NASA Astrophysics Data System (ADS)

Lu, W., Sr.; Xin, X.; Luo, J.; Jiang, X.; Zhang, Y.; Zhao, Y.; Chen, M.; Hou, Z.; Ouyang, Q.

2015-12-01

The purpose of this study was to identify an optimal surfactant-enhanced aquifer remediation (SEAR) strategy for aquifers contaminated by dense non-aqueous phase liquid (DNAPL) based on an ensemble of surrogates-based optimization technique. A saturated heterogeneous medium contaminated by nitrobenzene was selected as case study. A new kind of surrogate-based SEAR optimization employing an ensemble surrogate (ES) model together with a genetic algorithm (GA) is presented. Four methods, namely radial basis function artificial neural network (RBFANN), kriging (KRG), support vector regression (SVR), and kernel extreme learning machines (KELM), were used to create four individual surrogate models, which were then compared. The comparison enabled us to select the two most accurate models (KELM and KRG) to establish an ES model of the SEAR simulation model, and the developed ES model as well as these four stand-alone surrogate models was compared. The results showed that the average relative error of the average nitrobenzene removal rates between the ES model and the simulation model for 20 test samples was 0.8%, which is a high approximation accuracy, and which indicates that the ES model provides more accurate predictions than the stand-alone surrogate models. Then, a nonlinear optimization model was formulated for the minimum cost, and the developed ES model was embedded into this optimization model as a constrained condition. Besides, GA was used to solve the optimization model to provide the optimal SEAR strategy. The developed ensemble surrogate-optimization approach was effective in seeking a cost-effective SEAR strategy for heterogeneous DNAPL-contaminated sites. This research is expected to enrich and develop the theoretical and technical implications for the analysis of remediation strategy optimization of DNAPL-contaminated aquifers.

Computer-aided osteotomy design for harvesting autologous bone grafts in reconstructive surgery

NASA Astrophysics Data System (ADS)

Krol, Zdzislaw; Zerfass, Peter; von Rymon-Lipinski, Bartosz; Jansen, Thomas; Hauck, Wolfgang; Zeilhofer, Hans-Florian U.; Sader, Robert; Keeve, Erwin

2001-05-01

Autologous grafts serve as the standard grafting material in the treatment of maxillofacial bone tumors, traumatic defects or congenital malformations. The pre-selection of a donor site depends primarily on the morphological fit of the available bone mass and the shape of the part that has to be transplanted. To achieve sufficient incorporation of the autograft into the host bone, precise planning and simulation of the surgical intervention based on 3D CT studies is required. This paper presents a method to identify an optimal donor site by performing an optimization of appropriate similarity measures between donor region and a given transplant. At the initial stage the surgeon has to delineate the osteotomy border lines in the template CT data set and to define a set of constraints for the optimization of appropriate similarity measures between donor region and a given transplant. At the initial stage the surgeon has to delineate the osteotomy border lines in the template CT data set and to define a set of constraints for the optimization task in the donor site CT data set. The following fully automatic optimization stage delivers a set of sub-optimal and optimal donor sites for a given template. All generated solutions can be explored interactively on the computer display using an efficient graphical interface. Reconstructive operations supported by our system were performed on 28 patients. We found that the operation time can be considerably shortened by this approach.

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.

Selectivity and Efficiency of Late Transgene Expression by Transcriptionally Targeted Oncolytic Adenoviruses Are Dependent on the Transgene Insertion Strategy

PubMed Central

Quirin, Christina; Rohmer, Stanimira; Fernández-Ulibarri, Inés; Behr, Michael; Hesse, Andrea; Engelhardt, Sarah; Erbs, Philippe; Enk, Alexander H.

2011-01-01

Abstract Key challenges facing cancer therapy are the development of tumor-specific drugs and potent multimodal regimens. Oncolytic adenoviruses possess the potential to realize both aims by restricting virus replication to tumors and inserting therapeutic genes into the virus genome, respectively. A major effort in this regard is to express transgenes in a tumor-specific manner without affecting virus replication. Using both luciferase as a sensitive reporter and genetic prodrug activation, we show that promoter control of E1A facilitates highly selective expression of transgenes inserted into the late transcription unit. This, however, required multistep optimization of late transgene expression. Transgene insertion via internal ribosome entry site (IRES), splice acceptor (SA), or viral 2A sequences resulted in replication-dependent expression. Unexpectedly, analyses in appropriate substrates and with matching control viruses revealed that IRES and SA, but not 2A, facilitated indirect transgene targeting via tyrosinase promoter control of E1A. Transgene expression via SA was more selective (up to 1,500-fold) but less effective than via IRES. Notably, we also revealed transgene-dependent interference with splicing. Hence, the prodrug convertase FCU1 (a cytosine deaminase–uracil phosphoribosyltransferase fusion protein) was expressed only after optimizing the sequence surrounding the SA site and mutating a cryptic splice site within the transgene. The resulting tyrosinase promoter-regulated and FCU1-encoding adenovirus combined effective oncolysis with targeted prodrug activation therapy of melanoma. Thus, prodrug activation showed potent bystander killing and increased cytotoxicity of the virus up to 10-fold. We conclude that armed oncolytic viruses can be improved substantially by comparing and optimizing strategies for targeted transgene expression, thereby implementing selective and multimodal cancer therapies. PMID:20939692

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

Dynamic reserve selection: Optimal land retention with land-price feedbacks

Treesearch

Sandor F. Toth; Robert G. Haight; Luke W. Rogers

2011-01-01

Urban growth compromises open space and ecosystem functions. To mitigate the negative effects, some agencies use reserve selection models to identify conservation sites for purchase or retention. Existing models assume that conservation has no impact on nearby land prices. We propose a new integer program that relaxes this assumption via adaptive cost coefficients. Our...

Reserve selection with land market feedbacks.

PubMed

Butsic, Van; Lewis, David J; Radeloff, Volker C

2013-01-15

How to best site reserves is a leading question for conservation biologists. Recently, reserve selection has emphasized efficient conservation: maximizing conservation goals given the reality of limited conservation budgets, and this work indicates that land market can potentially undermine the conservation benefits of reserves by increasing property values and development probabilities near reserves. Here we propose a reserve selection methodology which optimizes conservation given both a budget constraint and land market feedbacks by using a combination of econometric models along with stochastic dynamic programming. We show that amenity based feedbacks can be accounted for in optimal reserve selection by choosing property price and land development models which exogenously estimate the effects of reserve establishment. In our empirical example, we use previously estimated models of land development and property prices to select parcels to maximize coarse woody debris along 16 lakes in Vilas County, WI, USA. Using each lake as an independent experiment, we find that including land market feedbacks in the reserve selection algorithm has only small effects on conservation efficacy. Likewise, we find that in our setting heuristic (minloss and maxgain) algorithms perform nearly as well as the optimal selection strategy. We emphasize that land market feedbacks can be included in optimal reserve selection; the extent to which this improves reserve placement will likely vary across landscapes. Copyright © 2012 Elsevier Ltd. All rights reserved.

Site Selection Appraisal for Tidal Turbine Development in the River Mersey

NASA Astrophysics Data System (ADS)

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

2018-03-01

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

Jointly optimizing selection of fuel treatments and siting of forest biomass-based energy production facilities for landscape-scale fire hazard reduction.

Treesearch

Peter J. Daugherty; Jeremy S. Fried

2007-01-01

Landscape-scale fuel treatments for forest fire hazard reduction potentially produce large quantities of material suitable for biomass energy production. The analytic framework FIA BioSum addresses this situation by developing detailed data on forest conditions and production under alternative fuel treatment prescriptions, and computes haul costs to alternative sites...

Applications of the Renewable Energy Network Optimization Tool

NASA Astrophysics Data System (ADS)

Alliss, R.; Link, R.; Apling, D.; Kiley, H.; Mason, M.; Darmenova, K.

2010-12-01

As the renewable energy industry continues to grow so does the requirement for atmospheric modeling and analysis tools to maximize both wind and solar power. Renewable energy generation is variable however; presenting challenges for electrical grid operation and requires a variety of measures to adequately firm power. These measures include the production of non-renewable generation during times when renewables are not available. One strategy for minimizing the variability of renewable energy production is site diversity. Assuming that a network of renewable energy systems feed a common electrical grid, site diversity ensures that when one system on the network has a reduction in generation others on the same grid make up the difference. The site-diversity strategy can be used to mitigate the intermittency in alternative energy production systems while still maximizing saleable energy. The Renewable Energy Network Optimization Tool (ReNOT) has recently been developed to study the merits of site optimization for wind farms. The modeling system has a plug-in architecture that allows us to accommodate a wide variety of renewable energy system designs and performance metrics. The Weather Research and Forecasting (WRF) mesoscale model is applied to generate high-resolution wind databases to support the site selection of wind farms. These databases are generated on High Performance Computing systems such as the Rocky Mountain Supercomputing Center (RMSC). The databases are then accessed by ReNOT and an optimized site selection is developed. We can accommodate numerous constraints (e.g., number of sites, the geographic extent of the optimization, proximity to high-voltage transport lines, etc.). As part of our collaboration with RMSC and the State of Montana a study was performed to estimate the optimal locations of a network of wind farms. Comparisons were made to four existing wind farm locations in Montana including Glacier with a 210 MW name plate capacity, Horseshoe Bend with a total capacity of 9 MW, Diamond Willow with a capacity of 20MW and Judith Gap with a total capacity of 135 MW. The goal of this study was to see if ReNOT could find a four site network that made more effective use of the existing four site network of wind farms' 374 MW nameplate capacity. We developed three different metrics in which to pick sites. Metric 3 (M3) picks sites based on the previous day's mean power, and accounts for short-term variability (i.e., 1 hour). M3 attempts to approximate usable power by minimizing ramping events which are so important to industry. In addition we investigated several performance metrics including Mean Power, Usable Power, and ramping event frequency. A ramping event is defined as an increase or decrease in power production over the course of one hour. Of interest was the frequency of ramping events that exceeded 10% of total capacity for the network. Networks with few ramping events are markedly superior to networks producing otherwise identical aggregate power. The optimization was run over the 15-year period of hub-height wind data (40 meters AGL). The ReNOT derived network produces 58% more usable power than the four existing and operating wind farms. In addition, the optimized four site network produces three times fewer significant ramping events.

Optimizing Mars Sphere of Influence Maneuvers for NASA's Evolvable Mars Campaign

NASA Technical Reports Server (NTRS)

Merrill, Raymond G.; Komar, D. R.; Chai, Patrick; Qu, Min

2016-01-01

NASA's Human Spaceflight Architecture Team is refining human exploration architectures that will extend human presence to the Martian surface. For both Mars orbital and surface missions, NASA's Evolvable Mars Campaign assumes that cargo and crew can be delivered repeatedly to the same destination. Up to this point, interplanetary trajectories have been optimized to minimize the total propulsive requirements of the in-space transportation systems, while the pre-deployed assets and surface systems are optimized to minimize their respective propulsive requirements separate from the in-space transportation system. There is a need to investigate the coupled problem of optimizing the interplanetary trajectory and optimizing the maneuvers within Mars's sphere of influence. This paper provides a description of the ongoing method development, analysis and initial results of the effort to resolve the discontinuity between the interplanetary trajectory and the Mars sphere of influence trajectories. Assessment of Phobos and Deimos orbital missions shows the in-space transportation and crew taxi allocations are adequate for missions in the 2030s. Because the surface site has yet to be selected, the transportation elements must be sized to provide enough capability to provide surface access to all landing sites under consideration. Analysis shows access to sites from elliptical parking orbits with a lander that is designed for sub-periapsis landing location is either infeasible or requires expensive orbital maneuvers for many latitude ranges. In this case the locus of potential arrival perigee vectors identifies the potential maximum north or south latitudes accessible. Higher arrival velocities can decrease reorientation costs and increase landing site availability. Utilizing hyperbolic arrival and departure vectors in the optimization scheme will increase transportation site accessibility and provide more optimal solutions.

Real Estate Site Selection: An Application of Artificial Intelligence for Military Retail Facilities

DTIC Science & Technology

2006-09-01

Information and Spatial Analysis (SCGISA), University of Sheffield. Kotler , P. (1984). Marketing Management: Analysis, Planning, and Control...Spatial Distribution of Retail Sales. Journal of Real Estate Finance and Economics, Vol. 31 Iss. 1, 53. Lilien, G., & Kotler , P. (1983). Marketing ...commissaries). The current business model for military retail facilities may not be optimized based upon current trends market data. Optimizing

Optimization of a CRISPR/Cas9-mediated Knock-in Strategy at the Porcine Rosa26 Locus in Porcine Foetal Fibroblasts.

PubMed

Xie, Zicong; Pang, Daxin; Wang, Kankan; Li, Mengjing; Guo, Nannan; Yuan, Hongming; Li, Jianing; Zou, Xiaodong; Jiao, Huping; Ouyang, Hongsheng; Li, Zhanjun; Tang, Xiaochun

2017-06-08

Genetically modified pigs have important roles in agriculture and biomedicine. However, genome-specific knock-in techniques in pigs are still in their infancy and optimal strategies have not been extensively investigated. In this study, we performed electroporation to introduce a targeting donor vector (a non-linearized vector that did not contain a promoter or selectable marker) into Porcine Foetal Fibroblasts (PFFs) along with a CRISPR/Cas9 vector. After optimization, the efficiency of the EGFP site-specific knock-in could reach up to 29.6% at the pRosa26 locus in PFFs. Next, we used the EGFP reporter PFFs to address two key conditions in the process of achieving transgenic pigs, the limiting dilution method and the strategy to evaluate the safety and feasibility of the knock-in locus. This study demonstrates that we establish an efficient procedures for the exogenous gene knock-in technique and creates a platform to efficiently generate promoter-less and selectable marker-free transgenic PFFs through the CRISPR/Cas9 system. This study should contribute to the generation of promoter-less and selectable marker-free transgenic pigs and it may provide insights into sophisticated site-specific genome engineering techniques for additional species.

Using Temporal Modulation Sensitivity to Select Stimulation Sites for Processor MAPs in Cochlear Implant Listeners

PubMed Central

Garadat, Soha N.; Zwolan, Teresa A.; Pfingst, Bryan E.

2013-01-01

Previous studies in our laboratory showed that temporal acuity as assessed by modulation detection thresholds (MDTs) varied across activation sites and that this site-to-site variability was subject specific. Using two 10-channel MAPs, the previous experiments showed that processor MAPs that had better across-site mean (ASM) MDTs yielded better speech recognition than MAPs with poorer ASM MDTs tested in the same subject. The current study extends our earlier work on developing more optimal fitting strategies to test the feasibility of using a site-selection approach in the clinical domain. This study examined the hypothesis that revising the clinical speech processor MAP for cochlear implant (CI) recipients by turning off selected sites that have poorer temporal acuity and reallocating frequencies to the remaining electrodes would lead to improved speech recognition. Twelve CI recipients participated in the experiments. We found that site selection procedure based on MDTs in the presence of a masker resulted in improved performance on consonant recognition and recognition of sentences in noise. In contrast, vowel recognition was poorer with the experimental MAP than with the clinical MAP, possibly due to reduced spectral resolution when sites were removed from the experimental MAP. Overall, these results suggest a promising path for improving recipient outcomes using personalized processor-fitting strategies based on a psychophysical measure of temporal acuity. PMID:23881208

Selection of Atmospheric Environmental Monitoring Sites based on Geographic Parameters Extraction of GIS and Fuzzy Matter-Element Analysis.

PubMed

Wu, Jianfa; Peng, Dahao; Ma, Jianhao; Zhao, Li; Sun, Ce; Ling, Huanzhang

2015-01-01

To effectively monitor the atmospheric quality of small-scale areas, it is necessary to optimize the locations of the monitoring sites. This study combined geographic parameters extraction by GIS with fuzzy matter-element analysis. Geographic coordinates were extracted by GIS and transformed into rectangular coordinates. These coordinates were input into the Gaussian plume model to calculate the pollutant concentration at each site. Fuzzy matter-element analysis, which is used to solve incompatible problems, was used to select the locations of sites. The matter element matrices were established according to the concentration parameters. The comprehensive correlation functions KA (xj) and KB (xj), which reflect the degree of correlation among monitoring indices, were solved for each site, and a scatter diagram of the sites was drawn to determine the final positions of the sites based on the functions. The sites could be classified and ultimately selected by the scatter diagram. An actual case was tested, and the results showed that 5 positions can be used for monitoring, and the locations conformed to the technical standard. In the results of this paper, the hierarchical clustering method was used to improve the methods. The sites were classified into 5 types, and 7 locations were selected. Five of the 7 locations were completely identical to the sites determined by fuzzy matter-element analysis. The selections according to these two methods are similar, and these methods can be used in combination. In contrast to traditional methods, this study monitors the isolated point pollutant source within a small range, which can reduce the cost of monitoring.

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.

Optimal networks of future gravitational-wave telescopes

NASA Astrophysics Data System (ADS)

Raffai, Péter; Gondán, László; Heng, Ik Siong; Kelecsényi, Nándor; Logue, Josh; Márka, Zsuzsa; Márka, Szabolcs

2013-08-01

We aim to find the optimal site locations for a hypothetical network of 1-3 triangular gravitational-wave telescopes. We define the following N-telescope figures of merit (FoMs) and construct three corresponding metrics: (a) capability of reconstructing the signal polarization; (b) accuracy in source localization; and (c) accuracy in reconstructing the parameters of a standard binary source. We also define a combined metric that takes into account the three FoMs with practically equal weight. After constructing a geomap of possible telescope sites, we give the optimal 2-telescope networks for the four FoMs separately in example cases where the location of the first telescope has been predetermined. We found that based on the combined metric, placing the first telescope to Australia provides the most options for optimal site selection when extending the network with a second instrument. We suggest geographical regions where a potential second and third telescope could be placed to get optimal network performance in terms of our FoMs. Additionally, we use a similar approach to find the optimal location and orientation for the proposed LIGO-India detector within a five-detector network with Advanced LIGO (Hanford), Advanced LIGO (Livingston), Advanced Virgo, and KAGRA. We found that the FoMs do not change greatly in sites within India, though the network can suffer a significant loss in reconstructing signal polarizations if the orientation angle of an L-shaped LIGO-India is not set to the optimal value of ˜58.2°( + k × 90°) (measured counterclockwise from East to the bisector of the arms).

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

Spatial optimization of watershed management practices for nitrogen load reduction using a modeling-optimization framework.

PubMed

Yang, Guoxiang; Best, Elly P H

2015-09-15

Best management practices (BMPs) can be used effectively to reduce nutrient loads transported from non-point sources to receiving water bodies. However, methodologies of BMP selection and placement in a cost-effective way are needed to assist watershed management planners and stakeholders. We developed a novel modeling-optimization framework that can be used to find cost-effective solutions of BMP placement to attain nutrient load reduction targets. This was accomplished by integrating a GIS-based BMP siting method, a WQM-TMDL-N modeling approach to estimate total nitrogen (TN) loading, and a multi-objective optimization algorithm. Wetland restoration and buffer strip implementation were the two BMP categories used to explore the performance of this framework, both differing greatly in complexity of spatial analysis for site identification. Minimizing TN load and BMP cost were the two objective functions for the optimization process. The performance of this framework was demonstrated in the Tippecanoe River watershed, Indiana, USA. Optimized scenario-based load reduction indicated that the wetland subset selected by the minimum scenario had the greatest N removal efficiency. Buffer strips were more effective for load removal than wetlands. The optimized solutions provided a range of trade-offs between the two objective functions for both BMPs. This framework can be expanded conveniently to a regional scale because the NHDPlus catchment serves as its spatial computational unit. The present study demonstrated the potential of this framework to find cost-effective solutions to meet a water quality target, such as a 20% TN load reduction, under different conditions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Bispecific small molecule–antibody conjugate targeting prostate cancer

PubMed Central

Kim, Chan Hyuk; Axup, Jun Y.; Lawson, Brian R.; Yun, Hwayoung; Tardif, Virginie; Choi, Sei Hyun; Zhou, Quan; Dubrovska, Anna; Biroc, Sandra L.; Marsden, Robin; Pinstaff, Jason; Smider, Vaughn V.; Schultz, Peter G.

2013-01-01

Bispecific antibodies, which simultaneously target CD3 on T cells and tumor-associated antigens to recruit cytotoxic T cells to cancer cells, are a promising new approach to the treatment of hormone-refractory prostate cancer. Here we report a site-specific, semisynthetic method for the production of bispecific antibody-like therapeutics in which a derivative of the prostate-specific membrane antigen-binding small molecule DUPA was selectively conjugated to a mutant αCD3 Fab containing the unnatural amino acid, p-acetylphenylalanine, at a defined site. Homogeneous conjugates were generated in excellent yields and had good solubility. The efficacy of the conjugate was optimized by modifying the linker structure, relative binding orientation, and stoichiometry of the ligand. The optimized conjugate showed potent and selective in vitro activity (EC50 ∼100 pM), good serum half-life, and potent in vivo activity in prophylactic and treatment xenograft mouse models. This semisynthetic approach is likely to be applicable to the generation of additional bispecific agents using drug-like ligands selective for other cell-surface receptors. PMID:24127589

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.

Hydrogen Oxidation-Selective Electrocatalysis by Fine Tuning of Pt Ensemble Sites to Enhance the Durability of Automotive Fuel Cells.

PubMed

Yun, Su-Won; Park, Shin-Ae; Kim, Tae-June; Kim, Jun-Hyuk; Pak, Gi-Woong; Kim, Yong-Tae

2017-02-08

A simple, inexpensive approach is proposed for enhancing the durability of automotive proton exchange membrane fuel cells by selective promotion of the hydrogen oxidation reaction (HOR) and suppression of the oxygen reduction reaction (ORR) at the anode in startup/shutdown events. Dodecanethiol forms a self-assembled monolayer (SAM) on the surface of Pt particles, thus decreasing the number of Pt ensemble sites. Interestingly, by controlling the dodecanethiol concentration during SAM formation, the number of ensemble sites can be precisely optimized such that it is sufficient for the HOR but insufficient for the ORR. Thus, a Pt surface with an SAM of dodecanethiol clearly effects HOR-selective electrocatalysis. Clear HOR selectivity is demonstrated in unit cell tests with the actual membrane electrode assembly, as well as in an electrochemical three-electrode setup with a thin-film rotating disk electrode configuration. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

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

NASA Astrophysics Data System (ADS)

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

1998-05-01

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

A methodology for optimal MSW management, with an application in the waste transportation of Attica Region, Greece.

PubMed

Economopoulou, M A; Economopoulou, A A; Economopoulos, A P

2013-11-01

The paper describes a software system capable of formulating alternative optimal Municipal Solid Wastes (MSWs) management plans, each of which meets a set of constraints that may reflect selected objections and/or wishes of local communities. The objective function to be minimized in each plan is the sum of the annualized capital investment and annual operating cost of all transportation, treatment and final disposal operations involved, taking into consideration the possible income from the sale of products and any other financial incentives or disincentives that may exist. For each plan formulated, the system generates several reports that define the plan, analyze its cost elements and yield an indicative profile of selected types of installations, as well as data files that facilitate the geographic representation of the optimal solution in maps through the use of GIS. A number of these reports compare the technical and economic data from all scenarios considered at the study area, municipality and installation level constituting in effect sensitivity analysis. The generation of alternative plans offers local authorities the opportunity of choice and the results of the sensitivity analysis allow them to choose wisely and with consensus. The paper presents also an application of this software system in the capital Region of Attica in Greece, for the purpose of developing an optimal waste transportation system in line with its approved waste management plan. The formulated plan was able to: (a) serve 113 Municipalities and Communities that generate nearly 2 milliont/y of comingled MSW with distinctly different waste collection patterns, (b) take into consideration several existing waste transfer stations (WTS) and optimize their use within the overall plan, (c) select the most appropriate sites among the potentially suitable (new and in use) ones, (d) generate the optimal profile of each WTS proposed, and (e) perform sensitivity analysis so as to define the impact of selected sets of constraints (limitations in the availability of sites and in the capacity of their installations) on the design and cost of the ensuing optimal waste transfer system. The results show that optimal planning offers significant economic savings to municipalities, while reducing at the same time the present levels of traffic, fuel consumptions and air emissions in the congested Athens basin. Copyright © 2013 Elsevier Ltd. All rights reserved.

DIDO Optimization of a Lunar Landing Trajectory with Respect to Autonomous Landing Hazard Avoidance Technology

DTIC Science & Technology

2009-09-01

22 b. Hazard Detection and Avoidance ( HDA )...............................22 c. Hazard Relative Navigation (HRN...Navigation (HRN) and Hazard Detection and Avoidance ( HDA ). In addition to the TRN and HDA sensors used during these phases, which will be discussed...and Avoidance ( HDA ) During the HAD phase, the expected landing site is examined and evaluated, and a new site may be selected. Using the HDA

Site Selection and Resource Allocation of Oil Spill Emergency Base for Offshore Oil Facilities

NASA Astrophysics Data System (ADS)

Li, Yunbin; Liu, Jingxian; Wei, Lei; Wu, Weihuang

2018-02-01

Based on the analysis of the historical data about oil spill accidents in the Bohai Sea, this paper discretizes oil spilled source into a limited number of spill points. According to the probability of oil spill risk, the demand for salvage forces at each oil spill point is evaluated. Aiming at the specific location of the rescue base around the Bohai Sea, a cost-benefit analysis is conducted to determine the total cost of disasters for each rescue base. Based on the relationship between the oil spill point and the rescue site, a multi-objective optimization location model for the oil spill rescue base in the Bohai Sea region is established. And the genetic algorithm is used to solve the optimization problem, and determine the emergency rescue base optimization program and emergency resources allocation ratio.

Optimal design of monitoring networks for multiple groundwater quality parameters using a Kalman filter: application to the Irapuato-Valle aquifer.

PubMed

Júnez-Ferreira, H E; Herrera, G S; González-Hita, L; Cardona, A; Mora-Rodríguez, J

2016-01-01

A new method for the optimal design of groundwater quality monitoring networks is introduced in this paper. Various indicator parameters were considered simultaneously and tested for the Irapuato-Valle aquifer in Mexico. The steps followed in the design were (1) establishment of the monitoring network objectives, (2) definition of a groundwater quality conceptual model for the study area, (3) selection of the parameters to be sampled, and (4) selection of a monitoring network by choosing the well positions that minimize the estimate error variance of the selected indicator parameters. Equal weight for each parameter was given to most of the aquifer positions and a higher weight to priority zones. The objective for the monitoring network in the specific application was to obtain a general reconnaissance of the water quality, including water types, water origin, and first indications of contamination. Water quality indicator parameters were chosen in accordance with this objective, and for the selection of the optimal monitoring sites, it was sought to obtain a low-uncertainty estimate of these parameters for the entire aquifer and with more certainty in priority zones. The optimal monitoring network was selected using a combination of geostatistical methods, a Kalman filter and a heuristic optimization method. Results show that when monitoring the 69 locations with higher priority order (the optimal monitoring network), the joint average standard error in the study area for all the groundwater quality parameters was approximately 90 % of the obtained with the 140 available sampling locations (the set of pilot wells). This demonstrates that an optimal design can help to reduce monitoring costs, by avoiding redundancy in data acquisition.

Forward-looking farmers owning multiple potential wetland restoration sites: implications for efficient restoration

NASA Astrophysics Data System (ADS)

Schroder (Kushch), Svetlana; Lang, Zhengxin; Rabotyagov, Sergey

2018-04-01

Wetland restoration can increase the provision of multiple non-market ecosystem services. Environmental and socio-economic factors need to be accounted for when land is withdrawn from agriculture and wetlands are restored. We build multi-objective optimization models to provide decision support for wetland restoration in the Le Sueur river watershed in Southern Minnesota. We integrate environmental objectives of sediment reduction and habitat protection with socio-economic factors associated with the overlap of private land with potential wetland restoration sites in the watershed and the costs representing forward-looking farmers voluntarily taking land out of agricultural production in favor of wetland restoration. Our results demonstrate that the inclusion of these factors early on in the restoration planning process affects both the total costs of the restoration project and the spatial distribution of optimally selected wetland restoration sites.

Synergism of virtual screening and medicinal chemistry: identification and optimization of allosteric antagonists of metabotropic glutamate receptor 1.

PubMed

Noeske, Tobias; Trifanova, Dina; Kauss, Valerjans; Renner, Steffen; Parsons, Christopher G; Schneider, Gisbert; Weil, Tanja

2009-08-01

We report the identification of novel potent and selective metabotropic glutamate receptor 1 (mGluR1) antagonists by virtual screening and subsequent hit optimization. For ligand-based virtual screening, molecules were represented by a topological pharmacophore descriptor (CATS-2D) and clustered by a self-organizing map (SOM). The most promising compounds were tested in mGluR1 functional and binding assays. We identified a potent chemotype exhibiting selective antagonistic activity at mGluR1 (functional IC(50)=0.74+/-0.29 microM). Hit optimization yielded lead structure 16 with an affinity of K(i)=0.024+/-0.001 microM and greater than 1000-fold selectivity for mGluR1 versus mGluR5. Homology-based receptor modelling suggests a binding site compatible with previously reported mutation studies. Our study demonstrates the usefulness of ligand-based virtual screening for scaffold-hopping and rapid lead structure identification in early drug discovery projects.

A multi-objective model for closed-loop supply chain optimization and efficient supplier selection in a competitive environment considering quantity discount policy

NASA Astrophysics Data System (ADS)

Jahangoshai Rezaee, Mustafa; Yousefi, Samuel; Hayati, Jamileh

2017-06-01

Supplier selection and allocation of optimal order quantity are two of the most important processes in closed-loop supply chain (CLSC) and reverse logistic (RL). So that providing high quality raw material is considered as a basic requirement for a manufacturer to produce popular products, as well as achieve more market shares. On the other hand, considering the existence of competitive environment, suppliers have to offer customers incentives like discounts and enhance the quality of their products in a competition with other manufacturers. Therefore, in this study, a model is presented for CLSC optimization, efficient supplier selection, as well as orders allocation considering quantity discount policy. It is modeled using multi-objective programming based on the integrated simultaneous data envelopment analysis-Nash bargaining game. In this study, maximizing profit and efficiency and minimizing defective and functions of delivery delay rate are taken into accounts. Beside supplier selection, the suggested model selects refurbishing sites, as well as determining the number of products and parts in each network's sector. The suggested model's solution is carried out using global criteria method. Furthermore, based on related studies, a numerical example is examined to validate it.

Selection, Identification, and Binding Mechanism Studies of an ssDNA Aptamer Targeted to Different Stages of E. coli O157:H7.

PubMed

Zou, Ying; Duan, Nuo; Wu, Shijia; Shen, Mofei; Wang, Zhouping

2018-06-06

Enterohemorrhagic Escherichia coli O157:H7 ( E. coli O157:H7) is known as an important food-borne pathogen related to public health. In this study, aptamers which could bind to different stages of E. coli O157:H7 (adjustment phase, log phase, and stationary phase) with high affinity and specificity were obtained by the whole cell-SELEX method through 14 selection rounds including three counter-selection rounds. Altogether, 32 sequences were obtained, and nine families were classified to select the optimal aptamer. To analyze affinity and specificity by flow cytometer, an ssDNA aptamer named Apt-5 was picked out as the optimal aptamer that recognizes different stages of E. coli O157:H7 specifically with the K d value of 9.04 ± 2.80 nM. In addition, in order to study the binding mechanism, target bacteria were treated by proteinase K and trypsin, indicating that the specific binding site is not protein on the cell membrane. Furthermore, when we treated E. coli O157:H7 with EDTA, the result showed that the binding site might be lipopolysaccharide (LPS) on the outer membrane of E. coli O157:H7.

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...

PRELIMINARY ASSESSMENT OF LIFE-CYCLE COSTS OF PROTECTIVE CLOTHING

EPA Science Inventory

Many different types of chemical protective clothing (CPC) are used to isolate workers at hazardous waste sites from contact with the potential hazards posed by chemical wastes. he goal in selecting the appropriate clothing for a particular occupational situation is to optimize w...

Prediction of Protein Modification Sites of Pyrrolidone Carboxylic Acid Using mRMR Feature Selection and Analysis

PubMed Central

Zheng, Lu-Lu; Niu, Shen; Hao, Pei; Feng, KaiYan; Cai, Yu-Dong; Li, Yixue

2011-01-01

Pyrrolidone carboxylic acid (PCA) is formed during a common post-translational modification (PTM) of extracellular and multi-pass membrane proteins. In this study, we developed a new predictor to predict the modification sites of PCA based on maximum relevance minimum redundancy (mRMR) and incremental feature selection (IFS). We incorporated 727 features that belonged to 7 kinds of protein properties to predict the modification sites, including sequence conservation, residual disorder, amino acid factor, secondary structure and solvent accessibility, gain/loss of amino acid during evolution, propensity of amino acid to be conserved at protein-protein interface and protein surface, and deviation of side chain carbon atom number. Among these 727 features, 244 features were selected by mRMR and IFS as the optimized features for the prediction, with which the prediction model achieved a maximum of MCC of 0.7812. Feature analysis showed that all feature types contributed to the modification process. Further site-specific feature analysis showed that the features derived from PCA's surrounding sites contributed more to the determination of PCA sites than other sites. The detailed feature analysis in this paper might provide important clues for understanding the mechanism of the PCA formation and guide relevant experimental validations. PMID:22174779

N- vs. C-Domain Selectivity of Catalytic Inactivation of Human Angiotensin Converting Enzyme by Lisinopril-Coupled Transition Metal Chelates

PubMed Central

Hocharoen, Lalintip; Joyner, Jeff C.; Cowan, J. A.

2014-01-01

The N- and C-terminal domains of human somatic Angiotensin I Converting Enzyme (sACE-1) demonstrate distinct physiological functions, with resulting interest in the development of domain-selective inhibitors for specific therapeutic applications. Herein, the activity of lisinopril-coupled transition metal chelates were tested for both reversible binding and irreversible catalytic inactivation of sACE-1. C/N domain binding selectivity ratios ranged from 1 to 350, while rates of irreversible catalytic inactivation of the N- and C-domains were found to be significantly greater for the N-domain, suggesting a more optimal orientation of the M-chelate-lisinopril complexes within the active site of the N-domain of sACE-1. Finally, the combined effect of binding selectivity and inactivation selectivity was assessed for each catalyst (double-filter selectivity factors), and several catalysts were found to cause domain-selective catalytic inactivation. The results of this study demonstrate the ability to optimize the target selectivity of catalytic metallopeptides through both binding and orientation factors (double-filter effect). PMID:24228790

N- versus C-domain selectivity of catalytic inactivation of human angiotensin converting enzyme by lisinopril-coupled transition metal chelates.

PubMed

Hocharoen, Lalintip; Joyner, Jeff C; Cowan, J A

2013-12-27

The N- and C-terminal domains of human somatic angiotensin I converting enzyme (sACE-1) demonstrate distinct physiological functions, with resulting interest in the development of domain-selective inhibitors for specific therapeutic applications. Herein, the activity of lisinopril-coupled transition metal chelates was tested for both reversible binding and irreversible catalytic inactivation of each domain of sACE-1. C/N domain binding selectivity ratios ranged from 1 to 350, while rates of irreversible catalytic inactivation of the N- and C-domains were found to be significantly greater for the N-domain, suggesting a more optimal orientation of M-chelate-lisinopril complexes within the active site of the N-domain of sACE-1. Finally, the combined effect of binding selectivity and inactivation selectivity was assessed for each catalyst (double-filter selectivity factors), and several catalysts were found to cause domain-selective catalytic inactivation. The results of this study demonstrate the ability to optimize the target selectivity of catalytic metallopeptides through both binding and catalytic factors (double-filter effect).

Optimization of hydrometric monitoring network in urban drainage systems using information theory.

PubMed

Yazdi, J

2017-10-01

Regular and continuous monitoring of urban runoff in both quality and quantity aspects is of great importance for controlling and managing surface runoff. Due to the considerable costs of establishing new gauges, optimization of the monitoring network is essential. This research proposes an approach for site selection of new discharge stations in urban areas, based on entropy theory in conjunction with multi-objective optimization tools and numerical models. The modeling framework provides an optimal trade-off between the maximum possible information content and the minimum shared information among stations. This approach was applied to the main surface-water collection system in Tehran to determine new optimal monitoring points under the cost considerations. Experimental results on this drainage network show that the obtained cost-effective designs noticeably outperform the consulting engineers' proposal in terms of both information contents and shared information. The research also determined the highly frequent sites at the Pareto front which might be important for decision makers to give a priority for gauge installation on those locations of the network.

Mars Mission Optimization Based on Collocation of Resources

NASA Technical Reports Server (NTRS)

Chamitoff, G. E.; James, G. H.; Barker, D. C.; Dershowitz, A. L.

2003-01-01

This paper presents a powerful approach for analyzing Martian data and for optimizing mission site selection based on resource collocation. This approach is implemented in a program called PROMT (Planetary Resource Optimization and Mapping Tool), which provides a wide range of analysis and display functions that can be applied to raw data or imagery. Thresholds, contours, custom algorithms, and graphical editing are some of the various methods that can be used to process data. Output maps can be created to identify surface regions on Mars that meet any specific criteria. The use of this tool for analyzing data, generating maps, and collocating features is demonstrated using data from the Mars Global Surveyor and the Odyssey spacecraft. The overall mission design objective is to maximize a combination of scientific return and self-sufficiency based on utilization of local materials. Landing site optimization involves maximizing accessibility to collocated science and resource features within a given mission radius. Mission types are categorized according to duration, energy resources, and in-situ resource utilization. Optimization results are shown for a number of mission scenarios.

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.

Penetrator role in Mars sample strategy

NASA Technical Reports Server (NTRS)

Boynton, William; Dwornik, Steve; Eckstrom, William; Roalstad, David A.

1988-01-01

The application of the penetrator to a Mars Return Sample Mission (MRSM) has direct advantages to meet science objectives and mission safety. Based on engineering data and work currently conducted at Ball Aerospace Systems Division, the concept of penetrators as scientific instruments is entirely practical. The primary utilization of a penetrator for MRSM would be to optimize the selection of the sample site location and to help in selection of the actual sample to be returned to Earth. It is recognized that the amount of sample to be returned is very limited, therefore the selection of the sample site is critical to the success of the mission. The following mission scenario is proposed. The site selection of a sample to be acquired will be performed by science working groups. A decision will be reached and a set of target priorities established based on data to give geochemical, geophysical and geological information. The first task of a penetrator will be to collect data at up to 4 to 6 possible landing sites. The penetrator can include geophysical, geochemical, geological and engineering instruments to confirm that scientific data requirements at that site will be met. This in situ near real-time data, collected prior to final targeting of the lander, will insure that the sample site is both scientifically valuable and also that it is reachable within limits of the capability of the lander.

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.

Climate variability slows evolutionary responses of Colias butterflies to recent climate change.

PubMed

Kingsolver, Joel G; Buckley, Lauren B

2015-03-07

How does recent climate warming and climate variability alter fitness, phenotypic selection and evolution in natural populations? We combine biophysical, demographic and evolutionary models with recent climate data to address this question for the subalpine and alpine butterfly, Colias meadii, in the southern Rocky Mountains. We focus on predicting patterns of selection and evolution for a key thermoregulatory trait, melanin (solar absorptivity) on the posterior ventral hindwings, which affects patterns of body temperature, flight activity, adult and egg survival, and reproductive success in Colias. Both mean annual summer temperatures and thermal variability within summers have increased during the past 60 years at subalpine and alpine sites. At the subalpine site, predicted directional selection on wing absorptivity has shifted from generally positive (favouring increased wing melanin) to generally negative during the past 60 years, but there is substantial variation among years in the predicted magnitude and direction of selection and the optimal absorptivity. The predicted magnitude of directional selection at the alpine site declined during the past 60 years and varies substantially among years, but selection has generally been positive at this site. Predicted evolutionary responses to mean climate warming at the subalpine site since 1980 is small, because of the variability in selection and asymmetry of the fitness function. At both sites, the predicted effects of adaptive evolution on mean population fitness are much smaller than the fluctuations in mean fitness due to climate variability among years. Our analyses suggest that variation in climate within and among years may strongly limit evolutionary responses of ectotherms to mean climate warming in these habitats. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

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.

Genetic evolutionary taboo search for optimal marker placement in infrared patient setup

NASA Astrophysics Data System (ADS)

Riboldi, M.; Baroni, G.; Spadea, M. F.; Tagaste, B.; Garibaldi, C.; Cambria, R.; Orecchia, R.; Pedotti, A.

2007-09-01

In infrared patient setup adequate selection of the external fiducial configuration is required for compensating inner target displacements (target registration error, TRE). Genetic algorithms (GA) and taboo search (TS) were applied in a newly designed approach to optimal marker placement: the genetic evolutionary taboo search (GETS) algorithm. In the GETS paradigm, multiple solutions are simultaneously tested in a stochastic evolutionary scheme, where taboo-based decision making and adaptive memory guide the optimization process. The GETS algorithm was tested on a group of ten prostate patients, to be compared to standard optimization and to randomly selected configurations. The changes in the optimal marker configuration, when TRE is minimized for OARs, were specifically examined. Optimal GETS configurations ensured a 26.5% mean decrease in the TRE value, versus 19.4% for conventional quasi-Newton optimization. Common features in GETS marker configurations were highlighted in the dataset of ten patients, even when multiple runs of the stochastic algorithm were performed. Including OARs in TRE minimization did not considerably affect the spatial distribution of GETS marker configurations. In conclusion, the GETS algorithm proved to be highly effective in solving the optimal marker placement problem. Further work is needed to embed site-specific deformation models in the optimization process.

Comparative evaluation of several docking tools for docking small molecule ligands to DC-SIGN.

PubMed

Jug, Gregor; Anderluh, Marko; Tomašič, Tihomir

2015-06-01

Five docking tools, namely AutoDock, FRED, CDOCKER, FlexX and GOLD, have been critically examined, with the aim of selecting those most appropriate for use as docking tools for docking molecules to the lectin dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN). This lectin has been selected for its rather non-druggable binding site, which enables complex interactions that guide the binding of the core monosaccharide. Since optimal orientation is crucial for forming coordination bonds, it was important to assess whether the selected docking tools could reproduce the optimal binding conformation for several oligosaccharides that are known to bind DC-SIGN. Our results show that even widely used docking programs have certain limitations when faced with a rather shallow and featureless binding site, as is the case of DC-SIGN. The FRED docking software (OpenEye Scientific Software, Inc.) was found to score as the best tool for docking ligands to DC-SIGN. The performance of FRED was further assessed on another lectin, Langerin. We have demonstrated that this validated docking protocol could be used for docking to other lectins similar to DC-SIGN.

Selection of actuator locations for static shape control of large space structures by heuristic integer programing

NASA Technical Reports Server (NTRS)

Haftka, R. T.; Adelman, H. M.

1984-01-01

Orbiting spacecraft such as large space antennas have to maintain a highly accurate space to operate satisfactorily. Such structures require active and passive controls to mantain an accurate shape under a variety of disturbances. Methods for the optimum placement of control actuators for correcting static deformations are described. In particular, attention is focused on the case were control locations have to be selected from a large set of available sites, so that integer programing methods are called for. The effectiveness of three heuristic techniques for obtaining a near-optimal site selection is compared. In addition, efficient reanalysis techniques for the rapid assessment of control effectiveness are presented. Two examples are used to demonstrate the methods: a simple beam structure and a 55m space-truss-parabolic antenna.

Evaluation and inversion of a net ecosystem carbon exchange model for grasslands and croplands

NASA Astrophysics Data System (ADS)

Herbst, M.; Klosterhalfen, A.; Weihermueller, L.; Graf, A.; Schmidt, M.; Huisman, J. A.; Vereecken, H.

2017-12-01

A one-dimensional soil water, heat, and CO2 flux model (SOILCO2), a pool concept of soil carbon turnover (RothC), and a crop growth module (SUCROS) was coupled to predict the net ecosystem exchange (NEE) of carbon. This model, further referred to as AgroC, was extended with routines for managed grassland as well as for root exudation and root decay. In a first step, the coupled model was applied to two winter wheat sites and one upland grassland site in Germany. The model was calibrated based on soil water content, soil temperature, biometric, and soil respiration measurements for each site, and validated in terms of hourly NEE measured with the eddy covariance technique. The overall model performance of AgroC was acceptable with a model efficiency >0.78 for NEE. In a second step, AgroC was optimized with the eddy covariance NEE measurements to examine the effect of various objective functions, constraints, and data-transformations on estimated NEE, which showed a distinct sensitivity to the choice of objective function and the inclusion of soil respiration data in the optimization process. Both, day and nighttime fluxes, were found to be sensitive to the selected optimization strategy. Additional consideration of soil respiration measurements improved the simulation of small positive fluxes remarkably. Even though the model performance of the selected optimization strategies did not diverge substantially, the resulting annual NEE differed substantially. We conclude that data-transformation, definition of objective functions, and data sources have to be considered cautiously when using a terrestrial ecosystem model to determine carbon balances by means of eddy covariance measurements.

Kynurenic acid analogues with improved affinity and selectivity for the glycine site on the N-methyl-D-aspartate receptor from rat brain.

PubMed

Foster, A C; Kemp, J A; Leeson, P D; Grimwood, S; Donald, A E; Marshall, G R; Priestley, T; Smith, J D; Carling, R W

1992-05-01

The glycine site on the N-methyl-D-aspartate (NMDA) subtype of receptors for the excitatory neurotransmitter glutamate is a potential target for the development of neuroprotective drugs. We report here two chemical series of glycine site antagonists derived from kynurenic acid (KYNA), with greatly improved potency and selectivity. Disubstitution with chlorine or bromine in the 5- and 7-positions of KYNA increased affinity for [3H]glycine binding sites in rat cortex/hippocampus P2 membranes, with a parallel increase of potency for antagonism of NMDA-evoked responses in the rat cortical wedge preparation. The optimal compound was 5-I,7-Cl-KYNA, with an IC50 for [3H]glycine binding of 29 nM and an apparent Kb in the cortical wedge preparation of 0.41 microM. Reduction of the right-hand ring of 5,7-diCl-KYNA reduced affinity by 10-fold, but this was restored by substitution in the 4-position with the trans-phenylamide and further improved in the trans-benzylamide. The optimal compound was the transphenylurea (L-689,560), with an IC50 of 7.4 nM and an apparent Kb of 0.13 microM. Both series of compounds displayed a high degree of selectivity for the glycine site, having IC50 values of greater than 10 microM versus radioligand binding to the glutamate recognition sites of NMDA, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), and kainate receptors and the strychnine-sensitive glycine receptor. Selectivity versus AMPA receptor-mediated responses was also apparent in the rat cortical wedge and in patch-clamp recordings of cortical neurons in culture. Experiments using [3H]dizocilpine (MK-801) binding indicated that 5,7-diBr-KYNA, 5,7-diCl-KYNA, 5-I,7-Cl-KYNA, and L-689,560 all behaved as full antagonists and were competitive with glycine. Patch-clamp recordings of cortical neurons in culture also indicated that NMDA-induced currents were antagonized by competition for the glycine site, and gave no evidence for partial agonist activity. pKi values for 5,7-diBr-KYNA and L-689,560 in these experiments were 7.2 and 7.98, respectively, similar to the affinities of these compounds in the glycine binding assay. The high affinity and selectivity of these new derivatives make them useful tools to investigate the function of the glycine site on the NMDA receptor.

Energy systems research and development for petroleum refineries

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

Robertson, J.L.

1982-08-01

For the past several years, Exxon Reasearch and Engineering has carried out a specific RandD program aimed at improving refinery energy efficiency through optimization of energy systems. Energy systems include: steam/power systems, heat exchange systems including hot oil and hot water belts and fuel systems, as well as some of the processes. This paper will describe the three major thrusts of this program which are: development of methods to support Site Energy Survey activities; development of energy management methods; and energy system optimization, which includes development of consistent, realistic, economic incentives for energy system improvements. Project selection criteria will alsomore » be discussed. The technique of a site energy survey will also be described briefly.« less

[Temporal and spatial heterogeneity analysis of optimal value of sensitive parameters in ecological process model: The BIOME-BGC model as an example.

PubMed

Li, Yi Zhe; Zhang, Ting Long; Liu, Qiu Yu; Li, Ying

2018-01-01

The ecological process models are powerful tools for studying terrestrial ecosystem water and carbon cycle at present. However, there are many parameters for these models, and weather the reasonable values of these parameters were taken, have important impact on the models simulation results. In the past, the sensitivity and the optimization of model parameters were analyzed and discussed in many researches. But the temporal and spatial heterogeneity of the optimal parameters is less concerned. In this paper, the BIOME-BGC model was used as an example. In the evergreen broad-leaved forest, deciduous broad-leaved forest and C3 grassland, the sensitive parameters of the model were selected by constructing the sensitivity judgment index with two experimental sites selected under each vegetation type. The objective function was constructed by using the simulated annealing algorithm combined with the flux data to obtain the monthly optimal values of the sensitive parameters at each site. Then we constructed the temporal heterogeneity judgment index, the spatial heterogeneity judgment index and the temporal and spatial heterogeneity judgment index to quantitatively analyze the temporal and spatial heterogeneity of the optimal values of the model sensitive parameters. The results showed that the sensitivity of BIOME-BGC model parameters was different under different vegetation types, but the selected sensitive parameters were mostly consistent. The optimal values of the sensitive parameters of BIOME-BGC model mostly presented time-space heterogeneity to different degrees which varied with vegetation types. The sensitive parameters related to vegetation physiology and ecology had relatively little temporal and spatial heterogeneity while those related to environment and phenology had generally larger temporal and spatial heterogeneity. In addition, the temporal heterogeneity of the optimal values of the model sensitive parameters showed a significant linear correlation with the spatial heterogeneity under the three vegetation types. According to the temporal and spatial heterogeneity of the optimal values, the parameters of the BIOME-BGC model could be classified in order to adopt different parameter strategies in practical application. The conclusion could help to deeply understand the parameters and the optimal values of the ecological process models, and provide a way or reference for obtaining the reasonable values of parameters in models application.

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...

Nonreciprocal signal routing in an active quantum network

NASA Astrophysics Data System (ADS)

Metelmann, A.; Türeci, H. E.

2018-04-01

As superconductor quantum technologies are moving towards large-scale integrated circuits, a robust and flexible approach to routing photons at the quantum level becomes a critical problem. Active circuits, which contain parametrically driven elements selectively embedded in the circuit, offer a viable solution. Here, we present a general strategy for routing nonreciprocally quantum signals between two sites of a given lattice of oscillators, implementable with existing superconducting circuit components. Our approach makes use of a dual lattice of overdamped oscillators linking the nodes of the main lattice. Solutions for spatially selective driving of the lattice elements can be found, which optimally balance coherent and dissipative hopping of microwave photons to nonreciprocally route signals between two given nodes. In certain lattices these optimal solutions are obtained at the exceptional point of the dynamical matrix of the network. We also demonstrate that signal and noise transmission characteristics can be separately optimized.

An Elitist Multiobjective Tabu Search for Optimal Design of Groundwater Remediation Systems.

PubMed

Yang, Yun; Wu, Jianfeng; Wang, Jinguo; Zhou, Zhifang

2017-11-01

This study presents a new multiobjective evolutionary algorithm (MOEA), the elitist multiobjective tabu search (EMOTS), and incorporates it with MODFLOW/MT3DMS to develop a groundwater simulation-optimization (SO) framework based on modular design for optimal design of groundwater remediation systems using pump-and-treat (PAT) technique. The most notable improvement of EMOTS over the original multiple objective tabu search (MOTS) lies in the elitist strategy, selection strategy, and neighborhood move rule. The elitist strategy is to maintain all nondominated solutions within later search process for better converging to the true Pareto front. The elitism-based selection operator is modified to choose two most remote solutions from current candidate list as seed solutions to increase the diversity of searching space. Moreover, neighborhood solutions are uniformly generated using the Latin hypercube sampling (LHS) in the bounded neighborhood space around each seed solution. To demonstrate the performance of the EMOTS, we consider a synthetic groundwater remediation example. Problem formulations consist of two objective functions with continuous decision variables of pumping rates while meeting water quality requirements. Especially, sensitivity analysis is evaluated through the synthetic case for determination of optimal combination of the heuristic parameters. Furthermore, the EMOTS is successfully applied to evaluate remediation options at the field site of the Massachusetts Military Reservation (MMR) in Cape Cod, Massachusetts. With both the hypothetical and the large-scale field remediation sites, the EMOTS-based SO framework is demonstrated to outperform the original MOTS in achieving the performance metrics of optimality and diversity of nondominated frontiers with desirable stability and robustness. © 2017, National Ground Water Association.

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.

A methodology for optimal MSW management, with an application in the waste transportation of Attica Region, Greece

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

Economopoulou, M.A.; Economopoulou, A.A.; Economopoulos, A.P., E-mail: eco@otenet.gr

2013-11-15

Highlights: • A two-step (strategic and detailed optimal planning) methodology is used for solving complex MSW management problems. • A software package is outlined, which can be used for generating detailed optimal plans. • Sensitivity analysis compares alternative scenarios that address objections and/or wishes of local communities. • A case study shows the application of the above procedure in practice and demonstrates the results and benefits obtained. - Abstract: The paper describes a software system capable of formulating alternative optimal Municipal Solid Wastes (MSWs) management plans, each of which meets a set of constraints that may reflect selected objections and/ormore » wishes of local communities. The objective function to be minimized in each plan is the sum of the annualized capital investment and annual operating cost of all transportation, treatment and final disposal operations involved, taking into consideration the possible income from the sale of products and any other financial incentives or disincentives that may exist. For each plan formulated, the system generates several reports that define the plan, analyze its cost elements and yield an indicative profile of selected types of installations, as well as data files that facilitate the geographic representation of the optimal solution in maps through the use of GIS. A number of these reports compare the technical and economic data from all scenarios considered at the study area, municipality and installation level constituting in effect sensitivity analysis. The generation of alternative plans offers local authorities the opportunity of choice and the results of the sensitivity analysis allow them to choose wisely and with consensus. The paper presents also an application of this software system in the capital Region of Attica in Greece, for the purpose of developing an optimal waste transportation system in line with its approved waste management plan. The formulated plan was able to: (a) serve 113 Municipalities and Communities that generate nearly 2 million t/y of comingled MSW with distinctly different waste collection patterns, (b) take into consideration several existing waste transfer stations (WTS) and optimize their use within the overall plan, (c) select the most appropriate sites among the potentially suitable (new and in use) ones, (d) generate the optimal profile of each WTS proposed, and (e) perform sensitivity analysis so as to define the impact of selected sets of constraints (limitations in the availability of sites and in the capacity of their installations) on the design and cost of the ensuing optimal waste transfer system. The results show that optimal planning offers significant economic savings to municipalities, while reducing at the same time the present levels of traffic, fuel consumptions and air emissions in the congested Athens basin.« less

Fuzzy multicriteria disposal method and site selection for municipal solid waste.

PubMed

Ekmekçioğlu, Mehmet; Kaya, Tolga; Kahraman, Cengiz

2010-01-01

The use of fuzzy multiple criteria analysis (MCA) in solid waste management has the advantage of rendering subjective and implicit decision making more objective and analytical, with its ability to accommodate both quantitative and qualitative data. In this paper a modified fuzzy TOPSIS methodology is proposed for the selection of appropriate disposal method and site for municipal solid waste (MSW). Our method is superior to existing methods since it has capability of representing vague qualitative data and presenting all possible results with different degrees of membership. In the first stage of the proposed methodology, a set of criteria of cost, reliability, feasibility, pollution and emission levels, waste and energy recovery is optimized to determine the best MSW disposal method. Landfilling, composting, conventional incineration, and refuse-derived fuel (RDF) combustion are the alternatives considered. The weights of the selection criteria are determined by fuzzy pairwise comparison matrices of Analytic Hierarchy Process (AHP). It is found that RDF combustion is the best disposal method alternative for Istanbul. In the second stage, the same methodology is used to determine the optimum RDF combustion plant location using adjacent land use, climate, road access and cost as the criteria. The results of this study illustrate the importance of the weights on the various factors in deciding the optimized location, with the best site located in Catalca. A sensitivity analysis is also conducted to monitor how sensitive our model is to changes in the various criteria weights. 2010 Elsevier Ltd. All rights reserved.

More complete gene silencing by fewer siRNAs: transparent optimized design and biophysical signature

PubMed Central

Ladunga, Istvan

2007-01-01

Highly accurate knockdown functional analyses based on RNA interference (RNAi) require the possible most complete hydrolysis of the targeted mRNA while avoiding the degradation of untargeted genes (off-target effects). This in turn requires significant improvements to target selection for two reasons. First, the average silencing activity of randomly selected siRNAs is as low as 62%. Second, applying more than five different siRNAs may lead to saturation of the RNA-induced silencing complex (RISC) and to the degradation of untargeted genes. Therefore, selecting a small number of highly active siRNAs is critical for maximizing knockdown and minimizing off-target effects. To satisfy these needs, a publicly available and transparent machine learning tool is presented that ranks all possible siRNAs for each targeted gene. Support vector machines (SVMs) with polynomial kernels and constrained optimization models select and utilize the most predictive effective combinations from 572 sequence, thermodynamic, accessibility and self-hairpin features over 2200 published siRNAs. This tool reaches an accuracy of 92.3% in cross-validation experiments. We fully present the underlying biophysical signature that involves free energy, accessibility and dinucleotide characteristics. We show that while complete silencing is possible at certain structured target sites, accessibility information improves the prediction of the 90% active siRNA target sites. Fast siRNA activity predictions can be performed on our web server at . PMID:17169992

Bioprospecting for hyper-lipid producing microalgal strains for sustainable biofuel production.

PubMed

Mutanda, T; Ramesh, D; Karthikeyan, S; Kumari, S; Anandraj, A; Bux, F

2011-01-01

Global petroleum reserves are shrinking at a fast pace, increasing the demand for alternate fuels. Microalgae have the ability to grow rapidly, and synthesize and accumulate large amounts (approximately 20-50% of dry weight) of neutral lipid stored in cytosolic lipid bodies. A successful and economically viable algae based biofuel industry mainly depends on the selection of appropriate algal strains. The main focus of bioprospecting for microalgae is to identify unique high lipid producing microalgae from different habitats. Indigenous species of microalgae with high lipid yields are especially valuable in the biofuel industry. Isolation, purification and identification of natural microalgal assemblages using conventional techniques is generally time consuming. However, the recent use of micromanipulation as a rapid isolating tool allows for a higher screening throughput. The appropriate media and growth conditions are also important for successful microalgal proliferation. Environmental parameters recorded at the sampling site are necessary to optimize in vitro growth. Identification of species generally requires a combination of morphological and genetic characterization. The selected microalgal strains are grown in upscale systems such as raceway ponds or photobireactors for biomass and lipid production. This paper reviews the recent methodologies adopted for site selection, sampling, strain selection and identification, optimization of cultural conditions for superior lipid yield for biofuel production. Energy generation routes of microalgal lipids and biomass are discussed in detail. Copyright © 2010 Elsevier Ltd. All rights reserved.

Prioritizing conservation activities using reserve site selection methods and population viability analysis.

PubMed

Newbold, Stephen C; Siikamäki, Juha

2009-10-01

In recent years a large literature on reserve site selection (RSS) has developed at the interface between ecology, operations research, and environmental economics. Reserve site selection models use numerical optimization techniques to select sites for a network of nature reserves for protecting biodiversity. In this paper, we develop a population viability analysis (PVA) model for salmon and incorporate it into an RSS framework for prioritizing conservation activities in upstream watersheds. We use spawner return data for three closely related salmon stocks in the upper Columbia River basin and estimates of the economic costs of watershed protection from NOAA to illustrate the framework. We compare the relative cost-effectiveness of five alternative watershed prioritization methods, based on various combinations of biological and economic information. Prioritization based on biological benefit-economic cost comparisons and accounting for spatial interdependencies among watersheds substantially outperforms other more heuristic methods. When using this best-performing prioritization method, spending 10% of the cost of protecting all upstream watersheds yields 79% of the biological benefits (increase in stock persistence) from protecting all watersheds, compared to between 20% and 64% for the alternative methods. We also find that prioritization based on either costs or benefits alone can lead to severe reductions in cost-effectiveness.

Model of the best-of-N nest-site selection process in honeybees.

PubMed

Reina, Andreagiovanni; Marshall, James A R; Trianni, Vito; Bose, Thomas

2017-05-01

The ability of a honeybee swarm to select the best nest site plays a fundamental role in determining the future colony's fitness. To date, the nest-site selection process has mostly been modeled and theoretically analyzed for the case of binary decisions. However, when the number of alternative nests is larger than two, the decision-process dynamics qualitatively change. In this work, we extend previous analyses of a value-sensitive decision-making mechanism to a decision process among N nests. First, we present the decision-making dynamics in the symmetric case of N equal-quality nests. Then, we generalize our findings to a best-of-N decision scenario with one superior nest and N-1 inferior nests, previously studied empirically in bees and ants. Whereas previous binary models highlighted the crucial role of inhibitory stop-signaling, the key parameter in our new analysis is the relative time invested by swarm members in individual discovery and in signaling behaviors. Our new analysis reveals conflicting pressures on this ratio in symmetric and best-of-N decisions, which could be solved through a time-dependent signaling strategy. Additionally, our analysis suggests how ecological factors determining the density of suitable nest sites may have led to selective pressures for an optimal stable signaling ratio.

Model of the best-of-N nest-site selection process in honeybees

NASA Astrophysics Data System (ADS)

Reina, Andreagiovanni; Marshall, James A. R.; Trianni, Vito; Bose, Thomas

2017-05-01

The ability of a honeybee swarm to select the best nest site plays a fundamental role in determining the future colony's fitness. To date, the nest-site selection process has mostly been modeled and theoretically analyzed for the case of binary decisions. However, when the number of alternative nests is larger than two, the decision-process dynamics qualitatively change. In this work, we extend previous analyses of a value-sensitive decision-making mechanism to a decision process among N nests. First, we present the decision-making dynamics in the symmetric case of N equal-quality nests. Then, we generalize our findings to a best-of-N decision scenario with one superior nest and N -1 inferior nests, previously studied empirically in bees and ants. Whereas previous binary models highlighted the crucial role of inhibitory stop-signaling, the key parameter in our new analysis is the relative time invested by swarm members in individual discovery and in signaling behaviors. Our new analysis reveals conflicting pressures on this ratio in symmetric and best-of-N decisions, which could be solved through a time-dependent signaling strategy. Additionally, our analysis suggests how ecological factors determining the density of suitable nest sites may have led to selective pressures for an optimal stable signaling ratio.

Energy optimization system

DOEpatents

Zhou, Zhi; de Bedout, Juan Manuel; Kern, John Michael; Biyik, Emrah; Chandra, Ramu Sharat

2013-01-22

A system for optimizing customer utility usage in a utility network of customer sites, each having one or more utility devices, where customer site is communicated between each of the customer sites and an optimization server having software for optimizing customer utility usage over one or more networks, including private and public networks. A customer site model for each of the customer sites is generated based upon the customer site information, and the customer utility usage is optimized based upon the customer site information and the customer site model. The optimization server can be hosted by an external source or within the customer site. In addition, the optimization processing can be partitioned between the customer site and an external source.

Martian resource locations: Identification and optimization

NASA Astrophysics Data System (ADS)

Chamitoff, Gregory; James, George; Barker, Donald; Dershowitz, Adam

2005-04-01

The identification and utilization of in situ Martian natural resources is the key to enable cost-effective long-duration missions and permanent human settlements on Mars. This paper presents a powerful software tool for analyzing Martian data from all sources, and for optimizing mission site selection based on resource collocation. This program, called Planetary Resource Optimization and Mapping Tool (PROMT), provides a wide range of analysis and display functions that can be applied to raw data or imagery. Thresholds, contours, custom algorithms, and graphical editing are some of the various methods that can be used to process data. Output maps can be created to identify surface regions on Mars that meet any specific criteria. The use of this tool for analyzing data, generating maps, and collocating features is demonstrated using data from the Mars Global Surveyor and the Odyssey spacecraft. The overall mission design objective is to maximize a combination of scientific return and self-sufficiency based on utilization of local materials. Landing site optimization involves maximizing accessibility to collocated science and resource features within a given mission radius. Mission types are categorized according to duration, energy resources, and in situ resource utilization. Preliminary optimization results are shown for a number of mission scenarios.

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

An information theory application to improve understanding of subsurface flow and transport conditions at the BARC OPE3 site

USDA-ARS?s Scientific Manuscript database

Improving understanding of subsurface conditions includes comparison and discrimination of concurrent models. Additional observations can be useful for that purpose. The objective of this work was to implement and test a novel method for optimization of selecting locations for additional observation...

Physiological and ecological consequences of sleeping-site selection by the Galapagos land iguana (Conolophus pallidus)

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

Christian, K.A.; Tracy, C.R.

1984-01-01

Field observations and biophysical models were combined to analyze sleeping-site selection by Galapagos land iguanas (Conolophus pallidus). Iguanas slept in different kinds of sleeping sites during different seasons. In the coolest season (garua), adult land iguanas were found in sleeping sites that were warmer than the coolest sites available. This may be because the garua season (cool, overcast, and foggy) is a time when environmental conditions mitigate against rapid warm-up in the mornings, so lizards may regulate nighttime body temperatures so that it is easier to warm up to preferred daytime body temperatures. In the warmest season, adult iguanas weremore » found in the coolest sleeping sites available. This observation is consistent with hypotheses of voluntary hypothermia, which can be advantageous in energy conservation and in avoiding detrimental effects associated with maintenance of constant body temperatures throughout the day and night. Juvenile iguanas were found sleeping in rock crevices regardless of the ambient thermal environments. Such sites are likely to be important as refugia for this life stage, which, unlike the adult stage, is vulnerable to predation. It was concluded that selection of sleeping sites is a process that may help in avoidance of predation, optimization of body temperature at the end of the sleeping period, and reduction of metabolic costs during sleeping. The importance of some of these factors may change with the thermal milieu (e.g., season).« less

Geospatial Analytics in Retail Site Selection and Sales Prediction.

PubMed

Ting, Choo-Yee; Ho, Chiung Ching; Yee, Hui Jia; Matsah, Wan Razali

2018-03-01

Studies have shown that certain features from geography, demography, trade area, and environment can play a vital role in retail site selection, largely due to the impact they asserted on retail performance. Although the relevant features could be elicited by domain experts, determining the optimal feature set can be intractable and labor-intensive exercise. The challenges center around (1) how to determine features that are important to a particular retail business and (2) how to estimate retail sales performance given a new location? The challenges become apparent when the features vary across time. In this light, this study proposed a nonintervening approach by employing feature selection algorithms and subsequently sales prediction through similarity-based methods. The results of prediction were validated by domain experts. In this study, data sets from different sources were transformed and aggregated before an analytics data set that is ready for analysis purpose could be obtained. The data sets included data about feature location, population count, property type, education status, and monthly sales from 96 branches of a telecommunication company in Malaysia. The finding suggested that (1) optimal retail performance can only be achieved through fulfillment of specific location features together with the surrounding trade area characteristics and (2) similarity-based method can provide solution to retail sales prediction.

PrAS: Prediction of amidation sites using multiple feature extraction.

PubMed

Wang, Tong; Zheng, Wei; Wuyun, Qiqige; Wu, Zhenfeng; Ruan, Jishou; Hu, Gang; Gao, Jianzhao

2017-02-01

Amidation plays an important role in a variety of pathological processes and serious diseases like neural dysfunction and hypertension. However, identification of protein amidation sites through traditional experimental methods is time consuming and expensive. In this paper, we proposed a novel predictor for Prediction of Amidation Sites (PrAS), which is the first software package for academic users. The method incorporated four representative feature types, which are position-based features, physicochemical and biochemical properties features, predicted structure-based features and evolutionary information features. A novel feature selection method, positive contribution feature selection was proposed to optimize features. PrAS achieved AUC of 0.96, accuracy of 92.1%, sensitivity of 81.2%, specificity of 94.9% and MCC of 0.76 on the independent test set. PrAS is freely available at https://sourceforge.net/p/praspkg. Copyright © 2016 Elsevier Ltd. All rights reserved.

Waste deposit influences on groundwater quality as a tool for waste type and site selection for final storage quality

NASA Astrophysics Data System (ADS)

Arneth, Jan-Dirk; Milde, Gerald; Kerndorff, Helmut; Schleyer, Ruprecht

Leachates from deposits of wastes may, in the long run, adversely influence groundwater quality. Since tipping still constitutes the most important form of waste disposal, strategies must be developed which are capable of protecting groundwater against contamination from leachates. In the first instance such protective measures must provide for a minimization of contamination by setting up optimal barriers. Since it would seem difficult to reach this goal in a forseeable future, the avoidance of substances with a high potential for groundwater hazards has to be attributed much importance. In former times, little attention was given to impermeability or avoidance of substances with a high potential for groundwater hazards contained in wastes. Therefore, results of the investigation of groundwater near abandoned sites can be used to optimize groundwater protection on future tipping sites. In the present study, the results of chemical investigation of groundwater from the vicinity of 92 waste disposal sites in the Federal Republic of Germany are presented and the changes in groundwater quality owing to the penetration of leachates are discussed separately for inorganic and organic contaminants.

Anterior wrist and medial malleolus: the optimal sites for tissue selection in electric death through hand-to-foot circuit pathway.

PubMed

Xu, Guangtao; Su, Ruibing; Lv, Junyao; Lai, Xiaoping; Li, Xianxian; Wu, Jiayan; Hu, Bo; Xu, Long; Shen, Ruilin; Gu, Jiang; Yu, Xiaojun

2017-03-01

Specific morphological changes may be absent in some cases of electrocution shocked by the voltage of 220 V or lower. In this study, we attempted to demonstrate that the anterior wrist and medial malleolus were the optimal sites with promising and significant changes in electric death through the hand-to-foot circuit pathway. We established an electric shock rat model and observed histopathologic changes in the anterior wrist and medial malleolus. The results showed that the current intensities in the left anterior wrist and right medial malleolus were remarkably higher than those in the other sites, and the nuclei long/short (L/S) axis ratios of the arterial endotheliocyte and the skeletal muscle cell in these two areas were significantly higher than those in other parts of the body. These findings suggested that the anterior wrist and/or medial malleolus soft tissues as the narrowest parts of the limbs could be used as promising and useful sites for the assessment of electrical shock death, especially in forensic pathologic evaluation.

Protein pharmacophore selection using hydration-site analysis

PubMed Central

Hu, Bingjie; Lill, Markus A.

2012-01-01

Virtual screening using pharmacophore models is an efficient method to identify potential lead compounds for target proteins. Pharmacophore models based on protein structures are advantageous because a priori knowledge of active ligands is not required and the models are not biased by the chemical space of previously identified actives. However, in order to capture most potential interactions between all potentially binding ligands and the protein, the size of the pharmacophore model, i.e. number of pharmacophore elements, is typically quite large and therefore reduces the efficiency of pharmacophore based screening. We have developed a new method to select important pharmacophore elements using hydration-site information. The basic premise is that ligand functional groups that replace water molecules in the apo protein contribute strongly to the overall binding affinity of the ligand, due to the additional free energy gained from releasing the water molecule into the bulk solvent. We computed the free energy of water released from the binding site for each hydration site using thermodynamic analysis of molecular dynamics (MD) simulations. Pharmacophores which are co-localized with hydration sites with estimated favorable contributions to the free energy of binding are selected to generate a reduced pharmacophore model. We constructed reduced pharmacophore models for three protein systems and demonstrated good enrichment quality combined with high efficiency. The reduction in pharmacophore model size reduces the required screening time by a factor of 200–500 compared to using all protein pharmacophore elements. We also describe a training process using a small set of known actives to reliably select the optimal set of criteria for pharmacophore selection for each protein system. PMID:22397751

Large-scale identification of core-fucosylated glycopeptide sites in pancreatic cancer serum using mass spectrometry.

PubMed

Tan, Zhijing; Yin, Haidi; Nie, Song; Lin, Zhenxin; Zhu, Jianhui; Ruffin, Mack T; Anderson, Michelle A; Simeone, Diane M; Lubman, David M

2015-04-03

Glycosylation has significant effects on protein function and cell metastasis, which are important in cancer progression. It is of great interest to identify site-specific glycosylation in search of potential cancer biomarkers. However, the abundance of glycopeptides is low compared to that of nonglycopeptides after trypsin digestion of serum samples, and the mass spectrometric signals of glycopeptides are often masked by coeluting nonglycopeptides due to low ionization efficiency. Selective enrichment of glycopeptides from complex serum samples is essential for mass spectrometry (MS)-based analysis. Herein, a strategy has been optimized using LCA enrichment to improve the identification of core-fucosylation (CF) sites in serum of pancreatic cancer patients. The optimized strategy was then applied to analyze CF glycopeptide sites in 13 sets of serum samples from pancreatic cancer, chronic pancreatitis, healthy controls, and a standard reference. In total, 630 core-fucosylation sites were identified from 322 CF proteins in pancreatic cancer patient serum using an Orbitrap Elite mass spectrometer. Further data analysis revealed that 8 CF peptides exhibited a significant difference between pancreatic cancer and other controls, which may be potential diagnostic biomarkers for pancreatic cancer.

Evolving artificial metalloenzymes via random mutagenesis

NASA Astrophysics Data System (ADS)

Yang, Hao; Swartz, Alan M.; Park, Hyun June; Srivastava, Poonam; Ellis-Guardiola, Ken; Upp, David M.; Lee, Gihoon; Belsare, Ketaki; Gu, Yifan; Zhang, Chen; Moellering, Raymond E.; Lewis, Jared C.

2018-03-01

Random mutagenesis has the potential to optimize the efficiency and selectivity of protein catalysts without requiring detailed knowledge of protein structure; however, introducing synthetic metal cofactors complicates the expression and screening of enzyme libraries, and activity arising from free cofactor must be eliminated. Here we report an efficient platform to create and screen libraries of artificial metalloenzymes (ArMs) via random mutagenesis, which we use to evolve highly selective dirhodium cyclopropanases. Error-prone PCR and combinatorial codon mutagenesis enabled multiplexed analysis of random mutations, including at sites distal to the putative ArM active site that are difficult to identify using targeted mutagenesis approaches. Variants that exhibited significantly improved selectivity for each of the cyclopropane product enantiomers were identified, and higher activity than previously reported ArM cyclopropanases obtained via targeted mutagenesis was also observed. This improved selectivity carried over to other dirhodium-catalysed transformations, including N-H, S-H and Si-H insertion, demonstrating that ArMs evolved for one reaction can serve as starting points to evolve catalysts for others.

Foraging Ecology of Fall-Migrating Shorebirds in the Illinois River Valley

PubMed Central

Smith, Randolph V.; Stafford, Joshua D.; Yetter, Aaron P.; Horath, Michelle M.; Hine, Christopher S.; Hoover, Jeffery P.

2012-01-01

Populations of many shorebird species appear to be declining in North America, and food resources at stopover habitats may limit migratory bird populations. We investigated body condition of, and foraging habitat and diet selection by 4 species of shorebirds in the central Illinois River valley during fall migrations 2007 and 2008 (Killdeer [Charadrius vociferus], Least Sandpiper [Calidris minutilla], Pectoral Sandpiper [Calidris melanotos], and Lesser Yellowlegs [Tringa flavipes]). All species except Killdeer were in good to excellent condition, based on size-corrected body mass and fat scores. Shorebird diets were dominated by invertebrate taxa from Orders Diptera and Coleoptera. Additionally, Isopoda, Hemiptera, Hirudinea, Nematoda, and Cyprinodontiformes contribution to diets varied by shorebird species and year. We evaluated diet and foraging habitat selection by comparing aggregate percent dry mass of food items in shorebird diets and core samples from foraging substrates. Invertebrate abundances at shorebird collection sites and random sites were generally similar, indicating that birds did not select foraging patches within wetlands based on invertebrate abundance. Conversely, we found considerable evidence for selection of some diet items within particular foraging sites, and consistent avoidance of Oligochaeta. We suspect the diet selectivity we observed was a function of overall invertebrate biomass (51.2±4.4 [SE] kg/ha; dry mass) at our study sites, which was greater than estimates reported in most other food selection studies. Diet selectivity in shorebirds may follow tenants of optimal foraging theory; that is, at low food abundances shorebirds forage opportunistically, with the likelihood of selectivity increasing as food availability increases. Nonetheless, relationships between the abundance, availability, and consumption of Oligochaetes for and by waterbirds should be the focus of future research, because estimates of foraging carrying capacity would need to be revised downward if Oligochaetes are truly avoided or unavailable for consumption. PMID:23028795

Adsorbate-mediated strong metal–support interactions in oxide-supported Rh catalysts

DOE PAGES

Matsubu, John C.; Zhang, Shuyi; DeRita, Leo; ...

2016-09-19

The optimization of supported metal catalysts predominantly focuses on engineering the metal site, for which physical insights based on extensive theoretical and experimental contributions have enabled the rational design of active sites. Although it is well known that supports can influence the catalytic properties of metals, insights into how metal–support interactions can be exploited to optimize metal active-site properties are lacking. Here in this paper, we utilize in situ spectroscopy and microscopy to identify and characterize a support effect in oxide-supported heterogeneous Rh catalysts. This effect is characterized by strongly bound adsorbates (HCO x) on reducible oxide supports (TiO 2more » and Nb 2O 5) that induce oxygen-vacancy formation in the support and cause HCO x-functionalized encapsulation of Rh nanoparticles by the support. The encapsulation layer is permeable to reactants, stable under the reaction conditions and strongly influences the catalytic properties of Rh, which enables rational and dynamic tuning of CO 2-reduction selectivity.« less

Improvement of the optimum pH of Aspergillus niger xylanase towards an alkaline pH by site-directed mutagenesis.

PubMed

Li, Fei; Xie, Jingcong; Zhang, Xuesong; Zhao, Linguo

2015-01-01

In an attempt to shift the optimal pH of the xylanase B (XynB) from Aspergillus niger towards alkalinity, target mutation sites were selected by alignment between Aspergillus niger xylanase B and other xylanases that have alkalophilic pH optima that highlight charged residues in the eight-residues-longer loop in the alkalophilic xylanase. Multiple engineered XynB mutants were created by site-directed mutagenesis with substitutions Q164K and Q164K+D117N. The variant XynB-117 had the highest optimum pH (at 5.5), which corresponded to a basic 0.5 pH unit shift when compared with the wild-type enzyme. However, the optimal pH of the XynB- 164 mutation was not changed, similar to the wild type. These results suggest that the residues at positions 164 and 117 in the eight-residues-longer loop and the cleft's edge are important in determining the pH optima of XynB from Aspergillus niger.

Selective Enrichment and Direct Analysis of Protein S-Palmitoylation Sites.

PubMed

Thinon, Emmanuelle; Fernandez, Joseph P; Molina, Henrik; Hang, Howard C

2018-05-04

S-Fatty-acylation is the covalent attachment of long chain fatty acids, predominately palmitate (C16:0, S-palmitoylation), to cysteine (Cys) residues via a thioester linkage on proteins. This post-translational and reversible lipid modification regulates protein function and localization in eukaryotes and is important in mammalian physiology and human diseases. While chemical labeling methods have improved the detection and enrichment of S-fatty-acylated proteins, mapping sites of modification and characterizing the endogenously attached fatty acids are still challenging. Here, we describe the integration and optimization of fatty acid chemical reporter labeling with hydroxylamine-mediated enrichment of S-fatty-acylated proteins and direct tagging of modified Cys residues to selectively map lipid modification sites. This afforded improved enrichment and direct identification of many protein S-fatty-acylation sites compared to previously described methods. Notably, we directly identified the S-fatty-acylation sites of IFITM3, an important interferon-stimulated inhibitor of virus entry, and we further demonstrated that the highly conserved Cys residues are primarily modified by palmitic acid. The methods described here should facilitate the direct analysis of protein S-fatty-acylation sites and their endogenously attached fatty acids in diverse cell types and activation states important for mammalian physiology and diseases.

Deep Sequencing of Random Mutant Libraries Reveals the Active Site of the Narrow Specificity CphA Metallo-β-Lactamase is Fragile to Mutations.

PubMed

Sun, Zhizeng; Mehta, Shrenik C; Adamski, Carolyn J; Gibbs, Richard A; Palzkill, Timothy

2016-09-12

CphA is a Zn(2+)-dependent metallo-β-lactamase that efficiently hydrolyzes only carbapenem antibiotics. To understand the sequence requirements for CphA function, single codon random mutant libraries were constructed for residues in and near the active site and mutants were selected for E. coli growth on increasing concentrations of imipenem, a carbapenem antibiotic. At high concentrations of imipenem that select for phenotypically wild-type mutants, the active-site residues exhibit stringent sequence requirements in that nearly all residues in positions that contact zinc, the substrate, or the catalytic water do not tolerate amino acid substitutions. In addition, at high imipenem concentrations a number of residues that do not directly contact zinc or substrate are also essential and do not tolerate substitutions. Biochemical analysis confirmed that amino acid substitutions at essential positions decreased the stability or catalytic activity of the CphA enzyme. Therefore, the CphA active - site is fragile to substitutions, suggesting active-site residues are optimized for imipenem hydrolysis. These results also suggest that resistance to inhibitors targeted to the CphA active site would be slow to develop because of the strong sequence constraints on function.

Tree Height and DBH Growth Model Establishment of Main Tree Species in Wuling Mountain Small Watershed

NASA Astrophysics Data System (ADS)

Luo, Jia; Zhang, Min; Zhou, Xiaoling; Chen, Jianhua; Tian, Yuxin

2018-01-01

Taken 4 main tree species in the Wuling mountain small watershed as research objects, 57 typical sample plots were set up according to the stand type, site conditions and community structure. 311 goal diameter-class sample trees were selected according to diameter-class groups of different tree-height grades, and the optimal fitting models of tree height and DBH growth of main tree species were obtained by stem analysis using Richard, Logistic, Korf, Mitscherlich, Schumacher, Weibull theoretical growth equations, and the correlation coefficient of all optimal fitting models reached above 0.9. Through the evaluation and test, the optimal fitting models possessed rather good fitting precision and forecast dependability.

Optimal allocation of invasive species surveillance with the maximum expected coverage concept

Treesearch

Denys Yemshanov; Robert G. Haight; Frank H. Koch; Bo Lu; Robert Venette; D. Barry Lyons; Taylor Scarr; Krista Ryall; Brian. Leung

2015-01-01

We address the problem of geographically allocating scarce survey resources to detect pests in their pathways of introduction given information about their likelihood of movement between origins and destinations. We introduce a model for selecting destination sites for survey that departs from the aim of reducing propagule pressure (PP) in pest destinations and instead...

An Integer Optimization Approch To A Probabilistic Reserve Site Selection Problem

Treesearch

Robert G. Haight; Charles S. Revelle; Stephanie A. Snyder

2000-01-01

Human economic and agricultural activities contribute to the endangerment of over 900 species that are currently listed or proposed for listing under the federal Endangered Species Act in the United States (Dobson et al. 1997). One approach to conserving the elements of biological diversity--including plants, animals, and ecological communities--is to establish and...

[Hyperspectral remote sensing image classification based on SVM optimized by clonal selection].

PubMed

Liu, Qing-Jie; Jing, Lin-Hai; Wang, Meng-Fei; Lin, Qi-Zhong

2013-03-01

Model selection for support vector machine (SVM) involving kernel and the margin parameter values selection is usually time-consuming, impacts training efficiency of SVM model and final classification accuracies of SVM hyperspectral remote sensing image classifier greatly. Firstly, based on combinatorial optimization theory and cross-validation method, artificial immune clonal selection algorithm is introduced to the optimal selection of SVM (CSSVM) kernel parameter a and margin parameter C to improve the training efficiency of SVM model. Then an experiment of classifying AVIRIS in India Pine site of USA was performed for testing the novel CSSVM, as well as a traditional SVM classifier with general Grid Searching cross-validation method (GSSVM) for comparison. And then, evaluation indexes including SVM model training time, classification overall accuracy (OA) and Kappa index of both CSSVM and GSSVM were all analyzed quantitatively. It is demonstrated that OA of CSSVM on test samples and whole image are 85.1% and 81.58, the differences from that of GSSVM are both within 0.08% respectively; And Kappa indexes reach 0.8213 and 0.7728, the differences from that of GSSVM are both within 0.001; While the ratio of model training time of CSSVM and GSSVM is between 1/6 and 1/10. Therefore, CSSVM is fast and accurate algorithm for hyperspectral image classification and is superior to GSSVM.

iCycle: Integrated, multicriterial beam angle, and profile optimization for generation of coplanar and noncoplanar IMRT plans

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

Breedveld, Sebastiaan; Storchi, Pascal R. M.; Voet, Peter W. J.

2012-02-15

Purpose: To introduce iCycle, a novel algorithm for integrated, multicriterial optimization of beam angles, and intensity modulated radiotherapy (IMRT) profiles. Methods: A multicriterial plan optimization with iCycle is based on a prescription called wish-list, containing hard constraints and objectives with ascribed priorities. Priorities are ordinal parameters used for relative importance ranking of the objectives. The higher an objective priority is, the higher the probability that the corresponding objective will be met. Beam directions are selected from an input set of candidate directions. Input sets can be restricted, e.g., to allow only generation of coplanar plans, or to avoid collisions betweenmore » patient/couch and the gantry in a noncoplanar setup. Obtaining clinically feasible calculation times was an important design criterium for development of iCycle. This could be realized by sequentially adding beams to the treatment plan in an iterative procedure. Each iteration loop starts with selection of the optimal direction to be added. Then, a Pareto-optimal IMRT plan is generated for the (fixed) beam setup that includes all so far selected directions, using a previously published algorithm for multicriterial optimization of fluence profiles for a fixed beam arrangement Breedveld et al.[Phys. Med. Biol. 54, 7199-7209 (2009)]. To select the next direction, each not yet selected candidate direction is temporarily added to the plan and an optimization problem, derived from the Lagrangian obtained from the just performed optimization for establishing the Pareto-optimal plan, is solved. For each patient, a single one-beam, two-beam, three-beam, etc. Pareto-optimal plan is generated until addition of beams does no longer result in significant plan quality improvement. Plan generation with iCycle is fully automated. Results: Performance and characteristics of iCycle are demonstrated by generating plans for a maxillary sinus case, a cervical cancer patient, and a liver patient treated with SBRT. Plans generated with beam angle optimization did better meet the clinical goals than equiangular or manually selected configurations. For the maxillary sinus and liver cases, significant improvements for noncoplanar setups were seen. The cervix case showed that also in IMRT with coplanar setups, beam angle optimization with iCycle may improve plan quality. Computation times for coplanar plans were around 1-2 h and for noncoplanar plans 4-7 h, depending on the number of beams and the complexity of the site. Conclusions: Integrated beam angle and profile optimization with iCycle may result in significant improvements in treatment plan quality. Due to automation, the plan generation workload is minimal. Clinical application has started.« less

The Application of Computer-Aided Discovery to Spacecraft Site Selection

NASA Astrophysics Data System (ADS)

Pankratius, V.; Blair, D. M.; Gowanlock, M.; Herring, T.

2015-12-01

The selection of landing and exploration sites for interplanetary robotic or human missions is a complex task. Historically it has been labor-intensive, with large groups of scientists manually interpreting a planetary surface across a variety of datasets to identify potential sites based on science and engineering constraints. This search process can be lengthy, and excellent sites may get overlooked when the aggregate value of site selection criteria is non-obvious or non-intuitive. As planetary data collection leads to Big Data repositories and a growing set of selection criteria, scientists will face a combinatorial search space explosion that requires scalable, automated assistance. We are currently exploring more general computer-aided discovery techniques in the context of planetary surface deformation phenomena that can lend themselves to application in the landing site search problem. In particular, we are developing a general software framework that addresses key difficulties: characterizing a given phenomenon or site based on data gathered from multiple instruments (e.g. radar interferometry, gravity, thermal maps, or GPS time series), and examining a variety of possible workflows whose individual configurations are optimized to isolate different features. The framework allows algorithmic pipelines and hypothesized models to be perturbed or permuted automatically within well-defined bounds established by the scientist. For example, even simple choices for outlier and noise handling or data interpolation can drastically affect the detectability of certain features. These techniques aim to automate repetitive tasks that scientists routinely perform in exploratory analysis, and make them more efficient and scalable by executing them in parallel in the cloud. We also explore ways in which machine learning can be combined with human feedback to prune the search space and converge to desirable results. Acknowledgements: We acknowledge support from NASA AIST NNX15AG84G (PI V. Pankratius)

Residues of selected antibiotics in the South Moravian Rivers, Czech Republic.

PubMed

Jarova, Katerina; Vavrova, Milada; Koleckarova, Alice

2015-01-01

The aim of this study was to assess the contamination level of aquatic ecosystems of the Oslava and the Jihlava Rivers, and of the Nove Mlyny Water Reservoir, situated in the South Moravian Region (Czech Republic), by residues of selected veterinary pharmaceuticals. We isolated and determined 10 sulfonamide antibiotics in samples of surface water and bottom sediments using optimized analytical methods. A representative number of sampling sites in the entire basin of selected waters were chosen. Samples were collected particularly near the larger cities in order to assess their possible impact to the aquatic ecosystems. Extraction, pre-concentration and purification of samples were performed using optimized methods of solid phase extraction and pressurized solvent extraction. Final identification and quantification were carried out by high-performance liquid chromatography coupled with diode array detector. The concentration of sulfonamides in water samples were all under the limit of detection. Regarding sediment samples, sulfadimidine was found at most sampling sites; its highest values were recorded in the Jihlava River (up to 979.8 µg.kg(-1) dry matter). Other frequently detected sulfonamides were sulfamethoxazole and sulfamerazine. Most other sulfonamides were under the limit of detection or limit of quantification. Monitoring of antibiotic residues in the environment, especially in the aquatic ecosystem, is a current topic due to the growing worldwide use in both human and veterinary medicine. According to obtained results, we document the pollution of selected rivers and water reservoir by particular sulfonamides which basically reflects their application in veterinary medicine.

Management decision of optimal recharge water in groundwater artificial recharge conditions- A case study in an artificial recharge test site

NASA Astrophysics Data System (ADS)

He, H. Y.; Shi, X. F.; Zhu, W.; Wang, C. Q.; Ma, H. W.; Zhang, W. J.

2017-11-01

The city conducted groundwater artificial recharge test which was taken a typical site as an example, and the purpose is to prevent and control land subsidence, increase the amount of groundwater resources. To protect groundwater environmental quality and safety, the city chose tap water as recharge water, however, the high cost makes it not conducive to the optimal allocation of water resources and not suitable to popularize widely. To solve this, the city selects two major surface water of River A and B as the proposed recharge water, to explore its feasibility. According to a comprehensive analysis of the cost of recharge, the distance of the water transport, the quality of recharge water and others. Entropy weight Fuzzy Comprehensive Evaluation Method is used to prefer tap water and water of River A and B. Evaluation results show that water of River B is the optimal recharge water, if used; recharge cost will be from 0.4724/m3 to 0.3696/m3. Using Entropy weight Fuzzy Comprehensive Evaluation Method to confirm water of River B as optimal water is scientific and reasonable. The optimal water management decisions can provide technical support for the city to carry out overall groundwater artificial recharge engineering in deep aquifer.

Age trends of genetic parameters, early selection and family by site interactions for growth traits in Larix kaempferi open-pollinated families.

PubMed

Diao, Shu; Hou, Yimei; Xie, Yunhui; Sun, Xiaomei

2016-07-07

Japanese larch (Larix kaempferi) as a successful exotic species has become one of the most important economic and ecological conifers in China. In order to broaden the genetic resource of Larix kaempferi, an effort was made in 1996 to introduce 128 families from seven seed orchards in Japan, with which to establish two progeny trials in climatically different environments. The experiment was aimed to determine the strategy of early selection, particularly important for long-rotated Japanese larch, and the optimal breeding program for specific environments. Growth trajectories revealed different growth performances of stem height (HGT) and diameter at breast height (DBH) in two different environments, Hubei and Liaoning. In both sites, there were marked variabilities in HGT, DBH and volume (VOL) among families at each year. The trends of individual and family heritability and age-age correlations were found to follow a certain dynamic pattern. Based on these trends, the optimum selection age was determined at four years for HGT and five years for DBH in Hubei and Liaoning. Genetic gains for VOL were 34.4 and 6.04 % in Hubei and Liaoning respectively when selection ratio was 10 % at age 16. Type-B correlations were less than 0.67 and rank correlations of breeding value were less than 0.4 for HGT, DBH and VOL between the two sites, revealing that there exist pronounced family-by-site interactions for the growth traits of Larix kaempferi. Early selection for Larix kaempferi is an effective strategy to overcome its long rotation age. In early selection, dual growth trait selection is more effective than single one. Regionalization deployment should be considered in Larix. kaempferi breeding program based on different environmental factors.

Parameter sensitivity analysis and optimization for a satellite-based evapotranspiration model across multiple sites using Moderate Resolution Imaging Spectroradiometer and flux data

NASA Astrophysics Data System (ADS)

Zhang, Kun; Ma, Jinzhu; Zhu, Gaofeng; Ma, Ting; Han, Tuo; Feng, Li Li

2017-01-01

Global and regional estimates of daily evapotranspiration are essential to our understanding of the hydrologic cycle and climate change. In this study, we selected the radiation-based Priestly-Taylor Jet Propulsion Laboratory (PT-JPL) model and assessed it at a daily time scale by using 44 flux towers. These towers distributed in a wide range of ecological systems: croplands, deciduous broadleaf forest, evergreen broadleaf forest, evergreen needleleaf forest, grasslands, mixed forests, savannas, and shrublands. A regional land surface evapotranspiration model with a relatively simple structure, the PT-JPL model largely uses ecophysiologically-based formulation and parameters to relate potential evapotranspiration to actual evapotranspiration. The results using the original model indicate that the model always overestimates evapotranspiration in arid regions. This likely results from the misrepresentation of water limitation and energy partition in the model. By analyzing physiological processes and determining the sensitive parameters, we identified a series of parameter sets that can increase model performance. The model with optimized parameters showed better performance (R2 = 0.2-0.87; Nash-Sutcliffe efficiency (NSE) = 0.1-0.87) at each site than the original model (R2 = 0.19-0.87; NSE = -12.14-0.85). The results of the optimization indicated that the parameter β (water control of soil evaporation) was much lower in arid regions than in relatively humid regions. Furthermore, the optimized value of parameter m1 (plant control of canopy transpiration) was mostly between 1 to 1.3, slightly lower than the original value. Also, the optimized parameter Topt correlated well to the actual environmental temperature at each site. We suggest that using optimized parameters with the PT-JPL model could provide an efficient way to improve the model performance.

Solubilization and characterization of haloperidol-sensitive (+)-( sup 3 H)SKF-10,047 binding sites (sigma sites) from rat liver membranes

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

McCann, D.J.; Su, T.P.

1991-05-01

The zwitterionic detergent 3-((3-cholamidopropyl)dimethylamino)-1-propanesulfonate (CHAPS) produced optimal solubilization of (+)-({sup 3}H)SKF-10,047 binding sites from rat liver membranes at a concentration of 0.2%, well below the critical micellular concentration of the detergent. The pharmacological selectivity of the liver (+)-({sup 3}H)SKF-10,047 binding sites corresponds to that of sigma sites from rat and guinea pig brain. When the affinities of 18 different drugs at (+)-({sup 3}H)SKF-10,047 binding sites in membranes and solubilized preparations were compared, a correlation coefficient of 0.99 and a slope of 1.03 were obtained, indicating that the pharmacological selectivity of rat liver sigma sites is retained after solubilization. In addition,more » the binding of 20 nM ({sup 3}H)progesterone to solubilized rat liver preparations was found to exhibit a pharmacological selectivity appropriate for sigma sites. A stimulatory effect of phenytoin on (+)-({sup 3}H)SKF-10,047 binding to sigma sites persisted after solubilization. When the solubilized preparation was subjected to molecular sizing chromatography, a single peak exhibiting specific (+)-({sup 3}H)SKF-10,047 binding was obtained. The binding activity of this peak was stimulated symmetrically when assays were performed in the presence of 300 microM phenytoin. The molecular weight of the CHAPS-solubilized sigma site complex was estimated to be 450,000 daltons. After solubilization with CHAPS, rat liver sigma sites were enriched to 12 pmol/mg of protein. The present results demonstrate a successful solubilization of sigma sites from rat liver membranes and provide direct evidence that the gonadal steroid progesterone binds to sigma sites. The results also suggest that the anticonvulsant phenytoin binds to an associated allosteric site on the sigma site complex.« less

Site Optimization Tracker: Crossley Farm Superfund Site, Hereford and Washington Townships, Berks County, Pennsylvania

EPA Pesticide Factsheets

Pilot Region-Based Optimization Program for Fund-Lead Sites in EPA Region 3. Site Optimization Tracking information for Crossley Farm Superfund Site, Hereford and Washington Townships, Berks County, Pennsylvania.

Systematic feature selection improves accuracy of methylation-based forensic age estimation in Han Chinese males.

PubMed

Feng, Lei; Peng, Fuduan; Li, Shanfei; Jiang, Li; Sun, Hui; Ji, Anquan; Zeng, Changqing; Li, Caixia; Liu, Fan

2018-03-23

Estimating individual age from biomarkers may provide key information facilitating forensic investigations. Recent progress has shown DNA methylation at age-associated CpG sites as the most informative biomarkers for estimating the individual age of an unknown donor. Optimal feature selection plays a critical role in determining the performance of the final prediction model. In this study we investigate methylation levels at 153 age-associated CpG sites from 21 previously reported genomic regions using the EpiTYPER system for their predictive power on individual age in 390 Han Chinese males ranging from 15 to 75 years of age. We conducted a systematic feature selection using a stepwise backward multiple linear regression analysis as well as an exhaustive searching algorithm. Both approaches identified the same subset of 9 CpG sites, which in linear combination provided the optimal model fitting with mean absolute deviation (MAD) of 2.89 years of age and explainable variance (R 2 ) of 0.92. The final model was validated in two independent Han Chinese male samples (validation set 1, N = 65, MAD = 2.49, R 2  = 0.95, and validation set 2, N = 62, MAD = 3.36, R 2  = 0.89). Other competing models such as support vector machine and artificial neural network did not outperform the linear model to any noticeable degree. The validation set 1 was additionally analyzed using Pyrosequencing technology for cross-platform validation and was termed as validation set 3. Directly applying our model, in which the methylation levels were detected by the EpiTYPER system, to the data from pyrosequencing technology showed, however, less accurate results in terms of MAD (validation set 3, N = 65 Han Chinese males, MAD = 4.20, R 2  = 0.93), suggesting the presence of a batch effect between different data generation platforms. This batch effect could be partially overcome by a z-score transformation (MAD = 2.76, R 2  = 0.93). Overall, our systematic feature selection identified 9 CpG sites as the optimal subset for forensic age estimation and the prediction model consisting of these 9 markers demonstrated high potential in forensic practice. An age estimator implementing our prediction model allowing missing markers is freely available at http://liufan.big.ac.cn/AgePrediction. Copyright © 2018 Elsevier B.V. All rights reserved.

Halogenase engineering and its utility in medicinal chemistry.

PubMed

Fraley, Amy E; Sherman, David H

2018-06-15

Halogenation is commonly used in medicinal chemistry to improve the potency of pharmaceutical leads. While synthetic methods for halogenation present selectivity and reactivity challenges, halogenases have evolved over time to perform selective reactions under benign conditions. The optimization of halogenation biocatalysts has utilized enzyme evolution and structure-based engineering alongside biotransformation in a variety of systems to generate stable site-selective variants. The recent improvements in halogenase-catalyzed reactions has demonstrated the utility of these biocatalysts for industrial purposes, and their ability to achieve a broad substrate scope implies a synthetic tractability with increasing relevance in medicinal chemistry. Copyright © 2018 Elsevier Ltd. All rights reserved.

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).

Planning for robust reserve networks using uncertainty analysis

USGS Publications Warehouse

Moilanen, A.; Runge, M.C.; Elith, Jane; Tyre, A.; Carmel, Y.; Fegraus, E.; Wintle, B.A.; Burgman, M.; Ben-Haim, Y.

2006-01-01

Planning land-use for biodiversity conservation frequently involves computer-assisted reserve selection algorithms. Typically such algorithms operate on matrices of species presence?absence in sites, or on species-specific distributions of model predicted probabilities of occurrence in grid cells. There are practically always errors in input data?erroneous species presence?absence data, structural and parametric uncertainty in predictive habitat models, and lack of correspondence between temporal presence and long-run persistence. Despite these uncertainties, typical reserve selection methods proceed as if there is no uncertainty in the data or models. Having two conservation options of apparently equal biological value, one would prefer the option whose value is relatively insensitive to errors in planning inputs. In this work we show how uncertainty analysis for reserve planning can be implemented within a framework of information-gap decision theory, generating reserve designs that are robust to uncertainty. Consideration of uncertainty involves modifications to the typical objective functions used in reserve selection. Search for robust-optimal reserve structures can still be implemented via typical reserve selection optimization techniques, including stepwise heuristics, integer-programming and stochastic global search.

Identifying functionally informative evolutionary sequence profiles.

PubMed

Gil, Nelson; Fiser, Andras

2018-04-15

Multiple sequence alignments (MSAs) can provide essential input to many bioinformatics applications, including protein structure prediction and functional annotation. However, the optimal selection of sequences to obtain biologically informative MSAs for such purposes is poorly explored, and has traditionally been performed manually. We present Selection of Alignment by Maximal Mutual Information (SAMMI), an automated, sequence-based approach to objectively select an optimal MSA from a large set of alternatives sampled from a general sequence database search. The hypothesis of this approach is that the mutual information among MSA columns will be maximal for those MSAs that contain the most diverse set possible of the most structurally and functionally homogeneous protein sequences. SAMMI was tested to select MSAs for functional site residue prediction by analysis of conservation patterns on a set of 435 proteins obtained from protein-ligand (peptides, nucleic acids and small substrates) and protein-protein interaction databases. Availability and implementation: A freely accessible program, including source code, implementing SAMMI is available at https://github.com/nelsongil92/SAMMI.git. andras.fiser@einstein.yu.edu. Supplementary data are available at Bioinformatics online.

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

PubMed

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

2011-01-01

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

Site-specific antibody-liposome conjugation through copper-free click chemistry: a molecular biology approach for targeted photodynamic therapy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Obaid, Girgis; Wang, Yucheng; Kuriakose, Jerrin; Broekgaarden, Mans; Alkhateeb, Ahmed; Bulin, Anne-Laure; Hui, James; Tsourkas, Andrew; Hasan, Tayyaba

2016-03-01

Nanocarriers, such as liposomes, have the ability to potentiate photodynamic therapy (PDT) treatment regimens by the encapsulation of high payloads of photosensitizers and enhance their passive delivery to tumors through the enhanced permeability and retention effect. By conjugating targeting moieties to the surface of the liposomal nanoconstructs, cellular selectivity is imparted on them and PDT-based therapies can be performed with significantly higher dose tolerances, as off-target toxicity is simultaneously reduced.1 However, the maximal benefits of conventional targeted nanocarriers, including liposomes, are hindered by practical limitations including chemical instability, non-selective conjugation chemistry, poor control over ligand orientation, and loss of ligand functionality following conjugation, amongst others.2 We have developed a robust, physically and chemically stable liposomal nanoplatform containing benzoporphyrin derivative photosensitizer molecules within the phospholipid bilayer and an optimized surface density of strained cyclooctyne moieties for `click' conjugation to azido-functionalized antibodies.3 The clinical chimeric anti-EGFR antibody Cetuximab is site-specifically photocrosslinked to a recombinant bioengineered that recognizes the antibody's Fc region, containing a terminal azide.4 The copper-free click conjugation of the bioengineered Cetuximab derivative to the optimized photosensitizing liposome provides exceptional control over the antibody's optimal orientation for cellular antigen binding. Importantly, the reaction occurs rapidly under physiological conditions, bioorthogonally (selectively in the presence of other biomolecules) and without the need for toxic copper catalysis.3 Such state-of-the-art conjugation strategies push the boundaries of targeted photodynamic therapy beyond the limitations of traditional chemical coupling techniques to produce more robust and effective targeted therapeutics with applications beyond conventional treatments.

A decision support system for prioritizing forested wetland restoration in the Yazoo Backwater Area, Mississippi

USGS Publications Warehouse

O'Hara, Charles G.; Davis, Angela A.; Kleiss, Barbara A.

2000-01-01

A working prototype decision support system (DSS) was developed for the Yazoo Backwater Area, Mississippi, to help planners and managers prioritize, plan, conduct, and optimize forested wetland restoration activities. The DSS comprises geographic information system (GIS) spatial data themes, application programs that provide a cumulative analysis of the relative ability of sites to function as wetlands, and output data that are specific to a given restoration analysis scenario. The DSS input includes GIS data themes such as geomorphology, soils, land use, elevation, farmed wetlands, flood frequency, topographic depressions, streams, public lands, roads, and permanent water bodies, which can be used as spatial templates to define areal hydrologic settings. These GIS data themes can then be ranked and combined to estimate the relative suitability of a potential wetland restoration site, thereby, determining relative wetland equivalence on the landscape. The GIS applications used in this DSS perform the following three functions: assess the ecology (the Eco-Assessor); reclassify land-use in areas selected for restoration (the Tree-Translator); and generate output data to compare restoration scenarios (the Parameter-Generator). Areas selected for reforestation are translated (in the GIS) into ?forested? land use, and the tree species that are ?planted? on the landscape (in the DSS) either compose an ecologically optimal or an economically optimal community of tree species. Output from the DSS can be compared and analyzed by using economic, statistical, graphical, and tabular methods. Output data for seven selected scenarios were generated for the Yazoo Backwater Area and are presented as examples to illustrate the flexibility of the DSS to identify areas that meet restoration objectives.

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.

Synthesis and optimization of thiadiazole derivatives as a novel class of substrate competitive c-Jun N-terminal kinase inhibitors

PubMed Central

De, Surya K.; Chen, Vida; Stebbins, John L.; Chen, Li-Hsing; Cellitti, Jason F.; Machleidt, Thomas; Barile, Elisa; Riel-Mehan, Megan; Dahl, Russell; Yang, Li; Emdadi, Aras; Murphy, Ria; Pellecchia, Maurizio

2009-01-01

A series of thiadiazole derivatives has been designed as potential allosteric, substrate competitive inhibitors of the protein kinase JNK. We report on the synthesis, characterization and evaluation of a series of compounds that resulted in the identification of potent and selective JNK inhibitors targeting its JIP-1 docking site. PMID:20045647

A Hierarchical Mechanism of RIG-I Ubiquitination Provides Sensitivity, Robustness and Synergy in Antiviral Immune Responses.

PubMed

Sun, Xiaoqiang; Xian, Huifang; Tian, Shuo; Sun, Tingzhe; Qin, Yunfei; Zhang, Shoutao; Cui, Jun

2016-07-08

RIG-I is an essential receptor in the initiation of the type I interferon (IFN) signaling pathway upon viral infection. Although K63-linked ubiquitination plays an important role in RIG-I activation, the optimal modulation of conjugated and unanchored ubiquitination of RIG-I as well as its functional implications remains unclear. In this study, we determined that, in contrast to the RIG-I CARD domain, full-length RIG-I must undergo K63-linked ubiquitination at multiple sites to reach full activity. A systems biology approach was designed based on experiments using full-length RIG-I. Model selection for 7 candidate mechanisms of RIG-I ubiquitination inferred a hierarchical architecture of the RIG-I ubiquitination mode, which was then experimentally validated. Compared with other mechanisms, the selected hierarchical mechanism exhibited superior sensitivity and robustness in RIG-I-induced type I IFN activation. Furthermore, our model analysis and experimental data revealed that TRIM4 and TRIM25 exhibited dose-dependent synergism. These results demonstrated that the hierarchical mechanism of multi-site/type ubiquitination of RIG-I provides an efficient, robust and optimal synergistic regulatory module in antiviral immune responses.

A Hierarchical Mechanism of RIG-I Ubiquitination Provides Sensitivity, Robustness and Synergy in Antiviral Immune Responses

PubMed Central

Sun, Xiaoqiang; Xian, Huifang; Tian, Shuo; Sun, Tingzhe; Qin, Yunfei; Zhang, Shoutao; Cui, Jun

2016-01-01

RIG-I is an essential receptor in the initiation of the type I interferon (IFN) signaling pathway upon viral infection. Although K63-linked ubiquitination plays an important role in RIG-I activation, the optimal modulation of conjugated and unanchored ubiquitination of RIG-I as well as its functional implications remains unclear. In this study, we determined that, in contrast to the RIG-I CARD domain, full-length RIG-I must undergo K63-linked ubiquitination at multiple sites to reach full activity. A systems biology approach was designed based on experiments using full-length RIG-I. Model selection for 7 candidate mechanisms of RIG-I ubiquitination inferred a hierarchical architecture of the RIG-I ubiquitination mode, which was then experimentally validated. Compared with other mechanisms, the selected hierarchical mechanism exhibited superior sensitivity and robustness in RIG-I-induced type I IFN activation. Furthermore, our model analysis and experimental data revealed that TRIM4 and TRIM25 exhibited dose-dependent synergism. These results demonstrated that the hierarchical mechanism of multi-site/type ubiquitination of RIG-I provides an efficient, robust and optimal synergistic regulatory module in antiviral immune responses. PMID:27387525

A Hierarchical Mechanism of RIG-I Ubiquitination Provides Sensitivity, Robustness and Synergy in Antiviral Immune Responses

NASA Astrophysics Data System (ADS)

Sun, Xiaoqiang; Xian, Huifang; Tian, Shuo; Sun, Tingzhe; Qin, Yunfei; Zhang, Shoutao; Cui, Jun

2016-07-01

RIG-I is an essential receptor in the initiation of the type I interferon (IFN) signaling pathway upon viral infection. Although K63-linked ubiquitination plays an important role in RIG-I activation, the optimal modulation of conjugated and unanchored ubiquitination of RIG-I as well as its functional implications remains unclear. In this study, we determined that, in contrast to the RIG-I CARD domain, full-length RIG-I must undergo K63-linked ubiquitination at multiple sites to reach full activity. A systems biology approach was designed based on experiments using full-length RIG-I. Model selection for 7 candidate mechanisms of RIG-I ubiquitination inferred a hierarchical architecture of the RIG-I ubiquitination mode, which was then experimentally validated. Compared with other mechanisms, the selected hierarchical mechanism exhibited superior sensitivity and robustness in RIG-I-induced type I IFN activation. Furthermore, our model analysis and experimental data revealed that TRIM4 and TRIM25 exhibited dose-dependent synergism. These results demonstrated that the hierarchical mechanism of multi-site/type ubiquitination of RIG-I provides an efficient, robust and optimal synergistic regulatory module in antiviral immune responses.

Applications of Optimal Building Energy System Selection and Operation

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

Marnay, Chris; Stadler, Michael; Siddiqui, Afzal

2011-04-01

Berkeley Lab has been developing the Distributed Energy Resources Customer Adoption Model (DER-CAM) for several years. Given load curves for energy services requirements in a building microgrid (u grid), fuel costs and other economic inputs, and a menu of available technologies, DER-CAM finds the optimum equipment fleet and its optimum operating schedule using a mixed integer linear programming approach. This capability is being applied using a software as a service (SaaS) model. Optimisation problems are set up on a Berkeley Lab server and clients can execute their jobs as needed, typically daily. The evolution of this approach is demonstrated bymore » description of three ongoing projects. The first is a public access web site focused on solar photovoltaic generation and battery viability at large commercial and industrial customer sites. The second is a building CO2 emissions reduction operations problem for a University of California, Davis student dining hall for which potential investments are also considered. And the third, is both a battery selection problem and a rolling operating schedule problem for a large County Jail. Together these examples show that optimization of building u grid design and operation can be effectively achieved using SaaS.« less

Optimized positioning of autonomous surgical lamps

NASA Astrophysics Data System (ADS)

Teuber, Jörn; Weller, Rene; Kikinis, Ron; Oldhafer, Karl-Jürgen; Lipp, Michael J.; Zachmann, Gabriel

2017-03-01

We consider the problem of finding automatically optimal positions of surgical lamps throughout the whole surgical procedure, where we assume that future lamps could be robotized. We propose a two-tiered optimization technique for the real-time autonomous positioning of those robotized surgical lamps. Typically, finding optimal positions for surgical lamps is a multi-dimensional problem with several, in part conflicting, objectives, such as optimal lighting conditions at every point in time while minimizing the movement of the lamps in order to avoid distractions of the surgeon. Consequently, we use multi-objective optimization (MOO) to find optimal positions in real-time during the entire surgery. Due to the conflicting objectives, there is usually not a single optimal solution for such kinds of problems, but a set of solutions that realizes a Pareto-front. When our algorithm selects a solution from this set it additionally has to consider the individual preferences of the surgeon. This is a highly non-trivial task because the relationship between the solution and the parameters is not obvious. We have developed a novel meta-optimization that considers exactly this challenge. It delivers an easy to understand set of presets for the parameters and allows a balance between the lamp movement and lamp obstruction. This metaoptimization can be pre-computed for different kinds of operations and it then used by our online optimization for the selection of the appropriate Pareto solution. Both optimization approaches use data obtained by a depth camera that captures the surgical site but also the environment around the operating table. We have evaluated our algorithms with data recorded during a real open abdominal surgery. It is available for use for scientific purposes. The results show that our meta-optimization produces viable parameter sets for different parts of an intervention even when trained on a small portion of it.

Multiobjective Optimization Combining BMP Technology and Land Preservation for Watershed-based Stormwater Management

NASA Astrophysics Data System (ADS)

McGarity, A. E.

2009-12-01

Recent progress has been made developing decision-support models for optimal deployment of best management practices (BMP’s) in an urban watershed to achieve water quality goals. One example is the high-level screening model StormWISE, developed by the author (McGarity, 2006) that uses linear and nonlinear programming to narrow the search for optimal solutions to certain land use categories and drainage zones. Another example is the model SUSTAIN developed by USEPA and Tetra Tech (Lai, et al., 2006), which builds on the work of Yu, et al., 2002), that uses a detailed, computationally intensive simulation model driven by a genetic solver to select optimal BMP sites. However, a model that deals only with best management practice (BMP) site selections may fail to consider solutions that avoid future nonpoint pollutant loadings by preserving undeveloped land. This paper presents results of a recently completed research project in which water resource engineers partnered with experienced professionals at a land conservation trust to develop a multiobjective model for watershed management. The result is a revised version of StormWISE that can be used to identify optimal, cost-effective combinations of easements and similar land preservation tools for undeveloped sites along with low impact development (LID) and BMP technologies for developed sites. The goal is to achieve the watershed-wide limits on runoff volume and pollutant loads that are necessary to meet water quality goals as well as ecological benefits associated with habitat preservation and enhancement. A nonlinear programming formulation is presented for the extended StormWISE model that achieves desired levels of environmental benefits at minimum cost. Tradeoffs between different environmental benefits are generated by multiple runs of the model while varying the levels of each environmental benefit obtained. The model is solved using piecewise linearization of environmental benefit functions where each linear segment of represents a different option for reducing stormwater runoff volumes and pollutant loadings. The solutions space is comprised of optimal levels of expenditure for categories of BMP's by land use category and optimal land preservation expenditures by drainage zone. To demonstrate the usefulness of the model, results from its application to the Little Crum Creek watershed in suburban Philadelphia are presented. The model has been used to assist a watershed association and four municipalities to develop an action plan for restoration of water quality on this impaired stream. References Lai, F., J. Zhen, J. Riverson, and L. Shoemaker (2006). "SUSTAIN - An Evaluation and Cost-Optimization Tool for Placement of BMPs," ASCE World Environmental and Water Resource Congress 2006. McGarity, A.E. (2006). A Cost Minimization Model to Priortize Urban Catchments for Stormwater BMP Implementation Projects. American Water Resources Association National Meeting, Baltimore, MD, November, 2006. Yu, S., J. X. Zhen, and S.Y. Zhai, (2002). Development of Stormwater Best Management Practice Placement Strategy for the Virginia Department of Transportation. Final Contract Report, VTRC 04-CR9, Virginia Transportation Research Council.

Application of an Optimal Search Strategy for the DNAPL Source Identification to a Field Site in Nanjing, China

NASA Astrophysics Data System (ADS)

Longting, M.; Ye, S.; Wu, J.

2014-12-01

Identification and removing the DNAPL source in aquifer system is vital in rendering remediation successful and lowering the remediation time and cost. Our work is to apply an optimal search strategy introduced by Zoi and Pinder[1], with some modifications, to a field site in Nanjing City, China to define the strength, and location of DNAPL sources using the least samples. The overall strategy uses Monte Carlo stochastic groundwater flow and transport modeling, incorporates existing sampling data into the search strategy, and determines optimal sampling locations that are selected according to the reduction in overall uncertainty of the field and the proximity to the source locations. After a sample is taken, the plume is updated using a Kalman filter. The updated plume is then compared to the concentration fields that emanate from each individual potential source using fuzzy set technique. The comparison followed provides weights that reflect the degree of truth regarding the location of the source. The above steps are repeated until the optimal source characteristics are determined. Considering our site case, some specific modifications and work have been done as follows. K random fields are generated after fitting the measurement K data to the variogram model. The locations of potential sources that are given initial weights are targeted based on the field survey, with multiple potential source locations around the workshops and wastewater basin. Considering the short history (1999-2010) of manufacturing optical brightener PF at the site, and the existing sampling data, a preliminary source strength is then estimated, which will be optimized by simplex method or GA later. The whole algorithm then will guide us for optimal sampling and update as the investigation proceeds, until the weights finally stabilized. Reference [1] Dokou Zoi, and George F. Pinder. "Optimal search strategy for the definition of a DNAPL source." Journal of Hydrology 376.3 (2009): 542-556. Acknowledgement: Funding supported by National Natural Science Foundation of China (No. 41030746, 40872155) and DuPont Company is appreciated.

A decision modeling for phasor measurement unit location selection in smart grid systems

NASA Astrophysics Data System (ADS)

Lee, Seung Yup

As a key technology for enhancing the smart grid system, Phasor Measurement Unit (PMU) provides synchronized phasor measurements of voltages and currents of wide-area electric power grid. With various benefits from its application, one of the critical issues in utilizing PMUs is the optimal site selection of units. The main aim of this research is to develop a decision support system, which can be used in resource allocation task for smart grid system analysis. As an effort to suggest a robust decision model and standardize the decision modeling process, a harmonized modeling framework, which considers operational circumstances of component, is proposed in connection with a deterministic approach utilizing integer programming. With the results obtained from the optimal PMU placement problem, the advantages and potential that the harmonized modeling process possesses are assessed and discussed.

Discovery of Clinical Candidate 1-{[(2 S ,3 S ,4 S )-3-Ethyl-4-fluoro-5-oxopyrrolidin-2-yl]methoxy}-7-methoxyisoquinoline-6-carboxamide (PF-06650833), a Potent, Selective Inhibitor of Interleukin-1 Receptor Associated Kinase 4 (IRAK4), by Fragment-Based Drug Design

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

Lee, Katherine L.; Ambler, Catherine M.; Anderson, David R.

Through fragment-based drug design focused on engaging the active site of IRAK4 and leveraging three-dimensional topology in a ligand-efficient manner, a micromolar hit identified from a screen of a Pfizer fragment library was optimized to afford IRAK4 inhibitors with nanomolar potency in cellular assays. The medicinal chemistry effort featured the judicious placement of lipophilicity, informed by co-crystal structures with IRAK4 and optimization of ADME properties to deliver clinical candidate PF-06650833 (compound 40). This compound displays a 5-unit increase in lipophilic efficiency from the fragment hit, excellent kinase selectivity, and pharmacokinetic properties suitable for oral administration.

The importance of scale-dependent ravine characteristics on breeding-site selection by the Burrowing Parrot, Cyanoliseus patagonus

PubMed Central

Rios, Rodrigo S.; Vargas-Rodriguez, Renzo; Novoa-Jerez, Jose-Enrique; Squeo, Francisco A.

2017-01-01

In birds, the environmental variables and intrinsic characteristics of the nest have important fitness consequences through its influence on the selection of nesting sites. However, the extent to which these variables interact with variables that operate at the landscape scale, and whether there is a hierarchy among the different scales that influences nest-site selection, is unknown. This interaction could be crucial in burrowing birds, which depend heavily on the availability of suitable nesting locations. One representative of this group is the burrowing parrot, Cyanoliseus patagonus that breeds on specific ravines and forms large breeding colonies. At a particular site, breeding aggregations require the concentration of adequate environmental elements for cavity nesting, which are provided by within ravine characteristics. Therefore, intrinsic ravine characteristics should be more important in determining nest site selection compared to landscape level characteristics. Here, we assess this hypothesis by comparing the importance of ravine characteristics operating at different scales on nest-site selection and their interrelation with reproductive success. We quantified 12 characteristics of 105 ravines in their reproductive habitat. For each ravine we quantified morphological variables, distance to resources and disturbance as well as nest number and egg production in order to compare selected and non-selected ravines and determine the interrelationship among variables in explaining ravine differences. In addition, the number of nests and egg production for each reproductive ravine was related to ravine characteristics to assess their relation to reproductive success. We found significant differences between non-reproductive and reproductive ravines in both intrinsic and extrinsic characteristics. The multidimensional environmental gradient of variation between ravines, however, shows that differences are mainly related to intrinsic morphological characteristics followed by extrinsic variables associated to human disturbance. Likewise, within reproductive ravines, intrinsic characteristics are more strongly related to the number of nests. The probability of producing eggs, however, was related only to distance to roads and human settlements. Patterns suggest that C. patagonus mainly selects nesting sites based on intrinsic morphological characteristics of ravines. Scale differences in the importance of ravine characteristics could be a consequence of the particular orography of the breeding habitat. The arrangement of resources is associated to the location of the gullies rather than to individual ravines, determining the spatial availability and disposition of resources and disturbances. Thus, nest selection is influenced by intrinsic characteristics that maximize the fitness of individuals. Scaling in nest-selection is discussed under an optimality approach that partitions patch selection based on foraging theory. PMID:28462019

Nature of the Active Sites for CO Reduction on Copper Nanoparticles; Suggestions for Optimizing Performance.

PubMed

Cheng, Tao; Xiao, Hai; Goddard, William A

2017-08-30

Recent experiments show that the grain boundaries (GBs) of copper nanoparticles (NPs) lead to an outstanding performance in reducing CO 2 and CO to alcohol products. We report here multiscale simulations that simulate experimental synthesis conditions to predict the structure of a 10 nm Cu NP (158 555 atoms). To identify active sites, we first predict the CO binding at a large number of sites and select four exhibiting CO binding stronger than the (211) step surface. Then, we predict the formation energy of the *OCCOH intermediate as a descriptor for C-C coupling, identifying two active sites, both of which have an under-coordinated surface square site adjacent to a subsurface stacking fault. We then propose a periodic Cu surface (4 by 4 supercell) with a similar site that substantially decreases the formation energy of *OCCOH, by 0.14 eV.

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

PubMed

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

2017-12-04

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

The Spleen as an Optimal Site for Islet Transplantation and a Source of Mesenchymal Stem Cells.

PubMed

Sakata, Naoaki; Yoshimatsu, Gumpei; Kodama, Shohta

2018-05-07

This review demonstrates the unique potential of the spleen as an optimal site for islet transplantation and as a source of mesenchymal stem cells. Islet transplantation is a cellular replacement therapy used to treat severe diabetes mellitus; however, its clinical outcome is currently unsatisfactory. Selection of the most appropriate transplantation site is a major factor affecting the clinical success of this therapy. The spleen has long been studied as a candidate site for islet transplantation. Its advantages include physiological insulin drainage and regulation of immunity, and it has recently also been shown to contribute to the regeneration of transplanted islets. However, the efficacy of transplantation in the spleen is lower than that of intraportal transplantation, which is the current representative method of clinical islet transplantation. Safer and more effective methods of islet transplantation need to be established to allow the spleen to be used for clinical transplantation. The spleen is also of interest as a mesenchymal stem cell reservoir. Splenic mesenchymal stem cells contribute to the repair of damaged tissue, and their infusion may thus be a promising therapy for autoimmune diseases, including type 1 diabetes mellitus and Sjogren’s syndrome.

Decision-Related Activity in Macaque V2 for Fine Disparity Discrimination Is Not Compatible with Optimal Linear Readout

PubMed Central

Clery, Stephane; Cumming, Bruce G.

2017-01-01

Fine judgments of stereoscopic depth rely mainly on relative judgments of depth (relative binocular disparity) between objects, rather than judgments of the distance to where the eyes are fixating (absolute disparity). In macaques, visual area V2 is the earliest site in the visual processing hierarchy for which neurons selective for relative disparity have been observed (Thomas et al., 2002). Here, we found that, in macaques trained to perform a fine disparity discrimination task, disparity-selective neurons in V2 were highly selective for the task, and their activity correlated with the animals' perceptual decisions (unexplained by the stimulus). This may partially explain similar correlations reported in downstream areas. Although compatible with a perceptual role of these neurons for the task, the interpretation of such decision-related activity is complicated by the effects of interneuronal “noise” correlations between sensory neurons. Recent work has developed simple predictions to differentiate decoding schemes (Pitkow et al., 2015) without needing measures of noise correlations, and found that data from early sensory areas were compatible with optimal linear readout of populations with information-limiting correlations. In contrast, our data here deviated significantly from these predictions. We additionally tested this prediction for previously reported results of decision-related activity in V2 for a related task, coarse disparity discrimination (Nienborg and Cumming, 2006), thought to rely on absolute disparity. Although these data followed the predicted pattern, they violated the prediction quantitatively. This suggests that optimal linear decoding of sensory signals is not generally a good predictor of behavior in simple perceptual tasks. SIGNIFICANCE STATEMENT Activity in sensory neurons that correlates with an animal's decision is widely believed to provide insights into how the brain uses information from sensory neurons. Recent theoretical work developed simple predictions to differentiate decoding schemes, and found support for optimal linear readout of early sensory populations with information-limiting correlations. Here, we observed decision-related activity for neurons in visual area V2 of macaques performing fine disparity discrimination, as yet the earliest site for this task. These findings, and previously reported results from V2 in a different task, deviated from the predictions for optimal linear readout of a population with information-limiting correlations. Our results suggest that optimal linear decoding of early sensory information is not a general decoding strategy used by the brain. PMID:28100751

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 new technique based on Artificial Bee Colony Algorithm for optimal sizing of stand-alone photovoltaic system.

PubMed

Mohamed, Ahmed F; Elarini, Mahdi M; Othman, Ahmed M

2014-05-01

One of the most recent optimization techniques applied to the optimal design of photovoltaic system to supply an isolated load demand is the Artificial Bee Colony Algorithm (ABC). The proposed methodology is applied to optimize the cost of the PV system including photovoltaic, a battery bank, a battery charger controller, and inverter. Two objective functions are proposed: the first one is the PV module output power which is to be maximized and the second one is the life cycle cost (LCC) which is to be minimized. The analysis is performed based on measured solar radiation and ambient temperature measured at Helwan city, Egypt. A comparison between ABC algorithm and Genetic Algorithm (GA) optimal results is done. Another location is selected which is Zagazig city to check the validity of ABC algorithm in any location. The ABC is more optimal than GA. The results encouraged the use of the PV systems to electrify the rural sites of Egypt.

A new technique based on Artificial Bee Colony Algorithm for optimal sizing of stand-alone photovoltaic system

PubMed Central

Mohamed, Ahmed F.; Elarini, Mahdi M.; Othman, Ahmed M.

2013-01-01

One of the most recent optimization techniques applied to the optimal design of photovoltaic system to supply an isolated load demand is the Artificial Bee Colony Algorithm (ABC). The proposed methodology is applied to optimize the cost of the PV system including photovoltaic, a battery bank, a battery charger controller, and inverter. Two objective functions are proposed: the first one is the PV module output power which is to be maximized and the second one is the life cycle cost (LCC) which is to be minimized. The analysis is performed based on measured solar radiation and ambient temperature measured at Helwan city, Egypt. A comparison between ABC algorithm and Genetic Algorithm (GA) optimal results is done. Another location is selected which is Zagazig city to check the validity of ABC algorithm in any location. The ABC is more optimal than GA. The results encouraged the use of the PV systems to electrify the rural sites of Egypt. PMID:25685507

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

Are there optimal densities for prairie birds?

USGS Publications Warehouse

Skagen, S.K.; Adams, A.A.Y.

2010-01-01

The major forces of food and predation shape fitness-enhancing decisions of birds at all stages of their life cycles. During the breeding season, birds can minimize nest loss due to predation by selecting sites with a lower probability of predation. To understand the environmental and social aspects and consequences of breedingsite selection in prairie birds, we explored variation in nest-survival patterns of the Lark Bunting (Calamospiza melanocorys) in the shortgrass prairie region of North America. Over four breeding seasons, we documented the survival of 405 nests, conducted 60 surveys to estimate bird densities, and measured several vegetative features to describe habitat structure in 24 randomly selected study plots. Nest survival varied with the buntings' density as described by a quadratic polynomial, increasing with density below 1.5 birds ha-1 and decreasing with density between 1.5 and 3 birds ha-1, suggesting that an optimal range of densities favors reproductive success of the Lark Bunting, which nests semi-colonially. Nest survival also increased with increasing vegetation structure of study plots and varied with age of the nest, increasing during early incubation and late in the nestling stage and declining slightly from mid-incubation to the middle of the nestling period. The existence of an optimal range of densities in this semi-colonial species can be elucidated by the "commodity-selection hypothesis" at low densities and density dependence at high densities. ?? The Cooper Ornithological Society 2010.

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.

Selecting an optimal number of binding site waters to improve virtual screening enrichments against the adenosine A2A receptor.

PubMed

Lenselink, Eelke B; Beuming, Thijs; Sherman, Woody; van Vlijmen, Herman W T; IJzerman, Adriaan P

2014-06-23

A major challenge in structure-based virtual screening (VS) involves the treatment of explicit water molecules during docking in order to improve the enrichment of active compounds over decoys. Here we have investigated this in the context of the adenosine A2A receptor, where water molecules have previously been shown to be important for achieving high enrichment rates with docking, and where the positions of some binding site waters are known from a high-resolution crystal structure. The effect of these waters (both their presence and orientations) on VS enrichment was assessed using a carefully curated set of 299 high affinity A2A antagonists and 17,337 decoys. We show that including certain crystal waters greatly improves VS enrichment and that optimization of water hydrogen positions is needed in order to achieve the best results. We also show that waters derived from a molecular dynamics simulation - without any knowledge of crystallographic waters - can improve enrichments to a similar degree as the crystallographic waters, which makes this strategy applicable to structures without experimental knowledge of water positions. Finally, we used decision trees to select an ensemble of structures with different water molecule positions and orientations that outperforms any single structure with water molecules. The approach presented here is validated against independent test sets of A2A receptor antagonists and decoys from the literature. In general, this water optimization strategy could be applied to any target with waters-mediated protein-ligand interactions.

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.

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

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).

Enzymatic Detoxication, Conformational Selection, and the Role of Molten Globule Active Sites*

PubMed Central

Honaker, Matthew T.; Acchione, Mauro; Zhang, Wei; Mannervik, Bengt; Atkins, William M.

2013-01-01

The role of conformational ensembles in enzymatic reactions remains unclear. Discussion concerning “induced fit” versus “conformational selection” has, however, ignored detoxication enzymes, which exhibit catalytic promiscuity. These enzymes dominate drug metabolism and determine drug-drug interactions. The detoxication enzyme glutathione transferase A1–1 (GSTA1–1), exploits a molten globule-like active site to achieve remarkable catalytic promiscuity wherein the substrate-free conformational ensemble is broad with barrierless transitions between states. A quantitative index of catalytic promiscuity is used to compare engineered variants of GSTA1–1 and the catalytic promiscuity correlates strongly with characteristics of the thermodynamic partition function, for the substrate-free enzymes. Access to chemically disparate transition states is encoded by the substrate-free conformational ensemble. Pre-steady state catalytic data confirm an extension of the conformational selection model, wherein different substrates select different starting conformations. The kinetic liability of the conformational breadth is minimized by a smooth landscape. We propose that “local” molten globule behavior optimizes detoxication enzymes. PMID:23649628

Detection of genomic loci associated with environmental variables using generalized linear mixed models.

PubMed

Lobréaux, Stéphane; Melodelima, Christelle

2015-02-01

We tested the use of Generalized Linear Mixed Models to detect associations between genetic loci and environmental variables, taking into account the population structure of sampled individuals. We used a simulation approach to generate datasets under demographically and selectively explicit models. These datasets were used to analyze and optimize GLMM capacity to detect the association between markers and selective coefficients as environmental data in terms of false and true positive rates. Different sampling strategies were tested, maximizing the number of populations sampled, sites sampled per population, or individuals sampled per site, and the effect of different selective intensities on the efficiency of the method was determined. Finally, we apply these models to an Arabidopsis thaliana SNP dataset from different accessions, looking for loci associated with spring minimal temperature. We identified 25 regions that exhibit unusual correlations with the climatic variable and contain genes with functions related to temperature stress. Copyright © 2014 Elsevier Inc. All rights reserved.

Capture of trace sulfur gases from binary mixtures by single-walled carbon nanotube arrays: a molecular simulation study.

PubMed

Wang, Wenjuan; Peng, Xuan; Cao, Dapeng

2011-06-01

Adsorption of H(2)S and SO(2) pure gases and their selective capture from the H(2)S-CH(4), H(2)S-CO(2), SO(2)-N(2), and SO(2)-CO(2) binary mixtures by the single-walled carbon nanotubes (SWNT) are investigated via using the grand canonical Monte Carlo (GCMC) method. It is found that the (20, 20) SWNT with larger diameter shows larger capacity for H(2)S and SO(2) pure gases at T = 303 K, in which the uptakes reach 16.31 and 16.03 mmol/g, respectively. However, the (6,6) SWNT with small diameter exhibits the largest selectivity for binary mixtures containing trace sulfur gases at T = 303 K and P = 100 kPa. By investigating the effect of pore size on the separation of gas mixtures, we found that the optimized pore size is 0.81 nm for separation of H(2)S-CH(4), H(2)S-CO(2), and SO(2)-N(2) binary mixtures, while it is 1.09 nm for the SO(2)-CO(2) mixture. The effects of concentration and temperature on the selectivity of sulfide are also studied at the optimal pore size. It is found that the concentration (ppm) of sulfur components has little effect on selectivity of SWNTs for these binary mixtures. However, the selectivity decreases obviously with the increase of temperature. To improve the adsorption capacities, we further modify the surface of SWNTs with the functional groups. The selectivities of H(2)S-CO(2) and SO(2)-CO(2) mixtures are basically uninfluenced by the site density, while the increase of site density can improve the selectivity of H(2)S-CH(4) mixture doubly. It is expected that this work could provide useful information for sulfur gas capture.

Bacillus cereus strain MCN as a debriding agent

NASA Technical Reports Server (NTRS)

Dalton, H. P.; Haynes, B. W.; Stone, L. L.

1978-01-01

Biologically active means are effective for rapidly removing scar tissue caused by burns or corrosive agents. Specially selected strain of bacteria applied to injury site releases enzymes which are active against eschar. These bacteria tend to locate between eschar and unburned tissue, thus providing optimal cell surface area arrangement for enzyme dispersal. Procedure may prove especially useful in treatment of disaster casualties under relatively primitive conditions.

Multi-Disciplinary Ocean Sensors for Environmental Analyses and Networks (MOSEAN)

DTIC Science & Technology

2004-01-01

will require optimization for their application . Modifications will include: a) Size and power reduction of the electro-fluidic component to match...be configured for detection of CDOM, phycocyanin , phycoerythrin, and chlorophyll-a depending upon the specific wavelengths chosen. Efforts on this...OPL in Santa Barbara. Discussions centered on new instrumentation designed for coastal applications and plans for the CHARM mooring (site selection

Multi-disciplinary Ocean Sensors for Environmental Analyses and Networks (MOSEAN)

DTIC Science & Technology

2003-09-30

will require optimization for their application . Modifications will include: a) Size and power reduction of the electro-fluidic component to match...instrument can be configured for detection of CDOM, phycocyanin , phycoerythrin, and chlorophyll-a depending upon the specific wavelengths chosen. Efforts...OPL in Santa Barbara. Discussions centered on new instrumentation designed for coastal applications and plans for the CHARM mooring (site selection

Spatial multiobjective optimization of agricultural conservation practices using a SWAT model and an evolutionary algorithm.

PubMed

Rabotyagov, Sergey; Campbell, Todd; Valcu, Adriana; Gassman, Philip; Jha, Manoj; Schilling, Keith; Wolter, Calvin; Kling, Catherine

2012-12-09

Finding the cost-efficient (i.e., lowest-cost) ways of targeting conservation practice investments for the achievement of specific water quality goals across the landscape is of primary importance in watershed management. Traditional economics methods of finding the lowest-cost solution in the watershed context (e.g.,(5,12,20)) assume that off-site impacts can be accurately described as a proportion of on-site pollution generated. Such approaches are unlikely to be representative of the actual pollution process in a watershed, where the impacts of polluting sources are often determined by complex biophysical processes. The use of modern physically-based, spatially distributed hydrologic simulation models allows for a greater degree of realism in terms of process representation but requires a development of a simulation-optimization framework where the model becomes an integral part of optimization. Evolutionary algorithms appear to be a particularly useful optimization tool, able to deal with the combinatorial nature of a watershed simulation-optimization problem and allowing the use of the full water quality model. Evolutionary algorithms treat a particular spatial allocation of conservation practices in a watershed as a candidate solution and utilize sets (populations) of candidate solutions iteratively applying stochastic operators of selection, recombination, and mutation to find improvements with respect to the optimization objectives. The optimization objectives in this case are to minimize nonpoint-source pollution in the watershed, simultaneously minimizing the cost of conservation practices. A recent and expanding set of research is attempting to use similar methods and integrates water quality models with broadly defined evolutionary optimization methods(3,4,9,10,13-15,17-19,22,23,25). In this application, we demonstrate a program which follows Rabotyagov et al.'s approach and integrates a modern and commonly used SWAT water quality model(7) with a multiobjective evolutionary algorithm SPEA2(26), and user-specified set of conservation practices and their costs to search for the complete tradeoff frontiers between costs of conservation practices and user-specified water quality objectives. The frontiers quantify the tradeoffs faced by the watershed managers by presenting the full range of costs associated with various water quality improvement goals. The program allows for a selection of watershed configurations achieving specified water quality improvement goals and a production of maps of optimized placement of conservation practices.

SU-D-BRC-02: Application of Six Sigma Approach to Improve the Efficiency of Patient-Specific QA in Proton Therapy

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

LAH, J; Shin, D; Manger, R

Purpose: To show how the Six Sigma DMAIC (Define-Measure-Analyze-Improve-Control) can be used for improving and optimizing the efficiency of patient-specific QA process by designing site-specific range tolerances. Methods: The Six Sigma tools (process flow diagram, cause and effect, capability analysis, Pareto chart, and control chart) were utilized to determine the steps that need focus for improving the patient-specific QA process. The patient-specific range QA plans were selected according to 7 treatment site groups, a total of 1437 cases. The process capability index, Cpm was used to guide the tolerance design of patient site-specific range. We also analyzed the financial impactmore » of this project. Results: Our results suggested that the patient range measurements were non-capable at the current tolerance level of ±1 mm in clinical proton plans. The optimized tolerances were calculated for treatment sites. Control charts for the patient QA time were constructed to compare QA time before and after the new tolerances were implemented. It is found that overall processing time was decreased by 24.3% after establishing new site-specific range tolerances. The QA failure for whole process in proton therapy would lead up to a 46% increase in total cost. This result can also predict how costs are affected by changes in adopting the tolerance design. Conclusion: We often believe that the quality and performance of proton therapy can easily be improved by merely tightening some or all of its tolerance requirements. This can become costly, however, and it is not necessarily a guarantee of better performance. The tolerance design is not a task to be undertaken without careful thought. The Six Sigma DMAIC can be used to improve the QA process by setting optimized tolerances. When tolerance design is optimized, the quality is reasonably balanced with time and cost demands.« less

OptSSeq: High-throughput sequencing readout of growth enrichment defines optimal gene expression elements for homoethanologenesis

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

Ghosh, Indro Neil; Landick, Robert

The optimization of synthetic pathways is a central challenge in metabolic engineering. OptSSeq (Optimization by Selection and Sequencing) is one approach to this challenge. OptSSeq couples selection of optimal enzyme expression levels linked to cell growth rate with high-throughput sequencing to track enrichment of gene expression elements (promoters and ribosomebinding sites) from a combinatorial library. OptSSeq yields information on both optimal and suboptimal enzyme levels, and helps identify constraints that limit maximal product formation. Here we report a proof-of-concept implementation of OptSSeq using homoethanologenesis, a two-step pathway consisting of pyruvate decarboxylase (Pdc) and alcohol dehydrogenase (Adh) that converts pyruvate tomore » ethanol and is naturally optimized in the bacterium Zymomonas mobilis. We used OptSSeq to determine optimal gene expression elements and enzyme levels for Z. mobilis Pdc, AdhA, and AdhB expressed in Escherichia coli. By varying both expression signals and gene order, we identified an optimal solution using only Pdc and AdhB. We resolved current uncertainty about the functions of the Fe 2+-dependent AdhB and Zn 2+- dependent AdhA by showing that AdhB is preferred over AdhA for rapid growth in both E. coli and Z. mobilis. Finally, by comparing predictions of growth-linked metabolic flux to enzyme synthesis costs, we established that optimal E. coli homoethanologenesis was achieved by our best pdc-adhB expression cassette and that the remaining constraints lie in the E. coli metabolic network or inefficient Pdc or AdhB function in E. coli. Furthermore, OptSSeq is a general tool for synthetic biology to tune enzyme levels in any pathway whose optimal function can be linked to cell growth or survival.« less

OptSSeq: High-throughput sequencing readout of growth enrichment defines optimal gene expression elements for homoethanologenesis

DOE PAGES

Ghosh, Indro Neil; Landick, Robert

2016-07-16

The optimization of synthetic pathways is a central challenge in metabolic engineering. OptSSeq (Optimization by Selection and Sequencing) is one approach to this challenge. OptSSeq couples selection of optimal enzyme expression levels linked to cell growth rate with high-throughput sequencing to track enrichment of gene expression elements (promoters and ribosomebinding sites) from a combinatorial library. OptSSeq yields information on both optimal and suboptimal enzyme levels, and helps identify constraints that limit maximal product formation. Here we report a proof-of-concept implementation of OptSSeq using homoethanologenesis, a two-step pathway consisting of pyruvate decarboxylase (Pdc) and alcohol dehydrogenase (Adh) that converts pyruvate tomore » ethanol and is naturally optimized in the bacterium Zymomonas mobilis. We used OptSSeq to determine optimal gene expression elements and enzyme levels for Z. mobilis Pdc, AdhA, and AdhB expressed in Escherichia coli. By varying both expression signals and gene order, we identified an optimal solution using only Pdc and AdhB. We resolved current uncertainty about the functions of the Fe 2+-dependent AdhB and Zn 2+- dependent AdhA by showing that AdhB is preferred over AdhA for rapid growth in both E. coli and Z. mobilis. Finally, by comparing predictions of growth-linked metabolic flux to enzyme synthesis costs, we established that optimal E. coli homoethanologenesis was achieved by our best pdc-adhB expression cassette and that the remaining constraints lie in the E. coli metabolic network or inefficient Pdc or AdhB function in E. coli. Furthermore, OptSSeq is a general tool for synthetic biology to tune enzyme levels in any pathway whose optimal function can be linked to cell growth or survival.« less

What determines selection and abandonment of a foraging patch by wild giant pandas (Ailuropoda melanoleuca) in winter?

PubMed

Zhang, Zejun; Zhan, Xiangjiang; Yan, Li; Li, Ming; Hu, Jinchu; Wei, Fuwen

2009-01-01

Foraging patches can be described as a nested hierarchy of aggregated resources, implying that study of foraging by wild animals should be directed across different spatial scales. However, almost all previous research on habitat selection by the giant panda has concentrated upon one scale. In this research, we carried out a field study to understand foraging patch selection by giant pandas in winter at both microhabitat and feeding site scales and, for the first time, attempted to understand how long it would stay at the feeding sites before moving on. The field survey was conducted from November 2002 to March 2003 at Fengtongzhai Nature Reserve (102 degrees 48'-103 degrees 00' E, 30 degrees 19'-30 degrees 47' N), Baoxing County of Sichuan Province, China, to collect data in both microhabitat and control plots. The microhabitat plots were located by fresh feces or foraging traces left by giant pandas, and the control plots were established to reflect the environment. Within each microhabitat plot, one 1x1 m2 plot was centralized at the center of each feeding site, in which numbers of old bamboos and old shoots, including eaten and uneaten, were counted, respectively. The results showed that winter microhabitats selected by this species were characteristic of gentle slopes and high old-shoot proportions and that the latter was even higher at feeding sites. Two selection processes, namely, from the environment to microhabitats and from the latter to feeding sites, were found during this species' foraging patch utilization. Giant pandas preferred to eat old shoots to old bamboo at feeding sites in winter and did not leave unless old-shoot density fell to lower than the average in the environment. Both microhabitats and feeding sites selected by giant pandas were characteristic of high old-shoot density, indicating that the preferred food item had a significant influence upon its foraging patch selection. The preference for gentle slopes by giant pandas was presumed to save energy in movement or reflect the need to sit and free its fore-limbs to grasp bamboo culms when feeding but also seemed to be correlated with an easier access to old shoots. The utilization of old shoots at feeding sites was assumed to help maximize energy or nutrient intake during their foraging. The difference between microhabitat plots and control plots and between microhabitats and feeding sites uncovered a continuous selection process from the environment via microhabitats to feeding sites. The utilization of old shoots at feeding sites was parallel to the marginal value theorem. The selection and abandonment of foraging patches by giant pandas was an optimal behavioral strategy adapted to their peculiar food with high cellulose and low protein. Our results uncovered the importance of multiple scales in habitat selection research. To further understand the process of habitat selection, future research should pay more attention to resolve the question of how to locate foraging patches under dense bamboo forests by the giant panda, which was traditionally considered to have poor eyesight, although our research has answered what type of habitats the giant panda prefers and when to leave.

Liver-selective glucocorticoid antagonists: a novel treatment for type 2 diabetes.

PubMed

von Geldern, Thomas W; Tu, Noah; Kym, Philip R; Link, James T; Jae, Hwan-Soo; Lai, Chunqiu; Apelqvist, Theresa; Rhonnstad, Patrik; Hagberg, Lars; Koehler, Konrad; Grynfarb, Marlena; Goos-Nilsson, Annika; Sandberg, Johnny; Osterlund, Marie; Barkhem, Tomas; Höglund, Marie; Wang, Jiahong; Fung, Steven; Wilcox, Denise; Nguyen, Phong; Jakob, Clarissa; Hutchins, Charles; Färnegårdh, Mathias; Kauppi, Björn; Ohman, Lars; Jacobson, Peer B

2004-08-12

Hepatic blockade of glucocorticoid receptors (GR) suppresses glucose production and thus decreases circulating glucose levels, but systemic glucocorticoid antagonism can produce adrenal insufficiency and other undesirable side effects. These hepatic and systemic responses might be dissected, leading to liver-selective pharmacology, when a GR antagonist is linked to a bile acid in an appropriate manner. Bile acid conjugation can be accomplished with a minimal loss of binding affinity for GR. The resultant conjugates remain potent in cell-based functional assays. A novel in vivo assay has been developed to simultaneously evaluate both hepatic and systemic GR blockade; this assay has been used to optimize the nature and site of the linker functionality, as well as the choice of the GR antagonist and the bile acid. This optimization led to the identification of A-348441, which reduces glucose levels and improves lipid profiles in an animal model of diabetes. Copyright 2004 American Chemical Society

A surrogate-based metaheuristic global search method for beam angle selection in radiation treatment planning.

PubMed

Zhang, H H; Gao, S; Chen, W; Shi, L; D'Souza, W D; Meyer, R R

2013-03-21

An important element of radiation treatment planning for cancer therapy is the selection of beam angles (out of all possible coplanar and non-coplanar angles in relation to the patient) in order to maximize the delivery of radiation to the tumor site and minimize radiation damage to nearby organs-at-risk. This category of combinatorial optimization problem is particularly difficult because direct evaluation of the quality of treatment corresponding to any proposed selection of beams requires the solution of a large-scale dose optimization problem involving many thousands of variables that represent doses delivered to volume elements (voxels) in the patient. However, if the quality of angle sets can be accurately estimated without expensive computation, a large number of angle sets can be considered, increasing the likelihood of identifying a very high quality set. Using a computationally efficient surrogate beam set evaluation procedure based on single-beam data extracted from plans employing equallyspaced beams (eplans), we have developed a global search metaheuristic process based on the nested partitions framework for this combinatorial optimization problem. The surrogate scoring mechanism allows us to assess thousands of beam set samples within a clinically acceptable time frame. Tests on difficult clinical cases demonstrate that the beam sets obtained via our method are of superior quality.

A surrogate-based metaheuristic global search method for beam angle selection in radiation treatment planning

PubMed Central

Zhang, H H; Gao, S; Chen, W; Shi, L; D’Souza, W D; Meyer, R R

2013-01-01

An important element of radiation treatment planning for cancer therapy is the selection of beam angles (out of all possible coplanar and non-coplanar angles in relation to the patient) in order to maximize the delivery of radiation to the tumor site and minimize radiation damage to nearby organs-at-risk. This category of combinatorial optimization problem is particularly difficult because direct evaluation of the quality of treatment corresponding to any proposed selection of beams requires the solution of a large-scale dose optimization problem involving many thousands of variables that represent doses delivered to volume elements (voxels) in the patient. However, if the quality of angle sets can be accurately estimated without expensive computation, a large number of angle sets can be considered, increasing the likelihood of identifying a very high quality set. Using a computationally efficient surrogate beam set evaluation procedure based on single-beam data extracted from plans employing equally-spaced beams (eplans), we have developed a global search metaheuristic process based on the Nested Partitions framework for this combinatorial optimization problem. The surrogate scoring mechanism allows us to assess thousands of beam set samples within a clinically acceptable time frame. Tests on difficult clinical cases demonstrate that the beam sets obtained via our method are superior quality. PMID:23459411

Photovoltaic design optimization for terrestrial applications

NASA Technical Reports Server (NTRS)

Ross, R. G., Jr.

1978-01-01

As part of the Jet Propulsion Laboratory's Low-Cost Solar Array Project, a comprehensive program of module cost-optimization has been carried out. The objective of these studies has been to define means of reducing the cost and improving the utility and reliability of photovoltaic modules for the broad spectrum of terrestrial applications. This paper describes one of the methods being used for module optimization, including the derivation of specific equations which allow the optimization of various module design features. The method is based on minimizing the life-cycle cost of energy for the complete system. Comparison of the life-cycle energy cost with the marginal cost of energy each year allows the logical plant lifetime to be determined. The equations derived allow the explicit inclusion of design parameters such as tracking, site variability, and module degradation with time. An example problem involving the selection of an optimum module glass substrate is presented.

Optimization of a Coastal Environmental Monitoring Network Based on the Kriging Method: A Case Study of Quanzhou Bay, China

PubMed Central

Chen, Kai; Ni, Minjie; Wang, Jun; Huang, Dongren; Chen, Huorong; Wang, Xiao; Liu, Mengyang

2016-01-01

Environmental monitoring is fundamental in assessing environmental quality and to fulfill protection and management measures with permit conditions. However, coastal environmental monitoring work faces many problems and challenges, including the fact that monitoring information cannot be linked up with evaluation, monitoring data cannot well reflect the current coastal environmental condition, and monitoring activities are limited by cost constraints. For these reasons, protection and management measures cannot be developed and implemented well by policy makers who intend to solve this issue. In this paper, Quanzhou Bay in southeastern China was selected as a case study; and the Kriging method and a geographic information system were employed to evaluate and optimize the existing monitoring network in a semienclosed bay. This study used coastal environmental monitoring data from 15 sites (including COD, DIN, and PO4-P) to adequately analyze the water quality from 2009 to 2012 by applying the Trophic State Index. The monitoring network in Quanzhou Bay was evaluated and optimized, with the number of sites increased from 15 to 24, and the monitoring precision improved by 32.9%. The results demonstrated that the proposed advanced monitoring network optimization was appropriate for environmental monitoring in Quanzhou Bay. It might provide technical support for coastal management and pollutant reduction in similar areas. PMID:27777951

Optimization of a Coastal Environmental Monitoring Network Based on the Kriging Method: A Case Study of Quanzhou Bay, China.

PubMed

Chen, Kai; Ni, Minjie; Cai, Minggang; Wang, Jun; Huang, Dongren; Chen, Huorong; Wang, Xiao; Liu, Mengyang

2016-01-01

Environmental monitoring is fundamental in assessing environmental quality and to fulfill protection and management measures with permit conditions. However, coastal environmental monitoring work faces many problems and challenges, including the fact that monitoring information cannot be linked up with evaluation, monitoring data cannot well reflect the current coastal environmental condition, and monitoring activities are limited by cost constraints. For these reasons, protection and management measures cannot be developed and implemented well by policy makers who intend to solve this issue. In this paper, Quanzhou Bay in southeastern China was selected as a case study; and the Kriging method and a geographic information system were employed to evaluate and optimize the existing monitoring network in a semienclosed bay. This study used coastal environmental monitoring data from 15 sites (including COD, DIN, and PO 4 -P) to adequately analyze the water quality from 2009 to 2012 by applying the Trophic State Index. The monitoring network in Quanzhou Bay was evaluated and optimized, with the number of sites increased from 15 to 24, and the monitoring precision improved by 32.9%. The results demonstrated that the proposed advanced monitoring network optimization was appropriate for environmental monitoring in Quanzhou Bay. It might provide technical support for coastal management and pollutant reduction in similar areas.

Martian Resource Locations - Identification and Optimization

NASA Astrophysics Data System (ADS)

Chamitoff, G.; James, G.; Barker, D.; Dershowitz, A.

2002-01-01

Many physical constituents of the Martian environment can be considered as possible material resources. The identification and utilization of these in-situ Martian natural resources is the key to enabling cost- effective long-duration missions and permanent human settlements on Mars. Also, access to local resources provides an essential safety net for the initial missions. The incident solar radiation, atmosphere, regolith, subsurface materials, polar deposits, and frozen volatiles represent planetary resources that can provide breathable air, water, energy, organic growth media, and building materials. Hence, the characterization and localization of these resources can be viewed as a component of the process of landing/outpost site selection. The locations of early permanent settlements will likely be near the imported and in-situ resources of the initial outposts. Therefore, the initial site selections can have significant long- term ramifications. Although the current information on the location, extent, purity, and ease of extraction of the in-situ resources is limited; this knowledge improves with each electronic bit of information returned from the planet. This paper presents a powerful software tool for the combined organization and analysis of Martian data from all sources. This program, called PROMT (Planetary Resource Optimization and Mapping Tool), is designed to provide a wide range of analysis and display functions that can be applied to raw data or photo- imagery. Thresholds, contours, custom algorithms, and graphical editing are some of the various methods that the user can use to process data. Individual maps can then be created to identify surface regions on Mars that meet specific criteria. For example, regions with possible subsurface ice can be identified and shown graphically by combining and analyzing various gamma ray and neutron emission data sets. Other examples might include regions with high atmospheric pressure, steep slopes, evidence of geothermal activity, surface albedo variations in a certain spectral range, similar average temperatures, surface flow features, high gravitational anomalies, etc. Surface maps can similarly be created to highlight regions of interest based on virtually any mathematical or remote sensing criteria. These maps can then be combined into composite maps for the purpose of collocating resources, surface features, and other scientific qualities of interest. Finally, PROMT has the capability to optimize the selection of potential landing/outpost sites based on a weighted combination of selected intermediate maps and data sets. This is done by searching the Martian surface for the point that maximizes accessibility to collocated features within a given radius. The use of this tool for analyzing data, generating maps, and collocating features is demonstrated using data from the Mariner, Viking, Hubble, Mars Global Surveyor, and the Odyssey spacecraft. The process of site selection is demonstrated through the combination of analyses performed to identify local resources for producing breathable air, water, and energy. However, any number of site selection objectives could be studied using PROMT. Some examples might be the search for life, water on Mars, geological features, weather observation, survivability of a human base, and so on. In this paper, a mission design objective of outpost self-sufficiency based on the accessibility of useful local materials is presented. Future studies can address a broad range of overall mission design objectives and can incorporate additional planetary data sets as they become available. These studies can be used to drive technology developments, mission planning, analog simulations, as well as precursor missions.

Unraveling patterns of site-to-site synonymous rates variation and associated gene properties of protein domains and families.

PubMed

Dimitrieva, Slavica; Anisimova, Maria

2014-01-01

In protein-coding genes, synonymous mutations are often thought not to affect fitness and therefore are not subject to natural selection. Yet increasingly, cases of non-neutral evolution at certain synonymous sites were reported over the last decade. To evaluate the extent and the nature of site-specific selection on synonymous codons, we computed the site-to-site synonymous rate variation (SRV) and identified gene properties that make SRV more likely in a large database of protein-coding gene families and protein domains. To our knowledge, this is the first study that explores the determinants and patterns of the SRV in real data. We show that the SRV is widespread in the evolution of protein-coding sequences, putting in doubt the validity of the synonymous rate as a standard neutral proxy. While protein domains rarely undergo adaptive evolution, the SRV appears to play important role in optimizing the domain function at the level of DNA. In contrast, protein families are more likely to evolve by positive selection, but are less likely to exhibit SRV. Stronger SRV was detected in genes with stronger codon bias and tRNA reusage, those coding for proteins with larger number of interactions or forming larger number of structures, located in intracellular components and those involved in typically conserved complex processes and functions. Genes with extreme SRV show higher expression levels in nearly all tissues. This indicates that codon bias in a gene, which often correlates with gene expression, may often be a site-specific phenomenon regulating the speed of translation along the sequence, consistent with the co-translational folding hypothesis. Strikingly, genes with SRV were strongly overrepresented for metabolic pathways and those associated with several genetic diseases, particularly cancers and diabetes.

Ligand recognition by RAR and RXR receptors: binding and selectivity.

PubMed

Sussman, Fredy; de Lera, Angel R

2005-10-06

Fundamental biological functions, most notably embriogenesis, cell growth, cell differentiation, and cell apoptosis, are in part regulated by a complex genomic network that starts with the binding (and activation) of retinoids to their cognate receptors, members of the superfamily of nuclear receptors. We have studied ligand recognition of retinoic receptors (RXRalpha and RARgamma) using a molecular-mechanics-based docking method. The protocol used in this work is able to rank the affinity of pairs of ligands for a single retinoid receptor, the highest values corresponding to those that adapt better to the shape of the binding site and generate the optimal set of electrostatic and apolar interactions with the receptor. Moreover, our studies shed light onto some of the energetic contributions to retinoid receptor ligand selectivity. In this regard we show that there is a difference in polarity between the binding site regions that anchor the carboxylate in RAR and RXR, which translates itself into large differences in the energy of interaction of both receptors with the same ligand. We observe that the latter energy change is canceled off by the solvation energy penalty upon binding. This energy compensation is borne out as well by experiments that address the effect of site-directed mutagenesis on ligand binding to RARgamma. The hypothesis that the difference in binding site polarity might be exploited to build RXR-selective ligands is tested with some compounds having a thiazolidinedione anchoring group.

Field Exploration and Life Detection Sampling for Planetary Analogue Research (FELDSPAR): Variability and Correlation in Biomarker and Mineralogy Measurements from Icelandic Mars Analogues

NASA Technical Reports Server (NTRS)

Gentry, D.; Amador, E.; Cable, M. L.; Cantrell, T.; Chaudry, N.; Cullen, T.; Duca, Z.; Jacobsen, M.; Kirby, J.; McCaig, H.;

Co-delivery of chemotherapeutics and proteins for synergistic therapy.

PubMed

He, Chaoliang; Tang, Zhaohui; Tian, Huayu; Chen, Xuesi

2016-03-01

Combination therapy with chemotherapeutics and protein therapeutics, typically cytokines and antibodies, has been a type of crucial approaches for synergistic cancer treatment. However, conventional approaches by simultaneous administration of free chemotherapeutic drugs and proteins lead to limitations for further optimizing the synergistic effects, due to the distinct in vivo pharmacokinetics and distribution of small drugs and proteins, insufficient tumor selectivity and tumor accumulation, unpredictable drug/protein ratios at tumor sites, short half-lives, and serious systemic adverse effects. Consequently, to obtain optimal synergistic anti-tumor efficacy, considerable efforts have been devoted to develop the co-delivery systems for co-incorporating chemotherapeutics and proteins into a single carrier system and subsequently releasing the dual or multiple payloads at desired target sites in a more controllable manner. The co-delivery systems result in markedly enhanced blood stability and in vivo half-lives of the small drugs and proteins, elevated tumor accumulation, as well as the capability of delivering the multiple agents to the same target sites with rational drug/protein ratios, which may facilitate maximizing the synergistic effects and therefore lead to optimal antitumor efficacy. This review emphasizes the recent advances in the co-delivery systems for chemotherapeutics and proteins, typically cytokines and antibodies, for systemic or localized synergistic cancer treatment. Moreover, the proposed mechanisms responsible for the synergy of chemotherapeutic drugs and proteins are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

GIS-based approach for optimal siting and sizing of renewables considering techno-environmental constraints and the stochastic nature of meteorological inputs

NASA Astrophysics Data System (ADS)

Daskalou, Olympia; Karanastasi, Maria; Markonis, Yannis; Dimitriadis, Panayiotis; Koukouvinos, Antonis; Efstratiadis, Andreas; Koutsoyiannis, Demetris

2016-04-01

Following the legislative EU targets and taking advantage of its high renewable energy potential, Greece can obtain significant benefits from developing its water, solar and wind energy resources. In this context we present a GIS-based methodology for the optimal sizing and siting of solar and wind energy systems at the regional scale, which is tested in the Prefecture of Thessaly. First, we assess the wind and solar potential, taking into account the stochastic nature of the associated meteorological processes (i.e. wind speed and solar radiation, respectively), which is essential component for both planning (i.e., type selection and sizing of photovoltaic panels and wind turbines) and management purposes (i.e., real-time operation of the system). For the optimal siting, we assess the efficiency and economic performance of the energy system, also accounting for a number of constraints, associated with topographic limitations (e.g., terrain slope, proximity to road and electricity grid network, etc.), the environmental legislation and other land use constraints. Based on this analysis, we investigate favorable alternatives using technical, environmental as well as financial criteria. The final outcome is GIS maps that depict the available energy potential and the optimal layout for photovoltaic panels and wind turbines over the study area. We also consider a hypothetical scenario of future development of the study area, in which we assume the combined operation of the above renewables with major hydroelectric dams and pumped-storage facilities, thus providing a unique hybrid renewable system, extended at the regional scale.

In Situ Chemical Oxidation for Groundwater Remediation: Site-Specific Engineering & Technology Application

DTIC Science & Technology

2010-10-01

PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Colorado School of Mines,1500 Illinois St, Golden ,CO,80401 8. PERFORMING ORGANIZATION REPORT NUMBER 9...Protocol page 13 Overall ISCO Protocol Flow Diagram addition, laboratory studies may be used to select optimal chemistry parameters to maximize oxidant...Design Process 5. Because of the complexity of these oxidants’ chemistry and implementation, with much of the knowledge base residing with those

Fluorescent sensor systems based on nanostructured polymeric membranes for selective recognition of Aflatoxin B1.

PubMed

Sergeyeva, Tetyana; Yarynka, Daria; Piletska, Elena; Lynnik, Rostyslav; Zaporozhets, Olga; Brovko, Oleksandr; Piletsky, Sergey; El'skaya, Anna

2017-12-01

Nanostructured polymeric membranes for selective recognition of aflatoxin B1 were synthesized in situ and used as highly sensitive recognition elements in the developed fluorescent sensor. Artificial binding sites capable of selective recognition of aflatoxin B1 were formed in the structure of the polymeric membranes using the method of molecular imprinting. A composition of molecularly imprinted polymer (MIP) membranes was optimized using the method of computational modeling. The MIP membranes were synthesized using the non-toxic close structural analogue of aflatoxin B1, ethyl-2-oxocyclopentanecarboxylate as a dummy template. The MIP membranes with the optimized composition demonstrated extremely high selectivity towards aflatoxin B1 (AFB1). Negligible binding of close structural analogues of AFB1 - aflatoxins B2 (AFB2), aflatoxin G2 (AFG2), and ochratoxin A (OTA) was demonstrated. Binding of AFB1 by the MIP membranes was investigated as a function of both type and concentration of the functional monomer in the initial monomer composition used for the membranes' synthesis, as well as sample composition. The conditions of the solid-phase extraction of the mycotoxin using the MIP membrane as a stationary phase (pH, ionic strength, buffer concentration, volume of the solution, ratio between water and organic solvent, filtration rate) were optimized. The fluorescent sensor system based on the optimized MIP membranes provided a possibility of AFB1 detection within the range 14-500ngmL -1 demonstrating detection limit (3Ϭ) of 14ngmL -1 . The developed technique was successfully applied for the analysis of model solutions and waste waters from bread-making plants. Copyright © 2017 Elsevier B.V. All rights reserved.

Gis-Based Site Selection for Underground Natural Resources Using Fuzzy Ahp-Owa

NASA Astrophysics Data System (ADS)

Sabzevari, A. R.; Delavar, M. R.

2017-09-01

Fuel consumption has significantly increased due to the growth of the population. A solution to address this problem is the underground storage of natural gas. The first step to reach this goal is to select suitable places for the storage. In this study, site selection for the underground natural gas reservoirs has been performed using a multi-criteria decision-making in a GIS environment. The "Ordered Weighted Average" (OWA) operator is one of the multi-criteria decision-making methods for ranking the criteria and consideration of uncertainty in the interaction among the criteria. In this paper, Fuzzy AHP_OWA (FAHP_OWA) is used to determine optimal sites for the underground natural gas reservoirs. Fuzzy AHP_OWA considers the decision maker's risk taking and risk aversion during the decision-making process. Gas consumption rate, temperature, distance from main transportation network, distance from gas production centers, population density and distance from gas distribution networks are the criteria used in this research. Results show that the northeast and west of Iran and the areas around Tehran (Tehran and Alborz Provinces) have a higher attraction for constructing a natural gas reservoir. The performance of the used method was also evaluated. This evaluation was performed using the location of the existing natural gas reservoirs in the country and the site selection maps for each of the quantifiers. It is verified that the method used in this study is capable of modeling different decision-making strategies used by the decision maker with about 88 percent of agreement between the modeling and test data.

Solar energy system economic evaluation: Fern Tunkhannock, Tunkhannock, Pennsylvania

NASA Astrophysics Data System (ADS)

1980-09-01

The economic performance of an Operational Test Site (OTS) is described. The long term economic performance of the system at its installation site and extrapolation to four additional selected locations to demonstrate the viability of the design over a broad range of environmental and economic conditions is reported. Topics discussed are: system description, study approach, economic analysis and system optimization, and technical and economical results of analysis. Data for the economic analysis are generated through evaluation of the OTS. The simulation is based on the technical results of the seasonal report simulation. In addition localized and standard economic parameters are used for economic analysis.

Solar energy system economic evaluation: Fern Tunkhannock, Tunkhannock, Pennsylvania

NASA Technical Reports Server (NTRS)

1980-01-01

The economic performance of an Operational Test Site (OTS) is described. The long term economic performance of the system at its installation site and extrapolation to four additional selected locations to demonstrate the viability of the design over a broad range of environmental and economic conditions is reported. Topics discussed are: system description, study approach, economic analysis and system optimization, and technical and economical results of analysis. Data for the economic analysis are generated through evaluation of the OTS. The simulation is based on the technical results of the seasonal report simulation. In addition localized and standard economic parameters are used for economic analysis.

Novel Triazole-Quinoline Derivatives as Selective Dual Binding Site Acetylcholinesterase Inhibitors.

PubMed

Mantoani, Susimaire P; Chierrito, Talita P C; Vilela, Adriana F L; Cardoso, Carmen L; Martínez, Ana; Carvalho, Ivone

2016-02-05

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide. Currently, the only strategy for palliative treatment of AD is to inhibit acetylcholinesterase (AChE) in order to increase the concentration of acetylcholine in the synaptic cleft. Evidence indicates that AChE also interacts with the β-amyloid (Aβ) protein, acting as a chaperone and increasing the number and neurotoxicity of Aβ fibrils. It is known that AChE has two binding sites: the peripheral site, responsible for the interactions with Aβ, and the catalytic site, related with acetylcholine hydrolysis. In this work, we reported the synthesis and biological evaluation of a library of new tacrine-donepezil hybrids, as a potential dual binding site AChE inhibitor, containing a triazole-quinoline system. The synthesis of hybrids was performed in four steps using the click chemistry strategy. These compounds were evaluated as hAChE and hBChE inhibitors, and some derivatives showed IC50 values in the micro-molar range and were remarkably selective towards hAChE. Kinetic assays and molecular modeling studies confirm that these compounds block both catalytic and peripheral AChE sites. These results are quite interesting since the triazole-quinoline system is a new structural scaffold for AChE inhibitors. Furthermore, the synthetic approach is very efficient for the preparation of target compounds, allowing a further fruitful new chemical library optimization.

Weight optimization of plane truss using genetic algorithm

NASA Astrophysics Data System (ADS)

Neeraja, D.; Kamireddy, Thejesh; Santosh Kumar, Potnuru; Simha Reddy, Vijay

2017-11-01

Optimization of structure on basis of weight has many practical benefits in every engineering field. The efficiency is proportionally related to its weight and hence weight optimization gains prime importance. Considering the field of civil engineering, weight optimized structural elements are economical and easier to transport to the site. In this study, genetic optimization algorithm for weight optimization of steel truss considering its shape, size and topology aspects has been developed in MATLAB. Material strength and Buckling stability have been adopted from IS 800-2007 code of construction steel. The constraints considered in the present study are fabrication, basic nodes, displacements, and compatibility. Genetic programming is a natural selection search technique intended to combine good solutions to a problem from many generations to improve the results. All solutions are generated randomly and represented individually by a binary string with similarities of natural chromosomes, and hence it is termed as genetic programming. The outcome of the study is a MATLAB program, which can optimise a steel truss and display the optimised topology along with element shapes, deflections, and stress results.

An Analysis of the DER Adoption Climate in Japan UsingOptimization Results for Prototype Buildings with U.S. Comparisons

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

Zhou, Nan; Marnay, Chris; Firestone, Ryan

2006-06-16

This research demonstrates economically optimal distributedenergy resource (DER) system choice using the DER choice and operationsoptimization program, the Distributed Energy Resources Customer AdoptionModel (DER-CAM). DER-CAM finds the optimal combination of installedequipment given prevailing utility tariffs and fuel prices, siteelectrical and thermal loads (including absorption cooling), and a menuof available equipment. It provides a global optimization, albeitidealized, that shows how site useful energy loads can be served atminimum cost. Five prototype Japanese commercial buildings are examinedand DER-CAM is applied to select the economically optimal DER system foreach. Based on the optimization results, energy and emission reductionsare evaluated. Significant decreases in fuelmore » consumption, carbonemissions, and energy costs were seen in the DER-CAM results. Savingswere most noticeable in the prototype sports facility, followed by thehospital, hotel, and office building. Results show that DER with combinedheat and power equipment is a promising efficiency and carbon mitigationstrategy, but that precise system design is necessary. Furthermore, aJapan-U.S. comparison study of policy, technology, and utility tariffsrelevant to DER installation is presented.« less

Selective adsorption of thiophenic compounds from fuel over TiO2/SiO2 under UV-irradiation.

PubMed

Miao, Guang; Ye, Feiyan; Wu, Luoming; Ren, Xiaoling; Xiao, Jing; Li, Zhong; Wang, Haihui

2015-12-30

This study investigates selective adsorption of thiophenic compounds from fuel over TiO2/SiO2 under UV-irradiation. The TiO2/SiO2 adsorbents were prepared and then characterized by N2 adsorption, X-ray diffraction and X-ray photoelectron spectroscopy. Adsorption isotherms, selectivity and kinetics of TiO2/SiO2 were measured in a UV built-in batch reactor. It was concluded that (a) with the employment of UV-irradiation, high organosulfur uptake of 5.12 mg/g was achieved on the optimized 0.3TiO2/0.7SiO2 adsorbent at low sulfur concentration of 15 ppmw-S, and its adsorption selectivity over naphthalene was up to 325.5; (b) highly dispersed TiO2 served as the photocatalytic sites for DBT oxidation, while SiO2 acted as the selective adsorption sites for the corresponding oxidized DBT using TiO2 as a promoter, the two types of active sites worked cooperatively to achieve the high adsorption selectivity of TiO2/SiO2; (c) The kinetic rate-determining step for the UV photocatalysis-assisted adsorptive desulfurization (PADS) over TiO2/SiO2 was DBT oxidation; (d) consecutive adsorption-regeneration cycles suggested that the 0.3TiO2/0.7SiO2 adsorbent can be regenerated by acetonitrile washing followed with oxidative air treatment. This work demonstrated an effective PADS approach to greatly enhance adsorption capacity and selectivity of thiophenic compounds at low concentrations for deep desulfurization under ambient conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

Assessing FPAR Source and Parameter Optimization Scheme in Application of a Diagnostic Carbon Flux Model

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

Turner, D P; Ritts, W D; Wharton, S

2009-02-26

The combination of satellite remote sensing and carbon cycle models provides an opportunity for regional to global scale monitoring of terrestrial gross primary production, ecosystem respiration, and net ecosystem production. FPAR (the fraction of photosynthetically active radiation absorbed by the plant canopy) is a critical input to diagnostic models, however little is known about the relative effectiveness of FPAR products from different satellite sensors nor about the sensitivity of flux estimates to different parameterization approaches. In this study, we used multiyear observations of carbon flux at four eddy covariance flux tower sites within the conifer biome to evaluate these factors.more » FPAR products from the MODIS and SeaWiFS sensors, and the effects of single site vs. cross-site parameter optimization were tested with the CFLUX model. The SeaWiFs FPAR product showed greater dynamic range across sites and resulted in slightly reduced flux estimation errors relative to the MODIS product when using cross-site optimization. With site-specific parameter optimization, the flux model was effective in capturing seasonal and interannual variation in the carbon fluxes at these sites. The cross-site prediction errors were lower when using parameters from a cross-site optimization compared to parameter sets from optimization at single sites. These results support the practice of multisite optimization within a biome for parameterization of diagnostic carbon flux models.« less

Cyanex based uranyl sensitive polymeric membrane electrodes.

PubMed

Badr, Ibrahim H A; Zidan, W I; Akl, Z F

2014-01-01

Novel uranyl selective polymeric membrane electrodes were prepared using three different low-cost and commercially available Cyanex extractants namely, bis(2,4,4-trimethylpentyl) phosphinic acid [L1], bis(2,4,4-trimethylpentyl) monothiophosphinic acid [L2] and bis(2,4,4-trimethylpentyl) dithiophosphinic acid [L3]. Optimization and performance characteristics of the developed Cyanex based polymer membrane electrodes were determined. The influence of membrane composition (e.g., amount and type of ionic sites, as well as type of plasticizer) on potentiometric responses of the prepared membrane electrodes was studied. Optimized Cyanex-based membrane electrodes exhibited Nernstian responses for UO₂(2+) ion over wide concentration ranges with fast response times. The optimized membrane electrodes based on L1, L2 and L3 exhibited Nernstian responses towards uranyl ion with slopes of 29.4, 28.0 and 29.3 mV decade(-1), respectively. The optimized membrane electrodes based on L1-L3 showed detection limits of 8.3 × 10(-5), 3.0 × 10(-5) and 3.3 × 10(-6) mol L(-1), respectively. The selectivity studies showed that the optimized membrane electrodes exhibited high selectivity towards UO₂(2+) ion over large number of other cations. Membrane electrodes based on L3 exhibited superior potentiometric response characteristics compared to those based on L1 and L2 (e.g., widest linear range and lowest detection limit). The analytical utility of uranyl membrane electrodes formulated with Cyanex extractant L3 was demonstrated by the analysis of uranyl ion in different real samples for nuclear safeguards verification purposes. The results obtained using direct potentiometry and flow-injection methods were compared with those measured using the standard UV-visible and inductively coupled plasma spectroscopic methods. © 2013 Published by Elsevier B.V.

Decision-Related Activity in Macaque V2 for Fine Disparity Discrimination Is Not Compatible with Optimal Linear Readout.

PubMed

Clery, Stephane; Cumming, Bruce G; Nienborg, Hendrikje

2017-01-18

Fine judgments of stereoscopic depth rely mainly on relative judgments of depth (relative binocular disparity) between objects, rather than judgments of the distance to where the eyes are fixating (absolute disparity). In macaques, visual area V2 is the earliest site in the visual processing hierarchy for which neurons selective for relative disparity have been observed (Thomas et al., 2002). Here, we found that, in macaques trained to perform a fine disparity discrimination task, disparity-selective neurons in V2 were highly selective for the task, and their activity correlated with the animals' perceptual decisions (unexplained by the stimulus). This may partially explain similar correlations reported in downstream areas. Although compatible with a perceptual role of these neurons for the task, the interpretation of such decision-related activity is complicated by the effects of interneuronal "noise" correlations between sensory neurons. Recent work has developed simple predictions to differentiate decoding schemes (Pitkow et al., 2015) without needing measures of noise correlations, and found that data from early sensory areas were compatible with optimal linear readout of populations with information-limiting correlations. In contrast, our data here deviated significantly from these predictions. We additionally tested this prediction for previously reported results of decision-related activity in V2 for a related task, coarse disparity discrimination (Nienborg and Cumming, 2006), thought to rely on absolute disparity. Although these data followed the predicted pattern, they violated the prediction quantitatively. This suggests that optimal linear decoding of sensory signals is not generally a good predictor of behavior in simple perceptual tasks. Activity in sensory neurons that correlates with an animal's decision is widely believed to provide insights into how the brain uses information from sensory neurons. Recent theoretical work developed simple predictions to differentiate decoding schemes, and found support for optimal linear readout of early sensory populations with information-limiting correlations. Here, we observed decision-related activity for neurons in visual area V2 of macaques performing fine disparity discrimination, as yet the earliest site for this task. These findings, and previously reported results from V2 in a different task, deviated from the predictions for optimal linear readout of a population with information-limiting correlations. Our results suggest that optimal linear decoding of early sensory information is not a general decoding strategy used by the brain. Copyright © 2017 the authors 0270-6474/17/370715-11$15.00/0.

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.

Stringent and reproducible tetracycline-regulated transgene expression by site-specific insertion at chromosomal loci with pre-characterised induction characteristics

PubMed Central

Brough, Rachel; Papanastasiou, Antigoni M; Porter, Andrew CG

2007-01-01

Background The ability to regulate transgene expression has many applications, mostly concerning the analysis of gene function. Desirable induction characteristics, such as low un-induced expression, high induced expression and limited cellular heterogeneity, can be seriously impaired by chromosomal position effects at the site of transgene integration. Many clones may therefore need to be screened before one with optimal induction characteristics is identified. Furthermore, such screens must be repeated for each new transgene investigated, and comparisons between clones with different transgenes is complicated by their different integration sites. Results To circumvent these problems we have developed a "screen and insert" strategy in which clones carrying a transgene for a fluorescent reporter are first screened for those with optimal induction characteristics. Site-specific recombination (SSR) is then be used repeatedly to insert any new transgene at the reporter transgene locus of such clones so that optimal induction characteristics are conferred upon it. Here we have tested in a human fibrosarcoma cell line (HT1080) two of many possible implementations of this approach. Clones (e.g. Rht14-10) in which a GFP reporter gene is very stringently regulated by the tetracycline (tet) transactivator (tTA) protein were first identified flow-cytometrically. Transgenes encoding luciferase, I-SceI endonuclease or Rad52 were then inserted by SSR at a LoxP site adjacent to the GFP gene resulting stringent tet-regulated transgene expression. In clone Rht14-10, increases in expression from essentially background levels (+tet) to more than 104-fold above background (-tet) were reproducibly detected after Cre-mediated insertion of either the luciferase or the I-SceI transgenes. Conclusion Although previous methods have made use of SSR to integrate transgenes at defined sites, none has effectively combined this with a pre-selection step to identify integration sites that support optimal regulatory characteristics. Rht14-10 and similar HT1080-derived clones can now be used in conjunction with a convenient delivery vector (pIN2-neoMCS), in a simple 3-step protocol leading to stringent and reproducible transgene regulation. This approach will be particularly useful for transgenes whose products are very active at low concentrations and/or for comparisons of multiple related transgenes. PMID:17493262

A Satellite Survey of Cloud Cover and Water Vapor in the Southwestern USA and Northern Mexico

NASA Astrophysics Data System (ADS)

Carrasco, E.; Avila, R.; Erasmus, A.; Djorgovski, S. G.; Walker, A. R.; Blum, R.

2017-03-01

Cloud cover and water vapor conditions in the southwestern USA and northern Mexico were surveyed as a preparatory work for the Thirty Meter Telescope (TMT) in situ site testing program. Although the telescope site is already selected, the TMT site testing team decided to make public these results for its usefulness for the community. Using 58 months of meteorological satellite observations between 1993 July and 1999 September, different atmospheric parameters were quantified from data of the 10.7 μm and of 6.7 μm windows. In particular, cloud cover and water vapor conditions were identified in preferred areas. As a result of the aerial analysis, 15 sites of existing and potential telescope were selected, compared, and ranked in terms of their observing quality. The clearest sites are located along the spine of the Baja peninsula and into southern California on mountain peaks above the temperature inversion layer. A steep gradient of cloudiness was observed along the coast where coastal cloud and fog are trapped below the inversion layer. Moving from west to east over the continent, a significant increase in cloudiness was observed. The analysis shows that San Pedro Mártir, San Gorgonio Mountain and San Jacinto Peak have the largest fraction of clear sky conditions (˜74%). The site with the optimal combination of clear skies and low precipitable water vapor is Boundary Peak, Nevada. An approach based in satellite data provided a reliable method for sites comparison.

Site preference of alloying elements in DO22-Ni3V phase: Phase-field and first-principles study

NASA Astrophysics Data System (ADS)

Zhang, Ding-Ni; Shangguan, Qian-Qian; Liu, Fu; Zhang, Ming-Yi

2015-07-01

Site preference of alloying elements in DO22-Ni3V phase was investigated using phase-field and first-principles method. The concentrations of alloying elements on sublattices of DO22-Ni3V phase were quantitatively studied using phase-field model based on microscopic diffusion equations. The phase-field computation results demonstrate that the concentration differences of alloying elements on the NiI and NiII site are attributed to the coordination environment difference. Host atoms Ni and substitutional ternary additions Al prefer to occupy NiI site. Antisite atoms V show site preference on the NiII site. Further reason of site preference of alloying elements on the two different Ni sites were studied using first-principles method to calculate the electronic structure of DO22-Ni3V phase. Calculation of density of states, orbitals population and charge population of the optimized Ni3V structure found that the electronic structures of NiI and NiII sites are different. Electronic structure difference, which is caused by coordination environment difference, is the essential reason for site selectivity behaviors of alloying elements on NiI and NiII sites.

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.

Generation of a pair of independently binding DNA aptamers in a single round of selection using proximity ligation.

PubMed

Chumphukam, O; Le, T T; Piletsky, S; Cass, A E G

2015-05-28

The ability to rapidly generate a pair of aptamers that bind independently to a protein target would greatly extend their use as reagents for two site ('sandwich') assays. We describe here a method to achieve this through proximity ligation. Using lysozyme as a target we demonstrate that under optimal conditions such a pair of aptamers, with nanomolar affinities, can be generated in a single round.

Optimal approach for complete liver tumor ablation using radiofrequency ablation: a simulation study.

PubMed

Givehchi, Sogol; Wong, Yin How; Yeong, Chai Hong; Abdullah, Basri Johan Jeet

2018-04-01

To investigate the effect of radiofrequency ablation (RFA) electrode trajectory on complete tumor ablation using computational simulation. The RFA of a spherical tumor of 2.0 cm diameter along with 0.5 cm clinical safety margin was simulated using Finite Element Analysis software. A total of 86 points inside one-eighth of the tumor volume along the axial, sagittal and coronal planes were selected as the target sites for electrode-tip placement. The angle of the electrode insertion in both craniocaudal and orbital planes ranged from -90° to +90° with 30° increment. The RFA electrode was simulated to pass through the target site at different angles in combination of both craniocaudal and orbital planes before being advanced to the edge of the tumor. Complete tumor ablation was observed whenever the electrode-tip penetrated through the epicenter of the tumor regardless of the angles of electrode insertion in both craniocaudal and orbital planes. Complete tumor ablation can also be achieved by placing the electrode-tip at several optimal sites and angles. Identification of the tumor epicenter on the central slice of the axial images is essential to enhance the success rate of complete tumor ablation during RFA procedures.

Discovery of 2-methylpyridine-based biaryl amides as γ-secretase modulators for the treatment of Alzheimer's disease.

PubMed

Chen, Jian Jeffrey; Qian, Wenyuan; Biswas, Kaustav; Yuan, Chester; Amegadzie, Albert; Liu, Qingyian; Nixey, Thomas; Zhu, Joe; Ncube, Mqhele; Rzasa, Robert M; Chavez, Frank; Chen, Ning; DeMorin, Frenel; Rumfelt, Shannon; Tegley, Christopher M; Allen, Jennifer R; Hitchcock, Stephen; Hungate, Randy; Bartberger, Michael D; Zalameda, Leeanne; Liu, Yichin; McCarter, John D; Zhang, Jianhua; Zhu, Li; Babu-Khan, Safura; Luo, Yi; Bradley, Jodi; Wen, Paul H; Reid, Darren L; Koegler, Frank; Dean, Charles; Hickman, Dean; Correll, Tiffany L; Williamson, Toni; Wood, Stephen

2013-12-01

γ-Secretase modulators (GSMs) are potentially disease-modifying treatments for Alzheimer's disease. They selectively lower pathogenic Aβ42 levels by shifting the enzyme cleavage sites without inhibiting γ-secretase activity, possibly avoiding known adverse effects observed with complete inhibition of the enzyme complex. A cell-based HTS effort identified the sulfonamide 1 as a GSM lead. Lead optimization studies identified compound 25 with improved cell potency, PKDM properties, and it lowered Aβ42 levels in the cerebrospinal fluid (CSF) of Sprague-Dawley rats following oral administration. Further optimization of 25 to improve cellular potency is described. Copyright © 2013 Elsevier Ltd. All rights reserved.

The role of CSP in the electricity system of South Africa - technical operation, grid constraints, market structure and economics

NASA Astrophysics Data System (ADS)

Kost, Christoph; Friebertshäuser, Chris; Hartmann, Niklas; Fluri, Thomas; Nitz, Peter

2017-06-01

This paper analyses the role of solar technologies (CSP and PV) and their interaction in the South African electricity system by using a fundamental electricity system modelling (ENTIGRIS-SouthAfrica). The model is used to analyse the South African long-term electricity generation portfolio mix, optimized site selection and required transmission capacities until the year 2050. Hereby especially the location and grid integration of solar technology (PV and CSP) and wind power plants is analysed. This analysis is carried out by using detailed resource assessment of both technologies. A cluster approach is presented to reduce complexity by integrating the data in an optimization model.

Engineering the donor selectivity of D-fructose-6-phosphate aldolase for biocatalytic asymmetric cross-aldol additions of glycolaldehyde.

PubMed

Szekrenyi, Anna; Soler, Anna; Garrabou, Xavier; Guérard-Hélaine, Christine; Parella, Teodor; Joglar, Jesús; Lemaire, Marielle; Bujons, Jordi; Clapés, Pere

2014-09-22

D-Fructose-6-phosphate aldolase (FSA) is a unique catalyst for asymmetric cross-aldol additions of glycolaldehyde. A combination of a structure-guided approach of saturation mutagenesis, site-directed mutagenesis, and computational modeling was applied to construct a set of FSA variants that improved the catalytic efficiency towards glycolaldehyde dimerization up to 1800-fold. A combination of mutations in positions L107, A129, and A165 provided a toolbox of FSA variants that expand the synthetic possibilities towards the preparation of aldose-like carbohydrate compounds. The new FSA variants were applied as highly efficient catalysts for cross-aldol additions of glycolaldehyde to N-carbobenzyloxyaminoaldehydes to furnish between 80-98 % aldol adduct under optimized reaction conditions. Donor competition experiments showed high selectivity for glycolaldehyde relative to dihydroxyacetone or hydroxyacetone. These results demonstrate the exceptional malleability of the active site in FSA, which can be remodeled to accept a wide spectrum of donor and acceptor substrates with high efficiency and selectivity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Wind Plant Power Optimization and Control under Uncertainty

NASA Astrophysics Data System (ADS)

Jha, Pankaj; Ulker, Demet; Hutchings, Kyle; Oxley, Gregory

2017-11-01

The development of optimized cooperative wind plant control involves the coordinated operation of individual turbines co-located within a wind plant to improve the overall power production. This is typically achieved by manipulating the trajectory and intensity of wake interactions between nearby turbines, thereby reducing wake losses. However, there are various types of uncertainties involved, such as turbulent inflow and microscale and turbine model input parameters. In a recent NREL-Envision collaboration, a controller that performs wake steering was designed and implemented for the Longyuan Rudong offshore wind plant in Jiangsu, China. The Rudong site contains 25 Envision EN136-4 MW turbines, of which a subset was selected for the field test campaign consisting of the front two rows for the northeasterly wind direction. In the first row, a turbine was selected as the reference turbine, providing comparison power data, while another was selected as the controlled turbine. This controlled turbine wakes three different turbines in the second row depending on the wind direction. A yaw misalignment strategy was designed using Envision's GWCFD, a multi-fidelity plant-scale CFD tool based on SOWFA with a generalized actuator disc (GAD) turbine model, which, in turn, was used to tune NREL's FLORIS model used for wake steering and yaw control optimization. The presentation will account for some associated uncertainties, such as those in atmospheric turbulence and wake profile.

Lower irritation microemulsion-based rotigotine gel: formulation optimization and in vitro and in vivo studies.

PubMed

Wang, Zheng; Mu, Hong-Jie; Zhang, Xue-Mei; Ma, Peng-Kai; Lian, Sheng-Nan; Zhang, Feng-Pu; Chu, Sheng-Ying; Zhang, Wen-Wen; Wang, Ai-Ping; Wang, Wen-Yan; Sun, Kao-Xiang

2015-01-01

Rotigotine is a potent and selective D1, D2, and D3 dopaminergic receptor agonist. Due to an extensive first-pass effect, it has a very low oral bioavailability (approximately 0.5% in rats). The present investigation aimed to develop a microemulsion-based hydrogel for transdermal rotigotine delivery with lower application site reactions. Pseudoternary phase diagrams were constructed to determine the region of oil in water (o/w)-type microemulsion. Central composite design was used to support the pseudoternary phase diagrams and to select homogeneous and stable microemulsions with an optimal amount of rotigotine permeation within 24 hours. In vitro skin permeation experiments were performed, using Franz diffusion cells, to compare rotigotine-loaded microemulsions with rotigotine solutions in oil. The optimized formulation was used to prepare a microemulsion-based hydrogel, which was subjected to bioavailability and skin irritancy studies. The selected formulations of rotigotine-loaded microemulsions had enhanced flux and permeation coefficients compared with rotigotine in oil. The optimum microemulsion contained 68% water, 6.8% Labrafil(®), 13.44% Cremophor(®) RH40, 6.72% Labrasol(®), and 5.04% Transcutol(®) HP; the drug-loading rate was 2%. To form a microemulsion gel, 1% Carbomer 1342 was added to the microemulsion. The bioavailability of the rotigotine-loaded microemulsion gel was 105.76%±20.52% with respect to the marketed rotigotine patch (Neupro(®)). The microemulsion gel irritated the skin less than Neupro. A rotigotine microemulsion-based hydrogel was successfully developed, and an optimal formulation for drug delivery was identified. This product could improve patient compliance and have broad marketability.

Organic antireflective coatings for 193-nm lithography

NASA Astrophysics Data System (ADS)

Trefonas, Peter, III; Blacksmith, Robert F.; Szmanda, Charles R.; Kavanagh, Robert J.; Adams, Timothy G.; Taylor, Gary N.; Coley, Suzanne; Pohlers, Gerd

1999-06-01

Organic anti-reflective coatings (ARCs) continue to play an important role in semiconductor manufacturing. These materials provide a convenient means of greatly reducing the resist photospeed swing and reflective notching. In this paper, we describe a novel class of ARC materials optimized for lithographic applications using 193 nm exposure tools. These ARCs are based upon polymers containing hydroxyl-alkyl methacrylate monomers for crosslinkable sites, styrene for a chromophore at 193 nm, and additional alkyl-methacrylate monomers as property modifiers. A glycouril crosslinker and a thermally-activated acidic catalyst provide a route to forming an impervious crosslinked film activate data high bake temperatures. ARC compositions can be adjusted to optimize the film's real and imaginary refractive indices. Selection of optimal target indices for 193 nm lithographic processing through simulations is described. Potential chromophores for 193 nm were explored using ZNDO modeling. We show how these theoretical studies were combined with material selection criteria to yield a versatile organic anti-reflectant film, Shipley 193 G0 ARC. Lithographic process data indicates the materials is capable of supporting high resolution patterning, with the line features displaying a sharp resist/ARC interface with low line edge roughness. The resist Eo swing is successfully reduced from 43 percent to 6 percent.

Discovery of CREBBP Bromodomain Inhibitors by High-Throughput Docking and Hit Optimization Guided by Molecular Dynamics.

PubMed

Xu, Min; Unzue, Andrea; Dong, Jing; Spiliotopoulos, Dimitrios; Nevado, Cristina; Caflisch, Amedeo

2016-02-25

We have identified two chemotypes of CREBBP bromodomain ligands by fragment-based high-throughput docking. Only 17 molecules from the original library of two-million compounds were tested in vitro. Optimization of the two low-micromolar hits, the 4-acylpyrrole 1 and acylbenzene 9, was driven by molecular dynamics results which suggested improvement of the polar interactions with the Arg1173 side chain at the rim of the binding site. The synthesis of only two derivatives of 1 yielded the 4-acylpyrrole 6 which shows a single-digit micromolar affinity for the CREBBP bromodomain and a ligand efficiency of 0.34 kcal/mol per non-hydrogen atom. Optimization of the acylbenzene hit 9 resulted in a series of derivatives with nanomolar potencies, good ligand efficiency and selectivity (see Unzue, A.; Xu, M.; Dong, J.; Wiedmer, L.; Spiliotopoulos, D.; Caflisch, A.; Nevado, C.Fragment-Based Design of Selective Nanomolar Ligands of the CREBBP Bromodomain. J. Med. Chem. 2015, DOI: 10.1021/acs.jmedchem.5b00172). The in silico predicted binding mode of the acylbenzene derivative 10 was validated by solving the structure of the complex with the CREBBP bromodomain.

Testing the mutant selection window hypothesis with Escherichia coli exposed to levofloxacin in a rabbit tissue cage infection model.

PubMed

Ni, W; Song, X; Cui, J

2014-03-01

The purpose of this study was to test the mutant selection window (MSW) hypothesis with Escherichia coli exposed to levofloxacin in a rabbit model and to compare in vivo and in vitro exposure thresholds that restrict the selection of fluoroquinolone-resistant mutants. Local infection with E. coli was established in rabbits, and the infected animals were treated orally with various doses of levofloxacin once a day for five consecutive days. Changes in levofloxacin concentration and levofloxacin susceptibility were monitored at the site of infection. The MICs of E. coli increased when levofloxacin concentrations at the site of infection fluctuated between the lower and upper boundaries of the MSW, defined in vitro as the minimum inhibitory concentration (MIC99) and the mutant prevention concentration (MPC), respectively. The pharmacodynamic thresholds at which resistant mutants are not selected in vivo was estimated as AUC24/MPC > 20 h or AUC24/MIC > 60 h, where AUC24 is the area under the drug concentration time curve in a 24-h interval. Our finding demonstrated that the MSW existed in vivo. The AUC24/MPC ratio that prevented resistant mutants from being selected estimated in vivo is consistent with that observed in vitro, indicating it might be a reliable index for guiding the optimization of antimicrobial treatment regimens for suppression of the selection of antimicrobial resistance.

Novel Rhizosphere Soil Alleles for the Enzyme 1-Aminocyclopropane-1-Carboxylate Deaminase Queried for Function with an In Vivo Competition Assay

PubMed Central

Jin, Zhao; Di Rienzi, Sara C.; Janzon, Anders; Werner, Jeff J.; Angenent, Largus T.; Dangl, Jeffrey L.; Fowler, Douglas M.

2015-01-01

Metagenomes derived from environmental microbiota encode a vast diversity of protein homologs. How this diversity impacts protein function can be explored through selection assays aimed to optimize function. While artificially generated gene sequence pools are typically used in selection assays, their usage may be limited because of technical or ethical reasons. Here, we investigate an alternative strategy, the use of soil microbial DNA as a starting point. We demonstrate this approach by optimizing the function of a widely occurring soil bacterial enzyme, 1-aminocyclopropane-1-carboxylate (ACC) deaminase. We identified a specific ACC deaminase domain region (ACCD-DR) that, when PCR amplified from the soil, produced a variant pool that we could swap into functional plasmids carrying ACC deaminase-encoding genes. Functional clones of ACC deaminase were selected for in a competition assay based on their capacity to provide nitrogen to Escherichia coli in vitro. The most successful ACCD-DR variants were identified after multiple rounds of selection by sequence analysis. We observed that previously identified essential active-site residues were fixed in the original unselected library and that additional residues went to fixation after selection. We identified a divergent essential residue whose presence hints at the possible use of alternative substrates and a cluster of neutral residues that did not influence ACCD performance. Using an artificial ACCD-DR variant library generated by DNA oligomer synthesis, we validated the same fixation patterns. Our study demonstrates that soil metagenomes are useful starting pools of protein-coding-gene diversity that can be utilized for protein optimization and functional characterization when synthetic libraries are not appropriate. PMID:26637602

Calculating an optimal box size for ligand docking and virtual screening against experimental and predicted binding pockets.

PubMed

Feinstein, Wei P; Brylinski, Michal

2015-01-01

Computational approaches have emerged as an instrumental methodology in modern research. For example, virtual screening by molecular docking is routinely used in computer-aided drug discovery. One of the critical parameters for ligand docking is the size of a search space used to identify low-energy binding poses of drug candidates. Currently available docking packages often come with a default protocol for calculating the box size, however, many of these procedures have not been systematically evaluated. In this study, we investigate how the docking accuracy of AutoDock Vina is affected by the selection of a search space. We propose a new procedure for calculating the optimal docking box size that maximizes the accuracy of binding pose prediction against a non-redundant and representative dataset of 3,659 protein-ligand complexes selected from the Protein Data Bank. Subsequently, we use the Directory of Useful Decoys, Enhanced to demonstrate that the optimized docking box size also yields an improved ranking in virtual screening. Binding pockets in both datasets are derived from the experimental complex structures and, additionally, predicted by eFindSite. A systematic analysis of ligand binding poses generated by AutoDock Vina shows that the highest accuracy is achieved when the dimensions of the search space are 2.9 times larger than the radius of gyration of a docking compound. Subsequent virtual screening benchmarks demonstrate that this optimized docking box size also improves compound ranking. For instance, using predicted ligand binding sites, the average enrichment factor calculated for the top 1 % (10 %) of the screening library is 8.20 (3.28) for the optimized protocol, compared to 7.67 (3.19) for the default procedure. Depending on the evaluation metric, the optimal docking box size gives better ranking in virtual screening for about two-thirds of target proteins. This fully automated procedure can be used to optimize docking protocols in order to improve the ranking accuracy in production virtual screening simulations. Importantly, the optimized search space systematically yields better results than the default method not only for experimental pockets, but also for those predicted from protein structures. A script for calculating the optimal docking box size is freely available at www.brylinski.org/content/docking-box-size. Graphical AbstractWe developed a procedure to optimize the box size in molecular docking calculations. Left panel shows the predicted binding pose of NADP (green sticks) compared to the experimental complex structure of human aldose reductase (blue sticks) using a default protocol. Right panel shows the docking accuracy using an optimized box size.

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.

Screening and identification of potential PTP1B allosteric inhibitors using in silico and in vitro approaches.

PubMed

Shinde, Ranajit Nivrutti; Kumar, G Siva; Eqbal, Shahbaz; Sobhia, M Elizabeth

2018-01-01

Protein tyrosine phosphatase 1B (PTP1B) is a validated therapeutic target for Type 2 diabetes due to its specific role as a negative regulator of insulin signaling pathways. Discovery of active site directed PTP1B inhibitors is very challenging due to highly conserved nature of the active site and multiple charge requirements of the ligands, which makes them non-selective and non-permeable. Identification of the PTP1B allosteric site has opened up new avenues for discovering potent and selective ligands for therapeutic intervention. Interactions made by potent allosteric inhibitor in the presence of PTP1B were studied using Molecular Dynamics (MD). Computationally optimized models were used to build separate pharmacophore models of PTP1B and TCPTP, respectively. Based on the nature of interactions the target residues offered, a receptor based pharmacophore was developed. The pharmacophore considering conformational flexibility of the residues was used for the development of pharmacophore hypothesis to identify potentially active inhibitors by screening large compound databases. Two pharmacophore were successively used in the virtual screening protocol to identify potential selective and permeable inhibitors of PTP1B. Allosteric inhibition mechanism of these molecules was established using molecular docking and MD methods. The geometrical criteria values confirmed their ability to stabilize PTP1B in an open conformation. 23 molecules that were identified as potential inhibitors were screened for PTP1B inhibitory activity. After screening, 10 molecules which have good permeability values were identified as potential inhibitors of PTP1B. This study confirms that selective and permeable inhibitors can be identified by targeting allosteric site of PTP1B.

Postpartum Family Planning During Sociopolitical Transition: Findings from an Integrated Community-Based Program in Egypt.

PubMed

Cooper, Chelsea M; Charurat, Elaine; El-Adawi, Issam; Kim, Young-Mi; Emerson, Mark R; Zaki, Wael; Schuster, Anne

2016-06-01

Limited information exists on postpartum family planning and implementation of integrated reproductive and maternal and child health programs in countries experiencing sociopolitical transition. A quasi-experimental evaluation of an integrated reproductive and maternal and child health program implemented in selected sites in Upper and Lower Egypt was conducted between 2012 and 2014. Preintervention and postintervention household surveys were conducted among 12,454 women in intervention sites and nonintervention comparison sites who at survey had a child younger than 24 months. Bivariate and multivariate analyses estimated the intervention's effects on postpartum family planning-related outcomes, including contraceptive use, knowledge of optimal birthspacing, reproductive intentions and decision making about contraceptive use. In Upper Egypt, modern contraceptive use decreased over the study period in both intervention and comparison sites (by six and 15 percentage points, respectively), and in Lower Egypt, contraceptive use remained unchanged in intervention sites and decreased slightly (by three points) in comparison sites; in both regions, the intervention was positively associated with the difference in differences between groups (odds ratios, 1.5 for Upper Egypt and 1.3 for Lower Egypt). The intervention appears to have had a positive effect on knowledge of optimal birthspacing in Upper Egypt, on wanting to delay the next pregnancy in Lower Egypt, and on pregnancy risk and joint decision making in both regions. Study findings demonstrate the feasibility and effectiveness of an integrated reproductive and maternal and child health program implemented in a changing sociopolitical context. Revitalized efforts to bolster family planning within the country are needed to avert further losses and spark a return to positive trends.

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

NASA Astrophysics Data System (ADS)

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

2017-04-01

The identification of representative soil moisture sampling sites is important for the validation of remotely sensed mean soil moisture in a certain area and ground-based soil moisture measurements in catchment or hillslope hydrological studies. Numerous approaches have been developed to identify optimal sites for predicting mean soil moisture. Each method has certain advantages and disadvantages, but they have rarely been evaluated and compared. In our study, surface (0-20 cm) soil moisture data from January 2013 to March 2016 (a total of 43 sampling days) were collected at 77 sampling sites on a mixed land-use (tea and bamboo) hillslope in the hilly area of Taihu Lake Basin, China. A total of 10 methods (temporal stability (TS) analyses based on 2 indices, K-means clustering based on 6 kinds of inputs and 2 random sampling strategies) were evaluated for determining optimal sampling sites for mean soil moisture estimation. They were TS analyses based on the smallest index of temporal stability (ITS, a combination of the mean relative difference and standard deviation of relative difference (SDRD)) and based on the smallest SDRD, K-means clustering based on soil properties and terrain indices (EFs), repeated soil moisture measurements (Theta), EFs plus one-time soil moisture data (EFsTheta), and the principal components derived from EFs (EFs-PCA), Theta (Theta-PCA), and EFsTheta (EFsTheta-PCA), and global and stratified random sampling strategies. Results showed that the TS based on the smallest ITS was better (RMSE = 0.023 m3 m-3) than that based on the smallest SDRD (RMSE = 0.034 m3 m-3). The K-means clustering based on EFsTheta (-PCA) was better (RMSE <0.020 m3 m-3) than these based on EFs (-PCA) and Theta (-PCA). The sampling design stratified by the land use was more efficient than the global random method. Forty and 60 sampling sites are needed for stratified sampling and global sampling respectively to make their performances comparable to the best K-means method (EFsTheta-PCA). Overall, TS required only one site, but its accuracy was limited. The best K-means method required <8 sites and yielded high accuracy, but extra soil and terrain information is necessary when using this method. The stratified sampling strategy can only be used if no pre-knowledge about soil moisture variation is available. This information will help in selecting the optimal methods for estimation the area mean soil moisture.

Sodium and Potassium Ions in Proteins and Enzyme Catalysis.

PubMed

Vašák, Milan; Schnabl, Joachim

2016-01-01

The group I alkali metal ions Na(+) and K(+) are ubiquitous components of biological fluids that surround biological macromolecules. They play important roles other than being nonspecific ionic buffering agents or mediators of solute exchange and transport. Molecular evolution and regulated high intracellular and extracellular M(+) concentrations led to incorporation of selective Na(+) and K(+) binding sites into enzymes to stabilize catalytic intermediates or to provide optimal positioning of substrates. The mechanism of M(+) activation, as derived from kinetic studies along with structural analysis, has led to the classification of cofactor-like (type I) or allosteric effector (type II) activated enzymes. In the type I mechanism substrate anchoring to the enzyme active site is mediated by M(+), often acting in tandem with a divalent cation like Mg(2+), Mn(2+) or Zn(2+). In the allosteric type II mechanism, M(+) binding enhances enzyme activity through conformational transitions triggered upon binding to a distant site. In this chapter, following the discussion of the coordination chemistry of Na(+) and K(+) ions and the structural features responsible for the metal binding site selectivity in M(+)-activated enzymes, well-defined examples of M(+)-activated enzymes are used to illustrate the structural basis for type I and type II activation by Na(+) and K(+).

Discovery of novel hydroxamates as highly potent tumor necrosis factor-[alpha] converting enzyme inhibitors. Part II: Optimization of the S3′ pocket

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

Mazzola Jr., Robert D.; Zhu, Zhaoning; Sinning, Lisa

2010-10-01

A series of cyclopropyl hydroxamic acids were prepared. Many of the compounds displayed picomolar affinity for the TACE enzyme while maintaining good to excellent selectivity profiles versus MMP-1, -2, -3, -7, -14, and ADAM-10. X-ray analysis of an inhibitor in the TACE active site indicated that the molecules bound to the enzyme in the S1{prime}-S3{prime} pocket.

Structure-based design of Aurora A & B inhibitors

NASA Astrophysics Data System (ADS)

Poulsen, Anders; William, Anthony; Lee, Angeline; Blanchard, Stéphanie; Teo, Eeling; Deng, Weiping; Tu, Noah; Tan, Evelyn; Sun, Eric; Goh, Kay Lin; Ong, Wai Chung; Ng, Chee Pang; Goh, Kee Chuan; Bonday, Zahid

2008-12-01

The Aurora family of serine/threonine kinases are mitotic regulators involved in centrosome duplication, formation of the bipolar mitotic spindle and the alignment of the chromosomes along the spindle. These proteins are frequently overexpressed in tumor cells as compared to normal cells and are therefore potential therapeutic oncology targets. An Aurora A high throughput screen revealed a promising sub-micromolar indazole-benzimidazole lead. Modification of the benzimidazole portion of the lead to a C2 linker with a phenyl ring was proposed to achieve novelty. Docking revealed that a conjugated linker was optimal and the resulting compounds were equipotent with the lead. Further structure-guided optimization of substituents on the 5 & 6 position of the indazole led to single digit nanomolar potency. The homology between the Aurora A & Aurora B kinase domains is 71% but their binding sites only differ at residues 212 & 217 (Aurora A numbering). However interactions with only the latter residue may be used for obtaining selectivity. An analysis of published Aurora A and Aurora B X-ray structures reveals subtle differences in the shape of the binding sites. This was exploited by introduction of appropriately sized substituents in the 4 & 6 position of the indazole leading to Aurora B selective inhibitors. Finally we calculate the conformational energy penalty of the putative bioactive conformation of our inhibitors and show that this property correlates well with the Aurora A binding affinity.

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

Ekmekcioglu, Mehmet, E-mail: meceng3584@yahoo.co; Kaya, Tolga; Kahraman, Cengiz

The use of fuzzy multiple criteria analysis (MCA) in solid waste management has the advantage of rendering subjective and implicit decision making more objective and analytical, with its ability to accommodate both quantitative and qualitative data. In this paper a modified fuzzy TOPSIS methodology is proposed for the selection of appropriate disposal method and site for municipal solid waste (MSW). Our method is superior to existing methods since it has capability of representing vague qualitative data and presenting all possible results with different degrees of membership. In the first stage of the proposed methodology, a set of criteria of cost,more » reliability, feasibility, pollution and emission levels, waste and energy recovery is optimized to determine the best MSW disposal method. Landfilling, composting, conventional incineration, and refuse-derived fuel (RDF) combustion are the alternatives considered. The weights of the selection criteria are determined by fuzzy pairwise comparison matrices of Analytic Hierarchy Process (AHP). It is found that RDF combustion is the best disposal method alternative for Istanbul. In the second stage, the same methodology is used to determine the optimum RDF combustion plant location using adjacent land use, climate, road access and cost as the criteria. The results of this study illustrate the importance of the weights on the various factors in deciding the optimized location, with the best site located in Catalca. A sensitivity analysis is also conducted to monitor how sensitive our model is to changes in the various criteria weights.« less

Application of experimental design for the optimization of artificial neural network-based water quality model: a case study of dissolved oxygen prediction.

PubMed

Šiljić Tomić, Aleksandra; Antanasijević, Davor; Ristić, Mirjana; Perić-Grujić, Aleksandra; Pocajt, Viktor

2018-04-01

This paper presents an application of experimental design for the optimization of artificial neural network (ANN) for the prediction of dissolved oxygen (DO) content in the Danube River. The aim of this research was to obtain a more reliable ANN model that uses fewer monitoring records, by simultaneous optimization of the following model parameters: number of monitoring sites, number of historical monitoring data (expressed in years), and number of input water quality parameters used. Box-Behnken three-factor at three levels experimental design was applied for simultaneous spatial, temporal, and input variables optimization of the ANN model. The prediction of DO was performed using a feed-forward back-propagation neural network (BPNN), while the selection of most important inputs was done off-model using multi-filter approach that combines a chi-square ranking in the first step with a correlation-based elimination in the second step. The contour plots of absolute and relative error response surfaces were utilized to determine the optimal values of design factors. From the contour plots, two BPNN models that cover entire Danube flow through Serbia are proposed: an upstream model (BPNN-UP) that covers 8 monitoring sites prior to Belgrade and uses 12 inputs measured in the 7-year period and a downstream model (BPNN-DOWN) which covers 9 monitoring sites and uses 11 input parameters measured in the 6-year period. The main difference between the two models is that BPNN-UP utilizes inputs such as BOD, P, and PO 4 3- , which is in accordance with the fact that this model covers northern part of Serbia (Vojvodina Autonomous Province) which is well-known for agricultural production and extensive use of fertilizers. Both models have shown very good agreement between measured and predicted DO (with R 2  ≥ 0.86) and demonstrated that they can effectively forecast DO content in the Danube River.

Predicting seasonal diet in the yellow-bellied marmot: success and failure for the linear programming model.

PubMed

Edwards, G P

1997-10-01

Seasonal diet selection in the yellow-bellied marmot (Marmota flaviventris) was studied at two sites in Montana during 1991 and 1992. A linear programming model of optimal diet selection successfully predicted the composition of observed diets (monocot versus dicot) in eight out of ten cases early in the active season (April-June). During this period, adult, yearling and juvenile marmots selected diets consistent with the predicted goal of energy maximisation. However, late in the active season (July-August), the model predicted the diet composition in only one out of six cases. In all six late-season determinations, the model underestimated the amount of monocot in the diet. Possible reasons why the model failed to reliably predict diet composition late in the active season are discussed.

Rationally reduced libraries for combinatorial pathway optimization minimizing experimental effort.

PubMed

Jeschek, Markus; Gerngross, Daniel; Panke, Sven

2016-03-31

Rational flux design in metabolic engineering approaches remains difficult since important pathway information is frequently not available. Therefore empirical methods are applied that randomly change absolute and relative pathway enzyme levels and subsequently screen for variants with improved performance. However, screening is often limited on the analytical side, generating a strong incentive to construct small but smart libraries. Here we introduce RedLibs (Reduced Libraries), an algorithm that allows for the rational design of smart combinatorial libraries for pathway optimization thereby minimizing the use of experimental resources. We demonstrate the utility of RedLibs for the design of ribosome-binding site libraries by in silico and in vivo screening with fluorescent proteins and perform a simple two-step optimization of the product selectivity in the branched multistep pathway for violacein biosynthesis, indicating a general applicability for the algorithm and the proposed heuristics. We expect that RedLibs will substantially simplify the refactoring of synthetic metabolic pathways.

On the placement of active members in adaptive truss structures for vibration control

NASA Technical Reports Server (NTRS)

Lu, L.-Y.; Utku, S.; Wada, B. K.

1992-01-01

The problem of optimal placement of active members which are used for vibration control in adaptive truss structures is investigated. The control scheme is based on the method of eigenvalue assignment as a means of shaping the transient response of the controlled adaptive structures, and the minimization of required control action is considered as the optimization criterion. To this end, a performance index which measures the control strokes of active members is formulated in an efficient way. In order to reduce the computation burden, particularly for the case where the locations of active members have to be selected from a large set of available sites, several heuristic searching schemes are proposed for obtaining the near-optimal locations. The proposed schemes significantly reduce the computational complexity of placing multiple active members to the order of that when a single active member is placed.

Puromycin and Methotrexate Resistance Cassettes and Optimized cre-recombinase Expression Plasmids for use in Yeast

PubMed Central

MacDonald, Chris; Piper, Robert C.

2015-01-01

Here we expand the set of tools for genetically manipulating Saccharomyces cerevisiae. We show that puromycin-resistance can be achieved in yeast through expression of a bacterial puromycin-resistance gene optimized to the yeast codon bias, which in turn serves as an easy to use dominant genetic marker suitable for gene disruption. We have constructed a similar DNA cassette expressing yeast codon-optimized mutant human dihydrofolate reductase (DHFR) that confers resistance to methotrexate and can also be used as a dominant selectable marker. Both of these drug-resistant marker cassettes are flanked by loxP sites allowing for their excision from the genome following expression of cre-recombinase. Finally, we have created a series of plasmids for low-level constitutive expression of cre-recombinase in yeast that allows for efficient excision of loxP-flanked markers. PMID:25688547

An Analytical Planning Model to Estimate the Optimal Density of Charging Stations for Electric Vehicles.

PubMed

Ahn, Yongjun; Yeo, Hwasoo

2015-01-01

The charging infrastructure location problem is becoming more significant due to the extensive adoption of electric vehicles. Efficient charging station planning can solve deeply rooted problems, such as driving-range anxiety and the stagnation of new electric vehicle consumers. In the initial stage of introducing electric vehicles, the allocation of charging stations is difficult to determine due to the uncertainty of candidate sites and unidentified charging demands, which are determined by diverse variables. This paper introduces the Estimating the Required Density of EV Charging (ERDEC) stations model, which is an analytical approach to estimating the optimal density of charging stations for certain urban areas, which are subsequently aggregated to city level planning. The optimal charging station's density is derived to minimize the total cost. A numerical study is conducted to obtain the correlations among the various parameters in the proposed model, such as regional parameters, technological parameters and coefficient factors. To investigate the effect of technological advances, the corresponding changes in the optimal density and total cost are also examined by various combinations of technological parameters. Daejeon city in South Korea is selected for the case study to examine the applicability of the model to real-world problems. With real taxi trajectory data, the optimal density map of charging stations is generated. These results can provide the optimal number of chargers for driving without driving-range anxiety. In the initial planning phase of installing charging infrastructure, the proposed model can be applied to a relatively extensive area to encourage the usage of electric vehicles, especially areas that lack information, such as exact candidate sites for charging stations and other data related with electric vehicles. The methods and results of this paper can serve as a planning guideline to facilitate the extensive adoption of electric vehicles.

Effects of transcriptional start site sequence and position on nucleotide-sensitive selection of alternative start sites at the pyrC promoter in Escherichia coli.

PubMed Central

Liu, J; Turnbough, C L

1994-01-01

In Escherichia coli, expression of the pyrC gene is regulated primarily by a translational control mechanism based on nucleotide-sensitive selection of transcriptional start sites at the pyrC promoter. When intracellular levels of CTP are high, pyrC transcripts are initiated predominantly with CTP at a site 7 bases downstream of the Pribnow box. These transcripts form a stable hairpin at their 5' ends that blocks ribosome binding. When the CTP level is low and the GTP level is high, conditions found in pyrimidine-limited cells, transcripts are initiated primarily with GTP at a site 9 bases downstream of the Pribnow box. These shorter transcripts are unable to form a hairpin at their 5' ends and are readily translated. In this study, we examined the effects of nucleotide sequence and position on the selection of transcriptional start sites at the pyrC promoter. We characterized promoter mutations that systematically alter the sequence at position 7 or 9 downstream of the Pribnow box or vary the spacing between the Pribnow box and wild-type transcriptional initiation region. The results reveal preferences for particular initiating nucleotides (ATP > or = GTP > UTP >> CTP) and for starting positions downstream of the Pribnow box (7 >> 6 and 8 > 9 > 10). The results indicate that optimal nucleotide-sensitive start site switching at the wild-type pyrC promoter is the result of competition between the preferred start site (position 7) that uses the poorest initiating nucleotide (CTP) and a weak start site (position 9) that uses a good initiating nucleotide (GTP). The sequence of the pyrC promoter also minimizes the synthesis of untranslatable transcripts and provides for maximum stability of the regulatory transcript hairpin. In addition, the results show that the effects of the mutations on pyrC expression and regulation are consistent with the current model for translational control. Possible effects of preferences for initiating nucleotides and start sites on the expression and regulation of other genes are discussed. Images PMID:7910603

SU-F-R-10: Selecting the Optimal Solution for Multi-Objective Radiomics Model

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

Zhou, Z; Folkert, M; Wang, J

2016-06-15

Purpose: To develop an evidential reasoning approach for selecting the optimal solution from a Pareto solution set obtained by a multi-objective radiomics model for predicting distant failure in lung SBRT. Methods: In the multi-objective radiomics model, both sensitivity and specificity are considered as the objective functions simultaneously. A Pareto solution set with many feasible solutions will be resulted from the multi-objective optimization. In this work, an optimal solution Selection methodology for Multi-Objective radiomics Learning model using the Evidential Reasoning approach (SMOLER) was proposed to select the optimal solution from the Pareto solution set. The proposed SMOLER method used the evidentialmore » reasoning approach to calculate the utility of each solution based on pre-set optimal solution selection rules. The solution with the highest utility was chosen as the optimal solution. In SMOLER, an optimal learning model coupled with clonal selection algorithm was used to optimize model parameters. In this study, PET, CT image features and clinical parameters were utilized for predicting distant failure in lung SBRT. Results: Total 126 solution sets were generated by adjusting predictive model parameters. Each Pareto set contains 100 feasible solutions. The solution selected by SMOLER within each Pareto set was compared to the manually selected optimal solution. Five-cross-validation was used to evaluate the optimal solution selection accuracy of SMOLER. The selection accuracies for five folds were 80.00%, 69.23%, 84.00%, 84.00%, 80.00%, respectively. Conclusion: An optimal solution selection methodology for multi-objective radiomics learning model using the evidential reasoning approach (SMOLER) was proposed. Experimental results show that the optimal solution can be found in approximately 80% cases.« less

Effects on noise properties of GPS time series caused by higher-order ionospheric corrections

NASA Astrophysics Data System (ADS)

Jiang, Weiping; Deng, Liansheng; Li, Zhao; Zhou, Xiaohui; Liu, Hongfei

2014-04-01

Higher-order ionospheric (HOI) effects are one of the principal technique-specific error sources in precise global positioning system (GPS) analysis. These effects also influence the non-linear characteristics of GPS coordinate time series. In this paper, we investigate these effects on coordinate time series in terms of seasonal variations and noise amplitudes. Both power spectral techniques and maximum likelihood estimators (MLE) are used to evaluate these effects quantitatively and qualitatively. Our results show an overall improvement for the analysis of global sites if HOI effects are considered. We note that the noise spectral index that is used for the determination of the optimal noise models in our analysis ranged between -1 and 0 both with and without HOI corrections, implying that the coloured noise cannot be removed by these corrections. However, the corrections were found to have improved noise properties for global sites. After the corrections were applied, the noise amplitudes at most sites decreased, among which the white noise amplitudes decreased remarkably. The white noise amplitudes of up to 81.8% of the selected sites decreased in the up component, and the flicker noise of 67.5% of the sites decreased in the north component. Stacked periodogram results show that, no matter whether the HOI effects are considered or not, a common fundamental period of 1.04 cycles per year (cpy), together with the expected annual and semi-annual signals, can explain all peaks of the north and up components well. For the east component, however, reasonable results can be obtained only based on HOI corrections. HOI corrections are useful for better detecting the periodic signals in GPS coordinate time series. Moreover, the corrections contributed partly to the seasonal variations of the selected sites, especially for the up component. Statistically, HOI corrections reduced more than 50% and more than 65% of the annual and semi-annual amplitudes respectively at the selected sites.

Economic decision making and the application of nonparametric prediction models

USGS Publications Warehouse

Attanasi, E.D.; Coburn, T.C.; Freeman, P.A.

2007-01-01

Sustained increases in energy prices have focused attention on gas resources in low permeability shale or in coals that were previously considered economically marginal. Daily well deliverability is often relatively small, although the estimates of the total volumes of recoverable resources in these settings are large. Planning and development decisions for extraction of such resources must be area-wide because profitable extraction requires optimization of scale economies to minimize costs and reduce risk. For an individual firm the decision to enter such plays depends on reconnaissance level estimates of regional recoverable resources and on cost estimates to develop untested areas. This paper shows how simple nonparametric local regression models, used to predict technically recoverable resources at untested sites, can be combined with economic models to compute regional scale cost functions. The context of the worked example is the Devonian Antrim shale gas play, Michigan Basin. One finding relates to selection of the resource prediction model to be used with economic models. Models which can best predict aggregate volume over larger areas (many hundreds of sites) may lose granularity in the distribution of predicted volumes at individual sites. This loss of detail affects the representation of economic cost functions and may affect economic decisions. Second, because some analysts consider unconventional resources to be ubiquitous, the selection and order of specific drilling sites may, in practice, be determined by extraneous factors. The paper also shows that when these simple prediction models are used to strategically order drilling prospects, the gain in gas volume over volumes associated with simple random site selection amounts to 15 to 20 percent. It also discusses why the observed benefit of updating predictions from results of new drilling, as opposed to following static predictions, is somewhat smaller. Copyright 2007, Society of Petroleum Engineers.

Marine turtles are not fussy nesters: a novel test of small-scale nest site selection using structure from motion beach terrain information

PubMed Central

Leon, Javier X.; Gilby, Ben L.; Olds, Andrew D.; Schlacher, Thomas A.

2017-01-01

Background Nest selection is widely regarded as a key process determining the fitness of individuals and viability of animal populations. For marine turtles that nest on beaches, this is particularly pivotal as the nesting environment can significantly control reproductive success.The aim of this study was to identify the environmental attributes of beaches (i.e., morphology, vegetation, urbanisation) that may be associated with successful oviposition in green and loggerhead turtle nests. Methods We quantified the proximity of turtle nests (and surrounding beach locations) to urban areas, measured their exposure to artificial light, and used ultra-high resolution (cm-scale) digital surface models derived from Structure-from-Motion (SfM) algorithms, to characterise geomorphic and vegetation features of beaches on the Sunshine Coast, eastern Australia. Results At small spatial scales (i.e., <100 m), we found no evidence that turtles selected nest sites based on a particular suite of environmental attributes (i.e., the attributes of nest sites were not consistently different from those of surrounding beach locations). Nest sites were, however, typically characterised by occurring close to vegetation, on parts of the shore where the beach- and dune-face was concave and not highly rugged, and in areas with moderate exposure to artificial light. Conclusion This study used a novel empirical approach to identify the attributes of turtle nest sites from a broader ‘envelope’ of environmental nest traits, and is the first step towards optimizing conservation actions to mitigate, at the local scale, present and emerging human impacts on turtle nesting beaches. PMID:28070454

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.

Molecularly imprinted covalent organic polymers for the selective extraction of benzoxazole fluorescent whitening agents from food samples.

PubMed

Ding, Hui; Wang, Rongyu; Wang, Xiao; Ji, Wenhua

2018-06-21

Molecularly imprinted covalent organic polymers were constructed by an imine-linking reaction between 1,3,5-triformylphloroglucinol and 2,6-diaminopyridine and used for the selective solid-phase extraction of benzoxazole fluorescent whitening agents from food samples. Binding experiments showed that imprinting sites on molecularly imprinted polymers had higher selectivity for targets compared with those of the corresponding non-imprinted polymers. Parameters affecting the solid-phase extraction procedure were examined. Under optimal conditions, actual samples were treated and the eluent was analyzed with high-performance liquid chromatography with diode-array detection. The results showed that the established method owned the wide linearity, satisfactory detection limits and quantification limits, and acceptable recoveries. Thus, this developed method possesses the practical potential to the selectively determine benzoxazole fluorescent whitening agents in complex food samples. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Estimation of in-situ bioremediation system cost using a hybrid Extreme Learning Machine (ELM)-particle swarm optimization approach

NASA Astrophysics Data System (ADS)

Yadav, Basant; Ch, Sudheer; Mathur, Shashi; Adamowski, Jan

2016-12-01

In-situ bioremediation is the most common groundwater remediation procedure used for treating organically contaminated sites. A simulation-optimization approach, which incorporates a simulation model for groundwaterflow and transport processes within an optimization program, could help engineers in designing a remediation system that best satisfies management objectives as well as regulatory constraints. In-situ bioremediation is a highly complex, non-linear process and the modelling of such a complex system requires significant computational exertion. Soft computing techniques have a flexible mathematical structure which can generalize complex nonlinear processes. In in-situ bioremediation management, a physically-based model is used for the simulation and the simulated data is utilized by the optimization model to optimize the remediation cost. The recalling of simulator to satisfy the constraints is an extremely tedious and time consuming process and thus there is need for a simulator which can reduce the computational burden. This study presents a simulation-optimization approach to achieve an accurate and cost effective in-situ bioremediation system design for groundwater contaminated with BTEX (Benzene, Toluene, Ethylbenzene, and Xylenes) compounds. In this study, the Extreme Learning Machine (ELM) is used as a proxy simulator to replace BIOPLUME III for the simulation. The selection of ELM is done by a comparative analysis with Artificial Neural Network (ANN) and Support Vector Machine (SVM) as they were successfully used in previous studies of in-situ bioremediation system design. Further, a single-objective optimization problem is solved by a coupled Extreme Learning Machine (ELM)-Particle Swarm Optimization (PSO) technique to achieve the minimum cost for the in-situ bioremediation system design. The results indicate that ELM is a faster and more accurate proxy simulator than ANN and SVM. The total cost obtained by the ELM-PSO approach is held to a minimum while successfully satisfying all the regulatory constraints of the contaminated site.

Efficient engineering of chromosomal ribosome binding site libraries in mismatch repair proficient Escherichia coli.

PubMed

Oesterle, Sabine; Gerngross, Daniel; Schmitt, Steven; Roberts, Tania Michelle; Panke, Sven

2017-09-26

Multiplexed gene expression optimization via modulation of gene translation efficiency through ribosome binding site (RBS) engineering is a valuable approach for optimizing artificial properties in bacteria, ranging from genetic circuits to production pathways. Established algorithms design smart RBS-libraries based on a single partially-degenerate sequence that efficiently samples the entire space of translation initiation rates. However, the sequence space that is accessible when integrating the library by CRISPR/Cas9-based genome editing is severely restricted by DNA mismatch repair (MMR) systems. MMR efficiency depends on the type and length of the mismatch and thus effectively removes potential library members from the pool. Rather than working in MMR-deficient strains, which accumulate off-target mutations, or depending on temporary MMR inactivation, which requires additional steps, we eliminate this limitation by developing a pre-selection rule of genome-library-optimized-sequences (GLOS) that enables introducing large functional diversity into MMR-proficient strains with sequences that are no longer subject to MMR-processing. We implement several GLOS-libraries in Escherichia coli and show that GLOS-libraries indeed retain diversity during genome editing and that such libraries can be used in complex genome editing operations such as concomitant deletions. We argue that this approach allows for stable and efficient fine tuning of chromosomal functions with minimal effort.

Optimized mixed Markov models for motif identification

PubMed Central

Huang, Weichun; Umbach, David M; Ohler, Uwe; Li, Leping

2006-01-01

Background Identifying functional elements, such as transcriptional factor binding sites, is a fundamental step in reconstructing gene regulatory networks and remains a challenging issue, largely due to limited availability of training samples. Results We introduce a novel and flexible model, the Optimized Mixture Markov model (OMiMa), and related methods to allow adjustment of model complexity for different motifs. In comparison with other leading methods, OMiMa can incorporate more than the NNSplice's pairwise dependencies; OMiMa avoids model over-fitting better than the Permuted Variable Length Markov Model (PVLMM); and OMiMa requires smaller training samples than the Maximum Entropy Model (MEM). Testing on both simulated and actual data (regulatory cis-elements and splice sites), we found OMiMa's performance superior to the other leading methods in terms of prediction accuracy, required size of training data or computational time. Our OMiMa system, to our knowledge, is the only motif finding tool that incorporates automatic selection of the best model. OMiMa is freely available at [1]. Conclusion Our optimized mixture of Markov models represents an alternative to the existing methods for modeling dependent structures within a biological motif. Our model is conceptually simple and effective, and can improve prediction accuracy and/or computational speed over other leading methods. PMID:16749929

Melibiose permease and alpha-galactosidase of Escherichia coli: Identification by selective labeling using a T7 RNA polymerase/promoter expression system

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

Pourcher, T.; Bassilana, M.; Sarkar, H.K.

1990-01-23

Identification and selective labeling of the melibiose permease and alpha-galactosidase in Escherichia coli, which are encoded by the melB and melA genes, respectively, have been accomplished by selectively labeling the two gene products with a T7 RNA polymerase expression system. Following generation of a novel EcoRI restriction site in the intergenic sequence between the two genes of the mel operon by oligonucleotide-directed, site-specific mutagenesis, melA and melB were separately inserted into plasmid pT7-6 of the T7 expression system. Expression of melB was markedly enhanced by placing a strong, synthetic ribosome binding site at an optimal distance upstream from the initiationmore » codon of melB. Expression of cloned gene products was characterized functionally and by performing autoradiographic analysis on total cell, inner membrane, and cytoplasmic proteins from cells pulse labeled with (35S)methionine in the presence of rifampicin and resolved by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The results first confirm that alpha-galactosidase is a cytoplasmic protein with an Mr of 50K; in contrast, the membrane-bound melibiose permease is identified as a protein with an apparent Mr of 39K, a value significantly higher than that of 30K previously suggested.« less

Directed evolution of glutathione transferases towards a selective glutathione-binding site and improved oxidative stability.

PubMed

Axarli, Irine; Muleta, Abdi W; Chronopoulou, Evangelia G; Papageorgiou, Anastassios C; Labrou, Nikolaos E

2017-01-01

Glutathione transferases (GSTs) are a family of detoxification enzymes that catalyze the conjugation of glutathione (GSH) to electrophilic compounds. A library of alpha class GSTs was constructed by DNA shuffling using the DNA encoding the human glutathione transferase A1-1 (hGSTA1-1) and the rat glutathione transferase A1-1 (rGSTA1-1). Activity screening of the library allowed the selection of a chimeric enzyme variant (GSTD4) that displayed high affinity towards GSH and GSH-Sepharose affinity adsorbent, higher k cat /K m and improved thermal stability, compared to the parent enzymes. The crystal structures of the GSTD4 enzyme in free form and in complex with GSH were determined to 1.6Šand 2.3Šresolution, respectively. Analysis of the GSTD4 structure showed subtle conformational changes in the GSH-binding site and in electron-sharing network that may contribute to the increased GSH affinity. The shuffled variant GSTD4 was further optimized for improved oxidative stability employing site-saturation mutagenesis. The Cys112Ser mutation confers optimal oxidative stability and kinetic properties in the GSTD4 enzyme. DNA shuffling allowed the creation of a chimeric enzyme variant with improved properties, compared to the parent enzymes. X-ray crystallography shed light on how recombination of a specific segment from homologous GSTA1-1 together with point mutations gives rise to a new functionally competent enzyme with improved binding, catalytic properties and stability. Such an engineered GST would be useful in biotechnology as affinity tool in affinity chromatography as well as a biocatalytic matrix for the construction of biochips or enzyme biosensors. Copyright © 2016 Elsevier B.V. All rights reserved.

Best Longitudinal Adjustment of Satellite Trajectories for the Observation of Forest Fires (Blastoff): A Stochastic Programming Approach to Satellite System Design

NASA Astrophysics Data System (ADS)

Hoskins, Aaron B.

Forest fires cause a significant amount of damage and destruction each year. Optimally dispatching resources reduces the amount of damage a forest fire can cause. Models predict the fire spread to provide the data required to optimally dispatch resources. However, the models are only as accurate as the data used to build them. Satellites are one valuable tool in the collection of data for the forest fire models. Satellites provide data on the types of vegetation, the wind speed and direction, the soil moisture content, etc. The current operating paradigm is to passively collect data when possible. However, images from directly overhead provide better resolution and are easier to process. Maneuvering a constellation of satellites to fly directly over the forest fire provides higher quality data than is achieved with the current operating paradigm. Before launch, the location of the forest fire is unknown. Therefore, it is impossible to optimize the initial orbits for the satellites. Instead, the expected cost of maneuvering to observe the forest fire determines the optimal initial orbits. A two-stage stochastic programming approach is well suited for this class of problem where initial decisions are made with an uncertain future and then subsequent decisions are made once a scenario is realized. A repeat ground track orbit provides a non-maneuvering, natural solution providing a daily flyover of the forest fire. However, additional maneuvers provide a second daily flyover of the forest fire. The additional maneuvering comes at a significant cost in terms of additional fuel, but provides more data collection opportunities. After data are collected, ground stations receive the data for processing. Optimally selecting the ground station locations reduce the number of built ground stations and reduces the data fusion issues. However, the location of the forest fire alters the optimal ground station sites. A two-stage stochastic programming approach optimizes the selection of ground stations to maximize the expected amount of data downloaded from a satellite. The approaches of selecting initial orbits and ground station locations including uncertainty will provide a robust system to reduce the amount of damage caused by forest fires.

Managing the Public Sector Research and Development Portfolio Selection Process: A Case Study of Quantitative Selection and Optimization

DTIC Science & Technology

2016-09-01

PUBLIC SECTOR RESEARCH & DEVELOPMENT PORTFOLIO SELECTION PROCESS: A CASE STUDY OF QUANTITATIVE SELECTION AND OPTIMIZATION by Jason A. Schwartz...PUBLIC SECTOR RESEARCH & DEVELOPMENT PORTFOLIO SELECTION PROCESS: A CASE STUDY OF QUANTITATIVE SELECTION AND OPTIMIZATION 5. FUNDING NUMBERS 6...describing how public sector organizations can implement a research and development (R&D) portfolio optimization strategy to maximize the cost

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

Remote controlled capsules in human drug absorption (HDA) studies.

PubMed

Wilding, Ian R; Prior, David V

2003-01-01

The biopharmaceutical complexity of today's new drug candidates provides significant challenges for pharmaceutical scientists in terms of both candidate selection and optimizing subsequent development strategy. In addition, life cycle management of marketed drugs has become an important income stream for pharmaceutical companies, but the selection of least risk/highest benefit strategies is far from simple. The proactive adoption of human drug absorption (HDA) studies using remote controlled capsules offers the pharmaceutical scientist significant guidance for planning a route through the maze of product development. This review examines the position of HDA studies in drug development, using a variety of case histories and an insightful update on remote controlled capsules to achieve site-specific delivery.

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.

How to Optimize Your Web Site

ERIC Educational Resources Information Center

Dysart, Joe

2008-01-01

Given Google's growing market share--69% of all searches by the close of 2007--it's absolutely critical for any school on the Web to ensure its site is Google-friendly. A Google-optimized site ensures that students and parents can quickly find one's district on the Web even if they don't know the address. Plus, good search optimization simply…

Lower irritation microemulsion-based rotigotine gel: formulation optimization and in vitro and in vivo studies

PubMed Central

Wang, Zheng; Mu, Hong-Jie; Zhang, Xue-Mei; Ma, Peng-Kai; Lian, Sheng-Nan; Zhang, Feng-Pu; Chu, Sheng-Ying; Zhang, Wen-Wen; Wang, Ai-Ping; Wang, Wen-Yan; Sun, Kao-Xiang

2015-01-01

Background Rotigotine is a potent and selective D1, D2, and D3 dopaminergic receptor agonist. Due to an extensive first-pass effect, it has a very low oral bioavailability (approximately 0.5% in rats). Purpose The present investigation aimed to develop a microemulsion-based hydrogel for transdermal rotigotine delivery with lower application site reactions. Methods Pseudoternary phase diagrams were constructed to determine the region of oil in water (o/w)-type microemulsion. Central composite design was used to support the pseudoternary phase diagrams and to select homogeneous and stable microemulsions with an optimal amount of rotigotine permeation within 24 hours. In vitro skin permeation experiments were performed, using Franz diffusion cells, to compare rotigotine-loaded microemulsions with rotigotine solutions in oil. The optimized formulation was used to prepare a microemulsion-based hydrogel, which was subjected to bioavailability and skin irritancy studies. Results The selected formulations of rotigotine-loaded microemulsions had enhanced flux and permeation coefficients compared with rotigotine in oil. The optimum microemulsion contained 68% water, 6.8% Labrafil®, 13.44% Cremophor® RH40, 6.72% Labrasol®, and 5.04% Transcutol® HP; the drug-loading rate was 2%. To form a microemulsion gel, 1% Carbomer 1342 was added to the microemulsion. The bioavailability of the rotigotine-loaded microemulsion gel was 105.76%±20.52% with respect to the marketed rotigotine patch (Neupro®). The microemulsion gel irritated the skin less than Neupro. Conclusion A rotigotine microemulsion-based hydrogel was successfully developed, and an optimal formulation for drug delivery was identified. This product could improve patient compliance and have broad marketability. PMID:25609965

An integrated multi criteria approach for landfill siting in a conflicting environmental, economical and socio-cultural area.

PubMed

Eskandari, Mahnaz; Homaee, Mehdi; Mahmodi, Shahla

2012-08-01

Landfill site selection is a complicated multi criteria land use planning that should convince all related stakeholders with different insights. This paper addresses an integrating approach for landfill siting based on conflicting opinions among environmental, economical and socio-cultural expertise. In order to gain optimized siting decision, the issue was investigated in different viewpoints. At first step based on opinion sampling and questionnaire results of 35 experts familiar with local situations, the national environmental legislations and international practices, 13 constraints and 15 factors were built in hierarchical structure. Factors divided into three environmental, economical and socio-cultural groups. In the next step, the GIS-database was developed based on the designated criteria. In the third stage, the criteria standardization and criteria weighting were accomplished. The relative importance weights of criteria and subcriteria were estimated, respectively, using analytical hierarchy process and rank ordering methods based on different experts opinions. Thereafter, by using simple additive weighting method, the suitability maps for landfill siting in Marvdasht, Iran, was evaluated in environmental, economical and socio-cultural visions. The importance of each group of criteria in its own vision was assigned to be higher than two other groups. In the fourth stage, the final suitability map was obtained after crossing three resulted maps in different visions and reported in five suitability classes for landfill construction. This map indicated that almost 1224 ha of the study area can be considered as best suitable class for landfill siting considering all visions. In the last stage, a comprehensive field visit was performed to verify the selected site obtained from the proposed model. This field inspection has confirmed the proposed integrating approach for the landfill siting. Copyright © 2012 Elsevier Ltd. All rights reserved.

Conformational exchange of aromatic side chains characterized by L-optimized TROSY-selected ¹³C CPMG relaxation dispersion.

PubMed

Weininger, Ulrich; Respondek, Michal; Akke, Mikael

2012-09-01

Protein dynamics on the millisecond time scale commonly reflect conformational transitions between distinct functional states. NMR relaxation dispersion experiments have provided important insights into biologically relevant dynamics with site-specific resolution, primarily targeting the protein backbone and methyl-bearing side chains. Aromatic side chains represent attractive probes of protein dynamics because they are over-represented in protein binding interfaces, play critical roles in enzyme catalysis, and form an important part of the core. Here we introduce a method to characterize millisecond conformational exchange of aromatic side chains in selectively (13)C labeled proteins by means of longitudinal- and transverse-relaxation optimized CPMG relaxation dispersion. By monitoring (13)C relaxation in a spin-state selective manner, significant sensitivity enhancement can be achieved in terms of both signal intensity and the relative exchange contribution to transverse relaxation. Further signal enhancement results from optimizing the longitudinal relaxation recovery of the covalently attached (1)H spins. We validated the L-TROSY-CPMG experiment by measuring fast folding-unfolding kinetics of the small protein CspB under native conditions. The determined unfolding rate matches perfectly with previous results from stopped-flow kinetics. The CPMG-derived chemical shift differences between the folded and unfolded states are in excellent agreement with those obtained by urea-dependent chemical shift analysis. The present method enables characterization of conformational exchange involving aromatic side chains and should serve as a valuable complement to methods developed for other types of protein side chains.

Voxel-based dose prediction with multi-patient atlas selection for automated radiotherapy treatment planning

NASA Astrophysics Data System (ADS)

McIntosh, Chris; Purdie, Thomas G.

2017-01-01

Automating the radiotherapy treatment planning process is a technically challenging problem. The majority of automated approaches have focused on customizing and inferring dose volume objectives to be used in plan optimization. In this work we outline a multi-patient atlas-based dose prediction approach that learns to predict the dose-per-voxel for a novel patient directly from the computed tomography planning scan without the requirement of specifying any objectives. Our method learns to automatically select the most effective atlases for a novel patient, and then map the dose from those atlases onto the novel patient. We extend our previous work to include a conditional random field for the optimization of a joint distribution prior that matches the complementary goals of an accurately spatially distributed dose distribution while still adhering to the desired dose volume histograms. The resulting distribution can then be used for inverse-planning with a new spatial dose objective, or to create typical dose volume objectives for the canonical optimization pipeline. We investigated six treatment sites (633 patients for training and 113 patients for testing) and evaluated the mean absolute difference in all DVHs for the clinical and predicted dose distribution. The results on average are favorable in comparison to our previous approach (1.91 versus 2.57). Comparing our method with and without atlas-selection further validates that atlas-selection improved dose prediction on average in whole breast (0.64 versus 1.59), prostate (2.13 versus 4.07), and rectum (1.46 versus 3.29) while it is less important in breast cavity (0.79 versus 0.92) and lung (1.33 versus 1.27) for which there is high conformity and minimal dose shaping. In CNS brain, atlas-selection has the potential to be impactful (3.65 versus 5.09), but selecting the ideal atlas is the most challenging.

An ACOR-Based Multi-Objective WSN Deployment Example for Lunar Surveying.

PubMed

López-Matencio, Pablo

2016-02-06

Wireless sensor networks (WSNs) can gather in situ real data measurements and work unattended for long periods, even in remote, rough places. A critical aspect of WSN design is node placement, as this determines sensing capacities, network connectivity, network lifetime and, in short, the whole operational capabilities of the WSN. This paper proposes and studies a new node placement algorithm that focus on these aspects. As a motivating example, we consider a network designed to describe the distribution of helium-3 (³He), a potential enabling element for fusion reactors, on the Moon. ³He is abundant on the Moon's surface, and knowledge of its distribution is essential for future harvesting purposes. Previous data are inconclusive, and there is general agreement that on-site measurements, obtained over a long time period, are necessary to better understand the mechanisms involved in the distribution of this element on the Moon. Although a mission of this type is extremely complex, it allows us to illustrate the main challenges involved in a multi-objective WSN placement problem, i.e., selection of optimal observation sites and maximization of the lifetime of the network. To tackle optimization, we use a recent adaptation of the ant colony optimization (ACOR) metaheuristic, extended to continuous domains. Solutions are provided in the form of a Pareto frontier that shows the optimal equilibria. Moreover, we compared our scheme with the four-directional placement (FDP) heuristic, which was outperformed in all cases.

Optimization of the in silico designed Kemp eliminase KE70 by computational design and directed evolution

PubMed Central

Khersonsky, Olga; Röthlisberger, Daniela; Wollacott, Andrew M.; Murphy, Paul; Dym, Orly; Albeck, Shira; Kiss, Gert; Houk, K. N.; Baker, David; Tawfik, Dan S.

2013-01-01

Although de novo computational enzyme design has been shown to be feasible, the field is still in its infancy: the kinetic parameters of designed enzymes are still orders of magnitude lower than those of naturally occurring ones. Nonetheless, designed enzymes can be improved by directed evolution, as recently exemplified for the designed Kemp eliminase KE07. Random mutagenesis and screening resulted in variants with >200-fold higher catalytic efficiency, and provided insights about features missing in the designed enzyme. Here we describe the optimization of KE70, another designed Kemp eliminase. Amino acid substitutions predicted to improve catalysis in design calculations involving extensive backbone sampling were individually tested. Those proven beneficial were combinatorially incorporated into the originally designed KE70 along with random mutations, and the resulting libraries were screened for improved eliminase activity. Nine rounds of mutation and selection resulted in >400-fold improvement in the catalytic efficiency of the original KE70 design, reflected in both higher kcat and lower KM values, with the best variants exhibiting kcat/KM values of >5x104 s−1M−1. The optimized KE70 variants were characterized structurally and biochemically providing insights into the origins of the improvements in catalysis. Three primary contributions were identified: first, the reshaping of the active site cavity to achieve tighter substrate binding; second, the fine-tuning of the electrostatics around the catalytic His-Asp dyad; and third, stabilization of the active-site dyad in a conformation optimal for catalysis. PMID:21277311

Spatio-Temporal Process Variability in Watershed Scale Wetland Restoration Planning

NASA Astrophysics Data System (ADS)

Evenson, G. R.

2012-12-01

Watershed scale restoration decision making processes are increasingly informed by quantitative methodologies providing site-specific restoration recommendations - sometimes referred to as "systematic planning." The more advanced of these methodologies are characterized by a coupling of search algorithms and ecological models to discover restoration plans that optimize environmental outcomes. Yet while these methods have exhibited clear utility as decision support toolsets, they may be critiqued for flawed evaluations of spatio-temporally variable processes fundamental to watershed scale restoration. Hydrologic and non-hydrologic mediated process connectivity along with post-restoration habitat dynamics, for example, are commonly ignored yet known to appreciably affect restoration outcomes. This talk will present a methodology to evaluate such spatio-temporally complex processes in the production of watershed scale wetland restoration plans. Using the Tuscarawas Watershed in Eastern Ohio as a case study, a genetic algorithm will be coupled with the Soil and Water Assessment Tool (SWAT) to reveal optimal wetland restoration plans as measured by their capacity to maximize nutrient reductions. Then, a so-called "graphical" representation of the optimization problem will be implemented in-parallel to promote hydrologic and non-hydrologic mediated connectivity amongst existing wetlands and sites selected for restoration. Further, various search algorithm mechanisms will be discussed as a means of accounting for temporal complexities such as post-restoration habitat dynamics. Finally, generalized patterns of restoration plan optimality will be discussed as an alternative and possibly superior decision support toolset given the complexity and stochastic nature of spatio-temporal process variability.

Contacts between the factor TUF and RPG sequences.

PubMed

Vignais, M L; Huet, J; Buhler, J M; Sentenac, A

1990-08-25

The yeast TUF factor binds specifically to RPG-like sequences involved in multiple functions at enhancers, silencers, and telomeres. We have characterized the interaction of TUF with its optimal binding sequence, rpg-1 (1-ACACCCATACATTT-14), using a gel DNA-binding assay in combination with methylation protection and mutagenesis experiments. As many as 10 base pairs appear to be engaged in factor binding. Analysis of a collection of 30 different RPG mutants demonstrated the importance of 8 base pairs at position 2, 3, 4, 5, 6, 7, 10, and 12 and the critical role of the central GC pair at position 5. Methylation protection data on four different natural sites confirmed a close contact at positions 4, 5, 6, and 10 and suggested additional contacts at base pairs 8, 12, and 13. The derived consensus sequence was RCAAYCCRYNCAYY. A quantitative band shift analysis was used to determine the equilibrium dissociation constant for the complex of TUF and its optimal binding site rpg-1. The specific dissociation constant (K8) was found to be 1.3 x 10(-11) M. The comparison of the K8 value with the dissociation constant obtained for nonspecific DNA sites (Kn8 = 8.7 x 10(-6) M) shows the high binding selectivity of TUF for its specific RPG target.

Programmed Evolution for Optimization of Orthogonal Metabolic Output in Bacteria

PubMed Central

Eckdahl, Todd T.; Campbell, A. Malcolm; Heyer, Laurie J.; Poet, Jeffrey L.; Blauch, David N.; Snyder, Nicole L.; Atchley, Dustin T.; Baker, Erich J.; Brown, Micah; Brunner, Elizabeth C.; Callen, Sean A.; Campbell, Jesse S.; Carr, Caleb J.; Carr, David R.; Chadinha, Spencer A.; Chester, Grace I.; Chester, Josh; Clarkson, Ben R.; Cochran, Kelly E.; Doherty, Shannon E.; Doyle, Catherine; Dwyer, Sarah; Edlin, Linnea M.; Evans, Rebecca A.; Fluharty, Taylor; Frederick, Janna; Galeota-Sprung, Jonah; Gammon, Betsy L.; Grieshaber, Brandon; Gronniger, Jessica; Gutteridge, Katelyn; Henningsen, Joel; Isom, Bradley; Itell, Hannah L.; Keffeler, Erica C.; Lantz, Andrew J.; Lim, Jonathan N.; McGuire, Erin P.; Moore, Alexander K.; Morton, Jerrad; Nakano, Meredith; Pearson, Sara A.; Perkins, Virginia; Parrish, Phoebe; Pierson, Claire E.; Polpityaarachchige, Sachith; Quaney, Michael J.; Slattery, Abagael; Smith, Kathryn E.; Spell, Jackson; Spencer, Morgan; Taye, Telavive; Trueblood, Kamay; Vrana, Caroline J.; Whitesides, E. Tucker

2015-01-01

Current use of microbes for metabolic engineering suffers from loss of metabolic output due to natural selection. Rather than combat the evolution of bacterial populations, we chose to embrace what makes biological engineering unique among engineering fields – evolving materials. We harnessed bacteria to compute solutions to the biological problem of metabolic pathway optimization. Our approach is called Programmed Evolution to capture two concepts. First, a population of cells is programmed with DNA code to enable it to compute solutions to a chosen optimization problem. As analog computers, bacteria process known and unknown inputs and direct the output of their biochemical hardware. Second, the system employs the evolution of bacteria toward an optimal metabolic solution by imposing fitness defined by metabolic output. The current study is a proof-of-concept for Programmed Evolution applied to the optimization of a metabolic pathway for the conversion of caffeine to theophylline in E. coli. Introduced genotype variations included strength of the promoter and ribosome binding site, plasmid copy number, and chaperone proteins. We constructed 24 strains using all combinations of the genetic variables. We used a theophylline riboswitch and a tetracycline resistance gene to link theophylline production to fitness. After subjecting the mixed population to selection, we measured a change in the distribution of genotypes in the population and an increased conversion of caffeine to theophylline among the most fit strains, demonstrating Programmed Evolution. Programmed Evolution inverts the standard paradigm in metabolic engineering by harnessing evolution instead of fighting it. Our modular system enables researchers to program bacteria and use evolution to determine the combination of genetic control elements that optimizes catabolic or anabolic output and to maintain it in a population of cells. Programmed Evolution could be used for applications in energy, pharmaceuticals, chemical commodities, biomining, and bioremediation. PMID:25714374

Programmed evolution for optimization of orthogonal metabolic output in bacteria.

PubMed

Eckdahl, Todd T; Campbell, A Malcolm; Heyer, Laurie J; Poet, Jeffrey L; Blauch, David N; Snyder, Nicole L; Atchley, Dustin T; Baker, Erich J; Brown, Micah; Brunner, Elizabeth C; Callen, Sean A; Campbell, Jesse S; Carr, Caleb J; Carr, David R; Chadinha, Spencer A; Chester, Grace I; Chester, Josh; Clarkson, Ben R; Cochran, Kelly E; Doherty, Shannon E; Doyle, Catherine; Dwyer, Sarah; Edlin, Linnea M; Evans, Rebecca A; Fluharty, Taylor; Frederick, Janna; Galeota-Sprung, Jonah; Gammon, Betsy L; Grieshaber, Brandon; Gronniger, Jessica; Gutteridge, Katelyn; Henningsen, Joel; Isom, Bradley; Itell, Hannah L; Keffeler, Erica C; Lantz, Andrew J; Lim, Jonathan N; McGuire, Erin P; Moore, Alexander K; Morton, Jerrad; Nakano, Meredith; Pearson, Sara A; Perkins, Virginia; Parrish, Phoebe; Pierson, Claire E; Polpityaarachchige, Sachith; Quaney, Michael J; Slattery, Abagael; Smith, Kathryn E; Spell, Jackson; Spencer, Morgan; Taye, Telavive; Trueblood, Kamay; Vrana, Caroline J; Whitesides, E Tucker

2015-01-01

Current use of microbes for metabolic engineering suffers from loss of metabolic output due to natural selection. Rather than combat the evolution of bacterial populations, we chose to embrace what makes biological engineering unique among engineering fields - evolving materials. We harnessed bacteria to compute solutions to the biological problem of metabolic pathway optimization. Our approach is called Programmed Evolution to capture two concepts. First, a population of cells is programmed with DNA code to enable it to compute solutions to a chosen optimization problem. As analog computers, bacteria process known and unknown inputs and direct the output of their biochemical hardware. Second, the system employs the evolution of bacteria toward an optimal metabolic solution by imposing fitness defined by metabolic output. The current study is a proof-of-concept for Programmed Evolution applied to the optimization of a metabolic pathway for the conversion of caffeine to theophylline in E. coli. Introduced genotype variations included strength of the promoter and ribosome binding site, plasmid copy number, and chaperone proteins. We constructed 24 strains using all combinations of the genetic variables. We used a theophylline riboswitch and a tetracycline resistance gene to link theophylline production to fitness. After subjecting the mixed population to selection, we measured a change in the distribution of genotypes in the population and an increased conversion of caffeine to theophylline among the most fit strains, demonstrating Programmed Evolution. Programmed Evolution inverts the standard paradigm in metabolic engineering by harnessing evolution instead of fighting it. Our modular system enables researchers to program bacteria and use evolution to determine the combination of genetic control elements that optimizes catabolic or anabolic output and to maintain it in a population of cells. Programmed Evolution could be used for applications in energy, pharmaceuticals, chemical commodities, biomining, and bioremediation.

Quantifying Construction Site Sediment Discharge Risk and Treatment Potential

NASA Astrophysics Data System (ADS)

Ferrell, L.; Beighley, R. E.

2006-12-01

Dealing with soil erosion and sediment transport can be a significant challenge during the construction process due to the potentially large spatial and temporal extent and conditions of bare soils. Best Management Practices (BMP) are commonly used to eliminate or reduce offsite discharge of sediment. However, few efforts have investigated the time varying risk of sediment discharge from construction sites, which often have dynamic soil conditions and the potential for less than optimal BMP installations. The goal of this research is to improve the design, implementation and effectiveness of sediment and erosion control at construction sites using site specific, temporal distributions of sediment discharge risk. Sediment risk is determined from individual factors leading to sediment expert, such as rainfall frequency, the adequacy of BMP installations, and the extent and duration of bare soil conditions. This research specifically focuses on quantifying: (a) the effectiveness of temporary sediment and control erosion control BMPs in preventing, containing, and/or treating construction site sediment discharge at varying levels of "proper" installation, and (b) sediment discharge potential from construction sites during different phases of construction, (ex., disturbed earth operations). BMPs are evaluated at selected construction sites in southern California and at the Soil Erosion Research Laboratory (SERL) in the Civil and Environmental Engineering department at San Diego State University. SERL experiments are performed on a 3-m by 10-m tilting soil bed with soil depths up to 1 meter, slopes ranging from 0 to 50 percent, and rainfall rates up to 150 mm/hr (6 in/hr). BMP performance is assessed based on experiments where BMPs are installed per manufacture specifications, potential less than optimal installations, and no treatment conditions. Soil conditions are also varied to represent site conditions during different phases of construction (i.e., loose lifts, stock piles, temporary roads, finished grade, others). Preliminary site monitoring, experimental results, and a conceptual model for estimating the time depend risk of sediment discharge over the duration of a construction project are presented.

Enhanced MALDI-TOF MS Analysis of Phosphopeptides Using an Optimized DHAP/DAHC Matrix

PubMed Central

Hou, Junjie; Xie, Zhensheng; Xue, Peng; Cui, Ziyou; Chen, Xiulan; Li, Jing; Cai, Tanxi; Wu, Peng; Yang, Fuquan

2010-01-01

Selecting an appropriate matrix solution is one of the most effective means of increasing the ionization efficiency of phosphopeptides in matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). In this study, we systematically assessed matrix combinations of 2, 6-dihydroxyacetophenone (DHAP) and diammonium hydrogen citrate (DAHC), and demonstrated that the low ratio DHAP/DAHC matrix was more effective in enhancing the ionization of phosphopeptides. Low femtomole level of phosphopeptides from the tryptic digests of α-casein and β-casein was readily detected by MALDI-TOF-MS in both positive and negative ion mode without desalination or phosphopeptide enrichment. Compared with the DHB/PA matrix, the optimized DHAP/DAHC matrix yielded superior sample homogeneity and higher phosphopeptide measurement sensitivity, particularly when multiple phosphorylated peptides were assessed. Finally, the DHAP/DAHC matrix was applied to identify phosphorylation sites from α-casein and β-casein and to characterize two phosphorylation sites from the human histone H1 treated with Cyclin-Dependent Kinase-1 (CDK1) by MALDI-TOF/TOF MS. PMID:20339515

Time optimized path-choice in the termite hunting ant Megaponera analis.

PubMed

Frank, Erik T; Hönle, Philipp O; Linsenmair, K Eduard

2018-05-10

Trail network systems among ants have received a lot of scientific attention due to their various applications in problem solving of networks. Recent studies have shown that ants select the fastest available path when facing different velocities on different substrates, rather than the shortest distance. The progress of decision-making by these ants is determined by pheromone-based maintenance of paths, which is a collective decision. However, path optimization through individual decision-making remains mostly unexplored. Here we present the first study of time-optimized path selection via individual decision-making by scout ants. Megaponera analis scouts search for termite foraging sites and lead highly organized raid columns to them. The path of the scout determines the path of the column. Through installation of artificial roads around M. analis nests we were able to influence the pathway choice of the raids. After road installation 59% of all recorded raids took place completely or partly on the road, instead of the direct, i.e. distance-optimized, path through grass from the nest to the termites. The raid velocity on the road was more than double the grass velocity, the detour thus saved 34.77±23.01% of the travel time compared to a hypothetical direct path. The pathway choice of the ants was similar to a mathematical model of least time allowing us to hypothesize the underlying mechanisms regulating the behavior. Our results highlight the importance of individual decision-making in the foraging behavior of ants and show a new procedure of pathway optimization. © 2018. Published by The Company of Biologists Ltd.

SDM-Assist software to design site-directed mutagenesis primers introducing “silent” restriction sites

PubMed Central

2013-01-01

Background Over the past decades site-directed mutagenesis (SDM) has become an indispensable tool for biological structure-function studies. In principle, SDM uses modified primer pairs in a PCR reaction to introduce a mutation in a cDNA insert. DpnI digestion of the reaction mixture is used to eliminate template copies before amplification in E. coli; however, this process is inefficient resulting in un-mutated clones which can only be distinguished from mutant clones by sequencing. Results We have developed a program – ‘SDM-Assist’ which creates SDM primers adding a specific identifier: through additional silent mutations a restriction site is included or a previous one removed which allows for highly efficient identification of ‘mutated clones’ by a simple restriction digest. Conclusions The direct identification of SDM clones will save time and money for researchers. SDM-Assist also scores the primers based on factors such as Tm, GC content and secondary structure allowing for simplified selection of optimal primer pairs. PMID:23522286

Simulating changes to emergency care resources to compare system effectiveness.

PubMed

Branas, Charles C; Wolff, Catherine S; Williams, Justin; Margolis, Gregg; Carr, Brendan G

2013-08-01

To apply systems optimization methods to simulate and compare the most effective locations for emergency care resources as measured by access to care. This study was an optimization analysis of the locations of trauma centers (TCs), helicopter depots (HDs), and severely injured patients in need of time-critical care in select US states. Access was defined as the percentage of injured patients who could reach a level I/II TC within 45 or 60 minutes. Optimal locations were determined by a search algorithm that considered all candidate sites within a set of existing hospitals and airports in finding the best solutions that maximized access. Across a dozen states, existing access to TCs within 60 minutes ranged from 31.1% to 95.6%, with a mean of 71.5%. Access increased from 0.8% to 35.0% after optimal addition of one or two TCs. Access increased from 1.0% to 15.3% after optimal addition of one or two HDs. Relocation of TCs and HDs (optimal removal followed by optimal addition) produced similar results. Optimal changes to TCs produced greater increases in access to care than optimal changes to HDs although these results varied across states. Systems optimization methods can be used to compare the impacts of different resource configurations and their possible effects on access to care. These methods to determine optimal resource allocation can be applied to many domains, including comparative effectiveness and patient-centered outcomes research. Copyright © 2013 Elsevier Inc. All rights reserved.

Method of interplanetary trajectory optimization for the spacecraft with low thrust and swing-bys

NASA Astrophysics Data System (ADS)

Konstantinov, M. S.; Thein, M.

2017-07-01

The method developed to avoid the complexity of solving the multipoint boundary value problem while optimizing interplanetary trajectories of the spacecraft with electric propulsion and a sequence of swing-bys is presented in the paper. This method is based on the use of the preliminary problem solutions for the impulsive trajectories. The preliminary problem analyzed at the first stage of the study is formulated so that the analysis and optimization of a particular flight path is considered as the unconstrained minimum in the space of the selectable parameters. The existing methods can effectively solve this problem and make it possible to identify rational flight paths (the sequence of swing-bys) to receive the initial approximation for the main characteristics of the flight path (dates, values of the hyperbolic excess velocity, etc.). These characteristics can be used to optimize the trajectory of the spacecraft with electric propulsion. The special feature of the work is the introduction of the second (intermediate) stage of the research. At this stage some characteristics of the analyzed flight path (e.g. dates of swing-bys) are fixed and the problem is formulated so that the trajectory of the spacecraft with electric propulsion is optimized on selected sites of the flight path. The end-to-end optimization is carried out at the third (final) stage of the research. The distinctive feature of this stage is the analysis of the full set of optimal conditions for the considered flight path. The analysis of the characteristics of the optimal flight trajectories to Jupiter with Earth, Venus and Mars swing-bys for the spacecraft with electric propulsion are presented. The paper shows that the spacecraft weighing more than 7150 kg can be delivered into the vicinity of Jupiter along the trajectory with two Earth swing-bys by use of the space transportation system based on the "Angara A5" rocket launcher, the chemical upper stage "KVTK" and the electric propulsion system with input electrical power of 100 kW.

TargetM6A: Identifying N6-Methyladenosine Sites From RNA Sequences via Position-Specific Nucleotide Propensities and a Support Vector Machine.

PubMed

Li, Guang-Qing; Liu, Zi; Shen, Hong-Bin; Yu, Dong-Jun

2016-10-01

As one of the most ubiquitous post-transcriptional modifications of RNA, N 6 -methyladenosine ( [Formula: see text]) plays an essential role in many vital biological processes. The identification of [Formula: see text] sites in RNAs is significantly important for both basic biomedical research and practical drug development. In this study, we designed a computational-based method, called TargetM6A, to rapidly and accurately target [Formula: see text] sites solely from the primary RNA sequences. Two new features, i.e., position-specific nucleotide/dinucleotide propensities (PSNP/PSDP), are introduced and combined with the traditional nucleotide composition (NC) feature to formulate RNA sequences. The extracted features are further optimized to obtain a much more compact and discriminative feature subset by applying an incremental feature selection (IFS) procedure. Based on the optimized feature subset, we trained TargetM6A on the training dataset with a support vector machine (SVM) as the prediction engine. We compared the proposed TargetM6A method with existing methods for predicting [Formula: see text] sites by performing stringent jackknife tests and independent validation tests on benchmark datasets. The experimental results show that the proposed TargetM6A method outperformed the existing methods for predicting [Formula: see text] sites and remarkably improved the prediction performances, with MCC = 0.526 and AUC = 0.818. We also provided a user-friendly web server for TargetM6A, which is publicly accessible for academic use at http://csbio.njust.edu.cn/bioinf/TargetM6A.

Prediction of serine/threonine phosphorylation sites in bacteria proteins.

PubMed

Li, Zhengpeng; Wu, Ping; Zhao, Yuanyuan; Liu, Zexian; Zhao, Wei

2015-01-01

As a critical post-translational modification, phosphorylation plays important roles in regulating various biological processes, while recent studies suggest that phosphorylation in bacteria is also critical for functional signaling transduction. Since identification of phosphorylation substrates and sites is fundamental for understanding the phosphorylation mediated regulatory mechanism, a number of studies have been contributed to this area. Since experimental identification of phosphorylation sites is time-consuming and labor-intensive, computational predictions attract much attention for its convenience to provide helpful information. However, although there are a large number of computational studies in eukaryotes, predictions in bacteria are still rare. In this study, we present a new predictor of cPhosBac to predict phosphorylation serine/threonine in bacteria proteins. The predictor is developed with CKSAAP algorithm, which was combined with motif length selection to optimize the prediction, which achieves promising performance. The online service of cPhosBac is available at: http://netalign.ustc.edu.cn/cphosbac/ .

Optimization of ultrahigh-speed multiplex PCR for forensic analysis.

PubMed

Gibson-Daw, Georgiana; Crenshaw, Karin; McCord, Bruce

2018-01-01

In this paper, we demonstrate the design and optimization of an ultrafast PCR amplification technique, used with a seven-locus multiplex that is compatible with conventional capillary electrophoresis systems as well as newer microfluidic chip devices. The procedure involves the use of a high-speed polymerase and a rapid cycling protocol to permit multiplex PCR amplification of forensic short tandem repeat loci in 6.5 min. We describe the selection and optimization of master mix reagents such as enzyme, buffer, MgCl 2 , and dNTPs, as well as primer ratios, total volume, and cycle conditions, in order to get the best profile in the shortest time possible. Sensitivity and reproducibility studies are also described. The amplification process utilizes a small high-speed thermocycler and compact laptop, making it portable and potentially useful for rapid, inexpensive on-site genotyping. The seven loci of the multiplex were taken from conventional STR genotyping kits and selected for their size and lack of overlap. Analysis was performed using conventional capillary electrophoresis and microfluidics with fluorescent detection. Overall, this technique provides a more rapid method for rapid sample screening of suspects and victims. Graphical abstract Rapid amplification of forensic DNA using high speed thermal cycling followed by capillary or microfluidic electrophoresis.

Identification of two integration sites in favor of transgene expression in Trichoderma reesei.

PubMed

Qin, Lina; Jiang, Xianzhang; Dong, Zhiyang; Huang, Jianzhong; Chen, Xiuzhen

2018-01-01

The ascomycete fungus Trichoderma reesei was widely used as a biotechnological workhorse for production of cellulases and recombinant proteins due to its large capacity of protein secretion. Transgenesis by random integration of a gene of interest (GOI) into the genome of T. reesei can generate series of strains that express different levels of the indicated transgene. The insertion site of the GOI plays an important role in the ultimate production of the targeted proteins. However, so far no systematic studies have been made to identify transgene integration loci for optimal expression of the GOI in T. reesei . Currently, only the locus of exocellobiohydrolases I encoding gene ( cbh1) is widely used as a promising integration site to lead to high expression level of the GOI. No additional sites associated with efficient gene expression have been characterized. To search for gene integration sites that benefit for the secreted expression of GOI, the food-and-mouth disease virus 2A protein was applied for co-expression of an Aspergillus niger lipA gene and Discosoma sp. DsRed1 gene in T. reesei, by random integration of the expression cassette into the genome. We demonstrated that the fluorescent intensity of RFP (red fluorescent protein) inside of the cell was well correlated with the secreted lipase yields, based on which, we successfully developed a high-throughput screening method to screen strains with relatively higher secreted expression of the GOI (in this study, lipase). The copy number and the insertion sites of the transgene were investigated among the selected highly expressed strains. Eventually, in addition to cbh1 gene locus, two other genome insertion loci that efficiently facilitate gene expression in T. reesei were identified. We have successfully developed a high-throughput screening method to screen strains with optimal expression of the indicated secreted proteins in T. reesei . Moreover, we identified two optimal genome loci for transgene expression, which could provide new approach to modulate gene expression levels while retaining the indicated promoter and culture conditions.

Transferability of optimally-selected climate models in the quantification of climate change impacts on hydrology

NASA Astrophysics Data System (ADS)

Chen, Jie; Brissette, François P.; Lucas-Picher, Philippe

2016-11-01

Given the ever increasing number of climate change simulations being carried out, it has become impractical to use all of them to cover the uncertainty of climate change impacts. Various methods have been proposed to optimally select subsets of a large ensemble of climate simulations for impact studies. However, the behaviour of optimally-selected subsets of climate simulations for climate change impacts is unknown, since the transfer process from climate projections to the impact study world is usually highly non-linear. Consequently, this study investigates the transferability of optimally-selected subsets of climate simulations in the case of hydrological impacts. Two different methods were used for the optimal selection of subsets of climate scenarios, and both were found to be capable of adequately representing the spread of selected climate model variables contained in the original large ensemble. However, in both cases, the optimal subsets had limited transferability to hydrological impacts. To capture a similar variability in the impact model world, many more simulations have to be used than those that are needed to simply cover variability from the climate model variables' perspective. Overall, both optimal subset selection methods were better than random selection when small subsets were selected from a large ensemble for impact studies. However, as the number of selected simulations increased, random selection often performed better than the two optimal methods. To ensure adequate uncertainty coverage, the results of this study imply that selecting as many climate change simulations as possible is the best avenue. Where this was not possible, the two optimal methods were found to perform adequately.

Percutaneous Epicardial Pacing using a Novel Insulated Multi-electrode Lead.

PubMed

Syed, Faisal F; DeSimone, Christopher V; Ebrille, Elisa; Gaba, Prakriti; Ladewig, Dorothy J; Mikell, Susan B; Suddendorf, Scott H; Gilles, Emily J; Danielsen, Andrew J; Lukášová, Markéta; Wolf, Jiří; Leinveber, Pavel; Novák, Miroslav; Stárek, Zdeněk; Kara, Tomas; Bruce, Charles J; Friedman, Paul A; Asirvatham, Samuel J

2015-08-01

Epicardial cardiac resynchronization therapy (CRT) permits unrestricted electrode positioning. However, this requires surgical placement of device leads and the risk of unwanted phrenic nerve stimulation. We hypothesized that shielded electrodes can capture myocardium without extracardiac stimulation. In 6 dog and 5 swine experiments, we used a percutaneous approach to access the epicardial surface of the heart, and deploy novel leads housing multiple electrodes with selective insulation. Bipolar pacing thresholds at prespecified sites were tested compare electrode threshold data both facing towards and away from the epicardial surface. In 151 paired electrode recordings (70 in 6 dogs; 81 in 5 swine), thresholds facing myocardium were lower than facing away (median [IQR] mA: dogs 0.9 [0.4-1.6] vs 4.6 [2.1 to >10], p<0.0001; swine 0.5 [0.2-1] vs 2.5 [0.5-6.8], p<0.0001). Myocardial capture was feasible without extracardiac stimulation at all tested sites, with mean ± SE threshold margin 3.6±0.7 mA at sites of high output extracardiac stimulation (p=0.004). Selective electrode insulation confers directional pacing to a multielectrode epicardial pacing lead. This device has the potential for a novel percutaneous epicardial resynchronization therapy that permits placement at an optimal pacing site, irrespective of the anatomy of the coronary veins or phrenic nerves.

Rhodobase, a meta-analytical tool for reconstructing gene regulatory networks in a model photosynthetic bacterium.

PubMed

Moskvin, Oleg V; Bolotin, Dmitry; Wang, Andrew; Ivanov, Pavel S; Gomelsky, Mark

2011-02-01

We present Rhodobase, a web-based meta-analytical tool for analysis of transcriptional regulation in a model anoxygenic photosynthetic bacterium, Rhodobacter sphaeroides. The gene association meta-analysis is based on the pooled data from 100 of R. sphaeroides whole-genome DNA microarrays. Gene-centric regulatory networks were visualized using the StarNet approach (Jupiter, D.C., VanBuren, V., 2008. A visual data mining tool that facilitates reconstruction of transcription regulatory networks. PLoS ONE 3, e1717) with several modifications. We developed a means to identify and visualize operons and superoperons. We designed a framework for the cross-genome search for transcription factor binding sites that takes into account high GC-content and oligonucleotide usage profile characteristic of the R. sphaeroides genome. To facilitate reconstruction of directional relationships between co-regulated genes, we screened upstream sequences (-400 to +20bp from start codons) of all genes for putative binding sites of bacterial transcription factors using a self-optimizing search method developed here. To test performance of the meta-analysis tools and transcription factor site predictions, we reconstructed selected nodes of the R. sphaeroides transcription factor-centric regulatory matrix. The test revealed regulatory relationships that correlate well with the experimentally derived data. The database of transcriptional profile correlations, the network visualization engine and the optimized search engine for transcription factor binding sites analysis are available at http://rhodobase.org. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Suitability of oyster restoration sites along the Louisiana coast: Examining site and stock × site interaction

USGS Publications Warehouse

Schwarting Miller, Lindsay; La Peyre, Jerome F.; LaPeyre, Megan K.

2017-01-01

Recognition of the global loss of subtidal oyster reefs has led to a rise in reef restoration efforts, including in the Gulf of Mexico. Created reef success depends entirely on selecting a location that supports long-term oyster growth and survival, including the recruitment and survival of on-reef oysters. Significant changes in estuarine salinity through management of freshwater inflows and through changed precipitation patterns may significantly impact the locations of optimal oyster restoration sites. These rapid shifts in conditions necessitate a need to better understand both impacts to on-reef oyster growth and population development, and variation in oyster stock performance. Oyster growth, mortality, condition, and disease prevalence were examined in three different stocks of oysters located in protected cages, as well as oyster recruitment and mortality on experimental reef units in three different locations representing a salinity gradient, along the Louisiana Gulf coast in 2011 and 2012. Over a 2-y period, the high-salinity site had highest oyster growth rate in protected cages but demonstrated the least likelihood for reef development based on on-reef oyster population failure, likely because of predation-related mortality (high recruitment and 100% mortality). In contrast, the midsalinity site with moderate oyster growth and on-reef recruitment and low mortality demonstrated a higher likelihood for reef development. The lowest salinity site exhibited extreme variability in all oyster responses between years because of extreme variation in environmental conditions during the study, indicating a low likelihood of long-term reef development. Whereas limited differences in stock performance between sites were found, the range of site environmental conditions tested was ultimately much lower than expected and may not have provided a wide enough range of conditions. In areas with limited, low recruitment, or rapidly changing environmental conditions, seeding with stocks selected for best growth and survival under expected future environmental conditions could better ensure reef development by using oyster populations best suited to the predicted conditions. With rapidly changing estuarine conditions from anthropogenic activities and climate change, siting of oyster reef restoration incorporating both oyster population dynamics and in situ biotic and abiotic interactions is critical in better directing site selection for reef restoration efforts.

Hydrologic Process-oriented Optimization of Electrical Resistivity Tomography

NASA Astrophysics Data System (ADS)

Hinnell, A.; Bechtold, M.; Ferre, T. A.; van der Kruk, J.

2010-12-01

Electrical resistivity tomography (ERT) is commonly used in hydrologic investigations. Advances in joint and coupled hydrogeophysical inversion have enhanced the quantitative use of ERT to construct and condition hydrologic models (i.e. identify hydrologic structure and estimate hydrologic parameters). However the selection of which electrical resistivity data to collect and use is often determined by a combination of data requirements for geophysical analysis, intuition on the part of the hydrogeophysicist and logistical constraints of the laboratory or field site. One of the advantages of coupled hydrogeophysical inversion is the direct link between the hydrologic model and the individual geophysical data used to condition the model. That is, there is no requirement to collect geophysical data suitable for independent geophysical inversion. The geophysical measurements collected can be optimized for estimation of hydrologic model parameters rather than to develop a geophysical model. Using a synthetic model of drip irrigation we evaluate the value of individual resistivity measurements to describe the soil hydraulic properties and then use this information to build a data set optimized for characterizing hydrologic processes. We then compare the information content in the optimized data set with the information content in a data set optimized using a Jacobian sensitivity analysis.

Holistic, model-based optimization of edge leveling as an enabler for lithographic focus control: application to a memory use case

NASA Astrophysics Data System (ADS)

Hasan, T.; Kang, Y.-S.; Kim, Y.-J.; Park, S.-J.; Jang, S.-Y.; Hu, K.-Y.; Koop, E. J.; Hinnen, P. C.; Voncken, M. M. A. J.

2016-03-01

Advancement of the next generation technology nodes and emerging memory devices demand tighter lithographic focus control. Although the leveling performance of the latest-generation scanners is state of the art, challenges remain at the wafer edge due to large process variations. There are several customer configurable leveling control options available in ASML scanners, some of which are application specific in their scope of leveling improvement. In this paper, we assess the usability of leveling non-correctable error models to identify yield limiting edge dies. We introduce a novel dies-inspec based holistic methodology for leveling optimization to guide tool users in selecting an optimal configuration of leveling options. Significant focus gain, and consequently yield gain, can be achieved with this integrated approach. The Samsung site in Hwaseong observed an improved edge focus performance in a production of a mid-end memory product layer running on an ASML NXT 1960 system. 50% improvement in focus and a 1.5%p gain in edge yield were measured with the optimized configurations.

Adsorption of lactic acid on chiral Pt surfaces—A density functional theory study

NASA Astrophysics Data System (ADS)

Franke, J.-H.; Kosov, D. S.

2013-02-01

The adsorption of the chiral molecule lactic acid on chiral Pt surfaces is studied by density functional theory calculations. First, we study the adsorption of L-lactic acid on the flat Pt(111) surface. Using the optimed PBE - van der Waals (oPBE-vdW) functional, which includes van der Waals forces on an ab initio level, it is shown that the molecule has two binding sites, a carboxyl and the hydroxyl oxygen atoms. Since real chiral surfaces are (i) known to undergo thermal roughening that alters the distribution of kinks and step edges but not the overall chirality and (ii) kink sites and edge sites are usually the energetically most favored adsorption sites, we focus on two surfaces that allow qualitative sampling of the most probable adsorption sites. We hereby consider chiral surfaces exhibiting (111) facets, in particular, Pt(321) and Pt(643). The binding sites are either both on kink sites—which is the case for Pt(321) or on one kink site—as on Pt(643). The binding energy of the molecule on the chiral surfaces is much higher than on the Pt(111) surface. We show that the carboxyl group interacts more strongly than the hydroxyl group with the kink sites. The results indicate the possible existence of very small chiral selectivities of the order of 20 meV for the Pt(321) and Pt(643) surfaces. L-lactic acid is more stable on Pt(321)S than D-lactic acid, while the chiral selectivity is inverted on Pt(643)S. The most stable adsorption configurations of L- and D-lactic acid are similar for Pt(321) but differ for Pt(643). We explore the impact of the different adsorption geometries on the work function, which is important for field ion microscopy.

Optimization of a hydrometric network extension using specific flow, kriging and simulated annealing

NASA Astrophysics Data System (ADS)

Chebbi, Afef; Kebaili Bargaoui, Zoubeida; Abid, Nesrine; da Conceição Cunha, Maria

2017-12-01

In hydrometric stations, water levels are continuously observed and discharge rating curves are constantly updated to achieve accurate river levels and discharge observations. An adequate spatial distribution of hydrological gauging stations presents a lot of interest in linkage with the river regime characterization, water infrastructures design, water resources management and ecological survey. Due to the increase of riverside population and the associated flood risk, hydrological networks constantly need to be developed. This paper suggests taking advantage of kriging approaches to improve the design of a hydrometric network. The context deals with the application of an optimization approach using ordinary kriging and simulated annealing (SA) in order to identify the best locations to install new hydrometric gauges. The task at hand is to extend an existing hydrometric network in order to estimate, at ungauged sites, the average specific annual discharge which is a key basin descriptor. This methodology is developed for the hydrometric network of the transboundary Medjerda River in the North of Tunisia. A Geographic Information System (GIS) is adopted to delineate basin limits and centroids. The latter are adopted to assign the location of basins in kriging development. Scenarios where the size of an existing 12 stations network is alternatively increased by 1, 2, 3, 4 and 5 new station(s) are investigated using geo-regression and minimization of the variance of kriging errors. The analysis of the optimized locations from a scenario to another shows a perfect conformity with respect to the location of the new sites. The new locations insure a better spatial coverage of the study area as seen with the increase of both the average and the maximum of inter-station distances after optimization. The optimization procedure selects the basins that insure the shifting of the mean drainage area towards higher specific discharges.

Internet Usage by Low-Literacy Adults Seeking Health Information: An Observational Analysis

PubMed Central

Birru, Mehret S; Monaco, Valerie M; Charles, Lonelyss; Drew, Hadiya; Njie, Valerie; Bierria, Timothy; Detlefsen, Ellen

2004-01-01

Background Adults with low literacy may encounter informational obstacles on the Internet when searching for health information, in part because most health Web sites require at least a high-school reading proficiency for optimal access. Objective The purpose of this study was to 1) determine how low-literacy adults independently access and evaluate health information on the Internet, 2) identify challenges and areas of proficiency in the Internet-searching skills of low-literacy adults. Methods Subjects (n=8) were enrolled in a reading assistance program at Bidwell Training Center in Pittsburgh, PA, and read at a 3rd to 8th grade level. Subjects conducted self-directed Internet searches for designated health topics while utilizing a think-aloud protocol. Subjects' keystrokes and comments were recorded using Camtasia Studio screen-capture software. The search terms used to find health information, the amount of time spent on each Web site, the number of Web sites accessed, the reading level of Web sites accessed, and the responses of subjects to questionnaires were assessed. Results Subjects collectively answered 8 out of 24 questions correctly. Seven out of 8 subjects selected "sponsored sites"-paid Web advertisements-over search engine-generated links when answering health questions. On average, subjects accessed health Web sites written at or above a 10th grade reading level. Standard methodologies used for measuring health literacy and for promoting subjects to verbalize responses to Web-site form and content had limited utility in this population. Conclusion This study demonstrates that Web health information requires a reading level that prohibits optimal access by some low-literacy adults. These results highlight the low-literacy adult population as a potential audience for Web health information, and indicate some areas of difficulty that these individuals face when using the Internet and health Web sites to find information on specific health topics. PMID:15471751

Using Physical Organic Chemistry To Shape the Course of Electrochemical Reactions.

PubMed

Moeller, Kevin D

2018-05-09

While organic electrochemistry can look quite different to a chemist not familiar with the technique, the reactions are at their core organic reactions. As such, they are developed and optimized using the same physical organic chemistry principles employed during the development of any other organic reaction. Certainly, the electron transfer that triggers the reactions can require a consideration of new "wrinkles" to those principles, but those considerations are typically minimal relative to the more traditional approaches needed to manipulate the pathways available to the reactive intermediates formed downstream of that electron transfer. In this review, three very different synthetic challenges-the generation and trapping of radical cations, the development of site-selective reactions on microelectrode arrays, and the optimization of current in a paired electrolysis-are used to illustrate this point.

Processing Technology Selection for Municipal Sewage Treatment Based on a Multi-Objective Decision Model under Uncertainty.

PubMed

Chen, Xudong; Xu, Zhongwen; Yao, Liming; Ma, Ning

2018-03-05

This study considers the two factors of environmental protection and economic benefits to address municipal sewage treatment. Based on considerations regarding the sewage treatment plant construction site, processing technology, capital investment, operation costs, water pollutant emissions, water quality and other indicators, we establish a general multi-objective decision model for optimizing municipal sewage treatment plant construction. Using the construction of a sewage treatment plant in a suburb of Chengdu as an example, this paper tests the general model of multi-objective decision-making for the sewage treatment plant construction by implementing a genetic algorithm. The results show the applicability and effectiveness of the multi-objective decision model for the sewage treatment plant. This paper provides decision and technical support for the optimization of municipal sewage treatment.

Fatigue Strength Prediction for Titanium Alloy TiAl6V4 Manufactured by Selective Laser Melting

NASA Astrophysics Data System (ADS)

Leuders, Stefan; Vollmer, Malte; Brenne, Florian; Tröster, Thomas; Niendorf, Thomas

2015-09-01

Selective laser melting (SLM), as a metalworking additive manufacturing technique, received considerable attention from industry and academia due to unprecedented design freedom and overall balanced material properties. However, the fatigue behavior of SLM-processed materials often suffers from local imperfections such as micron-sized pores. In order to enable robust designs of SLM components used in an industrial environment, further research regarding process-induced porosity and its impact on the fatigue behavior is required. Hence, this study aims at a transfer of fatigue prediction models, established for conventional process-routes, to the field of SLM materials. By using high-resolution computed tomography, load increase tests, and electron microscopy, it is shown that pore-based fatigue strength predictions for a titanium alloy TiAl6V4 have become feasible. However, the obtained accuracies are subjected to scatter, which is probably caused by the high defect density even present in SLM materials manufactured following optimized processing routes. Based on thorough examination of crack surfaces and crack initiation sites, respectively, implications for optimization of prediction accuracy of the models in focus are deduced.

Incorporation of isotopic, fluorescent, and heavy-atom-modified nucleotides into RNAs by position-selective labeling of RNA.

PubMed

Liu, Yu; Holmstrom, Erik; Yu, Ping; Tan, Kemin; Zuo, Xiaobing; Nesbitt, David J; Sousa, Rui; Stagno, Jason R; Wang, Yun-Xing

2018-05-01

Site-specific incorporation of labeled nucleotides is an extremely useful synthetic tool for many structural studies (e.g., NMR, electron paramagnetic resonance (EPR), fluorescence resonance energy transfer (FRET), and X-ray crystallography) of RNA. However, specific-position-labeled RNAs >60 nt are not commercially available on a milligram scale. Position-selective labeling of RNA (PLOR) has been applied to prepare large RNAs labeled at desired positions, and all the required reagents are commercially available. Here, we present a step-by-step protocol for the solid-liquid hybrid phase method PLOR to synthesize 71-nt RNA samples with three different modification applications, containing (i) a 13 C 15 N-labeled segment; (ii) discrete residues modified with Cy3, Cy5, or biotin; or (iii) two iodo-U residues. The flexible procedure enables a wide range of downstream biophysical analyses using precisely localized functionalized nucleotides. All three RNAs were obtained in <2 d, excluding time for preparing reagents and optimizing experimental conditions. With optimization, the protocol can be applied to other RNAs with various labeling schemes, such as ligation of segmentally labeled fragments.

Selecting and optimizing eco-physiological parameters of Biome-BGC to reproduce observed woody and leaf biomass growth of Eucommia ulmoides plantation in China using Dakota optimizer

NASA Astrophysics Data System (ADS)

Miyauchi, T.; Machimura, T.

2013-12-01

In the simulation using an ecosystem process model, the adjustment of parameters is indispensable for improving the accuracy of prediction. This procedure, however, requires much time and effort for approaching the simulation results to the measurements on models consisting of various ecosystem processes. In this study, we tried to apply a general purpose optimization tool in the parameter optimization of an ecosystem model, and examined its validity by comparing the simulated and measured biomass growth of a woody plantation. A biometric survey of tree biomass growth was performed in 2009 in an 11-year old Eucommia ulmoides plantation in Henan Province, China. Climate of the site was dry temperate. Leaf, above- and below-ground woody biomass were measured from three cut trees and converted into carbon mass per area by measured carbon contents and stem density. Yearly woody biomass growth of the plantation was calculated according to allometric relationships determined by tree ring analysis of seven cut trees. We used Biome-BGC (Thornton, 2002) to reproduce biomass growth of the plantation. Air temperature and humidity from 1981 to 2010 was used as input climate condition. The plant functional type was deciduous broadleaf, and non-optimizing parameters were left default. 11-year long normal simulations were performed following a spin-up run. In order to select optimizing parameters, we analyzed the sensitivity of leaf, above- and below-ground woody biomass to eco-physiological parameters. Following the selection, optimization of parameters was performed by using the Dakota optimizer. Dakota is an optimizer developed by Sandia National Laboratories for providing a systematic and rapid means to obtain optimal designs using simulation based models. As the object function, we calculated the sum of relative errors between simulated and measured leaf, above- and below-ground woody carbon at each of eleven years. In an alternative run, errors at the last year (at the field survey) were weighted for priority. We compared some gradient-based global optimization methods of Dakota starting with the default parameters of Biome-BGC. In the result of sensitive analysis, carbon allocation parameters between coarse root and leaf, between stem and leaf, and SLA had high contribution on both leaf and woody biomass changes. These parameters were selected to be optimized. The measured leaf, above- and below-ground woody biomass carbon density at the last year were 0.22, 1.81 and 0.86 kgC m-2, respectively, whereas those simulated in the non-optimized control case using all default parameters were 0.12, 2.26 and 0.52 kgC m-2, respectively. After optimizing the parameters, the simulated values were improved to 0.19, 1.81 and 0.86 kgC m-2, respectively. The coliny global optimization method gave the better fitness than efficient global and ncsu direct method. The optimized parameters showed the higher carbon allocation rates to coarse roots and leaves and the lower SLA than the default parameters, which were consistent to the general water physiological response in a dry climate. The simulation using the weighted object function resulted in the closer simulations to the measurements at the last year with the lower fitness during the previous years.

A Machine-Learning and Filtering Based Data Assimilation Framework for Geologic Carbon Sequestration Monitoring Optimization

NASA Astrophysics Data System (ADS)

Chen, B.; Harp, D. R.; Lin, Y.; Keating, E. H.; Pawar, R.

2017-12-01

Monitoring is a crucial aspect of geologic carbon sequestration (GCS) risk management. It has gained importance as a means to ensure CO2 is safely and permanently stored underground throughout the lifecycle of a GCS project. Three issues are often involved in a monitoring project: (i) where is the optimal location to place the monitoring well(s), (ii) what type of data (pressure, rate and/or CO2 concentration) should be measured, and (iii) What is the optimal frequency to collect the data. In order to address these important issues, a filtering-based data assimilation procedure is developed to perform the monitoring optimization. The optimal monitoring strategy is selected based on the uncertainty reduction of the objective of interest (e.g., cumulative CO2 leak) for all potential monitoring strategies. To reduce the computational cost of the filtering-based data assimilation process, two machine-learning algorithms: Support Vector Regression (SVR) and Multivariate Adaptive Regression Splines (MARS) are used to develop the computationally efficient reduced-order-models (ROMs) from full numerical simulations of CO2 and brine flow. The proposed framework for GCS monitoring optimization is demonstrated with two examples: a simple 3D synthetic case and a real field case named Rock Spring Uplift carbon storage site in Southwestern Wyoming.

Advanced Nuclear Technology. Using Technology for Small Modular Reactor Staff Optimization, Improved Effectiveness, and Cost Containment, 3002007071

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

Loflin, Leonard

Through this grant, the U.S. Department of Energy (DOE) will review several functional areas within a nuclear power plant, including fire protection, operations and operations support, refueling, training, procurement, maintenance, site engineering, and others. Several functional areas need to be examined since there appears to be no single staffing area or approach that alone has the potential for significant staff optimization at new nuclear power plants. Several of the functional areas will require a review of technology options such as automation, remote monitoring, fleet wide monitoring, new and specialized instrumentation, human factors engineering, risk informed analysis and PRAs, component andmore » system condition monitoring and reporting, just in time training, electronic and automated procedures, electronic tools for configuration management and license and design basis information, etc., that may be applied to support optimization. Additionally, the project will require a review key regulatory issues that affect staffing and could be optimized with additional technology input. Opportunities to further optimize staffing levels and staffing functions by selection of design attributes of physical systems and structures need also be identified. A goal of this project is to develop a prioritized assessment of the functional areas, and R&D actions needed for those functional areas, to provide the best optimization« less

Designing and building oncolytic viruses

PubMed Central

Maroun, Justin; Muñoz-Alía, Miguel; Ammayappan, Arun; Schulze, Autumn; Peng, Kah-Whye; Russell, Stephen

2017-01-01

Oncolytic viruses (OVs) are engineered and/or evolved to propagate selectively in cancerous tissues. They have a dual mechanism of action; direct killing of infected cancer cells cross-primes anticancer immunity to boost the killing of uninfected cancer cells. The goal of the field is to develop OVs that are easily manufactured, efficiently delivered to disseminated sites of cancer growth, undergo rapid intratumoral spread, selectively kill tumor cells, cause no collateral damage and pose no risk of transmission in the population. Here we discuss the many virus engineering strategies that are being pursued to optimize delivery, intratumoral spread and safety of OVs derived from different virus families. With continued progress, OVs have the potential to transform the paradigm of cancer care. PMID:29387140

MultiMiTar: a novel multi objective optimization based miRNA-target prediction method.

PubMed

Mitra, Ramkrishna; Bandyopadhyay, Sanghamitra

2011-01-01

Machine learning based miRNA-target prediction algorithms often fail to obtain a balanced prediction accuracy in terms of both sensitivity and specificity due to lack of the gold standard of negative examples, miRNA-targeting site context specific relevant features and efficient feature selection process. Moreover, all the sequence, structure and machine learning based algorithms are unable to distribute the true positive predictions preferentially at the top of the ranked list; hence the algorithms become unreliable to the biologists. In addition, these algorithms fail to obtain considerable combination of precision and recall for the target transcripts that are translationally repressed at protein level. In the proposed article, we introduce an efficient miRNA-target prediction system MultiMiTar, a Support Vector Machine (SVM) based classifier integrated with a multiobjective metaheuristic based feature selection technique. The robust performance of the proposed method is mainly the result of using high quality negative examples and selection of biologically relevant miRNA-targeting site context specific features. The features are selected by using a novel feature selection technique AMOSA-SVM, that integrates the multi objective optimization technique Archived Multi-Objective Simulated Annealing (AMOSA) and SVM. MultiMiTar is found to achieve much higher Matthew's correlation coefficient (MCC) of 0.583 and average class-wise accuracy (ACA) of 0.8 compared to the others target prediction methods for a completely independent test data set. The obtained MCC and ACA values of these algorithms range from -0.269 to 0.155 and 0.321 to 0.582, respectively. Moreover, it shows a more balanced result in terms of precision and sensitivity (recall) for the translationally repressed data set as compared to all the other existing methods. An important aspect is that the true positive predictions are distributed preferentially at the top of the ranked list that makes MultiMiTar reliable for the biologists. MultiMiTar is now available as an online tool at www.isical.ac.in/~bioinfo_miu/multimitar.htm. MultiMiTar software can be downloaded from www.isical.ac.in/~bioinfo_miu/multimitar-download.htm.

WGE: a CRISPR database for genome engineering.

PubMed

Hodgkins, Alex; Farne, Anna; Perera, Sajith; Grego, Tiago; Parry-Smith, David J; Skarnes, William C; Iyer, Vivek

2015-09-15

The rapid development of CRISPR-Cas9 mediated genome editing techniques has given rise to a number of online and stand-alone tools to find and score CRISPR sites for whole genomes. Here we describe the Wellcome Trust Sanger Institute Genome Editing database (WGE), which uses novel methods to compute, visualize and select optimal CRISPR sites in a genome browser environment. The WGE database currently stores single and paired CRISPR sites and pre-calculated off-target information for CRISPRs located in the mouse and human exomes. Scoring and display of off-target sites is simple, and intuitive, and filters can be applied to identify high-quality CRISPR sites rapidly. WGE also provides a tool for the design and display of gene targeting vectors in the same genome browser, along with gene models, protein translation and variation tracks. WGE is open, extensible and can be set up to compute and present CRISPR sites for any genome. The WGE database is freely available at www.sanger.ac.uk/htgt/wge : vvi@sanger.ac.uk or skarnes@sanger.ac.uk Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

Method of injection of onabotulinumtoxinA for chronic migraine: a safe, well-tolerated, and effective treatment paradigm based on the PREEMPT clinical program.

PubMed

Blumenfeld, Andrew; Silberstein, Stephen D; Dodick, David W; Aurora, Sheena K; Turkel, Catherine C; Binder, William J

2010-10-01

Chronic migraine (CM) is a prevalent and disabling neurological disorder. Few prophylactic treatments for CM have been investigated. OnabotulinumtoxinA, which inhibits the release of nociceptive mediators, such as glutamate, substance P, and calcitonin gene-related peptide, has been evaluated in randomized, placebo-controlled studies for the preventive treatment of a variety of headache disorders, including CM. These studies have yielded insight into appropriate patient selection, injection sites, dosages, and technique. Initial approaches used a set of fixed sites for the pericranial injections. However, the treatment approach evolved to include other sites that corresponded to the location of pain and tenderness in the individual patient in addition to the fixed sites. The Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) injection paradigm uses both fixed and follow-the-pain sites, with additional specific follow-the-pain sites considered depending on individual symptoms. The PREEMPT paradigm for injecting onabotulinumtoxinA has been shown to be safe, well-tolerated, and effective in well-designed, controlled clinical trials and is the evidence-based approach recommended to optimize clinical outcomes for patients with CM. © 2010 American Headache Society.

A Novel Feature Optimization for Wearable Human-Computer Interfaces Using Surface Electromyography Sensors

PubMed Central

Zhang, Xiong; Zhao, Yacong; Zhang, Yu; Zhong, Xuefei; Fan, Zhaowen

2018-01-01

The novel human-computer interface (HCI) using bioelectrical signals as input is a valuable tool to improve the lives of people with disabilities. In this paper, surface electromyography (sEMG) signals induced by four classes of wrist movements were acquired from four sites on the lower arm with our designed system. Forty-two features were extracted from the time, frequency and time-frequency domains. Optimal channels were determined from single-channel classification performance rank. The optimal-feature selection was according to a modified entropy criteria (EC) and Fisher discrimination (FD) criteria. The feature selection results were evaluated by four different classifiers, and compared with other conventional feature subsets. In online tests, the wearable system acquired real-time sEMG signals. The selected features and trained classifier model were used to control a telecar through four different paradigms in a designed environment with simple obstacles. Performance was evaluated based on travel time (TT) and recognition rate (RR). The results of hardware evaluation verified the feasibility of our acquisition systems, and ensured signal quality. Single-channel analysis results indicated that the channel located on the extensor carpi ulnaris (ECU) performed best with mean classification accuracy of 97.45% for all movement’s pairs. Channels placed on ECU and the extensor carpi radialis (ECR) were selected according to the accuracy rank. Experimental results showed that the proposed FD method was better than other feature selection methods and single-type features. The combination of FD and random forest (RF) performed best in offline analysis, with 96.77% multi-class RR. Online results illustrated that the state-machine paradigm with a 125 ms window had the highest maneuverability and was closest to real-life control. Subjects could accomplish online sessions by three sEMG-based paradigms, with average times of 46.02, 49.06 and 48.08 s, respectively. These experiments validate the feasibility of proposed real-time wearable HCI system and algorithms, providing a potential assistive device interface for persons with disabilities. PMID:29543737

Using "big data" to optimally model hydrology and water quality across expansive regions

USGS Publications Warehouse

Roehl, E.A.; Cook, J.B.; Conrads, P.A.

2009-01-01

This paper describes a new divide and conquer approach that leverages big environmental data, utilizing all available categorical and time-series data without subjectivity, to empirically model hydrologic and water-quality behaviors across expansive regions. The approach decomposes large, intractable problems into smaller ones that are optimally solved; decomposes complex signals into behavioral components that are easier to model with "sub- models"; and employs a sequence of numerically optimizing algorithms that include time-series clustering, nonlinear, multivariate sensitivity analysis and predictive modeling using multi-layer perceptron artificial neural networks, and classification for selecting the best sub-models to make predictions at new sites. This approach has many advantages over traditional modeling approaches, including being faster and less expensive, more comprehensive in its use of available data, and more accurate in representing a system's physical processes. This paper describes the application of the approach to model groundwater levels in Florida, stream temperatures across Western Oregon and Wisconsin, and water depths in the Florida Everglades. ?? 2009 ASCE.

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

A search game model of the scatter hoarder's problem

PubMed Central

Alpern, Steve; Fokkink, Robbert; Lidbetter, Thomas; Clayton, Nicola S.

2012-01-01

Scatter hoarders are animals (e.g. squirrels) who cache food (nuts) over a number of sites for later collection. A certain minimum amount of food must be recovered, possibly after pilfering by another animal, in order to survive the winter. An optimal caching strategy is one that maximizes the survival probability, given worst case behaviour of the pilferer. We modify certain ‘accumulation games’ studied by Kikuta & Ruckle (2000 J. Optim. Theory Appl.) and Kikuta & Ruckle (2001 Naval Res. Logist.), which modelled the problem of optimal diversification of resources against catastrophic loss, to include the depth at which the food is hidden at each caching site. Optimal caching strategies can then be determined as equilibria in a new ‘caching game’. We show how the distribution of food over sites and the site-depths of the optimal caching varies with the animal's survival requirements and the amount of pilfering. We show that in some cases, ‘decoy nuts’ are required to be placed above other nuts that are buried further down at the same site. Methods from the field of search games are used. Some empirically observed behaviour can be shown to be optimal in our model. PMID:22012971

Final Report: Pilot Region-Based Optimization Program for Fund-Lead Sites, EPA Region III

EPA Pesticide Factsheets

This report describes a pilot study for a Region-based optimization program, implemented by a Regional Optimization Evaluation Team (ROET) that was conducted in U.S. EPA Region III at Fund-lead sites with pump-and-treat (P&T) systems.

Monopolar Detection Thresholds Predict Spatial Selectivity of Neural Excitation in Cochlear Implants: Implications for Speech Recognition

PubMed Central

2016-01-01

The objectives of the study were to (1) investigate the potential of using monopolar psychophysical detection thresholds for estimating spatial selectivity of neural excitation with cochlear implants and to (2) examine the effect of site removal on speech recognition based on the threshold measure. Detection thresholds were measured in Cochlear Nucleus® device users using monopolar stimulation for pulse trains that were of (a) low rate and long duration, (b) high rate and short duration, and (c) high rate and long duration. Spatial selectivity of neural excitation was estimated by a forward-masking paradigm, where the probe threshold elevation in the presence of a forward masker was measured as a function of masker-probe separation. The strength of the correlation between the monopolar thresholds and the slopes of the masking patterns systematically reduced as neural response of the threshold stimulus involved interpulse interactions (refractoriness and sub-threshold adaptation), and spike-rate adaptation. Detection threshold for the low-rate stimulus most strongly correlated with the spread of forward masking patterns and the correlation reduced for long and high rate pulse trains. The low-rate thresholds were then measured for all electrodes across the array for each subject. Subsequently, speech recognition was tested with experimental maps that deactivated five stimulation sites with the highest thresholds and five randomly chosen ones. Performance with deactivating the high-threshold sites was better than performance with the subjects’ clinical map used every day with all electrodes active, in both quiet and background noise. Performance with random deactivation was on average poorer than that with the clinical map but the difference was not significant. These results suggested that the monopolar low-rate thresholds are related to the spatial neural excitation patterns in cochlear implant users and can be used to select sites for more optimal speech recognition performance. PMID:27798658

Selective robust optimization: A new intensity-modulated proton therapy optimization strategy

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

Li, Yupeng; Niemela, Perttu; Siljamaki, Sami

2015-08-15

Purpose: To develop a new robust optimization strategy for intensity-modulated proton therapy as an important step in translating robust proton treatment planning from research to clinical applications. Methods: In selective robust optimization, a worst-case-based robust optimization algorithm is extended, and terms of the objective function are selectively computed from either the worst-case dose or the nominal dose. Two lung cancer cases and one head and neck cancer case were used to demonstrate the practical significance of the proposed robust planning strategy. The lung cancer cases had minimal tumor motion less than 5 mm, and, for the demonstration of the methodology,more » are assumed to be static. Results: Selective robust optimization achieved robust clinical target volume (CTV) coverage and at the same time increased nominal planning target volume coverage to 95.8%, compared to the 84.6% coverage achieved with CTV-based robust optimization in one of the lung cases. In the other lung case, the maximum dose in selective robust optimization was lowered from a dose of 131.3% in the CTV-based robust optimization to 113.6%. Selective robust optimization provided robust CTV coverage in the head and neck case, and at the same time improved controls over isodose distribution so that clinical requirements may be readily met. Conclusions: Selective robust optimization may provide the flexibility and capability necessary for meeting various clinical requirements in addition to achieving the required plan robustness in practical proton treatment planning settings.« less

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.

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

DOE PAGES

Jia, Chuandong; Zuo, Wei; Yang, Dong; ...

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. Here, this similarity in structure leads to a similarly high selectivity of host 2 for choline over its derivatives,more » 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.« less

Optimal number of stimulation contacts for coordinated reset neuromodulation

PubMed Central

Lysyansky, Borys; Popovych, Oleksandr V.; Tass, Peter A.

2013-01-01

In this computational study we investigate coordinated reset (CR) neuromodulation designed for an effective control of synchronization by multi-site stimulation of neuronal target populations. This method was suggested to effectively counteract pathological neuronal synchrony characteristic for several neurological disorders. We study how many stimulation sites are required for optimal CR-induced desynchronization. We found that a moderate increase of the number of stimulation sites may significantly prolong the post-stimulation desynchronized transient after the stimulation is completely switched off. This can, in turn, reduce the amount of the administered stimulation current for the intermittent ON–OFF CR stimulation protocol, where time intervals with stimulation ON are recurrently followed by time intervals with stimulation OFF. In addition, we found that the optimal number of stimulation sites essentially depends on how strongly the administered current decays within the neuronal tissue with increasing distance from the stimulation site. In particular, for a broad spatial stimulation profile, i.e., for a weak spatial decay rate of the stimulation current, CR stimulation can optimally be delivered via a small number of stimulation sites. Our findings may contribute to an optimization of therapeutic applications of CR neuromodulation. PMID:23885239

Anthropometric protocols for the construction of new international fetal and newborn growth standards: the INTERGROWTH-21st Project.

PubMed

Cheikh Ismail, L; Knight, H E; Bhutta, Z; Chumlea, W C

2013-09-01

The primary aim of the INTERGROWTH-21(st) Project is to construct new, prescriptive standards describing optimal fetal and preterm postnatal growth. The anthropometric measurements include the head circumference, recumbent length and weight of the infants, and the stature and weight of the parents. In such a large, international, multicentre project, it is critical that all study sites follow standardised protocols to ensure maximal validity of the growth and nutrition indicators used. This paper describes, in detail, the selection of anthropometric personnel, equipment, and measurement and calibration protocols used to construct the new standards. Implementing these protocols at each study site ensures that the anthropometric data are of the highest quality to construct the international standards. © 2013 Royal College of Obstetricians and Gynaecologists.

Optimal doping control of magnetic semiconductors via subsurfactant epitaxy.

PubMed

Zeng, Changgan; Zhang, Zhenyu; van Benthem, Klaus; Chisholm, Matthew F; Weitering, Hanno H

2008-02-15

"Subsurfactant epitaxy" is established as a conceptually new approach for introducing manganese as a magnetic dopant into germanium. A kinetic pathway is devised in which the subsurface interstitial sites on Ge(100) are first selectively populated with Mn, while lateral diffusion and clustering on or underneath the surface are effectively suppressed. Subsequent Ge deposition as a capping layer produces a novel surfactantlike phenomenon as the interstitial Mn atoms float towards newly defined subsurface sites at the growth front. Furthermore, the Mn atoms that failed to float upwards are uniformly distributed within the Ge capping layer. The resulting doping levels of order 0.25 at. % would normally be considered too low for ferromagnetic ordering, but the Curie temperature exceeds room temperature by a comfortable margin. Subsurfactant epitaxy thus enables superior dopant control in magnetic semiconductors.

Remote Sensing for Detection of Prehistoric Landscape Use in NW Arizona, USA

NASA Astrophysics Data System (ADS)

Buck, P.; Sabol, D. E.

2012-12-01

Optimal maize field locations possibly used by prehistoric agriculturalists in the Mt. Trumbull portion of the Colorado Plateau in NW AZ were modeled using remotely sensed data and ground based observations. Over 400 prehistoric archaeological sites have been recorded in the study area; in some areas site density is ~120 sites/mi2, including many 1-2 room structures traditionally referred to as "field houses" that archaeologists have long assumed were located on or immediately adjacent to maize fields. Other site types are larger C-shaped pueblos with up to 20 rooms and somewhat smaller multi room structures. We collected and used ground-based field measurements and satellite image data from ASTER (Advanced Spaceborne Thermal Emission and Reflection Radiometer) to produce GIS layers to predict ancient maize fields and compare these with known "field house" sites. Input data layers for the model included early spring maximum solar illumination, surface gradient, surface radiant temperature, water surface flow collection, water infiltration, and soil type. We constructed 2 types of optimality models: "restrictive" (or classification) models and "fuzzy logic" (or grouping) models. Highest values were assigned to pixels with more surface water, warmer temperature, better soils, etc. and then assigned a color for display. Analyses of patterns for the "green" restrictive model shows a disproportionate number of large sites found within 200 m of the green optimal zone; for the yellow optimal zone there is a statistically significant relationship between larger sites and the yellow zones at 100 m or less. For the blue fuzzy logic model, again there is a strong relationship between the number of large sites and a blue zone both at 100 m and 200 m distances. So-called "field houses" are not located preferentially close to our optimal areas. Rather, there is a clear preference for larger sites to be found closer to optimal areas. Using the proportion of site types from the training area, we performed a chi square test using those proportions against the actual values found in a previously unknown area (area B). It was found that the proportions of large sites close to the fuzzy logic blue optimally zone is indistinguishable from the test area, meaning essentially the same pattern is found in area B; viz., there are disproportionally more large sites found closer to blue optimal areas in the fuzzy logic model than would be expected by chance alone. These smaller structural sites are not located closer to the most optimal places as might be expected if they are in fact "field houses". Smaller sites may have been established only after ~ AD 800 when the larger C- and L-shaped pueblos were settled near the most optimal field locations. These smaller structural sites did in fact act as field houses-- but in more marginal locations and later in time. As this portion of the Mt Trumbull area got increasingly "packed" during the later periods, it may be that kin groups from the larger residential sites established field houses to monitor their more marginal fields. This process might have intensified in the 12th and 13th centuries as environmental conditions deteriorated, or at any time when summer monsoonal rains needed for successful agriculture became reduced for long periods.

Plasticity of the Binding Site of Renin: Optimized Selection of Protein Structures for Ensemble Docking.

PubMed

Strecker, Claas; Meyer, Bernd

2018-05-29

Protein flexibility poses a major challenge to docking of potential ligands in that the binding site can adopt different shapes. Docking algorithms usually keep the protein rigid and only allow the ligand to be treated as flexible. However, a wrong assessment of the shape of the binding pocket can prevent a ligand from adapting a correct pose. Ensemble docking is a simple yet promising method to solve this problem: Ligands are docked into multiple structures, and the results are subsequently merged. Selection of protein structures is a significant factor for this approach. In this work we perform a comprehensive and comparative study evaluating the impact of structure selection on ensemble docking. We perform ensemble docking with several crystal structures and with structures derived from molecular dynamics simulations of renin, an attractive target for antihypertensive drugs. Here, 500 ns of MD simulations revealed binding site shapes not found in any available crystal structure. We evaluate the importance of structure selection for ensemble docking by comparing binding pose prediction, ability to rank actives above nonactives (screening utility), and scoring accuracy. As a result, for ensemble definition k-means clustering appears to be better suited than hierarchical clustering with average linkage. The best performing ensemble consists of four crystal structures and is able to reproduce the native ligand poses better than any individual crystal structure. Moreover this ensemble outperforms 88% of all individual crystal structures in terms of screening utility as well as scoring accuracy. Similarly, ensembles of MD-derived structures perform on average better than 75% of any individual crystal structure in terms of scoring accuracy at all inspected ensembles sizes.

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

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

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

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

Multi-kilobase homozygous targeted gene replacement in human induced pluripotent stem cells.

PubMed

Byrne, Susan M; Ortiz, Luis; Mali, Prashant; Aach, John; Church, George M

2015-02-18

Sequence-specific nucleases such as TALEN and the CRISPR/Cas9 system have so far been used to disrupt, correct or insert transgenes at precise locations in mammalian genomes. We demonstrate efficient 'knock-in' targeted replacement of multi-kilobase genes in human induced pluripotent stem cells (iPSC). Using a model system replacing endogenous human genes with their mouse counterpart, we performed a comprehensive study of targeting vector design parameters for homologous recombination. A 2.7 kilobase (kb) homozygous gene replacement was achieved in up to 11% of iPSC without selection. The optimal homology arm length was around 2 kb, with homology length being especially critical on the arm not adjacent to the cut site. Homologous sequence inside the cut sites was detrimental to targeting efficiency, consistent with a synthesis-dependent strand annealing (SDSA) mechanism. Using two nuclease sites, we observed a high degree of gene excisions and inversions, which sometimes occurred more frequently than indel mutations. While homozygous deletions of 86 kb were achieved with up to 8% frequency, deletion frequencies were not solely a function of nuclease activity and deletion size. Our results analyzing the optimal parameters for targeting vector design will inform future gene targeting efforts involving multi-kilobase gene segments, particularly in human iPSC. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

A 4 μW/Ch analog front-end module with moderate inversion and power-scalable sampling operation for 3-D neural microsystems.

PubMed

Al-Ashmouny, Khaled M; Chang, Sun-Il; Yoon, Euisik

2012-10-01

We report an analog front-end prototype designed in 0.25 μm CMOS process for hybrid integration into 3-D neural recording microsystems. For scaling towards massive parallel neural recording, the prototype has investigated some critical circuit challenges in power, area, interface, and modularity. We achieved extremely low power consumption of 4 μW/channel, optimized energy efficiency using moderate inversion in low-noise amplifiers (K of 5.98 × 10⁸ or NEF of 2.9), and minimized asynchronous interface (only 2 per 16 channels) for command and data capturing. We also implemented adaptable operations including programmable-gain amplification, power-scalable sampling (up to 50 kS/s/channel), wide configuration range (9-bit) for programmable gain and bandwidth, and 5-bit site selection capability (selecting 16 out of 128 sites). The implemented front-end module has achieved a reduction in noise-energy-area product by a factor of 5-25 times as compared to the state-of-the-art analog front-end approaches reported to date.

An Analytical Planning Model to Estimate the Optimal Density of Charging Stations for Electric Vehicles

PubMed Central

Ahn, Yongjun; Yeo, Hwasoo

2015-01-01

The charging infrastructure location problem is becoming more significant due to the extensive adoption of electric vehicles. Efficient charging station planning can solve deeply rooted problems, such as driving-range anxiety and the stagnation of new electric vehicle consumers. In the initial stage of introducing electric vehicles, the allocation of charging stations is difficult to determine due to the uncertainty of candidate sites and unidentified charging demands, which are determined by diverse variables. This paper introduces the Estimating the Required Density of EV Charging (ERDEC) stations model, which is an analytical approach to estimating the optimal density of charging stations for certain urban areas, which are subsequently aggregated to city level planning. The optimal charging station’s density is derived to minimize the total cost. A numerical study is conducted to obtain the correlations among the various parameters in the proposed model, such as regional parameters, technological parameters and coefficient factors. To investigate the effect of technological advances, the corresponding changes in the optimal density and total cost are also examined by various combinations of technological parameters. Daejeon city in South Korea is selected for the case study to examine the applicability of the model to real-world problems. With real taxi trajectory data, the optimal density map of charging stations is generated. These results can provide the optimal number of chargers for driving without driving-range anxiety. In the initial planning phase of installing charging infrastructure, the proposed model can be applied to a relatively extensive area to encourage the usage of electric vehicles, especially areas that lack information, such as exact candidate sites for charging stations and other data related with electric vehicles. The methods and results of this paper can serve as a planning guideline to facilitate the extensive adoption of electric vehicles. PMID:26575845

Analysis of low flows and selected methods for estimating low-flow characteristics at partial-record and ungaged stream sites in western Washington

USGS Publications Warehouse

Curran, Christopher A.; Eng, Ken; Konrad, Christopher P.

2012-01-01

Regional low-flow regression models for estimating Q7,10 at ungaged stream sites are developed from the records of daily discharge at 65 continuous gaging stations (including 22 discontinued gaging stations) for the purpose of evaluating explanatory variables. By incorporating the base-flow recession time constant τ as an explanatory variable in the regression model, the root-mean square error for estimating Q7,10 at ungaged sites can be lowered to 72 percent (for known values of τ), which is 42 percent less than if only basin area and mean annual precipitation are used as explanatory variables. If partial-record sites are included in the regression data set, τ must be estimated from pairs of discharge measurements made during continuous periods of declining low flows. Eight measurement pairs are optimal for estimating τ at partial-record sites, and result in a lowering of the root-mean square error by 25 percent. A low-flow survey strategy that includes paired measurements at partial-record sites requires additional effort and planning beyond a standard strategy, but could be used to enhance regional estimates of τ and potentially reduce the error of regional regression models for estimating low-flow characteristics at ungaged sites.

Nest-site selection in the acorn woodpecker

USGS Publications Warehouse

Hooge, P.N.; Stanback, M.T.; Koenig, Walter D.

1999-01-01

Acorn Woodpeckers (Melanerpes formicivorus) at Hastings Reservation in central California prefer to nest in dead limbs in large, dead valley oaks (Quercus lobata) and California sycamores (Platanus racemosa) that are also frequently used as acorn storage trees. Based on 232 nest cavities used over an 18-year period, we tested whether preferred or modal nest-site characters were associated with increased reproductive success (the "nest-site quality" hypothesis). We also examined whether more successful nests were likely to experience more favorable microclimatic conditions or to be less accessible to terrestrial predators. We found only equivocal support for the nest-site quality hypothesis: only 1 of 5 preferred characters and 2 of 10 characters exhibiting a clear modality were correlated with higher reproductive success. All three characteristics of nests known or likely to be associated with a more favorable microclimate, and two of five characteristics likely to render nests less accessible to predators, were correlated with higher reproductive success. These results suggest that nest cavities in this population are built in part to take advantage of favorable microclimatic conditions and, to a lesser extent, to reduce access to predators. However, despite benefits of particular nest characteristics, birds frequently nested in apparently suboptimal cavities. We also found a significant relationship between mean group size and the history of occupancy of particular territories and the probability of nest cavities being built in microclimatically favorable live limbs, suggesting that larger groups residing on more stable territories were better able to construct nests with optimal characteristics. This indicates that there may be demographic, as well as ecological, constraints on nest-site selection in this primary cavity nester.

Does the choice of nucleotide substitution models matter topologically?

PubMed

Hoff, Michael; Orf, Stefan; Riehm, Benedikt; Darriba, Diego; Stamatakis, Alexandros

2016-03-24

In the context of a master level programming practical at the computer science department of the Karlsruhe Institute of Technology, we developed and make available an open-source code for testing all 203 possible nucleotide substitution models in the Maximum Likelihood (ML) setting under the common Akaike, corrected Akaike, and Bayesian information criteria. We address the question if model selection matters topologically, that is, if conducting ML inferences under the optimal, instead of a standard General Time Reversible model, yields different tree topologies. We also assess, to which degree models selected and trees inferred under the three standard criteria (AIC, AICc, BIC) differ. Finally, we assess if the definition of the sample size (#sites versus #sites × #taxa) yields different models and, as a consequence, different tree topologies. We find that, all three factors (by order of impact: nucleotide model selection, information criterion used, sample size definition) can yield topologically substantially different final tree topologies (topological difference exceeding 10 %) for approximately 5 % of the tree inferences conducted on the 39 empirical datasets used in our study. We find that, using the best-fit nucleotide substitution model may change the final ML tree topology compared to an inference under a default GTR model. The effect is less pronounced when comparing distinct information criteria. Nonetheless, in some cases we did obtain substantial topological differences.

Structural insights into binding of small molecule inhibitors to Enhancer of Zeste Homolog 2

NASA Astrophysics Data System (ADS)

Kalinić, Marko; Zloh, Mire; Erić, Slavica

2014-11-01

Enhancer of Zeste Homolog 2 (EZH2) is a SET domain protein lysine methyltransferase (PKMT) which has recently emerged as a chemically tractable and therapeutically promising epigenetic target, evidenced by the discovery and characterization of potent and highly selective EZH2 inhibitors. However, no experimental structures of the inhibitors co-crystallized to EZH2 have been resolved, and the structural basis for their activity and selectivity remains unknown. Considering the need to minimize cross-reactivity between prospective PKMT inhibitors, much can be learned from understanding the molecular basis for selective inhibition of EZH2. Thus, to elucidate the binding of small-molecule inhibitors to EZH2, we have developed a model of its fully-formed cofactor binding site and used it to carry out molecular dynamics simulations of protein-ligand complexes, followed by molecular mechanics/generalized born surface area calculations. The obtained results are in good agreement with biochemical inhibition data and reflect the structure-activity relationships of known ligands. Our findings suggest that the variable and flexible post-SET domain plays an important role in inhibitor binding, allowing possibly distinct binding modes of inhibitors with only small variations in their structure. Insights from this study present a good basis for design of novel and optimization of existing compounds targeting the cofactor binding site of EZH2.

Topographic and geologic analysis of the Pre-selection landing sitesfor Chang 'E 5(CE-5) lunar sample returning mission of China

NASA Astrophysics Data System (ADS)

Zeng, Xingguo; Zuo, Wei; Zhang, Zhoubin; Liu, Yuxuan; Li, Chunlai

2017-04-01

China Lunar Exploration Program has successfully launched 3 missions since the year of 2007:CE-1(2007), CE-2(2009), and CE-3(2013), and it is planning to launch two lunarLanders in the upcoming years- CE-5(2017) and CE-4(2020). Few decades after the last lunar sample returning mission, CE-5 will be the first lunar sample returning mission in the 21 century. The Pre-selection landing site of CE-5 will be located at a geographic extent of:41 degrees to 45 degrees north latitude and 49 degrees to 69 west longitude, which lies in the near side of the moon, the north-east of the Oceanus Procellarum, to the west of Monte Jura and to the north of Monte Rümker. To ensure the safety of the CE-5 Lander and get lunar samples with more scientific interest, it is essential to take an investigation from the research aspects of topography and geology to select optimal precise landing sites from the Pre-selection area.From the topography aspect, the safety of the Lander is greatly involved with the rugged terrain, conditions of solar illumination and necessity of direct radio communicationwith the Earth, We present the method of preciselandingsites selection using CE-2 high resolution lunar topographic data, which is based on geographical information systems (GIS) technologies to perform analysis, utilizing the criteria of surface suitability for landing, such as slopes, waviness, craters distribution, illumination conditions and Earth visibility.Inaddition, the scientific interest is related to the complexity of the geological conditions, so that estimations of geological background based on USGS lunar geology map data were used to evaluatelanding site candidates on possible lunar volcanicmaterials. The method gave us 7possible candidates to land, which are around the location of-55°W, 43°N. In the further research, the main parameters of these possible sites will be presented with possible prioritization based on both technical requirements and scientific interest.

Engineering a plant community to deliver multiple ecosystem services.

PubMed

Storkey, Jonathan; Döring, Thomas; Baddeley, John; Collins, Rosemary; Roderick, Stephen; Jones, Hannah; Watson, Christine

2015-06-01

The sustainable delivery of multiple ecosystem services requires the management of functionally diverse biological communities. In an agricultural context, an emphasis on food production has often led to a loss of biodiversity to the detriment of other ecosystem services such as the maintenance of soil health and pest regulation. In scenarios where multiple species can be grown together, it may be possible to better balance environmental and agronomic services through the targeted selection of companion species. We used the case study of legume-based cover crops to engineer a plant community that delivered the optimal balance of six ecosystem services: early productivity, regrowth following mowing, weed suppression, support of invertebrates, soil fertility building (measured as yield of following crop), and conservation of nutrients in the soil. An experimental species pool of 12 cultivated legume species was screened for a range of functional traits and ecosystem services at five sites across a geographical gradient in the United Kingdom. All possible species combinations were then analyzed, using a process-based model of plant competition, to identify the community that delivered the best balance of services at each site. In our system, low to intermediate levels of species richness (one to four species) that exploited functional contrasts in growth habit and phenology were identified as being optimal. The optimal solution was determined largely by the number of species and functional diversity represented by the starting species pool, emphasizing the importance of the initial selection of species for the screening experiments. The approach of using relationships between functional traits and ecosystem services to design multifunctional biological communities has the potential to inform the design of agricultural systems that better balance agronomic and environmental services and meet the current objective of European agricultural policy to maintain viable food production in the context of the sustainable management of natural resources.

Semirational Approach for Ultrahigh Poly(3-hydroxybutyrate) Accumulation in Escherichia coli by Combining One-Step Library Construction and High-Throughput Screening.

PubMed

Li, Teng; Ye, Jianwen; Shen, Rui; Zong, Yeqing; Zhao, Xuejin; Lou, Chunbo; Chen, Guo-Qiang

2016-11-18

As a product of a multistep enzymatic reaction, accumulation of poly(3-hydroxybutyrate) (PHB) in Escherichia coli (E. coli) can be achieved by overexpression of the PHB synthesis pathway from a native producer involving three genes phbC, phbA, and phbB. Pathway optimization by adjusting expression levels of the three genes can influence properties of the final product. Here, we reported a semirational approach for highly efficient PHB pathway optimization in E. coli based on a phbCAB operon cloned from the native producer Ralstonia entropha (R. entropha). Rationally designed ribosomal binding site (RBS) libraries with defined strengths for each of the three genes were constructed based on high or low copy number plasmids in a one-pot reaction by an oligo-linker mediated assembly (OLMA) method. Strains with desired properties were evaluated and selected by three different methodologies, including visual selection, high-throughput screening, and detailed in-depth analysis. Applying this approach, strains accumulating 0%-92% PHB contents in cell dry weight (CDW) were achieved. PHB with various weight-average molecular weights (M w ) of 2.7-6.8 × 10 6 were also efficiently produced in relatively high contents. These results suggest that the semirational approach combining library design, construction, and proper screening is an efficient way to optimize PHB and other multienzyme pathways.

An efficient approach to selective electromembrane extraction of naproxen by means of molecularly imprinted polymer-coated multi-walled carbon nanotubes-reinforced hollow fibers.

PubMed

Tahmasebi, Zeinab; Davarani, Saied Saeed Hosseiny; Asgharinezhad, Ali Akbar

2016-10-28

In this work, a novel microextraction technique using molecularly imprinted polymer-coated multi-walled carbon nanotubes (MIP-MWCNTs) in electromembrane extraction (EME) procedure is described. The method in combination with HPLC-UV was utilized to determine naproxen, as an acidic model drug, in urine, plasma and wastewater samples. For this purpose, MIP-MWCNTs were placed in the pores of polypropylene hollow fiber. The MIP-MWCNTs-EME method has the advantages of high selectivity and cleanup of MIP along with high enrichment ability of the EME in a single step extraction. Continuing with the research, optimization of the factors affecting the migration of naproxen from sample solutions to MIP-MWCNTs sites and then into the lumen of hollow fiber was explored. Under the optimized conditions, the limit of detection (LOD) of the developed method was calculated to be 0.3μgL -1 . All relative standard deviations (RSDs) were lower than 3%. Linearity of the method was obtained within the range of 1-1000μgL -1 with the coefficient of determination (r 2 ) being higher than 0.999. Under the optimized conditions, an extraction recovery of 66% was obtained, which corresponded to a preconcentration factor of 88. Finally, the developed method was satisfactorily used to determine naproxen in urine, plasma and wastewater samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Crispr-mediated Gene Targeting of Human Induced Pluripotent Stem Cells.

PubMed

Byrne, Susan M; Church, George M

2015-01-01

CRISPR/Cas9 nuclease systems can create double-stranded DNA breaks at specific sequences to efficiently and precisely disrupt, excise, mutate, insert, or replace genes. However, human embryonic stem or induced pluripotent stem cells (iPSCs) are more difficult to transfect and less resilient to DNA damage than immortalized tumor cell lines. Here, we describe an optimized protocol for genome engineering of human iPSCs using a simple transient transfection of plasmids and/or single-stranded oligonucleotides. With this protocol, we achieve transfection efficiencies greater than 60%, with gene disruption efficiencies from 1-25% and gene insertion/replacement efficiencies from 0.5-10% without any further selection or enrichment steps. We also describe how to design and assess optimal sgRNA target sites and donor targeting vectors; cloning individual iPSC by single cell FACS sorting, and genotyping successfully edited cells.

The potential for distributed generation in Japanese prototype buildings: A DER-CAM analysis of policy, tariff design, building energy use, and technology development (English Version)

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

Zhou, Nan; Marnay, Chris; Firestone, Ryan

The August 2003 blackout of the northeastern U.S. and CANADA caused great economic losses and inconvenience to New York City and other affected areas. The blackout was a warning to the rest of the world that the ability of conventional power systems to meet growing electricity demand is questionable. Failure of large power systems can lead to serious emergencies. Introduction of on-site generation, renewable energy such as solar and wind power and the effective utilization of exhaust heat is needed, to meet the growing energy demands of the residential and commercial sectors. Additional benefit can be achieved by integrating thesemore » distributed technologies into distributed energy resource (DER) systems. This work demonstrates a method for choosing and designing economically optimal DER systems. An additional purpose of this research is to establish a database of energy tariffs, DER technology cost and performance characteristics, and building energy consumption for Japan. This research builds on prior DER studies at the Ernest Orlando Lawrence Berkeley National Laboratory (LBNL) and with their associates in the Consortium for Electric Reliability Technology Solutions (CERTS) and operation, including the development of the microgrid concept, and the DER selection optimization program, the Distributed Energy Resources Customer Adoption Model (DER-CAM). DER-CAM is a tool designed to find the optimal combination of installed equipment and an idealized operating schedule to minimize a site's energy bills, given performance and cost data on available DER technologies, utility tariffs, and site electrical and thermal loads over a test period, usually an historic year. Since hourly electric and thermal energy data are rarely available, they are typically developed by building simulation for each of six end use loads used to model the building: electric-only loads, space heating, space cooling, refrigeration, water heating, and natural-gas-only loads. DER-CAM provides a global optimization, albeit idealized, that shows how the necessary useful energy loads can be provided for at minimum cost by selection and operation of on-site generation, heat recovery, cooling, and efficiency improvements. This study examines five prototype commercial buildings and uses DER-CAM to select the economically optimal DER system for each. The five building types are office, hospital, hotel, retail, and sports facility. Each building type was considered for both 5,000 and 10,000 square meter floor sizes. The energy consumption of these building types is based on building energy simulation and published literature. Based on the optimization results, energy conservation and the emissions reduction were also evaluated. Furthermore, a comparison study between Japan and the U.S. has been conducted covering the policy, technology and the utility tariffs effects on DER systems installations. This study begins with an examination of existing DER research. Building energy loads were then generated through simulation (DOE-2) and scaled to match available load data in the literature. Energy tariffs in Japan and the U.S. were then compared: electricity prices did not differ significantly, while commercial gas prices in Japan are much higher than in the U.S. For smaller DER systems, the installation costs in Japan are more than twice those in the U.S., but this difference becomes smaller with larger systems. In Japan, DER systems are eligible for a 1/3 rebate of installation costs, while subsidies in the U.S. vary significantly by region and application. For 10,000 m{sup 2} buildings, significant decreases in fuel consumption, carbon emissions, and energy costs were seen in the economically optimal results. This was most noticeable in the sports facility, followed the hospital and hotel. This research demonstrates that office buildings can benefit from CHP, in contrast to popular opinion. For hospitals and sports facilities, the use of waste heat is particularly effective for water and space heating. For the other building types, waste heat is most effectively used for both heating and cooling. The same examination was done for the 5,000 m{sup 2} buildings. Although CHP installation capacity is smaller and the payback periods are longer, economic, fuel efficiency, and environmental benefits are still seen. While these benefits remain even when subsidies are removed, the increased installation costs lead to lower levels of installation capacity and thus benefit.« less

Burial Duration and Frequency Influences Resilience of Differing Propagule Types in a Subtidal Seagrass, Posidonia australis

PubMed Central

2016-01-01

Sedimentation that leads to periodic, and often prolonged, burial events is becoming more common on the world’s coastlines as human populations expand and create urbanised marine environments. Different seagrass species react differently to sediment burial but many species in the southern hemisphere are yet to be examined. How seagrasses react to burial has restoration implications. There is a need to critically assess seagrass transplant propagule responses to periodic (pulse) and prolonged (press) burial events before selecting the most appropriate species, transplant propagule, and transplant site. In my study, mesocosm experiments, coupled with field measurements were used to assess how sexual (seedlings) and vegetative (sprigs) propagules of Posidonia australis responded to pulse and press burial events. Seedlings were highly susceptible to burial (both pulse and press), with no survival at the end of the experimental period. In contrast, rhizome growth in vegetative propagules was stimulated by pulse burial, although press burial events resulted in mortality. The implication for Posidonia australis restoration efforts in areas where burial is periodic, was that vegetative propagules are optimal transplant units, in comparison to seedlings. Press burial however, renders a transplant site sub-optimal for both seedling and sprig transplants. PMID:27526020

Substituted 4-carboxymethylpyroglutamic acid diamides as potent and selective inhibitors of fibroblast activation protein.

PubMed

Tsai, Ting-Yueh; Yeh, Teng-Kuang; Chen, Xin; Hsu, Tsu; Jao, Yu-Chen; Huang, Chih-Hsiang; Song, Jen-Shin; Huang, Yu-Chen; Chien, Chia-Hui; Chiu, Jing-Huai; Yen, Shih-Chieh; Tang, Hung-Kuan; Chao, Yu-Sheng; Jiaang, Weir-Torn

2010-09-23

Fibroblast activation protein (FAP) belongs to the prolyl peptidase family. FAP inhibition is expected to become a new antitumor target. Most known FAP inhibitors often resemble the dipeptide cleavage products, with a boroproline at the P1 site; however, these inhibitors also inhibit DPP-IV, DPP-II, DPP8, and DPP9. Potent and selective FAP inhibitor is needed in evaluating that FAP as a therapeutic target. Therefore, it is important to develop selective FAP inhibitors for the use of target validation. To achieve this, optimization of the nonselective DPP-IV inhibitor 8 led to the discovery of a new class of substituted 4-carboxymethylpyroglutamic acid diamides as FAP inhibitors. SAR studies resulted in a number of FAP inhibitors having IC(50) of <100 nM with excellent selectivity over DPP-IV, DPP-II, DPP8, and DPP9 (IC(50) > 100 μM). Compounds 18a, 18b, and 19 are the only known potent and selective FAP inhibitors, which prompts us to further study the physiological role of FAP.

Protein-protein interaction site predictions with minimum covariance determinant and Mahalanobis distance.

PubMed

Qiu, Zhijun; Zhou, Bo; Yuan, Jiangfeng

2017-11-21

Protein-protein interaction site (PPIS) prediction must deal with the diversity of interaction sites that limits their prediction accuracy. Use of proteins with unknown or unidentified interactions can also lead to missing interfaces. Such data errors are often brought into the training dataset. In response to these two problems, we used the minimum covariance determinant (MCD) method to refine the training data to build a predictor with better performance, utilizing its ability of removing outliers. In order to predict test data in practice, a method based on Mahalanobis distance was devised to select proper test data as input for the predictor. With leave-one-validation and independent test, after the Mahalanobis distance screening, our method achieved higher performance according to Matthews correlation coefficient (MCC), although only a part of test data could be predicted. These results indicate that data refinement is an efficient approach to improve protein-protein interaction site prediction. By further optimizing our method, it is hopeful to develop predictors of better performance and wide range of application. Copyright © 2017 Elsevier Ltd. All rights reserved.

Long-term function and optimization of mouse and human islet transplantation in the subcutaneous device-less site

PubMed Central

Pepper, Andrew R.; Pawlick, Rena L.; Gala-Lopez, Boris

2016-01-01

ABSTRACT Clinical islet transplantation has routinely been demonstrated to be an efficacious means of restoring glycemic control in select patients with autoimmune diabetes. Notwithstanding marked progress and improvements, the broad-spectrum application of this treatment option is restricted by the complications associated with intrahepatic portal cellular infusion and the scarcity of human donor pancreata. Recent progress in stem cell biology has demonstrated that the potential to expand new β cells for clinical transplantation is now a reality. As such, research focus is being directed toward optimizing safe extrahepatic transplant sites to house future alternative β cell sources for clinical use. The present study expands on our previous development of a prevascularized subcutaneous device-less (DL) technique for cellular transplantation, by demonstrating long-term (>365 d) durable syngeneic murine islet graft function. Furthermore, histological analysis of tissue specimens collected immediately post-DL site creation and acutely post-human islet transplantation demonstrates that this technique results in close apposition of the neovascularized collagen to the transplanted cells without dead space, thereby avoiding hypoxic luminal dead-space. Murine islets transplanted into the DL site created by a larger luminal diameter (6-Fr.) (n = 11), reversed diabetes to the similar capacity as our standard DL method (5-Fr.)(n = 9). Furthermore, glucose tolerance testing did not differ between these 2 transplant groups (p > 0 .05). Taken together, this further refinement of the DL transplant approach facilitates a simplistic means of islet infusion, increases the transplant volume capacity and may provide an effective microenvironment to house future alternative β cell sources. PMID:27820660

Long-term function and optimization of mouse and human islet transplantation in the subcutaneous device-less site.

PubMed

Pepper, Andrew R; Bruni, Antonio; Pawlick, Rena L; Gala-Lopez, Boris; Rafiei, Yasmin; Wink, John; Kin, Tatsuya; Shapiro, A M James

2016-11-01

Clinical islet transplantation has routinely been demonstrated to be an efficacious means of restoring glycemic control in select patients with autoimmune diabetes. Notwithstanding marked progress and improvements, the broad-spectrum application of this treatment option is restricted by the complications associated with intrahepatic portal cellular infusion and the scarcity of human donor pancreata. Recent progress in stem cell biology has demonstrated that the potential to expand new β cells for clinical transplantation is now a reality. As such, research focus is being directed toward optimizing safe extrahepatic transplant sites to house future alternative β cell sources for clinical use. The present study expands on our previous development of a prevascularized subcutaneous device-less (DL) technique for cellular transplantation, by demonstrating long-term (>365 d) durable syngeneic murine islet graft function. Furthermore, histological analysis of tissue specimens collected immediately post-DL site creation and acutely post-human islet transplantation demonstrates that this technique results in close apposition of the neovascularized collagen to the transplanted cells without dead space, thereby avoiding hypoxic luminal dead-space. Murine islets transplanted into the DL site created by a larger luminal diameter (6-Fr.) (n = 11), reversed diabetes to the similar capacity as our standard DL method (5-Fr.)(n = 9). Furthermore, glucose tolerance testing did not differ between these 2 transplant groups (p > 0 .05). Taken together, this further refinement of the DL transplant approach facilitates a simplistic means of islet infusion, increases the transplant volume capacity and may provide an effective microenvironment to house future alternative β cell sources.

Siting and sizing of distributed generators based on improved simulated annealing particle swarm optimization.

PubMed

Su, Hongsheng

2017-12-18

Distributed power grids generally contain multiple diverse types of distributed generators (DGs). Traditional particle swarm optimization (PSO) and simulated annealing PSO (SA-PSO) algorithms have some deficiencies in site selection and capacity determination of DGs, such as slow convergence speed and easily falling into local trap. In this paper, an improved SA-PSO (ISA-PSO) algorithm is proposed by introducing crossover and mutation operators of genetic algorithm (GA) into SA-PSO, so that the capabilities of the algorithm are well embodied in global searching and local exploration. In addition, diverse types of DGs are made equivalent to four types of nodes in flow calculation by the backward or forward sweep method, and reactive power sharing principles and allocation theory are applied to determine initial reactive power value and execute subsequent correction, thus providing the algorithm a better start to speed up the convergence. Finally, a mathematical model of the minimum economic cost is established for the siting and sizing of DGs under the location and capacity uncertainties of each single DG. Its objective function considers investment and operation cost of DGs, grid loss cost, annual purchase electricity cost, and environmental pollution cost, and the constraints include power flow, bus voltage, conductor current, and DG capacity. Through applications in an IEEE33-node distributed system, it is found that the proposed method can achieve desirable economic efficiency and safer voltage level relative to traditional PSO and SA-PSO algorithms, and is a more effective planning method for the siting and sizing of DGs in distributed power grids.

kmos: A lattice kinetic Monte Carlo framework

NASA Astrophysics Data System (ADS)

Hoffmann, Max J.; Matera, Sebastian; Reuter, Karsten

2014-07-01

Kinetic Monte Carlo (kMC) simulations have emerged as a key tool for microkinetic modeling in heterogeneous catalysis and other materials applications. Systems, where site-specificity of all elementary reactions allows a mapping onto a lattice of discrete active sites, can be addressed within the particularly efficient lattice kMC approach. To this end we describe the versatile kmos software package, which offers a most user-friendly implementation, execution, and evaluation of lattice kMC models of arbitrary complexity in one- to three-dimensional lattice systems, involving multiple active sites in periodic or aperiodic arrangements, as well as site-resolved pairwise and higher-order lateral interactions. Conceptually, kmos achieves a maximum runtime performance which is essentially independent of lattice size by generating code for the efficiency-determining local update of available events that is optimized for a defined kMC model. For this model definition and the control of all runtime and evaluation aspects kmos offers a high-level application programming interface. Usage proceeds interactively, via scripts, or a graphical user interface, which visualizes the model geometry, the lattice occupations and rates of selected elementary reactions, while allowing on-the-fly changes of simulation parameters. We demonstrate the performance and scaling of kmos with the application to kMC models for surface catalytic processes, where for given operation conditions (temperature and partial pressures of all reactants) central simulation outcomes are catalytic activity and selectivities, surface composition, and mechanistic insight into the occurrence of individual elementary processes in the reaction network.

Optimization of selection for growth in Menz Sheep while minimizing inbreeding depression in fitness traits

PubMed Central

2013-01-01

The genetic trends in fitness (inbreeding, fertility and survival) of a closed nucleus flock of Menz sheep under selection during ten years for increased body weight were investigated to evaluate the consequences of selection for body weight on fitness. A mate selection tool was used to optimize in retrospect the actual selection and matings conducted over the project period to assess if the observed genetic gains in body weight could have been achieved with a reduced level of inbreeding. In the actual selection, the genetic trends for yearling weight, fertility of ewes and survival of lambs were 0.81 kg, –0.00026% and 0.016% per generation. The average inbreeding coefficient remained zero for the first few generations and then tended to increase over generations. The genetic gains achieved with the optimized retrospective selection and matings were highly comparable with the observed values, the correlation between the average breeding values of lambs born from the actual and optimized matings over the years being 0.99. However, the level of inbreeding with the optimized mate selections remained zero until late in the years of selection. Our results suggest that an optimal selection strategy that considers both genetic merits and coancestry of mates should be adopted to sustain the Menz sheep breeding program. PMID:23783076

Dexterity optimization by port placement in robot-assisted minimally invasive surgery

NASA Astrophysics Data System (ADS)

Selha, Shaun; Dupont, Pierre; Howe, Robert D.; Torchiana, David F.

2002-02-01

A computer-based algorithm has been developed which uses preoperative images to provide a surgeon with a list of feasible port triplets ranked according to tool dexterity and endoscopic view quality at each surgical site involved in a procedure. A computer simulation allows the surgeon to select from among the proposed port locations. The procedure selected for the development of the system consists of a coronary artery bypass graft (CABG). In this procedure, the interior mammary artery (IMA) is mobilized from the interior chest wall, and one end is attached to the coronary arteries to provide a new blood supply for the heart. Approximately 10-20 cm is dissected free, using blunt dissection and a harmonic scalpel or electrocautery. At present, the port placement system is being evaluated in clinical trials.

Raster-based outranking method: a new approach for municipal solid waste landfill (MSW) siting.

PubMed

Hamzeh, Mohamad; Abbaspour, Rahim Ali; Davalou, Romina

2015-08-01

MSW landfill siting is a complicated process because it requires integration of several factors. In this paper, geographic information system (GIS) and multiple criteria decision analysis (MCDA) were combined to handle the municipal solid waste (MSW) landfill siting. For this purpose, first, 16 input data layers were prepared in GIS environment. Then, the exclusionary lands were eliminated and potentially suitable areas for the MSW disposal were identified. These potentially suitable areas, in an innovative approach, were further examined by deploying Preference Ranking Organization Method for Enrichment Evaluations (PROMETHEE) II and analytic network process (ANP), which are two of the most recent MCDA methods, in order to determine land suitability for landfilling. PROMETHEE II was used to determine a complete ranking of the alternatives, while ANP was employed to quantify the subjective judgments of evaluators as criteria weights. The resulting land suitability was reported on a grading scale of 1-5 from 1 to 5, which is the least to the most suitable area, respectively. Finally, three optimal sites were selected by taking into consideration the local conditions of 15 sites, which were candidates for MSW landfilling. Research findings show that the raster-based method yields effective results.

Optimal-adaptive filters for modelling spectral shape, site amplification, and source scaling

USGS Publications Warehouse

Safak, Erdal

1989-01-01

This paper introduces some applications of optimal filtering techniques to earthquake engineering by using the so-called ARMAX models. Three applications are presented: (a) spectral modelling of ground accelerations, (b) site amplification (i.e., the relationship between two records obtained at different sites during an earthquake), and (c) source scaling (i.e., the relationship between two records obtained at a site during two different earthquakes). A numerical example for each application is presented by using recorded ground motions. The results show that the optimal filtering techniques provide elegant solutions to above problems, and can be a useful tool in earthquake engineering.

Pursestring closure of the stoma site leads to fewer wound infections: results from a multicenter randomized controlled trial.

PubMed

Lee, Janet T; Marquez, Thao T; Clerc, Daniel; Gie, Olivier; Demartines, Nicolas; Madoff, Robert D; Rothenberger, David A; Christoforidis, Dimitrios

2014-11-01

Surgical site infection after stoma reversal is common. The optimal skin closure technique after stoma reversal has been widely debated in the literature. We hypothesized that pursestring near-complete closure of the stoma site would lead to fewer surgical site infections compared with conventional primary closure. This study was a parallel prospective multicenter randomized controlled trial. This study was conducted at 2 university medical centers. Patients (N = 122) presenting for elective colostomy or ileostomy reversal were selected. Pursestring versus conventional primary closure of stoma sites were compared. Stoma site surgical site infection within 30 days of surgery, overall surgical site infection, delayed healing (open wound for >30 days), time to wound epithelialization, and patient satisfaction were the primary outcomes measured. The pursestring group had a significantly lower stoma site infection rate (2% vs 15%, p = 0.01). There was no difference in delayed healing or patient satisfaction between groups. Time to epithelialization was measured in only 51 patients but was significantly longer in the pursestring group (34.6 ± 20 days vs 24.1 ± 17 days, p = 0.02). This study was limited by the variability in procedures and surgeons, the limited follow-up after 30 days, and the inability to perform blinding. Pursestring closure after stoma reversal has a lower risk of stoma site surgical site infection than conventional primary closure, although wounds may take longer to heal with the use of this approach. NCT01713452 (www.clinicaltrials.gov).

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.

Optimal energy harvesting from vortex-induced vibrations of cables.

PubMed

Antoine, G O; de Langre, E; Michelin, S

2016-11-01

Vortex-induced vibrations (VIV) of flexible cables are an example of flow-induced vibrations that can act as energy harvesting systems by converting energy associated with the spontaneous cable motion into electricity. This work investigates the optimal positioning of the harvesting devices along the cable, using numerical simulations with a wake oscillator model to describe the unsteady flow forcing. Using classical gradient-based optimization, the optimal harvesting strategy is determined for the generic configuration of a flexible cable fixed at both ends, including the effect of flow forces and gravity on the cable's geometry. The optimal strategy is found to consist systematically in a concentration of the harvesting devices at one of the cable's ends, relying on deformation waves along the cable to carry the energy towards this harvesting site. Furthermore, we show that the performance of systems based on VIV of flexible cables is significantly more robust to flow velocity variations, in comparison with a rigid cylinder device. This results from two passive control mechanisms inherent to the cable geometry: (i) the adaptability to the flow velocity of the fundamental frequencies of cables through the flow-induced tension and (ii) the selection of successive vibration modes by the flow velocity for cables with gravity-induced tension.

Optimal energy harvesting from vortex-induced vibrations of cables

PubMed Central

de Langre, E.; Michelin, S.

2016-01-01

Vortex-induced vibrations (VIV) of flexible cables are an example of flow-induced vibrations that can act as energy harvesting systems by converting energy associated with the spontaneous cable motion into electricity. This work investigates the optimal positioning of the harvesting devices along the cable, using numerical simulations with a wake oscillator model to describe the unsteady flow forcing. Using classical gradient-based optimization, the optimal harvesting strategy is determined for the generic configuration of a flexible cable fixed at both ends, including the effect of flow forces and gravity on the cable’s geometry. The optimal strategy is found to consist systematically in a concentration of the harvesting devices at one of the cable’s ends, relying on deformation waves along the cable to carry the energy towards this harvesting site. Furthermore, we show that the performance of systems based on VIV of flexible cables is significantly more robust to flow velocity variations, in comparison with a rigid cylinder device. This results from two passive control mechanisms inherent to the cable geometry: (i) the adaptability to the flow velocity of the fundamental frequencies of cables through the flow-induced tension and (ii) the selection of successive vibration modes by the flow velocity for cables with gravity-induced tension. PMID:27956880

Optimal energy harvesting from vortex-induced vibrations of cables

NASA Astrophysics Data System (ADS)

Antoine, G. O.; de Langre, E.; Michelin, S.

2016-11-01

Vortex-induced vibrations (VIV) of flexible cables are an example of flow-induced vibrations that can act as energy harvesting systems by converting energy associated with the spontaneous cable motion into electricity. This work investigates the optimal positioning of the harvesting devices along the cable, using numerical simulations with a wake oscillator model to describe the unsteady flow forcing. Using classical gradient-based optimization, the optimal harvesting strategy is determined for the generic configuration of a flexible cable fixed at both ends, including the effect of flow forces and gravity on the cable's geometry. The optimal strategy is found to consist systematically in a concentration of the harvesting devices at one of the cable's ends, relying on deformation waves along the cable to carry the energy towards this harvesting site. Furthermore, we show that the performance of systems based on VIV of flexible cables is significantly more robust to flow velocity variations, in comparison with a rigid cylinder device. This results from two passive control mechanisms inherent to the cable geometry: (i) the adaptability to the flow velocity of the fundamental frequencies of cables through the flow-induced tension and (ii) the selection of successive vibration modes by the flow velocity for cables with gravity-induced tension.

Selectivity optimization in green chromatography by gradient stationary phase optimized selectivity liquid chromatography.

PubMed

Chen, Kai; Lynen, Frédéric; De Beer, Maarten; Hitzel, Laure; Ferguson, Paul; Hanna-Brown, Melissa; Sandra, Pat

2010-11-12

Stationary phase optimized selectivity liquid chromatography (SOSLC) is a promising technique to optimize the selectivity of a given separation by using a combination of different stationary phases. Previous work has shown that SOSLC offers excellent possibilities for method development, especially after the recent modification towards linear gradient SOSLC. The present work is aimed at developing and extending the SOSLC approach towards selectivity optimization and method development for green chromatography. Contrary to current LC practices, a green mobile phase (water/ethanol/formic acid) is hereby preselected and the composition of the stationary phase is optimized under a given gradient profile to obtain baseline resolution of all target solutes in the shortest possible analysis time. With the algorithm adapted to the high viscosity property of ethanol, the principle is illustrated with a fast, full baseline resolution for a randomly selected mixture composed of sulphonamides, xanthine alkaloids and steroids. Copyright © 2010 Elsevier B.V. All rights reserved.

Esophageal-guided biopsy with volumetric laser endomicroscopy and laser cautery marking: a pilot clinical study.

PubMed

Suter, Melissa J; Gora, Michalina J; Lauwers, Gregory Y; Arnason, Thomas; Sauk, Jenny; Gallagher, Kevin A; Kava, Lauren; Tan, Khay M; Soomro, Amna R; Gallagher, Timothy P; Gardecki, Joseph A; Bouma, Brett E; Rosenberg, Mireille; Nishioka, Norman S; Tearney, Guillermo J

2014-06-01

Biopsy surveillance protocols for the assessment of Barrett's esophagus can be subject to sampling errors, resulting in diagnostic uncertainty. Optical coherence tomography is a cross-sectional imaging technique that can be used to conduct volumetric laser endomicroscopy (VLE) of the entire distal esophagus. We have developed a biopsy guidance platform that places endoscopically visible marks at VLE-determined biopsy sites. The objective of this study was to demonstrate in human participants the safety and feasibility of VLE-guided biopsy in vivo. A pilot feasibility study. Massachusetts General Hospital. A total of 22 participants were enrolled from January 2011 to June 2012 with a prior diagnosis of Barrett's esophagus. Twelve participants were used to optimize the laser marking parameters and the system platform. A total of 30 target sites were selected and marked in real-time by using the VLE-guided biopsy platform in the remaining 10 participants. Volumetric laser endomicroscopy. Endoscopic and VLE visibility, and accuracy of VLE diagnosis of the tissue between the laser cautery marks. There were no adverse events of VLE and laser marking. The optimal laser marking parameters were determined to be 2 seconds at 410 mW, with a mark separation of 6 mm. All marks made with these parameters were visible on endoscopy and VLE. The accuracies for diagnosing tissue in between the laser cautery marks by independent blinded readers for endoscopy were 67% (95% confidence interval [CI], 47%-83%), for VLE intent-to-biopsy images 93% (95% CI, 78%-99%), and for corrected VLE post-marking images 100% when compared with histopathology interpretations. This is a single-center feasibility study with a limited number of patients. Our results demonstrate that VLE-guided biopsy of the esophagus is safe and can be used to guide biopsy site selection based on the acquired volumetric optical coherence tomography imaging data. ( NCT01439633.). Copyright © 2014 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Esophageal-guided biopsy with volumetric laser endomicroscopy and laser cautery marking: a pilot clinical study

PubMed Central

Suter, Melissa J.; Gora, Michalina J.; Lauwers, Gregory Y.; Arnason, Thomas; Sauk, Jenny; Gallagher, Kevin A.; Kava, Lauren; Tan, Khay M.; Soomro, Amna R.; Gallagher, Timothy P.; Gardecki, Joseph A.; Bouma, Brett E.; Rosenberg, Mireille; Nishioka, Norman S.; Tearney, Guillermo J.

2018-01-01

Background Biopsy surveillance protocols for the assessment of Barrett’s esophagus can be subject to sampling errors, resulting in diagnostic uncertainty. Optical coherence tomography is a cross-sectional imaging technique that can be used to conduct volumetric laser endomicroscopy (VLE) of the entire distal esophagus. We have developed a biopsy guidance platform that places endoscopically visible marks at VLE-determined biopsy sites. Objective The objective of this study was to demonstrate in human participants the safety and feasibility of VLE-guided biopsy in vivo. Design A pilot feasibility study. Setting Massachusetts General Hospital. Patients A total of 22 participants were enrolled from January 2011 to June 2012 with a prior diagnosis of Barrett’s esophagus. Twelve participants were used to optimize the laser marking parameters and the system platform. A total of 30 target sites were selected and marked in real-time by using the VLE-guided biopsy platform in the remaining 10 participants. Intervention Volumetric laser endomicroscopy. Main Outcome Measurements Endoscopic and VLE visibility, and accuracy of VLE diagnosis of the tissue between the laser cautery marks. Results There were no adverse events of VLE and laser marking. The optimal laser marking parameters were determined to be 2 seconds at 410 mW, with a mark separation of 6 mm. All marks made with these parameters were visible on endoscopy and VLE. The accuracies for diagnosing tissue in between the laser cautery marks by independent blinded readers for endoscopy were 67% (95% confidence interval [CI], 47%–83%), for VLE intent-to-biopsy images 93% (95% CI, 78%–99%), and for corrected VLE post-marking images 100% when compared with histopathology interpretations. Limitations This is a single-center feasibility study with a limited number of patients. Conclusion Our results demonstrate that VLE-guided biopsy of the esophagus is safe and can be used to guide biopsy site selection based on the acquired volumetric optical coherence tomography imaging data. (Clinical trial registration number: NCT01439633.) PMID:24462171

Optimal river monitoring network using optimal partition analysis: a case study of Hun River, Northeast China.

PubMed

Wang, Hui; Liu, Chunyue; Rong, Luge; Wang, Xiaoxu; Sun, Lina; Luo, Qing; Wu, Hao

2018-01-09

River monitoring networks play an important role in water environmental management and assessment, and it is critical to develop an appropriate method to optimize the monitoring network. In this study, an effective method was proposed based on the attainment rate of National Grade III water quality, optimal partition analysis and Euclidean distance, and Hun River was taken as a method validation case. There were 7 sampling sites in the monitoring network of the Hun River, and 17 monitoring items were analyzed once a month during January 2009 to December 2010. The results showed that the main monitoring items in the surface water of Hun River were ammonia nitrogen (NH 4 + -N), chemical oxygen demand, and biochemical oxygen demand. After optimization, the required number of monitoring sites was reduced from seven to three, and 57% of the cost was saved. In addition, there were no significant differences between non-optimized and optimized monitoring networks, and the optimized monitoring networks could correctly represent the original monitoring network. The duplicate setting degree of monitoring sites decreased after optimization, and the rationality of the monitoring network was improved. Therefore, the optimal method was identified as feasible, efficient, and economic.

Location Distribution Optimization of Photographing Sites for Indoor Panorama Modeling

NASA Astrophysics Data System (ADS)

Zhang, S.; Wu, J.; Zhang, Y.; Zhang, X.; Xin, Z.; Liu, J.

2017-09-01

Generally, panoramas image modeling is costly and time-consuming because of photographing continuously to capture enough photos along the routes, especially in complicated indoor environment. Thus, difficulty follows for a wider applications of panoramic image modeling for business. It is indispensable to make a feasible arrangement of panorama sites locations because the locations influence the clarity, coverage and the amount of panoramic images under the condition of certain device. This paper is aim to propose a standard procedure to generate the specific location and total amount of panorama sites in indoor panoramas modeling. Firstly, establish the functional relationship between one panorama site and its objectives. Then, apply the relationship to panorama sites network. We propose the Distance Clarity function (FC and Fe) manifesting the mathematical relationship between panoramas and objectives distance or obstacle distance. The Distance Buffer function (FB) is modified from traditional buffer method to generate the coverage of panorama site. Secondly, transverse every point in possible area to locate possible panorama site, calculate the clarity and coverage synthetically. Finally select as little points as possible to satiate clarity requirement preferentially and then the coverage requirement. In the experiments, detailed parameters of camera lens are given. Still, more experiments parameters need trying out given that relationship between clarity and distance is device dependent. In short, through the function FC, Fe and FB, locations of panorama sites can be generated automatically and accurately.

Development of optimization-based probabilistic earthquake scenarios for the city of Tehran

NASA Astrophysics Data System (ADS)

Zolfaghari, M. R.; Peyghaleh, E.

2016-01-01

This paper presents the methodology and practical example for the application of optimization process to select earthquake scenarios which best represent probabilistic earthquake hazard in a given region. The method is based on simulation of a large dataset of potential earthquakes, representing the long-term seismotectonic characteristics in a given region. The simulation process uses Monte-Carlo simulation and regional seismogenic source parameters to generate a synthetic earthquake catalogue consisting of a large number of earthquakes, each characterized with magnitude, location, focal depth and fault characteristics. Such catalogue provides full distributions of events in time, space and size; however, demands large computation power when is used for risk assessment, particularly when other sources of uncertainties are involved in the process. To reduce the number of selected earthquake scenarios, a mixed-integer linear program formulation is developed in this study. This approach results in reduced set of optimization-based probabilistic earthquake scenario, while maintaining shape of hazard curves and full probabilistic picture by minimizing the error between hazard curves driven by full and reduced sets of synthetic earthquake scenarios. To test the model, the regional seismotectonic and seismogenic characteristics of northern Iran are used to simulate a set of 10,000-year worth of events consisting of some 84,000 earthquakes. The optimization model is then performed multiple times with various input data, taking into account probabilistic seismic hazard for Tehran city as the main constrains. The sensitivity of the selected scenarios to the user-specified site/return period error-weight is also assessed. The methodology could enhance run time process for full probabilistic earthquake studies like seismic hazard and risk assessment. The reduced set is the representative of the contributions of all possible earthquakes; however, it requires far less computation power. The authors have used this approach for risk assessment towards identification of effectiveness-profitability of risk mitigation measures, using optimization model for resource allocation. Based on the error-computation trade-off, 62-earthquake scenarios are chosen to be used for this purpose.

Progress on Optimizing Miscanthus Biomass Production for the European Bioeconomy: Results of the EU FP7 Project OPTIMISC.

PubMed

Lewandowski, Iris; Clifton-Brown, John; Trindade, Luisa M; van der Linden, Gerard C; Schwarz, Kai-Uwe; Müller-Sämann, Karl; Anisimov, Alexander; Chen, C-L; Dolstra, Oene; Donnison, Iain S; Farrar, Kerrie; Fonteyne, Simon; Harding, Graham; Hastings, Astley; Huxley, Laurie M; Iqbal, Yasir; Khokhlov, Nikolay; Kiesel, Andreas; Lootens, Peter; Meyer, Heike; Mos, Michal; Muylle, Hilde; Nunn, Chris; Özgüven, Mensure; Roldán-Ruiz, Isabel; Schüle, Heinrich; Tarakanov, Ivan; van der Weijde, Tim; Wagner, Moritz; Xi, Qingguo; Kalinina, Olena

2016-01-01

This paper describes the complete findings of the EU-funded research project OPTIMISC, which investigated methods to optimize the production and use of miscanthus biomass. Miscanthus bioenergy and bioproduct chains were investigated by trialing 15 diverse germplasm types in a range of climatic and soil environments across central Europe, Ukraine, Russia, and China. The abiotic stress tolerances of a wider panel of 100 germplasm types to drought, salinity, and low temperatures were measured in the laboratory and a field trial in Belgium. A small selection of germplasm types was evaluated for performance in grasslands on marginal sites in Germany and the UK. The growth traits underlying biomass yield and quality were measured to improve regional estimates of feedstock availability. Several potential high-value bioproducts were identified. The combined results provide recommendations to policymakers, growers and industry. The major technical advances in miscanthus production achieved by OPTIMISC include: (1) demonstration that novel hybrids can out-yield the standard commercially grown genotype Miscanthus x giganteus; (2) characterization of the interactions of physiological growth responses with environmental variation within and between sites; (3) quantification of biomass-quality-relevant traits; (4) abiotic stress tolerances of miscanthus genotypes; (5) selections suitable for production on marginal land; (6) field establishment methods for seeds using plugs; (7) evaluation of harvesting methods; and (8) quantification of energy used in densification (pellet) technologies with a range of hybrids with differences in stem wall properties. End-user needs were addressed by demonstrating the potential of optimizing miscanthus biomass composition for the production of ethanol and biogas as well as for combustion. The costs and life-cycle assessment of seven miscanthus-based value chains, including small- and large-scale heat and power, ethanol, biogas, and insulation material production, revealed GHG-emission- and fossil-energy-saving potentials of up to 30.6 t CO 2eq C ha -1 y -1 and 429 GJ ha -1 y -1 , respectively. Transport distance was identified as an important cost factor. Negative carbon mitigation costs of -78€ t -1 CO 2eq C were recorded for local biomass use. The OPTIMISC results demonstrate the potential of miscanthus as a crop for marginal sites and provide information and technologies for the commercial implementation of miscanthus-based value chains.

Progress on Optimizing Miscanthus Biomass Production for the European Bioeconomy: Results of the EU FP7 Project OPTIMISC

PubMed Central

Lewandowski, Iris; Clifton-Brown, John; Trindade, Luisa M.; van der Linden, Gerard C.; Schwarz, Kai-Uwe; Müller-Sämann, Karl; Anisimov, Alexander; Chen, C.-L.; Dolstra, Oene; Donnison, Iain S.; Farrar, Kerrie; Fonteyne, Simon; Harding, Graham; Hastings, Astley; Huxley, Laurie M.; Iqbal, Yasir; Khokhlov, Nikolay; Kiesel, Andreas; Lootens, Peter; Meyer, Heike; Mos, Michal; Muylle, Hilde; Nunn, Chris; Özgüven, Mensure; Roldán-Ruiz, Isabel; Schüle, Heinrich; Tarakanov, Ivan; van der Weijde, Tim; Wagner, Moritz; Xi, Qingguo; Kalinina, Olena

2016-01-01

This paper describes the complete findings of the EU-funded research project OPTIMISC, which investigated methods to optimize the production and use of miscanthus biomass. Miscanthus bioenergy and bioproduct chains were investigated by trialing 15 diverse germplasm types in a range of climatic and soil environments across central Europe, Ukraine, Russia, and China. The abiotic stress tolerances of a wider panel of 100 germplasm types to drought, salinity, and low temperatures were measured in the laboratory and a field trial in Belgium. A small selection of germplasm types was evaluated for performance in grasslands on marginal sites in Germany and the UK. The growth traits underlying biomass yield and quality were measured to improve regional estimates of feedstock availability. Several potential high-value bioproducts were identified. The combined results provide recommendations to policymakers, growers and industry. The major technical advances in miscanthus production achieved by OPTIMISC include: (1) demonstration that novel hybrids can out-yield the standard commercially grown genotype Miscanthus x giganteus; (2) characterization of the interactions of physiological growth responses with environmental variation within and between sites; (3) quantification of biomass-quality-relevant traits; (4) abiotic stress tolerances of miscanthus genotypes; (5) selections suitable for production on marginal land; (6) field establishment methods for seeds using plugs; (7) evaluation of harvesting methods; and (8) quantification of energy used in densification (pellet) technologies with a range of hybrids with differences in stem wall properties. End-user needs were addressed by demonstrating the potential of optimizing miscanthus biomass composition for the production of ethanol and biogas as well as for combustion. The costs and life-cycle assessment of seven miscanthus-based value chains, including small- and large-scale heat and power, ethanol, biogas, and insulation material production, revealed GHG-emission- and fossil-energy-saving potentials of up to 30.6 t CO2eq C ha−1y−1 and 429 GJ ha−1y−1, respectively. Transport distance was identified as an important cost factor. Negative carbon mitigation costs of –78€ t−1 CO2eq C were recorded for local biomass use. The OPTIMISC results demonstrate the potential of miscanthus as a crop for marginal sites and provide information and technologies for the commercial implementation of miscanthus-based value chains. PMID:27917177

A machine-learning approach for predicting palmitoylation sites from integrated sequence-based features.

PubMed

Li, Liqi; Luo, Qifa; Xiao, Weidong; Li, Jinhui; Zhou, Shiwen; Li, Yongsheng; Zheng, Xiaoqi; Yang, Hua

2017-02-01

Palmitoylation is the covalent attachment of lipids to amino acid residues in proteins. As an important form of protein posttranslational modification, it increases the hydrophobicity of proteins, which contributes to the protein transportation, organelle localization, and functions, therefore plays an important role in a variety of cell biological processes. Identification of palmitoylation sites is necessary for understanding protein-protein interaction, protein stability, and activity. Since conventional experimental techniques to determine palmitoylation sites in proteins are both labor intensive and costly, a fast and accurate computational approach to predict palmitoylation sites from protein sequences is in urgent need. In this study, a support vector machine (SVM)-based method was proposed through integrating PSI-BLAST profile, physicochemical properties, [Formula: see text]-mer amino acid compositions (AACs), and [Formula: see text]-mer pseudo AACs into the principal feature vector. A recursive feature selection scheme was subsequently implemented to single out the most discriminative features. Finally, an SVM method was implemented to predict palmitoylation sites in proteins based on the optimal features. The proposed method achieved an accuracy of 99.41% and Matthews Correlation Coefficient of 0.9773 for a benchmark dataset. The result indicates the efficiency and accuracy of our method in prediction of palmitoylation sites based on protein sequences.

Landing Area Narrowed for 2016 InSight Mission to Mars

NASA Image and Video Library

2013-09-04

The process of selecting a site for NASA's next landing on Mars, planned for September 2016, has narrowed to four semifinalist sites located close together in the Elysium Planitia region of Mars. The mission known by the acronym InSight will study the Red Planet's interior, rather than surface features, to advance understanding of the processes that formed and shaped the rocky planets of the inner solar system, including Earth. The location of the cluster of semifinalist landing sites for InSight is indicated on this near-global topographic map of Mars, which also indicates landing sites of current and past NASA missions to the surface of Mars. The mission's full name is Interior Exploration Using Seismic Investigations, Geodesy and Heat Transport. The location of Elysium Planitia close to the Martian equator meets an engineering requirement for the stationary InSight lander to receive adequate solar irradiation year-round on its photovoltaic array. The location also meets an engineering constraint for low elevation, optimizing the amount of atmosphere the spacecraft can use for deceleration during its descent to the surface. The number of candidate landing sites for InSight was trimmed from 22 down to four in August 2013. This down-selection facilitates focusing the efforts to further evaluate the four sites. Cameras on NASA's Mars Reconnaissance Orbiter will be used to gather more information about them before the final selection. The topographic map uses data from the Mars Orbiter Laser Altimeter on NASA's Mars Global Surveyor spacecraft. The color coding on this map indicates elevation relative to a reference datum, since Mars has no "sea level." The lowest elevations are presented as dark blue; the highest as white. The difference between green and orange in the color coding is about 2.5 miles (4 kilometers) vertically. Note: After thorough examination, NASA managers have decided to suspend the planned March 2016 launch of the Interior Exploration using Seismic Investigations Geodesy and Heat Transport (InSight) mission. The decision follows unsuccessful attempts to repair a leak in a section of the prime instrument in the science payload. http://photojournal.jpl.nasa.gov/catalog/PIA17357

A parallel optimization method for product configuration and supplier selection based on interval

NASA Astrophysics Data System (ADS)

Zheng, Jian; Zhang, Meng; Li, Guoxi

2017-06-01

In the process of design and manufacturing, product configuration is an important way of product development, and supplier selection is an essential component of supply chain management. To reduce the risk of procurement and maximize the profits of enterprises, this study proposes to combine the product configuration and supplier selection, and express the multiple uncertainties as interval numbers. An integrated optimization model of interval product configuration and supplier selection was established, and NSGA-II was put forward to locate the Pareto-optimal solutions to the interval multiobjective optimization model.

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…

An efficient strategy for producing a stable, replaceable, highly efficient transgene expression system in silkworm, Bombyx mori

PubMed Central

Long, Dingpei; Lu, Weijian; Zhang, Yuli; Bi, Lihui; Xiang, Zhonghuai; Zhao, Aichun

2015-01-01

We developed an efficient strategy that combines a method for the post-integration elimination of all transposon sequences, a site-specific recombination system, and an optimized fibroin H-chain expression system to produce a stable, replaceable, highly efficient transgene expression system in the silkworm (Bombyx mori) that overcomes the disadvantages of random insertion and post-integration instability of transposons. Here, we generated four different transgenic silkworm strains, and of one the transgenic strains, designated TS1-RgG2, with up to 16% (w/w) of the target protein in the cocoons, was selected. The subsequent elimination of all the transposon sequences from TS1-RgG2 was completed by the heat-shock-induced expression of the transposase in vivo. The resulting transgenic silkworm strain was designated TS3-g2 and contained only the attP-flanked optimized fibroin H-chain expression cassette in its genome. A phiC31/att-system-based recombinase-mediated cassette exchange (RMCE) method could be used to integrate other genes of interest into the same genome locus between the attP sites in TS3-g2. Controlling for position effects with phiC31-mediated RMCE will also allow the optimization of exogenous protein expression and fine gene function analyses in the silkworm. The strategy developed here is also applicable to other lepidopteran insects, to improve the ecological safety of transgenic strains in biocontrol programs. PMID:25739894

Using GIS data and satellite derived irradiance to optimize siting of PV installations in Switzerland

NASA Astrophysics Data System (ADS)

Kahl, Annelen; Nguyen, Viet-Anh; Bartlett, Stuart; Sossan, Fabrizio; Lehning, Michael

2016-04-01

For a successful distribution strategy of PV installations, it does not suffice to choose the locations with highest annual total irradiance. Attention needs to be given to spatial correlation patterns of insolation to avoid large system-wide variations, which can cause extended deficits in supply or might even damage the electrical network. One alternative goal instead is to seek configurations that provide the smoothest energy production, with the most reliable and predictable supply. Our work investigates several scenarios, each pursuing a different strategy for a future renewable Switzerland without nuclear power. Based on an estimate for necessary installed capacity for solar power [Bartlett, 2015] we first use heuristics to pre-select realistic placements for PV installations. Then we apply optimization methods to find a subset of locations that provides the best possible combined electricity production. For the first part of the selection process, we use a DEM to exclude high elevation zones which would be difficult to access and which are prone to natural hazards. Then we use land surface cover information to find all zones with potential roof area, deemed suitable for installation of solar panels. The optimization employs Principal Component Analysis of satellite derived irradiance data (Surface Incoming Shortwave Radiation (SIS), based on Meteosat Second Generation sensors) to incorporate a spatial aspect into the selection process that does not simply maximize annual total production but rather provides the most robust supply, by combining regions with anti-correlated cloud cover patterns. Depending on the initial assumptions and constraints, the resulting distribution schemes for PV installations vary with respect to required surface area, annual total and lowest short-term production, and illustrate how important it is to clearly define priorities and policies for a future renewable Switzerland.

Ribosomal binding site sequences and promoters for expressing glutamate decarboxylase and producing γ-aminobutyrate in Corynebacterium glutamicum.

PubMed

Shi, Feng; Luan, Mingyue; Li, Yongfu

2018-04-18

Glutamate decarboxylase (GAD) converts L-glutamate (Glu) into γ-aminobutyric acid (GABA). Corynebacterium glutamicum that expresses exogenous GAD gene, gadB2 or gadB1, can synthesize GABA from its own produced Glu. To enhance GABA production in C. glutamicum, ribosomal binding site (RBS) sequence and promoter were searched and optimized for increasing the expression efficiency of gadB2. R4 exhibited the highest strength among RBS sequences tested, with 6 nt the optimal aligned spacing (AS) between RBS and start codon. This combination of RBS sequence and AS contributed to gadB2 expression, increased GAD activity by 156% and GABA production by 82% compared to normal strong RBS and AS combination. Then, a series of native promoters were selected for transcribing gadB2 under optimal RBS and AS combination. P dnaK , P dtsR , P odhI and P clgR expressed gadB2 and produced GABA as effectively as widely applied P tuf and P cspB promoters and more effectively than P sod promoter. However, each native promoter did not work as well as the synthetic strong promoter P tacM , which produced 20.2 ± 0.3 g/L GABA. Even with prolonged length and bicistronic architecture, the strength of P dnaK did not enhance. Finally, gadB2 and mutant gadB1 were co-expressed under the optimal promoter and RBS combination, thus converted Glu into GABA completely and improved GABA production to more than 25 g/L. This study provides useful promoters and RBS sequences for gene expression in C. glutamicum.

Oligometastatic Disease in the Peritoneal Space with Gastrointestinal Cancer

PubMed Central

Rau, Beate; Brandl, Andreas; Pascher, Andreas; Raue, Wieland; Sugarbaker, Paul

2017-01-01

Objectives Treatment options for patients with gastrointestinal cancer and oligometastastic disease remain the domain of the medical oncologist. However, in selected cases, attempts to remove or destroy the tumor burden seem appropriate. Background Data During the last decade, the treatment of localized and isolated tumor nodules, such as lung, liver or peritoneal metastasis, has changed. Previously, these patients with metastatic disease only received palliative chemotherapy. Combined treatment approaches and new techniques demonstrate that additional surgery to destroy or remove the metastases seem to be of major benefit to patients. Methods The recently published important literature regarding peritoneal metastases and oligometastases in gastrointestinal cancer was analyzed. Results The most important factor in the treatment of peritoneal metastases and in cytoreductive surgery is patient selection. Resection of peritoneal metastases should be considered. Hyperthermic intraperitoneal chemotherapy is feasible. However, further results of randomized trials are necessary. Several randomized trials are on the way and will be available in 1–2 years. Systemic chemotherapy alone as an adequate management plan for all sites of metastatic disease is not compatible with a high standard of care. Formulating an optimal plan combining re-operative surgery with regional plus systemic chemotherapy is a necessary task of the multidisciplinary team. Conclusions In oligometastastic disease of gastrointestinal cancer origin, the selection process is the most important factor for survival. Further studies are needed to determine optimal treatment options. PMID:28612016

Comparison of Genetic Algorithm, Particle Swarm Optimization and Biogeography-based Optimization for Feature Selection to Classify Clusters of Microcalcifications

NASA Astrophysics Data System (ADS)

Khehra, Baljit Singh; Pharwaha, Amar Partap Singh

2017-04-01

Ductal carcinoma in situ (DCIS) is one type of breast cancer. Clusters of microcalcifications (MCCs) are symptoms of DCIS that are recognized by mammography. Selection of robust features vector is the process of selecting an optimal subset of features from a large number of available features in a given problem domain after the feature extraction and before any classification scheme. Feature selection reduces the feature space that improves the performance of classifier and decreases the computational burden imposed by using many features on classifier. Selection of an optimal subset of features from a large number of available features in a given problem domain is a difficult search problem. For n features, the total numbers of possible subsets of features are 2n. Thus, selection of an optimal subset of features problem belongs to the category of NP-hard problems. In this paper, an attempt is made to find the optimal subset of MCCs features from all possible subsets of features using genetic algorithm (GA), particle swarm optimization (PSO) and biogeography-based optimization (BBO). For simulation, a total of 380 benign and malignant MCCs samples have been selected from mammogram images of DDSM database. A total of 50 features extracted from benign and malignant MCCs samples are used in this study. In these algorithms, fitness function is correct classification rate of classifier. Support vector machine is used as a classifier. From experimental results, it is also observed that the performance of PSO-based and BBO-based algorithms to select an optimal subset of features for classifying MCCs as benign or malignant is better as compared to GA-based algorithm.

Developing Methods for Detection of Munitions and Explosives of Concern in Offshore Wind Energy Areas

NASA Astrophysics Data System (ADS)

DuVal, C.; Trembanis, A. C.; Miller, J. K.; Carton, G.

2016-12-01

Munitions and Explosives of Concern (MEC) have been acknowledged globally as a topic of concern. Increasing use of coastal and continental shelf environments for renewable energy development and other activities has and continues to place humans in contact with legacy military munitions. The Bureau of Ocean Energy Management (BOEM) recognized the need to develop guidance concerning methods for MEC detection in the case of offshore energy development. The study was designed to identify the most likely MEC to be encountered in the Atlantic Outer Continental Shelf (OCS) Wind Energy Areas (WEA), review available technologies and develop a process for selecting appropriate technologies and methodologies for their detection. The process for selecting and optimizing technologies and methods for detection of MEC in BOEM OCS WEAs was developed and tested through the synthesis of historical research, physical site characterization, remote sensing technology review, and in-field trials. To test the selected approach, designated personnel were tasked with seeding a portion of the Delaware WEA with munitions surrogates, while a second group of researchers not privy to the surrogate locations, tested and optimized the selected methodology. The effectiveness of a methodology will be related to ease of detection and other associated parameters. The approach for the in-field trial consists of a combination of wide-area assessment surveying by vessel mounted 230/550 kHz Edgetech 6205 Phase Measuring sonar and near-seafloor surveying using a Teledyne Gavia autonomous underwater vehicle (AUV) equipped with high-resolution 900/1800 kHz Marine Sonics side-scan sonar, Geometrics G880-AUV cesium-vapor magnetometer, and 2 megapixel Point Grey color camera. Survey parameters (e.g. track-line spacing, coverage overlap, AUV altitude) were varied to determine the optimal survey methods, as well as simulate MEC burial to test magnetometer range performance. Preliminary results indicate the combination of high-resolution, near-bed side-scan sonar and magnetometry yields promising results for MEC identification, addressing the potential for both surficial and buried MEC.

Application of threshold concepts to ecological management problems: occupancy of Golden Eagles in Denali National Park, Alaska: Chapter 5

USGS Publications Warehouse

Eaton, Mitchell J.; Martin, Julien; Nichols, James D.; McIntyre, Carol; McCluskie, Maggie C.; Schmutz, Joel A.; Lubow, Bruce L.; Runge, Michael C.; Edited by Guntenspergen, Glenn R.

2014-01-01

In this chapter, we demonstrate the application of the various classes of thresholds, detailed in earlier chapters and elsewhere, via an actual but simplified natural resource management case study. We intend our example to provide the reader with the ability to recognize and apply the theoretical concepts of utility, ecological and decision thresholds to management problems through a formalized decision-analytic process. Our case study concerns the management of human recreational activities in Alaska’s Denali National Park, USA, and the possible impacts of such activities on nesting Golden Eagles, Aquila chrysaetos. Managers desire to allow visitors the greatest amount of access to park lands, provided that eagle nesting-site occupancy is maintained at a level determined to be acceptable by the managers themselves. As these two management objectives are potentially at odds, we treat minimum desired occupancy level as a utility threshold which, then, serves to guide the selection of annual management alternatives in the decision process. As human disturbance is not the only factor influencing eagle occupancy, we model nesting-site dynamics as a function of both disturbance and prey availability. We incorporate uncertainty in these dynamics by considering several hypotheses, including a hypothesis that site occupancy is affected only at a threshold level of prey abundance (i.e., an ecological threshold effect). By considering competing management objectives and accounting for two forms of thresholds in the decision process, we are able to determine the optimal number of annual nesting-site restrictions that will produce the greatest long-term benefits for both eagles and humans. Setting a utility threshold of 75 occupied sites, out of a total of 90 potential nesting sites, the optimization specified a decision threshold at approximately 80 occupied sites. At the point that current occupancy falls below 80 sites, the recommended decision is to begin restricting access to humans; above this level, it is recommended that all eagle territories be opened to human recreation. We evaluated the sensitivity of the decision threshold to uncertainty in system dynamics and to management objectives (i.e., to the utility threshold).

Design and Synthesis of a Pan-Janus Kinase Inhibitor Clinical Candidate (PF-06263276) Suitable for Inhaled and Topical Delivery for the Treatment of Inflammatory Diseases of the Lungs and Skin

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

Jones, Peter; Storer, R. Ian; Sabnis, Yogesh A.

By use of a structure-based computational method for identification of structurally novel Janus kinase (JAK) inhibitors predicted to bind beyond the ATP binding site, a potent series of indazoles was identified as selective pan-JAK inhibitors with a type 1.5 binding mode. Optimization of the series for potency and increased duration of action commensurate with inhaled or topical delivery resulted in potent pan-JAK inhibitor 2 (PF-06263276), which was advanced into clinical studies.

Optimization in expression and purification of modified apoptin as selective anti-cancer therapy

NASA Astrophysics Data System (ADS)

Sahlan, Muhamad; Wiseso, Anggoro; Hermansyah, Heri; Yohda, Masafumi

2017-02-01

Cancer is a disease caused by abnormal growth of tissue cells of the body that turn into cancer cells. Apoptin from Chicken Anemia Virus is known to have the ability to trigger apoptosis in cancer cells in vitro and in vivo, but not in normal cells. The production of Apoptin was done on Escherichia coli via plasmid pET9a and modified to improve the efficiency and ease of purification using IMAC nickel, by adding a few tags and cleavage site. The expected result is modified Apoptin and evidence of proteins expressed through SDS-PAGE analysis.

Method for Improving Separation of Carbohydrates from Wood Pulping Liquors and Wood or Biomass Hydrolysis Liquors

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

Compere, A L; Marcoccia, B S; Elliott, J

2012-08-31

Work with industrial partners to perform the studies needed to commercialize U.S. patent 7,699,958 for separation of carbohydrates from wood pulping liquors and wood or biomass hydrolysis liquors. These include: 1) selection of the best pulp mill liquor withdrawal sites, 2) additional purification or enzyme hydrolysis required to obtain acceptable sugar feedstocks, 3) and work with partners to optimize the stream and purification methods to provide acceptable feedstocks for algal fuels and industrial chemicals production, and 4) preparation of samples large enough for testing by downstream partners.

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...

School Site Selection and Approval Guide.

ERIC Educational Resources Information Center

California State Dept. of Education, Sacramento. Div. of School Facilities Planning.

This guide is designed to assist school districts in selecting school sites that provide both a safe and supportive environment for the instructional program and the learning process, and gain state approval for the selected sites. The guide includes a set of selection criteria that have proven helpful to site selection teams, information about…

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...

Profiling charge complementarity and selectivity for binding at the protein surface.

PubMed

Sulea, Traian; Purisima, Enrico O

2003-05-01

A novel analysis and representation of the protein surface in terms of electrostatic binding complementarity and selectivity is presented. The charge optimization methodology is applied in a probe-based approach that simulates the binding process to the target protein. The molecular surface is color coded according to calculated optimal charge or according to charge selectivity, i.e., the binding cost of deviating from the optimal charge. The optimal charge profile depends on both the protein shape and charge distribution whereas the charge selectivity profile depends only on protein shape. High selectivity is concentrated in well-shaped concave pockets, whereas solvent-exposed convex regions are not charge selective. This suggests the synergy of charge and shape selectivity hot spots toward molecular selection and recognition, as well as the asymmetry of charge selectivity at the binding interface of biomolecular systems. The charge complementarity and selectivity profiles map relevant electrostatic properties in a readily interpretable way and encode information that is quite different from that visualized in the standard electrostatic potential map of unbound proteins.

Self-extinction through optimizing selection.

PubMed

Parvinen, Kalle; Dieckmann, Ulf

2013-09-21

Evolutionary suicide is a process in which selection drives a viable population to extinction. So far, such selection-driven self-extinction has been demonstrated in models with frequency-dependent selection. This is not surprising, since frequency-dependent selection can disconnect individual-level and population-level interests through environmental feedback. Hence it can lead to situations akin to the tragedy of the commons, with adaptations that serve the selfish interests of individuals ultimately ruining a population. For frequency-dependent selection to play such a role, it must not be optimizing. Together, all published studies of evolutionary suicide have created the impression that evolutionary suicide is not possible with optimizing selection. Here we disprove this misconception by presenting and analyzing an example in which optimizing selection causes self-extinction. We then take this line of argument one step further by showing, in a further example, that selection-driven self-extinction can occur even under frequency-independent selection. Copyright © 2013 Elsevier Ltd. All rights reserved.

Optimal Item Selection with Credentialing Examinations.

ERIC Educational Resources Information Center

Hambleton, Ronald K.; And Others

The study compared two promising item response theory (IRT) item-selection methods, optimal and content-optimal, with two non-IRT item selection methods, random and classical, for use in fixed-length certification exams. The four methods were used to construct 20-item exams from a pool of approximately 250 items taken from a 1985 certification…

Methods for Optimizing CRISPR-Cas9 Genome Editing Specificity

PubMed Central

Tycko, Josh; Myer, Vic E.; Hsu, Patrick D.

2016-01-01

Summary Advances in the development of delivery, repair, and specificity strategies for the CRISPR-Cas9 genome engineering toolbox are helping researchers understand gene function with unprecedented precision and sensitivity. CRISPR-Cas9 also holds enormous therapeutic potential for the treatment of genetic disorders by directly correcting disease-causing mutations. Although the Cas9 protein has been shown to bind and cleave DNA at off-target sites, the field of Cas9 specificity is rapidly progressing with marked improvements in guide RNA selection, protein and guide engineering, novel enzymes, and off-target detection methods. We review important challenges and breakthroughs in the field as a comprehensive practical guide to interested users of genome editing technologies, highlighting key tools and strategies for optimizing specificity. The genome editing community should now strive to standardize such methods for measuring and reporting off-target activity, while keeping in mind that the goal for specificity should be continued improvement and vigilance. PMID:27494557

Optimizing Parking Orbits for Roundtrip Mars Missions

NASA Technical Reports Server (NTRS)

Qu, Min; Merill, Raymond G.; Chai, Patrick; Komar, David R.

2017-01-01

A roundtrip Mars mission presents many challenges to the design of a transportation system and requires a series of orbital maneuvers within Mars vicinity to capture, reorient, and then return the spacecraft back to Earth. The selection of a Mars parking orbit is crucial to the mission design; not only can the parking or-bit choice drastically impact the ?V requirements of these maneuvers but also it must be properly aligned to target desired surface or orbital destinations. This paper presents a method that can optimize the Mars parking orbits given the arrival and departure conditions from heliocentric trajectories, and it can also en-force constraints on the parking orbits to satisfy other architecture design requirements such as co-planar subperiapsis descent to planned landing sites, due east or co-planar ascent back to the parking orbit, or low cost transfers to and from Phobos and Deimos.

Looking for the optimal rate of recombination for evolutionary dynamics

NASA Astrophysics Data System (ADS)

Saakian, David B.

2018-01-01

We consider many-site mutation-recombination models of evolution with selection. We are looking for situations where the recombination increases the mean fitness of the population, and there is an optimal recombination rate. We found two fitness landscapes supporting such nonmonotonic behavior of the mean fitness versus the recombination rate. The first case is related to the evolution near the error threshold on a neutral-network-like fitness landscape, for moderate genome lengths and large population. The more realistic case is the second one, in which we consider the evolutionary dynamics of a finite population on a rugged fitness landscape (the smooth fitness landscape plus some random contributions to the fitness). We also give the solution to the horizontal gene transfer model in the case of asymmetric mutations. To obtain nonmonotonic behavior for both mutation and recombination, we need a specially designed (ideal) fitness landscape.

Influence of substrate modification and C-terminal truncation on the active site structure of substrate-bound heme oxygenase from Neisseriae meningitidis; A 1H NMR study†

PubMed Central

Peng, Dungeng; Satterlee, James D.; Ma, Li-Hua; Dallas, Jerry L.; Smith, Kevin M.; Zhang, Xuhong; Sato, Michihiko; La Mar, Gerd N.

2011-01-01

Heme oxygenase, HO, from the pathogenic bacterium N. meningitidis, NmHO, which secures host iron, shares many properties with mammalian HOs, but also exhibits some key differences. The crystal structure appears more compact and the crystal-undetected C-terminus interacts with substrate in solution. The unique nature of substrate-protein, specifically pyrrole-I/II-helix-2, peripheral interactions in NmHO are probed by 2D 1H NMR to reveal unique structural features controlling substrate orientation. The thermodynamics of substrate orientational isomerism are mapped for substrates with individual vinyl → methyl → hydrogen substitutions and with enzyme C-terminal deletions. NmHO exhibits significantly stronger orientational preference, reflecting much stronger and selective pyrrole-I/II interactions with the protein matrix, than in mammalian HOs. Thus, replacing bulky vinyls with hydrogens results in a 180° rotation of substrate about the α,γ-meso axis in the active site. A "collapse" of the substrate pocket as substrate size decreases is reflected in movement of helix-2 toward the substrate as indicated by significant and selective increased NOESY cross peak intensity, increase in steric Fe-CN tilt reflected in the orientation of the major magnetic axis, and decrease in steric constraints controlling the rate of aromatic ring reorientation. The active site of NmHO appears "stressed" for native protohemin and its "collapse" upon replacing vinyls by hydrogen leads to a factor ~102 increase in substrate affinity. Interaction of the C-terminus with the active site destabilizes the crystallographic protohemin orientation by ~0.7 kcal/mol, which is consistent with optimizing the His207-Asp27 H-bond. Implications of the active site "stress" for product release are discussed. PMID:21870860

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.

Balancing forest-regeneration probabilities and maintenance costs in dry grasslands of high conservation priority

USGS Publications Warehouse

Bolliger, Janine; Edwards, Thomas C.; Eggenberg, Stefan; Ismail, Sascha; Seidl, Irmi; Kienast, Felix

2011-01-01

Abandonment of agricultural land has resulted in forest regeneration in species-rich dry grasslands across European mountain regions and threatens conservation efforts in this vegetation type. To support national conservation strategies, we used a site-selection algorithm (MARXAN) to find optimum sets of floristic regions (reporting units) that contain grasslands of high conservation priority. We sought optimum sets that would accommodate 136 important dry-grassland species and that would minimize forest regeneration and costs of management needed to forestall predicted forest regeneration. We did not consider other conservation elements of dry grasslands, such as animal species richness, cultural heritage, and changes due to climate change. Optimal sets that included 95–100% of the dry grassland species encompassed an average of 56–59 floristic regions (standard deviation, SD 5). This is about 15% of approximately 400 floristic regions that contain dry-grassland sites and translates to 4800–5300 ha of dry grassland out of a total of approximately 23,000 ha for the entire study area. Projected costs to manage the grasslands in these optimum sets ranged from CHF (Swiss francs) 5.2 to 6.0 million/year. This is only 15–20% of the current total estimated cost of approximately CHF30–45 million/year required if all dry grasslands were to be protected. The grasslands of the optimal sets may be viewed as core sites in a national conservation strategy.

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

Demonstration and Validation of the Geostatistical Temporal-Spatial Algorithm (GTS) for Optimization of Long-Term Monitoring (LTM) of Groundwater at Military and Government Sites

DTIC Science & Technology

2010-08-01

Long - Term Monitoring (LTM) of Groundwater at Military and...Geostatistical Temporal-Spatial Algorithm (GTS) for Optimization of Long - Term Monitoring (LTM) of Groundwater at Military and Government Sites 5a. CONTRACT NUMBER...Council LTM long - term monitoring LTMO long - term monitoring optimization LWQR locally weighted quadratic regression LZ Lower Zone MCL

The nature of chemical innovation: new enzymes by evolution.

PubMed

Arnold, Frances H

2015-11-01

I describe how we direct the evolution of non-natural enzyme activities, using chemical intuition and information on structure and mechanism to guide us to the most promising reaction/enzyme systems. With synthetic reagents to generate new reactive intermediates and just a few amino acid substitutions to tune the active site, a cytochrome P450 can catalyze a variety of carbene and nitrene transfer reactions. The cyclopropanation, N-H insertion, C-H amination, sulfimidation, and aziridination reactions now demonstrated are all well known in chemical catalysis but have no counterparts in nature. The new enzymes are fully genetically encoded, assemble and function inside of cells, and can be optimized for different substrates, activities, and selectivities. We are learning how to use nature's innovation mechanisms to marry some of the synthetic chemists' favorite transformations with the exquisite selectivity and tunability of enzymes.

Optimization Review Report: Saunders Supply Company Superfund Site Suffolk County, Virginia, EPA Region 3

EPA Pesticide Factsheets

This site is a 7-1/3 acre former wood treating plant. The source areas included wastewater ponds, treatment areas, and burn pits. This report summarizes the findings and recommendations of the optimization review team.

Expression, characterization of a novel nitrilase PpL19 from Pseudomonas psychrotolerans with S-selectivity toward mandelonitrile present in active inclusion bodies.

PubMed

Sun, Huihui; Gao, Wenyuan; Wang, Hualei; Wei, Dongzhi

2016-03-01

To identify a novel nitrilase with S-selectivity toward mandelonitrile that can produce (S)-mandelic acid in one step. A novel nitrilase PpL19 from Pseudomonas psychrotolerans L19 was discovered by genome mining. It showed S-selectivity with an enantiomeric excess of 52.7 % when used to hydrolyse (R, S)-mandelonitrile. No byproduct was observed. PpL19 was overexpressed in Escherichia coli BL21 (DE3) and formed inclusion bodies that were active toward mandelonitrile and stable across a broad range of temperature and pH. In addition, PpL19 hydrolysed nitriles with diverse structures; arylacetonitriles were the optimal substrates. Homology modelling and docking studies of both enantiomers of mandelonitrile in the active site of nitrilase PpL19 shed light on the enantioselectivity. A novel nitrilase PpL19 from P. psychrotolerans L19 was mined and distinguished from other nitrilases as it was expressed as an active inclusion body and showed S-selectivity toward mandelonitrile.

A novel sgRNA selection system for CRISPR-Cas9 in mammalian cells.

PubMed

Zhang, Haiwei; Zhang, Xixi; Fan, Cunxian; Xie, Qun; Xu, Chengxian; Zhao, Qun; Liu, Yongbo; Wu, Xiaoxia; Zhang, Haibing

2016-03-18

CRISPR-Cas9 mediated genome editing system has been developed as a powerful tool for elucidating the function of genes through genetic engineering in multiple cells and organisms. This system takes advantage of a single guide RNA (sgRNA) to direct the Cas9 endonuclease to a specific DNA site to generate mutant alleles. Since the targeting efficiency of sgRNAs to distinct DNA loci can vary widely, there remains a need for a rapid, simple and efficient sgRNA selection method to overcome this limitation of the CRISPR-Cas9 system. Here we report a novel system to select sgRNA with high efficacy for DNA sequence modification by a luciferase assay. Using this sgRNAs selection system, we further demonstrated successful examples of one sgRNA for generating one gene knockout cell lines where the targeted genes are shown to be functionally defective. This system provides a potential application to optimize the sgRNAs in different species and to generate a powerful CRISPR-Cas9 genome-wide screening system with minimum amounts of sgRNAs. Copyright © 2016 Elsevier Inc. All rights reserved.

Imaging spectroscopy in soil-water based site suitability assessment for artificial regeneration to Scots pine

NASA Astrophysics Data System (ADS)

Middleton, Maarit; Närhi, Paavo; Sutinen, Raimo

In a humid northern boreal climate, the success rate of artificial regeneration to Scots pine ( Pinus sylvestris L.) can be improved by including a soil water content (SWC) based assessment of site suitability in the reforestation planning process. This paper introduces an application of airborne visible-near-infrared imaging spectroscopic data to identify suitable subregions of forest compartments for the low SWC-tolerant Scots pine. The spatial patterns of understorey plant species communities, recorded by the AISA (Airborne Imaging Spectrometer for Applications) sensor, were demonstrated to be dependant on the underlying SWC. According to the nonmetric multidimensional scaling and correlation results twelve understorey species were found to be most abundant on sites with high soil SWCs. The abundance of bare soil, rocks and abundance of more than ten species indicated low soil SWCs. The spatial patterns of understorey are attributed to time-stability of the underlying SWC patterns. A supervised artificial neural network (radial basis functional link network, probabilistic neural network) approach was taken to classify AISA imaging spectrometer data with dielectric (as a measure volumetric SWC) ground referencing into regimes suitable and unsuitable for Scots pine. The accuracy assessment with receiver operating characteristics curves demonstrated a maximum of 74.1% area under the curve values which indicated moderate success of the NN modelling. The results signified the importance of the training set's quality, adequate quantity (>2.43 points/ha) and NN algorithm selection over the NN algorithm training parameter optimization to perfection. This methodology for the analysis of site suitability of Scots pine can be recommended, especially when artificial regeneration of former mixed wood Norway spruce ( Picea abies L. Karst) - downy birch ( Betula pubenscens Ehrh.) stands is being considered, so that artificially regenerated areas to Scots pine can be optimized for forestry purposes.

Strategy for long-term 3D cloud-resolving simulations over the ARM SGP site and preliminary results

NASA Astrophysics Data System (ADS)

Lin, W.; Liu, Y.; Song, H.; Endo, S.

2011-12-01

Parametric representations of cloud/precipitation processes continue having to be adopted in climate simulations with increasingly higher spatial resolution or with emerging adaptive mesh framework; and it is only becoming more critical that such parameterizations have to be scale aware. Continuous cloud measurements at DOE's ARM sites have provided a strong observational basis for novel cloud parameterization research at various scales. Despite significant progress in our observational ability, there are important cloud-scale physical and dynamical quantities that are either not currently observable or insufficiently sampled. To complement the long-term ARM measurements, we have explored an optimal strategy to carry out long-term 3-D cloud-resolving simulations over the ARM SGP site using Weather Research and Forecasting (WRF) model with multi-domain nesting. The factors that are considered to have important influences on the simulated cloud fields include domain size, spatial resolution, model top, forcing data set, model physics and the growth of model errors. The hydrometeor advection that may play a significant role in hydrological process within the observational domain but is often lacking, and the limitations due to the constraint of domain-wide uniform forcing in conventional cloud system-resolving model simulations, are at least partly accounted for in our approach. Conventional and probabilistic verification approaches are employed first for selected cases to optimize the model's capability of faithfully reproducing the observed mean and statistical distributions of cloud-scale quantities. This then forms the basis of our setup for long-term cloud-resolving simulations over the ARM SGP site. The model results will facilitate parameterization research, as well as understanding and dissecting parameterization deficiencies in climate models.

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

PubMed

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

2016-10-15

As one of the most important reversible types of post-translational modification, protein methylation catalyzed by methyltransferases carries many pivotal biological functions as well as many essential biological processes. Identification of methylation sites is prerequisite for decoding methylation regulatory networks in living cells and understanding their physiological roles. Experimental methods are limitations of labor-intensive and time-consuming. While in silicon approaches are cost-effective and high-throughput manner to predict potential methylation sites, but those previous predictors only have a mixed model and their prediction performances are not fully satisfactory now. Recently, with increasing availability of quantitative methylation datasets in diverse species (especially in eukaryotes), there is a growing need to develop a species-specific predictor. Here, we designed a tool named PSSMe based on information gain (IG) feature optimization method for species-specific methylation site prediction. The IG method was adopted to analyze the importance and contribution of each feature, then select the valuable dimension feature vectors to reconstitute a new orderly feature, which was applied to build the finally prediction model. Finally, our method improves prediction performance of accuracy about 15% comparing with single features. Furthermore, our species-specific model significantly improves the predictive performance compare with other general methylation prediction tools. Hence, our prediction results serve as useful resources to elucidate the mechanism of arginine or lysine methylation and facilitate hypothesis-driven experimental design and validation. The tool online service is implemented by C# language and freely available at http://bioinfo.ncu.edu.cn/PSSMe.aspx CONTACT: jdqiu@ncu.edu.cnSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The effect of top-level domains and advertisements on health web-site credibility.

PubMed

Walther, Joseph B; Wang, Zuoming; Loh, Tracy

2004-09-03

Concerns over health information on the Internet have generated efforts to enhance credibility markers; yet how users actually assess the credibility of online health information is largely unknown. This study set out to (1) establish a parsimonious and valid questionnaire instrument to measure credibility of Internet health information by drawing on various previous measures of source, news, and other credibility scales; and (2) to identify the effects of Web-site domains and advertising on credibility perceptions. Respondents (N = 156) examined one of 12 Web-site mock-ups and completed credibility scales in a 3 x 2 x 2 between-subjects experimental design. Factor analysis and validity checks were used for item reduction, and analysis of variance was employed for hypothesis testing of Web-site features' effects. In an attempt to construct a credibility instrument, three dimensions of credibility (safety, trustworthiness, and dynamism) were retained, reflecting traditional credibility sub-themes, but composed of items from disparate sources. When testing the effect of the presence or absence of advertising on a Web site on credibility, we found that this depends on the site's domain, with a trend for advertisements having deleterious effects on the credibility of sites with .org domain, but positive effects on sites with .com or .edu domains. Health-information Web-site providers should select domains purposefully when they can, especially if they must accept on-site advertising. Credibility perceptions may not be invariant or stable, but rather are sensitive to topic and context. Future research may employ these findings in order to compare other forms of health-information delivery to optimal Web-site features.

Optimizing the design of vertical seismic profiling (VSP) for imaging fracture zones over hardrock basement geothermal environments

NASA Astrophysics Data System (ADS)

Reiser, Fabienne; Schmelzbach, Cedric; Maurer, Hansruedi; Greenhalgh, Stewart; Hellwig, Olaf

2017-04-01

A primary focus of geothermal seismic imaging is to map dipping faults and fracture zones that control rock permeability and fluid flow. Vertical seismic profiling (VSP) is therefore a most valuable means to image the immediate surroundings of an existing borehole to guide, for example, the placing of new boreholes to optimize production from known faults and fractures. We simulated 2D and 3D acoustic synthetic seismic data and processed it through to pre-stack depth migration to optimize VSP survey layouts for mapping moderately to steeply dipping fracture zones within possible basement geothermal reservoirs. Our VSP survey optimization procedure for sequentially selecting source locations to define the area where source points are best located for optimal imaging makes use of a cross-correlation statistic, by which a subset of migrated shot gathers is compared with a target or reference image from a comprehensive set of source gathers. In geothermal exploration at established sites, it is reasonable to assume that sufficient à priori information is available to construct such a target image. We generally obtained good results with a relatively small number of optimally chosen source positions distributed over an ideal source location area for different fracture zone scenarios (different dips, azimuths, and distances from the surveying borehole). Adding further sources outside the optimal source area did not necessarily improve the results, but rather resulted in image distortions. It was found that fracture zones located at borehole-receiver depths and laterally offset from the borehole by 300 m can be imaged reliably for a range of the different dips, but more source positions and large offsets between sources and the borehole are required for imaging steeply dipping interfaces. When such features cross-cut the borehole, they are particularly difficult to image. For fracture zones with different azimuths, 3D effects are observed. Far offset source positions contribute less to the image quality as fracture zone azimuth increases. Our optimization methodology is best suited for designing future field surveys with a favorable benefit-cost ratio in areas with significant à priori knowledge. Moreover, our optimization workflow is valuable for selecting useful subsets of acquired data for optimum target-oriented processing.

It takes a team: reflections on insecticide discoveries, toxicological problems and enjoying the unexpected.

PubMed

Wing, Keith D

2017-04-01

Absorption/distribution/metabolism/excretion (ADME)-related studies are mandatory in agrochemical development/registration, but can also play a valuable role in the discovery process. In combination with target-site potency, bioavailability/ADME characteristics determine agrochemical bioactivity and selectivity, and these concerns can dictate the fate of a discovery lead area. Bioavailability/ADME research was critical to the eventual commercialization of three different insecticide chemistries examined in this paper. In one situation, improved systemicity in anthranilic diamides was required to expand pest spectrum. In another, ADME tools were needed to improve the selective toxicity and non-target safety of sodium channel blocker insecticides. Finally, differential ADME characteristics of two classes of hormone agonists dictated differential insecticidal activity, and were useful in optimizing the dibenzoylhydrazine ecdysone agonists. ADME discovery research will help companies to advance novel, efficacious and selective agrochemicals, but organizational patience and a desire to understand lead areas in depth are required. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Reprogramming of orientation columns in visual cortex: a domino effect

PubMed Central

Bachatene, Lyes; Bharmauria, Vishal; Cattan, Sarah; Rouat, Jean; Molotchnikoff, Stéphane

2015-01-01

Cortical organization rests upon the fundamental principle that neurons sharing similar properties are co-located. In the visual cortex, neurons are organized into orientation columns. In a column, most neurons respond optimally to the same axis of an oriented edge, that is, the preferred orientation. This orientation selectivity is believed to be absolute in adulthood. However, in a fully mature brain, it has been established that neurons change their selectivity following sensory experience or visual adaptation. Here, we show that after applying an adapter away from the tested cells, neurons whose receptive fields were located remotely from the adapted site also exhibit a novel selectivity in spite of the fact that they were not adapted. These results indicate a robust reconfiguration and remapping of the orientation domains with respect to each other thus removing the possibility of an orientation hole in the new hypercolumn. These data suggest that orientation columns transcend anatomy, and are almost strictly functionally dynamic. PMID:25801392

DNA sequence variation and selection of tag single-nucleotide polymorphisms at candidate genes for drought-stress response in Pinus taeda L.

PubMed

González-Martínez, Santiago C; Ersoz, Elhan; Brown, Garth R; Wheeler, Nicholas C; Neale, David B

2006-03-01

Genetic association studies are rapidly becoming the experimental approach of choice to dissect complex traits, including tolerance to drought stress, which is the most common cause of mortality and yield losses in forest trees. Optimization of association mapping requires knowledge of the patterns of nucleotide diversity and linkage disequilibrium and the selection of suitable polymorphisms for genotyping. Moreover, standard neutrality tests applied to DNA sequence variation data can be used to select candidate genes or amino acid sites that are putatively under selection for association mapping. In this article, we study the pattern of polymorphism of 18 candidate genes for drought-stress response in Pinus taeda L., an important tree crop. Data analyses based on a set of 21 putatively neutral nuclear microsatellites did not show population genetic structure or genomewide departures from neutrality. Candidate genes had moderate average nucleotide diversity at silent sites (pi(sil) = 0.00853), varying 100-fold among single genes. The level of within-gene LD was low, with an average pairwise r2 of 0.30, decaying rapidly from approximately 0.50 to approximately 0.20 at 800 bp. No apparent LD among genes was found. A selective sweep may have occurred at the early-response-to-drought-3 (erd3) gene, although population expansion can also explain our results and evidence for selection was not conclusive. One other gene, ccoaomt-1, a methylating enzyme involved in lignification, showed dimorphism (i.e., two highly divergent haplotype lineages at equal frequency), which is commonly associated with the long-term action of balancing selection. Finally, a set of haplotype-tagging SNPs (htSNPs) was selected. Using htSNPs, a reduction of genotyping effort of approximately 30-40%, while sampling most common allelic variants, can be gained in our ongoing association studies for drought tolerance in pine.

Residues of E. coli topoisomerase I conserved for interaction with a specific cytosine base to facilitate DNA cleavage

PubMed Central

Narula, Gagandeep; Tse-Dinh, Yuk-Ching

2012-01-01

Bacterial and archaeal topoisomerase I display selectivity for a cytosine base 4 nt upstream from the DNA cleavage site. Recently, the solved crystal structure of Escherichia coli topoisomerase I covalently linked to a single-stranded oligonucleotide revealed that R169 and R173 interact with the cytosine base at the −4 position via hydrogen bonds while the phenol ring of Y177 wedges between the bases at the −4 and the −5 position. Substituting R169 to alanine changed the selectivity of the enzyme for the base at the −4 position from a cytosine to an adenine. The R173A mutant displayed similar sequence selectivity as the wild-type enzyme, but weaker cleavage and relaxation activity. Mutation of Y177 to serine or alanine rendered the enzyme inactive. Although mutation of each of these residues led to different outcomes, R169, R173 and Y177 work together to interact with a cytosine base at the −4 position to facilitate DNA cleavage. These strictly conserved residues might act after initial substrate binding as a Molecular Ruler to form a protein–DNA complex with the scissile phosphate positioned at the active site for optimal DNA cleavage by the tyrosine hydroxyl nucleophile to facilitate DNA cleavage in the reaction pathway. PMID:22833607

A method to predict different mechanisms for blood-brain barrier permeability of CNS activity compounds in Chinese herbs using support vector machine.

PubMed

Jiang, Ludi; Chen, Jiahua; He, Yusu; Zhang, Yanling; Li, Gongyu

2016-02-01

The blood-brain barrier (BBB), a highly selective barrier between central nervous system (CNS) and the blood stream, restricts and regulates the penetration of compounds from the blood into the brain. Drugs that affect the CNS interact with the BBB prior to their target site, so the prediction research on BBB permeability is a fundamental and significant research direction in neuropharmacology. In this study, we combed through the available data and then with the help of support vector machine (SVM), we established an experiment process for discovering potential CNS compounds and investigating the mechanisms of BBB permeability of them to advance the research in this field four types of prediction models, referring to CNS activity, BBB permeability, passive diffusion and efflux transport, were obtained in the experiment process. The first two models were used to discover compounds which may have CNS activity and also cross the BBB at the same time; the latter two were used to elucidate the mechanism of BBB permeability of those compounds. Three optimization parameter methods, Grid Search, Genetic Algorithm (GA), and Particle Swarm Optimization (PSO), were used to optimize the SVM models. Then, four optimal models were selected with excellent evaluation indexes (the accuracy, sensitivity and specificity of each model were all above 85%). Furthermore, discrimination models were utilized to study the BBB properties of the known CNS activity compounds in Chinese herbs and this may guide the CNS drug development. With the relatively systematic and quick approach, the application rationality of traditional Chinese medicines for treating nervous system disease in the clinical practice will be improved.

Optimizing DMPK Properties: Experiences from a Big Pharma DMPK Department.

PubMed

Sohlenius-Sternbeck, Anna-Karin; Janson, Juliette; Bylund, Johan; Baranczewski, Pawel; Breitholtz-Emanuelsson, Anna; Hu, Yin; Tsoi, Carrie; Lindgren, Anders; Gissberg, Olle; Bueters, Tjerk; Briem, Sveinn; Juric, Sanja; Johansson, Jenny; Bergh, Margareta; Hoogstraate, Janet

2016-01-01

The disposition of a drug is dependent on interactions between the body and the drug, its molecular properties and the physical and biological barriers presented in the body. In order for a drug to have a desired pharmacological effect it has to have the right properties to be able to reach the target site in sufficient concentration. This review details how drug metabolism and pharmacokinetics (DMPK) and physicochemical deliveries played an important role in data interpretation and compound optimization at AstraZeneca R&D in Södertälje, Sweden. A selection of assays central in the evaluation of the DMPK properties of new chemical entities is presented, with guidance and consideration on assay outcome interpretation. Early in projects, solubility, LogD, permeability and metabolic stability were measured to support effective optimization of DMPK properties. Changes made to facilitate high throughput, efficient bioanalysis and the handling of large amounts of samples are described. Already early in drug discovery, we used an integrated approach for the prediction of the fate of drugs in human (early dose to man) based on data obtained from in vitro experiments. The early dose to man was refined with project progression, which triggered more intricate assays and experiments. At later stages, preclinical in vivo pharmacokinetic (PK) data was integrated with pharmacodynamics (PD) to allow predictions of required dose, dose intervals and exposure profile to achieve the desired effect in man. A well-defined work flow of DMPK activities from early lead identification up to the selection of a candidate drug was developed. This resulted in a cost effective and efficient optimization of chemical series, and facilitated informed decision making throughout project progress.

Developmental stage related patterns of codon usage and genomic GC content: searching for evolutionary fingerprints with models of stem cell differentiation

PubMed Central

2007-01-01

Background The usage of synonymous codons shows considerable variation among mammalian genes. How and why this usage is non-random are fundamental biological questions and remain controversial. It is also important to explore whether mammalian genes that are selectively expressed at different developmental stages bear different molecular features. Results In two models of mouse stem cell differentiation, we established correlations between codon usage and the patterns of gene expression. We found that the optimal codons exhibited variation (AT- or GC-ending codons) in different cell types within the developmental hierarchy. We also found that genes that were enriched (developmental-pivotal genes) or specifically expressed (developmental-specific genes) at different developmental stages had different patterns of codon usage and local genomic GC (GCg) content. Moreover, at the same developmental stage, developmental-specific genes generally used more GC-ending codons and had higher GCg content compared with developmental-pivotal genes. Further analyses suggest that the model of translational selection might be consistent with the developmental stage-related patterns of codon usage, especially for the AT-ending optimal codons. In addition, our data show that after human-mouse divergence, the influence of selective constraints is still detectable. Conclusion Our findings suggest that developmental stage-related patterns of gene expression are correlated with codon usage (GC3) and GCg content in stem cell hierarchies. Moreover, this paper provides evidence for the influence of natural selection at synonymous sites in the mouse genome and novel clues for linking the molecular features of genes to their patterns of expression during mammalian ontogenesis. PMID:17349061

Conceptual design of multi-source CCS pipeline transportation network for Polish energy sector

NASA Astrophysics Data System (ADS)

Isoli, Niccolo; Chaczykowski, Maciej

2017-11-01

The aim of this study was to identify an optimal CCS transport infrastructure for Polish energy sector in regards of selected European Commission Energy Roadmap 2050 scenario. The work covers identification of the offshore storage site location, CO2 pipeline network design and sizing for deployment at a national scale along with CAPEX analysis. It was conducted for the worst-case scenario, wherein the power plants operate under full-load conditions. The input data for the evaluation of CO2 flow rates (flue gas composition) were taken from the selected cogeneration plant with the maximum electric capacity of 620 MW and the results were extrapolated from these data given the power outputs of the remaining units. A graph search algorithm was employed to estimate pipeline infrastructure costs to transport 95 MT of CO2 annually, which amount to about 612.6 M€. Additional pipeline infrastructure costs will have to be incurred after 9 years of operation of the system due to limited storage site capacity. The results show that CAPEX estimates for CO2 pipeline infrastructure cannot be relied on natural gas infrastructure data, since both systems exhibit differences in pipe wall thickness that affects material cost.

DNA origami metallized site specifically to form electrically conductive nanowires.

PubMed

Pearson, Anthony C; Liu, Jianfei; Pound, Elisabeth; Uprety, Bibek; Woolley, Adam T; Davis, Robert C; Harb, John N

2012-09-06

DNA origami is a promising tool for use as a template in the design and fabrication of nanoscale structures. The ability to engineer selected staple strands on a DNA origami structure provides a high density of addressable locations across the structure. Here we report a method using site-specific attachment of gold nanoparticles to modified staple strands and subsequent metallization to fabricate conductive wires from DNA origami templates. We have modified DNA origami structures by lengthening each staple strand in select regions with a 10-base nucleotide sequence and have attached DNA-modified gold nanoparticles to the lengthened staple strands via complementary base-pairing. The high density of extended staple strands allowed the gold nanoparticles to pack tightly in the modified regions of the DNA origami, where the measured median gap size between neighboring particles was 4.1 nm. Gold metallization processes were optimized so that the attached gold nanoparticles grew until gaps between particles were filled and uniform continuous nanowires were formed. Finally, electron beam lithography was used to pattern electrodes in order to measure the electrical conductivity of metallized DNA origami, which showed an average resistance of 2.4 kΩ per metallized structure.

Sunscreen use optimized by two consecutive applications

PubMed Central

Torsnes, Linnea R.; Philipsen, Peter A.; Wulf, Hans Christian

2018-01-01

Sunscreen users are often inadequately protected and become sunburned. This study aimed to investigate how much two consecutive sunscreen applications increased the quantity of sunscreen applied and decreased the skin area left without sunscreen (missed area) compared to a single application. Thirty-one healthy volunteers wearing swimwear were included and applied sunscreen two consecutive times in a laboratory environment. Participants had pictures taken in black light before and after each application. As sunscreens absorb black light, the darkness of the skin increased with increasing amounts of sunscreen applied. We conducted a standard curve establishing a link between change in picture darkness and quantity of sunscreen. The quantity of sunscreen at selected skin sites as well as the percentage of missed area was determined after each application. Participants had missed a median of 20% of their available body surface after a single application. After double application they had missed 9%. The decrease in missed areas was significant for the whole body surface and for each of the body regions separately. The median participant had applied between 13% and 100% more sunscreen at the selected skin sites after double application than after single application. We recommend double application, especially before intense sun exposure. PMID:29590142

Isolation of site-specific anharmonicities of individual water molecules in the I-·(H2O)2 complex using tag-free, isotopomer selective IR-IR double resonance

NASA Astrophysics Data System (ADS)

Yang, Nan; Duong, Chinh H.; Kelleher, Patrick J.; Johnson, Mark A.; McCoy, Anne B.

2017-12-01

We reveal the microscopic mechanics of iodide ion microhydration by recording the isotopomer-selective vibrational spectra of the I-·(H2O)·(D2O), I-·(HOD)·(D2O), and I-·(DOH)·(H2O) isotopologues using a new class of ion spectrometer that is optimized to carry out two-color, IR-IR photodissociation in a variety of pump-probe schemes. Using one of these, we record the linear absorption spectrum of a cryogenically cooled cluster without the use of a messenger ;tag;. In another protocol, we reveal the spectra of individual H2O and D2O molecules embedded in each of the two possible binding sites in the iodide dihydrate, as well as the bands due to individual OH and OD groups in each of the four local binding environments. Finally, we demonstrate how temperature dependent isotopic scrambling among the spectral features can be used to monitor the onset of large amplitude motion, heretofore inferred from changes in the envelope of the OH stretching vibrational manifold.

Detection of Pathways Affected by Positive Selection in Primate Lineages Ancestral to Humans

PubMed Central

Moretti, S.; Davydov, I.I.; Excoffier, L.

2017-01-01

Abstract Gene set enrichment approaches have been increasingly successful in finding signals of recent polygenic selection in the human genome. In this study, we aim at detecting biological pathways affected by positive selection in more ancient human evolutionary history. Focusing on four branches of the primate tree that lead to modern humans, we tested all available protein coding gene trees of the Primates clade for signals of adaptation in these branches, using the likelihood-based branch site test of positive selection. The results of these locus-specific tests were then used as input for a gene set enrichment test, where whole pathways are globally scored for a signal of positive selection, instead of focusing only on outlier “significant” genes. We identified signals of positive selection in several pathways that are mainly involved in immune response, sensory perception, metabolism, and energy production. These pathway-level results are highly significant, even though there is no functional enrichment when only focusing on top scoring genes. Interestingly, several gene sets are found significant at multiple levels in the phylogeny, but different genes are responsible for the selection signal in the different branches. This suggests that the same function has been optimized in different ways at different times in primate evolution. PMID:28333345

Economic decision making and the application of nonparametric prediction models

USGS Publications Warehouse

Attanasi, E.D.; Coburn, T.C.; Freeman, P.A.

2008-01-01

Sustained increases in energy prices have focused attention on gas resources in low-permeability shale or in coals that were previously considered economically marginal. Daily well deliverability is often relatively small, although the estimates of the total volumes of recoverable resources in these settings are often large. Planning and development decisions for extraction of such resources must be areawide because profitable extraction requires optimization of scale economies to minimize costs and reduce risk. For an individual firm, the decision to enter such plays depends on reconnaissance-level estimates of regional recoverable resources and on cost estimates to develop untested areas. This paper shows how simple nonparametric local regression models, used to predict technically recoverable resources at untested sites, can be combined with economic models to compute regional-scale cost functions. The context of the worked example is the Devonian Antrim-shale gas play in the Michigan basin. One finding relates to selection of the resource prediction model to be used with economic models. Models chosen because they can best predict aggregate volume over larger areas (many hundreds of sites) smooth out granularity in the distribution of predicted volumes at individual sites. This loss of detail affects the representation of economic cost functions and may affect economic decisions. Second, because some analysts consider unconventional resources to be ubiquitous, the selection and order of specific drilling sites may, in practice, be determined arbitrarily by extraneous factors. The analysis shows a 15-20% gain in gas volume when these simple models are applied to order drilling prospects strategically rather than to choose drilling locations randomly. Copyright ?? 2008 Society of Petroleum Engineers.

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...

Where to deliver baits for deworming urban red foxes for Echinococcus multilocularis control: new protocol for micro-habitat modeling of fox denning requirements.

PubMed

Ikeda, Takako; Yoshimura, Masashi; Onoyama, Keiichi; Oku, Yuzaburo; Nonaka, Nariaki; Katakura, Ken

2014-08-06

Deworming wild foxes by baiting with the anthelmintic praziquantel is being established as a preventive technique against environmental contamination with Echinococcus multilocularis eggs. Improvement of the cost-benefit performance of baiting treatment is required urgently to raise and maintain the efficacy of deworming. We established a spatial model of den site selection by urban red foxes, the definitive host, to specify the optimal micro-habitats for delivering baits in a new modeling approach modified for urban fox populations. The model was established for two cities (Obihiro and Sapporo) in Hokkaido, Japan, in which a sylvatic cycle of E. multilocularis is maintained. The two cities have different degrees of urbanization. The modeling process was designed to detect the best combination of key environmental factors and spatial scale that foxes pay attention to most (here named 'heeding range') when they select den sites. All possible models were generated using logistic regression analysis, with "presence" or "absence" of fox den as the objective variable, and nine landscape categories customized for urban environments as predictor variables to detect the best subset of predictors. This procedure was conducted for each of ten sizes of concentric circles from dens and control points to detect the best circle size. Out of all models generated, the most parsimonious model was selected using Akaike's Information Criterion (AIC) inspection. Our models suggest that fox dens in Obihiro are located at the center of a circle with 500 m radius including low percentages of wide roads, narrow roads, and occupied buildings, but high percentages of green covered areas; the dens in Sapporo within 300 m radius with low percentages of wide roads, occupied buildings, but high percentages of riverbeds and green covered areas. The variation of the models suggests the necessity of accumulating models for various types of cities in order to reveal the patterns of the model. Our denning models indicating suitable sites for delivering baits will improve the cost-benefit performance of the campaign. Our modeling protocol is suitable for the urban landscapes, and for extracting the heeding range when they select the den sites.

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

Mackillop, William J., E-mail: william.mackillop@krcc.on.ca; Kong, Weidong; Brundage, Michael

Purpose: Estimates of the appropriate rate of use of radiation therapy (RT) are required for planning and monitoring access to RT. Our objective was to compare estimates of the appropriate rate of use of RT derived from mathematical models, with the rate observed in a population of patients with optimal access to RT. Methods and Materials: The rate of use of RT within 1 year of diagnosis (RT{sub 1Y}) was measured in the 134,541 cases diagnosed in Ontario between November 2009 and October 2011. The lifetime rate of use of RT (RT{sub LIFETIME}) was estimated by the multicohort utilization tablemore » method. Poisson regression was used to evaluate potential barriers to access to RT and to identify a benchmark subpopulation with unimpeded access to RT. Rates of use of RT were measured in the benchmark subpopulation and compared with published evidence-based estimates of the appropriate rates. Results: The benchmark rate for RT{sub 1Y}, observed under conditions of optimal access, was 33.6% (95% confidence interval [CI], 33.0%-34.1%), and the benchmark for RT{sub LIFETIME} was 41.5% (95% CI, 41.2%-42.0%). Benchmarks for RT{sub LIFETIME} for 4 of 5 selected sites and for all cancers combined were significantly lower than the corresponding evidence-based estimates. Australian and Canadian evidence-based estimates of RT{sub LIFETIME} for 5 selected sites differed widely. RT{sub LIFETIME} in the overall population of Ontario was just 7.9% short of the benchmark but 20.9% short of the Australian evidence-based estimate of the appropriate rate. Conclusions: Evidence-based estimates of the appropriate lifetime rate of use of RT may overestimate the need for RT in Ontario.« less

Systematically biological prioritizing remediation sites based on datasets of biological investigations and heavy metals in soil

NASA Astrophysics Data System (ADS)

Lin, Wei-Chih; Lin, Yu-Pin; Anthony, Johnathen

2015-04-01

Heavy metal pollution has adverse effects on not only the focal invertebrate species of this study, such as reduction in pupa weight and increased larval mortality, but also on the higher trophic level organisms which feed on them, either directly or indirectly, through the process of biomagnification. Despite this, few studies regarding remediation prioritization take species distribution or biological conservation priorities into consideration. This study develops a novel approach for delineating sites which are both contaminated by any of 5 readily bioaccumulated heavy metal soil contaminants and are of high ecological importance for the highly mobile, low trophic level focal species. The conservation priority of each site was based on the projected distributions of 6 moth species simulated via the presence-only maximum entropy species distribution model followed by the subsequent application of a systematic conservation tool. In order to increase the number of available samples, we also integrated crowd-sourced data with professionally-collected data via a novel optimization procedure based on a simulated annealing algorithm. This integration procedure was important since while crowd-sourced data can drastically increase the number of data samples available to ecologists, still the quality or reliability of crowd-sourced data can be called into question, adding yet another source of uncertainty in projecting species distributions. The optimization method screens crowd-sourced data in terms of the environmental variables which correspond to professionally-collected data. The sample distribution data was derived from two different sources, including the EnjoyMoths project in Taiwan (crowd-sourced data) and the Global Biodiversity Information Facility (GBIF) ?eld data (professional data). The distributions of heavy metal concentrations were generated via 1000 iterations of a geostatistical co-simulation approach. The uncertainties in distributions of the heavy metals were then quantified based on the overall consistency between realizations. Finally, Information-Gap Decision Theory (IGDT) was applied to rank the remediation priorities of contaminated sites in terms of both spatial consensus of multiple heavy metal realizations and the priority of specific conservation areas. Our results show that the crowd-sourced optimization algorithm developed in this study is effective at selecting suitable data from crowd-sourced data. By using this technique the available sample data increased to a total number of 96, 162, 72, 62, 69 and 62 or, that is, 2.6, 1.6, 2.5, 1.6, 1.2 and 1.8 times that originally available through the GBIF professionally-assembled database. Additionally, for all species considered the performance of models, in terms of test-AUC values, based on the combination of both data sources exceeded those models which were based on a single data source. Furthermore, the additional optimization-selected data lowered the overall variability, and therefore uncertainty, of model outputs. Based on the projected species distributions, our results revealed that around 30% of high species hotspot areas were also identified as contaminated. The decision-making tool, IGDT, successfully yielded remediation plans in terms of specific ecological value requirements, false positive tolerance rates of contaminated areas, and expected decision robustness. The proposed approach can be applied both to identify high conservation priority sites contaminated by heavy metals, based on the combination of screened crowd-sourced and professionally-collected data, and in making robust remediation decisions.

Selection of optimal sensors for predicting performance of polymer electrolyte membrane fuel cell

NASA Astrophysics Data System (ADS)

Mao, Lei; Jackson, Lisa

2016-10-01

In this paper, sensor selection algorithms are investigated based on a sensitivity analysis, and the capability of optimal sensors in predicting PEM fuel cell performance is also studied using test data. The fuel cell model is developed for generating the sensitivity matrix relating sensor measurements and fuel cell health parameters. From the sensitivity matrix, two sensor selection approaches, including the largest gap method, and exhaustive brute force searching technique, are applied to find the optimal sensors providing reliable predictions. Based on the results, a sensor selection approach considering both sensor sensitivity and noise resistance is proposed to find the optimal sensor set with minimum size. Furthermore, the performance of the optimal sensor set is studied to predict fuel cell performance using test data from a PEM fuel cell system. Results demonstrate that with optimal sensors, the performance of PEM fuel cell can be predicted with good quality.

Modeling Training Site Vegetation Coverage Probability with a Random Optimizing Procedure: An Artificial Neural Network Approach.

DTIC Science & Technology

1998-05-01

Coverage Probability with a Random Optimization Procedure: An Artificial Neural Network Approach by Biing T. Guan, George Z. Gertner, and Alan B...Modeling Training Site Vegetation Coverage Probability with a Random Optimizing Procedure: An Artificial Neural Network Approach 6. AUTHOR(S) Biing...coverage based on past coverage. Approach A literature survey was conducted to identify artificial neural network analysis techniques applicable for

To Eat or Not to Eat: An Easy Simulation of Optimal Diet Selection in the Classroom

ERIC Educational Resources Information Center

Ray, Darrell L.

2010-01-01

Optimal diet selection, a component of optimal foraging theory, suggests that animals should select a diet that either maximizes energy or nutrient consumption per unit time or minimizes the foraging time needed to attain required energy or nutrients. In this exercise, students simulate the behavior of foragers that either show no foraging…

Method of generating features optimal to a dataset and classifier

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

Bruillard, Paul J.; Gosink, Luke J.; Jarman, Kenneth D.

A method of generating features optimal to a particular dataset and classifier is disclosed. A dataset of messages is inputted and a classifier is selected. An algebra of features is encoded. Computable features that are capable of describing the dataset from the algebra of features are selected. Irredundant features that are optimal for the classifier and the dataset are selected.

Profiling Charge Complementarity and Selectivity for Binding at the Protein Surface

PubMed Central

Sulea, Traian; Purisima, Enrico O.

2003-01-01

A novel analysis and representation of the protein surface in terms of electrostatic binding complementarity and selectivity is presented. The charge optimization methodology is applied in a probe-based approach that simulates the binding process to the target protein. The molecular surface is color coded according to calculated optimal charge or according to charge selectivity, i.e., the binding cost of deviating from the optimal charge. The optimal charge profile depends on both the protein shape and charge distribution whereas the charge selectivity profile depends only on protein shape. High selectivity is concentrated in well-shaped concave pockets, whereas solvent-exposed convex regions are not charge selective. This suggests the synergy of charge and shape selectivity hot spots toward molecular selection and recognition, as well as the asymmetry of charge selectivity at the binding interface of biomolecular systems. The charge complementarity and selectivity profiles map relevant electrostatic properties in a readily interpretable way and encode information that is quite different from that visualized in the standard electrostatic potential map of unbound proteins. PMID:12719221

FISH-Based Analysis of Clonally Derived CHO Cell Populations Reveals High Probability for Transgene Integration in a Terminal Region of Chromosome 1 (1q13).

PubMed

Li, Shengwei; Gao, Xiaoping; Peng, Rui; Zhang, Sheng; Fu, Wei; Zou, Fangdong

A basic goal in the development of recombinant proteins is the generation of cell lines that express the desired protein stably over many generations. Here, we constructed engineered Chinese hamster ovary cell lines (CHO-S) with a pCHO-hVR1 vector that carried an extracellular domain of a VEGF receptor (VR) fusion gene. Forty-five clones with high hVR1 expression were selected for karyotype analysis. Using fluorescence in situ hybridization (FISH) and G-banding, we found that pCHO-hVR1 was integrated into three chromosomes, including chromosomes 1, Z3 and Z4. Four clones were selected to evaluate their productivity under non-fed, non-optimized shake flask conditions. The results showed that clones 1 and 2 with integration sites on chromosome 1 revealed high levels of hVR1 products (shake flask of approximately 800 mg/L), whereas clones 3 and 4 with integration sites on chromosomes Z3 or Z4 had lower levels of hVR1 products. Furthermore, clones 1 and 2 maintained their productivity stabilities over a continuous period of 80 generations, and clones 3 and 4 showed significant declines in their productivities in the presence of selection pressure. Finally, pCHO-hVR1 localized to the same region at chromosome 1q13, the telomere region of normal chromosome 1. In this study, these results demonstrate that the integration of exogenous hVR1 gene on chromosome 1, band q13, may create a high protein-producing CHO-S cell line, suggesting that chromosome 1q13 may contain a useful target site for the high expression of exogenous protein. This study shows that the integration into the target site of chromosome 1q13 may avoid the problems of random integration that cause gene silencing or also overcome position effects, facilitating exogenous gene expression in CHO-S cells.

Optimal rates for phylogenetic inference and experimental design in the era of genome-scale datasets.

PubMed

Dornburg, Alex; Su, Zhuo; Townsend, Jeffrey P

2018-06-25

With the rise of genome- scale datasets there has been a call for increased data scrutiny and careful selection of loci appropriate for attempting the resolution of a phylogenetic problem. Such loci are desired to maximize phylogenetic information content while minimizing the risk of homoplasy. Theory posits the existence of characters that evolve under such an optimum rate, and efforts to determine optimal rates of inference have been a cornerstone of phylogenetic experimental design for over two decades. However, both theoretical and empirical investigations of optimal rates have varied dramatically in their conclusions: spanning no relationship to a tight relationship between the rate of change and phylogenetic utility. Here we synthesize these apparently contradictory views, demonstrating both empirical and theoretical conditions under which each is correct. We find that optimal rates of characters-not genes-are generally robust to most experimental design decisions. Moreover, consideration of site rate heterogeneity within a given locus is critical to accurate predictions of utility. Factors such as taxon sampling or the targeted number of characters providing support for a topology are additionally critical to the predictions of phylogenetic utility based on the rate of character change. Further, optimality of rates and predictions of phylogenetic utility are not equivalent, demonstrating the need for further development of comprehensive theory of phylogenetic experimental design.

Access to site-specific Fc-cRGD peptide conjugates through streamlined expressed protein ligation.

PubMed

Frutos, S; Jordan, J B; Bio, M M; Muir, T W; Thiel, O R; Vila-Perelló, M

2016-10-12

An ideal drug should be highly effective, non-toxic and be delivered by a convenient and painless single dose. We are still far from such optimal treatment but peptides, with their high target selectivity and low toxicity profiles, provide a very attractive platform from which to strive towards it. One of the major limitations of peptide drugs is their high clearance rates, which limit dosage regimen options. Conjugation to antibody Fc domains is a viable strategy to improve peptide stability by increasing their hydrodynamic radius and hijacking the Fc recycling pathway. We report the use of a split-intein based semi-synthetic approach to site-specifically conjugate a synthetic integrin binding peptide to an Fc domain. The strategy described here allows conjugating synthetic peptides to Fc domains, which is not possible via genetic methods, fully maintaining the ability of both the Fc domain and the bioactive peptide to interact with their binding partners.

Pediatric thermal injury: acute care and reconstruction update.

PubMed

Armour, Alexis D; Billmire, David A

2009-07-01

The acute and reconstructive care of each pediatric burn patient presents unique challenges to the plastic surgeon and the burn care team. : The purpose of this review article is to highlight the interdependence between the acute and reconstructive needs of pediatric burn patients as it pertains to each anatomical site. Relevant principles of acute pediatric burn care and burn reconstruction are outlined, based on the authors' experience and review of the literature. The need for late reconstruction in pediatric burn survivors is significantly influenced by the acute surgical and rehabilitative treatments. With their vulnerability to airway swelling, hypothermia, pulmonary edema, and ischemia-reperfusion injury, pediatric patients with large burns require precise, life-saving treatment in the acute phase. Decision-making in pediatric burn reconstruction must take into account the patient's future growth, maturity, and often lack of suitable donor sites. Appropriately selected reconstructive techniques are essential to optimize function, appearance, and quality of life in pediatric burn survivors.

Factors affecting microbial 2,4,6-trinitrotoluene mineralization in contaminated soil

USGS Publications Warehouse

Bradley, P.M.; Chapelle, F.H.

1995-01-01

The influence of selected environmental factors on microbial TNT mineralization in soils collected from a TNT-contaminated site at Weldon Spring, MO, was examined using uniformly ring-labeled [14C]TNT. Microbial TNT mineralization was significantly inhibited by the addition of cellobiose and syringate. This response suggests that the indigenous microorganisms are capable of metabolizing TNT but preferentially utilize less recalcitrant substrates when available. The observed inhibition of TNT mineralization by TNT concentrations higher than 100 ??mol/kg of soil and by dry soil conditions suggests that toxic inhibition of microbial activity at high TNT concentrations and the periodic drying of these soils have contributed to the long-term persistence of TNT at Weldon Spring. In comparison to aerobic microcosms, mineralization was inhibited in anaerobic microcosms and in microcosms with a headspace of air amended with oxygen, suggesting that a mosaic of aerobic and anaerobic conditions may optimize TNT degradation at this site.

A further step toward an optimal ensemble of classifiers for peptide classification, a case study: HIV protease.

PubMed

Nanni, Loris; Lumini, Alessandra

2009-01-01

The focuses of this work are: to propose a novel method for building an ensemble of classifiers for peptide classification based on substitution matrices; to show the importance to select a proper set of the parameters of the classifiers that build the ensemble of learning systems. The HIV-1 protease cleavage site prediction problem is here studied. The results obtained by a blind testing protocol are reported, the comparison with other state-of-the-art approaches, based on ensemble of classifiers, allows to quantify the performance improvement obtained by the systems proposed in this paper. The simulation based on experimentally determined protease cleavage data has demonstrated the success of these new ensemble algorithms. Particularly interesting it is to note that also if the HIV-1 protease cleavage site prediction problem is considered linearly separable we obtain the best performance using an ensemble of non-linear classifiers.

The Use of Epicardial Electrogram as a Simple Guide to Select the Optimal Site of Left Ventricular Pacing in Cardiac Resynchronization Therapy

PubMed Central

Fatemi, Marjaneh; Le Gal, Grégoire; Blanc, Jean-Jacques; Mansourati, Jacques; Etienne, Yves

2011-01-01

Cardiac resynchronization therapy (CRT) has been demonstrated to improve symptoms and survival in patients with left ventricular (LV) systolic dysfunction and dyssynchrony. To achieve this goal, the LV lead should be positioned in a region of delayed contraction. We hypothesized that pacing at the site of late electrical activation was also associated with long-term response to CRT. We conducted a retrospective study on 72 CRT patients. For each patient, we determined the electrical delay (ED) from the onset of QRS to the epicardial EGM and the ratio of ED to QRS duration (ED/QRS duration). After a followup of 30 ± 20 months, 47 patients responded to CRT. Responders had a significantly longer ED and greater ratio of ED/QRS duration than nonresponders. An ED/QRS duration ≥0.38 predicted a response to CRT with 89% specificity and 53% sensitivity. PMID:21403903

Motif discovery and motif finding from genome-mapped DNase footprint data.

PubMed

Kulakovskiy, Ivan V; Favorov, Alexander V; Makeev, Vsevolod J

2009-09-15

Footprint data is an important source of information on transcription factor recognition motifs. However, a footprinting fragment can contain no sequences similar to known protein recognition sites. Inspection of genome fragments nearby can help to identify missing site positions. Genome fragments containing footprints were supplied to a pipeline that constructed a position weight matrix (PWM) for different motif lengths and selected the optimal PWM. Fragments were aligned with the SeSiMCMC sampler and a new heuristic algorithm, Bigfoot. Footprints with missing hits were found for approximately 50% of factors. Adding only 2 bp on both sides of a footprinting fragment recovered most hits. We automatically constructed motifs for 41 Drosophila factors. New motifs can recognize footprints with a greater sensitivity at the same false positive rate than existing models. Also we discuss possible overfitting of constructed motifs. Software and the collection of regulatory motifs are freely available at http://line.imb.ac.ru/DMMPMM.

Myrmecophagy by Yellowstone grizzly bears

USGS Publications Warehouse

Mattson, D.J.

2001-01-01

I used data collected during a study of radio-marked grizzly bears (Ursus arctos horribilis) in the Yellowstone region from 1977 to 1992 to investigate myrmecophagy by this population. Although generally not an important source of energy for the bears (averaging 8 mm long) nested in logs over small ants (6 mm long) nested under stones. Optimal conditions for consumption of ants occurred on the warmest sites with ample substrate suitable for ant nests. For ants in mounds, this occurred at low elevations at non-forested sites. For ants in logs, this occurred at low elevations or on southerly aspects where there was abundant, large-diameter, well-decomposed woody debris under an open forest canopy. Grizzly bears selected moderately decomposed logs 4a??5 dm in diameter at midpoint. Ants will likely become a more important food for Yellowstone's grizzly bears as currently important foods decline, owing to disease and warming of the regional climate.

Binding modes of dihydroquinoxalinones in a homology model of bradykinin receptor 1.

PubMed

Ha, Sookhee N; Hey, Pat J; Ransom, Rick W; Harrell, C Meacham; Murphy, Kathryn L; Chang, Ray; Chen, Tsing-Bau; Su, Dai-Shi; Markowitz, M Kristine; Bock, Mark G; Freidinger, Roger M; Hess, Fred J

2005-05-27

We report the first homology model of human bradykinin receptor B1 generated from the crystal structure of bovine rhodopsin as a template. Using an automated docking procedure, two B1 receptor antagonists of the dihydroquinoxalinone structural class were docked into the receptor model. Site-directed mutagenesis data of the amino acid residues in TM1, TM3, TM6, and TM7 were incorporated to place the compounds in the binding site of the homology model of the human B1 bradykinin receptor. The best pose in agreement with the mutation data was selected for detailed study of the receptor-antagonist interaction. To test the model, the calculated antagonist-receptor binding energy was correlated with the experimentally measured binding affinity (K(i)) for nine dihydroquinoxalinone analogs. The model was used to gain insight into the molecular mechanism for receptor function and to optimize the dihydroquinoxalinone analogs.

Solar energy system economic evaluation for Elcam-Tempe, Tempe, Arizona and Elcam-San Diego, San Diego, California

NASA Technical Reports Server (NTRS)

1980-01-01

The long term economic performance of the solar energy system at its installation site is analyzed and four additional locations selected to demonstrate the viability of the design over a broad range of environmental and economic conditions. The economic analysis of the solar energy systems that were installed at Tempe, Arizona and San Diego, California, is developed for these and four other sites typical of a wide range of environmental and economic conditions in the continental United States. This analysis is accomplished based on the technical and economic models in the f Chart design procedure with inputs based on the characteristics of the installed system and local conditions. The results are expressed in terms of the economic parameters of present worth of system cost over a projected twenty year life: life cycle savings; year of positive savings; and year of payback for the optimized solar energy system at each of the analysis sites. The sensitivity of the economic evaluation to uncertainites in constituent system and economic variables is also investigated. The results demonstrate that the solar energy system is economically viable at all of the sites for which the analysis was conducted.

Photoacoustic imaging of angiogenesis in a subcutaneous islet transplant site in a murine model

NASA Astrophysics Data System (ADS)

Shi, Wei; Pawlick, Rena; Bruni, Antonio; Rafiei, Yasmin; Pepper, Andrew R.; Gala-Lopez, Boris; Choi, Min; Malcolm, Andrew; Zemp, Roger J.; Shapiro, A. M. James

2016-06-01

Islet transplantation (IT) is an established clinical therapy for select patients with type-1 diabetes. Clinically, the hepatic portal vein serves as the site for IT. Despite numerous advances in clinical IT, limitations remain, including early islet cell loss posttransplant, procedural complications, and the inability to effectively monitor islet grafts. Hence, alternative sites for IT are currently being explored, with the subcutaneous space as one potential option. When left unmodified, the subcutaneous space routinely fails to promote successful islet engraftment. However, when employing the previously developed subcutaneous "deviceless" technique, a favorable microenvironment for islet survival and function is established. In this technique, an angiocatheter was temporarily implanted subcutaneously, which facilitated angiogenesis to promote subsequent islet engraftment. This technique has been employed in preclinical animal models, providing a sufficient means to develop techniques to monitor functional aspects of the graft such as angiogenesis. Here, we utilize photoacoustic imaging to track angiogenesis during the priming of the subcutaneous site by the implanted catheter at 1 to 4 weeks postcatheter. Quantitative analysis on vessel densities shows gradual growth of vasculature in the implant position. These results demonstrate the ability to track angiogenesis, thus facilitating a means to optimize and assess the pretransplant microenvironment.

Predicting recreational fishing use of offshore petroleum platforms in the Central Gulf of Mexico

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

Gordon, W.R. Jr.

1987-01-01

This study is based on the premise that properly sited artificial reefs for optimal human recreational use, a predictive model based upon the marine travel patterns and behavior of marine recreational fishermen, is needed. This research used data gathered from a previous study that addressed the recreational fishing use of offshore oil and gas structures (Ditton and Auyong 1984); on-site data were also collected. The primary research objective was to generate a predictive model that can be applied to artificial-reef development efforts elsewhere. This study investigated the recreational-user patterns of selected petroleum platforms structures in the Central Gulf of Mexico.more » The petroleum structures offshore from the Louisiana coastline provide a unique research tool. Although intended to facilitate the exploration and recovery of hydrocarbons, petroleum platforms also serve as defacto artificial reefs, providing habitat for numerous species of fish and other marine life. Petroleum platforms were found to be the principal fishing destinations within the study area. On-site findings reveal that marine recreational fishermen were as mobile on water, as they are on land. On-site findings were used to assist in the development of a predictive model.« less

Technical approach to groundwater restoration. Final report

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

Not Available

1993-11-01

The Technical Approach to Groundwater Restoration (TAGR) provides general technical guidance to implement the groundwater restoration phase of the Uranium Mill Tailings Remedial Action (UMTRA) Project. The TAGR includes a brief overview of the surface remediation and groundwater restoration phases of the UMTRA Project and describes the regulatory requirements, the National Environmental Policy Act (NEPA) process, and regulatory compliance. A section on program strategy discusses program optimization, the role of risk assessment, the observational approach, strategies for meeting groundwater cleanup standards, and remedial action decision-making. A section on data requirements for groundwater restoration evaluates the data quality objectives (DQO) andmore » minimum data required to implement the options and comply with the standards. A section on sits implementation explores the development of a conceptual site model, approaches to site characterization, development of remedial action alternatives, selection of the groundwater restoration method, and remedial design and implementation in the context of site-specific documentation in the site observational work plan (SOWP) and the remedial action plan (RAP). Finally, the TAGR elaborates on groundwater monitoring necessary to evaluate compliance with the groundwater cleanup standards and protection of human health and the environment, and outlines licensing procedures.« less

Molecular Hybridization of Potent and Selective γ-Hydroxybutyric Acid (GHB) Ligands: Design, Synthesis, Binding Studies, and Molecular Modeling of Novel 3-Hydroxycyclopent-1-enecarboxylic Acid (HOCPCA) and trans-γ-Hydroxycrotonic Acid (T-HCA) Analogs.

PubMed

Krall, Jacob; Jensen, Claus Hatt; Bavo, Francesco; Falk-Petersen, Christina Birkedahl; Haugaard, Anne Stæhr; Vogensen, Stine Byskov; Tian, Yongsong; Nittegaard-Nielsen, Mia; Sigurdardóttir, Sara Björk; Kehler, Jan; Kongstad, Kenneth Thermann; Gloriam, David E; Clausen, Rasmus Prætorius; Harpsøe, Kasper; Wellendorph, Petrine; Frølund, Bente

2017-11-09

γ-Hydroxybutyric acid (GHB) is a neuroactive substance with specific high-affinity binding sites. To facilitate target identification and ligand optimization, we herein report a comprehensive structure-affinity relationship study for novel ligands targeting these binding sites. A molecular hybridization strategy was used based on the conformationally restricted 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) and the linear GHB analog trans-4-hydroxycrotonic acid (T-HCA). In general, all structural modifications performed on HOCPCA led to reduced affinity. In contrast, introduction of diaromatic substituents into the 4-position of T-HCA led to high-affinity analogs (medium nanomolar K i ) for the GHB high-affinity binding sites as the most high-affinity analogs reported to date. The SAR data formed the basis for a three-dimensional pharmacophore model for GHB ligands, which identified molecular features important for high-affinity binding, with high predictive validity. These findings will be valuable in the further processes of both target characterization and ligand identification for the high-affinity GHB binding sites.

Optimization of heavy metals total emission, case study: Bor (Serbia)

NASA Astrophysics Data System (ADS)

Ilić, Ivana; Bogdanović, Dejan; Živković, Dragana; Milošević, Novica; Todorović, Boban

2011-07-01

The town of Bor (Serbia) is one of the most polluted towns in southeastern Europe. The copper smelter which is situated in the centre of the town is the main pollutant, mostly because of its old technology, which leads to environmental pollution caused by higher concentrations of SO 2 and PM 10. These facts show that the word is about a very polluted region in Europe which, apart from harming human health in the region itself, poses a particular danger for wider area of southeastern Europe. Optimization of heavy metal's total emission was undertaken because years of long contamination of the soil with heavy metals of anthropogenic origin created a danger that those heavy metals may enter the food chains of animals and people, which can lead to disastrous consequences. This work represents the usage of Geographic Information System (GIS) for establishing a multifactor assessment model to quantitatively divide polluted zones and for selecting control sites in a linear programming model, combined with PROMETHEE/GAIA method, Screen View modeling system, and linear programming model. The results show that emissions at some control sites need to be cut for about 40%. In order to control the background of heavy metal pollution in Bor, the ecological environment must be improved.

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.

Nursing performance under high workload: a diary study on the moderating role of selection, optimization and compensation strategies.

PubMed

Baethge, Anja; Müller, Andreas; Rigotti, Thomas

2016-03-01

The aim of this study was to investigate whether selective optimization with compensation constitutes an individualized action strategy for nurses wanting to maintain job performance under high workload. High workload is a major threat to healthcare quality and performance. Selective optimization with compensation is considered to enhance the efficient use of intra-individual resources and, therefore, is expected to act as a buffer against the negative effects of high workload. The study applied a diary design. Over five consecutive workday shifts, self-report data on workload was collected at three randomized occasions during each shift. Self-reported job performance was assessed in the evening. Self-reported selective optimization with compensation was assessed prior to the diary reporting. Data were collected in 2010. Overall, 136 nurses from 10 German hospitals participated. Selective optimization with compensation was assessed with a nine-item scale that was specifically developed for nursing. The NASA-TLX scale indicating the pace of task accomplishment was used to measure workload. Job performance was assessed with one item each concerning performance quality and forgetting of intentions. There was a weaker negative association between workload and both indicators of job performance in nurses with a high level of selective optimization with compensation, compared with nurses with a low level. Considering the separate strategies, selection and compensation turned out to be effective. The use of selective optimization with compensation is conducive to nurses' job performance under high workload levels. This finding is in line with calls to empower nurses' individual decision-making. © 2015 John Wiley & Sons Ltd.

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...

Optimization of monitoring networks based on uncertainty quantification of model predictions of contaminant transport

NASA Astrophysics Data System (ADS)

Vesselinov, V. V.; Harp, D.

2010-12-01

The process of decision making to protect groundwater resources requires a detailed estimation of uncertainties in model predictions. Various uncertainties associated with modeling a natural system, such as: (1) measurement and computational errors; (2) uncertainties in the conceptual model and model-parameter estimates; (3) simplifications in model setup and numerical representation of governing processes, contribute to the uncertainties in the model predictions. Due to this combination of factors, the sources of predictive uncertainties are generally difficult to quantify individually. Decision support related to optimal design of monitoring networks requires (1) detailed analyses of existing uncertainties related to model predictions of groundwater flow and contaminant transport, (2) optimization of the proposed monitoring network locations in terms of their efficiency to detect contaminants and provide early warning. We apply existing and newly-proposed methods to quantify predictive uncertainties and to optimize well locations. An important aspect of the analysis is the application of newly-developed optimization technique based on coupling of Particle Swarm and Levenberg-Marquardt optimization methods which proved to be robust and computationally efficient. These techniques and algorithms are bundled in a software package called MADS. MADS (Model Analyses for Decision Support) is an object-oriented code that is capable of performing various types of model analyses and supporting model-based decision making. The code can be executed under different computational modes, which include (1) sensitivity analyses (global and local), (2) Monte Carlo analysis, (3) model calibration, (4) parameter estimation, (5) uncertainty quantification, and (6) model selection. The code can be externally coupled with any existing model simulator through integrated modules that read/write input and output files using a set of template and instruction files (consistent with the PEST I/O protocol). MADS can also be internally coupled with a series of built-in analytical simulators. MADS provides functionality to work directly with existing control files developed for the code PEST (Doherty 2009). To perform the computational modes mentioned above, the code utilizes (1) advanced Latin-Hypercube sampling techniques (including Improved Distributed Sampling), (2) various gradient-based Levenberg-Marquardt optimization methods, (3) advanced global optimization methods (including Particle Swarm Optimization), and (4) a selection of alternative objective functions. The code has been successfully applied to perform various model analyses related to environmental management of real contamination sites. Examples include source identification problems, quantification of uncertainty, model calibration, and optimization of monitoring networks. The methodology and software codes are demonstrated using synthetic and real case studies where monitoring networks are optimized taking into account the uncertainty in model predictions of contaminant transport.

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

NASA Astrophysics Data System (ADS)

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

2018-03-01

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

Development of an advanced support system for site investigations

NASA Astrophysics Data System (ADS)

Mizuno, T.; Hama, K.; Iwatsuki, T.; Semba, T.

2009-12-01

JAEA has the responsibility for R&D to enhance reliability of High Level Waste (HLW) disposal technology and to develop safety assessment methodology with associated databases; these should support both the implementer (NUMO) and the relevant regulatory organizations. With this responsibility, JAEA has initiated development of advanced technology in the field of Knowledge Engineering. Known as the Information Synthesis and Interpretation System (ISIS), it incorporates knowledge currently being obtained in the Underground Research Laboratory (URL) projects in Expert System (ES) modules for the Japanese HLW disposal program. This knowledge includes fundamental understanding of relevant geological environments, technical know-how for the application of complex investigation techniques, experience gained in earlier site work, etc. However, much knowledge is not undocumented because the knowledge is treated as tacit knowledge and, without focused action soon, may be permanently lost. Therefore, a new approach is necessary to transfer the knowledge obtained in these URL projects to support the site characterization and subsequent safety assessment of potential repository sites by NUMO and the formulation of guidelines by regulatory organizations. In this paper, we introduce the ES for selecting tracers for borehole drilling. ES is the system built by applying electronic information technology to support the planning, conducting investigations and assessing of investigation results. Tracers are generally used for borehole drilling to monitor and quantitatively assess the degree of contamination of groundwater by drilling fluid. JAEA uses fluorescent dye as tracer in drilling fluid. When a fluorescent dye is used for drilling, suitable type and concentration must be selected. The technical points to be considered are; 1) linearity of fluorescent spectrum intensity with variations in concentration, 2) pH dependence of fluorescent spectrum intensity, 3) stability of fluorescent dye, 4) sorption/adsorption properties for rock being investigated, 5) detection limit of analyzer, 6) comparison of the fluorescent spectrum with dissolved organics and tracers used in other boreholes. In addition, costs and environmental impact are important factors to be considered. Thus, significant knowledge is needed in selecting the tracer for actual investigations. Fortunately, the ES for tracer selection already contains much knowledge needed. For example, the chemical data set for a suite of fluorescence dyes is in the ES, along with guidelines for their use. Therefore, this ES can support the use of fluorescent dye as tracer in actual investigations, even if the investigating scientists have little or no experience with it. In conclusion, the ES modules are and will be built as a support system for future researchers to perform optimized site investigations in a user-friendly manner. In this paper, we introduce the ES for selection of borehole drilling fluid tracer. Eventually, ES covering the full range of site investigation methods will be developed.

Modelling Carbon Emissions in Calluna vulgaris-Dominated Ecosystems when Prescribed Burning and Wildfires Interact.

PubMed

Santana, Victor M; Alday, Josu G; Lee, HyoHyeMi; Allen, Katherine A; Marrs, Rob H

2016-01-01

A present challenge in fire ecology is to optimize management techniques so that ecological services are maximized and C emissions minimized. Here, we modeled the effects of different prescribed-burning rotation intervals and wildfires on carbon emissions (present and future) in British moorlands. Biomass-accumulation curves from four Calluna-dominated ecosystems along a north-south gradient in Great Britain were calculated and used within a matrix-model based on Markov Chains to calculate above-ground biomass-loads and annual C emissions under different prescribed-burning rotation intervals. Additionally, we assessed the interaction of these parameters with a decreasing wildfire return intervals. We observed that litter accumulation patterns varied between sites. Northern sites (colder and wetter) accumulated lower amounts of litter with time than southern sites (hotter and drier). The accumulation patterns of the living vegetation dominated by Calluna were determined by site-specific conditions. The optimal prescribed-burning rotation interval for minimizing annual carbon emissions also differed between sites: the optimal rotation interval for northern sites was between 30 and 50 years, whereas for southern sites a hump-backed relationship was found with the optimal interval either between 8 to 10 years or between 30 to 50 years. Increasing wildfire frequency interacted with prescribed-burning rotation intervals by both increasing C emissions and modifying the optimum prescribed-burning interval for minimum C emission. This highlights the importance of studying site-specific biomass accumulation patterns with respect to environmental conditions for identifying suitable fire-rotation intervals to minimize C emissions.

Construction of a directed hammerhead ribozyme library: towards the identification of optimal target sites for antisense-mediated gene inhibition.

PubMed Central

Pierce, M L; Ruffner, D E

1998-01-01

Antisense-mediated gene inhibition uses short complementary DNA or RNA oligonucleotides to block expression of any mRNA of interest. A key parameter in the success or failure of an antisense therapy is the identification of a suitable target site on the chosen mRNA. Ultimately, the accessibility of the target to the antisense agent determines target suitability. Since accessibility is a function of many complex factors, it is currently beyond our ability to predict. Consequently, identification of the most effective target(s) requires examination of every site. Towards this goal, we describe a method to construct directed ribozyme libraries against any chosen mRNA. The library contains nearly equal amounts of ribozymes targeting every site on the chosen transcript and the library only contains ribozymes capable of binding to that transcript. Expression of the ribozyme library in cultured cells should allow identification of optimal target sites under natural conditions, subject to the complexities of a fully functional cell. Optimal target sites identified in this manner should be the most effective sites for therapeutic intervention. PMID:9801305

A multi-model approach to nucleic acid-based drug development.

PubMed

Gautherot, Isabelle; Sodoyer, Regís

2004-01-01

With the advent of functional genomics and the shift of interest towards sequence-based therapeutics, the past decades have witnessed intense research efforts on nucleic acid-mediated gene regulation technologies. Today, RNA interference is emerging as a groundbreaking discovery, holding promise for development of genetic modulators of unprecedented potency. Twenty-five years after the discovery of antisense RNA and ribozymes, gene control therapeutics are still facing developmental difficulties, with only one US FDA-approved antisense drug currently available in the clinic. Limited predictability of target site selection models is recognized as one major stumbling block that is shared by all of the so-called complementary technologies, slowing the progress towards a commercial product. Currently employed in vitro systems for target site selection include RNAse H-based mapping, antisense oligonucleotide microarrays, and functional screening approaches using libraries of catalysts with randomized target-binding arms to identify optimal ribozyme/DNAzyme cleavage sites. Individually, each strategy has its drawbacks from a drug development perspective. Utilization of message-modulating sequences as therapeutic agents requires that their action on a given target transcript meets criteria of potency and selectivity in the natural physiological environment. In addition to sequence-dependent characteristics, other factors will influence annealing reactions and duplex stability, as well as nucleic acid-mediated catalysis. Parallel consideration of physiological selection systems thus appears essential for screening for nucleic acid compounds proposed for therapeutic applications. Cellular message-targeting studies face issues relating to efficient nucleic acid delivery and appropriate analysis of response. For reliability and simplicity, prokaryotic systems can provide a rapid and cost-effective means of studying message targeting under pseudo-cellular conditions, but such approaches also have limitations. To streamline nucleic acid drug discovery, we propose a multi-model strategy integrating high-throughput-adapted bacterial screening, followed by reporter-based and/or natural cellular models and potentially also in vitro assays for characterization of the most promising candidate sequences, before final in vivo testing.

Optimal management of substrates in anaerobic co-digestion: An ant colony algorithm approach.

PubMed

Verdaguer, Marta; Molinos-Senante, María; Poch, Manel

2016-04-01

Sewage sludge (SWS) is inevitably produced in urban wastewater treatment plants (WWTPs). The treatment of SWS on site at small WWTPs is not economical; therefore, the SWS is typically transported to an alternative SWS treatment center. There is increased interest in the use of anaerobic digestion (AnD) with co-digestion as an SWS treatment alternative. Although the availability of different co-substrates has been ignored in most of the previous studies, it is an essential issue for the optimization of AnD co-digestion. In a pioneering approach, this paper applies an Ant-Colony-Optimization (ACO) algorithm that maximizes the generation of biogas through AnD co-digestion in order to optimize the discharge of organic waste from different waste sources in real-time. An empirical application is developed based on a virtual case study that involves organic waste from urban WWTPs and agrifood activities. The results illustrate the dominate role of toxicity levels in selecting contributions to the AnD input. The methodology and case study proposed in this paper demonstrate the usefulness of the ACO approach in supporting a decision process that contributes to improving the sustainability of organic waste and SWS management. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mapping carbon flux uncertainty and selecting optimal locations for future flux towers in the Great Plains

USGS Publications Warehouse

Gu, Yingxin; Howard, Daniel M.; Wylie, Bruce K.; Zhang, Li

2012-01-01

Flux tower networks (e. g., AmeriFlux, Agriflux) provide continuous observations of ecosystem exchanges of carbon (e. g., net ecosystem exchange), water vapor (e. g., evapotranspiration), and energy between terrestrial ecosystems and the atmosphere. The long-term time series of flux tower data are essential for studying and understanding terrestrial carbon cycles, ecosystem services, and climate changes. Currently, there are 13 flux towers located within the Great Plains (GP). The towers are sparsely distributed and do not adequately represent the varieties of vegetation cover types, climate conditions, and geophysical and biophysical conditions in the GP. This study assessed how well the available flux towers represent the environmental conditions or "ecological envelopes" across the GP and identified optimal locations for future flux towers in the GP. Regression-based remote sensing and weather-driven net ecosystem production (NEP) models derived from different extrapolation ranges (10 and 50%) were used to identify areas where ecological conditions were poorly represented by the flux tower sites and years previously used for mapping grassland fluxes. The optimal lands suitable for future flux towers within the GP were mapped. Results from this study provide information to optimize the usefulness of future flux towers in the GP and serve as a proxy for the uncertainty of the NEP map.

Copper-catalyst-controlled site-selective allenylation of ketones and aldehydes with propargyl boronates.

PubMed

Fandrick, Keith R; Ogikubo, Junichi; Fandrick, Daniel R; Patel, Nitinchandra D; Saha, Jaideep; Lee, Heewon; Ma, Shengli; Grinberg, Nelu; Busacca, Carl A; Senanayake, Chris H

2013-03-15

A practical and highly site-selective copper-PhBPE-catalyst-controlled allenylation with propargyl boronates has been developed. The methodology has shown to be tolerant of diverse ketones and aldehydes providing the allenyl adducts in high selectivity. The BPE ligand and boronate substituents were shown to direct the site selectivity for which either propargyl or allenyl adducts can be acquired in high selectivity. A model is proposed that explains the origin of the site selectivity.

COMPARISON OF RANDOM AND SYSTEMATIC SITE SELECTION FOR ASSESSING ATTAINMENT OF AQUATIC LIFE USES IN SEGMENTS OF THE OHIO RIVER

EPA Science Inventory

This report is a description of field work and data analysis results comparing a design comparable to systematic site selection with one based on random selection of sites. The report is expected to validate the use of random site selection in the bioassessment program for the O...

A novel channel selection method for optimal classification in different motor imagery BCI paradigms.

PubMed

Shan, Haijun; Xu, Haojie; Zhu, Shanan; He, Bin

2015-10-21

For sensorimotor rhythms based brain-computer interface (BCI) systems, classification of different motor imageries (MIs) remains a crucial problem. An important aspect is how many scalp electrodes (channels) should be used in order to reach optimal performance classifying motor imaginations. While the previous researches on channel selection mainly focus on MI tasks paradigms without feedback, the present work aims to investigate the optimal channel selection in MI tasks paradigms with real-time feedback (two-class control and four-class control paradigms). In the present study, three datasets respectively recorded from MI tasks experiment, two-class control and four-class control experiments were analyzed offline. Multiple frequency-spatial synthesized features were comprehensively extracted from every channel, and a new enhanced method IterRelCen was proposed to perform channel selection. IterRelCen was constructed based on Relief algorithm, but was enhanced from two aspects: change of target sample selection strategy and adoption of the idea of iterative computation, and thus performed more robust in feature selection. Finally, a multiclass support vector machine was applied as the classifier. The least number of channels that yield the best classification accuracy were considered as the optimal channels. One-way ANOVA was employed to test the significance of performance improvement among using optimal channels, all the channels and three typical MI channels (C3, C4, Cz). The results show that the proposed method outperformed other channel selection methods by achieving average classification accuracies of 85.2, 94.1, and 83.2 % for the three datasets, respectively. Moreover, the channel selection results reveal that the average numbers of optimal channels were significantly different among the three MI paradigms. It is demonstrated that IterRelCen has a strong ability for feature selection. In addition, the results have shown that the numbers of optimal channels in the three different motor imagery BCI paradigms are distinct. From a MI task paradigm, to a two-class control paradigm, and to a four-class control paradigm, the number of required channels for optimizing the classification accuracy increased. These findings may provide useful information to optimize EEG based BCI systems, and further improve the performance of noninvasive BCI.

Integrated Building Energy Systems Design Considering Storage Technologies

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

Stadler, Michael; Marnay, Chris; Siddiqui, Afzal

The addition of storage technologies such as flow batteries, conventional batteries, and heat storage can improve the economic, as well as environmental attraction of micro-generation systems (e.g., PV or fuel cells with or without CHP) and contribute to enhanced demand response. The interactions among PV, solar thermal, and storage systems can be complex, depending on the tariff structure, load profile, etc. In order to examine the impact of storage technologies on demand response and CO2 emissions, a microgrid's distributed energy resources (DER) adoption problem is formulated as a mixed-integer linear program that can pursue two strategies as its objective function.more » These two strategies are minimization of its annual energy costs or of its CO2 emissions. The problem is solved for a given test year at representative customer sites, e.g., nursing homes, to obtain not only the optimal investment portfolio, but also the optimal hourly operating schedules for the selected technologies. This paper focuses on analysis of storage technologies in micro-generation optimization on a building level, with example applications in New York State and California. It shows results from a two-year research projectperformed for the U.S. Department of Energy and ongoing work. Contrary to established expectations, our results indicate that PV and electric storage adoption compete rather than supplement each other considering the tariff structure and costs of electricity supply. The work shows that high electricity tariffs during on-peak hours are a significant driver for the adoption of electric storage technologies. To satisfy the site's objective of minimizing energy costs, the batteries have to be charged by grid power during off-peak hours instead of PV during on-peak hours. In contrast, we also show a CO2 minimization strategy where the common assumption that batteries can be charged by PV can be fulfilled at extraordinarily high energy costs for the site.« less

Heat tolerance around flowering in wheat identified as a key trait for increased yield potential in Europe under climate change

PubMed Central

Stratonovitch, Pierre; Semenov, Mikhail A.

2015-01-01

To deliver food security for the 9 billon population in 2050, a 70% increase in world food supply will be required. Projected climatic and environmental changes emphasize the need for breeding strategies that delivers both a substantial increase in yield potential and resilience to extreme weather events such as heat waves, late frost, and drought. Heat stress around sensitive stages of wheat development has been identified as a possible threat to wheat production in Europe. However, no estimates have been made to assess yield losses due to increased frequency and magnitude of heat stress under climate change. Using existing experimental data, the Sirius wheat model was refined by incorporating the effects of extreme temperature during flowering and grain filling on accelerated leaf senescence, grain number, and grain weight. This allowed us, for the first time, to quantify yield losses resulting from heat stress under climate change. The model was used to optimize wheat ideotypes for CMIP5-based climate scenarios for 2050 at six sites in Europe with diverse climates. The yield potential for heat-tolerant ideotypes can be substantially increased in the future (e.g. by 80% at Seville, 100% at Debrecen) compared with the current cultivars by selecting an optimal combination of wheat traits, e.g. optimal phenology and extended duration of grain filling. However, at two sites, Seville and Debrecen, the grain yields of heat-sensitive ideotypes were substantially lower (by 54% and 16%) and more variable compared with heat-tolerant ideotypes, because the extended grain filling required for the increased yield potential was in conflict with episodes of high temperature during flowering and grain filling. Despite much earlier flowering at these sites, the risk of heat stress affecting yields of heat-sensitive ideotypes remained high. Therefore, heat tolerance in wheat is likely to become a key trait for increased yield potential and yield stability in southern Europe in the future. PMID:25750425

Optimization Review, Optimization Review, Sidney and Richardson Hill Road Landfills, Delaware County, New York

EPA Pesticide Factsheets

The Sidney Landfill site is located on Richardson Hill Road approximately 10 miles southeast of Sidney, New York. In March 1989, the site was added to the National Priorities List (NPL) based on investigations completed by the New York State Department...

Site selection for MSFC operational tests of solar heating and cooling systems

NASA Technical Reports Server (NTRS)

1978-01-01

The criteria, methodology, and sequence aspects of the site selection process are presented. This report organized the logical thought process that should be applied to the site selection process, but final decisions are highly selective.

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.

2013 Philip S. Portoghese Medicinal Chemistry Lectureship: Drug Discovery Targeting Allosteric Sites†

PubMed Central

2015-01-01

The identification of sites on receptors topographically distinct from the orthosteric sites, so-called allosteric sites, has heralded novel approaches and modes of pharmacology for target modulation. Over the past 20 years, our understanding of allosteric modulation has grown significantly, and numerous advantages, as well as caveats (e.g., flat structure–activity relationships, species differences, “molecular switches”), have been identified. For multiple receptors and proteins, numerous examples have been described where unprecedented levels of selectivity are achieved along with improved physiochemical properties. While not a panacea, these novel approaches represent exciting opportunities for tool compound development to probe the pharmacology and therapeutic potential of discrete molecular targets, as well as new medicines. In this Perspective, in commemoration of the 2013 Philip S. Portoghese Medicinal Chemistry Lectureship (LindsleyC. W.Adventures in allosteric drug discovery. Presented at the 246th National Meeting of the American Chemical Society, Indianapolis, IN, September 10, 2013; The 2013 Portoghese Lectureship), several vignettes of drug discovery campaigns targeting novel allosteric mechanisms will be recounted, along with lessons learned and guidelines that have emerged for successful lead optimization. PMID:25180768

A novel photoaffinity ligand for the phencyclidine site of the N-methyl-D-aspartate receptor labels a Mr 120,000 polypeptide

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

Sonders, M.S.; Barmettler, P.; Lee, J.A.

1990-04-25

A radiolabeled photoaffinity ligand has been developed for the N-methyl-D-aspartate (NMDA)-preferring excitatory amino acid receptor complex. (3H)3-Azido-(5S, 10R)(+)-5-methyl-10,11-dihydro-5H- dibenzo(a,d)cyclohepten-5,10-imine (3H)3-azido-MK-801 demonstrated nearly identical affinity, density of binding sites, selectivity, pH sensitivity, and pharmacological profile in reversible binding assays with guinea pig brain homogenates to those displayed by its parent compound, MK-801. When employed in a photo-labeling protocol designed to optimize specific incorporation, (3H)3-azido-MK-801 labeled a single protein band which migrated in sodium dodecyl sulfate-polyacrylamide gels with Mr = 120,000. Incorporation of tritium into this band was completely inhibited when homogenates and (3H)3-azido-MK-801 were coincubated with 10 microM phencyclidine. These datamore » suggest that the phencyclidine site of the NMDA receptor complex is at least in part comprised of a Mr = 120,000 polypeptide.« less

Structure-Guided Design of Peptides as Tools to Probe the Protein-Protein Interaction between Cullin-2 and Elongin BC Substrate Adaptor in Cullin RING E3 Ubiquitin Ligases.

PubMed

Cardote, Teresa A F; Ciulli, Alessio

2017-09-21

Cullin RING E3 ubiquitin ligases (CRLs) are large dynamic multi-subunit complexes that control the fate of many proteins in cells. CRLs are attractive drug targets for the development of small-molecule inhibitors and chemical inducers of protein degradation. Herein we describe a structure-guided biophysical approach to probe the protein-protein interaction (PPI) between the Cullin-2 scaffold protein and the adaptor subunits Elongin BC within the context of the von Hippel-Lindau complex (CRL2 VHL ) using peptides. Two peptides were shown to bind at the targeted binding site on Elongin C, named the "EloC site", with micromolar dissociation constants, providing a starting point for future optimization. Our results suggest ligandability of the EloC binding site to short linear peptides, unveiling the opportunity and challenges to develop small molecules that have the potential to target selectively the Cul2-adaptor PPI within CRLs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Optimel: Software for selecting the optimal method

NASA Astrophysics Data System (ADS)

Popova, Olga; Popov, Boris; Romanov, Dmitry; Evseeva, Marina

Optimel: software for selecting the optimal method automates the process of selecting a solution method from the optimization methods domain. Optimel features practical novelty. It saves time and money when conducting exploratory studies if its objective is to select the most appropriate method for solving an optimization problem. Optimel features theoretical novelty because for obtaining the domain a new method of knowledge structuring was used. In the Optimel domain, extended quantity of methods and their properties are used, which allows identifying the level of scientific studies, enhancing the user's expertise level, expand the prospects the user faces and opening up new research objectives. Optimel can be used both in scientific research institutes and in educational institutions.

Sandhill crane roost selection, human disturbance, and forage resources

USGS Publications Warehouse

Pearse, Aaron T.; Krapu, Gary; Brandt, David

2017-01-01

Sites used for roosting represent a key habitat requirement for many species of birds because availability and quality of roost sites can influence individual fitness. Birds select roost sites based on numerous factors, requirements, and motivations, and selection of roosts can be dynamic in time and space because of various ecological and environmental influences. For sandhill cranes (Antigone canadensis) at their main spring-staging area along the Platte River in south-central Nebraska, USA, past investigations of roosting cranes focused on physical channel characteristics related to perceived security as motivating roost distribution. We used 6,310 roost sites selected by 313 sandhill cranes over 5 spring migration seasons (2003–2007) to quantify resource selection functions of roost sites on the central Platte River using a discrete choice analysis. Sandhill cranes generally showed stronger selection for wider channels with shorter bank vegetation situated farther from potential human disturbance features such as roads, bridges, and dwellings. Furthermore, selection for roost sites with preferable physical characteristics (wide channels with short bank vegetation) was more resilient to nearby disturbance features than more narrow channels with taller bank vegetation. The amount of cornfields surrounding sandhill crane roost sites positively influenced relative probability of use but only for more narrow channels < 100 m and those with shorter bank vegetation. We confirmed key resource features that sandhill cranes selected at river channels along the Platte River, and after incorporating spatial variation due to human disturbance, our understanding of roost site selection was more robust, providing insights on how disturbance may interact with physical habitat features. Managers can use information on roost-site selection when developing plans to increase probability of crane use at existing roost sites and to identify new areas for potential use if existing sites become limited.

Docking and scoring in virtual screening for drug discovery: methods and applications.

PubMed

Kitchen, Douglas B; Decornez, Hélène; Furr, John R; Bajorath, Jürgen

2004-11-01

Computational approaches that 'dock' small molecules into the structures of macromolecular targets and 'score' their potential complementarity to binding sites are widely used in hit identification and lead optimization. Indeed, there are now a number of drugs whose development was heavily influenced by or based on structure-based design and screening strategies, such as HIV protease inhibitors. Nevertheless, there remain significant challenges in the application of these approaches, in particular in relation to current scoring schemes. Here, we review key concepts and specific features of small-molecule-protein docking methods, highlight selected applications and discuss recent advances that aim to address the acknowledged limitations of established approaches.

A method for simultaneous echo planar imaging of hyperpolarized 13C pyruvate and 13C lactate

NASA Astrophysics Data System (ADS)

Reed, Galen D.; Larson, Peder E. Z.; von Morze, Cornelius; Bok, Robert; Lustig, Michael; Kerr, Adam B.; Pauly, John M.; Kurhanewicz, John; Vigneron, Daniel B.

2012-04-01

A rapid echo planar imaging sequence for dynamic imaging of [1-13C] lactate and [1-13C] pyruvate simultaneously was developed. Frequency-based separation of these metabolites was achieved by spatial shifting in the phase-encoded direction with the appropriate choice of echo spacing. Suppression of the pyruvate-hydrate and alanine resonances is achieved through an optimized spectral-spatial RF waveform. Signal sampling efficiency as a function of pyruvate and lactate excitation angle was simulated using two site exchange models. Dynamic imaging is demonstrated in a transgenic mouse model, and phantom validations of the RF pulse frequency selectivity were performed.

Actuator placement for active sound and vibration control of cylinders

NASA Technical Reports Server (NTRS)

Kincaid, Rex K.

1995-01-01

Active structural acoustic control is a method in which the control inputs (used to reduce interior noise) are applied directly to a vibrating structural acoustic system. The control concept modeled in this work is the application of in-plane force inputs to piezoceramic patches bonded to the wall of a vibrating cylinder. The cylinder is excited by an exterior noise source -- an acoustic monopole -- located near the outside of the cylinder wall. The goal is to determine the force inputs and sites for the piezoelectric actuators so that (1) the interior noise is effectively damped; (2) the level of vibration of the cylinder shell is not increased; and (3) the power requirements needed to drive the actuators are not excessive. We studied external monopole excitations at two frequencies. A cylinder resonance of 100 Hz, where the interior acoustic field is driven in multiple, off-resonance cylinder cavity modes, and a cylinder resonance of 200 Hz are characterized by both near and off-resonance cylinder vibration modes which couple effectively with a single, dominant, low-order acoustic cavity mode at resonance. Previous work has focused almost exclusively on meeting objective (1) and solving a complex least-squares problem to arrive at an optimal force vector for a given set of actuator sites. In addition, it has been noted that when the cavity mode couples with cylinder vibration modes (our 200 Hz case) control spillover may occur in higher order cylinder shell vibrational modes. How to determine the best set of actuator sites to meet objectives (1)-(3) is the main contribution of our research effort. The selection of the best set of actuator sites from a set of potential sites is done via two metaheuristics -- simulated annealing and tabu search. Each of these metaheuristics partitions the set of potential actuator sites into two disjoint sets: those that are selected to control the noise (on) and those that are not (off). Next, each metaheuristic attempts to improve this initial solution by calculating the change in the objective value when one selected actuator site is turned off and one actuator site that previously was not selected is turned on. All such pairwise exchanges are performed and the exchange that improves the objective the most is made. Eventually the search is unable to improve the objective value and a local optimum (with respect to pairwise exchanges) is reached. Both simulated annealing and tabu search provide mechanisms to escape local optima and allow the search to continue until (hopefully) a global optimum is found. Our experiments with the 100 Hz and 200 Hz cases confirm that both metaheuristics are able to uncover better solutions than those selected based upon engineering judgement alone. In addition, the high quality solutions generated by these metaheuristics, when minimizing interior noise, do not further excite the cylinder shell. Thus, we are able to meet objective (2) without imposing an additional constraint or forming a multiobjective performance measure. An additional observation is that in many cases the amplitude and phase values for several chosen actuator sites were nearly identical. This natural grouping means that fewer control channels are needed and the resulting control system is simpler. Currently no power requirements have been set, so objective (3) cannot be addressed. A set of experiments is planned with a laboratory test article (a cylinder). For these experiments the transfer matrices will be generated experimentally. It is hoped that the predicted performance of the best actuator sites found by our metaheuristics will correlate well with the measured performance.

Computational Intelligence Modeling of the Macromolecules Release from PLGA Microspheres-Focus on Feature Selection.

PubMed

Zawbaa, Hossam M; Szlȩk, Jakub; Grosan, Crina; Jachowicz, Renata; Mendyk, Aleksander

2016-01-01

Poly-lactide-co-glycolide (PLGA) is a copolymer of lactic and glycolic acid. Drug release from PLGA microspheres depends not only on polymer properties but also on drug type, particle size, morphology of microspheres, release conditions, etc. Selecting a subset of relevant properties for PLGA is a challenging machine learning task as there are over three hundred features to consider. In this work, we formulate the selection of critical attributes for PLGA as a multiobjective optimization problem with the aim of minimizing the error of predicting the dissolution profile while reducing the number of attributes selected. Four bio-inspired optimization algorithms: antlion optimization, binary version of antlion optimization, grey wolf optimization, and social spider optimization are used to select the optimal feature set for predicting the dissolution profile of PLGA. Besides these, LASSO algorithm is also used for comparisons. Selection of crucial variables is performed under the assumption that both predictability and model simplicity are of equal importance to the final result. During the feature selection process, a set of input variables is employed to find minimum generalization error across different predictive models and their settings/architectures. The methodology is evaluated using predictive modeling for which various tools are chosen, such as Cubist, random forests, artificial neural networks (monotonic MLP, deep learning MLP), multivariate adaptive regression splines, classification and regression tree, and hybrid systems of fuzzy logic and evolutionary computations (fugeR). The experimental results are compared with the results reported by Szlȩk. We obtain a normalized root mean square error (NRMSE) of 15.97% versus 15.4%, and the number of selected input features is smaller, nine versus eleven.

Computational Intelligence Modeling of the Macromolecules Release from PLGA Microspheres—Focus on Feature Selection

PubMed Central

Zawbaa, Hossam M.; Szlȩk, Jakub; Grosan, Crina; Jachowicz, Renata; Mendyk, Aleksander

2016-01-01

Poly-lactide-co-glycolide (PLGA) is a copolymer of lactic and glycolic acid. Drug release from PLGA microspheres depends not only on polymer properties but also on drug type, particle size, morphology of microspheres, release conditions, etc. Selecting a subset of relevant properties for PLGA is a challenging machine learning task as there are over three hundred features to consider. In this work, we formulate the selection of critical attributes for PLGA as a multiobjective optimization problem with the aim of minimizing the error of predicting the dissolution profile while reducing the number of attributes selected. Four bio-inspired optimization algorithms: antlion optimization, binary version of antlion optimization, grey wolf optimization, and social spider optimization are used to select the optimal feature set for predicting the dissolution profile of PLGA. Besides these, LASSO algorithm is also used for comparisons. Selection of crucial variables is performed under the assumption that both predictability and model simplicity are of equal importance to the final result. During the feature selection process, a set of input variables is employed to find minimum generalization error across different predictive models and their settings/architectures. The methodology is evaluated using predictive modeling for which various tools are chosen, such as Cubist, random forests, artificial neural networks (monotonic MLP, deep learning MLP), multivariate adaptive regression splines, classification and regression tree, and hybrid systems of fuzzy logic and evolutionary computations (fugeR). The experimental results are compared with the results reported by Szlȩk. We obtain a normalized root mean square error (NRMSE) of 15.97% versus 15.4%, and the number of selected input features is smaller, nine versus eleven. PMID:27315205

Pilot Project to Optimize Ground Water Remediation Systems at RCRA Corrective Action Facilities: Summary Report and Lessons Learned

EPA Pesticide Factsheets

Based on previous success with conducting independent optimization evaluations at Fund-lead pump and treat sites (i.e., those sites with pump and treat systems funded and managed by Superfund and the States), the EPA Office of Superfund .....

Bed site selection by neonate deer in grassland habitats on the northern Great Plains

USGS Publications Warehouse

Grovenburg, T.W.; Jacques, C.N.; Klaver, R.W.; Jenks, J.A.

2010-01-01

Bed site selection is an important behavioral trait influencing neonate survival. Vegetation characteristics of bed sites influence thermal protection of neonates and concealment from predators. Although previous studies describe bed site selection of neonatal white-tailed deer (Odocoileus virginianus) in regions of forested cover, none determined microhabitat effects on neonate bed site selection in the Northern Great Plains, an area of limited forest cover. During summers 2007–2009, we investigated bed site selection (n  =  152) by 81 radiocollared neonate white-tailed deer in north-central South Dakota, USA. We documented 80 (52.6%) bed sites in tallgrass–Conservation Reserve Program lands, 35 (23.0%) bed sites in forested cover, and 37 (24.3%) in other habitats (e.g., pasture, alfalfa, wheat). Bed site selection varied with age and sex of neonate. Tree canopy cover (P < 0.001) and tree basal area (P < 0.001) decreased with age of neonates, with no bed sites observed in forested cover after 18 days of age. Male neonates selected sites with less grass cover (P < 0.001), vertical height of understory vegetation (P < 0.001), and density of understory vegetation (P < 0.001) but greater bare ground (P  =  0.047), litter (P  =  0.028), and wheat (P  =  0.044) than did females. Odds of bed site selection increased 3.5% (odds ratio  =  1.035, 95% CI  =  1.008–1.062) for every 1-cm increase in vertical height of understory vegetation. Management for habitat throughout the grasslands of South Dakota that maximizes vertical height of understory vegetation would enhance cover characteristics selected by neonates.

Learning from Past Classification Errors: Exploring Methods for Improving the Performance of a Deep Learning-based Building Extraction Model through Quantitative Analysis of Commission Errors for Optimal Sample Selection

NASA Astrophysics Data System (ADS)

Swan, B.; Laverdiere, M.; Yang, L.

2017-12-01

In the past five years, deep Convolutional Neural Networks (CNN) have been increasingly favored for computer vision applications due to their high accuracy and ability to generalize well in very complex problems; however, details of how they function and in turn how they may be optimized are still imperfectly understood. In particular, their complex and highly nonlinear network architecture, including many hidden layers and self-learned parameters, as well as their mathematical implications, presents open questions about how to effectively select training data. Without knowledge of the exact ways the model processes and transforms its inputs, intuition alone may fail as a guide to selecting highly relevant training samples. Working in the context of improving a CNN-based building extraction model used for the LandScan USA gridded population dataset, we have approached this problem by developing a semi-supervised, highly-scalable approach to select training samples from a dataset of identified commission errors. Due to the large scope this project, tens of thousands of potential samples could be derived from identified commission errors. To efficiently trim those samples down to a manageable and effective set for creating additional training sample, we statistically summarized the spectral characteristics of areas with rates of commission errors at the image tile level and grouped these tiles using affinity propagation. Highly representative members of each commission error cluster were then used to select sites for training sample creation. The model will be incrementally re-trained with the new training data to allow for an assessment of how the addition of different types of samples affects the model performance, such as precision and recall rates. By using quantitative analysis and data clustering techniques to select highly relevant training samples, we hope to improve model performance in a manner that is resource efficient, both in terms of training process and in sample creation.

Artificial Intelligence Based Selection of Optimal Cutting Tool and Process Parameters for Effective Turning and Milling Operations

NASA Astrophysics Data System (ADS)

Saranya, Kunaparaju; John Rozario Jegaraj, J.; Ramesh Kumar, Katta; Venkateshwara Rao, Ghanta

2016-06-01

With the increased trend in automation of modern manufacturing industry, the human intervention in routine, repetitive and data specific activities of manufacturing is greatly reduced. In this paper, an attempt has been made to reduce the human intervention in selection of optimal cutting tool and process parameters for metal cutting applications, using Artificial Intelligence techniques. Generally, the selection of appropriate cutting tool and parameters in metal cutting is carried out by experienced technician/cutting tool expert based on his knowledge base or extensive search from huge cutting tool database. The present proposed approach replaces the existing practice of physical search for tools from the databooks/tool catalogues with intelligent knowledge-based selection system. This system employs artificial intelligence based techniques such as artificial neural networks, fuzzy logic and genetic algorithm for decision making and optimization. This intelligence based optimal tool selection strategy is developed using Mathworks Matlab Version 7.11.0 and implemented. The cutting tool database was obtained from the tool catalogues of different tool manufacturers. This paper discusses in detail, the methodology and strategies employed for selection of appropriate cutting tool and optimization of process parameters based on multi-objective optimization criteria considering material removal rate, tool life and tool cost.

Tuning the ion selectivity of tetrameric cation channels by changing the number of ion binding sites

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

Derebe, Mehabaw G.; Sauer, David B.; Zeng, Weizhong

2015-11-30

Selective ion conduction across ion channel pores is central to cellular physiology. To understand the underlying principles of ion selectivity in tetrameric cation channels, we engineered a set of cation channel pores based on the nonselective NaK channel and determined their structures to high resolution. These structures showcase an ensemble of selectivity filters with a various number of contiguous ion binding sites ranging from 2 to 4, with each individual site maintaining a geometry and ligand environment virtually identical to that of equivalent sites in K{sup +} channel selectivity filters. Combined with single channel electrophysiology, we show that only themore » channel with four ion binding sites is K{sup +} selective, whereas those with two or three are nonselective and permeate Na{sup +} and K{sup +} equally well. These observations strongly suggest that the number of contiguous ion binding sites in a single file is the key determinant of the channel's selectivity properties and the presence of four sites in K{sup +} channels is essential for highly selective and efficient permeation of K{sup +} ions.« less

π-Clamp-mediated cysteine conjugation

NASA Astrophysics Data System (ADS)

Zhang, Chi; Welborn, Matthew; Zhu, Tianyu; Yang, Nicole J.; Santos, Michael S.; van Voorhis, Troy; Pentelute, Bradley L.

2016-02-01

Site-selective functionalization of complex molecules is one of the most significant challenges in chemistry. Typically, protecting groups or catalysts must be used to enable the selective modification of one site among many that are similarly reactive, and general strategies that selectively tune the local chemical environment around a target site are rare. Here, we show a four-amino-acid sequence (Phe-Cys-Pro-Phe), which we call the ‘π-clamp’, that tunes the reactivity of its cysteine thiol for site-selective conjugation with perfluoroaromatic reagents. We use the π-clamp to selectively modify one cysteine site in proteins containing multiple endogenous cysteine residues. These examples include antibodies and cysteine-based enzymes that would be difficult to modify selectively using standard cysteine-based methods. Antibodies modified using the π-clamp retained binding affinity to their targets, enabling the synthesis of site-specific antibody-drug conjugates for selective killing of HER2-positive breast cancer cells. The π-clamp is an unexpected approach to mediate site-selective chemistry and provides new avenues to modify biomolecules for research and therapeutics.

Discovery, structure-activity relationship, and pharmacological evaluation of (5-substituted-pyrrolidinyl-2-carbonyl)-2-cyanopyrrolidines as potent dipeptidyl peptidase IV inhibitors.

PubMed

Pei, Zhonghua; Li, Xiaofeng; Longenecker, Kenton; von Geldern, Thomas W; Wiedeman, Paul E; Lubben, Thomas H; Zinker, Bradley A; Stewart, Kent; Ballaron, Stephen J; Stashko, Michael A; Mika, Amanda K; Beno, David W A; Long, Michelle; Wells, Heidi; Kempf-Grote, Anita J; Madar, David J; McDermott, Todd S; Bhagavatula, Lakshmi; Fickes, Michael G; Pireh, Daisy; Solomon, Larry R; Lake, Marc R; Edalji, Rohinton; Fry, Elizabeth H; Sham, Hing L; Trevillyan, James M

2006-06-15

A series of (5-substituted pyrrolidinyl-2-carbonyl)-2-cyanopyrrolidine (C5-Pro-Pro) analogues was discovered as dipeptidyl peptidase IV (DPPIV) inhibitors as a potential treatment of diabetes and obesity. X-ray crystallography data show that these inhibitors bind to the catalytic site of DPPIV with the cyano group forming a covalent bond with the serine residue of DPPIV. The C5-substituents make various interactions with the enzyme and affect potency, chemical stability, selectivity, and PK properties of the inhibitors. Optimized analogues are extremely potent with subnanomolar K(i)'s, are chemically stable, show very little potency decrease in the presence of plasma, and exhibit more than 1,000-fold selectivity against related peptidases. The best compounds also possess good PK and are efficacious in lowering blood glucose in an oral glucose tolerance test in ZDF rats.

Tag SNP selection via a genetic algorithm.

PubMed

Mahdevar, Ghasem; Zahiri, Javad; Sadeghi, Mehdi; Nowzari-Dalini, Abbas; Ahrabian, Hayedeh

2010-10-01

Single Nucleotide Polymorphisms (SNPs) provide valuable information on human evolutionary history and may lead us to identify genetic variants responsible for human complex diseases. Unfortunately, molecular haplotyping methods are costly, laborious, and time consuming; therefore, algorithms for constructing full haplotype patterns from small available data through computational methods, Tag SNP selection problem, are convenient and attractive. This problem is proved to be an NP-hard problem, so heuristic methods may be useful. In this paper we present a heuristic method based on genetic algorithm to find reasonable solution within acceptable time. The algorithm was tested on a variety of simulated and experimental data. In comparison with the exact algorithm, based on brute force approach, results show that our method can obtain optimal solutions in almost all cases and runs much faster than exact algorithm when the number of SNP sites is large. Our software is available upon request to the corresponding author.

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.

Experimental mixture design as a tool for the synthesis of antimicrobial selective molecularly imprinted monodisperse microbeads.

PubMed

Benito-Peña, Elena; Navarro-Villoslada, Fernando; Carrasco, Sergio; Jockusch, Steffen; Ottaviani, M Francesca; Moreno-Bondi, Maria C

2015-05-27

The effect of the cross-linker on the shape and size of molecular imprinted polymer (MIP) beads prepared by precipitation polymerization has been evaluated using a chemometric approach. Molecularly imprinted microspheres for the selective recognition of fluoroquinolone antimicrobials were prepared in a one-step precipitation polymerization procedure using enrofloxacin (ENR) as the template molecule, methacrylic acid as functional monomer, 2-hydroxyethyl methacrylate as hydrophilic comonomer, and acetonitrile as the porogen. The type and amount of cross-linker, namely ethylene glycol dimethacrylate, divinylbenzene or trimethylolpropane trimethacrylate, to obtain monodispersed MIP spherical beads in the micrometer range was optimized using a simplex lattice design. Particle size and morphology were assessed by scanning electron microscopy, dynamic light scattering, and nitrogen adsorption measurements. Electron paramagnetic resonance spectroscopy in conjunction with a nitroxide as spin probe revealed information about the microviscosity and polarity of the binding sites in imprinted and nonimprinted polymer beads.

Study on Topology Optimization Design, Manufacturability, and Performance Evaluation of Ti-6Al-4V Porous Structures Fabricated by Selective Laser Melting (SLM)

PubMed Central

Xu, Yangli; Zhang, Dongyun; Zhou, Yan; Wang, Weidong; Cao, Xuanyang

2017-01-01

The combination of topology optimization (TOP) and selective laser melting (SLM) provides the possibility of fabricating the complex, lightweight and high performance geometries overcoming the traditional manufacturing “bottleneck”. This paper evaluates the biomechanical properties of porous structures with porosity from 40% to 80% and unit cell size from 2 to 8 mm, which are designed by TOP and manufactured by SLM. During manufacturability exploration, three typical structures including spiral structure, arched bridge structure and structures with thin walls and small holes are abstracted and investigated, analyzing their manufacturing limits and forming reason. The property tests show that dynamic elastic modulus and compressive strength of porous structures decreases with increases of porosity (constant unit cell size) or unit cell size (constant porosity). Based on the Gibson-Ashby model, three failure models are proposed to describe their compressive behavior, and the structural parameter λ is used to evaluate the stability of the porous structure. Finally, a numerical model for the correlation between porous structural parameters (unit cell size and porosity) and elastic modulus is established, which provides a theoretical reference for matching the elastic modulus of human bones from different age, gender and skeletal sites during innovative medical implant design and manufacturing. PMID:28880229

Study on Topology Optimization Design, Manufacturability, and Performance Evaluation of Ti-6Al-4V Porous Structures Fabricated by Selective Laser Melting (SLM).

PubMed

Xu, Yangli; Zhang, Dongyun; Zhou, Yan; Wang, Weidong; Cao, Xuanyang

2017-09-07

The combination of topology optimization (TOP) and selective laser melting (SLM) provides the possibility of fabricating the complex, lightweight and high performance geometries overcoming the traditional manufacturing "bottleneck". This paper evaluates the biomechanical properties of porous structures with porosity from 40% to 80% and unit cell size from 2 to 8 mm, which are designed by TOP and manufactured by SLM. During manufacturability exploration, three typical structures including spiral structure, arched bridge structure and structures with thin walls and small holes are abstracted and investigated, analyzing their manufacturing limits and forming reason. The property tests show that dynamic elastic modulus and compressive strength of porous structures decreases with increases of porosity (constant unit cell size) or unit cell size (constant porosity). Based on the Gibson-Ashby model, three failure models are proposed to describe their compressive behavior, and the structural parameter λ is used to evaluate the stability of the porous structure. Finally, a numerical model for the correlation between porous structural parameters (unit cell size and porosity) and elastic modulus is established, which provides a theoretical reference for matching the elastic modulus of human bones from different age, gender and skeletal sites during innovative medical implant design and manufacturing.

Optimal selection of biochars for remediating metals ...

EPA Pesticide Factsheets

Approximately 500,000 abandoned mines across the U.S. pose a considerable, pervasive risk to human health and the environment due to possible exposure to the residuals of heavy metal extraction. Historically, a variety of chemical and biological methods have been used to reduce the bioavailability of the metals at mine sites. Biochar with its potential to complex and immobilize heavy metals, is an emerging alternative for reducing bioavailability. Furthermore, biochar has been reported to improve soil conditions for plant growth and can be used for promoting the establishment of a soil-stabilizing native plant community to reduce offsite movement of metal-laden waste materials. Because biochar properties depend upon feedstock selection, pyrolysis production conditions, and activation procedures used, they can be designed to meet specific remediation needs. As a result biochar with specific properties can be produced to correspond to specific soil remediation situations. However, techniques are needed to optimally match biochar characteristics with metals contaminated soils to effectively reduce metal bioavailability. Here we present experimental results used to develop a generalized method for evaluating the ability of biochar to reduce metals in mine spoil soil from an abandoned Cu and Zn mine. Thirty-eight biochars were produced from approximately 20 different feedstocks and produced via slow pyrolysis or gasification, and were allowed to react with a f

Guide RNA selection for CRISPR-Cas9 transfections in Plasmodium falciparum.

PubMed

Ribeiro, Jose M; Garriga, Meera; Potchen, Nicole; Crater, Anna K; Gupta, Ankit; Ito, Daisuke; Desai, Sanjay A

2018-06-12

CRISPR-Cas9 mediated genome editing is addressing key limitations in the transfection of malaria parasites. While this method has already simplified the needed molecular cloning and reduced the time required to generate mutants in the human pathogen Plasmodium falciparum, optimal selection of required guide RNAs and guidelines for successful transfections have not been well characterized, leading workers to use time-consuming trial and error approaches. We used a genome-wide computational approach to create a comprehensive and publicly accessible database of possible guide RNA sequences in the P. falciparum genome. For each guide, we report on-target efficiency and specificity scores as well as information about the genomic site relevant to optimal design of CRISPR-Cas9 transfections to modify, disrupt, or conditionally knockdown any gene. As many antimalarial drug and vaccine targets are encoded by multigene families, we also developed a new paralog specificity score that should facilitate modification of either a single family member of interest or multiple paralogs that serve overlapping roles. Finally, we tabulated features of successful transfections in our laboratory, providing broadly useful guidelines for parasite transfections. Molecular studies aimed at understanding parasite biology or characterizing drug and vaccine targets in P. falciparum should be facilitated by this comprehensive database. Published by Elsevier Ltd.

A novel orbiter mission concept for venus with the EnVision proposal

NASA Astrophysics Data System (ADS)

de Oliveira, Marta R. R.; Gil, Paulo J. S.; Ghail, Richard

2018-07-01

In space exploration, planetary orbiter missions are essential to gain insight into planets as a whole, and to help uncover unanswered scientific questions. In particular, the planets closest to the Earth have been a privileged target of the world's leading space agencies. EnVision is a mission proposal designed for Venus and competing for ESA's next launch opportunity with the objective of studying Earth's closest neighbor. The main goal is to study geological and atmospheric processes, namely surface processes, interior dynamics and atmosphere, to determine the reasons behind Venus and Earth's radically different evolution despite the planets' similarities. To achieve these goals, the operational orbit selection is a fundamental element of the mission design process. The design of an orbit around Venus faces specific challenges, such as the impossibility of choosing Sun-synchronous orbits. In this paper, an innovative genetic algorithm optimization was applied to select the optimal orbit based on the parameters with more influence in the mission planning, in particular the mission duration and the coverage of sites of interest on the Venusian surface. The solution obtained is a near-polar circular orbit with an altitude of 259 km that enables the coverage of all priority targets almost two times faster than with the parameters considered before this study.

Stochastic injection-strategy optimization for the preliminary assessment of candidate geological storage sites

NASA Astrophysics Data System (ADS)

Cody, Brent M.; Baù, Domenico; González-Nicolás, Ana

2015-09-01

Geological carbon sequestration (GCS) has been identified as having the potential to reduce increasing atmospheric concentrations of carbon dioxide (CO2). However, a global impact will only be achieved if GCS is cost-effectively and safely implemented on a massive scale. This work presents a computationally efficient methodology for identifying optimal injection strategies at candidate GCS sites having uncertainty associated with caprock permeability, effective compressibility, and aquifer permeability. A multi-objective evolutionary optimization algorithm is used to heuristically determine non-dominated solutions between the following two competing objectives: (1) maximize mass of CO2 sequestered and (2) minimize project cost. A semi-analytical algorithm is used to estimate CO2 leakage mass rather than a numerical model, enabling the study of GCS sites having vastly different domain characteristics. The stochastic optimization framework presented herein is applied to a feasibility study of GCS in a brine aquifer in the Michigan Basin (MB), USA. Eight optimization test cases are performed to investigate the impact of decision-maker (DM) preferences on Pareto-optimal objective-function values and carbon-injection strategies. This analysis shows that the feasibility of GCS at the MB test site is highly dependent upon the DM's risk-adversity preference and degree of uncertainty associated with caprock integrity. Finally, large gains in computational efficiency achieved using parallel processing and archiving are discussed.

CPAC: Energy-Efficient Data Collection through Adaptive Selection of Compression Algorithms for Sensor Networks

PubMed Central

Lee, HyungJune; Kim, HyunSeok; Chang, Ik Joon

2014-01-01

We propose a technique to optimize the energy efficiency of data collection in sensor networks by exploiting a selective data compression. To achieve such an aim, we need to make optimal decisions regarding two aspects: (1) which sensor nodes should execute compression; and (2) which compression algorithm should be used by the selected sensor nodes. We formulate this problem into binary integer programs, which provide an energy-optimal solution under the given latency constraint. Our simulation results show that the optimization algorithm significantly reduces the overall network-wide energy consumption for data collection. In the environment having a stationary sink from stationary sensor nodes, the optimized data collection shows 47% energy savings compared to the state-of-the-art collection protocol (CTP). More importantly, we demonstrate that our optimized data collection provides the best performance in an intermittent network under high interference. In such networks, we found that the selective compression for frequent packet retransmissions saves up to 55% energy compared to the best known protocol. PMID:24721763

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

PubMed

Becker, Jamie E; Brown, Christopher A

2016-01-01

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

Extensively Parameterized Mutation-Selection Models Reliably Capture Site-Specific Selective Constraint.

PubMed

Spielman, Stephanie J; Wilke, Claus O

2016-11-01

The mutation-selection model of coding sequence evolution has received renewed attention for its use in estimating site-specific amino acid propensities and selection coefficient distributions. Two computationally tractable mutation-selection inference frameworks have been introduced: One framework employs a fixed-effects, highly parameterized maximum likelihood approach, whereas the other employs a random-effects Bayesian Dirichlet Process approach. While both implementations follow the same model, they appear to make distinct predictions about the distribution of selection coefficients. The fixed-effects framework estimates a large proportion of highly deleterious substitutions, whereas the random-effects framework estimates that all substitutions are either nearly neutral or weakly deleterious. It remains unknown, however, how accurately each method infers evolutionary constraints at individual sites. Indeed, selection coefficient distributions pool all site-specific inferences, thereby obscuring a precise assessment of site-specific estimates. Therefore, in this study, we use a simulation-based strategy to determine how accurately each approach recapitulates the selective constraint at individual sites. We find that the fixed-effects approach, despite its extensive parameterization, consistently and accurately estimates site-specific evolutionary constraint. By contrast, the random-effects Bayesian approach systematically underestimates the strength of natural selection, particularly for slowly evolving sites. We also find that, despite the strong differences between their inferred selection coefficient distributions, the fixed- and random-effects approaches yield surprisingly similar inferences of site-specific selective constraint. We conclude that the fixed-effects mutation-selection framework provides the more reliable software platform for model application and future development. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The Global Seismographic Network (GSN): Deployment of Next Generation VBB Borehole Sensors and Improving Overall Network Noise Performance

NASA Astrophysics Data System (ADS)

Hafner, K.; Davis, P.; Wilson, D.; Sumy, D.

2017-12-01

The Global Seismographic Network (GSN) recently received delivery of the next generation Very Broadband (VBB) borehole sensors purchased through funding from the DOE. Deployment of these sensors will be underway during the end of summer and fall of 2017 and they will eventually replace the aging KS54000 sensors at approximately one-third of the GSN network stations. We will present the latest methods of deploying these sensors in the existing deep boreholes. To achieve lower noise performance at some sites, emplacement in shallow boreholes might result in lower noise performance for the existing site conditions. In some cases shallow borehole installations may be adapted to vault stations (which make up two thirds of the network), as a means of reducing tilt-induced signals on the horizontal components. The GSN is creating a prioritized list of equipment upgrades at selected stations with the ultimate goal of optimizing overall network data availability and noise performance. For an overview of the performance of the current GSN relative to selected set of metrics, we are utilizing data quality metrics and Probability Density Functions (PDFs)) generated by the IRIS Data Management Centers' (DMC) MUSTANG (Modular Utility for Statistical Knowledge Gathering) and LASSO (Latest Assessment of Seismic Station Observations) tools. We will present our metric analysis of GSN performance in 2016, and show the improvements at GSN sites resulting from recent instrumentation and infrastructure upgrades.

The Effect of Top-Level Domains and Advertisements on Health Web Site Credibility

PubMed Central

Wang, Zuoming; Loh, Tracy

2004-01-01

Background Concerns over health information on the Internet have generated efforts to enhance credibility markers; yet how users actually assess the credibility of online health information is largely unknown. Objective This study set out to (1) establish a parsimonious and valid questionnaire instrument to measure credibility of Internet health information by drawing on various previous measures of source, news, and other credibility scales; and (2) to identify the effects of Web-site domains and advertising on credibility perceptions. Methods Respondents (N = 156) examined one of 12 Web-site mock-ups and completed credibility scales in a 3 x 2 x 2 between-subjects experimental design. Factor analysis and validity checks were used for item reduction, and analysis of variance was employed for hypothesis testing of Web-site features' effects. Results In an attempt to construct a credibility instrument, three dimensions of credibility (safety, trustworthiness, and dynamism) were retained, reflecting traditional credibility sub-themes, but composed of items from disparate sources. When testing the effect of the presence or absence of advertising on a Web site on credibility, we found that this depends on the site's domain, with a trend for advertisements having deleterious effects on the credibility of sites with .org domain, but positive effects on sites with .com or .edu domains. Conclusions Health-information Web-site providers should select domains purposefully when they can, especially if they must accept on-site advertising. Credibility perceptions may not be invariant or stable, but rather are sensitive to topic and context. Future research may employ these findings in order to compare other forms of health-information delivery to optimal Web-site features. PMID:15471750

What is the Optimal Strategy for Adaptive Servo-Ventilation Therapy?

PubMed

Imamura, Teruhiko; Kinugawa, Koichiro

2018-05-23

Clinical advantages in the adaptive servo-ventilation (ASV) therapy have been reported in selected heart failure patients with/without sleep-disorder breathing, whereas multicenter randomized control trials could not demonstrate such advantages. Considering this discrepancy, optimal patient selection and device setting may be a key for the successful ASV therapy. Hemodynamic and echocardiographic parameters indicating pulmonary congestion such as elevated pulmonary capillary wedge pressure were reported as predictors of good response to ASV therapy. Recently, parameters indicating right ventricular dysfunction also have been reported as good predictors. Optimal device setting with appropriate pressure setting during appropriate time may also be a key. Large-scale prospective trial with optimal patient selection and optimal device setting is warranted.

Combinatorial Optimization in Project Selection Using Genetic Algorithm

NASA Astrophysics Data System (ADS)

Dewi, Sari; Sawaluddin

2018-01-01

This paper discusses the problem of project selection in the presence of two objective functions that maximize profit and minimize cost and the existence of some limitations is limited resources availability and time available so that there is need allocation of resources in each project. These resources are human resources, machine resources, raw material resources. This is treated as a consideration to not exceed the budget that has been determined. So that can be formulated mathematics for objective function (multi-objective) with boundaries that fulfilled. To assist the project selection process, a multi-objective combinatorial optimization approach is used to obtain an optimal solution for the selection of the right project. It then described a multi-objective method of genetic algorithm as one method of multi-objective combinatorial optimization approach to simplify the project selection process in a large scope.